EHC 2024 Abstracts

AL001 Overuse of analgesics can affect the fertility biomarker Anti-Müllerian hormone in females. A translational study L. Carlsen1 1Rigshospitalet Glostrup, Neurology Department, Glostrup, Denmark clinical (7.3)) prospective Objective: Over-the-counter analgesics (OTC) have been associated with disrupted male endocrinology, while effects on female endocrinology remains nearly unknown. The aim was to understand the effect of in long-term analgesic exposure females with medication overuse headache (MOH) on Anti- Müllerian Hormone (AMH), a surrogate measure of female fertility. translational approach, an Methods: Using a observational study was conducted to determine AMH-levels in females with MOH, in combination with pre-clinical investigation of primary granulosa cells (GC) to understand the effects of analgesics on GC-function. Results: We included 21 females (mean-age 30.0 years; SD for AMH-measurement. AMH increased by 21% from baseline (mean 20.1 pmol/L; SD (8.7)) after withdrawal of analgesics ((mean 24.3pmol/L; SD (12.0)); p=0.0023). Exposing primary GCs to analgesics (acetaminophen (100 and 200 µM, n = 9-10) and ibuprofen (150 and 200 µM, n = 12-13)) did not reduce AMH-levels. In contrast, de novo DNA synthesis in GCs (n=6) exposed to acetaminophen was reduced with 78% (p=0.0036) compared to controls, suggesting that cellular proliferation was restricted. Conclusion: Frequent use of OTC was associated with repressed AMH-levels likely through disruption of GC proliferation. Further research is crucial to investigate a potential effect of analgesics on adult female reproductive endocrinology. AL002 Sex differences in RAMP1/RAMP2 expression in the human middle meningeal artery match functional response to CGRP T. de Vries1, D. Schutter1, R. Dammers2, A. Vincent2, A. H. J. Danser1, A. Maassen van den Brink1 1Erasmus MC University Medical Center, Internal Medicine, Division of Pharmacology and Vascular Medicine, Rotterdam, Netherlands 2Erasmus MC University Medical Center, Neurosurgery, Rotterdam, Netherlands Objective: CGRP induces vasodilation after binding to the CGRP receptor (CLR-RAMP1), but can activate the adrenomedullin (CLR-RAMP2) as well. Previously, age-dependent sex differences were observed for CGRP-induced relaxation of human receptor ratio middle meningeal arteries1. In addition, RAMP1 and RAMP2 mRNA expression was highly variable between patients2. The current study aims to investigate whether RAMP1 and RAMP2 expression differs between men and women and varies throughout life. Methods: RNA was isolated from homogenized human middle meningeal arteries (14 F, 12 M, age 51±3 years) and qPCR was performed for RAMP1 and RAMP2 mRNA expression. The ratio between RAMP1 and RAMP2 expression with increasing age was investigated for men and women separately. Results: The RAMP1/RAMP2 significantly decreases with age in men, while a positive trend can be observed for women. These findings match the pattern of maximum relaxation to CGRP as observed in a previous study1, with a significant decrease with age in men and a trend for increased maximum relaxation with age in women. Conclusion: The current study suggests that the maximum effect of CGRP-induced relaxation of human middle meningeal arteries matches the ratio of RAMP1/RAMP2 expression, and changes in a sex- dependent manner with increasing age. Interestingly, migraine in pre- menopausal women. Here, these young women show a relatively high RAMP2 and low RAMP1 expression, suggesting predominance of the adrenomedullin receptor over the canonical CGRP receptor in this population. Possibly, increased exposure of CGRP in young women results in downregulation of RAMP1. Future research should investigate whether RAMP1 and RAMP2 expression is altered in migraine patients. References 1) de Vries T., Boucherie D. M., et al. 2024. Cephalalgia In Press 2) de Vries T., Schutter D. et al. 2023. P200 European Headache Congress 2023, Barcelona, Spain. is generally most prevalent Fig. 1

Fig. 1 Fig. 2 Fig. 3 AL003 Enhancing migraine prediction with behavioral dynamics and transformer models M. Ouellet1,2, C. Siebra1,3, K. Wac1 1University of Geneva, Quality of Life Technologies Lab, Carouge, Switzerland 2Hasso Plattner Institute, Digital Health Cluster, Postdam, Germany 3Federal University of Paraiba, Informatics Center, João Pessoa, Brazil selected Objective: Our study explores the feasibility of using behavioral features and transformer models to improve forecasting next-day migraine attacks, aiming to enhance the quality of life for migraine sufferers. Methods: Leveraging data from the Migraine Buddy mobile app (Healint Pte. Ltd.), we analyzed daily occurrences of self-reported triggers (behavioral, non- behavioral), passively-collected activities (e.g. time spent running), drug intake, and metrics on sleep (duration, interruptions) as well as migraine (duration, intensity). We predicted next-day attack starting with 4 commonly used machine learning techniques (see table). To investigate temporal dependencies and behavioral patterns, we time-series transformer models (Time Series Transformer, and Temporal Fusion Transformer) along with the Long Short-Term Memory and vanilla Transformer models for baseline comparison. Models were adjusted for class imbalance and evaluated with 3-fold cross- validation and stratified sampling. Results: Our sample included 2,733 individuals aged 18 to 65 with 1 to 7 (ICHD-3 non-chronic) migraines per month over 31 consecutive days (n=84,723). The Temporal Fusion Transformer performed the best, and feature importance using expected gradients was investigated 30 days prior to attack for triggers and activities. Cycling, dietary habits, walking, and running reduced the likelihood of a next-day attack, while staying still, allergies/sinuses, and environmental triggers increased it. Examining at the daily level, we see the sustained benefits of walking and cycling. The 3-day window prior shows the highest magnitude of feature importance, and the benefit of sequence models in understanding effects over time given the change in direction of some feature effects as early as 1 day prior. Conclusion: This research highlights the significance of everyday behavior for migraine sufferers, particularly physical activity. Future studies could examine longer and more granular time sequences using similar deep learning models.

AL004 Predicting migraine attacks using nighttime wearable sensor data S. Andruskevicius1, V. Kapustynska2, K. Ryliškienė1 1Vilnius University, Center of Neurology, Vilnius, Lithuania 2Vilnius Gediminas Technical University, Faculty of Electronics, Vilnius, Lithuania AL005 Artificial neural network applied to neurophysiology may assist in migraine classification G. Sebastianelli1, D. Secci2, F. Casillo1, C. Abagnale1, C. Di Lorenzo1, G. Coppola1 1Sapienza University of Rome, Department of Medico- Surgical Sciences and Biotechnologies, Latina, Italy 2University of Parma, Department of Engineering and Architecture, Parma, Italy Objective: Autonomic nervous system alterations during the migraine prodrome phase may offer valuable predictive indicators for impending attacks. The study analyzed changes in biosignals during the pre-migraine night. Methods: Wrist-worn biosensor device was used for continuous monitoring of physiological parameters. Patients reported the onset of migraine headaches marking the event on a wearable device and documenting it in a headache diary, providing a double control to ensure data accuracy and reliability. Sleep signals were segmented into 10-minute analysis frames to construct the training and testing datasets. Signals from electrodermal activity (EDA), pulse rate (PR), pulse rate variability (PRV), and skin temperature were employed for predictions. Random forests were implemented for training the network, with 5-fold cross-validation utilized to improve model training quality. The implementation extensively leveraged Python libraries and tools; Scikit-learn was used for deploying forest algorithm and conducting cross-validation, while NumPy and Pandas were and manipulation. Results: Data from 10 migraineurs were analyzed. The average monitoring period was 29.7 ± 15.3 days and the average headache days was 4.4 ± 1.17. A minimum of 3 migraine episodes were recorded. The accuracy of the model in predicting migraines on the following day, based on alterations observed during night monitoring, was 0.8646 ± 0.0646, indicating high overall correctness. The precision was 0.8054 ± 0.0833, reflecting reliable identification of positive instances. The recall was 0.6802 ± 0.1466, suggesting a moderate ability to capture actual positive cases. The F1-score was 0.6895 ± 0.1538, indicating a solid overall performance of the model. Conclusion: Findings underscore the potential of using wearable biosensors and advanced predictive models for early detection of migraine attacks by capturing autonomic nervous system changes the night before the headache. instrumental handling random data the for Objective: Finding a biomarker to diagnose migraine is one of the long-standing challenges in the headache field. Individuals with migraine have dynamic and recurrent alterations in the brainstem-thalamus- cortex loop, with reduced thalamocortical activity and abnormal habituation in the interictal phase. Although these alterations were helpful in understanding migraine pathogenesis, they are not currently used in clinical settings. This study aims to investigate the potential of Artificial Neural Network (ANN) in discriminating migraine patients from healthy subjects using neurophysiology recordings. Methods: We recorded somatosensory evoked potentials (SSEPs) to collect electrophysiological data from low- and high-frequency signal"s bands in 177 individuals, including 91 individuals with migraine during their interictal period (MO) and 86 healthy subjects (HS). Eleven neurophysiological variables were analyzed, and a priori Principal Component Analysis (PCA) and Forward Feature Selection (FFS) techniques were applied to select relevant variables, refine feature space, and bolster model interpretability. We trained the ANN as a data-driven model to delineate the relationship between the electrophysiological input variables and the desired output, testing its accuracy in discriminating between MO and HS. Results: The achieved results underscored a robust performance of the neural network, yielding a final accuracy individuals with migraine exceeding 70%, along with sensitivity, specificity, and F1 scores surpassing the value of 0.7. Conclusion: Our ANN trained with variables from SSEP recordings revealed good accuracy in distinguishing between migraine patients and healthy individuals. The ANN could potentially serve as a powerful tool for implementing neurophysiology techniques and gaining new insights into migraine classification. noninvasive identifying the in

AL006 The diagnostic accuracy of dynamic and static tests for the diagnosis of headache attributed to TMD – a retrospective study H. van der Meer1,2, S. Buitenhuis1, F. Lobbezoo1, M. Koutris1, C. Visscher1 1Academic Center for Dentistry Amsterdam, Orofacial Pain and Dysfunction, Amsterdam, Netherlands 2SOMT University of Physiotherapy, Amersfoort, Netherlands Headache attributed to Objective: temporomandibular disorders (TMD) occurs in around 2- 5% of the general population, and requires a primary diagnosis of a painful TMD. In order to obtain these diagnoses, an extensive assessment using the Diagnostic Criteria for TMD is needed, which includes palpation tests. In patients with chronic pain, palpation tests are less reliable and static and dynamic tests might offer an alternative. Therefore, the aim of this study was to determine the diagnostic accuracy, expressed in sensitivity and specificity, of dynamic and static tests for the diagnosis of headache attributed to TMD. Methods: A retrospective study was conducted at the clinic for Orofacial Pain and Dysfunction of the Academic Centre for Dentistry Amsterdam (ACTA). Initially, patients were included if they were at least 18 years old, exhibited TMD pain, experienced headache in the temple area which could be provoked by palpation or daily function and was confirmed by a clinician. The outcomes of the dynamic and static tests (index test) were compared to the DC/TMD diagnosis (reference test). Results: A total of 233 patients were included with a mean age of 39 years, and the majority (86.3%) was female. The overall diagnostic accuracy of the dynamic and static tests was 69.1%, with a sensitivity and specificity of 53.8% and 89.1%, respectively. Conclusion: The dynamic and static tests showed a sufficient degree of accuracy in detecting headache attributed to TMD, with a low sensitivity and good specificity. Even though it is not recommended the dynamic and static tests replace the palpation tests of the DC/TMD, clinicians who are not trained in the full DC/TMD protocol may use the dynamic and static tests as a first test to screen for headache attributed to TMD. AL007 Blood and cerebrospinal fluid footprints in new- onset idiopathic intracranial hypertension – an exploratory case-control study N. S. Hansen1,2, I. Schmidt1,2, T. Wallentin3,4, C. Bjerring3,4, N. Rye Jørgensen2,5,6, C. S. J. Westgate1,2,6, S. Hamann2,7, D. Beier3,4, R. Højland Jensen1,2 1Danish Headache Center, Copenhagen University Hospital – Rigshospitalet, Department of Neurology, Rigshospitalet-Glostrup, Denmark, Glostrup, Denmark 2University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark 3Headache Clinic, Department of Neurology, Odense University Hospital, Odense, Denmark 4University of Southern Denmark, Medicine Department, Odense, Denmark 5Department of Clinical Biochemistry, Department of Clinical Biochemistry, Copenhagen, Denmark 6Translational Research Center - TRACE, Clinical Biochemistry, Copenhagen, Denmark 7Neuro-ophthalmology, Ophthalmology, Glostrup, Denmark with biochemical IIH: papilledema grade and Objective: We aimed to search for indices of disrupted organ systems and biomarkers in new-onset idiopathic intracranial hypertension (IIH). Methods: We registered results of all blood- and cerebrospinal fluid analyses done at time of diagnostic investigation for suspected IIH in a prospective cohort at two tertiary headache centers and compared females with a final diagnosis of IIH with IIH mimics in whom IIH was disproven (controls). We excluded patients with significant disease, use of drugs associated abnormalities, secondary- or relapse intracranial hypertension, males, pregnant, and age >50 years. We assessed the correlation of significant findings with clinical markers of lumbar opening pressure (OP). Results: Of 325 referred patients we compared 138 females with confirmed IIH to 79 controls with similar age and BMI. We found elevated levels in IIH of leukocytes (p=0.02), neutrophils (p=0.04), and alkaline phosphatase (p=0.03), and levels of urea (p=0.04) (p=0.02). Leukocytes significantly increased the odds of having IIH after adjustment for age, BMI, and smoking, OR 1.22 and neutrophils correlated with lumbar opening pressure and severe papilledema, and urea and cerebrospinal protein did so inversely. We found no other significant differences in blood tests covering liver-, kidney- metabolic-, hematologic-, and inflammatory systems. cross-sectional Conclusion: population of consecutive new-onset IIH restricted by careful exclusion of secondary cases and coincident of inflammation, cerebrospinal protein a well-defined (1.03-1.47). Leukocytes lower we found signs and In

to cerebrospinal OP correlation increased leukocytes driven by neutrophils with clinical and papilledema grade. We reproduced previous findings of in IIH. Findings were not explained by obesity or smoking. Whether these findings are cause, consequence or epiphenomena remains speculative. lower cerebrospinal protein and urea Fig. 3 Fig. 1 Fig. 2 AL008 Higher thalamic myo-Inositol measured at 7T using 1H-MR spectroscopy suggests novel mechanisms in chronic cluster headaches A. Jain1, A. Xiu Rørnes2, A. Farestveit2, M. Tunset Grinde3, A. Karl Gottfrid Nyman4, B. Sitter5, E. A. Tronvik1, T. Wergeland Meisingset1, G. Genovese6 1Norwegian University of Science & Technology, St Olav’s University Hospital, Norwegian Centre for Headache Research, Department of Neuromedicine and Movement Science, Neuroclinic, Faculty of Medicine and Health Sciences, Trondheim, Norway 2Norwegian University of Science & Technology, Faculty of Medicine and Health Sciences, Trondheim, Norway 3St. Olavs University hospital, Department of Radiology and Nuclear Medicine, Trondheim, Norway 4Norwegian University of Science & Technology, St Olav’s University Hospital, Department of Neuromedicine and Movement Science, Trondheim, Norway 5Norwegian University of Science & Technology, Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Trondheim, Norway 6Norwegian University of Science & Technology, Norwegian Centre for Headache Research, Department of Neuromedicine and Movement Science, Faculty of Medicine and Health Sciences, Trondheim, Norway Objective: Studying the metabolic profile of chronic cluster headache (cCH) in pain perception-related areas could provide novel, useful clinical information.

Fig. 2 Fig. 3 Methods: In-vivo MR spectra (Figure 1) were acquired at 7.0 T [1] in 12 cCHs (40±11 years) in interictal state and 17 healthy volunteers (HVs) (36±11 years). The area investigated were the left and right thalamus (data merged; Tha), and hypothalamus (Hyp). Ratio concentration of metabolites with respect to total creatine (tCr) were compared using LCModel, for cCH vs HV in Tha and in Hyp (Table 1). Results: In Tha, a significant increase (Figure 2) in myo-inositol (mIns) was observed in cCH vs HV. Also, significant decrease in N-acetyleaspartate (NAA) and in glutamate (Glu) were observed (Figure 2). After Bonferroni correction only mIns/tCr alteration remained significant. Conclusion: The significant increase in mIns/tCr may be linked with astrogliosis [2], which is a mechanism not previously considered in association with cCH pathophysiology [3]. Additionally, trends observed in NAA/tCr and Glu/tCr may be related to compromised In contrast with previous neuronal viability [3]. findings in metabolite concentrations were found in Hyp, likely due to limited statistical power. Figures and Tables Figure 1. In-vivo MR spectra from thalamus and hypothalamus. Table 1. Metabolite concentrations in cCH and HV. Figure 2. Box plots of mIns, NAA and Glu concentrations from the thalami. References: differences [3], no 1. Tkáč, I et al., In vivo 1H NMR spectroscopy of the human brain at 7 T. Magn. Reson. Med., 2001. DOI: 10.1002/mrm.1213. 2. Harris Janna L et al., Probing astrocyte metabolism vivo: proton magnetic resonance spectroscopy in the injured and aging brain, Front Aging Neurosci, 2015. DOI: 10.3389/fnagi.2015.00202. in 3. Wang SJ, et al., Reduction in hypothalamic 1H- MRS metabolite ratios in patients with cluster headache. J Neurol Neurosurg Psychiatry, 2006. DOI: 10.1136/jnnp.2005.081836. Fig. 1 AL009 Inflammatory biomarkers in cluster headache N. Lund1, C. S. J. Westgate1, M. L. K. Soeborg1, T. F. Hansen1, R. Højland Jensen1, A. S. Petersen1 1Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark Objective: The role of the inflammatory system in cluster headache (CH) has long been a topic of debate. Therefore, we aimed to explore its role by measuring 45 different cytokines in CH patients and controls. Methods: Episodic CH (ECH) patients and Chronic CH (CCH) patients (ICHD-3) from the Danish Cluster Headache Biobank were included and compared with headache-free controls matched for age and sex. Serum was analyzed by the well-established and validated Olink Target 48 Cytokine kit. Results: 99 CCH patients, 110 ECH patients in bout and in remission, and 100 controls participated. For all patient groups, oncostatin m, a pro-inflammatory cytokine, was elevated compared with controls (2.87 pg/ml (p<0.0001), 3.06 pg/ml (p<0.0001), 2.99 pg/ml (p<0.001) and 1.91 pg/ml for CCH, ECH bout, ECH remission and HC). The pro-inflammatory tumor in necrosis factor superfamily 12 was reduced

AL010 Cluster tics in cluster headache M. L. Kulas Søborg1, M. Carney1, S. Maarbjerg1, N. Lund1, J. Worm1, L. Bendtsen1, R. Højland Jensen1, A. S. Petersen1 1Rigshospitalet Glostrup, Department of Neurology, Glostrup, Denmark the investigate the Objective: Short-lasting, sharp attacks of facial pain in patients with cluster headache have traditionally been classified as the co-occurrence of trigeminal neuralgia and vaguely referred to as cluster tics or cluster tic syndrome. We aimed to lifetime prevalence of cluster tics in patients with cluster headache, including a characterization of clinical traits and differentiation from trigeminal neuralgia. Methods: We performed a retrospective cross- sectional cohort study based on a semi-structured interview of patients with cluster headache. A comparator cohort of patients with trigeminal neuralgia were included from a prior semi-structured interview-study. Diagnoses were validated according to International Classification of Headache Disorders and participants were recruited from the Danish Headache Center. Results: We included 424 cluster headache patients and 576 trigeminal neuralgia patients. Cluster tics were reported in 200 (47%) of patients with cluster headache. The odds of experiencing cluster tics were higher for females compared to males (OR: 1.94, 95% CI: 1.27–2.96, p=0.002), and for participants with chronic as to episodic cluster headache (OR: 1.74, 95% CI: 1.15–2.63, p=0.008). The odds of a triggerable paroxysm were much lower in cluster tics compared to trigeminal neuralgia attacks (OR: 0.02, CI: 0.01– 0.04, p<2e-16). Conclusion: Cluster tics are prevalent in almost half of patients with cluster headache and are associated to female sex and chronic cluster headache. Of great clinical and therapeutic importance cluster tics are different from trigeminal neuralgia paroxysms, being primarily located in the orbital region and are largely non-triggerable. In this comparison to controls (656.07 pg/ml (p<0.01), 642.96 pg/ml (pp<0.0001), 661.30 pg/ml (p<0.05), 752.96 pg/ml for CCH, ECH bout, ECH remission and HC, respectively). In addition, the cytokine profile of CCH and ECH in bout exhibited distinct alterations from controls with a spectrum of cytokines being elevated in CCH, whereas others were reduced in ECH in bout. inflammatory Conclusion: involvement of the biomarkers, we confirm the its receptors" inflammatory system presence in the trigeminal ganglion, we identified oncostatin m as a potential new target of interest. In addition, the distinct patterns of inflammation in CCH and ECH is interesting as treatment response differs between the two groups. A more comprehensive understanding of the differences could potentially have clinical implications in relation to treatment and prognosis. large study of in CH. With Fig. 1

Fig. 1 AL011 Activation of CaMKII-α+ neurons in the ventrolateral orbitofrontal cortex exerts analgesic effect in a mouse model of triptan- associated medication overuse headache D. Zhai1, Z. Gong2, Y. Liu1, X. Lin1, Z. Dong1, S. Yu1 1Chinese PLA General Hospital, Department of Neurology, Beijing, China 2Bethune International Peace Hospital, Department of Neurology, Hebei, China role the involvement of the OFC in and may play involved a Objective: Medication-overuse headache (MOH) is a secondary headache disorder. However, due to a limited understanding of its neural mechanisms, it remains undertreated. The orbitofrontal cortex (OFC) in pain has been demonstrated to be modulation in the pathophysiology of MOH. Methods: In this study, we developed a preclinical MOH model in wild-type (WT) mice by overusing rizatriptan benzoate (RIZ, 4 mg/kg, i.g.) and verified it using the von Frey test. Subsequently, we performed immunofluorescent staining for c-Fos in MOH mice to explore the pathophysiology of MOH. We then co-stained CaMKII- α and Vgat with c-Fos to investigate the types of neurons activated in the ventrolateral orbitofrontal cortex (VLO). Following this, we observed changes in the pain threshold of mice by either activating or inhibiting CaMKII-α+ neurons in the VLO. Additionally, we injected fluoro-ruby into the VLO to explore its projection. Results: We observed that the overuse of RIZ led to the development of cutaneous allodynia in mice. Histologically, we noted activation of neurons in the VLO compared the control group. Using immunofluorescent co-labeling, we found that the activated neurons were predominantly CaMKII-α+ neurons, rather than Vgat+ neurons. Subsequently, by activating CaMKII-α+ neurons, we discovered their analgesic effects in MOH mice. Additionally, we identified neuronal projections from the VLO to the pain-related ventrolateral periaqueductal gray (vlPAG). Conclusion: Our findings suggest that the VLO may be a critical brain region involved in the pathophysiology of MOH, providing a direction for further research into this condition. brain area, to the

responses systemic injection of the KATP channel opener levcromakalim (LEV) induced progressive sensitization to cutaneous tactile stimulation (e.g. allodynia) that was prevented by the KATP channel blocker glibenclamide (GLI). Whether KATP channel-related vascular underlie migraine-relevant behaviors remains unclear. Here, we provide in vivo mouse data on meningeal arterial diameters, blood pressure, heart rate, and grimace behavior in response to single and repeated LEV injections. implanted with a Methods: C57Bl/6J mice were cranial window for meningeal 2-photon imaging, a telemetric device for hemodynamic measures, or allocated to grimace analysis. LEV (1 mg/kg) +/- GLI (1 mg/kg) or vehicle was injected i.p. on experimental days 1, 3, and 5. All data were obtained in awake mice (n=5-13). Repeated measure mixed models were used to compare groups. Results: LEV induced dural artery dilation within minutes and reached a max change from baseline (index 0%) of 84% on day 1 and 87% on day 5 (p <0.0001 and 0.005). Pial arteries dilated 47% on day 1 and 23% on day 5 (p <0.001 both days). Dilation was sustained throughout the 120 min of imaging. Hemodynamic responses were identical on days 1, 3, and 5 characterized by a rapid drop in blood pressure and an in heart rate. Both responses returned to baseline within 120 min. LEV injections evoked grimace behavior on days 1 and 5 (p = 0.038). Preliminary analysis that LEV-induced meningeal vasodilation and grimace were not prevented by GLI. Conclusion: LEV is a potent dilator of mouse dural in vivo, generating consistent vascular, arteries hemodynamic, and grimace responses on days 1 and 5. Migraine-relevant cutaneous sensitization may not be related to meningeal arterial diameter per se. Subsequent events from vascular KATP channel opening are likely drivers of sensitization and migraine headache. increase suggests Fig. 2 AL012 KATP channel opening and inhibition: Effects on meningeal arterial diameters, hemodynamics, and migraine-relevant behaviors in mice S. L. Christensen1,2,3, K. Obelitz-Ryom2,3, O. S. Kudryavtseva4, M. B. Thomsen4, S. Carneiro- Nascimento1, D. Levy1 1Beth Israel Deaconess Medical Center, Department of Anesthesia, Critical Care and Pain Medicine, Boston, MA, United States 2Danish Headache Center, Copenhagen University Hospital – Rigshospitalet, Department of Neurology, Glostrup, Denmark 3Copenhagen University Hospital – Rigshospitalet, Translational Research Centre, Glostrup, Denmark 4University of Copenhagen, Department of Biomedical Sciences, Copenhagen, Denmark Objective: Meningeal sensitive potassium (KATP) channels are of high interest due to their role in migraine induction. In mice, repeated vascular ATP

Fig. 1 these two human Results: Ubrogepant and atogepant were antagonists of the human CGRP receptor and were also able to antagonize the AMY1(a) receptor. Selectivity estimates between receptors varied depending on assay format and agonist used. As an example of the results, Table 1 shows IC50 values at the human CGRP and AMY1(a) receptors. Antagonism was weaker at mouse and rat receptors, compared to human. Depending on the species, antagonism of other receptors was sometimes observed. Overall, there were some differences in selectivity between receptors in the different species. Conclusion: Ubrogepant and atogepant are capable of antagonizing additional receptors in the calcitonin receptor family, beyond the canonical CGRP receptor. Fig. 1 AL013 Pharmacological characterization of ubrogepant and atogepant in cAMP assays at human, rat and mouse calcitonin family receptors in transfected cells D. Hay1, M. Nimick1, M. Garelja1, T. Alexander1, C. Walker2, P. Banerjee3 1University of Otago, Pharmacology and Toxicology, Dunedin, New Zealand 2University of Auckland, School of Biological Sciences, Auckland, New Zealand 3AbbVie, Chicago, IL, United States Objective: Ubrogepant and atogepant belong to the "gepant" class of CGRP receptor antagonists. There are limited data on their ability to antagonize different members of the wider calcitonin receptor family. This study aimed to address this by comparing antagonism by ubrogepant and atogepant at the CGRP, calcitonin, adrenomedullin, and amylin receptors from three species. Methods: Cos7 cells transiently transfected with human, rat or mouse receptor subunits for all seven calcitonin family receptors were exposed to species- matched agonists in the absence or presence of ubrogepant and atogepant. Two other gepants (rimegepant and telcagepant) were also studied as comparators in some experiments. As all of these receptors robustly couple to the Gαs G protein, cAMP production was quantified and antagonist potency calculated. AL014 In-depth analysis of CGRP Isoforms: only αCGRP localizes in Axons of the mouse Trigeminal Ganglion S. L. Wæver1, K. A. Haanes1,2 1Rigshospitalet Glostrup, Glostrup, Denmark 2University of Copenhagen, Department of Biology, Copenhagen, Denmark Objective: The neuropeptide calcitonin gene related peptide (CGRP) has been established to be a key signaling molecule in migraine, but little is known about the differences between the two isoforms: αCGRP and βCGRP. Previous studies have been hampered by their close similarity, making the development of specific antibodies near impossible. In this study we sought to test the hypothesis that αCGRP and βCGRP localize differently within the neurons of the mouse trigeminal ganglion (TG), using knock out (KO) animals. Methods: We applied immunohistochemistry (IHC) on 15 TGs from three different genotypes of mice (wild type, αCGRP heterozygotes and αCGRP KOs) with a primary antibody targeting the mature neuropeptide sequence of both αCGRP and βCGRP. Subsequently, the localization patterns of the two isoforms were analyzed. Moreover, bioinformatical analyses of the primary, secondary, and tertiary structure of both mouse and human isoforms were conducted. Results: The IHC, evidently showed that the key isoform localized within the axons of the mouse TG neurons, is αCGRP and not βCGRP. Furthermore,

differences in intensities indicate that the model used in this report successfully knocks out αCGRP, which is the most dominant isoform present in the TG. We further categorized the localization patterns of CGRP in neuronal cell bodies in the TG and found using bioinformatic analyses that differences in localization might be explained by intracellular peptide sorting. Although there were notable differences, similar bioinformatic variations were observed between the two human isoforms. Conclusion: Our data suggests that only αCGRP and not βCGRP locate within the axons of the mouse TG neurons. Furthermore, the isoforms appear to be sorted differentially into secretory vesicles in the cell bodies of TG neurons. AL015 αCGRP and βCGRP are co-expressed in the trigeminal ganglia T. Rees1, M. Garelja2, C. Walker3, D. Hay2 1King's College London, Headache Group, Wolfson Sensory, Pain and Regeneration Centre, London, United Kingdom 2The University of Otago, Department of Pharmacology and Toxicology, Dunedin, New Zealand 3University of Auckland, School of Biological Sciences, Auckland, New Zealand involved Objective: Calcitonin gene-related peptide (CGRP) is a neuropeptide in pain transmission and migraine pathogenesis. CGRP has two major isoforms, αCGRP and βCGRP, which differ by three amino acids in humans and mice. αCGRP is highly expressed in the trigeminal ganglia (TG) and has a well-established role in pain sensitisation and migraine. In contrast, βCGRP expression is poorly defined and is often reported to be primarily expressed in the enteric nervous system, with limited relevance to migraine. Therefore, this study aimed to compare the relative distribution of αCGRP and βCGRP in the mouse TG. Methods: Detection of the mouse CGRP isoforms by anti-CGRP antibodies was tested by dot blot. Wildtype (WT) and αCGRP knockout (KO) adult mouse TG (C57BL/6J background, WT 3M/1F, KO 4F) were immunostained for CGRP relative to neuronal markers (β tubulin III and NF200) and the calcitonin receptor (CTR). RNA-fluorescent in situ hybridisation (RNA- FISH) probes against αCGRP (Calca) and βCGRP (Calcb) mRNA were validated in transfected HEK293S cells. These probes were then used to examine isoform expression in WT adult mouse TG (C57BL/6J, 2F/3M). Results: All anti-CGRP antibodies tested detected both isoforms of CGRP. CGRP-like immunoreactivity was present in WT and αCGRP KO mouse TG in neuronal cell bodies, often colocalising with CTR. However, compared to the WT mice, CGRP immunoreactivity in the αCGRP KO TG was of a lower fluorescence intensity and lacked pearl-like fibre immunoreactivity. The RNA-FISH probes were specific to each isoform and indicated that αCGRP and βCGRP mRNA were often present in the same neuronal cell bodies, although some neuronal cell bodies only expressed one CGRP isoform. Conclusion: βCGRP is expressed in mouse TG neurons, suggesting it plays a role in neuromodulation and nociception, alongside αCGRP. Both isoforms may be important for mediating CGRP's pathogenic activity in migraine. AL016 Non-paralytic botulinum toxin A in trigeminal neuralgia A. David-Pereira1, J. Lloyd1, C. Leese2, B. Davletov2,3, A. P. Andreou1,4 1King's College Londom, Institute of Psychiatry, London, United Kingdom 2University of Sheffield, Sheffield, United Kingdom 3Neuresta Inc., San Diego, CA, United States 4Headache Centre, Guy’s and St Thomas’ NHS Foundation Trust, London, United Kingdom the efficacy of a treatments are Objective: Trigeminal neuralgia (TN) is the most common type of craniofacial chronic neuropathic pain. TN is characterized by short electric shock-like pain paroxysms in areas enervated by the trigeminal nerve. Acute ineffective, and preventative drugs lack specificity, efficacy, and often have severe side effects. To address these limitations, recombinant botulinum toxin-based molecules with retained analgesic effects and minimal paralytic side effects have been developed. This study aims to investigate non-paralytic recombinant botulinum toxin A (BoNT/A) molecule - el-Bitox/A, compared to native BoNT/A in a model of TN. Methods: Nociceptive behavioral responses in a rat infraorbital nerve chronic constriction injury (IoN-CCI) model of TN were measured for 7 weeks post-surgery. von Frey filaments were used to assess the efficacy of el-Bitox/A (20ng) and BoNT/A (5U) in reversing mechanical allodynia. Compounds were injected subcutaneously into the ipsilateral side. Bodyweight was monitored as an indirect measure of facial paralysis. Results: Both el-Bitox/A (n=7; P<0.05) and BoNT/A (n=6; P<0.05) reversed IoN-CCI-induced mechanical allodynia, while vehicle had no effect (n=6; P<0.05). This effect lasted for both botulinum toxins for at least 30 days after injections. Injections into the cheek could cause paralysis, reducing jaw strength, impairing food consumption, and significant in loss. BoNT/A bodyweight leading injections resulted to

significant bodyweight loss (P<0.05), while el-Bitox/A injections had no effect on bodyweight (P=0.2), confirming the non-paralytic profile of el-Bitox/A. Conclusion: Both BoNT/A and el-Bitox/A can reverse mechanical hypersensitivity caused by the TN model for prolonged periods. However, BoNT/A has significant serious side effects that can be avoided by using the non-paralytic el-Bitox/A, highlighting its potential as an innovative treatment for neuropathic pain conditions. AL017 Frequency and clinical features of space headache experienced by astronauts during long-haul space flights R. (. van Oosterhout1,2, M. Perenboom2, G. M. Terwindt2, M. D. Ferrari2, A. Vein2 1Zaans Medisch Centrum, Neurologie, Zaandam, Netherlands 2Leiden University Medical Center, Neurology, Leiden, Netherlands is lacking. We aimed Objective: Few anecdotal cases and one small retrospective study during short-duration space missions suggest that headache may occur early in- flight, as part of the space motion syndrome. Whether headaches may also occur at later stages of space- flights to prospectively characterise the incidence, timing, clinical features, and management of space headaches during long- duration flights. Methods: We prospectively evaluated the occurrence, characteristics and evolution of space headaches and the effects of treatment during long-haul flights with on-board questionnaires, and correlated them with prevailing temperature and ambient, on-board O2 and CO2 pressure and levels. Retrospective headache data from a different astronaut cohort. Headache data were reported using descriptive statistics, correlation data with logistic regression models. Results: In the prospective study, 22/24 (91·7%) astronauts experienced >1 episode of headache during a total of 3,596 space-days. A total of 378 episodes were reported with detailed information on 189. Phenotypically, 89·9% episodes were tension- type were migraine. Phenotypically, migraine-like episodes occurred more in the first week vs later (vs TTH): 23·5% vs 5·1% (TTH (76·5% vs. 94·9%; overall p=0·0002). Accompanying symptoms were more prevalent in the first week: nausea: 17·6% vs. 6·9%, p=0·05; vomiting: 9·8% vs. 0·7%, p=0·005; nasal congestion: 52·9% vs. 29·7%, p=0·004; facial oedema: 41·2% duration (p=0·001). Headache occurrence was not associated with temperature, ambient pressure, or (C)O2 levels headache vs. 1·4%, p<0·001; and and 10·1% (all p>0·05). The retrospective study in 42 astronaut showed similar results. Conclusion: Astronauts during space flights frequently experience headaches, phenotypically mostly TTH but sometimes with migrainous features, particularly during the first week of flight, in astronauts without a history of recurrent headaches. Space motion sickness and cephalad fluid shift are hypothesised causal mechanisms. Fig. 1 Fig. 2

Fig. 3 AL018 Blood pressure profile in chronic migraine patients treated with anti-CGRP monoclonal antibodies – a retrospective analysis of Swedish real-world data S. Uzun1,2, P. Nerjovaj3, P. Petersson1, G. Sahin1,2,4 1Lund University, Department of Experimental Medical Sciences, Lund, Sweden 2Skåneuro Neurology Clinic, Lund, Sweden 3Skane university hospital, Neurology Department, Malmö, Sweden 4Lund University, Department of Clinical Sciences of Malmö and Lund, Lund, Sweden Objective: To investigate blood pressure (BP) changes in chronic migraine patients treated with anti- calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) in real-world settings. Methods: This is an observational retrospective study conducted at SkåNeuro Neurology Clinic, Lund, Sweden. BP values were collected at the baseline visit and regular follow-up visits up to 24 months. Results: A total of 69 patients with a complete BP profile, treated with anti-CGRP mAbs were included (22 erenumab, 29 fremanezumab, 20 galcanezumab) in the study. Baseline mean systolic BP was 119,0 mmHg in the erenumab, 117,0 in the fremanezumab and 119,5 in the galcanezumab group (p=0.71). Baseline mean diastolic BP was 80,5 mmHg in the erenumab, 77,0 in the fremanezumab and 76,5 in the galcanezumab BP measurements have shown a transient increase of 9 mmHg in median systolic BP and 3 mmHg in median diastolic BP in the erenumab group within 3 months. However, this increase was not statistically significant and has normalized after 9 months. No increase in BP was shown in neither of the other treatment groups during the whole two-year follow up period. Three patients in the erenumab group, one patient in the fremanezumab group and one patient the Follow-up in group (p=0.8). galcanezumab group developed hypertension (HT) during the treatment. Conclusion: BP values could increase transiently in the early phase of anti-CGRP treatment and there is a risk for the development of HT especially in patients having high-normal BP. Our findings suggest that careful monitoring of BP is beneficial and further studies are required for mechanism of action of abovementioned transient blood pressure increase in chronic migraine patients undergoing anti-CGRP mAbs treatment. AL020 Optogenetically-induced spreading depolarization evokes rapid influx but delayed clearance of the glymphatic flow Z. Jiang1, S. P. Chen1,2,3,4,5, S. J. Wang2,6,4, J. C. Yen7 1National Yang Ming Chiao Tung University, Institute of Clinical Medicine, Taipei, Taiwan 2National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan 3Taipei Veterans General Hospital, Division of Translational Research, Department of Medical Research, Taipei, Taiwan 4Taipei Veterans General Hospital, Department of Neurology, Neurological Institute, Taipei, Taiwan 5National Yang Ming Chiao Tung University, Brain Research Center, Taipei, Taiwan 6National Yang Ming Chiao Tung University, Brain Research Center, Taipei, Taiwan 7National Yang Ming Chiao Tung University, Pharmacology and Toxicology, Taipei, Taiwan interrogate this controversial Objective: Cortical spreading depolarization (SD), the pathophysiological substrate of migraine aura, was found to impair glymphatic flow observed with two- photon imaging. In contrast, SD was found to induce massive paravascular cerebrospinal fluid (CSF) influx in a middle cerebral artery occlusion model. This study aims to issue and delineate the role of glymphatics in SD. Methods: To characterize the dynamics of glymphatic flow during SD, CSF tracers were injected into cisterna magna and allowed to circulate along the perivascular spaces. A single SD event was induced using either conventional KCl or a novel optogenetic method before or after CSF tracer injection. Real-time macroscopic imaging was employed to monitor glymphatic dynamics during SD. The function of glymphatic clearance was evaluated by CSF tracer drainage into the deep cervical lymph node (dCLN). Results: In the KCl-induced SD model, we observed an increase in CSF influx at SD-induction site, with a significant tracer accumulation at burr holes, which potentially confounded CSF flow dynamics. To craniotomy artifacts, we utilized a minimize

matter changes between both MRI acquisitions are shown in Table 2. Most changes were observed for the CC, showing an increase, in regions such as the cingulate, and fusiform gyri, although a decrease was found in the paracentral cortex ot the postcentral gyrus. The main trend for CT and GMV was an increase for the responders, in the cingulate gyrus or the thalamus, and decrease for SA in multiple regions, even though the opposite significant trend was also detected. Illustrative examples for each parameter are shown in Figure 1. The non-responders showed CC increase in the left superior temporal gyrus (β=1.3 [0.3, 2.4] • 10-5, p=0.028). Conclusion: This study suggests that migraine patients present 12-week gray matter changes associated with positive response to fremanezumab. Fig. 1 noninvasive optogenetically-induced SD model. In the optogenetic SD model, CSF tracer exhibited a rapid periarterial influx with a subsequent stagnant efflux after the first SD event. Moreover, SD reduced CSF tracer drainage into the ipsilateral dCLN in both KCl and optogenetic SD model, suggesting an impaired glymphatic clearance following SD. Conclusion: SD induces rapid glymphatic influx but delays its clearance, potentially altering the transport of CSF and brain-derived neurogenic wastes during SD. AL021 Short-term longitudinal gray matter morphometry changes in patients with migraine responding to fremanezumab Á. Planchuelo-Gómez1, Á. Sierra Mencia2, Y. González- Osorio2, Á. L. Guerrero2,3, A. Recio García2, R. Moro4, S. Aja-Fernández1, R. de Luis-García1, D. García-Azorín3,5 1Universidad de Valladolid, Imaging Processing Laboratory, Valladolid, Spain 2Hospital Clínico Universitario de Valladolid, Headache Unit, Valladolid, Spain 3Universidad de Valladolid, Department of Medicine, Valladolid, Spain 4Hospital Clínico Universitario de Valladolid, Department of Radiology and Nuclear Medicine, Valladolid, Spain 5Hospital Universitario Río Hortega, Department of Neurology, Valladolid, Spain Objective: To determine MRI-based gray matter morphometry longitudinal changes in patients with chronic migraine (CM) or high frequency episodic migraine (HFEM) who responded to fremanezumab 12 weeks after the first administration. Methods: A total of 22 patients with CM or HFEM underwent high-resolution 3D brain T1-weighted MRI 1-2 weeks prior fremanezumab administration, and again 12 weeks later. Positive response to treatment was defined as reduction of at least 50% in the monthly migraine frequency. The morphometry parameters were obtained with FreeSurfer (v6.0) were cortical curvature (CC) and thickness (CT), surface area (SA) and gray matter volume (GMV) from 68 cortical and 14 subcortical regions, and the cerebellum. Generalized Linear Mixed Models were used to evaluate the longituindal changes and differences between responders and non-responders, correcting the models by age, and intracranial volume the GMV analysis. The threshold for statistical significance was set at p<0.05. Results: Clinical characteristics of the patients are summarized in Table 1. Thirteen patients (59.1%) showed positive response to fremanezumab. In the gray responders, statistically significant the to the initial in

Fig. 2 Fig. 3 AL022 The burden of migraine in Spain: results from the 2022 national health and wellness survey P. Irimia1, D. García-Azorín2, M. Sánchez del Río3, C. Peral4, B. Armada4, J. Porta-Etessam5 1Clínica Universidad de Navarra, Neurology, Pamplona, Spain 2Hospital Universitario Río Hortega de Valladolid, Headache Unit, Valladolid, Spain 3Clínica Universidad de Navarra, Madrid, Spain 4Pfizer S.L.U., Madrid, Spain 5Institute for Sanitary and Biomedical Research Clínico San Carlos (IdISSC), University Hospital Clínico San Carlos, Neurological Disorders Study Group, Madrid, Spain resource utilization Objective: To describe the impact of migraine on healthcare (HCRU), work productivity and estimate the resulting direct and indirect costs in Spain. Methods: A cross-sectional study using the 2022 National Health and Wellness Survey (NHWS) assessed patient-reported data from a representative sample of the Spanish adult population. In 2022 NHWS, respondents who reported having diagnosis of migraine by a physician and experienced migraine in the preceding 12 months were considered active migraine patients and reported on their Work Productivity and Activity Impairment (WPAI) and HCRU. Reported HCRU in the past 6 months were doubled to provide estimates for a complete year, assuming constant HCRU. Results were compared

with those from the 2020 NHWS, for both available migraine case definitions and for population without migraine, all updated at 2024 prices. Results: In the 6 months prior to answering the survey, 68.4% of migraine patients had visited the general practitioner (GP), 14.2% had visited the neurologist, 45.6% had visited the emergency room (ER), and 11.8% had been hospitalized. For those visiting, the mean number of visits per person were: 3.0 to the GP, 1.5 to the neurologist, and 2.3 to the ER. The HCRU was lower than the one observed in the 2020 NHWS for all resources, except for the visits to neurologists (Figure 1). The 2022 HCRU resulted in annual direct costs of €672 per migraine patient, 84.5% higher than in people without migraine. Employed migraine patients (62.9%) reported mean absenteeism of 13.1%, mean presenteeism of 32.2% and a total work productivity loss of 35.8%, resulting in an annual indirect cost of €9,591 per employed migraine patient. Mean work productivity loss was 62.4% higher in the population without migraine. In 2022, migraine still produced a Conclusion: substantial impact on productivity and healthcare resource utilization in Spain, despite the differences to 2020. in migraine patients than Fig. 1 AL023 Increased systemic arterial stiffness is associated with blood-brain barrier disruption in reversible cerebral vasoconstriction syndrome Y. H. Ling1,2, S. P. Chen3,4, S. J. Wang1,2,5 1Neurological Institute, Taipei Veterans General Hospital, Department of Neurology, Taipei, Taiwan 2National Yang Ming Chiao Tung University, College of Medicine, Taipei, Taiwan 3National Yang Ming Chiao Tung University, Institute of Clinical Medicine, Taipei, Taiwan 4Taipei Veterans General Hospital, Department of Medical Research, Taipei, Taiwan 5National Yang Ming Chiao Tung University, Brain Research Center, Taipei, Taiwan cerebral (RCVS) vasoconstriction Objective: Reversible syndrome is characterized by recurrent thunderclap headaches and reversible intracranial vasoconstriction. Recent findings shows blood-brain barrier (BBB) disruption in patients with RCVS, demonstrated by contrast medium extravasation over the cortical sulci on contrast-enhanced T2 fluid- attenuated inversion recovery (CE-T2 FLAIR) imaging (Fig. 1). BBB disruption in RCVS is associated with episodic blood pressure surges and dysfunction in cerebral autoregulation. We hypothesized that the pathogenesis of BBB disruption in RCVS is associated with increased systemic arterial stiffness, resulting in the excessive transmission of central pulsatile flow to the cerebral microcirculation. Methods: Patients with RCVS were recruited and underwent 3D isotropic CE-T2 FLAIR to visualize BBB disruption. Systemic arterial stiffness was assessed using hemodynamic parameters derived from applanation tonometry, including carotid-femoral pulse wave velocity (cfPWV), augmentation index (AI), and central blood pressure. Systemic arterial stiffness was compared between RCVS and age- and sex- matched healthy controls (HCs), and between RCVS with and without BBB disruption. Results: Sixty-five RCVS (44.3±9.6 years old, 42 F) and 65 HCs (45.4±8.9 years old, 42 F) completed the study. In RCVS, 33 presented BBB disruption. Table 1 showed the demographic data. RCVS showed increased systemic arterial stiffness, indicated by a higher cfPWV than HC. RCVS with BBB disruption had stiffer arteries than those without, indicated by higher cfPWV and AI (Table 2). Conclusion: Increased systemic arterial stiffness was in those with BBB observed disruption. Our increased systemic arterial stiffness may play a pivotal role in the pathogenesis of BBB disruption and RCVS pathophysiology by facilitating excessive pulsatile flow transmission to the cerebral microcirculation, leading to the vessel tone dysregulation. findings suggest that in RCVS, especially

Fig. 1 Fig. 2 Fig. 3 AL024 Consistency between headache diagnoses and ICHD- 3 criteria across different levels of care L. H. Overeem1,2, M. Ulrich1, M. P. Fitzek1,3, K. S. Lange1,3, J. B. Hong1, U. Reuter1,4, B. Raffaelli1,3 1Charité – Universitätsmedizin Berlin, Department of Neurology with Experimental Neurology - Headache center, Berlin, Germany 2Humboldt Graduate School, International Graduate Program Medical Neurosciences, Berlin, Germany 3Berlin Institute of Health at Charité (BIH), Clinician Scientist Program, Berlin, Germany 4Universitätsmedizin Greifswald, Greifswald, Germany characteristics Objective: Correctly diagnosing headache disorders presents significant challenges, especially at the primary and secondary levels of care (PSLC), often leading to misdiagnoses and underdiagnoses. This study aims to assess the diagnostic agreement for migraine, tension-type headache (TTH), and cluster headache (CH) between PSLC and the tertiary level of care (TLC), as well as to evaluate adherence to the International Classification of Headache Disorders, 3rd edition (ICHD-3) guidelines. Methods: This cross-sectional study involved patients visiting the tertiary headache center of Charité - Universitätsmedizin Berlin for the first time. Data on headache and diagnoses were collected from standardized anamnesis questionnaires and doctors' letters. Diagnostic agreement was assessed using Cohen's Kappa (κ) statistics. Results: The study cohort consisted of 1,468 patients (43.4 ± 14.4 years; 74.5% women). A total of 69.5% received a headache diagnosis at PSLC, whereas 99.5% were diagnosed during their first visit at TLC. Of the 1,457 migraine, TTH, and CH diagnoses given in PSLC, 948 (65.1%) were confirmed in TLC, κ=0.546 (95%CI 0.519 - 0.573), p<0.001 (Figure 1). From the 1,112 diagnoses meeting all ICHD-3 criteria for migraine, TTH, and CH, 749 (67.4%) received the respective diagnosis in PSLC (κ=0.596, 95% CI 0.568- 0.623, p<0.001), and 1,104 (99.3%) in TLC (κ=0.984, 95% CI 0.978-0.990, p<0.001). TTH was the least correctly diagnosed, with only 32% of patients fulfilling all ICHD-3 criteria for TTH in PSLC. Conclusion: Our substantial diagnostic agreement across different levels of care according to the ICHD-3 guidelines. However, since diagnostic accuracy is essential for optimizing patient care and treatment outcomes, efforts should focus on improving early recognition and diagnostic accuracy of primary headaches. findings indicate

Fig. 1 AL025 European triptan profile trial (Eurotrip trial): real- world prospective evaluation of the 2022 European Headache Federation (EHF) critearia on effective triptan treatment of a migraine attack S. Jeddens1, A. Hostens1, J. Versijpt1, E. Ekizoglu2, R. Ornello3, L. H. Overeem4, B. Raffaelli4, D. Uluduz2, U. Reuter4, S. Sacco3, V. Chirivì5 1Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Neurology, Brussels, Belgium 2Istanbul University Faculty of Medicine, Neurology, Istanbul, Turkey 3University of L'Aquila, Biotechnological and Applied Clinical Sciences, L'Aquila, Italy 4Charité – Universitätsmedizin Berlin, Neurology, Berlin, Germany 5University of L'Aquila, Clinical Medicine, Public Health, Life and Environmental Sciences, L'Aquila, Italy Objective: A consensus definition on triptan response was published by the European Headache Federation (EHF) in October 2022. Using this definition on effective treatment, 5 different triptan profiles have been defined: responder, non-responder, resistant, refractory and ineligibile patients. The present study aimed at prospectively assign migraine patients visiting 4 migraine clinics in Europe to one of these categories in a real-world setting and to compare findings with patient-reported outcomes both on efficacy and tolerability. Methods: Data were collected during headache consultations at 4 specialised headache clinics in Europe Istanbul and Rome). Demographics, triptan profile and patient-reported outcomes were assessed. Results: A total of 678 patients were included of whom 574 (85%) were female. 143 (21%) patients were triptan naive. The distribution of triptan profiles in the non-naive group was as follows: 262 (49%) were responders, 177 (33%) were non-responders, 73 (14%) were resistant, 23 (4%) were refractory and 1 patient (Berlin, Brussels, ineligible (0.1%). was classified as In the non- responders, resistant and refractory group (273 patients), most patients (38%) cited both at least one efficacy and a tolerability reason for triptan failure and the most common single efficacy reason for being a non-responder was relapse within 24 hours (7%). Patient-reported outcomes showed that the majority of patients was either somewhat or very satisfied with their triptan treatment (77%) and preferred triptans over non-migraine specific painkillers (76%). Conclusion: Triptans are still largely underused. In the triptan non-naive group, 49% can be classified as a triptan-responder. A large majority of patients are satisfied with their triptan(s), even within the patient group not labelled as a responder reflecting either the strictness of the EHF criteria or a true unmet need concerning acute ineligible patients were almost non-existent in the current sample. treatment. Triptan LBO001 Machine learning can predict migraine from genotype and non-headache clinical data with high accuracy A. Danelakis1,2, H. K. Abildsnes2,3, F. Faisal2,3, B. Winsvold2,4,5,6, M. H. Bjørk2,7,8, D. Giles9, P. Nachev9, T. Kumelj2,3, K. Hagen2,10, M. Matharu9, I. Author11, E. A. Tronvik2,3, H. Langseth1,2, A. Stubberud2 1Norwegian University of Science and Technology (NTNU), Computer Science, Trondheim, Norway 2Norwegian Centre for Headache Research (NorHead), Trondheim, Norway 3Norwegian University of Science and Technology (NTNU), Neuromedicine and Movement Science, Trondheim, Norway 4Oslo University Hospital - Division of Clinical Neuroscience, Research and Innovation, Oslo, Norway 5Oslo University Hospital, Neurology, Oslo, Norway 6Norwegian University of Science and Technology (NTNU), Public Health and Nursing, Trondheim, Norway 7University of Bergen, Clinical Medicine, Bergen, Norway 8Haukeland University Hospital, Neurology, Bergen, Norway 9University College London, Queen Square Institute of Neurology, London, United Kingdom 10St. Olav University Hospital, Neuroclinic, Trondheim, Norway 11International Headache Genetic Consortium, Brisbane Queensland, Australia Objective: While migraine is diagnosed based on symptomatology, it is associated with a wide range of comorbid, environmental and genetic factors that are of uncertain diagnostic value. Machine learning (ML)

Fig. 1 Fig. 2 can take advantage of complex and non-intuitive patterns to make accurate predictions—and may potentially exploit these associations. The objectives of this study were to develop ML models to predict migraine based on genotypic data, general clinical data, and combined genotypic and clinical data—and compare their performance. Methods: This was a cross-sectional study using data from the 2nd and 3rd Nord-Trøndelag Health Study (HUNT). ML models were developed to predict individuals with migraine versus headache-free controls. The input features for the ML models were genetic risk variants selected from the summary statistics from the largest available GWAS meta- analysis for migraine; and general clinical data from HUNT including demographics, socioeconomic status, comorbid disorders, self-reported non-headache- related complaints, and medication and stimulant use. A series of ML classifiers were trained and optimized on a training set and evaluated with 10-fold cross validation. The area under the receiver operating characteristics curve (AUC) was used as the main scoring metric for training and optimizing the models. The top performing model for each dataset was assessed on an unseen test set to quantify out-of- sample performance (Figure 1). Results: 10,286 subjects with migraine and 32,911 controls were included in the analyses (Figure 2). The top performing model was the light gradient boosting machine classifier with test-set AUCs of 0.63, 0.79 and 0.80 for the genotype, the clinical and the combined datasets respectively. Conclusion: Using ML, migraine can be diagnosed with surprisingly high accuracy without information typically used for diagnosis. General clinical data is alone highly predictive, but the use of genotype data provides little additional information.

LBO003 Potential therapeutic role of DPP-4 Inhibitors in reducing migraine risk in diabetic patients C. Ting-Chuan1, C. Chi-Hsiang1, H. Tsung-Wei1, C. H. Lin1 1Taichung Veterans General Hospital, Department of Neurology, Neurological Institute, Taichung, Taiwan Objective: Both type 2 diabetes mellitus (DM) and migraine are common conditions, and emerging evidence suggests there may be links between their underlying mechanisms. A previous study in mice indicated that chronic migraine was associated with reduced GLP-1 receptor activity, raising the possibility that anti-diabetic agents, such as GLP-1 receptor agonists, could influence migraine onset in humans. This study investigates the impact of three types of anti-diabetic agents—DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors—on the incidence of migraine in diabetic patients. Methods: We analyzed data from the TriNetX database, focusing on patients aged 18 and older diagnosed with DM between 2012 and 2022. The primary outcome measured was the development of migraine or chronic migraine following the treatment of DM. Patients with pre-existing migraines or fewer than two clinical visits were excluded. Propensity score matching was used to randomize patients into treatment groups for comparison. Results: A total of 216,631 patients were included in the DPP-4 inhibitor groups, 212,954 in the DPP-4 inhibitor and GLP-1 agonist groups, and 177,611 in the GLP-1 agonist and SGLT2 inhibitor groups. DPP-4 inhibitor treatment was associated with a significantly lower hazard ratio (HR) for both migraine and chronic migraine compared to GLP-1 receptor agonists and SGLT2 inhibitors. No significant differences were observed between GLP-1 agonists and SGLT2 inhibitors. Conclusion: DPP-4 inhibitors may reduce the risk of migraine in diabetic patients, suggesting potential therapeutic benefits. Further research is needed to confirm these findings and explore their clinical implications. inhibitor and SGLT2 LBO002 Intact white matter in adults with Migraine: a REFORM MRI study C. Gollion1,2, H. Ashina2,3, R. H. Christensen2,4, H. M. Al- Khazali2,4, D. Tolnai5, M. Ashina2,4, F. Mohammad Amin2,4 1University Hospital of Toulouse, Neurology, Toulouse, France 2Danish Headache Center, Neurology, Copenhagen, Denmark 3Copenhagen University Hospital, Translational Research Center, Copenhagen, Denmark 4University of Copenhagen, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Copenhagen, Denmark 5Copenhagen University Hospital, Radiology, Copenhagen, Denmark included Objective: Diffusion tensor imaging (DTI) provides valuable insights into the white matter integrity of people with migraine. This study compares the microstructural white matter integrity between a large sample of people with migraine and healthy controls, as well as across different migraine subtypes. Methods: This cross-sectional case-control study included adults with migraine experiencing at least four monthly migraine days and age- and sex-matched healthy controls. Each participant and control underwent a single brain magnetic resonance imaging session, including DTI, to assess microstructural white matter integrity using Tract-Based Spatial Statistics. The DTI outcome measures fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity. Comparisons were made between participants with migraine and controls, as well as among different migraine subtypes (migraine with aura, migraine without aura, episodic migraine, and chronic migraine). Additional comparisons were conducted between participants during and outside of migraine and between hemispheres ipsilateral and contralateral to the pain side in those scanned during unilateral migraine attacks. Results: A total of 293 participants with migraine and 154 healthy controls provided DTI data eligible for analysis. Among the participants, 181 (61.7%) had chronic migraine, 103 (35.1%) had migraine with aura, and 79 (26.9%) were scanned during a migraine attack. No significant differences in white matter integrity were identified between participants with migraine and controls, nor among the different migraine subtypes. Conclusion: Our results suggest that migraine does not result in microstructural alterations within the cerebral white matter. Further research is necessary to explore other potential radiologic biomarkers and pathophysiologic mechanisms underlying migraine. attacks,

Fig. 1 Fig. 2 Fig. 3 LBO004 PACAP38-induced migraine attacks are independent of CGRP signaling H. Ashina1, M. Al-Karagholi1, M. Ashina1 1Copenhagen University Hospital - Rigshospitalet, Neurology, Glostrup, Denmark To can mediate migraine Objective: Objective: evaluate whether eptinezumab, a monoclonal antibody directed against the calcitonin gene-related peptide (CGRP) ligand, can prevent migraine attacks induced by pituitary adenylate cyclase-activating polypeptide-38 (PACAP- 38). This investigation aims to ascertain whether PACAP-38 attacks independently of CGRP signaling. In a double-blind, placebo- Methods: Methods: controlled, parallel-group randomly allocated adults with migraine without aura to receive either an intravenous infusion of 300-mg eptinezumab or placebo (isotonic saline). Two hours post-infusion, all participants were administered PACAP-38 intravenously at 10 pmol/kg/min for 20 minutes. The primary endpoint was the incidence of migraine study, we attacks during the 24-hour observational period post- infusion of eptinezumab or placebo. Results: Results: A total of 38 participants completed the study. No significant difference was observed in the incidence of PACAP-38 induced migraine attacks between the eptinezumab (10 [53%] of 19) and placebo (12 [63%] of 19) groups (P = 0.74). Headache of any intensity was reported by 15 (79%) participants in the eptinezumab group, compared to 16 (84%) participants in the placebo group (P > 0.99). The area under the curve for headache intensity scores did not differ between the two groups during the first 12 hours post-infusion of PACAP-38 (P = 0.96). Conclusion: Our results suggest that PACAP-38 can mediate its signaling independently of CGRP signaling in migraine pathogenesis. Therapies targeting PACAP signaling are thus a promising new avenue for treating migraine. LBO005 The brainstem locus coeruleus and migraine V. Munday1, I. Rosenzweig1, P. Holland1 1King's College London, Wolfson Sensory Pain and Regeneration Centre, London, United Kingdom to Objective: Objective: The locus coeruleus (LC) has been shown to have divergent effects on migraine- related phenotypes. A bidirectional relationship between migraine and sleep is well noted; however, the underlying pathophysiological mechanisms remain incompletely understood. The LC is a key brainstem nuclei of interest as a shared circuit which is proposed to regulate both migraine and arousal. Thus, the aim of the present study was to investigate the role of the noradrenergic LC, a prominent arousal-promoting nucleus, in migraine-related pain processing. were C57Bl/6J mice Methods: Methods: injected with a canine adenovirus stereotaxically (CAV-PRS-hM3Dq-mCherry) specific expression of the designer receptor hM3Dq in LC noradrenergic neurons, via a PRS promoter. Acute intraperitoneal injection of nitroglycerin, the clinical migraine trigger, was used to induce periorbital hypersensitivity. Periorbital sensitivity thresholds were assessed using von-Frey filaments following chemogenetic activation of the LC using designer ligands both at baseline, and following acute nitroglycerin to assess its modulation of periorbital hypersensitivity. Results: Results: Compared to empty-vector controls, chemogenetic activation of the LC resulted in a significant increase in periorbital sensory thresholds (p<0.05). Furthermore, chemogenetic activation of the LC following acute nitroglycerin administration was sufficient to reverse periorbital hypersensitivity, returning sensory thresholds to baseline levels. drive

Conclusion: Conclusions: Acute activation of the LC produced anti-nociceptive effects on migraine-related cutaneous allodynia, highlighting the LC as a key structure in the regulation of migraine-related pain processing. Given its additional roles in the regulation of sleep, further exploration is warranted to assess the role of the LC in the bidirectional relationship between migraine and sleep. LBO006 Pharmaceutical insights into nitroglycerin effects on meningeal blood vessel imaging, sensory threshold, and motor function in mice C. Ernstsen Lauritzen1, E. Canko1, C. Degel1, K. Pedersen1, T. Bruun1, S. Falk1, A. Asuni1, B. Hall1, P. Botta1, F. Gastambide1 1Lundbeck, Copenhagen, Denmark Objective: This study examined the effects of nitroglycerin (NTG) on vascular tone, mechanical sensory threshold, and dynamic balance in mice. The efficacy of sumatriptan, topiramate, and anti-PACAP antibody (aPACAP mAb) on NTG-induced mechanical hypersensitivity was studied. Methods: C57Bl/6 mice received NTG (10 mg/kg, i.p.) or vehicle every other day for 9 days. vF responses and beam walk performance were measured 2 hrs. after NTG injection on days 1 and 9 [1]. Meningeal blood vessel imaging was performed on freely moving mice post cranial window surgery prior to NTG injections. Sumatriptan (2 mg/kg, s.c.) and topiramate (30 mg/kg, i.p.) were given 30 min and 2 hrs. before vF test on day 1, respectively [2,3]. Topiramate was also given daily with effects measured on day 9 [4,5]. aPACAP mAb (10 mg/kg, i.v.) was given on day 0 [6 – 9] (Fig. 1). Results: Acute and chronic NTG induced significant mechanical hypersensitivity (P = 0.0001 and 0.002). Sumatriptan blocked acute NTG-induced effects (P = 0.001, Fig. 2A) while topiramate blocked chronic effects (P = 0.01, Fig. 2B). aPACAP mAb prevented acute (P = 0.009) and chronic (P = 0.002) NTG effects (Fig. 3). Acute NTG increased time crossing the balance beam (P = 0.02) while chronic NTG increased the foot slip count (P = 0.03) with no effect on falls (P > 0.05, Fig. 4). Acute and chronic NTG caused significant vasodilation of meningeal blood vessels (P = 0.05 – 0.0001, Fig. 5). Longitudinal imaging following mice across chronic administration of NTG lead to vascular with enhanced vasodilation (P = 0.02 day 9 vs. 1, Fig. 5E). Conclusion: Acute and chronic NTG administration induced mechanical hypersensitivity which was blocked by distinct pharmacological agents including an aPACAP mAb. NTG altered dynamic balance, its relevance for vestibular migraine supporting hyper-sensitization [10]. Chronic NTG studies to progressive vasodilation of meningeal blood vessels, suggesting a migraine-like sensitization in disease-relevant tissues. led Fig. 1 Fig. 2 Fig. 3

P001 Constipation as an adverse effect of all the subcutaneous anti CGRP monoclonal antibodies: relation to pre-existing constipation and impact on migraine treatment T. Ascensão Pinheiro1, M. Henriques1, R. Pinheiro1, M. Saraiva1, S. Machado1, E. Parreira1 1Hospital Amadora-Sintra, Neurology, Amadora, Portugal P002 Calcitonin gene-related peptide monoclonal antibodies and concomitant autoimmune related disorders B. Carvalho1, C. Correia1, R. Costa1, M. Pinto1, R. Dias1, A. Costa1 1Hospital São João, Neurology Department, Porto, Portugal Objective: CGRP targeted therapies are generally well tolerated and constipation is the most frequent side effect, more prevalent with erenumab. Predisposing factors, possibly contributing to the onset of this effect, such as pre-existing constipation, have not been previously evaluated. Our goal was to determine the prevalence of constipation as an adverse effect of mAbs therapy in patients with and without pre- existing constipation. Methods: This is a retrospective, single-center study of all migraine patients treated at our clinic with mABs. Clinical data on pre-existing constipation, constipation as a side effect, and its treatment was collected from the clinical files. This constitutes a statistical descriptive analysis (SPSS). Results: Of 170 patients (60 treated with erenumab, 46 galcanezumab, 42 fremanezumab, 7 eptinezumab), 92.7% were women, median age 45.2 years. 35 patients (21.3%) had previous constipation. 50 patients (29,4%) reported constipation as side effect (either de novo/worsening of the constipation). Constipation was reported as a side effect in 19,2% of patients without prior constipation and in 54% of previously constipated patients. Most complaints were successfully managed with laxatives but in 6% treatment had to be interrupted; in 1 of these, constipation was complicated by rectal bleeding and hemorrhoids. Of reported constipation as an adverse effect, 52% were treated with erenumab, 28% galcanezumab and 20% fremanezumab. None of the patients treated with eptinezumab reported it. Conclusion: Approximately one third (29,4%) of our patients reported constipation as a side effect from treatment (most of them had previous constipation that worsened). Pre-existing constipation should be to determinant when administer or fremanezumab). Constipation treatment suspension in a not so small percentage of our patients. eptinezumab led the antibody the patients (preferably selecting that to center, involving Objective: Migraines often co-occur with chronic autoimmune diseases, increasing patient disability and medication interaction concerns. Calcitonin gene- related peptide monoclonal antibodies (CGRP mAbs) manage both episodic and chronic migraines by reducing mean monthly migraine days (MMD) and enhancing life quality. This study evaluates the efficacy and safety of CGRP mAbs for migraine prophylaxis in patients with coexisting autoimmune disorders. Methods: A retrospective study was conducted at our tertiary consecutive patients diagnosed with migraine who were receiving CGRP mAb therapy alongside treatment for coexisting autoimmune disorders. Data were collected from electronic health records, covering demographic, clinical, and therapy-related information. Results: Twenty-two patients aged 38-50 years (91.3% female), mean age 43.2 years, were included, with a median CGRP mAbs treatment duration of 9 months. Seventeen patients were on fremanezumab, four on erenumab, and one on eptinezumab. The most common autoimmune disorders were immune thyroiditis (n=4) and Systemic Lupus Erythematosus (SLE; n=3). Ten patients used both CGRP mAbs and disease-specific immunomodulatory therapy (4-18 months overlap). Migraine improvement frequencies compared to baseline MMD, assessed at 3, 6, 9, and 12 months, showed median reductions of 58%, 67%, 64%, and 63%, respectively. Adverse effects were absent in 68.2% (n=15); 22.7% (n=5) reported mild constipation and rash; only one patient had worse control of immune disease. Treatment discontinuation occurred in 9.1% (n=2) due to an SLE flare and pancreatitis (mean time after CGRP mAbs initiation: 5 months). Conclusion: This study suggests CGRP mAbs reduce migraine burden in autoimmune disorder patients, with most effects. Discontinuation was rare. The small sample size limits generalizability. Further research with larger cohorts is needed to confirm the safety and efficacy of CGRP mAbs in this patient population. experiencing mild their side

Fig. 1 Fig. 2 P003 Blood pressure in migraine patients undergoing treatment with CGRP monoclonal antibodies in patients with migraine – a systematic review and potential implications for clinical practice B. W. H. van der Arend1,2, F. van Welie1, M. Olsen3,4, J. Versijpt5, A. Maassen van den Brink2, G. M. Terwindt1 1Leiden University Medical Center, Neurology, Leiden, Netherlands 2Erasmus MC University Medical Center, Internal Medicine, Rotterdam, Netherlands 3Holbaek Hospital, Internal Medicine, Holbaek, Denmark 4University of Southern Denmark, Regional Health Research, Odense, Denmark 5UZ Brussel, Neurology, Brussels, Belgium the of impact Objective: Monoclonal antibodies targeting Calcitonin Gene-Related Peptide (CGRP) or the CGRP-receptor have revolutionized the prevention of migraine. Despite their effectiveness, worries have surfaced regarding potential unwanted cardiovascular effects linked to CGRP's vasodilation function, suggesting a potential influence on blood pressure (BP). In this systematic review, the aim was to evaluate the evidence regarding the effect of treatment with anti- CGRP(R)-mAbs on blood pressure in patients with migraine. Methods: Studies were systematically retrieved from PubMed, CDSR, WoS, MEDLINE, and EMBASE up to 1 May 2024. We focused on randomized controlled trials and observational cohort or case-control studies examining anti-CGRP(R)-mAbs compared to control treatments on BP in patients with migraine. independently conducted study selection, data extraction, and risk of bias assessment. Results: The literature search yielded 693 articles. After removing duplicates and conducting screening, 22 full-text articles were evaluated with only four studies meeting the inclusion criteria. Among these, only one study had a low risk of bias and reported elevated BP following initiation of anti-CGRP(R)-mAb treatment. Conclusion: While offer substantial benefits for migraine prevention, the potential risk of increased BP requires attention. Despite the current limited evidence, clinicians are urged to monitor BP of migraine patients undergoing treatment with anti-CGRP(R)-mAbs and to remain aware of the increased risk of cardiovascular events in these patients. anti-CGRP(R)-mAbs Two reviewers

P004 Anti-CGRP monoclonal antibodies treatment discontinuation in migraine: when and why T. Mateu1,2,3, V. J. Gallardo López2, E. Caronna1,2, A. Alpuente1,2, E. Giné Ciprés1,2, M. Torres-Ferrús1,2, P. Pozo-Rosich1,2 1Hospital Universitari Vall d'Hebron, Neurology, Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Barcelona, Spain 3Hospital de Mollet, Neurology, Mollet del Vallès, Spain the preventive treatments and (65.6% 300/457), first year 70.1 % Objective: To analyse the pattern of discontinuation of anti-CGRP monoclonal antibodies (anti-CGRP MAbs) in our centre. Methods: We have included patients with episodic and chronic migraine who failed to 3 previous migraine started treatment with erenumab, galcanezumab and fremanezumab from February 2019 to May 2024. We have analysed the time (<6, 6-12, 12-24, >24 months), the reason for discontinuation and the evolution after its cessation. Discontinuation occurred at the discretion of the treating physician. Results: A total of 1026 patients started anti-CGRP MAbs treatment, and 457 (44.5%) were suspended during the observation period. The main reasons for discontinuation were lack of efficacy improvement (12.9% 59/457) and poor tolerability (11.8% 54/457). During (24/354) of discontinuations were due to lack of efficacy and after 12-48 months, 36.89% to improvement. 11.6% (53/457) switched between anti-CGRP MAbs due to either lack of efficacy or to poor tolerability. 81.1% (43/53) discontinued the second treatment because of lack of efficacy, 13.2% (7/53) for poor tolerability and 5.7% (3/53) for improvement. after 47.4% treatment improvement because of discontinuation worsening in subsequent visits (mean time to restart 132 days, change in headache frequency +5 headache days/month). Conclusion: The main reason for discontinuation is lack of efficacy, which occurs during the first 12 months of treatment. Near half of patients that discontinued after migraine improvement restarted treatment due to worsening after the treatment cessation. We did not record severe adverse events. (38/103) were due (36/56) restarted for P005 Efficacy and safety of rimegepant for the preventive treatment of fasting-related headache during Ramadan in the UAE T. Alsaadi1, R. Suliman1, J. Yang2, E. Agarwal2, T. Fullerton3, D. E. Chou4, E. Whalen3, C. El Jadam1, I. Al Qaisi1, Y. Amin1, A. Alkhateri1, K. Alsaffarini1, L. Abraham5, Z. Zunaed2, H. M. Ahmed6, M. Fathy6, M. Hegab6, N. Vainstein7 1American Center for Psychiatry and Neurology, Department of Neurology, Abu Dhabi, United Arab Emirates 2Pfizer, Inc, New York, NY, United States 3Pfizer, Inc, Groton, CT, United States 4Pfizer IncPfizer, Inc, Cambridge, MA, United States 5Pfizer Ltd, Tadworth, United Kingdom 6Pfizer Gulf FZ LLC, Dubai Media City, United Arab Emirates 7Pfizer, Buenos Aires, Argentina Objective: Fasting-related headache is common during Ramadan, especially in the first week and in those with primary headache disorders. Rimegepant (RIM) is a CGRP receptor antagonist approved for treatment (Tx) of acute migraine and prevention of episodic migraine in adults. Here we report results from a single-center, 2-arm, randomized, staggered- start, open-label study designed to evaluate the efficacy and safety of RIM for the prevention of fasting-related headache during Ramadan. Methods: Patients (pts) aged 18–65 years and with a diagnosis of fasting-related headache/migraine prior to age 50 years were eligible. Pts could continue standard-of-care preventive treatment for migraine if the regimen was stable for ≥6 months and would continue throughout the fast. All pts received RIM 75 mg orally disintegrating tablet (ODT) once daily (QD) during the study. Pts were randomized to RIM for Days 1–28 of the fast (Arm 1) or to RIM for Days 8–28 of the fast (Arm 2). Primary endpoint was number of headache days (HDs) during Week 1 of the fast (Days 1–7). Secondary endpoints included number of HDs during Weeks 2–4, proportion of pts with moderate- to-severe headache, and pt satisfaction with Tx. Safety endpoints included proportion of pts discontinuing Tx due to adverse events (AEs) and frequency of serious AEs (SAEs). Results: 105 pts (82 female) were treated with RIM (Arm 1 n=52, Arm 2 n=53). HDs during Week 1 were fewer in Arm 1 compared with Arm 2 (mean: 1.75 vs 2.85). Proportion of pts with moderate-to-severe headache during Week 1 was smaller in Arm 1 compared with Arm 2 (28 vs 60%). HDs during the 4- week study were fewer in Arm 1 compared with Arm 2 (mean: 4.23 vs 6.08). Most pts (81%) reported being satisfied, very satisfied, or extremely satisfied with Tx.

[95% CI 12.0, 26.8], p<0.0001). Findings for secondary endpoints were consistent with the primary endpoint (Table 1). Any on-treatment AEs were experienced by 7.1% (RIM 25 mg), 9.2% (RIM 75 mg) and 6.6% (PBO) of participants (Table 2). Conclusion: RIM 75 mg demonstrated efficacy superior to PBO for the acute treatment of migraine, with a favourable safety profile, in participants in Japan. A dose-response relationship was observed for RIM. Funded by Pfizer. Fig. 1 Fig. 2 Rate of Tx discontinuation due to AEs was low and no Tx-related SAEs occurred. Conclusion: Analysis to date suggests that RIM 75 mg ODT QD may be effective and well tolerated for the prevention of fasting-related headache/migraine during Ramadan. P006 Efficacy and safety of rimegepant for the acute treatment of migraine in Japan Y. Matsumori1, K. Ikeda2, M. Kudo3, T. Ishikawa4, Y. Hoshino4, H. Yoshimatsu4, A. Thiry5, A. Arakawa4, R. Croop6, T. Fullerton5, F. Sakai7, T. Takeshima8 1Sendai Headache and Neurology Clinic, Sendai-shi, Miyagi, Japan 2Ikeda Neurosurgical Clinic, Kasuga-shi, Fukuoka, Japan 3Iwate Medical University, Department of Neurology and Gerontology, Morioka-shi, Iwate, Japan 4Pfizer R&D Japan, Shibuya-ku, Tokyo, Japan 5Pfizer, Inc, Groton, CT, United States 6Biohaven Pharmaceuticals, New Haven, CT, United States 7Saitama Neuropsychiatric Institute, Saitama International Headache Center, Saitama, Japan 8Tominaga Hospital, Headache Center, Department of Neurology, Osaka-shi, Osaka, Japan Objective: The primary objective was to compare the efficacy of rimegepant (RIM) 75 mg with placebo (PBO) for the acute treatment of migraine in participants living in Japan. A secondary objective was to compare the efficacy of RIM 25 mg with PBO to assess dose response. Methods: This phase 2/3 trial (NCT05399459) was a double-blind, randomized, multicentre, outpatient evaluation of the efficacy and safety of RIM orally disintegrating tablet compared with PBO for the acute treatment of migraine in participants living in Japan. Adults with a history of 2–8 migraine attacks/month of moderate or severe pain intensity treated a single migraine attack of moderate or severe pain intensity with RIM 25 mg, RIM 75 mg or PBO. The primary endpoint was participants (%) with pain freedom at 2 h postdose; secondary endpoints included pain relief, most bothersome symptom (MBS) freedom, return to normal function (all at 2 h postdose), and sustained pain relief and sustained pain freedom (each through 2–24 and 2–48 h postdose). Formal hypothesis testing was only conducted for RIM 75 mg vs PBO. Safety was assessed based on adverse events (AEs). Results: A total of 706 treated participants were evaluable for efficacy and safety. Response rates for the primary endpoint, pain freedom at 2 h postdose, were 21.0% (RIM 25 mg), 32.4% (RIM 75 mg) and 13.0% (PBO) (difference RIM 75 mg vs PBO = 19.4%

endpoints numerically favoured RIM vs PBO (Table 1). RIM was well tolerated during the DB phase (Table 2). There were no Hy's law cases. Conclusion: RIM 75 mg EOD demonstrated efficacy superior to PBO for migraine prevention with a favourable safety profile. Funded by Pfizer. Fig. 1 Fig. 2 P007 Efficacy and safety of rimegepant for the prevention of migraine in Japan Y. Matsumori1, S. Kitamura2, T. Yamamoto3, T. Ishikawa4, Y. Hoshino4, H. Yoshimatsu4, A. Thiry5, A. Arakawa4, R. Croop6, T. Fullerton5, F. Sakai7, T. Takeshima8 1Sendai Headache and Neurology Clinic, Sendai-shi, Miyagi, Japan 2Konan Medical Center, Department of Neurology, Kobe-shi, Hyogo, Japan 3Saitama Medical University, Department of Neurology, Iruma-gun, Saitama, Japan 4Pfizer R&D Japan, Shibuya-ku, Tokyo, Japan 5Pfizer, Inc, Groton, CT, United States 6Biohaven Pharmaceuticals, New Haven, CT, United States 7Saitama Neuropsychiatric Institute, Saitama International Headache Center, Saitama, Japan 8Tominaga Hospital, Headache Center, Department of Neurology, Osaka-shi, Osaka, Japan (DB), Objective: The primary objective was to compare the efficacy of rimegepant (RIM) with placebo (PBO) for the preventive treatment of migraine in participants living in Japan. Methods: This phase 3 trial (NCT05399485) was a double-blind randomized, multicentre evaluation of the efficacy and safety of RIM orally disintegrating tablet compared with PBO for the preventive treatment of migraine in participants living in Japan. Adults with a history of 4–18 migraine attacks/month of moderate or severe pain intensity completed a 28-day observation phase (OP), then took RIM 75 mg or PBO every other day (EOD) during the 12-week DB phase, followed by RIM 75 mg EOD and up to once daily as needed on nonscheduled dosing days during the 40-week open-label phase. for efficacy and Hierarchical testing was used outcomes research endpoints to for multiplicity. The primary endpoint was mean change from OP in the number of monthly migraine days (MMDs) in the last 4 weeks of the DB phase. Safety was assessed based on adverse events (AEs) and laboratory test abnormalities. Data are presented for the DB phase. Results: A total of 484 (efficacy) and 496 (safety) treated participants were evaluable. During the OP, participants reported a mean ± SD of 9.3 ± 3.08 (RIM) and 9.0 ± 3.14 (PBO) MMDs. The study met its primary endpoint with a statistically significant difference in mean change from OP in the number of MMDs in the last 4 weeks of the DB phase for RIM vs PBO (difference –1.1 [95% CI –1.73, –0.38], p=0.0021). Given first secondary endpoint was not statistically significant, formal hypothesis testing did not proceed, but results for secondary efficacy control the

Fig. 1 P008 Consistency of effect of rimegepant as an acute treatment for migraine attacks: Data from a real- world survey L. Abraham1, J. Brown2, K. Hygge Blakeman3, F. Dai2, J. Jackson4, W. Whitton4, L. Hancock4 1Pfizer, Tadworth, United Kingdom 2Pfizer, Inc, New York, NY, United States 3Pfizer AB, Stockholm, Sweden 4Adelphi Real World, Bollington, United Kingdom survey with Objective: Rimegepant, a next-generation, oral, calcitonin gene-related peptide receptor antagonist, is the only therapy approved for both acute and preventive treatment of migraine. This study assessed consistency of effect and satisfaction with rimegepant as an acute treatment for migraine attacks in real- world clinical practice. Methods: Data were drawn from the 2022/23 Adelphi Migraine Disease Specific Programme™, a real-world cross-sectional retrospective data in the USA. This analysis collection undertaken focussed on data collected from physicians and their patients receiving rimegepant as acute monotherapy. Where treatment duration was known, patients were categorised into those receiving rimegepant for <365 days and >365 days. Analyses were descriptive. Results: Ninety one patients were currently receiving rimegepant acute monotherapy. Duration of treatment was known for 76 patients (n=46 ≤365 days vs n=30 >365 days). Physicians reported 67% of patients receiving rimegepant <365 days (n=45) and 83% of patients receiving rimegepant >365 days (n=29) achieved pain freedom at 2 hours on more than half of occasions (Table 1). Patient reported pain freedom at 2 hours on 4 or 5 out of 5 occasions was 76%. All patients receiving rimegepant <365 days (n=11) and 92% of patients receiving rimegepant >365 days reported being satisfied/extremely satisfied with their acute treatment. All but one patient reported being willing to continue taking rimegepant (Table 1). In addition, 87% of patients were adequately optimized on their acute treatment with rimegepant. Conclusion: Consistency of rimegepant treatment effect across multiple attacks was reported by both physicians and patients in a real-world clinical setting. Patients were well optimised on rimegepant as an acute levels of satisfaction and willingness to continue its use, supporting sustained efficacy and satisfaction seen in the clinical trials. treatment, and reported high findings of (n=12) P009 Cognitive improvement in a patient undergoing Eptinezumab for the treatment of chronic migraine – a case report M. Hirt1, N. Peters1, B. Anders1 1Klinik Hirslanden Zürich, Department of Neurology, Zürich, Switzerland the results of Objective: Calcitonin gene-related peptide (CGRP) plays an important role in the pathophysiology of migraine. Progress in the preventive treatment has been achieved with the approval of monoclonal antibodies against CGRP. There can be multiple symptoms accompanying migraine, one of them being cognitive dysfunction. As the effects of CGRP blockade on cognition are not well known yet, we report a case study on this topic. Methods: We present a clinical case of a patient treated with the CGRP antibody Eptinezumab and the development of cognitive symptoms during the therapy using an extended neuropsychological evaluation before and after treatment initiation. Written consent for publishing is given. Results: A 39-year-old female has been treated for chronic migraine with frequent headache and daily visual aura for several years. The patient also reported attention about difficulties. evaluation showed deficits in the attention domain (alertness, selective attention and impulse control, shared attention, information processing speed, sustained attention) and in cognitive flexibility. Eptinezumab treatment was started shortly thereafter with clinically relevant response. After four cycles, we performed a control neuropsychological testing which showed normalization except one remaining deficit in alertness. Conclusion: Our patient showed relevant cognitive improvement during CGRP blockade. Eptinezumab has concentration, memory neuropsychological The and

alopecia 7 (10.1%), exanthema 5 (7.2%) and dyspnoea 3 (4.3%). After drug switches was observed only 9 AE (local reactions at the injection site 8 and constipation 1). In the group of "efficacy failures" were AE slightly more common after the change (13 versus 8), but more atypical (fatigue, drowsiness). We have found no specific registry parameters leading to the primary efficacy or tolerability failure. Conclusion: The switching between CGRP MAbs is effective and well tolerated. Fig. 1 shown reduction in mean monthly migraine days. The effects of CGRP inhibition on cognitive symptoms have been addressed in a limited number of studies using screening tests or surveys. The strength of our case is the use of an extended neuropsychological evaluation demonstrating cognitive improvement during Eptinezumab therapy. P010 Real-world effectivenes and tolerability of switching between CGRP pathway tageting antibodies: Czech Migraine Registry (ReMig) T. Nežádal1, B. Turková2, T. Doležal2, J. Marková3, A. Bártková4, L. Klečka5 1Military University Hospital, Neurology, Prague, Czech Republic 2Value Outcomes, Prague, Czech Republic 3University Thomayer Hospital, Neurology, Prague, Czech Republic 4University Hospital Olomouc, Neurology, Olomouc, Czech Republic 5Municipal Hospital of Ostrava, Neurology, Ostrava, Czech Republic Objective: Evaluation of the efficiency and tolerability of switching between CGRP antibodies (MAbs) in the Czech Registry of patients with Migraine on biological treatment (ReMig). Methods: We assessed the reasons for switches between CGRP MAbs, their outcomes and a possible influence of registry monitored parameters. The data were collected from January 2021 to June 2024. Results: A total of 3523 registry patients were analysed. We have found 154 (4.4%) patients with the CGRP MAbs switch (146 one, 7 two and 1 four: 164 switches at total). The reasons for switch were: lack of efficiency (61.6%), adverse events (AE,30.5%) and others (7,9%). We observed switches between all CGRP MAbs (Figure 1), mostly between MAbs with a different mechanism of action to fremanezumab 49 (29.9%), from fremanezumab to erenumab 41 (25.0%) and from galcanezumab to erenumab 19 (11.6%). The primary endpoint of switching CGRP MAbs was to achieve ≥ 50% monthly migraine day (MMD) reduction in the failure group and it was 68.7% in month (M)3 with the retention rate in M6, 9 and 12: 91.5%, 91.9% and 92.3% respectively. Surprisingly, in the AE group was ≥ 50% MMD reduction at M3 40.0% with the approximately same reduction in M6, 9 and 12 from the view that a lot of patients started in M0 with a small number of MMD. The commonest AE leading to discontinuation of the original medication were: constipation 23 (33.3%). local reactions at the injection site 20 (29.0%), diffuse from erenumab - P011 Fremanezumab for the treatment of migraine and medication overuse headache – a systematic review and meta-analysis I. Hajjaj1, C. Baraldi1, L. Pellesi1 1University of Southern Denmark, Clinical Pharmacology, Pharmacy and Environmental Medicine, Odense, Denmark (MOH) targeting fremanezumab, are effective Objective: Monoclonal antibodies the calcitonin gene-related peptide (CGRP) pathway, such as for migraine prevention. Despite fremanezumab"s proven efficacy, in treating medication overuse its effectiveness headache remains underexplored. This systematic review and meta-analysis aim to evaluate the efficacy of fremanezumab in adults with migraine complicated by MOH. Methods: We systematically searched PubMed and Embase on fremanezumab and MOH, selecting primary studies that included adults with migraine and MOH and reported at least one efficacy outcome. Data extraction and analysis followed PRISMA guidelines, using R software for meta-analytical computations. Results: Our search identified 175 records, of which 2 clinical trials and 6 real-world studies were included. The clinical trials encompassed 907 patients and databases (Ovid) for studies

that fremanezumab demonstrated significantly reduced monthly migraine days, days with acute headache medication use, and HIT-6 scores compared to placebo during a 12-week period. The real-world studies, including 371 patients, reported a reduction in monthly headache days from 17.0 at baseline to 9.8 at 6 months, and a high reversion rate from MOH after one year of treatment (Figure 1 and Figure 2). Conclusion: Both clinical trials and real-world studies support fremanezumab benefits in reducing migraine frequency, medication use, and headache-related disability in adults with migraine complicated by MOH. Given the limited quality of the current data, further research is needed to substantiate long-term benefits and establish optimal treatment protocols. Fig. 1 Fig. 2 P012 Effectiveness and safety of anti-CGRP treatment in migraine patients with autoimmune diseases: multicenter "ImmunoCGRP" case-control study M. C. García-Castillo1, Á. Sierra Mencia2, Y. González- Osorio2, Á. L. Guerrero-Peral2, A. Muñoz-Vendrell3, S. Campoy4, M. Huerta4, S. Santos-Lasaosa5, M. Polanco Fernández6, V. González Quintanilla6, J. Pascual6, C. Trevino-Peinado7, A. B. Gago-Veiga8,9, A. González Martínez8,9 1Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain 2Unidad de Cefaleas, Departamento de Neurología, Hospital Clínico Universitario de Valladolid., Valladolid, Spain 3Unidad de Cefaleas, Servicio de Neurología, Hospital de Bellvitge., Bellvitge, Spain 4Servicio de Neurología. Hospital de Viladecans, Viladecans, Spain 5Servicio de Neurología. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain 6Servicio de Neurología. Hospital Universitario Marqués de Valdecilla., Santander, Spain 7Headache Unit, Leganés, Spain 8Hospital Universitario de la Princesa, Neurology Department, Madrid, Spain 9Instituto de Investigación Sanitaria Princesa (IIS- Princesa), Madrid, Spain Objective: This study evaluates the effectiveness and safety of anti-CGRP monoclonal antibodies (anti-CGRP mAbs) in patients with migraine and comorbid autoimmune diseases. Methods: A multicenter observational case-control study including patients with migraine treated with anti-CGRP mAbs with autoimmune disease (AD) and age- and sex-matched controls without autoimmune disease (no AD) was performed. Demographic and headache variables were registered within Headache Units/specialized Headache clinics. Results: The study comprised 160 patients (80 AD and 80 no AD), with 95% women and a median age of 49.1 years. Patients with chronic migraine and antiCGRP mAbs duration were similar between the two groups (P>0.05). Baseline monthly headache days (MHD) and monthly migraine days (MMD) did not differ between groups. Both groups showed a significant reduction in MMD at 6, 9, and 12 months (p<0.05). However, the AD group had a lower reduction in MMD at 6 (7(SD:6) vs 5(SD:6); P=0.033), 9 (7(SD:6) vs 5(SD:4); P=0.041), (7(SD:7) vs 5(SD:4); P=0.034) and 12 months compared to the No AD group. Autoimmune disease worsened in 22% of the AD group at an average of 8 months. There were no major adverse events (AE). AE were similar between groups (47% vs 49%,P>0.05) and constipation was significantly higher in the AD group (46.3% vs. 21.6%, P=0.040).

Conclusion: This case-control study supports the overall effectiveness and safety of anti-CGRP drugs in patients with migraine and comorbid autoimmune diseases. However, our findings emphasize the need for further research on the clinical implications of anti-CGRP therapies in the context of autoimmunity. P013 Establishing relationships between efficacy, tolerability and the serum concentration of candesartan when used as migraine prophylaxis H. Skogum Riise1,2, T. Wergeland Meisingset1,2, E. A. Tronvik1,2, M. Rae Simpson2, K. A. Espnes3, A. Kattem Husøy1,2 1NorHEAD, Trondheim, Norway 2Norwegian University of Science and Technology, Trondheim, Norway 3St.Olavs Hospital, Trondheim, Norway and serum information was collected Objective: What are the relationships between efficacy, tolerability and the serum concentration of candesartan when used as migraine prophylaxis? Methods: A Norwegian prospective observational study on migraine patients initiating per oral prophylactic treatment. Participants had first a 4- week baseline period prior to treatment initiation and then a 12-week follow-up period with telephone consultations concentration measurements every four weeks. Daily headache diary registration through smartphone application. Side effect in every telephone consultation and in case of patient inquiries. Analysis was prespecified in a SAP. Mixed logistic regression model was used to estimate efficacy and multilevel mixed logistic regression model was used for the relationship between serum concentration and efficacy. Results: 167 (of the total study population of 256) initiated candesartan. Of participants initiating candesartan, 89% were female and 54% had chronic migraine. 20% had medication overuse headache. Candesartan led to a reduction of 2,4 moderate- severe headache days from baseline to week 9-12 (p=0.000). We also found that for every 10th unit increase of candesartan serum concentration, the odds of having a headache day were 0.97 (p=0.002). The average number of related side effects was 1,3 with orthostatic dizziness as the most common one. Most side effects (86%) were graded mild. Analysis on side effect and serum concentration relationships is currently ongoing. tolerated and Conclusion: Candesartan efficacious in candesartan serum concentration does very slightly reduce the odds of having a headache day. is well in a real word setting. Increase P014 Vaporized Cannabis versus placebo for acute migraine – a randomized controlled trial N. Schuster1, M. Wallace1, T. Marcotte2, D. C. Buse3, E. Lee4, L. Liu5, M. Sexton6 1University of California, San Diego, Center for Pain Medicine, Department of Anesthesiology, San Diego, CA, United States 2University of California, San Diego, Department of Psychiatry, San Diego, CA, United States 3Albert Einstein College of Medicine, Department of Neurology, Bronx, NY, United States 4University of California, San Diego, Altman Clinical and Translational Research Institute, San Diego, CA, United States 5University of California, San Diego, Department of Biostatistics and Bioinformatics, Herbert Wertheim School of Public Health and Human Longevity Science, San Diego, CA, United States 6University of California, San Diego, Department of Family Medicine, San Diego, CA, United States Objective: To test the efficacy of cannabis for acute migraine in a randomized, double-blind, placebo- controlled, crossover trial. Methods: In this randomized, double-blind, placebo- controlled, crossover trial, adults with migraine treated up to 4 separate migraine attacks, 1 each with 4 different treatments. The 4 treatments were 1) 6% THC; 2) 11% CBD; 3) 6% THC/11% CBD mix; and 4) Placebo flower from the NIDA Drug Supply Program. They were vaporized in a randomized order, with ≥1 week washout between treatments. The primary endpoint was pain relief at 2 hours from vaporization. Secondary endpoints were pain freedom and most bothersome symptom (MBS) freedom at 2 hours from vaporization. Results: 92 participants were and randomized and 71 participants treated at least one migraine attack. Mean age was 41 and 82.6% were female. Participants entered 2-hour data for 234 attacks. THC/CBD mix was superior to placebo at achieving pain relief (67.2% vs 46.6%, p=0.016), pain freedom (34.5% vs. 15.5%, p=0.017) and MBS freedom (60.3% vs. 34.5%, p=0.005) at 2 hours, sustained pain freedom at 24 hours, and sustained MBS freedom at 24 and 48 hours. THC only was superior to placebo at achieving pain relief (68.9% vs. 46.6%, p=0.008), but not pain freedom or MBS freedom at 2 hours. CBD only was not superior to placebo for any outcomes at 2 hours. There were no serious adverse events. Conclusion: Acute migraine treatment with vaporized cannabis flower containing 6% THC/11% CBD was efficacious at 2 hours post-treatment with sustained pain freedom at 24 hours and sustained MBS freedom at 24 and 48 hours. enrolled

to the (MAMMs). these the criteria of associated with travel through the SPG provided the rationale for symptoms syndromes. SphenoCath® is a catheter device that block SPG with a common local anesthetic (Lidocaine). In literature, there are no randomised controlled trials about the use of SphenoCath® device for SPG blockade in treatment and prevention of migraine. The object of this study is to assess the effectiveness of SPG block by Sphenocath® in a migraine population. Methods: We retrospectively enrolled patients affected by high frequency episodic or chronic migraine with or without medication overuse, according International Classification of Headache Disorders, 3rd edition. We assessed changes in Migraine Disability Assessment Questionnaire (MIDAS), Numeric Pain Rating Scale (NPRS), Monthly Migraine Days (MMDs) and Monthly Acute Migraine Medications The questionnaires were performed at baseline and one, three, six, and twelve months after SphenoCath® treatment. Results: A total of 76 participants were screened and 30 were included. A significant reduction of MIDAS (p<0,001), NPRS (p<0,001), MMDs (p<0,001), and MAMMs (p<0,001) was detected, mostly after one and three months of treatment, but also after six months for MMDs (p=0,039), NPRS (p=0,011), and monthly triptan medications (p=0,018). At one-year follow-up, a slightly significant decrement of NPRS (p=0,039), and monthly triptan medications (p=0,043) was observed. Half of patients reached a 50% reduction in MAMMs and 40% of subjects reported 50% reduction in MMDs at 1 month follow-up. There were 17 non severe adverse events, mostly local discomfort. using Conclusion: Sphenocath® is an emerging, effective and safe option for the treatment of disabling migraine. Prospective studies are needed to further confirm these findings. Trans-nasal SPG blockade rimegepant for acute treatment of migraine may provide an additional preventive effect. Methods: Data were pooled from 2 uncontrolled long- term open-label trials of rimegepant (NCT03266588, NCT05371652). Participants in this analysis had ≥6 monthly migraine days (MMDs) during a 30-day observation period (OP). Participants took oral rimegepant 75 mg as needed, up to once per day for up to 52 weeks, for acute treatment of migraine attacks of any severity. Adverse events (AEs) and change in the number of MMDs (relative to the OP) were summarized descriptively. Results: Of 1288 treated participants, 68.7% reported an AE, 4.7% reported a severe AE, 2.9% reported a serious AE, and 2.4% reported an AE leading to rimegepant discontinuation. Upper respiratory tract infection (9.5%), nasopharyngitis (7.8%), and COVID- 19 (7.6%) were reported by ≥5% of participants. Among 1269 participants in the MMD analysis, the mean (SD) number of MMDs during the OP was 11.1 (4.3). The number of MMDs decreased, relative to the OP, over the course of 52-week treatment with rimegepant (Table). The mean (SD) change in MMDs was –2.0 (4.6) for the overall 52- week treatment period. Conclusion: Long-term use of rimegepant 75 mg for acute treatment of migraine, up to once per day for up to 52 weeks, was well tolerated and may provide an additional preventive effect as evidenced in a reduction in MMDs. The observation that MMDs were reduced over time suggests that medication overuse headache to be associated with rimegepant. is unlikely included Fig. 1 P017 Use of Rimegepant 75 mg for the acute treatment of migraine is associated with a reduction in monthly migraine days – a pooled analysis of 2 open-label trials S. Yu1, T. Fullerton2, G. Pixton2, Y. Zou3, Q. Zhong3, H. Zhu3 1Chinese PLA General Hospital, Beijing, China 2Pfizer, Inc, Groton, CT, United States 3Pfizer (China) Research and Development Co Ltd, Shanghai, China Objective: Rimegepant, a calcitonin gene-related peptide receptor antagonist, is indicated for acute and preventive treatment of migraine in adults. This long-term use of analysis examined whether P018 A multidisciplinary multicentric approach to the identification of BIOmarkers of MIGraine (BIOMIGA project): an open-label, prospective clinical study based on the stratification of responders to Erenumab D. Martinelli1, E. Caronna2, H. Basedau3, M. M. Pocora1,4, E. Ballante1, R. Greco5, G. Castellazzi6, V. J. Gallardo López2, L. Asskour2, E. Giné Ciprés2, A. Alpuente2, M. Torres-Ferrús2,7, A. M. Zanaboni5, J. Mehnert3, A. May3, P. Pozo-Rosich2,7, C. Tassorelli1,4 1Fondazione Mondino IRCCS, headache science and rehabilitation unit, Pavia, Italy 2Vall Hebron Institute of Research (VHIR), Headache and Neurological Pain Research Group, Barcelona, Spain 3University Clinic of Hamburg Eppendorf, Dept. of

Systems Neuroscience, Hamburg, Germany 4University of Pavia, Brain and Behavioral Science Department, Pavia, Italy 5Fondazione Mondino IRCCS, Laboratory of Neurophysiology of Integrative Autonomic Systems, Pavia, Italy 6Fondazione Mondino IRCCS, Pavia, Italy 7Hospital Universitari Vall d'Hebron, Headache Clinic, Barcelona, Spain in the clinical Objective: In this multicenter prospective study, we aim to identify multimodal biomarkers predicting response to CGRP monoclonal antibodies in subjects with migraine. Methods: Clinical, molecular and radiological data were collected in three headache centers: IRCCS Mondino Foundation (Italy), Vall d"Hebron University Hospital (Spain), and University of Hamburg (Germany). Participants were deeply phenotyped at baseline before 3-month treatment with erenumab (prescribed according to local reimbursement guidelines if ≥8 headache/days/months (MHD)), and classified as responders if a reduction ≥ 50% headadche/days in the last month of treatment was achieved. Here we present the differences variables between groups. Results: 164 participants were included, 137 (83.5%) female, median age 42 years , 62/164 (38 %) had a diagnosis of chronic migraine (CM), and 102/164 (62%) had high-frequent episodic migraine (EM). The median MHD at baseline was 13 [8-25 95% non- parametric C.I] . In the third month of treatment, 76/164 (48.%) were "responders" with a mean of 4 [1- 8] MHDs; whilst non-responders had 11 (6-25) MHD. CM was more prevalent among non-responders (p=0.024). No differences were detected between females and males in MHDs reduction after 3 months, although females showed a significant reduction in MIDAS score (p=0.038) and a significant higher Beck Anxiety Inventory (p=0.004) and Mig-SCog scores (p<0.001). Before treatment, females had higher scores on the Mig-SCog (p=0.041) and MIDAS scales (p=0.043). Conclusion: At a clinical level there are no significant differences between responders and non-responders after 3 months of erenumab treatment. However, less headache days/month at baseline were correlated with higher responder rates; and females had higher disability scores at baseline. This cohort is similar to other ones described. Acknowledgment: This study was funded by ERANet Neuron under the project code BIOMIGA. The funding source did not influence the way the study was conducted P019 Rimegepant effectiveness and tolerability as acute migraine treatment (GAINER) – a real-world multicentric study M. Corrado1,2, R. De Icco1,2, L. F. Iannone3, A. Burgalassi3, G. Vaghi1,2, E. De Matteis4, F. De Santis4, C. Fasano3, E. M. Piella5, M. Romozzi6, G. Sebastianelli7, G. Avino8, S. Cevoli9, G. Coppola7, G. Dalla Volta10, A. Granato11, E. Mampreso12, R. Ornello4, F. Pistoia3, S. Sacco3, I. Rainero5, M. Trimboli13, A. Russo14, M. Valente15, C. Vollono16, C. Tassorelli1,2, F. Cammarota1 1University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 2Fondazione Mondino IRCCS, Headache Science and Rehabilitation Centre, Pavia, Italy 3Headache Centre and Clinical Pharmacology Unit, Careggi University Hospital, Florence, Italy 4University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy 5University of Torino, Department of Neurosciences, Torino, Italy 6Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Neurologia, Rome, Italy 7Sapienza University of Rome Polo Pontino ICOT, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy 8Ospedale di Prato Santo Stefano, Prato, Italy 9IRCCS Istituto delle Scienze Neurologiche, Bologna, Italy 10Headache Centre of Istituto clinico città di Brescia, Brescia, Italy 11Azienda Ospedaliero-Universitaria di Trieste, Trieste, Italy 12Headache Centre, Neurology - Euganea Health Unit, Padova, Italy 13Centro Interaziendale Cefalee, Azienda Ospedaliero- Universitaria Renato Dulbecco, Catanzaro, Italy 14University of Campania "Luigi Vanvitelli", Department of Advanced Medical and Surgical Sciences, Napoli, Italy 15Azienda Sanitaria Universitaria Friuli Centrale, Presidio Ospedaliero Santa Maria della Misericordia, Udine, Italy 16Università Cattolica del Sacro Cuore, Department of Neurosciences, Rome, Italy Objective: Rimegepant has been recently approved for the acute migraine treatment. While its efficacy has been proven in clinical trials, real-world data are currently lacking. Thus, we designed a prospective multicentric rimegepant effectiveness and tolerability in the real-world setting (NCT05903027). Methods: We enrolled 87 patients (76% females, 44.3+11.7 years, 28% with chronic migraine, baseline evaluate study to

to rule out idiopathic intracranial papilledema hypertension. Duration of follow-up was 3 months. The primary outcome of this study was the reduction of mean monthly days with headache. The secondary outcomes were the reduction of BMI, and the rate of adverse events. Results: Mean monthly days with headache decreased from a baseline mean of 20.04 ± 6.38 days to 8.81 ± 6.01 days post-treatment. This change was statistically significant with a mean difference of 11.23 days (95% CI: 7.96 to 14.50, t(25) = 14.50, p < 0.001). Conversely, BMI decreased slightly from 34.01 to 33.65, and this change was not statistically significant (mean difference = 0.36, 95% CI: -0.02 to 0.74, t(25) = 1.97, p = 0.060). Regression analysis indicated no significant effect of BMI reduction on headache frequency. Conclusion: This pilot study suggests that GLP-1 agonists may be a suitable and effective treatment for chronic migraine and that efficacy is unrelated from weight loss. This may shed new light on migraine physiopathology and its relation with CSF volume and pressure homehostasis. Fig. 1 monthly migraine days 9.4+7.8) from 13 Italian headache centers. Patients were instructed to treat up to four migraine attacks with rimegepant 75 mg. Using an ad hoc diary, we prospectively collected migraine-attack features every 30 minutes after rimegepant administration, up to 2 hours (2h). Results: Preliminary analyses were conducted on 43 reported first-treated attacks (8/43 in CM patients), and on 91 total attacks. At rimegepant intake, 38.5% of patients rated migraine intensity as severe (3 on a 0-3 rating scale). Pain freedom 2h post-dose was reported in 58.1% (25/43) of first-treated attacks, and in 53.8% (49/91) of total attacks. The 2h pain freedom response was not influenced by timing of rimegepant intake (p=0.204), baseline pain severity (p=0.171) and the diagnosis of chronic/episodic migraine (p=0.626). Freedom from the most bothersome symptom 2h post-dose was reported in 60.4% of attacks. Mild adverse events were reported in 18% total attacks (8/91), namely gastrointestinal discomforts (n=4), fatigue (n=2), dizziness (n=1) and somnolence (n=2). Tolerability was rated as good-to-excellent in 92.3% cases (84/91). Conclusion: Our real-world data support rimegepant effectiveness, safety, and tolerability as acute In the preliminary analysis, migraine treatment. rimegepant effectiveness was not influenced by pain severity and timing of drug intake. P020 GLP-1 agonists for the treatment of chronic migraine: a pilot prospective observational cohort study S. Braca1, C. V. Russo1, A. Stornaiuolo1, G. Cretella1, R. De Simone1 1University of Naples "Federico II", Department of Neurosciences, Naples, Italy IIH drugs fluid common surpassing influencing cerebrospinal Objective: Glucagon-like peptide-1 receptor (GLP-1R) agonists, used for diabetes and obesity, control fluid secretion, (CSF) production in the brain's choroid plexus. Studies show GLP-1R agonists reduce intracranial pressure (ICP) in rodents, in effectiveness. Clinical trials have confirmed their ability to lower ICP and improve headache frequency in IIH patients. There is evidence that reducing ICP benefits not only IIH patients but may also be beneficial to those with borderline normal CSF pressure, indicating that even isolated intracranial compliance reduction might be crucial in migraine development. Interestingly, GLP-1R agonists have also been found to suppress pain pathway sensitization in trigeminal nucleus caudalis. Methods: We enrolled 26 patients with chronic migraine and a concomitant BMI equal or greater than included the presence of 30. Exclusion criteria

Fig. 1 P021 Real-world experience of Lasmiditan for the acute treatment of migraine – a single clinic-based prospective study H. J. Jeong1, M. J. Lee1,2 1Seoul National University Hospital, Neurology, Seoul, South Korea 2Seoul National University, College of Medicine, Seoul, South Korea to Objective: We aimed to report the response rate, side effects, and predictors of response and side effects from lasmiditan treatment in Korean patients with migraine. Methods: We prospectively recruited patients who received lasmiditan at Seoul National University Hospital from April 2023 to March 2024. Patients' demographics, headache-specific variables, and previous treatment experience were collected at Visit1. We collected the treatment response and side effect profile. Maintenance, dose adjustment, and discontinuation were collected at Visit2, and we defined the tolerability as maintenance or dose increment. The univariable and multivariable logistic regression analysis was performed identify predictors measured at Visit2. Results: 154 patients were included in our study. At Visit1, 110(71.4%) and 44(28.6%) patients were prescribed lasmiditan 50mg and 100mg, respectively. At Visit2, treatment response was observed in 49(44.5%) patients receiving 50mg and 20(45.5%) receiving 100mg. 75(48.7%) patients patients reported side effects. Dizziness(N=45, 60.0%), somnolence(N=15, 20.0%), and nausea(N=13, 17.3%) were the most common side effects. The multivariable logistic model showed that female sex(HR 4.51, 95% CI 1.43–14.19, p=0.01) and higher dose(100mg vs. 50mg; HR 2.35, 95% CI 1.14–4.83, p=0.02) were independently associated with side effects. Lasmiditan dosage was adjusted as follows: dose escalation in 56(36.4%), dose in 17(11.0%), and treatment discontinuation in 40(26.0%) patients. The remaining 41(26.6%) subjects maintained their initial dosage. in 63.0%(97/154) of patients. is the first real-world data of Conclusion: This lasmiditan response and side effects in Korean patients with migraine. Although used as low dose, lasmiditan was effective in approximately a half of patients in our study regardless of their demographics and headache characteristics. Dizziness was the most common side effects with a higher rate than that reported in clinical trials. Lasmiditan was well reduction tolerated Fig. 2

Fig. 3 P022 Conditioned pain modulation is associated with the prognosis in patients with migraine L. L. H. Pan1, Y. H. Ling2,3, S. P. Chen1,2,3,4,5, Y. F. Wang2,3, S. J. Wang1,2,3 1National Yang Ming Chiao Tung University, Brain Research Center, Taipei, Taiwan 2Taipei Veterans General Hospital, Department of Neurology, Neurological Institute, Taipei, Taiwan 3National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan 4National Yang Ming Chiao Tung University, Institute of Clinical Medicine, Taipei, Taiwan 5Taipei Veterans General Hospital, Division of Translational Medicine, Department of Medical Research, Taipei, Taiwan Objective: Conditioned pain modulation (CPM) measures the capacity for endogenous analgesia, which is known to decrease in individuals with acute or chronic pain, including patients with migraine. In this study, we aimed to investigate whether CPM capacity is associated with the prognosis in patients with migraine. Methods: Patients with migraine were identified by headache specialists according to ICHD-3 criteria and were instructed to maintain a headache diary throughout the study. Responders (R) were defined as participants who showed a reduction of ≧50% monthly migraine day (MMD) by the third month compared to baseline. All participants underwent cold pressor tests (CPT) before starting routine treatment. During CPT, pressure pain thresholds (PPTs) were assessed on the left thenar eminence before and interference. immediately after the immersion of 4±2℃ water of the right hand and forearm as long as the participants could bear or with a time limit of 4 minutes. The CPM capacity was defined as the increase in PPT after CPT. Only participants who finished CPT during the ictal phase were included in analyses to avoid phase- Independent t-tests or Chi- related squared tests were used to identify the differences between R and non-responders (nR). Results: Eighty-seven patients with migraine were prospectively included (71 females, 36.0±10.2 yrs., 7.1±6.6 MMD), and 48 were identified as R by the third month. R (6.9±5.2 vs. 1.3±1.5 days, pp=0.152) presented with minimal changes. Tables 1 and 2 show the baseline characteristics and CPT outcomes of R and nR. Despite similar immersion times and post- immersion pain ratings, R exhibited a more significant increase in PPT after CPT compared to nR (33.3±39.8 vs. 16.3±34.4 kPa, p=0.039), indicating better CPM capacity. Conclusion: The capacity of intrinsic pain modulation, as assessed by CPT, is associated with the prognosis of patients with migraine. Fig. 1 Fig. 2

P023 Patients satisfaction to triptans and to available oral and injectable medications (OnabotulinumtoxinA/anti-CGRP MAbs) for migraine prophylaxis. Results of a web-based survey E. V. Dermitzakis1, A. Argyriou2, K. Bilias3, D. Rikos4, G. Xiromerisiou5, P. Soldatos6, M. Vikelis7 1Euromedica General Clinic, Thessaloniki, Greece 2Agios Andreas State General Hospital of Patras, Department of Neurology, Patras, Greece 3Greek Society of Migraine and Headache Patients, Athens, Greece 4404 Military Hospital, Larisa, Greece 5University Hospital of Larissa, University of Thessaly, Department of Neurology, Larisa, Greece 6Private Praxis, Kalamata, Greece 7Headache Clinic, Mediterraneo Hospital, Athens, Greece Objective: The Greek Society of Migraine and Headache Patients conducted a web-based survey in 2023 to ascertain the patients" satisfaction with conventional and novel migraine therapies. Methods: The sampling process was based on a random call to participants to reply to a specific migraine-focused self-administered questionnaire, including 83 questions in Greek, which was distributed nationwide through the online research software SurveyMonkey. Results: We eventually enrolled 2565 patients, the majority of which were females. Our findings clearly demonstrate that migraine is still a burdensome condition. Triptans seem to be partly effective as acute therapies. OnabotulinumtoxinA seems to be effective for almost half of chronic migraine patients (43.9%) to report adequate satisfaction with this treatment (27.8% were "fairly happy", 10.6% were "very happy", and 5.5% were "extremely happy"). Due to their high rates of preventative effectiveness, most respondents treated with anti-CGRP Mabs expressed their optimism concerning their future while living with their migraine (88.25%), as well as towards further improvements in their quality of life (82.8%) status, mostly with fremanezumab. Conclusion: The patients recognize the usefulness of anti-CGRP Mabs in migraine prevention. Considering the market change that is anticipated with the use of gepants and ditans, larger longitudinal population- based studies are warranted to further explore if the new era of migraine therapeutics might further lessen the burden of the disease. P024 Migraine patients treating with remote electrical neuromodulation (REN) shows significant and clinically meaningful benefits and utilization in a Coverage with evidence development (CED) study A. Stark-Inbar1, A. Synowiec2, D. D. Santamaria2, M. Fickie3, S. Ross3,4 1Theranica Bio-Electronics Ltd., Netanya, Israel 2Allegheny Health Network, Neurology, Pittsburgh, PA, United States 3Highmark Inc, Pittsburgh, PA, United States 4Penn State Health, Hershey, PA, United States Objective: The Remote Electrical Neuromodulation (REN) wearable device (Nerivio) is FDA-cleared and CE-marked non-invasive drug-free option for acute and preventive treatment of migraine in patients aged ≥12 years. REN was shown to be efficacious and safe in multiple trials and real-world studies. Highmark Inc. (Highmark) conducted a CED study to evaluate REN migraine treatment in real-world clinical setting, and to assess the medical necessity of coveraging REN as a standard-of-care therapy. Methods: Highmark commercial members diagnosed with migraine were prescribed REN per clinical judgement of their provider and used it for ≥ 3 months. Efficacy was evaluated by the Migraine Disability Assessment (MIDAS) test at baseline and after at least 3 months of use, and by prospective pain and disability reports per treatment. Safety was monitored via adverse event reports. Results: 381 patients participated (mean age 40.5, SD=13.2; 91.1% female). Average MIDAS score decreased from 58.3 (SD=59.0) to 46.2 (SD=44.1) after ≥3 months, a statistically significant reduction of 12.1 points (SD=51.8; n=116; p=0.014). 77.8% of patients reported pain relief and 33.3% reported pain freedom 2 hours post-treatment in ≥50% of their treatments. Relief from functional disability was reported by 70.6% of patients, and freedom from disability by 50.0%. Satisfaction, effectiveness and tolerability were reported by 74.2%, 78.1%, and 93.8%, respectively. Three patients reported minor adverse events. The average number of REN devices used per patient per year, extrapolated over all patients for one year, was 4.0 (SD=3.1). significant Results Conclusion: improvement in migraine-related disability, pain, and functional impairment in real-world setting. Following this study, REN was added as a standard treatment for migraine under Highmark policy. Members of other health plans worldwide can benefit from similar coverage decisions. demonstrate

Fig. 1 Fig. 3 Fig. 2 P025 Deep brain stimulation for four patients with new daily persistent headache: initiating precision therapy via stereoelectroencephalography Z. Dong1, H. Zhao2, C. H. Yeh3, S. Zhang1, Y. Wang3, C. Zhang3 1Chinese PLA General Hospital, Department of Neurology, Beijing, China 2Chinese PLA General Hospital, Department of Neurosurgery, Beijing, China 3School of Information and Electronics, Beijing Institute of Technology, Key Laboratory of Brain Health Intelligent Evaluation and Intervention,, Beijing, China of NDPH presented in affected Objective: New Daily Persistent Headache (NDPH) is widely recognized as one of the most challenging primary headache disorders to manage, often leading to significant disability individuals. However, The continuous occurrence and intricate pathogenesis significant challenges in its treatment. The precision therapy of DBS based on SEEG has shown promise and feasibility in refractory diseases. Methods: In this pioneering study, SEEG and DBS implantation were conducted on four patients with NDPH. Following the implantation of SEEG electrodes, the study procedure was divided into monitoring and stimulation period, during which clinical and electrophysiological recordings were received. We utilized the VAS to assess changes in headache the corresponding real-time electrophysiological data. First, Statistical analysis and cross-validated machine learning models were employed to analyze the spectral power features of specific brain regions to characterise different headache states. Second, the clinical effects of stimulation of different brain severity and matched baseline it to

calibration identified clinical coupling regions, as well as the validation of biomarkers, were used to determine the optimal stimulation targets. and Through Results: analysis, different electrophysiological frequency bands of RAMY were to consistently characterize the fluctuation in NDPH headache severity. The bilateral VPM and PAG regions were identified as potential precise targets for DBS treatment in NDPH. All four patients safely completed DBS showcasing enhancements in headache severity and associated comorbidities. Conclusion: This study provided novel insights into the pathogenesis and potential treatment targets for NDPH. Most importantly, the concept of SEEG-driven precision DBS is expected to open up new therapeutic areas for refractory headache and to be widely validated in the future. implantation and follow-up, Fig. 1

Fig. 2 Fig. 3 P026 True versus misinformation classification in headache medicine using BERT based AI model J. Dave1, P. Patel2, P. Zhang1 1Rutgers University, Neurology, New Brunswick, NJ, United States 2Columbia University, New York, NY, United States content, potentially treatment, combined with Objective: The rise of technology and the availability of blogs and social media have contributed to the proliferation of non-evidence-based content in the field of headache medicine. The broad interest in headache-related the potential for misinformation, poses risks such as inadequate harmful interventions, and difficulties in patient-physician interactions. We seek to train an Artificial Intelligence (AI) model that identifies misinformation and true- information in headache medicine. Methods: We first algorithmically generated 1950 statements of misinformation and true information by prompting GPT 3.5 turbo on topics from The International Classification of Headache Disorders 3 (ICHD-3). The databased was manually checked by two authors (JD and PZ) for accuracy. We then trained Bidirectional from Transformers (BERT) based transformer AI models to classify the true and misinformation content. To avoid catastrophic forgetting, meaning the model forgets the initial task it was trained on, we freeze the model weights and only unfreeze last three layers. We then fine-tune last 3 layers of distil-BERT model on our 90% training dataset and test the trained model on unseen 10% dataset. Results: Of the validation set, 86 of 97 statements of misinformation's were correctly identified and 93 of 98 true information were correctly identified. Our results indicate a 91.80% classification accuracy on previously unseen data. The outcomes reveal the model's capability to distinguish between true and Encoder Representations

patients using NCCT. The model confirmed brain changes in SIH patients, even with thin-cut imaging. Further research is needed to explore the potential of deep learning models in diagnosing SIH with simple NCCT images and to identify specific brain changes detected by these models. Fig. 1 Fig. 2 misinformation instances with accuracy exceeding chance levels. Conclusion: A transformer model is able to classify the true versus misinformation from headache content database and may be a useful tool for physicians and patients alike for misleading information. to help screen P027 Accurate detection of spontaneous intracranial hypotension using Ddensenet201 based deep learning model – a pilot study C. Ting-Yu1, C. Chi-Hsiang1, H. Tsung-Wei1, C. Hung- Chieh2,3 1Taichung Veterans General Hospital, Department of Neurology, Neurological Institute, Taichung, Taiwan 2Taichung Veterans General Hospital, Department of Radiology and Nuclear Medicine, Taichung, Taiwan 3National Yang -Ming Chiao- Tung University, College of Medicine, Taipei, Taiwan Objective: Spontaneous intracranial hypotension (SIH) is usually caused by cerebrospinal fluid (CSF) leakage without prior trauma or medical procedure. Detecting this leakage using standard imaging techniques, such as CT or MRI, can be challenging. Non-contrast brain CT (NCCT) is widely used in clinical settings due to its rapid availability. This study aimed to determine if a deep learning model could enhance the detection of SIH on NCCT scans, thereby supporting clinicians with a readily accessible and efficient diagnostic tool. Methods: This cross-sectional study involved SIH patients and healthy controls from headache clinics at a tertiary medical center. Patients were selected based on Magnetic Resonance Myelography (MRM) diagnosis of SIH, and their NCCT images were compared to those of normal individuals. The study utilized the DenseNet201 architecture within a Convolutional Neural Network (CNN) algorithm to analyze the images. We randomly divided all images into test (20%) and training/validation (80%) sets. DenseNet201 trained on 90% and validated on 10% of the training set, repeating the process. The final evaluation was conducted on the test set to assess DenseNet201's accuracy. Results: We included 20 SIH patients (15F/5M, mean age 46.6±12.5 years) and 20 normal patients (15F/5M, mean age 46.5±12.2 years) in the analysis. A total of 1304 non-contrast brain CT images from 40 cases were evaluated. The training results showed an accuracy of 94.3%, a sensitivity of 94.3%, and a specificity of 94.2%. Our algorithm was then tested, yielding an accuracy of 93.8%, a sensitivity of 94.7%, and a specificity of 93.0%. Conclusion: Our DenseNet201 deep learning model identifying SIH demonstrated high accuracy in

Fig. 3 P028 AI-generated question bank for headache boards exam: innovation in neurology education J. Dave1, P. Patel1, F. Traore2, I. Hakkinen3, J. Dawe4, P. Olson5, S. Malhan6, P. Zhang7 1Mount Sinai, New York, NY, United States 2UCLA, Los Angeles, CA, United States 3Eastside Neuroscience Institute, Seattle, WA, United States 4University of Ottawa, Ontario, Canada 5Indiana University, Bloomington, IN, United States 6Thomas Jefferson University, Philadelphia, PA, United States 7Rutgers University, New Brunswick, NJ, United States Objective: This study aims to develop and review an Artificial Intelligence (AI)-generated question bank specifically for the headache board exam, leveraging AI to create high-quality, dynamic, and scalable study materials, and to assess their quality through expert review. Methods: We utilized a Retrieval-Augmented Generation (RAG) approach to create an AI-generated question bank for headache neurology. This method aggregates information from textbooks, research articles, and guidelines from the American Headache Society to generate multiple-choice questions (MCQs) with detailed explanations. After creation, a panel of headache medicine neurologists the relevance, accuracy, clarity, and questions alignment with current board exam content. reviewed for identified areas Results: The question bank featured a broad array of MCQs reflecting current advancements in headache neurology. The AI model ensures comprehensive exam coverage and allows for annual updates. Neurologists found the questions relevant and consistent with the complexity and style of the actual board exam questions. Feedback indicated that the AI-generated materials could be a valuable study tool, with for to be addressed in future updates. The AI-generated question bank Conclusion: represents a significant advancement in producing up- to-date and comprehensive study materials. Expert review validated the questions' quality and relevance, demonstrating AI"s potential in creating dynamic educational resources. This work lays the foundation for future studies to validate these materials' effectiveness in exam preparation and explore their use in other neurology subspecialties. improvement P029 Digital health literacy in people with headache disorders – a multicentre cross-sectional study F. Pastore1, G. Cicolini2, M. Totaro3, B. Forastefano3, V. Simonetti2, D. Comparcini1 1University of Bari "Aldo Moro", DiBrain, Italy, Italy 2University of Chieti, Chieti, Italy 3University of Rome Tor Vergata, Rome, Italy a with collected via three Objective: To measure the level of Digital Health Literacy (DHL) among patients with headache disorders and to analyse the correlation between patients" level of DHL, clinical and sociodemographic factors. Methods: A multicentre cross-sectional study was conducted from November 2023 to May 2024, enrolling patients aged over 18 with a medical diagnosis of headache using a convenience sampling. self-assessment Data were questionnaire sections: (I) sociodemographic data (age, gender, education, type of headache); (II) HLS19-DIGI questionnaire assessing DHL through three subscales: HL-DIGI (difficulty in dealing with digital health information), HL-DIGI-INT (difficulty in interaction with digital health resources), HL-DIGI-DD (frequency of digital device use for health); (III) Headache Impact Test (HIT-6) measuring headache impact on their daily life. HLS19-DIGI scores range from 0 to 100, with higher scores indicating a higher DHL; HIT-6 scores range from 36 to 78, with ≤49 indicating minimal impact and higher scores indicating greater impact. Results: Among 263 participants, 81.4% (n=214) were female, with a mean age of 43.4 years (SD=12.0), 43.7% (n=115) had a high school diploma, and 56.6% (n=149) were from Southern Italy. Participants had

sufficient DHL level (HL-DIGI=62.5; HL-DIGI-INT=68.5), but low digital device use per week (HL-DIGI-DD mean=1.4, SD=0.9). HIT-6 median score was 66, indicating severe headache impact. Higher education was significantly and positively associated with HL- DIGI-INT (95% CI) 15.9 (8.30; 23.6), p<0.001 and HL- DIGI-DD 95% CI) 0.19 (0.01; 0.36), p=0.034. No association were found between DHL levels, other sociodemographic variables, and HIT-6 score. Conclusion: Higher education were correlated with higher DHL levels, particularly in digital interaction (HL-DIGI-INT) and device usage frequency (HL-DIGI- DD). Digital educational interventions could improve DHL in patients with lower levels of education. P030 Advancing headache care: AI innovations addressing ICHD-3 guidelines M. Babaei1, R. Cowan1 1Stanford University, Neurology, Palo Alto, CA, United States Objective: This narrative review reports recent AI models addressing the International Classification of Headache Disorders (ICHD-3) gaps. Methods: A comprehensive search across PubMed, Scopus, and Web of Science was conducted using keywords "Artificial Intelligence", "Machine Learning", "Headache Disorders". Relevant papers were screened and included. Results: AI addresses: • Overlap and Ambiguity classified headache migraines, in Criteria: AI types, effectively distinguishing tension-type headaches, TACs, epicranial, and thunderclap It headaches differentiates from medication-overuse post-traumatic headaches, which share similarities and pose clinical and management challenges. chronic migraines diagnostic accuracy. with high and • Under-Representation of improved Blood-sample-based Secondary ML Headaches: algorithms representation of secondary headaches, using age, sex, and CBC parameters. Neuroimaging in deep learning has also detected brain biomarkers for secondary post- headaches traumatic headaches.3-5 Inadequate Attention to Comorbidities: AI has developed prediction models forecasting migraine attacks based on interactions with comorbidities including depression, anxiety, and for comprehensive care. cardiovascular including diseases • • • • based attacks Lack of Specificity for Pediatric Headaches: AI has improved pediatric headache guidelines with high accuracy and sensitivity. Impact of Headache on Quality of Life: AI uses mobile health apps, wearables, and ML to forecast migraine on physiological data, enhancing diagnosis and management, personalized treatment strategies based on individualized data, decreasing the negative headache impact on a patient"s quality of life. Insufficient Integration: AI simplifies triage and differentiates primary from secondary headaches using age, sex, CBC parameters, neuroimaging, and biochemical markers. Biomarker aiding and Conclusion: AI is promising to address the diagnostic and management gaps and advance headache care and personalized treatment approaches. P031 Reporting quality and risk of bias analysis of published RCTs assessing anti-CGRP monoclonal antibodies in migraine prophylaxis – a systematic review D. Rikos1, M. Vikelis2, E. V. Dermitzakis3, P. Soldatos4, D. Rallis5, J. Rudolf6, A. P. Andreou7,8, A. Argyriou9 1404 Military Hospital, Neurology, Larisa, Greece 2Mediterraneo Hospital, Headache Clinic, Athens, Greece 3Euromedica General Clinic, Thessaloniki, Greece 4Independent Researcher, Kalamata, Greece 5Tzaneio General Hospital of Piraeus, Neurology, Athens, Greece 6Papageorgiou General Hospital, Neurology, Thessaloniki, Greece 7King's College, Headache Research-Wolfson Sensory, Pain and Regeneration Centre, Institute of Psychiatry, Psychology and Neuroscience, London, Greece 8Guy's and St Thomas' NHS Foundation Trust, Headache Centre, London, United Kingdom 9Agios Andreas General Hospital of Patras, Headache outpatient Clinic, Patras, Greece involving migraine patients Objective: Phase II/III randomized clinical trials (RCTs) are vulnerable to many types of bias beyond randomization. Insights into the reporting quality of RCTs treated with monoclonal antibodies targeting the calcitonin gene- related peptide system (anti-CGRP MAbs) are lacking. Our aim was to analyze the currently reporting quality of phase involving migraine patients treated with anti-CGRP MAbs Methods: A systematic search was performed on the PubMed and EMBASE databases, according to PRISMA II/III RCTs

guidelines, for relevant RCTs in either episodic or chronic migraine prevention. An adapted version of the 2010 CONSORT (Consolidated Standards of Reporting Trials) checklist was utilized to document the trials" quality of reporting. The RoB2 and ROBvis online tools were used to document and visualize the risk of bias. Results: From the initially identified 179 articles, we finally found 31 RCTs that were eligible for evaluation. The average CONSORT compliance was 88.7% (69.7– 100%), while 93.5% (N = 29) of the articles had a compliance greater than 75%. Twenty-eight CONSORT items were reported in more than 75% of the articles. The average compliance of the analyzed RCTs was 93.9% for Galcanezumab, 91.3% for Fremanezumab, followed by 85.4% for Erenumab and Eptinezumab studies. Implementation of the ROB2 tool showed some concerning "missing information" arising from the inadequate reporting. Specifically, 50% of the studies were categorized as having inadequate information regarding the randomization process Conclusion: Adequate reporting quality was disclosed in the evaluated RCTs with anti-CGRP MAbs in migraine prevention. However, some methodological issues need to be highlighted to be addressed in future studies assessing the efficacy of new molecules targeting CGRP or other candidate pathways implicated in migraine pathophysiology P032 Therapeutic effect of a single lumbar puncture in idiopathic intracranial hypertension S. Zaic1,2, N. Krajnc1,2, S. Macher1,2, M. Michl3, N. Müller1,2, C. Mitsch3, W. Marik2,4, K. Novak2,5, C. Wöber1,2, B. Pemp3, G. Bsteh1,2 1Medical University of Vienna, Department of Neurology, Vienna, Austria 2Medical University of Vienna, Comprehensive Center for Clinical Neurosciences & Mental Health, Vienna, Austria 3Medical University of Vienna, Department of Ophthalmology, Vienna, Austria 4Medical University of Vienna, Department of Neuroradiology, Vienna, Austria 5Medical University of Vienna, Department of Neurosurgery, Vienna, Austria Objective: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by increased intracranial pressure. Whilst lumbar puncture (LP) is necessary for diagnosis, its therapeutic effect remains unclear. Our aim was to evaluate the therapeutic effect of a single LP in patients with IIH (pwIIH). Methods: In this prospective observational study, we analysed clinical and ophthalmological outcomes in pwIIH the week before (D0), one (D1) and seven days (D7) after LP. Our primary endpoint was the change in papilledema degree from baseline. Secondary endpoints included further visual outcomes (change in optical coherence tomography (peripapillary retinal nerve fibre layer thickness [pRNFL] and ganglion cell layer [GCL] volume), ocular sonography (arachnoid optic nerve sheath diameter [AONSD])) and headache outcomes (peak and median headache severity). Results: We included 30 pwIIH (mean age 32.8 years (SD 8.4), 93.3% female, median CSF opening pressure 33.0 cmH2O (IQR 26.9-35.3), median body mass index (BMI) 34.8 kg/m2 (IQR 30.9-40.9). The median papilledema grading at baseline was 2 (1-3) and was significantly reduced at D7 (2 (1-2), p=0.026), median headache severeity did not significantly decrease. Median pRNFL decreased significantly at D7 (-9μm (- 62.5, -1.3), p=0.035), with pRNFL at baseline being associated with pRNFL change (F1,11=18.79, p=0.001). Mean AONSD decreased significantly at both D1 (-0,74 (0.14), p<0.001) and D7 (-0.65mm (0.17), p=0.01), with AONSD at baseline being associated with the change in AONSD (D1:β=-0.89, 95% CI -1.37, -0.42, p=0.002; D7:β= -0.85, 95% CI -1.42, -0,28, p=0.007). Conclusion: In short-term follow-up, a single LP has moderate therapeutic effect in IIH. Thus, it may be considered in pwIIH with papilledema, specifically in those with in pregnancy or IIH treatment. limited therapeutic options, e.g., intolerance of pharmacological P033 Matrix representation of the primary headache syndromes in the International classification of Headache Disorders (ICHD3) – a basis for automated diagnosis and analysis of criteria P. Zhang1, R. Cheng1 1Rutgers University, Neurology, New Brunswick, NJ, United States Objective: We attempt to represent the ICHD3 in matrix form and show that this representation allows for automated diagnosis and additional insights into headache classification. Methods: Each diagnosis in the ICHD3 is defined by a list of characteristics; combinations of characteristics form phenotypes. Multiple phenotypes may fit a given diagnosis. We first translated all characteristics for primary headache diagnoses into true/false statements. We generated a matrix of valid ICHD3 diagnosis as follows: 1. Each row of the matrix represents a phenotype. 2. Each column of the matrix If any phenotype represents a characteristic. 3. contains a characteristic, then that element is encoded as 1. Otherwise, it is encoded as 0. its bipartite From projection, non-negative matrix factorization (NMF), this matrix, we calculated in the ICHD3

and Markov cluster. We also row reduced to derive the basis vectors that span the space of all headache phenotype. Results: Automated diagnosis can be accomplished as follows: each row in the ICHD3 matrix can be compared with a patient"s headache phenotype. If all the 1"s in that row correspond with 1"s in the patient phenotype, then the patient"s headache matches the corresponding diagnosis. Migraine diagnoses has the strongest associations based on bipartite projection. NMF replicates ICHD3 diagnoses; Markov clustering yields either phenotype or characteristics clusters, but not both. Various combinations of probable TACs as well as presence/absence of individual autonomic features also appear to cluster together in novel fashion. Finally, row reduction of our matrix implying that all headache diagnoses in the ICHD3 can be represented as linear combinations of 55 characteristics. Conclusion: Our result demonstrates that clustering algorithms on the matrix representation of headache suggests the possibility for automated diagnosis, reclassification, as well as simplification of ICHD3. P034 The hidden causes of headaches: insights from a retrospective neurology ward study C. Borges da Silva1, S. Lima1, A. J. Marques1, P. Guimarães1, A. Matas1 1Unidade Local de Sáude de Trás-os-Montes e Alto Douro, Neurology, Vila Real, Portugal seeking emergency medical Objective: Headache complaints are a leading reason for assistance. Recognizing key red flags is vital to suspect secondary etiologies. Methods: This retrospective observational study analyzed adult patients admitted to the Neurology ward for headaches over five years (2019-2023). Demographic and clinical data were retrieved from medical records and subsequently analyzed. Results: The study included 128 patients, mostly female (57%) with a median age of 56 (IQ=31). Most were diagnosed with secondary headaches (88%), including CNS infection (21%), brain tumor (16%), and cerebral-vascular disease (16%). Predominant red flags were altered neurological exam (43%), age ≥65 (31%), persistent new onset headache (28%), poor response to analgesics (21%), headache worsening with postural changes (20%), visual alterations (19%), and fever (17%). An altered neurological exam strongly (p=0.003). Certain red flags correlated with specific etiologies. linked to Persistent new onset headache was cerebral-vascular (p=0.028), especially (p=0.006). Visual venous cerebral indicated secondary etiology disease thrombosis Postural (p=0.002), Comorbidities change-related associated with analysis associated with alterations were intracranial hypertension (p=0.021) and CNS inflammatory disease (p=0.021). headache indicated CSF hypotension (p=0.0001). Fever was infection (p=0.0001), along with linked to CNS meningeal signs altered behavior/confusion (p=0.006), and cancer history revealed (p=0.037). hypertension was secondary headaches (p=0.01), particularly hemorrhagic stroke- related headaches (p=0.017). Mood disorders (p=0.021) and a history of headaches (p=0.002) were linked to primary headaches. Conclusion: As described in literature, several red flags strongly suggest secondary headache etiologies. This study also emphasizes the association between certain comorbidities and specific causes of secondary headaches. P035 Creutzfeldt-Jakob disease presenting as a new daily persistent headache M. Kholodova1, A. Matsko1 1Medical Center "Dobrobut-Clinic", LLC, Neurology & Neurosurgery, Kyiv, Ukraine Objective: The new-onset headache in the elderly should be approached with great caution, and usually, it is necessary to exclude secondary causes. Methods: A single clinical case. Results: We present the case of a 63-year-old woman with new-onset headache, neck pain, and episodic vestibular symptoms. At her first visit to the neurologist two months before admission to our clinic, the clinical presentation was unremarkable except for neck stiffness. She was treated with NSAIDs and manual therapy without improvement. A few weeks later, cognitive decline began, as well as hallucinations and marked vestibular symptoms with unsteadiness. Later, psychiatric symptoms appeared: depression, sleep disturbances, and anxiety, which progressed examination revealed: rigidity, mutism, and myoclonus. Her first brain MRI was unremarkable and negative. And three months later, an MRI showed bilateral lesions in the basal ganglia and parieto-temporal cortical T2 FLAIR and DWI hyperintensity (Figure 1). She was treated empirically with methylprednisolone without effect. The CSF was negative for all bacteria, viruses, and autoimmune antibodies, but positive for 14-3-3 protein and PrPSc. Her EEG was unremarkable. Thus, the diagnosis of sporadic Creutzfeldt-Jakob disease was made according to the criteria. Conclusion: It is very important to exclude other possible organic diseases in order to make a correct diagnosis and to plan a treatment strategy without rapidly. Neurological

delay. It is always necessary to exclude secondary causes, even the rare ones. Fig. 1 P036 The use of LSD, Psilocybin and 2-Bromo-LSD (BOL- 148) for the treatment of cluster headache T. Passie1 1Hannover Medical School, Hannover, Germany (CH). CH from cluster headache Objective: Fließtext: In 1996 it was reported for the first time that psilocybin may provide relief from relentless pain resulting is characterized by migraine-like, severe pain perceived in one or both sides of the head typically accompanied by several autonomic symptoms. Attacks last between 20-90 minutes and, as observed with the episodic form of CH, typically continue for weeks or even months. Chronic CH is characterized by 2-10 attacks per day which can carry on for years. For this reason, severe CH is also referred to as "suicide headache" since 50% of those patients commit suicide. Information exchange between patients suffering from CH on the internet began to indicate that self treatment with hallucinogens such as psilocybin appeared to offer a form of self-styled treatment opportunities. A study initiated by researchers at Harvard Medical School also revealed that LSD seemed to show preventative effects resulting in symptom-free periods that lasted for weeks or months without taking the drug more than a few times. Further research led to trials with the non- hallucinogenic LSD-derivative BOL-148, which was developed as an "LSD-placebo" in the late 1950s. BOL treatment does not produce significant side effects. It has been used as a preventative for cluster headaches and has shown high efficacy. Since it has been patented by the Harvard Medical School and Hanover Medical School in a corporative endeavour, BOL-148 has been tested in some more patient and has recently gone on medication development track. The medication has to be given just three times to provide a preventative effects lasting six months to two more years. Therefore, it could revolutionize the treatment of CH. The lecture provides an overview about the history and results of the use of BOL-148 in CH treatment. Recent results from new trials with BOL-148 will be presented plus an outline of the further development of the implementation of BOL- 148. Methods: --- Results: --- Conclusion: --- P037 ROC analysis of questionnaires for the ability to differentiate types of primary chronic headache Y. Bukreieva1 1Dnipropetrovsk State Medical University, Neurology, Dnipro, Ukraine were Short Form used: Visual Questionnaire (MPQ). Objective: To assess the possibility of using different questionnaires for differentiation between chronic migraine (CM) and chronic tension headache (CTH). Methods: The 60 patients were included to the study, they were divided to the two groups: 30 patients with CM and 30 patients with CTH (according to the ICHD-3). The following questionnaires and criteria scales Analogue Scale (VAS), Migraine Disability Assessment (MIDAS), Headache Impact Test (HIT-6), Neck Disability Index (NDI), Hospital Anxiety and Depression Scale (HADS), Survey (SF-12) and the 12-item The McGill Pain Receiver Operating Characteristic was performed to evaluate the possibilities of using different questionnaires to differentiate between CTH and CM. Results: The areas under the ROC curve for all the studied questionnaires statistically significant level (p<0.05) and had average (SF-12 psychological component), good (MIDAS, HADS-A), very good (HADS-D, SF-12 physical component, MPQ evaluative psychological component) and excellent (HIT-6, NDI, VAS, MPQ motivational-affective component, MPQ sensory- discriminative component) characteristics of the differential ability between CTH and CM. Conclusion: Therefore, questionnaires HIT-6, VAS, MPQ sensory- to discriminative (motivational-affective components) can be used reached a component, SF-12 and

differentiate CTH from CM in patients. Optimal cut-off points that can be used to make a decision in favor of CM when differentiating between CTH and CM are for HIT-6 ≥ 63, VAS ≥ 7, MPQ: Motivational-affective component ≥ 8, MPQ: Sensory -discriminative component ≥ 23. Fig. 3 Fig. 1 Fig. 2 P038 Primary laugh-induced headache: case report M. Moncyte1, A. Dapkutė2, K. Ryliškienė2,1 1Kardiolitos klinikos, Center of Neurology, Vilnius, Lithuania 2Vilnius University, Center of Neurology, Vilnius, Lithuania Objective: Laugh and other Valsalva maneuver- induced headaches are often secondary to structural brain abnormalities. However, primary laugh-induced headache is rare and poorly described. Here we present a case of a primary laugh-induced headache not provoked by other Valsalva maneuvers. Methods: Case report. Results: A 21-year-old male presented with a history of typical headaches since the age of 11-12, with increased frequency over the last 3 years due to lifestyle cahnges (e.g. singing along to loud music), from once per year to once per month. Attacks occurred after vigorous laughter or yelling, featuring sudden headaches of moderate to severe intensity lasting less than 3 seconds, localized in the frontal area. On some days, he experienced up to 10 bouts per day, accompanied by a sense of pressure in the head and painful eye movements throughout the day. He did not experience any associated autonomic symptoms, and no other Valsalva maneuvers could provoke such headaches. The patient also reported a distinct type of headache after increased physical activity, specifically prolonged jogging. This headache was of low intensity, pressing in nature, dispersed throughout the head, lasting up to 1 hour, associated with bilateral ear congestion, and improved after cessation of physical activity Neurological and cardiological examinations, including vital signs, were unremarkable. Carotid and vertebral duplex ultrasound results were normal. Brain MRI

sinuses and ethmoidal detected no structural brain abnormalities but reported thickened mucous membranes of the maxillary cells. An otolaryngologist diagnosed chronic rhinitis and concluded that the headaches were unlikely to be associated with these findings. The patient was diagnosed with primary laugh-induced and primary exercise headaches. Conclusion: This case illustrates an occurrence of two rare types of primary headaches: primary laugh- induced headache in combination with primary exercise headache, with no detected structural brain abnormalities. P039 Targeting pain of burning mouth syndrome: onabotulinum toxin A injection as a promising symptomatic treatment L. Barbosa1,2, A. Costa1,3 1Unidade Local de Saúde de São João, Neurology, Porto, Portugal 2Unidade Local de Saúde do Tâmega e Sousa, Neurology, Penafiel, Portugal 3Faculty of Medicine, University of Porto, Clinical Neurosciences and Mental Health, Porto, Portugal is a Objective: Burning mouth syndrome (BMS) to craniofacial pain disorder often resistant in pharmacological treatments. Recent advances neuropathic pain management exhibited promising analgesic effects with onabotulinum toxin A (BoNT-A) injections. We present two BMS cases treated with BoNT-A following a pain management protocol, reporting positive outcomes. Methods: We administered intradermal BoNT-A injections as monotherapy to two patients with BMS (injection details in image 1). An anesthetic spray was used to minimize discomfort during the technique. The procedure was repeated every three months. Results: Patient 1 (P1) is a 48-year-old woman with idiopathic BMS since 2020. Previous treatments with gabapentin and topical clonazepam were ineffective and caused significant side effects. BoNT-A injections began in June 2022, at which time she reported persistent pain with an intensity of 7/10. Patient 2 (P2) is a 39-year-old woman with secondary BMS due to scleroderma since 2012. Treatments with carbamazepine, pregabalin, and topical clonazepam provided no relief and had side effects. BoNT-A treatment started in November 2023, with baseline persistent pain severity of 6/10. At 15-day follow-up, both patients reported significant pain relief (P1: 1/10; P2: 4/10), no daily life restrictions due to BMS, and no need for additional analgesics or topical anesthetics. Both patients found the procedure simple, fast, and mildly uncomfortable due to the punctures. P1 reported temporary lip asymmetry after one procedure and P2 experienced no adverse effects. After 7 and 3 trimestral procedures, respectively, both patients maintained pain relief and expressed satisfaction and desire to continue the treatment. Conclusion: Previous studies suggested BoNT-A to be effective in managing pain of craniofacial pain disorders. Our results indicate that this treatment may be an option for managing pain in BMS patients who do not respond to or experience side effects from first-line therapies. Fig. 1 P040 Targeting noradrenergic tone to compensate for glymphatic dysfunction in post-traumatic headaches after mild traumatic brain injury A. Della Pietra1, A. Kuburas1, E. Partridge1, M. Sevao2, J. Cho2, A. Schindler2, M. Raskind3,4, J. Iliff2,3,4, A. Russo1,5 1University of Iowa, Molecular Physiology & Biophysics, Iowa City, IA, United States 2University of Washington, Psychiatry and Behavioral Sciences, Seattle, WA, United States 3University of Washington, Neurology, Seattle, WA, United States 4Veterans Affairs (V.A.), Seattle, WA, United States 5Veterans Affairs (V.A.), Iowa City, IA, United States Objective: Mild traumatic brain injury (mTBI) is a common and complex head injury, affecting 69 million people worldwide. This condition results in many symptoms, including migraine-like post-traumatic headaches (PTH). The mechanisms underlying these headaches are unknown. A clue to PTH may be the shared clinical associations between mTBI, migraine, and sleep-wake disruption. Indeed, sleep disruption, which is common after mTBI, is also a migraine trigger. Instead, sleep is known as migraine abortive. In this setting, sleep disruption may impair the glymphatic system, a recently characterized brain- wide network of perivascular spaces that supports the rapid exchange of cerebrospinal and interstitial fluid. Glymphatic function is most rapid during sleep, while

is is tone and inhibited during wakefulness by central it noradrenergic reduced by mTBI. Therefore, our hypothesis is that the disruption of glymphatic function after mTBI may contribute to the trigger and endurance of PTH symptoms. Methods: Repetitive impact mTBI mouse models have been used to develop PTH phenotypes. The mice were treated with the α1-adrenergic antagonist prazosin (PZN). Their PTH symptoms, induced by the injection of a sub-threshold calcitonin gene-related peptide (CGRP) dose, the main migraine mediator, were assessed through light aversion and mechanical facial allodynia system impairment was measured via glymphatic CSF tracer influx compared to sham control mice. Results: Our data demonstrate that treatment with PZN prevents and treats sub-threshold CGRP cephalic allodynia sensitivity in mice, with faster rescue in males than females. Finally, prazosin administration in mice increases glymphatic CSF tracer influx compared to vehicle-treated mice. Conclusion: These results suggest noradrenergic tone improve PTH symptoms and as novel target to glymphatic improving sleep disruption as therapeutic strategies for mTBI patients. tests. Moreover, glymphatic function, potentially P041 Barriers to accessing anti-CGRP monoclonal antibodies (mAbs) in Spain: a survey of neurologists, Hospital Pharmacists (HP), and patients P. Irimia1, P. Díaz-Ruiz2, I. Colomina3, R. Belvís4, J. M. Lainez5 1Clínica Universidad de Navarra, Neurology, Pamplona, Spain 2Hospital Universitario Nuestra Señora de Candelaria., Servicio de Farmacia Hospitalaria., Santa Cruz de Tenerife, Spain 3Asociación de Pacientes de Migraña y Cefalea (AEMICE), Madrid, Spain 4Hospital de la Santa Creu i Sant Pau, Neurology, Barcelona, Spain 5Hospital Clínico Universitario, Universidad Católica de Valencia, Neurology, Valencia, Spain Objective: To identify the barriers to accessing anti- CGRP mAbs in Spain Methods: Cross-sectional study was conducted using online surveys targeting neurologists, HP, and patients. Descriptive statistics were employed to the data. Categorical variables were evaluate expressed and percentage. The Therapeutic Positioning Report (TPR) elaborated by the Spanish Ministry of Health has limited the funding of mAbs targeting CGRP in Spain to patients with ≥8 migraine days/month and at least 3 prior therapeutic failures, one of which must be frequency terms of in botulinum toxin in the case of chronic migraine. Additionally, anti-CGRP mAbs have been included within the hospital dispensing regime and, therefore, must be dispensed by HP, for reasons of economic efficiency Results: 55.1% of neurologists and 67.4% of HP reported that their hospital follows the Therapeutic Positioning Report elaborated by the Spanish Ministry of Health (TPR) criteria on a case-by-case basis to authorize the dispensing of anti-CGRP mAbs. However, more than 30% of neurologists and HP indicated that they have their own protocols. 62.8% of neurologists and 23.3% of HP expressed disagreement with some of the TPR criteria, and according to 41.9% of HP, not all neurologists in their hospital can prescribe anti-CGRP mAbs. Neurologists and HP estimate that the TPR criteria should be periodically reviewed and changed according to new scientific evidence. 32.9% of patients found it difficult to access a migraine specialist. 88.4% of neurologists and 81.4% of HP believed that the referral from primary care to neurology should be improved. Conclusion: The main barriers to accessing anti-CGRP mAbs are the difficulty in accessing a neurology specialist, the stringent TPR criteria elaborated by the Spanish Ministry of Health, and their variable application across different autonomous communities and hospitals. Referral systems to neurology should be improved, and the TPR criteria should be periodically reviewed. P042 Knowledge and attitudes of migraine diagnosis and treatment methods among Armenian neurologists and general practitioners G. Yeganyan1,2, S. Khachatryan3,4 1Wigmore Clinic, Yerevan, Armenia 2Gyumri Medical Center, Department of Neurology and Stroke Unit, Gyumri, Armenia 3Somnus Neurology Clinic, Yerevan, Armenia 4National Institute of Health, Department of Neurology and Neurosurgery, Yerevan, Armenia Objective: Migraine is one of the leading neurological diseases causing disability both globally and in Armenia. According to the Global Burden of Disease study, more than half a million patients with migraines live in Armenia. The availability of modern migraine management methods in our country is quite low, which affects both patients and the state. The aim of our research is to understand the awareness of Armenian doctors regarding modern methods of migraine management and the applicability of these methods in everyday practice. Methods: Data collection was conducted through an electronic survey. Neurologists, family doctors, and

general practitioners from different regions of Armenia participated. They were asked about their awareness of modern guidelines for diagnosing and treating migraine and how well they could adhere to these guidelines given limited resources. Results: A total of 52 doctors (mean age 34) participated in the survey, of which 86.5% (n=45) were neurologists. Among the respondents 46 work in the capital Yerevan, 6 of whom also work in regional areas, and 6 participants work only in regions. The work experience (including residency) was "up to 10 years" (65.4%) and "more than 10 years" (34.6%). Awareness of the SNNOOP10 red flags list and ICHD-3 was 65.4% and 69.2% respectively. Many of them (86.5%) use headache diaries. Preferred drug groups for preventive and abortive treatments are shown in table 1. The awareness and applicability of modern migraine treatment options among Armenian doctors are presented in table 2. Conclusion: In summary, it can be noted that absence of the latest generation of migraine drugs hinders the full guideline-based management of migraine patients. Nevertheless, level of doctors' awareness of these guidelines is quite high, and they are ready to apply them in everyday practice if possible. the Fig. 1 Fig. 2 P043 Awareness, case management, and Influencing factors of migraine among family physicians in Denizli city center, Turkey N. Ergin1, E. Barış2, A. Ergin2 1Pamukkale University, Neurology, Denizli, Turkey 2Pamukkale University, Public Health, Denizli, Turkey to determine Objective: This study aims the awareness, case management, and influencing factors of migraine among family physicians in Denizli city center, Turkey. Methods: This cross-sectional study's population consists of family physicians working in primary care in Denizli city center. The minimum sample size was calculated as 109 individuals. The study was conducted without sample selection, covering the entire population. The dependent variables are the family physicians' status of asking all three questions of the ID Migraine Screening Test to patients who presented with headaches in the last three months and their knowledge of the Migraine Diagnosis Criteria without Aura (ICHD-3 Beta). Data were collected between March 1-31, 2023, through face-to-face administration of a 22-question survey to family physicians. Ethics committee approval, institutional permissions, and participants' consent were obtained before the study. Results: A total of 135 Family Physician participated in the study. Of the participants, 47.4% were aged 42-54, 57.8% were male, 45.2% graduated between 1990 and 2000, 13.3% had a migraine diagnosis, 18.8% had a family history of migraine, 69.6% found their pre- graduation education on migraines adequate, 31.1% received post-graduation education on migraines, 65.9% wanted to receive education on migraines, 83.0% asked all three questions of the ID Migraine Screening Test to patients who presented with headaches in the last three months, and 31.1% and 3.7% knew 5 and all of the Migraine Diagnosis Criteria without Aura, respectively. Conclusion: Our study shows that eight out of ten family physicians are proficient in migraine screening, but there are significant deficiencies in migraine diagnosis. P044 Challenges for CGRP mAb prescribing in Egypt M. Nada1 1Cairo University, Neurology, Cairo, Egypt Objective: To assess the efficacy, safety as well as availability of anti-CGRP therapies in Egypt Methods: A cross-sectional prospective study in Egypt, the efficacy and safety of anti-CGRP therapies (Erenumab and galcanzuimab) were assessed in 50

patients (22 episodic and 28 chronic patients) as well as availability and socioeconomic burden. Results: Efficacy was reported from the first week in around 12% of patients. At nine weeks, almost 75% of patients reported a significant reduction not only in their monthly migraine days by at least 50%, but also in their headache severity (using both the validated Arabic version of the migraine disability assessment [MIDAS] test. The majority of patients reported efficacy and significant reduction of their MMD after the third injection. Most of those patients continued anti-CGRP therapies for an average six months; 20% of patients received treatment for only three months but this was due to financial issues and not due to tolerability issues or lack of efficacy. Absenteeism was significantly reduced in 74% of patients, with marked improvement of quality of life. The most common side effect reported was constipation (46%) without discontinuation of treatment and was managed by anti-constipation medications and diet control. None of the patients in the study reported injection site reaction or pain or other notable side effects. If anti-CGRP therapies failed after three months, treatment was terminated. This occurred in five patients, and two were moved to galcanezumab. Both responded better than to erenumab, though one patient failed after six months on galcanezumab. Conclusion: Anti-CGRP therapies is an effective and well-tolerated treatment, but in Egypt, due to the high cost, limited use and restricted treatment duration limits the value of anti-CGRPs P045 Efficacy and safety of Onabotulinum Toxin A across different etiologies of Trigeminal Neuralgia F. Ferreira1,2, R. Rato1, B. Martins1,2, P. Abreu1,2, A. Costa1,2 1Unidade Local de Saúde de São João, Neurology, Porto, Portugal 2Faculdade de Medicina da Universidade do Porto, Clinical Neurosciences and Mental Health, Porto, Portugal Objective: Onabotulinum toxin A (BoTN-A) has been described as an effective alternative treatment for patients with refractory Trigeminal Neuralgia (TN). Our aim is to evaluate its effectiveness and safety across different etiologies of TN. Methods: We observational retrospective study of refractory TN patients who received BoTN-A treatment (follow the pain protocol – 30-50U) between January 2021 and March 2024 at our center. Clinical data regarding TN characteristics was obtained from patient records. The Portuguese version of the Patient Global Impression of Change conducted an (PGIC) score was used at the time of data collection to access patient-reported outcomes. Results: We included 48 patients, among which 31 (64,8%) were female, with a mean age of 66 years (standard deviation [SD] 13). The primary etiologies were classical TN (19 patients, 39,6%), secondary TN (14 patients, 31%) and idiopathic TN (13 patients, 28%). The mean duration of disease was 11 (SD 8) years. Facial asymmetry was reported by 40% of patients as the main adverse effect of treatment. There was a statistically significant reduction in the frequency of paroxysmal attacks: from daily in 46 (96%) patients to weekly in 6 (13%), bi-monthly in 3 (7%) and sporadic in 4 (9%), with 8 (17%) patients becoming attack-free (p=0.002). Maximum pain intensity, assessed by numeric pain score, showed significant reductions for paroxysmal attacks (-4.7, p<0.001) and continuous pain (-3.4, p<0.001). This effect significant across different etiologies of TN, except for continuous pain in patients with secondary TN (p=0,617). Most patients (56%) reported a significant improvement following BoTN treatment (PGIC ≥5). There was no statistically significant difference in PGIC scores among patients with different TN etiologies. Conclusion: In our cohort, BoTN proved to be safe and effective in managing refractory TN, irrespective of its etiology. statistically remained P046 Lacosamide, gabapentin, and baclofen as second-line treatments for trigeminal neuralgia – a retrospective comparison of treatment strategies P. Valín Villanueva1, R. Tena-Cucala1, S. Campoy1, S. Martínez Yélamos1, M. Huerta-Villanueva1, A. Muñoz- Vendrell1 1Hospital de Bellvitge, Neurology, Barcelona, Spain is common. Despite Objective: Therapeutic failure with carbamazepine in trigeminal neuralgia, due to intolerance or loss of efficacy, limited evidence, gabapentin and baclofen are recommended second- line treatments, and emerging evidence suggests lacosamide may also be effective. This study aims to compare these strategies in a real-life series Methods: This retrospective study included patients with trigeminal neuralgia treated with gabapentin, baclofen, or lacosamide following therapeutic failure with carbamazepine. Clinical and demographic characteristics were collected, along with response variables after 3 months. We compared the percentage of pain relief (reported by the patient and without the need for further treatments or emergency consultations after 3 months) and side effects Results: A total of 49 patients were included:13 in the gabapentin group, 14 in the baclofen group and 22 in

the lacosamide group. The median age was 65.2 years (IQR 54-73), with 53.1% women, and a median of 3.35 years (IQR 1.4-8.9) since diagnosis. Carbamazepine failure was due to inefficacy in 75.5% of cases and intolerance in 24.5%. No significant demographic or clinical differences were observed between the treatment groups, except for the concomitant use of carbamazepine during second-line treatment (53.8% with gabapentin, 100% with baclofen and 68.2% with lacosamide, p=0.019). Pain relief rates were 53.8% for gabapentin, 64.3% for baclofen and 68.2% for lacosamide (p=0.694),and the incidence of adverse effects was 30.8% for gabapentin, 35.7% for baclofen and 45.5% for lacosamide (p=0.664). Conclusion: Lacosamide could be a viable alternative to gabapentin or baclofen as a second-line treatment for refractory trigeminal neuralgia. In our study, lacosamide towards greater effectiveness but more adverse effects showed a trend P047 Design of an enriched randomized withdrawal, placebo-controlled phase 2/3 trial of basimglurant, a mGluR5 NAM, first-in-disease approach to treat pain associated with Trigeminal Neuralgia (LIBRA Study) S. A. Tahiri1, R. Lasser1, R. Silva1, D. Bedoya1 1Noema Pharma AG, Basel, Switzerland to (nuclear) intracellular Objective: Trigeminal neuralgia (TN) is a debilitating neuropathic pain condition with high unmet need. Emerging evidence indicates that type 5 metabotropic glutamate receptors 5 (mGluR5) are overactivated and overexpressed on the cellular and nuclear membranes in neuropathic pain conditions. Basimglurant is a potent mGluR5 NAM with selectivity > 1000-fold compared to other mGluR NAMs and high receptors. An affinity release oral optimized modified formulation demonstrates robust receptor occupancy, good bioavailability, and half-life that allows once daily dosing. In previous trials, basimglurant has been well tolerated. The LIBRA study (NOE-TGN-201) is an ongoing enriched controlled randomized withdrawal trial, assessing basimglurant, a selective negative allosteric modulator (NAM) of mGluR5 and first-in-disease approach, in patients with trigeminal neuralgia (TN). Methods: LIBRA (NOE-TGN-201) is a phase 2/3, global, multi-center study to evaluate safety and efficacy of basimglurant in TN (NCT NCT05217628). Adults with primary or idiopathic TN, purely paroxysmal or with continuous pain, experiencing suboptimal response to their current therapy, are enrolled. LIBRA starts with a 4W screening, followed by an 8W run-in (Period 1) and a 12W, double blind, placebo-controlled, randomized withdrawal period (Period 2). In Period 1, In Period 1, response Participants are dosed up to 3.5mg basimglurant once daily. Responders to therapy are then randomized during Period 2 to basimglurant or placebo according to the randomized withdrawal design. Patients who completed Period 2 are offered a 52W open label extension. Results: Enrolment is ongoing and aiming to include 200 participants to randomize 70 participants in the Period 2. is defined as improvement of ≥30% of paroxysm severity or frequency or interference of pain. In the double-blind randomized withdrawal period, the primary endpoint loss of efficacy. Secondary efficacy is time to endpoints include proportion of pain free days, changes in severity of paroxysms, changes in pain interference, change in Penn-FPS-R, PGI-C and MSQ. In addition, safety and tolerability are assessed. Conclusion: The LIBRA trial will characterise the efficacy and safety profile of the novel mGluR5 NAM basimglurant in patients with TN. This trial is funded by Noema Pharma AG. P048 Effectiveness of onabotulinumtoxinA (BTX-A) and anti-calcitonin gene-related peptide (CGRP) antibodies in menstrual migraine R. Mas de les Valls1, L. Gómez-Dabó2, V. J. Gallardo López1, A. Alpuente1,2, M. Torres-Ferrús1,2, E. Caronna1,2, E. Giné Ciprés1,2, P. Pozo-Rosich1,2 1Vall Hebron Institute of Research (VHIR), Neuroscience, Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Neurology Department, Barcelona, Spain (BTX-A) in study including Prospective Objective: To analyse the efficacy of anti-calcitonin gene-related peptide (CGRP) monoclonal antibodies (mABs) or onabotulinumtoxinA the reduction of menstrually related migraine (MRM) compared to menstrual-unrelated migraine (MUM) headache days per month. non- Methods: menopausal females treated with anti-CGRP mAbs or BTX-A for three months. E-diary data was collected for one complete month before treatment and for one complete month after three months of treatment, between January 2020 and December 2023. Clinical data, use, migraine characteristics, and frequencies, were collected. A comparative analysis of MRM and MUM headache days before and after treatment was performed, with an additional analysis of MUM split by contraceptive intake. Subset analyses considered aura, migraine diagnosis (episodic or chronic), and treatment. Results: Data from 113 females was collected, with a median (IQR) age of 39(33-45) years. At baseline, the median (IQR) number of headache days/month, MRM contraceptive including

reduced from 13(9-17) and MUM, was 15(11-19) from which 13.6%(10.7- 17.7%) were MRM. After three months of treatment, MUM was to 8(5-13) days/month, p<0.001, while the reduction in MRM was not significant from 2(2-3) to 2(1-3)). There were no statistically significant clinical differences (aura, migraine diagnosis, treatment used) between MRM and MUM either pre- or after-treatment. A trend of higher probability of headache per day on the menstrual cycle was observed in patients taking hormonal contraceptives (61%(44-68%) vs 50%(36- 70%)). Still, a mixed-effect logistic model showed no significant overall differences (p=0.389). Conclusion: BTX-A and anti-CGRP mAbs effectively reduce MUM days but have limited effect on improving MRM days after 3-months of treatment. Clinical trials are needed to assess the longer-term effectiveness of migraine preventive treatments on menstrual migraine. P049 New-onset headache after SARS-CoV-2 infection and vaccination: results from three population-based cohorts in Norway K. Blix1, I. Laake2, I. H. Caspersen2, B. Feiring2, A. Hayman Robertson2, S. Skodvin2, S. Mjaaland2, P. Magnus2, E. A. Tronvik3, A. Stubberud3, M. H. Bjørk3, L. Trogstad2 1The Norwegian Institute of Public Health, Department of Infectious Disease Control and Prevention, Oslo, Norway 2The Norwegian Institute of Public Health, Oslo, Norway 3Norwegian Centre for Headache Research, Trondheim, Norway Objective: Persistent headache after SARS-CoV-2 infections and vaccination have been reported. We aim to investigate the risk of new-onset headache after these exposures compared to unexposed periods in the general population. Methods: We collected data in three population- based cohorts: The Norwegian Mother, Father and Child Cohort study (MoBa), the Young Adult Cohort and the Senior Cohort (N = 85 774). Information about SARS-CoV-2 vaccinations and infections was obtained through linkage to national registries and multiple questionnaires. At two time points (pre- and post- Omicron emergence), participants were asked if they had been suffering from headache during the past year, to provide the time of onset and headache characteristics. Time-dependent exposure variables were used in a Cox-regression model to investigate the impact of primary SARS-CoV-2 vaccination and infection on the risk of new-onset headache. Subtypes of headache were secondary outcomes. severity of the (1.3-1.9) and 1.7 Results: SARS-CoV-2 infection, and the 1st and 2nd COVID-19 vaccine dose, was associated with increased risk of headache. In MoBa, the relative risk after pre- Omicron infections was 6.7 (4.8-9.2) and 6.5 (3.8-11.1) for women and men, respectively, whereas Omicron- infections were associated with relative risks of 4.7 (4.1-5.4) and 4.5 (3.7-5.4), respectively. The risk increased with infection. Corresponding HRs for 1st and 2nd COVID-19 vaccine doses were 1.6 (1.5-2.0), respectively, in women, and 1.5 (1.1-2.2) and 1.5 (1.2- 1.9) in men. The 3rd dose, administered to most subjects shortly before the first Omicron surge, was associated with a 20-40% protective effect on new-onset headache during a 60- day window post-vaccination. Conclusion: SARS-CoV-2 strongly associated with new-onset headache. Primary vaccination, administered during a low-transmission period, was associated with increased risk of headache, whereas booster vaccination during high- transmission period offered protection. for these doses infection was P050 Development and preliminary validation of the Danish Headache questionnaire K. Dissing1, R. Jensen1,2, H. Christensen1, M. Jensen3, H. Lauridsen2 1Chiropractic Knowledge Hub, Odense, Denmark 2University of Southern Denmark, Department of Sports Science and Clinical Biomechanics, Odense, Denmark 3Private chiropractic practice, Copenhagen, Denmark Objective: Headache disorders represent a growing public health burden. In primary healthcare settings, including chiropractic practices, patients frequently present with headache complaints. Currently, there is an absence of validated questionnaires tailored for assessing headache prevalence and management in primary care. The aim of this study was to develop a standardised headache questionnaire to assess the prevalence of headache and the management of patients with headache in primary care. Methods: The Danish Headache Questionnaire (DHQ) was developed through a three-phase process: a development phase, a subsequent testing phase assessing content validity (2020 to 2022), and a final phase generating a generic version. The Danish Headache Questionnaire includes a survey that covers diagnostic procedures, management strategies, and treatment modalities, and a logbook for tracking the prevalence of headaches. Results: The survey was developed based on an Australian survey and adjusted to encompass topics specific to Danish circumstances. The testing phase

resulted in some modifications to the survey: questions on managing headaches, medical history, radiographic imaging, and potential side effects. The logbook was improved to facilitate the recording of multiple headaches and a separate form for recording the total number of consultations. The DHQ was adapted to a generic version by modifying profession- specific terms to suit other clinical environments. Conclusion: The DHQ has been demonstrated to be a valid and feasible instrument for assessing clinicians' knowledge in managing patients with headaches and gathering data on headache prevalence in primary care. The generic version promotes a uniform approach and enables comparative analysis across different that the DHQ is not just a valuable instrument for clinical assessment and research in primary care but also has the potential to improve the management of headache disorders with widespread application. settings. These findings indicate for prophylactic treatment. In primary/secondary care, the most frequently recommended medications were anticonvulsants (33%), beta-blockers (31%), and tricyclic antidepressants (29%). These medications were also among the top three prescribed migraine prophylactics at the tertiary headache center (18-20% each). However, Onabotulinumtoxin-A (16% vs. 6%, p <0.001) and Calcitonin-Gene-Related Peptide targeted therapies (6% vs. 2%, p <0.001) were prescribed significantly more often in tertiary care compared to primary/secondary care. Data on acute treatment are currently being analyzed and will be presented at the European Headache Congress (EHC). significant Conclusion: differences in frequency and type of pharmacological migraine across primary/secondary and tertiary headache care centers. recommendations treatment This study highlights P051 Differences in pharmacological migraine treatment across different levels of care M. P. Fitzek1,2, M. Ulrich1, K. S. Lange1,3, L. H. Overeem1, U. Reuter1,4, B. Raffaelli1,3 1Charité – Universitätsmedizin Berlin, Neurologie, Berlin, Germany 2Berlin Institute of Health at Charité (BIH), Berlin, Germany 3Berlin Institute of Health at Charité (BIH), Berlin, Germany 4Universitätsmedizin Greifswald, Greifswald, Germany Objective: Pharmacological treatment is an important pillar of migraine care. Physicians can choose from a wide range of nonspecific and specific acute and prophylactic options. This study aimed to assess differences in pharmacological recommendations for acute and prophylactic migraine treatment across various levels of headache care. Methods: This cross-sectional study involved migraine patients visiting the tertiary headache center at Charité – Universitätsmedizin Berlin between 12/2017 and 01/2023 for the first time. Data on headache characteristics and recommendations for acute and prophylactic treatments from primary and secondary levels of care were collected from questionnaires completed by patients before their visit. For the tertiary level, data were retrieved from medical letters generated after their consultation. Results: Among 1,047 migraine patients (mean age: 42 years, 84% women), 30% had previously used migraine prophylaxis, 23% were on prophylactic treatment at the time of their visit, and 46% had never used migraine prophylaxis. After consultation at our tertiary center, 73% received a recommendation P052 Effect of migraine on suicide mortality in young adults – a nationwide cohort study in South Korea S. A. Kim1,2, K. Han3, M. J. Lee1,2 1Seoul National University Hospital, Department of Neurology, Seoul, South Korea 2Seoul National University College of Medicine, Seoul, South Korea 3Soongsil University, Department of Statistics and Actuarial Science, Seoul, South Korea suicide mortality Objective: Migraine is prevalent among young adults and is linked to increased suicidal behavior, but its relationship with remains underexplored. This study aimed to investigate the effect of migraine on suicide mortality in young Korean adults. Methods: We conducted a longitudinal cohort study from 2009 to 2021. Participants aged 20–39 years (n=6 539 547) were categorized based on their migraine status. Cox proportional hazard regression models assessed the association between migraine and suicide mortality, adjusting for demographic factors, health behaviors, and comorbidities. Results: Among participants, 113 681 had migraine (6620 with aura and 107 061 without aura). Over 11 years, 21 suicides occurred among patients with migraine with aura, 219 among patients with migraine without aura, and 13 040 among no migraine. All migraine was not significantly associated with suicide risk (adjusted hazard ratio [HR] 1.065, 95% CI 0.936– 1.212). However, migraine with aura was associated with a higher risk of suicide (adjusted HR 1.606, 95% CI 1.046–2.465), whereas migraine without aura was (adjusted HR 1.032, 95% CI 0.902–1.181). not Depression significantly modified the effect of

migraine on suicide risk, with varying directions across migraine subtypes. Conclusion: Although all migraine and migraine without aura did not have an impact on suicidal risk, migraine with aura was associated with a higher risk of suicide mortality. The presence of depression significantly modified this relationship, with differing effects observed across migraine subtypes. Fig. 3 Fig. 1 Fig. 2 P053 Impact of Saharan dust pollutants on visits in primary care emergency departments due to migraine attacks A. Bartolomé1, C. Morales1, M. J. Hernández1, M. Paredes2, R. Bartolomé3 1Hospital Universitario de Canarias, Neurology, San Cristobal de La Laguna, Spain 2Centro de salud de Taco, Primary Care, San Cristobal de La Laguna, Spain 3Centro de salud Barrio de la Salud, Primary Care, Santa Cruz de Tenerife, Spain is natural association with Objective: There increasing evidence of an association between air pollution and migraine. Nevertheless, there are conflicting data between the specific pollutants, specifically with Saharan dust. The aim was to determine the correlation between the number of visits per day to Primary Care emergency services due to migraine attacks and concentration of <2.5 μm and <10 μm particles (PM2.5 and PM10 respectively), nitrogen di-oxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO). Methods: We identified 1373 patients who visited SNU Services) and PAC (Continuous Care Points) for migraine as a primary disease in the metropolitan area of Santa Cruz de Tenerife (SCT) between January 1, 2021, to December 31, 2022. We gathered data of the concentration levels of PM2.5, PM10, NO2, SO2, O3, and CO from the eight air quality monitoring (Normal Emergency stations in

implemented metropolitan area of SCT, measured by the European Air Quality Network in the Canary Islands. We performed a Spearman's rank correlation coefficient between the number of visits per day in the SNU-PAC due to migraine and the concentration of particulate and gaseous pollutants in the last 7 days. Results: Average concentration of SO2, PM10, PM25, O3, NO2 observed 0 to 7 days before the visit to SNU- PAC was not significantly associated with the number of visits to Primary Care emergency services. Conclusion: We did not find a relation between the exposure to environmental pollutants and the number of visits to Primary Care emergency services due to migraine attacks. P054 Nationwide migraine trends in Italy: a study of demographic, social, and clinical insights from the I- GRAINE registry G. Egeo1, C. Aurilia1, B. Orlando1, G. Fiorentini1, A. Doretti2, R. Messina2, F. d'Onofrio3, C. Finocchi4, L. Di Clemente5, M. Zucco5, M. Autunno6, A. Ranieri7, A. Carnevale8, B. Colombo9, M. Filippi9, S. Rinalduzzi10, F. Zoroddu11, C. Camarda12, F. Pistoia13, P. Torelli14, L. Borrello15, G. Querzola16, F. Frediani16, G. Viticchi17, C. Tomino18, S. Bonassi19, P. Barbanti20 1IRCCS San Raffaele, Headache and Pain Unit, Rome, Italy 2Istituto Auxologico Italiano, IRCCS, Department of Neurology-Stroke Unit, Laboratory of Neuroscience, Milano, Italy 3San Giuseppe Moscati Hospital, Neurology Unit, Avellino, Italy 4San Paolo Hospital, ASL 2, Neurology Unit, Savona, Italy 5San Camillo-Forlanini Hospital, Headache Centre, Rome, Italy 6University of Messina, Department of Clinical and Experimental Medicine, Messina, Italy 7AORN A. Cardarelli, Neurology Unit and Stroke-Unit, Naples, Italy 8San Filippo Neri Hospital, Headache Centre, Rome, Italy 9Scientific Institute San Raffaele Hospital, Vita-Salute University, Headache Unit, Milano, Italy 10S. Camillo de Lellis Hospital, Headache Centre, Rieti, Italy 11University of Sassari, Pediatric Headache Center, Neurology Unit, Sassari, Italy 12University of Palermo, Department of Biomedicine, Neurosciences, and Advanced Diagnostics, Palermo, Italy 13University of L'Aquila, Neurology and Stroke Unit, L'Aquila, Italy 14University of Parma, Neurology Unit, Department of Medicine and Surgery, Headache Center, Parma, Italy 15Frosinone Hospital, Headache Center, Frosinone, Italy 16ASST Santi Paolo Carlo, Headache Center, Milano, Italy 17Marche Polytechnic University of Ancona,, Neurological Clinic, Ancona, Italy 18IRCCS San Raffaele Rome, Scientific Direction, Rome, Italy 19IRCCS San Raffaele Rome, Clinical and Molecular Epidemiology, Rome, Italy 20IRCCS San Raffaele Rome, Headache and Pain Unit, Rome, Italy Information on Objective: The Italian Migraine Registry (I-GRAINE) provides comprehensive migraine data to support effective clinical and therapeutic management of the disease, based on scientific and sustainability criteria. Methods: I-GRAINE is a strategic, nationwide, multi- centre (n=38), prospective, observational study on consecutive subjects with episodic or chronic migraine, selected using a systematic random method. socio-demographic characteristics, lifestyle, migraine features, patient journey, and healthcare resources was gathered using face-to-face interviews with a shared web-based questionnaire. Results: As of 31 December 2023, 1524 patients had been enrolled (female 85.4%, mean age 46 yrs, >13 education years 86.2%, married 52%). Mean monthly migraine frequency was 9.6 days, MIDAS 48.6 and HIT- 6 61.4. Commonly reported symptoms included osmophobia (41%), unilateral cranial autonomic symptoms (24.8%), cephalalgiophobia (32.2%), and vertigo (15.6%). Only 37.0% had previously visited a headache center. Response rates were higher for to triptans (72%) compared to analgesics (42.4%-64.4%), and for anti- CGRP monoclonal antibodies (82% -84.1%) compared to traditional prophylaxis (32.5%-41.5%). Over the past 3 years, 61.2% of patients had specialist visits for migraine (6.3 visits per patient), and 64.8% underwent more than one diagnostic procedure (brain MRI: 86.2%). Many visits (43.1%) and investigations (MRI: 76.5%) were subsidized by the national health system. Conclusion: Migraine symptoms not in current diagnostic criteria are often referred by patients upon specific request. Specific and selective acute and preventive treatments are more effective than traditional ones. Many visits and diagnostic investigation indicating inefficiencies and overuse of healthcare resources due to misdiagnosis, lack of adherence to guidelines, or overcautious approaches by healthcare providers. inappropriate, allodynia (29.6%), are included

P055 Handling HaNDL syndrome – a case series from a tertiary hospital in Portugal S. Moreira1, S. Lopes1, A. Costa1, J. Pinto1, A. R. Silva1, J. M. Araújo1, L. M. Marques1 1Unidade Local de Saúde de Braga, Neurology, Braga, Portugal intolerance Objective: To describe a case series of Syndrome of Transient Headache and Neurological Deficits with Cerebrospinal Fluid Lymphocytosis (HaNDL) from a Portuguese tertiary hospital over the last two decades. Methods: Retrospective revision of the diagnoses of consecutive patients admitted to the Neurology Department between 2002 and 2024. Selection of cases considering the IHC-3 criteria for HaNDL. Results: Five cases were identified, including three men, with a mean age at diagnosis of 31 years (range: 25-38 years). One patient had a previous history of migraines with sensory aura. Two patients reported headaches before the episode, and one patient had viral prodrome. The pain was holocranial or predominantly frontal and occipital, mostly throbbing in nature. Additional frequent symptoms included nausea, vomiting, to environmental stimuli, fever, and neck stiffness; two patients reported headaches with a postural component. Focal aphasia, hemiparesis, and sensory disturbances, lasting a mean of 16.5 hours (range: 20 minutes to 24 hours). Lumbar puncture revealed elevated opening pressure in all cases (range: 24-35 cmH2O), pleocytosis (range: 22- 259 cells/μl), with lymphocytosis (range: 89-95%) and elevated protein levels (range: 0.74-1.66 g/L; normal range: 0.15-0.45 g/L). All patients reported residual headache complaints lasting 5-15 days. Three cases experienced repeated episodes with neurological deficits (range: 2-10 episodes) with variable durations (range: 5 minutes-5 hours). Conclusion: Similarly to other series previously published, HaNDL syndrome is quite rare. One patient did not meet the criteria regarding the duration of deficits; however, shorter durations have been reported in the literature. Although one patient kept suffering from episodic migraine, the prognosis is generally good. neurological deficits included P056 Disability burden in migraine – a systematic review and meta-analysis M. Matharu1, S. Silberstein2, S. Yuan2, M. Lantéri- Minet3, M. Obermann4, D. Edgar5, R. Coleman6 1The National Hospital for Neurology and Neurosurgery, London, United Kingdom 2Jefferson Headache Centre, Neurology, Philadelphia, PA, United States 3Nice University Hospital, Neurology, Nice, France 4Klinikum Weser-Egge, Neurology, Höxter, Germany 5Commexus Ltd, Dunblane, United Kingdom 6Coleman Statistics, Lokeren, Belgium We (including at systematically Objective: This systematic review and meta-analysis synthesized data from studies that evaluated the burden of disability across headache (HA) frequency subcategories of migraine, including high-frequency episodic migraine (HFEM) and chronic migraine (CM), focusing on characterizing the disability burden in HFEM. reviewed Methods: noninterventional studies categorizing migraine by HA frequency least HFEM and CM), searching literature up to April 23, 2024. Of 31 studies meeting the inclusion criteria, 27 were grouped according to the use of monthly migraine days (MMD) or monthly headache days (MHD), HFEM definition (8- 14, 9-14, or 10-14 MHD/MMD), and disability parameter. 3 disability parameter groups met predefined criteria for meta-analysis, all with HFEM defined as 8-14 MHD: mean Migraine Disability Assessment (MIDAS) score (4 studies/6078 patients), the proportion with severe disability (MIDAS score >20; 7 studies/61402 patients), and mean Work Productivity and Activity Impairment (WPAI) scores (8 studies/29528 patients). Results: The meta-analyses consistently showed a pattern of increasing disability with higher HA frequency. For the pooled HFEM subgroups, the estimated overall mean MIDAS score was 25.3 (95% CI, 14.7-35.8), the estimated overall proportion with severe disability was 43.4% (95% CI, 30.8-57.0), and the estimated overall work productivity and activity impairment scores were 43.1% (95% CI, 38.7-47.6) and 45.5% (95% CI, 42.6-48.3), respectively. Conclusion: Our meta-analyses revealed the severe disability burden in HFEM, highlighting significant implications for clinical practice and public health. These findings emphasize the need for improved management strategies in the HFEM population, with a shift towards prioritizing headache-related disability over monthly headache days as a criterion for treatment access.

P057 One-year prevalence of migraine in Spain at national and regional level: results from the 2022 national health and wellness survey M. Sánchez del Río1, P. Irimia2, J. Porta-Etessam3, C. Peral4, B. Armada4, D. García-Azorín5 1Clínica Universidad de Navarra, Madrid, Spain 2Clínica Universidad de Navarra, Neurology, Pamplona, Spain 3Institute for Sanitary and Biomedical Research Clínico San Carlos (IdISSC), University Hospital Clínico San Carlos, Neurological Disorders Study Group, Madrid, Spain 4Pfizer S.L.U., Madrid, Spain 5Hospital Universitario Río Hortega de Valladolid, Headache Unit, Valladolid, Spain the sample of Objective: To estimate the prevalence of migraine in Spain, at a national and regional level. Methods: A cross-sectional study using the 2022 National Health and Wellness Survey (NHWS) captured data reported by migraine patients from a representative Spanish adult population. Respondents who reported a physician- diagnosis of migraine and at least one migraine episode in the prior 12 months were considered active migraine patients. Demographic, health, and clinical characteristics were summarized by weighted descriptive statistics. Migraine burden measures included monthly migraine days (MMD) and monthly headache days (MHD) in the preceding 30 days. Results: A total of 7,002 respondents completed the NHWS survey, of whom 930 (13.3%) had a lifetime diagnosis of migraine by a physician and experienced migraine in the past 12 months. This represented a weighted prevalence of 13.1% in Spain, ranging from 8.1% in Navarra to 19.1% in Cantabria (Figure 1). Migraine patients had a mean age of 45.3 years. The prevalence of migraine gradually decreased with age (ranging from 17.2% in the 18-29 to 8.2% in the ≥60 age group (Figure 1). Females accounted for 69.8% of the population with migraine and had higher prevalence rates than males (17.7% vs. 8.2%, respectively). Migraine patients reported a mean (standard deviation) of 3.2 (±5.0) MMD and of 7.4 (±7.1) MHD, with 75.3% of patients reporting less than 4 MMD (Figure 2). Regarding treatment, 61.4% reported using prescribed medication, 15.5% used only over-the-counter treatments, and 23.1% reported no treatment for migraine. Conclusion: Each year, one in eight Spanish adults suffers from migraine, with 16% of them experiencing 15 or more headache days per month. The prevalence rates show significant cross-country variation. Fig. 1 Fig. 2 P058 Exploring the COVID-19 associated headache in the acute phase in a healthcare personnel population A. J. Marques1, A. Costa1, C. Borges1, M. Mendes1, A. Matas1, A. Veiga1 1Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Neurology, Vila Real, Portugal complaints. Multiple infection brings more that Objective: SARS-CoV2 neurological respiratory symptoms have been reported. Headache is the most common, with a prevalence ranging between 6.5-23%. However, there is still scarce information about its characteristics and relation with the rest of COVID-19 syndrome. We aim to describe and study patients with headache as manifestation of COVID-19 disease.Observational, retrospective study of COVID- 19 disease cases in healthcare professionals of a

hospital center between March 2020 and April 2021. A questionnaire was applied. Sociodemographic and clinical characteristics were obtained and analyzed. Methods: Observational, retrospective study of COVID-19 disease cases in healthcare professionals of a hospital center between March 2020 and April 2021. A questionnaire was applied. Sociodemographic and clinical characteristics were obtained and analyzed. Results: We identified 89 cases (52.1%) of COVID-19 in which headache was the primary manifestation. This group had a mean age of 38 years (24-63) and a higher prevalence of women (75.3%). Most representative healthcare class were nurses and doctors (67.4%). Accompanying symptoms, in order of prevalence, were myalgias (73.0%), anosmia (56.2%) and dysgeusia (53.9%). Headache occurred at the same day as the other symptoms in 47 patients (52.8%) whilst the mean time between the beginning of disease and headache was 3.6 days. Regarding headache characteristics, it was bilateral in 82% of cases and phonophobia was present in 56 patients (62.9%). Most patients have reported a continuous headache (64.0%) without positional modification (64.0%). In more than 80% of cases headache remained only up until 4 weeks pos-infection. Conclusion: Headache is a highly prevalent symptom in COVID-19 disease. In most cases it happens during the initial phase of the infection and is characterized by being bilateral, continuous, with phonophobia and doesn"t have postural changing. P059 Depression and anxiety in Chinese patients hospitalized with primary headache – a cross- sectional multicenter study Z. Dong1, Z. Jia2, D. Wan3, Z. Yin4, Z. Fan5, P. Xu6, X. Yuan7, M. Chen8, D. Wang9, H. Wang10, S. Wang11, S. Zhang11, R. Liu11, X. Wang11, R. Wang11, H. Su11, X. Han11, Z. Yu11, Y. Li11, S. Yu1 1Chinese PLA General Hospital, Department of Neurology, Beijing, China 2Chinese PLA General Hospital, Health Management Institute, Beijing, China 3The 940Th Hospital of Chinese People's Liberation Army, Lanzhou, China 4University of Shanghai for Science and Technology, Shanghai, China 5Xing Tai People's Hospital, Xingtai, China 6Affiliated Hospital of Jining Medical University, Jining, China 7Zhengzhou People's Hospital, Zhengzhou, China 8The Affiliated Hospital of Zhengzhou University, Zhengzhou, China 9General Hospital of Northern Theatre Command, Shenyang, China 10Hebei General Hospital, Shijiazhuang, China 11Chinese PLA General Hospital, Beijing, China specialists. The Patient Objective: Primary headache disorders are major causes of disability worldwide and are associated with psychiatric comorbidities such as depression and anxiety. However, primary headache with comorbid depression or anxiety is often overlooked. The prevalence and clinical features of depression and anxiety in Chinese patients hospitalized for primary headache remain unclear. Methods: This cross-sectional study enrolled patients attending one of eight China headache centers from October 2022 to September 2023. A WeChat mini- program was designed for data collection via a questionnaire. Headache was diagnosed through the clinical decision support system and confirmed by two headache Health Questionnaire-9 (PHQ-9) and Generalized Anxiety Disorder-7 (GAD-7) were used to measure depression and anxiety, respectively. Results: This study analyzed 1963 primary headache patients; the prevalence of depression and anxiety in patients with primary headache was 20.1% and 14.8%, respectively. Patients with both headache and depression or headache and anxiety were more likely to be women, have more severe headache, experience greater life. Depression and anxiety were more common among those with chronic migraine (CM) than among those with episodic migraine (EM), and more common in those with chronic TTH (CTTH) than among those with episodic TTH (ETTH). CM and CTTH were more prevalent in participants with depression/anxiety than in those without these conditions. Conclusion: The prevalence of depression and anxiety in Chinese patients with primary headache is 20.1% and 14.8%, respectively. Depression and anxiety in primary headache disorders are inadequately diagnosed in China.To improve the health of primary headaches, screening for depression and anxiety should be performed early. impacts on quality of Fig. 1

Fig. 2 Fig. 3 P060 Prevalence and co-occurrence of allergic Rhinitis and migraine in pediatric patients M. Togha1,2, F. Vahabizad3, F. Mirashrafi4, F. Rezazadeh5, M. Noormohammadi6 1Tehran University of Medical Sciences, Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran, Iran 2Tehran University of Medical Sciences, Headache Department, Neurology ward, School of Medicine, Tehran, Iran 3Tehran University of Medical Sciences, Neurology Department, School of Medicine, Tehran, Iran 4Tehran University of Medical Sciences, Otorhinolaryngology Research Center, Otorhinolaryngology Head and Neck Surgery Department, Imam Khomeini Hospital Complex, Tehran, Iran 5Tehran University of Medical Sciences, Student Research Committee, Tehran, Iran 6Iran University of Medical Sciences, Department of Nutrition, School of Public Health, Tehran, Iran Objective: Allergic rhinitis and migraines are prevalent conditions among pediatric patients. While existing literature suggests a potential link between these two, the precise relationship remains inconclusive. Our study aimed to investigate the prevalence of allergic rhinitis and migraines in this population and explore their association systematically. Methods: We conducted a cross-sectional study involving 385 pediatric patients aged 6 to 18 years. Participants were randomly selected from a Tehran independent pediatric otolaryngology clinic. Our variables included the presence of allergic rhinitis, patient age, and gender. Dependent variables focused on migraine occurrence. Results: Among the participants, about 12 percent had allergic rhinitis, and about seven percent of them also experienced migraines. In the non-allergic rhinitis group, about six percent had migraines. Overall, about seven percent suffered from migraines. The average age of females with and without migraines significantly differed. However, overall, there was no significant difference in age between people with and without migraines. Additionally, binary logistic regression in the allergic rhinitis group yielded an Odds Ratio (OR) of 1.8 (95% CI, P-value = 0.25) for migraine risk. Conclusion: Our study showed a higher risk of occurrence of migraine in the studied group of children and adolescents who suffered from allergic rhinitis, though it was not statistically significant. While the evidence remains inconclusive, our findings underscore the importance of targeted investigations specifically addressing allergic rhinitis. It"s worth noting that other studies may explore migraine associations with additional allergies, such as asthma and study intentionally focused on the relationship between this specific allergic population. To advance our understanding, larger prospective studies are warranted to unravel the intricate interplay between these conditions. conditions. However, our atopic rhinitis and migraines in P061 Enlarged parietal foramina in monozygotic twins- case report N. Gogatishvili1,2, S. Kasradze1,2 1Caucasus International University, Tbilisi, Georgia 2Institute Of Neurology And Neuropsychology, Caucasus International University, Tbilisi, Georgia Objective: Enlarged Parietal Foramina (EPF) is a rare congenital defect of the skull with variable symmetric ossifications in the parietal bones, ranging from a few millimeters to several centimeters, and caused by the mutation in MSX2 and ALX4 genes. The majority of cases are asymptomatic, but headache, vomiting, pain over unprotected areas of the cerebral cortex, and seizures may occur. Methods: We describe a case report of two 17-year- old monozygotic twin females with EPF, who are the children of non-consanguineous parents and were born at 38 weeks by cesarean section. One girl did not present any complaints, while in the other the headache was presenting. Case 1: At birth the weight of the first sister was 2200 g. She started having almost daily headaches, mostly with onset in the early morning and sometimes accompanied by numbness

of the right hand. The headaches were localized in the parietal regions, where small defects of the skull were felt by palpation. Both parietal foramina were soft to the touch and were pulsating. CT scan demonstrated EPF situated bilaterally and symmetrically, oval in shape ,measuring in size with 1,64 cm right and 1,45 cm left. Brain MRT excluded structural brain abnormalities . Since starting of orally Duloxetine, 60 mg once per day, the headache has improved. Case 2: The second twin sister who did not represented any complaint, at the birth has weight of 2000 g. Brain MRI was without any structural abnormalities in this case as well but similar bone defects in her skull, measuring in size with 1,29 cm right and 1,28 cm left. Results: The mentioned rare syndrome was detected in monozygotic twins, indicating the presence of the same gene mutation in both Conclusion: However, since genetic studies could not be carried out, it provides the basis for the limitations of this case report. Fig. 1 Fig. 2 Fig. 3

P062 Prevalence and characteristics of Hemodialysis- related headache – a cross-sectional study M. Togha1, Y. Mokary2, Z. Salami1,3, M. Noormohammadi1,4,5, N. Rahman1 1Tehran University of Medical Sciences, Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran, Iran 2Shahrekord University of Medical Sciences, Shahrekord, Iran 3Kharazmi University, Department of Molecular Genetics, Faculty of Biological Sciences, Tehran, Iran 4Iran University of Medical Sciences, Department of Nutrition, School of Public Health, Tehran, Iran 5Iran University of Medical Sciences, Student Research Committee, Tehran, Iran Objective: Hemodialysis-related headache (HRH) significantly impacts the quality of life for patients undergoing dialysis. Despite its high prevalence, the exact pathophysiology remains unclear. This study aims to explore HRH prevalence and characteristics, bridging the knowledge gap and informing better preventive and treatment strategies. Methods: A cross-sectional investigation was carried out between 2020 and 2022, involving 143 individuals receiving hemodialysis. The identification of headache subtypes was based on the utilization of the 3rd edition of the International Classification of Headache Disorders (ICHD-3). All participants underwent thrice- weekly bicarbonate hemodialysis utilizing homophone membranes measuring 1.3 square meters. Results: Out of the total of 143 subjects, 115 patients (80.4%) were diagnosed with HRH, showing a higher occurrence among male individuals (69.6%). The systolic blood pressure registered before dialysis was notably elevated in those experiencing HRH (14.04 (2.58)) compared to 13.26 (1.29), with a P-value of 0.014. A considerable reduction in systolic blood pressure was noted post-dialysis in individuals with HRH (-1.74 (2.11)) and those without headache (-1.13 (1.40)), with statistical significance (P-value < 0.001). Conclusion: The prevalence of HRH among hemodialysis recipients highlights the necessity for healthcare practitioners to discern and comprehend the diverse characteristics of this type of headache. is crucial for enhancing the This understanding management of patients, thereby leading to an improvement in their quality of life. Such findings underscore the significance of continuous research endeavors and educational initiatives in this particular domain. P063 The SUD-SEM protocol – An observational exploration of headaches, comorbidities, and substance use disorders in older U.S. adults S. Malhan1, A. Lin2, J. Sorkin2, B. Siaton2, B. Hogans3 1Thomas Jefferson University, Neurology, Philadelphia, PA, United States 2University of Maryland School of Medicine, Neurology, Baltimore, MD, United States 3VA Maryland Health Care System, Neurology, Baltimore, MD, United States ICD-10 codes. Frequencies, links between common Objective: To examine (SUDs) and headache substance use disorders in older U.S. adults, using structural disorders equation modeling (SEM) to assess the impact of demographic factors and comorbidities. Methods: 2017 CMS Medicare Standard Analytical 5% Sample Files was analyzed, including carrier and outpatient claims. The study population included 1.1 million older adults aged 65-100, with 12- months Part B Medicare enrollment, alive throughout 2017, and having 6 to 180 claims; Medicare Part C participants and Medicare Part B enrollees without active claims were excluded. Condition definition files were created utilizing rates, and adjusted rates (logistic regression) were analyzed. Results: The SEM model explored relationships between demographic characteristics, headache disorders, SUDs, and comorbidities. It estimated the direct effects of demographics on headache disorders, the direct effects of headache disorders on SUDs, and the moderating effects of comorbidities. SEM provided a comprehensive understanding of these in older adults. Significant variables' associations were found between demographic factors, such as age and gender, and the prevalence of headache disorders. Additionally, comorbidities such as depression, anxiety, and cardiovascular diseases were identified as key moderators in the relationship between headache disorders and SUDs, highlighting their complex interactions. Conclusion: SEM offers a robust framework for characterizing associations, accounting for mediation and moderation. This study, considering demographic factors and comorbidities, provides insights into the relationships between SUDs and headache disorders, supporting hypothesis testing and enhancing clinical research. The findings underscore the importance of in managing addressing in older adults, headache disorders and SUDs suggesting avenues targeted interventions and improved patient outcomes. potential interplay comorbid conditions for

Fig. 1 Fig. 3 P065 αCGRP versus βCGRP: don't overlook the differences D. M. Boucherie1, A. van den Bogaerdt2, R. Dammers3, A. Vincent3, A. H. J. Danser1, A. Maassen van den Brink1 1Erasmus University Medical Center, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands 2ETB-BISLIFE, Heart Valve Department, Beverwijk, Netherlands 3Erasmus MC University Medical Center, Department of Neurosurgery, Rotterdam, Netherlands Fig. 2 from patients obtained Objective: The precise role of βCGRP in migraine remains unclear. We aimed to assess functional responses to αCGRP and βCGRP in human arteries and investigate the potency of CGRP pathway-targeting drugs to block αCGRP versus βCGRP. Methods: Distal human coronary arteries (HCA; small: <1 mm internal diameter, large: >2 mm internal diameter) were obtained from post-mortem human heart valve donors (n=8; 75% female; aged 64 ± 5 years). Human middle meningeal arteries (HMMA) were undergoing neurosurgery (n=7; 71% female, aged 49 ± 18 years). Upon precontraction with 30 mM KCl, concentration- response curves to αCGRP and βCGRP (10 pM–1 μM) were constructed in HCA and HMMA segments in the presence or absence of 1–3 μM CGRP8-37. Results: The potency of αCGRP and βCGRP was similar in large distal HCA (pEC50 αCGRP 8.2 ± 0.5; βCGRP 8.3 ± 0.3), whereas βCGRP was more potent in small distal HCA (pEC50 αCGRP 8.7 ± 0.4; βCGRP 9.1 ± 0.4; p<0.05). Both isoforms were more potent in small than large distal HCA (p<0.05). In HMMA, potency was similar across isoforms (pEC50 αCGRP 8.3 ± 0.4; βCGRP 8.7 ± 0.5). Based on the median pKB, CGRP8-37 (1 μM) was ~2x more potent at blocking βCGRP than αCGRP in

small distal HCA, but equally potent across isoforms in large distal HCA. CGRP8-37 (3 μM) was ~3x more potent at blocking βCGRP than αCGRP in HMMA. Conclusion: The functional responses to αCGRP and βCGRP, along with their inhibition by antagonists, exhibit subtle differences across vascular beds, which should not be overlooked. Elucidating these functional differences, combined with increasing understanding about the relative role of αCGRP and βCGRP in different parts of the body, can provide insight into the side effect profiles related to CGRP pathway- targeting drugs, including constipation. Fig. 1 and CGRP provocation calcitonin-gene related peptide (CGRP) signaling pathway. Oxytocin levels fluctuate in parallel with estrogen, suggesting that drops in both hormones may increase migraine frequency. Thus, blocking oxytocin receptors (OTR) could help investigate the impact of oxytocin withdrawal on migraine. Methods: This study is a monocentric, double-blind, randomized, placebo-controlled, cross-over human provocation study, utilizing the OTR antagonist atosiban substance (DRK00033341). We hypothesize that inhibiting the effect of oxytocin through receptor antagonization will lead to migraine attacks in women with migraine. Secondary endpoints include analyses of vascular parameters The study began in February 2024 and will enroll 20 female patients with episodic migraine. Key inclusion criteria include continuous hormonal contraception (to maintain stable sex hormone levels), 1-5 monthly migraine days, and no daily medication intake. Results: not applicable immediate significance of this Conclusion: The research in enhancing our understanding of oxytocin"s role in migraine pathophysiology and its interaction with the vascular system and the CGRP pathway. If OTR blockade under stable estrogen levels induces migraine attacks, it could challenge the estrogen withdrawal hypothesis. Ultimately, these findings could lead to new therapeutic applications, emphasizing the importance of oxytocin in migraine treatment. concentrations. as the lies P066 Effects of oxytocin receptor antagonization in migraine: Rationale and study protocol of a randomized, double-blind, placebo-controlled human provocation study C. Handtmann1, M. P. Fitzek1, L. H. Overeem1, U. Reuter1,2, B. Raffaelli1 1Charité – Universitätsmedizin Berlin, Neurology, Berlin, Germany 2Universitätsmedizin Greifswald, Greifswald, Germany Objective: Sex hormone fluctuations are discussed as triggers for migraine attacks, with past research focusing on estrogen levels ("estrogen withdrawal hypothesis"). However, the evidence supporting this hypothesis is limited and often conflicted, indicating that estrogen withdrawal alone may not fully explain the phenomenon. Recent interest has shifted towards other hormones such as oxytocin. Oxytocin modulates the trigeminovascular system and vascular tone, exhibits analgesic properties, and interacts with the P067 Pain profiling with Quantitative Sensory Testing (QST) in episodic and chronic migraine G. M. Terwindt1, F. van Welie1, A. Dahan1, R. van Welie1, M. van Velzen1 1Leiden University Medical Center, Neurology, Leiden, Netherlands Objective: Studies on pain profiling in subjects with migraine vary due to differences in measuring sensory modalities, applied methods, anatomical sites, and migraine characteristics. This study aimed to identify pain profiling parameters using Quantitative Sensory Testing (QST). Methods: We enrolled 59 migraine patients from the Leiden Headache Center, 29 with episodic migraine (EM) and 30 with chronic migraine (CM). To assess sensory profiles, various QST methods were applied on the cheek and hand, comparing findings to a healthy control group. Each QST test yielded scores converted to normalized Z-scores, adjusted for sex, age, and anatomical location. Key outcomes focused on mean Z-scores per test and the prevalence of abnormal Z-scores (<-1.96 or >1.96) among migraine

participants. A Z-score > 1.96 indicates heightened sensation (lower threshold) relative to controls, while a Z-score < -1.96 indicates diminished sensation (higher threshold). These metrics were further analyzed across EM and CM groups to discern differences in sensory processing profiles. Results: Among subject with migraine, Cold Detection Threshold was higher in 18.6% (hand)/25.4% (cheek), Warm Detection Threshold (WDT) was higher in 15.2% (MPS) was (hand), Mechanical Pain Sensitivity increased the Vibration Detection Threshold (VDT) was higher in 18.6% (cheek) (all p<0.001). The Threshold for Pressure Pain (PPT) was lower in 39.0% (hand)/ 32.8% (cheek) (p<0.001). No differences were observed between EM versus CM. Conclusion: One-third of individuals with migraine have a reduced PPT in both the trigeminal and distal regions, indicating heightened sensory sensitivity. Additionally, migraine patients have elevated thresholds for CDT, WDT, VDT, MPS suggesting decreased sensory processing in other modalities. (hand), and in 17.0% Fig. 1 P068 A human provocation model with capsaicin (TRPV1) and cinnamaldehyde (TRPA1) to evaluate CGRP- mediated neurogenic responses in patients with endometriosis and comorbid endometriosis and migraine L. F. Iannone1, E. Lombardo1, A. Burgalassi1, F. De Cesaris1, G. Vigani1, B. Pasquini1, S. Vannuccini1, F. Petraglia1, V. Serravalli1 1University of Florence, Dpt of Health sciences, Florence, Italy Objective: To evaluate differences in the CGRP- mediated neurogenic responses through TRPV1 and TRPA1 activation in patients with endometriosis and comorbid endometriosis-migraine using a human provocation model Methods: The study included two cohorts: patients affected by endometriosis-migraine and patients with endometriosis-only. Two additional cohorts are ongoing (patients with migraine-only and healthy controls). An established provocation test was used to evaluate cutaneous neurogenic responses (DBF, dermal blood flow) to the topical application of capsaicin (TRPV1), cinnamaldehyde (TRPA1), and placebo solutions at the forearm. Enrolled subjects underwent a single experimental session with measurements at baseline and 30, 45, 60, and 90 minutes (post solutions application). DBF were assessed using Laser Doppler perfusion imaging and reported as a percentage of change compared to baseline (DBF%). The primary outcome was the DBF difference after stimulation between patients with endometriosis or endometriosis- migraine. Results: Thirty-five patients (21 endometriosis and 14 endometriosis-migraine) were No significant changes were reported between patients with endometriosis and those with endometriosis- migraine with capsaicin (DBF% mean difference ± SEM, -25.74±44.03, p=0.58) or cinnamaldehyde (- 13.51±61.33, the endometriosis-only group had a not significative higher DBF% in response to capsaicin at t30 (32.51±27.9, p=0.25) and t45 (39.23±26.5, p = 0.14) compared to endometriosis-migraine. A similar lower trend was observed for cinnamaldehyde at t30 (25.7 ± 31.5, p=0.42) and t45 (25.06±27.2, p=0.36). The peak of DBF% was reported at t45 for capsaicin and at t30 for cinnamaldehyde. The peak of DBF% was reported at t45 for capsaicin and at t30 for cynnamaldehyde. Conclusion: No DBF differences have been reported between patients with migraine and endometriosis- migraine. The endometriosis-only group seems to be more sensitized. Interestingly, recruited. solutions p=0.83).

P069 What caffeine brings to Paracetamol R. Pegahi1, M. Lantéri-Minet1 1UPSA, Medical, Rueil Malmaison, France of glycinergic transmission. Objective: The aim of this work is to provide an overview of data on the cumulative analgesic effects of Paracetamol-Caffeine combination and to clarify the mechanisms underlying the potentiation by caffeine of the antinociceptive effect of paracetamol in migraine and TTH. Methods: A search was conducted in PubMed, MEDLINE, ClinicalTrials.gov and Cochrane Database from inception to March 2024 with a focus on paracetamol 1000 mg in combination with caffeine 130 mg. Results: In preclinical studies caffeine has been shown to increase the antinociceptive effects of paracetamol with various mechanisms: inhibition of microglial COX2 via antagonism of adenosine A2A receptors or activation Two in healthy subject have pharmacokinetic studies shown that caffeine increases paracetamol absorption rate and decreases paracetamol clearance. Two randomized double blind clinical studies have both demonstrated that in patients suffering from TTH, the combination offers a significant higher pain relief compared to paracetamol alone. Two other TTH clinical trials have shown that the efficacy and safety of combination was comparable to Naproxen 550 mg and Ibuprofen 400 mg. One randomized, cross-over trial has shown a comparable efficacy/safety profile of the combination vs sumatriptan 50 mg in treatment of migraine attack. No data are available on the risk of medication overuse with the combination compared to paracetamol alone. Conclusion: Caffeine accelerates and prolongs the analgesic effect of paracetamol over time with a significant improvement of pain relief in patients with primary headaches without added safety issues. P070 Effects of Calcitonin Gene-Related Peptide (CGRP) and Cilostazol on Plasma CGRP levels in migraine patients treated with Erenumab: an exploratory analysis from a randomized clinical trial T. P. Do1,2, C. Deligianni1, S. Amirguliyev1, J. Snellman3, T. Maio-Twofoot3, M. A. Al-Karagholi1, S. Guo1,4,5, N. R. Jørgensen4,2,6, D. Hay7,8, M. Ashina1,2 1Copenhagen University Hospital – Rigshospitalet, Danish Headache Center, Copenhagen, Denmark 2University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark 3Novartis Pharma AG, Basel, Switzerland 4Translational Research Centre, Rigshospitalet, Copenhagen, Denmark 5Zealand University Hospital, Roskilde, Denmark 6Copenhagen University Hospital – Rigshospitalet, Centre of Diagnostic Investigation, Copenhagen, Denmark 7University of Otago, Department of Pharmacology and Toxicology, Dunedin, New Zealand 8University of Auckland, Maurice Wilkins Centre for Molecular Biodiscovery, Auckland, New Zealand received a 20-minute Objective: Erenumab is a monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor and is able to mitigate CGRP-induced migraine attacks. However, erenumab has no effect on cilostazol-induced migraine attacks, which arise through the inhibition of cAMP degradation. This investigates whether erenumab exploratory study influences plasma CGRP levels differently when challenged with CGRP versus cilostazol. Methods: Individuals with migraine were randomized to erenumab 140mg or placebo. The trial involved two study days, 7 to 21 days post-administration, in which participants intravenous infusion of 1.5μg/min CGRP or 200mg of oral cilostazol. Blood samples were collected prior to administration of CGRP or cilostazol and at 20, 30, and 60 minutes post-administration for plasma CGRP concentration analysis. Plasma CGRP levels were compared using a linear mixed-effects model. Results: Seventy-five participants completed the study. Following CGRP administration, a significant increase in plasma CGRP levels was observed in both groups, with the erenumab group exhibiting significantly higher levels (p = 0.0002) and a more pronounced peak (p = 0.0232) compared to the placebo group at the end of administration. In participants treated with erenumab, we found a significantly higher plasma CGRP levels in those who did not develop a migraine attack in comparison to those who did develop a migraine attack (p = 0.0350). After cilostazol administration, neither group showed significant differences levels or migraine occurrence. in plasma CGRP

>77% resided in Europe (Table 1). Mean duration of migraine since onset was similar among cohorts (23.0- 23.8 years) (Table 2). Past use of preventive treatments was high (cohort 1, 81.8%; cohort 2, 81.4%; cohort 3, 92.3%). The most prevalent migraine- related comorbidity was hypertension (cohort 1: 4.4%; cohort 2: 7.7%; cohort 3: 9.0%). Conclusion: CAPTURE aims to provide pivotal data on the longitudinal course of migraine and associated treatment patterns, stratified by headache frequency. This study promises to provide insights for developing tailored treatment approaches for people with migraine. Fig. 1 Fig. 2 levels Conclusion: Administration of erenumab leads to higher plasma CGRP following CGRP administration, potentially due to the blockade of CGRP receptors by erenumab. Participants in the erenumab arm who did not experience migraine attacks post-CGRP administration had higher CGRP levels over time, suggesting that the increased plasma CGRP might indicate a more effective blockade. P071 Contemporary prospective understanding of migraine real-world evidence (CAPTURE): baseline clinical characteristics M. Ashina1,2, M. F. P. Peres3, R. J. Stark4, M. Lantéri- Minet5,6, E. Tucker7, Y. Liu8, J. Lam7, H. Ha7, L. Delahaye7, P. Pozo-Rosich9 1Danish Headache Center – Rigshospitalet, Department of Neurology, Copenhagen, Denmark 2University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark 3Universidade de São Paulo, São Paulo, Brazil 4Alfred Hospital and Monash University, Melbourne, Australia 5CHU Nice and Côte Azur University, Pain Department and FHU InovPain, Nice, France 6Auvergne University, INSERM U1107 Migraine and Trigeminal Pain, Clermont-Ferrand, France 7AbbVie, Toronto, Canada 8AbbVie, North Chicago, IL, United States 9Vall Hebron Institute of Research (VHIR), Headache Unit, Barcelona, Spain is a 2-year, Objective: CAPTURE international, prospective, longitudinal study that aims to enhance our understanding of disease burden and treatment patterns among people living with migraine, stratified by headache frequency. Methods: Adults with >=1-year migraine diagnosis aged <50 years at onset who were taking >=1 medication indicated for migraine and had >=4 monthly headache days (MHDs) in the 3 months before screening were assigned to cohorts based on MHD frequency (cohort 1: 4-<8; cohort 2: 8-<15; cohort 3: >=15; Figure). Descriptive data for baseline demographics and clinical characteristics (migraine duration, MHDs, monthly migraine days [MMDs], monthly acute medication use days, migraine-related comorbidities) are presented. Changes from baseline in MHDs, MMDs, acute medication use days, and patient-reported outcomes across the study period and durations of current and subsequent migraine treatment use will be assessed. Results: As of December 2023, among the 239 participants (cohort 1: n=68; cohort 2: n=104; cohort 3: n=67), mean age was 40.8-42.6 years, >95% of participants were White, >78% were female, and

Fig. 3 P072 Difference in sensitization mechanism across low- frequency episodic, high-frequency episodic, and chronic migraine S. Di Antonio1, M. Castaldo1, L. Arendt-Nielsen1 1Aalborg University, Department of Health Science and Technology, Aalborg, Denmark in study across interictally, preictally, This observational sensitization assessed Objective: differences chronic migraine(CM), low-frequency(LFEM), high-frequency episodic migraine(HFEM), and healthy controls Methods: Signs of sensitization were assessed with Quantitative sensory tests(QST) (trigeminal Wind-up ratio(WUR); trigeminal and upper-cervical pressure pain-threshold(PPT). CM were assessed ictally and interictally and compared vs controls. LFEM and HFEM were assessed ictally, and postictally and compared vs. 1) each other"s, matched for the phase; 2) CM (ictal-LFEM and HFEM vs. ictal- CM; postictal, interictal, preictal LFEM and HFEM vs interictal-CM); 3) control. Symptoms of sensitization were assessed with the Central Sensitization Inventory(CSI) questionnaire and CSI results of CM, HFEM, and LFEM were compared. Results: 56 controls, 32 CM, 105 LFEM, and 74 HFEM were included. Compared to controls: lower trigeminal and cervical 1) PPTs(p<0.001), and higher trigeminal WUR(p=0.020); no differences were observed with interictal-CM; 2) preictal-HFEM had lower cervical PPT(p=0.014); ictal-HFEM had trigeminal(p=0.002) and trigeminal cervical(p=0.009) PPTs, and higher WUR(p=0.002); lower trigeminal(p=0.004) and cervical(p=0.010) PPT. No differences were observed with interictal-HFEM. postictal-HFEM ictal-CM had lower had had and Ictal-LFEM 3) interictal-LFEM had lower trigeminal(p=0.002) and lower cervical(p=0.016) PPTs; preictal-LFEM had cervical PPT(p=0.014); postictal-LFEM had lower cervical PPT(p=0.006). No differences were observed with higher ictal-LFEM. trigeminal(p=0.013) cervical(p=0.012) PPTs compared to CM. No other differences were observed between HFEM and LFEM or HFEM and CM Patients with HFEM and CM had increased symptoms related to sensitization (HFEM, p=0.003; CM, p<0.001) compared to LFEM with no differences between HFEM and CM(p> 0.05) Conclusion: HFEM patients have a sensory profile matching CM better than LFEM. P073 Comorbidity rates in a large cohort of patients with migraine – a real-world data analysis A. Shifrin1, E. Domany1, M. Tirosh2, D. Davidovici2, S. Vinker3, I. Forschner4, A. Y. Israel3 1Rambam medical center, Haifa, Israel 2Pfizer Pharmaceuticals Israel LTD., Herzliya, Israel 3Leumit Health Services, Tel Aviv, Israel 4Rambam medical center, Haifa, Israel Objective: Migraine is often associated with additional medical conditions. However, existing data regarding the prevalence of comorbidities among migraine patients remain inconclusive. This study aimed to characterize comorbidity rates among migraine patients and compare them to non-migraine populations. Methods: We conducted a retrospective study utilizing electronic health records from Leumit Healthcare Services (LHS), a national healthcare provider, to assess migraine comorbidities among adults from 2017 to 2022. The migraine population was matched 1:1 to a control group on age, gender, ethnic group, regional district, and socioeconomic status. Results: Migraine patients exhibited a higher prevalence of smoking (OR=1.14,P=0.0004) but a slightly lower proportion of obesity (body mass index (BMI>30) compared to the control group (OR=0.94, P<0.001). Hypertension was more prevalent among migraine patients, while diabetes mellitus was less prevalent (OR=0.86, P<0.001). We observed higher incidences of transient ischemic attack (TIA) and cerebrovascular accidents (CVA) in the migraine group, with no significant increase in myocardial infarction significantly associated with vertigo/dizziness (OR=2.05, P<0.001), backache (OR=2.26, P<0.001), depression (OR=1.71, P<0.001), and fibromyalgia (OR=2.33, P<0.001). We observed chronic ankylosing inflammatory significant associations with events,.Migraine conditions, including was

in and milk atogepant concentrations determined using LC- MS/MS, and PK parameters calculated. The safety and tolerability of atogepant were evaluated by assessing adverse events, physical examinations, 12-lead ECGs, laboratory tests (hematology, serum chemistry, and urinalysis), and vital sign measurements. atogepant Results: Mean plasma concentrations are shown in Fig 1, and PK parameters in Table 1. Atogepant milk concentrations were much lower than plasma concentrations and were below the LLOQ beyond 16 hours the majority participants. The average milk:plasma concentration ratio was 0.076, and the RID was 0.189%. Mean cumulative amount of atogepant excreted in breast milk after a 60 mg dose was 0.016 mg, representing the actual infant dose should the infant drink all the milk produced. There were 2 mild adverse events, one abdominal pain upper and one dyspepsia, and no serious adverse events, clinically relevant changes in clinical labs, vital signs, or ECGs. average milk:plasma Conclusion: concentration ratio was 0.076 following a 60mg dose in lactating women. Based on lack of atogepant accumulation upon daily dosing, the low cumulative amount of atogepant excreted in breast milk, and the low RID of 0.189%, atogepant may be considered, for the preventive treatment of migraine in lactating women Atogepant Fig. 1 systemic (OR=1.74, P<0.001), (OR=1.94, P<0.001), lupus spondylitis erythematosus inflammatory bowel disease (OR=1.45, P<0.001), and psoriasis (OR=1.25, P<0.001). Conclusion: Individuals with migraine experience a higher incidence of CVA/TIA despite having reduced rates of conventional cardiovascular risk factors compared control population. Individuals with migraine exhibit higher rates of concurrent suggesting potential inflammatory mechanisms and/or deficient pain regulation/suppression of the central nervous system, in the development of migraines. to a matched inflammatory conditions, Fig. 1 Fig. 2 P074 Milk and plasma pharmacokinetics of single-dose atogepant in healthy lactating women R. Boinpally1, J. H. Smith1, R. Ferreira1, J. Trugman1 1AbbVie, North Chicago, IL, United States To and evaluate milk plasma Objective: pharmacokinetics (PK) and relative infant dose (RID) of atogepant following single-dose administration to healthy lactating women. Methods: In a Phase 1 open-label study, 12 healthy lactating women, one to six months post-partum, were administered 60mg single dose atogepant. Milk and plasma samples were collected for 24 hours,

Fig. 2 P075 Evidence of visual hyperexcitability during and outside of migraine attacks – a reform functional MRI study R. Häckert Christensen1, H. Ashina1, H. M. Al-Khazali1, C. Gollion1,2, M. Ashina1 1The Danish Headache Center, Neurology, Glostrup, Denmark 2University Hospital of Toulouse, Neurology, Toulouse, France investigate differences in sensory Objective: To processing of visual stimuli in people with migraine and matched healthy controls using functional magnetic resonance imaging (fMRI). Methods: Adults with migraine and age- and sex- matched healthy controls underwent fMRI with a visual stimulation paradigm (flickering checkerboard). We compared participants with migraine (including subgroups) and healthy controls using whole-brain permutation tests (voxel-wise threshold P < 0.001, cluster-wise threshold P < 0.05, familywise error corrected, adjusted for age and sex). In addition, we conducted region-of-interest (ROI) analyses of visual and pain processing regions pertinent to migraine. Results: A total of 261 participants with migraine and 143 age- and gender-matched healthy controls provided eligible fMRI data. Participants with migraine had greater activation of the bilateral visual (calcarine) cortex compared to controls (P = 0.017), in whole-brain analysis. The cortex was hyperexcitable in all subgroups of migraine (ictal, headache-free, with aura, without aura, chronic, and episodic migraine) compared to healthy controls in whole-brain and/or ROI analyses. During migraine attacks (n = 109), the left insula/operculum was hyperexcitable compared to controls (P = 0.017) in whole-brain analysis, while the bilateral anterior cingulate cortex was hyperexcitable compared to both headache-free participants with migraine (P = 0.026) and controls (P = 0.017) in ROI analysis. We found no other significant differences between participants with migraine, migraine subgroups, and controls. visual indicating hyperexcitable neurons Conclusion: In the current, largest fMRI study to date, migraine was associated with altered sensory processing, in specific brain regions. Increased activation of the primary visual cortex suggests persistent visual dysfunction in both migraine with and without aura. Furthermore, activation of the pain-processing insula and reflect hypersensitivity to light during migraine attacks. cortex might anterior cingulate Fig. 1 P076 Impact of Atogepant on daily functioning in patients with episodic migraine and chronic migraine: Activity Impairment in Migraine-Diary (AIM-D) Item-Level analysis R. B. Lipton1, P. Gandhi2, D. C. Buse1, R. Halker Singh3, H. Yuan4, J. Stokes2, K. Umashankar2, B. Dabruzzo2, M. Duan2, A. R. Gantenbein5 1Albert Einstein College of Medicine, Department of Neurology and the Montefiore Headache Center, Bronx, NY, United States 2AbbVie, North Chicago, IL, United States 3Mayo Clinic, Rochester, NY, United States 4Thomas Jefferson University, Jefferson Headache Center, Department of Neurology, Philadelphia, PA, United States 5ZURZACH Care, Neurology Department, Bad Zurzach, Switzerland Objective: Evaluate the percent change in individual Activity Impairment in Migraine-Diary (AIM-D) item scores from baseline to Weeks 1-4 across three atogepant (Ato) trials. Methods: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo (Pbo)-controlled, 12-week trials that included adults with episodic migraine (EM), EM with inadequate to 2-4 oral preventive treatments, and chronic migraine (CM), respectively. AIM-D is an 11-item daily measure that assesses migraine burden on the ability to perform daily activities and physical impairment. Item responses range from 0="not difficult at all" to 5="I could not do it at all". Post-hoc analyses evaluated the percent change from baseline mean score in each AIM-D item responses

in all AIM-D to Weeks 1-4 in participants taking Ato 60 mg once daily compared with Pbo. Results: The modified intent-to-treat populations included: ADVANCE (Ato N=222; Pbo N=214); ELEVATE (Ato N=151; Pbo N=154); PROGRESS (Ato N=256; Pbo N=246). In ADVANCE, a greater percent change from baseline items (46.9%-54.8%) was observed among Ato-treated participants compared with Pbo (17.2%-27.3%) at Week 1 (nominal P<0.05 in 10 of 11 items). In ELEVATE, a greater percent change from baseline in all AIM-D items (47.8%-57.7%) was observed among Ato-treated participants compared with Pbo (12.1%-20.2%) at Week 1 (nominal P<0.05 in all items). In PROGRESS, a greater percent change in all AIM-D items (31.0%-38.5%) was observed among Ato-treated participants compared with Pbo (13.8%- 23.4%) at Week 1 (nominal P<0.05 in 10 of 11 items). Similar to Week 1, during Weeks 2-4 a greater percent change from baseline in all AIM-D items was found in Ato-treated participants. Conclusion: As early as Week 1, a higher percent change from baseline in all AIM-D items was observed among Ato-treated participants compared with Pbo, demonstrating early improvements in function. P077 The impact of the migraine treatment Botulinum toxin on inflammatory and pain responses: insights from an animal model P. V. Reducha1,2, J. Bömers1,2,3, L. Edvinsson1,3,4, K. A. Haanes1,2 1Rigshospitalet, Translational Research Centre, Copenhagen, Denmark 2University of Copenhagen, Biology, Copenhagen, Denmark 3Rigshospitalet, Neurosurgery, Copenhagen, Denmark 4Lund University Hospital, Department of Clinical Sciences, Lund, Sweden its use interest due to Objective: The current study utilizes the complete Freund"s adjuvant (CFA) model of inflammation, with botulinum neurotoxin type A (BoNT/A) as a treatment of in clinical migraine management. The study sought to investigate the role of BoNT/A in modulating CFA-induced inflammation, alterations in pain sensitivity, and the regulation of calcitonin gene-related peptide release. Further, we aimed to assess the changes in SNAP-25 through Western blot analysis, to gain insights into the mechanistic action of BoNT/A. Methods: BoNT/A or saline was administered subcutaneously at the periorbital region three days before the induction of inflammation using CFA on the right periorbital Periorbital mechanical sensitivity was assessed four and six days post- inflammation. Alterations in CGRP release in the dura (CGRP) area. were evaluated and changes in SNAP-25 levels in the trigeminal ganglion were determined using Western blot analysis. Results: Upon CFA-induced inflammation, there was a marked increase in periorbital mechanical sensitivity (p < 0.001, on day 4 and 6 compared to day -3), with the inflammation side showing increased sensitivity compared to other periorbital areas. BoNT/A did not decrease the withdrawal thresholds in the electronical von Frey test. Despite not being able to observe differences in pain thresholds, BoNT/A reduced baseline CGRP release under CFA inflamed conditions (p = 0.015). Analysis of SNAP-25 levels in the TG and revealed cleaved (p = 0.004) forms that were notably elevated in BoNT/A-treated animals compared to saline-treated animals. Conclusion: Our investigation highlights the role of BoNT/A in reducing baseline CGRP in the context of inflammation and in SNAP-25 cleavage. In contrast, BoNT/A did not appear to alter facial pain sensitivity inflammation, suggesting that mechanisms other than baseline CGRP could be implicated in the elevated thresholds in the CFA model. (p = 0.039) induced by involvement intact both its P078 Results from the 2nd Italian interim analysis of the PEARL study: concomitant acute medication use Over 12 months of Fremanezumab treatment G. Egeo1, F. De Cesaris2, F. Baldacci3, S. Usai4, G. Allais5, M. P. Prudenzano6, P. Kokturk7, M. Cepparulo8 1Headache and Pain Unit, Department of Neurological, Motor and Sensorial Sciences, IRCCS San Raffaele Pisana, Rome, Italy 2Headache Center and Clinical Pharmacology Unit, Careggi University Hospital, Florence, Italy 3University of Pisa, Neurology Unit, Department of Clinical and Experimental Medicine, Pisa, Italy 4Headache Unit, Department of Clinical Neuroscience, C. Besta Neurological Institute and Foundation, Milano, Italy 5University of Turin, Department of Surgical Sciences, Turin, Italy 6Headache Center, Amaducci Neurological Clinic, Policlinico General Hospital, Bari, Italy 7Teva Netherlands B.V., Amsterdam, Netherlands 8Teva Italia Srl, Milano, Italy a is 24-month, Objective: The Pan-European Real-Life study (PEARL; EUPAS35111) prospective, observational study aiming to assess the real-world effectiveness of fremanezumab (225 mg monthly/675 mg quarterly) in adults with episodic (EM) and chronic migraine safety of in fremanezumab has been demonstrated both (CM). The efficacy and

randomised controlled trials and real-world studies. Here we focus on the impact of fremanezumab treatment over 12 months on concomitant acute migraine medication use and the reversion from CM to EM in the Italian migraine population enrolled in PEARL. Methods: This subgroup analysis was conducted on participants enrolled in 30 Italian headache centres. The primary endpoint of PEARL was the proportion of participants with ≥50% reduction in monthly migraine days (MMD) over 6 months. Secondary endpoints included average monthly days with any acute migraine medication use and proportion of participants with ≥50% reduction in the mean number of days with triptan use. The rate of reversion from CM to EM was also considered. Results: The full analysis set consisted of 343 participants. All endpoints were analysed at Month 12. Average monthly days with acute migraine medication use, triptan and other analgesics, decreased from 13.0±6.5 days at baseline to 4.7±4.7 days. Acute medication use decreased to 4.2±3.6 days and 5.0±5.2 days in participants with EM and CM, respectively. Among participants using triptans at baseline, 60.4% (137/277) achieved a ≥50% reduction in mean monthly days of triptan use. Of the participants with CM, 82.1% (92/112) reverted to EM. Conclusion: These results provide a comprehensive picture of the effectiveness of fremanezumab in real- world clinical practice, in terms of reduction of triptans/analgesic use and conversion from CM to EM. These findings suggest that fremanezumab not only reduces MMD but also improves the manageability of remaining migraine days, potentially leading to a reduced burden on patients. including P079 Differences in cortical activity in interictal, ictal, and chronic migraine M. Lisicki1,2, M. Filipchuk3,1, M. Carpinella3, T. Castro Zamparella3,4, D. Conci3, G. Coppola4, J. Schoenen5 1Hospital Universitario Ramón y Cajal, Neurology Department, Madrid, Spain 2Instituto de Investigaciones Médicas Mercedes y Martín Ferreyra, Headache Laboratory, Córdoba, Argentina 3Conci-Carpinella Institute, Neuroscience Unit, Córdoba, Argentina 4Sapienza University of Rome Polo Pontino, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy 5University of Liège, Headache Research Unit, Department of Neurology, Liège, Belgium Objective: *Contributed equally to the supervision of this study and healthy controls using resting-state between groups using Introduction Migraine is a fluctuating disorder. Analyzing changes in cerebral activity at different stages of migraine has significantly advanced our understanding of its pathophysiology. However, most neuroimaging methods evaluate indirect markers of brain activation, such as regional metabolism or blood flow. In contrast, electrophysiological assessments provide direct information about underlying neuronal processes. This study aimed to compare cortical activity among interictal, ictal, and chronic migraine patients an electrophysiological-based neuroimaging approach Methods: One hundred participants (25 healthy controls and 75 migraine patients: 25 ictal, 25 interictal, and 25 chronic) were included. A sixty- second low-artifact 22-channel electroencephalogram (EEG) segment from each individual was analyzed using Exact Low Resolution Brain Electromagnetic Tomography (eLORETA). Mean subject-normalized Delta, Theta, Alpha, Beta, and Gamma band activity was compared (whole brain, voxel-wise) Statistical Parametric Mapping (SPM) nested in MATLAB. Brain areas showing differences in neural activation were selected for data-driven post-hoc region of interest (ROI) analyses Results: Significantly decreased activity in the left subcallosal area was observed ictal migraine patients compared to other groups. Additionally, increased activity temporoparietal in junction was noted ictal migraine patients compared interictal migraine patients, and increased activity in the left temporoparietal junction in interictal patients compared to healthy controls Conclusion: Our results are anatomically consistent, but mostly physiologically discordant with previous neuroimaging studies.(1) Notably, we observed increased right temporoparietal junction and decreased activity in the left subcallosal area in ictal patients, both areas previously reported to be activated in this stage using conventional techniques. We hypothesize that these discrepancies arise because inhibitory and excitatory neuronal activity produces changes, making similar metabolic them conventional neuroimaging indistinguishable to techniques, using electrophysiological methods. The decreased activity in the left subcallosal area appears to be a homeostasis-restoring mechanism, absent in healthy in controls and ictal patients, and dysfunctional in chronic migraine. interictal patients, maximal the right in neuroimaging but easily discriminated neuronal activity in the in to

P080 Decreased intracortical inhibition in patients with hemiplegic migraine – a transcranial magnetic stimulation (TMS) study G. Demarquay1, S. Boulogne1, S. Rheims1, X. Moisset1, N. André-Obadia1 1Neurological Hospital, Neurology, Bron, France role in hemiplegic migraine Objective: Neuronal hyperexcitability might have a pivotal (HM) pathogenesis. Cortical excitability of the motor cortex can be assessed by transcranial magnetic stimulation (TMS). The aim of this study was to investigate intracortical inhibitory and facilitatory networks in HM patients using single- and paired-pulse TMS applied to the motor cortex. Methods: Single- and paired-pulse TMS paradigms were used to assess MP, CSP, short-interval intracortical inhibition (SICI), long-interval intracortical inhibition (LICI), and intracortical facilitation (ICF). 12 HM patients including four patients with a ATP1A2 mutation (FM2), three patients with a SCN1A mutation (FHM3) and five patients with no identified mutation, and 26 healthy volunteers participated in this study. Results: Between attacks, patients exhibited shorter cortical silent period duration, decreased SICI and LICI which indicate a decrease of inhibitory mechanisms. The altered cortical inhibition predominated on the hemisphere usually affected by attacks regarding SICI. Intracortical facilitation was normal in HM patients. Conclusion: Our study suggests that a dysfunction of cortical inhibition, involving both GABA-A and GABA-B receptors, may play a crucial role in the pathogenesis of HM. In contrast, our results do not support the hypothesis glutamatergic neurotransmission. increased of an Fig. 1 P081 Long-term (72-week) improvement in headache frequency, severity, and burden following early headache reduction with eptinezumab for migraine prevention C. Tassorelli1, A. J. Starling2, S. F. Awad3, X. Y. Lee3, L. P. Boserup3, B. Sperling3, P. J. Goadsby4,5 1University of Pavia, Pavia, Italy 2Mayo Clinic Arizona, Scottsdale, AZ, United States 3H. Lundbeck A/S, Copenhagen, Denmark 4UCLA Goldberg Migraine Program, Department of Neurology, David Geffen School of Medicine at University of California, Los Angeles, CA, United States 5NIHR King’s Clinical Research Facility and Headache Group, King’s College London, London, United Kingdom Objective: To explore the maintenance of monthly headache day (MHD) reduction and improvements in headache intensity and disease state in patients with <8 MHDs following their first eptinezumab dose. Methods: In the DELIVER study (NCT04418765), adults with migraine and 2–4 prior preventive treatment failures were randomized to eptinezumab 100 mg, 300 mg, or placebo, given IV every 12 weeks (wks). This regimen was maintained for a 24-wk placebo- controlled period followed by a 48-wk dose-blinded period where patients remained on the same eptinezumab dose or switched to an eptinezumab dose in a randomized manner. This post hoc analysis grouped patients treated with eptinezumab by their MHDs over Wks1–12 (<8 or ≥8). Patients with <8 MHDs were further grouped by maintained response (<8 MHDs with all 6 doses or first but not all). We evaluated the % of remaining headache episodes with severe intensity and the % of Patient Global Impression of Change (PGIC) responders (i.e., "much improved" or "very much improved"). Results: Of eptinezumab-treated patients, 10% had <8 MHDs at baseline, increasing to 55% over Wks1–12. Of patients with <8 MHDs over Wks1–12, 73% reported <8 MHDs for all dosing intervals (100 mg 71%, 300 mg 74%), and 93% reported <8 MHDs for more than half the total treatment period (≥3 remaining intervals; 100 mg 93%, 300 mg 94%). In patients with <8 MHDs for all dosing intervals, the % of severe headache episodes decreased from 42% at baseline to 12% over Wks61–72 (vs 47% to 21% in those with <8 MHDs with the first but not all doses), and the % of PGIC responders increased from 81% at Wk12 to 92% at Wk72 (vs 73% to 81% in those with <8 MHDs with the first but not all doses). Conclusion: Most patients reporting <8 MHDs over Wks1–12 with eptinezumab maintained this response for the entire 72-wk treatment period; <8 MHDs with all doses was associated with decreased % of

headache episodes with increased % of PGIC responders. severe intensity and P082 Impact of Atogepant on achieving complete improvement as early as week 1 based on the Activity impairment in Migraine-Diary (AIM-D) domains: post hoc analysis from the ADVANCE, ELEVATE, and PROGRESS trials A. R. Gantenbein1, P. Gandhi2, D. C. Buse3, R. Halker Singh4, H. Yuan5, J. Stokes2, N. Chalermpalanupap2, B. Dabruzzo2, M. Duan2, R. B. Lipton3 1ZURZACH Care, Neurology Department, Bad Zurzach, Switzerland 2AbbVie, North Chicago, IL, United States 3Albert Einstein College of Medicine, Department of Neurology and the Montefiore Headache Center, Bronx, NY, United States 4Mayo Clinic, Rochester, NY, United States 5Thomas Jefferson University, Jefferson Headache Center, Department of Neurology, Philadelphia, PA, United States responses Objective: Evaluate the proportion of participants who achieved complete improvement (score=0) in the Performance of Daily Activities (PDA) or Physical Impairment (PI) domains of the Activity Impairment in Migraine-Diary (AIM-D) over Weeks 1-4 across three atogepant (Ato) trials. Methods: ADVANCE, ELEVATE, and PROGRESS were phase 3, multicenter, randomized, double-blind, placebo (Pbo)-controlled, 12-week trials that included adults with episodic migraine (EM), EM with prior inadequate to 2-4 oral preventive treatments, and chronic migraine (CM), respectively. AIM-D comprises 2-domains assessing PDA and PI. Each daily domain score is transformed to a 0-100 scale, with higher scores indicating greater migraine burden. Post-hoc analyses evaluated the proportion of participants treated once daily with Ato 60 mg who achieved score=0 in the PDA or PI domains compared with Pbo over Weeks 1-4 in all three trials, among participants with non-zero values at baseline. Results: For the PDA and PI domains in ADVANCE (Ato N=192,181;Pbo N=167,162), the proportion of Ato- treated participants who achieved a score=0 at Week 1 were 33.3% and 39.2%, compared with 23.4% and 27.8% for Pbo, respectively. For PDA and PI in ELEVATE the proportion of Ato-treated participants who achieved a score=0 at Week 1 were 24.1% and 25.4%, compared with 7.6% and 8.5% for Pbo, respectively. For PDA and PI in PROGRESS (Ato N=249,244;Pbo N=241,238), the proportion of Ato-treated participants who achieved a score=0 at Week 1 were 8.0% and 10.2%, compared with 1.2% and 3.8% for Pbo, respectively (nominal (Ato N=141,134;Pbo N=144,141), P<0.05 for both domains across all trials). Similar to Week 1, a greater proportion of Ato-treated participants achieved score=0 compared with Pbo at weeks 2-4 for both PDA and PI across all three trials. Conclusion: As early as Week 1, a greater proportion of Ato-treated participants, compared with Pbo, achieved complete in the AIM-D domains. improvement P083 Predictors of sleep quality in patients with chronic migraine – a clinical study from Taiwan Y. M. Chen1,2, J. H. Wang3 1Tzu Chi University, School of Medicine, Hualien City, Taiwan 2Halien Tzu Chi Hospital, Department of Neurology, Hualien City, Taiwan 3Halien Tzu Chi Hospital, Department of Medical Research, Hualien City, Taiwan time, linear analyses Inventory regression Objective: To identify demographic and clinical predictors of sleep quality in chronic migraine patients in Taiwan, focusing on an Asian population. Methods: This cross-sectional study involved 46 chronic migraine patients (7 males, 39 females) from Taiwan. Data collected included age, monthly headache days (MHD), numerical rating scale (NRS) for pain, Migraine Disability Assessment (MIDAS) scores, weekly exercise regular exercise participation, Pittsburgh Sleep Quality Index (PSQI), Beck Anxiety (BAI), Beck Depression Inventory (BDI), and preventive medication usage. Multiple identified significant predictors of PSQI, considering sex, MIDAS scores, exercise habits, BAI, and BDI as potential confounders. Results: The mean age of participants was 42.50±13.86 years. PSQI scores were higher in males (14.71±6.60) than in females (11.41±5.29), though not statistically significant (p=0.149). Significant predictors of poor sleep quality included higher anxiety (BAI: β=0.23, 95% CI [0.12, 0.34], p<0.001) and depression scores (BDI: β=0.19, 95% CI [0.08, 0.29], p=0.001). Exercise variables, MIDAS scores, and other factors such as age, sex, MHD, and NRS did not significantly impact PSQI. Conclusion: Anxiety and depression are significant predictors of poor sleep quality in chronic migraine patients, even when accounting for sex, MIDAS scores, and exercise habits. This study highlights the need to address psychological comorbidities to improve sleep quality in chronic migraine sufferers in Asian populations.

Fig. 1 Fig. 2 P084 Primary senses and migraine – an observational study D. D. Das1, A. S. Singh2 1Fortis Hospital, Emergency Medicine, Mohali, India 2Forits Hospital, Neurology, Mohali, India fulfilling Objective: Every individual has five primary senses: vision, hearing, touch, smell, and taste. Various studies individually confirm the alteration of these senses in migraine. These alterations in the senses in migraine manifest as photophobia, phonophobia, allodynia, osmophobia, and specific food-related headaches. Methods: 435 consecutive newly diagnosed, drug naïve, migraine patients International Classification of Headache Disorders (ICHD-3) criteria interviewed for photophobia, phonophobia, were allodynia, osmophobia and specific food-related headaches. Demographic features and headache characteristics were evaluated in these patients. Results: Out of 435 patients, 15% were males and 85% females. 79% of patients had episodic migraine, and 11% of patients had chronic migraine. Photophobia was present in 95% of patients, phonophobia in 96%, osmophobia in 17% of patients, allodynia in 38% and 13% of patients had specific food-related headaches. Different studies suggest occurrence rates of photophobia and phonophobia in migraine patients ranging from 49-95% and 61-98% respectively. Osmophobia was seen in 25-40% of patients in different studies, compared to 17% in our study. Allodynia is seen in around 50-80% of patients with migraine in different studies, like in our study. Whereas, food-related triggers of migraine attacks from differences characteristics, weather were seen in 12-60% of patients of migraine in different studies, compared to 13% in our study. The results of our study are similar to those of previous studies regarding the occurrence of these related symptoms of primary sense alteration; however, discrepancies may arise in patterns, population individual lifestyles, dietary habits, and other confounding factors. Conclusion: Those who suffer from migraines are more likely to experience sensory dysfunctions. These sensory symptoms are essential to the diagnosis process and provide insight into the severity of the condition. They support the creation of treatment plans as well. Fig. 1 P085 Migraine experiences beyond typical symptoms and interventions S. Ahmad1, V. P. Senese1 1universita degli studi campania luigi vanvitelli, Caserta, Italy and exploring Objective: This study examines the subjective experiences of episodic migraineurs by examining individualized associated symptoms experienced during an episode subjective interventions they utilize to alleviate these symptoms. Methods: A sample of 20 participants (n = 10 women, n = 10 men) aged 27 to 32 (M = 29 years; SD = 1.86), engaged in semi-structured interviews. Findings reveal substantial inter-coder reliability (Kappa coefficient = .74), emphasizing the robustness of the study's qualitative analysis. This study visualizes data by utilizing a network analysis approach. Results: The the most dominating nodes from the subjective intervention trigger theme are avoidance, and psychological nodes of comorbid symptoms. Other nodes belonging to comorbid symptoms were social- symptoms. behavioral, cognitive, and physical techniques and results indicated that relaxation followed by the emotional

isolation, Similarly, social interpersonal support, assertive communication, distraction, and medical, and dietary interventions were identified as nodes of subjective interventions employed to alleviate these symptoms. The network metrics showed a density value of 0.97 indicating an almost connected network, further elaborating the relationship between nodes by visualizing directional edges. Conclusion: Understanding these factors is crucial for halting migraine progression and fostering effective treatment plans. P086 Headache in mediterranean anemias – a comparative study of Albanian patients E. Rraklli1, A. Papa1, M. Lekbello2, O. Cibuku3 1Regional Hospital of Berat, Neurology, Tirana, Albania 2Kamez Health Care Center, Tirana, Albania 3American Hospital, Tirana, Albania To investigate the thalassemia major prevalence, Objective: in characteristics, and correlates of headaches patients with sickle cell disease (SCD) and thalassemia major compared to a control group, aiming to enhance understanding and management of this symptom in Mediterranean anemias. Methods: A retrospective study at Berat Hospital included 66 SCD, 20 thalassemia major patients, and 35 controls. Clinical data and hematological parameters were analyzed. Headache characteristics were documented through patient interviews and records. Results: Headache prevalence was higher in SCD (68.2%) and (35.0%) versus controls (22.86%). Headaches were predominantly throbbing, of moderate intensity, and lasting 4-72 hours. Low hemoglobin correlated significantly with headache prevalence in both groups (p < 0.05). SCD patients experienced more headaches during vaso- occlusive crises (p < 0.01). Fatigue (42.6% SCD, 40.0% thalassemia major) and dizziness (36.8% SCD, 35.0% thalassemia major) were commonly associated with headaches. Correlation analysis revealed associations between headache frequency and fatigue (p < 0.01 for SCD, p < 0.05 for thalassemia major) and dizziness (p < 0.05 for both groups). in Conclusion: SCD and Mediterranean anemias, particularly headache thalassemia major. Understanding characteristics and associations, including with anemia severity and vaso-occlusive crises, is crucial for effective management. Further research is needed to elucidate underlying mechanisms and optimize treatment strategies, ultimately improving the quality of life for affected individuals. Headaches prevalent are Fig. 1 Fig. 2 Fig. 3 P087 Which combination of comorbidity makes migraine treatment impossible? A graphical approach P. Zhang1, J. Dave1 1Rutgers University, Neurology, New Brunswick, NJ, United States Objective: Medical comorbidities affect migraine care. We seek to determine the minimum combinations of comorbidities that would make it impossible to select a prevention or abortive medication. Methods: We obtain FDA package insert for every AHS recommended medications, documenting all contraindicating comorbidities, excluding pregnancy, drug-drug interactions, and conditions rarely seen in outpatient settings.[1] We then generate graphs for abortive/preventive as follow: 1. Each medication is a node. 2. If a pair of medication share a contradicting comorbidity, then an edge exists between them. We will show during the meeting that minimal spanning tree (MST) for each of the above graph yields a set of edges – and therefore comorbidity – which would be minimally contradicting to all medication in the component. Results: There is no contraindication for lasmiditan, memantine, fremanezumab, eptinezumab, and the gepants. Assuming the failure of the above, then the minimum combination of galcanezumab,

selection prevention uncontrolled comorbidities that makes picking an abortive medication impossible is the following: ischemic heart disease, hypertension, basilar/hemiplegic migraine, gastric ulcer, CABG, heart failure, tardive dyskinesia, epilepsy, and hepatic impairment. Similarly, the following comorbidities makes impossible: thyrotoxicosis, myasthenia gravis, hyper/hypotension, hyperammonemia, and glaucoma. Conclusion: No combination of abortive or prevention medications was found to be entirely contraindicating. However, cardiac comorbidities significantly limit the possibility of abortive and preventive treatments if hepatic diseases or other neurological disorders comes into the clinical picture. References: [1] Ailani et al. The American Headache Society Consensus Statement: Update on integrating new migraine treatments into clinical practice. Headache. 2021;61:1021-1039 P088 Which types of headaches in the migraine and tension-type spectrum cannot be diagnosed by ICHD3? P. Zhang1, A. Metzler2, R. Cheng1 1Rutgers University, Neurology, New Brunswick, NJ, United States 2University of Minnesota, Neurology, Minneapolis, MN, United States etc. Do combinations of Objective: ICHD3 differentiates migraine without aura (MwoA) and tension type headache (TTH) with combinations of characteristics such as laterality, phonophobia, the characteristics exist which are impossible to diagnose as either disorder? We enumerate these impossible diagnoses (ID) mathematically. Methods: We extracted a comprehensive list of characteristics from ICHD3 used to diagnose MwoA, probable MwoA, TTH, and probable TTH. Each combination of characteristics forms a phenotype. We generated all possible combinations of characteristics in the form of a "phenotype matrix" using the following: each row represents a phenotype, and each column represents a characteristic, with a value of "1" or "0" representing its presence and absence, respectively. We constructed a set of rules excluding phenotypes logical contradictions. Similarly, we generate a "diagnosis matrix" consisting of all combinations of required characteristics fitting diagnosis according to ICHD3. We now take the dot product between the diagnosis matrix and the transpose of the phenotype matrix. Matching the resultant column with corresponding row-wise summations of the diagnosis matrix yields that contain are that the The rows remaining the rows in which phenotype matrix is diagnosable by ICHD3. therefore undiagnosable. Results: There are 336 IDs. None of the ID are both "more than 10 episodes" and "constant". Other ID either did not meet the criteria D of TTH/MwoA or did not satisfy at least 2 out of the 4 characteristics in criteria C. Any headache > 4 hours with more than 10 episodes can be diagnosed as probable MwoA or TTH. Conclusion: Our comprehensive list of ID within the MwoA the spectrum assumption ICHD3 classifications are complete. Our findings invite the question of whether an alternative structure of classification criteria would be more effective. versus TTH challenges P089 Acute Migraine in CADASIL S. Zamanian1 1Social Security organization, Mashhad, Iran by in sensorium, transient alteration Objective: Acute confusion in migraine (ACM) is a in consciousness, cause of characterized by defects impaired awareness of environment, agitation and amnesia, mainly seen in children .Around 30-60% of cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients get affected by migraine attacks, often with aura. Acute confusional state during migraine has been rarely described in CADASIL . Methods: A 54-year-old female presented bimonthly episodes of migraine associated with visual aura since the age of 30. She had an ischemic stroke with left brachio-crural hemiparesis at the age of 43. Nine years later, she was admitted to another hospital because of severe migraine attack with aura characterized speech disturbance, mild psychomotor agitation and delirium. At 53 years-old, she was evaluated in our Emergency Room for a similar episode. Results: Brain MRI was negative for new ischemic lesions but showed typical CADASIL neuroimaging; EEG revealed bilateral sharp slow delta waves .A complete neuropsychological assessment during the acute phase showed complex visual hallucinations, severe cognitive global alteration with attention and executive impairment .The psychomotor agitation and confusional status suddenly disappeared and EEG recording returned normal seven days later. After excluding other possible causes, a diagnosis of ACM was made. Conclusion: Our case highlighted the lack of adequate knowledge about this entity and prompting further studies larger incidence and characteristics. to explore impairment, visual its

Fig. 1 Fig. 2 P090 Retrospective study in patients with chronic and refractory migraine treated with Eptinezumab M. Serrano Jiménez1, C. Adan Diaz1, A. I. Dengra Maldonado1, C. Santillana Avila1 1Hosptital Universitario San Cecilio, Neurologia, Granada, Spain Objective: Migraine headache affects 14% of the population, being one of the main causes of disability in people under 50 years of age. The development of treatment has been evidenced by preventive monoclonal antibodies (MCA) that block CGRP. Eptinezumab is a recently approved intravenous AMC that has demonstrated efficacy from the first day of administration. The main objectives are to know the different demographic characteristics of those patients, study the different preventatives used Know the results of these patients prior to treatment with Eptinezumab and study the results, in terms of efficacy and safety, after treatm Methods: Cross-sectional prevalence study with a nested, retrospective observational study of patients with chronic migraine refractory to preventive treatments and for whom Eptinezumab therapy has been proposed as a last option. Registry of patients treated in 2023 at the San Cecilio University Clinical Hospital in Granada. To collect data and obtain results, the Diraya system, the Microsoft Excel program and the SPSS Statistics program were used. Results: The sample consisted of 12 female patients, the average number of oral preventives used by the patients was 4 drugs prior to starting Eptinezumab. Before receiving it, patients in the study experienced an average of 26.08 headache days per month (DCM), an average of 24 days of analgesia use, and an average HIT 6 scale score of 72 points. In the statistical analysis, there were significant post- treatment differences in both DCM, HIT-6 score and need for analgesics per month Conclusion: Treatment-refractory chronic migraine is largely associated with mental health comorbidities. The rise in the availability of new preventive treatments such as Eptinezumab makes real-life studies with finding improvements in the quality of life of the treated patients in these very refractory patients this new drug relevant, Fig. 1 Fig. 2 P091 Pattern and adherence to Prophylactic treatment in migraine: a multi-center study in Egypt S. Abo Al-Azayem1, M. K Moawad1, M. Nada1, A. Dahshan1 1Cairo University, Neurology, Cairo, Egypt Objective: Prophylactic treatment plays a crucial role in reducing the frequency, severity, and duration of migraine attacks. This cross-sectional study aimed to study treatment the patterns of prophylactic

utilization among migraine patients and assess adherence levels to prescribed regimens. Methods: A cross-sectional study was conducted on 200 migraine patients. The following data were assessed: type of migraine, duration of attacks, frequency of headache per month and treatment history including both prophylactic and abortive treatment. Prophylactic treatments were evaluated regarding type, dose, adherence using Adherence to Refills and Medications Scale (ARMS) and efficacy was assessed using monthly migraine days (MMD), Migraine Disability Assessment Scale (MIDAS) and visual analogue scale (VAS) before and after prophylactic medication. Results: This study included migraine patients with median age was 32 and 70.6% were women. As regards prophylactic treatment, most of the patients (83.3%) received monotherapy, AED was the most common regimen (40%). Paracetamol was the most common prescribed abortive medication (42%). Polytherapy regimen was found to be associated with decreased duration of migraine headache attacks, MMD, VAS and MIDAS scores (P-value < 0.001). Only 30.4% of patients were adherent to their prophylactic treatment. Multivariate regression analysis was done to detect independent predictors of adherence. The independent variables were use of antidepressant as prophylactic treatment. Conclusion: nonadherence to prophylactic medication is prevalent among migraine patients. The severity of migraine attacks in patients receiving polytherapy regimen however using antidepressants is associated with treatment adherence. lower is were collected before starting eptinezumab therapy (T0) and at the time of drug infusion every three months thereafter (T1, T2, T3, T4). The first dose of eptinezumab was 100 mg for all patients; thereafter, the dosage was increased to 300 mg. Results: During January 2023 - April 2024, we evaluated 29 migraineurs treated with eptinezumab: 24 of 29 patients were eptinezumab-responders (83%), with a reduction in MMDs of at least 50%. Only one patient (3%) presented side effects that required suspension. We divided patients on eptinezumab therapy into two groups: Group 1 (17 patients who had never had mAbs before eptinezumab) and Group 2 (12 patients who had already tried other mAbs). Both groups achieved a great headache improvement, with a difference in MMDs before (T0) and after (T1- T3) eptinezumab very statistically significant (in G1 two-tailed P value equals 0.0078, in G2 is less than 0.0001). Furthermore, the number of responders in G1 was 14 out of 17 patients (82%), and in G2 the number was 10 out of 12 patients (83%); therefore, no statistically significant difference in response to eptinezumab was found between patients who had already failed with other mAbs and those who had never tried this therapy (chi-square 0.0047. The p- value 0.945119) Conclusion: Eptinezumab show an high efficacy and safety also in migraineurs with previous failures with other mAbs, making it the most effective therapeutic alternative at the present Fig. 1 P092 Eptinezumab treatment in patients with previous anti-CGRP(R) monoclonal antibodies therapy (mAbs) – a retrospective study of real-world clinical evidence of efficacy A. Bellotti1,2, C. Podella2, P. Sarchielli1 1University of Perugia, S. Maria della Misericordia Hospital, Neurology Clinic, Perugia, Italy 2Dya Swiss Institute SA, Headache Center, Lugano, Switzerland the efficacy and Objective: The aim of the following study is to demonstrate tolerability of eptinezumab in migraineurs non-responsive to other mAbs. Methods: This real-world observational study was conducted at the Day Swiss Institute Headache Center of Lugano, Switzerland. Inclusion criteria were: diagnosis of migraine according to the criteria of failures with ICHD-III; at conventional prophylactic least 8 migraine days per month (MMDs). Clinical variables two previous least therapies; at

Fig. 2 Fig. 3 P093 Effectiveness and tolerability of lasmiditan in the acute migraine treatment (DART) – a real-world multicentric study G. Vaghi1,2, R. De Icco1,2, L. F. Iannone3, M. Corrado1,2, A. Burgalassi3, E. De Matteis4, F. De Santis4, C. Fasano3, E. M. Piella5, M. Romozzi6, G. Sebastianelli7, G. Avino8, S. Cevoli9, G. Coppola7, G. Dalla Volta10, A. Granato11, E. Mampreso12, F. Boscain12, R. Ornello4, F. Pistoia4, I. Rainero13, M. Trimboli14, A. Russo15, I. Orologio15, M. Valente16, C. Vollono17, G. Sances2, C. Tassorelli1,2 1University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 2Fondazione Mondino IRCCS, Headache Science & Neurorehabilitation Unit, Pavia, Italy 3Careggi University Hospital, Headache Centre and Clinical Pharmacology Unit, Florence, Italy 4University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy 5University of Torino, Department of Neurosciences, Torino, Italy 6Fondazione Policlinico Universitario A. Gemelli IRCCS, UOC Neurologia, Rome, Italy 7Sapienza University of Rome Polo Pontino ICOT, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy 8Ospedale di Prato Santo Stefano, Prato, Italy 9IRCCS Istituto delle Scienze Neurologiche Bologna, Bologna, Italy 10Istituto clinico città di Brescia (gruppo SAN DONATO), Headache Centre, Brescia, Italy 11Azienda Ospedaliero-Universitaria di Trieste, Trieste, Italy 12Euganea Health Unit, Headache Centre, Padua, Italy 13University of Torino, Headache Center, Department of Neuroscience, Torino, Italy 14Azienda Ospedaliero-Universitaria Renato Dulbecco, Centro Interaziendale Cefalee, Catanzaro, Italy 15University of Campania "Luigi Vanvitelli", Department of Advanced Medical and Surgical Sciences, Naples, Italy 16Azienda Sanitaria Universitaria Friuli Centrale, Presidio Ospedaliero Santa Maria della Misericordia, Udine, Italy 17Università Cattolica del Sacro Cuore, Department of Neurosciences, Rome, Italy to evaluate Objective: Lasmiditan, a serotonin 5-HT1F receptor agonist, has been recently approved in Italy for the acute treatment of migraine attacks. We designed a prospective multicentric study its effectiveness and tolerability in the real-world setting. Methods: We enrolled 55 subjects (87.3% females, 45.4+14.4 years, 21.8% with chronic migraine, mean baseline monthly migraine days 9.1±7.2) from 13 Italian headache centers. Participants were instructed to treat up to 4 migraine attacks with lasmiditan 50 mg (20.4%) or 100 mg (79.6%). We collected migraine- attack features at baseline and every 30 minutes up to 2 hours post-dose (2h) with an ad hoc diary. Results: Preliminary analysis conducted on 38 first- treated attacks (10/38 in CM subjects) and 81 total attacks shows 2h pain freedom in 42.1% (16/38) of first-treated attacks and in 40.7% (33/81) of total attacks. The rate of pain freedom was not influenced by timing of lasmiditan intake (p=0.145), baseline pain severity (p=0.262) and presence of chronic vs. episodic migraine (p=0.683). Freedom from the most bothersome symptom 2h post-dose was reported in 44.4% (36/81) of attacks. All the subjects who reported data for the first- treated attack had previously used triptans. They declared a better effectiveness of in 42.10% of cases (16/38) related to a faster onset of action (21%) and complete effectiveness (28.9%). Adverse events were reported in 33 of total attacks treated (40.7%), of which 17 were first-treated attacks. Predominantly as dizziness (n=14), fatigue (n=15) and paresthesia (n=6). Tolerability was rated as good-to-excellent in 50% of cases. Conclusion: Our real-world data supports lasmiditan effectiveness in the acute migraine treatment. Adverse events were reported in > 40% of attacks. lasmiditan

P094 Evaluating safety, effectiveness, and impact on multiple sclerosis disease course of Anti-CGRP monoclonal antibodies combined with disease- modifying treatments – a multicentric study M. Romozzi1, P. Annovazzi2, R. Fantozzi3, C. Tortorella4, M. Vercellino5, L. F. Iannone5,6, G. De Luca7, T. Valentina7, M. Di Filippo8, L. Lorefice9, G. T. Maniscalco10, D. Paolicelli11, F. Pinardi12, V. Torri Clerici13, C. M. Solaro14, C. Gasperini4, C. Vollono1, P. Calabresi1, E. Cocco9, V. Nociti1 1Fondazione Policlinico Univeristario Agostino Gemelli, Neurology, Rome, Italy 2MS Centre, ASST Valle Olona, Gallarate Hospital, Gallarate, Italy 3Neurology Unit, IRCCS Neuromed, Pozzilli, Italy 4Department of Neurosciences, Ospedale San Camillo Forlanini, Rome, Italy 5Multiple Sclerosis Center & Neurologia I U, Department of Neuroscience, University Hospital AOU Città della Salute e della Scienza di Torino, Turin, Italy 6Section of Clinical Pharmacology and Oncology, Department of Health Sciences, University of Florence, Florence, Italy 7Neurology Unit, Policlinico SS. Annunziata, Chieti, Italy 8University of Perugia, Neurology Unit, Medicine Department, Perugia, Italy 9Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy 10Neurology and Stroke Unit, A. Cardarelli Hospital, Naples, Italy 11University of Bari, Department of Basic Medical Sciences, Bari, Italy 12IRCCS Istituto delle scienze neurologiche di Bologna, UOSI Riabilitazione Sclerosi Multipla, Bologna, Italy 13Neuroimmunology and Neuromuscular Diseases Unit, Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta, Milano, Italy 14Rehabilitation Department, Mons. L. Novarese, Moncrivello, Vercelli, Italy Objective: Migraine affects approximately 40% of people with multiple sclerosis (PwMS). This study aimed to evaluate the effectiveness and tolerability of combination of anti-CGRP monoclonal antibodies (mAbs) with disease-modifying treatments (DMTs) for MS and their impact on MS course. retrospective, multicentric study Methods: This enrolled treated concomitantly with anti-CGRP mAb and a DMT for MS (mAb or non-mAb) for at least three months or less in case of discontinuation for adverse events (AEs). MS outcome measures relapses, Expanded Disability Status Scale (EDSS), and MRI activity from the year before starting anti-CGRP mAbs, at time of initiation (baseline), during treatment, and included Centers, clinical PwMS from 14 to at last follow-up of concomitant treatment. Migraine outcomes included reductions in Monthly Headache Days(MHDs) and analgesic use(AMNs). Results: 27 PwMS (26 relapsing MS) treated with a DMT and concomitant anti-CGRP mAb were included (mean duration of anti-CGRP mAbs treatment of 13.5±9.0 months and concomitant DMT of 11.4±7.7). Nine PwMS (33.3%) were treated with non-mAb DMTs and 18 (66.7%) with mAbs. During the concomitant treatment, 6 PwMS (22.2%) stopped anti-CGRP mAbs after 14.2±12.6 months due ineffectiveness (n=4,14.8%), clinical remission, and new-onset of trigeminal neuralgia (n=1 each). MHDs significantly decreased from baseline (22.0±8.2) to last follow-up (11.5±13.7)(p=0.002), (baseline: 29.0±13.1 to last follow-up: 13.3±16.9)(p=0.002). EDSS score did not significantly change from the year before initiating anti-CGRP mAb to baseline and last follow-up. Two patients (7.4%) had clinical relapses, and lesions.Three patients(11.1%) changed DMT during treatment with anti-CGRP mAbs for AEs, poor adherence, and missing data(n=1 each). Mild AEs were reported in 4 PwMS(14.8%),none leading to discontinuation. anti- treatment with Conclusion: CGRPmAbs and MS DMTs showed safety and effectiveness with no significant effect on MS course. (7.4%) had new T2 as did AMNs Long-term two P095 A multidisciplinary multicentric approach to the identification of BIOmarkers of MIGraine (BIOMIGA project): an open-label, prospective biochemical study based on the stratification of responders to Erenumab R. Greco1, M. M. Pocora2,3, E. Caronna4, H. Basedau5, D. Martinelli2, E. Ballante2, G. Castellazzi6, C. Demartini1, A. M. Zanaboni1, A. Alpuente4, L. Asskour4, V. J. Gallardo López4, E. Giné Ciprés4, M. Torres- Ferrús4,7, J. Mehnert5, A. May5, P. Pozo-Rosich4,7, C. Tassorelli2,3 1Fondazione Mondino IRCCS, Laboratory of Neurophysiology of Integrative Autonomic Systems, Pavia, Italy 2Fondazione Mondino IRCCS, headache science and rehabilitation unit, Pavia, Italy 3University of Pavia, Brain and Behavioral Science Department, Pavia, Italy 4Vall Hebron Institute of Research (VHIR), Headache and Neurological Pain Research Group, Barcelona, Spain 5University Clinic of Hamburg Eppendorf, Dept. of Systems Neuroscience, Hamburg, Germany 6Fondazione Mondino IRCCS, Pavia, Italy 7Hospital Universitari Vall d'Hebron, Headache Clinic, Barcelona, Spain

Austria 3Headache Center Frankfurt, Frankfurt a. M., Germany 4Teva GmbH, Ulm, Germany 5Hospital Sankt Georg Leipzig gGmbH, Neurology, Leipzig, Germany 6University Hospital Halle, Headache Center, Neurology, Halle, Germany 7Helios Global Health, Berlin, Germany 8Charité – Universitätsmedizin Berlin, Neurology, Berlin, Germany is a multicentre Objective: To evaluate long-term real-world data on the effectiveness and tolerability of fremanezumab. (Germany, Methods: FINESSE in Austria), prospective non-interventional study adults with episodic or chronic migraine (EM, CM). Observation period: 24-months. Primary endpoint: proportion of patients reaching ≥ 50% reduction in the monthly average number of migraine days (MMD) during the 6-month period after the first dose of fremanezumab. Further secondary endpoints: change in the number of MMD, MIDAS (Migraine Disability Assessment), HIT-6 (Six-Item Headache Impact Test) and acute medication use. Adverse events as reported in routine clinical practice. Results: 1016 patients were included in the full analysis set (FAS) (88.7% female; 45.7 ± 12.4 years old; EM: 55.0%, CM: 45.0%). Of 987 patients (PES, Primary Endpoint Set), 52.8% achieved an MMD reduction of ≥ 50% during the 6 months post-fremanezumab initiation (EM: 57.0%, CM: 47.8%; Table 1). Table 2 depicts further effectiveness data up to month 24. Of 1083 patients included in the safety analysis set (received at least one dose of fremanezumab), 570 patients (52.6%) reported a total of 1511 adverse events throughout the 24-month observation period. COVID-19-related the most commonly reported events (N=201, 13.3%), followed by injection site reactions (N=191, 12.6%), drug ineffective (N=146, 9.7%), migraine-related events (N=38, 2.5%) and constipation (N=31, 2.1%). Conclusion: 52.8% of patients achieved the primary endpoint (≥ 50% reduction in MMD). The final results of the FINESSE study demonstrate a sustained, clinically meaningful reduction in MMD, migraine and headache-related disability and acute medication use over the entire 24-month observation period. No new safety findings were identified based on the real- world data on tolerability and the safety profile of fremanezumab remains favorable. terms represented response Objective: Calcitonin Gene-Related Peptide (CGRP), Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β) are circulating molecules that play a pivotal role in migraine pathogenesis. Here we investigate their potential role as biomarkers predictive of to a migraine-specific preventive treatment that targets the CGRP pathway. Methods: This molecular study was performed in the BIOMIGA multicentric international prospective study cohort, which comprised of 164 subjects with migraine. Plasma levels before and after 3-month treatment with erenumab of α-CGRP (OKEH00875 ELISA kit), IL-1β and TNF-α were analyzed. Moreover, CGRP mRNA expression, as well as TNF-α and IL-1β in peripheral blood mononuclear cells (PBMCs) using real-time PCR (rtPCR) was quantified. "Responders" (R) were classified if a reduction ≥ 50% headache/days in the last month (MHD) of treatment was achieved. Participants were also stratified according to sex and migraine subtype: chronic (CM) or episodic (EM) migraine. Results: Baseline The levels of plasma α-CGRP were significantly higher in R (361 vs 344 pg/ml; p=0.017), particularly among the CM subgroup (384 vs 342 pg/ml; p=0.039). IL-1β gene expression in PBMCs was higher in the R group (p= 0.033), specifically in subjects with EM (p=0.029). End of treatment Subjects with CM qualifying as NR had higher CGRP gene expression in PBMCs (p=0.018). No other difference was detected between the R and NR groups. Conclusion: Higher plasma α-CGRP leves correlate with a better response after 3 months of erenumab treatment, specially among those living with chronic migraine. Profiling of peripheral biomolecular mediators, known to be involved in migraine pathogenesis, emerges as a promising tool for identifying a panel of features associated with treatment response to migraine- specific prevention drugs. Acknowledgment: This study was funded by ERANet Neuron under the project code BIOMIGA. The funding source did not influence the way the study was conducted. P096 Effectiveness and tolerability of fremanezumab in real-world clinical practice:Results of the 24-month prospective observational study FINESSE A. Straube1, G. Broessner2, C. Gaul3, X. Hamann4, T. Kraya5,6, L. Neeb7,8 1University Clinic Munich, LMU, Neurology, Munich, Germany 2Innsbruck Medical University, Neurology, Innsbruck,

Fig. 1 P097 Real-world long-term effectiveness of fremanezumab in patients with migraine who switched from another mAb targeting the CGRP pathway – subgroup analysis of the FINESSE full analysis A. Straube1, G. Broessner2, C. Gaul3, X. Hamann4, T. Kraya5,6, L. Neeb7,8 1University Clinic Munich, LMU, Neurology, Munich, Germany 2Innsbruck Medical University, Neurology, Innsbruck, Austria 3Headache Center Frankfurt, Frankfurt a. M., Germany 4Teva GmbH, Ulm, Germany 5Hospital Sankt Georg Leipzig gGmbH, Neurology, Leipzig, Germany 6University Hospital Halle, Headache Center, Neurology, Halle, Germany 7Helios Global Health, Berlin, Germany 8Charité – Universitätsmedizin Berlin, Neurology, Berlin, Germany Objective: To evaluate real-world long-term data on the effectiveness of fremanezumab in migraine patients who switched from a previous mAb (monoclonal antibody) targeting the CGRP (Calcitonin gene-related peptide) pathway. (Germany, Methods: FINESSE Austria), prospective non-interventional study in adults with episodic or chronic migraine (EM, CM). Observation period: 24-months. Primary endpoint: proportion of patients reaching ≥ 50% reduction in the monthly average number of migraine days (MMD) during the 6-month period after the first dose of is a multicentre in patients who had switched fremanezumab. Further secondary endpoints: change in the number of MMD, MIDAS (Migraine Disability Assessment), HIT-6 (Six-Item Headache Impact Test) and acute medication use. This subgroup analysis of the FINESSE full analysis presents real-world long- term data to fremanezumab from another mAb targeting the CGRP pathway. Results: The two most common reasons for switching to fremanezumab were insufficient response and intolerability to prior therapy with another mAb targeting the CGRP pathway. Of 166 patients, 37.3% (62 patients) achieved ≥ 50% reduction in the monthly average number of migraine days (MMD) during the 6-month period after the first dose of fremanezumab (EM: 43.0%, CM: 31.3%). Table 1 depicts further effectiveness data up to month 24. Conclusion: 37.3% of patients in this subgroup analysis achieved an MMD reduction of ≥ 50% within 6 months post-fremanezumab initiation. A clinically meaningful in MMD, migraine and headache-related disability, and acute medication use the entire 24-month was demonstrated over treatment For patients experiencing inadequate effectiveness or poor tolerability with other mAbs targeting the CGRP pathway, switching to fremanezumab may be a sustained effective treatment option. reduction period. Fig. 1

P098 Lessons with fremanezumab as the third CGRP antibody in our hospital: focus on factors predicting response M. Polanco Fernández1,2,3, J. Madera Fernandez1,2,3, V. González Quintanilla1,2,3, S. Pérez Pereda1,2,3, G. Gárate3, J. Pascual1,2,3 1University Hospital Marqués de Valdecilla, Neurology, Santander, Spain 2Universidad de Cantabria, Santander, Spain 3IDIVAL, Santander, Spain P099 Restarting migraine preventive treatment with CGRP antibodies after drug holiday: Insights from Pavia real-world experience L. Costantino1, D. Martinelli1,2, G. Vaghi1,2, G. Salis1, M. M. Pocora1,2, G. Sances2, G. Castellazzi2, C. Tassorelli1,2 1University of Pavia, Headache Science and Neurorehabilitation Unit , IRCCS Mondino Foundation, Pavia, Italy., Department of Brain and Behavioral Sciences, Pavia, Italy 2Headache Science and Neurorehabilitation Unit , IRCCS Mondino Foundation, Pavia, Italy., Pavia, Italy for refractory high Objective: Fremanezumab was the third CGRP antibody frequency/chronic migraine (HF/CM) available. Here we analyze our experience with fremanezumab focusing on factors predicting response. Methods: This is a prospective, observational study in which we included HF/CM patients who were prescribed fremanezumab during 2023. We collected data on demographics, diagnoses, acute treatment, previous prophylactic treatments and comorbidities. Headache frequency was recorded the quarter before and after fremanezumab. Results: 89 patients were treated with fremanezumab (86.5% female, 45.8±12.5 years, 70.1% naive). During the first quarter headache days fell from 21.1±7.6 to 12.4±11.2 (-8.7 days) and 55 patients (61.8%) were 50% responders (75.8% in naïves). Half (54.5%) of patients with no response for > 6 months to erenumab responded to fremanezumab. Factors associated with non-response were: failure to both erenumab and galcanezumab (p<0.0001), length of HF/CM (11.9±7.1 years in non-responders vs 5.8±4.8 in responders; p<0.001), fibromyalgia (p<0.001) and depression (p<0.001), almost daily headache baseline (>25 days/month) (p<0.0001) and daily use of opiods. Age and sex did not influence response rate. After multivariate analysis almost daily headache (p<0.001; OR for non-response 13.1), length of HF/CM >6 years (p=0.015; OR 4.4) and depression (p=0.017; OR 4.5) remained significant. Fremanezumab was well tolerated (constipation rate 12.4%), without serious adverse events. confirm Conclusion: fremanezumab efficacy. Main factors associated with lack of response were almost daily headache, disease duration > 6 years and depression. Half of the patients with on fremanezumab, making it sensible one switch to a different mechanism of action, but trying a third anti- CGRP in patients with no response to both one receptor and one ligand CGRP antibody seems hardly justifiable from our experience. erenumab improved failure These real-life results to indicated (MIDAS). Both were the migraine disability assessment Objective: Monoclonal antibodies targeting the CGRP pathway (mAbs) are in the preventive treatment of migraine, being prescribed for cycles lasting 12 months separated by mandatory discontinuations. Knowledge about their effectiveness when restarted after the discontinuation is limited. Here, we evaluated the effectiveness of mAbs in migraine prevention after treatment resumption in a cohort of subjects seen at the tertiary headache centre of the Mondino Foundation. Methods: Retrospective, monocentric, open-label real-life study. Endpoints considered were, among others, the variation of monthly migraine days (MMD) score and questionnaire collected prospectively. Results: We enrolled 337 outpatients from 2019 to 2023. Of these, 175 were treated with erenumab, 93 with galcanezumab, and 69 with fremanezumab. At baseline they reported 21 ± 7.2 MMD and a median MIDAS score of 60. 267 subjects completed 1 year- cycle of treatment obtaining a statistically significant median reduction of 11 MMD (-62,5%) and a median decrease in MIDAS score of 46 points compared to baseline. After a drug holiday of a median duration of 4 months, subjects presented a median increase of 6 MMD (+62.5%) and 20 points at the MIDAS compared to the last trimester of treatment. 210 subjects restarted the mAbs, and after 3 months of treatment, they had a median reduction of 5 MMD (-40%) and a median reduction of 18 points at the MIDAS compared to the suspension period. Conclusion: CGRP mAbs are effective in reducing both MMDs and MIDAS score. Their effectiveness wanes after discontinuation, but reappears after a drug holiday of a few months

P100 Clinical impact of Rimegepant in acute migraine management for triptan non-responders D. Mascarella1, B. Carandente1, A. Garavalli1, V. Favoni2, E. M. Bruno2, G. Pierangeli1,2, S. Cevoli2 1Alma Mater Studiorum Bologna, DIBINEM - Department of Biomdical and Neuromotor Sciences, Bologna, Italy 2IRCCS, Institute of Neurological Science of Bologna, Bologna, Italy Objective: The acute treatment of migraine is crucial for patients' quality of life. In this context, it is crucial to introduce new medications such as Rimegepant into the real-world clinical setting and to delineate their potential role in patients who are non- responders or have contraindications to current acute therapies. Methods: This prospective observational study included a cohort of patients with episodic or chronic migraine, who had an unsatisfactory or absent response to triptans. All patients were provided with two doses of Rimegepant to treat two attacks, using Rimegepant as the primary drug for acute treatment. Results: 22 patients were recruited, including 18 women (81.8%) and 4 men (18.2%), with a mean age of 49 years and an average of 8.45 monthly migraine days (MMD). Rimegepant was used for 35 migraine attacks, and in 57% of cases, it was preferred over the usual therapy, especially among those using NSAIDs or triptans. 63% of patients rated Rimegepant positively, with 80% expressing overall satisfaction. Pain relief was achieved within two hours in 74.3% of attacks. Rimegepant effectively alleviated nausea (81.26%), photophobia (88.23%), phonophobia (88.88%), and osmophobia (100%). Mild side effects, primarily nausea, were reported in six attacks (17.14%). A slight correlation was observed between the time of drug administration and its effectiveness, while a weak negative correlation was noted between the time of administration and the frequency of migraine attacks. Conclusion: Rimegepant demonstrated effectiveness and patient satisfaction in acute migraine treatment, particularly for those unresponsive to triptans. It provided rapid pain relief and alleviated associated symptoms with minimal side effects, highlighting its potential as a valuable therapeutic option. P101 Switching anti-CGRP monoclonal antibodies benefits 25% of non-responders – an observational study of 82 cases A. Muñoz-Vendrell1, S. Campoy1,2, J. Campdelacreu1, L. Termens1, J. Prat1, M. Huerta-Villanueva1,2 1Hospital de Bellvitge, Headache Unit, Barcelona, Spain 2Hospital de Viladecans, Neurology, Viladecans, Spain rates, and reduction in headache Objective: The benefit of switching to a different anti- CGRP monoclonal antibody (MAb) following the failure of an initial treatment, whether targeting the receptor (CGRP-R: erenumab) or the ligand (CGRP-L: galcanezumab or fremanezumab), remains uncertain due to a lack of solid evidence. Methods: This observational study analysed patients who switched to a second anti-CGRP MAb and had at least 3 months of follow-up. Baseline characteristics and responses at 3 months were evaluated, focusing on the percentage of patients achieving ≥30%, ≥50%, and ≥75% frequency. Additionally, reductions in monthly migraine days (MMD), discontinuation subgroup differences were assessed. Results: The study included 82 patients (mean age 49.9 ± 11.7 years, 86.6% women), with 84.1% having chronic migraine and a median of 16 MMD (IQR 12- 24). 53.7% switched from CGRP-R to CGRP-L, 37.8% from CGRP-L to CGRP-R, and 8.5% between CGRP-Ls, primarily due to inefficacy (90.2%). After 3 months, 24.4% achieved a ≥30% response, 11% achieved a ≥50% response, and 3.7% achieved a ≥75% response. No significant differences were observed between episodic and chronic migraine subgroups or between different types of switches. Overall, 79.3% continued with the new MAb, while 20.7% discontinued treatment (94.1% due to inefficacy). Conclusion: Switching to a second anti-CGRP MAb after the failure of the first can result in a ≥30% reduction in headache frequency in a quarter of the cases and a ≥50% reduction in 10% of cases.

Fig. 1 Fig. 2 P102 Evaluating the efficacy of monoclonal antibodies targeting CGRP in migraine treatment and the effect of combination therapy with Onabotulinum Toxin Type-A – a retrospective study C. Correia1,2, R. Costa1,3, M. Pinto1,3, R. Dias1,3, A. Costa1,3 1ULS São João, Neurology, Porto, Portugal 2Faculty of Medicine, University of Porto, Medicine Department, Porto, Portugal 3Faculty of Medicine, University of Porto, Clinical Neurosciences and Mental Health, Porto, Portugal Objective: Combination therapy with monoclonal antibodies (mAbs) targeting calcitonin gene-related peptide (CGRP) and onabotulinum toxin type-A (BoNT- A) may be considered given the possible synergistic mechanism, for migraine patients who do not respond or maintain significant disability with one of the treatments. This study aimed to evaluate the impact of preventive migraine treatment with mAbs in a therapy due tertiary centre and to assess the differences in treatment response among those with simultaneous exposure to BoNT-A. Methods: Retrospective, descriptive study of all patients with migraine treated with mAbs before March 2024. Results: 201 patients were included, mainly female (72.9%), with a mean age of 44±11years. 53.7% had episodic migraine, and 20.4% experienced aura. 50.2% had previously received BoNT-A treatment, and 6 patients underwent combined to suboptimal response to one of the treatments. Before mAbs initiation, median monthly headache days was 12, with a mean HIT-6 score (HIT-6) of 70. After 6 months of treatment, median monthly headache days decreased to 3.3, and HIT-6 to 52, reflecting a mean reduction of 59.4% in headache frequency and a median reduction of 24.6% in HIT-6. After 12 months of mAbs treatment, benefits persisted, with a median monthly headache frequency of 2.8 days, and a median HIT-6 of 57.5, corresponding to a 60.0% mean reduction in headache frequency and a 16.3% median reduction in HIT-6. No significant differences were found in treatment response to mAbs between patients who had prior BoNT-A treatment and those who didn"t. Combined therapy didn't show to be superior to monotherapy with mAbs and patients who underwent this strategy didn't experience more adverse effects. Conclusion: Our results emphasize the benefit of treatment with mAbs. Likely due to the small sample size in the combination therapy group, the benefits of this strategy weren't demonstrated. Previous BoNT-A treatment wasn't a predictive factor for clinical response to mAbs. P103 Characteristics of people with migraine using rimegepant in the Adelphi migraine Disease Specific ProgrammeTM (DSP) J. Brown1, A. Jenkins2, B. Galabova2, J. Cirillo1, K. Hygge Blakeman3, L. Hancock4, J. Jackson4, W. Whitton4, L. Abraham2 1Pfizer, Inc, New York, NY, United States 2Pfizer Ltd, Tadworth, United Kingdom 3Pfizer AB, Stockholm, Sweden 4Adelphi Real World, Bollington, United Kingdom is little Objective: Rimegepant the only migraine medication indicated for both the acute treatment and prevention of migraine, but is known regarding real-world rimegepant users. This analysis described the demographic and migraine-associated characteristics of people using rimegepant. Methods: Patient and physician data were drawn Specific from the Adelphi Migraine Disease

including consecutively, symptoms, migraine Programme (DSP), a real-world, cross-sectional survey with retrospective data collection of physicians and their adult patients with migraine in the United States, conducted in 2022. Physicians provided treatment practice data for the next 10 people with migraine treatments, consulted migraine frequency, and migraine severity. Results: A total of 154 rimegepant users were included. Among these, 98 (63.6%) reported only acute use, 26 (16.9%) only preventative use, and 30 (19.5%) used rimegepant for both indications. The mean age was 40.6 ± 13.7 years and 74.7% of rimegepant users were female. Race and ethnicity were 74.0% white, 12.3% African American, and 8.4% Hispanic/Latinx. Physicians identified 19.1% of women as having menstrual migraine. Moderate, severe, or very severe migraines over the last 3 months were reported for 46.8% of rimegepant users. Migraine with aura was present for 49.0% and common migraine symptoms included pulsating/throbbing pain (78.4%), photophobia (76.4%), and nausea (70.6%). The mean monthly migraine day frequency was 4.7 ± 4.5 for acute users, 6.5 ± 6.4 for prevention users, and 4.4 ± 3.3 for users of both indications. Conclusion: This work provided the first real-world description of migraine characteristics among these patients. Additional research is needed to further characterize patients and assess real-world outcomes with rimegepant use. P104 Exploring comorbidities in resistant and refractory migraine: results from the REFINE study C. Rosignoli1, R. Ornello1, V. Caponnetto2, A. Onofri1, M. Braschinsky3, R. Gil-Gouveia4, C. Lampl5, P. Martelletti6, D. Mitsikostas7, A. Özge8, M. P. Prudenzano9, I. Pavão Martins10, P. Pozo-Rosich11, K. Ryliškienė12, M. Sánchez del Río13, F. Vernieri14, M. Waliszewska-Prosol15, Z. Katsarava16, S. Sacco1 1Department of Biotechnological and Applied Clinical Sciences University of L'Aquila, L'Aquila, Italy 2Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy 3University of Tartu, Tartu, Estonia 4Hospital da Luz, Lisboa, Portugal 5Headache Medical Center Linz, Linz, Austria 6Unitelma Sapienza University of Rome, Rome, Italy 71st Neurology Department, Eginition Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece 8Mersin University School of Medicine, Department of Neurology, Algology and Clinical Neurophysiology, Mersin, Turkey 9Headache Center, Amaducci Neurological Clinic, Policlinico General Hospital, Bari, Italy 10Faculdade de Medicine and Hospital Universitário de Santa Maria, Centro Hospitalar, Lisboa, Portugal 11Hospital Universitari Vall d'Hebron, Barcelona, Spain 12Vilnius University, Center of Neurology, Faculty of Medicine, Vilnius, Lithuania 13Neurology Department, Clínica Universidad de Navarra, Madrid, Spain 14Department of Medicine and Surgery, Unit of Headache and Neurosonology, Unit of Neurology, Università Campus Bio-Medico di Roma, Rome, Italy 15Wroclaw Medical University, Department of Neurology, Wroclaw, Poland 16Christian Hospital Unna, Unna, Germany Objective: Does identifying the specific comorbidities in Resistant Migraine (ResM) and Refractory Migraine (RefM) uncover pathophysiological mechanisms and potential new treatment targets linked to migraine? Methods: The REFINE is a multicenter, prospective observational study involving participants from 15 different headache centers. Participants were categorized into three groups based on the EHF criteria: non-resistant and non-refractory migraine (NRNRM), ResM and RefM. We collected demographic details, information on headache characteristics and comorbidities. Results: Of the 689 patients included in the study (82.8% women), median age 47 [Interquartile Range (IQR) 38-56] 262 (38.0%) were classified as having ResM, 73 (10.4%) as RefM, and 354 (51.4%) as NRNRM. We found a significant difference in several of the considered comorbidities among the three groups. All comorbidities were more common in the RefM group compared to the ResM and NRNRM groups: anxiety (34.7% vs. 25.2% vs. 11.3%; p<0.001), bipolar and other psychiatric disorders (13.9% vs. 9.2% vs. 5.1%; p=0.032), cerebrovascular diseases (16.7% vs. 2.3% vs. 2.3%; p<0.001), depression (39.7% vs. 34.1% vs. 15.8%; p<0.001), sleep disturbances (33.3% p=0.025), temporomandibular joint disorders (23.6% vs. 13.6% vs. 10.7%; p=0.033), and trigger points (33.3% vs. 21.3% vs. 12.4%; p<0.001). Patients with chronic migraine showed significant differences among the three groups regarding anxiety (p<0.001), asthma and (p=0.013), bipolar and other psychiatric rhinitis disorders diseases (p<0.001), depression (p<0.001), obesity (p=0.002), thyroiditis (p<0.001), and trigger points (p=0.008) Conclusion: Our findings suggest that ResM and RefM substantial burden of show a comorbidities, potentially influencing migraine progression from manageable to treatment-resistant forms. Further research is necessary to explore whether addressing these comorbidities can prevent migraine progression or improve treatment outcomes. cerebrovascular (p=0.049), 28%; vs. 40.3% vs.

P105 Multicenter study on the evolution of insomnia in patients with migraine treated with anti-CGRP: expanding the impact of new treatments A. González Martínez1, E. Hierro Roselló2, J. Madera Fernandez3, V. García4, Y. González-Osorio5, E. Caronna6, G. Gárate6, L. Asskour6, I. Fernández- Lázaro7, D. García-Azorín5, S. Santos-Lasaosa8, P. Pozo- Rosich6, Á. L. Guerrero-Peral5, J. Pascual3, A. Mínguez Olaondo4, A. B. Gago-Veiga1,9 1Hospital Universitario de la Princesa, Neurology Department, Madrid, Spain 2Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain 3Servicio de Neurología. Hospital Universitario Marqués de Valdecilla., Santander, Spain 4Servicio de Neurología. Hospital Donostia-Donostia Ospitalea. Donostia, San Sebastián, Spain 5Unidad de Cefaleas, Departamento de Neurología, Hospital Clínico Universitario de Valladolid., Valladolid, Spain 6Servicio de Neurología. H. Universitari General de la Vall D'hebron., Barcelona, Spain 7Fundación de Investigación BIomédica, Hospital Universitario de la Princesa, Madrid, Spain 8Servicio de Neurología. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain 9Instituto de Investigación Sanitaria Princesa (IIS- Princesa), Madrid, Spain Objective: Insomnia is one of the most frequent and least studied comorbidities in patients with migraine treated with anti-CGRP drugs. The objective of the present study was to evaluate the usefulness of these drugs and their influence on insomnia in patients with migraine. Methods: We present a prospective multicenter study in patients with migraine and anti-CGRP drugs. Demographic and clinical variables, anxiety scales (HAD-S/BAI), depression (HADS-D/ BDI-II), impact insomnia (ISI) were recorded (MIDAS/HIT6) and quarterly/semestrally. The primary objective was to evaluate the effectiveness/safety of anti-CGRP in patients with and without insomnia. As secondary objectives, demographic variables, improvement in ISI scale, as well as predictors of improvement were studied using a logistic regression model. were included, Results: 119/135(88%) women, mean age 46 (SD:11.9) years[18-70 years]. A reduction in monthly headache days (MHD) of 9 and 11 days at 6 and 12 months, respectively, was observed without statistically significant differences depending on insomnia. An improvement in ISI at 6-12 months was found in 75/135 (56%). Likewise, a greater consumption of supplements (P = 0.028), greater anxiety (P = 0.029) and greater depression (P = 0.004) at baseline will be participants 135 observed in patients with insomnia, with depression (p = 0.0171) being an independent predictor of improvement in the ISI scale at 6-12 months in the regression model. Conclusion: Anti-CGRP drugs are effective and safe in patients with migraine with and without insomnia, with depression being an independent baseline predictor of ISI. These findings in improvement underscore the importance of addressing baseline comorbidities to optimize treatment outcomes. P106 Selenium serum levels and Selenium-rich dietary sources are associated with lower risk of migraine in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) A. Belitardo de Oliveira1, F. Barbosa Jr.2, I. Santos3,4, M. F. P. Peres5,6, P. Lotufo3,4, I. Benseñor3,4, A. Goulart3,7 1Universidade de São Paulo, Center For Clinical and Epidemiological Research, Casa Branca, Brazil 2Universidade de São Paulo, Laboratório de Toxicologia Analítica e de Sistemas (ASTOx), Ribeirão Preto, Brazil 3Universidade de São Paulo, Center For Clinical and Epidemiological Research, São Paulo, Brazil 4Universidade de São Paulo, Department of Internal Medicine, São Paulo, Brazil 5Universidade de São Paulo, Psychiatric Institute, São Paulo, Brazil 6Albert Einstein Israeli Hospital, Brain Institute, São Paulo, Brazil 7Universidade de São Paulo, School of Public Health, Epidemiology, São Paulo, Brazil links migraine with Objective: Growing evidence selenium (Se), but prospective studies on serum Se levels and dietary sources are limited. Thus, our objective was to estimate the risk of migraine based on serum Se levels and Se-rich food groups in the ELSA-Brasil Study. Methods: This prospective analysis used baseline serum Se levels and Se-rich food intake (2008-2010) to diagnose migraine at inter-wave (2012-2014). Serum Se levels was quantified by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), and a validated Food Frequency Questionnaire assessed diet. Diet patterns and Se-rich food groups were determined by Mediterranean Eating Diet for Americans (MEPA) scores. Migraine diagnosis followed ICHD-3 criteria. Modified Poisson regression models estimated risk ratios (RR) with 95% confidence intervals for migraine, according to Se concentration terciles and MEPA scores for Se-rich food groups. Adjustments were made for sex, age, BMI, education, race, smoking,

intake, cardiometabolic risk factors, and alcohol migraine prophylactic medication. Results: Among 2,127 adults (mean age: 52.6 ±9.1 years, 50.1% female), 20.2% were diagnosed with migraine 4 years after baseline. The migraine group had significantly lower mean serum Se levels [77.3 μg/L (28.3) vs. 81.9 (34.7), p = .005] and a lower, non- significant proportion in the 3rd tercile of MEPA scores for Se-rich food groups (9.9% vs. 13.0%, p = 0.140). The Se-rich food groups most strongly associated with serum Se levels were Nuts, Fish, Whole Cereals, and Olive oil. In adjusted models, the 3rd tercile of Se [RR: .70 (.53, .93), p = .019] and the interaction between the 3rd tercile of Se and the 3rd tercile of MEPA score for Se-rich food groups [RR: .46 (.230, .94), p = .034] were associated with a lower risk of migraine. Conclusion: In the ELSA-Brasil Study, higher serum Se concentration and its relation with Se-rich food groups were associated with a lower risk of migraine, suggesting a protective effect of a high-Se diet within recommended levels. P109 Rapid eye movement sleep-dependent obstructive sleep apnea among patients with mild obstructive sleep Apnea and migraine or cluster headache Y. Hong1, M. K. Kang1, S. J. Cho1 1Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Nrurology, Hwaseong, South Korea on OSA and suspicion study aims to elucidate Objective: This the relationship between mild OSA, REM sleep-dependent OSA patterns, and sleep parameters in patients with migraine or cluster headache (CH). Methods: This single-centered, retrospective study analyzed data from patients with CH and migraine who underwent polysomnography (PSG). Assessing the relationship between mild OSA and these primary headache disorders. Mild OSA was defined as an apnea- hypopnea index (AHI) of 5 or more and less than 15. REM sleep-dependent OSA was defined as overall AHI ≥ 5, Non-REM-AHI < 15, and REM AHI/Non-REM-AHI ≥ 2. Results: A total of 136 patients (105 migraine, 31 CH) underwent PSG. OSA was diagnosed in 85 migraine and 25 CH patients. Among these, 47 (44.8%) migraine and 14 (45.2%) CH patients had mild OSA. Mean ages were 43.43 ± 10.59 for migraine and 38.86 ± 7.86 years for CH. In the migraine group, 29 (61.7%) were male; all CH patients were male. Average REM sleep durations were 49.61 ± 20.46 minutes for migraine and 39.82 ± 21.10 for CH. While total AHI was mild, REM AHI per hour was higher at 20.82 ± 17.25 for in migraine and 10 (71.4%) migraine and 22.59 ± 15.39 for CH, compared to non- REM AHI of 7.26 ± 2.99 and 5.46 ± 1.88, respectively. The prevalence of REM sleep-dependent OSA was 24 (51.1%) in CH; the difference was not statistically significant (p=0.178). Conclusion: Despite mild OSA based on AHI, many migraine and cluster headache patients showed moderate-to-severe REM-related apnea/hypopnea events, highlighting sleep-disordered breathing during REM sleep in these groups. The study suggests a link between REM sleep-dependent OSA and primary headache disorders like migraine and cluster headaches, meriting further investigation. Total AHI may vary with REM sleep duration during polysomnography, so repeat tests might be needed for patients with REM sleep-dependent OSA and headache disorders. P110 Concomitant anti-CGRP drug and immunomodulator treatment in patients with autoimmune diseases: results of the multicenter "ImmunoCGRP" study on migraine M. C. García-Castillo1, Á. Sierra Mencia2, A. Recio García2, Á. L. Guerrero-Peral2, A. Sánchez Soblechero3, E. Luque Buzo3, A. Lozano Ros3, S. Urtiaga4, M. Gonzalez Salaices4, D. Toledo5, A. Muñoz-Vendrell6, S. Campoy7, M. Huerta7, G. Martín Ávila8, J. Casas9, S. Santos-Lasaosa10, M. Polanco Fernández11, V. González Quintanilla11, J. Pascual11, V. García12, A. Mínguez Olaondo12, M. L. Cuadrado13, L. Portocarrero Sánchez14, J. Díaz-De-Terán14, E. Caronna15, P. Pozo- Rosich15, L. Rubio-Flores16, A. B. Gago-Veiga17,18, A. González Martínez17,18 1Faculty of Medicine, Universidad Autónoma de Madrid, Madrid, Spain 2Unidad de Cefaleas, Departamento de Neurología, Hospital Clínico Universitario de Valladolid., Valladolid, Spain 3Unidad de Cefaleas, Servicio de Neurología, Hospital Universitario Gregorio Marañón, Madrid, Spain 4Unidad de Cefaleas, Servicio de Neurología, Hospital de Torrejón, Torrejón, Spain 5Unidad de Cefaleas, Servicio de Neurología, Hospital 12 de octubre, Madrid, Spain 6Unidad de Cefaleas, Servicio de Neurología, Hospital de Bellvitge., Bellvitge, Spain 7Servicio de Neurología. Hospital de Viladecans, Viladecans, Spain 8Servicio de Neurología. Hospital Universitario de Getafe, Getafe, Spain 9Servicio de Neurología. Hospital Universitario Fundación Alcorcón., Alcorcón, Spain 10Servicio de Neurología. Hospital Clínico Universitario Lozano Blesa, Zaragoza, Spain 11Servicio de Neurología. Hospital Universitario

Marqués de Valdecilla., Santander, Spain 12Servicio de Neurología. Hospital Donostia-Donostia Ospitalea. Donostia, San Sebastián, Spain 13Servicio de Neurología. Complejo Universitario de San Carlos., Madrid, Spain 14Servicio de Neurología. Complejo Universitario la Paz., Madrid, Spain 15Servicio de Neurología. H. Universitari General de la Vall D'hebron., Barcelona, Spain 16Servicio de Neurología. Instituto de Neurociencias Vithas, Madrid, Spain 17Hospital Universitario de la Princesa, Neurology Department, Madrid, Spain 18Instituto de Investigación Sanitaria Princesa (IIS- Princesa), Madrid, Spain combined an and role in Preclinical evidence suggests performed CGRP-mAbs (CGRP-mAbs) that Objective: calcitonin gene-related peptide (CGRP) plays an immunoregulatory migraine pathophysiology.This study aims to evaluate the effect of CGRP blockade by anti-CGRP monoclonal antibodies with immunosuppressants in patients with migraine and autoimmune diseases. Methods: We observational multicenter study including patients with migraine treated with concomitant immunomodulatory drugs, registered in Headache Units/specialized headache clinics. Results: Among a total of 170 patients with migraine with comorbid autoimmune disorders, 51 patients were treated with CGRP-mAbs and concomitant immunomodulatory drugs. Among them, 46 (90%) women, with a median age of 47 (SD: 10) years, 43 (84%) had chronic migraine. There were 17 (33%) patients with rheumatoid arthritis, 10 (20%) with multiple sclerosis, 14 (27%) with inflammatory bowel disease and 2 (4%) with psoriasis, with an average of concomitant 22 immunomodulatory serious adverse events were recorded in 14 (27%) with no significant differences between the autoimmune diseases (p=0.533). No infections or serious adverse effects were observed. A reduction of 10, 11 and 10 days per month and 9, 10 and 6 days per month at 6, 12, and 24 months respectively was observed. Autoimmune disease worsened in 10 (20%) patients, and 1 (10%) had to discontinue treatment due to associated worsening. Conclusion: Our study supports the effectiveness and safety using other in patients with immunomodulatory migraines and autoimmune diseases. This research paves the way for future studies on the role of CGRP in the immune system and its clinical implications. CGRP-mAbs with 19) months treatments treatment. (SD: of Non of P111 How depression outweighs anxiety and vertigo in sleep quality of migraineurs M. D. Villar Martinez1, Z. Lahrie1, R. Lim1, P. J. Goadsby1 1King's College London, London, United Kingdom patients Fifty-nine completed Objective: To investigate the relationship between vertigo, mental health variables and sleep quality in a cohort of patients with chronic migraine. Methods: A negative binomial regression model with log link function was employed using rStudio (version 4) given the overdispersion of the dependent variable. As dependent variable we included the total score of the Pittsburgh Sleep Quality Index, and the results of the Patient Health Questionnaire-8 (PHQ-8), General Anxiety Disorder Test-7 (GAD-7), Situational Vertigo Questionnaire (SVQ), Dizziness Handicap Inventory (DHI) and Patient Global Impression of Change (PGIC), as predictors. the Results: questionnaires. The overall model fit was acceptable, with a residual deviance of 63.164 on 53 degrees of freedom and an AIC of 329.39. The model revealed that only PHQ-8 (B = 0.0252, P = 0.0419) was a significant predictor of sleep quality, indicating that higher depression scores are associated with poorer sleep quality. However, GAD (B = 0.0075, P = 0.5881), SVQ (B = 0.0017, P = 0.5187), PGIC (B = 0.0086, P = 0.2451), and DHI (B = -0.0009, P = 0.7525) were not significant predictors. Conclusion: The findings suggest that depression severity, is significantly associated with sleep quality in the studied population. However, anxiety, vertigo, perceived and dizziness handicap do not appear to have a significant impact. These results highlight the importance of addressing depressive symptoms to improve sleep quality among patients with sleep disturbances. Further research is needed to explore these relationships in larger and more diverse samples. improvement, global P112 Psychological and biological markers of refractory migraine – data from a 6-month follow-up S. Bottiroli1,2, R. Greco2, V. Franco3, A. M. Zanaboni2, M. Palmisani2,3, G. Vaghi1,2, E. Guaschino2, N. Ghiotto2, R. De Icco1,2, G. Sances2, C. Tassorelli1,2 1University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 2Fondazione Mondino IRCCS, Pavia, Italy 3University of Pavia, Pavia, Italy Objective: Refractory migraine is an aggressive form of the disease in which the patient does not respond to any preventive medications, including monoclonal

of are unknown. Dysfunction antibodies (mAB). Compelling evidence indicates that psychopathological disorders may have a detrimental outcome, although the underlying neurobiological reasons the endocannabinoid (EC) system may also play a role. The current study seeks to discover psychological and peripheral endocannabinoid components changes related to resistance to mAB treatment. Methods: Eighty subjects with chronic (CM) or episodic (EM) migraine received mABs treatment and were followed up at 6 months for their clinical condition. At T0, the patients underwent a psychological evaluation according to the DSM-V for mood, anxiety, and personality disorders. Gene expression of enzymes involved in the synthesis and degradation of ECs and their receptors were assessed in peripheral blood mononuclear cells, while levels of ECs and related lipids were evaluated in plasma. Results: At the 6-month follow-up, 45 subjects reported a reduction ≥50% in monthly migraine days (Responders); whereas 28 did not (Refractories). When compared to Responders, Refractories were characterized by a higher prevalence of anxiety disorders (67% vs 40%, p=.019), personality disorders belonging to Cluster C (64% vs 33%, p=.009), more alexithymic traits (45.3±10.8 vs 39.8±8.4, p=.016), and a higher prevalence of childhood trauma (57% vs 29%, p=.016). Refractories had higher levels of gene expression of the enzymes NAPE-PLD (1.7±0.5 vs 1.4±0.5, p=.006) and MAGL (1.7±0.7 vs 1.4±0.5, p =.049) compared to Responders. No other differences resulted between groups. Conclusion: The findings suggest that psychological vulnerability associated with a peripheral alteration in the metabolism of N-acyl ethanolamines (NAEs) and 2-AG is indicative of a negative outcome of mAB treatment in migraine. P113 Pediatric onset multiple sclerosis and primary headaches – Is there a link? L. Papetti1, G. Tiralongo2, G. Monte1, M. A. N. Ferilli1, S. Tarantino1, M. Proietti Checchi1, M. Valeriani1 1IRCCS Bambino Gesù, Tor Vergata University, Developmental Neurology Unit, Rome, Italy 2IRCCS Bambino Gesù, Tor Vergata University, Accademia Pediatrica, Rome, Italy Objective: The objective of our study is to study what impact primary headaches have on the clinical, neuroradiological and therapeutic course in our patients with pediatric mulitple sclerosis (MSp) Methods: We conducted a retrospective analysis from January to April 2024 on a PMS population to verify whether there are differences between the two populations of PMS patients with headache and symptoms associated without headache. The definition of headache and its respective categories is based on the ICHD-3 criteria. For each cephalalgic patient, the frequency of headaches and any chronicity, aura, location, side, and quality of the pain were evaluated in the analysis, together with (photo- phonophobia, nausea and vomiting), and then the response to painkillers and prophylactic therapies. We used the chi-test for the categorical variables [type of therapy, sex and lesion load, defined as low with lesions 10] and Anova test for the continuous variables (age at onset of the disease) and placed significance at p < 0.05. Results: Our sample consists of 64 patients with PMS (average onset: 13.6 years - 5.4 and 17.8), of which 50 with headache and 14 without headache. From our analysis no significant relationships emerged between age at onset, type of therapy or lesion load. However, a relationship with sex emerged (F-SMp 37/50; M- SMp 13/50 - p < 0.05), with prevalences of primary headaches similar to those of the general population. Similarly, patients with migraine are those who most frequently may present a high frequency of attacks compared to tension headaches and the need to resort to prophylactic therapies (p < 0.05). Conclusion: Our data support the hypothesis that in pediatric age there is no relationship between primary headache and some parameters related to MS such as age at onset, type of drug and extent of lesion load. The progress of the two diseases therefore seems independent. P115 Fatigue in migraine patients and its clinical correlates H. Tsung-Wei1, T. Yi-Shiang2, C. Shih-Pin2,3,4,5,6, L. Yu- Hsiang2,4, C. Wei-Ta2,4,6,7, W. Shuu-Jiun2,4,6, W. Yen- Feng2,4,6 1Taichung Veterans General Hospital, Department of Neurology, Neurological Institute, Taichung, Taiwan 2Taipei Veterans General Hospital, Department of Neurology, Neurological Institute, Taipei, Taiwan 3Aipei Veterans General Hospital, Division of Translational Research, Department of Medical Research, Taipei, Taiwan 4National Yang Ming Chiao Tung University, College of Medicine, Taipei, Taiwan 5National Yang Ming Chiao Tung University, Institute of Clinical Medicine, Taipei, Taiwan 6National Yang Ming Chiao Tung University, Brain Research Center, Taipei, Taiwan 7Ministry of Health and Welfare Keelung Hospital, Department of Neurology, Keelung, Taiwan Objective: There was limited data on fatigue in migraine patients. The objectives of the study were to

(1) determine the prevalence of fatigue in migraine patients,(2) compare the clinical manifestations between migraine patients with and without fatigue,and (3) identify risk factors for fatigue in migraine. Methods: This cross-sectional study involved migraine patients from the headache clinic of a tertiary medical center. Fatigue was assessed using Fatigue Severity Scale (FSS), and the presence of fatigue was defined as FSS ≥4. Questionnaire-based interviews were used to collect demographics and other clinical profiles, including Migraine Disability Assessment (MIDAS), Hospital Anxiety and Depression Scale (HADS), and Pittsburgh Sleep Quality Index (PSQI). Results: 2082 migraine patients (1635F/447M, mean age 38.3±12.5 years) were analyzed, including 1195 with fatigue (950F/245M, mean age 37.4 ± 12.0 years) (57.4%). The proportions of patients with fatigue were positively correlated with the severities on HADS-A, HADS-D, and MIDAS (all p<0.001, Cochran-Armitage test for trend), and patients with fatigue were more likely to have poor sleep quality (63.0% vs. 29.7%, p<0.001). Factors associated with fatigue included younger age (odds ratio [OR] 0.98 per year, [95% interval 0.97-0.99], p<0.001), and the confidence presence of depression [1.68-2.71], p<0.001), anxiety (OR 3.26 [2.37-4.54], p<0.001), poor sleep quality (OR 3.02 [2.31-3.97], p<0.001), and at least moderate disability [1.72-2.59], p<0.001) after controlling for demographics, and frequencies of migraine and acute medication use. Conclusion: Fatigue was reported by more than half of the patients in the present cohort. Screening for fatigue should be considered in the evaluation of migraine patients, especially in those with a more severe phenotype. Whether appropriate management for psychiatric comorbidities and sleep problems, in addition to migraine treatment, could reduce the severity of fatigue needs to be further explored. (OR 2.13 (OR 2.11 Fig. 1 Fig. 2

Fig. 3 P116 Characteristics of patients with cluster headache presenting to a tertiary headache center – a cross- sectional study K. S. Lange1,2, L. H. Overeem1,3, M. Ulrich1, M. P. Fitzek1,4, J. Dorn1, J. B. Hong1, U. Reuter1,5, B. Raffaelli1,2 1Charité – Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany 2Berlin Institute of Health at Charité (BIH), Berlin, Germany 3Doctoral Program, International Graduate Program Medical Neurosciences, Humboldt Graduate School, Berlin, Germany 4Berlin Institute of Health at Charité (BIH), Berlin, Germany 5Universitätsmedizin Greifswald, Greifswald, Germany Objective: Cluster headache (CH) as one of the most disabling primary headache disorders is considered underdiagnosed and often inappropriately treated. We aimed to assess characteristics of patients with CH referred to our tertiary headache center, and to compare those to patients with migraine. Methods: This analysis is part of a cross-sectional study conducted at the Headache Center of the Charité – Universitätsmedizin Berlin between December 2015 and January 2023. All patients who came for their first visit were asked to complete an anamnesis questionnaire including data on disease duration, treatments. Moreover, we collected Patient-Reported Outcome Measures (PROMs), using the Headache Impact Test (HIT-6), the Depression, Anxiety and Stress Scale 21 (DASS-21), and the Short Form 12 (SF-12). We compared characteristics of patients diagnosed with CH to patients with migraine matched for age and sex. comorbities, and prior Results: Of 1468 patients presenting for the first time at our tertiary headache center (43 ± 14 years; 74.5% women), 56 (44 ± 9 years; 23.2% women) were diagnosed with CH. Compared to patients with migraine, patients with CH had a shorter disease duration from onset to referral (5.5 [7.3] years vs. 18.0 [16.8] years, p <0.001), but the same number of prior treatment attempts for acute and preventive medication (2 [2] vs. 2 [1], p=0.337 and 1 [2] vs. 1 [2], p=0.675, respectively). Smoking and illicit drug use were more frequent among patients with CH (51.8% vs. 19.6, p<0.001 and 30.4% vs. 7.1%, p=0.003, respectively). scores did not differ significantly. indicate an adequate Conclusion: These results medical attention for CH among referring physician to a tertiary headache center. A higher prevalence of lifestyle risk factors among CH patients warrants further research on a possible role for development or exacerbation of CH and preventive measures. PROMs P117 Elevated cytokine levels in the central nervous system of cluster headache patients in bout and in remission C. Ran1, F. Jennysdotter Olofsgård1, K. Wellfelt1, A. Steinberg2,3, A. Carmine Belin1 1Karolinska Institutet, Department of Neurosciences, Stockholm, Sweden 2Karolinska Institutet, Department of Clinical Neuroscience, Stockholm, Sweden 3Karolinska University Hospital, Department of Neurology, Stockholm, Sweden To further pathophysiology. in cluster headache, Objective: Cluster headache is characterized by activation of the trigeminovascular pathway with subsequent pain signalling in the meningeal vessels, and inflammation has been suggested to play a role in the investigate inflammatory inflammation markers were analysed in biological tissue from patients with cluster headache and in heathy controls. Methods: We performed a case-control study, analysing cerebrospinal fluid and serum samples from 40 healthy controls, and 34 cluster headache patients. Samples were collected in remission, active bout, and during an attack to compare the different phases of cluster headache. Inflammatory markers were quantified using Target 48 OLINK cytokine panels at SciLifeLab Affinity Proteomics Uppsala, and analyzed in R using the OlinkAnalyze package. Results: Altered levels of several cytokines were found in patients with cluster headache compared to controls. CCL8, CCL13, CCL11, CXCL10, CXCL11, HGF, MMP1, TNFSF10 and TNFSF12 levels were elevated in cerebrospinal fluid from cluster headache patients. In

group (p = 4.07e-8). This association became stronger when we selected patients that report a diurnal rhythmicity to their attacks (p = 3.16e-8). Conclusion: Globally these results further strengthen the role of the circadian clock in CH. P119 The epilogue study: Exploration of patients in remission, life course, onset and disease proGression in cluster headache W. Naber1, P. van Tilborg1, R. Brandt1, R. Fronczek1 1Leiden University Medical Center, Neurology, Leiden, Netherlands Objective: This study aims to gain insight into the intriguing yet sparsely documented phenomenon of cluster headache (CH) remission. Methods: In this single-center, cross-sectional study all persons (N=1803) with CH in our database were invited to complete a screening survey. Participants in remission were included and invited for a structured interview. Remission was defined as (1) no current CH prophylactic treatment and (2) an attack free period of either ≥ 5 years or twice the mean between-bout time. Outcomes included average age at remission onset, years with active CH, incidence rate and predictors of remission. Results: 150 remission participants were identified and 97 were interviewed (Table1). Mean age at remission onset was 55±11. This was 55±10 in males, 53±14 in females, 54±11 in episodic CH (ECH) and 61±6 in chronic CH (CCH, Figure 1). Mean age of CH onset was 31±14 overall, 32±13 for males, 31±14 for females, 35±13 for CCH and 29±13 for ECH. On average, CH lasted 24±12 years before remission. This was 26±12 years in males, 20±12 in females, 17±9 in CCH and 25±12 in ECH. This cohort"s incidence rate was 9.4 new cases of remission per 1000 persons/year. In 61(63%) remission occurred abruptly. Of those with gradual remission(N=35), attack frequency (63%) and intensity (51%) decreased and between-bout increased (56%) prior to remission (Figure 2). Conclusion: In this rare insight in CH remission, CH started in the early 30s, lasted for 25 years before remission mid-50s. Possible premonitory signs of remission were decreasing attack frequency and intensity plus lengthening between-bout times. intervals serum samples, CCL11 and CXCL11 levels were lower in patients than controls. Comparing the different phases of cluster headache, we found that cytokine levels were similar in active bout and remission. Only one cytokine, IL-13 was increased in serum during cluster headache attacks. Conclusion: Our data shows signs of possible neuroinflammation occurring in biological samples from cluster headache patients. Also, cytokine levels are increased in cerebrospinal fluid from patients in active bout and during indicating neuroinflammation could be considered a marker for cluster headache and is unrelated to the different phases of the disorder. remission, P118 Higher occurrence of genetic variants in core clock genes among patients with cluster headache C. Deborgies Sanches1, C. Fourier1, F. Jennysdotter Olofsgård1, A. Steinberg2,3, A. Sundholm1,2, M. Lantz3,4, C. Sjöstrand3,4, E. Waldenlind2,3, C. Ran1, A. Carmine Belin1 1Karolinska Institutet, Neuroscience, Solna, Sweden 2Karolinska Institutet, Neurology, Stockholm, Sweden 3Karolinska Institutet, Clinical Neurosciences and Mental Health, Stockholm, Sweden 4Danderyd Hospital, Neurology, Stockholm, Sweden remain (CH) pathophysiology Objective: The full mechanisms underlying cluster headache to be elucidated. The rhythmicity of the attacks and seasonality of the bouts hint towards a dysfunction of the molecular clock. We therefore investigated genetic variants of Brain and muscle ARNT-like 1 (BMAL1) and Neuronal PAS domain protein 2 (NPAS2), two central regulators of the molecular clock. Methods: Six genetic variants were selected based on their link with circadian alterations and were genotyped using QuantStudio 5 Real-Time PCR System in patients with a verified CH diagnosis (n = 708) and controls (n = 682). A multiple allelic risk analysis was done to investigate if a combination of several risk alleles located in clock genes were more present in CH patients than in the general population. Risk alleles were selected from previous publications and the present study. Results: The minor allele of the BMAL1 variant, rs3789327, previously associated with bipolar disorder, was found to be significantly more present among CH patients (p < 0.01). Another significant variant whose minor allele was more common in the CH group was rs3768984 (p < 0.05), an NPAS2 variant associated with sleep disturbances. The multiple allelic risk analysis revealed that carriers of higher numbers of risk variants are significantly more likely to belong to the CH group rather than the control

Fig. 1 Fig. 3 Fig. 2 P120 Transition of cluster headache: Depicting side- changing attacks as a chronic trait. An interview- based follow-up study M. L. Kulas Søborg1, A. S. Petersen1, N. Lund1, M. Barloese1, R. Højland Jensen1 1Rigshospitalet Glostrup, Department of Neurology, Glostrup, Denmark Objective: Cluster headache presents in an episodic and chronic form, between which patients can convert during the course of disease. We aimed to quantify the rate of cluster headache patients changing phenotype within one- and five-years and investigate the earlier proposed association between chronification and having side-shifting attacks. Methods: 430 cluster headache patients well- characterized according to current ICHD-criteria, all participants in a prior transition-study, were re- interviewed in an observational, retrospective, cross- sectional follow-up study design at the Danish Headache Center. Results: The transition-rate for the whole cohort was 6.5% within one year and19.8% within five years. The risk of becoming chronic if episodic was 4.0% within one year and 12.3% within five years. For conversion from chronic to episodic, the corresponding risk was 11.1% and 25.0%, respectively. Alterations in attack- side were reported in 32% of all chronic patients, generating an odds-ratio of 2.24 of being chronic as opposed to episodic if experiencing side-shifting attacks Conclusion: A higher transition-rate since the original cross-sectional study demonstrates cluster headache as a non-static condition. Identifying a risk of transition within one- and five years based on current phenotype along with high odds of being chronic when experiencing a shift of attack-side, offers a valuable clinical compass in the dialogue with the patient.

was longer. Patients overused simple analgesics and opioids, indicating inappropriate CH treatment. We suggest that future studies should investigate the effect of withdrawal of analgesics with respect for triptans being effective and allowed for CH attacks. P122 Variability in circadian patterns of activity in cluster headache patients S. Spulber1, C. Ran1, A. Belin1 1Karolinska Institutet, Neuroscience, Stockholm, Sweden Objective: Cluster headache (CH) is the most common form of the trigeminal autonomic cephalalgias with a strong genetic component, but currently unknown pathophysiology. About 2/3 of all patients report symptoms with well-defined circadian distribution, prompting chronobiological investigations. The aim of this study was to investigate the variability in circadian patterns of activity in CH patients. Methods: We used actigraphy recordings spanning at least 4 consecutive days acquired on CH patients validated according to ICHD-3, either episodic (n=13) or chronic (n=12), and on healthy controls (n=34). Each individual recording was split in 2h-epochs (50% overlap) then a set of features describing the variability and complexity of the time series was calculated on each epoch. Next, we applied a dimensionality reduction procedure using exclusively control recordings, then mapped the time series from CH patients on the model developed on controls and used a self-similarity metric to yield synthetic series summarizing the circadian variations in activity patterns. Affinity propagation clustering identified 6 distinct clusters of circadian activity patterns within the CH patient group. Results: We found that each cluster was particularly enriched in days recorded in either chronic or episodic CH patients, yielding clear separation between patient groups. In addition, within-patient variability in cluster assignment was restricted to a limited number of clusters (3±0.2, mean±sem) throughout the duration of the recording. Conclusion: Taken together, our data indicate that chronic and episodic CH patients have distinct circadian patterns of activity. Fig. 1 P121 Medication overuse headache does also occur in cluster headache N. Lund1, M. L. K. Soeborg1, R. Højland Jensen1, A. S. Petersen1 1Danish Headache Center, Department of Neurology, Rigshospitalet Glostrup, Glostrup, Denmark Objective: It is a topic of debate if medication overuse headache (MOH) exists in cluster headache (CH). We aimed to examine this, describe associated clinical characteristics and impact on treatment. Methods: Data derived from a retrospective cohort of interview-validated CH patients (ICHD-3) recruited from a tertiary headache clinic. MOH was very conservatively defined as a medication overuse (excluding triptans) according to ICHD-3 and a daily bilateral headache. Patients with triptan overuse (n=3) were excluded as this treatment is specifically indicated for CH. Results: A total of 433 CH patients with a male:female ratio of 2:1 were included. MOH was present in 8.7% chronic patients and 2.1% episodic. A bilateral daily headache was only present in 5.1% without MOH. Among patients with MOH, 73.7% overused simple analgesics, 31.6% opioids, and 15.8% combination therapies. Comparing patients with and without MOH, patients with MOH more often reported comorbid migraine (37 vs 15%, p<0.01), comorbid tension-type headache (37 vs 11%, p<0.01) and median treated attack duration was longer (30 vs 25 minutes, p<0.01). Median weekly attack frequency and sex did not differ significantly between the two groups (11 vs 17 attacks/week and male sex for 47 vs 68%). In a multivariate regression model, MOH was associated with chronic CH (p<0.05) and comorbid tension-type headache (p<0.05), whereas migraine, sex and age were not significantly associated factors. Conclusion: Our data indicate that it is also clinically relevant to address MOH in CH, especially in patients with tension-type headache.Besides from their CH attacks, CH patients with MOH are burdened with a daily bilateral headache and their attack duration with treatment chronic CH and comorbid

P123 Role of specific microRNAs in cluster headache: correlation with disease phenotype and neuropeptide levels F. Cammarota1,2, R. De Icco1,2, F. Bighiani1,2, M. Corrado1,2, G. Vaghi1,2, A. Antoniazzi1,2, E. Mazzotta1,2, V. Grillo1,2, R. Greco2, C. Demartini1,2, A. M. Zanaboni1,2, M. Francavilla1,2, S. Franchini1,2, M. Allena2, G. Sances2, C. Tassorelli1,2 1University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 2Fondazione Mondino IRCCS, Headache and Neurorehabilitation Research Center, Pavia, Italy in cluster headache Objective: The role of specific microRNAs was studied in episodic and chronic migraine, but their possible involvement is yet to be elucidated. Our objective is to evaluate the role of specific microRNAs in episodic cluster headache in active phase (AeCH), remission phase (ReCH), chronic cluster headache (cCH), and healthy controls (HCs). Methods: In this cross-sectional study, we enrolled 18 AeCH patients, 7 ReCH patients, 10 cCH patients, and 14 HCs. All subjects underwent a single fasting blood sampling. We assessed gene expression of miR-382- 5p, miR-34a-5p, and miR-155 in peripheral blood mononuclear cells (unit of measure: Relative Quantification respect to U6 housekeeping gene). AeCH and cCH patients were assessed outside of an acute cluster headache attack. Results: We enrolled 18 AeCH (45.7±12.8 years, 14 males, 16.3±9.6 attacks/week), 7 ReCH (48.6±19.8 years, 5 males), 10 cCH (50.1±16.2 years, 9 males, 21.4±18.8 attacks/week), and 14 HCs (45.4±15.2 years, 2 males). miR-382-5p expression was higher in AeCH (1.7±0.8) when compared to ReCH (0.8±0.2) and HCs (0.3±0.1) (p<0.005 for all comparisons). miR-34a expression was higher in AeCH (1.7±0.4) when compared with ReCH (1.0±0.3), cCH (1.2±0.3) and HCs (0.5±0.2) (p<0.001 for all comparisons). miR-155 expression was higher all CH subgroups compared to HCs (0.4±0.1; p=0.001 for all comparisons), with no difference among AeCH (1.7±0.5), ReCH (1.3±0.3) and cCH (1.3±0.5). Conclusion: miR-382-5p, miR-34a-5p and miR-155 expression are increased in cluster headache when compared to HCs. Specifically, miR-382-5p and miR- 34a-5p were associated with disease activity, being higher in AeCH patients when compared to ReCH. microRNAs expression of cCH was in-between active and remission phases of episodic cluster headache patients. Our data supports the role of specific microRNAs in the pathophysiology of different primary headaches. P124 Gradual treatment of refractory cluster headache with NMDA receptor antagonists L. Granata1, A. Pantovic2, L. Sakellaris1 1Cluster competence center Granata, Zürich, Switzerland 2Neurology clinic MMA, University of Defence, Belgrade, Serbia responders (reduction Objective: Cluster headaches (CH) could be resistant to recommended treatments. The activation of NMDA receptors has been associated with abnormal central pain processing. Ketamine and opioid methadone are both NMDA receptor antagonists with different mechanisms of action and potential to be synergistic co-analgesics. The objective of the study is to investigate the efficacy and safety of intravenous ketamine and oral methadone in the gradual treatment of refractory cluster headache Methods: We conducted an open-label pilot study evaluating 47 refractory CH patients (no response despite three consecutive trials of recommended preventive drugs). The patients have been divided into 3 groups: responders (complete cessation of attacks), partial in pain intensity or frequency) and non-responders (no changes in pain intensity and frequency). The patients received low-dose intravenous ketamine, once daily over 40 minutes at the dosage of 0.5 mg/kg, administered in 3 to 11 sessions. Non-responders and partial responders to ketamine were co-treated with oral methadone. In a short-duration regimen, the dose of methadone was increased up to a maximum of 40 mg daily. In 38.3% of ketamine-treated patients Results: cessation of attacks was achieved (ketamine responders group). In the partial responders ketamine group and non-responders ketamine group (61.7%) oral methadone was added on. An additional 31.9% of cessation patients (ketamine/methadone The favourable response was 70.2%, either with ketamine alone or in combination with oral methadone. Partial in response of ketamine/methadone gradually treated patients (ketamine/methadone partial responders group), 4.3% of patients had no response to gradual treatment (ketamine/methadone non-responders group) and 6.4% were drop-out patients. No serious adverse events were identified Conclusion: Ketamine with or without methadone plays a role in the interruption of prolonged episodes and chronic form of refractory CH. attacks responders observed was 19.1% achieved group).

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P125 Predictors of premonitory symptoms in patients with cluster headache and comparative study with migraine patients A. González Martínez1, D. Wei1,2, N. Karsan1, K. Nagaraj1, H. Gosalia1, P. J. Goadsby1,2,3 1NIHR King’s Clinical Research Facility and Wolfson SPaRCKing’s College London, London, United Kingdom 2King's College Hospital, Department of Neurology, London, United Kingdom 3University of California, Los Angeles, CA, United States Objective: Our knowledge of premonitory symptoms in cluster headache (CH) is limited. Here we aimed to identify possible predictors of premonitory symptoms in patients with CH, including a comparison with patients with migraine. Methods: Premonitory symptom presence and type in a clinical cohort of CH and migraine patients were interview. collected using a standardised clinical Demographic data and premonitory symptoms patients were analyzed. The primary focus was on premonitory symptom presence and phenotype in CH patients, with secondary analysis exploring predictors of the presence of premonitory symptoms in the CH patient cohort. Moreover, we compared premonitory symptoms in patients with CH to those in patients with migraine. Results: In the clinical CH cohort (n=164), 122 (74%) were males, with a mean age of 45.9 (SD: 13.8) years. Chronic CH was present in 66 (40%), and 36 (22%) had comorbid migraine. Premonitory symptoms were reported by 85%, most commonly mood changes, cognitive impairment and neck discomfort. A forward and backward stepwise logistic regression model was estimated to evaluate differences between patients with and without premonitory symptoms. The logistic regression analysis revealed that oxygen treatment and smoking were significantly associated with the presence of premonitory symptoms in the clinical CH cohort in CH patients were more similar in frequency to those in migraine patients (n=286) than in CH patients without comorbid migraine. recognizable Conclusion: This identifies in CH, with spontaneous premonitory symptoms predictors potentially impacting CH management. Understanding these relationships may aid in tailoring treatment strategies, treatment prediction and early intervention. (P<0.05). Premonitory symptoms study P126 The effect of an injection with methylprednisolone and lidocaine around the greater occipital nerve on the R2 component of the blink reflex and the clinical response in patients with episodic and chronic cluster headache W. Naber1, P. van Tilborg1, M. Tannemaat1, M. Niesters1, M. Hellinga1, R. Brandt1, R. Fronczek1 1Leiden University Medical Center, Neurology, Leiden, Netherlands blink nociceptive Objective: Infiltration of the greater occipital nerve (GON) with a local anesthetic and corticosteroids is effective in the treatment of both episodic and chronic cluster headache. This effect is hypothesized to be due to altered trigeminal transmission. We aim to explore the effect of GON-infiltration on trigeminal transmission in relation to clinical response Methods: In this single-center, prospective cohort study, participants with either episodic (n=17) or chronic cluster headache (n=16) were followed 12 weeks post-GON injection with daily e-diary monitoring reflex and measurements at four timepoints: 30 minutes before injection; and 30 minutes, one week, and four weeks post-injection. The primary outcome was the R2 latency. Primary and secondary outcomes were compared using linear mixed models. Results: 41 participants were included (Table 1). No differences in R2 latencies were observed, except for a faster R2 latency ipsilateral to the injection side four weeks after the GON injection (Figure 1). Attack frequency and intensity lowered after infiltration of the GON. The daily attack frequency lowered in week 1 and week 4 compared to baseline (Δ -1.0 [ 95% CI 0.90 to 2.36], P <0.001; Δ -1.6 [95% CI 1.26 to 2.86], P<0.001, Figure 2). 75.8% (25/33) of participants had ≥30% reduction of their cluster headache attacks and 27.3% (9/33) was attack-free at week four. No correlation between R2 latency and clinical response was observed. Conclusion: Although effective, the mechanism of the GON-injection remains enigmatic. Our results suggest that clinical efficacy is not primarily due to altered trigeminal neurotransmission.

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Fig. 1 Fig. 2 Fig. 3 P127 Impact of smoking on clinical features and treatment responses in cluster headache patients – a cross- sectional study P. Yalinay Dikmen1, B. Baykan2, E. Ilgaz Aydinlar1, E. Kocasoy Orhan2, E. Ekizoglu2, F. Selcuk3, A. Özge4, A. Sahin Misir1, T. Erdogan Soyukibar1, E. Hacilar2, Y. Karatas1, M. Ertas2 1Acibadem University School of Medicine, Neurology, Istanbul, Turkey 2Istanbul University, Istanbul Faculty of Medicine, Neurology, Istanbul, Turkey 3Burhan Nalbantoglu Hospital, Neurology, Nicosia, Cyprus 4Mersin University Faculty of Medicine, Neurology, Mersin, Turkey Objective: Smoking is thought to be significantly associated with cluster headache (CH). This study aimed to evaluate the impact of cigarette exposure on the clinical features and treatment responses of patients with CH. Methods: A total of 318 individuals (mean (SD) age: 45.0 (10.9) years; 76.7% males), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi- structured survey that included questions addressing sociodemographic characteristics, detailed clinical features, treatment experiences, and smoking-related information. Results: Of the participants, 73.9% (n= 235) had episodic CH, while the remaining 26.1% (n= 83) had chronic CH. The mean age at CH onset was 29.1 (11.9) years. The mean age at correct diagnosis of CH was 34.7 (11.1) years. Family history was identified in 10.4% (n=33) of the patients. Our cohort consisted of 21.4% (n=68) who never smoked (non-smoker) and 78.6% (n=250) who had quit (n=78) or were still smoking (n=172) (smoker). The average age at which smoking began was 20.0 (5.5) years. Current smokers had been smoking for an average of 24.4 (SD: 10.3) years, smoked an average of 21.3 (SD: 11.4) cigarettes per day, and maintained this level for 18.4 (SD: 11.5) years. Nasal congestion (60.3% (n= 41) vs. 73.2% (n=183); p=0.03), facial sweating (22.1% (n=15) vs. 35.6% (n=89); p=0.04), suicidal thoughts (16.2% (n=11) vs. 30.8% (n= 77; p= 0.02), the effectiveness of subcutaneous sumatriptan (82.4% (n= 56) vs. 57.6%) n=144); p<0.001) and oral triptans (51.5% vs. 31.6; p= 0.004) during an attack, the usefulness of ergotamine (25.0% (n=17) vs. 44.4% (n=111); p=0.005) and melatonin (20.6% (n= 14) vs. 10.8% (n=27) ; p=0.04) as preventive treatments were found to be statistically different between non-smokers and smokers. Conclusion: Smoking may influence certain clinical features and treatment responses in patients with CH.

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Large-scale prospective studies are needed understand the epigenetic effects of smoking in CH. to P128 Insights into the involvement of TRPA1 channels in the neuroinflammatory machinery of trigeminal neuralgia C. Demartini1, R. Greco1, A. M. Zanaboni1,2, M. Francavilla1,2, S. Facchetti1,2, C. Nativi3, C. Tassorelli1,2 1Fondazione Mondino IRCCS, Pavia, Italy 2University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 3University of Florence, Dipartimento di Chimica "Ugo Schiff", Sesto Fiorentino, Italy pathways following after inflammatory ADM_12/vehicle Objective: Antagonism of transient receptor potential ankyrin type-1 (TRPA1) channels counteracts the experimentally-induced trigeminal neuralgia pain. TRPA1 channels activated/sensitized by inflammatory stimuli can modulate glial cells activity, a driving force for pathological pain. Additionally, a functional interaction between the inflammatory-related toll-like receptor-7 (TLR7), activated by miR-let-7b, and TRPA1 was reported in vitro. Here, we aimed at investigating the potential mechanisms involving TRPA1 channels in the the development of trigeminal neuralgia. Methods: Adult male rats undergoing chronic constriction injury of the infraorbital nerve (IoN- CCI)/sham surgery were treated with the TRPA1 antagonist allodynia development. Trigeminal system-related areas and plasma samples were used to evaluate central and peripheral inflammatory mediators (by rt-PCR and ELISA) and immunofluorescence staining of glial activation in the trigeminal nucleus caudalis (TNC). Results: IoN-CCI rats showed a significantly higher activation of microglia and astroglia in the TNC compared to sham-operated rats. Additionally, in the trigeminal-related areas, IoN-CCI animals showed increased gene expression levels of pro-inflammatory cytokines, associated to lower gene expression levels of anti-inflammatory together with consistent altered changes in the respective protein plasma levels. ADM_12 in IoN-CCI rats prevented the observed alterations regarding cytokines, but did not affect glial activation in the TNC. It also counteracted the IoN-CCI-induced increase in miR-let-7b and TLR7 mRNA gene expression in all the considered areas, supporting a possible interplay with TRPA1 channels. Conclusion: The findings suggest that, besides their known involvement in the nociceptive pathway, TRPA1 channels may also play a direct or indirect role in pain-related inflammation, through the activation of the miR-let-7b/TLR7/TRPA1 axis at neuronal and glial level. cytokines, P129 Altered functional connectivity of the thalamus and medulla-pons in a rat model of migraine based on nitroglycerin administration R. Greco1, G. Castellazzi1, M. Francavilla1,2, S. Facchetti1,2, C. Demartini1, A. M. Zanaboni1,2, D. Martinelli1, C. Tassorelli1,2 1Fondazione Mondino IRCCS, Pavia, Italy 2University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy to other symptoms. The Objective: Migraine is a burdensome neurological disease that manifests with recurrent attacks of pain associated complex mechanisms underlying the disorder are only partly known. Resting-state functional magnetic resonance imaging (rs-fMRI) has provided important information in brain functional connectivity (FC) changes during migraine attacks, showing a reduction in FC between sensorimotor brain regions and other areas in migraine sufferers, impacting various processes such as visual processing, sensory integration, pain signal processing, attention, and cognitive assessment. In this pilot study, we used a validated animal model of migraine induced by a single administration of nitroglycerin (NTG) to explore the alterations in brain FC in a well-controlled experimental setting. Methods: Male Sprague-Dawley rats were injected with NTG (10mg/kg, i.p.) or vehicle (control group) 3 hours before undergoing rs-fMRI. Each acquired rs- fMRI series was preprocessed with the RABIES tool for removing noise and then parcellated using the rat brain anatomical SIGMA atlas to obtain a functional connectome. Parcellated rs-fMRIs were then analysed with the Brain Connectivity Toolbox in Matlab to calculate graph theoretical metrics for each atlas area. Results: A Statistical comparison (t-test) of graph metrics" values between NTG-treated rats and controls revealed a significant more marked in betweenness centrality (0.03±0.02 vs 0.007± 0.002) in the thalamus and increased Clustering Coefficient (0.05±0.032 vs 0.004 ±0.008) and Local Efficiency (0.085±0.05vs vs 0.048±0.108) in the pons. Conclusion: These findings suggest the enhanced functional influence of these brain regions on the networks of NTG-stimulated rats, shedding light on potential mechanisms underlying migraine-related alterations in brain connectivity. 0.004±0.008; 1.115±0.73

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P130 Intestinal dysbiosis and chronic migraine: preliminary assessment in an animal model S. Facchetti1,2, R. Greco1, A. M. Zanaboni1,2, C. Demartini1, M. Francavilla1,2, C. Tassorelli1,2 1Fondazione Mondino IRCCS, Section of Translational Neurovascular Research, Pavia, Italy 2University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy P131 Intravitreal CGRP administration results in retinal vessel dilation and an increased flicker ERG response in the rat K. M. Nordahl1, K. A. Haanes1 1Translational Research Centre, Copenhagen University Hospital, Sensory Biology Unit, Glostrup, Denmark and pathological processes Objective: The gut microbiota influences numerous physiological and modulates the bidirectional communication network between the gut and the brain, contributing to migraine pathogenesis. Here, we investigated changes in the gut microbiota composition in the chronic migraine-like animal model based on chronic nitroglycerin (NTG) administration. We also assessed the circulating levels of lipopolysaccharide binding protein (LBP) and the protein expression of occludin - tight junction protein - in the small intestine. Methods: Adult male Sprague-Dawley rats were treated with NTG or vehicle every two days over nine days. On day nine, four hours after the last administration of NTG or vehicle, rats underwent the orofacial formalin test. Then rats were sacrificed and serum and small intestine samples were collected to assess LBP by ELISA and occludin protein levels by Western blot. Fecal 16S ribosomal RNA gene sequencing was conducted to analyse changes in the gut microbiota. Results: NTG administration increased nocifensive behavior in phase II of the orofacial formalin test, confirming the development of migraine-like hyperalgesia at level. The gut microbiota analyses revealed significant differences in beta diversity and gut microbial composition between the NTG-treated and vehicle groups. Specifically, several bacteria belonging to the Lachnospiraceae family and Gastranaerophilales order were more represented in NTG-treated animals. NTG-treated animals also had significantly higher serum levels of LBP. Conversely, no substantial alterations were found in the levels of occludin. Conclusion: These findings confirm a link between the gut microbiota and migraine-like pain. In support of this relationship, it seems conceivable that dysbiosis may influence trigeminal pain, probably via the release of gut LPS into the systemic circulation, which is probably unrelated to intestinal tight junction changes. trigeminal the increasing the rat Objective: We have previously found that calcitonin gene-related peptide (CGRP) is important for light sensitivity, scotopic electroretinogram (ERG) response following topical administration. Others have similarly seen an improvement in the photopic ERG in rabbits following intravitreal (i.vt.) CGRP injection.[1] The present study was conducted on light-adapted rats to investigate the effects of i.vt. CGRP on the flicker response and correlate this with intraocular CGRP concentration. Methods: CGRP or phosphate-buffered saline (PBS) was administered i.vt. to Sprague-Dawley rats (n=5-10 per group) on day 0. Fundus imaging was conducted at baseline, a few minutes post-injection, 30 minutes post-injection, on day 1, and on day 3. CGRP concentration was measured on intraocular fluid from enucleated eyes collected at 30 minutes, 1 day, and 3 days post-injection. ERG was recorded at baseline, 30 minutes post-injection, and on day 1. Results: Fundus imaging showed retinal vessel dilation in all CGRP-treated eyes on day 1. This was not seen at 30 min, nor on day 3, or following PBS treatment. CGRP concentrations were significantly higher in CGRP-treated eyes (5676 ± 2249 pg/ml) compared to PBS-treated eyes (131 ± 33 pg/ml, p<0.0001) on day 1 and exceeded relevant threshold of 1nM. ERG revealed a significantly larger flicker response (mean trough-to-peak amplitude) in CGRP-treated eyes compared to contralateral PBS- treated eyes on day 1 (p=0.0014), which was not seen at baseline (p=0.4469) or at 30 minutes (p=0.2009). Conclusion: Intravitreal administration of CGRP in rats resulted in retinal vessel dilation and an enhanced flicker response on day 1. These effects correlated with elevated intraocular CGRP concentrations, suggesting a modulatory role of CGRP in the retinal response to light stimuli. Further investigation is warranted in conditions such as photophobia and migraine- associated visual discomfort. 1. Neuropeptides.1993;24(3):151-7 the pharmacologically to explore CGRP's involvement

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P132 Spontaneous spreading depolarizations in a novel mouse model of familial hemiplegic migraine type 2 E. Tolner1, N. Jansen2, C. Linnenbank2, M. Schenke2, R. Voskuyl2, S. van Heiningen2, A. van den Maagdenberg1,2 1Leiden University Medical Center, Neurology, Leiden, Netherlands 2Leiden University Medical Center, Human Genetics, Leiden, Netherlands Objective: Mechanisms of initiation of cortical spreading depolarization (SD) are understudied due to a paucity of disease models with spontaneously occurring events. Familial hemiplegic migraine type 2 (FHM2) is a rare subtype of migraine with severe auras caused by loss-of-function mutations in the ATP1A2 gene. ATP1A2 encodes the α2 subunit of the Na+/K+ adenosine triphosphatase (α2NKA), which acts as a Na+/K+-ATPase pump that is predominantly expressed in astrocytes. Objective: functional characterization of a novel mouse model of FHM2 expressing the missense T345A-mutated α2NKA subunit. Heterozygous and homozygous Atp1a2T345A knock-in (KI) mice were generated to study effects of the T345A mutation on brain function. Methods: The human FHM2 T345A missense mutation was introduced in the mouse Atp1a2 gene by gene targeting. Following molecular and general behavioral characterization, long-term recordings of cortical and hippocampal direct-current and local field potentials were performed in freely behaving mice to assess brain activity features including SD. Results: Homozygous mutant mice were viable without overt behavioral impairments. Decreased survival with spontaneous death was identified to relate to risk for sudden fatal apnea. Homozygous mutants showed spontaneous SDs that exhibited a diurnal rhythm and originated from the hippocampus, next spreading from the visual to motor cortex. Despite hippocampal hyperexcitability, spontaneous SDs in Atp1a2T345A mice were rarely associated with epileptic behavior, and seizure expression during kindling was decreased. Conclusion: Occurrence of spontaneous SDs in this FHM2 mouse model provides an excellent basis for studying mechanisms of SD initiation and developing selective therapies targeting SD and its consequences. This can benefit people suffering from migraine with aura but also other neurological disorders involving SD, such as stroke and certain epilepsy syndromes. P133 Atogepant inhibits Calcitonin Gene-Related Peptide (CGRP)-induced coronary vasodilation in swine: implications for cardiovascular safety assessment R. W. A. van Drie1,2, O. Sorop2, A. H. J. Danser1, D. J. Duncker2, D. Merkus2,3,4,5, A. Maassen van den Brink1 1Erasmus MC University Medical Center, Division of Pharmacology and Vascular Medicine, Department of Internal Medicine, Rotterdam, Netherlands 2Erasmus MC University Medical Center, Division of Experimental Cardiology, Department of Cardiology, Rotterdam, Netherlands 3University Clinic Munich, LMU, Walter Brendel Center of Experimental Medicine (WBex), Munich, Germany 4Munich Heart Alliance (MHA), Center for Cardiovascular Research (DZHK), Munich, Germany 5University Clinic Munich, LMU, Interfaculty Center for Endocrine and Cardiovascular Disease Network Modelling and Clinical Transfer (ICONLMU), Munich, Germany shown that In six ischemia induce myocardial Objective: Calcitonin gene-related peptide (CGRP) is a potent vasodilator involved in the pathophysiology of migraine, that also protects against myocardial ischemia. Drugs targeting the CGRP receptor are used as acute and prophylactic anti-migraine treatments. However, anecdotal evidence suggests that migraine [1]. treatment can Previously, we have atogepant equipotently blocks CGRP-induced vasorelaxation in vitro, in small isolated human and porcine coronary arteries [2]. In the current study we studied in the porcine coronary vasculature in vivo 1) potency of atogepant to block exogenous CGRP-induced vasodilatation, 2) whether atogepant impacts coronary vascular conductance (CVC). female Aachen mini-swine, Methods: anesthetized with pentobarbital, human αCGRP was infused intracoronarily in consecutive doses of 30– 100–300 pmol/min, and coronary flow (CBF) was continuously measured. The infusion was repeated upon treatment with 0.5 mg and 5 mg atogepant i.v., resulting in circulating concentrations in the same order of magnitude as observed with clinical use of atogepant in patients [3]. Intracoronary infusion of saline was used as a vehicle control. Results: CGRP increased CBF in a dose-dependent manner (26 ± 1 at baseline to 42 ± 3 mL/min at 300 pmol/min, P = 0.013, Fig A), as a consequence of increased CVC (0.28 ± 0.03 at baseline to 0.51 ± 0.04 mL/min/mmHg at 300 pmol/min, P = 0.003, Fig B), while vehicle had no effect on either CBF or CVC. Atogepant had no effect on basal CVC, but blocked the effects of the CGRP on CBF and CVC (Figure). Conclusion: Although atogepant had no significant effect on basal CVC, it blocked CGRP-induced vasodilation in vivo in the coronary vasculature of

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swine. Future studies will therefore further assess the cardiovascular safety of atogepant in this model. [1] Perino et al. Pharmocotherapy (2022), [2] Van Drie et al., 17th EHC 2023 meeting abstracts. J Headache and Pain, [3] Boinpally et al., Clin Pharmacol Drug Dev (2021) Fig. 1 P134 Effects of dual inhibition of fatty acid amide hydrolase and transient receptor potential vanilloid 1 in an animal model of migraine M. Francavilla1,2, R. Greco2, C. Demartini2, A. M. Zanaboni1,2, S. Facchetti1,2, C. Tassorelli1,2 1University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 2Fondazione Mondino IRCCS, Section of Translational Neurovascular Research, Pavia, Italy representing a promising the effect of AA-5-HT on Objective: Fatty acid amide hydrolase (FAAH) inhibition is a potential target for treating pain, including migraine. Dual-acting drugs, like N- arachidonoylserotonin (AA-5-HT), inhibit FAAH and antagonize transient receptor potential vanilloid 1 (TRPV1), therapeutic approach for pain management, minimizing side effects associated with single-target agents. We assessed trigeminal hyperalgesia and anxiety-like behavior in migraine animal model induced by acute nitroglycerin (NTG) administration, in addition to the action of AA-5-HT on CGRP and inflammatory cytokines mRNA levels in specific cranial areas. Methods: The study was performed in male Sprague- Dawley rats pre-treated with NTG/vehicle (4 hours before) and with the AA-5-HT/vehicle 15 minutes before behavioral testing. Gene expression of CGRP and inflammatory cytokines were assessed in the cranial regions of rats that underwent the orofacial formalin test by rt-PCR. We also investigated the in test. formalin the orofacial modulation of NTG-induced anxiety-like behavior in elevated plus maze (EPM) test. Results: AA-5-HT did not reverse NTG-induced changes in distance travelled and time spent into the open arms of EPM, while it inhibited NTG-induced hyperalgesia It significantly decreased the mRNA levels of CGRP, TNF- alpha and IL-6 in the trigeminal ganglia and central areas. However, treatment with AA-5-HT, in basal conditions, induced an anxiogenic effect without modifying nocifensive behavior. Conclusion: The study confirms that anandamide (AEA) has therapeutic potential in treating migraine pain. It also suggests that increasing endogenous endocannabinoid levels and blocking the TRPV1 receptor in specific areas reduces the inflammatory pathway associated with trigeminal hyperalgesia, but it does not affect anxiogenic behavior. Further studies are needed to assess AEA levels in brain areas involved in the trigeminal system and those involved in emotional regulation. P135 Characterization of migraine- and depressive-like symptoms in mice models of migraine and depression show significant sex differences O. Gliga1, M. Vila-Pueyo1, V. J. Gallardo López1, E. Araya1, L. Asskour1, P. Pozo-Rosich1 1Vall Hebron Institute of Research (VHIR), Barcelona, Spain Objective: Migraine often coexists with depression, increasing the disease burden. Cohort studies show a bidirectional relationship between migraine and major depressive disorder (MDD), but the mechanisms are unclear. This study aims to explore these shared mechanisms using mice models. Methods: C57BL/6J 8-week female and male mice were divided into 4 groups: (1) Control, (2) Migraine, (3) Depression, and (4) Migraine+Depression. The Migraine group received 5 nitroglycerin injections (10mg/kg) every other day for 9 days. The Depression group underwent a 21-day chronic unpredictable mild stress protocol. The Migraine+Depression group followed both protocols. Behavioural tests (orofacial Von Frey, tail suspension, and open field tests) were performed to assess migraine- and depressive-like symptoms. Data were analyzed using mixed-effect models, with p-values adjusted for multiple comparisons with the FDR procedure. Results: Orofacial mechanical allodynia thresholds the Migraine, were groups Depression compared group (F(6)=74.32,adj.p<0.001), with no differences between the three interventional groups. These three groups and Migraine+Depression significantly decreased Control the in to

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while also showed a decreased latency to immobility time in the tail suspension test compared to the Control group for both sexes (F(3)=18.7,adj.p=0.001). In the open field test, males in the Migraine group spent more time in the corners compared to the Control group (z=-2.52,adj.p=0.023). In contrast, females in the Depression group spent less time in the corners (z=2.29,adj.p=0.033), the Migraine+Depression group spent more time (z=- 2.40,adj.p=0.032). Conclusion: Mice in the Migraine, Depression and Migraine+Depression groups developed migraine- and depressive-like symptoms, with sex differences. These the shared pathophysiological findings highlight mechanisms and MDD, demonstrating the translatability of mice models for studying both conditions. between migraine those in revealed (Migraine: F(6)=9.76, Depression (F(9)=39.15,adj.p=0.007) and the (F(9)=171.68,adj.p<0.001) Migraine+Depression models. Post-hoc analysis sex-specific differences, with males showing none to partial F(3)=8.46,adj.p=0.043; reversion adj.p=0.180; Depression: F(6)=20.60,adj.p=0.003). Migraine+Depression: Responses were similar across treatments. In the tail suspension test, all models showed improved latency to untreated animals to (Migraine: Depression: F(3)=22.64,adj.p<0.001; Migraine+Depression: F(3)=19.43,adj.p<0.001). Treatments had no effect in the open field test. Conclusion: The beneficial effects of olcegepant and fluoxetine in migraine- and depression- like symptoms in mice increase our understanding of both disorders opening up new treatment strategies. F(3)=6.47,adj.p<0.001; immobility compared P136 Olcegepant and fluoxetine modulate the development of migraine – and depressive-like symptoms in mice models of both disorders in a sex- dependent manner M. Vila-Pueyo1, O. Gliga1, V. J. Gallardo López1, E. Araya1, L. Asskour1, P. Pozo-Rosich1,2 1Vall Hebron Institute of Research (VHIR), Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Neurology Department, Barcelona, Spain P137 Mechanisms of GTN-induced migraine: Role of NOS isoforms, sGC, and peroxynitrite in a migraine relevant mouse model C. Ernstsen1, K. Obelitz-Ryom1, D. M. Kristensen1, J. Olesen1, S. L. Christensen1, S. Guo1 1Copenhagen University Hospital – Rigshospitalet, Department of Neurology, Danish Headache Center, Copenhagen, Denmark received 5 nitroglycerin Objective: Migraine often coexists with depression, increasing the disease burden. Anti-CGRP treatments reduce depressive symptoms in migraine patients besides reducing headache days, but the underlying mechanisms remain unclear. This study aims to explore the effects of anti-migraine and anti- depressive treatments on preclinical models of both disorders. Methods: C57BL/6J 8-week female and male mice were divided into 4 groups: Control, Migraine, Depression and Migraine+Depression. The Migraine group intraperitoneal injections (10mg/kg) every other day for 9 days. The Depression group underwent a 21-day chronic unpredictable mild The Migraine+Depression group followed both protocols. Mice in each group were administered Olcegepant (1mg/kg) or fluoxetine (10mg/kg) for 14 days. Orofacial Von Frey, tail suspension, and open field tests depressive-like symptoms. Data were analyzed using mixed-effect models, with p-values adjusted for multiple comparisons with the FDR procedure. Results: Partial reversion of allodynia thresholds was observed model (F(9)=63.32,adj.p<0.001), and complete reversion in assessed migraine- protocol. Migraine stress and in the Objective: Migraine research has highlighted the in migraine pivotal role of nitric oxide (NO) pathophysiology. Nitric oxide donors like glyceryl trinitrate (GTN) induce migraine attacks in humans, while spontaneous migraine attacks can be aborted by inhibiting NO production. This study aimed to investigate how GTN triggers migraine through its three nitric oxide synthase (NOS) isoforms (nNOS, eNOS, and iNOS) via a suspected feed-forward phenomenon. Methods: Migraine-relevant hypersensitivity was induced by repeated injection of GTN in an in vivo mouse model. Cutaneous tactile sensitivity was assessed using von Frey filaments. Signaling pathways involved in this model were dissected using non- selective and selective NOS inhibitors, knockout (KO) mice lacking eNOS or nNOS and their wildtype (WT) control mice. Also, we tested a soluble guanylate cyclase a peroxynitrite decomposition catalyst (Ntotal = 312). Results: Non-selective NOS inhibition blocked GTN- induced hypersensitivity. This response was partially associated with iNOS, and potentially nNOS and eNOS conjointly. Furthermore, we found that the GTN response was largely dependent on the generation of peroxynitrite and partly sGC. inhibitor (sGC) and

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Conclusion: Migraine-relevant hypersensitivity induced by GTN is mediated by a possible feed- forward phenomenon of NO driven mainly by iNOS but with contributions from other isoforms. The involvement of peroxynitrite adds to the notion that oxidative stress reactions are also involved. Fig. 1 Fig. 2 Fig. 3 P138 Unravelling the gut-brain connection: a systematic review of migraine and the microbiome C. Mugo1, E. Church1, R. Horniblow2, H. Botfield3, S. Mollan4, A. Sinclair1, L. Hill2, O. Grech1 1University of Birmingham, Institute of Metabolism and Systems Research, Birmingham, United Kingdom 2University of Birmingham, Biomedical Sciences, Birmingham, United Kingdom 3University of Birmingham, Institute of inflammation and ageing, Birmingham, United Kingdom 4University Hospitals Birmingham NHS Foundation Trust, Birmingham Neuro-Ophthalmology, Birmingham, United Kingdom focusing on studies about targeting is substantial evidence Objective: There linking migraines to gastrointestinal (GI) issues. Conditions such as irritable bowel syndrome and colitis often co- occur with migraines and GI symptoms are common among migraine sufferers. However, the evidence on the effectiveness of gut microbiome-targeted therapies in managing migraines is limited. This systematic review aimed to elucidate the differences in gut microbiome composition among migraine sufferers. Additionally, it examined how therapies the gut microbiome might influence migraine. Methods: We searched Embase, PubMed, and the Cochrane Library for studies on migraines and the gut microbiome, gut microbiome composition (GMC) and gut microbiome- targeted therapies (GMTTs). Key data extracted and analysed included study details, patient demographics, migraine type, comorbidities, and outcomes. For GMC studies, we noted bacterial diversity and abundance. For GMTT studies, we recorded treatment types, dosages, and patient outcomes. Results: We identified a significant difference between various genera of microbes between migraineurs Bacteroidetes, proteobacteria, and firmicutes phyla groups were in migraine, while found significantly abundant studies were conflicted in the abundance of actinobacteria and Clostridia in increased migraine risk in migraineurs. Synbiotic and synbiotic/probiotic treatments showed a significant decrease in the migraine index, migraine frequency, migraine painkiller consumption while probiotics showed a non- significant decrease in migraine duration. Conclusion: The significant alterations of certain in migraine sufferers suggests a microbial phyla potential role for these microbes in migraine pathogenesis or as biomarkers for migraine risk. Moreover, synbiotic and synbiotic/probiotic therapies interventions for migraine emerge as promising controls. and duration and

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management, offering significant migraine severity and painkiller use. reductions in P140 Migraine friendly hospital E. Aciman Demirel1,2, M. F. P. Peres3, D. Uluduz4, E. Ruiz de la Torre5, A. Maassen van den Brink6, A. Özge7, R. Burstein8, R. B. Martins9 1Zonguldak Bulent Ecevit University, Neurology, Zonguldak, Turkey 2Zonguldak Bulent Ecevit Faculty of Medicine, Neurology, Kozlu/Zonguldak, Turkey 3Universidade Federal de São Paulo, Neurology, São Paulo, Brazil 4Chair of LTB – Lifting The Burden, Neurology, Istanbul, Turkey 5European Migraine & Headache Alliance (EMHA), Brussels, Belgium 6Division of Pharmacology, Department of Internal Medicine, Erasmus MC University Medical Center Rotterdam,, President of the EHF, Rotterdam, Netherlands 7Mersin University, Neurology, Mersin, Turkey 8Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Department of Anesthesia, Boston, MA, United States 9Betanho Martins Medical Education, Santa Bárbara D'Oeste, São Paulo, Brazil to Objective: Adherence the migraine-friendly hospital campaign will decrease underdiagnosis and under treatment among hospital workers. An empathetic approach to health workers with migraine not only increases work peace, but also has a widespread impact on public health. This initiative aims to educate healthcare workers, promote empathy, and enhance understanding of patients" experiences with migraines. Methods: The Migraine-Friendly Hospital campaign has been initiated with the joint decision of societies that have come together for a common purpose and charity work in the field of headache. "The Migraine- Friendly Hospital" concept was developed by taking inspiration from the "Migraine-Friendly Workplaces", project led by EMHA and successfully implemented in many countries. In conjunction with the Headache Week Action from 17 March to 24 March 2024, LTB, IHS, EHF, EMHA, GMPS and other local stakeholders collaborated to realize the Migraine Friendly Hospitals campaign. Results: 59 centers in 17 countries have completed this training. Migrainefriendlyhospital name, logo of the brand and Migrainefriendlyhospital joint web page has been created. Common slide set, visuals and certificates have been completed and sent to everyone who completed the training. Conclusion: We wanted to make the hospitals we work in migraine-friendly institutions and mark the headache awareness week activities we started this year with the support of WHO with such an awareness project. The developments at the point we have reached with the determination of each of us and the unconditional cooperation of the institutions without any financial support are like this . If we agree to continue the project, we should take more ownership on an institutional basis and we should strive for more organisations to initiate this process. P141 Clinical and epidemiological characteristics of persistent idiopathic facial pain I. Rukhadze1, O. Koniashvili2, G. Chakhava2 1Central University Clinic Named after Acad. N.Kipshidze, Neurology, Tbilisi, Georgia 2MediClub Georgia, Neurology, Tbilisi, Georgia (PIFP) does not Objective: Unlike trigeminal neuralgia, Persistent Idiopathic Facial Pain involve neurovascular compression. This study aimed to examine specific clinical and epidemiological features of PIFP and understand its clinical progression. Methods: A retrospective analysis was conducted on 17 patients diagnosed with PIFP. The diagnosis was based on the International Classification of Headache Disorders by the International Headache Society. Results: Of the patients diagnosed with atypical facial pain, 88% (n=15) were female, while only two were male. In most cases (82.3%; n=14), the pain was localized to one side of the face, with nine patients experiencing right-sided pain and five left-sided. Bilateral pain distribution was observed in 17.6% (n=3) of the cases. The majority (41%; n=9) reported that their pain was primarily in the maxillary, mandibular, or temporal regions. Other patients indicated pain in the frontal, orbital, parietal, occipital, gingival, or nasal areas. Severe pain necessitating the use of analgesics was reported by 64% of the patients, while the rest experienced milder pain. The duration of symptom onset varied from 8 months to 4 years, with an average of 17.8 months Conclusion: PIFP presents with severe, episodic, chronic, and frequently recurring symptoms that significantly impair the patient's quality of life, mood, and productivity. The shows resistance treatment, making management challenging for healthcare providers. condition often to

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P142 Mood disorders: The association with disabeling migraine M. Zaletel1, B. Žvan1 1University Clinical Centre of Ljubljana, Vascular Neurology, Grosuplje, Slovenia Objective: Anxiety and depression, including migraine, represent dangerous signals for organisms. Migraine itself or by common mechanism creates a vicious cycle. To break this cycle is necessary to control the migraine attacks such as anti-CGRP monoclonal antibodies. The other way to control migraine is cognitive improvement. Therefore we studied self- assessed disability in migraine. Methods: In our study, we used the European Health Interview Survey (EHIS). The purpose of EHIS was to assess the health status of residents. The survey EHIS (European Health Interview Survey), conducted in 2019, included 9900 adults, aged 15 years or older. Binary logistic regression was used in univariate as well as multivariate analysis. We analyzed relf-rated disability (SRD)and compared disabled, very disabled to non-disabled. Results: In the general population, the frequency of three groups (non-disabled, disabled, and disabled was 64.2%, 27.4%, and 7.6% in migraine 54.6%, 34.5%, and 10.9%. The differences were significant (p<0.001). In migraine, the correlation showed a significant association between anxiety and disabled (OR 1.81 95%CI 1.40-2.37; p<0.001) and very disabled (OR 2.63 95%CI 1.78-3.88; p<0.001). The association between depression and disability was (OR 3.44 95%CI 2.52-4.69; p<0.001) and very disabled (OR 6.40 95%CI 4.20-9.75; p<0.001). analysis, depression stayed significantly associated with very disabled (p<0.001) while anxiety did not (p=0.492). Conclusion: Our data have shown an association between mood disorders and migraine. Both anxiety and depression are connected to migraine. For migraine management is essential to diminish the intensity of mood disorder. Pain reprocessing therapy is beneficial in managing migraine. In multivariant P143 Blocking CB receptors as therapy for (neuro)vascular disorders: sex differences in (endo)cannabinoid vascular effects E. Rivera-Mancilla1, U. M. Musterd-Bhaggoe1, A. van den Bogaerdt2, C. M. Villalón3, A. H. J. Danser1, A. Maassen van den Brink1 1Erasmus MC University Medical Center, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands 2ETB-BISLIFE, Heart Valve Department, Beverwijk, Netherlands 3Cinvestav-Coapa, Department of Pharmacobiology, Mexico City, Mexico agonist) (CGRP nociceptive in vascular responses Objective: The (endo)cannabinoid system modulates trigeminovascular transmission, contributing to migraine pathophysiology. Moreover, its peripheral antinociceptive effect and ability to modulate vascular tone highlight it as a potential therapeutic target for migraine. We pharmacologically investigated the role of CB receptors in vasodilation induced by (endo)cannabinoid agonists and explored sex differences in human isolated coronary arteries (HCA). Methods: HCA segments (males, n=11; 55±2 years and females, n=17; 51±4 years) were used to evaluate the vasorelaxant responses to anandamide (AEA, CB1/CB2 receptor or arachidonyl-2'-chloroethylamide (ACEA, CB1 receptor agonist) in the absence or presence of the antagonists AM6545 (CB1 receptor, 1 µM), AM630 (CB2 receptor, 1 µM), or olcegepant receptor, 1 µM). Additionally, Western blot was performed to analyse the expression of CB receptors in intact HCA from males and females. Results: Both AEA and ACEA induced concentration- dependent vasodilation. The maximum relaxant response (Emax) to AEA and ACEA was significantly enhanced in HCA from females (Emax AEA: 61±2%, Emax ACEA: 50±3%) compared to males (Emax AEA: 43±3%, Emax ACEA: 33±4%). Moreover: (i) the response to AEA was inhibited by AM6545 or olcegepant, but not by AM630; and (ii) the response to ACEA was inhibited by AM6545 or olcegepant. Finally, Western blot analysis revealed a higher expression of CB1 receptor in HCA from the expression of the CB2 receptor showed no differences between males and females. Conclusion: There is a differential vasoactive role of CB1 receptors in females and males, which might correlate with the expression of the receptor protein level in HCA. Targeting CB1 receptors may provide new therapeutic options to address the sex dimorphism in (neuro)vascular causing vasoconstrictor side effects. females compared to males, while disorders, without

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P144 Characterisation and treatment of patients with menstrual migraine in real-world clinical practice J. Ailani1, G. M. Terwindt2, B. Galabova3, J. Cirillo4, A. Jenkins3, L. Abraham3, K. Hygge Blakeman5, J. Jackson6, S. Barlow6, W. Whitton6, L. Hancock6 1MedStar Georgetown University Hospital, Washington, DC, United States 2Leiden University Medical Center, Department of Neurology, Leiden, Netherlands 3Pfizer, Tadworth, United Kingdom 4Pfizer, Inc, New York, NY, United States 5Pfizer AB, Stockholm, Sweden 6Adelphi Real World, Bollington, United Kingdom Fig. 1 Fig. 2 to assess survey with the demographics, Objective: Patients with menstrual migraine (MM) experience more frequent and severe migraine attacks than patients without MM. Despite this, MM is underdiagnosed and patients with MM are often treated similarly to patients without MM. This study aimed clinical characteristics, treatment patterns and satisfaction of patients with and without MM. Methods: Data were drawn from the 2022/23 Adelphi Migraine Disease Specific Programme™, a real-world cross-sectional retrospective data collection, conducted in France, Germany, Italy, Spain, the UK, and the USA. Physicians and their female patients provided data on migraine diagnosis, including the presence or absence of MM, prescribed acute treatment, and acute treatment satisfaction. Patients with MM and patients without MM were compared using Mann-Whitney U tests, t-test, and Fisher exact tests. Results: Primary care practitioners (n=264) and neurologists (n=340) provided data on 3,049 female patients aged <55 years old, of which 32% (n=986) had a diagnosis of MM. Patients with MM were significantly younger than patients without MM and experienced more severe migraine attacks (all p<0.01). Patients with MM were significantly more likely to receive acute treatment (p<0.01) (Table 1). However, there was no significant difference in most types of acute treatment prescribed between both groups with the exception of NSAIDs and serotonin 5- HT1F agonists (ditans) (Table 1). Physicians reported being extremely satisfied with patient"s acute treatment for a higher proportion of patients without MM than patients with MM (Figure 1). Conclusion: Despite patients with MM exhibiting different clinical characteristics and increased severity relative to patients without MM, treatment regimens were similar between groups. Physician education and awareness is essential to ensure optimal treatment for patients with MM and to improve satisfaction with therapy received. P145 Understanding the prevalence of headaches in individuals undergoing hormone therapy for gender transition in Argentina L. Zavala1 1University of Copenhagen, Neurology, Copenhagen, Denmark included Objective: The aim of this research is to investigate the onset, frequency, characteristics, and potential relationship between gender-affirming hormone therapy (GAHT) and headache in transgender and nonbinary individuals in Argentina. individuals Methods: Transgender and non-binary in a voluntary and using GAHT were cross-sectional observational anonymous online survey from October 2023 to February 2024 in Argentina. A validated Migraine Screen–Questionnaire (MS-Q) was used to arrive at a migraine-like headache diagnosis in the participants. Results: The analysis was based on data from 160 responders; 63.7% reported headaches, and only 15% had a previous headache diagnosis (migraine or tension-type headache). Using the MS-Q scale, we identified a total of 34 participants with a migraine- like headache. 21.3% of the participants reported experiencing new or worsening headaches, while 15% reported an improvement or complete disappearance of headaches. We observed 66% of patients with estrogen treatment presented worsened new pain compared to 27.2% of patients with testosterone treatment. Similarly, 26% of testosterone users had an

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improvement or disappearance of the headache compared to only the 8% of patients using Estrogens. Conclusion: This research found that the effects of Estrogen and Testosterone differ significantly. Further research is necessary to better understand the underlying mechanisms of this condition and improve treatment strategies. P146 Menopause and its impact on the effectiveness of fremanezumab for migraine prophylaxis: Post-hoc analysis of a prospective, real-world Greek registry A. Argyriou1, E. V. Dermitzakis2, G. Xiromerisiou3, D. Rikos4, D. Rallis5, P. Soldatos6, P. Litsardopoulos1, A. P. Andreou7, M. Vikelis8 1Agios Andreas General Hospital of Patras, Headache Outpatients Clinic, Patras, Greece 2Euromedica General Clinic, Thessaloniki, Greece 3University Hospital of Larissa, Neurology, Larisa, Greece 4404 Military Hospital, Larisa, Greece 5Tzaneio General Hospital of Piraeus, Neurology, Athens, Greece 6Headache Clinic, Kalamata, Greece 7Headache Research-Wolfson CARD, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom 8Headache Clinic, Athens, Greece Objective: Few studies have tested the effectiveness of anti-CGRP monoclonal antibodies for migraine prophylaxis at post-menopause. In this post-hoc analysis of data extracted from a prospective, multicentre study, we aimed to explore for the first time if the anti-migraine preventative efficacy of fremanezumab is differentiated in difficult-to-treat women with migraine, based on the menopausal status. Methods: A total of 171 (aged 18-70 years) fremanezumab-treated female migraine patients for six consecutive months were classified to those at reproductive age (n=82) or post-menopausal (n=89). Treatment-related including monthly headache days (MHD), disability and quality of life (QOL) outcomes were assessed at baseline and week 24 post-fremanezumab within subgroups and were then compared between them. Safety and tolerability were also compared between groups. treatment with Results: fremanezumab demonstrated significant reductions in monthly headache days, reduced disability and higher QOL scores at week 24 post-treatment initiation, the between compared subgroups comparison documented those women at childbearing age and those at menopause comparably benefited with significant reductions in to baseline. However, efficacy, groups, In both that overall MHD (95% CI: 0.17 – 1.50; P = 0.883), MHD with moderate/severe pain, according to VAS (95% CI: 0.36 – 1.09; P = 0.828) and MHD with intake of any acute medication (95% CI: 0.46 – 2.70; P = 0.208). Less disability, according to MIDAS (95% CI: 0.46 – 20.71; P = 0.696) and HIT-6 scores (95% CI: 0.22 – 3.24; P = 0.912) as well as higher QOL at week 24 post- fremanezumab initiation was also evident in both groups at comparable rates. Safety was excellent across both subgroups. Conclusion: Fremanezumab can be considered a very effective treatment option for preventing migraines in difficult-to-treat women, aged 18-70 years, regardless of their menstrual status. P147 The effect of sex on CGRP therapeutics – a real-world longitudinal outcome study from a tertiary headache center H. Yuan1, A. Wrem2, M. Li2, J. Ren2, S. Keith2, A. Nisar1, M. Marmura1, R. Hass2, S. Ghosh2, P. Phan2 1Thomas Jefferson University, Neurology, Philadelphia, PA, United States 2Thomas Jefferson University, Philadelphia, PA, United States the longitudinal Objective: The effect of sex on gepant and CGRP monoclonal antibody (mAb) remains understudied. Using patient-reported outcomes (PROs), this study investigated response during gepant/mAb use at the Jefferson Headache Center. Methods: In this single-center study (IRB# iRISID- 2022-0848), PROs data captured during each visit from December 2018 to April 2024 were evaluated. Key headache PROs, such as monthly headache days (MHD), monthly moderate/severe days (MSD), monthly acute medication use days (AMD), worst pain intensity (WPI), average pain intensity (API), and migraine disability assessment (MIDAS), were evaluated before/after their first mAb or gepant orders (index day). Medication orders and PROs data underwent multiple cleaning steps and were combined. Each PRO was analyzed by mixed model (jamovi) with subjects as cluster variables to examine the fixed effect of time (-180 to 180 days from index day), age, sex, and concurrent onabotulinumtoxinA (conc_onaB). Missing data were considered random, and no data was imputed. Results: 1377 subjects (age 44.1±14.9, female 1122, Caucasian 1201) used first-time preventive mAb (n=1149) or gepant (n=228) with a total of 3432 visits (2.5±1.9, range 1-17) and 56.6±57.9 days before and 93.0±46.0 after index day. There were significant main effects on MHD from time (b=-0.00374), sex (b=2.64), and conc_onaB (b=2.46) (Table 1, Fig 1). The interaction between sex and time was not significant.

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showed a [-0.006, 0.007]) In the subgroup analysis, those with first-time gepant (b=-0.02 [-0.04, -0.002]) but not first-time mAb (b=- 0.0035 significant interaction between sex and time. Conclusion: In this longitudinal retrospective study, there were significant time and sex effects on MHD but without interaction. Male subjects receiving the first gepant seemed associated with greater MHD change in time. The study was limited by the small male sample size and EMR data availability. Larger prospective studies are needed to determine the effect of sex on gepant response. Fig. 1 Fig. 2 P148 Fremanezumab for the prevention of menstrually- related migraine attacks – a prospective observational phase 4 study according to routine neurological care in Switzerland (FROMM) A. Scutelnic1,2, G. S. Merki Feld3, R. Agosti4, P. Balcerak5, A. R. Gantenbein6, A. Kleinschmidt7, A. Papadopoulou8, P. Ryvlin9, S. Wegener10, C. Zecca11, B. Haertel12, C. J. Schankin13 1Inselspital, Neurology, Bern, Germany 2University of Bern, Neurology, Bern, Switzerland 3USZ, Gynecology, Zürich, Switzerland 4Kopfwehzentrum Hirslanden, Zurich, Switzerland, Zürich, Switzerland 5Cantonal Hospital St. Gallen, St. Gallen, Switzerland, Department of Neurology and Stroke Center, St. Gallen, Switzerland 6Praxis Neurologie am Untertor, Bülach, Switzerland 7University Hospital Geneva (HUG) and Medical Faculty Geneva, Geneva, Switzerland, Division of Neurology, Department of Clinical Neurosciences, Geneve, Switzerland 8University Hospital Basel, Basel, Switzerland 9Centre hospitalier universitaire vaudois (CHUV), Department of Clinical Neurosciences, Lausanne, Switzerland 10University Hospital and University of Zurich, Department of Neurology, Zürich, Switzerland 11Neurology department, Neurocenter of Southern Switzerland, EOC, Lugano, Switzerland. Faculty of biomedical Sciences, Università della Svizzera Italiana, Lugano, Switzerland, Lugano, Switzerland 12TEVA Pharma AG, Basel, Switzerland, Basel, Switzerland 13Inselspital, University Hospital Bern, Bern, Switzerland treatment) study with longer duration and respond Objective: Menstrually-related migraine attacks (MM) occurring during cycle days -2 to + 2, are more severe, of less to acute medications. For many women those attacks induce a high burden with significant impact on quality of life. Data on the prevention of MM by anti-CGRP antibodies are scarce. The aim of this abstract is to introduce the study FROMM. The study will assess the response of MM to preventive treatment with fremanezumab in women with migraine. We hypothesize that MM respond equally well to treatment with fremanezumab as non-menstrual attacks. Methods: This is a 30-month (24-month recruitment, 6-month fremanezumab treatment according to the Summary of Product Characteristics. Recruitment is planned at 10 sites in Switzerland. Pre-menopausal women with at least 2 days of MM and at least 8 migraine days per month will be is the difference in relative reduction of migraine days between MM and non-MM at follow-up. Estimates of the effectiveness of relative reduction from baseline to follow-up in MM days comparing to non-MM days will be assessed. Exploratory endpoints are the change from baseline at follow-up in disability scores, migraine-specific quality of life, sleep quality, number of days and intensity with typical symptoms of endometriosis, and number of migraine days in patients with and without concomitant hormonal treatment. Data will be collected using a headache diary (migraine days, migraine characteristics, aura, headache medication) and patient records (data on endometriosis, hormonal included. The primary end-point fremanezumab in

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1 Figure visualizes comorbidities). therapy, procedures and visits. Results: Three interim analyses are planned after 6 months treatment with fremanezumab of one third, two thirds and of all planned participants. Conclusion: FROMM will provide insights into the treatment of MM and on the education of the largest group of people with migraine. Fig. 1 P149 Non-aura visual symptoms in migraine M. Dias da Costa1, F. Dourado Sotero1, B. Nunes Vicente1, M. Almeida2, C. Fernandes2, L. Silva3, R. Franco4,5, G. Bonifácio6, C. Lemos7, I. Luzeiro2, I. Pavão Martins1 1Santa Maria Local Health Unit, Neurology, Lisboa, Portugal 2Coimbra Local Health Unit, Coimbra, Portugal 3Santo António Local Health Unit, Porto, Portugal 4São João Local Health Unit, Porto, Portugal 5Hospital Dr. Nélio Mendonça, Funchal, Portugal 6Arrábida Local Health Unit, Setúbal, Portugal 7School of Medicine and Biomedical Sciences, University of Porto, Porto, Portugal (MwoA) frequently Objective: Visual aura is one of the most common types of migraine aura. [1,2] Patients with migraine without aura report visual symptoms related to the migraine attack that do not meet aura. Its pathophysiology is not completely understood. [3, 4] We aim to characterize non-aura visual symptoms (NAVS) reported by patients with MwoA and to compare characteristics of patients with and without NAVS. criteria typical for visual A excluded. Methods: Longitudinal, prospective, multicentric study in adult patients followed in Headache Clinics, with diagnosis of episodic MwoA according to the ICHD-3 criteria. Patients with other concomitant headaches and ophthalmological and psychiatric diseases were self-completed questionnaire about migraine characteristics and visual symptoms was filled out at a baseline visit and after 3-6 months. Results: One hundred and thirty-three patients were included, 87.9% female. Ninety patients (67.6%) reported NAVS related to migraine attacks. Patients who reported NAVS had higher average number of migraine days per month (4.9±3.0 vs. 4.0±2.7 days), were more likely to have first-degree relatives with migraine (68.9%), and experienced associated migraine symptoms such as sensitivity changes. The majority type of visual symptom, most commonly blurred vision (42.2%), which was concomitant with the headache (34.6%), bilateral (35.3%), short duration (19.5%), and fixed in the visual field (35.3%). In half, symptoms had a moderate to severe impact in daily activities. in patients with Conclusion: NAVS are common episodic MwoA and include a wide range of symptoms. Although sometimes phenomenologically similar to aura, they do not exhibit its typical characteristics, particularly in terms of duration and onset. Identifying these symptoms helps broaden the understanding of visual symptoms in migraine, with possible clinical implications, from the definition of visual aura to in therapeutic management. its consideration reported one (48.1%) P150 Effects of onabotulinumtoxinA on interictal burden and cutaneous allodynia of patients with chronic migraine A. Argyriou1, E. V. Dermitzakis2, D. Rikos3, G. Xiromerisiou4, P. Soldatos5, P. Litsardopoulos1, M. Vikelis6 1Agios Andreas General Hospital of Patras, Headache Outpatients Clinic, Patras, Greece 2Euromedica General Clinic, Thessaloniki, Greece 3404 Military Hospital, Larisa, Greece 4University Hospital of Larissa, Neurology, Larisa, Greece 5Headache Clinic, Kalamata, Greece 6Headache Clinic, Athens, Greece Objective: Although the negative impact of migraine attacks (ictal phase) on patients" daily living and quality of life (QoL) has previously been well documented, little attention has been paid to the effect of the interictal burden on the domains of patients" QoL. We primarily aimed to ascertain if the

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the extent of treatment with ΟnabotulinumtoxinA (BoNTA) might influence interictal burden and cutaneous allodynia in patients with chronic migraine (CM). Methods: Seventy CM patients, who attained three consecutive cycles of BoNTA, were studied. The interictal burden was assessed with the Migraine Interictal Burden Scale (MIBS-4), while cutaneous allodynia was examined with the Allodynia Symptom Checklist (ASC-12) together with PI-NRS VAS to hair brushing scores and then compared from baseline (T0) to the last efficacy evaluation follow-up (T1). Efficacy outcomes, mostly mean headache days (MHD) and "Headache Impact-6 Test" scores were also assessed between T0 and T1. Results: BONTA improved the interictal burden, with a decrease in MIBS-4 scoring by a median of −7 at T1, compared to baseline (p<0.001). The percentage of patients with moderate/severe interictal burden was substantially decreased. Likewise, BoNTA reduced the extent of cutaneous allodynia, with a significant reduction of both ASC-12 (1 vs 6; p<0.001) and PI-NRS VAS (1 vs 5; p<0.001) to hair brushing median scores at T1, compared to baseline. The reduced MHD rates were significantly associated with interictal burden at T1. The efficacy of BoNTA with a significant reduction in MHD and HIT-6 scores at T1, compared with T0, were re-confirmed. Conclusion: BoNTA statistically significant reduction in interictal burden and also improved cutaneous allodynia. The reduction in ictal burden was associated with the down-scaling of the interictal burden. Hence, BoNTA improved the full spectrum of migraine impairment by diminishing the clinical expression of central sensitization. resulted in a less P151 Systematic review of late-onset aura related to migraine – an overlooked phenomenon A. Ç. Atalar1, E. Ur Özçelik2, E. N. Vanli-Yavuz3, B. Baykan4 1Istanbul Physical Therapy and Rehabilitation Education and Research Hospital, Neurology, Istanbul, Turkey 2Acıbadem Bakirkoy Hospital, Neurology, Istanbul, Turkey 3Demiroğlu Bilim University, Faculty of Medicine, Neurology, Istanbul, Turkey 4EMAR Medical Center, Neurology, Istanbul, Turkey investigate the Objective: This study aimed to literature on the onset of migraine aura after the age of 50 (late-onset aura, LOA) to shed light on this underexplored topic, which creates confusion among clinicians. and onset" "late-life literature search Methods: A systematic from PubMed and Cochrane databases was performed using the search terms "migraine with aura and late onset or over 50 or after 50 or onset in elderly or delayed migraine accompaniments" for articles published between July 1987 to October 2023. A total of 660 papers were scanned blindly on Rayyan"s platform, and the review, data extraction, and resolution of discrepancies were performed by the authors. Finally,7 studies and 8 case reports were evaluated Results: A total of 346 patients (75% female) with LOA were evaluated. The mean age of onset was 56.25±1.65 years. The most prominent type of aura was visual (324/346 patients with LOA; 93.6%) akin to the migraine of early age of onset populations but the duration of auras was shorter (frequently ≤20 minutes). A substantial number of auras might emerge solely, without a succeeding headache in the LOA group (50%, data available in n=56/122). In patients whose aura was followed by a headache, non-migrainous features were more pronounced (n=65/112, 53.3%). Family history of headache in LOA group was also similar to the early onset cases, accounting for 47.7% of LOA cases with available data. Secondary LOA-mimics were also reported but the neuroimaging data were very limited in the available studies. Conclusion: Late onset aura is a phenomenon that is often overlooked,yet it poses a significant challenge, particularly due to the presence of secondary etiologies and higher rates of comorbidities in elderly migraineurs. The absence of an accompanying headache or the presence of non-migrainous headache features are significant aspects that should be considered when performing a differential diagnosis P152 miR-382-5p and miR-34a in migraine: gene expression in monocytes and post-hoc comparison with peripheral blood mononuclear cells levels F. Bighiani1,2, R. Greco2, R. De Icco1,2, C. Demartini2, A. M. Zanaboni1,2, M. Francavilla1,2, S. Facchetti1,2, G. Vaghi1,2, M. Allena2, D. Martinelli1,2, E. Guaschino1,2, N. Ghiotto1,2, A. Antoniazzi1,2, M. Corrado1,2, F. Cammarota1,2, E. Mazzotta1,2, G. Sances2, C. Tassorelli1,2 1University of Pavia, Brain and Behavioral Science Department, Pavia, Italy 2Fondazione Mondino IRCCS, Headache Science & Neurorehabilitation Unit, Pavia, Italy Objective: We previously demonstrated altered gene expression of miR-382-5p and miR-34a in peripheral (PBMCs) of migraine blood mononuclear cells

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to obtain then normalized patients. PBMCs include a variety of cells with immune function, thus it is not possible to determine the exact origin of this dysfunctional expression. In the present study we aim to: i) define the specific monocytic expression of miR-382-5p and miR-34a; and ii) compare microRNAs expression between PBMCs and monocytes. Methods: Monocytic gene expression by means of rtPCR Relative Quantification (RQ) of miR-382-5p and miR-34a. We also conducted a post-hoc analysis comparing expression in monocytes and PBMCs. Data of PBMCs gene expression came from a previously published dataset. The inclusion/exclusion criteria and study design, with particular reference laboratory procedures, were comparable between the two studies. Results: We enrolled 50 episodic migraine patients (EM), 35 chronic migraine with medication overuse patients (CM-MO), and 30 healthy controls (HC). miR- 382-5p monocytic gene expression was higher in EM (1.2±0.5 RQ) and CM-MO (1.7±0.6 RQ) when compared to HCs (0.4±0.1 RQ, p=0.001). miR-34a monocytic gene expression was higher in EM (1.1±0.4 RQ) and CM-MO (2.2±0.9 RQ) when compared to HCs (0.6±0.2 RQ, p=0.001). Expression of miR-382-5pand miR-34a were higher in CM-MO when compared to EM (p=0.001). Comparison between PBMCs and monocytes: mir-382-5p and mir-34a gene expressions were higher in PBMCs when compared to monocytes (p=0.001), and in CM-MO when compared to EM (p=0.001). For both microRNAs, increased expression in PBMCs was mainly explained by the higher expression described in CM-MO patients (interaction: p=0.001). Conclusion: miR-382-5p and miR-34a were increased in monocytes of migraine patients, being higher in CM-MO when compared to EM. miR-382-5p and miR- 34a expressions were higher in PBMCs when compared to monocyte, with a pronounced increased in CM-MO group. to the Fig. 1 Fig. 2

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P153 A multidisciplinary multicentric approach to the identification of BIOmarkers of MIGraine (BIOMIGA project): DNA methylation patterns in migraine R. Mas de les Valls1, V. J. Gallardo López1, L. Asskour1, E. Caronna1,2, D. Martinelli3, H. Basedau4, M. M. Pocora3, R. Greco3, A. M. Zanaboni3, E. Giné Ciprés1,2, A. Alpuente1,2, M. Torres-Ferrús1,2, A. May4, C. Tassorelli3, P. Pozo-Rosich1,2 1Vall Hebron Institute of Research (VHIR), Headache and Neurological Pain Research Group, Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Neurology Department, Barcelona, Spain 3Fondazione Mondino IRCCS, Headache Science & Neurorehabilitation Centre, Pavia, Italy 4University Medical center Eppendorf, Department of Systems Neuroscience, Hamburg, Germany including identify differentially methylated individuals with migraine Objective: To regions (DMRs) associated with migraine. Methods: DNA methylation study performed in the BIOMIGA multicentric international prospective study cohort, (≥8 monthly headache days) and healthy controls (HC) from Spain, Italy and Germany. We collected demographic, clinical data and blood samples. DNA methylation was quantified using MethylationEPIC BeadChip (Illumina, Inc.). Two simultaneous studies, using Rstudio v4.4.0, were conducted: (1) a supervised pipeline using the minfi package, with a focus on normalization and data filtering, correcting batch effects using either Combat or BEclear and integrating the corrected m-values with covariables and limma; and (2) an intraspecific variations using unsupervised pipeline employing missMethyl which integrates minfi normalization, automating batch correction, and emphasizing gene set testing and pathway analysis. Results: Data was collected from 163 individuals with migraine and 96 HC, with a median (IQR) age of 39(30- 48) years, and a female proportion of 83.0%(215/259). Migraine participants were significantly older than controls (p=0.004) and presented higher BDI-II (p<0.001). Cell composition for each individual was predicted and included in the supervised model, along with age, sex, BDI-II, smoking status, and the first two principal components, resulting in 279 significant CpGs, while the unsupervised model only contained the grouping variable and found 32 significant CpGs. The resulting significant DMRs from each pipeline, selected with a p-value threshold of 9.42e-8, were mapped to genes, pathways and functions. Conclusion: We identified DMRs associated with migraine through both supervised and unsupervised pipelines, highlighting role of epigenetics in migraine. This study was funded by significant the under ERANet Neuron code BIOMIGA(NCT04503083). The funding source did not influence the way the study was conducted. project the P154 Idiopathic intracranial hypertension in monozygotic twins – and what it teaches us about disease pathophysiology J. Korsbæk1, E. A. Wibroe2, S. M. Hagen2, T. F. Hansen1,3, C. S. J. Westgate1,3, S. Hamann2, D. Beier4, R. Højland Jensen1,3 1Rigshospitalet Glostrup, Danish Headache Center, Glostrup, Denmark 2Rigshospitalet Glostrup, Ophthalmology, Glostrup, Denmark 3Translational Research Centre, Rigshopitalet, Glostrup, Denmark 4Odense University Hospital, Neurology, Odense, Denmark potential especially unknown, twins with Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease that primarily affects young, obese females. The underlying pathophysiology of IIH is genetic the case of underpinnings. Here we present concordant monozygotic IIH who underwent whole genome sequencing to elucidate potential genetic factors. Methods: Whole genome sequencing of twins and their mother from whole blood via nanopore sequencing followed by interrogation of the ClinVar database to assess clinically linked genetic variants followed by KEGG pathway analysis. Results: Female monozygotic twins presented with new-onset IIH 7 months apart in their late teenage years with florid polycystic ovarian syndrome, androgen excess, type 2 diabetes (T2D), obesity and severe daily headache. The mother was previously diagnosed with early onset T2D and PCOS but not IIH. We identified 415 ClinVar variants which were shared between the mother and twins and 158 ClinVar variants were specific to the twins. 9 variants were identified as having a pathogenic consequence by ClinVar and 8 as being likely-pathogenic. Of note 3 potentially pathogenic variants exist in the ITPKB gene, 2 single nucleotide variants from the mother and an in-frame deletion of a microsatellite of unknown provenance which together may represent pathogenic Steroid biosynthesis pathways (q=1.31E-7) and the PI3K-Akt signaling pathway (q=0.0012), the canonical insulin signaling pathway, were significantly overrepresented in terms of variant burden in the twins. Conclusion: We present the case of monozygotic twins with IIH, whose genetic variance is concordant with their physiological phenotype of androgen excess heterogeneity. compound

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and T2D and likely contributing to IIH development. Moreover, the potential compound heterogeneity in the ITPKB gene may drive aspects of the disease, as ITPKB is involved in the regulation of cerebrospinal fluid transport and regulation, highlighting a future research avenue for understanding IIH. P155 The impact of the virtual "Enfacement Illusion" on pain perception in persons with chronic migraine – a randomized controlled trial S. Bottiroli1,2, M. Matamala-Gomez3,4, E. Guaschino2, N. Ghiotto2, R. De Icco1,2, G. Sances2, C. Tassorelli1,2 1University of Pavia, Department of Brain and Behavioural Sciences, Pavia, Italy 2Fondazione Mondino IRCCS, Pavia, Italy 3University of Barcelona, Barcelona, Spain 4University of Girona, Girona, Spain the Given limited efficacy of Objective: pharmacological treatments for chronic migraine (CM), new non-pharmacological therapeutic strategies are gaining attention. In this frame, body ownership illusions have been proposed as a strategy for pain relief. This study reports data from a randomized controlled trial (RCT) evaluating the efficacy of reducing pain perception through the enfacement illusion of a happy face observed via an immersive virtual reality (VR) system in people with CM. Methods: Persons with CM were assigned to either the experimental or the control intervention. The experimental group (EG) experienced the enfacement illusion, while the control group (CG) was exposed to a pleasant immersive VR environment. Both groups underwent 3 VR sessions (approximately 20 min/each) over one week. At baseline (T0) and at the end of the intervention (T1), patients completed behavioral measures related to their emotional and psychological state, and body image perception. Before and after each VR session, we assessed pain levels using the Visual Analogue Scale (VAS), body image perception, and the affective state of the patients. Results: We enrolled 85 subjects with CM patients. Forty-four subjects (age: 43.8±10.1) received the experimental (age: 44.3±11.0) were exposed to the control condition. Subjects were comparable in terms of clinical and psychological variables. The data showed a decrease in pain perception on the VAS score in the EG from session one to session three (z=-2.75, p=0.02) and from session two to session three (z=-3-04, p=0.01). Further, a decrease in pain perception was observed in the CG but only from session one to session three (z=-2.93, p=0.014). Conclusion: The results showed the effectiveness of immersive VR, as an effective strategy for distraction treatment forty-one and of pain perception. Further, inducing body ownership illusions illusion may enhance the analgesic effect of VR interventions. the enfacement through P156 The duration of therapeutic response to laser acupuncture in chronic migraine prevention – a six- month follow-up study H. Y. Wu1, C. S. Wang2 1Taichung Veterans General Hospital, Department of Traditional Chinese Medicine, Taichung, Taiwan 2Taichung Veterans General Hospital, Division of Neurology, Neurological Institute, Taichung, Taiwan in monthly migraine days Objective: Laser acupuncture (LA) has shown therapeutic effects in treating various headaches. We aim to investigate the long-term effects of LA as an add-on preventive therapy for chronic migraine (CM). Methods: Patients over 20 years old with CM managed pharmacologically were enrolled as the comparator group from Jan 2022 to Nov 2023. Among these, those who completed an LA protocol as add-on treatment formed the experimental group and were followed for 6 months. The LA protocol consisted of 8 sessions, each involving 13 acupoints, conducted over 1 month by 810 nm low-level laser. The baseline change (MMD) was recorded, defined as the change in MMD of the comparator group from 1 month before enrollment. The primary outcome was the change in MMD of the experimental group compared with the baseline change in MMD of the comparator group. Evaluations were conducted monthly from the 1st month (treatment completion) to the 6th month. Results: A total of 98 patients were enrolled as the comparator group, including 30 patients who completed the LA protocol as the experimental group. The baseline demographics of both groups were similar. The baseline change in MMD was 0.0 days. Compared with the experimental group had a significant reduction in MMD in the first 4 months (3.4 days at 1st month, p = 0.005; 5.2 days at 2nd month, p = 0.001; 7.3 days at 3rd month, p < 0.001; 3.2 days at 4th month, p = 0.006), but no statistical difference at 5th month (2.2 days, p = 0.110) and 6th month (1.2 days, p = 0.200) (Figure 1). No serious adverse events were observed throughout the follow-up period. a Conclusion: progressively effect in reducing MMD, reaching its peak in third month. The duration of the long-term effect of LA can last for four months. We suggest that LA is a promising add-on preventive therapy for CM, and performing LA treatment every four months is more appropriate. acupuncture comparator exhibited group, Laser the

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Conclusion: Our anatomical observations indicate variation in GON anatomy, particularly the exit points through the aponeurosis. The heatmap shows the GON nerves do not consistently traverse the injection site in all specimens. Anatomical variation may explain non-response to treatment. For these cases, image- guided ultrasound could enhance injection accuracy and improve efficacy. Fig. 1 Fig. 1 P157 Anatomical variability of the Greater Occipital Nerve (GON): implications for GON injection techniques in headache disorders R. Fronczek1, F. Huygen2, W. Naber1, P. Morris3, W. Pollet3, N. Van Vlasselaer4, E. Cattrysse4 1Leiden University Medical Centre, Neurology, Leiden, Netherlands 2Erasmus MC University Medical Center, Pain Medicine, Rotterdam, Netherlands 3Salvia Bioelectronics, Eindhoven, Netherlands 4VUB, Anatomy, Jette, Belgium efficacy, necessitating a in GON anatomy, Objective: Greater occipital nerve (GON) injections are used in the treatment of various headache disorders, notably cluster headache, leveraging the presumed anatomical consistency of the GON for relief (1,2,3). Traditional techniques use anatomical landmarks between the inion and mastoid process (4). However, variability in GON anatomy may affect injection better understanding of the nerve"s anatomical course. investigated the anatomical Methods: This study variability of the GON and its potential impact on GON injection outcomes. We evaluated the location of the GON exit point and the bifurcation of its branches by dissecting 10 formaldehyde-fixed human cadaver heads. Variations such as differences in trajectory, orientation, and bifurcation, were identified through detailed measurements observed intra- and inter-individually. A CT scan was acquired for all specimens, and the measurements were projected onto a 3D model. We measured 1/3 of the distance between the external occipital protuberance and mastoid process, then 2 cm lower, marking the proposed GON injection site. We visualised the spread of the injection to assess if the GON nerves traverse this path Results: Our measurements revealed significant variations in the GON's anatomy, notably at the exit through trajectory, orientation, These variations were observed within and between individuals. Heatmap visualisations of injection fluid spread pathways, underscoring the variability in GON anatomy. trapezius aponeurosis, location, and bifurcations. showed inconsistent GON the P158 Greater occipital block at the C2 Level for migraine: identifying the responders B. Pflantzer1,2, E. Magiel1,2 1Sheba Medical Center, Neurology, Ramat Gan, Israel 2Tel Aviv University, Department of Neurology and Neurosurgery, Tel Aviv, Israel Objective: Migraine is a prevalent neurological disorder causing significant disability. Despite various treatments, many patients remain resistant[1]. Recent studies have shown the efficacy of occipital nerve blocks at the C2 level[2]. This study aims to identify patient profiles most likely to benefit from this treatment. study enrolled 30 Methods: This prospective participants diagnosed with migraine. Data were collected on aura, length of attack, location and side. Participants reported the number of monthly migraine days (MMD) at baseline and were categorized as Responders or Non-responders based on a 50% reduction in MMD over a 3-month post-treatment period. The treatment administered was a GONC2 block. Repeated measures tests assessed changes in MMD, controlling for covariates. Chi-square tests determined the correlation between covariates and changes in MMD. Results: A significant reduction in MMD among responders (F=4.76, p<0.05) was revealed, figure 1. Side-locked variant contributed the most for the reduction in MMD (χ²=9.37, p<0.01), figure 2.

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Our study characteristics that predict demonstrated the Conclusion: effectiveness of GONC2 block in reducing headache frequency in migraine patients over 3 months, especially side-locked headaches, demonstrating sustained efficacy. We suggest that personalized treatment approaches are crucial in managing migraines, and further research is needed to identify patient successful outcomes. Ref: 1. Ornello R, Andreou AP, De Matteis E, Jürgens TP, Minen MT, Sacco S. Resistant and refractory migraine: clinical and management. EBioMedicine. 2024 Jan;99:104943. doi: 10.1016/j.ebiom.2023.104943. Epub 2023 Dec 23. PMID: 38142636; PMCID: PMC10788408. 2.Karaoğlan M, İnan LE. A comparison of the clinical efficacy of GON block at the C2 level and GON block at the classical distal occipital level in the treatment of migraine. 2022 Apr;215:107190. doi: 10.1016/j.clineuro.2022.107190. Epub 2022 Mar 1. PMID: 35286995. pathophysiology, presentation, Clin Neurol Neurosurg. Fig. 1 Fig. 2 P159 Effectiveness of transcranial direct current stimulation as add-on therapy to monoclonal antibodies acting on the CGRP pathway for migraine (TACTIC) F. De Santis1, C. Rosignoli1, R. Ornello1, A. Onofri1, A. D'Atri1, F. Salfi1, D. Corigliano1, R. De Icco2, V. Grillo2, M. Corrado2, F. Bighiani2, G. Vaghi2, G. Sances2, M. Ferrara1, C. Tassorelli2, S. Sacco1 1University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy 2University of Pavia, IRCCS Mondino Foundation, Department of Brain and Behavioural Sciences, Pavia, Italy targeting Objective: Monoclonal antibodies the calcitonin gene-related pathway (CGRP-MAbs) act peripherally on the trigeminal ganglion. In contrast, neuromodulation techniques like transcranial direct current stimulation (tDCS) act centrally by influencing cortical neuronal firing rates. This study aims to assess whether tDCS, when combined with CGRP-MAbs, effectively reduces migraine severity. Methods: Our study is a randomized, double-blind, multicenter, sham-controlled trial including patients with migraine in CGRP-Mabs treatment with residual monthly migraine days (MMDs) ≥8. After 5-day of tDCS bilateral occipital cathodal and frontal anodal stimulation (sham/active sessions lasting 20 minutes, Figure 1). We closely monitored patients for 28 days, assessing changes in monthly migraine days and clinical scales such as MIDAS, HIT6, HADS. We analyzed the change in migraine days and clinical scales using two-way mixed-design ANCOVAs, with Session (baseline vs. follow-up) as the within-subjects factor and Treatment (Sham vs. Active) as the between-subjects factor. Results: We included 29 patients (mean age 46±11.5 years, 82.8% female), with 15 in the active session and 14 in the sham group. At baseline, the active group reported a mean of 13.20±6.16 MMDs, while the sham group reported 17.38±7.71 MMDs (Figure 2). tDCS led to a significant reduction in MMDs in the active group (mean 10.10±1.25) compared to the sham group (mean 15.38±1.29; p=0.008). Additionally, a significant improvement was observed in the HIT-6 scale for both the active (p=0.005) and sham (p=0.003) groups. Conclusion: tDCS, as add-on therapy to CGRP-Mabs, exerts a significant effectiveness to MMDs reduction. It could offer a more effective management strategy for individuals suffering from chronic migraines. Further research is warranted to fully understand the underlying mechanisms and long-term effects of this combined therapy.

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Fig. 1 Fig. 2 reduction simultaneous Results: We included 8 female patients, including 5 patients with frequent episodic migraine and 3 with chronic migraine. Six patients completed the rTMS protocol, with a median time elapsed since the last session of 2 months (IQR:1-9.25). Half of our sample perceived a positive/very positive overall change after rTMS regarding migraine, including 3 patients with TRMD and one patient with OCD. Four patients reported in migraine frequency and the need for rescue analgesia, of whom 3 also reported a decrease in maximum pain intensity. Prior to rTMS the mean days-per-week with migraine was 3, which was significantly reduced to 1.7 days- per-week (p=0.03). Worsening of migraine was observed in one patient, in terms of frequency and intensity of pain. Transient peri-procedural headache was associated with lack of efficacy of rTMS regarding migraine (p=0.071). Conclusion: This preliminary investigation suggests a potential sustained benefit of rTMS in reducing the number and the severity of attacks in migraine. Future prospective randomized trials, incorporating placebo- controlled designs and comparisons with established preventive therapies, are imperative to elucidate the precise therapeutic role of rTMS in the management of migraine. P161 Repetitive transcranial magnetic stimulation for major depression and obsessive-compulsive disorder – exploring the potential therapeutic effect in migraine A. Fernandes1, A. Alves2, J. Borges2, P. Sousa Martins2, R. Moreira2, A. Costa1 1Unidade Local de Saúde de São João, Neurology, Porto, Portugal 2Unidade Local de Saúde de São João, Psychiatry, Porto, Portugal to protocols impact of unilateral rTMS Objective: Assess the targeting the dorsolateral or dorsomedial prefrontal cortex, performed according for treatment-resistant major depression (TRMD) or obsessive-compulsive disorder (OCD) respectively, on migraine control. Methods: Clinical characterization of a cohort of patients who underwent rTMS in the last 10 months for TRMD or OCD, with a concomitant diagnosis of migraine. We conducted a questionnaire regarding migraine frequency, pain intensity, use of rescue analgesia, before and after rTMS. P162 Influence of music in postural stability in episodic migraine M. D. Villar Martinez1, A. Bronstein1, P. J. Goadsby1 1King's College London, London, United Kingdom "The Flight of Objective: In this study, we utilized a modified Wii Balance Board to gather center of pressure data as part of pre-tests and calibration procedures in a group of healthy volunteers. Methods: During the assessments, participants with episodic migraine were exposed to one minute of the renowned musical piece the Bumblebee" while standing on the board. Analysis of the gathered data was conducted using Acquire and Analysis 32 for Windows. Version 2.0 2005 by D. Buckwell, with statistical assessment including t-test and post-hoc power studies performed utilizing RStudio 4. Results: The cohort consisted of six females and one male who completed the test protocol. Our findings revealed a general trend towards increased stability among participants when exposed to the musical stimulus, despite the opposite subjective sensation, although these differences did not reach statistical significance. A post-hoc power analysis revealed an achieved power of 0.13 (Cohen"s d 0.5, P = 0.05). The required sample for achieving statistical significance would be 63.

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Conclusion: Despite our underpowered sample, the observed trend in the preliminary tests prompts intriguing considerations regarding the potential therapeutic and pathophysiological implications for individuals with vestibular migraine and other forms of dizziness. Music, with its ability to engage multiple sensory pathways and potentially synchronize with motor movements, holds promise as a non-invasive intervention for understanding postural stability. Fig. 1 Fig. 2 Fig. 3 P163 Transcutaneous pulsed radiofrequency treatment in patients with chronic headache and fibromyalgia M. Chondrogianni1, K. Foska1, A. Theodorou1, E. Bakola1, G. Papagiannopoulou1, S. Fanouraki1, N. Nana1, A. Sterpi1, C. Arvaniti2, G. Tsivgoulis1,3 1"Attikon" University Hospital, 2nd Neurological Department of NKUA, Chaidari, Greece 2Red Cross Hospital, Neurology, Athens, Greece 3University of Tennessee, Neurology, Memphis, TN, United States in patients with Objective: Fibromyalgia is a disabling syndrome characterized by widespread pain, fatigue, sleep disorders and headache. It is associated with all types of chronic headache with higher prevalence in migraineurs and tension-type headache. Transcutaneous pulsed radiofrequency treatment is used to alleviate several types of pain including neuralgia, joint pain and muscle pain. Methods: We report consecutive patients diagnosed with fibromyalgia and chronic headache that have been followed in our tertiary headache center during a 3-year period (January 2022 – December 2024). We performed transcutaneous pulsed radiofrequency treatment every six months applying the electrodes in different anatomical sites guided by the symptoms for a duration of 15 minutes in each site. Pain relief is estimated using the Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) and the Visual Analog Scale (VAS). Results: A total of 28 patients with chronic headache (tension n=22;chronic migraine,n=3occipital nevralgia,n=3) and fibromyalgia were pulsed radiofrequency. In our preliminary results patients experienced (>50%), as measured by the scales, following each treatment session, both in the acute phase post-treatment and in the followings days until the next session. No adverse events were reported during and after treatment. No patient discontinued the therapeutic protocol. Conclusion: Application of non-invasive techniques, such as transcutaneous pulsed radiofrequency, in chronic like fibromyalgia, should be considered in order to avoid medication overuse and prior to implantation of a neurostimulator. Further studies larger cohorts are needed to establish standardized protocols and to confirm the long-term safety and efficacy of this procedure. headaches with significant pain relief comorbidities treasted using transcutaneous type headache, including

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P164 Combined supra-orbital and occipital nerve stimulation for resistant migraine – implantation technique and early feasibility with a novel neurostimulation system K. Hanssens1, B. Billet1, R. De Vos1, M. Goethals2, W. Pollet3, P. Frank4, F. Huygen5 1AZ Delta Campus Roeselare, Roeselare, Belgium 2AZ Delta Campus Torhout, Torhout, Belgium 3Salvia Bioelectronics, Eindhoven, Netherlands 4Resolve Pain, Buderim, Australia 5Erasmus MC University Medical Center, Pain Medicine, Rotterdam, Netherlands disorder to increase spreading to add supra-orbital with central depression, is a disabling Objective: Chronic migraine (CM) complex a neurological pathophysiology—including sensitisation, cortical neurogenic inflammation, and dysfunctional processing of pain signals. Despite new pharmaceutical solutions able to help many patients, an important group still experiences limited efficacy and/or intolerable side effects. Occipital nerve stimulation is effective in a selective group of refractory chronic migraine patients. However, when looking at the pathogenesis, it makes to occipital nerve sense stimulation the effectiveness of neuromodulation in the treatment of these very disabled patients. Several observational studies have confirmed the effectiveness of combined supra-orbital and occipital nerve stimulation. Methods: Available implantable PNS systems, initially designed for spinal cord stimulation, can induce device-related complications like lead breakage, lead migration, skin erosion, and pain at the IPG site. This prevents the widespread use of this solution. implantable Results: neurostimulator system has been developed to address this medical need. The system comprises two implants, each with an ultra-thin lead connected to an integrated, battery-free stimulator; one covering both the left and right supra-orbital nerves, and the other covering both the left and right occipital nerves. The implants are placed during a short, minimally invasive, non-traumatic procedure using specially designed surgical instruments. Conclusion: We present the surgical technique and the initial data of an early feasibility study with this system in refractory chronic migraine patients. craniofacial A novel P165 Safety and effectiveness of a novel implantable neurostimulator in the prevention of resistant migraine M. Matharu1, L. Simmonds1, W. Pollet2, B. Billet3, K. Hanssens3, R. De Vos3, M. Goethals4 1The National Hospital for Neurology and Neurosurgery, London, United Kingdom 2Salvia Bioelectronics, Eindhoven, Netherlands 3AZ Delta Campus Roeselare, Roeselare, Belgium 4AZ Delta Campus Torhout, Torhout, Belgium (MMD) and inadequate. A novel Objective: Migraine is a debilitating neurological disorder. Many with high-frequency episodic migraine (HFEM) or chronic migraine (CM) find existing treatments implantable neurostimulator targets the supraorbital and greater occipital nerves. We report 3-month safety and efficacy outcomes. Methods: Participants had HFEM or CM, with ≥8 monthly migraine days failed ≥3 preventive treatments. System implantation was done as a day case, under local anesthesia and sedation. They used the device for 1 hour twice daily and during headaches. Outcome measures: MMD, MCCD, and HRQoL. Seven participants were evaluated after 3 months. Results: The study cohort (5 female; 2 male) included participants with CM, HFEM, probable daily headache, and probable medication overuse. Their mean (SD) age was 32.9 (6.4) years. At baseline, they reported mean (SD) MMD and MCCD of 13.4 (4.8) and 5.2 (3.9) days. No serious adverse events were observed during or after implantation. Minor, transient adverse events included pain, numbness, and fatigue. Mean daily stimulation was 3.3 hours. At 3 months, mean (SD) reduction in MMD was 5.0 (6.0) days. Quality of life improved significantly across various domains. Conclusion: Combined occipital and supraorbital nerve stimulation with implantable neurostimulation system was well-tolerated and had a favorable safety profile. The observed reduction in migraine frequency and improved HRQoL highlight its potential as an effective preventive therapy for resistant migraine. These preliminary results warrant a larger-scale study to confirm the safety and efficacy of the system. this novel

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P166 Migraine does not rest in the arms of Morpheus – a descriptive analysis of sleep quality M. Polanco Fernández1,2,3, J. Madera Fernandez1,2,3, V. González Quintanilla1,2,3, S. Pérez Pereda1,2,3, G. Gárate3, J. Pascual1,2,3 1University Hospital Marqués de Valdecilla, Neurology, Santander, Spain 2Universidad de Cantabria, Santander, Spain 3IDIVAL, Santander, Spain chronic migraine information about Objective: The aim of this study is to evaluate the impact of sleep quality on migraine among patients attending specialized headache consultations at our center. Methods: We gathered the characteristics of migraine, pain triggers, previously used treatments, and the disability experienced (MIDAS scale) in a sample of patients. We prospectively studied the level of daytime sleepiness using the Barcelona Sleeping Index (BSI), Epworth Scale (ES), and Stanford Scale (SS), as well as sleep quality (Pittsburgh Sleep Quality Index, PSQI) in patients who specialized headache attended consultations in May 2024. Results: A total of 103 patients (85.4% women; 40% with the questionnaire. 61.7% recognized sleep as one of their main migraine triggers, with only 12.1% reporting good sleep quality. Patients with CM exhibited a higher disability score (MIDAS:X2=4.451, p=0.035), increased daytime sleepiness (BSI:X2=9.984, p=0.002; SS:U Mann Whitney p=0.000), and worse sleep quality (PSQI:X2=5.973, p=0.015) compared to patients with episodic migraine (EM). Only 33% of the participants did not require hypnotics at some point, and 25.5% consumed them regularly. Conclusion: Patients with migraine, especially those with CM, experience poorer subjective sleep quality and increased daytime sleepiness. Neurologists should be aware of the possible impact of these aspects on the treatment response and migraine chronification. Long-term empirical studies are necessary to enhance our understanding of this connection. completed (CM)) P167 French migraine patients ineligible for or resistant to triptans: a primary care real-world study – France- Mig study V. Raclot1, M. Gugenheim2, E. Casarotto3, O. Bretin3, H. Lefebvre4, P. A. Squara4, M. Lantéri-Minet5,6 1Cabinet de Médecine Générale, Dijon, France 2Cabinet de Neurologie, Rambouillet, France 3IQVIA, Paris, France 4Pfizer, Paris, France 5Université Côte d'Azur, CHU Nice, Département Evaluation et Traitement de la Douleur, FHU InovPain, Nice, France 6CHU Nice and Côte Azur University, Nice, France triptans. Patient Objective: Identify and describe patients ineligible for or resistant to triptans in French primary care. Methods: France-Mig study is a non-interventional longitudinal retrospective cohort analysis from the IQVIA longitudinal patient databases. Adult migraine patients followed in 2022, with a minimum of 5-year previous history in the database, were identified from Electronic Medical Records via migraine diagnosis or specific migraine treatment (acute or preventive) prescriptions. Patients with contraindications or aged 65 or over (precautionary principle) were considered ineligible for triptans. Resistance to triptans was defined as the prescription of a third acute migraine two treatment after successive prescription of different characteristics and treatment prescriptions were described from 2017 to 2022. Results: Among 16 888 migraine patients, 4 024 (23.8%) were ineligible (1,364 due to cardiovascular contraindication, 605 due to a non-cardiovascular contraindication and 2,055 due to an age greater than or equal to 65 years old, these 3 groups being constructed as mutually exclusive) and 604 (3.6%) showed resistance to triptans (Table 1). The average age was 65 years and 46 years, respectively. Half (55.5%) of ineligible patients had received triptan prescriptions. Between 2017 and 2022, an association between a triptan and another attack treatment was observed in 878 (39.3%) triptan-ineligible patients and in 485 (80.3%) triptan-resistant patients. As a sensitive analysis, refractoriness to triptan was described to determine the proportion of triptan-resistant patients who would respond to a third triptan. Of the sample of 604 patients with triptan resistance only 81 (13.4%) were considered as refractory. Conclusion: This is the first real-world French study describing acute migraine treatment unmet needs in primary care. Over a quarter of French migraine patients care presented ineligibility for or resistance to triptans. in primary followed

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included based on their initial efficacy response at weeks 13- 16: ≥50%, ≥75%, and 100% reduction in monthly migraine days (MMDs) from lead in study baseline. The sustained responses were assessed at Weeks 29- 32 and Weeks 45-48. Results: Of 595 participants, 88% (N=524; ELEVATE, n=240; PROGRESS, n=284) were in the modified intent-to-treat population. Among all participants who achieved an initial response of ≥50%, ≥75%, and 100% reduction in MMDs from the lead-in study baseline at Weeks 13-16, 78.1% (214/274), 64.9% (111/171) and 40.3% (29/72) sustained the same response at both Weeks 29-32 and Weeks 45- 48, respectively (Figure). Sustained response rates in the lead-in study subgroups were similar to those observed in the total population. The overall safety results of this study were consistent with the previously reported safety profile of atogepant. Conclusion: Most initially experienced clinically meaningful improvements in migraine frequency with atogepant sustained these benefits over 48 weeks, affirming the long-term efficacy of the treatment. participants who Fig. 1 Fig. 1 P168 Long-term sustained response of Atogepant in episodic and chronic migraine: an interim analysis of a phase 3, open-label, 156-week safety extension study P. Pozo-Rosich1,2, S. Sacco3, S. J. Cho4, U. Najib5, H. Ashina6, Y. Liu7, J. H. Smith7, K. Carr7, B. Dabruzzo7, N. Chalermpalanupap7, D. Friedman8 1Universitari Vall d'Hebron, Barcelona, Spain 2Universitat Autònoma de Barcelona, Barcelona, Spain 3University of L'Aquila, L'Aquila, Italy 4Hallym University College of Medicine, Hwaseong, South Korea 5West Virginia University, Morgantown, WV, United States 6Translational Research Center, Copenhagen University Hospital – Rigshospitalet, Copenhagen, Denmark 7AbbVie, Neuroscience, North Chicago, IL, United States 8Yellow Rose Headache and Neuro-Ophthalmology, Dallas, TX, United States Objective: To evaluate the long-term sustained response of atogepant for the preventive treatment of migraine. Methods: This interim analysis of a Phase 3, open- label, 156-week long-term safety extension study assessed the long-term safety, tolerability, and efficacy of atogepant 60 mg once daily for preventive treatment of migraine. Participants with episodic migraine who had an inadequate response to 2-4 classes of conventional oral preventive migraine treatment and completed the Phase 3 ELEVATE trial or participants with chronic migraine who had completed the Phase 3 PROGRESS trial were included. In analysis, participants were categorized into three non-mutually exclusive groups this post-hoc

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P169 Salivary CGRP1/CT ratio and Cytokine profile as potential biomarkers of migraine H. Nersesyan1,2, Y. Nersesyan3,4, C. Gondi3,5,6,7, L. Demirkhanyan3,5 1University of Illinois Colllege of Medicine at Peoria, Neurology, Peoria, IL, United States 2OSF Saint Francis Medical Center, Osf Illinois Neurological Institute, Peoria, IL, United States 3University of Illinois College of Medicine in Peoria, Medicine Department, Peoria, IL, United States 4University of Illinois College of Medicine in Peoria, Cancer Biology and Pharmacology, Peoria, IL, United States 5University of Illinois College of Medicine in Peoria, Surgery, Peoria, IL, United States 6University of Illinois Urbana Champaign, The Grainger College of Engineering, Urbana Champaign, IL, United States 7University of Illinois College of Medicine in Peoria, Health Sciences Education and Pathology, Peoria, IL, United States Objective: Migraine significantly impacts daily life for millions of people worldwide. Despite its prevalence and established clinical diagnostic criteria, accurate and timely diagnosis of migraine is still lacking. This pilot study investigates the potential of salivary biomarkers as an objective, efficient, and non-invasive aid for migraine diagnosis. Methods: Saliva samples were collected from 10 migraineurs and 6 healthy controls, ensuring a standardized collection process. Analysis focused on Calcitonin Gene-Related Peptide alpha (CGRP1), Calcitonin (CT), and cytokine levels. Results: We observed strong correlation in the CGRP1 to CT ratio between migraineurs and controls, which suggests its diagnostic potential. Additionally, cytokine analysis revealed a distinct inflammatory profile in migraineurs. Specifically, there was up to 7- fold levels of pro-inflammatory molecule CXCL5, while other pro-inflammatory cytokines, such as IL-1 alpha and IL-8, were decreased by nearly 2-fold. Interestingly, the anti-inflammatory marker adiponectin also showed a 1.6-fold decrease. These future therapeutic targets, focusing on modulating the activity of CXCL5 and adiponectin. Conclusion: This study highlights the value of saliva as a non-invasive, readily available vehicle for migraine traditional diagnosis, potentially complementing clinical approach. The significant differences in CGRP1/CT ratio between migraineurs and non- migraineurs, along with a unique cytokine profile, suggest that saliva-based diagnostics can potentially enhance and expedite diagnostic accuracy of migraine. By providing insights into the inflammatory findings may have potential increase in the for processes associated with migraine, this approach could also revolutionize current diagnostic methods. Integrating salivary biomarker analysis into clinical practice of migraine management holds promise for earlier diagnosis, personalized treatment strategies, and improved patient outcomes for this debilitating neurological condition. P170 Interictal burden before initiating Calcitonin gene- related peptide monoclonal antibody for migraine prevention C. Lampl1, E. Seng2, M. Vincent3, M. Hoyt3, W. R. Lenderking4, K. Malley4, L. Hetherington5, D. Ruff3, G. Kim3, L. Viktrup3 1Konventhospital Barmherzige Brüder Linz, Department of Neurology & Headache Medical Center, Linz, Austria 2Yeshiva University, Ferkauf Graduate School of Psychology, New York, NY, United States 3Eli Lilly and Company, Indianapolis, IN, United States 4Evidera, Bethesda, Bethesda, MD, United States 5Evidera, London, United Kingdom IIB in patients with migraine Objective: To assess interictal burden (IIB) in patients initiating their first calcitonin gene–related peptide (CGRP) monoclonal antibody (mAb) for migraine prevention. Migraine is disabling, but the factors occurring within headache-free intervals are key for treatment seeking behavior. Hence, drivers understanding is important. Methods: We conducted a 20–30 minute, non- interventional, online survey in the US among 500 patients who recently enrolled in the galcanezumab Patient Support Program between Jul–Dec 2022. Patients were ≥18 years of age, diagnosed with episodic (EM, n=250) or chronic (CM, n=250) migraine, and had initiated galcanezumab ≤6 months prior to survey completion/were naïve to galcanezumab. IIB was estimated using the Migraine IIB Scale (MIBS–4) total score (0=no burden, 1–2=mild, 3–4=moderate, 5–12=severe). Analyses were descriptive. Results: Overall, mean time since first migraine symptom was 18.1 years. Anxiety (45%) and depression the most prevalent comorbidities. Mean (SD) MIBS-4 total score was 4.3 (3.2) (EM:3.8 [3.0], CM:4.8 [3.4]). MIBS–4 results indicated approximately half (46%; EM:40%, CM:53%) of the patients had severe IIB, while the rest had moderate (19%; EM:22%, CM:16%), or no (16%; EM:18%, CM: 14%) IIB. Most patients (71%; EM:64%, CM:79%) often/always had less energy for work/school during the headache- free intervals and most (70%; EM:64%, CM:76%) (19%; EM:21%, CM:17%), mild (44%) were

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often/always worried about the impact of migraine on work/school. Conclusion: Patients with migraine, particularly those with chronic migraine, experience moderate to severe interictal burden at the time of their first CGRP mAb. Conclusion: Anti-CGRP mAbs improve sleep quality in both responders and non-responders, with sleep correlated with mood amelioration improvement. A better sleep-wake cycle is an additional beneficial effect of anti-CGRP mAbs. being P171 Anti-CGRP monoclonal antibodies improve sleep quality in migraine patients – a 1-year, multicenter, longitudinal study C. Aurilia1, G. Egeo1, D. Le Pera1, F. d'Onofrio2, B. Orlando1, G. Fiorentini1, S. Bonassi3, P. Barbanti1 1IRCCS San Raffaele Rome, Headache and Pain Unit, Rome, Italy 2San Giuseppe Moscati Hospital, Headache Center Neurology Unit, Avellino, Italy 3IRCCS San Raffaele Rome, Clinical and Molecular Epidemiology, Rome, Italy implicated in (CGRP) Objective: Calcitonin-gene-related-peptide seems in circadian rhythm. We thus evaluated the effects of anti-CGRP monoclonal antibodies (mAbs) on sleep individuals with migraine. Methods: This prospective, multicenter study (n=2) evaluated consecutive adults with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who were treated with anti-CGRP mAbs for >12 months. The primary endpoint was the change in sleep quality from baseline at week 48, assessed using the Pittsburgh Sleep Quality Index (PSQI), with a score >5 indicating poor sleep. Secondary endpoints included changes in PSQI score at 3 and 6 months, variations in excessive daytime somnolence (EDS, Epworth Sleepiness Scale score >10), depression (BDI), migraine frequency (MMD/MHD), monthly analgesic intake (MAI), Numerical Rating Scale (NRS), migraine disability (HIT-6, MIDAS), and response rates (RR) at 3, 6, and 12 months. Results: We enrolled 64 migraine patients (M/F: 6/58; HFEM/CM: 20/44; mean age: 46.6 years) treated with galcanezumab (n=30). Baseline PSQI scores >5 correlated with migraine disability (p=0.012), EDS (p=0.047), and depression (p=0.001). Anti-CGRP mAbs significantly (p<0.001) reduced the proportion of poor sleepers at months 3 (51.6%), 6 (43.8%), and 12 (35.9%) compared to baseline (78.1%), irrespective of sex, age, responder status, MMD/MHD, or mAb type. Anti-CGRP mAbs also significantly (p<0.001) decreased EDS, BDI, MMD/MHD, MAI, NRS, HIT-6, and MIDAS scores across months 3, 6, and 12 compared to baseline. Response rates were >50% at 79.7%, 93.7%, and 98.4%, >75% at 25%, 35.9%, and 45.3%, and 100% at 1.6%, 0%, and 1.6%, respectively. PSQI score variation was positively associated with BDI values (p<0.021). fremanezumab (n=34) or P172 Differences in structural neuroimaging in migraine and healthy controls J. Rosell-Mirmi1, E. Caronna1,2, V. J. Gallardo López1, D. Pareto3, A. Alpuente1,2, M. Torres-Ferrús1,2, À. Rovira3, P. Pozo-Rosich1,2 1Vall Hebron Institute of Research (VHIR), Headache and Neurological Pain Research Group, Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Headache Unit, Barcelona, Spain 3Hospital Universitari Vall d'Hebron, Radiology Department, Barcelona, Spain Objective: To describe baseline differences in brain structure in healthy (HC) and migraine participants, and evaluate whether if after 6 months of preventive treatment these can predict response. Methods: Prospective interventional study including HC and episodic (EM) and chronic migraine (CM) participants, all right handed. 3T brain MRI imaging T1-MPRAGE protocols were done before and after 6 months of treatment with onabotulinumtoxinA and anti-CGRP mABs. Clinical variables were collected, and responders were defined having ≥50% reduction in headache days/month. FreeSurfer® software (v7.4.1) was used to segment the regions of interest (ROI) and extract the values. Cortical thickness (CT) and brain volumes values were analysed using generalized linear mixed models. Groups were compared, and p-values were adjusted for multiple comparisons using FDR. Pairwise Pearson correlations were performed between MRI measures and clinical variables. Results: We included 147 M and 63 HC with a mean age 39.8±9.7 years. In M, compared to HC, no CT area was significantly different, but increased volumes were observed in both, left and right pallidum and mid and central corpus callosum (p<0.05). These same areas showed an increase in volume according to diagnosis (CM>EM>HC, p<0.05). In EM, higher CT was observed in the right cuneus and left inferior parietal lobe (p<0.05) and; in CM, in the left paracentral lobe (p<0.05). There was a significant positive correlation between corpus callosum volume and years of migraine disease evolution (r=0.21, p<0.05). No structural brain baseline differences were found between responders and non-responders, but the interaction between response and the treatment received was significant for right caudate and left choroid plexus (p<0.05).

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Conclusion: Migraine is associated with brain structural changes, particularly characterized by a proportional to diagnosis volume increase which is mainly linked to multimodal sensory and pain processing areas. P173 Switching between triptans: real-life findings from a headache outpatient clinic L. Pereira1, M. Rodrigues1 1Hospital Garcia de Orta, Unidade Local de Saúde Almada-Seixal, Neurology, Almada, Portugal Objective: Triptans are established acute migraine treatments, but 30-40% of patients fail to respond or experience side effects. While switching between triptans is advised, the evidence comes from small open-label studies with strict criteria and limited triptan options. This study aims to report the results of triptan switching, including the effectiveness of additional switch after failure, in a real-life setting. Methods: Retrospective review of patients using triptans from a single-center headache clinic was conducted. A standardized interview was used to collect data on triptan response in terms of the percentage of attacks, time to pain freedom, and side effects. EHF 2022 Consensus definitions were applied to these reports. We present descriptives and clinical outcomes with triptans. Results: Among 208 migraineurs, 136 returned after filling a triptan prescription, 91.2% female, median age 40.5 years. The median number of triptan attempts ranged from 1 to 6, with 58.1% using 1 triptan, 25.7% 2 triptans, 7.4% 3 triptans, and 8.8% more than 3. The response rate to the 1st triptan was 44.9%, 16.9% to the 2nd, 3.7% to the 3rd and 4th, with only 2.9% responding to further attempts. Failure of at least 2 triptans was observed in 26.5%, and of at least 3 triptans on 13.2%. The most successful switches were from eletriptan (E) to zolmitriptan (Z) with a 60% success rate, from E to rizatriptan (R) 55.6%, from R to E 50% and from Z to sumatriptan 50%. Tailing the top 6 combination switches were from Z to E with a 35.3% success rate and from Z to R 12.5%. Conclusion: A quarter of our patients are triptan- resistant and nearly one sixth triptan-refractory. Per the guidelines they were offered a new triptan, with best chance of response at the second attempt, with marginal benefit of further trials. Switches between fast-acting triptans were the most common, without evidence of a single better second-line triptan. Gepants and other future acute migraine treatments may fill this unmet need. P174 Comparing candesartan and Vitamin E for prophylactic treatment in episodic migraine patients A. Oosterlee1, B. W. H. van der Arend1, E. W. Van Zwet1, N. Pelzer1, G. M. Terwindt1 1Leiden University Medical Center, Neurology, Leiden, Netherlands Objective: To investigate the efficacy of candesartan compared to vitamin E as prophylactic treatment in patients with episodic migraine Methods: This cohort study gathered headache e- diary data from individuals with episodic migraine (EM) at the Leiden Headache Center. We compared female patients with EM who were prescribed candesartan or vitamin E. Our e-diary has a validated algorithm capable of distinguishing between monthly migraine days (MMD) and monthly headache days (MHD). The baseline period was defined as the 28 days preceding the start of treatment. Primary outcome was the 50% responder rate for reduction in MMD from baseline to the last 28-day period with the highest achieved dosage of candesartan (≥4 mg daily) or vitamin E (400 IU daily). Secondary outcomes were change in MMD, MHD, and monthly acute medication days (MAMD). Groups were adjusted for baseline differences using propensity score matching, with each patient receiving a score based on age, MMD and MAMD, and then matched 3:1 (candesartan to vitamin E). Chi-square test was used for the primary outcome, t-tests were used for secondary outcomes Results: After matching, n=183 subjects were in the candesartan group and n=61 in the vitamin E group. The mean age was 46.17 ± 11.66 years for candesartan and 43.44 ± 8.44 for vitamin E. At baseline, the groups were comparable for MMD (5.89 ± 2.38 vs. 5.20 ± 2.77), MHD (9.65 ± 4.31 vs. 8.16 ± 3.69), and MAMD (5.57 ± 3.27 vs. 5.77 ± 3.37). 29.5% of patients in the candesartan group and 31.1% in the vitamin E group had a ≥50% response (OR=1.1; 95% CI: 0.6-2.0). No differences were found between candesartan and vitamin E in the mean reduction of MMD (0.83 ± 3.46 vs. 0.66 ± 3.08, p=0.73), MHD (1.25 ± 4.23 vs. 0.74 ± 3.31, p=0.39), and MAMD (0.31 ± 4.18 vs. 0.44 ± 2.90, p=0.82) Conclusion: Both candesartan and vitamin E treatments achieved comparable 50% responder rates, similar to CGRP-Mabs treatments in clinical trials, indicating significant efficacy

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P175 Impact of neck pain with headache among people with migraine, adjusting for headache frequency – Multicountry results from the chronic migraine epidemiology and outcomes – International cross- sectional study R. B. Lipton1, Z. Katsarava2,3, M. Matharu4, D. C. Buse1, I. Shakhmantsir5, L. Delahaye6, K. Fanning7, E. Leroux8 1Albert Einstein College of Medicine, Bronx, NY, United States 2Christian Hospital Unna, Unna, Germany 3University of Duisburg-Essen, Essen, Germany 4Institute of Neurology, London, United Kingdom 5AbbVie, North Chicago, IL, United States 6AbbVie, Rungis, France 7MIST Research, Wilmington, NC, United States 8Montreal Neurological Clinic, Montreal, Canada anxiety (PHQ-4; Objective: Assess the impact of neck pain with headache (NPWH) on disease burden in migraine, adjusting for monthly headache day (MHD) frequency. Methods: CaMEO-I was a cross-sectional web-based study in Canada, France, Germany, Japan, UK, and US from Jul 2021–Mar 2022. Respondents with migraine (per modified International Classification of Headache Disorders 3rd ed. [ICHD3] criteria) indicated how often they had neck pain during headaches; those answering "never" or "rarely" were classified as having no NPWH; those answering "less than half the time" or "half the time or more" were classified as having NPWH. Disease burden was assessed using the (MIDAS), Patient Migraine Disability Assessment Health Questionnaire-4 and depression screener), Migraine Symptom Severity Score, Migraine-Specific Quality of Life questionnaire (MSQ), and Allodynia Symptom Checklist-12 (ASC-12). Results were pooled across countries and stratified by NPWH or no NPWH within MHD frequency groups (0– 3, 4–7, 8–14, 15–22, 23–30). Binary logistic regression models assessed the association of neck pain with disease burden adjusted for age, sex, MHD category, and MHD category by neck pain interaction. included 14,492 respondents Results: The study identified with ICHD3 migraine (n=4596 without NPWH; n=9896 with NPWH). In lower MHD groups, a higher proportion of participants with NPWH vs without NPWH had a self-reported medical diagnosis (SRMD) of migraine (Figure 1A). Migraine disease burden and allodynia prevalence were higher among respondents with migraine with NPWH vs without NPWH (Figure 1B–D; Table 1). NPWH was associated with a higher adjusted odds ratio (OR [95% CI]) of migraine SRMD (1.37 [1.19, 1.58]), allodynia (1.96 [1.69, 2.27]), moderate-severe disability (2.41 [2.03, 2.86]), and anxiety and depression symptoms (1.70 [1.45, 1.98] and 1.64 [1.40, 1.91], respectively). Conclusion: Across most MHD groups, CaMEO-I respondents with migraine with NPWH vs without NPWH had higher disease burden and allodynia prevalence. Fig. 1 Fig. 2 P176 Tryptophan metabolism in migraine M. Fila1, L. Przyslo1, J. Chojnacki2, M. Derwich2, C. Chojnacki2, E. Pawlowska2, J. Blasiak3 1Polish Mother Memorial Hospital Research Institute, Department of Developmental Neurology and Epileptology, Lodz, Poland 2Medical University of Lodz, Lodz, Poland 3Mazovian Academy in Plock, Faculty of Medicine, Plock, Poland Objective: Tryptophan (TRP) metabolism is associated with neurological and psychiatric disorders. In this work, we investigated the urinary levels of TRP and its main metabolites in migraine patients. Methods: A total of 21 low-frequency episodic migraine patients and 32 headache-free controls were enrolled in this study. Urine samples were taken in the interictal phase of migraine and the levels of TRP and its main metabolites 5-Hydroxyindoleacetic (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA), quinolinic acid (QA), vanillylmandelic acid (VMA), homovanillic acid (XA) were determined with liquid chromatography-tandem mass spectrometry. Results: Migraine patients displayed lower urinary levels of 5-HIAA (p < 0.01) and KYNA (p < 0.05), but (HVA) and xanthurenic acid

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the levels of KYN and QA were enhanced, as compared with the controls (p < 0.05 and 0.001, respectively). Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios (p < 0.001 for all). Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score and monthly migraine and monthly headache days. There was a negative correlation between Patient Health Questionnaire 9 scores assessing the occurrence and severity of depression. Conclusion: Tryptophan metabolism may be involved in migraine pathogenesis and the urinary 5-HIAA level may be a candidate as a non-invasive and easy-to- determine marker of migraine. 5-HIAA levels and P178 Migraine preventive treatment with eptinezumab improved patient-reported outcomes in patients with non-response on frequency of monthly migraine days J. Ailani1, P. Barbanti2,3, S. J. Tepper4, S. A. Regnier5, S. W. Grossman5, S. F. Awad6, A. Ettrup6, A. J. Starling7 1Department of Neurology, Georgetown University Hospital, Washington, DC, United States 2Headache and Pain Unit, IRCCS San Raffaele Roma, Rome, Italy 3San Raffaele University, Rome, Italy 4New England Institute for Neurology and Headache, Stamford, CT, United States 5Lundbeck LLC, Deerfield, IL, United States 6H. Lundbeck A/S, Copenhagen, Denmark 7Mayo Clinic Arizona, Scottsdale, AZ, United States study impact of preventive Objective: To explore the migraine treatment beyond monthly migraine day (MMD) reduction, this post hoc analysis assessed the effect of eptinezumab (epti) on Patient Global Impression of Change (PGIC) and Headache Impact Test (HIT-6) in patients with <50% MMD reduction. Methods: The DELIVER (NCT04418765) randomized adults with migraine and 2–4 prior preventive failures to epti 100mg, 300mg, or placebo (IV every 12 weeks [wks]) for a 24-wk, placebo- controlled period before a 48-wk, dose-blinded extension period. PGIC responder rates (% of patients reporting "very much improved" or "much improved") and HIT-6 total score were assessed in patients who had <50% MMD reduction during Wks1–24 and in patients receiving epti for all 6 doses and had <50% MMD reduction for each dosing interval. Results: Of 892 patients randomized (epti pooled n=593; placebo n=299), 865 (97%) entered the extension period and 782 (88%) completed the study. Of patients with <50% MMD reduction over Wks1–24, 40% (110/272) receiving epti (100mg 41% 57/140; 300mg 40% 53/132) vs 17% (39/232) receiving placebo were PGIC responders at Wk24 (OR 3.88, P<0.001). Of 494 patients treated with epti for all 6 doses and had MMD data for each, 92 (19%) had <50% MMD reduction for all dosing intervals. Of these patients, 32/88 (36%) were PGIC responders, 44/85 (52%) were HIT-6 responders (≥5-point improvement), and 57/88 (65%) had either response at Wk72. In the subset who were not PGIC responders (n=56), Wk72 mean change from baseline in HIT-6 was a 4.7-point improvement. Conclusion: This post hoc DELIVER analysis highlighted that patients with <50% MMD reduction showed higher rates of much/very much improved PGIC after epti vs placebo treatment over 24 wks. Similarly, a cohort of patients with <50% MMD reduction who opted to complete the 72-wk study reported improvement via PGIC or HIT-6, suggesting that benefits of epti are not sufficiently captured solely by evaluating MMD reductions. P179 Treatment with Zavegepant offers improvements in pain severity over 48-hours when compared with Placebo – post hoc results from a randomized Placebo-controlled trial (BHV3500-301) P. Jayasinghe1, F. O'Sullivan1, E. Popoff1, L. Powell1, J. Cirillo2, L. Abraham3, J. Ailani4 1Broadstreet Health Economics and Outcomes Research, Vancouver, Canada 2Pfizer R&D US Ltd, New York, NY, United States 3Pfizer R&D UK Ltd, Surrey, United Kingdom 4Medstar Georgetown University Hospital, Neurology, Washington, DC, United States placebo-controlled Objective: To evaluate pain severity trajectories over 48-hours in patients treating a single migraine attack with zavegepant 10 mg nasal spray or placebo. Methods: Eligible patients for this post-hoc analysis were from BHV3500-301: a phase III double-blind, randomized, study (NCT04571060). Patients included adults with ≥1-year history of migraine. Pain severity (0mins-48hrs) was measured on a 4-point Likert scale, from no to severe pain. Outcomes included the percentage of patients by pain state and time point, and average time spent in each state across treatment arms over 48-hours. Trajectories were analyzed for cases with complete data (n=630) and using missing not at random (MNAR) imputation (n=1269). T-tests were conducted to determine differences between groups. Results: Among 1,269 patients (zavegepant=623, placebo=646), pain severity distribution was similar at time experiencing moderate/severe pain. No/mild pain was achieved patients with 0, all

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among both groups as early as 15-minutes post-dose, but in a larger proportion of zavegepant patients (16.5% vs 8.3%). At 1-hr 45.8% of zavegepant arm were experiencing no/mild pain vs. 38.6% on placebo (Figure 1). The proportion of patients experiencing moderate/severe pain continued to reduce in both study arms over 48-hrs. Averaging across patients, the mean (standard deviation) time spent with no pain/mild pain was higher for zavegepant (36.8hrs (34.0hrs [15.4]). Zavegepant [13.9]) vs. placebo patients in moderate/severe pain (11.2hrs [13.9]) compared to placebo patients [15.4]), p-value=0.001 (Table 1). Results were similar when analyzing complete cases versus MNAR. Conclusion: Acute treatment of a single migraine attack with nasal zavegepant was associated with an increased reduction in pain severity over 48-hours, when compared to placebo. zavegepant patients spent more time in no/mild pain and less time in moderate/severe pain when compared with placebo. significantly (14.0hrs spent time less Fig. 1 Fig. 2 P180 Contemporary prospective understanding of migraine real-world evidence (CAPTURE): baseline patient-reported outcomes E. Leroux1, P. J. Goadsby2,3, Z. Katsarava4, M. Lantéri- Minet5,6, E. Tucker7, Y. Liu8, J. Lam7, H. Ha7, L. Delahaye7, P. Pozo-Rosich9 1Montreal Neurological Clinic, Montreal, Canada 2King's College London, NIHR-King’s Clinical Research Facility, London, United Kingdom 3University of California, Los Angeles, CA, United States 4Evangelical Hospital Unna, Unna, Germany 5CHU Nice and Côte Azur University, Pain Department and FHU InovPain, Nice, France 6Auvergne University, INSERM U1107 Migraine and Trigeminal Pain, Clermont-Ferrand, France 7AbbVie, Toronto, Canada 8AbbVie, North Chicago, IL, United States 9Vall Hebron Institute of Research (VHIR), Headache Unit, Barcelona, Spain and Activity Productivity is a 2-year, [WPAI], Headache Objective: CAPTURE international, prospective, longitudinal study aiming to elevate the understanding of disease burden and treatment patterns among people living with migraine, stratified by headache frequency. Methods: Adults with migraine diagnosed for >=1 year, aged <50 years at onset, and taking >=1 medication indicated for migraine with >=4 monthly headache days (MHDs) in the prior 3 months were assigned to cohorts based on headache frequency (cohort 1: 4-<8 MHDs; cohort 2: 8-<15 MHDs; cohort 3: >=15 MHDs; Figure). Descriptive data for baseline characteristics and patient-reported outcomes (PROs) (Migraine Disability Assessment [MIDAS], Migraine- Specific Quality of Life questionnaire v2.1 [MSQv2.1], Work Impairment Questionnaire Impact Test-6, Patient Global Impression–Severity, Hospital Anxiety and Depression Scale, Migraine Interictal Burden Scale) are presented. Endpoints include durations of current/subsequent migraine treatment use and change from baseline of clinical outcomes (eg, MHDs, medication use, PROs). Results: Among 239 participants (as of December 2023; cohort 1: n=68; cohort 2: n=104; cohort 3: n=67) (Table 1), baseline PROs indicated greater impairment and poorer quality of life with higher MHDs (Table 2). For cohorts 1, 2, and 3, respectively, baseline mean (SD) MIDAS total scores were 29 (40), 33 (30), and 61 (52); MSQv2.1 Role Function–Restrictive scores were 58.9 (17.5), 53.4 (20.8), and 44.8 (22.0); and WPAI migraine-related impairment was 39.4 (27.2), 40.6 (24.8), and 52.0 (22.8). Conclusion: Baseline PROs suggest greater disease burden among participants with higher MHD

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frequency. CAPTURE will provide critical data on migraine disease patterns and the associated burden over time. Fig. 3 Fig. 1 Fig. 2 P181 Long-term safety and discontinuation for rimegepant versus lasmiditan – a matching-adjusted indirect comparison B. Rogula1, C. de Brún1, L. Powell1, A. Jenkins2, T. Kitano3, J. Atkinson2, L. Abraham2 1Broadstreet Health Economics and Outcomes Research, Vancouver, Canada 2Pfizer R&D UK Ltd, Surrey, United Kingdom 3Pfizer Japan Inc., Tokyo, Japan using matching adjusted Objective: Rimegepant 75mg and lasmiditan 100 and 200mg are novel therapies for the acute treatment of migraine that have established safety and efficacy vs placebo but have not been compared in head-to-head trials. The aim of this analysis was to compare rates of discontinuation and adverse events (AEs) over 52- weeks of PRN (as needed) use of rimegepant and lasmiditan indirect comparisons (MAICs). Methods: MAIC was performed in accordance with recommendations from the National Institute for Health and Care Excellence Decision Support Unit. The lasmiditan (NCT02565186) was chosen for comparison to rimegepant trial BHV3000- 201 (NCT03266588) based on similarities in trial design, patient population, and outcomes. Individual patient data from BHV3000-201 were weighted to match the aggregate baseline covariates reported in GLADIATOR. were discontinuation rates and rates of AEs. For each outcome, odds ratios (ORs), risk ratios, and risk trial GLADIATOR Outcomes of interest

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differences were estimated, with 95% confidence intervals (CIs). Results: The odds of discontinuation were lower for rimegepant than for either lasmiditan dose, OR: 0.5 (95%CI: 0.4, 0.6) for both 100mg and 200mg. Patients were also less likely to discontinue rimegepant than lasmiditan 100mg due to AEs, OR: 0.3 (95% CI: 0.2, 0.4). Rimegepant patients had a reduced risk of experiencing dizziness (2.2% vs 15.7%), somnolence (1.4% vs 7.8%), paresthesia (0.7% vs 5.3%), nausea (3.2% vs 3.9%), fatigue (1.7% vs 4.7%), asthenia (0.1% vs 1.5%), and lethargy (0.2% vs 2.0%), compared to lasmiditan 100mg, all p<0.05. Results vs lasmiditan 200mg showed even greater differences favouring rimegepant. Conclusion: This MAIC supports the favourable safety profile of rimegepant, demonstrating that patients using rimegepant PRN for the acute treatment of migraine were to discontinue and experience AEs compared to lasmiditan 100mg and 200mg over 52-weeks. likely less P182 Chronic migraine and ergots use cause higher serum pentraxin 3 levels and endothelial dysfunction in migraine M. Nada1, E. Fahmy1, N. Alaa1, S. Sharaf2, W. Osama1, H. Elshebawy1 1Cairo University, Neurology, Cairo, Egypt 2Cairo University, Clinical pathology, Cairo, Egypt Objective: To measure serum pentraxin 3, as an indicator of endothelial dysfunction, in migraine and to examine its correlation with clinical characteristics. Methods: A case-control study was conducted on forty migraineurs and forty healthy matched controls. intensity of headache were The severity and quantified using Headache Impact Test and the translated Arabic version of Migraine Disability assessment questionnaires. Both patients and controls underwent measurement of serum pentraxin 3 level. Results: Patients with migraine had a significantly higher mean serum pentraxin 3 when compared to controls. Patients with chronic migraine and those taking ergots also had significantly higher serum pentraxin 3 there levels. were statistically significant positive correlations between frequency of headaches and duration of the disease with serum pentraxin 3 level. For diagnosing endothelial dysfunction in migraine patients, the sensitivity and specificity of serum pentraxin 3 were 85% and 95%, respectively with cut-off value of 3.100 ng/ml. Additionally, Conclusion: Serum pentraxin 3 could be used as a chemical biomarker for endothelial dysfunction in migraine with high sensitivity and specificity. P183 Impact of Fremanezumab cessation and reinitiation in migraine management: PEARL study 4th interim analysis D. Mitsikostas1, M. Ashina2,3, F. Mohammad Amin1,4, P. Kokturk5, C. J. Schankin6, G. Sahin7, P. Pozo-Rosich8, P. Dorman9, T. Nežádal10, I. Pavão Martins11, M. L. Sumelahti12, V. Ramirez Campos13, X. Ning13, H. Akcicek5, C. Tassorelli14,15 1Aeginition Hospital, National and Kapodistrian University of Athens, Department of First Neurology, Athens, Greece 2Danish Headache Center – Rigshospitalet, Department of Neurology, Copenhagen, Denmark 3University of Copenhagen, Copenhagen, Denmark 4Rigshospitalet Glostrup, University of Copenhagen, Department of Neurorehabilitation/Traumatic Brain Injury, Copenhagen, Denmark 5Teva Netherlands B.V., Amsterdam, Netherlands 6Inselspital, University Hospital Bern, Bern, Switzerland 7Lund University, Skåneuro Neurology Clinic, Department of Clinical Sciences of Lund, Lund, Sweden 8Hospital Universitari Vall d'Hebron, Barcelona, Spain 9The Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, United Kingdom 10Charles University, Institute of Neuropsychiatric Care, First Faculty of Medicine, Prague, Czech Republic 11University of Lisboa, Centro de Estudos Egas Moniz, Faculty of Medicine, Lisboa, Portugal 12Faculty of Medicine and Health Technology, University of Tampere, Tampere, Pirkanmaa, Finland 13Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, United States 14University of Pavia, Department of Brain and Behavioral Sciences, Pavia, Italy 15Fondazione Mondino IRCCS, Pavia, Italy Objective: Despite recent updates to the guidelines, some reimbursement authorities still mandate a pause in preventive treatment with calcitonin gene- related peptide (CGRP) pathway monoclonal antibodies (mAbs) after 1 year of continuous use. frequently return However, migraine symptoms following treatment effectiveness can be reduced upon reinitiation. Methods: PEARL (EUPAS35111) is a Phase 4 study evaluating of fremanezumab in adults with episodic or chronic migraine. The fourth interim analysis was conducted effectiveness real-world treatment cessation and the

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when all participants completed ≥12 months of treatment; this sub-analysis explored the impact of fremanezumab cessation and reinitiation on monthly migraine days (MMD). Results: Of 220 participants with documented cessation of fremanezumab, 98 stopped treatment for reimbursement, and 192 reinitiated after a mean (SD) period of 2.6 (2.0) months (Table 1). Over 40% of participants experienced worsening of migraine (≥50% increase in MMD) at Months 1 and 2 post-cessation (Figure 1). Mean MMD decreased after reinitiation but remained higher than before cessation (Figure 2). The proportion of participants achieving ≥50% in MMD at Month 1 and Month 3, reduction respectively, was 49.0% and 58.9% in the first treatment period (before cessation) versus 35.7% and 45.5% (after reinitiation). Conclusion: Post-fremanezumab cessation, a notable rise reduced effectiveness upon reinitiation. This challenges the rationale behind mandated treatment pauses, underscoring the need for individualised patient management strategies. Disclosures: This study was Pharmaceuticals. in MMD was observed, with funded by Teva in the second treatment period Fig. 1 Fig. 2 Fig. 3 P184 Physical activity levels analysis in patients with chronic migraine treated with Fremanezumab. Phy- My-Mig Study Á. Sierra Mencia1, D. García-Azorín2, A. Recio García1, A. J. Molina de la Torre3, Y. González-Osorio1, R. Areses-Calderon1, Á. L. Guerrero-Peral1 1Hospital Clinico de Valladolid, Headache Unit, Valladolid, Spain 2Hospital Universitario Río Hortega, Neurology Department, Valladolid, Spain 3Universidad de León, Preventive Medicine and Public Health Area, León, Spain Objective: The aim of this study is to evaluate changes in physical activity and sitting time levels in patients with chronic migraine treated with Fremanezumab, comparing responders with no responders and correlating this with clinical variables. Methods: Observational, longitudinal, prospective study was carried out. All consecutive patients starting treatment with fremanezumab were included. Clinical, physical activity and sitting time variables were collected: before treatment, and 30 and 90 days after treatment initiation. Validated "International

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lack often studies countries conducted Objective: Introduction Ascertaining the prevalence of headache disorders is fundamental for designing effective public health strategies. Epidemiologic in individual consistent methodologies, limiting broader interpretation. The Americas" Migraine Observatory Study (AMIGOS) is a Pan-American epidemiological study designed to evaluate the burden and access to treatment of migraine and other headache disorders across the Americas. Here, we present preliminary data on migraine prevalence. Objectives To describe the prevalence of migraine in the Americas using a unified sampling methodology at a specific time point. Methods: Data were collected online from a sample representative of the demographic and social characteristics of each country, with a confidence level of 98% and a margin of error of 5%. We conducted both qualitative and quantitative research on key aspects of headaches among 17,037 individuals in 20 countries from Canada to Chile. Migraine diagnosis was made based on the ICHD-3 criteria. Results: The overall prevalence of migraine was 9.74% (12.6% among females, 6.8% among males). The highest prevalence was observed in Brazil (14.1%), Canada (13.3%), and the United States (13.1%), while the lowest prevalence was found in Bolivia (5.6%), Paraguay (6.7%), and Guatemala (7.5%). On average, migraine sufferers reported experiencing headaches 6.5 days per month, with 14% experiencing headaches on fifteen or more days per month. Conclusion: This is the first comprehensive Pan- American migraine epidemiological study. Results indicate that migraine is highly prevalent in the Americas, with significant variations among different countries. Genetic and environmental factors may explain these observed differences. rate failure Physical Activity Questionnaire (IPAQ) - long version" was used as a measurement instrument. Results: 71 patients were included, with a median age of 46 IQR [38 – 55] years, 83.1% were women. The median for previous preventive treatments was 5 IQR [4-6]. 64.8% of the patients were responders to fremanezumab. At baseline, patients reported median total physical activity levels of 2232 IQR [1080 – 3930] METs/minute/week, walking 210 IQR [100-390] minutes/week and median time sitting levels of 334 IQR [184 – 480] minutes/day. Differences between responders and non-responders (p<0.05) were found in sitting time levels at 30 days and in total physical activity, time spent walking and sitting time levels at 90 days. Among non-responders, migraine days per month, pain intensity and triptan days consumption, correlated with an increased sitting time (p<0.05). Conclusion: Total physical activity levels, walking and sitting to fremanezumab the variables migraine days per month, mean intensity, and triptan days the variables that positively correlate with time sitting in non-responder patients responding patients treatment, being time vary in P185 Migraine prevalence: findings from the Americas' Migraine Observatory Study (AMIGOS) M. Lisicki1, J. Munoz-Cerón2, E. Machado Sarmento3, A. Belitardo de Oliveira4, M. Moraes Valença5, J. Ramos de Andrade6, K. Vélez-Jiménez7, I. Rodriguez- Leyva8, A. R. Espinoza Giacomozzi9, E. Bancalari10, P. Schubaroff11, M. F. P. Peres12 1Instituto Mercedes y Martín Ferreyra, Córdoba, Argentina 2Hospital Universitario Mayor Mederi - Universidad del Rosario, Bogotá, Colombia 3Centro Universitário de Volta Redonda – UniFOA, Volta Redonda, Brazil 4Universidade de São Paulo, Center for Clinical and Epidemiological Research, Hospital Universitário, São Paulo, Brazil 5Universidade Federal de Pernambuco, Centro de Ciências Médicas, Recife, Brazil 6Universidade Federal de Pernambuco, Recife, Brazil 7Hospital Angeles Lomas, Department of Neurology, Ciudad de México, Mexico 8Universidad Autónoma de San Luis Potosí, Neurology Department, San Luis Potosí, Mexico 9Clínica Red Salud, Santiago, Chile 10Universidad Católica Santo Toribio de Mogrovejo, Faculty of Medicine, Santo Toribio de Mogrovejo, Peru 11Hospital Bernardo Housay, Servicio de Neurología, Buenos Aires, Argentina 12University of São Paulo. Hospital Israelita Albert Einstein, Institute of Psychiatry, São Paulo, Brazil

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P186 Changes in acute migraine medications use after initiating or switching to a migraine preventive medication: 12-month findings from the observational TRIUMPH study M. Matharu1, S. Ashina2, F. Sakai3, M. Vincent4, L. Viktrup5, G. Martimianaki5, R. Robinson5 1Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Headache and Facial Pain Group, London, United Kingdom 2Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Neurology, Boston, MA, United States 3Saitama International Headache Center, Saitama, Japan 4Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 5Eli Lilly and Company, Indianapolis, IN, United States in In to galcanezumab this multi-country, patients with migraine Objective: Do acute migraine treatment patterns change after starting/switching (GMB) or traditional oral migraine preventive medications (TOMP)? prospective Methods: observational (TRIUMPH) study of adults diagnosed with migraine, use of acute migraine treatments was compared in the 12 months before and after starting GMB or TOMP. Nonpharmacologic and other therapies for migraine were also studied. Data presented here are based on interim analyses. Results: Of the 2111 eligible patients, 973 (46.1%) received GMB, and 1138 (53.9%) received TOMP. Most patients were female (>80%). During the study, the GMB cohort was less likely to take triptans (18.5% vs. 26.8%) and NSAIDs (7.8% vs. 14.9%) but more likely to receive gepants than TOMP (7.0% vs. 4.8%). The NSAIDs, acetaminophen/paracetamol, and butalbital declined for the GMB cohort (-4.7%; -1.0%; -0.6%; -0.3%) and increased for TOMP (7.6%; 5.1%; 0.1%; 0.2%), whereas gepants use increased for both cohorts (GMB: 0.9%; TOMP: 2.7%). For GMB and TOMP, the use of opioids for migraine attacks was low before (0.3% vs. 0.4%) and during the study (1% vs. 0.3%), respectively. The weighted mean change in the number of days with acute medications from baseline (in the last 30 days) declined in both cohorts at 3, 6, and 12 months (GMB, -5.1, -5.1, -5.3; TOMP, -3.4, -4.2, -4.3; p<.01; p=.02; p=.02), respectively. For GMB and TOMP, the use of nonpharmacologic (3.3% and 4.0%, e.g., massage, acupuncture) or alternative (1.0% and 2.1%, e.g., herbal remedies) migraine therapies was infrequent. Conclusion: In this 12-month real-world study, there was a greater decrease in acute treatment usage after triptans, use of patients initiated or switched to GMB compared to those on TOMP, indicating that migraine prevention with GMB may reduce the number or intensity of attacks TOMP. Nonpharmacologic treatments and other migraine therapies were infrequently used. greater extent than to a P187 Real-world evidence of adding atogepant to OnabotulinumtoxinA for control of chronic migraine – a retrospective chart review A. Blumenfeld1, L. Mechtler2, L. Cook3, C. Rhyne4, B. Jenkins5, O. Hughes6, B. Dabruzzo7, A. Manack Adams8, M. Diamond9 1The Los Angeles and San Diego Headache Centers, San Diego, CA, United States 2Dent Neurologic Institute, Buffalo, NY, United States 3The Los Angeles Headache Center, Los Angeles, CA, United States 4Norton Neuroscience Institute, Louisville, KY, United States 5Neuroscience Group,, Neenah, WI, United States 6ICON plc, Blue Bell, PA, United States 7AbbVie, Madison, WI, United States 8AbbVie, Irvine, CA, United States 9Diamond Headache Clinic, Chicago, IL, United States for treatment to onabotulinumtoxinA Objective: To collect real-world data to evaluate the effectiveness, safety, and tolerability of adding (onabotA) as atogepant combination preventive chronic migraine (CM). Methods: This retrospective, longitudinal, multi- center chart review included adults with CM receiving ≥2 consecutive onabotA cycles before ≥3mo of onabotA and atogepant combination treatment. Charts at first atogepant prescription (index date) and 2 onabotA injection visits (~3 and 6mo post-index) were reviewed for change from baseline in monthly headache days (MHDs), ≥50% reduction in MHDs, and rates and types of adverse events (AEs). Charts with CGRP agents for migraine prevention during baseline (~3mo pre-index) were excluded. Results: 31 charts met eligibility criteria (mean age 46.7yrs, 94% female). Atogepant 60mg and 30mg were administered QD to 30 and 1 patients, respectively. Throughout the study, patients received a mean dose of 170U onabotA. Pre-onabotA, the mean MHD was 24.0d, reduced by a mean -8.15d (95%CI -11.44,-4.85; n=25) after onabotA pre-index (mean 3.97yr). MHD additionally decreased by mean - 4.53d [95%CI -7.44,-1.61] after ~3mo of combination treatment (n=31) and -8.75d total [95%CI -13.21, - 4.29] after ~6mo of combination treatment in patients with data available (n=23). Nearly half (n=14/31) achieved ≥50% reduction in MHDs ~3mo post-index.

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95% CIs indicate that reductions from baseline were statistically significant. No new safety signals were identified when atogepant was added to onabotA. The most commonly reported AEs (≥5%) were constipation and fatigue. Conclusion: This real-world pilot study of patients with CM clinically meaningful treatment benefit in the reduction of headache days with onabotA alone and additive benefits with co- administration of atogepant. Safety results were consistent with the known safety profiles of onabotA and atogepant. demonstrated P188 Real-world treatment patterns of Galcanezumab and traditional oral migraine preventives: 12-month results from the TRIUMPH study S. Ashina1, M. Matharu2, F. Sakai3, M. Vincent4, L. Viktrup5, G. Martimianaki5, R. Robinson5 1Harvard Medical School, Beth Israel Deaconess Medical Center, Boston, MA, USA, Department of Neurology, Boston, MA, United States 2Queen Square Institute of Neurology and The National Hospital for Neurology and Neurosurgery, Headache and Facial Pain Group, London, United Kingdom 3Saitama International Headache Center, Saitama, Japan 4Federal University of Rio de Janeiro, Rio de Janeiro, Brazil 5Eli Lilly and Company, Indianapolis, IN, United States log-rank Objective: What are the 12-month treatment patterns in patients (pts) with migraine who initiated/switched to galcanezumab (GMB) or traditional oral migraine preventive medications (TOMP)? Methods: In this ongoing, multi-country, prospective observational TRIUMPH study, treatment patterns and reasons for discontinuation were described in pts with migraine. Time to treatment discontinuation was compared among pts with migraine receiving GMB vs. TOMP using test and weighted Cox proportional hazards models. Data presented here are based on interim analyses. Results: Of the 2111 pts, 973 (46.1%) received GMB (mean ± SD age: 45.2 ± 13.6 years) and 1138 (53.9%) received TOMP (mean ± SD age: 40.4 ± 13.2 years). At 12 months, the GMB cohort had similar rates of persistence (59.2% vs. 59.8%), less combination treatments received during the study (3.1% vs. 8.1%), and fewer switches vs. TOMP cohort (7.7% vs. 10.1%). The GMB cohort more often used a subsequent line of other CGRP mAbs than the TOMP cohort (9.6% vs. 4.8%) but less often to other TOMP medications (6.8% vs. 18.3%). Negative reasons for discontinuation in GMB vs. TOMP were inadequate treatment response (6.2% vs. 4.3%), no treatment response (2.9% vs. 4.1%), drug intolerability (3.0% vs. 8.5%), and drug unavailability (0.7% vs. 0.4%). The mean GMB and TOMP exposure were 9.3±4.1 and 9.4±3.9 months, respectively. Total discontinuation rates were significantly lower in the GMB cohort than in the TOMP cohort for negative reasons (12.7% vs. 17.4%; p=.002), and "all causes" (17.8% vs. 23.2%; p=.003). The weighted hazard for discontinuation due to negative reasons and all-cause reasons were 0.53 (0.41, 0.68) and 0.57 (0.46, 0.70), respectively. pts Conclusion: initiated/switched to GMB or TOMP, fewer pts discontinued GMB, or combined it with other preventive medications compared to those on TOMP. The GMB cohort was more likely to switch to other CGRP mAbs, while the TOMP cohort mainly switched to other TOMP medications. (95% CI) months Twelve ratios after P189 Real-world evaluation of Eptinezumab in Italy: effectiveness, tolerability, and safety in high- frequency and chronic migraine at 12 weeks – the EMBRACE study C. Aurilia1, B. Orlando1, G. Egeo1, F. d'Onofrio2, A. Doretti3, R. Messina3,4, M. Autunno5, M. Filippi4, G. Fiorentini1, C. Rotondi6, S. Bonassi6, P. Barbanti1 1IRCCS San Raffaele Rome, Headache and Pain Unit, Rome, Italy 2San Giuseppe Moscati Hospital, Headache Center Neurology Unit, Avellino, Italy 3Istituto Auxologico Italiano, IRCCS, Laboratory of Neurosciences, Department of Neurology-Stroke Unit, Milano, Italy 4IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Neurology Unit, Milano, Italy 5University of Messina, Department of Clinical and Experimental Medicine, Messina, Italy 6IRCCS San Raffaele Rome, Clinical and Molecular Epidemiology, Rome, Italy of an targeting Objective: We aimed to assess real-world evidence (RWE) data on the effectiveness, safety, and intravenous tolerability eptinezumab, humanized monoclonal antibody the calcitonin gene-related peptide (anti-CGRP mAb) indicated for migraine prophylaxis. ID: Methods: NCT05570149) is a multicenter (n=5), prospective study including all consecutive patients with high- frequency episodic migraine (HFEM) or chronic migraine (CM). treated with eptinezumab (100 mg or 300 mg quarterly). The initial eptinezumab dose,100 mg or 300 mg, was chosen based on patient preference. The primary endpoint was the change in (ClinicalTrials.gov EMBRACE

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(MHD) in MMD Interictal Burden Scale monthly migraine days (MMD) for HFEM or monthly headache days for CM at weeks 9-12 compared to baseline. Secondary endpoints included changes in monthly analgesic intake (MAI), Numerical Rating Scale (NRS), Headache Impact Test (HIT-6), (MIDAS), Migraine Disability Assessment Scale Migraine (MIBS-4), and responder rates at the same time points. Results: As of 30 April 2024, the safety analysis included 44 subjects, while the effectiveness analysis involved 26 individuals. Eptinezumab was well- tolerated. Among CM patients, it significantly reduced MHD (-16.1, p<0.001), MAI, NRS, HIT-6, MIDAS, and MIBS-4. For HFEM patients, there were significant reductions in NRS, HIT-6, MIDAS, and MIBS-4, though reductions (-3.3) and MAI were not statistically significant. Overall, >50% and >75% responder rates were 61.5% and 30.8%, respectively (60% and 30% in non-responders to subcutaneous anti-CGRP mAbs). Clinical improvement was rated as much/very much improved by 61.0% of patients and by 50% of non-responders to subcutaneous anti-CGRP mAbs. high Conclusion: effectiveness, safety, and tolerability at 3 months in real-world settings also in who previously failed multiple treatments including subcutaneous anti- CGRP mAbs. demonstrates Eptinezumab P190 A cross-sectional analysis evaluating the humanistic and economic burden of migraine with comorbid depression using the national health and wellness survey A. E. Guevara Morel1, V. Ramirez Campos2, H. Akcicek1, R. Ribalov3, G. Kivelevitch3, Y. Zhang2, M. T. Driessen1, H. Raad4, K. Modi4, G. M. Terwindt5 1Teva Pharmaceuticals, Amsterdam, Netherlands 2Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, United States 3Teva Pharmaceutical Industries Ltd., Tel Aviv, Israel 4Oracle Life Sciences, Austin, TX, United States 5Leiden University Medical Centre, Department of Neurology, Leiden, Netherlands of migraine with/without Objective: To evaluate the humanistic and economic burden comorbid depression, in adults in France, Germany, Italy, Spain (EU4), United Kingdom (UK), South Korea (SK) and Brazil (BR). Methods: This observational, cross-sectional study included respondents with migraine participating in the 2020 (SK and BR) and 2022 (EU4+UK) National Health and Wellness Survey. Participants self-reported physician-diagnosed migraine for ≥12 months, active migraine in the last 12 months, and ≥4 headache days depression (self-reported, in the month prior to the survey, with/without comorbid physician- diagnosed depression with active depressive symptoms in the last 12 months, and a Patient Health [PHQ-9] score ≥10). Descriptive Questionnaire-9 statistics with bivariate and multivariable analyses were used to describe and compare demographic and clinical characteristics, health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilisation (HCRU), and direct and indirect costs between patients with migraine with/without comorbid depression. Results: Among total participants with migraine in EU4+UK (N=1073), BR (N=331) and SK (N=219), 35.7%, 32.9% and 36.5% had comorbid depression, respectively. Across all regions/countries, among participants with migraine and comorbid depression, there was a significantly higher mean number of migraines in the past 30 days and proportion of participants who reported severe disability, compared with participants without comorbid depression (Table 1). Participants with comorbid depression had significantly lower mean HRQoL scores, higher WPAI measures and higher mean total annualised direct and indirect costs, compared with participants without comorbid depression (Table 2). Conclusion: Patients with migraine and active depression experience higher humanistic and economic burden compared with those patients without depression. Disclosures: This study was Pharmaceuticals. funded by Teva Fig. 1

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Fig. 2 gabapentine and flunarizine; 35% of preventive"s treatment presented mild AEs. 52.94% suspended lasmiditan due to AEs and/or ineffectiveness, while the literature reports 36%. Conclusion: Despite the small sample size, we confirmed previous findings on the use of lasmiditan in migraine, strengthening the evidence on its efficacy and safety. Reports with larger cohorts are necessary to further validate these results, consolidating the role of lasmiditan in migraine. Fig. 1 Fig. 2 P191 Lasmiditan for migraine. Experience in a headache center in Barcelona A. I. Gilbert1, V. Obach Baurier1, S. Fernández1, M. N. Fabregat1 1Hospital Clinic de Barcelona, Barcelona, Barcelona, Spain treatments and response Objective: Report the experience of patients who started lasmiditan in the last year at the Hospital Clinic of Barcelona (HCB) and compare it with already published data. Methods: Observational descriptive study. Patients with migraine with and without aura according to ICHD-III criteria, who used lasmiditan 100 milligrams as acute treatment between September 2023 and May 2024 at HCB were included. Demographic data, personal history, headache characteristics and duration, other to lasmiditan (efficacy and adverse effects) were obtained. Results: 29 patients reported. 13 haven"t yet reported start of treatment. The mean age was 45.89 +/- 12.25 years, with prevalence of the female sex (86.21%), similar to SAMURAI and SPARTAN results of 42.2 (SD 12.3). The improvement in pain was 47% (N=8), as in CENTURION study, which was 65%. 58.8% reported AEs, being those of central nervous system the most frequent, dizziness 17.65% (N=3), confusion 11.76% (N=2), tremor 11.76% (N=2), paresthesias 11.76% (N=2), (N=2), data consistent with SAMURAI and SPARTAN. Visual disturbance was also reported in 5.88% (N=1), generalized weakness 5.88% (N=1), nausea and/or vomiting 5.88% (N=1), diarrhea 5.88% (N=1), anxiety or nervousness 5.88%. (N=1) and drowsiness 5.88% (N=1). None were serious or associated with serotonin syndrome. 50% of the patients were under preventive treatment, 20.69% (N=6) with ampitriptyline, 13.79% (N=4) duloxetine, 10.34% (N=3) beta-blockers, 6.9% zonisamide, (N=2) sensation 11.76% topiramate, strange 3.45% (N=1)

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P192 Integrative analysis of omics markers associated with neuronal damage in migraine V. J. Gallardo López1, D. Pareto2, J. Rosell-Mirmi1, E. Caronna1,3, L. Asskour1, M. Torres-Ferrús1,3, A. Alpuente1,3, N. Ikumi1, À. Rovira2, P. Pozo-Rosich1,3 1Vall Hebron Institute of Research (VHIR), Headache and Neurological Pain Research Group, Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Radiology Department, Barcelona, Spain 3Hospital Universitari Vall d'Hebron, Neurology Department, Barcelona, Spain analyzed Objective: To study neuronal damage in migraine by integrating serum biomarkers with MRI-derived measure Methods: Prospective case-control study with healthy controls (HC) and individuals diagnosed with migraine. Clinical data, blood samples, and 3T brain MRI (3D T1- weighted, diffusion-weighted, SWI) were collected during the screening visit. Serum biomarkers were measured with NEUROLOGY 4-PLEX A using Simoa®. iron deposition (ID) and DTI-derived SWI-derived fractional anisotropy (FA) were assessed using FreeSurfer segmentation of 3D T1-weighted MRI. Linear mixed-effect models group differences, with p-values adjusted for multiple comparisons using the FDR procedure Results: A total of 134 right-handed, sex- and age- matched participants (66 HC and 68 migraine) were included, 84.3% females with a median [IQR] age of 40.5 [34.0-47.0] years. Only neurofilament light chain levels (Nf-L) were statistically significantly higher in migraine (HC: 8.9 [7.1-11.4] pg/mL vs. migraine: 9.9 [8.0-13.0] pg/mL; p=0.049). Individuals with migraine also presented higher SWI-ID in the periaqueductal (RN, gray (NAc, adj.p=0.011), adj.p=0.047), (both adj.p=0.049), and the left rostral anterior cingulate cortex (rACC, adj.p=0.049), as well as lower FA values in the left cortex of the caudal middle frontal (adj.p=0.048), postcentral (adj.p=0.041), precentral (adj.p=0.041), superior frontal (adj.p=0.041), and in (adj.p=0.049) and precuneus the (adj.p=0.049). Moreover, significant differential correlations were found between Nf-L and the ID of the left NAc and the left rACC, and the FA of the superior frontal cortex and the right precuneus cortex among the study groups Conclusion: Individual with migraine showed higher Nf-L levels, indicating potential neuronal damage, along with distinct brain structural differences compared to HC accumbens left putamen left left caudate, (PAG, adj.p=0.049), left red nucleus right cuneus statistically nucleus P193 Exploring the link between inhibitory cognitive control and sensory sensitivity in migraine – a case- control study N. Ikumi1, P. Pozo-Rosich1,2 1Vall Hebron Institute of Research (VHIR), Migraine Adaptive Brain Center, Barcelona, Spain 2Headache Unit, Department of Neurology, Hospital Universitari Vall d'Hebron, Barcelona, Spain et al. and task 2014) (mean headache (Stroop, 1935). Objective: In this study we aimed to compare the inhibitory cognitive control in participants with migraine (M) and healthy volunteers (HC) using a Stroop In addition, we investigated whether the reported increased visual sensitivity in migraine may exert a modulatory influence on the ability of patients to inhibit irrelevant visual information. Methods: To study this, we measured sensory sensitivities using the Sensory Perception Quotient (Tavassoli recorded electroencephalography (EEG) during a Stroop task, in 60 M with high-frequency episodic or chronic migraine days/month=15.38 (range:8-27)) and in 28 HC. A headache specialist according to the ICHD-3 diagnosed M. Participants completed a daily eDiary, to confirm they had more than 8 headache days per month. Clinical and sociodemographic data were collected. We assessed the reaction times (RT) and N450 components for congruent and incongruent conditions in the Stroop task and examined the capacity to inhibit irrelevant visual interferences (interference suppression effect) between groups. Mixed-effect regression models and correlation analyses were applied. All patients gave their informed consent to publish their details in an open access journal. Results: EEG recordings of 52 M and 28 gender- and age-matched HC (p>0.57) were analysed. Eight M were excluded for reporting pain above 3 during the session. The results showed that M have similar RT (p=0.27) and N450 (p=0.16) values than HC, indicating they are similar at ignoring the distractors. However, we found a correlation between Stroop interference suppression and SPQ Vision scores (p=0.01) in M and not in HC. Conclusion: The ability to ignore external visual distractors does not differ between participants with migraine and healthy volunteers. However, we found that migraine participants with lower SPQ Vision scores (higher sensory sensitivity) had larger Stroop interference effect (RT), meaning they were worst at ignoring the distractors. linear

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P195 Switching between Ligand and receptor anti-CGRP antibodies in non-responders N. van Veelen1, B. W. H. van der Arend1,2, E. Hiele1, E. W. Van Zwet1, G. M. Terwindt1 1Leiden University Medical Center, Neurology, Leiden, Netherlands 2Erasmus MC University Medical Center, Internal Medicine, Rotterdam, Netherlands largely on fremanezumab. Patients for migraine Objective: Limited options exist prevention after stopping anti-calcitonin gene-related peptide monoclonal antibodies. A systematic review examining the benefits of switching between different classes (ligand versus receptor mAb) is essential, alongside well-designed real-world-studies. In this cohort study, we aimed to examine the effectiveness of switching to a second CGRP-mAb following treatment discontinuation in comparison to standard care. Methods: In this cohort study, we included 67 patients, who discontinued their first treatment with erenumab or (n=31) switched to another monoclonal antibody class within three months, while those in the control group (n=36) received standard care. Allocation to either group the availability of alternate relied introducing monoclonal treatments, pseudorandom allocation. Changes in monthly migraine days were compared between groups three months post-discontinuation of the first monoclonal antibody or initiation of a different monoclonal antibody class. A multivariate regression model was conducted that accounted for potential confounding factors. Results: The groups were comparable at baseline and poor treatment response was the main reason for treatment discontinuation of the first monoclonal antibody. The switching cohort experienced a - reduction of 3.9 monthly migraine days (95% CI [-6.4, - 1.3], p=0.004) compared with the control group. Conclusion: Transitioning to a different anti-calcitonin gene-related peptide monoclonal yields reduction in monthly migraine days compared to returning for patients with inadequate initial treatment response. to standard care antibody class P194 Manual therapy as a prophylactic treatment for migraine. A randomized controlled trial A. Amons1, R. Castien1,2, W. De Hertogh3, J. C. van der Wouden1, J. Dekker4, H. van der Horst1 1Amsterdam University Medical Centers, Department of General Practice, Amsterdam, Netherlands 2Vrije Universiteit Amsterdam, Faculty of Behavioural and Movement Sciences, Amsterdam, Netherlands 3University of Antwerp, Department of Rehabilitation Sciences and Physiotherapy, Antwerp, Belgium 4Amsterdam University Medical Centers, Department of Rehabilitation Medicine and Department of Psychiatry, Amsterdam, Netherlands for (GP) impacts daily Objective: Migraine affects 15% of the population and severely life. Despite effective medication, many patients still experience pain and disability and look for non-pharmacologic treatments. We performed a randomized controlled trial to assess the effectiveness of a multi-modal manual therapy (MT) treatment compared to usual care by the general practitioner the prophylactic treatment of migraine. Methods: The trial consisted of a 12-week treatment period and follow-up measurements at 12, 26 and 52 weeks. Participants were randomly allocated to MT treatment or usual care by the GP. The primary outcome measure was the number of migraine days per 4 weeks. Secondary outcome measures included disability due to migraine, severity of migraine and neck pain, medication use and global perceived effect (GPE). Results: Due to recruitment problems and the Covid- 19 pandemic, less than the targeted number of participants were included (n = 67 instead of 196 participants). Mixed-model analysis showed no significant between-group differences in migraine frequency, severity and disability or neck pain. The number of migraine days reduced in both groups; in the MT group, migraine days decreased from 7.28 days at baseline to 3.67 at 12 weeks, 4.78 at 26 weeks and 4.35 days at 52 weeks follow-up; in the GP group, from 5.52 days at baseline to 4.36 at 12 weeks; 3.76 at 26 weeks and 4.63 days at 52 weeks follow-up. In the GP group, prophylactic medication use significantly increased during treatment at all time points. Participants in the MT group reported significantly higher GPE scores on average over time (P= 0.012) and at 12 weeks (P = 0.017) and 52 weeks follow-up (P = 0.002); but not at 26 weeks follow-up (P = 0.245). Conclusion: No significant differences between the two groups were found in the primary outcome, migraine frequency. Except for GPE, we also found no effect on secondary outcomes of MT treatment compared to the usual medical care by the GP

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Fig. 1 P196 Migraine under treatment: Findings from the Americas' Migraine Observatory Study (AMIGOS) M. Lisicki1, J. Munoz-Cerón2, E. Machado Sarmento3, A. Belitardo de Oliveira4, M. Moraes Valença5, J. Ramos de Andrade6, K. Vélez-Jiménez7, I. Rodriguez- Leyva8, A. R. Espinoza Giacomozzi9, E. Bancalari10, P. Schubaroff11, M. F. P. Peres12 1Instituto Mercedes y Martín Ferreyra, Córdoba, Argentina 2Hospital Universitario Mayor Mederi - Universidad del Rosario, Bogotá, Colombia 3Centro Universitário de Volta Redonda – UniFOA, Volta Redonda, Brazil 4Universidade de São Paulo, Center for Clinical and Epidemiological Research, Hospital Universitário, São Paulo, Brazil 5Universidade Federal de Pernambuco, Centro de Ciências Médicas, Recife, Brazil 6Universidade Federal de Pernambuco, Recife, Brazil 7Hospital Angeles Lomas, Department of Neurology, Ciudad de México, Mexico 8Universidad Autónoma de San Luis Potosí, Neurology Department, San Luis Potosí, Mexico 9Clínica Red Salud, Santiago, Chile 10Universidad Católica Santo Toribio de Mogrovejo, Faculty of Medicine, Santo Toribio de Mogrovejo, Peru 11Hospital Bernardo Housay, Servicio de Neurología, Buenos Aires, Argentina 12University of São Paulo. Hospital Israelita Albert Einstein, Institute of Psychiatry, São Paulo, Brazil Objective: Introduction Migraine patients face significant challenges that limit their access to treatment. Epidemiologic studies conducted in individual countries often lack consistent methodologies, hindering broader interpretation. The Americas' Migraine Observatory Study (AMIGOS) is a Pan-American epidemiological study designed to evaluate the burden and treatment of migraine and other headache disorders across the Americas. Here, we present preliminary data on migraine treatment rates. Objectives To describe the percentage of individuals suffering from migraine in the Americas using acute and prophylactic treatment through a unified sampling methodology at a specific time point. Methods: Data were collected online from a sample representative of the demographic and social characteristics of each country, with a confidence level of 98% and a margin of error of 5%. We conducted both qualitative and quantitative research on key aspects of headaches among 17,037 individuals in 20 countries from Canada to Chile. Migraine diagnosis was made based on the ICHD-3 criteria. Results: Overall, 73.3% of migraine patients reported using acute medication for their attacks. Higher percentages of acute medication use were observed in Bolivia (88.2%), while lower rates were found in Brazil (59.8%). Current and past use of preventives were reported by 19.5% and 8.1% of migraine patients, respectively. Preventive use was highest in Peru (42.6%) and lowest in Uruguay (7.2%). Among those who were not taking and had not taken prophylactic medications the past, 54.7% experienced headaches on four or more days per month. This percentage rose above 60% in Venezuela (64.3%), Guatemala (63.9%), Costa Rica (63.3%), Nicaragua (61.7%), and the USA (60.7%), and was lowest in Uruguay (40.5%). Conclusion: This is the first comprehensive Pan- American migraine epidemiological study. Results indicate that migraine is largely undertreated in the Americas, with the most alarming figures related to prophylactic treatment. Improving access to headache care in the region is essential. in P197 MultiHEAD – work-focused multidisciplinary headache treatment O. V. Lunder1,2, T. Wisloeff3,4, K. Aaseth1,2, E. S. Kristoffersen1,2,5, K. G. Vetvik1,2 1Akershus University Hospital, Department of Neurology, Oslo, Norway 2NorHEAD – The Norwegian Headache Research Center, Trondheim, Norway 3Akershus University Hospital, Health Services Research Unit,, Oslo, Norway 4University of Oslo, Institute of Clinical Medicine, Oslo, Norway 5University of Oslo, Department of General Practice, Oslo, Norway Objective: The costs related to lost workdays and reduced productivity are high among people with headache. The objectives of this project are to evaluate the effects of combined pharmacological and

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non-pharmacological treatment in a multidisciplinary team on headache frequency, health-related quality of life and work participation. Methods: Patients aged 18-67 years referred to Department of Neurology, Akershus University Hospital, due to headaches, and currently on sick leave or had a history of recurrent sick leave periods were included. All patients were treated by a team of headache specialists, headache nurses, psychologists, physiotherapists, and job experts. The patients were followed-up with structured clinical follow-up and self-administered questionnaires at baseline, and after 3, 6 and 12 months. Between visits hey were also offered follow-up based on individual needs. We used Wilcoxon and Chi-square test to compare variables from baseline to 12 months follow up. Results: 101 patients (87 females) completed the 12 months follow-up. Migraine was the most common diagnosis (n=84), followed by tension-type headache (n=14). The majority (n=84) suffered from chronic headache at baseline, 46 used preventive drugs and 68 had already several different non- pharmacological treatments. Half of the patients (n=52) were currently on sick leave due to headache at baseline. A significant reduction of headache days from 22.1 (SD 8.1) to 12.4 (SD 19.4) (p<0.01) per month, days with use of acute medication from 7.7 (SD 7.1) to 4.7 (SD 5.1) (p< 0.01) and Headache Impact Test 6 (HIT-6) scores from 64.8 (SD 4.4) to 59.2 (SD 8.2) (p<0.01) was observed after 12 months. A ≥75% and ≥50% reduction in headache frequency per month was observed in 37% (n=37) and 52% (n=52) of the patients. After 12 months, 50% of those who were on sick leave at baseline returned to work (p<0.01). Conclusion: Treatment in a multidisciplinary team had significant effects on headache burden and work participation after one year. tried P198 Migraine epidemiology in Israel – a retrospective database study A. Shifrin1, E. Domany1, M. Tirosh2, D. Davidovici2, S. Vinker3, I. Forschner4, A. Y. Israel3 1Rambam medical center, Neurology department, Haifa, Israel 2Pfizer Pharmaceuticals Israel LTD., Herzliya, Israel 3Leumit Health Services, Tel Aviv, Israel 4Rambam medical center, Haifa, Israel Objective: Migraine is a common primary headache disorder. Knowledge gaps persist regarding migraine epidemiology, its geographic distribution, and temporal trends, especially since the introduction of new migraine-specific therapies. In this study, we describe the prevalence and annual incidence of migraine in Israel, stratified by age and gender. Methods: We conducted a retrospective descriptive study using electronic health records from Leumit Healthcare Services (LHS) to assess the prevalence and annual incidence of migraine among adult members between 2017 and 2022. Migraine patients were identified based on migraine diagnosis codes or the use of migraine-specific treatments. Results: In 2022, 24,300 LHS members, aged >18 years, were diagnosed with migraine. Migraine prevalence slightly increased over the years, from 4.53% in 2017 to 5.20% in 2022, with higher rates among women compared to men (8.02% vs. 2.36%). The mean age of migraine patients was 47.6 years, and the prevalence was highest in the fifth and sixth decades of life. Migraine annual incidence in 2022 was 3.6 cases per 1,000 subjects, with ~75% of new cases occurring in women, with a mean age of 37.6 years. Interestingly, the number of new migraine cases decreased (1686). Approximately, two-thirds of new migraine patients were diagnosed by neurologists. Conclusion: This study represents a comprehensive evaluation of migraine epidemiology in a national health provider database. While the prevalence of migraine increased slightly between 2017 and 2022, the annual incidence decreased from 2018 to 2022. It appears that the introduction of new medications did not lead to overdiagnosis. from 2018 (2108) to 2022 Fig. 1 Fig. 2

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P199 Examining trajectories of functional disability – a post-hoc analysis of Zavegepant L. Powell1, F. O'Sullivan1, P. Jayasinghe1, B. Rogula1, F. Dai2, J. Cirillo2, L. Abraham3, J. Ailani4 1Broadstreet Health Economics and Outcomes Research, Vancouver, Canada 2Pfizer R&D US Ltd, New York, NY, United States 3Pfizer R&D UK Ltd, Surrey, United Kingdom 4Medstar Georgetown University Hospital, Neurology, Washington, DC, United States III double-blind, Objective: To evaluate trajectories of functional disability over 48-hours and predictors of functioning for patients treated with either zavegepant 10 mg nasal spray or placebo for a migraine attack of moderate or severe pain intensity. Methods: Eligible patients for this post-hoc analysis were patients from BHV3500-301 (NCT04571060): a phase randomized, placebo- controlled study. Patients were adults with >1-year history of migraine. Functional disability was measured on a 4-point ordinal scale over 12 timepoints. The proportion of patients in each functional disability state at each timepoint and the time spent in each category, over 48-hours, were calculated. Trajectories were analyzed for cases with complete data (n=641) and using missing not at random (MNAR) imputation (n=1269). Predictors of functional disability were assessed using a mixed effects logistic regression model, using a binary outcome for functioning (normal/mild impairment versus severe impairment/bedrest). Results: From 30-minutes post-dose, a higher proportion of zavegepant-treated patients reported normal function compared to placebo (Figure 1). Over 48-hours, zavegepant patients spent approximately 3 hours longer on average with normal function compared to placebo (Table 1). Results were similar when analyzing complete cases versus MNAR. The regression analysis results indicated that over 48- hours, lower pain severity, fewer historical moderate or severe monthly migraine attacks, and absence of photophobia, phonophobia, and nausea were associated with better functioning (p<0.05). Conclusion: Return to normal function is linked to quality-of-life related disability. Zavegepant was associated with rapid and sustained return to function compared to placebo, resulting in more time spent with normal functioning over 48- hours. Reduced pain severity and the absence of nausea, photophobia, and phonophobia were predictors of better functioning. treatment with zavegepant, and migraine Fig. 1 Fig. 2 P200 Clinical characteristics and outcomes of status migrainosus in a tertiary hospital G. Cabral1, M. Serôdio1, M. V. Baptista1,2 1Hospital de Egas Moniz, ULSLO, Lisboa, Portugal, Neurology, Lisboa, Portugal 2Universidade NOVA de Lisboa, Lisboa, Portugal, Chronic Diseases Research Center (CEDOC) - NOVA Medical School, Lisboa, Portugal Objective: To characterize patients with status migrainosus (SM) and evaluate factors for recurrence and migraine frequency. Methods: Retrospective analysis of consecutive cases of patients diagnosed with SM, (ICHD-3 criteria), 2020-2022. Descriptive statistics and non-parametric tests were performed. Results: We included 40 patients [37 (92.5%) female]. The median age of SM was 35.5 years, with the median duration of SM being seven days. The median time between migraine onset and first SM was 12 years, but only four (10.0%) had a previous formal migraine diagnosis. Before the first SM, patients experienced a median of five headache days/month. The main precipitating factors for SM included infections (5;12.5%) and hormonal changes (4;10%), though most patients (26;65%) had no obvious factor. The median number of acute medications used before ED admission was two. Additional investigation beyond head CT scans was needed in 19 patients (47.5%). Most patients (65.7%) required only one drug in the ED for improvement, with NSAIDs being the

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(30.8%) most common drug used (50%). During follow-up, 35 patients (87.5%) were diagnosed with episodic migraine, and 5 (12.5%) had chronic migraine (CM), with median headache days per month remaining unchanged. Twelve patients required prophylactic drugs, and 3 (7.5%) experienced SM recurrence. Patients with NSAIDs response appear to have less frequent SM recurrence (p=0.056), less frequent worsening headache frequency (p=0.056), and less common CM diagnosis post-SM (p=0.006), with no other statistically significant association. Conclusion: Our study disclosed a significant number of patients with SM without a previous diagnosis of migraine, a low recurrence rate, and a similar frequency of migraine attacks before and after SM. Response to NSAIDs was associated with less recurrence, lower migraine frequency, and less risk of CM. These findings highlight the need for early migraine diagnosis and effective SM therapy. P201 Combined effects of cannabidiol and Δ9- tetrahydrocannabinol alleviate migraine-like sensitivity without motor impairment in FHM1 and WT mice G. Krivoshein1, M. Schenke1, A. Dehghani Mohammadi1, S. van Heiningen1, A. MJM van den Maagdenberg1,2, E. A. Tolner1,2 1Leiden University Medical Center, Department of Human Genetic, Leiden, Netherlands 2Leiden University Medical Center, Department of Neurology, Leiden, Netherlands Objective: The endocannabinoid system exerts various physiological functions, including processing and modulating pain, and it was suggested that the system is involved in migraine headache. Clinical reports suggest a therapeutic potential of cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC) to treat migraine attacks, yet the efficacy of their combination is understudied. Here we assessed effects of the 30:1 and 100:1 CBD:THC ratios on optogenetically induced cortical spreading depolarization (CSD) as well as subsequent headache-relevant readouts and motor function in genetically sensitized familial hemiplegic migraine type 1 (FHM1) mutant mice and wildtype (WT) littermates. Methods: To investigate effects of 30:1 (30 mg/kg : 1 mg/kg) and 100: 1 (100 mg/kg : 1 mg/kg) ratios of CBD:THC on headache features, mouse grimace scale (MGS) scores (as readouts for pain sensitivity) were assessed. To investigate effects of the CBD:THC on aura features (propagation, amplitude, half-width) by optogenetically inducing CSD events DC potential recordings were performed. CSD consequences on motor function were studied with wire grip testing. FHM1 mutant and WT mice were crossed with blue- light sensitive Thy1-Channelrhodopsin-2 expressing mutant mice so CSD events were induced upon blue light exposure to the intact skull. Results: A 100:1 ratio of CBD:THC effectively reduced MGS scores after CSD, both in FHM1 mutant and WT mice, whereas 30:1 CBD:THC showed a partial alleviation. Neither a 30:1 nor a 100:1 ratio of CBD:THC affected CSD characteristics in FHM1 mutant and WT mice. No adverse effects of any of the cannabinoid treatments were observed in motor function. Conclusion: Most profoundly a ratio of 100:1 CBD:THC had a beneficial effect on migraine-related features in mice. Our findings support potential efficacy of combined CBD and THC as therapy in both migraine with and without aura. P202 Long-term effectiveness of eptinezumab in patients with migraine and 2-4 prior preventive treatment failures who self-reported psychiatric comorbidities at screening P. Pozo-Rosich1,2, C. Tassorelli3, L. P. Boserup4, S. F. Awad4, X. Y. Lee4, J. Ailani5 1Hospital Universitari Vall d'Hebron, Barcelona, Spain 2Vall Hebron Institute of Research (VHIR), Barcelona, Spain 3University of Pavia, Pavia, Italy 4H. Lundbeck A/S, Copenhagen, Denmark 5Georgetown University Hospital, Washington, DC, United States Objective: This post hoc analysis of the DELIVER study examined the long-term effectiveness of eptinezumab (EPTI) in a subgroup of patients self-reporting psychiatric conditions. Methods: DELIVER (NCT04418765) studied preventive migraine treatment with EPTI in adults with migraine and documented history of 2‒4 failed preventive therapies. Patients were initially randomized (1:1:1) to intravenous EPTI 100mg, 300mg, or placebo every 12 weeks. Patients receiving placebo during the placebo- controlled period (Weeks 1‒24) were switched to EPTI 100mg or 300mg in the dose-blinded extension (Weeks 25–72), while those initially randomized to EPTI continued their assigned dose. 858 patients were in the extension analysis set and, of these, the subgroup self-reporting psychiatric conditions at screening was analyzed for 72 weeks. Outcomes were change from baseline (CFB) in monthly migraine days (MMDs), ≥50% migraine responder rates (MRRs), and Patient Global Impression of Change (PGIC) responder rates (% patients reporting being much or very much improved vs baseline). Outcomes were analyzed in patients with data available at the corresponding

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for repeated timepoint using a mixed model measures. Results: Within the extension analysis set, 115/858 (13%) patients reported psychiatric conditions at screening. Mean CFB in MMDs over Weeks 69‒72 in patients continuing EPTI (pooled) reporting psychiatric conditions was –6.0 (n=68; baseline: n=80, 14.7 MMDs) and was –3.8 in those switched from placebo to EPTI (n=30; baseline: n=35, 16.6 MMDs). Patients switched to EPTI reported higher mean CFB in MMDs after switching (Weeks 25–28: n=78, CFB –4.8) versus before the switch (Weeks 21–24: n=79, CFB –1.5). ≥50% MRRs over Weeks 69‒72 were 56% (38/68) for patients continuing EPTI and 37% (11/30) for patients switched to EPTI. PGIC responder rates at Week 72 ranged 63–80%. Conclusion: Long-term (72-week) EPTI effectiveness was seen in patients with migraine self-reporting psychiatric conditions. P203 Contemporary prospective understanding of migraine real-world evidence (CAPTURE): baseline migraine treatment patterns C. Tassorelli1, M. Matharu2, J. Ailani3, M. Lantéri- Minet4,5, E. Tucker6, J. Lam6, Y. Liu7, H. Ha6, L. Delahaye6, P. Pozo-Rosich8 1University of Pavia and C. Mondino Foundation, Pavia, Italy 2Queen Square Institute of Neurology, London, United Kingdom 3Georgetown University Hospital, MedStar, Washington, DC, United States 4CHU Nice and Côte Azur University, Pain Department and FHU InovPain, Nice, France 5Auvergne University, INSERM U1107 Migraine and Trigeminal Pain, Clermont-Ferrand, France 6AbbVie, Toronto, Canada 7AbbVie, North Chicago, IL, United States 8Vall Hebron Institute of Research (VHIR), Headache Unit, Barcelona, Spain is a 2-year, Objective: CAPTURE international, prospective, longitudinal study that aims to elevate understanding of burden of illness, disease course, and treatment patterns among people living with migraine, stratified by headache frequency. Methods: Adults with migraine diagnosed for >=1 year, aged <50 years at onset, and taking >=1 medication indicated for migraine with >=4 monthly headache days (MHDs) in the 3 months before screening were assigned to cohorts based on MHD frequency (cohort 1: 4-<8; cohort 2: 8-<15; cohort 3: >=15; for baseline current/prior migraine characteristics, medications, are presented. Endpoints include change Figure). Descriptive data including from baseline in MHDs, monthly migraine days, monthly acute medication use days, and patient- reported outcomes across the study period. Durations of current and subsequent migraine treatment use and migraine-related healthcare resource utilisation will also be assessed. Results: This analysis set (December 2023) included 239 participants (cohort 1: n=68; cohort 2: n=104; cohort 3: n=67; mean age 40.8-42.6 years); more than 78% were female (Table 1). In cohorts 1, 2, and 3, current use of acute migraine medication only was reported for 5.9%, 2.9%, and 0% of participants; preventive medication only for 19.1%, 27.9%, and 32.8%; and both acute and preventive medication for 27.9%, 20.2%, and 26.9%, respectively (Table 2). Most common current acute medications were triptans and propionic acid derivatives; most common current preventive topiramate, amitriptyline and calcitonin gene–related peptide receptor monoclonal antibodies. Conclusion: The CAPTURE study will build a large, longitudinal database on migraine treatment patterns in the contemporary era and associated disease trajectories. medications were Fig. 1 Fig. 2

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Fig. 3 P204 Efficacy of fremanezumab treatment for migraine prevention in patients with migraine and major depressive disorder: results from the open-label extension of the UNITE study R. B. Lipton1, V. Ramirez Campos2, Z. Roth-Ben Arie3, M. Ortega4, P. Barbanti5, M. Galic6, D. Mitsikostas7 1Albert Einstein College of Medicine, Departments of Neurology, Psychiatry and Behavioral Sciences, New York, NY, United States 2Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, United States 3Teva Branded Pharmaceutical Products R&D, Inc., Tel Aviv, Israel 4Teva Branded Pharmaceutical Products R&D, Inc., Parsippany, NJ, United States 5Headache and Pain Unit, IRCCS San Raffaele, Rome, Italy 6Teva-Pharma, Produtos Farmacêuticos, Lda., Porto Salvo, Portugal 7Kapodistrian University of Athens, Athens, Greece Objective: In the 12-week, double-blind period (DBP) of the UNITE study, treatment with fremanezumab, a humanised monoclonal targets calcitonin gene-related peptide, resulted in significant antibody that quarterly fremanezumab reductions in monthly migraine days (MMD) and depressive symptoms. The open-label extension (OLE) of UNITE aimed to explore the longer-term efficacy and safety of fremanezumab. Methods: UNITE was a randomised, Phase 4 study with a 12-week OLE (NCT0401284). Eligible patients with episodic or chronic migraine and major depressive disorder were randomised to monthly fremanezumab (225 mg) or matched placebo. All completers were invited to enter the OLE where they received (675 mg). Exploratory endpoints included mean change from baseline to Week 24 in MMD, Hamilton Depression Rating Scale-17 (HAM-D 17) score, 6-Item Headache Impact Test (HIT-6) score, Clinical Global Impression of Severity of Illness (CGI-S) rating and Patient Health Questionnaire-9 (PHQ-9) score. Safety was measured through adverse events (AEs). Results: 330/353 patients entered the OLE. Mean change for fremanezumab and –3.4 for placebo at Week 12, and –6.9 for fremanezumab-fremanezumab and –7.0 for placebo-fremanezumab at Week 24 (Figure 1). Reductions in HAM-D 17 scores were –6.8 and –5.4 at Week 12, and –7.6 and –8.4 at Week 24 for the fremanezumab-fremanezumab placebo- fremanezumab Clinically meaningful reductions in HIT-6, CGI-S and PHQ-9 scores were observed at Week 24 in both treatment groups. 60 (18%) patients reported ≥1 AE in the OLE. Conclusion: Despite the complex treatment history of this high-risk population, patients with migraine and major depressive disorder experienced sustained reductions in MMD and depressive symptom scores over the OLE, suggesting that fremanezumab may reduce the symptoms and cumulative burden of both diseases. Safety was consistent with that in the DBP and pivotal fremanezumab randomised controlled trials. in MMD was –5.4 from baseline respectively. and groups, Fig. 1

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P205 White matter hyperintensities in a Portuguese cohort of migraine patients: prevalence, characterization and clinical correlations S. Moreira1, R. Coutinho2, M. Gomes2, A. Costa1, S. Lopes1, J. M. Araújo1, S. Varanda1 1Unidade Local de Saúde de Braga, Neurology, Braga, Portugal 2Unidade Local de Saúde de Braga, Neuroradiology, Braga, Portugal design; selection Objective: Recent evidence indicates a heightened risk of white matter hyperintensities (WMHs) in patients with migraine, visible as hyperintense brain foci on T2-weighted and fluid-attenuated inversion recovery MRI sequences. We aimed to evaluate the presence and location of WMHs and correlate them with clinical variables. Methods: Retrospective of consecutive migraine patients from a public headache outpatient clinic, over 36 months. Demographic and clinical data collection included age, sex, comorbid medical history and migraine characterization. Patients with major central nervous system diseases, significant traumatic brain injury history, autoimmune diseases, HIV infection and/or uncontrolled vascular risk factors were excluded. Categorization of patients who underwent brain MRI into two groups based on WMHs presence. Statistical approach included chi- square tests for nominal variables, t-tests (confirmed with non-parametric tests) for numerical variables and binary logistic regression to identify independent predictors of WMHs. Results: A total of 1046 appointments reviewed, identifying 323 migraine patients, 127 of whom underwent brain MRI; 37 excluded, resulting in a final sample of 90 patients (majority female, mean age 37.8 years). Thirty-nine patients (43.3%) with WMHs and 51 patients (56.7%) without WMHs. The most susceptible areas for WMHs were the frontal lobe subcortical bilateral predominance. There were no statistically significant differences between the two groups for each variable analyzed, including age and migraine characteristics. The logistic regression model was significant (χ²(2) = 6.19, p = 0.045, R² = 0.09), with age as a predictor for WMHs (p = 0.038). Conclusion: Despite the reduced sample size and the monocentric nature of this study, WMHs seem common in migraine patients, particularly in those who are older, appearing more often in the frontal lobe subcortical white matter. white matter, with P206 Risk factors for migraine onset – a systematic review and three-level meta-analysis M. Terhart1, L. H. Overeem1,2, J. B. Hong1, U. Reuter1,3, B. Raffaelli1,4 1Charité – Universitätsmedizin Berlin, Department of Neurology, Berlin, Germany 2Humboldt Graduate School, Doctoral Program, International Graduate Program Medical Neurosciences, Berlin, Germany 3Universitätsmedizin Greifswald, Greifswald, Germany 4Berlin Institute of Health at Charité (BIH), Clinician Scientist Program, Berlin, Germany is a debilitating neurological Objective: Migraine disorder with a complex and not fully understood etiology. Despite numerous studies identifying various predisposing factors for migraine, a comprehensive and structured overview of these risk factors remains lacking. This review aims to systematically summarize and evaluate risk factors associated with the onset of migraine. Methods: Studies on risk factors for new migraine onset were systematically searched using PubMed and EMBASE. Risk factors had to be present before migraine onset. Three-level meta-analyses with restricted maximum likelihood were performed, and pooled risk ratios (pRR) were evaluated. Subgroup and sensitivity analyses tested data robustness. Results: Out of 17,330 records, we identified 53 studies across 33 cohorts, comprising 337 endpoints and 142 exposures. The majority of studies had low Risk of Bias (RoB, n=37, 71%). Heterogeneity was high (>90%), mainly due to within-study differences (>50%). Tests of Moderators and excluding outliers did not affect heterogeneity. Egger's test did not suggest that publication bias is likely to be a major concern. We found a significant increased risks for migraine onset for psychiatric [pRR=2.63 (1.79, 3.85)], atopic [(pRR=1.53 (1.15, 2.03)], sleep [(pRR=1.89 (1.26, 2.85)], and cardiovascular [pRR=1.72 (1.07, 2.76)] disorders. Further factors increasing the risk of migraine included: prenatal factors, e.g. maternal alcohol and tobacco use, behavioral factors, and family-related factors, e.g. family conflicts. Conclusion: Several factors, including comorbidities and environmental influences, show a strong association with migraine onset. These associations may be due to shared genetic predispositions and common mediating factors such as stress and inflammation. Future research should focus on these findings targeted prevention and treatment strategies. to develop

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P207 Long-term outcomes (over 24 months) of anti-CGRP therapy in migraine – a real-world single-center study M. Henriques1, T. Ascensão Pinheiro1, J. Moniz Dionísio1, R. Pinheiro1, E. Parreira1 1Hospital Prof Doutor Fernando Fonseca, Neurologia, Lisboa, Portugal P208 Electrophysiological disparities in trigeminal ganglion neurons induced by serotonin depletion: Implications for migraine in rats model S. Vongseenin1, S. Thanprasertsuk1, N. Ha-ji-a-sa1, S. Bongsebandhu-phubhakdi1 1Chulalongkorn University, Faculty of Medicine, Bangkok, Thailand Objective: Anti-CGRP monoclonal antibodies have proven to be effective and safe in the treatment of migraine, but real-world studies evaluating their long- term effects are still lacking. Objective: To investigate the efficacy and safety of anti-CGRP or anti-CGRPr monoclonal antibody treatment for more than 24 months (M). Methods: Single-center, observational, retrospective study involving patients who were refractory to three previous preventives or more and were treated with an anti-CGRP monoclonal antibody (erenumab, fremanezumab, or galcanezumab) for at least 24M. Patients who discontinued medication for more than 3M were excluded. Clinical data was collected from clinical files and headache days/intensity evaluation was confirmed with patient diaries. Adverse effects were also evaluated. Patient-Reported Outcome Measures (PGI, MIDAS, HURT, HIT-6, SF-12) as well as anxiety and depression scales were collected every 3M. Descriptive analysis with SPSS®️. Results: We included 28 patients with a median age of 44 years. Fifty percent were on erenumab (n=14), 21.4% on fremanezumab (n=6), and 28.6% on galcanezumab (n=8). Twenty-five percent had chronic migraine. The median duration of treatment was 28M (minimum 24; maximum 42 months). Most adverse effects were gastrointestinal. No serious adverse events occurred. At 12M, 39.3% of patients had migraine days reduced by more than 50% and 28.6% more than 75% (p=0.004). At 24M, 50.0% of patients had a 50% reduction (39.3% more than 75%). At 36M, all patients had 50% reduction in headache days compared to baseline, with 40.0% reducing it by more than 75%. Disability progressively improved with MIDAS score decreased from 72.9 to 25.7 at 12M and 20.4 at 24M (p=0.021). that Conclusion: This monoclonal anti-CGRP to improve clinical outcomes even after 24M of therapy with excellent response in the long run. They have not only sustained but improved clinical benefits with improved disability and minimal side effects. treatments continue real-world study shows Objective: While numerous studies have identified serotonin (5-HT) depletion as a critical mechanism that can exacerbate migraine pain within the trigeminal nociceptive pathway at both molecular and electrophysiological levels, the specific role of 5-HT depletion in modulating pain within trigeminal ganglion neurons remains unclear. This study aims to elucidate the effects of 5-HT depletion on the excitability of first-order trigeminal ganglion neurons, focusing the electrophysiological disparities among small to medium sized nociceptive neurons and large sized nociceptive and non-nociceptive neurons. Methods: We studied the resting membrane potential (RMP) and action potential properties of TG neurons using the patch-clamp recording technique in male rats. Serotonin depletion was induced by parachloro- L-phenylalanine (PCPA). TG neurons were divided into the following four groups: small to medium and large neurons from 5-HT-depleted rats (PCPA-SM and PCPA- L groups, respectively) and small to medium and large neurons from control rats (control-SM and control-L groups, respectively). Results: The RMP was significantly less negative in the PCPA-SM group than in the PCPA-L group (p = 0.017). The rheobase of the PCPA-L group was significantly higher than that of the PCPA-SM group (p = 0.002). The total spike of PCPA-SM was significantly greater than that of PCPA-L (p = 0.031). Such significant differences were not detected among other groups. Conclusion: A significant in excitability contrast between small to medium and large sized TG neurons under serotonin depletion conditions plays a crucial role in the peripheral sensitization of first- order TG neurons through electrophysiological disparities between nociceptive and somatosensory signals. This exacerbates migraine headaches and induces abnormal sensitization during migraine attacks, like allodynia and hyperalgesia. This will help in screening patients with migraine and in alleviating migraine pain as well. including symptoms increase

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Fig. 1 Fig. 2 Fig. 3 P209 Comparison of brain structural MRI before and after 6-months of preventive treatment with anti-CGRP monoclonal antibodies and onabotulinumtoxinA in people with migraine J. Rosell-Mirmi1, E. Caronna1,2, V. J. Gallardo López1, D. Pareto3, A. Alpuente1,2, M. Torres-Ferrús1,2, À. Rovira3, P. Pozo-Rosich1,2 1Vall Hebron Institute of Research (VHIR), Headache and Neurological Pain Research Group, Barcelona, Spain 2Hospital Universitari Vall d'Hebron, Headache Unit, Barcelona, Spain 3Hospital Universitari Vall d'Hebron, Radiology Department, Barcelona, Spain Objective: To compare the impact of two different preventive treatments for migraine, anti-CGRP mABs and onabotulinumtoxinA (BTX-A), in cortical thickness and brain volumes, before and after 6 months of treatment. Methods: Prospective interventional study recruiting migraine participants with ≥8 headache days/month who were eligible for preventive treatment with anti- CGRP mAbs or BTX-A, who were not on any other preventive treatment, and all right handed. 3T brain MRI imaging T1-MPRAGE protocols were done before and after 6 months of treatment. Regions of interest (ROIs) were segmented and cortical thickness (CT) and brain values were extracted using FreeSurfer® software (v7.4.1). Baseline and post- treatment data were analysed using generalized linear mixed-effect models and p-values were adjusted using FDR for multiple comparisons. Results: A total of 96 patients, 88.5% (85/96) women, mean age 39.9±9.7 years, and 40% (38/96) ³15 headache days/month were included. A mean reduction of -5.7±6.1 monthly headache days was observed (p<0.001). Right pars-opercularis and right pars-orbitalis CT were significantly reduced at month 6 (p<0.05). A statistically significant interaction was found between time and treatment in volume of thalamus, caudate, hippocampus and amygdala left hemisphere, and putamen and pallidum in right hemisphere, showing a volume reduction in individuals treated with anti-CGRP mAbs (p<0.05), and not for BTX-A. Conclusion: 6-month treatment with anti-CGRP mAbs and BTX-A reduces cortical thickness in brain areas associated with production and processing of language and cognition, instead same brain volumes only decrease in anti-CGRP mAbs treated patients. statistically volumes in

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P210 Is migraine a severity predictor in CADASIL patients? Early results from CADA-Migraine study D. A. Montisano1, N. Rifino1, S. Lazzari1, E. Zacarias1, A. González Martínez2, L. Grazzi1, A. Bersano1 1Fondazione IRCCS, Milano, Italy 2Hospital Universitario La Princesa, Madrid, Spain Objective: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary microangiopathy in wich is a common migraine, especially with aura, presentation symptom. Aim of the study is to investigate if there is a link between migraine and severity of clinical phenotype of CADASIL. Methods: We conducted a cross-sectional analysis of data from 86 CADASIL patients prospectively collected at a specialized center at IRCCS C.Besta. We evaluated: phenotype of migraine, Fazekas score and type of mutation, divided in high, moderate and low risk. Descriptive statistics were generated for patients with positive Migraine Screening Questionnaire (MS_Q) >=4. Associations between Fazekas scores and migraine and CADASIL variables were analyzed using chi-square tests for categorical variables and ANOVA for quantitative variables. Results: We included 26 patients, 18/26 (69%) female, median age 50 (IQR:21), 11/18 (61%) Fazekas score of 3, 9/18 (50%) had high risk mutation. Among them, 18/26 (69%) were MS-Q positive and 15/18 (83%) fulfilled ICHD-3 criteria for migraine; 13/18 (72%) were female, 52 (IQR:17.25) years, 8/17 (47%) with aura. The mean number of monthly headache days (MHD) at baseline was 5.00 (6.84) and migraine days (MMD) was 6.00 (SD = 6.74).The mean HIT-6 score was 53.78 (SD = 7.41) in patients with probable migraine and 47.2 (8.08) in patients without probable migraine (p= 0.074). Conclusion: This analysis provides a comprehensive overview of the prevalence of migraine in patients with CADASIL. Patient with migraine in CADASIL population show high burden at imaging; in this prelminary investigation no association with risk mutation was observed. Further research including a larger sample size is guaranteed to explore the association between migraine and Fazekas scores, type of mutation and other variables such as aura, migraine type or phenotype. P211 Analysis of serum alpha-CGRP levels in different disorders and its meaning regarding the specificity of increased concentrations of the peptide for chronic migraine G. Gárate1,2,3, V. González-Quintanila1,2, M. Pascual- Mato4, T. García-Rivero5, J. M. Olmos6, J. Madera Fernandez1,2, M. Rivero4, J. Pascual1,2,3 1IDIVAL, Santander, Spain 2Hospital Universitario Marqués de Valdecilla, Neurologia, Santander, Spain 3Universidad de Cantabria, Santander, Spain 4Hospital Universitario Marqués de Valdecilla, Gastroenterología, Santander, Spain 5Hospital Universitario Marqués de Valdecilla, Cardiología, Santander, Spain 6Hospital Universitario Marqués de Valdecilla, Medicina Interna, Santander, Spain testing the individuals with specificity of elevated Objective: circulating concentrations of alpha-CGRP in chronic migraine (CM). Methods: we have recruited subjects suffering from different entities where CGRP is or may be involved such as migraine, autoimmune disorders, infections with hyperimmune response and vascular events. subjects with Consequently, we included (IBD), COVID-19 inflammatory bowel disease inpatients, acute myocardial infarction (MI) and chronic migraineurs without any active anti-CGRP therapy. Each group was paired by sex and age with a corresponding control group. Serum alpha-CGRP levels were measured by ELISA using a kit from ABBEXA. Results: CM (n=174; 55.1±35.7pg/mL), IBD (n=96; 61.3±39.7pg/mL), COVID-19 (n=52; 57.9±35.8pg/mL) and MI (n=26; 96.0±77.4pg/mL) groups showed increased alpha-CGRP levels compared to controls (45.2±27.5pg/mL, p<0.01; 45.9±28.0pg/mL, p<0.01; 41.8±25.4pg/mL, p<0.01; 46.7±26.3pg/mL, p<0.001; respectively). The increase found in IBD patients was even more pronounced in those who had an history of migraine (73.0±27.9pg/mL; p<0,001). In the MI group, alpha-CGRP concentrations were also increased when compared these got normalized acute the cardiovascular event. alpha-CGRP Conclusion: concentrations described literature and confirmed in this work is only partially specific for this entity as the results point out there are other conditions is potentially involved and which show similar behaviour of the peptide. The presence of this conditions as comorbidities of the patients should be taken into account when performing comparative studies of alpha-CGRP levels. in whose pathophysiology CGRP (p<0.00001) and (45.1±26.7pg/mL) after to CM the alteration of in the

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evaluable 4-week period of post-baseline data. 50.5% enrolled directly from the end of lead-in double-blind treatment. Remaining participants enrolled after a 4- week safety period or later. 70.0% achieved ≥50% reduction in MMDs at weeks 13-16; similar rates were observed to week 48 (figure). Direct rollovers had a similar ≥50% RR to the full mITT population. At weeks 13-16, 43.9% and 18.1% reported ≥75% and 100% improvement from lead-in baseline, respectively, maintained through week 48. At week 12, participants reported a mean in RFR domain scores, consistent through week 52. As previously reported, the overall safety results were consistent with the known safety profile of atogepant. study Conclusion: baseline in responder rates and functional impacts of migraine on daily activity were sustained over the first year of this open-label extension. improvement of 34.79 lead-in Improvements from Fig. 1 Work funded by ISCIII through projects PI20/01358 and PMP22/00183. P212 Impact of Atogepant on long-term response rates and migraine-specific quality of life in migraine prevention: interim analysis of a phase 3, multicenter, open-label, 156-week extension study P. J. Goadsby1,2, D. Holle-Lee3, C. Tassorelli4, S. J. Cho5, M. Y. He6, P. Gandhi6, K. Carr6, B. Dabruzzo6, J. H. Smith6, S. Ashina7,8,9 1King's College London, NIHR-King’s Clinical Research Facility, London, United Kingdom 2University of California, Los Angeles, CA, United States 3West German Headache and Vertigo Center Essen, University of Essen, Department of Neurology, Essen, Germany 4University of Pavia and C. Mondino Foundation, Pavia, Italy 5Hallym University College of Medicine, Department of Neurology, Dongtan Sacred Heart Hospital, Hwaseong, South Korea 6AbbVie, North Chicago, IL, United States 7Beth Israel Deaconess Medical Center, BIDMC Comprehensive Headache Center, Boston, MA, United States 8Harvard Medical School, Department of Neurology and Department of Anesthesia, Critical Care and Pain Medicine, Boston, MA, United States 9University of Copenhagen, Department of Clinical Medicine, Copenhagen, Denmark Objective: Atogepant is an oral calcitonin gene- related peptide receptor antagonist approved for the preventive treatment of migraine. ELEVATE and PROGRESS were phase 3, randomized, double-blind, placebo-controlled trials evaluating atogepant for the preventive treatment of episodic migraine (EM) in participants who had previously been failed by 2-4 classes of conventional oral preventives, or chronic migraine (CM), respectively. The objective of this study was to evaluate long-term response rates(RR) and migraine-specific quality of life(MSQ) across one year of atogepant treatment in those subjects. Methods: This interim analysis of an open-label, 156- week, long-term safety extension study, enrolling completers of ELEVATE and PROGRESS, evaluated participants who completed week 48 or terminated early. The proportion reporting ≥50%, ≥75%, 100% improvement in monthly migraine days(MMDs) from the lead-in study baseline period was assessed at weeks 13-16,29-32,45-48 by eDiary collection. MSQv2.1 was completed at weeks 12,20,28,36,44,52. Results: The mITT population included 524 participants who received ≥1 dose and had ≥1

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Fig. 2 P213 Psychiatric comorbidities in migraine patients and the influence of monoclonal antibody therapy against CGRP – preliminary results C. Fernandes1, J. Cancela1, M. Almeida1, F. Gomes1, S. Matos1, I. Costa1, F. Magalhães1, B. Rodrigues1, A. Maduro1, H. Gens1, S. Batista1, I. Luzeiro1 1Local Unit of Health of Coimbra, Neurology Department, Coimbra, Portugal in more detail the is a chronic disease that Objective: Migraine associates different comorbidities, such as depression and anxiety. Preventive treatment has evolved in efficacy and safety with the introduction of anti-CGRP monoclonal antibodies (mAbs). Our study aimed to identify predictors of treatment response to mAbs and influence of comorbid depression or anxiety. Methods: We conducted an observational prospective unicentric study which included patients diagnosed with frequent episodic (fEM) or chronic migraine (CM) and who were proposed for mAbs. Patients completed a clinical survey, headache calendar, Beck Anxiety Inventory (BAI), Beck Depression Inventory (BDI) and Headache Impact Test 6 (HIT-6), at baseline, at 3 and 6 months after treatment. Results: Thirty-nine patients with a median age of 44.0±12.0 years were surveyed, 87.2% were women and 81.6% were diagnosed with chronic migraine. Currently, 25 and 13 patients have reached the 3 and 6-month follow-up, respectively. Regarding mAbs, 20 patients were under erenumab (51.3%), 15 fremanezumab (38.5%) and 4 galcanezumab (10.3%). At baseline, 24 patients (68.6%) scored for anxiety at BAI and 10 (42.9%) for depression at BDI, these percentages at 3 months decreased to 60.0% and 40.0%. Migraine pain duration was correlated with BAI score (p<0.014) and BDI score (p=0.038) and intensity with HIT-6 score (p=0.006). Also, anxiety levels were associated with higher HIT-6 scores (p=0.001). Treatment was effective in 46.2% and 80.0%, at 3 and 6 months. No correlation was found between anxiety and depression at baseline and mAbs efficacy. Conclusion: Preliminary results that a previous diagnosis of anxiety or depression does not influence mAbs response. Although, mAbs seems to reduce the punctuation in depression and anxiety scales. Interestingly, pain intensity and duration are the characteristics with the greatest impact on day-to- day life and anxiety scales. indicate P214 Psychiatric and sleep disorders in migraine patients: common comorbidities J. Cancela1, C. Fernandes1, M. Almeida1, R. Cagigal2, I. Costa1, F. Magalhães1, B. Rodrigues1, A. Maduro1, H. Gens1, S. Batista1, I. Luzeiro1 1ULS Coimbra, Neurology, Coimbra, Portugal 2ULS Gaia e Espinho, Neurology, Vila Nova de Gaia, Portugal included Beck study which Objective: Migraine is associated with different comorbidities, such as depression and anxiety. Not only migraine but also these psychiatric disorders could influence the quality of sleep. Our study aimed to study the association between psychiatric and sleep disorders in migraine patients. Methods: We conducted an observational prospective unicentric frequent episodic(fEM) or chronic migraine(CM) patients that initiated mAbs therapy. Patients completed Beck Anxiety Depression Inventory(BAI), Inventory(BDI), Headache Impact Test 6(HIT-6), Pittsburgh Sleep Quality Index(PSQI), and Epworth scale(ES), at baseline and at 3 months after treatment. Results: Thirty-nine patients, 87.2% female, with a mean age of 43.5±12.5 years were surveyed, and 81.6% were diagnosed with CM. Nine (29.0%) patients had a previous history of a sleep disorder. Regarding mAbs, 20 patients initiated erenumab (51.3 %), 15 fremanezumab (38.5%) and 4 galcanezumab (10.3%). At baseline, 19 patients (65.5%) demonstrated sleep impairment and 10 (34.5%) excessive daytime sleepiness. According to BAI and BDI scores, 24 (68.6%) reported anxiety and 15 (42.9%) depression. At 3 months, these percentages decreased to 60.0% and 40.0%, respectively, and an improvement in PSQI

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occurred in 8 (40.0%) and at ES in 11 (55.0%) patients. We found an association between anxiety and sleep impairment (r=11.474;p=0.001) and a correlation between PSIQ and BDI scores at baseline (p=0.039). No correlation was found between different mAbs treatment or response and punctuation in PSIQ or ES. Conclusion: Our both underdiagnosed psychiatric disorders and sleep disturbances are common in migraine patients. Patients with worse sleep quality presented with depressive symptoms with an impact on the quality of life. These findings importance of addressing the comorbidities in migraine patients. increase the indicates study that P215 Cortical spreading depolarization-evoked cortical inflammation correlates with activation of meningeal macrophages Y. H. Chang1, S. P. Chen1,2,3,4,5, M. T. Ho1, S. J. Wang2,3,4, J. C. Yen6 1National Yang Ming Chiao Tung University, Clinical Medicine, Taipei, Taiwan 2National Yang Ming Chiao Tung University, Faculty of Medicine, Taipei, Taiwan 3National Yang Ming Chiao Tung University, Brain Research Center, Taipei, Taiwan 4Taipei Veterans General Hospital, Neurology, Neurological Institute, Taipei, Taiwan 5Taipei Veterans General Hospital, Medical Research, Taipei, Taiwan 6National Yang Ming Chiao Tung University, Pharmacology and Toxicology, Taipei, Taiwan to the cells activate immune between correlation Objective: Cortical Spreading Depolarization (CSD) is an electrophysiological phenomenon underlying migraine aura. Previous studies have showed that CSD can evoke cortical inflammation and activation of the meningeal trigeminovascular system. This study aimed to investigate cortical inflammation and activation level of macrophages on meninges after CSD. Methods: We used topical application of KCl to induce CSD and observed the effects of CSD on cortical inflammation and meningeal macrophage activation in mice. To investigate the effect of meningeal lymphatic drainage on cortical inflammation and meningeal macrophage activation, we ablated meningeal lymphatic vessels and dissected cervical lymph nodes, respectively. Quantitative polymerase chain reaction and Western blot were used to confirm the the cortex and immunofluorescence staining was used to observe activation of macrophages on meninges. inflammatory response in Results: We found that after KCl-evoked CSD, the expression levels of inflammatory genes, IL-1β and Ccl2/mcp-1 increased on the ipsilateral cortex and COX-2 protein level increased as well. Meningeal lymphatic ablation and cervical lymph nodes dissection both demonstrated that the dysfunction of meningeal lymphatic drainage aggravated cortical inflammatory response and meningeal macrophage activation, as indicated by the proportion of area in macrophages increased after CSD. Conclusion: CSD induction could cause the activation of meningeal macrophage and cortical inflammatory response. Dysfunction of meningeal lymphatic drainage exacerbated the cortical and meningeal inflammatory events, providing future pathogenic and therapeutic implications. P216 Preliminary results utilizing the Ussing Chamber to investigate meningeal properties M. N. Jensen1,2, K. A. Haanes1,2 1Rigshospitalet, Sensory Biology Unit, Glostrup, Denmark 2University of Copenhagen, Department of Biology, Copenhagen, Denmark to investigate Objective: In the migraine literature it has long been assumed that the meninges are impermeable in both health and disease. However, to our knowledge this has never been investigated. The Ussing Chamber is a method from the 1940"s, normally utilized to investigate membrane properties. This method was explored the barrier properties, including permeability, channel and transporter activity and receptor mediation, of the meninges from a rat. Methods: Meninges from male Sprague-Dawley rats were isolated and placed in the Ussing Chamber with known polarization. Randomly and blinded to the experimenter, fluoresceine was added to either the brain-facing or the skull-facing meningeal side. Simultaneously, the Ussing Chamber was current- clamped at -5 μA allowing direct measurements of voltage changed from the different sides of the meninges to calculate the potential resistance. Results: The meninges could be isolated from the rat skull and kept viable. The low resistance between the brain-facing meningeal side and the skull-facing meningeal side rendered it difficult to draw specific conclusions the membrane. Nevertheless, the meninges showed low investigation permeability continues layers isolated, using the current method. Conclusion: This study demonstrated that while the low resistance observed between the brain-facing and into understanding the specific fluoresceine. The transport across about ion to

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ion sides limits transport, definitive skull-facing meningeal conclusions the low regarding permeability to fluorescein indicates a degree of selective barrier function in the meninges. Future work will focus on identifying the specific ion channels and transporters present in the meninges to better understand their barrier properties. P217 Reliability and validity of Turkish version of migraine specific quality of life v2.1 questionnaire P. Yalinay Dikmen1, A. Sahin Misir1, E. Ilgaz Aydinlar1, T. Erdogan Soyukibar1, A. Özge2, R. Karaci3, B. Polat4, T. Cerrahoglu Sirin5, D. H. Saral6, B. Tasdelen6 1Acibadem University School of Medicine, Neurology, Istanbul, Turkey 2Mersin University Faculty of Medicine, Neurology, Mersin, Turkey 3University of Health Sciences, Neurology, Istanbul, Turkey 4Duzce University School of Medicine, Neurology, Bolu, Turkey 5University of Health Sciences, Neurology, Istanbul, Turkey 6Mersin University Faculty of Medicine, Bioistatistics and Medical Informatics, Mersin, Turkey in included patient-physician Objective: This study aims to assess the reliability and validity of the Turkish version of the Migraine Specific Quality of Life (MSQ), a validated tool that measures the impact of migraine on a patient's daily life and overall quality of life. Methods: A total of 182 patients suffering from migraine were this multicenter, prospective, descriptive study, which was conducted over two consecutive visits, 4 weeks apart. The comprehensibility, reliability, internal consistency, test-retest reliability, and validity of the translated MSQ were analyzed. Results: Patients identified that MSQ items were "well-understood" in both visit 1 (ranging from 94% to 97.8%) and visit 2 (ranging from 98.4% to 100%). A highly positive correlation (R = 0.916, p < 0.001) was noted between the visit 1 scores related to self- administered and physician-administered MSQ scores. Internal consistency, analyzed via Cronbach"s α values for visit 1 and visit 2 MSQ scores in all patients, was 0.932 (excellent) and 0.912 (excellent), respectively. MSQ scores of patients (29.18 (15.25) and 22.34 (15.48) at visits 1 and 2, respectively, p < 0.001) showed moderate test-retest reliability (R = 0.468, p < 0.001). The MSQ scores for visits 1 and 2 positively correlated with Headache Impact Test-6 (HIT-6) (R = 0.751 and R = 0.772, p < 0.001), monthly headache days (MHDs) (R = 0.453 and 0.553, respectively, p < 0.001), and Numeric Analogue Scale (NAS) (R = 0.539 and 0.564, respectively, p < 0.001) scores. Conclusion: These results demonstrate that the Turkish translation is equivalent to the English version of the MSQ in terms of internal consistency and has moderate test-retest reliability and validity, as correlated with HIT-6, MHDs, and NAS. P218 Influence of precipitants on the characteristics of Chronic migraine study. Study in a series of 1584 patient Á. Sierra Mencia1, I. Ros Gonzalez1, M. L. Peñas Martinez1, Y. González-Osorio1, A. Recio García1, C. Garcia-Iglesias1, S. García García1, D. García-Azorín2, Á. L. Guerrero-Peral1 1Hospital Clinico de Valladolid, Headache Unit, Valladolid, Spain 2Hospital Universitario Río Hortega, Neurology Department, Valladolid, Spain clinical Objective: We aim to evaluate whether the presence of these precipitants modify the characteristics of chronic migraine and its management before referral to a headache unit Methods: Prospective registry of patients firstly admitted with the diagnosis of CM to a headache unit in a tertiary hospital from January 2013 to May 2024. Demographic and characteristics were gathered including latency between beginning of CM its diagnosis, the presence of symptomatic and medication overuse and the previous use of symptomatic and preventive treatments. Results: We included 1584 patients (87.8% women) with an age of 39.1 ± 13.7 (12-80) years and a latency of 33.9 ± 57 (3-580) months between onset and diagnosis of CM. 684 (43.2%) identified a precipitant in the chronic migraine situation, with working stress being the most frequent (481 patients, 30.4%). Patients with a precipitant had a shorter latency in the diagnosis of CM (24.9 ± 41.2 vs. 40.8 ± 65.9 months, p<0.001) and had less frequently received any preventive treatment (49.7% vs. 55.4%, p: 0.025). No difference was seen in the rest of the variables considered. Conclusion: The is common in patients with migraine that progress to CM and does not imply a change in their clinical characteristics. faster implies a identification of the chronic migraine situation. identification of precipitants Its presence

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P219 MIGARGILE tool: How can it help for patient with migraine recruitment in randomized clinical trial? M. d. l. Á. Sosa1, M. T. Marco1, A. Grajea1, A. Rizo1, J. R. Roma1, N. Pola1, M. N. Fabregat1, S. Fernandez- Fernandez1, V. Obach1 1Hospital Clinic Barcelona, Neurology, Barcelona, Spain Objective: Randomized clinical trials (RCT) in migraine usually cover a broad range of inclusion criteria from less disabled patients (4 to 14 migraine per month) resistant to 2-4 oral preventive drugs to more severe daily migraine with medication overuse, needing stable or withdrawn preventive treatment for at least 3 months before screening. Moreover, patients are usually followed in Headache Units and are under OnabotulinumToxinA or Monoclonal anti CGRP antibodies which are exclusion criteria for most RCT. Our aim is to increase early detection of patient candidates for migraine RCT using an electronic tool (MIGRAGILE project) at primary care setting. Methods: We designed MIGRAGILE e-survey with 15 questions, self-completed by patients with headache. It allowed to characterize 1) migraine diagnosis, 2) degree of headache disability, 3) acute and preventive treatment prescribed, and 4) need to be assessed by general neurologist or more specialized headache neurologist. In a routine medical appointment, the General Practitioner provided the MIGRAGILE e- survey and recommended patients with headache to fill in the QR code survey in RedCap platform. The reference population was 317.647 inhabitants distributed in 10 Primary care centers. Results: From July 2023 to July 2024, 185 patients completed diagnosis distribution was: 1) Low frequency episodic migraine: 62 (33.6%), 2) High Frequency Episodic Migraine: 72 (38.2%) 3) Chronic Migraine: 19 (10.5%) 4) Medication overuse headache: 18 (9.9%) and 5) Other non- migraine headaches: 14 (7.8%). Twenty-four patients (12%) were included in RCTs. During the same period, 47 patients had been enrolled in migraine RCTs in our Headache Unit and 24/47 (51%) were referred by the MIGRAGILE tool. Conclusion: MIGRAGILE tool helped to increase the number of patients included in RCTs in our Headache unit and may be a useful approach for other Headache Units. survey. Headache the P220 Structural connectivity changes in migraine involving the cerebellum A. Matoso1, A. R. Fouto1, I. Esteves1, A. Ruiz-Tagle1, G. Caetano1, N. A. Silva2, P. Vilela3, R. Gil-Gouveia4,5, R. G. Nunes1, P. Figueiredo1 1Lisboa and Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, Institute for Systems and Robotics, Lisboa, Portugal 2Hospital da Luz, Lisboa, Portugal 3Hospital da Luz, Lisboa, Portugal 4Hospital da Luz, Lisboa, Portugal 5Universidade Católica Portuguesa, Center for Interdisciplinary Research in Health, Lisboa, Portugal two brain using to play a significant role Objective: Although the pathophysiology of migraine remains poorly understood, structural disruptions across brain networks have been reported. Migraine connectivity studies primarily focus on cortical networks, neglecting crucial subcortical (SC) regions like the thalamus and the cerebellum (CB), which are known in migraine pathophysiology. Here, we investigate structural connectivity in a group of episodic migraine patients without aura compared to controls using diffusion- weighted MRI (dMRI). Methods: Multi-shell dMRI data was acquired in Hospital da Luz Lisboa and structural connectivity was determined parcellations (Schaefer+SC+CB and AAL116). The connectivity was assessed using the network-based statistics (NBS) toolbox and graph metrics were calculated including the global efficiency (GE) and the characteristic path length (L) and their correlation with clinical data. Groups were compared using the Wilcoxon Rank Sum Test. A p-value of 0.05 was considered significant. Results: Results showed significant connectome differences increased structural connectivity between the left crus and left posterior lobe of the cerebellum (PLC) and between the occipital lobe/visual network and cerebellar regions (Figure 1). Patients showed decreased L and increased GE in both parcellations (Figure 2), with a positive correlation (r=0.56) between L and disease duration (Figure 3). in pain The cerebellum plays an inhibitory role processing, having several connections to the prefrontal cortex (via the thalamus). The increased connectivity between the cerebellum and other regions may indicate a dysfunctional negative feedback loop where the inhibitory signal is not sensed by the thalamus. The decreased L and increased GE can be indicative of higher pain information dissemination in the brain circuitry. Conclusion: These results showcase cerebellum's importance in migraine pathophysiology, highlighting the necessity of including it in connectome studies. in patients, with

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Fig. 1 Fig. 2 Fig. 3 P221 Effectiveness of laser acupuncture for anxiety and depression among patients with chronic migraine – propensity score matching study C. C. Chung1, C. H. Chou2, C. S. Wang2, H. Y. Wu1, Y. C. Liu1, C. Y. Hsu3, W. L. Chen1, C. I. Tsai1 1Taichung veterans general hospital, Traditional Chinese Medicine, Taichung, Taiwan 2Taichung Veterans General Hospital, The Department of Neurological Institute, Taichung, Taiwan 3Taichung Veterans General Hospital, Department of Medical Research, Taichung, Taiwan its effectiveness Objective: Laser acupuncture (LA) has shown efficacy in migraine prevention, but in addressing anxiety and depression related to chronic migraine (CM) remains inconclusive. We aimed to examine the effectiveness of LA in CM related anxiety and depression. Methods: From February 2022 to August 2023, patients over 20 with CM who completed an LA add- on treatment were included in the experimental group. A comparator group was established using 1:1 propensity score matching (PSM), matching for age, gender, body mass index, headache duration, and scores of Hospital Anxiety and Depression Scale (HADS) from the migraine database of Taichung Veterans General Hospital, which enrolled CM patients managed pharmacologically. Migraine diagnosis was confirmed by a neurologist, and anxiety and depression were assessed using the HADS. The LaserPen-Expert 511A, a device emitting 810 nm light at 5 W/cm², was used to deliver laser radiation at 150 mW to each acupoint. The baseline was defined as the start of LA treatment for the experimental group or enrollment in the database for the comparator group. The primary outcome was HADS scores in the 12th week from baseline. Results: The LA group comprised 30 patients, and 30 matched migraine patients were selected as the comparator group. After the PSM process, the two groups had no significant differences in age, gender, body mass index, headache duration, or HADS scores. The LA group experienced a mean of 20.8 ± 4.5 headache days per month at baseline, compared to 19.3± 3.6 days in the comparator group (p=0.80). After four weeks of LA treatment followed by eight weeks of follow-up, HADS scores in the LA group significantly decreased from a mean of 11.9 ± 6.5 to 8.7 ± 6.1 by the 12th week (p < 0.01), while scores in the comparator group changed from 11.7 ± 6.9 to 11.0 ± 6.1 (p = 0.24). Conclusion: LA has a beneficial effect on reducing anxiety and depression in CM patients. We recommend LA as an adjunctive treatment for CM related anxiety and depression.

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Fig. 1 Conclusion: Our study presents a developed machine learning model for predicting the suitability of telemedicine for migraine patients. The proposed model can be useful for optimizing the allocation of health care system resources and improving patient- centred care. Fig. 1 P222 Telemedicine suitability prediction in migraine care – a machine learning approach D. Petrosian1, S. Andruskevicius2, A. Dapkutė2, K. Ryliškienė2 1Vilnius University, Faculty of Medicine, Vilnius, Lithuania 2Vilnius University, Center of Neurology, Vilnius, Lithuania learning models telemedicine experiences Objective: Artificial intelligence is being integrated into many areas of medicine. We aim to develop a machine learning model to predict the suitability of telemedicine for migraineurs. Methods: An electronic anonymous survey was administered to collect sociodemographic details, migraine history, management, comorbidities, and prior from migraine patients, which served as the dataset for developing the machine learning models. Using Python 3.11.4 four machine including Random Forest (RF), Logistic Regression, Support Vector Machine (SVM) and XGBoost were developed. Results: From 847 patients 601 (71.0%) would agree to participate in teleconsultation in the future. Upon implementing the machine learning models, it was found that the RF model outperforms the XGBoost, SVM and Logistic Regression ones. RF model demonstrated significant performance with an accuracy of 81.7%, sensitivity of 85.0%, and specificity of 78.2%. RF model had the highest area under the ROC curve value (0.90), followed by XGBoost (0.87), SVM (0.81) and Logistic Regression (0.81). Confusion matrix results were: 159 True Positive, 136 True Negative, 38 False Positive, 28 False Negative. Not the migraine features, but sociodemographic details such as higher education (SHAP value=0.101), intellectual work (SHAP value=0.080) were most impactful factors for the prediction of telemedicine suitability. (SHAP value=0.093), remote work P223 Phenotyping migraine patients according to clinical and psychophysical characteristics S. Di Antonio1, M. Castaldo1, L. Arendt-Nielsen1 1Aalborg University, Department of Health Science and Technology, Aalborg, Denmark This observational study identify those with in different Objective: Assess migraine patients phases and increased pain sensitivity; identify variables that could predict the presence of IPS independently by the phase of the assessment could be identified included Methods: Episodic(EM) and Chronic Migraine(CM). Patients were firstly divided into two cohorts according to the phase in which the evaluation occurs (interictal; ictal/perictal). In each cohort, distinct subgroups of migraine patients were identified according to clinical and psychophysical characteristics. Then, migraine patients were treated as one cohort, and clinical predictors able to include patients in each subgroup were assessed Results: 198 EM and CM were included (98 assessed during the interictal phase, while 100 assessed during the In both cohorts, two subgroups of migraine patients were identified: 18- 19% of had No Increased pressure-Pain Sensitivity (NoIPS), while the remaining 81-82% had Increased pressure-Pain Sensitivity (IPS). In both cohorts, the IPS groups had reduced pressure pain threshold (PPT) ictal/perictal phase).

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over all tested areas (temporalis, cervical spine, hand, and leg) compared to NoIPS and a group of healthy subjects, while the NoIPS groups had either no difference or increased PPT compared with healthy subjects PPT over temporalis and over the hand correctly identify the IPS group with a sensitivity of 96%, a specificity of 81%, a positive predictive value of 96 %, and a negative predictive value of 81%. The overall accuracy of the model was 93% (model error: mean= 0.07; Standard error=0.02). Conclusion: These results suggest that trigeminal and hand PPT cut-off values could be used in a clinical setting to identify patients with IPS P224 Cabergoline as a preventive migraine treatment – a randomized clinical pilot trial A. Hjelholt1,2,3,4, F. Winther Bach2, H. Kasch2,5, H. Støvring1,2, T. Staehelin Jensen2, J. O. Jørgensen2,6 1Aarhus University Hospital, Steno Diabetes Center Aarhus, Aarhus, Denmark 2Aarhus University Hospital, Clinical Medicine, Aarhus, Denmark 3Aarhus University Hospital, Clinical Pharmacology, Aarhus, Denmark 4Aalborg University Hospital, Clinical Pharmacology, Aalborg, Denmark 5Aarhus University Hospital, Neurology, Aarhus, Denmark 6Aarhus University Hospital, Endocrinology and Internal Medicine, Aarhus, Denmark Objective: Beneficial effects of dopamine receptor agonist treatment in migraine have been reported but remain to be properly tested. The aim of this study was to examine the effect of cabergoline as preventive treatment for migraine. Methods: In a double-blind, placebo-controlled pilot study, 36 adults with > 6 monthly migraine days (MMD) were enrolled at Aarhus University Hospital. Following a 28-days baseline period, participants were randomized to receive cabergoline 0.5 mg or placebo once weekly for 12 weeks as add-on treatment. Participants completed a daily electronic headache diary, and headache questionnaires along with blood tests were collected at baseline and after the treatment period. Primary outcome was change in MMD. Results: Between September, 2022, and February, 2023, 101 adults were assessed for eligibility. At baseline, mean MMD was 13.6 (SD = 4.1) in the cabergoline group and 14.0 (SD = 5.3) in the placebo group. In participants with episodic migraine (n= 20), mean reduction in MMD was -5.4 (SE = 1.3) after treatment with cabergoline as compared to -1.8 (SE = increase after cabergoline 0.9) after placebo [odds ratio: 0.79 (95% CI 0.65 – 0.95), p=0.014]. In participants with chronic migraine (n=13), there was no significant change in number of MMD during cabergoline treatment as compared to placebo. Patients" global impression of change significantly improved after cabergoline as compared to placebo in the entire group of participants (p=0.006). The number of participants with episodic migraine achieving ≥ 50% reduction in MMD tended to (p=0.07). Seven participants receiving cabergoline and 4 receiving placebo experienced adverse effects, none of which were serious. treatment Conclusion: in exhibited clinically meaningful episodic migraine without serious adverse effects. This provides proof-of-concept to justify a sufficiently powered phase 2 trial with different cabergoline dosing regimens as preventive treatment of episodic migraine. improvement cabergoline Preventive P225 The RELEASE umbrella study: An international, non- interventional, prospective cohort study assessing the effectiveness of Eptinezumab in patients initiating preventive treatment for migraine J. Bougie1, M. Hubert1, N. Paúl2, S. Gómez-Lus2, H. Löhr3, J. Yerrapareddy4, G. Luna5, L. Hammer-Helmich5 1Lundbeck Canada Inc., Saint-Laurent, Canada 2Lundbeck España S.A., Barcelona, Spain 3Lundbeck GmbH, Hamburg, Germany 4Lundbeck Limited, Watford, United Kingdom 5H. Lundbeck A/S, Valby, Denmark local, analogue studies conducted Objective: The RELEASE study aims to assess the real- world effectiveness of eptinezumab to address limited real-world evidence (RWE) currently available, adding to scientific evidence on eptinezumab efficacy from randomized controlled trials (RCTs). Methods: This novel umbrella design involves a series of in each participating country to generate data that will be pooled into a global sample. Approximately 700 patients globally are planned to be evaluated, with each to contribute at least 50 patients. Eligible patients will be followed initiating eptinezumab treatment. They will record daily migraines/headaches and acute medication use in an electronic diary and will complete patient-reported outcome measures, including a modified Migraine Disability Assessment, Headache Impact Test-6, Patient Global Impression of Change, Work Productivity and Activity Impairment, and Patient Health Questionnaire-9. Clinicians will also record clinical patients' for up to 12 months after local study expected sociodemographic and

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Conclusion: Migraine episodes in this patient seem closely linked to testosterone levels, worsening as the next injection approaches, suggesting that low or fluctuating testosterone levels may trigger headaches. He experienced fewer episodes with a more stable and prolonged testosterone release, highlighting the significant impact of hormonal fluctuations. While migraine is often associated with other hormones, this case indicates that testosterone may also be an important factor. P227 Migraine is associated with a significantly increased risk for breast cancer – data of more than 1.5 million women R. Preissner1, G. S. Merki Feld2 1Institute of Physiology, Berlin, Germany 2Universität Zürich, Reproduktion-Endokrinologie, Zürich, Switzerland increased overall BC Objective: Migraine affects around 15-17% of women during the reproductive years and is the number one burden of disease in this period of life. Breast cancer (BC) is the most prevalent cancer in women with 1 in 8 women developing this condition during their lifetime. Evidence of the association between migraine and breast cancer is inconsistent. A recently published GWAS study found that women with migraine have an risk. Interestingly, migraine with and without aura differed in the type of estrogen receptor found in the BC cells. Methods: Data were extracted from a global federated health research network providing access to electronic medical records. We searched for female patients with migraine and without migraine. The time window the occurrence of the index event. The index event includes only events, that started up to 20 years ago. Results: After matching for age, family history of BC, genetic susceptibility for BC, and life-birth each cohort included 776,303 women. In the cohort with migraine, the risk for BC was significantly higher (OR 1.25; CI 95% 1.22-1.28). Conclusion: x started after inclusion for characteristics, treatment details, migraine-related healthcare resource utilization, and adverse events in the study. A unique feature of RELEASE is its flexibility, allowing countries to customize their local protocols to fit specific study objectives while maintaining the scientific integrity of the global study. For instance, the Canadian protocol includes the General Anxiety Disorder-7 scale to assess anxiety symptoms in patients receiving eptinezumab. The umbrella design also allows for inclusion of new countries on an ongoing basis, following the regulatory approval and launch of eptinezumab in each country. Results: The umbrella design will enable RWE generation on eptinezumab effectiveness locally and globally across varied settings, ensuring a large and heterogeneous sample size and robust analyses. Conclusion: The RELEASE umbrella study will assess local and real-world effectiveness of eptinezumab to complement scientific evidence from RCTs. global P226 Effect of testosterone therapy on migraine in a patient with congenital bilateral anorchia S. Moreira1, A. Costa1, S. Lopes1, J. M. Araújo1, S. Varanda1 1Unidade Local de Saúde de Braga, Neurology, Braga, Portugal anorchia, subcutaneous testosterone. Referred Objective: Migraine is closely linked to hormonal levels. The literature increasingly discusses the role of testosterone. Methods: Case report. Results: A 33-year-old man with a history of congenital bilateral JAK2 mutation- associated myelofibrosis, splenic vein thrombosis, and former smoker. Regular medications include warfarin and to neurology for episodic headaches since adolescence: right frontal, throbbing, moderate to severe, with slow onset and progressive increase, accompanied by nausea, vomiting, photo-phonophobia, kinesophobia, and osmophobia. Visual disturbances lasting 20-45 minutes precede the episodes. Neurological exam was normal and brain MRI with angiography showed no abnormalities. He noted worsening symptoms near the time of his next testosterone injection. Two subcutaneous testosterone medications with different testosterone esters and release forms were tried, resulting in fewer pain episodes with the medication containing fewer esters and a more stable and prolonged release. Treated with flunarizine, with partial improvement. Switched to amitriptyline due to incomplete significant improvement. response, resulting in

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P228 Perspectives and expectations of chronic migraine patients receiving and not receiving OnabotulinumtoxinA on physiotherapy and rehabilitation treatment D. Onan1, H. Arıkan2, İ. Can3, A. Özge4, P. Martelletti5 1Yozgat Bozok University, Physiotherapy and Rehabilitation, Yozgat, Turkey 2Tokat Gaziosmanpasa University, Physiotherapy and Rehabilitation, Tokat, Turkey 3Headache and Cognition Clinic of Aynur Ozge, Mersin, Turkey 4Mersin University, Faculty of Medicine, Mersin, Turkey 5Unitelma Sapienza University, School of Health Sciences, Rome, Italy (PRT) as a complement importance Demographic characteristics, Objective: Neurologists attach to directing patients to physiotherapy and rehabilitation treatment to OnabotulinumtoxinA to reduce medication overuse, problems caused by chronicity, or keep the patient active. This study aims to investigate the expectations and perspectives of chronic migraine (CM) patients who receive (OnaBot+) and do not receive (OnaBot-) OnabotulinumtoxinA regarding PRT. PRT Methods: expectations and perspectives of 108 CM patients were evaluated with clinical questions in a neurology clinic. Headache intensity (HI) was evaluated with the Visual Analog Scale, and quality-of-life (OoL) was evaluated with the Headache Impact Test-6. Results: There were 55 patients in OnaBot+ and 53 patients in OnaBot-. HI was similar in both groups (6.9±2.3 and 7.4±1.8, respectively;p=0.21). QoL in OnaBot- (66.02±5.76) was lower than in OnaBot+ (63.49±6.10;p=0.03). average OnabotulinumtoxinA session received by the patients was 2.20±1.70; The rate of those who benefited from the treatment was 72.7%, and the rate of those who did not benefit was 25.5%. The percentage of receiving PRT was higher in OnaBot+ (41.8%,p=0.01). The rate of those who benefited from PRT in OnaBot+ was 65.4%(n=17), and in OnaBot- it was 72.7%(n=8). The most commonly received treatments in OnaBot+ were neck stabilization exercise 12.7% (n=7) and pilates exercises 12.7%(n=7), while in OnaBot- it was massage 3.8%(n=3). The benefits of treatments were improvement in the number of attacks, headache days, HI, QoL, and disability. Conclusion: Considering the benefits that CM patients obtain from PRT, a complementary approach to CM may have positive effects on the recovery process. The P229 Utilization of healthcare resources and sick leave in a large cohort of migraine patients – a real-world data analysis A. Shifrin1, E. Domany1, M. Tirosh2, D. Davidovici2, S. Vinker3, I. Forschner4, A. Y. Israel3 1Rambam medical center, Haifa, Israel 2Pfizer Pharmaceuticals Israel LTD., Herzliya, Israel 3Leumit Health Services, Tel Aviv, Israel 4Rambam medical center, Haifa, Israel life. However, Objective: Migraine is a common condition among individuals aged 35-49 years, and the associated disability significantly impacts the most productive years of inconclusive data exist regarding the extent of healthcare resource utilization (HCRU) among migraine patients. In this study, we investigated the extent of HCRU and sick leave among migraine and non-migraine patients. Methods: We conducted a retrospective descriptive study using electronic health records to assess the extent of HCRU and sick leave among adult members of Leumit Healthcare Services (LHS) between 2017 and 2022. Migraine patients were 1:1 compared to control patients of the same age, gender, ethnic group, regional district, and socioeconomic status. Results: Compared to matched control individuals, migraine patients had a significantly higher number of annual general practitioner (GP) visits (SMD=0.361, p<0.001), higher rates of visits to neurologists (OR=3.60; 95%CI, 3.38 to 3.84), pain specialists (OR=2.42;CI 2.13 to 2.77), and other physicians. Migraine patients had higher rates of nurse visits (OR=1.42; 95%CI, 1.37 to 1.48), emergency department (ER) visits (OR=1.44; 95%CI, 1.38 to 1.51), hospitalizations (OR=1.22; 95%CI, 1.13 to 1.31), and day hospitalizations to 1.43).The rate of sick days was significantly higher among migraine patients (OR=1.43; 95%CI, 1.38 to 1.49). Conclusion: Individuals with migraine utilize HCRU to a greater extent, exhibiting higher rates of visits, primarily to GPs, neurologists, and pain physicians. They have elevated rates of ER visits and hospitalizations, and more frequently request 'sick certificates' from their treating physicians, which may reflect increased healthcare costs but also additional burden on the economy. (OR=1.28; 95%CI, 1.15

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Fig. 1 Fig. 2 a deep goniometer, standard treatment alone. The stabilization group was given CSET-T in addition to standard treatment 3 days a week for 8 weeks (Figure 1). Pain characteristics were assessed by using a pain diary, whereas forward head posture and cervical mobility were measured using cervical muscle performance (DCMP) by using a pressure biofeedback unit, functional status by using the Migraine Disability Assessment Scale (MIDAS), sleep quality by using the Jenkins Sleep Scale (JSS), and quality of life by using the Headache Impact Test-6 (HIT-6). The adherence to standard treatment in both groups and the adherence of the stabilization group to exercise training were recorded weekly by using the numerical rating scale. Results: It was found that pain frequency, intensity and duration, MIDAS, JSS, and HIT-6 scores decreased more in the stabilization group when compared to the control group (p<0.05)(Table 1). Moreover, the craniovertebral angle, cervical range of motions, and DCMP values increased more in the stabilization group (p<0.05)(Table 2). It was found that there was no difference between the groups in terms of compliance with standard treatment (p>0.05). Conclusion: The study revealed that CSET-T in addition to standard treatment is superior to standard treatment alone in reducing pain, improving forward head posture, cervical mobility, muscle performance, functional status, and quality of life in individuals with migraine. Fig. 1 P230 Cervical stabilization exercise training via telerehabilitation in individuals with migraine – a randomized controlled trial E. S. Dusgun1, N. Karahan2, S. Toprak Celenay3 1Fenerbahce University, Physiotherapy and Rehabilitation, Istanbul, Turkey 2Ankara Gazi Mustafa Kemal Occupational and Environmental Diseases Hospital, Neurology, Ankara, Turkey 3Ankara Yildirim Beyazit University, Physiotherapy and Rehabilitation, Ankara, Turkey Objective: To compare the effects of cervical stabilization exercise training via telerehabilitation (CSET-T) in addition to standard treatment on pain, forward head posture, cervical mobility, muscle performance, functional status, sleep quality, and quality of in comparison to the standard treatment alone. Methods: Individuals with migraine were randomly divided into two as stabilization group (n=20, age=29 (22.00-40.75) years) and control group (n=20, age= 29.50 (24.00-35.00) years). The control group received individuals with migraine life in

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Fig. 2 Fig. 3 P231 Possibilities of mindfulness-based cognitive therapy in the treatment of chronic headaches D. Perczel-Forintos1, D. Sal1 1Semmelweis University, Clinical Psychology, Budapest, Hungary Objective: Chronic headache as a persistent stressor can lead to maladaptive coping strategies such as avoidance, rumination and pain- catastrophisation. Deterioration in quality of life can cause depression and helplessness also. According to the bio-psycho- social view, attention should be paid to non- pharmacological treatments since the effectiveness of pharmacotherapy limited. Mindfulness-based cognitive therapy (MBCT) has been shown to be effective in the management of chronic headaches, primarily catastrophisation, increasing self-efficacy, improving quality of life, and depression, coping, quality of self- compassion. Methods: Patients, suffering from chronic tension headache and migraine (N=44) participated in the from a study. Inclusion criteria were: referral life and is in reducing pain

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neurologist, age 18-65. The intervention was an 8- session mindfulness-based cognitive therapy for pain (Day, 2017) led by an MBCT teacher and a clinical psychology resident. MBCT took place in group format with 7-10 patients / group. All patients had an individual intake interview. There was a waiting list control group. Measures: Beck Depression Inventory, Pain Catastrophizing Scale, Comprehensive Headache- related Quality of Life Q, Five Facet Mindfulness Q, Cognitive Emotion Regulation Q and Self-compassion Scale. Results: Following MBCT there was a significant reduction in the frequency of headaches, negative (p<0.001), pain impact of pain on QofLife catastrophization depression (p<0.001). Mindfulness skills e.a. non-reactivity and being non-judgemental (p<0.05), self-compassion as well as adaptive cognitive emotion regulation strategies increased. In addition, medication use also decreased. Conclusion: MBCT is a promising intervention in reducing frequency of headaches, medication intake, depression, pain catastrophisation and in helping people to a more adaptive way of coping with chronic pain. (p<0.001), and P232 Diagnostic workup of acute headache and subarachnoid hemorrhage in a Norwegian population – an observational study K. Aaseth1,2, S. K. G. Dhami1, G. Kravdal3, S. Zarnovicky4, K. W. Faiz5, K. G. Vetvik1,2, E. S. Kristoffersen1,6,2 1Akershus University Hospital, Department of Neurology, Lørenskog, Norway 2Akershus University Hospital, Norwegian Research Centre for Headache, Lørenskog, Norway 3Akershus University Hospital, Multidisciplinary Laboratory Medicine and Medical Biochemistry, Lørenskog, Norway 4Akershus University Hospital, Department of Diagnostic Imaging, Lørenskog, Norway 5Lovisenberg Diaconal University College, Oslo, Norway 6University of Oslo, Department of General Practice, Oslo, Norway Objective: Acute headache may be the primary symptom of subarachnoid hemorrhage (SAH). Recent guidelines suggest that non-contrast computed tomography (CT) is adequate to exclude aneurysmal SAH if performed within 6 hours after symptom onset. However, most studies of acute headache including CT, lumbar puncture and SAH are multicenter studies from referral hospitals with highly selected patient populations. The main purpose of this study was to fluid (CSF) spectrophotometry describe the diagnostic properties of head CT and cerebrospinal for detecting SAH in an unselected primary hospital population with acute headache. Methods: A retrospective cross-sectional study conducted at a large primary hospital serving roughly 10% of the Norwegian population. Diagnostic workup from consecutive patients evaluated for acute in 2009–2020 were collected. All CSF- headache spectrophotometry reports were standardized and the same CT scanner was used during the study. Results: A total of 3227 patients were included. Median age was 45 years and 63% were women. In total, 170 (5.3% of all acute headache patients) had SAH. Of 3071 CT- negative patients, 2852 (93%) underwent lumbar puncture. Of the CSF reports, 2796 (98%) were negative for xanthochromia. Overall, the rate for detection of aneurysmal SAH by positive xanthochromia was 9 in 2852 cases (3‰). The miss rate for the detection of an aneurysmal SAH with a CT scan within 6 hours was 0 and within 12 hours 1 in 2852 cases (0.3‰). Conclusion: In acute headache, a CT scan taken within 6 hours is practically 100% sensitive for detecting any SAH. P233 Recognizing Posterior Circulation Infarct (POCI) with headache as a key symptom A. J. Marques1, A. Costa1, S. Lima1, R. Almendra1, A. Matas1 1Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Neurology, Vila Real, Portugal Objective: Headache occurs as a presenting symptom in acute stroke in up to one third of patients. Higher prevalence has been associated with posterior circulation infarcts (POCI). We aim to study the occurrence of headache in an acute stroke setting and to examine the differences between POCI patients with and without headache at admission. Methods: Retrospective, observational study of a cohort of 10 years of POCI patients admitted in a Sociodemographic stroke clinical unit. characteristics (including headache data) were collected. Comparative analyses were conducted between two groups (with and without headache at admission) and p<0.05 was considered statistically significant. Results: We included 491 POCI patients, of whom 86 (17.5%) had headache as a presenting symptom. This group had a mean age of 67.8±14.0 and 64% were male. Accompanying symptoms were, in order of frequency, vertigo (51.2%), nausea/vomiting (47.7%) and ataxia (46.5%). Commonest neurological findings cranial nerve were cerebellar and signs (59.3%),

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involvement (50.0%) and motor deficit (39.5%). Stroke code activation occurred in 18.6% of cases and thrombolysis was performed in 5.8%. Majority of patients (60.5%) had an NIHSS<5. CT brain scan showed established lesion in 52.3%, with cerebellum being the most frequently affected region (43.7%). The 30 days post-event mortality was 4.7%. Comparing groups with and without headache at admission the headache group had a statistically significant lower prevalence of atrial fibrillation, impaired consciousness, cranial nerve dysfunction and functional motor deficits. Conversely, independence and younger age were higher in patients with headache. Headache at admission did not show a statistically significant association with 30- day mortality (p=0.163). Conclusion: Headache in the acute POCI setting is common. These patients are usually younger and more likely to experience vertigo. The presence of headache at admission did not impact their prognosis. vertigo, P234 Calcitonin gene-related peptide receptor antagonist prevents cephalic allodynia in raised intracranial pressure O. Grech1, E. Rubio-Beltran2, E. Stanyer3, A. Labastida- Ramirez2, G. Lavery4, L. Hill5, P. Holland2, A. Sinclair1 1University of Birmingham, Institute of Metabolism and Systems Research, Birmingham, United Kingdom 2King's College London, Wolfson Sensory, Pain and Regeneration Centre, London, United Kingdom 3University of Oxford, Sleep and Circadian Neuroscience Institute, Oxford, United Kingdom 4Nottingham Trent University, Centre for Systems Health and Integrated Metabolic Research, Nottingham, United Kingdom 5University of Birmingham, Biomedical Sciences, Birmingham, United Kingdom Results: Olcegepant did not significantly impact ICP in the model (mean (SD): olcegepant: 20.84 mmHg (7.36), n=18; vehicle: 20.47 mmHg (6.37), n=15). Vehicle-treated animals showed decreased periorbital withdrawal thresholds at day 7 compared to baseline (baseline: 6.83g (1.00), day 7: 3.29g (2.39), n=9, p=0.003). In contrast, animals with raised ICP treated with olcegepant did not show significant changes in mechanical thresholds between baseline and day 7 (baseline: 7.69g (0.71), day 7: 6.35g (2.32), n=10, p=0.057). Conclusion: Inhibition of the nociceptive peptide CGRP in the presence of elevated ICP improved cephalic allodynia. Our findings suggest that CGRP signaling contributes to cephalic pain in raised ICP and that blocking CGRP has therapeutic potential. Notably, olcegepant did not directly affect ICP levels, indicating its efficacy in reducing pain was due to its action on nociceptive pathways rather than any impact on ICP itself. These results imply that CGRP inhibition could be a promising therapeutic approach for managing headaches in patients with raised ICP. P235 Use of the ID migraine and Sinonasal outcomes test in differentiating Rhinogenic vs. non-Rhinogenic facial pain or pressure D. Jang1, H. J. Lee2, F. Godley III3, D. Witsell1, R. Abi Hachem1, B. Goldstein1, T. Coles4 1Duke University, Head and Neck Surgery & Communications Sciences, Durham, NC, United States 2Duke University, Biostatistics and Bioinformatics, Durham, NC, United States 3University Otolaryngology, Providence, RI, United States 4Duke University, Population Health, Durham, NC, United States (ICP) limited, preventing intracranial pressure is Objective: Raised associated with altered cerebral hemodynamics and cephalic pain. The efficacy of calcitonin gene-related peptide (CGRP) therapies for headaches caused by elevated their widespread use in such patients. This study aimed to explore the role of the nociceptive peptide CGRP in cephalic pain due to raised ICP by inhibiting CGRP and measuring changes in cephalic allodynia. Methods: We used a validated rat model of raised ICP induced by intracisternal kaolin injection to impede cerebrospinal (CSF) drainage. Mechanical hyperalgesia was assessed using von Frey filaments to measure mechanical withdrawal thresholds. These responses were further evaluated after daily injections of the CGRP receptor antagonist olcegepant or a vehicle control. ICP remains fluid instruments Objective: Facial pain or pressure is often non- rhinogenic and migraine-related in etiology. However, these patients are frequently misdiagnosed with sinusitis, leading to inappropriate antibiotic utilization and unnecessary surgeries. We assessed the utility of commonly used patient-reported in differentiating rhinogenic vs non-rhinogenic facial pain/pressure. Methods: Patients presenting with facial pain or pressure to an otolaryngology clinic completed the 22- Item Sinonasal Outcomes Test (SNOT-22) and the 3- Item ID Migraine. Patients were divided into chronic rhinosinusitis facial (CRS) (NRFP) groups based on nasal pain/pressure endoscopy and CT imaging. Receiver Operating Characteristics (ROC) and areas under the ROC curves (AUC) were determined to evaluate the ability of each instrument to differentiate CRS and NRFP. and non-rhinogenic

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Fig. 2 Results: 251 patients met the inclusion criteria. 114 had CRS and 137 had NRFP. Mean (SD) age was 50 (16), and 69.3% (n=174) were women. A higher proportion of women were in the NRFP group (n=104, 76% vs n=70, 61%). Congestion (n=158, 63%) and runny nose (n=84, 34%) were common concurrent symptoms in both groups. 84 patients (61%) with NRFP and 43 patients (38%) with CRS screened positive for the ID Migraine. The ID Migraine had a positive predictive value of 0.66 (95% CI: 0.57 to 0.74) and a negative predictive value of 0.57 (95% CI: 0.48 to 0.66), with an AUC of 0.64 (95% CI: 0.58 to 0.71) using the ID Migraine total score (Figure 1). Using the 5 sub-domain scores of the SNOT-22, AUC was 0.64 (95% CI: 0.58 to 0.71) (Figure 2). Conclusion: Existing patient reported instruments have limitations when used to differentiate between rhinogenic and non-rhinogenic etiology in patients presenting with facial pain/pressure. A screening questionnaire needs to be developed and validated specifically for this purpose to assist clinicians in appropriately managing these patients. Fig. 1 P236 Idiopathic or Secondary Intracranial Hypertension – a comparison of demographic, clinical and etiological factors T. Albert Albelda1, L. Vigués Jorba2, P. Arroyo Pereiro1, S. Campoy1,3, A. Martínez Yélamos1, S. Martínez Yélamos1, S. Muñoz Quiñones2, M. Huerta- Villanueva1,3, A. Muñoz-Vendrell1 1Bellvitge University hospital, Neurology, Barcelona, Spain 2Bellvitge University hospital, Ophthalmology, Barcelona, Spain 3Viladecans Hospital, Neurology, Barcelona, Spain Objective: In the diagnostic process of papilledema, it is crucial to exclude secondary causes before diagnosing idiopathic intracranial hypertension (IIH). We conducted a comparison of demographic and clinical characteristics between patients with idiopathic and secondary intracranial hypertension to identify potential diagnostic predictors and describe secondary etiologies. Methods: This retrospective observational study included patients diagnosed with papilledema between 2021-2024 at the intracranial hypertension unit of a tertiary hospital. Demographic data, clinical information were characteristics and etiological collected. The study aimed to describe the distribution of secondary causes and compare demographic, clinical, and visual characteristics

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between idiopathic and secondary cases. Headache phenotypes were also recorded. Results: A total of 58 patients with papilledema were included, with 37 diagnosed with IIH and 21 with secondary etiologies. The most frequent secondary causes were cerebral space-occupying lesions (7), cerebral venous thrombosis (4), meningitis (4), and arteriovenous fistula (3). A higher percentage of women were in the IIH group (91.9% vs. 42.9% in the secondary etiologies group, p<0.001) and had a higher body mass index (BMI) (36.7 ±7.7 vs. 29.6 ±6.5, p=0.001), with a non-significant trend towards younger age (35.2±12 years vs. 44.5±16.7, p=0.07). No significant differences were observed in clinical presentation, headache phenotype, visual field, or OCT variables. Multivariate analysis showed that sex and BMI were independently associated with IIH (p=0.007 and p=0.01, respectively). Conclusion: Secondary causes of papilledema are common. Although clinical and visual presentations do not differentiate the cause, female sex and elevated BMI appear to be predictive factors of IIH. P237 Cerebral autoregulation in acute headache attributed or probably attributed to reversible cerebral vasoconstriction syndrome (RCVS) M. Castille1, B. Guidolin1, M. Munio1, F. Lerebours1, V. Larrue1, C. Gollion1 1University Hospital of Toulouse, Neurology, Toulouse, France Objective: Demonstrating cerebral artery stenosis is a major diagnostic criterion of RCVS, but it may be absent at the beginning of the disease, rendering the diagnosis probable. Other diagnostic tools are therefore warranted to support the diagnosis of RCVS. In the present study, we evaluated cerebral autoregulation index Mx in the diagnosis of RCVS and probable RCVS, i.e. without visible cerebral artery stenosis on imaging. Methods: From January 2023 to May 2024, patients presenting to the University Hospital of Toulouse with a diagnosis of RCVS with visible stenosis on imaging or probable SVCR without visible stenosis on initial imaging were included. Cerebral autoregulation was assessed by calculating the Mx index, a correlation index between cerebral blood velocities monitored by cranial trans Doppler and blood pressure measured by photoplethysmography. A low Mx index indicates preserved cerebral autoregulation. Patients with RCVS were compared with a group of healthy subjects. Results: A total of 39 patients with RCVS, including 13 with cerebral artery stenosis, and 26 probable SVCR, were included. The median age was 36(IQR = 11.5) years, and patients were mostly men 24/39 (61%). Compared with healthy controls, patients with RCVS had a higher Mx, median (IQR): 0.37 (0.29) vs 0.19 (0.26), p = 0.004. Mx was also significantly higher in the subset of patients with probable RCVS: 0.34 (0.26) vs. 0.19 (0.26), p = 0.01 and in the subset of patients with cerebral arteries stenoses on imaging: 0.42 (0.31) vs. 0.19 (0.26), p = 0.02. Conclusion: Mx was significantly increased in both SVCR and probable SVCR, indicating an impairment of cerebral autoregulation. Higher Mx may contribute to the diagnosis of RCVS at the stage of micro-circulation compromise, when cerebral artery stenosis are not yet visible on imaging. P238 Cerebral venous thrombosis and headache – key features and findings A. J. Marques1, M. Vargas1, R. Jesus1, R. Almendra1, A. Matas1, J. P. Gabriel1 1Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Neurology, Vila Real, Portugal variable information In 82.3% of included. Clinical Objective: Cerebral Venous Thrombosis (CVT) has an extremely clinical presentation with headache being one of the most reported symptoms. We aim to describe the characteristics of the headache associated to this disease and to try to identify useful features for an earlier diagnosis. Methods: Patients with confirmed CVT consecutively admitted to our department from 2013 to 2023 were reviewed. Those with headache as initial symptom were regarding headache descriptions and additional findings was analyzed and a retrospective study was performed. Results: We report 75 CVT cases, of whom 62 (82.7%) presented with headache. those, headache was the sole symptom. Mean age was 44.4 years (16-85) and 79.0% were women. Mean duration of hospitalization of 8 days (2-35). The median time from onset of symptoms to hospital admission was 4 days (1-28). Headache was mostly tightening (35, 56.5%), had a continuous quality in 28 (45.2%) and was frontal in 20 (32.3%) patients. Additionally, there was nausea in 75.8%, vomiting in 58.1% and postural change in 38.7%. Commonest risk factor globally was obesity, in women, oral contraceptives - 71.4%. CT scan was performed in all cases and was normal in 16 (25.8%) cases. In 16.1% of patients there was either cerebral hemorrhage or infarct. The transverse sinus was the most frequently involved (91.9%) and most patients (70.9%) had more than one site of thrombosis. Warfarin was the most used oral anticoagulant (30.6%) and most patients (52, 83.9%) were totally recovered at discharge. Conclusion: Headache is a key symptom in CVT. might suggest Accompanying in 17 (27.4%), and features that

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intracranial hypertension should prompt investigation. further P239 Frequency of different headache types in patients referred to the sleep clinic S. Nasergivehchi1,2, M. Togha1, F. Ghannadi3, Z. Salami1,4, M. Noormohammadi1,5,6, A. Najafi7,8, K. Sadeghniiat Haghighi7,8 1Tehran University of Medical Sciences, Headache Department, Iranian Center of Neurological Research, Neuroscience Institute, Tehran, Iran 2Tehran University of Medical Sciences, Department of Neurology, Baharloo University Hospital, Tehran, Iran 3Tehran University of Medical Sciences, School of Medicine, Tehran, Iran 4Kharazmi University, Department of Molecular Genetics, Faculty of Biological Sciences, Tehran, Iran 5Iran University of Medical Sciences, Department of Nutrition, School of Public Health, Tehran, Iran 6Iran University of Medical Sciences, Student Research Committee, Tehran, Iran 7Tehran University of Medical Sciences, Occupational Sleep Research Center, Baharloo Hospital, Tehran, Iran 8Tehran University of Medical Sciences, Sleep Breathing Disorders Research Center, Tehran, Iran This study patients Numerous cross-sectional encountering Objective: headaches eventually experience disruptions in sleep quality and patterns. Conversely, sleep disturbances can lead to the development of chronic headaches. This study aims to explore the prevalence of headaches among patients referred to a sleep clinic. included Methods: individuals referred to a sleep clinic for various reasons related to sleep disorders or quality in 2011. Headache diagnoses were made according to the International Classification of Headache Disorders, third edition (ICHD-3). The duration of headaches was documented, and a Visual Analog Scale (VAS) was utilized to assess headache severity, ranging from zero (no severe headache). Insomnia severity was assessed by the insomnia severity index questionnaire. Results: Out of the 149 participants, 88 presented with migraines, 23 had other headache types (9 tension headaches, 8 medication-overuse headaches, 1 hypertension-related headache, 4 sleep apnea- induced headaches, and 1 other headache type). Moreover, 38 participants did not report any headache symptoms. The mean age of participants was 46.59 ± 11.55 years. Regression analyses revealed a significant association between increased headache headache) (most to ten index severity severity and higher insomnia (coefficient=1.848, P-value = 0.047). Conclusion: The prevalence of headaches is elevated among individuals diagnosed with sleep disorders, its severity demonstrates a and the degree of significant direct correlation with the insomnia severity index. P240 Headache in adult onset Moyamoya vasculopathy: systematic literature review A. Romeiro1, V. Harvey2, R. Simister2 1Sygehus Lillebælt, Neurology, Kolding, Denmark 2National Hospital for Neurology & Neurosurgery, London, United Kingdom the the headache as Objective: Study initial manifestation of Moyamoya vasculopathy in adults through a comprehensive review and analysis of the existing literature. Methods: Electronic databases were searched on October and December 2023 (Pubmed, Embase and MEDLINE). Patient registries, cohorts, cases series and case reports describing headache as the initial manifestation on adult onset Moyamoya vasculopathy were included. Data on study design, clinical and vasculopathy baseline characteristics, treatment and headache outcome were extracted. Patients" headaches were classified as "new headache" or "pre- existing worse / progression to chronic headache", according to the ICHD-3 headache attributed to cranial and/or cervical vascular disorder. Results: 92 publications were included, which reported a total of 350 adult headache-onset Moyamoya vasculopathy patients. The mean age at headache-onset was 36.3 (SD 11.8) for Moyamoya disease and 44.3 (SD 13.6) for Moyamoya syndrome patients. 69 patients were classified as "new headache" "pre-existing headache". The "new headache" subgroup was significantly older and intracerebral haemorrhage was significantly more reported as the index vascular event, whereas ischemia was more significantly reported in the "pre-existing headache" subgroup. The headache outcome data was extracted from 19 publications, with 50% of the described cases reporting headache remission, of which 47.4% were submitted to revascularization surgery. Conclusion: Moyamoya vasculopathy can present with headache, either as a new onset headache or as a worse, chronic progression pre-existing headache. The reported data suggest that older individuals frequently with new headache present more associated with an index haemorrhagic cerebral event, suggesting the importance of including not only chronic pre-existing headache but also new onset twenty-two cerebral and as

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Methods: A 62-year-old hypertensive and diabetic patient presented to the emergency room with a three-day history of acutely beginning blurred vision in the right eye. His medical history was relevant for hypertension, uncontrolled diabetes mellitus type 2, and an ischemic stroke six months ago. Brain imaging showed a left occipital ischemic lesion without any vassal abnormalities. Neurologic examination showed right homonymous hemianopsia; and his ECG revealed AFib. Two days after admission, the patient started to complain of a very intense, never before experienced headache, confined to a small, round area in the left parietal region of the scalp that persisted for hours. It was not associated with nausea, vomiting, or photo- phonophobia, or any other discomfort. Based on the patient description and head imaging, NH was suspected, and pregabalin 150 mg/daily and Paracetamol was added to the treatment regimen, which did not provide pain relief. During the 24-hour cardiac monitoring, as part of stroke evaluation, it was noted the headache corresponded with a cardioversion from AFib to sinusal rhythm with half the frequency, with a pause of 2.58 seconds associated with the cardioversion. Results: After starting Amiodarone, the episodes of AFib decreased as well as the patient's headache episodes. Conclusion: The the headache and the cardiac arrhythmia as well as the response to the antiarrhythmic medication made us consider a causal correlation between these two entities. time correlation between the beginning of that Fig. 1 headache in the classification of headache associated to Moyamoya vasculopathy. P241 Arteriovenous fistula, a rare cause of occipital neuralgia L. Abraira1, P. Santamaría Montero1, L. Ramos Rúa1, R. Pego Reigosa1 1Hospital Universitario Lucus Augusti, Neurologia, Lugo, Spain in Chiari malformation, (dysesthesias/hypoesthesia) left occipital pain radiating to Objective: Occipital neuralgia is defined as unilateral or bilateral pain located in the back of the scalp, in the occipital nerve territory. It is usually associated with hypersensitivity at the nerve exit point, also known as Arnold"s point, and may be accompanied by sensory disturbances the corresponding territory. In most cases the etiology is unknown or attributed to cervical contractures, but secondary causes such as trauma, neoplasms, fibromyalgia, infections, vascular malformations or giant cell arteritis must be ruled out. Methods: We present a case of occipital neuralgia secondary to an arteriovenous fistula. Results: A 60-year-old woman with paroxysmal and the lancinating ipsilateral with hypersensitivity of the scalp and pain on palpation of the left Arnold's point. She was treated with amitripitline and eslicarbazepine with poor success. Arnold's point blockage was performed with corticosteroid and local anesthetic with dissapearance of pain for 2-3 weeks. Brain MRI showed an arteriovenous fistula of the left transverse sinus, which was confirmed by arteriography. After embolization of the fistula, the pain disappeared. Conclusion: Although most cases are considered idiopathic, secondary causes must be ruled out in all patients with occipital neuralgia. Performing an imaging test is mandatory for the correct etiological diagnosis and the selection of the most appropriate treatment. temporoparietal region, P242 Nummular headache and atrial fibrillation: Is there a causal correlation? B. Qazimllari1, E. Basha2 1Saranda Hospital "Petro Nako", Saranda, Albania 2UHC Mother Teresa, Neurovascular Department, Tirana, Albania Objective: To present a case of nummular headache (NH) in a patient with a cardioembolic stroke and paroxysmal atrial fibrillation (AFib).

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Fig. 2 P243 Headache as an atypical initial symptom of corticotropic deficiency S. Horváthová1, O. Duraníková1, P. Valkovič1 1Comenius University, 2nd Department of Neurology, Bratislava, Slovakia for and vomiting, accentuated Objective: To present a case study. Methods: 38-year-old male patient presented with intense diffuse headache of dull character with a maximum in the bifrontal region with photophobia, nausea, with verticalization. There was no history of headache or any other significant illness other than atopic eczema. Patient had quit using nicotine pouches days prior to start of the headache. Neurological examination was normal. Considering sudden onset of headache that lasted more than 4 days, was unresponsive to analgesics, accompanied by fatigue and increased sleepiness patient was admitted further diagnostics. Results: Initial CT brain scan showed no acute focal changes or haemorrhage, CT angiography was without any significant pathology. MRI studies showed a lesion in the adenohypophysis with a convex upper contour and contact with optohypothalamic structures. The following were under consideration: either a Rathke's cyst with thickened contents, or bleeding into the adenoma. A targeted MRI of the pituitary region revealed Rathke's cleft cyst occupying almost the entire sella turcica, propagating to the intercarotid line without the optochiasmatic structures. Perimeter examination was normal. Extended focusing on adenohypophysial hormones revealed corticotropic deficiency. endocrinologist's recommendation, hydrocortisone was added to the treatment and then gradually reduced as per protocol. The headache resolved within a day of introducing hydrocortisone. Neurosurgeons were consulted and did not recommend surgery, advising periodic follow- up instead. Conclusion: The headache and associated symptoms were likely secondary to the Rathke´s cyst causing hormonal corticotropic deficiency. The introducton of hydrocortisone in symptomatic relief. This case report resulted emphasizes considering corticotropic deficiency in the differential diagnosis of headache, as it can be life-threatening. compressing significantly imbalance, specifically lab tests the importance of Following the

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P244 Headache presentation in brain tumor patients – a retrospective analysis S. Lima1, A. J. Marques1, M. Perdicoúlis1, A. Matas1 1Unidade Local de Saúde de Trás-os-Montes e Alto Douro, Neurology, Vila Real, Portugal tumors, 25 Objective: To describe the demographic, clinical, diagnostic and therapeutic characteristics of patients with intracranial tumors that had headache as the first presenting symptom. Methods: We conducted a single-center retrospective study including patients admitted to the neurology inpatient department diagnosed with intracranial tumors from January 2019 to December 2023. Demographic, clinical, diagnostic, and therapeutic data were collected. Results: Of the 163 patients diagnosed with intracranial reported headache at admission. Of these patients, 48% (n=12) were women, with a mean age of 62,3±13,1 years. 4 patients experienced tension-type headaches and 2 reported migraine-type headaches. One patient complained of worsening of a pre-existing headache and 3 patients noted worsening headache with the valsalva maneuver. Neurological focal deficits were present at 28% of the patients (n=7) at admission. 84% of the tumors were in the supratentorial region (n=21) with the majority in the left hemisphere (n=11). Histological diagnosis was obtained in 88% of the cases (n=22). Most of the intracranial lesions were primary tumors of the central nervous system (n=21), being glioblastoma (n=12) the most frequent. Tumor resection, radiotherapy and chemotherapy were performed in 14 patients. Total remission was achieved in 4 four patients. One patient died 6 months after the diagnosis of glioblastoma. Conclusion: Headaches, a common clinical complaint, range to indicators of life-threatening conditions. A detailed history and neurological exam were essential for the identification of possible red flags in 11 patients, which prompted further investigation leading to an accurate diagnosis, effective patient management and timely intervention. tension-type headaches from benign P245 Overlapping primary headaches phenotypes post- internal carotid artery dissection F. Assis Jacinto1, J. M. F. Machado1, P. Salgado1, R. Rocha1, S. Duarte1 1Hospital Pedro Hispano - ULS Matosinhos, Neurology, Matosinhos, Portugal Objective: Internal carotid artery dissection (ICAD) can present with headache phenotypes that mimic to aura, presented primary headaches, leading to delayed or missed diagnosis. It is postulated that symptoms can derive from stimulation of the trigemino-vascular system and disruption of the pericarotid sympathetic nerve fibers. Methods: Clinical case description. Results: A 49-year-old man, with history of migraine without the emergency department with a 2-month history of a daily continuous pulsating right temporo-parieto-occipital and orbitary headache with different characteristics from his typical migraine. The headache had moderate to severe intensity and was associated with nausea and vomiting, photo and phonophobia, allodynia, ipsilateral miosis, ptosis, lacrimation and nasal congestion. Neurological examination revealed a constant right Horner syndrome. CT angiography showed a right ICAD with no ischemic lesion on the brain CT. He initiated antiplatelet therapy and NSAID. The patient was readmitted due to persisting pain. A great occipital nerve block was performed with large but not sustained benefit. High-flow oxygen and a course effective. Considering the pain features, resembling both migraine and trigeminal autonomic headache, he was sequentially started on indomethacin and topiramate. After 4-months, a new CT angiography showed complete resolution of the right ICAD, but he continued experience pulsating moderate unilateral headache 5-days per week. Due to the partial response observed, onabotulinumtoxin A was tried, with significant improvement. Conclusion: We described a case of an ICAD dissection presenting as a chronic headache with coexisting symptoms of different primary headaches, requiring a comprehensive diagnosis and pain management approach. Additionally, this case highlights the potential use of onabotulinumtoxin A in the off-label treatment of secondary headaches with trigeminal- autonomic features, beyond its established role in chronic migraine. corticotherapy weren't to of P246 Onabotulinumtoxin A as a treatment for Post- Craniotomy headache:reults in 7 patients I. Ros1, Á. Sierra Mencia1, M. L. Peñas Martinez1, Y. González-Osorio1, A. Recio García1, C. García Iglesias1, S. García García1, D. García-Azorín1, Á. L. Guerrero- Peral1 1Hospital Clínico Universitario de Valladolid, Neurology, Valladolid, Spain Objective: OnabotulinumtoxinA (OnabotA) has shown efficacy treatment of epicranial headaches, both primary and secondary to head trauma. We aim to evaluate the effectiveness of this local the in

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treatment in a series of patients with post-craniotomy headache. Methods: Prospective registry of patients treated with OnabotA from June 2012 to June 2024 in a headache unit of a tertiary hospital. In 7 cases, treatment was indicated because of a localized headache appeared after a craniotomy. We gathered clinical and demographic characteristics, the dose of OnabotA administered, response to treatment, and appearance of adverse events. Response was defined as a decrease of at least 50% in the number of headache days. Results: We included 7 patients, 6 of them women, with treatment initiation between 38 and 74 years of age. Between 1 and 6 procedures were carried out, at a dose between 12.5 and 50 U. In 2 patients (women aged 52 and 68) there was no response despite dose increasing and treatment were suspended after 2 procedures. In two patients (38 and 66-year-old women) excellent response with disappearance of pain after a single procedure. In the remaining 3 patients (71-year-old man and 48- and 74-year-old women) partial response, mainly when dose increasing, and requiring repetition of the procedure every 3-6 months. No adverse events were recorded. Conclusion: OnabotA injection may be safe and potentially effective in patients with post-craniotomy headache, with a dose-dependent response and requiring repeat procedures. P247 Seronegative neurobrucellosis with meningeal involvement, diagnosed by CSF PCR – report on seven cases E. Jafari1, M. Togha1, Z. Salami2, N. Rahman1, S. Alamian3 1Tehran University of Medical Sciences, Tehran, Iran 2Kharazmi University, Molecular Genetics, Tehran, Iran 3Razi Vaccine and Serum Research institute, Research and Production Department of Brucellosis Antigens and Vaccine, Tehran, Iran Objective: Neurobrucellosis (NB) can be associated with meningitis and present as a headache with or without meningeal signs. Pseudotumor presentation of NB has been reported to be accompanied by lymphocytic predominant cerebrospinal fluid(CSF) pleocytosis. NB is diagnosed by means of isolation of Brucella from blood or CSF and/or the presence of anti-Brucella antibodies the CSF. Molecular techniques have been used in chronic or challenging cases of NB. in In involvement. Methods: We report on seven cases of NB presenting with different types of headache and signs of meningeal five cases, signs of intracranial hypertension were evident in the form of papilledema, sixth nerve palsy and blurred vision. All patients gave their consent to publish their details in an open access journal. Results: MRIs of the brain revealed signs of intracranial hypertension in three patients, basal meningeal enhancement in one patient and white matter lesions in one patient. Brucella serology in the blood and CSF was negative in all patients. It was interesting that four patients had normocellular CSF analysis with normal glucose and protein results. The diagnosis was made by Brucella PCR in all patients. in the Conclusion: NB should be considered differential diagnoses of pseudotumor cerebri syndrome in endemic areas. It is important to employ molecular techniques using sterile CSF samples in the investigation of Brucella P248 Identifying headache attributed to internal carotid artery dissection in migraine sufferers: How to recognize and prevent misdiagnosis as migraine exacerbation M. Bozhenko1, N. Bozhenko1 1Danylo Halytsky Lviv National Medical University, Neurology, Lviv, Ukraine Objective: Making a diagnosis of a secondary headache, which in its characteristics is similar to a pre-existing migraine, is a diagnostic challenge which needs to be well analyzed. Methods: We analyzed the clinical case of a patient with a migraine whose headache pattern has changed, explored the challenges encountered in the differential diagnosis process, and identified crucial indicators for differentiating secondary headaches from migraine excerebration. Results: A 42-year-old woman with migraine complained that her headaches had abruptly changed over the past two weeks. Her headache was accompanied by nausea, photo-, phonophobia and was aggravated by physical activity, like previous migraine attacks. Her family doctor interpreted it as an exacerbation of migraine. However, after she visited the pain medicine centre of Danylo Halytsky Lviv National Medical University, we recognized red flags: 1. Thunderclap headache after physical activity; 2. Headache pattern changed to permanent; 3. Headache became always left-sided; 4. Previously effective medications no longer provide relief; 5. Occurrence of left-sided Horner's syndrome. This led involving to diagnostic search a detailed

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forward new modalities to treat all chronic headache sufferers, along with crucial emphasis on their complex mental health needs. P250 Real-life experience of rimegepant in episodic migraine C. Santillana Avila1, C. Adan Diaz1, M. Serrano Jiménez1, A. I. Dengra Maldonado1, A. Gómez Camello1 1H. Clinico San Cecilio, Neurology, Armilla, Spain (HFEM) refractory Objective: Migraine affects between 10-16% of the population and it is one of the leading causes of disability in young adults. The development of anti- CGRP therapies has improved the quality of life for patients with migraine. The objective of this study is to corroborate real-life data on the efficacy and safety of rimegepant, a CGRP receptor antagonist with dual preventive and symptomatic action for migraine attacks. Methods: This is a prospective observational before- and-after study of patients with high-frequency episodic migraine to oral preventives. Patients were treated in 2024 at a headache unit, and data collection was done using REDCap. Statistical analysis was performed using IBM SPSS Statistics 25. Results: In our samplem 75% of the patients were women with HFEM. The number of previous oral preventive treatments was 4, the most common were amitriptyline, and propranolol. At the start, patients had 10 days of migraine per month (DMM), 7 days of headache per month (DHM), and 6 days of analgesic use. After 3 months of treatment, a significant decrease of 3 DMM per month was observed compared to the baseline. There was also a trend towards a reduction in DHM, baseline HIT-6 and MIDAS scores. Most patients reported a decrease in pain intensity, although this was not assessed with specific scales. Conclusion: The increase of anti-CGRP drugs like Rimegepant needs real-life studies to determine their efficacy and safety in clinical practice in specific headache units. With this study we aim to assess long- term efficacy and safety profile. topiramate, flunarizine, neuroimaging. CT angiography revealed recanalized thrombosis of the C7 segment of the left internal carotid artery (ICA) due to spontaneous dissection. Prescription of a conservative treatment resulted in a positive outcome. Conclusion: Migraine patients may experience secondary in characteristics to migraine attacks. Therefore, paying attention to the occurrence of red flags is essential to prevent complications. headaches similar that are P249 Investigating a case of an Isotretinoin-induced chronic headache – exploring treatment modalities to address an unresolved side effect lasting over two years U. Kumar1, J. Posas1 1Ochsner Clinical School, Neurology, Jefferson, LA, United States in for changes. She has report highlights a rare Objective: This case intractable presentation of a patient with an multifactorial headache short-term induced by Isotretinoin treatment with an emphasis on efforts to find correct therapies. Methods: A 22-year-old female presented to the clinic for a headache that started in December 2021, two months after initiating Isotretinoin for acne. Since then she has suffered a chronic headache for 30 out of 30 days. It is described as a unilateral pain on temples and occipital regions, pressure-like, with 4- 9/10 severity, worse with positional and temperature trialed many treatments including Topamax, Botox, and Diamox but without relief. She required Sertraline to cope with escalating depression. Results: Patient was worked up idiopathic intercranial hypertension (IIH) which is in line with a typical Isotretinoin side effect yet lumbar puncture was unremarkable (opening pressure of 18 cmH2O). Papilledema was not detected and she was not obese. Further MRI workup for suspected transverse sinus stenosis was also negative. MRI also excluded intracranial pathology. Spironolactone 50mg was initiated and ultrasound-guided bilateral recently greater and lesser occipital nerve blocks were administered with instruction to maintain a headache diary. Conclusion: This illustrates an unusual presentation of a prolonged adverse effect despite cessation of the offending agent and rule out of IIH. Conventional drug therapies are not providing relief to be but accomplished while patient"s comorbidities such as her sleep apnea. Expert collaboration on this striking case can help pave trialing of all modalities has yet exploring case the

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P251 Anti-CGRP antibodies in patients with migraine and autoimmune disease with concomitant immunosuppressants/immunomodulators treatment: interactions, safety and effectiveness M. R. Córdova Infantes1, N. Guerrero Carmona1, M. Fernández Recio1 1University Virgen de Valme Hospital, Neurology, Sevilla, Spain P252 Response to eptinezumab in chronic cluster headache – a case report M. Polanco Fernández1,2,3, J. Madera Fernandez1,2,3, V. González Quintanilla1,2,3, S. Pérez Pereda1,2,3, J. Pascual1,2,3 1University Hospital Marqués de Valdecilla, Neurology, Santander, Spain 2Universidad de Cantabria, Santander, Spain 3IDIVAL, Santander, Spain or or study Objective: Some patients with migraine suffer autoimmune diseases and we are treated with immunosuppressants immunomodulators treatment. We aimed to evaluate the combination anti-CGRP antibodies and immunosuppressants or immunomodulators treatments. Methods: Retrospective cohort included patients with migraine and other autoimmune disease treated with anti-CGRP antibodies and other immunosuppressants immunomodulators treatments. We assessed which anti-CGRP antibodies and immunosuppressants/immunomodulators were combined, adverse effects, interactions, reduction from baseline of Monthly Headache Days (MHDs), MIDAS and HIT-6 scores. included: 14 women Results: 15 patients were (93,3%); average age 46 y±8,4. Episodic migraine 5 (33,3%) and chronic migraine 10 (66,7%). 5 (33,3%) were switched from one class of anti-CGRP antibody to another. Anti-CGRP antibodies were galcanezumab, erenumab. fremanezumab, Immunosuppressants/immunomodulators were prednisone, methotrexate, hydroxychloroquine, tocilizumab, azatrioprine, natalizumab, adalimumab, golimumab ofatumumab, rituximab. Adverse events: 4 (26,7%) for anti-CGRP antibodies and 2 (13,3%) for other treatment. No one suffered worsening of the autoimmune disease neither interaction between treatments. MHDs (22.3±9 vs 16,07±10,9; p=0.008) and MIDAS scores (101± [46,5-173,5] vs 36±[19- 86,50];p=0.011) significantly decreased from baseline to 2 years. Conclusion: Our results suggested that treatment with anti-CGRP and immunosuppressants/immunomodulators may be considered safe and effective although more studies with larger sample sizes are needed. antibodies Objective: At present there is no scientific evidence from clinical trials that supports the use of anti-CGRP drugs in chronic cluster headache, although positive responses to Galcanezumab have been described in real life. To our knowledge, the effectiveness of Eptinezumab in the treatment of chronic cluster headache is unknown or whether there are cases of response to this drug after failure of Galcanezumab. Methods: We present the case of a patient with chronic cluster headache refractory to conventional preventive treatments who presented excellent response to Eptinezumab 300mg and relapsed after switching to Galcanezumab 240mg. Results: A 48-year-old woman, who presented with an episodic cluster headache at the age of 30 and met chronic cluster headache criteria since the age of 45, consulted because she has had 2 daily cluster headache attacks for the past year. Attacks were located in the right periocular region, with a variable duration between 20 and 180 minutes and associated with trigemino-autonomic symptoms and occasionally restlessness. Preventive treatment was tried with verapamil, topiramate, lithium and valproic acid without response. It was decided to start preventive treatment with Eptinezumab 300 mg every 3 months, with the attacks disappearing after the first week of treatment. The patient remained attack-free for 6 months, so it was decided to withdraw Eptinezumab. After its withdrawal, the patient relapsed early so, with the current evidence, it was decided to start Galcanezumab 240 mg monthly, however the patient did not obtain any response. After 6 months with Galcanezumab, it was decided to suspend it and restart Eptinezumab, observing again a remission of the attacks. experience, Conclusion: Eptinezumab 300 mg quarterly could be considered a therapeutic option in patients with refractory chronic cluster headache, even in those who do not respond to Galcanezumab. According our to

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P254 Is Erenumab effective and safe in long term migraine treatment? A three-years observational study E. M. Bruno1, D. Mascarella2, B. Carandente2, V. Favoni1, G. Pierangeli2,1, S. Cevoli1 1IRCCS, Institute of Neurological Science of Bologna, Bologna, Italy 2Alma Mater Studiorum Bologna, DIBINEM - Department of Biomdical and Neuromotor Sciences, Bologna, Italy Objective: Erenumab has proven to be a highly effective and well tolerated Migraine preventive medication since its approval in 2018. Although the abundant real-world scientific production on this topic confirmed long-term tolerability, most studies have relatively short follow-up. Hence, longer follow-up data with a high level of surveillance for efficacy and safety are warranted in a potential life-long using medication Methods: This observational prospective study included all patients with a diagnosis of Episodic or treatment with Chronic Migraine who started Erenumab between May-2019 to August-2020. Patients were followed up with a minimum of two outpatients" evaluations per year and for a total duration of three years. Mean Headache days (MHD) were collected throughout the study period as well as adverse events Results: A total of 164 patients were included. After the first year of treatment, 34% of the total cohort showed a sustained reduction of at least 50% (50%RR) in MHD and 84/164(50.9%) continued the treatment. Three patients dropped-out due to side effects (1.8% of the total cohort) whereas 23/164 patients dropped- out due to inefficacy. During the subsequent therapy cycles, we observed a relative stabilization of dropouts (64/84 patients started the 3rd cycle) and a slight relative increase in 50% responders (50.9% 1° cycle, 55%3° cycle). No baseline feature was predictive of long-term response Conclusion: We observed a halving of the treated patients at 1 year, followed by a stabilization of dropouts and a 'selection' of the most responsive patients, with a very high 50%RR at the end of the third year. P253 Characteristics of patients prescribed rimegepant vs. all patients seeking migraine care via telemedicine M. Lewis1, C. Xiang2, A. Jenkins3, L. Abraham3, K. Hygge Blakeman4, J. Cirillo1, S. Crystal5, M. Livingston5, J. Song6, E. Faust Murdoch5, J. Brown1 1Pfizer, Inc, New York, NY, United States 2Analysis Group, Inc, Boston, MA, United States 3Pfizer Ltd, Tadworth, United Kingdom 4Pfizer AB, Stockholm, Sweden 5Thirty Madison, New York, NY, United States 6Analysis Group, Inc, Los Angeles, CA, United States is those the initial seeking care from Cove, interest collected at impairment, productivity, Objective: Rimegepant the only medication approved by FDA for both acute treatment and prevention of migraine. Cove is a telemedicine platform for migraine. This study aimed to describe patients comparing characteristics at intake of those who subsequently received rimegepant to the overall population. Methods: The study population comprised all individuals with an initial consultation from Cove between Jan 2021 and Dec 2023; the rimegepant subsequently prescribed subgroup were consultation. rimegepant after Characteristics of intake consultation were demographics, treatment history, migraine-related and healthcare resource use. Results: 57,218 patients were included, of whom subsequently prescribed 6,380 (11.2%) were rimegepant after their initial consultation. Most (78.6%) rimegepant prescriptions were issued within 3 months, primarily for acute treatment (74.7%) of migraine. prescribed rimegepant had a mean (SD) age of 39.3 (10.4) years, 76.4% were female, and 57.2% were White. 95.6% of rimegepant patients had previously tried at least one other OTC or prescription medication for migraine, while a majority (52.9%) had tried 5 or more meds. Patients subsequently prescribed rimegepant had more mean headache days per month than the overall population (12.8 vs. 11.3) but a similar mean pain intensity (7.7 vs. 7.5). Based on the Migraine Disability Assessment (MIDAS), more patients who were subsequently prescribed rimegepant had moderate- to-severe disability than the overall population (78.0% vs. 65.0%). Conclusion: This study, which assessed patients from an asynchronous seeking migraine care telemedicine platform, suggests that patients subsequently prescribed rimegepant presented with a distinct and greater disease burden compared to the overall population. Further research is needed to determine the potential impact of rimegepant in reducing this migraine burden. subsequently Patients

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P256 The effect of 9-months fremanezumab preventive treatment on the triptan response and on the incidence of triggers and prodromal symptoms in patients with HFEM E. V. Dermitzakis1, A. Argyriou2, D. Rikos3, P. Soldatos4, M. Vikelis5 1Euromedica General Clinic, Thessaloniki, Greece 2Agios Andreas State General Hospital of Patras, Department of Neurology, Patras, Greece 3404 Military Hospital, Larisa, Greece 4Private Praxis, Kalamata, Greece 5Headache Clinic, Mediterraneo Hospital, Athens, Greece to triptans (the use of Objective: To investigate whether the incidence of triggers, prodromal symptoms, hypersensitivity symptoms accompanying headache and responses to triptans were modified during a continuous 9-month fremanezumab therapy for migraine prophylaxis. Methods: We studied 63 patients with high-frequency episodic migraine (HFEM). Enrolled patients received fremanezumab for 9 consecutive months before defining the response rates and being stratified into treatment responders (50–74% reduction in monthly headache days (MHDs)), super responders (>75%), partial non-responders (<50%) and super non- responders (<30%). Through headache diaries, patients provided data in order to document the impact of fremanezumab on the incidence of triggers, associated symptoms followed by headache and response themigraine treatment optimization questionnaire-4 (mTOQ-4)) during the 9-month treatment period. Results: Fremanezumab had early beneficial effects on the response to triptans in most responders with relevant increases in mTOQ-4 scoring, but also in half of partial non-responders. A significant reduction in median days with migraine-associated symptoms was seen in responders after 6 months of therapy with fremanezumab, mostly for osmophobia, photophobia, phonophobia and nausea/vomiting, but partial non- responders also benefited. Likewise, the incidence of self-reported prodromal symptoms was significantly reduced in responders and was modestly diminished in partial non-responders. remained unaffected in both responders and non-responders. Conclusion: Fremanezumab given for 9 months may exert neuromodulatory effects in the migraine brain. These effects could result both in the inhibition of migraine chronification, but also in the diminishing of the magnitude of migraine-associated symptoms, mostly in responders and in partial non-responders. Triggers P257 Multi-parametric efficacy assessment of Eptinezumab in patients with chronic migraine and medication overuse headache – early results from a third level headache center D. A. Montisano1, S. Lazzari1, L. Grazzi1 1Fondazione IRCCS, Milano, Italy Objective: Migraine is a very common and disabling condition especially in his chronic form and when complicated by medication overuse. Among the new preventive treatment anti-CGRP, recently a new intravenous monoclonal antibody Eptinezumab have been approved in Italy.. Methods: We collected 20 patients, eligible according to AIFA criteria for mAbs anti-CGRP treatment. We started treatment with Eptinezumab 100mg, and moved to Eptinezumab 300mg, according to the patient"s response. We investigated clinical history, days of headache and medication for month, MIDAS, HIT-6, ASC-12, PIGC, MIBS4, PCS, at baseline, 3 and 6 months of treatment. Results: In our sample: 11 patients out of 20, underwent to one or more withdrawal treatment in their history, they failed at least 3 preventive classes, at baseline MHD 17 ± 5.5, MAM 20±6, NRS 9±0,75, MIDAS 47±31,2, HIT-6 66±3.23, ASC-12 6±5,71, PCS 20±7,8, MIBS 9±3,2; at 3 months MHD 10±6,7, MAM 11±7,7, NRS 8±1,1, MIDAS 27,5±28, HIT-6 64±7,45, ASC 1,5±5,5, PCS 19,5±7, MIBS 7,5±3,4, PGIC 4±1,56: at 6 months 7 patients moved to 300mg dose, MHD 6±2,31, MAM 10±3,46, NRS 8±2,89, MIDAS 13±25, HIT-6 63±4,16, ASC 1±7,8, PCS 24±11, MIBS 2±1,73, PGIC 3±2. Conclusion: We observed a ≥ 50% rate response at 6 months in terms of MHD, MAM, MIDAS and HIT-6. Also, the interictal burden decreased in our patients. The patient impression of change was good, and a slightly catastrophizing improvement was observed. Eptinezumab showed a good outcome even in such complicated migraine population. trait P258 Quarterly fremanezumab: assessing migraine relief and patient satisfaction C. Trevino-Peinado1,2, S. García Martínez1,2, H. G. Clara1,2, C. González Yela1,2, M. Gilot Sancho1,2, I. Hernando Jiménez1,2 1Hospital Universitario Severo Ochoa, Leganés, Spain 2Hospital Universitario Severo Ochoa, Neurology, Leganés, Spain Objective: To evaluate the efficacy and patient satisfaction quarterly fremanezumab (675 mg). treatment with after

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Methods: This retrospective observational study includes patients diagnosed with high-frequency episodic migraine (HFEM) or chronic migraine (CM) who received quarterly fremanezumab in a headache unit. During the study, several Patient-Reported Outcome Measures (PROMs) were evaluated, including the HIT-6 (Headache Impact Test) and the PGI-I (Patient Global Impression of Improvement). Results: Data from 30 patients were analyzed, with 96.7% being women and an average age of 45 years at the start of treatment. The average number of previous preventive treatments was 4.5; 66.7% had chronic migraine. 90% began treatment monthly and 10% quarterly, with an average switch time to quarterly of 3.7 months. 13.3% patients had switched from another antibody (erenumab). 90% had received prior treatment with botulinum toxin. The average number of headache days was 17.9, and migraine days 13.4. Baseline HIT-6 was 66.8 and at one year 54.3. The average number of days of acute treatment use before fremanezumab was 16; at three months, 7; at six months, 5.8; and at one year, 6.1. 80% of the patients reported an improvement in quality of life. 70% of the patients showed a 50% reduction in migraine days after one year. The PGI-I score was 1.4 at six months and remained similar at 1.5 at one year Conclusion: Quarterly fremanezumab treatment is effective in reducing migraine days and the use of acute medication, life, and patient satisfaction. improving quality of P259 Refractory chronic migraine: no symptomatic relief after 20 preventive medications S. Moreira1, A. Costa1, A. Ferreira1, S. Marques1, S. Lopes1, J. M. Araújo1, S. Varanda1 1Unidade Local de Saúde de Braga, Neurology, Braga, Portugal numerous Nowadays, therapeutic Objective: strategies exist for managing migraine. Typically, some treatments provide significant relief, and it is unusual to be non-responsive to all available options. Methods: Case report. Results: A 41-year-old man with episodic headaches since the age of 20 recently developed nearly daily chronic bifrontal pain, gradually in intensity, pressure-like, and associated with photo- phonophobia, anorexia. Complicated by medication overuse headaches from frequent aspirin use, he has been hospitalized multiple times for headache management. Various pharmacological classes have been tried, including antihypertensives and calcium channel blockers (propranolol, candesartan, flunarizine), antiepileptics oxcarbazepine), (valproic kinesiophobia and topiramate, increasing acid, preventives (amitriptyline, (prednisolone, antidepressants nortriptyline, venlafaxine, fluvoxamine, sertraline, clomipramine), other oxitriptan, melatonin) and two series of botulinum toxin (BoNT) injections per the PREEMPT protocol. Additionally, anti-CGRP (galcanezumab, fremanezumab) and anti- CGRPr (erenumab) monoclonal antibodies, were tried. Currently, authorization for eptinezumab is pending and the patient keeps being treated with three-month interval of BoNT. Conclusion: This patient currently suffers from 26 monthly migraine days and seems a case in which CGRP fisiopathology might be less important. Thus, although he waits eptinezumab approval, he might benefit more from non-pharmacological approaches combined with future treatments directed to different underlying fisiopathological mechanisms. P260 Lower CD4+ T-cells serum levels as a possible predictor of COVID-19 associated headache O. Duraníková1, S. Horváthová1, P. Sabaka2, M. Minár1, I. Straka1, P. Valkovič1 1Comenius University, 2nd Department of Neurology, Faculty of Medicine, Comenius University, Bratislava, Slovakia, Bratislava, Slovakia 2Comenius University, Department of Infectology and Geographical Medicine, Faculty of Medicine, Comenius University, Bratislava, Slovakia, Bratislava, Slovakia patients videocall with Objective: Headache is one of the most common and disabling non-respiratory symptoms of COVID-19, that can persist for months in the form of long-COVID headache. The aim of our study was to find possible biomarkers of COVID-19 associated headache. Methods: We conducted a retrospective analysis of 295 (126 women) hospitalized patients with COVID-19 in Slovakia after 12-15 months. Retrospectively we contacted self- administered questionnaire. In headache patients we evaluated its possible biomarkers. Results: 34.6% (n=102) of patients had COVID-19 associated headache, with persisting headache for 12- 15 months accounted for 41.2%. In comparison with patients without headache, headache patients were predominantly women (65.4% vs. 34.6%, p=0.002) and younger (N= 51 vs. 58 years, p<0.001), with fewer days at hospital (N= 8 vs. 9 days, p=0.005). The headache group had significantly lower serum levels of CD4+ T-cells (p=0.038), also confirmed with multivariate as independent predictor of COVID-19 related headache (p=0,011), another independent predictor was younger age (p=0,005). regression analysis via logistic

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Conclusion: Headache was present in 1/3 of patients, predominantly in women and younger people. Lower levels of CD4 + T-cells were established as an independent predictor of COVID-19 headache, which could play an important role not only in pathogenesis, but also in the therapeutic management. P261 Diagnosis roulette: the misplaced bet on a presumed linear case of intracranial hypotension S. Moreira1, A. Costa1, S. Gomes1, L. Francisco2, S. Lopes1, J. M. Araújo1, S. Varanda1 1Unidade Local de Saúde de Braga, Neurology, Braga, Portugal 2Unidade Local de Saúde do Alto Minho, Neurology, Viana do Castelo, Portugal to a Objective: Intracranial hypotension is one of the most common causes of orthostatic headache, usually accompanied by other position-dependent symptoms, such as tinnitus and dizziness. Methods: Case report. Results: A 49-year-old man with dyslipidemia and smoking habits presented the emergency three-month history of department with progressively worsening occipital headache, described as pressure-type, moderate-to-severe intensity, accompanied by nausea and dizziness, occurring exclusively when upright. He could maintain an upright position for only ten minutes before severe symptoms began and experienced immediate relief when lying down. His neurological examination, including fundoscopy, was normal. During hospitalization, an MRI revealed no signs of CSF hypotension or a CSF leak. No improvement after five days in recumbent position, with fluids, caffeine and fixed analgesia. An epidural blood patch (20 mL of autologous blood) was performed without benefit. A bupivacaine bilateral greater occipital nerve block was also performed without lumbar puncture showed an opening pressure of 13 cmH2O with normal cytochemical analysis. Cardiology was consulted, and both exercise stress test and tilt test were normal. An angio-CT and dynamic Doppler study of the cervical and intracranial vessels ruled out vertebrobasilar insufficiency. The final hypothesis was a somatoform/functional disorder, with no key precipitant identified. Later, during an emergency visit for other symptoms, the patient admitted being treated for pathological gambling, which resolved his symptoms. Conclusion: After a month of investigations for suspected intracranial hypotension, during which all diagnostic and therapeutic options were exhausted, serious involving parenchyma, vessels and CSF were excluded. Despite improvement. A and treatable pathologies the specificity of the symptoms, this case highlights the necessity of considering a broad range of differential diagnoses and value the patient entire context. P262 Patterns of prior COVID19 infection in primary headache disorders K. Pardo1,2, M. Mermelstein1,2, S. Yust1,2 1Rabin Medical Center, Neurology, Petah Tikva, Israel 2Tel-Aviv University, School of Medicine, Tel Aviv, Israel Objective: Viral illness is known to trigger chronic headaches, a phenomenon mostly known with EBV infection. Following the Sars-Cov-2 pandemic many survivors reported long standing headaches, classified as part of the long-COVID syndrome, however the effect on primary headache disorders is not yet clear. We aimed to evaluate whether there are higher rates of Sars-Cov-2 infection among primary headache patients. Methods: We used data from the Clalit Health Services (CHS) database to conduct a case control study comparing patients with new diagnosis of primary headache to non-headache patients, with regards to past infection with Sars-Cov-2 and EBV. We included patients aged 18 years or older at the time of a new diagnosis of primary headache, including Migraine, Cluster headache (CH) and Tension type headache (TTH), between June 2020 and June 2023. The control group was comprised of matched individuals by age and sex. Results: Our cohort of new primary headache disorders included a total of 50,662 patients: 39,938 with Migraine, 9,835 with TTH and 889 with CH. The control group included 106,413 patients. Rates of past Sars-Cov-2 infection were highest for patients with migraine (20,201 patients, 50.58%) followed by TTH (4,785 patients, 48.65%) and CH (385 patients, 43.16%), compared to control group (49,151 patients, 46.2%), P<0.0001. Rates of past EBV infection were also highest within migraine patients (7,287, 18.25%), followed by TTH (1,556, 15.82%) and CH (137, 15.36%), compared with control group (16,762, 15.75%), P<0.0001. Conclusion: Migraine and TTH patients had higher rates of Sars-Cov-2 infection, suggesting a possible association between Sars-Cov-2 infection and a new diagnosis of either Migraine or TTH. Similar pattern was shown with regards to past EBV infection which implies analogous mechanism in these two viral diseases.

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Fig. 2 Fig. 3 P263 Age of onset of migraine and its relation to medications response H. Younis1, R. Alsubaie1, M. Badr1 1King Fahad Military Hospital, neuroscience, Jeddah, Saudi Arabia Objective: the aim of our study to investigate the role of age of onset of migraine and timing to start preventive treatment on the response to medications Methods: our study is retrospective cohort analytic study in which we define refractory migraine as failure to at least two of the current approved medications and data was analyzed by SPSS. Results: 41 patients were included(12 male and 29 female, mean age 38.8) ,31 patients were below age of 25 (60%) at time of onset of migraine with mean delay in diagnosis 2.048 years and mean delay in treatment was4.76 years . Conclusion: early onset and delay in diagnosis is associated with high rate of treatment failure Fig. 1 P264 Validation of the Portuguese version of the Cluster Headache Impact Questionnaire (CHIQ) – study protocol T. Millner1,2, M. Cabral2,3, B. Barreto2,4, L. Silva5, R. Castro6, P. Almeida7, C. Morgado8, S. Varanda8, A. L. Rocha7, I. Alves6, C. Andrade5, M. Pinto2, R. Dias2,4, A. Costa2,4 1Hospital Central do Funchal, Neurology, Funchal, Portugal 2Unidade Local de Saúde São João, Neurology, Porto, Portugal 3Hospital Divino Espírito Santo, Neurology, Ponta Delgada, Portugal 4Faculty of Medicine of University of Porto, Clinical Neurosciences and Mental Health, Porto, Portugal 5Unidade Local de Saúde Santo António, Neurology, Porto, Portugal 6Unidade Local de Saúde Entre Douro e Vouga, Neurology, Santa Maria da Feira, Portugal 7Unidade Local de Saúde Gaia/Espinho, Neurology, Vila Nova de Gaia, Portugal 8Unidade Local de Saúde de Braga, Neurology, Braga, Portugal

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to the reveal treatment Stereoelectroencephalography it is essential to explore precise treatment strategies based on the pathophysiological mechanisms of CH. Methods: This study conducted 7.0T RS-fMRI scans and (SEEG) implantation in a patient diagnosed with rCCH to determine the precise intervention target for DBS. In terms of neuroimaging, research utilized Amplitude of Low Frequency Fluctuations (ALFF) and functional connectivity analysis the characteristics of abnormal brain activity during headache attacks. In terms of electrophysiology, based on the implantation of 14 SEEG electrodes, monitoring biomarkers characterizing headache attacks were identified through correlation analysis and machine learning. Furthermore, the optimal modulation target for rCCH was determined by validating targets based on clinical responses and biomarkers. Subsequently, the patient underwent DBS precision therapy and follow-up. Results: During CH attacks, there were abnormal activities and functional connectivity changes in local brain regions such asVTA, PMH, various VPL/VPM, and DN. The alpha frequency band of bilateral DN had the best discriminative effect on distinguishing different state of CH. Stimulation of the left ventral posteromedial nucleus (LVPM) showed relief in headache severity and reduction of the power of the alpha frequency band in DN. Therefore, using the classical regulatory target LVTA of rCCH and the personalized target LVPM discovered in this study as the patient's DBS regulatory targets, a follow-up at six months showed an in CH attack frequency by over 50%. Conclusion: This study, for the first time, identified the DBS treatment target for rCCH based on neuroimaging, intracranial electrophysiology, and clinical information, providing conceptual validation for precise DBS for refractory headaches and even pain. improvement the into Portuguese by two Objective: Cluster headache (CH) affects 0.1% of the population, often causing significant disability and job loss. The Cluster Headache Impact Questionnaire (CHIQ), addresses lack of patient-reported outcome (PRO) data for CH. This study aims to validate the Portuguese version of the CHIQ for clinical and research use. Methods: The English version of the CHIQ will be translated independent translators and back-translated to English to resolve discrepancies. Patients aged 18 or older with a diagnosis of episodic or chronic cluster headache will be consecutively recruited between July and October 2024, from multiple Portuguese headache centers that are currently being included (expected sample of 60 patients). The study was submitted to the local ethics committee. Results: Demographic and clinical data, including sex, age, attack frequency, medication use, smoking, and alcohol consumption, will be collected. The CHIQ and other to Portuguese questionnaires assessing psychological dimensions (DASS-21) and (SF-36) will be administered quality of electronically. Statistical analysis will occur in November 2024 and will include descriptive statistics, non-parametric comparisons, Cronbach's alpha for internal consistency, and ICC for test-retest reliability, with a significance cutoff of p < 0.05. Conclusion: The validation of the Portuguese version of the CHIQ is expected to enhance the assessment the and management of cluster headache Portuguese-speaking This tool's applicability can lead to improved follow-up and treatment outcomes for CH patients, contributing to better clinical practice and research in this field. population. validated group tests life for in P265 Precision Deep Brain Stimulation for refractory chronic cluster headache: a pilot study based on SEEG and ultra-high field MRI D. Zhao1, S. Zhang1, H. Zhao2, Y. Wang3, C. Zhang3, C. H. Yeh3 1Chinese PLA General Hospital, Department of Neurology, Beijing, China 2Chinese PLA General Hospital, Department of Neurosurgery, Beijing, China 3School of Information and Electronics, Beijing Institute of Technology, Key Laboratory of Brain Health Intelligent Evaluation and Intervention,, Beijing, China Objective: Currently, the outcome of deep brain stimulation for refractory chronic cluster headache (rCCH) is highly heterogeneous. Therefore, (DBS)

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P266 Unveiling the burden of cluster headache: insights from epidemiology to treatment strategies from a Portuguese tertiary center B. Barreto1,2, I. Sá Pereira1, M. Pinto1, A. Costa1,3, R. Dias1,3 1Unidade Local de Saúde de São João, Neurology Department, Porto, Portugal 2Faculty of Medicine, University of Porto, Medicine Department, Porto, Portugal 3Faculty of Medicine, University of Porto, Clinical Neurosciences and Mental Health, Porto, Portugal P267 Brain resting state networks in episodic cluster headache: cerebral connectivity analysis with HD- EEG A. Antoniazzi1,2, R. De Icco1,2, G. Vaghi1,2, M. Corrado1,2, F. Cammarota1,2, F. Bighiani1,2, E. Mazzotta1,2, V. Grillo1,2, M. Semprini3, E. Fenoglio3, G. Sances2, M. Allena2, C. Tassorelli1,2 1University of Pavia, Brain and Behavioral Science Department, Pavia, Italy 2Fondazione Mondino IRCCS, Headache Science & Neurorehabilitation Unit, Pavia, Italy 3Italian Institute of Technology, Genova, Italy to tearing lives. Our aim was Objective: Cluster headache is a debilitating primary headache, often underdiagnosed despite its impact on patients' analyze epidemiological, clinical, and therapeutic aspects of a cohort of patients with cluster headache. Methods: A retrospective observational study was performed, including cluster headache patients followed at the Neurology department of a tertiary center from 2009 to 2024. Results: We included 36 patients (80.6% male, mean age 49.9 years). The median age of symptom onset was 30 years, with a median diagnostic delay of 2 years. Most patients (83.3%) had history of smoking. The majority (83.3%) had episodic cluster headache, and all but one had autonomic symptoms, the most common being (80.3%). Agitation was reported by 86.1% of patients, and 58.3% described migraine features, which were more common in men (p=0.013) and in chronic cases (p=0.03). Four patients initially misdiagnosed with migraine experienced a delayed of more than 2 years in receiving the correct diagnosis (p=0.045). Most patients had 2 or more attacks daily (54.3%), with 55.6% predominantly reporting nighttime episodes. Over half of the patients (52.9%) had cluster bouts lasting less than one month. The most used acute treatment was nasal zolmitriptan (80.6%) and most patients received transitional treatment with corticosteroids and/or greater occipital nerve blocks (91.7%). The primary preventive treatment was verapamil (80.6%), with seven patients receiving anti-CGRP antibodies (19.4%). Chronic cases required more preventive medications (5.33 vs. 3.07, p=0.004), and patients with longer cluster bouts more frequently needed anti-CGRP antibodies (p=0.006). Conclusion: This study highlights the epidemiological, clinical and therapeutic aspects of cluster headache, emphasizing male predominance and link to smoking. It identifies a significant diagnostic delay, especially in cases initially misdiagnosed as migraine, underscoring the importance of early recognition and heightened awareness. its by means Objective: A convincing explanation for the switch between the active and remission phases of episodic cluster headache (eCH) is lacking. In this study, we aim to shed some light on these mechanisms by analyzing internodal connectivity patterns in the brains of eCH patients high-density of electroencephalography (HD-EEG). Methods: Twenty-four eCH patients underwent HD- EEG recordings in two conditions: active phase (T0) and remission period (T1). Nineteen sex and age matched controls underwent a single HD-EEG evaluation. Through these data we reconstructed the inter-networks and intra-network connectivity of six resting state networks: default mode network (DMN), dorsal attention network (DAN), ventral attention network (VAN), language attention network (LAN), somatomotor network (SMN), visual network (VN). Results: At T1 there was a significant difference in alpha band connectivity between eCH patients and HCs in the intra-network connectivity of the DMN (eCH=0,089±0,007; HC=0,115±0,009; mean difference 0,026±0,012;p=0,034) VN (eCH=0,085±0,007; HC=0,109±0,008: mean difference 0,025±0,011; p=0,034). Moreover, eCH patients and HCs showed a significant difference at T1 in alpha band inter-network connectivity between the DMN and the VN (eCH=0,089±0,007; HC=0,114±0,008; mean difference 0,025±0,012; p=0,038). Conclusion: Our findings show how eCH patients have a reduced alpha band connectivity during the remission period within and between the DMN and the VN networks. These alterations may be associated to the shift between the two states of the disease and support the relevance of electrophysiological studies in providing cluster headache physiopathology. insights into and of the

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P268 Stop cluster headache project: case series of sphenopalatine ganglion block with intranasal device in refractory chronic cluster headache D. Asín Díaz1, A. Cots2, D. Moraleja1, D. J. Ramis1, A. Grajea1, M. d. l. Á. Sosa1, M. T. Marco1, M. N. Fabregat1, S. Fernández1, T. Topczewski1, R. Armand1, V. Obach1 1Hospital Clínic de Barcelona, Headache and Facial Pain Unit, Barcelona, Spain 2Hospital Clínic de Barcelona, Primary Care Consortium Barcelona Esquerra, Barcelona, Spain Objective: Patients with refractory chronic cluster headache (rcCH) have limited therapeutic options. Procedures targeting the sphenopalatine ganglion (SPG) have shown efficacy in alleviating attacks. We aim to evaluate the effectiveness of SPG block (SPGB) via intranasal approach using the Tx360 device as a transitional treatment in rcCH patients. Methods: Patients with rcCH exacerbation underwent ipsilateral intranasal SPGB with 0.6 ml of lidocaine 2% and daily follow-up via WhatsApp for 4 weeks post- treatment. We collected demographics, treatments used, and analyzed the Headache Burden Index (HBI = weekly attacks × (intensity (VAS)/10) × duration in minutes). Improvement variables were defined as the percentage of patients achieving free-attack status, those achieving a 50% reduction in weekly attack frequency or a 50% reduction in HBI score compared to the week prior to treatment. Results: Eight patients with rcCH received SPGB from September 2019 to September 2023. The mean age (SD) was 45.5 (+/-13.3) years old, and 5 patients (62.5%) were male. All patients were under stable dose of Verapamil (350 mg/day on average) and used triptans and oxygen for acute therapy. Additionally, 5 patients were simultaneously treated with lithium, 4 with topiramate, 3 with valproate, and 6 with OnabotulinumtoxinA (195UI PREEMPT protocol). All patients were also refractory to bilateral Great Occipital Nerve block (BGONB) with lidocaine 2ml at 2% and 40 mg of triamcinolone, performed at least 1 week before SPGB. The median [IQR] duration of the current episode before SPGB was 46.5 [39.75-86.75] days. Two patients (25%) were attack-free at week 1 maintaining this status throughout follow-up. Five patients their weekly attack frequency by 50% in the first week, and 7 patients (87.5%) achieved a 50% reduction in HBI. Conclusion: Despite the limitations of a descriptive study, our data suggest a significant benefit of SPGB with Tx360 device as a transitional treatment during bout exacerbation in rcCH. reduced (62.5%) Fig. 1 Fig. 2 P269 The effect of invasive vagus nerve stimulation in a patient with both chronic cluster headache and focal epilepsy – a Case Report P. van Tilborg1, A. Bosch2, R. Thijs1,2, R. Fronczek1,2 1Leiden University Medical Center, Neurology, Leiden, Netherlands 2Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, Netherlands Objective: Treatment options for chronic cluster headache (CCH) are often insufficient. While non-

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invasive vagus nerve stimulation (nVNS) can be effective as acute treatment in episodic CH, this is not observed in CCH. The effect of invasive vagus nerve stimulation (iVNS) has not been studied in CH. Methods: We report the effect of iVNS in a 71 y/o male, diagnosed with CCH in 1965. Attacks present as extreme left-sided orbital pain with autonomic symptoms and fulfil the ICHD-3 criteria. In the past decade he usually had 1-2 attacks per day. Sumatriptan is used as abortive treatment. He did not tolerate prophylactic medication. In addition to CCH, he was diagnosed with right frontotemporal focal epilepsy. This was proven using ictal video electroencephalography recording and treated with cenobamate and pregabaline. In June 2023 a VNS was implanted as epilepsy treatment. The VNS duty cycle was increased per standard epilepsy protocol. Medication dosages were not altered post- implantation. Results: 3 months post implantation, CH attack frequency had decreased from 7 to 3 weekly attacks. 5 months post implantation, only 1 weekly CH attack remained. The decrease in attack frequency was still in May 2024. present during Interestingly, when temporarily deactivated for an unrelated procedure in Sept. 2023, the patient reported an in CH attack frequency. Once the VNS was reactivated 5 days later, the attack frequency decreased again (fig 1). Conclusion: In this case iVNS lead to a considerable decrease in weekly CH attack frequency. While natural disease course or placebo effect can't be excluded, the continued effect 1 year post-surgery in a patient with daily attacks since childhood suggests VNS is at least partly responsible for the decreased attack frequency. This is further supported by the change in attack temporary VNS deactivation. As CCH patients need more treatment options, more research into VNS as preventive treatment for CCH could be beneficial. frequency during the VNS was the last follow-up increase Fig. 1 P270 Emotional dynamics during prednisone treatment in cluster headache (CH) patients: insights from dynamic time warp analysis of daily assessments P. van Tilborg1, A. S. Koning2, W. Naber1, O. Meijer2, R. Fronczek1, E. Giltay3,4 1Leiden University Medical Center, Neurology, Leiden, Netherlands 2Leiden University Medical Center, Endocrinology, Leiden, Netherlands 3Leiden University Medical Center, Psychiatry, Leiden, Netherlands 4University of Antwerp, Collaborative Antwerp Psychiatric Research Institute (CAPRI), Antwerp, Belgium the Objective: Cluster headache (CH) patients can experience various emotional symptoms due to the severe attacks. CH can be treated with high-dose prednisone. These synthetic glucocorticoids can cause neuropsychiatric side effects. Our study aims to examine interaction between psychological symptoms and CH burden during glucocorticoid treatment. Methods: Seven chronic CH patients who received oral prednisone were included. Prednisone therapy started with 60mg/day and was tapered with 5mg per 5 days. Participants completed daily ecological momentary assessments regarding emotions and CH symptoms for 67 days (treatment period + 7 days). Dynamic time warp (DTW) identifies the covariation of symptoms over time and indicates whether a change in one symptom preceded or followed a change in other symptoms. Undirected and directed DTW analyses were performed to assess fluctuations in emotions and CH burden. Results: Undirected group-level (nomothetic) DTW analyses showed 5 symptom clusters with similar dynamics. Positive emotions were associated to each other with a negative relation to CH burden (fig. 1). During tapering of the prednisone treatment, a decline in positive emotions and an increase in negative emotions and CH burden was found (fig. 2). Directed time-lag nomothetic analyses revealed "cheerful", "enthusiastic" and "feeling good" as the highest instrength items, indicating they followed a change in other symptoms the previous day. "Being upset" had the highest outstrength, decreasing "enthousiastic" and "feeling good" the next day. In the directed network analysis, CH burden was not associated with any of the emotion items (fig. 3). Conclusion: During the tapering of prednisone treatment, CH burden increased as expected. Interestingly, this coincided with a decrease all of the assessed positive emotions and an increase of the negative emotions. While the fluctuating emotions may be part of the natural disease course, we should

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be aware that treatment with glucocorticoids may strengthen this effect. Fig. 1 Fig. 2 Fig. 3 P271 Sleep habits in patients with cluster headache C. Guerreiro1,2, C. Gavancho1,2, M. Cazola2, M. Sequeira2, P. Esperança2 1NOVA Medical School, Universidade Nova de Lisboa, Neurosciences department, Lisboa, Portugal 2Unidade Local de Saúde São José, Neurology Department, Lisboa, Portugal (CH) Objective: Cluster headache is a primary headache that presents with circadian rhythm, often during nighttime. Patients with CH report poor sleep quality and irregular sleep patterns are an established trigger for CH. The relationship between CH and sleep pathology is not yet clear. Methods: We collected retrospective data from patients with CH followed in our Headache clinic since 2020, analysing their demographics, comorbidities, treatment history and CH circadian pattern. The Pittsburgh Sleep Quality Index (PSQI) was applied through phone interview in remission and crisis. Results: We obtained data from 8 patients (n=23) with an average age of 48. Three were under prophylaxis with verapamil or lithium and the most used acute phase treatment was zolmitriptan. The most common comorbidity was insomnia (50%), followed by obstructive sleep apnea (OSA). Two were shift workers and three presented nighttime attacks exclusively. Three patients presented insufficient sleep time (<7h) in remission period and 50% were under medication for insomnia. Average PSQI during crisis was 13, with higher values in patients with nighttime attacks exclusively. Conclusion: In this population, the most common comorbidities were sleep disorders and 50% presented with high PSQI. Patients under prophylaxis registered higher values, suggesting an association between the severity of CH and worse sleep quality. Possible iatrogenic effect should be considered. Further studies are needed to clarify the relationship between CH and sleep habits and pathology. P272 Investigating glymphatic dysfunction in migraine – A role in headache pain and migraine chronification? R. Messina1,2, E. Pagani2, F. Genovese1,2, I. Cetta1,2, L. Zanandrea1,2, B. Colombo2, M. A. Rocca1,2, M. Filippi1,2 1Vita-Salute San Raffaele University, Milano, Italy 2IRCCS San Raffaele Scientific Institute, Milano, Italy glymphatic in Objective: Aim of this study was to evaluate the role of migraine pathophysiology and to investigate its contribution in the acute headache phase and in mechanisms of chronification and medication overuse (MO). dysfunction

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Objective: Idiopathic intracranial hypertension (IIH) is a neurometabolic disease that primarily affects young, obese females. Steroid hormone dysregulation has been described in IIH but is presence at time of diagnosis is unknown and a full steroid profile is yet to be assessed. We aimed to define the steroid profile in newly diagnosed IIH and to search for prognostic factors. Methods: In a prospective cohort of newly diagnosed, treatment naïve IIH patients with follow up at ocular remission (N=60), we performed targeted quantitative liquid chromatography tandem mass-spectrometry for 19 steroid hormones (corticosteroids, androgens, progestogens, and estrogens) in paired serum and cerebrospinal fluid (CSF) with age, sex and BMI matched healthy controls (N=35). Results: In the serum, dihydrotestosterone (DHT) (P<0.0001) and dehydroepiandrosterone (DHEA) (P=0.0005) were lower, whereas DHEA-sulphate (DHEAS) (P=0.019) was higher in IIH patients. No other steroids were altered in the serum. In the CSF, testosterone (P=0.004), DHT (P=0.001), progesterone (P=0.009), 17OH- pregnenolone (P=0.0004), DHEAS (P<0.0001) and 17β- estradiol (P<0.0001) were higher in IIH, whereas DHEA was lower (P=0.01) compared to controls. All other CSF steroids were unaltered. Higher CSF DHEA (ROC area 0.69, P=0.017) and lower CSF DHT (ROC area 0.66, P=0.04) at diagnosis predicts the development of bilateral optic nerve atrophy in IIH. No predictors were identified for developing any type of atrophy or other clinical outcome. None of the steroid levels correlated with intracranial pressure or headache parameters. Conclusion: We demonstrate that sex steroids in the CNS are highly perturbed in new onset IIH, whereas in the peripherary, only androgens are dysregulated. Moreover, higher CSF DHEA and lower CSF DHT in IIH can predict which patients develop bilateral atrophy, suggesting a role in the pathogenesis of IIH. These findings require further clinical validation. pregnenolone (P=0.008), Methods: One hundred twenty migraine patients (95 headache-free, 25 with headache during the MRI, 93 episodic migraine (EM), 24 chronic migraine (CM) with MO) and 52 controls underwent diffusion tensor (DTI) and susceptibility weighted (SWI) magnetic resonance imaging (MRI). We calculated the Diffusion Along Perivascular Space (DTI-ALPS) index, which provides an indirect measure of glymphatic function at the perivascular space, and evaluated voxel-wise maps of white matter extracellular (EVF) and intracellular (IVF) volume fraction, serving as an indirect index of glymphatic clearance activity. Age- and sex-adjusted between-group comparisons were run using R and FSL software. Results: We found no significant differences between patients and controls, neither concerning the DTI- ALPS index nor regarding EVF and IVF. No differences in the DTI-ALPS index were observed between subgroups of patients. Compared to controls and headache-free experiencing headache during the MRI had a decrease in EVF and an increase in IVF. Likewise, compared to controls, CM with MO patients showed decreased in EVF and increased in IVF. Conclusion: Despite no significant differences observed in DTI-ALPS index between patients and controls, or among patient subgroups, suggesting no alterations at the perivascular level, our findings of reduced EVF and concomitant expansion of IVF in patients experiencing headache during MRI scan and those with CM and MO, suggest impaired glymphatic clearance. potential involvement of glymphatic dysfunction in the acute pain phase of migraine and the mechanisms underlying chronification and MO. patients, patients These findings suggest P273 Deranged sex steroids in the central nervous system predict retinal atrophy in patients with newly diagnosed idiopathic intracranial hypertension C. Kamp-Jensen1,2, T. Lylloff1,2, J. Korsbæk1, E. A. Wibroe3, S. M. Hagen3, K. A. Haanes2,4, B. Styrishave5, D. Beier6, R. Højland Jensen1,2, C. S. J. Westgate1,2 1Rigshospitalet Glostrup, Danish Headache Center, Glostrup, Denmark 2Translational Research Centre, Rigshopitalet, Glostrup, Denmark 3Rigshospitalet Glostrup, Ophthalmology, Glostrup, Denmark 4University of Copenhagen, Biology, Copenhagen, Denmark 5University of Copenhagen, Pharmacy, Copenhagen, Denmark 6Odense University Hospital, Neurology, Odense, Denmark

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Fig. 1 Fig. 2 Fig. 3 P274 Potential negative correlations of white matter free water volume fraction (WM-FWVF) with diffusivity along the perivascular space (ALPS) index and kurtosis fractional anisotropy (KFA) in healthy volunteers E. Qiu1, P. Phan1, A. Nisar1, D. Middleton2, M. Alizadeh2, J. Chaganti2, K. Talekar2, P. Mondel2, S. Naghizadehkashani2, F. Mohamed2, S. Faro2, H. Yuan1 1Jefferson Headache Center, Thomas Jefferson University, Philadelphia, PA, United States 2Thomas Jefferson University, Radiology, Philadelphia, PA, United States Objective: The diffusivity along the perivascular space (ALPS) index, global white matter (WM) kurtosis measurements, and global WM free water volume fraction (WM-FWVF) are potential imaging biomarkers to assess glymphatic system function. This study aims to investigate the correlation among WM-FWVF, ALPS index, and WM kurtosis measures, utilizing diffusion- weighted MRI (DW-MRI) to elucidate the potential interrelationship among these parameters. Methods: Multi-shell DW-MRI data were acquired from 10 healthy controls (6 females, 31.5±9.3 years) using a 3T Siemens Scanner. All subjects gave their consent to publish their details in an open access journal.The ALPS index was calculated using single- shell (b=1000 s/mm²) DW-MRI based on the JHU DTI- 81 White Matter Atlas ROIs. The mean kurtosis (MK), radial kurtosis (RK), axial kurtosis (AK), and kurtosis fractional anisotropy (KFA) values in the WM were derived from two-shell (b=1000, 2800 s/mm²) DW- MRI employing a diffusion kurtosis model. The FWVF index was obtained from multi-shell (b=250, 1000, 2800 s/mm²) DW-MRI using a free water correction model. Pearson correlation analysis was performed between WM-FWVF and ALPS index, as well as WM- MK, WM-RK, WM-AK, and WM-KFA. Results: The WM-FWVF showed a negative correlation with the left-sided ALPS index (r=-0.66, P=0.037) and WM-KFA (r=-0.72, P=0.019). There were no significant correlations between WM-FWVF and right-sided ALPS index (r=-0.17, P=0.635), bilateral ALPS index (r=-0.52, P=0.127), WM-MK (r=-0.40, P=0.254), WM-RK (r=-0.58, P=0.079), or WM-AK (r=- 0.20, P=0.573). Conclusion: The observed inverse associations between WM-FWVF fluid dynamics) and the left-sided ALPS index (evaluating perivascular fluid transport) along with WM-KFA (reflecting axonal density or fiber orientation complexity) may indicate potential reflections of glymphatic system alterations. Multi-shell DW-MRI could thus be a valuable tool for studying glymphatic function in neurological disorders. interstitial (assessing

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Fig. 1 P275 Characterization and advances in the study and treatment of patients with intracranial hypotension C. Gavancho1,2, D. Kuroedov3, R. Lindeza3, C. Guerreiro1,2, M. Pimenta1, J. Rosa1 1Hospital de São José – Unidade Local de Saúde São José, Neurology, Lisboa, Portugal 2NOVA Medical School - Universidade Nova de Lisboa, Neurosciences, Lisboa, Portugal 3Hospital de São José – Unidade Local de Saúde São José, Neuroradiology, Lisboa, Portugal according to the fail due to inadequate Objective: Spontaneous intracranial hypotension (SIH) is a potentially severe condition, secondary to CSF leak caused by a dural tear, leaking meningeal diverticulum or CSF-venous fistula. Diagnosis may be challenging due to a variable clinical presentation and treatment may fistula identification. New algorithms have been developed to more appropriately manage this pathology, which we have recently implemented in our center. We aimed to characterize patients with intracranial hypotension clinical presentation/headache phenotype and discuss novel diagnostic and therapeutic approaches. Methods: Retrospective study with a descriptive analysis of patients admitted to the Neurology Department of Hospital de São José between 2016 and 2023 with intracranial hypotension. Results: All 13 patients admitted with intracranial hypotension (69,2% females, 30,8% males, average age 43 years) presented with headache (77% orthostatic headache, 8% migrainous phenotype, 1 thunderclap intracranial hypertension phenotype). The most frequently associated symptom was neck pain (46%), followed by diplopia (31%), tinnitus, vertigo and sensorimotor deficits (15%) and cognitive symptoms (8%). A clear CSF fistula was only documented in 2 patients (15%) - 1 dural tear and 1 CSF-venous fistula (Fig. 1), the latter managed with transvenous embolization via the azygos system (Figs. 2 and 3). Conclusion: Given its variable clinical presentation, a high suspicion is needed for the diagnosis of intracranial hypotension . Although 30–70% of SIH patients following epidural blood patches applied via various techniques, definite cure mostly requires surgical closure of ventral dural tears and surgical ligations of leaking nerve root sleeves associated with meningeal diverticulae or CSF-venous fistulas. For the latter, transvenous embolization with liquid embolic agents via the azygos vein system is a novel and valuable therapeutic alternative. show marked improvement phenotype and 1 Fig. 2

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Fig. 3 P276 Comprehensive evaluation of diagnostic criteria, neuroimaging, and treatment outcomes in refractory idiopathic intracranial hypertension based on venous manometry insights – a single-center retrospective study A. Nisar1, E. Qiu1, N. Spare1, M. Marmura1, R. Gooch2, H. Yuan1 1Thomas Jefferson University, Department of Neurology, Philadelphia, PA, United States 2Thomas Jefferson University, Department of Neurosurgery, Philadelphia, PA, United States in refractory idiopathic Objective: The objective of the study is to evaluate the current diagnostic criteria and neuroimaging criteria intracranial hypertension (rIIH) based on venous manometry- confirmed transverse sinus stenosis (vTSS), followed by assessing the treatment response of venous sinus stenting. Methods: A retrospective review of electronic medical records and institutional standardized neuroimaging assessment (MRI & MRV) was done on patients with rIIH without pertinent past brain or spine surgery undergoing venous manometry at Thomas Jefferson University Hospital between January 2022 and October 2023. Results: 48 rIIH patients (age 38.9±9.9, BMI 36.8±9.1 kg/m2, all female, Caucasian 22, African American 21) underwent Trans-stenotic pressure gradient ≥8 mmHg (i.e., vTSS) was identified in 35 (72.9%) patients. The 4 IIH criteria (Friedman, Wall, Korsbaek, and modified-2023) showed a venous manometry. sensitivity of 75.8-87.8% and a specificity of 26.7- 60.0%. Among radiographic parameters, the vascular parameters were more sensitive (96.3%) than non- vascular parameters (55.2-90.0%) in detecting vTSS. On evaluating patients with complete follow-up data post venous sinus stenting, 27 (75.0%) reported relief of headache, with improvement also seen in pulsatile tinnitus 17 (56.7%), visual problems 22 (62.3%), and stable or improved papilledema in 13 (46.4%) patients after 6 months of stenting. IIH diagnostic criteria are Conclusion: Current sensitive yet not specific enough to identify TSS. A standardized neuroimaging approach should be applied to detect TSS for further workup. Venous manometry in assessing TSS in rIIH patients and should be considered for patients with clinical and imaging suspicion of stenosis. Venous stenting may be considered in selected rIIH candidates. is a standardized objective tool for managing TSS Fig. 1 Fig. 2

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Fig. 3 P277 A case of Idiopathic Intracranial Hypertension (IIH) remission with Semaglutide T. Ascensão Pinheiro1, B. Madureira1, M. Henriques2, I. Cosme3, S. Machado1 1Hospital Amadora-Sintra, Neurology, Amadora, Portugal 2Hospital Amadora-Sintra, Ophthalmology, Amadora, Portugal 3Hospital de Santa Maria, Endocrinology, Lisboa, Portugal in Idiopathic revolution relationship intracranial hypertension is Objective: defined by the signs and symptoms of intracranial hypertension, with increased cerebrospinal fluid (CSF) pressure in the absence of structural lesions. It is more prevalent in obese women of childbearing age, with an established to metabolic disorders.There has been a its treatment, whose primary goal is the maintenance of vision through weight loss and the use of innovative medications such as glucagon-like peptide-1 (GLP-1) receptor agonists. Methods: We present the case of a 27 year old woman with obesity (BMI 45kg/m²) and a history of headache since 2017. She was observed by Neurology in the emergency department due to a recent worsening of the headache, described as constant, present upon waking up, of high intensity, pulsatile, with photophobia. She also reported pulsatile tinnitus and negative scotomas. She was also examined by Ophthalmology, with visualization of papilledema and hemorrhages bilaterally. Results: The OCT showed increased thickness of the retinal nerve layer. Due to suspicion of intracranial hypertension, she underwent a CT scan with no alterations, and a lumbar puncture with an opening pressure of 36 cmH20 and an otherwise fiber that discussing the ruled out was cerebral medicated unremarkable CSF study. She also did an MRI and MR venous venography thrombosis.She with acetazolamide. After case with Endocrinology, she started semaglutide 0.25mg per week, progressively increasing the dosage, with a 13% reduction in BMI in 3 months, remission of the symptoms, resolution of papilledema and significant improvement in OCT findings. Thus, with rapid BMI reduction, disease remission was achieved Conclusion: Despite the off label use of semaglutide, studies available in the literature demonstrate that GLP-1 agonists are effective in controlling this disease by reducing CSF secretion and controlling BMI. The multidisciplinary treatment of is, nowadays, fundamental, and metabolic strategies should be considered. IIH P278 Acute headache treatment in idiopathic intracranial hypertension – Treating to the phenotype? G. Bsteh1,2, N. Krajnc1,2, S. Zaic1,2, N. Müller1,2, W. Marik2,3, M. Michl4, K. Novak2,5, S. Macher1,2, B. Pemp4, C. Wöber1,2 1Medical University of Vienna, Neurology, Vienna, Austria 2Medical University of Vienna, Comprehensive Center for Clinical Neurosciences & Mental Health, Vienna, Austria 3Medical University of Vienna, Neuroradiology, Vienna, Austria 4Medical University of Vienna, Ophthalmology, Vienna, Austria 5Medical University of Vienna, Neurosurgery, Vienna, Austria This analysis retrospective Objective: Effective acute headache treatment is essential for improving quality of life in people with IIH (pwIIH), with experts recommending "treating to the phenotype" despite limited data. used Methods: standardized headache diaries of pwIIH from the Vienna Idiopathic Intracranial Hypertension (VIIH) database from 1-JUL-2021 to 30-JUN-2023. We acute medication analyzed three (acetaminophen anti- inflammatory drugs [NSAIDs], and triptans) with NSAIDs as reference and nine substances combining different doses and formulations by their generic names with ibuprofen as reference. Headache attacks were classified according to ICHD-3 as migraine without / with aura (M), tension-type (TTH), or other (O). We used 2-level nested logistic regression models to analyze odds ratio (OR) of patient reported good response, adjusting for covariance within individual classes of [APAP], nonsteroidal

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pwIIH and concurrent medication with propensity- weighting for age, sex, and headache severity. Results: We examined 35,640 medication-outcome pairs from 23,507 headache attacks (45.3% M, 21.1% TTH, 33.6% O) in 156 patients (89.7% female, mean age 32.9 years). NSAIDs were most frequently used across all headache types (M: 60.5%, TTH: 69.8%, O: 70.7%), followed by APAP (M: 21.5%, TTH: 21.1%, O: 27.7%) and triptans (M: 18%, TTH: 10.1%, O: 12.8%). Compared to NSAIDs, triptans were most effective across all headache types (OR for M: 4.8 [CI 3.9-6.1], TTH: OR 2.9 [CI 1.8-4.3], O: OR 3.1 [CI 2.2-4.3]), while APAP was less effective for M (OR 0.81 [CI 0.74-0.90]) but similarly effective in TTH and O. In M, eletriptan and zolmitriptan (OR 6.0 and 5.8) were slightly more effective than sumatriptan (OR 5.0). Conclusion: Triptans are more effective than NSAIDs and APAP in the acute management of headaches in pwIIH, particularly – but not exclusively – for migraine-type attacks. These findings support the preferential use of triptans, questioning the "treating to the phenotype" approach. P279 Evaluating prevalence of orthostatic headaches in patients with postural tachycardia syndrome D. Mehta1, S. Cheema1, V. Iodice1, M. Matharu1 1National Hospital for Neurology & Neurosurgery, London, United Kingdom PoTS and of Headache spontaneous Objective: Examine the prevalence of headache disorders in patients with postural tachycardia syndrome (PoTS) and conduct detailed phenotyping of orthostatic headache (OH) characteristics to identify disease-specific differences that can help differentiate between intracranial hypotension (SIH). Methods: A structured interview was conducted with consecutive patients diagnosed with PoTS at a tertiary autonomics unit. Headaches were systematically phenotyped and diagnosed using the International Classification OH characteristics were assessed for baseline severity while recumbent, time to onset or exacerbation upon standing, and time to return to baseline severity upon lying down. OH frequency was also documented. Results: All ninety-eight patients had at least one primary headache disorder, with migraine being the most common (86.7%). OH was present in 20.4% of patients, and 49.0% experienced a primary headache disorder with an orthostatic component. OH was present consistently with postural change in only 5.3%. Among patients with headaches that had an orthostatic component, the median number of headache days per month was 9.5 (IQR 21.4, range the orthostatic component being 29.9), with Disorders. consistently present in only 12.8%. In the OH cohort, the median baseline headache severity when recumbent was 0 (IQR 0, range 7) on the verbal response scale. The median time to onset upon standing was 0.5 minutes (IQR 25, range 210) and time to return to baseline severity upon lying down was 27.5 minutes (IQR 41.5, range 508). Conclusion: Primary headache disorders, especially migraines, are ubiquitous among patients with PoTS. Nearly 50% of these patients experience headaches with an orthostatic component, and a further 20% have independent OHs. Unlike SIH patients, presence of orthostatic quality in association with postural changes in PoTS is often inconsistent and typically occurs episodically as part of a primary headache disorder. P280 Difficulties in differential diagnosis in idiopathic intracranial hypertension: Case report of three patients I. Kazaishvili1, V. Zhurauliou1, H. Aliashkevich2, N. Khorava1 1Belarusian State Medical University, Department of Nervous and Neurosurgical Diseases, Minsk, Belarus 2R3 Biotechnologies, Richmond, CA, United States in from ideal situation Objective: Idiopathic Intracranial Hypertension (IIH) is a condition characterized with increased intracranial pressure without apparent cause. Although, as of the moment, we have plethora of tools to combat this disease, there are clear signs that this is only temporary solution and the idiopathic nature of IIH would be unraveled and solved. In this Case report we wish to demonstrate three patients, whom could be very well be treated as IIH but further analysis of their conditions revealed other pathologies. Methods: We retrospectively examine three patients, utilizing data their MRI, CT scans, CT angiography, visual acuity fundus examinations conducted before and after surgical treatment. Despite initially presenting symptoms resembling idiopathic intracranial hypertension, these patients exhibited complex clinical profiles indicative of various neurosurgical pathologies, necessitating meticulous treatment approaches. Results: Significant improvements were observed in the radiological findings and quality of life of all three patients following surgical interventions targeting their primary pathologies. Specifically, a 36-year-old male with transverse sinus stenosis, a 41-year-old female with meningioma, and a 68-year-old female with arteriovenous malformation demonstrated notable progress without encountering further complications. tests, and

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Fig. 3 Conclusion: While initially suggestive of IIH, these cases underscore the importance of considering all available resources when treating such a condition. Effective management demands comprehensive utilization of communication channels with patients, collaboration with other medical specialists, and an understanding of the intricate interactions among cerebrovascular, cerebrospinal fluid, and functional brain systems. Fig. 1 Fig. 2 P281 Exploring venous sinus stenosis in patients with intracranial hypertension C. Gavancho1,2, R. Lindeza3, M. Pimenta1, M. Cazola1, J. Rosa1 1Hospital de São José – Unidade Local de Saúde São José, Neurology, Lisboa, Portugal 2NOVA Medical School - Universidade Nova de Lisboa, Neurosciences, Lisboa, Portugal 3Hospital de São José – Unidade Local de Saúde São José, Neuroradiology, Lisboa, Portugal Objective: Venous sinus stenosis (VSS) is described in idiopathic intracranial hypertension (IH), but its role in its pathophysiology isn't entirely established. We aimed to characterize VSS in intracranial hypertension and its possible influence in cerebrospinal fluid (CSF) opening pressure and clinical response to medical therapy. Methods: We retrospectively analyzed data from 21 patients admitted to the Neurology Ward of our hospital in 2016-2023 with intracranial hypertension and did a statistical analysis of the variables after reviewing the neuroimaging studies for evidence of venous sinus stenosis. Results: We identified VSS in 33,3% (n=7) patients [in contrast to 19% (n=4) according to the official reports] - 5 with transverse sinus and 2 with transverse- sigmoid transition stenosis. The median CSF opening pressure was 32,00cmLCR, higher in the group without stenosis (mean 37,07cmLCR) and lower in the group with stenosis (mean 30,43cmLCR), suggesting a negative impact of the stenosis on this measure (p=0,013). Despite a good initial response to medical therapy in the majority of patients with idiopathic IH (94,7%, n=18), some later experienced clinical worsening (26,7% at 6 months and 25% after 12 months), 5 needing additional medical therapy, 3 referenced for ventriculoperitoneal shunt and 1 proposed for venous sinus stenting. There was no

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the stenosis, although significant correlation between statistically the presence of VSS and the clinical response to medical therapy. Conclusion: Our finding that patients with venous sinus stenosis have a tendentially lower CSF opening pressure suggests a potential pathophysiological role of further characterization. We can't establish a correlation between VSS and the response to medical treatment but patients in both groups, after an initial response, had a clinical worsening and were referred for invasive treatments. The role of VSS should be further explored to clarify its pathophysiology and the therapeutic potential of venous sinus stenting. this needs P282 Extracellular vesicles of human glial progenitor cells exhibit neuroprotection by modulating the PI3K-Akt pathway in glutamate excitotoxicity M. Shedenkova1,2,3, D. Salikhova1,2, A. Nekrasova4, Z. Bakaeva4, D. Goldshtein1,2 1RUDN University, Moscow, Russian Federation 2Research Centre for Medical Genetics, Moscow, Russian Federation 3Lomonosov Moscow State University, Moscow, Russian Federation 4National Medical Research Center for Children’s Health, Moscow, Russian Federation were is to EV-GPCs obtained Objective: Extracellular vesicles (EVs) have recently entered the group of neurotherapeutic agents. The study aim investigate the neuroprotective mechanisms of EVs derived from a new type of cells - glial progenitor cells (GPCs) of human induced pluripotent stem cells (iPSCs) using proteomic assay and inhibitor assay in the glutamate excitotoxicity model. Methods: GPCs cultures were obtained previously from a healthy donor by differentiating iPSCs in a glial direction. by ultracentrifugation. Primary cultures of cortical neurons were used to establish a glutamate excitotoxicity model. Proteomic analysis of EV-GPCs was performed using an Ultimate 3000 Nano LC System chromatography system interfaced with a Q Exactive HF mass spectrometer. The proteins peak list was generated and analyzed by MASCOT and X! Tandem using the UniProtKB database. A selective inhibitor AS605240 (1µg/ml), was used to confirm the PI3K-Akt pathway activation. Results: According to the bioinformatic analysis, the represented protein groups of biological most processes were: (60%); "negative regulation of cell death" (9%); "redox processes" regulation of neurogenesis" (5%). Among the signaling pathways "metabolic processes' (8%) and "positive completely the most representative one was the "PI3K-Akt signaling pathway" (51 proteins). In the model of glutamate excitotoxicity, a 37.5% decrease in the viable neurons number was observed with the addition of glutamate compared to the control group. The presence of EV-GPCs (10 μg/mL) significantly increased survivability to control values. However, AS605240 drug"s neuroprotective effect. Conclusion: The obtained results indicate that EV- GPCs have neuroprotective effect due the contained proteins, among which the presence of PI3K-Akt signaling pathway ones was confirmed. It suggests that EV-GPCs may become a new type of therapeutic drug for the neurological disease"s treatment. offset the to P283 Glucagon-like peptide-1 (GLP-1) receptor agonists for headache and pain disorders – a systematic review W. Halloum1, Y. Al Dughem1, D. Beier2, L. Pellesi1 1University of Southern Denmark, Clinical Pharmacology, Pharmacy and Environmental Medicine, Odense, Denmark 2Odense University Hospital, Department of Neuroogy, Odense, Denmark systematic Objective: Glucagon-like peptide-1 (GLP-1) plays a crucial role in metabolic disorders by enhancing insulin secretion, inhibiting glucagon release, and slowing gastric emptying, thereby improving glycemic control. In recent years, GLP-1 role in neuronal pathways has expanded its therapeutic potential. We aim to comprehensively evaluate the relevance of GLP-1 in headache and pain disorders. search was Methods: A literature conducted on PubMed and Embase (Ovid) databases using the search terms "GLP-1" and "pain". Animal and human studies published in English language were included. Abstracts, reviews, and articles on other disorders than "pain" were excluded. Results: The search strategy identified 833 hits, of which 42 studies were included in the final review (Figure 1). The studies were categorized into four inflammatory pain and osteoarthritis, groups: headaches, diabetic neuropathy, and visceral pain and irritable bowel syndrome (GLP-1R) agonists, like liraglutide, have shown analgesic effects by modulating pain hypersensitivity in animal models of is involved in migraine mechanisms and GLP-1R agonists are beneficial idiopathic hypertension. Additionally, GLP-1R intracranial agonists and inflammatory and neuropathic pain. GLP-1 visceral hypersensitivity (Figure 2). GLP-1 individuals with neuropathic receptor reduce pain and in

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Fig. 2 ameliorate symptoms in patients with irritable bowel syndrome. Conclusion: The therapeutic scope of GLP-1R agonists is expanding beyond traditional metabolic targets, its potential for headache and pain highlighting disorders. Engineering bimodal molecules that integrate GLP-1R agonism with specific pain-related mechanisms may offer therapeutic options. innovative Fig. 1 P284 Intravenous dihydroergotamine for primary headache disorders: factors to consider for an optimal outcome – a service evaluation P. Amarasena1,2, F. Greenwood2, P. J. Goadsby1,3,4 1King's College London, Headache Group, Wolfson Sensory, Pain and Regeneration Centre, London, United Kingdom 2King's College Hospital NHS Foundation Trust, London, United Kingdom 3NIHR King's Clinical Research Facility, King's College London, London, United Kingdom 4University of California, Los Angeles, CA, United States Objective: Dihydroergotamine (DHE) has been used to treat headache for nearly eighty years. We aimed to identify patient factors and factors related to DHE administration affecting the response to our DHE infusion protocol. Methods: Data on 160 successive DHE admissions were collected from clinic letters and discharge summaries as part of a service evaluation. The response to DHE was categorized by patients on an ordinal scale: complete, good, partial and nil. Generalized linear logistic regression modelling was employed, with response to DHE as an ordinal dependent variable and a cumulative link logit

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to response identify predictors of outcome. function, Significance level was set at P < 0.05. Results: Data from 160 hospital admissions for DHE of 131 patients were analysed. Their median age was 47 years and 73% were females. Only active primary headache disorders were considered for analysis: 82 (63%) had migraine, 11 (8%) had cluster headache (CH), 3 (2%) had hemicrania alternans (HA) and 30 (23%) had new daily persistent headache (NDPH), while 5 (4%) had both migraine and CH (MC). The median DHE dose was 11.25mg. Of the patients, 47 with migraine (54%), 13 with CH (81%), 10 with NDPH (33%) and 1 (33%) with HA had a response to DHE. A model for patient factors (X2=23.254, df=7, P=0.002). predicted Compared to migraine, DHE was more effective for (OR=19.479, X2=9.265, P<0.001) and CH MC (OR=4.226, X2=4.920, P=0.027), but less effective for NDPH (OR=0.414, X2=3.950, P=0.047). The model for factors related to DHE administration (X2=38.098, df=11, P<0.001) showed absence of nausea was associated with a better outcome than uncontrolled nausea (OR=4.870, X2=6.352, P=0.012), while muscle cramps predicted a better response (OR=1.984, X2=4.244, P=0.039). Conclusion: DHE by infusion over five days is an effective treatment for primary headache disorders. DHE can be more beneficial for CH and adequate control of nausea is essential for an optimal response while muscle cramps may predict a better outcome. P285 Rimegepant for the acute treatment of migraine – a phase 3, multicenter, open-label, long-term safety study in adults from China S. Yu1, L. Ma2, Q. Zhong2, X. Han2, J. Atkinson2 1Chinese PLA General Hospital, Beijing, China 2Pfizer (China) Research and Development Co Ltd, Shanghai, China Objective: To evaluate the safety and tolerability of 75 mg rimegepant (RIM) orally disintegrating tablet and the number of monthly migraine days (MMDs) during long-term treatment (LTT), relative to the Observation Period (OP). Methods: This was a phase 3, multicenter, open-label, single arm study in Chinese adults (NCT05371652). Eligible participants (pts) had ≥1 year history of migraine (with or without aura), history of 6–18 moderate to severe migraine attacks/month ≤3 months prior to the screening visit, and ≥6 migraine days during the OP. After the 30-day OP, pts could take RIM as needed (PRN, max. of 1 tablet/day), at the onset of mild to severe migraine attack. The treatment phase was 52 weeks. Results: Of 330 screened adults, 241 were enrolled. Of those enrolled, 240 (99.6%) were treated, and 208 (86.3%) completed the study. Pts had a mean (SD) age of 39.1 (11.0) years and 192 (80.0%) were female. Mean age at migraine onset was 27.3 (9.7) years. The median (Q1, Q3) average RIM dose during LTT was 4.6 (3.1, 7.1) tablets/month. A total of 203 (84.6%) pts reported at least one TEAE during LTT, of which, 46 (19.2%) RIM-related. One pt experienced a TEAE of CTCAE grade ≥3, which was RIM-related. There were no RIM-related serious AEs and no RIM-related TEAEs that led to treatment interruption or discontinuation. Most abnormal laboratory parameters were of Grade 1-2. For all migraine attacks, the mean reduction from the OP in the number of MMDs was observed as early as the first 4 weeks (-1.7 [95% CI -2.2, -1.2]) with a trend of continued reduction to Month 11 (-5.7 [95% CI -6.3, -5.1]), followed by a plateau through Month 13. The mean monthly reduction across LTT was -4.4 (95% CI -4.9, -3.9) days. Conclusion: RIM had a favorable safety profile and was well tolerated in Chinese pts during LTT. The reduction in the number of MMDs was observed as early as the first 4 weeks and continued to improve for 11 months with a maintained reduction through to the end of LTT. P286 Moderate to vigorous intensity exercise for cluster headaches: insights from case summaries and literature review M. K. Kang1, Y. Hong1, S. J. Cho1 1Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Nrurology, Hwaseong, South Korea Objective: To investigate the effectiveness of exercise for the acute management of cluster headaches (CH) and review previous reports on its efficacy. Methods: Headache diaries were prospectively collected from two male patients. The patients recorded headache intensity using Numeric Rating Scale (NRS) and oxygen saturation levels before and after treatments. A literature review was conducted to provide context on the relationship between exercise and CH. Results: Case 1 (A 29-year-old male) experienced significant relief from CH through exercise and traditional reduced headache intensity from NRS 4 to 0 within 37 minutes, increasing oxygen saturation from 97% to 98% with a maximum pulse rate (PR) of 167/min. Combined exercise and oral sumatriptan decreased headache intensity from NRS 7 to 0 over 120 minutes, increasing oxygen saturation from 97% to 98% with a maximum pulse rate of 168/min. Oral sumatriptan alone did not treatments. Exercise alone

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change oxygen saturation or PR but reduced intensity from NRS 5 to 0 within 35 minutes. Case 2 (A 38-year- old male) also reported effective relief using exercise alone. Exercise reduced intensity from NRS 2 or 3 to 0 within 10 to 15 minutes, increasing oxygen saturation to 98-99% with a maximum PR of 126- 165/min. Literature review: Physical activity alleviates headache symptoms in other primary headache disorders. Di Lorenzo et al. (2011) reported that exercise helps release endorphins and reduce stress, aiding headache relief in migraines. Combining exercise with treatments like triptans can enhance relief, leading to faster pain reduction and improved outcomes. Conclusion: Moderate to vigorous exercise may resolve cluster headaches with increased oxygen saturation in CH patients, especially with mild pain. The vasoconstriction related to relative hyperoxia may contribute to CH pain control similar to oxygen therapy. Future the mechanisms of exercise in controlling acute CH and develop evidence-based recommendations for CH patients. should elucidate studies Fig. 1 P287 Intravenous valproic acid treatment in patients with chronic refractory migraine: our experience in pediatric age F. Ursitti1, G. Sforza1, L. Papetti1, G. Monte1, S. Tarantino1, M. Proietti Checchi1, M. Valeriani1 1Ospedale Pediatrico Bambino Gesù, Neurologia dello Sviluppo, Rome, Italy Objective: In adults with migraine, valproic acid (VPA) is an effective prophylactic treatment. There are few pediatric studies that demonstrate the efficacy of intravenous VPA in chronic migraine. Methods: We included 8 patients, 4 females and 4 males, with a median age of 15.6 years, with chronic refractory migraine. All underwent neuroimaging puncture with measurement of intracranial pressure. A standardized patients and lumbar the severity, monthly protocol of repetitive infusion of VPA was applied (first dose at 15 mg/kg, in 30 minutes and thereafter at 5 mg/kg every 6 hours for 12 doses). Prophylactic therapy with oral VPA was initiated in patients with positive response to intravenous treatment. The response to treatment at VPA was evaluated by analyzing frequency of headache and the use of attack medications before, during, after VPA infusions and during oral therapy. Results: 4 patients reported a good response to treatment for pain reduction and so oral treatment with VPA was continued. At the revaluation to 12 weeks: 2 patients, for a high frequency of migraine, have needed to undertake other prophylactic treatments; 2 patients reported a decrease in monthly frequency and intensity of attacks. The headache frequency, as well as the intensity of pain and the use of drugs for attack did not show a significant reduction compared to before intravenous treatment with VPA in the 4 patients, who had a good response on the intensity of pain during infusion: the median of frequency of monthly attacks was 20, the median of intensity was 6.5/10 and the median of the use of drugs for the attack 16. Conclusion: We observed how intravenous treatment with VPA in pediatric patients with chronic refractory migraine can reduce in acute the intensity of the attack during the infusion and in the days following treatment; while the continuation of oral treatment in following three months would not show as much effectiveness in reducing frequency, intensity of pain and the use of drugs. P288 Acute medication overuse in people with migraine from the 2022 European National Health & wellness survey M. Lewis1, A. Jenkins2, J. Cirillo1, K. Hygge Blakeman3, J. Yang1, L. Abraham2, J. Brown1 1Pfizer, Inc, New York, NY, United States 2Pfizer Ltd, Tadworth, United Kingdom 3Pfizer AB, Stockholm, Sweden Objective: Acute medication overuse (AMO) is a cycle of high-frequency analgesic use, such as triptans and non-steroidal anti-inflammatory drugs (NSAIDs), that may result in medication overuse headache (MOH). There is limited understanding of the frequency of analgesic use of both prescription and over-the- counter analgesics among people with migraine (PwM) in Europe. Methods: Using the 2022 5-country European National Health and Wellness Survey (NHWS, Oracle Life Sciences), patients diagnosed with migraine receiving >=1 acute medication were described. AMO

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criteria were: 1) >=10 cumulative days per month with use of triptans, combination analgesics, ergotamines, or opioids; or 2) >=15 days of nonopioid analgesic, acetaminophen, or NSAID use. AMO was assessed separately among analgesics for migraine only and those used for migraine plus other pain conditions. Results: Among over 16.7 million PwM represented by the survey, 21.2% reported AMO of migraine-specific medications and 36.9% had AMO after including medications used for other conditions (Table 1). Over half (51.4%) met the first AMO criterion with a cumulative mean [SD] of 21.0 [14.1] days and 61.5% met the second criterion with 28.3 [15.9] cumulative days. PwM with AMO versus without AMO reported higher use of prescribed triptans (38.4% vs. 29.9%), NSAIDs (66.4% vs. 51.4%), and opioids (33.6% vs. 12.5%). People with AMO had higher migraine disability scores, productivity loss, and healthcare resource utilization with life compared to those without AMO. Conclusion: AMO is common in over 20% of PwM and related to poorer quality of life. Treatments not associated with MOH are needed in this population. lower quality of Fig. 1 P289 Influence of withdrawal from overused drug on central sensitization mechanisms in chronic migraine with medication overuse headache G. Sebastianelli1, F. Casillo1, C. Abagnale1, C. Di Lorenzo1, G. Coppola1 1Sapienza University of Rome, Department of Medico- Surgical Sciences and Biotechnologies, Latina, Italy Objective: Chronic migraine with medication overuse neurophysiologically headache (CM-MOH) is influence by the analyzing investigate drugs characterized by increased cortical excitability with sensitization at both thalamocortical and cortical levels. It is unclear whether the increased cortical excitability is due to a brain state (due to the medication overuse) or a brain trait. In this study, we if the withdrawal from the aim to can overused these neurophysiological variables. Methods: Somatosensory evoked potentials (SSEPs) were performed by electrical stimulation of the median nerve (M), ulnar nerve (U) and simultaneous stimulation of both nerves (MU) in 14 patients with MOH before (T0) and after (T1) a three-week withdrawal protocol. We measured the level of thalamocortical (pre-HFO) and cortical activation (post-HFO) high-frequency oscillations (HFOs) embedded in parietal N20 median SSEPs and calculated the habituation and the degree of cortical lateral inhibition (dLI) of N20-P25 low- frequency SSEPs. Results: After the three-week withdrawal protocol (T1), we observed a normalization of the baseline (T0) habituation deficit (T0: +0.096 ± 0.538; T1: -0.532 ± 0.803; p= 0.040) and a reduction in the amplitude for both pre-HFO (p< 0.009) and post-HFO (p= 0.042), while no effects were observed on the dLI at T1 (p= 0.141). These changes were not influenced by the reduction in headache days as no differences emerged between responders (RR ≥50%) and non- responders. Conclusion: Our findings showed that withdrawal from overused drugs can influence and restore the increased excitability at both thalamocortical and cortical CM-MOH independently from the reduction of headache days. It could be hypothesized increased excitability is a brain state due to medication overuse rather than the headache frequency. patients with that the levels in P290 Iron deposition in periaqueductal gray matter for migraine and medication-overuse headache: an observational study based on quantitative susceptibility mapping K. Liu1 1The Second Affiliated Hospital, Zhejiang University School of Medicine, Neurology Department, Hang Zhou, China Objective: Medication overuse headache (MOH) is a complex headache disorder most secondary to migraine and excessive analgesic intake. We aim to investigate the regional iron deposition in subcortical nuclei of chronic migraine (CM) patients with MOH as compared to those without MOH (wMOH), and their relationship to the disease outcome.

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Impact iron content in subcortical Test, Migraine Methods: Chronic migraineurs with or without MOH were recruited. All subjects underwent Magnetic Resonance Imaging and recorded clinical variables including migraine duration, analgesic use, 6-item Headache Disability Assessment, depression，anxiety and sleep quality. MOH patients were assessed for relapse rate among one year and Severity of Dependence Scale. Quantitative susceptibility mapping quantified the regional regions. Associations between clinical variables and regional iron deposition were analyzed. Results: We recruited 72 chronic migraine (CM) patients [40 MOH and 32 wMOH]. MOH patients showed decreased in the ventral pallidum (VeP) and putamen (Pu) when compared to wMOH patients. Iron deposition in the VeP emerged as the most valuable markers, negatively associated with analgesic dependence and relapse. The volume of iron in the VeP could distinguish MOH patients with or without relapse, with a sensitivity of 78.6% and specificity of 90.0%. Conclusion: These findings provide evidence that iron content in the VeP and Pu may distinguish CM those without patients with MOH MOH,particularly,the VeP may serve as the biomarkers for analgesics dependence and relapse in MOH patients.This insight could ehhance our understanding of the vascular and neural mechanisms underlying MOH and aid in predicting recurrence rates in these patients. iron content from Fig. 1 Fig. 2 Fig. 3

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P291 Analysis of demographic and comorbid factors in age- and sex matched groups of patients with and without medication overuse headache E. Lebedeva1, I. Kniazeva1, D. Gilev1, J. Olesen1 1the Ural State Medical University, International Headache Center, Yekaterinburg, Russian Federation Objective: The purpose of the study: to conduct a comparative analysis of demographic factors and comorbid pathology in patients with medication overuse headache (MOH) and age- and sex matched controls. Methods: A prospective study was conducted at the International Headache Center "Europe-Asia". The main group included patients with primary headache disorders aged 18 years and older who had MOH. The control group consisted of patients with primary headache disorders equal in gender and age to patients with MOH. Patients of both groups underwent a semi-structured interview and additional examinations including MRI of the brain when indicated. Results: The study included 171 patients with MOH (mean age 43.3 years, 82% women) and 173 patients without MOH (mean age 41.4 years, 75% women). Chronic migraine was more prevalent in the MOH group (53% and 16%, respectively, p < 0.001; OR 5.9; 95% CI 3.6–9.8). A third of patients in both groups had chronic tension-type headaches. Episodic migraine and episodic TTH were more prevalent in patients without MOH (p < 0.001). Patients in the MOH group were more likely to be divorced (11.7% and 2.9%, respectively, p=0.002; OR 4.5; 95% CI 1.6-12.2). Most patients (76%) in both groups were employed and had higher education (65% with MOH and 74% without MOH). Out of analysing be exact 20 comorbid disorders, three factors were most often associated with MOH: chronic insomnia (60.2% and 47.4%, respectively, p=0.02, OR 1.7, 95% CI 1.1-2.6), restless legs syndrome (37.4% and 22%, respectively, p=0.002, OR 2.1, 95% CI 1.3-3.4) and subjective cognitive deficit (76% and 53.2%, respectively, p <0.001, OR 2.8, 95% CI 1.8- 4.8). Conclusion: Sleep disturbances, subjective cognitive deficits, and divorced status of patients are most often associated with MOH, which indicates the role of these factors in MOH pathophysiology and opens up new opportunities for their prevention. P292 Is the 15-day threshold in the definition of migraine worsening associated to medication overuse reasonable L. Zanandrea1,2, R. Messina1,2,3, I. Cetta1,2,3, F. Genovese1,2,3, I. Chinali1, B. Colombo1,2, M. Filippi1,2,3 1IRCCS San Raffaele Scientific Institute, Neurology Unit, Milano, Italy 2Vita Salute San Raffaele University, Milano, Italy 3IRCCS San Raffaele Scientific Institute, Neuroimaging Research Unit, Milano, Italy According to the collected. Between-group differences International Objective: Classification of Headache Disorder (ICHD) criteria, migraine worsening related to medication overuse (MO) can occur only in patients with chronic migraine. This study aimed to evaluate whether a cut-off of 15 headache days is adequate to identify those patients with significant MO-related burden. Methods: Ninety (45 episodic and 45 chronic) patients met the criteria for MO and were enrolled. Migraine- related disability and impact were assessed using the MIDAS and HIT-6 scales. The severity of the attacks was assessed in terms of pain intensity and presence of ictal cutaneous allodynia, using the NRS and ASC-12 scales. Symptoms experienced by patients during the premonitory, headache and postdromal phases were also in demographic and clinical variables were assessed with the Chi-squared, Exact Fisher, independent Student's t-tests or the Mann–Whitney test. Results: There were no significant between-group differences in migraine-related disability. Compared to episodic patients with MO (EM-MO), patients with chronic migraine and MO (CM-MO) showed higher median HIT-6 scores. Neither the headache pain intensity nor allodynia symptoms differed between EM-MO groups experienced a high number of migraine-associated symptoms. Except for an increased trend of fatigue occurrence during the prodromal phase in patients with CM-MO compared to patients with EM-MO, no significant between-group differences were found for all other symptoms. Conclusion: Regardless of the type of migraine, MO is associated with high disease impact, and severe headache attacks with a broad spectrum of symptoms. Limitations include the clinic-based sample and lack of non-MO control groups. Adhering strictly to the 15-day cut-off recommended by the ICHD criteria for migraine worsening associated with MO might result in underestimating the prevalence of this phenomenon and its consequences. and CM-MO patients. Both

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P293 The evaluation of childhood trauma, theory of mind, and Alexithymia in patients with migraine and medication overuse headache T. Bektaş1,2, E. Aciman Demirel1,2, B. Açıkgöz3, M. Açıkgöz1,4, U. Çelebi1,2, H. T. Atasoy1,4 1Zonguldak Bulent Ecevit University, Neurology, Zonguldak, Turkey 2Zonguldak Bulent Ecevit Faculty of Medicine, Neurology, Kozlu/Zonguldak, Turkey 3Zonguldak Bulent Ecevit Faculty of Medicine, public health, Kozlu/Zonguldak, Turkey 4Zonguldak Bulent Ecevit Faculty of Medicine, Neurology, Kozlu/Zonguldak, Turkey (RMET), alexithymia Objective: Investigate childhood trauma, theory of mind, and alexithymia in migraine and medication overuse headache (MOH) patients. This is the first such study in our country. We compared the frequency of these conditions to assess if they are risk factors for MOH development. Methods: Prospective study enrolling migraine and MOH patients at Zonguldak Bülent Ecevit University Neurology Clinic (Jan 16, 2023 - Jan 16, 2024). We used validated scales to assess childhood trauma, theory of mind (TAS-20), depression/anxiety (BDI/BAS), and quality of life (SF- 36). Results: 54 migraine and 50 MOH patients participated. MOH patients had significantly lower quality of life, higher TAS-20 scores (indicating more alexithymia), and lower CTQ total scores (suggesting less overall childhood trauma) but higher scores on specific CTQ subscales. MOH patients also performed worse on the RMET (theory of mind test). showed greater Conclusion: MOH symptoms, and alexithymia, depression/anxiety specific childhood trauma experiences compared to migraine patients. Additionally, the MOH group performed worse on the theory of mind test. These findings suggest that psychological factors may be risk factors for MOH development. patients P295 Shall we treat children with migraine? M. Valeriani1, F. Ursitti1, G. Sforza1, G. Monte1, S. Tarantino1, M. Proietti Checchi1, I. Frattale2, M. Tarantini1, L. Papetti1 1Ospedale Pediatrico Bambino Gesù, Developmental Neurology Unit, Rome, Italy 2Tor Vergata University, Child Neuropsychiatry, Rome, Italy In 2017, the prophylaxis of pediatric Objective: migraine was revolutionized by the results of CHAMP study showing that placebo was not inferior to both aimed at chronic migraine topiramate and amitriptyline (Powers et al, 2017). This raised several doubts about the utility of medications in young migraineurs. In the present study, we investigating whether pharmacological prophylaxis of pediatric migraine could: 1) improve the efficacy of the medications for the acute migraine attack, and 2) counteract the progression of an episodic migraine toward a chronic form. Methods: In the first study, we recruited 70 pediatric patients with undergone pharmacological prophylaxis. We compared the percentage of non-responders to acute treatment before and after migraine prophylaxis. In the second study, 165 pediatric patients with episodic migraine at T0 were divided in two groups: the fist undergone prophylactic treatment (PT), and the second without prophylaxis the percentage of patients with chronic migraine between PT and noPT groups. Results: In the first study, we showed that after prophylaxis, the prevalence of patients responding to the analgesic drugs increased from 27% to 71.4%. The bivariate analysis identified only prophylactic therapy as a factor associated with response to acute therapy (R 0.9; C.I. 0.7–0.95; p < 0.05). In the second study, among PT patients only 14% evolved into chronic migraine, while migraine chronicization was observed in 89% of noPT patients (Chi-squared test, p<0.001). Conclusion: We showed that, in children and adolescents with migraine, prophylactic treatment is able to: 1) improve the efficacy of the medications for the acute attack, and 2) to reduce the risk of migraine chronification. (noPT). At T1, we compared P296 REPICEF Project. High prevalence of primary headaches in school-age children – an Italian school- based study A. Onofri1, C. Rosignoli1, V. Trozzi1, R. Ciuffini2, R. Ornello1, S. Sacco1 1University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy 2University of L'Aquila, Department of Clinical Medicine, L'Aquila, Italy Objective: The "Registro EPIdemiologico delle CEFalee in età evolutiva" project (REPICEF) aims to provide a comprehensive analysis of headache prevalence, characteristics, and comorbidities in school-aged children. Methods: REPICEF is a prospective study involving students aged 6 to 17 from schools in L'Aquila, Italy. Parents provided Italian the Headache-Attributed Restriction, version of informed consent. The

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Disability, Social Handicap and Impaired Participation questionnaire (HARDSHIP) was used to evaluate headache characteristics and diagnoses, while the KINDL® test assessed quality of life. Results: From January to May 2024, 286 students (55.2% female, mean age 11.6±3.4 years) were included. Of these, 244 (85.3%; 95% CI:74.9-96.7) experienced at least one headache in the past year; 64 (22.4%;95% CI: 17.2-28.6) were diagnosed with migraine and 27 (9.4%; 95% CI: 6.2-13.7) with tension- type headache (TTH). Fifty-four students (84.4%; 95% CI: 63.4-1) had episodic migraine. Probable diagnoses included 87 children (30.4%; 95% CI: 24.4-37.5) with probable migraine (pMigraine) and 66 (23.1%; 95% CI: 17.8-29.4) with probable TTH (pTTH); 32 (11.2%; 95% CI: 7.7-15.8) had unspecified headache. The KINDL® test showed a mean score of 29.1±3.6 for children with any headache, indicating poor quality of life. Conclusion: REPICEF project highlights the high prevalence of headaches in children and adolescents. It is crucial to educate families and teachers on this condition's for children. managing Understanding in this population for developing effective interventions and long-term management plans. impact and provide and affected trajectories is essential supporting strategies headache P297 Diagnosing migraine in children and adolescence using ID-Migraine: results of an Italian multicenter validation I. Frattale1, V. Sciruicchio2, D. D'Agnano2, V. Raieli3, S. Lo Cascio4, G. Santangelo3, E. Correnti3, F. Ursitti5, G. Sforza5, G. Monte5, L. Mazzone1, M. Valeriani1,5, L. Papetti5 1Tor Vergata University of Rome, Rome, Italy 2PO San Paolo, children epilepsy and EEG center, Bari, Italy 3Ismep-Arnas Civico Palermo, Child Neuropsychiatry, Palermo, Italy 4University of Paleremo, Child Neuropsychiatry, Palermo, Germany 5Bambino Gesù Children Hospital, IRCCS, Developmental Neurology Unit, Rome, Italy Objective: Migraine is the most frequent neurological condition. For adulthood ID-Migraine, is a screening tool that allows migraine diagnosis. For pediatric age no validated tools are available. The aim of this study is to validate ID-Migraine for diagnose migraine in developmental age. Methods: All patients attending the Headache Center of the Bambino Gesù Children"s Hospital in Rome, San Paolo Hospital in Bari and Civico Hospital in Palermo (Italy), in the period January 2022 - February 2024 aged 6-17 years were included in the study. and neurological The administered questionnaire was that validated in Italian for adult migraineurs by Brighina et al. The diagnosis according with the ICHD3 criteria, formulated at the end of visit, was matched with the answers provided to the ID-migraine. Specificity, sensitivity, negative and positive predictive factor were statistically evaluated. They were considered reliable for values >80%. Results: 289 pediatric patients (mean of 12.14 years ± 3.15, range 6-17), were enrolled and answered to the Italian version of the ID-migraine for adulthood. Clinical examination were performed, and headache diagnosis was postulate according to ICHD3 criteria. 230 patients received migraine diagnosis and were included in the migraine group, while 59 received other headache diagnosis and were included in the control group. Considering ID-Migraine, the specificity, sensitivity, negative and positive predictive values were statistically evaluated. Considering the positive response to the ID-Migraine, i.e the presence of 2 positive responses, the sensitivity was 0.86 (86%), the specificity 0.95 (95%), the PPV 0.98 (98%) and NPV 0.64 (64%). Conclusion: From our results ID-Migraine can be considered a valid tool to diagnose migraine also in pediatric age starting from 6 years. response the to P298 Pediatric migraine severity: Understanding the association with cognitive and psychological dimensions S. Tarantino1, M. Proietti Checchi1, L. Papetti1, F. Ursitti1, G. Monte1, G. Sforza1, M. Valeriani1,2,3 1Bambino Gesù Hospital, Rome, Italy 2Tor Vergata University of Rome, Systems Medicine Department, Rome, Italy 3Aalborg University, Center for Sensory-Motor Interaction, Aalborg, Denmark between cognitive Objective: This study explores the prevalence of neuropsychological difficulties and learning disabilities in pediatric migraine patients and examines the association performance, psychological symptoms, and migraine severity. Methods: We included 34 children with migraine (m.a=12.6, SD=2.47; F=21, M=13). We assessed the following variables: verbal memory (forward and fluency, attention and backward span), verbal executive the naming, inhibition and switching subtest), processing speed, anxiety and depression symptoms. Migraine episodes were categorized as:1) high frequency (weekly to daily) and 2) low frequency (≤3 per month). Moreover, subjects were divided into those who were taking prophylactic drugs (or needed prophylactic (the visual attention, functions

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lower scores switching tasks. A frequency exhibited treatment within the past year) and those who did not require medications. Results: We identified borderline and clinical scores in 51.85% of our sample for naming, and in 62.96% for inhibition and substantial proportion of patients (>40%) scored below the normal range in the speed performance of these tasks. We found that 64.70% of the patients tested positive for learning disabilities. Patients with high migraine in backward digit span (p=0.030); on the other hand, they had higher scores in school anxiety (p=0.022) and irritable mood (p=0.036). The use of prophylactic treatment with neuropsychological fragilities or the presence of learning disabilities (p>0.05), but it was associated with school-anxiety (p=0.007) and irritable mood (p=0.015). Conclusion: Our study suggests that pediatric migraines may be associated with difficulties in speed performance tasks, involving executive functions, and learning difficulties. Since no association was found between the need for prophylactic treatments and neuropsychological performance, we suppose that anxiety may be the most relevant factor associated with migraine severity. associated was not in emerged differences (p=<0.001). While (p=0.004). No the catastrophizing domains among patients based on headache family history (p=>0.050). Migraine-affected parents had significantly lower scores compared to non-migraine-affected parents in the "Rumination" (p=0.003) and "PCS-total score" (p=0.025) domains. Comparing patients and their migraine-affected parent, we observed significantly higher scores in patients in the "PCS-total score" and "Helplessness" domains the catastrophizing tendency of migraine-affected parents does not correlated with that of their children, we observed a positive correlation between the "Helplessness" of non-migraine-affected parents and some domains in their children, such as "Magnification" (p=0.025), "Helplessness" score" (p=0.004). Additionally, a positive correlation is also present between the "PCS-total score" of the non- migraine-affected parent and the "PCS-total score" of their child (p=0.030). Conclusion: Migraine-affected parents show lower catastrophizing levels than those unaffected. Although not significantly different, patients with a migraine- affected parent show slightly levels of catastrophizing suggesting a potential influence on pain management approaches. (p=0.004) and "PCS-total lower P299 Pain catastrophizing in parents and their children – a comparison between parents with and without migraine M. Proietti Checchi1, S. Tarantino1, F. Ursitti1, G. Monte1, G. Sforza1, M. Valeriani1,2,3, L. Papetti1 1Bambino Gesù Children Hospital, IRCCS, Developmental Neurology Unit, Rome, Italy 2Tor Vergata University, Systems Medicine Department, Rome, Italy 3Aalborg University, Center for Sensory-Motor Interaction, Aalborg, Denmark 2) aimed compare potential relationships characteristics; Objective: We to: 1) explore pain catastrophizing in children and its association with headache pain catastrophizing between patients and parents; 3) analyze between catastrophizing domains in patients and parents. Methods: We included 90 patients (m.a. 12.3±2.6) with migraine without aura, along with one of their parents. Patients were divided based on: (1) attack frequency; (2) pain intensity; (3) medication efficacy; (4) migraine status of parents. Pain catastrophizing was assessed using the PCS/PCS-C. Results: In our sample, there were no significant differences in catastrophizing domains according to migraine pattern except for pain intensity. Patients with severe pain showed higher "Magnification" score P300 Idiopathic Intracranial hypertension: long-term follow-up finding in children and adolescent patients G. Aliyeva1, G. Altıokka Uzun1, P. Topaloğlu1, M. Eraksoy2, Z. Yapıcı2 1Istanbul Faculty of Medicine, Istanbul University, Department of Neurology, Istanbul, Turkey 2Istanbul University, Istanbul Faculty of Medicine, Department of Neurology, Division of Child Neurology, Istanbul, Turkey cerebri. Idiopathic Objective: Idiopathic intracranial hypertension (IIH) is a syndrome of increased intracranial pressure that develops without a secondary cause and is also called pseudotumor intracranial hypertension is a diagnosis made by excluding structural and vascular lesions and systemic causes.IIH prevalence is 0.6-0.71/100,000. Headache is one of the most common symptoms of IIH in pediatric patients. the Methods: We demographic data, and treatment responses of 29 patients (F/M 23/6) diagnosed with IIH (2000-2022) in our clinic. Results: The average age of patients was 12.45 (±2.85)years, and clinical onset was 11.90 years. Five had a family history of migraine. Common admission reasons were headache (24) and double vision (12). Headache was migrainous in 37.9% and tension-like in examined imaging, retrospectively radiological

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acetazolamide, treated with 34.5%, often in the frontal and temporal regions, with 65.5% bilateral. Nausea was present in 41.4%. Neurological exams showed CN VI palsy in 10 patients and bilateral papilledema in 21. Cranial MRI was normal; 13.8% had transverse sinus hypoplasia. The average lumbar puncture opening pressure was 327.14. The average follow-up was 45.73 months. Of those 34.48% discontinued without recurrence, 13.79% had normal visual fields, 37.93% had no papilledema, and 20.68% resolved CN VI paralysis. One had recurrent headaches after 2 months, and one developed severe optic atrophy. Conclusion: IIH in children is a rare disease that requires attention to most important distinguishing clinical findings such as vision loss or papilledema. The clinical picture in children can be variable and less pronounced than in adults. Follow-up of patients after remission and discontinuation of treatment is also important due to the possibility of recurrence of the disease. P301 Six months real-world evidence analysis of Remote electrical neuromodulation (REN) for migraine prevention in adolescents D. N. Lax1, S. Shmulei2, L. Rabany2, Y. Asmar2, D. Harris2, A. Ironi2, T. S. Monteith3 1Albert Einstein College of Medicine, New York, NY, United States 2Theranica Bio-Electronics Ltd., Natanya, Israel 3University of Miami, Miller School of Medicine, Miami, FL, United States Objective: The current analysis focuses on a subset of adolescents with migraine who participated in a real- world evidence study, examining the safety and effectiveness of Remote Electrical Neuromodulation (REN) preventive treatment over six months of use. Methods: Nerivio-naïve adolescents who were prescribed Nerivio for migraine prevention by their healthcare provider and treated with the device once between July 2023-January 2024 were electronically invited to participate. Following electronic screening, patients electronically signed informed consent. Participants (N=62) were requested to treat for prevention and report symptoms daily via Nerivio"s in-app electronic-diary for six months. MITT criteria: treatments≥10 and reports≥22 per month. Wilcoxon non-parametric paired test was used to compare the average number of monthly migraine days (MMDs). Results: Twenty mITT participants aged 12-17 (mean 15.6±1.5) years were analyzed at the end of the third month, and 14 at the end of the sixth month. The average number of MMDs was reduced by 2.81 at the least some degree of end of the third month (p=0.067), and by 5.06 at the end of the sixth month (p=0.048), see figure. In the patient global impression of change (PGI-C) at the end of the sixth month, 81.8% of participants indicated at improvement (36.4% minimally improved, 45.5% much improved, 0% very much improved), 9.1% reported no change, and 9.1% reported being worse. Of 62 ITT participants, four reported mild device- related adverse events reported moderate/severe DAEs. Conclusion: The reduction of 2.81 MMDs at the end of the third month, and 5.06 MMDs at the end of the sixth month support the long-term effectiveness of REN for migraine prevention in adolescents, and highlight REN's effective non- pharmacological treatment option. A high rate of self- reported improvement was also documented, along with a low incidence of adverse events. Further research in a larger sample is needed. (DAEs). None an role as Fig. 2 P302 Contraception in girls and young women with epilepsy and migraines L. Knedlíková1, P. Mužlayová1, K. Česká1, S. Kolář1, P. Danhofer1 1Faculty of Medicine of Masaryk University and University Hospital Brno, Pediatric Neurology Department, Bron, Czech Republic Objective: This project aimed to map the current situation regarding the awareness of patients with epilepsy and migraines on issues of planned parenthood and the use of hormonal contraception (HC), particularly considering the interactions with antiseizure medication and the risk of vascular complications. Methods: The study included patients diagnosed with migraines and epilepsy at the Department of Pediatric Neurology at Faculty of Medicine of Masaryk University and University Hospital Brno, as well as in

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the outpatient sector. Data were collected using printed and online questionnaires completed by patients or their legal guardians. The questionnaires included demographic information, general questions about reproductive health, awareness, and experience with HC. included 56 patients with Results: The study migraines, 12 with epilepsy, and 13 control subjects. The results showed that 30.36% of patients with migraines and only 5.26% with epilepsy used HC. Only 15% of patients with migraines consulted the initiation of HC with a neurologist, while 36% were informed about the increased risk of thrombophilia. The analysis also revealed that 70% of patients with migraines experienced a worsening of symptoms when using HC. Conclusion: The study revealed insufficient awareness and communication between patients with migraines and epilepsy and their doctors regarding the use of HC and associated risks. The results highlight the need for interdisciplinary improved patient education and communication and gynecologists to optimize care and reduce the risks associated with HC use. neurologists between included This meta-analysis interstudy heterogeneity. A heterogeneity of I2 > 50% was considered significant. 26,967 Results: participants with mean age of 15.32 ±5.2 years and 49.4% of the total were males. The average reported screen-time was 5.54 ±2.3 hours/day. The pooled prevalence of screen-related headache was 35% (7182/26967) [95% CI 28%-41%, I2=98.97%], migraine was 40% (362/1846) [95% CI 22%-59%, I2=97.6%], tension-type headache was 17% (78/457) [95% CI 5%- 30%, I2=94.75%], migraine without aura was 27.7% (101/362) [95% CI 23%-32%, I2=0%) and migraine with aura was 18% (59/337) [95% CI 9%-28%, I2=79%] among children and adolescents. The pooled prevalence of participants having 2-6 hours/day screen-time was 45% (1460/4289) (95% CI 21%-68%, I2=99.38%). Conclusion: We found a high prevalence of headache, migraine, tension-type headache, migraine with and without aura among children and adolescent due to increased screen exposure. This suggests a potential relationship between screen-time and headache. Robust studies with larger sample size are required to establish conclusive association between increased screen-time and headache. Fig. 1 P303 Prevalence of screen-related headache and migraine among children and adolescents – a systematic review and single-arm meta-analysis M. N. Saddique1, M. Safiullah1, H. Javaid1, N. U. A. Saleem2, M. Qadri3, S. U. Muneer4, A. Naseem1, A. R. Azam1, S. Shamoon5 1King Edward Medical Univseristy, Lahore, Pakistan 2FMH College of Medicine and Dentistry, Lahore, Lahore, Pakistan 3Jinnah Sindh Medical University, Karachi, Pakistan 4Shaikh Khalifa Bin Zayed Al Nahyan Medical and Dental College, Lahore, Pakistan 5Rawalpindi Medical University, Rawalpindi, Pakistan Objective: Prolonged screen exposure is often linked to headaches. This study explores the link between screen time and headache types in children and adolescents, examining how screen time duration contributes to headache prevalence. Methods: The PubMed, Embase, Scopus and Cochrane databases were systematically searched using relevant keywords from inception until May 31, 2024. A total of 7 studies fulfilling predefined selection criteria were included in this meta-analysis. We performed meta-analysis of prevalence using "metafor" package in R Studio (version 4.3). We pooled the prevalence rate presented with the corresponding 95% confidence interval (CI) using the random effects model. I2 test was used to evaluate

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P304 Headache in children and adolescents – a school- based screening study F. Pistoia1, G. Saporito1, F. Guerra2, D. Di Giacomo2, A. Cavicchio2, E. Tozzi2 1University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy 2University of L'Aquila, Department of Life, Health and Environmental Sciences, L'Aquila, Italy using (HARDSHIP) Participation self-completed Objective: The objective of this study was to investigate the burden of headache among children (aged 6–11 years) and adolescents (aged 12–15 years), through a school-based screening study. Methods: This study was a cross-sectional survey conducted structured questionnaires administered in five primary and secondary schools in the L'Aquila district. After obtaining a signed informed consent from parents, the child or adolescent versions of the Headache- Attributed Restriction, Disability, Social Handicap and Impaired structured questionnaires were administered. Results: A total of 431 students were included in the study (mean age±SD 9.82±2.28, 53% females; 290 attending the primary school and 141 the secondary school). At least one headache attack in the past year was reported by 178 primary school children (61%) and by 122 adolescents attending secondary school (87%). In both age groups, the pain was not strictly unilateral (45% bilateral pain; 38% pain at vertex onset; 17% unilateral), lasted less than an hour (56% elementary school children; 34% adolescents), and was of mild intensity (51% primary school children; 62% adolescents). The pain was mainly described as constrictive/gravative by primary school children (50%) and as throbbing (49%) by adolescents. The most symptom was phonophobia (80%), followed by photophobia (40%), nausea (24%) and vomiting (8%). A high percentage of participants (49%) reported at least one attack in the past 4 weeks (minimum 2 - maximum 28), with the need of at least one symptomatic drug (17%; minimum 2- maximum 10), more than one day missed at school (8%; minimum 2 - maximum 20) and for leisure activities (17%; minimum 2 - maximum 10). Conclusion: Pediatric migraine shows a different clinical pattern as compared to adult migraine, presenting with shorter attacks, less pronounced lateralized and pulsating pain, and milder intensity. Headache disability is relevant. associated frequently P305 Familial visual snow syndrome – a case report I. Frattale1, F. Ursitti2, G. Sforza2, G. Monte2, M. Valeriani1,2, L. Papetti2 1Tor Vergata University of Rome, Rome, Italy 2Bambino Gesù Children Hospital, IRCCS, Developmental Neurology Unit, Rome, Italy It (VSS) Snow syndrome Objective: Visual is characterized by continuous tiny dots across the entire visual field persisting for >3 months with at least 2 between palinopsia, enhanced entoptic phenomena, photophobia and nyctalopia. is frequently associated with migraine. Differentiating VSS from persistent migraine aura can be a challenge, as some symptoms are common to both conditions. Neuroimaging studies have shown that the lingual gyrus is involved in photophobia during migraine; these data suggest that VSS and migraine share pathophysiological mechanisms. Methods: We describe the case of a boy who came to our attention at the age of 10 years for persistent headache with vomiting and evidence of papilledema. Results: Brain MRI was performed which showed signs of intracranial hypertension, lumbar puncture with evidence of raised ICP (40 cmH20) and normal ERG-Flash and VEP. Once the diagnosis of idiopathic intracranial hypertension was confirmed, therapy with acetazolamide was started for about a year until the papilledema he have continued migraine episodes.During a follow up visit he reported enhanced entoptic phenomena and photophobia and persistent colored dot vision in association with sporadic episodes of migraine lasting for 6 months. A repeat brain MRI and ERG-Flash and VEP were normal. Investigating the family history, the mother reports having the same type of persistent vision since she was a child and having undergone ERG-Flash and VEP, brain MRI, EEG and psychiatric evaluation over time, all reported normal. He also presents episodes of migraine with aura in which the reported visual symptom is scotoma. Conclusion: The symptoms described by th patient and his mother fill the criteria for Visual Snow Syndrome with co-occurrence of migraine. To date, no other familial visual snow cases are reported in the literature. It would be interesting to evaluate a common genetic implication on a larger sample of patients. disappearance. Subsequently occasional to

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P306 Molecular-enriched functional connectivity changes after mindfulness practice in serotonin and dopamine systems of medication overuse headache patients D. Fedeli1, G. Ciullo1,2, G. Demichelis1, J. P. Medina Carrion1, M. G. Bruzzone1, E. Ciusani3, A. Erbetta1, M. Grisoli1, E. Guastafierro4, D. A. Montisano5, D. D'Amico5, A. Raggi4, A. Nigri1, L. Grazzi5 1Fondazione IRCCS, Department of Neuroradiology, Milano, Italy 2University of Parma, Department of Medicine and Surgery, Parma, Italy 3Fondazione IRCCS, Department of Diagnostic and Technology, Milano, Italy 4Fondazione IRCCS, Neurology, Public Health and Disability Unit, Milano, Italy 5Fondazione IRCCS, Neuroalgology Unit and Headache Center, Milano, Italy changes in brain is effective Objective: Mindfulness in managing Chronic Migraine associated with Medication Overuse improvements Headache (CM-MOH), with clinical associated with functional connectivity (FC). However, the relationship between these findings and the underlying neurotransmitter systems remains unexplored. In this study, we adopted the recent molecular-enriched connectivity framework to investigate one-year longitudinal FC changes associated with serotonin, dopamine, and noradrenaline receptors and transporters distribution in CM-MOH patients treated with mindfulness practice alongside treatment as usual. Methods: 34 adult CM-MOH patients from a previous RCT (Grazzi et al., 2023) were divided into two groups: Treatment as Usual (TaU, 17) and mindfulness-added- to-TaU (TaU+MIND, 17). Participants underwent rs- fMRI scans before and after 1 year. Longitudinal and differences noradrenaline molecular-enriched were investigated with REACT. Results: TaU+MIND group compared with TaU showed increased dopamine-enriched FC in the right anterior insula and increased serotonin-enriched FC in caudate/accumbens nuclei. Conclusion: Dopamine-enriched insular connectivity may reflect a mindfulness-related remodulation of the emotional processing of nociceptive information, as dopamine regulates motivation, mood, and addiction. Insular FC changes have been recently observed in TaU+MIND CM-MOH patients and associated with diminished depression and with sensory input integration through the Salience Network (Fedeli et Increased serotonin-enriched FC with al., 2024). caudate/accumbens a normalization of the serotonergic system, which is dysregulated in chronic pain conditions and in mood nuclei may dopamine, serotonin, in FC indicate disorders. These regions play an important role in the emotional, cognitive, and sensory modulation of pain experience. Our deeper understanding of the neural correlates of mindfulness practice, highlighting its beneficial clinical effects for CM-MOH treatment. provides study a P307 Analysis of MRI-based microstructural and functional resting-state network correlation: insights into the activity of the hypothalamic-thalamo-cortical network in patients with episodic cluster headache C. Abagnale1, A. Di Renzo2, G. Giuliani3, G. Sebastianelli1, F. Casillo1, F. Caramia3, V. Di Piero3, G. Coppola1 1Sapienza, Department of Medico-Surgical Sciences and Biotechnologies, Latina, Italy 2IRCCS, Fondazione Bietti, Rome, Italy 3Sapienza, Department of Human Neurosciences, Rome, Italy Objective: We searched for differences in resting- state functional connectivity (FC) between brain networks and its relationship with the microstructure of the hypothalamus and the thalamus between episodic CH patients during the bout and healthy controls (HCs). Methods: We collected 3T MRI data from 26 patients with CH between attacks and compared them with data from 20 HCs. We collected resting state data among independent component (IC) networks. We calculated fractional anisotropy (FA), mean (MD), axial (AD), and radial (RD) diffusivity values of the hypothalamus and bilateral thalami and correlated them with resting state ICs Z-scores and CH clinical features. Results: Patients with CH had less FC between the salience network and the left executive control network (ECN) than HCs but more FC between the default mode network and the right ECN. CH patients showed lower FA and higher MD, AD, and RD microstructural hypothalamic metrics than HCs. CH patients had a higher bilateral FA metric of the thalamus than HCs. AD and RD diffusivity metrics of the hypothalamus correlated positively with the duration of disease history. We found no correlations between hypothalamus and thalamus diffusivity metrics and cortical networks' FC. Conclusion: This study's findings highlight the first evidence of abnormal intra-network connectivity at rest, coupled with significant differences in thalamic and hypothalamic microstructure. These factors may independently contribute to the pathophysiology of cluster headaches, marking a significant step forward in our understanding of this condition.

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P308 Functional connectivity alterations in medication overuse headache G. Demichelis1, D. Fedeli1, J. P. Medina Carrion1, G. Ciullo1, D. A. Montisano2, D. D'Amico2, A. Erbetta1, S. Ferraro1,3, M. G. Bruzzone1, M. Grisoli1, L. Grazzi2, A. Raggi2, A. Nigri1 1Fondazione IRCCS, Neuroradiology, Milano, Italy 2Fondazione IRCCS, Neuroalgology Unit and Headache Center, Milano, Italy 3University of Electronic Science and Technology of China, School of Life Science and Technology, MOE Key Laboratory for Neuroinformation, Chengdu, China Objective: Medication overuse headache (MOH) is a secondary headache characterized by overuse of medications including mainly triptans, NSAIDs, and a combination of them. Functional connectivity (FC) dysfunction has been reported in pain-related and non-pain-related areas in these patients. Generally, alterations in the FC of Default Mode Network (DMN), Salience Network (SN) and Central Executive Network (CEN) (triple model) have been associated with cognitive-affective dysfunction and chronic pain. This study aims to elucidate the FC patterns in MOH chronic migraine (CM-MOH) patients, examining the relationship between FC of these 3 networks, medication abuse profiles, and clinical variables. Methods: 91 CM-MOH patients without severe psychiatric or neurological comorbidities and 35 healthy participants (CTRL) underwent neuroimaging and clinical assessments. The DMN, CEN, and SN FC were analyzed using a seed-to-voxel approach. Clinical variables such as drug abuse profile, chronification, attack frequency, migraine duration, cutaneous allodynia, anxiety, and depression were evaluated. Results were FWE corrected at p < .05 (cluster level) and p < .001 (voxel level). Results: CM-MOH patients, compared to CTRL, showed increased SN and DMN FC with primary motor areas. Triptan abusers exhibited greater SN, CEN and DMN connectivity with the sensorimotor area. SN connectivity strength was positively associated with allodynia scores in CM-MOH patients. Polyabusers showed a significant positive effect of medication intake, with increased SN connectivity with insular, cingulate, CEN connectivity with temporal cortex. Conclusion: Pronounced disruptions in FC between the DMN and SN with sensorimotor regions were observed. FC of all networks was modulated by the severity of medication overuse and clinical symptoms. This link between network dysfunction and CM-MOH. indicates a pathophysiological somatosensory cortices and P309 Molecular-enriched functional connectivity alterations in serotonin and dopamine systems in medication overuse headache patients G. Ciullo1,2, D. Fedeli1, G. Demichelis1, J. P. M. Carrion1, M. G. Bruzzone1, E. Ciusani3, A. Erbetta1, M. Grisoli1, E. Guastafierro4, D. A. Montisano5, D. D'Amico5, A. Raggi4, L. Grazzi5, A. Nigri1 1Fondazione IRCCS, Department of Neuroradiology, Milano, Italy 2University of Parma, Department of Medicine and Surgery, Parma, Italy 3Fondazione IRCCS, Department of Diagnostic and Technology, Milano, Italy 4Fondazione IRCCS, Neurology, Public Health and Disability Unit, Milano, Italy 5Fondazione IRCCS, Neuroalgology Unit and Headache Center, Milano, Italy study has provided an overview in MOH mainly the molecular-enriched associated with Objective: Chronic Migraine Medication Overuse Headache (CM-MOH) is a secondary headache disorder. Neuroimaging studies showed functional alterations in regions involved in pain modulation, reward and habitual behavior[1]. These changes may be due to the derangement of neurotransmitter systems, with a pivotal role of serotonin and dopamine circuits. However, the pathophysiology of MOH is unclear and no of neurotransmitter systems in this condition. Methods: Ninety-one CM-MOH patients and 35 healthy individuals (CTRL) underwent a rs-fMRI scan. Receptor-Enriched Analysis of Functional Connectivity by Targets (REACT)[2] approach was applied to compare functional connectivity (meFC) between groups in serotonin (5- HT1a, 5-HT1b, 5-HT2a, 5-HT4 and 5-HTT distribution), norepinephrine (NET distribution), mesocorticolimbic and nigrostriatal dopamine (D1, D2 and DAT distribution) systems. Results: In serotonin system (5-HT1a, 5-HT1b, 5-HT2a , 5-HTT networks) CM-MOH patients, compared to CTRL, showed decreased meFC in cingulate (anterior and posterior cingulate cortex) and frontal (frontal pole and medial frontal cortex) regions, and enhanced meFC in the fusiform gyrus. In dopamine system these patients the mesocorticolimbic pathway (medial superior frontal gyrus and hippocampus in D2 network) and increased meFC in the nigrostriatal pathway (putamen in D1 and D2 networks). Conclusion: CM-MOH patients showed dysfunctional activity in both serotonin and dopamine circuits. Serotonin-related alterations may be linked to pain modulation and headache pathogenesis, promoting MOH[3]. Dopamine-related the mesocorticolimbic and nigrostriatal systems could reduced meFC alterations in reported in

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affect the reward system, similar to addictions[4], and the drugs overuse habits[5]. These findings shed light on the functional neural mechanisms underlying MOH and provide evidence for a serotonin and dopamine involvement in the pathophysiology. P310 Stroke etiology and white matter hyperintensities in women with and without migraine A. Wilms1, N. van der Weerd1,2, T. van Harten3,4, K. Linstra1,5, H. van Os6, I. de Boer1, M. Kruit3, A. Maassen van den Brink5, M. Wermer1,7, G. M. Terwindt1 1Leiden University Medical Center, Neurology, Leiden, Netherlands 2Leiden University Medical Center, Human Genetics, Leiden, Netherlands 3Leiden University Medical Center, Radiology, Leiden, Netherlands 4Massachusetts General Hospital, Neurology, Boston, MA, United States 5Erasmus Medical Center, Internal Medicine, Rotterdam, Netherlands 6Leiden University Medical Center, Department of Public health & Primary Care, Leiden, Netherlands 7UMCG, Neurology, Groningen, Netherlands Objective: Women with migraine, especially those with migraine with aura (MA), have a higher risk of white matter hyperintensities (WMH) and ischemic stroke. We aimed to determine whether stroke etiology differs between women with and without migraine and whether migraine has additional impact on WMH volume in women with stroke. Methods: Middle-aged women diagnosed with ischemic stroke, both with and without a history of migraine, as well as those with MA alone, were included in this cross-sectional study. Stroke etiology was categorized according to the TOAST criteria. Evaluation of WMH volume on 3D fluid-attenuated inversion recovery (FLAIR) images was conducted using our semi-automated segmentation software in MeVisLab (version 3.4.1). Presence or absence of cerebellar WMH was scored. We used regression analysis to assess differences between groups, with adjustments for age, smoking status, and BMI. Results: We included 148 women: 55 stroke without migraine, and 55 stroke with migraine, and 38 MA. Patients with stroke only more often had a history of smoking compared o patients with both stroke and migraine and MA only (74 vs. 46 and 41%, p=.004). Women with both stroke and migraine more often had a stroke of undetermined origin than women with stroke alone (49 vs. 27%,p=.019). Total and preiventricular WMH volumes were higher in women in-house developed with stroke and migraine than in those with MA only (0.63 vs. 0.46mL, B -0.27, p=.030 and 0.55 vs. 0.42mL, B -0.26, p=.012). Crucially, there was no additional effect in WMH volume for women with ahistory of migraine and stroke compared to those with stroke alone. Conclusion: Women with both stroke and migraine demonstrated a distinct stroke etiology from women with stroke without migraine, where smoking emerged as a more prevalent risk factor. There is no observed increase in WMH volume due to migraine in women with stroke. that physicians inquire about migraine history, especially in non-smoking women with ischemic stroke. recommended It is Fig. 1 Fig. 2

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non-responders and 11 responders were correctly classified. Conclusion: Baseline gray matter morphometry is a potential tool to predict response to fremanezumab. Fig. 1 Fig. 2 P311 Prediction of response to fremanezumab in patients with migraine via magnetic resonance imaging gray matter morphometry Á. Planchuelo-Gómez1, Á. Sierra Mencia2, Y. González- Osorio2, Á. L. Guerrero2,3, A. Recio García2, R. Moro4, S. Aja-Fernández1, R. de Luis-García1, D. García-Azorín3,5 1Universidad de Valladolid, Imaging Processing Laboratory, Valladolid, Spain 2Hospital Clínico Universitario de Valladolid, Headache Unit, Valladolid, Spain 3Universidad de Valladolid, Department of Medicine, Valladolid, Spain 4Hospital Clínico Universitario de Valladolid, Department of Radiology and Nuclear Medicine, Valladolid, Spain 5Hospital Universitario Río Hortega, Department of Neurology, Valladolid, Spain to the initial (v6.0) Objective: To predict the response to fremanezumab in patients with chronic migraine (CM) or high frequency episodic migraine (HFEM) 12 weeks after the first administration of the treatment using baseline MRI-based gray matter morphometry. Methods: A total of 22 patients with CM or HFEM underwent high-resolution 3D brain T1-weighted MRI 1-2 weeks prior fremanezumab administration. Response to treatment was evaluated 12 weeks later, and defined positive when there was reduction of at least 50% in the monthly migraine frequency. Cortical curvature (CC) and thickness (CT), surface area (SA) and gray matter volume (GMV) were extracted with FreeSurfer to evaluate morphometry in 68 cortical and 14 subcortical regions, and the cerebellum (288 values). General Linear Models and logistic regression were used to predict the response to treatment and baseline differences between responders and non-responders, correcting the models by age, and total intracranial volume (TIV) in the GMV analysis. The threshold for statistical significance was p<0.05. Results: A summary of the clinical features of the sample is shown in Table 1. There were 13 patients (59.1%) with positive response to treatment. The parameters with statistically significant lower values in the responders were the CC in the right lingual cortex and supramarginal gyrus, SA in the left pars triangularis and GMV in the left entorhinal cortex. Significant higher CT values the bilateral pericalcarine cortex were found in the responders. The accuracy and area under the curve (AUC) improved from 86.3% (GMV model) and 0.89 (CC supramarginal gyrus model) to 90.9% and 0.94, respectively, when changing from a univariate to a multivariate model composed of the CT in the right pericalcarine cortex, GMV left entorhinal cortex, age and TIV (see Table 2 and Figure 1). All the in the in

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Fig. 3 P312 Uncovering functional connectivity variations throughout the migraine cycle I. Esteves1, A. R. Fouto1, A. Ruiz-Tagle1, G. Caetano1, R. G. Nunes1, N. A. da Silva2, P. Vilela3, R. Gil-Gouveia3,4, I. Pavão Martins5, C. Caballero-Gaudes6, P. Figueiredo1 1ISR-Lisboa and Department of Bioengineering, Instituto Superior Técnico – Universidade de Lisboa, Lisboa, Portugal 2Hospital da Luz, Lisboa, Portugal 3Hospital da Luz, Lisboa, Portugal 4Universidade Católica Portuguesa, Center for Interdisciplinary Research in Health, Lisboa, Portugal 5University of Lisboa, Centro de Estudos Egas Moniz, Faculty of Medicine, Lisboa, Portugal 6Basque Center on Cognition, Brain and Language, Donostia - San Sebastian, Spain low Objective: Lack of case-control fMRI studies covering the migraine cycle hinders the understanding of brain functional connectivity (FC) in migraine. Our goal was to determine how the migraine cycle affects individual FC fingerprints. Methods: We studied resting-state FC in 10 patients with frequency episodic menstrual-related migraine without aura across 4 sessions (preictal, ictal and postictal phases; and interictal phase) and 14 matched healthy controls in 2 sessions (perimenstrual and post-ovulation, matching the peri- ictal and interictal phases, respectively). fMRI was preprocessed and parcellated into cortical, subcortical and cerebellar regions. We computed individual FC matrices and the corresponding identifiability matrix (correlation between all pairs of FC matrices). Next, we employed a multilevel clinical connectome fingerprinting approach, by combining the differential identifiability within-subject, within-session and within-group. The FC fingerprints were analyzed to identify variations in FC within-group and between groups. (HC) Results: We observed increased FC heterogeneity in the preictal/ictal phases, which decreased with the progression of the attack. Interictally, patients were more homogeneous, and this homogeneity did not differ from the HC. FC significantly increased among migraine patients during the ictal phase compared to the preictal, as well as compared to HC in the same menstrual cycle phase, observed during both the ictal and postictal phases (Figure 1). Conclusion: Our findings of FC fingerprint variations across the migraine cycle may help fill the gap on the occurrence of migraine attacks and lead to more personalized clinical fingerprinting. [This work was supported by LARSyS FCT 10.54499/LA/P/0083/2020, 10.54499/UIDP/50009/2020, and 10.54499/UIDB/50009/2020), PRR project Center for Responsible AI C645008882-00000055 and FCT grants PD/BD/150356/2019, PTDC/EMD-EMD/29675/2017, LISBOA-01-0145-FEDER-029675.] treatments funding upon (DOI: built Fig. 1 P313 Brain dural arteriovenous fistulas – a case study and literature review S. del Aguila Romero1, C. Morales Hernandez1, D. Martin Rodriguez1, Z. Mendoza Plasencia1, M. Millet Oval1, I. N. Owrang Calvo1, A. Bartolomé Yumar1, M. Lobato González1, J. Rojo Alandro1 1Hospital Universitario de Canarias, La Laguna, Spain Objective: To review the literature on dAVF based on a case study. Methods: Case report Results: A 39-year-old male, with a history of active smoking and right transverse and sigmoid sinus thrombosis six months prior, presented with progressive worsening of residual symptoms. Initial investigations included a follow-up brain MRI at four partial months recanalization. visual disturbances (myodesopsia and inferior altitudinal visual field defect) and oppressive holocranial headaches occurring 1-2 times per week, partially to acetaminophen. Ophthalmological responsive evaluation found papilledema, clinical suspicion of dural fistula. Subsequent angiography post-thrombosis, revealing reported patient raising The

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confirmed the presence of a Cognard Type 2A dAVF, with arterial supply from branches of both external carotid arteries and vertebral arteries, draining into the superior sagittal sinus and torcula. The patient provided consent for the use of all images Conclusion: dAVFs with bilateral and posterior arterial supply are exceedingly rare. Treatment options include arterial embolization and neurosurgery. These fistulas should always be considered in patients with compatible clinical symptoms and a history of venous sinus thrombosis, as untreated cases may lead to intracranial hemorrhage P314 Contralateral cranial autonomic symptoms in migraine patients, in Azerbaijani population I. Azizova1, R. Hasanov2,1 1Neurological Clinic "New Medical Technologies", Baku, Azerbaijan 2Azerbaijan State Advanced Training Institute for Doctors named after A.Aliyev, Baku, Azerbaijan These each for symptoms evaluating forehead and Objective: Migraine is a complex neurological disorder characterized by a range of symptoms beyond headache, including cranial autonomic symptoms trigeminal autonomic typically associated with cephalalgias. encompass conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, facial sweating, miosis, and ptosis. Methods: From July 1, 2022, to June 25, 2024, we enrolled 1012 migraine patients in Azerbaijan, meticulously autonomic manifestations and their laterality. Cranial autonomic symptoms were categorized as bilateral or unilateral, with unilateral symptoms further subdivided into ipsilateral and contralateral. The inclusion criteria for the study included a defined diagnosis of migraine, according to the ICHD-3 criteria. indicated that 763 of 1012 Results: The results (75.4%) documented cranial autonomic patients symptoms. Among these, 589 (77.2%) patients presented with bilateral autonomic features, including lacrimation, conjunctival injection, eyelid edema, ptosis, and facial sweating. Additionally, 170 patients (22.3%) experienced unilateral ipsilateral symptoms, which also included nasal congestion. Notably, 4 patients showed unilateral-contralateral symptoms, with 2 displaying lacrimation and conjunctival injection, and 2 presenting with conjunctival injection and eyelid edema. Conclusion: Based on our extensive review of the literature, no such data on migraine with contralateral autonomic manifestations has been described before. Our study highlights a significant observation: the presence of contralateral cranial autonomic (0.5%) symptoms in migraine, challenging conventional views of symptom lateralization. These findings underscore the complexity of migraine pathophysiology and emphasize the need for further research into the underlying mechanisms and clinical implications of contralateral autonomic manifestations. P315 A hidden burden – the impact of medication collection in hospital pharmacies in multiple sclerosis and migraine patients M. Henriques1, J. Moniz Dionísio1, T. Ascensão Pinheiro1, D. Antão2, A. Rêgo1, S. Delgado1, M. Saraiva1, S. Machado1, L. Leitão1, M. Santos1, E. Parreira1 1Hospital Prof Doutor Fernando Fonseca, Neurologia, Lisboa, Portugal 2Instituto Português de Oncologia de Lisboa Francisco Gentil, Neurologia, Lisboa, Portugal the Hospital Pharmacy can negatively affect patients' Objective: Besides dosage, monitoring, and adverse effects, difficulties in accessing therapeutics are part of the impact associated with medication. Collecting therapeutics for Multiple Sclerosis (MS) and Migraine from (HP) promotes adherence, but the distance and possible delays in the process lives. Objectives: To evaluate the impact of collecting therapeutics for MS and migraine from HP. Methods: Single-center observational cross-sectional study using an anonymous online questionnaire. Data includes therapeutic collection details, treatment satisfaction (PGIC) and disability scales (MSIS-29; MIDAS). Participants are patients collecting MS disease-modifying drugs or migraine monoclonal antibodies from HP for >3 months. Analysis with SPSS® for descriptive statistics. Results: A total of 294 questionnaires were sent, with 154 responses (MS=116; Migraine=38), 66.2% were women, median age of 47. Average scores on the scales were: PGIC 4/7; MSIS-29 35.7%; MIDAS: 59.3/90. In 76.0% of cases, the patient collected their medication; 29.2% of collectors frequently or very frequently missed work. On average, it took 2.3 hours (σ=1.39) to obtain the medication. The estimated annual time spent collecting (TGA) the medication was 10,7h (σ=21,7) for the MS group and 21,5h (σ=16,7) the migraine group. The overall satisfaction with the collection method was 3 in the MS group and 2 in the migraine group (1=strongly disagree, 5=strongly agree), negatively correlated with TGA (p<0.001,R^2=-0.491). Over 75% preferred collecting medication from a community pharmacy, 49.7% preferred home delivery, and 75.2% preferred longer collection periods from the HP. for

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Conclusion: Our study demonstrates a greater impact of the time spent and satisfaction with treatment in patients with migraine. For patients with MS and migraine, optimizing the hospital or community dispensing process of their medication could result in a significant improvement in their quality of life. P316 Low-level 810nm laser acupuncture for patients with chronic migraine – a follow-up phase of randomized controlled trial Y. C. Liu1, C. H. Chou2, C. S. Wang2, H. Y. Wu1, C. C. Chung1, W. L. Chen1, C. I. Tsai1, C. Y. Hsu3 1Taichung veterans general hospital, Traditional Chinese Medicine, Taichung, Taiwan 2Taichung veterans general hospital, The Department of Neurological Institute, Taichung, Taiwan 3Taichung veterans general hospital, Department of Medical Research, Taichung, Taiwan trial randomized Controlled Objective: Laser acupuncture (LA) has shown efficacy in migraine prevention. Our aim is to verify the efficacy of laser acupuncture as preventive treatment for chronic migraine (CM) by a follow-up phase of our unpublished (RCT) (Registration Number: ISRCTN11208146). In our previous unpublished RCT, Methods: participants were randomly assigned to either the LA group or the sham treatment group. Both groups received eight treatments over one month, followed by a three-month follow-up period. After five months from the initial treatment, participants in the sham group received compensatory LA treatment, followed by an additional three-month follow-up. LA and compensatory LA were performed by LaserPen-Expert 511A in 810 nm wavelength with an output power density of 5 W/cm², with the same acupoint. Each acupoint received 150 mW of output power in continuous mode for 30 seconds, delivering a stimulation energy of 4.5 J. The primary outcome was the change MMD in 3 months after receiving sham treatment or compensatory LA treatment. Results: This follow-up phase included 24 patients, 75% of whom were female, with a mean age of 44.69 (± 15.83) years and a mean headache duration of 15.31 (± 11.31) years. The MMD in the sham group of our original RCT was 19.92 days at baseline and 17.79 days in the 3rd month. The MMD in the compensatory LA group was 18.25 days at baseline (the 6th month) and 12.44 days after 3 months later(the 9th month). The reduction in MMD revealed significantly larger decrease (5.81 vs. 2.13 days, p=0.044). Conclusion: This the RCT confirmed that LA is an effective preventive treatment for CM, significantly reducing MMD compared to the follow-up phase of sham group. We suggested that LA preventive treatment choice in chronic migraines. is one of Fig. 1 Fig. 2 P317 Relationships between migraine and interoception S. Jones1, W. Sedley1, J. Komes1, Q. Vuong1, E. Benzaquen1 1Newcastle University, Translational and Clinical Research Institute, Newcastle upon Tyne, United Kingdom Objective: Background: Migraine is understood to be precipitated by unaccustomed changes in one's internal state and/or external environment. Migraine symptoms largely involve increased, noxious, awareness of bodily changes and external stimuli. Links have been proposed between migraine and interoception (sensing and interpreting internal states), but direct evidence is limited. Methods: Methods: Unmedicated, otherwise healthy, age-matched female participants were grouped by migraine tendency: control (no unprovoked headaches, n=20); low- (<=3 migraines/month, n=20); high- frequency frequency (>=4 n=19). Interoception was interictally, with standardised questionnaires and a widely-used heartbeat counting task. Results: Results: The questionnaire-based notable difference was in the "not distracting" domain of the migraines/month, significant assessed,

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least MAIA-2; controls were likely to continue activities when experiencing (non-migraine-related) physical discomfort, and high-frequency migraineurs most likely. The heartbeat task found no differences in accuracy, but lower confidence in the low-frequency migraine group than the control and high-frequency groups. Conclusion: Conclusions: Migraine is not necessarily related to deficits in interoceptive accuracy, but more likely to how interoceptive information is utilised. We propose that low interoceptive confidence is a risk factor for migraine, whilst amplification of interoceptive signals caused by migraine restores this confidence, but at the price of migraine"s disabling symptoms. Self- reported tendency to deliberately ignore physical discomfort may result in more migraine attacks. These data offer insight into the role that migraine tries to help safely regulate our physiology, which support our recently-proposed model of migraine as a "failsafe" to stabilise homeostasis, and may help lead to a conceptual framework for patients to help them understand and non-pharmacologically manage their migraine by addressing its underlying "causes". P318 Attentional network deficits in migraine patients: neural indicators and implications Y. X. Chen1,2, S. Y. Xie3,4, X. J. Lu1,2, L. Hu1,2, Z. Dong3,4 1CAS Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing, China 2University of Chinese Academy of Sciences, Department of Psychology, Beijing, China 3Nankai University, College of Medicine, Tianjin, China 4the First Medical Centre, Chinese PLA General Hospital, Department of Neurology, Tianjin, China assess Objective: Migraineurs not only suffer from headache pain but also frequently report cognitive decline, which receives inadequate attention in evaluation and treatment. Here, we utilize the Attentional Networks Test for Interactions and Vigilance–Executive and Arousal Components (ANTI-Vea) paradigm combined (EEG) recording to with electroencephalography comprehensively in migraineurs. Methods: This study included a total of 86 subjects, comprising 52 migraineurs and 34 healthy controls. Behavior performance and EEG responses, reflecting the phasic alerting, orienting, executive control, executive vigilance (EV), and arousal vigilance (AV), were compared between migraineurs and healthy controls. Based on features with significant group differences, random forest binary classifier was trained to discriminate migraineurs from healthy attention deficits Whereas migraineurs controls. Moreover, a partial least squares (PLS) regression model was developed using features reflecting attentional deficits in migraineurs to predict their clinical characteristics. exhibited Results: hypersensitivity to external stimuli, they experienced general attention system deficits and weak vigilance. Using features reflecting attentional deficits, the binary classification model achieved an accuracy of 83.89% to discriminate migraineurs from healthy controls. Crucially, the PLS regression model was able to predict some important clinical characteristics, such as headache duration per episode, attack frequency per month over the last three months, and pain intensity score. Conclusion: Deficits in attentional functions were observed in migraineurs as compared with healthy controls. These attentional deficits could be applied to differentiate migraine healthy populations clinical headache symptoms in migraineurs. These findings highlight the need for increased focus on cognitive decline in migraineurs, attentional deficits. and predicting particularly regarding patients from P319 Melatonin for migraine prevention – a meta-analysis of efficacy and safety S. Warudkar1, A. B. Jain1, N. Dave1, A. Chaturvedi1 1Intas Pharmaceuticals Ltd, Medical Affairs, Ahmedabad, India in the 12-20% of is a chronic brain disorder Objective: Migraine affecting global population, significantlyi mpacting quality of life and imposing social and economic burdens. Studies have shown melatonin's potential in preventing migraines due to its analgesic, antioxidant properties, and ability to normalize circadian rhythms. Hence this meta-analysis was conducted to assess the efficacy and safety of melatonin for migraine prophylaxis in adults. Methods: An electronic database search was carried out EBM Based Medicine) Reviews,Cochrane and PubMed using keywords "migraine, migraine prophylaxis, melatonin, headache "based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline to include relevant randomized controlled trials (RCT) s. The meta-analysis was performed by Review Manager 5.4 (RevMan 5.4) software. Results: Total 158 studies were identified out of which, 5 RCTs involving a total of 380patients were eligible for analysis. In comparison placebo, melatonin resulted in significantly higher responder rate (OR =- 0.43; 95% CI: 0.26 to 0.70, P=- 0.0008) and significant reduction in the frequency of migraine attacks (MD =- (Evidence Library

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0.84; 95% CI: -1.16 to -0.52, P< 0.00001). In terms of safety, there was no significant difference in the occurrence of adverse effects such as drowsiness or daytime sleepiness (OR = 1.61; 95% CI: 0.73 to 3.55, P = 0.24) between placebo and melatonin treatment groups. Conclusion: Melatonin therapy appears to be a promising option for the prophylactic management ofi migraine, with the potential to improve responder rate, reduction in attack frequency and comparable safety outcomes like drowsiness or daytime sleepiness. Fig. 1 Results: Among the 22 M cases, 6 exhibited changes in linear blood flow velocity (LBFV) on TD, while 5 out of 13 MA cases showed similar changes. Decreased LBFV in the vertebral artery (VA) was observed in 10 out of 35 cases (6 M, 4 MA), and increased LBFV in both middle cerebral arteries (MCA) were noted in 3 cases (2 M, 1 MA). During the observation period, 4 patients developed spontaneous migraine attacks, during which TD was repeated (Table 1). Table 1. LBFV on TD before and during attack Interictally Normal in both in increased MCA, decrease right VA Normal Normal in MCA, and ACA During attack decreased from right side (side of pain). Increasement in both MCA > from right (side of pain), in VA no changements Significant increasement in right MCA pain), decreasement in left VA Increasement LBFV in right MCA (side of pain) (side of ACA – anterior cerebral artery As shown in Table 1, in 3 cases with normal interictal TD, changes were mainly observed in the MCA on the side of pain during a migraine attack. Conclusion: Our findings suggest that changes in blood flow in the cerebral arteries (MCA and VA) detected by TD during different stages of migraine may have diagnostic value. Further detailed investigations with larger patient cohorts and comparisons with other primary headaches and healthy controls are necessary. P321 Migraine and cognitive dysfunction: a narrative review C. Fernandes1, A. Dapkutė2, E. Watson3, I. Kazaishvili4, P. Chądzyński5, S. Varanda6, S. Di Antonio7,8, V. Munday3, A. Maassen van den Brink9, C. Lampl10 1Local Unit of Health of Coimbra, Neurology Department, Coimbra, Portugal 2Vilnius University, Center of Neurology, Vilnius, Lithuania 3King’s College London, Wolfson sensory, Pain and Regeneration centre, London, United Kingdom 4Belarusian State Medical University, Department of Nervous and Neurosurgical Diseases, Minsk, Belarus 5Faculty of Medicine and Dentistry, Medical University of Warsaw, Bielański Hospital, Neurology Department, Warsaw, Poland 6Hospital de Braga, Neurology Department, Braga, Portugal 7Centre for Pain and Neuroplasticity (CNAP), SMI, School of Medicine, Aalborg University, Department P320 Transcranial Doppler in migraine H. Vekilyan1,2,3, N. Santrosyan3, H. Manvelyan3 12nd Medical Union, Neurology, Yerevan, Armenia 2Cito MC, Neurology, Yerevan, Armenia 3YSMU, Neurology, Yerevan, Armenia Objective: In recent years many researches have focused on the investigation of migraine. In our observational study we aimed to evaluate the diagnostic value of transcranial doppler (TD) in migraine. Methods: We included 1546 male patients (mean age 18 years) undergoing check-up in neurological department for military service eligibility. Migraine was diagnosed in 35 patients: 22 migraine without aura (M), 13 migraine with aura - (MA), 2 of them - sporadic hemiplegic migraine (HM). Diagnose were made according to ICHD -3 diagnostic criteria. All patients underwent TD as part of their check-up.

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of Health Science and Technology, Aalborg, Denmark 8University of Genoa, - Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, Genoa, Italy 9Erasmus University Medical Center, Internal Medicine Department, Rotterdam, Netherlands 10Konventhospital Barmherzige Brüder Linz, Neurology Department, Linz, Austria in Objective: The association between migraine and cognitive impairment has been studied, however, the relationship is not well established. Regarding the prevalence of migraine and the aging of the population, this topic has substantial public health implications. Thus, we aim to review the topic of cognition in migraine patients. Methods: Based on non-systematic research in PubMed, we performed a narrative review of cognitive dysfunction and impairment in migraine. We included studies that reported cognitive symptoms the different or/and cognitive performance migraine phases, subtypes, and their impact on migraine patients. All authors made both descriptive and interpretive analyses. Results: Cognitive complaints are widespread in migraine patients, not only during the migraine episode but also in the inter-ictal phase. Cognitive dysfunction negatively affects the quality of life and daily functioning of migraine patients. Studies confirm that a reduction in cognitive performance occurs during the ictal phase and can persist in the postictal period. However, these cognitive impairments could be considered an epiphenomenon due to the ongoing pain processing. No consensus exists according to the phenotype with aura (MwA) and without aura (MwoA). Some studies reported that MwA patients have impaired attention and processing speed but findings are is no significant difference in executive control network functional connectivity between MwA and MwoA. Functional neuroimaging studies captured brain changes according to migraine phases but only during attacks the existence of a neural basis for cognitive performance was found. Conclusion: The fact that migraine presents as a paroxysmal disorder might affect the estimation of the association between migraine and cognitive outcomes. Although evidence suggests a reduction in cognitive performance the migraine episode, it is not possible to conclude the presence of cognitive impairment during the pre-ictal and postictal phases. inconsistent. However, there throughout P322 Occipital nerve block as a safe and effective treatment for the management of refractory migraine in a pregnant woman A. Foska1, M. Chondrogianni1, A. Theodorou1, G. P. Paraskevas1,2, E. Bakola1, G. Papagiannopoulou1, S. Fanouraki1, N. Nana1, A. Sterpi1, C. Arvaniti1,3, G. Tsivgoulis1,4 1"Attikon" University Hospital, Second Department of Neurology, Athens, Greece 2Neurochemistry and Biological Markers Unit, "Eginition" Hospital, First Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece 3Red Cross Hospital, Department of Neurology, Athens, Greece 4University of Tennessee Health Science Center, Department of Neurology, Memphis, TN, United States intensity Objective: Refractory migraine during pregnancy can be challenging to manage due to the limited treatment options that are safe for both the mother and the fetus. However, occipital nerve blocks have emerged as a potential therapeutic option for refractory migraine, even in pregnant women. Methods: We report a 38-year-old pregnant woman who presented in our tertiary headache center during her 19th week of pregnancy. The patient had a history of low frequency episodic migraine and a micro pituitary adenoma. Since the first month of her pregnancy, she complained of unilateral, pressing, tightening pain of severe in the areas overlying the right occipital nerves, accompanied by nausea, photophobia and phonophobia for about 25 days per month. Extensive diagnostic work-up excluded nocious etiologies, while various therapeutic regiments did not relieve the pain. We performed block of the right occipital nerves that we identified with anatomical signs. The applied technique was aseptic and the needle that penetrated injected lidocaine 1% (10 mg/mL). Results: The patient experienced significant pain relief following the occipital nerve block that lasted for 6 weeks, allowing her to avoid other medications that might pose risks during pregnancy. Subsequently, we repeated the procedure and the pain relief was maintained until the successful completion of pregnancy. Conclusion: Occipital nerve blocks can be a safe and effective treatment option for managing persisting migraine in pregnant women. This approach can provide significant pain relief and improve the quality of limited treatment options due to pregnancy. Further studies including a larger cohort of pregnant women are needed to life for patients who have

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establish standardized protocols and to confirm the long-term safety and efficacy of this intervention. Acknowledgments: Written informed consent for use of deidentified patient information was provided by the patient. Fig. 1 P323 Assessment of Cutaneous Allodynia and its relation to Proinflammatory blood markers in migraine M. Nada1, D. Labib1, S. Wehiby1, M. Edrees1 1Cairo University, Neurology, Cairo, Egypt the role of P324 Understanding the anti-migraine effect of MG25, a novel curcumin derivative through invitro and invivo perspectives K. Deepika1, S. Shrikant Sonak1, V. Nayana Koumudi1, V. Dayaram Nimbarte1, P. Yogeeswari1 1Birla institute of technology and Science, Pilani- Hyderabad campus, Pharmacy, Secunderabad, India Objective: According to a global burden of disease study in 2019, about 15% of the global population suffers from headaches each day. Approximately half of the migraine sufferers do not experience relief from the current therapeutic options, highlighting a significant need for new treatment alternatives. New and innovative approaches are essential to address this unmet medical need and improve the quality of life for individuals with migraines. Therefore, in this study, we tried to investigate the anti-migraine potential of MG25 in cell lines and animal models. Methods: For invitro studies, RAW 264.7 cells were induced with LPS and the levels of inflammatory mediators(IL1-beta, TNF-alpha, IL18) and migraine- specific markers(CGRP, PACAP) were assessed after MG25 (10,20uM) treatment. Also, the effect of MG25 on migraine-relevant behaviour will be assessed in Sprague nitroglycerin administration. Further, the levels of inflammatory mediators and migraine-specific markers in the trigeminovascular system and plasma will be assessed by ELISA, Western blot and RT-PCR studies. Results: Invitro studies showed that MG25 treatment decreased IL1-beta and CGRP levels in ELISA and confocal studies. The results from the invivo studies will be presented at the congress Conclusion: The invitro studies suggest that the anti- migraine effects of MG25 act via their potential anti- inflammatory and anti-nociceptive effects. The invivo findings will be presented at the congress Dawley after rats ratio Scale Evaluate neutrophil/lymphocyte thirty migraine patients were serum Objective: proinflammatory/inflammatory and hematological biomarkers in migraine patients and their relation to cutaneous allodynia in migraine Methods: A case control study was conducted in which randomly recruited and compared to 30 healthy controls. Migraine Disability Assessment (MIDAS) Questionnaire (Arabic version) was used. Cutaneous allodynia Scoring Test was used to assess the occurrence of different allodynia symptoms in conjunction with headache episodes. Complete blood picture (CBC), Erythrocyte sedimentation rate (ESR), C-reactive protein /Albumin (CRP/Alb) ratio (CAR), Serum (NLR), Monocyte/lymphocyte ratio (MLR), as well as serum IL-6 and IL-1b were assessed by sandwich Enzyme- Linked Immune-Sorbent Assay technology (sandwich ELISA) on serum samples Results: Our results showed that 86.7% had episodic migraine while only 4 patients (13.3%) had chronic migraine. The longest headache free period was 6.03 ± 4.1 months (ranging from 1 to 12 months). In addition, 70% of our patients had CA. In addition, females who had CA showed increased severity of migraine attacks compared with those without CA (P < 0.05). The duration of headache and headache frequency were higher in migraine patients with CA. Females and higher education level were risk factors with CA. In addition, low IL-1, neutrophils, PLR and NLR were correlated with higher CA. Platelets, interleukin-1 (IL-1), Platelets/Lymphocyte Ratio, and Neutrophil/Lymphocyte negatively correlated with cutaneous allodynia. Conclusion: This study is the first to assess the role of proinflammatory markers with cutaneous allodynia among migraine patients. Low IL-1, neutrophils, PLR and NLR were correlated with higher CA. Ratio were

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P325 Serum melatonin levels and migraine headache: results from a cross-sectional study in Iran M. Togha1, M. Noormohammadi2, Z. Ghorbani3, F. Karimzadeh2, S. Z. Bathaie4 1Tehran University of Medical Sciences, Tehran, Iran 2Iran University of Medical Sciences, Tehran, Iran 3Guilan University of Medical Sciences, Guilan, Iran 4Tarbiat Modares University, Tehran, Iran P326 Atogepant in clinical practice – the experience of a tertiary centre A. L. Neves1,2, R. Dias1,2, M. Pinto1, A. Costa1,2 1Local Health Unit of São João, E.P.E., Neurology, Porto, Portugal 2Faculty of Medicine of University of Porto, Clinical Neurosciences and Mental Health, Porto, Portugal in the third edition of Objective: Recent studies underscore the significance of serum melatonin levels in patients with chronic and episodic migraine headaches, the focus of this study. Methods: This case-control study, carried out in Tehran, Iran from September 2017 to June 2020, involved the selection of potential participants aged 18-65 from a headache clinic at Sina Hospital, which is affiliated with Tehran University of Medical Sciences. The diagnosis of both episodic and chronic migraines was conducted in accordance with the diagnostic criteria outlined the International Classification of Headache Disorders (ICHD-III). The measurement of melatonin levels was performed following the instructions provided by the manufacturers of the ELISA kits. Results: A notable disparity was noted in the frequency of headache occurrences and the duration of abortive drug utilization between the two cohorts (P-value < 0.001). Individuals with episodic migraine displayed a higher intake of vitamin B2 and non- steroidal anti-inflammatory medications. Subsequent analysis indicated a markedly elevated level of serum melatonin in the control group (237.5 ± 114.5) in comparison to those suffering from episodic (84.7 ± 64.4) and chronic migraine headaches (121 ± 104.4, P- value < 0.001). Conclusion: Although there were no noteworthy distinctions identified between patients with episodic and chronic migraine, the present investigation revealed a notable disparity in serum melatonin concentrations, which were markedly elevated in individuals without migraine compared to those experiencing migraine headaches. longitudinal in migraine patients Objective: Atogepant is an antagonist of calcitonin gene-related peptide receptor, whose clinical trials have shown promising results in the preventive treatment of migraine. However, real-life studies are needed to assess these results. We aimed to evaluate the efficacy, safety and side-effect profile of atogepant in a Portuguese tertiary centre. Methods: Prospective study of a consecutive sample of migraine patients treated preventively with atogepant. Sociodemographic and clinical data, adverse effects and application of the Headache Impact Test - 6 (HIT-6), Migraine Disability Assessment Scale (MIDAS), migraine Treatment Optimization Questionnaire (mTOQ-6) and Hospital Anxiety and Depression Scale (HADS) were collected. Results: Patient inclusion began in March 2024 and 23 patients have been included to date: 87% female (n=20), with a median age of 41 years (minimum: 37, maximum: 46). Most of the patients had previously been treated with multiple prophylactic therapies, including: antidepressants (n=16), antiepileptics (n=19), antihypertensives (n=19), botulinum toxin (n=13), monoclonal antibodies (n=11) and anaesthetic blocks (n=9). The median frequency of headaches in the 3 months prior to starting therapy was 12 days/month (minimum: 7, maximum: 16) and they scored 68 on the HIT-6 (minimum: 61, maximum: 76). Preliminary results point to a reduction in headache days. Side effects were reported in some patients, namely nausea, loss of appetite, fatigue, drowsiness, vertigo, constipation, and depressive symptoms. Treatment was discontinued in only two patients (due to adverse effects). Conclusion: Preliminary results suggest that the use of atogepant seems to be effective in reducing migraine days, with no major adverse effects reported. However, the study is still in the patient inclusion phase, so we hope to obtain more results to attest to its efficacy and safety.

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LP001 Herpes Zoster Ophthalmicus presenting as Raeder syndrome: a case report F. Vahabizad1, A. Bahmani1, H. R. Farhadi Shabestari1 1Tehran University of Medical Sciences, Neurology Department, School of Medicine, Tehran, Iran Objective: To report a case of Raeder syndrome secondary to herpes zoster ophthalmicus (HZO) and highlight the importance of considering varicella- zoster virus (VZV) as an etiology for facial pain even in the absence of an evident rash. Methods: A 53-year-old man presented with unilateral, stabbing, and excruciating pain in the left V1, V2, and V3 distributions of the trigeminal nerve, associated with paresthesia. Clinical examination revealed miosis and ptosis, suggestive of Horner syndrome. Corneal reflex and other cranial nerve examinations were normal. Brain MRI was unremarkable. Two days later, periorbital edema developed, and on the fourth day, a rash consistent with herpes zoster appeared on the left frontal region. The patient became febrile, prompting a lumbar puncture, which revealed elevated white blood cells with lymphocytic predominance, normal glucose, and elevated protein. CSF PCR for VZV was positive. HIV testing was negative. The patient was treated with intravenous acyclovir for two weeks, resulting in complete recovery. Results: This case demonstrates that HZO can present as Raeder syndrome, characterized by unilateral oculosympathetic paresis and trigeminal nerve involvement. The reactivation of VZV in the trigeminal ganglion can inflammation and damage, causing severe pain and neurological symptoms. Early recognition and treatment with antiviral therapy are crucial for optimal outcomes. Conclusion: Herpes zoster can be an underlying cause of Raeder syndrome. Clinicians should consider VZV in the differential diagnosis of facial pain, even when a rash is not initially evident. Early antiviral therapy is crucial for optimal patient outcomes. lead to LP002 HeaRT-Headache, Resilience and Trauma in Adolescence: a multicentre Italian project N. Faedda1, L. Papetti2, I. Sabuzi1, N. Grelli1, P. Verdecchia1, C. Celino1, S. Tarantino3, M. Proietti Checchi3, M. Valeriani3, P. Alaimo Di loro4, E. Tozzi5, P. Silva5, G. Saporito5, F. Pistoia5, V. Sciruicchio6, V. Misciagna6, L. Grazzi7, M. Canella7, C. Bravaccio8, I. Toldo9, M. Locallo9, M. Reimers9, V. Raieli10, N. Vaccaro10, M. Quartana10, V. Savarino10, D. Pandolfo10, G. Abrate11, C. Caprioli11, F. Re11, M. Vigna Taglianti11, T. Oliaro11, S. S. Racalbuto11, A. Versace11, V. Guidetti1 1Sapienza University of Rome, Human Neuroscience, Rome, Italy 2IRCCS Bambino Gesù, Developmental Neurology Unit, Rome, Italy 3IRCCS Bambino Gesù, Tor Vergata University, Developmental Neurology Unit, Rome, Italy 4Lumsa University, GEPLI Department, Rome, Italy 5L'Aquila University, L'Aquila, Italy 6PO San Paolo, ASL, Bari, Italy 7IRCCS Besta, Milan, Italy 8Federico II University, Naples, Italy 9University of Padova, Padova, Italy 10Palermo University, Palermo, Italy 11Regina Margherita Children's Hospital, Turin, Italy involves several Objective: This project juvenile headache centres in Italy, and aims to explore levels of resilience in adolescent subjects between 14 and 18 years of age, with and without primary headache, in relation to levels of psychopathology and trauma Methods: A total of 1008 adolescents (14-18 years old) were involved. The sample was divided into (a) Experimental Group (EG) consisting of 293 subjects with a diagnosis of primary headache and (b) Control Group (CG) including 715 subjects without a diagnosis of headache. All participants completed Youth Self Report for Ages 11-18 (YSR, Achenbach, 2001) to assess behavioral competency and behavioral problems, Connor Davidson Resilience Scale (CD-RISC, Connor, Davidson 2003) to assess the resilience and ITEM-Revised to assess traumatic events Results: Higher rates of emotional and behavioral problems were found in the adolescents of the CG (M: 65.3; sd: 10.4) in comparison to the adolescents of the EG (M: 57.7; sd: 17.5) (pvalue: <0.01). The differences between the two groups in the CD-RISC total score were not significant. In the total group, 95.2% report at least one stressful event; in particular CG reported a higher percentage of stressful events (96.2%) than the EG (92.8%), showing a statistically significant difference inverse/negative correlation between the total YSR and CD-RISC and the positive correlation between YSR and ITEM were significant for both groups (pvalue: 0.03). The

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Conclusion: The controls had higher levels of psychopathology than the headache patients and reported a higher number of traumatic events. This suggests that the presence of headache may be a protective factor for the onset of psychopathology and helps shed light on the high psychic distress of adolescents that goes unnoticed and remains unseen. LP003 Network meta-analysis comparing efficacy and safety outcomes of Atogepant, Rimegepant, and Galcanezumab in patients with episodic migraine after including CHALLENGE-MIG trial J. Ailani1, P. Gandhi2, A. Lalla2, P. McAllister3, T. Bilchik4, S. Nahas5, D. Rowe6, C. Piron6, K. Kelton6, R. Halker Singh7 1MedStar Georgetown University Hospital, Washington, DC, United States 2AbbVie, North Chicago, IL, United States 3New England Institute for Neurology and Headache, Stamford, CT, United States 4Yale School of Medicine, New Haven, CT, United States 5Thomas Jefferson University, Philadelphia, PA, United States 6Medical Decision Modeling Inc., Indianapolis, IN, United States 7Mayo Clinic, Phoenix, AZ, United States included 5 Objective: Network meta-analysis of atogepant (Ato) relative to rimegepant (Rime) and galcanezumab (Galc) after inclusion of the CHALLENGE-MIG trial for efficacy and safety outcomes in episodic migraine (EM) patients. Methods: The NMA randomized, controlled trials for the preventive treatment of EM (ADVANCE[Ato 60 mg], BHV3000-305[Rime 75 mg], EVOLVE-1, EVOLVE-2[Galc 120 mg], and CHALLENGE- MIG[Rime 75 mg, Galc 120 mg]). A fixed-effects model was chosen to compare the efficacy and safety of Ato versus Rime, Galc based on model fit statistics. Efficacy results at 12 weeks are presented as odds ratio (OR) or estimates of mean difference with corresponding 95% confidence intervals (CI). Safety results are presented as hazard ratio and 95% CI. Results: After including CHALLENGE-MIG, the NMA showed Ato significantly increased the odds of achieving 50% RR in MMD compared to Rime (OR 2.29 (95% CI 1.43-3.66)), Galc (1.68 (1.07-2.64)), and placebo showed numerically higher MMD reductions compared to Rime and Galc, and significantly higher reductions compared to Pbo. Ato showed significantly greater reductions in acute medication use days compared to Rime and Pbo, and numerically greater reductions compared to Galc. Ato demonstrated significant (2.55-5.67)). Ato (Pbo) (3.80 higher events emergent numerically (d/c) and numerically adverse improvement in Migraine Specific Quality of Life questionnaire version 2.1 Role Function-Restrictive domain score compared to Rime and Pbo, and numerical improvement compared to Galc. Ato all-cause demonstrated lower discontinuations treatment (TEAEs) compared to Rime, Galc, and Pbo; however, these differences were not significant. Conclusion: Ato 60 mg demonstrated significant improvements in 3 of the 4 efficacy outcomes compared to Rime 75 mg and significantly increased odds of achieving ≥50% RR in MMD relative to Galc 120 mg. Other efficacy outcomes were not significantly different. Ato 60 mg demonstrated comparable all-cause d/c and TEAEs relative to Rime and Galc. LP004 Migraine and Neuroinflammation: correlation of Adipokines and Cytokines with clinical features C. Ulutaş1, B. R. Hasırcı Bayır1, Y. Çetinkaya1, E. M. Güler2, D. Ağırcan3 1Haydarpasa Numune Trainig and Research Hospital, Neurology, Istanbul, Turkey 2University of Health Sciences, Biochemistry, Istanbul, Turkey 3Harran University, Faculty of Medicine, Neurology, Şanlıurfa, Turkey included a Objective: The aim of our study is to investigate the potential biomarker properties of adipokines and cytokines in migraine and to assess their relationship with the clinical features of the condition. Methods: The study total of 90 participants: 30 with episodic migraines, 30 with chronic migraines, and 30 healthy volunteers, all aged between 18 and 50 years. Data were collected on patients age, sex, migraine characteristics (pain location, type), attack frequency over the past 3 months, duration of the disease, attack severity, and body mass index. During the interictal period, blood levels of adiponectin, leptin, resistin, IL-6, TNF-α, and IL-1β were measured using ELISA kits. Results: There were no significant differences in age, sex, or body mass index between the patient and control groups. Levels of adiponectin, resistin, IL-6, TNF-α, and IL-1β were significantly higher in the patient group compared to the control group (p < 0.001 for each). Adiponectin and IL-6 levels were significantly higher in chronic migraine patients compared to the episodic migraine group (p = 0.004 and p < 0.001, respectively), while no significant differences were found for the other molecules between the two groups.

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of Conclusion: The higher levels of cytokines and adipokines, except for leptin, in migraine patients compared to the control group suggest a potential role migraine pathophysiology. The elevated levels of adiponectin and IL-6 in chronic migraine patients indicate that these molecules may be associated with the mechanisms involved in the chronicization of migraine neuroinflammation in Fig. 1 Fig. 2 Fig. 3 LP005 In silico predicted circulating microRNAs let-7e-5p and let-7b-5p differ in migraine patients compared to healthy individuals: A pilot study of microRNAs putative role in migraine diagnosis O. Grodzka1,2, C. Eyileten Postuła3, Z. Wicik3, P. Chądzyński1, A. Stankowska1, E. Post1, S. Ahmadova3,2, M. Postuła3, D. Mirowska-Guzel3, I. Domitrz1 1Medical University of Warsaw, Department of Neurology, Warsaw, Poland 2Medical University of Warsaw, Doctoral School, Warsaw, Poland 3Medical University of Warsaw, Department of Experimental and Clinical Pharmacology, Warsaw, Poland Objective: In the current study, we aimed to assess the circulating miRNA profile based on re-analyzed transcriptomic data in patients with migraine to evaluate their diagnostic utility between healthy individuals and tension-type headache (TTH) and migraine. Methods: Plasma samples were collected from 15 migraine patients, 10 TTH patients, and 21 healthy individuals, matched by age and sex. Cerebrospinal fluid (CSF) samples were collected from 7 migraine patients. Bioinformatical in silico analysis predicted the most differentially expressed miRNAs" families (including let-7b-5p, let-7e-5p, and miR-548ar-3p). The expression of indicated miRNAs was evaluated with qRT-PCR. Statistical analysis was performed using the relevant tests. Results: in silico analysis: We identified, via in silico analysis, inflammation-related miRNAs and their families in migraine, namely, let-7g-5p, miR-548j-3-p, miR-155-5p, miR-192-5p, and miR-1277-5p. Moreover, we predicted the genes targeting those miRNAs inflammation process. q-PCR validation: Migraine patients and healthy controls differed significantly in the expression of let-7e-5p and let-7b-5p (p=0.001, p=0.001, respectively). For both studied miRNAs, expression was increased in migraine patients compared to the control group. Moreover, the expression of let-7b-5p and let-7e-5p was significantly higher in CSF (p=0,001, p=0,008, respectively). For miR-548ar-3p, the difference between plasma and CSF did not reach significance. However, the expression of miR-548ar-3p in more than half of the plasma samples could not be detected. Conclusion: Let-7e-5p and let-7b-5p can be used as biomarkers for indicating inflammation in the course of migraine and, therefore, differentiate migraineurs from healthy individuals. In particular, circulating plasma miRNAs are interesting candidates as bearers of circulating biomarkers due to their high stability in in plasma than the in

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the blood and making biomarkers for migraine diagnosis. them highly relevant Fig. 3 Fig. 1 Fig. 2 LP006 The role of weight loss in headache management: evidence-based case report of systematic reviews and meta-analyses A. R. Faiq1, I. S. Madjid1, E. R. Indrapriambada1, H. R. Sofyan1, T. Aninditha1 1Dr. Cipto Mangunkusumo National Central General Hospital, Department of Neurology, Central Jakarta, Indonesia Objective: A 44-year-old male with chronic, moderate-intensity headaches occurring 2-3 times per week, unresponsive to acute treatments, and a BMI of 29.5 kg/m² was evaluated to determine whether weight loss, alongside standard care, could improve headache outcomes. Methods: A literature search was conducted on PubMed and the Cochrane Database for systematic reviews and meta-analyses from the last 10 years. The search included headaches of any type and onset as the population, weight loss (surgical or non-surgical) as the intervention, with or without pharmacological treatment, compared to standard care or no treatment. The outcomes focused on headache characteristics and impact. Critical appraisal was performed using the Oxford Centre for Evidence- Based Medicine checklist. Results: Three studies were included. In studies focusing on migraine, the specific headache spectrum and diagnostic methods (self-reported vs. ICHD-3 criteria) were unclear. All included randomized and non-randomized studies, though one lacked critical appraisal. The first study found that weight loss significantly reduced headache frequency (ES − 0.78, p < 0.0001), pain severity (ES − 1.04, p < 0.0001), disability (ES − 0.68, p < 0.0001), and attack duration (ES − 0.25, p = 0.017) [1]. The second study reported a in migraine frequency, fewer symptomatic days per month after surgery (MD − 5.56 days, 95% CI 0.14 to 10.99, p = 0.04), and a borderline significant reduction in pain severity [2]. The third study showed that 90.2% of patients improved after surgery (95% CI [67.4, 113]; p significant reviews reduction

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loss < 0.005), compared to 23.2% in the non-surgical group (95% CI [11.5, 34.9]; p < 0.005) [3]. Conclusion: Weight is an effective non- pharmacological approach for improving headache outcomes. However, the reviews are heterogenous in terms of headache spectrum, methods of included studies, and synthesis of results. For our case scenario, weight loss is an applicable treatment plan. LP007 Association between migraine and blood pressure in women with hypertensive disorders of pregnancy: preliminary results N. R. A. Bruijn1, J. E. Roeters van Lennep1, H. J. Duvekot2, G. M. Terwindt3, A. Maassen van den Brink1, L. Al-Hassany1 1Erasmus MC, University Medical Center Rotterdam, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands 2Erasmus MC, University Medical Center Rotterdam, Department of Gynecology and Obstetrics, Division of Obstetrics and Prenatal Medicine, Rotterdam, Netherlands 3Leiden University Medical Center, Department of Neurology, Leiden, Netherlands Objective: Migraine and hypertensive disorders of pregnancy (HDP) are associated with cardiovascular (CV) disease, but the exact role of other CV risk factors is yet unclear. We studied the association of migraine with blood pressure (BP) in postpartum women with HDP. Methods: A prospective observational study was conducted among HDP patients. A history of migraine (i.e., prepartum) was based on IHS criteria using the validated LUMINA questionnaire. BP measurements were part of standard care in an outpatient clinic designed for HDP patients at 6 weeks and 3 months postpartum. We applied descriptive statistics using unpaired T-tests and Mann-Whitney U tests (significance level P<0.05). Results: A total of 201 women with HDP (age 31.2±4.8 years) and without preexisting hypertension were included (Table 1), consisting of 78 women (38.8%) with prevalent migraine, of whom 56 (71.8%) had aura. At 6 weeks postpartum, 86 BP measurements were available, including 19 women (22.1%) with migraine and 14 women (16.3%) without migraine using antihypertensives. of antihypertensives in migraine patients, a higher systolic BP was observed in women with migraine (131.9±14.5 mmHg) compared to those without (125.5±12.8 mmHg) (P=0.035). Also, a higher diastolic BP was observed in women with migraine (85.0 [78.0- Despite higher use 92.0] mmHg) compared to those without migraine (80.0 [72.0-85.0] mmHg) (P=0.008). At 3 months postpartum, 114 BP measurements were available, including 16 women (14.0%) with migraine and 14 women (12.3%) without migraine using antihypertensives. No differences were observed for systolic BP (P=0.127) and diastolic BP (P=0.115) between women with and without migraine. Conclusion: Although causality has not yet been established, women with both migraine and HDP tend to have higher BP compared to those with HDP alone, particularly shortly after delivery. Whether closer monitoring of patients with these female-specific CV risk factors is warranted remains to be determined. Fig. 1 LP008 Health inEqualities Associated with socioDemographic characteristics in migraine within Primary cAre IN England (HEAD-PAIN) D. P. Watson1, R. Pawinski2, M. Czachorowski2, A. Williams2, L. Camidge3, E. Rottier3, H. Gowman3, S. Law3, K. Alexiou3, G. O'Neil2 1Hamilton Medical Group, Aberdeen, United Kingdom 2Pfizer Ltd, Tadworth, United Kingdom 3Adelphi Real World, Bollington, United Kingdom To understand sociodemographic Objective: inequalities among adults with migraine in England by comparing coded comorbidities in medical records. Methods: A retrospective cohort study using English primary healthcare data from the Clinical Practice Research Datalink Aurum linked to 2019 Index of Multiple Deprivation and Rural Urban Classification datasets. Adults aged ≥18-years with ≥1 migraine diagnosis between 19th September 2012 and 1st May 2023 were included. The 10 most prevalent comorbidities (based on diagnoses in the 1-year before migraine) and sociodemographic characteristics were outputted. Comparisons across sociodemographic stratifications were made with Fisher's exact tests. Results: N=476,191 people with migraine were included – 78% female, mean (SD) age 42.1 (15.6) years, 55.1% white ethnicity (Table 1).

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Fig. 2 Fig. 3 The comorbidity with the highest prevalence was asthma (9.7%) (Table 2). Statistical differences existed across age, sex, deprivation, ethnicity, area and region stratifications in all top 10 comorbidities (p<0.05). Generally, prevalence of comorbidities increased as deprivation increased (Figure 1). Depression and anxiety were most common in females versus males, in those with white versus black or Asian ethnicity, and young versus older adults (18-44 versus ≥45 years). Generally, conditions required to be coded in line with an English incentive programme had a higher prevalence (Table 2: noted by *). Conclusion: The World Health Organization defines health inequalities as measurable differences in health across population subgroups. This study shows statistical differences exist across age, sex, ethnicity, deprivation, area and region stratifications in all top 10 migraine comorbidities. Further research will describe healthcare utilisation in people with migraine by these stratifications. Fig. 1 LP009 Headache characteristics before, during and after Ramadhan fasting in Jakarta, Indonesia: a case series I. S. Madjid1, A. R. Faiq1, E. R. Indrapriambada1, H. R. Sofyan1, T. Aninditha1 1Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Department of Neurology, Jakarta, Indonesia Objective: As a country with the largest Moslem population in the world, fasting from sunrise until sunset during the holy Ramadhan month followed by performing prayers at night is a common observation in Indonesia. Headache, a commonly found diagnosis in Indonesia, is largely influenced by eating and sleep patterns. In this case series, we would like to describe the headache characteristics before, during, and after Ramadhan fasting in patients who attended our neurology outpatient clinic during the Ramadhan month in 2023. Methods: We observed 8 patients with various headache entities who presented to our outpatient clinic 1 month before, during, and 1 month after Ramadhan. We collected data regarding demographic characteristics, in headache phenotypes as well as medication use. Headache was classified using the 3rd edition of International Classification of Headache Disorders (ICHD-3) criteria. Results: Our group of patients consist of 8 women with a mean age of 44.62 years old. We identified 5 patients with migraine-type, 1 patient with tension- type and 3 patients with mixed-type headache. comorbidities, and changes

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Among those 8 patients, 3 patients have both autoimmune and psychiatric comorbidities. We observed no remarkable changes regarding the intensity of headache in terms of numerical pain rating scale (NPRS) or frequency 1 month before, during, and after Ramadhan, as well as no remarkable changes in the use of nonspecific or specific acute medications. Conclusion: In our group of patients, fasting during the Ramadhan month did not worsen any remarkable clinical features of their headache phenotypes and use of acute medications. We acknowledge that our data quality can still be in terms of completeness. We suggested that this case series can be developed into a prospective study with a bigger sample size and more rigorous methods to adjust to confounding the relationship between fasting and headache. that might improved influence factors LP010 Multicenter study on quality of life in patients with cluster headaches in Portugal: preliminary data. C. Morgado1, S. Gomes1, A. Ferreira1, S. Lopes1, S. Reis Marques1, C. Machado1, S. Varanda1, -. Consórcio Português para o Estudo da Cefaleia em S2 1Hospital de Braga, Neurologia, Braga, Portugal 2CPECS, Portugal, Portugal in part, due to Objective: Introduction: Cluster headaches are likely to be associated with poor quality of life and impaired social, familial and professional functioning. Studies on quality of life are scarce worldwide and no data is available for Portuguese population, lack of validated tools to evaluate cluster headache impact on daily life. Aim: We aimed to validate a questionnaire for evaluate the impact of cluster headache on quality of life and functioning of Portuguese population. Methods: Methods: We performed a cross-sectional, multicenter study, including patients with cluster headache diagnosis, older than 17 years, attending 17 Headache Health Units distributed accross the country. Linguistic and cultural adaptation of Cluster Headache Quality of Life Questionnaire (CHQ), was performed by TRAPD model. Time consumed answering the questionnaire and items comprehension were assessed. Reliability of the questionnaire was assessed using Cronbach's alpha and the intraclass correlation coefficient (ICC). Results: Results: We included 29 participants, with a median age of 46 (min 29; máx 66) years, mostly male (24 patients) and with diagnosis of episodic cluster headaches (76,9%). Participants spent about 5 minutes (2–15 min) in questionnaire answering. One patient reported difficulties in answering item 10, 21 and 22. Overall Cronbach's alpha was 0.940, ranging from 0.724 to 0.928 for the subscales. ICC values ranged from 0.553 (for item 1) to 0,991 (for item 26). Conclusion: Conclusion: This study provided a reliable tool to evaluate quality of life and daily functioning of patients suffering from cluster headache in Portugal. Studies of quality of life predicting factors will be performed using this tool in the near future. LP011 The epidemiology, management, and the associated burden of migraine in Australia N. Limberg1, J. Ray2,3, B. Harvey4, G. Stratton4, A. Cuskelly5, C. S. Tam6,5, D. Witcombe4 1Migraine Specialist. St Andrews's Place, Brisbane, Australia 2Alfred Health, Department of Neurology, Melbourne, Australia 3Monash University, Department of Neurosciences, Melbourne, Australia 4Pfizer Australia, Sydney, Australia 5Telstra Health (MedicalDirector), Sydney, Australia 6University of Sydney, Faculty of Medicine and Health, Sydney, Australia Objective: There have been no recent large-scale studies on the epidemiology or treatment of migraine in an Australian setting. The primary objective was to describe the incidence and prevalence of diagnosed migraine in a primary care dataset. The secondary objectives were to describe referral and treatment pathways of these patients. Methods: Using a clinician opt-in consent model, de- identified data were extracted from electronic medical records (MedicalDirector Clinical®) in patients with a clinical diagnosis of migraine from 1/1/10 to 28/2/24. Incidence and prevalence estimates were calculated in subgroups of interest both directly from the data within each subgroup (unadjusted) and using a relevant demographic factors (adjusted). Results: The study population comprised of 37,579 patients (74.2% female; median (IQR) age=38 (27-50y) with 30,417 patients included for follow-up analyses ≥ 2 years of data. The adjusted point prevalence of diagnosed migraine was 7.02 per 1,000 persons (95% CI 6.79-7.25). The estimated incidence rate of migraine per 1,000 person-years was 5.14 (95% CI 4.99-5.30) for females and 2.35 for males (95% CI 2.27-2.44) IRs). Physiotherapist and neurologist referrals occurred in 32.0% and 18.6% of patients, however the reason for referral was not specified. Overall, 51.1% of patients received a triptan Poisson modelling (adjusted adjusted for

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prophylactic medications prescription, were prescribed to 46.6% of patients and 54.8% of all migraine patients were prescribed an opioid. Conclusion: Using a real-world, national dataset, the overall point prevalence and incidence of migraine in the Australian population appears lower compared to previous studies and the global burden of disease results. This could be due to patients not presenting to their GP specifically for migraine treatment or the reason for visit to their GP not being coded as migraine, which is a limitation of this study. Most patients were prescribed an opioid which are not recommended in migraine management. LP012 Impact of migraine on productivity and efficiency in India among working professionals S. Saha1, I. Patel2, V. Madaan2, A. Bondia2, M. Wadhwa1, R. Sarkar1, D. Raval1 1Indian Institute of Public Health Gandhinagar, Gandhinagar, India 2Pfizer, Medical Affairs, Mumbai, India PRISMA Following Objective: This review synthesizes literature on the impact of migraine on productivity among working professionals in India & identifies its determinants a guidelines, Methods: comprehensive search was conducted across major databases (PubMed, Scopus, Google Scholar, Web of Science) using keywords like "Migraine," "Economic burden," & "Productivity loss." Studies from 2015 to 2023 were included. Eligibility criteria focused on observational studies & clinical trials involving adults aged 18 & older diagnosed with migraines. Data extraction was standardized to capture key study characteristics & findings. The methodological quality of included studies was assessed using the Newcastle- Ottawa Scale. Pooled estimates of productivity loss were adjusted with per capita national income. Results: The search identified 8 relevant articles from India, showing migraine-related productivity losses ranging from 3% to 4.3% of productive time, leading to significant economic implications. The one-year prevalence of migraines is approx. 14.12% to 28.99%, affecting around 213 million cases annually. Pooled analysis from two studies shows a productivity loss of 17.3 days/year due to migraines. This translates to an economic loss of INR 8731/- annually/person, based on daily per capita the prevalence of migraines in India, the total economic loss is about INR 18,674.35 crore, representing around 4.74% of the country"s per capita national income. Additionally, gender disparities were notable, with women constituting 81.87% of diagnosed cases, particularly in the 30-44 age group, highlighting the for gender-sensitive healthcare strategies. need income. Considering Individuals with migraines also reported higher healthcare costs & a greater prevalence of comorbid mental health issues, exacerbating the economic burden. Conclusion: The substantial economic burden of migraines in India calls for targeted interventions to improve workplace productivity & enhance the quality of life for those affected. LP013 Classifying primary headache disorders through secondary headache differentials P. Zhang1,2 1Beth Israel Deaconness Medical Center, Neurology, Boston, MA, United States 2Harvard Medical School, Boston, MA, United States diagnosis of all in matrix differential Objective: Definitions of primary headaches (PH) change with iterations of ICHD. However, differential diagnosis for each PH tends to remain invariant regardless of intrinsic classification criteria. In this study, we attempt to explore the possibility of classification of PH through its secondary headache (SH) differential diagnosis. Methods: Using a differential diagnosis generator derived from the comments section of the ICHD3, we generated PH. (https://www.mdpi.com/2075-4418/12/11/2589.) We exclude any differential diagnosis containing a PH. The result is a list of SH differential diagnosis for each PH. To make the result more concise, we encode the the results form: 1. Each columns represent SH and rows PH. 2. Each element is encoded as "1" if that SH is a differential diagnosis of the corresponding PH; otherwise, it is denoted as "0". We then obtain the row echelon form of the matrix. Here, the pivot columns represent SH which can act as basis vectors sufficient to differentiate their PH counterparts. into Results: We generated matrices that takes account non- hierarchical structures of ICHD; these contain 65 and 53 columns of SH, respectively. After row reduction, 34 and 27 columns are sufficient to separate between PH in both models, respectively. Although separation is possible through this schema, some PH are not successfully captured as their differential diagnosis are significantly limited according our differential diagnosis generator. We will present this differential diagnosis classifications schema during the meeting. Conclusion: Defining primary headache disorders in terms of their differential diagnosis, rather than internal phenotype, may ensure in classification schema. However, our experimentation shows that this strategy is limited significantly by the hierarchical invariance the and

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0.11% [95% CI 0.04%, 0.28%] for men). The median age of the patients was 33 (interquartile range 27–44) years, and 18 (81.8%) were women. Sixteen (72.7%) patients were obese (≥25 kg/m2) according to the criteria of the Asian-Pacific classification; only 11 (50%) had BMI ≥30 kg/m2. All patients with IIH reported one or more red flags of SNNOOP10 list. Papilledema was the most common red flag (n = 14, 63.6%). When we excluded papilledema and flags irrelevant to IIH, 10 (45.5%) had no red flags. Among the headache-related red flags, pattern change or new-onset headache (n = 6, 27.3%) was the most common. Positional headache (n = 2, 9.1%) and precipitation by sneezing, coughing, or exercise (n = 1, 4.5%) were uncommon. Conclusion: The frequency of IIH in headache clinics in Korea was low. Typical obesity profile, clinical characteristics, and papilledema were less common in Korean patients with IIH. Although the SNNOOP10 list seems to be feasible, clinical suspicion alone may be insufficient IIH, particularly in Koreans. the effective screening of for Fig. 1 Fig. 2 differential diagnosis generator being used. Therefore, more research needs to be done in this promising area. LP014 Frequency of Idiopathic Intracranial Hypertension in Korea: a prospective multicenter study B. S. Kim1, S. J. Cho2, K. H. Cho3, S. H. Baek3, J. H. Sohn4, T. J. Song5, W. Lee6, H. K. Park7, S. Cho8, J. Han9, S. Rhiu10, M. J. Lee11, M. K. Chu12 1Ewha Womans University Mokdong Hospital, Ewha Womans University College of Medicine, Neurology, Seoul, South Korea 2Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Neurology, Hwaseong, South Korea 3Korea University Anam Hospital, Korea University College of Medicine, Neurology, Seoul, South Korea 4Chuncheon Sacred Heart Hospital, Hallym University College of Medicine, Neurology, Chuncheon, South Korea 5Seoul Hospital, Ewha Womans University college of Medicine, Neurology, Seoul, South Korea 6Yongin Severance Hospital, Yonsei University College of Medicine, Neurology, Yongin, South Korea 7Inje University Ilsan Paik Hospital, Inje University College of Medicine, Goyang, South Korea 8Uijeongbu Eulji Medical Center, Eulji University School of Medicine, Neurology, Uijeongbu, South Korea 9Hallym University, Statistics, Gangwon, South Korea 10Dongtan Sacred Heart Hospital, Hallym University College of Medicine, Ophthalmology, Hwaseong, South Korea 11Seoul National University Hospital, Seoul National University College of Medicine, Neurology, Seoul, South Korea 12Severance Hospital, Yonsei University College of Medicine, Neurology, Seoul, South Korea prospectively Objective: The aim of this prospective study was to examine the frequency of idiopathic intracranial hypertension (IIH) in headache clinics and assess the presence of red flag signs in patients with IIH. Methods: We new collected consecutive patients with IIH among first-visit patients who visited headache clinics of 11 hospitals in Korea between January 2022 and March 2024. Clinical characteristics, lumbar puncture opening pressures, and neuroimaging findings are collected. We used the SNNOOP10 list to identify the presence of red flags of the patients with IIH. Results: Among 13,028 new headache patients visited to 11 headache clinics, 22 patients were finally diagnosed with IIH (frequency: 0.17% [95% CI 0.11%, 0.25%], 0.19% [95% CI 0.12%, 0.30%] for women and

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LP015 Altered amyloid plasma profile in patients with disabling headaches after SARS-CoV-2 infection and vaccination A. H. Aamodt1, T. Ueland2,3,4, M. Boldingh5, B. Bezgal5, M. Argren5, K. Otterdal2, I. Gregersen2, A. Husøy6,7, Å. H. Morsund8, K. Devik9, S. M. Mathisen10, K. Schlüter10, A. C. Poole11, K. Gjendemsjø12, T. B. Dahl2, P. Aukrust2,3,13, E. A. Tronvik6,7, B. E. Halvorsen2,3,14 1Oslo University Hospital and the Norwegian University of Science and Technology, Neuology, Oslo, Norway 2Oslo University Hospital, Research Institute for Internal Medicine, Oslo, Norway 3University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, Norway 4University Hospital of North Norway, Thrombosis Research Center (TREC), Division of internal medicine, Tromsø, Norway 5Oslo University Hospital, Neurology, Oslo, Norway 6The Norwegian University of Science and Technology, Dept of Neuroscience and Movement Science, Trondheim, Norway 7St. Olav Hospital, Neurology, Trondheim, Norway 8Molde Hospital, Neurology, Molde, Norway 9Namsos Hospital, Neurology, Namsos, Norway 10Stavanger University Hospital, Stavanger, Norway 11Oslo Headache Centre, Oslo, Norway 12Sandvika Neurocentre, Sandvika, Norway 13Oslo University Hospital, Clinical Immunology and Infectious Diseases, Oslo, Norway 14Harvard Medical School, Department of Medicine, Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, United States Objective: New onset persistent headache occurs in a subset of individuals after COVID-19 and to some extent after SARS-CoV-2 vaccine. However, the pathophysiological mechanisms are unknown. The purpose of this study was to assess levels of amyloid related biomarkers in patients with persistent headache after COVID-19 and SARS-CoV-2 vaccine. Methods: In this prospective observational cohort study, patients with persistent headache as the dominating symptom after COVID-19 disease (n=29) and SARS-CoV-2 vaccination (n=31), had neurological assessments at baseline and 6-month follow-up. Plasma levels of amyloid precursor protein (APP), pregnancy zone protein (PZP), cathepsin L1 (CTSL) and serum Amyloid A (SAA1) were measured by ELISA at the two time points in relation to levels in healthy controls (n=16). Results: We strong and persistent upregulation of APP in patients with headache after COVID-19 as compared to the two other groups (Figure 1). At both inclusion and after additional 6- month follow-up, APP levels were also increased in found a those with accompanying cognitive symptoms (Figure 2). In contrast, plasma levels of PZP were elevated in both headache groups as compared to healthy controls, but with no relation to cognitive symptoms. CTSL was only elevated in those with headache after COVID-19 at baseline, whereas SAA1 showed levels comparable in all groups. Conclusion: Altered plasma levels of soluble markers potentially reflecting changes in amyloid processing was found in patients with persistent headache after SARS-CoV-2 vaccine and particular in those with persistent headache after COVID-19 disease where APP were associated with accompanying cognitive symptoms. Our data point to plausible mechanism of amyloid processing and neuroinflammation in relation to COVID-19 and SARS-CoV-2 vaccine (Figure 3). Fig. 1 Fig. 2

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Fig. 3 Division of Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA, United States is persistent Objective: Although new onset persistent headaches have been reported following acute COVID-19 disease and in some degree also reported after SARS-CoV-2 vaccination, the mechanisms for these headache types are unclear. One possible mechanism immune activation triggered by SARS-CoV-2 or vaccination with the trigeminovascular system as a potential target. The purpose of this study was to assess plasma levels markers of T-cell activation/exhaustion in patients with persistent headache after COVID-19 and SARS- CoV-2 vaccine and healthy controls. Methods: In this prospective observational cohort patients with severe headache as the dominating symptom after COVID-19 and SARS-CoV-2 vaccination, had clinically neurological assessments and 6-month follow-up. Plasma levels of soluble (s) CD25, soluble T- cell immunoglobulin mucin domain-3 (sTIM-3), soluble lymphocyte activation gene-3 (sLAG-3) and soluble siglec-7 were measured by ELISA at both visits and compared to healthy controls. Results: Plasma levels of sCD25, sTIM-3 and sLAG-3, but not siglec-7, were increased among patients with persistent headache after COVID-19 compared to participants with headache SARS-CoV-2 vaccination and healthy controls, and for sTIM-3, this increase was seen also after 6 months follow-up (Figure 1). Conclusion: The findings of this study demonstrating signs of persistent T cell activation and exhaustion in patients with headache as the dominating symptom following COVID-19, but not in those with similar symptoms following SARS-CoV-2 vaccination. Further studies should clarify the role of persistent T cell activation/exhaustion in persistent headache following COVID-19 disease. after LP016 Plasma biomakers of T-cell exhaustion in patients with disabling headaches after COVID-19 compared to healthy controls and patients with persistent headache after SARS-CoV-2 vaccination A. H. Aamodt1, T. Ueland2,3,4, M. Boldingh5, B. Bezgal5, K. Otterdal2, I. Gregersen2, A. Husøy6,7, K. Devik8, Å. H. Morsund9, S. M. Mathisen10, K. Schlüter10, A. C. Poole11, K. Gjendemsjø12, T. B. Dahl2, P. Aukrust2,3,13, E. A. Tronvik6,7, B. E. Halvorsen2,3,14 1Oslo University Hospital and the Norwegian University of Science and Technology, Neuology, Oslo, Norway 2Oslo University Hospital, Research Institute for Internal Medicine, Oslo, Norway 3University of Oslo, Institute of Clinical Medicine, Faculty of Medicine, Oslo, Norway 4University Hospital of North Norway, Thrombosis Research Center (TREC), Division of internal medicine, Tromsø, Norway 5Oslo University Hospital, Neurology, Oslo, Norway 6The Norwegian University of Science and Technology, Dept of Neuroscience and Movement Science, Trondheim, Norway 7St. Olav Hospital, Neurology, Trondheim, Norway 8Namsos Hospital, Neurology, Namsos, Norway 9Molde Hospital, Neurology, Molde, Norway 10Stavanger University Hospital, Stavanger, Norway 11Oslo Headache Centre, Oslo, Norway 12Sandvika Neurocentre, Sandvika, Norway 13Oslo University Hospital, Clinical Immunology and Infectious Diseases, Oslo, Norway 14Harvard Medical School, Department of Medicine,

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Fig. 1 Fig. 3 Fig. 2 LP017 Transcutaneous Auricular Vagus nerve stimulation for radiotherapy-related neuropathic pain in head and neck cancer survivors (RELAX): a phase 3, multicentre, double blind, randomised sham- controlled trial X. Zuo1, Y. Xu1, J. Jiang1, J. Wang1, Y. Zhu1, D. Pan2, H. Li1, Y. Chen1, X. Rong1, D. Zheng3, K. Lu4, H. Mai5, M. Chen5, C. B. Simone6, Q. Shen1, S. Xiao1, Y. Li1, Y. Tang1 1Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Guangzhou, China 2The Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, China 3The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, China 4The Zhongshan City People’s Hospital, Zhongshan, China 5Sun Yat-sen University Cancer Center, Guangzhou, China 6New York Proton Center, New York, NY, United States Objective: Radiotherapy-related neuropathic pain (RRNP) is a late complication affecting more than 30% of head and neck cancer (HNC) survivors after radiation therapy. Although the benefit of pregabalin has been verified, it provides limited pain relief in the early stage, and rapid dose increase can lead to serious side effects. The transcutaneous auricular vagus nerve stimulation (taVNS) has shown promising efficacy in pain relief with few adverse events. Nevertheless, it remains unknown whether taVNS is effective in treating neuropathic pain, and high- quality randomized data are currently lacking. Methods: HNC survivors with medium-to-severe RRNP (as defined by Numeric Rating Scale score≥4) , recruited from 4 hospitals in China, were randomly assigned to receive taVNS or sham stimulation for 30

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minutes twice daily of 7 days. All patients also received a basal dose of pregabalin (75 mg twice daily). The primary outcome was pain intensity reduction, as measured by the change of NRS scores from baseline to day 7. Results: A total of 116 randomized patients were included in the intent-to-treat population, with 58 allocated in each arm. Treatment with taVNS resulted in a higher reduction of the mean [standard deviation] pain intensity reduction at day 7 than the sham- stimulation (-2.43 [2.19] vs -1.12 [1.64] points; net difference, -1.31 points; 95% confidence interval, - 2.02 to -0.60; P<0.001). There were similar frequency of any (28, 48.3%) and Control group (26, 44.8%). The most common device-related AEs related was mild, transient local skin irritations at the electrode site (8.6% vs 1.7%). Conclusion: This trial found taVNS could effectively and rapidly relief the RNNP at the initial stage of pregabalin treatment, which suggest taVNS should be considered as an option for HNC survivors with medium-to-severe RRNP. between taVNS group AEs Fig. 1 LP018 A critical overview of neuromodulatory devices for migraine M. Freeman1 1Headache Wellness Center, Greensboro, NC, United States Objective: To understand the scope and limitations of non-invasive neuromodulatory device studies for migraine Methods: From 2014 to 2024 there have been six non-invasive neuromodulatory devices for migraine cleared by the Food and Drug Administration (FDA) of the United States (all are CE-marked): single-pulse to (Nerivio), stimulation studies contributing transcutaneous electrical nerve transcranial magnetic (SAVI Dual), external trigeminal neurostimulator (Cefaly), non- invasive vagus nerve stimulator (gammaCore), remote electrical neuromodulation combined occipital and trigeminal nerve stimulator (Relivion), and stimulator (HeadaTerm). Most, but not all, device manufacturers have multiple studies published in peer-reviewed journals. The design and quality of these studies vary across the same device. Results may be inconsistent between studies of the same device leading to confusion regarding use, effectiveness, safety, and product expectations. A review of the published literature of the six current FDA-cleared (CE-marked) devices was performed with a focus on manufacturer- sponsored their FDA- clearance. Results: FDA-cleared (CE-marked) status is a distinctly lower designation than FDA-approved (EU-approved) status and only requires comparison to a prior predicate device or less rigorous de novo clinical trials. Current double-blind sham-controlled device studies often enroll only dozens (rather than hundreds) of subjects. Studies of the same device rarely follow the same methods, routinely changing the number and frequency of device stimulations; consequently, manufacturer recommended treatments are often arbitrary and do not conform to study parameters. No definitive mechanisms of action in humans have been established. No definitive studies in pregnancy exist. Conclusion: Prescribers of neuromodulatory devices for migraine should be aware of important differences between FDA-cleared (CE-marked) versus FDA- approved (EU-approved) designations and be mindful of limitations of the current devices. LP019 Endocannabinoid cerebrospinal fluid levels in migraine A. Harder1,2, X. Di3, W. Winter2, B. He3, R. van Dongen2, G. Onderwater2, E. W. Van Zwet4, E. Krekels3, I. Kohler3, M. D. Ferrari2, A. Harms3, A. van den Maagdenberg1,2, T. Hankermeier3, G. M. Terwindt2 1Leiden University Medical Center, Human Genetics, Leiden, Netherlands 2Leiden University Medical Center, Neurology, Leiden, Netherlands 3Leiden Academic Center for Drug Research, Analytical BioSciences and Metabolomics, Leiden, Netherlands 4Leiden University Medical Center, Biomedical Data Sciences, Leiden, Netherlands Objective: The disruption of the endocannabinoid system might be implicated in both migraine and depression, which comorbid conditions. Nevertheless, the supporting evidence for frequently are

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the (2-AG), and healthy volunteers, (DHEA) linear regression analyses for this hypothesis is limited. Our aim was to investigate whether the endocannabinoid system is disrupted in people with migraine during the interictal phase and whether depression was of influence. Methods: Here we measured levels of endocannabinoids (eCBs) anandamide (AEA) and 2- arachidonoylglycerol the analogue endocannabinoid docosahexaenoylethanolamine in the cerebrospinal fluid (CSF) of n = 194 individuals with episodic migraine between attacks (n = 97 migraine with aura and n = 97 migraine without aura) and n = 94 using micro-liquid chromatography – tandem mass spectrometry (micro- LC-MS/MS). Groups were age- and sex-matched. Timing and processing of sampling was protocolized. Multivariate log10- transformed eCB concentrations were performed to compare groups. Covariates that were included were sex, age, BMI, (lifetime) depression. Results: No differences were detected between individuals with migraine with or without aura and healthy controls in the CSF for AEA (P = 0.46, P = 0.08), 2-AG (P = 0.46, P = 0.90) and DHEA (P = 0.58, P = 0.79), respectively. For 2-AG, levels were positively correlated with depression (β = 0.053; 95% CI: 0.014 to 0.093, P = 0.008). Conclusion: CSF endocannabinoid 2-AG is linked with depression, although CSF endocannabinoids do not appear to be effective biomarkers for distinguishing interictal migraine sufferers from controls. This study highlights the intricate nature of the endocannabinoid system concerning migraine and depression, two comorbid conditions. substance use and Fig. 1 LP020 Environmental triggers in migraine patients in Riyadh: a cross-sectional study A. AL Harbi1 1PNU, Riyadh, Saudi Arabia factors and environmental Objective: A migraine is a disabling condition that is characterized by persistent headaches which vary in severity. Migraines are extremely common and represent a major public health concern due to their effect on the quality of life and job performance, which can also lead to a significant financial burden on global economies In this cross-sectional study, a self- Methods: administered questionnaire was distributed among migraineurs attending primary healthcare centers and hospitals in Riyadh, Saudi Arabia. The survey included questions about sociodemographic data, number of attacks, triggering migraines, in order to assess their prevalence. Results: A total of 415 participants were recruited. The most common age group was 31– 50 years old (46.5%), with females dominating the males (84.8% vs 15.2%). The prevalence of migraines that affected activities of daily living (ADL) was 80% (CI=75.7% - 84.3%). The most common environmental factors that triggered migraines were noise (87.7%), followed by outdoor light exposure (81.4%), and indoor lighting, such as fluorescent light, and computer systems (79%). that interfered with ADL were more common in patients with a bachelor"s degree (p=0.019) and those who were taking migraine medication (p=0.003). Conclusion: Migraines are highly prevalent in our region, most specifically among women. Noise, outdoor light exposure, indoor lighting, fluorescent lights, and computer systems usage were the most triggering environmental factors of migraines. These factors dissuade patients from doing their daily activities. In univariate analyses, migraines LP021 Exploring the role of music therapy as alternative treatment for non-acute migraines: an evidence- based case report W. A. Isaac1, I. S. Madjid1, H. R. Sofyan1, T. Aninditha1 1Dr. Cipto Mangunkusumo Hospital, Neurology, Jakarta, Indonesia Objective: A 30-year-old woman visited the neurology outpatient clinic with a long-standing history of migraines. Despite adhering to standard medication, there has been little improvement in her condition. Neurological revealed no discernible underlying issues. The physician then questioned the possibility of music therapy as an alternative form of imaging

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literature search was conducted treatment for the patient. This case report aims to assess how music therapy can impact migraines by reducing the frequency, intensity, and duration of headaches, as well as the amount of medication needed, especially when standard treatments have not been effective. in Methods: A PubMed and Cochrane Library using the keywords "music therapy," "chronic migraine," and "primary headache." Selected studies were screened based on their title and abstract. Four relevant studies were identified and appraised using the Centre of Evidence- Based Medicine Oxford Critical Appraisal Form. Results: Two moderate-quality and two low-quality studies were found in this study. The studies did not use a standardized music therapy program due to limited research but utilized a form of receptive music as treatment. However, the methods and lengths of the interventions differed. The interventions included various approaches such as binaural beats, music- based sessions, and smartphone-based music. The post-treatment findings from all studies indicated a noteworthy decrease in migraine frequency from baseline. While the effectiveness of reducing headache intensity and reported a considerable duration, reduction in medication taken. Conclusion: The effectiveness of music therapy in non-acute migraines remains inconclusive. This may be attributed to the absence of standardized interventions. However, using music therapy to decrease migraine frequency could be a potential treatment goal in specific clinical contexts, ultimately improving patients' quality of life. two studies there was variability in Fig. 1 Fig. 2 LP022 Galcanezumab in a 28-year old female with Myasthenia gravis and chronic migraine V. Tischler-Strasser1, K. Lehner1, C. Lampl1, A. Maassen van den Brink2 1Saint John of God Hospital Linz, Neurology, Linz, Austria 2Erasmus MC, Clinical Pharmacology, Rotterdam, Netherlands is (MG) gravis Objective: Myasthenia a neuromuscular, immune mediated disease, resulting in muscle weakness. Any medical treatment in individuals with Myasthenia gravis can lead to precarious clinical decisions, as various drugs can worsen the symptoms in patients with Myasthenia gravis. This is especially true in patients suffering from other neurologic diseases like chronic migraine. Methods: We present the case of a 28-year-old female suffering from Myasthenia gravis and chronic migraine at the same time. After a detailed risk- included extensive benefit assessment, which database the administration of Galcanezumb was initiated. Results: The medication was well-tolerated, no further worsening of the symptoms of Myasthenia could be observed. Conclusion: The treatment of chronic migraine with Galcanezumab in patients with MG seems to be possible. Although it seems to have an effect on the immune system, until now no hint for Galcanezumab triggered antibody-production of any kind (with exception from allergic reactions) could be observed. To ensure for patients and medical professionals further research is needed. Not only should this aim on additional patient characteristics, research, safety

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that may indicate worsening, but also the possible influence of MG medication. LP023 Migraine epidemic or policy effect? How reimbursement shaped diagnosis trends in Lithuania G. Makarevičius1, A. Dapkutė1, K. Ryliškienė1 1Vilnius University, Center of Neurology, Faculty of Medicine, Vilnius, Lithuania before the implementation Objective: We aimed to ascertain how reimbursement changes of novel monoclonal antibodies acting against calcitonin-gene related peptide or its receptor (anti- CGRP/R) (erenumab became reimbursed since 2020 June 01 and fremanezumab since 2021 January 28) has influenced the diagnostic rates of migraine and other headaches. Methods: The annual numbers of people diagnosed with G43, G44 and G50 as defined by the ICD-10 were obtained from the Institute of Hygiene, Ministry of Health of the Republic of Lithuania. Medical sales (defined daily doses (DDD) and monthly doses sold) data was obtained from the State Medicines Control Agency of Lithuania. Number of diagnoses and sale data of migraine-specific acute and preventive medications of reimbursement policies of anti-CGRP/R monoclonals (2017-2019) were compared with years after policy implementation (2021-2023). All statistical analyses were performed using R software. Results: In post-reimbursement years, the number of total migraine diagnoses (G43) increased by 40.6% from 14088 cases in 2019 to 23705 in 2023. In 2021- 2023, there were more yearly new migraine diagnoses than in 2017-2019 (3417.67 and 894.33 per year on average respectively, p=0.015). The rate of change for migraine statistically significantly increased post- reimbursement (p<0.001). Other headache disorders (ICD code G44) and trigeminal neuralgia (ICD code G50) did not face a significant change in new yearly diagnoses (p=0.116 and p=0.420, respectively). Sales of triptans increased by 54.02% from 954389 DDD sold in 2019 to 1469973 DDD in 2023. Sales of anti- CGRP/R monoclonals increased by 6483.8% from 462 monthly doses in 2019 to 30417 in 2023. Conclusion: The reimbursement of anti-CGRP/R monoclonals by the National Health Insurance Fund under the Ministry of Health of Lithuania has significantly increased the number of migraine diagnoses. This trend underscores the importance of access to effective treatments in encouraging patients to seek medical care proactively. LP024 Two types or two diseases? A comprehensive review of migraine with and without aura O. Grodzka1,2, K. Dzagoevi3, T. Rees4, G. Cabral5, P. Chądzyński1, S. Di Antonio6,7, P. Sochań1, A. Maassen van den Brink8, C. Lampl9 1Medical University of Warsaw, Faculty of Medicine and Dentistry, Department of Neurology, Warsaw, Poland 2Medical University of Warsaw, Doctoral School, Warsaw, Poland 3Tbilisi State Medical University, Department of Molecular and Medical Genetics, Tbilisi, Georgia 4Institute of Psychiatry, Psychology and Neuroscience, King’s College London, Headache Group, Wolfson Sensory Pain and Regeneration Centre, London, United Kingdom 5Unidade Local de Saúde Lisboa Ocidental, Neurology Department, Lisboa, Portugal 6University of Genoa, Department of Neuroscience, Rehabilitation, Ophthalmology, Genetics and Maternal Child Health, Genova, Italy 7Aalborg University, Department of Health Science and Technology, Center for Pain and Neuroplasticity (CNAP), SMI, School of Medicine, Aalborg, Denmark 8University Medical Center Rotterdam, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Erasmus MC, Rotterdam, Netherlands 9Konventhospital Barmherzige Brüder Linz, Department of Neurology, Linz, Austria clinical features, Objective: For a long time, there have been discussions about the entity of migraine without aura (MwoA) and migraine with aura (MwA), with some evidence for the same pathogenesis of both and other arguments against it. In this work, we analysed multiple factors from the perspective of similarities and differences between these two types of migraine. The aim was to better understand the bases underlying both types of migraine, including aspects such as genetics, molecular bases, relation with hormones, neuroimaging, electroencephalography, treatment response, and migraine complications. Methods: A search was performed to find the most adequate articles to include in the narrative review. Results: Although epidemiology remains similar for both types, there are slight alterations in sex and age distribution. Genetics and pathogenesis showed some crucial differences. Conditions, such as vestibular symptoms and depression, were found to correlate similarly with both types of migraine. For some features, including increased cardiovascular risk, the tendency appeared to be the same; however, migraine types differ in the strength of correlation. literature thorough

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Finally, in cases such as hormones, the influence has shown opposite directions. Conclusion: Therefore, although MwA and MwoA are considered two types of the same disease, more research should focus on their differences, thus finally enabling better specific treatment options for both types of migraine. Fig. 3 Fig. 1 Fig. 2 LP025 Associations of sleep quality and stress with migraine attack characteristics: findings from the MECH-HK cohort Q. Yang1, Y. J. Xie1, K. Cheung1, T. Ma2, C. Hao3 1The Hong Kong Polytechnic University, School of Nursing, Hong Kong, China 2The Hong Kong Polytechnic University, Department of Rehabilitation Sciences, Hong Kong, China 3Sun Yat-sen University, School of Public Health, Guangzhou, China Objective: To investigate the associations of sleep quality and stress with migraine frequency, duration and intensity among Hong Kong Chinese women. Methods: Data were obtained from an ongoing cohort study named "MECH-HK" (Migraine Exposures and Cardiovascular Health in Hong Kong Chinese Women). Baseline assessment was conducted between October 2019 and October 2021. Sleep quality and stress were assessed using the Pittsburgh Sleep Quality Index (PSS), (PSQI) and respectively. Migraine by the International Classification of Headache Disorders 3 (ICHD-3). Migraine frequency, duration and intensity (0-10 visual scale) were prospectively collected from monthly migraine diaries, and the average values for the three months following baseline assessment were adopted for analyses. Linear models, restricted cubic the Perceived diagnosed Stress Scale was

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spline terms, and interaction terms were used to examine the associations and potential non-linear and interaction effects. Results: Among 413 participants with migraine, the mean baseline PSQI and PSS scores were 7.74 and 26.14, respectively. The median baseline migraine frequency, duration, and intensity were 1.00 attacks/month, 4.50 hours/attack, and 5 scores, respectively. After adjusting for confounding factors, poor sleep quality (PSQI score > 5) was associated with a 1.46 attack/month in migraine frequency (β=1.46, 95% CI: 0.51-2.41, P = 0.003), and high perceived stress (PSS score > 26) was associated with a 0.96 attack/month in migraine frequency (β=0.96, 95% CI: 0.14-1.77, P = 0.02). No significant non-linear relationships or interactions between PSQI and PSS scores were observed. No significant associations were found with migraine duration and intensity. Conclusion: Poorer sleep quality and higher stress were associated with increased migraine frequency in Hong Kong Chinese women. increase increase LP026 How to evaluate success of preventive migraine therapy: the role of disability assessment. An analysis from the DMKG headache registry R. Ruscheweyh1, G. Goßrau2, T. Kraya3, L. Neeb4, V. Ruschil5, T. Dresler6, J. Scheidt7, T. Jürgens8 1Klinikum der LMU München, Munich, Germany 2University Hospital and Faculty of Medicine Carl Gustav Carus, TU Dresden, Interdisciplinary Pain Center, Dresden, Germany 3Hospital Sankt Georg Leipzig gGmbH, Department of Neurology, Leipzig, Germany 4Universitätsklinikum Brandenburg an der Havel GmbH, Department of Neurology, Brandenburg an der Havel, Germany 5Hertie Institute for Clinical Brain Research, University Hospital Tuebingen, Department of Neurology and Epileptology, Tübingen, Germany 6Tuebingen Center for Mental Health, University Hospital Tuebingen, Department of Psychiatry and Psychotherapy, Tübingen, Germany 7University of Applied Sciences Hof, Institute for Information Systems, Hof, Germany 8KMG Klinikum Güstrow, Department of Neurology, Güstrow, Germany Objective: Especially for specific migraine therapies, treatment success needs to be clearly demonstrated to allow continued reimbursement. In clinical practice, a reduction in monthly headache days (MHD) by ≥50% (or by ≥30% in chronic migraine) is often used to detect success. However, this does not adequately improvement for all patients. Therefore, capture et al, Cephalalgia (MIDAS) score several national guidelines state that success can also be detected based on a Migraine Disability Assessment reduction of ≥30% (subjects with a baseline MIDAS >20 points). This has also recently been confirmed to correspond to the Minimal Important Difference (MID) of the MIDAS (Ruscheweyh (2024) 44:3331024241261077). However, it is unclear how many additional patients can be classified as responders when combining the MIDAS and the MHD criteria. Methods: From the DMKG Headache Registry, we identified 285 adult migraine patients before and 3 months after start with a CGRP antibody and evaluated treatment success regarding the MHD criterion, the MIDAS criterion, or both. Part (28.1%) of the patients had switched from a previous CGRP antibody therapy. Results: 67 patients (23.1%) had a 50% reduction of MHD. If a 30% MHD reduction for chronic migraine patients was accepted, responders increased to 92 (32.3%). 118 patients (41.4%) had a MIDAS reduction of ≥30%. If both criteria were combined, 147 (51.5%) of patients were classified as responders. Improvement of migraine under Conclusion: preventive therapy is not adequately captured by 50% MHD reduction alone. Adding the 30% MIDAS criterion increases the number of responders by 28.4%. This might be especially important in severely affected patients where improvement of headache severity and disability might be achieved more easily than reduction in headache frequency. LP027 A smart digital headache dairy; real life experiences H. Nugteren1, R. C. J. Donders2, F. A. de Graaf2, R. van der Ven2, N. A. van Doorn2 1Curavista, Healthcare pathways, Raamsdonksveer, Netherlands 2Diakonessenhuis Ziekenhuis Utrecht, Neurologie, Utrecht, Netherlands Objective: Headache Diary is a telemonitoring module on Curavista.health. The module supports HealthCare Providers (HCP) in the diagnoses and monitoring of headache via a smart rule-based algorithm. The module is designed for patients with (suspected) migraine, chronic migraine, tension (suspected) headache, and medication overuse headache. Methods: General practitioners referred patients to the Diakonessenhuis hospital from February to July 2024. All 60 patients with an initial diagnosis within the scope of the headache diary were included. in Utrecht

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Goals were (1) the specialized nurse should become the first in line (2) to reduce waiting time to first consultation (3) increase patient and HCP satisfaction. In September 2024 the results were evaluated. Results: 45 women, 7 men and 8 "unknown" were included. Average age 33. 49 (82%) patients submitted at least one diary and 45 (75%) submitted diaries for 25 days or more during the initial 30-day diagnostic phase. The specialized nurse validated the algorithm; in 43 of the 45 patients the diagnoses matched between the manual method and the rule-based algorithm. The two casus with a different diagnosis could be explained. The specialized nurse became the first-in-line. The waiting time too the first consultation was reduced from 90 to 30 days during which the patient completes the dairy. An example of a completed diary can be found in figure 1. Five patients were interviewed. Their feedback was positive: easy to use and insightful. Conclusion: The Headache Dairy supports regular care processes with high satisfaction both for patients and HCPs. The Diakonessenhuis hospital will continue to use the diary and expand its usage to young adults. LP028 Efficacy of the digital therapeutic sinCephalea in migraine Prophylaxis: 12-Week RCT with Episodic migraine patients S. Evers1,2, H. C. B. Grube3, A. Gendolla4, C. Gaul5, K. Ewald6, O. Witt6, J. Voggel6, M. Nitschke7, C. Sina8, D. Thaçi9, I. R. König3, T. Schröder6 1University of Münster, Medical Faculty, Münster, Germany 2Lindenbrunn Hospital, Department of Neurology, Coppenbrügge, Germany 3University Medical Center Schleswig-Holstein, Institute of Medical Biometry and Statistics University of Lübeck, Lübeck, Germany 4Practice for Neurology and Pain Therapy, Essen, Germany 5Headache Center Frankfurt, Frankfurt a. M., Germany 6Perfood GmbH, Lübeck, Germany 7Department of Neurology, University of Lübeck, Lübeck, Germany 8University Medical Center Schleswig-Holstein, Campus Lübeck & University of Lübeck, Institute for Nutritional Medicine, Lübeck, Germany 9University of Lübeck, Institute and Comprehensive Center for Inflammation Medicine, Lübeck, Germany Fig. 1 low-glycemic intelligence diet Objective: Migraine is a severe neurological disorder with unmet needs. sinCephalea, a digital therapeutic (DTx) powered by continuous glucose monitoring (CGM) and artificial (AI), uses a personalized for migraine prophylaxis. This study aimed to confirm the efficacy of sinCephalea in reducing migraine days compared to standard of care. Methods: The 12-week digital open-label randomized controlled trial (registration: DRKS00024657) included 1,070 patients with episodic migraine and was conducted following Internation Headache Society standards. After a 4-week baseline, 842 patients were randomized 1:1 into control (standard treatment and e-diary) and intervention (sinCephalea) arm. Primary endpoint was the change in migraine days per 4 weeks (MMD) baseline vs. weeks 9-12 and secondary endpoints included response rates and HIT-6. Primary endpoint was tested using a linear model and two- sided test in the full analysis set (alpha=0.05, n=835). Results: Patients in the intervention arm achieved a mean reduction in MMD of 1.73 (SD 3.4) and showed a higher reduction in MMD compared to the control (difference between arms -0.53, p=0.0195). The frequency of clinical response (defined as 30%- responder rate) was 55% and significantly higher compared 1.63, p=0.0012). Additionally, the 50%-responder rate, an exploratory endpoint, reached 38% compared to control (OR 1.76, p=0.0004). The intervention arm also showed a clinically relevant reduction in HIT-6 score, measured to control (OR

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improvement with a reduction of 2.76 points (difference between arms -1.26, p=0.0001). The PGIC further indicated patient-perceived significant in the intervention, with a mean score of 2.96 (SD 0.86, p<0.0001). Conclusion: Our study demonstrates the efficacy of the DTx sinCephalea. It is the first prophylactic therapy using CGM influencing glycemic variation to reduce migraine frequency. This novel approach represents a clinically relevant advance in the management of migraine. Fig. 1 outcomes were assessed using the The Duke University Religion Index (DUREL) scale for religiosity scores and the Functional Assessment of Chronic Illness Therapy -Spiritual Well-Being (FACIT-Sp) scale to evaluate spirituality scores in both groups. Results: Among the 88 participants, 42 were in the migraine group and 46 in the non-migraine group. The sample was predominantly female (77.3%). Of the 11 religious affiliations selected, the most common were Catholic (26.1%), Evangelical (26.1%), and Spiritist (15.9%). Individuals with migraine scored lower on the DUREL scale, indicating higher levels of religiosity, with a statistically significant difference observed in the Intrinsic Religiosity domain (p = 0.001) (Figure 1. - Religiosity scores in people with and without migraine (DUREL)). On the FACIT-Sp scale, the migraine group also scored higher than the non- migraine group, with a significant difference in the "faith" domain (p = 0.03) (Figure 2. - Spirituality scores in people with and without migraine (FACIT- Sp)), individuals with migraine. Conclusion: Chronic pain not only causes physical suffering but also has psychological and social impacts on In this study, people with migraine appeared to utilize more resources related to religiosity and spirituality compared to those without migraine. In cases of chronic pain, certain beliefs are associated with better adjustment. Religion, religiosity, and spiritual beliefs and practices can significantly influence pain perception and adaptation. This influence is mediated through their effects on coping mechanisms. indicating higher scores pain-related individuals' lives. in beliefs and Fig. 1 LP029 Differences in religiosity and spirituality scores between individuals with and without migraine: a cross-sectional analysis G. Kleinschmitt Westenhofen1, M. Fernando Prieto Peres1 1Faculty of Medicine at the University of São Paulo, Institute of Psychiatry, São Paulo, Brazil Objective: To examine the differences in religiosity and spirituality scores between individuals with and without migraine. Methods: This cross-sectional study included men and women aged 18 to 60 years, with and without a diagnosis of chronic or episodic migraine. The study

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Fig. 2 this study suggest a growing interest in understanding the pathophysiology and treatment of VM. The insights gained from this analysis may guide future research efforts, inform clinical practice, and ultimately improve the diagnosis and management of patients with Vestibular Migraine. Fig. 1 Fig. 2 LP030 A bibliometric analysis of vestibular migraine research N. A. Amir1, W. A. Wan Sulaiman1, S. F. Sarkam2 1Universiti Putra Malaysia, Serdang, Malaysia 2Universiti Teknologi MARA, Technology, Melaka, Malaysia insights in This study aims to conduct vertigo," and a Objective: comprehensive bibliometric analysis of research on Vestibular Migraine, providing into the growth of publications, collaborative networks, and thematic trends that have shaped the field over past years. Methods: We conducted a bibliometric analysis using the Bibliometrix package in R to examine publications related to Vestibular Migraine from major databases (Scopus). Keywords such as "vestibular migraine," "migrainous "migraine-associated vertigo" were used to ensure comprehensive data collection. Key metrics, including annual publication trends, citation counts, prolific authors, collaboration networks, and thematic clusters, were analyzed. Results: The most cited articles highlighted diagnostic criteria, pathophysiology, and therapeutic approaches for VM. Collaborative networks the few high-impact authors and dominance of a institutions, and otolaryngology. Analysis of keyword co-occurrences revealed (1) pathophysiology (2), diagnostic criteria and disease classification, (3) case report. In recent years, themes such as audiometry testing, paediatric vestibular migraine, and benign paroxynormal positional vertigo indicating new research directions in the field. The three main countries with significant collaboration in Vestibular Migraine research are the USA, Sweden, and Norway. Conclusion: Findings from this study suggest a growing the pathophysiology and treatment of VM. Findings from understanding three main thematic clusters: particularly neurology indicated interest in

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Fig. 3 LP031 A systematic review and meta-analysis of placebo and nocebo response in the acute and prophylactic treatment of migraine in randomized controlled trials: rationale and design of the PANORAMIC study N. R. A. Bruijn1, A. Maassen van den Brink1, R. Fronczek2, E. M. Huessler3, H. C. Diener3, M. D. Ferrari2, L. Al-Hassany1 1Erasmus MC, University Medical Center Rotterdam, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands 2Leiden University Medical Center, Department of Neurology, Leiden, Netherlands 3University Hospital Essen, University Duisburg-Essen, Institute for Medical Informatics, Biometry and Epidemiology, Essen, Germany Objective: Placebo and nocebo response can significantly influence the results of migraine trials. The "PlAcebo and NocebO in acute and prophylactic tRiAls headache" (PANORAMIC) study is a systematic review and meta- in MIgraine Cluster and analysis of the magnitude and determinants of placebo and nocebo effects of different classes of acute and prophylactic antimigraine drugs over a period of nearly forty years. Methods: A systematic search strategy will be conducted in Medline ALL, Embase, Cochrane, Web of Science, and Google Scholar from 1988 onward. Only double-blind, randomized, placebo-controlled trials with ≥50 adult patients with episodic and/or chronic migraine meeting the ICHD criteria in each arm will be included. The acute treatments include, NSAIDs, triptans, and gepants, and the prophylactic treatments include antihypertensives, antiepileptics, antidepressants, CGRP(-receptor) inhibitors, and botulinum toxin A. The main study endpoints are shown in Table 1. Pooled estimates of the placebo and nocebo effects will be calculated using random- effects meta-analyses. Meta-regressions will be conducted to analyze the impact of determinants on placebo/nocebo the relationship between placebo and nocebo response as well as between placebo and active drug response. Results: The protocol has been submitted to and approved by PROSPERO (CRD42024583499). As of 09- 08-2024, a total of 5,701 unique search records have been identified. The project is currently ongoing, with expected to be completed by mid-2025. Conclusion: This research will enhance our understanding of placebo and nocebo responses in migraine trials. This is crucial for optimizing trial designs and improving clinical practice, which will ultimately improved migraine therapy. Other PANORAMIC follow-up projects involve evaluating placebo and nocebo effects in cluster headache trials. response and to analyze contribute to Fig. 1

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LP032 Association of migraine with COVID-19 infection in Hong Kong Chinese women: findings from the MECH- HK cohort study Y. J. Xie1, J. Liang1, Q. Sun2,3, J. Qin1, H. H. Wang4, T. Ma5 1The Hong Kong Polytechnic Univerisity, School of Nursing, Hong Kong, Hong Kong 2Harvard T.H. Chan School of Public Health, Department of Epidemiology, Boston, MA, United States 3Brigham and Women's Hospital and Harvard Medical School, Channing Division of Network Medicine, Boston, MA, United States 4Sun Yat-Sen University, School of Public Health, Guangzhou, China 5The Hong Kong Polytechnic University, Department of Rehabilitation Sciences, Hong Kong, Hong Kong to the named "Migraine Exposures Objective: The COVID-19 pandemic has posed significant challenges for individuals with migraine. This study aimed to explore the association of migraine with COVID-19 infection severity and the impact of infection on migraine features. Methods: Data were extracted from an ongoing cohort and Cardiovascular Health in Hong Kong Chinese Women (MECH-HK)". Baseline assessment was conducted between 2019 and 2021. Migraine was diagnosed according International Classification of Headache Disorders, 3rd edition. Migraine features (attack frequency, headache duration, and intensity) were longitudinally tracked using migraine diaries. The COVID-19 severity was assessed by number of infection symptoms, severity scores, and the post- COVID symptoms. Results: In total 1,085 adult women diagnosed with COVID-19 were enrolled, with a mean age of 54.3±9.4 years. Among them, 122 (11.2%) were migraineurs. The most frequently reported symptoms were cough (75% vs. 67%) and sore throat (58% vs. 52%) in migraineurs and non-migraineurs, respectively (Both P<0.05). Migraineurs had significantly higher counts of mild symptoms [mean difference (MD): 1.0; 95% CI: 0.6–1.5] and moderate/severe symptoms (MD: 0.3; 95% CI: 0.1–0.5) during infection, along with higher severity scores (MD: 0.2; 95% CI: 0.0–0.3) and more post-COVID symptoms (MD: 0.5; 95% CI: 0.3–0.8) than non-migraineurs. Within 1–3 months post-infection, migraineurs had a significant in attack frequency compared with before infection (2.5 vs. 3.6 attacks/month, P<0.05), while no significant changes in headache duration and intensity. Conclusion: Women with migraine experienced greater COVID-19 severity and a higher burden of post-COVID symptoms. COVID-19 infection was also linked to increased migraine attack frequency. These increase the findings emphasize tailored migraine management for people comorbid migraine and infection disease. importance of LP033 Beyond Triptans and NSAIDs: The emerging role of rimegepant in refractory acute migraine management – insights from a Portuguese unicentric perspective M. Henriques1, J. Moniz Dionísio1, E. Parreira1 1Hospital Prof Doutor Fernando Fonseca, Neurologia, Lisboa, Portugal is triptans are real-world data on least once. Patients first-line Objective: NSAIDs and treatments for acute migraine. While generally effective, these treatments do not benefit all patients and may cause significant side effects. Rimegepant is a newer option, but its effectiveness limited. Our objective is to assess the safety and efficacy of rimegepant for acute migraine in cases unresponsive to other treatments, with an additional focus on patient preferences. Methods: This is a single-center, observational, cross- sectional study involving patients resistant to three or more acute migraine treatments who have used rimegepant at received rimegepant during headache appointments and subsequently completed online questionnaires. Data analysis was performed using SPSS. Results: Data were collected from 18 patients, with 17 having trialed the medication. 82.4% were female, median age of 43 years. All patients were on preventive therapy (64.7% with anti-CGRP). 76.5% reported using rimegepant due to the ineffectiveness of prior medications. 47.1% deemed rimegepant completely effective. The majority experienced relief within 30 minutes, with pain cessation occurring within 1 hour. 70.6% did not require any additional medications. Adverse effects were reported by only one patient. Additionally, 41.2% believed that rimegepant improved other migraine-associated symptoms. A significant 58.8% indicated a preference for rimegepant over their usual treatment due to its efficacy and rapid onset of relief. The primary barrier to more widespread use was identified as cost. perspective, Conclusion: rimegepant appears to be a highly effective and safe alternative for the treatment of resistant acute migraine. However, its use remains limited due to high market costs. patients' From our

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distinct from the biomarker profile typically seen in PE. Fig. 1 LP034 Association between migraine and sFlt-1/PlGF levels in women with suspected and confirmed preeclampsia L. Al-Hassany1, N. R. A. Bruijn1, R. I. Neümañ1, L. Saleh2, B. W. H. van der Arend1,3, G. M. Terwindt3, W. Visser1, A. H. J. Danser1, A. Maassen van den Brink1 1Erasmus MC, University Medical Center Rotterdam, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands 2Erasmus MC, University Medical Center Rotterdam, Department of Gynecology and Obstetrics, Rotterdam, Netherlands 3Leiden University Medical Center, Department of Neurology, Leiden, Netherlands Objective: Migraine is associated with an increased odds of pre-eclampsia (PE), though the vascular etiologies of both remain unclear. Soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and their ratio are predictive biomarkers of PE- related complications, but to what degree they are affected by migraine is unresolved. Here we studied whether migraine affects these biomarkers in women with suspected/confirmed PE. We hypothesized that migraine is associated with elevated sFlt-1/PlGF ratios. Methods: This secondary analysis evaluated women who had previously participated in the prospective, multicenter PreRatio study[LA1] , which assessed the predictive value of sFlt-1, PlGF and their ratio in singleton pregnant women with suspected/confirmed PE. All sFlt-1/PlGF levels were measured during pregnancy. Migraine diagnoses before/during the index pregnancy were retrospectively assessed through standardized phone interviews according to ICHD-3 criteria. Comparisons between women with and without migraine were conducted using the Mann-Whitney U test (significance level P<0.05). Results: A total of 234 women (mean age 31.7±5.1 years) were included in the analyses, of whom 91 (38.9%) had (a history of) migraine. Among those with migraine, 33 (36.3%) experienced aura symptoms. Eventually, 110 (47.0%) were diagnosed with PE, 52 (22.2%) with gestational hypertension, and 72 (30.8%) with neither. Women with migraine had levels (P=0.018) and sFlt-1/PlGF ratios (P=0.013) compared to women without migraine. No differences were observed for PlGF levels (P=0.088) (Fig 1). Conclusion: Migraine appears to be associated with lower sFlt-1 levels and sFLT-1/PlGF ratios in women with PE. Hypothetically, migraine might lead to a PE-like phenotype and raise suspicion for this condition, independent of sFlt/PlGF levels or ratios. This finding suggests a unique vascular profile among these pregnant migraine patients, suspected/confirmed lower sFlt-1 LP035 Optimizing an e-headache diary for migraine care through active patient participation: a study design C. Doelman1, N. van Veelen1, D. Determann1, P. Wilbrink1, E. Ruiz de la Torre1, E. Giltay1,2, N. Pelzer1, G. M. Terwindt1 1LUMC, Psychiatry, Leiden, Netherlands 2Health Campus the Hague, Leiden University Medical Center, the Hague, Department of Public Health and Primary Care, The Hague, Netherlands Objective: The Leiden Headache Center has developed a validated e-headache tool to enhance migraine care. This digital diary tracks patient- reported headache characteristics, medication use, well-being, and outcomes, including

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and patient participation. depressive symptoms, using validated algorithms to provide diagnostic insights for patients and healthcare providers. The app supports real-time monitoring, telemedicine, In collaboration with the European Headache Migraine Alliance (EHMA), national migraine patient groups, and healthcare providers, we aim to provide and evaluate patient-driven outcomes of disease burden. Special attention is given to depression as a risk factor for chronic migraine. The project also focuses on optimizing the digital tool based on psychometric analyses of the E-diary and user feedback, with the goal of offering personalized, patient-centered care. For this we have the following three aims. Methods: Objective 1: Simplify the e-headache diary by performing psychometric analysis of diary data of over 1,000 migraine patients. Based on the Item Response Theory analysis we will refine or reduce response options of items in the diary, such as items. We will also simplifying nausea-related evaluate depression and anxiety (HADS) in the migraine population. Objective 2: Develop a more comprehensive primary outcome measure for disease burden beyond monthly like disease migraine days, considering severity, disability, migraine and depression/anxiety symptoms. We aim to correlate these with the Headache Impact Test, to create a model reflecting overall disease impact, with sub- analyses for menstrual migraine. Objective 3: Use network analyses to study individual symptom patterns, including depressive symptoms, and tailor treatments to patient needs. Group-level analyses will identify common symptom interactions, enhancing understanding of migraine mechanisms and subgroups. Results: - Conclusion: - recurrence, factors LP036 Efficacy and safety of Fremanezumab for the preventive treatment of episodic migraine in children and adolescents: a phase 3, randomised, double-Blind, placebo-controlled study A. D. Hershey1, C. L. Szperka2, P. Barbanti3,4, P. Pozo- Rosich5, P. Bittigau6, S. Barash7, S. Garnett7, J. Bryson7, Y. Kessler8, Y. Carmeli Schwartz8, X. Ning7 1Cincinnati Children’s Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, OH, United States 2Children’s Hospital of Philadelphia and Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, United States 3Headache and Pain Unit, IRCCS San Raffaele, Rome, Italy 4San Raffaele University, Rome, Italy 5Headache Unit and Research Group, Vall d’Hebron Hospital and Research Institute, Universitat Autonoma de Barcelona, Barcelona, Spain 6Charité – Universitätsmedizin Berlin, Berlin, Germany 7Teva Branded Pharmaceutical Products R&D, Inc., West Chester, PA, United States 8Teva Pharmaceutical Industries Ltd., Tel Aviv, Israel Objective: Fremanezumab is a calcitonin gene-related peptide pathway monoclonal antibody approved for preventive migraine treatment in adults. The SPACE study (NCT04458857) evaluated the efficacy, safety and tolerability of fremanezumab in children and adolescents with episodic migraine (EM). Methods: In this multicentre, double-blind, parallel- group, Phase 3 study, participants aged 6–17 years, with a migraine diagnosis for ≥6 months and history of ≤14 headache days/month, were randomised (1:1) to monthly fremanezumab (<45kg, 120 mg; ≥45kg, 225 mg) or placebo for 12 weeks. Primary endpoint: least- squares (LS) mean change from baseline in average monthly migraine days (MMD) during the double- blind period. Secondary endpoints included LS mean change from baseline in monthly headache days of at least moderate severity (MHD) and proportion of participants achieving a ≥50% reduction in MMD. Subgroup analyses were conducted by age (6–11 and 12–17 years) and sex. Results: Of 237 randomised participants, 234 (6–11 years, n=63; 12–17 years, n=171; male, n=105; female, n=129) were included in the efficacy analysis (fremanezumab, n=111). Fremanezumab significantly reduced MMD versus placebo (–2.5 vs –1.4; p=0.0210) over 3 months. LS mean changes from baseline in MMD favoured fremanezumab over placebo in subgroups stratified by age (6–11 years: –3.4 vs –1.7; 12–17 years: –2.7 vs –1.8) and sex (male: –3.5 vs –2.2; female: –2.3 vs – 1.5). The reduction in MHD was significantly greater with fremanezumab versus placebo (–2.6 vs –1.5; placebo, n=123;

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p=0.0172), as was the 50% response rate (47.2% vs 27.0%; p=0.0016). The proportion of participants reporting ≥1 adverse event (AE) was similar across treatment groups (fremanezumab, 55%; placebo, 49%). The proportion of participants with serious AEs (≤3%) and AEs leading to discontinuation (<1%) were low. Conclusion: These findings demonstrate the efficacy, safety and tolerability of fremanezumab in children and adolescents with EM. Teva Pharmaceuticals funded this study. LP037 Comparing the use of Erenumab and Galcanezumab for migraine prevension in patients with chronic and episodic migraine: prospective observational study M. El lahawi1, S. Baroud2, S. Mohammed2 1Sheikh Khalifa Medical City, Neurology, Abu Dhabi, United Arab Emirates 2SKMC, Internal Medicine, Abu Dhabi, United Arab Emirates Objective: To assess the efficacy of Galcanezumab and Erenumab in the of Chronic and Episodic Migraine. The primary outcome is the overall mean change from baseline in the number of monthly migraine headache days during the treatment period (MMD). Secondary measures included a reduction in migraine headache days with acute medication use per month (AMSMD). Treatment-emergent adverse events and serious adverse events were reported. Methods: Retrospective Study of adult patients with migraine following in Neurology clinic at Sheikh Khalifa Medical City, Abu Dhabi and receiving either galcanezumab or erenumab. Tools: Questionnaires filled out over the phone , face to face interview and from patient records. Adult patients age18+ Total number : 342 Must have either episodic or chronic migraine with or without aura 171 patients out of 342 were excluded Patient must be taking either Galcezumab or Erutunamb for at least 3 months Total number included : 171 – (85 used Erunumab and 86 used Galcezumab) Results: Exclusion Criteria- Total number excluded: 171 - Non-Chronic or Non-Episodic Migraines. - Discontinuation of the medication after less than 3 months use. -Lost follow up. -Transfer care to different facility. - Not responding to the calls , - Failed to return the questionnaire. 85 patients were on erenumab and 86 patients on galcanuzemab is slightly superior to Conclusion: Galcanezumab Erenumab in improving the headache within first week in 38 patient compared to 26 patients. Improvement within the 1st month after injection , Erenumab as . improvement is 73 patient compared to 44 , Reasons: is superior to Galcanezumab Regarding the number of migraine days per months , the two drugs are similar in reducing the number of migraine days per months. The number of patient reduce Acute migraine-specific medication days (AMSM) after starting the injection is similar in both drugs Side effects is similar regarding constipation, and more with the injection site reaction with Galcanezumab ( Itching and redness). LP038 Headache and migraine attack prediction accuracy in those with migraine G. Dumkrieger1, T. Schwedt1 1Mayo Clinic, Neurology, Phoenix, AZ, United States Objective: We examined the ability of participants with migraine to predict headache and migraine attacks. Methods: Participants were enrolled for up to 4 months. Each evening participants were asked to predict if they would have a migraine the following day. Available answers were "Definitely Not", "Probably Not", "Probably Will" and "Definitely Will". Reported headache duration, symptoms and migraine specific medication use were used to classify each headache as a migraine or non-migraine. The percentage of correct predictions made each evening about the following day were calculated and by confidence of their answer. A separate analysis of migraine-only attacks was made. The accuracies were compared to the no information rate (NIR) to determine if the predictions are more accurate than chance, an important consideration when classes are unbalanced. Results: 34 participants were enrolled. Average headache frequency was 9.4/28 days (median 9.5, IQR: [5 12]). When predicting next day headache occurrence the overall accuracy was 69.8% (Table1). Positive responses were correct 50.4% of the time. NIR was 0.70; not significantly different than the prediction accuracy (p = 0.43). 82.1% of "Definitely Will" predictions were correct (Table2). When examining only migraine headaches overall accuracy of predicting next-day migraine occurrence was 74.7%. 34.5% percent of positive responses were correct. The NIR was 0.81, not significantly different than the accuracy (p = 1). "Definitely Will" responses were correct 65.6 % of the time. Conclusion: Affirmative predictions of next day headaches were slightly more accurate than chance. "Definitely" predictions were more accurate than "Probably" predictions but less common. This analysis highlights the need to carefully examine multiple metrics when evaluating migraine or headache prediction ability. Low headache rates will

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lead to high NIR and a high overall accuracy is easily achieved. Additional measures (sensitivity, PPV) should be considered. Fig. 1 Fig. 2 LP039 418 million migraine sufferers without preventive treatment worldwide: distribution among GBD superregions I. Liger Riso1, M. Fernando Prieto Peres1 1Hospital Albert Einstein Sao Paulo, Neurologia, São Paulo, Brazil Objective: The objective of this study was to review the patterns of access to healthcare treatment for preventive migraine medication among individuals diagnosed with migraine in various GBD regions. Methods: A search of PubMed for articles published between January 1, 2000, and June 25, 2024, was conducted. Studies included those that reported on healthcare resource utilization, treatment access, unmet needs, and undertreatment of migraines. The American Headache Society (AHS) 2021 Consensus Statement algorithm was used to determine candidacy for preventive treatment. Results: Out of 431 publications retrieved, 80 met the inclusion criteria. The prevalence of preventive treatment in the migraine population ranged from 0% in Nigeria to 36.2% in Japan, with a global 1-year-age adjusted prevalence of 17.8%. Based on the AHS consensus statement algorithm, approximately 38.7% of the global migraine population would qualify for preventive treatment. However, around 79.8% of these candidates are not receiving to approximately 418 million people globally. treatment, preventive equating Dividing it among GBD super-regions, Central Europe, Eastern Europe and Central Asia 30,6 million people, High-Income 49 million, Latin America and Caribbean 30,5million, North Africa and Middle East 48,1 million, South Asia 109,9 million, Southeast Asia, East Asia and Oceania 115,3 million and Sub-Saharan Africa 35,6 million. Conclusion: There are significant gaps and a lack of recent information in the literature regarding the preventive treatment of migraines. More recent, population-based studies are necessary to assess the recognition of migraine preventive candidates and those undergoing preventive treatment, to inform better public health strategies for migraine diagnosis and treatment. LP040 Does missing information necessary implies Misdiagnosis in ICHD3? P. Zhang1,2 1Beth Israel Deaconness Medical Center, Neurology, Boston, MA, United States 2Harvard Medical School, Boston, MA, United States between it headache ICHD3. Furthermore, Objective: Intuitively, if elements are missing from clinical history taking, difficulty should arise in differentiating disorders. However, it is unclear if this would truly be the case under is unclear how classification would change if a specific phenotype is eliminated from ICHD3 altogether. This project asks the following question: Which headache disorders would be indistinguishable if specific characteristics are taken away from ICHD3? Methods: We translate ICHD3 into their numerical encoding using the methodology established in Which headache disorders can be diagnosed concurrently? An analysis of ICHD3 criteria using prime encoding system; doi.org/10.3389/fneur.2023.1221209. We then eliminate either location, autonomic features, duration, frequency, laterality, photo/phonophobia, nausea, severity, and headache triggers from the ICHD3. We extract the pairings of encoding of diagnosis which become in the ICHD3 upon the above phenotypes. Results: Removal of headache frequency leads to indistinguishability between the subtypes of tension type headaches whereas removal of headache location indistinguishability between 20 different pairing of ICHD3 diagnoses. Surprisingly, the elimination of any other phenotypes did not cause indistinguishability headache disorders. Conclusion: This study suggests that elimination of most of the above criteria from ICHD3 will not yield a removal of each of indistinguishable between primary leads to

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different classification of headache disorders. However, eliminations of frequency and/or location will lead to a significant reordering/merging of ICHD3 headache diagnoses. LP041 Does ICHD3 Inheritantly allows for misrecognition in cases of multiple headaches? P. Zhang1,2 1Beth Israel Deaconness Medical Center, Neurology, Boston, MA, United States 2Harvard Medical School, Boston, MA, United States into then diagnose the encoding. yields this numerical Objective: In clinical circumstances of more than one headache disorder, misrecognition can occur if each headache disorder is not separately and individually evaluated. For example, consider the case of a patient with baseline tension type headaches lasting hours who now develops cluster headaches with nausea. Merging the characteristics of both disorders may yield the illusion of migraine. Do these types of misrecognition occurs necessarily as a result of ICHD3 criteria? Are there combinations of ICHD3 criteria, if any, which necessarily type of misrecognition? ICHD3 primary headache Methods: We encode disorders (See http://doi.org/10.3389/fneur.2023.1221209) We then model the encoding of two concurrent diagnoses in an individual by multiplying all pairing of ICHD3 encoding while keeping track of which two diagnoses we are "merging". We result algorithmically to see which pairings, if any, generate "new"/"illusionary" diagnoses. Results: A total of 92,723 pairings of ICHD3 phenotypes were generated/merged. After duplicate pairing of diagnoses were removed we derived a total of 38 pairings of unique ICHD3 diagnoses that yields a "new" diagnoses. However, none of these pairings were judged to be "illusionary": they simply arise from our model"s idiosyncrasy of being able to encode chronic migraine without encoding migraine with or without aura. Conclusion: "Illusionary diagnosis" that arises when merging the phenotypes of two headache diagnoses does not arise itself. Therefore "illusionary diagnoses" in clinical practice are likely to be results of idiosyncracies of specific headache presentations. from ICHD3 LP042 The role of Artificial Intelligence (AI) in migraine diagnosis and prophylactic indication based on headache diary: a comparison with physician clinical judgement W. M. Ramschie1, H. R. Sofyan1, I. S. Madjid1, T. Aninditha1 1Faculty of Medicine, Universitas Indonesia, Neurology, Kota Bekasi, Indonesia Objective: This study aims to compare AI-based recommendations for migraine diagnosis and prophylaxis with clinical decisions made by physicians. It also assesses migraine prevalence, patient characteristics, and the use of prophylactic therapy at Dr. Cipto Mangunkusumo Hospital (DCMH) Methods: A retrospective cohort study was conducted in 2023 on headache patients at the DCMH neurology clinic, utilizing headache diaries and medical records. Migraine diagnosis was based on the International Classification of Headache Disorders, 3rd edition (ICHD-3) criteria [1]. The need for prophylaxis was determined using criteria set by the International Headache Society (IHS) [2]. Inter-rater reliability between AI and physician diagnoses was evaluated using Cohen's kappa Results: Seventy patients participated, 82.85% were female, with an average age of 34. The majority (58.57%) reported moderate headache intensity (NRS 4-6), and 88.57% had episodic migraines. Physicians diagnosed migraines in 71.43% of patients, while AI identified migraines in 90% (Table 1). Inter-rater reliability showed substantial agreement in diagnosis (Cohen's kappa = 0.71, p < 0.0001). Physicians prescribed prophylaxis to 64.28% of patients, while AI recommended it to 85.71%. There was strong agreement in prophylaxis recommendations (Cohen's kappa = 0.73, p < 0.0001) (Table 2). Propranolol (25.71%) and Amitriptyline (21.42%) were the most frequently prescribed agents by physicians. Conclusion: The study shows significant agreement between AI and physicians in diagnosing migraines and recommending prophylaxis. AI identified more cases and recommended prophylaxis more often than physicians, line with previous study [3] that mentioned substantial agreement of Cohen"s kappa value in comparing. Further research is needed to explore discrepancies, as AI could improve decision- making in migraine management. in

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Fig. 1 Fig. 2 LP043 Prediction of new-onset migraine for clinical- genotypic data: a machine learning analysis F. Faisal1,2, A. Danelakis1,3, M. H. Bjørk1,4,5, B. Winsvold1,6,7,8, P. Nachev9, M. Matharu9, K. Hagen1,10, I. Author11, E. A. Tronvik1,2, A. Stubberud1,2 1Norwegian Centre for Headache Research (NorHead), Trondheim, Norway 2NTNU Norwegian University of Science and Technology, Department of Neuromedicine and Movement Science, Trondheim, Norway 3NTNU Norwegian University of Science and Technology, Department of Computer Science, Trondheim, Norway 4University of Bergen, Department of Clinical Medicine, Bergen, Norway 5Haukeland University Hospital, Department of Neurology, Bergen, Norway 6Oslo University Hospital, Department of Research and Innovation, Oslo, Norway 7Oslo University Hospital, Department of Neurology, Oslo, Norway 8NTNU Norwegian University of Science and Technology, Department of Public Health and Nursing, Trondheim, Norway 9University College London, UCL Queen Square Institute of Neurology, London, United Kingdom 10St Olav University Hospital, Neuroclinic, Trondheim, Norway 11The International Headache Genetic Consortium, Brisbane Queensland, Australia the Objective: To develop and evaluate machine learning (ML) models in order to predict new-onset of migraine based on genetic and a wide range of clinical and demographic data. Methods: This study was a population-based cohort study from the second and third Health Surveys in Nord-Trøndelag (HUNT2 1995-1997 and HUNT3 2006- 2008). Clinical data was captured in validated questionnaires and a large proportion of participants underwent genome-wide genotyping. Phenotype assignment was based on validated modified criteria of International Classification of Headache Disorders. The primary outcome was new onset migraine defined as a change in disease status from headache-free in HUNT3. Migraine risk variants identified in the largest GWAS meta-analysis were used as genetic input features. The clinical features included demographics, selected comorbidities, medication and stimulant use and certain non-headache symptoms and complaints. Several standard ML architectures were constructed, trained, optimized and scored with area under the receiver operating characteristics (ROC-AUC) curve. SHAP summary plots were created for model explainability. in HUNT2 to migraine

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Results: A total of 12995 individuals were included in the predictive modelling (12504 headache-free, 491 new onset migraine). We included 108 variants in the genotype models, while 67 clinical variables were included in the clinical and combined models. The top performing classifier achieved an AUC of 0.51 with genotypic variables, 0.66 with clinical data and 0.67 with both genetic and clinical variables in a held-out t- est set (Fig. 1, Table 1). The most important clinical variables were age, marital status and work situation while several genetic variants were also considered vital (Fig. 2). Conclusion: The new onset of migraine in adult age is poorly predicted by genotypic data, however, routine demographic and clinical data (mostly non-headache- related) correctly predict the new onset of migraine in approximately 2 out of 3 cases. Fig. 1 Fig. 2 Fig. 3 LP044 Remote examination of reaction time during and between headaches in those with migraine G. Dumkrieger1, T. Schwedt1 1Mayo Clinic, Neurology, Phoenix, AZ, United States Individuals with moderate Objective: We examined if performance on digital tests of reaction time differed during vs between headaches in those with migraine. frequency Methods: migraine were enrolled. Participants were asked to complete digital Choice Reaction Time (CRT) and Corsi block tapping tasks each morning for 3-4 months and during headaches. Participants were able to use their computer (desktop or laptop) or mobile device (phone or tablet) to complete the tasks. Headache status and device type were recorded at the time of task completion. The CRT three symbols. Participants signalled which symbol was shown as quickly as possible by clicking or tapping the matching test flashed one of

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symbol displayed at the bottom of the screen or by pressing the appropriate key. The Corsi test displayed a set of rectangles and then highlighted a sequence, starting with a sequence of 3. Participants replicated the sequence by selecting the rectangles on screen with mouse or by tapping the screen. If the participant correctly repeated the sequence a longer sequence was displayed. CRT accuracy, CRT response time and Corsi average click time per block during vs between headaches were compared using Welch"s two sample t-tests. Corsi longest sequence was compared between headache and non-headache status by device type using Wilcoxon rank sum test. Results: 34 participants completed 2939 test sessions (computer:1193, mobile: 1746)CRT accuracy was high and did not differ based on headache status (p = 0.05). Reaction time was slower during headaches for mobile (p<0.0001) and computer (p=0.0003) users. Longest sequence length did not differ between the headache for computer(p=0.241) or mobile (p=0.054) users. Mean click time differed between headache and non- headache status for computer (p=0.005) and mobile users (p = 0.001). Conclusion: Differences in response time between and during headaches in those with migraine can be detected in assessments delivered at home or via mobile device. non-headache and status LP045 Erenumab-treated patients and the risk of hypertension: a retrospective real-world study T. Alsaadi1, R. Suliman1, V. Santos1, I. Al Qaisi1, Y. Amin1, A. Alkhateri1, B. Pagdato1, P. Carmina1, A. Maassen van den Brink2, C. Lampl3 1American Center for Psychiatry and Neurology, Department of Neurology, Abu Dhabi, United Arab Emirates 2Erasmus MC Medical Center, Department of Internal Medicine, Rotterdam, Netherlands 3Konventhospital Barmherzige Brüder Linz, Department of Neurology and Stroke Unit, Linz, Austria Objective: CGRP mAbs havce shown promising effectiveness in migraine prevention compared to other older preventatives. Erenumab is the first CGRP mAb approved by the FDA. Although there was no evidence of hypertension in preclinical models or clinical trials involving patients treated with erenumab recent post marketing studies have suggested a link between erenumab and hypertension. However these studies are limited in various aspects. This study seeks to explore and assess the risk of hypertension in erenumab treated patients in the UAE. Methods: This was a retrospective, real world exploratory study. Participants were ≥18 years with a confirmed diagnosis of migraine as per the ICHD-3 criteria. Data was collected from ACPN Abu Dhabi for all patients treated with erenumab. 347 were identified and screened. Those who previously received other mAbs or gepants were excluded. Only patients who received treatment for a min of 12 months and had data on their bp atleast once every 3 months were included. 125 were eligible and analyzed, 54 of them completed 24 months. Systolic and diastolic bps were compared between baseline and follow up visits. Results: 93% of the study population were of Arab ethnicity. The average bp fell within the normal range for systolic (<120 mmHg) and diastolic (<80 mmHg). Across various visits and doses both mean systolic (118-121 mmHg) and diastolic pressures (78-80 mmHg) remained stable. No significant diferences across different age groups. Results were similar for those who completed 24 months. indicate that Conclusion: Findings of this study erenumab does not impact systolic or diastolic bp. The bp readings remained within normal ranges across various visits doses and age groups. The consistent bp readings suggest that erenumab is well tolerated among patients without causing significant elevations in bp regardless of their age family history of hyepertension or comorbid conditions. Future studies are waranted to further validate these findings and explore long term outcomes. LP046 Arthralgia: A potential side effect of CGRP inhibitors R. van Eekeren1, P. Zweers1, L. Al-Hassany2, D. M. Boucherie2, A. Maassen van den Brink2 1The Netherlands Pharmacovigilance Centre Lareb, 's- Hertogenbosch, Netherlands 2Erasmus MC, University Medical Center Rotterdam, Division of Vascular Medicine and Pharmacology, Department of Internal Medicine, Rotterdam, Netherlands For Objective: Calcitonin gene-related peptide(-receptor) inhibitors (CGRPi) are a new class of antimigraine drugs with a yet incomplete safety profile. Joint- related disorders are not known as adverse drug reactions (ADR) within this class. purposes, Methods: spontaneously reported individual case safety reports of joint disorders associated with CGRPi (fremanez-, galcanez-, erenumab) in the Netherlands were analysed until September 2024. Results: Joint disorders were reported in 132 unique cases (98% women; mean age 49.9 yrs (sd 11.1); mean BMI 27.3 (sd 6.3)), most often with fremanezumab pharmacovigilance

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continued (n=69). Historic or comorbid joint diseases were present in 23 cases (17.4%). A total of 144 joint reactions were reported, of which arthralgia without inflammatory signs (n=105) and arthropathy (n=18) most frequently. In 93 cases, multiple joints were affected, most commonly concerning knees (30.3%), hips (22.7%), shoulders (21.2%) and hands (20.5%). Time-to-onset was < 1 day –1 week after the first administration in 60 (41.2%) adverse reactions. A recurrent pattern of complaints following subsequent administrations is described in 19 (13.2%) cases. 17/36 (47.2%) patients who stopped using CGRPi recovered from the joint disorder; 17/68 (25.0%) of those who recovered spontaneously. Myalgia (n=36), fatigue (n=27) and weight gain (n=20) were the most commonly co- reported symptoms with the use of CGRPi. Conclusion: Spontaneous reporting can generate, but not prove, a potential signal of a yet unknown ADR. The current data suggest a possible relationship, although causality cannot yet be established. Hypothetical mechanisms that may be involved include the modulatory role of CGRP in pain and sensory function, as well as de novo inflammation. Therefore, awareness and information from clinical practice concerning joint-related symptoms with CGRPi is essential to strengthen the evidence for this potential ADR. the CGRPi LP047 Real-world insights into migraine associated with menstruation, prodrome, and aura: patient-reported outcomes of Gepant treatment in a tertiary care center S. Malhan1, A. Nisar1, S. Ghosh1, V. Wang1, N. Spare1, M. Marmura1, H. Yuan1 1Thomas Jefferson University, Neurology, Philadelphia, PA, United States Objective: To investigate the real-world effectiveness of gepants for migraine attacks associated with menstruation (MM), prodrome, and aura through an online survey. Methods: A REDCap survey was emailed to adult patients prescribed gepants at Jefferson Headache Center (June 2020 - July 2024). Patients provided demographics, usage, and response to gepants for MM ("yes", "no", or "unsure"). Response consistency of gepants to prevent headache when taken at onset of prodrome and/or aura was rated on a scale from "never" to "always" (0-100). Data were presented in percentages or mean±standard deviation or median (interquartile range) if non-normal distribution. Results: Of 3545 invitations, 478 (13.4%) individuals (age 49.9±14.5 years, 429 (89.7%) Caucasian, 19 (4.0%) African American) completed the survey. Of (36.3%) females who the 150 reported MM, 56.7%/43.3% were current/past rimegepant users (n=104), 63.1%/36.9% ubrogepant users (n=103), and 58.7%/41.3% atogepant users (n=46). Positive responses for MM attacks were seen in 32.7% (34/104) rimegepant, 35.0% (36/103) ubrogepant, and 19.6% (9/46) atogepant, with negative responses in 35.5%, 27.1%, and 47.8% respectively. The remainder were "unsure." Of all users, 55.2% (264/478) reported having prodrome, and 29.3% (140/478) reported aura. For those who reported either prodrome or aura (n=302), the median response consistencies were: rimegepant 44 (54), and atogepant 23 (50). Potential selection bias existed, as patients using gepants often have a history of triptan failure or intolerance. Conclusion: This real-world survey suggests some patients with MM found relief with gepants. Among those with prodrome and/or aura, response consistency ranged widely between gepants. These findings suggest variability in individual responses, emphasizing the need for larger, more diverse studies to better assess gepants' role in migraine-associated attacks to menstruation, prodrome, and aura. (62), ubrogepant 50 Fig. 1 Fig. 2

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LP048 Patient characteristics and clinical response to Fremanezumab in Episodic cluster headache: insights into CGRP and PACAP pathways N. Vashchenko1, J. Azimova1, K. Skorobogatykh1 1University Headache Clinic, Moscow, Russian Federation Objective: To characterize the clinical features of patients with episodic cluster headache who responded favorably to fremanezumab and to explore the role of CGRP and PACAP pathways in cluster headache pathophysiology. included 20 Methods: This observational study cluster headache, all patients with episodic responding to fremanezumab, treated at a tertiary headache center between March 2021 and October 2024, with a minimum follow-up of 2 years. During each active cluster period, patients received a 225 mg injection of fremanezumab at onset. Clinical characteristics, including baseline attack frequency, headache intensity, cluster period duration, and time between cluster periods, were documented. Patient responses were assessed using headache diaries, patient-reported outcomes, and adverse event monitoring. In addition, response patterns were examined to understand the therapeutic role of CGRP and the potential involvement of PACAP in residual symptoms. baseline Results: characteristics, with high attack intensity (mean 9.8/10) and prolonged cluster periods (mean 77.5 ± 6.2 days). Fremanezumab significantly reduced cluster period duration (mean reduction of 22%) and pain intensity (mean reduction of 6.9 points on the pain scale). Autonomic symptoms such as lacrimation, eye redness and rhinorrhea remained unchanged and consistently marked the onset of attacks, with most attacks occurring at a specific time, predominantly at night. reduced Conclusion: episodic cluster headache in patients with specific clinical profiles, presumably by blocking the CGRP pathway. The persistence of autonomic symptoms and temporal attack patterns suggests a continued involvement of PACAP in the disease mechanism. Further investigation of PACAP inhibition alongside CGRP blockade may in these patients. Fremanezumab effectively improve outcomes Responders had distinct LP049 Exercise as part of multidisciplinary management of migraine: an evidence-based case report of systematic reviews and meta-analyses E. R. Indrapriambada1, I. S. Madjid1, A. R. Faiq1, H. R. Sofyan1, T. Aninditha1 1Faculty of Medicine, Universitas Indonesia/Cipto Mangunkusumo Hospital, Department of Neurology, Jakarta, Indonesia therapy intensity, is beneficial to Objective: A 24-year-old male presented to our clinic with a chronic headache of migraine phenotype that occurred at least once a week and did not respond well to acute medications. Patient was informed to fill a headache diary as well as to modify his lifestyle. As a physician, you are interested whether exercise, as part of the SEEDS (sleep, exercise, eat, diary, and stress) mnemonic improve his headache outcomes. Methods: Our clinical question components are adult patients with migraine-type headache (population); planned and structured exercise with/without (intervention); standard pharmacological usual care or no treatment (comparison); and headache frequency, and/or duration (outcome). We systematically searched PubMed and Cochrane for systematic reviews and meta-analyses published during the last 10 years. Critical appraisal was performed using the Center of Evidence Based Medicine Oxford checklist. Results: We found 4 articles. All systematic reviews included clinical trials as individual studies, although not all required randomization. Interventions included aerobic or endurance exercise of various intensity, resistance training, and other specific forms (such as tai chi and yoga) without any specified duration. Most studies used the Cochrane Risk of Bias (RoB/RoB2) toolkit and one used the Tool for the Assessment of Study Quality and Reporting in Exercise (TESTEX). 5 studies had moderate risk of bias and 1 study had low risk of bias. Our results showed that exercise, particularly moderate-high intensity aerobics and strength training, was beneficial in migraine in terms of decreasing frequency and intensity. Conclusion: Exercise is useful in improving migraine outcomes. Most systematic reviews in this case report had moderate risk of bias, possibly due to inclusion of individual studies with variations of intervention design and heterogenous types of exercise regimen. Results from the assessed evidence are applicable for our clinical scenario.

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LP050 Home-based biofeedback therapy for migraine prevention in adults with episodic migraine using a novel therapist-independent smartphone system: a randomized, waitlist-controlled trial A. C. Poole1,2,3,4, A. Stubberud1,2,3, M. Simpson5, L. Øie1,2,3, M. H. Bjørk1,6,7, E. Saxhaug Kristoffersen1,8,9, K. G. Vetvik1,9, A. Olsen1,10,11, I. C. Keim Larsen1,12, M. Linde1,2,4, E. A. Tronvik1,2,3, T. Meisingset1,2,3,4 1NorHEAD, Trondheim, Norway 2NTNU, Department of Neuromedicine and Movement Sciences, Trondheim, Norway 3St. Olavs hospital, Trondheim University Hospital, Department of Neurology and Neurophysiology, Trondheim, Norway 4Sahlgrenska University Hospital, Regional Migraine Unit, Gothenburg, Sweden 5NTNU, Department of Public Health and Nursing, Trondheim, Norway 6Haukeland University Hospital, Department of Neurology, Bergen, Norway 7University of Bergen, Department of Clinical Medicine, Bergen, Norway 8University of Oslo, Department of General Practice, Institute of Health and Society, Oslo, Norway 9Akershus University Hospital, Department of Neurology, Lørenskog, Norway 10NTNU, Department of Psychology, Trondheim, Norway 11St. Olavs hospital, Trondheim University Hospita, Clinic of Rehabilitation, Trondheim, Norway 12University Hospital of North Norway, Department of Neurology, Tromsø, Norway the sessions via Objective: The aim of this study was to evaluate the efficacy and safety of a novel therapist-independent biofeedback app and sensor system (Cerebri) for the preventive treatment of episodic migraine in adults. Methods: The study was an open-label, randomized, waitlist-controlled multicenter trial. Adults with episodic migraines were randomly assigned (1:1) to daily biofeedback "Cerebri" smartphone system or waitlist control. The primary endpoint was the change in the mean number of migraine days from baseline to the last 28 days during the 12-week treatment phase. The primary analysis was conducted on the intent-to-treat population. ClinicalTrials.gov (NCT05616741). Results: Between January 2023 and January 2024, 279 were randomized to Cerebri treatment (n=140) or waitlist control (n=139). The average age was 41.9 years in the biofeedback arm (92.9% female) and 40.6 years in the control arm (91.4% female). Baseline migraine days averaged 4.8 (SD 2.4) the biofeedback group and 4.6 (SD 2.3) in the control. By weeks 9-12, migraine days were reduced by 0.9 days in the Cerebri group (95% CI -1.4 to -0.5) and 0.0 days in in the control group (95% CI -0.5 to 0.4). The between- group difference was -0.9 days (95% CI -1.5 to -0.3, p=0.002). 30% responder rates were 44.3% for Cerebri versus 29.9% for the control (OR 1.86, 95 % CI 1.05 to 3.30, p=0.033), and 50% responder rates were 32.7% for Cerebri versus 21.7% for the control (OR 1.75, 95 % CI 0.94 to 3.27, p=0.078). There were 139 treatment-emergent adverse events (AEs), with 132 assessed as unrelated, five possibly related, (pruritus, lightheadedness). There were two unrelated serious adverse events (appendicitis, severe menorrhagia). Conclusion: The Cerebri biofeedback treatment app is a safe and effective preventive treatment for adults with episodic migraine. causally related and two LP051 We present a case report of a patient with treatment resistent chronic cluster headache which has massively improved after male to female gender transformation. The case is discussed with review of the current literature L. Granata1, A. R. Gantenbein1 1Schmerzzentrum Granata, Zürich, Switzerland including CH. While more research Objective: This is a case report and therefore this is n/a. Methods: This is a case report and therefore this is n/a. Results: This is a case report and therefore this is n/a. Conclusion: Conclusion This case contributes to a growing body of literature suggesting that hormonal factors may significantly impact the clinical course of primary headache disorders, is needed, particularly in the context of transgender patients and hormone replacement therapy, this case suggests that hormonal modulation may offer an adjunct or alternative approach for managing chronic and treatment-resistant CH. Transgender individuals, therapy, especially represent in headache studies. Given the profound improvement in this patient's headache pattern following gender- affirming hormone therapy, further investigation into the role of sex hormones in CH pathophysiology is warranted. Prospective should explore whether hormonal fluctuations or therapy may serve as a therapeutic target in refractory CH, potentially leading to more personalized and effective treatment strategies. those undergoing hormone an under-researched population studies

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Fig. 1 LP052 Chronic Paroxysmal Hemicrania imitating dental pathology: case report E. Reka1 1Regional Hospital of Elbasan, neurology, Elbasan, Albania to to disorder headache characterized several hours according Objective: Chronic Paroxysmal Hemicrania (CPH) is a primary by recurrent, unilateral attacks of severe headache that occur in clusters, with each attack lasting from a few minutes the International Classification of Headache Disorders-3. Unlike other headache disorders, CPH typically features frequent episodes, often occurring multiple times daily, and is associated with autonomic symptoms such as conjunctival injection, lacrimation, nasal congestion and ptosis. Methods: A 48-year-old woman was referred to the neurologist after seeking treatment in dental office for a unilateral attack of severe headache with left eye injection that occurred in clusters and woke up the patient at night. The pain was rigorously unilateral and presented most commonly in the ocular area with red eye injection and maxillary area as well with no other autonomic signs. Results: The patient was previously treated by an ophtalmologist with topical dexamethasone for the eye injection although the Intraocular pressure and fundus Oculi were normal. After being mistreated for migraine with flunarizine and with other over the counter NSAIDs the patient had a marked response to indomethacin and a decrease of headache intensity and frequency with indomethacin prophylaxis. Brain magnetic resonance imaging did not show any abnormalities. Conclusion: In conclusion, a thorough understanding of CPH's clinical features, treatment responsiveness, and potential overlaps with other headache disorders is essential for accurate diagnosis and effective management. The intense, throbbing pain of CPH can be misdiagnosed as pain associated with dental pathology, especially when located in the maxillary area. Moreover, pain manifesting in the maxillary and temporal confused with temporomandibular disorders. Accordingly, dentists should be familiar with CPH in order to avoid unnecessary, irreversible dental treatment and refer these cases to the neurologist. areas can be Fig. 1 Fig. 2

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LP053 Optical coherence Tomography in cluster headaches J. Fernandes1, J. H. Marques2, M. Araujo2, C. Andrade1 1Unidade Local de Saúde de Santo António, Neurology, Porto, Portugal 2Unidade Local de Saúde de Santo António, Ophthalmology, Porto, Portugal is Objective: Despite of the striking and typical clinical presentation of Cluster headaches (CH), delays in diagnosis are common, and there are currently no well-established biomarkers to facilitate diagnosis. The sphenopalatine ganglion the peripheral structure responsible for these autonomic symptoms and provides parasympathetic innervation to the choroid, which may influence its thickness. This study aims to determine whether patients with episodic and/or chronic cluster headaches exhibit differences in choroidal thickness, as measured by optical coherence tomography (OCT), between the symptomatic and asymptomatic sides during the cluster period. Methods: We conducted a single-center, prospective, observational, case-control study involving patients diagnosed with cluster headaches who are followed at our center, starting in March 2024. Choroidal macular thickness was evaluated and compared between the symptomatic and asymptomatic sides using OCT in patients with CH during the cluster period. Results: The study included seven male patients with a mean age of 51 years (±13). Manual measurements revealed a significantly greater subfoveal choroidal thickness on the symptomatic side (397.57 ± 78.82 μm) compared to the asymptomatic side (337.86 ± 94.95 μm), with a statistically significant difference (p = 0.028, 95% confidence interval, t-test). Automatic measurements significant differences in the 1 mm average thickness, central choroidal area, and total vessel area. Overall, all and choroidal vasodilation—tended the symptomatic side. Conclusion: Choroidal thickness differed significantly between the symptomatic and asymptomatic sides, suggesting that this measurement could serve as a potential biomarker for cluster headaches, aiding in the early identification of patients as they enter the cluster period. Given our small sample size, we will continue to recruit new patients to further establish our results. parameters—thickness, demonstrated greater on to be area, also LP054 Indomethacin-responsive headache disorders: long- term outcome on efficacy, tolerability, and treatment alternatives M. Jokubaitis1, A. Sinker2, S. Maniataki1, L. Griffiths2, S. Mehbob2, L. Fernandes2, D. Moreno-Ajona1, L. Idrovo2, P. J. Goadsby1 1King's College London, Headache Group, London, United Kingdom 2Leeds Teaching Hospitals, Neurosciences- Neurology, Leeds, United Kingdom included patients Indomethacin-responsive headache Objective: disorders: hemicrania continua and paroxysmal hemicrania, are distinct, and rare in clinical practice. We described the long-term outcome followed up to 10 years. Methods: We (January 2014- October 2024) referred to Headache clinics (KCH, LTH). We collected age, sex, comorbidities, onset, efficacy, tolerability, duration and alternative therapies. Proportions compared utilising McNemar test for paired data; binomial logistic regression model with a logit link function with treatment discontinuation as dependent variable. Significance was evaluated at P < 0.05 Results: We reviewed 4099 letters with the word indomethacin, namely 165 patients. HC was diagnosed in 87 and PH in 54; 67.9% females, median age 46 (± 14.5 years). Up to 130 patients followed for 5 years, 35 for more. Indomethacin was stopped due to side effects in 29.7% (36.0% gastrointestinal, 25.0% CNS = headache worsening and dizziness), 54.4% continued. Efficacious alternatives included melatonin 17/43, GON blocks 37/59, non-invasive vagus nerve stimulation 20/39, anti-CGRP monoclonal antibodies 3/12. Response to anti-CGRP was associated with migraine (P < 0.001). The regression model showed side effects predicted treatment discontinuation (B = 2.408; P < 0.001) and CGRP treatments continuation (B = -2.478 P = 0.007). Patients on CGRP-mabs were on higher doses of indomethacin (182mg ± 59 vs 130mg ± 60; df= 11; t = 2.78 P = 0.017 Conclusion: The showed treatment discontinuation predicted by side effects. Patients benefitted from other therapies such as CGRP antibodies which on indomethacin independently of the dose, which could point to a synergist mechanism in indomethacin- sensitive headaches. continuation long-term predicted follow-up

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LP055 Tryptophan deficiency reduces the effectiveness of sumatriptan in a mouse model of migraine Y. Mrad1, M. Grevet1, V. Rajcic1, I. Erkizia-Santamaria2, I. Horrillo2,3, R. Dallel1, I. Ranchon-Cole1, C. Alba- Delgado1 1Université Clermont Auvergne, Inserm, NeuroDol, Clermont-Ferrand, France 2University of the Basque Country UPV/EHU, Department of Pharmacology, Leioa, Bizkaia, Spain 3Centro de Investigacion Biomedica en Red de Salud Mental, Instituto de Salud Carlos III, Salamanca, Spain Objective: Triptans are a specific acute treatment for migraine attacks by activating serotonin (5-HT) 1B/1D receptors (5-HTR1B/1D). However, approximately 30% of patients with migraine do not respond to it or only partially. The mechanisms of this inefficacy are unclear. Tryptophan (Trp), 5-HT precursor, has been involved in migraine pathophysiology and can modulate the 5-HTR expression. Thus, we studied the contribution of Trp on sumatriptan efficacy in a preclinical model of migraine. Methods: Adult female C57BL/6 mice were subjected to a Trp-deficient diet for one week before migraine- like pain induction by an acute injection of isosorbide dinitrate (ISDN i.p.). Behavioral cephalic mechanical sensitivity and light sensitivity, cFos-immunoreactivity (IR) in the trigeminal nucleus caudalis (Sp5C), plasma protein extravasation (PPE) and 5-HTR1B/1D expression in the trigeminal ganglion (TG) and Sp5c were evaluated. Results: Trp-deficient diet reduced circulating Trp and 5-HT concentrations by 70% and 13% respectively. In control mice, Trp deficiency had no effect on the baseline cutaneous or light sensitivities, but induced cFos-IR in the Sp5C and PPE in the brain. Additionally, Trp-deficient diet worsened ISDN-induced cephalic mechanical hypersensitivity without impacting ISDN- induced light hypersensitivity or cFos-IR. Interestingly, Trp deficiency also blocked the antalgic effect of an acute injection of sumatriptan (1 mg/kg i.p.) on both cutaneous and light hypersensitivities. Finally, Trp deficient mice treated with ISDN exhibited increased 5-HTR1D expression in the TG and the Sp5C, without any changes in 5-HTR1B levels. Conclusion: These findings highlight the critical role of Trp in regulating the effectiveness of migraine treatments like sumatriptan. in modulating the sensory response and LP056 Optogenetic cortical spreading depression originating from the primary visual cortex induces migraine-like pain and anxiety behaviors in freely moving C57BL/6J mice S. Yu1, H. Yuan1,2 1Chinese PLA General Hospital, Department of Neurology, Beijing, China 2Nankai University, School of Medicine, Tianjin, China is the second disabling Objective: Migraine neurological disorder with a high prevalence. Aura occurs in one-third of migraineurs and visual aura accounts for over 90%. However, there is no universal animal model for migraine with aura. Cortical spreading depression (CSD) underlies aura and might trigger migraine headaches. Compared with invasive electrical, chemical, or mechanical stimulation, optogenetics was relatively non-invasive to the dura mater. Reported optogenetic CSD-induced models in transgenic mice were hard to achieve in the primary visual cortex (VISp) or limited in neuronal network research. This study aimed to establish an optogenetic CSD-induced migraine model originating from VISp in C57BL/6J mice. Methods: We performed viral transduction for the expression of light-sensitive channelrhodopsin-2 in pyramidal neurons of VISp in C57BL/6J mice. Regional cerebral blood flow (rCBF) was measured by laser speckle flowmetry to confirm CSD induction. The von Frey test, light-dark box test, elevated plus maze test, and open field test in time-dependent manners were conducted to verify migraine-like behaviors in freely moving mice. Results: An optogenetic stimulus induced triphasic rCBF change, confirming CSD occurrence. A single unilateral CSD in freely moving C57BL/6J mice triggered bilateral periorbital and hind-paw allodynia lasting for 4-24 h. Notably, the ipsilateral periorbital mechanical threshold was significantly lower than the contralateral at 1 h. It also generated photophobia and anxiety behaviors persisting for 24-48 h. Furthermore, cutaneous allodynia and anxiety behaviors were resolved by sumatriptan. Conclusion: This study establishes an optogenetic CSD-induced migraine model originating from VISp in freely moving C57BL/6J mice for migraine with aura. For the feature of avoiding direct stimulation of the dura mater induction process and a behavioral paradigm closer to the clinical characters of migraine, it is a promising model for migraine with aura. in the CSD

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LP057 Predictors of primary stabbing headache in patients with migraine M. D. Villar Martinez1, Z. Lahrie1, P. J. Goadsby1 1King's College London, London, United Kingdom (CAS) logistic (ocular, symptoms sensitisation Objective: To identify clinical predictors associated with primary stabbing headache (PSH) in migraine. Methods: We applied a generalized linear model with binomial dependent variable and a link function in migraine patients (n=70), as part of a service evaluation. Predictors included age, sex, headache days, migraine biology features (motion sickness, ice-pick headaches, abdominal migraine, childhood colic or cyclic vomiting), nummular analgesics, phenotype, symptoms (movement sensitivity, photosensitivity, photic allodynia-ocullodynia, phonophobia, osmophobia, nausea, vomiting, allodynia), aura and cranial autonomic cochlear, cutaneous, oropharyngeal). Results: Sixty-two percent had symptoms of PSH. Significant predictors were male sex (β = -2.39, P = 0.046), nummular phenotype (β = 2.59, P = 0.007), aura (β = 1.55, P = 0.032), and more CAS (β = 0.26, P = 0.016). Age, headache frequency, sensitization, and use of analgesia were not significant. Conclusion: The findings of this study highlight significant predictors of PSH in migraineurs, specifically emphasizing male sex as protective, and nummular phenotype, aura, and cranial autonomic symptoms (CAS) as positive predictors. The strong association between nummular presentations and PSH alongside the positive association with aura could suggest an involvement of cortical excitability in this presentation in migraineurs, which could be playing a role in somatotopic pain focalisation. Its association with the number of CAS reinforces a potential protective reaction activating trigeminal autonomic reflexes, as we have described. Interestingly, the lack of from sensitization symptoms and analgesia challenges previous views, underscoring the need for a nuanced understanding of PSH. influence LP058 Morphology of human choroid plexus under high intracranial pressure J. Ramos de Andrade1,2, A. H. Galvão Bruno da Cunha2, G. Gazzoni Araújo Gonçalves2, F. André Brayner2, L. L. Barbosa Menezes da Mota3, L. Gomes Ribeiro3, F. J. Morais Vasconcelos Junior2, M. Moraes Valenca2, C. Stanley James Westgate1, R. Højland Jensen1 1Rigshospitalet, Danish Headache Center, Glostrup, Denmark 2Federal University of Pernambuco, Recife, Brazil 3Pernambuco University, Recife, Brazil but (ICP) traumatic intracranial pressure is Objective: Raised inherently its microstructural consequences of on the choroid plexus (CP), the organ that determines ICP, remains unelucidated. We sought to describe the ultrastructural consequences of raised ICP on the CP. Methods: Choroid plexus (CP) samples were collected from pediatric patients during surgical procedures for third ventriculostomy and CP coagulation as treatment for hydrocephalus, uncoagulated portion assessed. Samples were compared to choroid plexus from cadaveric donors (normal ICP). Tissue was prepared for scanning electron microscopy (SEM). This was a qualitative study. Results: Typical choroid plexus (CP) structures, including villi, microvilli, invaginations, and vesicles (or interdigitations), were observed across all samples. The luminal surface of the CP epithelium, typically covered by abundant microvilli, displayed notable differences under conditions of elevated intracranial pressure (ICP). The apical portion of the microvilli showed signs of flattening and reduced interdigitation compared to controls. Despite this reduction in interdigitation, an increased density of cilia or possibly epiplexus cells was inferred in the high ICP samples. These findings indicate that elevated ICP induces significant ultrastructural changes in the CP, impacting both cellular organization and surface morphology. Conclusion: Morphological changes were observed in the CP under high ICP, suggesting that elevated pressure induces significant structural alterations. Factors such as age may influence these results, warranting further investigation. This study provides essential in hydrocephalus, offering insights into the impact of ICP on CP morphology. Future research is needed to clarify the molecular basis of these changes and their broader implications. pediatric CP images SEM of

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LP059 CGRP-related genes inversely affect migraine and depression D. Baksa1,2,3, D. Torok1,3, G. Juhasz1,3 1Semmelweis University, Department of Pharmacodynamics, Budapest, Hungary 2Pazmany Peter Catholic University, Department of Personality and Clinical Psychology, Budapest, Hungary 3Hungarian Brain Research Program, NAP3.0-SE Neuropsychopharmacology Research Group, Budapest, Hungary Objective: Anti-CGRP migraine medications may also diminish symptoms of depression, a frequent comorbid disease of migraine. At the moment, the underlying factors of this phenomenon are not known. Considering the association between CGRP genes and migraine, furthermore the genetic overlap of the two diseases, our goal was to test the effect of the polygenic risk score (PRS) of a CGRP-related gene set on migraine and depression. Methods: In a sample of the UK Biobank (Application no. 71718) (N=134197, 57.9% female, mean age ±standard deviation: 54.94±8.39), ICD-10 codes were used to capture migraine (G43) and depression (F32- F33) status. Questionnaire data was also used to measure current depression symptoms. The CGRP- related gene set was constructed according to the Pathway Commons database (Ngenes=29). PRS calculation was made with LDpred2, and logistic and linear regressions were ran in R (4.1.2) to test the effect of the CGRP PRS separately on migraine, depression, and current depression symptoms. PRS was calculated with LDpred2, and next, the effect of the CGRP PRS was tested with linear and logistic regressions (4.1.2) separately on migraine, depression, and current depression symptoms. Results: The CGRP PRS showed a significant risk effect on migraine (OR=1.9, p=0.002), but not on diagnosed depression, however a protective effect on current depression symptoms (β=-0.247, p=0.032) was found. Conclusion: Our results suggest that CGRP-related genetic processes elevating migraine (but not depression) liability might contribute to a more beneficial mental health state among migraine patients, possibly due to a better treatment response. In the future, the effect of the CGRP-related PRS on anti-CGRP therapy efficacy should be directly tested in association with migraine and depression symptoms. in R LP060 Effects of Sumatriptan on ATP-Sensitive Potassium channel opening in migraine Z. A. Zhuang1, M. Al-Mahdi al-Karagholi1, H. Ashina1, T. Phu Do1, M. Ashina1 1Danish Headache Center, Department of Neurology, Copenhagen University Hospital – Rigshospitalet, Glostrup, Denmark IV by levcromakalim, Objective: To investigate whether early treatment with sumatriptan can prevent migraine attacks induced an ATP-sensitive potassium channel (KATP) opener, in individuals with migraine without aura. Methods: A double-blind, placebo-controlled, 2-way crossover study involving adults with 1 to 5 migraine attacks per month without aura. The participants received a 20-minute intravenous (IV) infusion of levcromakalim (0.05 mg/min) on two separate days, followed by a 10-minute infusion of either sumatriptan (0.4 mg/min) or placebo (isotonic saline). The primary endpoint was the difference in incidence of levcromakalim-induced migraine attacks after sumatriptan and placebo during a 720-minute observational period post-levcromakalim. A key secondary endpoint was the difference in area under the curve (AUC) for headache intensity scores between sumatriptan and placebo days. underwent Results: randomization and completed both experimental days. The levcromakalim-induced migraine attacks was similar on sumatriptan and placebo days (75% vs. 85%; P = .688). We found no difference intensity scores between the two study days (AUC0-720 min, P = .123; post-hoc baseline corrected AUC40-720 min, P = .097). Post-hoc analysis with additional intensity correction at 40 minutes post-infusion, however, indicated a significantly lower AUC for headache intensity scores after sumatriptan compared with placebo (P = .002). Conclusion: Early treatment with sumatriptan does not prevent migraine attacks induced by KATP channel opening. This finding suggests that the migraine- inducing effects of KATP channel opening occur downstream of sumatriptan"s mechanism of action. Nevertheless, attenuate levcromakalim-induced headache intensity scores, indicating a need for further research. in AUC for headache sumatriptan might Twenty participants incidence of

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LP062 Trigeminovascular activity using a forehead dermal blood flow model: preliminary results of a validation study R. van Lohuizen1, L. Al-Hassany1, A. Maassen van den Brink1 1Erasmus MC, Internal Medicine, Rotterdam, Netherlands Objective: To investigate physiological mechanisms and treatments in migraine, a human forehead model was previously developed. In this model, topical application of capsaicin and electrical stimulation (ES) were both used to induce dermal blood flow (DBF) responses. Capsaicin causes vasodilation through activation of the transient receptor potential vanilloid type 1 (TRPV1 receptor) leading to CGRP release, in contrast to vasodilation caused by ES. To assess the forehead DBF, studies mainly used a Laser Doppler Perfusion Imager (LDPI). Alternatively, the newer Laser Speckle Contrast Imager (LSCI), provides real- time and higher resolution DBF responses. We validated the LSCI using a forehead model by assessing its agreement with LDPI. Methods: We performed a cross-sectional study including healthy non-smoking female subjects without migraine, aged 18-40, not using hormones. LDPI and LSCI were compared by measuring forehead DBF responses to topical capsaicin (0.06 mg/mL), and to stepwise increase of ES (0.2-1.0 mA). The area under the curve from 0-37 minutes (AUC 0-37) was calculated for both ES and capsaicin, using both lasers. We analyzed both absolute AUCs and baseline corrected AUCs. Pearson and Spearman rank correlation obtained with corresponding 95% confidence intervals. Results: A total of 20 participants were included (age 27.4±5.6 years), of whom 19 ES measurements and 20 capsaicin measurements were analyzed. Correlation coefficients indicate moderate positive relationships for all outcome measures between the LDPI and LSCI (Table 1). Conclusion: The LDPI and LSCI measurements using a human significantly, in healthy females and indicating their validity potential future migraine studies. forehead model correlate coefficients were LP061 Effects of Soluble Guanylate Cyclase stimulation on cranial vasodilation and headache in healthy adults N. B. Rasmussen1, C. E. Christensen1, H. Ashina1, F. Mohammad Amin1, R. D. Moreno1, J. Abdulla2, J. Carlsen3, M. Ashina1 1Danish Headache Center, Department of Neurology, Glostrup, Denmark 2Amager-Hvidovre Hospital, Department of Cardiology, Copenhagen, Denmark 3Rigshospitalet, Department of Cardiology, Copenhagen, Denmark lingering question Objective: Headache is a highly prevalent symptom. Insight into the pathomechanism of headache pave the way for novel drug development. Though strides have been made in advancing our understanding of headache pathogenesis, a is whether cranial vasodilation plays an important role. Central to the discussion is the cyclic guanosine monophosphate signaling pathway, which has been shown to promote both vasodilation and headache. We hypothesized that the soluble guanylate cyclase stimulator riociguat would induce cranial vasodilation alongside headache in healthy adults. Methods: This randomized, double-blind, placebo- controlled, two-way crossover study investigated the effect of riociguat on cranial arteries and headache induction compared to placebo. Twelve healthy adults received a single oral dose of riociguat 2.5 mg or placebo on two separate experiment days. Superficial temporal artery (STA), a marker for extracranial vasodilation, and middle cerebral artery blood flow velocity (VMCA) were measured with ultrasound technique for four hours in-hospital after intake of riociguat or placebo. Also, headache including associated symptoms and adverse effects were reported for 12 hours after intake of riociguat or placebo. Results: Analysis of primary outcome showed no significant change of STA diameter at 90 minutes following the intake of riociguat compared to placebo (P = 0.54). Post-hoc and exploratory analysis revealed a significant increase in STA diameter after riociguat at 120min (P = 0.02) and 240min (P < 0.01), respectively. Riociguat caused a decrease in VMCA after 240min (P < 0.01) and induced headache within 12 hours (P = 0.02) compared to placebo. Conclusion: Riociguat arterial vasodilation and headache in healthy adults. The findings accentuate the prospect of selectively targeting soluble guanylate cyclase in future headache research and drug development. Next step could be to investigate whether riociguat can induce primary headaches such as migraine. induces cranial

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Fig. 1 LP063 Characterization of Immune markers in the acute and chronic NTG mouse model C. Ratner1, F. Russo2, R. Christensen1, K. Pedersen3, A. Asuni1 1Lundbeck, Preclinical fluid biomarkers and occupancy, Valby, Denmark 2Lundbeck, Bioinformatics, Valby, Denmark 3Lundbeck, Symptom Biology, Valby, Denmark to behavior evoked-pain Objective: Neurogenic inflammation has been suggested as an important contributor to migraine pathophysiology. Migraine patients present with elevated levels of pro-inflammatory cytokines such as interleukin (IL)-6, IL-1β and tumor necrosis factor α and decreased levels of anti-inflammatory markers such as IL-10 during and between attacks. The nitric oxide donor nitroglycerin (NTG) induces headache in humans and is extensively used to model episodic and chronic migraine. NTG elicits both neuronal and vascular effects including neurogenic inflammation contributing and sensitization. In the present study we aimed to characterize the immune profile in an acute and chronic NTG model. Methods: Mice were injected with NTG (10 mg/kg; IP) acutely or chronically (5 injections over 9 days) and sacrificed at different time-points following NTG (acute: 30min, 2h, 6h or 24h; chronic: day9, 2h post- dose). Additionally, one group was sacrificed on day9 without the final NTG injection. Plasma was analyzed for immune markers using the Olink T48 Mouse Cytokine Panel. Results: NTG induced several changes in plasma immune markers. Some proteins (e.g. IL-33) were upregulated both acutely and chronically, while others (e.g. FGF21, IL-16) were only upregulated acutely. IL-17f, IL-1β and Ifnl2 were dysregulated in chronically sensitized plasma without an acute NTG challenge. Downregulated proteins included IL-1a and Ccl5 (acute and chronic) as well as Ccl17 (chronic). IL-10 and IL-6, Conclusion: The present data identifies dysregulated immune plasma markers in a mechanistic migraine model. Several of these markers e.g. FGF21 and IL-6 are dysregulated in people with migraine. A better understanding of inflammatory processes contributing to migraine can provide insights into potential new migraine biomarkers and drug targets. LP064 Lupus headache: a case series of an underrecognized and overlooked neurological symptom of Systemic Lupus Erythematosus (SLE) with its impact on life using Headache Impact Test (HIT-6) D. Sharma1, C. Brincker1 1St John of God Hospital Midland, Neurology, Perth, Australia impact on and meningitis Objective: The term lupus headache is defined as a severe persistent headache, mostly migrainous, that does not respond to narcotic analgesia in a patient with SLE. However, secondary causes of headaches in these patients should be excluded, such as cerebral vasculitis, cerebral venous sinus thrombosis, posterior reversible encephalopathy syndrome, subarachnoid haemorrhage, imaging using modalities. This series highlights five cases of headache in SLE patients, the medications used and explores their life using a structured questionnaire called the HIT-6 score. Methods: This study included five patients, who had been diagnosed with SLE according to the European League against Rheumatism (EULAR) criteria and presented with headaches at a single centre in India. All 5 patients were evaluated consecutively on outpatient basis for new onset persistent headaches with or without aura symptoms. Full diagnostic evaluation including history, examination, biochemical and imaging workup was done to establish a diagnosis of a primary headache. Results: 4 out of 5 patients had migraine headache managed with triptans and 1 had tension type headache maintained on amitriptyline. In the six-item HIT-6 score, all 5 patients answered 'very often' or 'always' on most of the questions which indicate substantial to severe impact in daily life. is a challenging Conclusion: symptom, both to diagnose and treat as is refractory to analgesics by definition. Moreover, its cause and predictors cannot be ascertained. Another lingering question is a co-existing headache or evolution of cerebral involvement of SLE. Our series highlight that it is prudent to be on the lookout for primary headaches early in the diagnostic journey of SLE in order to mitigate its impact on life later. Lupus headache is whether it it

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LP066 Allodynia detection in neuropathic facial Pain by VPT (Very Point Technique) derived from acupuncture U. Kock1, A. L. Szettele1, S. Sator1 1Med.Univ. Vienna, Dept. of Special Anaesthesia and Pain Medicine, Vienna, Austria can be information already very early (VPT), developed by Gleditsch Objective: Trigeminal Neuralgia (TN) and Trigeminal Neuropathy (TNO) are different entities (ICHD), but sometimes difficult to differentiate in the clinical setting. Defining borders of affected facial areas and finding areas of allodynia valuable informations already in the first setting of an outpatient clinic. The Very-Point-Technique (VPT) ist a cheap, easy to learn "on-site"-technique giving important in the diagnostic process. Methods: The well established "Very Point Technique" for localizing acupuncture points in ear acupuncture, was used as an investigative tool in patients with facial pain: Skin areas are investigated by applying quick and gentle uniform strikes , perpendicularly to structures of interest, using an acupuncture needle (for small areas) or cotton swabs (larger sites); indicators are changing sensation (reported by the patient) , and/or triggering a blink reflex Results: In the absence of allodynia, the outline of the facial area affected by TN could clearly show the involved trigeminal branches, whereas the presence and the patchy shape of allodynic areas gave a broad hint towards a focal origin oft the TNO., and also towards the area to be treated by local capsaicin application to desensitize these areas (by acting on TRPV1 vanilloid receptors) resulting improved success of pharmacologic treatment and other procedures. Conclusion: The VPT ("Very Point Technique"), derived from ear acupuncture, is an established, simple, inexpensive, and easy to learn and to apply neurophsiological test for everyday pain clinic practise when caring for patients with neuropathic facial pain, before proceeding to more complex procedures. VPT is a tool NOT triggering pain attacks when examining a patient for neuropathic facial pain. in LP065 A Joint Neuro-otology clinic: results of a joint approach to vertigo and headache U. Kannathasan1, J. Moraleda1, D. Allan2, D. Moreno- Ajona1 1King's College London, London, United Kingdom 2Queen Elizabeth Hospital, Audiology, London, United Kingdom reviewed Objective: Patients with vestibular symptoms and headaches can be referred to either ENT doctors, audiologists or Neurology/ headache specialists typically depending on which is the predominant symptom. The diagnoses and approach to these patients may vary depending the type of clinic patients are referred to. We set up a Joint neuro-otology clinic with a simultaneous multidisciplinary approach involving a headache specialist, ENT specialised in vertigo and an audiologist. Herein we aimed to review the diagnoses and treatment of consecutive patients referred to this clinic. Methods: We consecutive patients attending the Joint Neurootology clinic at Queen Elizabeth Hospital (London). We used descriptive statistics as well as proportion of different diagnoses and comorbidities, treatment options and outcomes where available. We compared this to the main reasons for consultation in ENT clinics. Results: In total, 39 patients were seen in monthly consecutive clinics from January till October 2024. The median age is 55 (14) with 30/45 females. The most frequent diagnosis was vestibular migraine (24/39) followed by Meniere's disease (5/39), BPPV (5/39), canal paresis (3/39), PPPD (2/39), parkinsonism (2/39), hemicrania continua limb ischemia causing balance problems (1/39) and semi- circular canal dehiscence (1/39). The group of patients were not selected and represent a random group of patients referred for dizziness/ headaches. Recent series in ENT settings point to higher prevalence of PPPD, being superior or comparable to VM. In total 75% were recommended vestibular rehabilitation although this was preceded by the recommendation of a migraine preventive, namely melatonin (6/39) and flunarizine (5/39) all of them showing some benefit. Conclusion: The colaboration of different specialties in an MDT approach to Neurootology clinics led to a higher frequency of VM and lower of PPPD compared to ENT clinics. Migraine patients benefited from prevention prior to vestibular rehabilitation. (1/39), lower

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Fig. 1 LP067 Hypersensitivity to BKCa channel opening in persistent post-traumatic headache H. M. Al-Khazali1, R. H. Christensen1, D. Dodick2, B. A. Chaudhry1, A. G. Melchior1, R. Burstein3, H. Ashina1 1University of Copenhagen, Copenhagen, Denmark 2Mayo Clinic, Department of Neurology, Scottsdale, United States 3Beth Israel Deoconess Medical Center, Department of Anesthesia, Critical Care and Pain Medicine, Boston, MA, United States Large conductance underpinnings infused induce migraine-like headache calcium-activated Objective: potassium (BKCa) channels have been implicated in the neurobiological of migraine. Considering the clinical similarities between migraine and persistent post-traumatic headache (PPTH), we aimed to examine whether MaxiPost (a BKCa channel opener) could in persons with PPTH. Methods: This is a randomized double-blind, placebo- controlled, two-way crossover study from September 2023 to December 2023. Eligible participants were adults with PPTH after mild traumatic brain injury who reported having no personal history of migraine. The randomized participants received a single dose of either MaxiPost (0.05 mg/min) or placebo (isotonic intravenously over 20 saline) that was minutes. The sessions were scheduled at least one week apart to avoid potential carryover effects. The primary endpoint was the induction of migraine-like headache after MaxiPost as compared to placebo within 12 hours of drug administration. Results: Twenty-one adult participants (comprising 14 females and 7 males) with PPTH were enrolled and completed both experiment sessions. The proportion of participants who developed migraine-like headache was 11 (52%) of 21 participants after MaxiPost infusion, in contrast to four (19%) participants following placebo (P = .02). Conclusion: Our results indicate that BKCa channel opening can elicit migraine-like headache in persons with PPTH. Thus, pharmacologic blockade of BKCa channels might present a novel avenue for drug discovery. two experiment LP068 AHA Life's Essential 8 factors and its association with migraine disorders in ELSA-Brasil study A. B. Oliveira1, I. Santos2,3, M. F. P. Peres4,5, A. Conforto5,6, P. Lotufo2,3, I. Benseñor2,3, A. Goulart7,2 1Universidade de São Paulo, Center For Clinical and Epidemiological Research, Casa Branca, Brazil 2Universidade de São Paulo, Center For Clinical and Epidemiological Research, São Paulo, Brazil 3Universidade de São Paulo, Department of Internal Medicine, São Paulo, Brazil 4Universidade de São Paulo, Psychiatric Institute, São Paulo, Brazil 5Albert Einstein Israeli Hospital, Brain Institute, São Paulo, Brazil 6Universidade de São Paulo, Clinical Neurology Division, São Paulo, Brazil 7Universidade de São Paulo, School of Public Health, Epidemiology, São Paulo, Brazil Objective: Would lifestyle habits and cardiovascular risk factors be associated with migraine disorders? We aimed to evaluate the associations between the Life´s Essential 8 (LE8) factors proposed by American Heart Association (AHA) and migraine disorders in the Brazilian Longitudinal Study of Adult Health (ELSA- Brasil). Methods: LE8 factors (total, health behavior and health factors domains), migraine disorders (migraine without – MWO and with aura - MWA) and migraine frequency (< 15 or ≥ 15 days/month) were evaluated among participants with these variables on the Wave 2 (2013-2014) of the ELSA- Brasil. The LE8 factors" metrics were computed following the AHA´s scoring system. Migraine diagnoses were based on ICHD-3 criteria. Binary logistic regression models estimated the odds ratio (OR) with 95 % confidence interval (CI) for the and associations between migraine disorders information on

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adherence levels to the LE8 factors categorized as low (reference), moderate, and high. Results: Of 4,293 participants (mean age: 55.3, SD±8.9 years, 54.6 % female), MWO and MWA were verified in 19.4 % and 10.5 % of participants, respectively. Overall, high adherence to LE8 total factors was associated with lower odds for migraine disorders, with stronger inverse associations with MWA [OR (95 % CI): 0.370 (0.235, 0.58), p < 0.001] than MWO [OR (95 % CI): 0.51 (0.369, 0.72), p < 0.001]. In the analysis by headache attack frequency, frequent headache attack (≥ 15 days/month) showed the strongest inverse association with LE8 total factors [OR (95 % CI): 0.257 (0.147, 0.45), p < 0.001]. The main findings remained in the sensitivity analysis, after excluding probable migraine, non-migraine headache, and self- reported cardiovascular diseases. Conclusion: High adherence to AHA LE8 factors, mainly behavior factors was inversely associated with migraine disorders, particularly MWA, while high adherence to health factors was inversely related to frequent headache attacks. Fig. 1 Methods: To present a clinical case of exacerbated migraine due to Semaglutide treatment for weight loss. Results: A 46-year-old woman, with long-standing migraine with visual and sensory aura complained of worsening severity and frequency of migraine attacks. It started 3 weeks after she had started s.c. treatment with Semaglutide. Previously her attacks' frequency was 1 to 2 per month, while after intiating the new tretment they became daily. The pain was always accompanied by nausea and vomiting, while in the past these were present only occasionally. The recent attacks did not respond to OTC drugs or triptans. After Semaglutide was stopped, the migraine attacks" severity and frequency returned to the usual for the patient. Conclusion: The GLP-1RAs effects lead to a reduction in glucose levels. It can be speculated that this may result in migraine worsening. The disrupted gastrointestinal mechanisms and the gut-brain axis may also have an impact. The basic science studies show evidence for a role of the vagus and the circumventricular organs in the effect of the GLP-1R agonism on brain neuronal activation. GLP-1RAs are known also to lower intracranial pressure. Due to their direct effect on the choroid plexus to reduce CSF secretion, Idiopathic Intracranial Hypertension. However, little is known how exactly GLP- 1RAs affect migraine. More research is needed the exact etiological mechanisms. Evidence is growing that drugs like Semaglutide have broad therapeutic benefits which are to be studied further. they are used to elucidate to treat LP069 Migraine exacerbated by semaglutide obesity treatment: a case report V. Grozeva1 1Private Headache Practice, Sofia, Bulgaria Objective: Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1RA), which is available for weight management. Gastrointestinal disorders such as nausea, diarrhea, vomiting, and constipation are frequent adverse events with Semaglutide. Headache is less frequently reported and the pathophysiological mechanisms behind are not fully understood. the most LP070 Exploring gender disparities in the effects of long- term Botulinum Toxin A treatment for chronic migraine M. P. Barillari1, C. Mummolo1, A. Pascarella2, L. Vadalà1, A. Gambardella3, F. Bono3,1 1Academic Hospital, Magna Graecia University, Headache Center, Neurology Unit, Catanzaro, Italy 2Great Metropolitan "Bianchi-Melacrino-Morelli" Hospital, Regional Epilepsy Centr, Reggio Calabria, Italy 3Academic Hospital, Magna Graecia University, Neurology Unit, Catanzaro, Italy Objective: We investigate gender differences in the response to long-term treatment with repeated injections of botulinum toxin type A (BTX-A) for patients with chronic migraine. Methods: In this study conducted at a single center, an equal number of men and women with refractory chronic migraine and overuse of analgesic drugs were enrolled for repeated treatment with BoNT A for more

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the baseline assessment with than 2 years. The baseline assessment included recording the monthly frequency of headache days, pain intensity using a visual analogue scale (VAS), and monthly analgesic medication consumption, all collected through diaries from the month before the first treatment. The response to BoNT A treatment was evaluated by comparing these parameters at the final values. Additionally, the impact of BoNT A on these parameters was compared between men and women. Results: Twenty-one women and twenty-one men,received BoNT-A injections every three months for 5.5 years (for men) and 4.8 years (for women). At the initial assessment, there was a significant gender difference in pain intensity, with women experiencing the highest level of pain (p < 0.05). However, the monthly days of headache and use of pain medications were similar in both groups. When comparing the effects of BoNT A treatment on the examined parameters at the final evaluation with the baseline values, it was observed that the monthly headache days for men and women were 10.4 and 6.5, respectively. There was a statistically significant (p=0.01) greater reduction in monthly headache days in women than in men. Conclusion: The results of our preliminary study indicate that the response to long-term treatment injections of BoNT A for chronic with repeated migraine prevention in women than in men. This finding suggests that there are gender differences the mechanisms of headache pain and puts the focus on gender- dependent therapy of chronic migraine patients. is significantly different in Fig. 1 LP071 Results from study NOE-PRO-001: Content validity of a new tool for collecting daily symptom data in Trigeminal Neuralgia: Trigeminal Neuralgia Pain Electronic Diary (TnED©) S. A. Tahiri1, S. Dodhia2, S. Chotaliya2, H. Ansari3, G. Garibaldi1, R. Lasser1, J. Zakrewska2 1Noema Pharma AG, Basel, Switzerland 2University College London, London, United Kingdom 3Kaizen Brain Centre, La Jolla, CA, United States individual"s paroxysms Objective: Trigeminal neuralgia (TN) is an orphan chronic pain condition involving sudden attacks of severe facial pain which maintains significant unmet need. There is no validated instrument that gathers daily information on paroxysms, continuous pain, and their interference with daily life. For a controlled trial with NOE-101 (basimglurant) in TN (NOE-TGN-201), the Trigeminal Neuralgia Electronic Diary (TnED©) was developed. The purpose of this study (NOE-PRO-201) was to explore the content validity of the items that make up the TnED©. Methods: The TnED© is a daily 5-question diary which asks about an (severity, frequency), continuous pain (CP, if present; severity, duration), and pain interference (from paroxysms and CP). NOE-PRO-001 (NCT06019338) was a non- interventional study conducted at 2 centers (US, UK). After consenting, participants completed the TnED daily at bedtime for 14 days, as well as a semi-guided interview to collect feedback on the instrument. Results: 30 patients were enrolled (15 with paroxysms only, 15 with paroxysms and CP) with a mean age (SD) of 54.9 (15.2); 80% were female. TnED items were seen as clear, easy to understand, and relevant, with a suitable recall period and response options. TnED was characterized as easy to use, with a suitable set of reminders and notifications. Daily completion rates were acceptable, with no in completing the TnED over an extended period in a research context (over 20 weeks). Conclusion: NOE-PRO-001 confirmed the content validity of the TnED items, including pain dimensions for both purely paroxysmal pain and continuous background pain. The electronic format was convenient and reduced the burden associated with paper-based diaries. The study also reinforced several concepts about the lived experience of TN patients - pain and its impact - that have been reported in previous qualitative research. This trial was funded by Noema Pharma AG. foreseen issues

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LP072 Microvascular decompression and medical management in Trigeminal Neuralgia: prospective five-year insights on pain relief J. Worm1, T. Heinskou2, P. Rochat3, J. Springborg3, E. Smilkov4, L. Bendtsen1, H. Schytz1, S. Maarbjerg5 1Copenhagen University Hospital - Rigshospitalet, Department of Neurology, Danish Headache Center, Glostrup, Denmark 2Copenhagen University Hospital - Rigshospitalet, Department of Neurology, Glostrup, Denmark 3Copenhagen University Hospital - Rigshospitalet, Department of Neurosurgery, Copenhagen, Denmark 4Copenhagen University Hospital - Rigshospitalet, Department of Radiology, Glostrup, Denmark 5Copenhagen University Hospital - Rigshospitalet, Department of Brain and Spinal Cord Injury, Bodil Eskesen Centre, Glostrup, Denmark limit issues clinical tolerability assessments, MRI, Objective: Trigeminal neuralgia is a debilitating facial pain disorder that presents significant management challenges. While the effectiveness of medical treatments and impact quality of life, microvascular decompression (MVD) has consistently demonstrated its efficacy. This study evaluates long-term efficacy of trigeminal neuralgia treatments, focusing on pain relief, prognostic factors, and patient satisfaction to guide future treatment. Methods: In this prospective cohort study at the Danish Headache Center, we included newly referred trigeminal neuralgia patients from 2012-2019 who underwent and standardized pain evaluations. Primary outcomes assessed pain reduction and freedom from pain or medication, while secondary outcomes included, recurrence, satisfaction, gender differences, and self- reported complications. Results: Among 184 patients completing five-year follow-up, 102 received medical management, and 82 had MVD. Demographics were similar across groups. MVD provided superior outcomes, with 57.3% achieving complete pain freedom versus 25.5% in the medical group; 75.6% had discontinued medication entirely by year five post-MVD compared to 36.3% in the medical group (p < 0.001). Males had higher rates of pain freedom without medication after MVD than females (70% vs. 47%, OR 3.4, p = 0.05). In the medically managed group, 37.7% of reported side effects, with 12.2% experiencing moderate and 6.1% severe effects. Self-reported complications to MVD included hypoesthesia (21%, severe 6.1%), mild (8.5%) to severe (14.6%) permanent hearing impairment, diplopia (6.1%), and facial weakness (3.7%). Conclusion: These findings support MVD as a highly effective long-term treatment with marked gender- specific outcomes, favoring males for achieving pain relief without medication. MVD may be considered as an earlier intervention carefully selected trigeminal neuralgia patients in the future. LP073 A single-centre retrospective audit of prevalence of constipation as a side-effect of Erenumab (Aimovig) treatment in the management of refractory chronic migraine J. Barton1, S. Broadhurst1, J. Sheridan1, M. Ghadiri- Sani1 1The Walton Centre NHS Foundation Trust, Neurology, Liverpool, United Kingdom antibody licensed constipation reported, single-centre retrospective these patients is an oral CGRP for migraine Objective: Erenumab (Aimovig) monoclonal prevention. A previous study by the Walton Centre in 2019 showed 12% of patients on Erenumab reported side- effects, with 4% of reporting constipation. This is not fully in keeping with the data noted in other trials internationally, and thus this further audit was conducted in order to help determine the true prevalence of constipation. Methods: A retrospective audit was conducted of 493 patients who received Erenumab from June 2021 to Feburary 2024. Demographics, reported side effects, discontinuation rate and reasons for discontinuation, frequency of rate of discontinuation due to constipation, and subsequent alternative CGRP inhibitors offered were all recorded. Results: 493 patients received Erenumab since June 2021. The mean number of alternative preventative medications patients had trialled before Erenumab was 6.4, with 27 medications being the most and 3 being the minimum. 113 of the 493 patients stopped Erenumab. 95 of these attributed discontinuation to inefficacy of to constipation. Of the 8 patients who stopped Erenumab specifically due to constipation, all of them had been receiving the 140mg dose and had previously adhered to the recommended lifestyle advice. The mean number of preventative medications they had trialled beforehand was 6.4. 7 of the patients stopped taking Erenumab between 5 and 14 weeks from initiation of treatment. Notably 3 patients all stopped at approximately 5 weeks from initiation of treatment. Conclusion: Patients typically stopped Erenumab due inefficacy. <2% of patients stopped due to to constipation. an effective therapeutic option for management of refractory chronic migraine. Despite the increased prevalence of constipation noted on other studies, overall prevalence of constipation with Erenumab use was low in this cohort the medication, and 8 due Erenumab remains

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LP074 Retrospective real-world study of Calcitonin Gene- related Peptide monoclonal antibody (CGRP mAb) for migraine in a Singapore neurology clinic C. W. Yip1, Y. L. Lo1 1National Neuroscience Institute (SGH Campus), Neurology, Singapore, Singapore , is to evaluate Objective: Our objective the effectiveness of CGRP mAb therapy in a Singapore hospital neurology clinic cohort under real world conditions, as there are few such studies in Asian migraineurs. Methods: We retrospectively included all migraine patients from our hospital neurology clinic who were given either erenumab fremanezumab or galcanezumab. The monthly migraine days (MMD) before CGRP mAb treatment and at 3 months , migraine years, preventive medication used, and presence of medication overuse headache (MOH) were recorded. The primary outcome measure is the percentage of patients achieving 50% or more reduction in MMD at 3 months (responder rate). Results: 22 patients were included (3 males ;19 females), mean age 47.9 years (range 22 to 69 years). There were 7 (31.8%) episodic migraine (EM) and 15 (68.2%) chronic migraine (CM) patients. The primary outcome was seen in 16 patients (72.7%). 22.7% had 0 MMD at 3 months 73.3% CM and 71.4 % EM were responders. . Similar responder rate of 87.5% was seen in patients diagnosed with either MOH, or vestibular migraine. Responder rates after failing 1 ,2 and 3 preventive medication were 85.7%, 88.9% and 50 % respectively. Conclusion: Our study primary outcome showed a high responder rate (72.7%) , with 22.7% being complete responders. Patients with vestibular migraine or MOH responded similarly well. Even in patients who failed 3 preventives, 50% were responders. Multivariate logistic regression analysis did not find any significant predictive effect of age, preventive medication failures, MMD ,MOH or migraine history. LP075 The regulatory role of CGRP-relating neural circuits in medication overuse headache: based on an animal model more in line with clinical characteristics Z. Ma1, C. Li2, S. Yu1 1Chinese PLA general hospital, department of neurology, Beijing, China 2The 96607 hospital of Chinese PLA, neurology, Baoji, Shanxi Province, China a the novel MOH model. Objective: To explore the therapeutic and preventive effects of Rimegepant, a calcitonin generelated peptide (CGRP) receptor antagonist on medication overuse headache(MOH). Methods: Repeated administration of nitroglycerin (NTG) was conducted to stimulate chronic migraine- like pain in mice, while Rizatriptan(Riz) was continuously provided for active drinking, so as to construct Sodium nitroprusside(SNP) was injected to elevate central sensitization. Mechanical pain threshold and emotion state were evaluated. The activated brain rigons of model mice were explored by immunofluorescence. Behavioral and histological tests were performed after repeated administration of Rimegepant at different stage of modeling. Optogenetics genetics, chemical genetics and other technologies were used to regulate nerve circuits. Results: The active intake of Riz in CM+MOH group was significantly higher than the control groups. Compared with control groups, the pain threshold decreased more significantly and recovered more slowly in CM+MOH group, especially after the use of low-dose SNP.CM+MOH group spent less time in open arms of elevated plus maze(EPM) and central areas of open field(OF). The number of FOS+ neurons in some brain regions in CM+MOH group was higher than that in control groups. Repeated administration of Rimegepant after model construction significantly increased Repeated administration of Rimegepant during modeling slowly decresed the pain threshold. No significant difference of EPM and OF were found at any stage of Rimegepant intervention. Rimegepant applied at different stages of modeling changed the number of FOS+ neurons in some brain regions. Conclusion: The new MOH mouse model was constructed by a method more in line with the disease progression of MOH. The use of CGRP receptor antagonist can delay the development of MOH to some extent, but the format of anxiety cannot be prevented. Nevertheless, Rimegepant has ideal therapeutic effect after the formation of MOH. threshold. pain

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Fig. 1 Fig. 2 Fig. 3 LP076 Review of the clinical experience and literature on GONB in paediatric headache clinic M. Morozova1, S. MacLeod1, R. Carragher2, I. Abu- Arafeh1 1Royal Hospital for Children, Neurosciences Unit, Glasgow, United Kingdom 2University of the West of Scotland, School of Computing, Engineering and Physical Sciences, Paisley, United Kingdom Objective: The aim of the study was to overview the evidence for administration of Greater Occipital Nerve Block (GONB) in children with chronic headache and evaluate the safety and benefits of the procedure. Methods: GONB was offered to patients where clinically indicated. Injection of 1 ml of Depo-Medrone (10mg lidocaine and 40mg methylprednisolone) given to infiltrate the area around GON on one or both sides. Diagnosis was made on ICHD3. Good response was defined as resolution of headache for at least 2 weeks and partial response as relief of headache for less than 2 weeks or reduction in headache intensity. Statistical analysis performed using R software. The literature search included PubMed, google Scholar, Embase and Cochrane databases. Results: 98 patients (10-17 years old, 77% females) with chronic headache were given 164 treatment sessions on one (32%) or both sides (68%). 64% of treatment sessions resulted in good or partial response (51% and 13% respectively) which was associated with a diagnosis of chronic or episodic migraine and younger age of patients at the first treatment. There were no statistical predictive value in response rate for other variables such as gender, number of previously used medications, site of injections (unilateral or bilateral), presence or absence of tenderness over pressure points before injections or achieving scalp numbness immediately after injection. Response to the first treatment can predict response to subsequent treatments. The procedure was well tolerated with only mild to moderate adverse reactions in 20% of treatment sessions. Data on 271 patients from 8 publications were very similar to our study with overall response rate of 66% for the whole group of patients and 67% for patients with chronic migraine. Conclusion: GONB is a safe, well tolerated and an effective children and adolescents with chronic headache and migraine in particular, even for those patients who have failed to respond to multiple preventative strategies. treatment option for

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LP077 Grey matter volume alterations in patients with Thalamic post-stroke pain K. Schönholzer1,2,3,4, G. Sanabria Diaz3,4, K. A. Ebner1,2,3,4, P. Zuber5, L. Gaetano6, S. Magon7, K. Berati2, S. Sellathurai1,2,3,4, M. Ocampo-Pineda3,4, A. Cagol3,4, L. Melie-Garcia3,4, L. Kappos1,2,3,4, C. Granziera1,3,4, T. Sprenger8, A. Papadopoulou1,2,3,4 1University Hospital Basel, Department of Neurology, Basel, Switzerland 2University Hospital and University of Basel, Department of Clinical Research, Basel, Switzerland 3University Hospital and University of Basel, Research Center for Clinical Neuroimmunology and Neuroscience (RC2NB), Basel, Switzerland 4University Hospital and University of Basel, Translational Imaging in Neurology (ThINK), Department of Biomedical Engineering, Basel, Switzerland 5Leiden University, Health, Medical and Neuropsychology, Institute of Psychology, Faculty of Behavioural Sciences, Leiden, Netherlands 6Novartis Pharma AG, Basel, Switzerland 7F. Hoffmann-La Roche Ltd., Roche Pharma Research and Early Development, Roche Innovation Center Basel, Basel, Switzerland 8University Hospital of Zürich, Zürich, Switzerland involved Objective: Thalamic post-stroke pain (TPSP) is a debilitating neuropathic pain syndrome. Secondary structural brain changes may be its pathophysiology. Thus, we aimed at investigating grey matter (GM) volume alterations in TPSP-patients vs. "stroke controls" (SC), who had thalamic stroke, but no pain. Methods: Ten patients with TPSP (prospectively recruited and diagnosed according to the criteria by Klit et al.) and 14 SC, matched for age and sex, underwent 3T magnetic resonance imaging of the brain. Volumetric analyses were performed using FreeSurfer, after lesion filling. Group comparisons were performed with ANCOVA adjusting for age, sex, and total intracranial volume. Results: Patients with TPSP were on average 69 years (y) old and 60% male. Mean time since stroke was 5.5 y and mean pain intensity 5.4/10 (numeric rating scale), involving the contralateral arm in 100% and the head/face in 50%. Lesion volume in thalamus (p= 0.77) and whole brain (p=0.292) did not differ between the two groups, nor did total GM volume (p=0.185). Regarding regional GM differences, volumes of hippocampus (β=0.657, p=0.035) and amygdala the thalamic lesion were lower in TPSP vs. SC. Moreover, ipsilateral parieto-occipital sulcus (β=0.597, p=0.003), circular insular superior sulcus (β=0.223, p=0.024) and lower lingual gyrus (β=0.647, p=0.034) showed (β=0.284, p=0.023) ipsilateral in to cortical volumes compared to SC. TPSP patients also showed cortical changes contralateral to the thalamic lesion (lower volume of middle occipital gyrus: β=0.676, p=0.043 and temporal inferior sulcus: β=0.501, p=0.020, higher volume of gyrus rectus: β=- 0.272, p=0.022). Conclusion: The hippocampus and amygdala, known to be involved in emotional pain processing, may be associated with development of TPSP after thalamic stroke. Bilateral differences, particularly in parieto-occipital and insular areas, may also play a role. Further structural and functional connectivity analysis is ongoing. volume cortical LP078 Negative correlation between amygdala functional connectivity and genetic risk of kynurenine pathway for depression in migraine patients K. Gecse1,2, D. Torok1,2, B. Nagy1,2, D. Baksa1,2,3, C. Aranyi4, M. Emri4, G. Bagdy1,2, G. Juhasz1,2 1Semmelweis University, Department of Pharmacodynamics,Faculty of Pharmaceutical Sciences, Budapest, Hungary 2Semmelweis University, NAP3.0-SE Neuropsychopharmacology Research Group, Hungarian Brain Research Program, Budapest, Hungary 3Pazmany Peter Catholic University, Department of Personality and Clinical Psychology, Institute of Psychology,Faculty of Humanities and Social Sciences, Budapest, Hungary 4University of Debrecen, Division of Nuclear Medicine and Translational Imaging, Department of Medical Imaging, Faculty of Medicine, Debrecen, Hungary could Objective: The alterations of emotion regulation brain network could contribute to the increased risk of migraine patients for depressive symptoms. The kynurenine pathway, a metabolic route associated with inflammation and neurotoxicity, has been implicated in both migraine and depression pathogenesis, indicating a biochemical overlap. The kynurenine pathway influence neuronal projections in amygdala, a key region in emotion regulation. However, less is known about the risk of migraine patients for depression related to amygdala network influenced by the kynurenine pathway. Methods: Sixty-three episodic migraine without aura patients underwent a resting-state fMRI session in their headache-free period the functional connectivity matrix of amygdala. Polygenic risk score (PRS) was calculated to investigate the individual genetic risk of kynurenine pathway for depression. The relationship between depression- related kynurenine pathway PRS and amygdala in multiple regression connectivity was assessed investigate to

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analysis using the Statistical Parametric Mapping (SPM12). Results: Negative correlation was found between the depression-related kynurenine pathway PRS and amygdala connectivity with middle temporal gyrus (pFWE=0.027, k=132, Peak-T value=-3.741). and inferior parietal gyrus (pFWE=0.005, k=185, Peak-T value=-4.411). Conclusion: Our results suggest that the kynurenine pathway might contribute to the increased risk of depressive symptoms in migraine patients by influencing amygdala connectivity with regions involved in emotion perception and regulation. Previous studies identified decreased connectivity of amygdala with middle temporal and inferior parietal gyri in patients with depression. Furthermore, these connections were higher inflammatory markers, a possible mechanism of action of kynurenine pathway. 2017-1.2.1-NKP-2017- Funding: 00002, NAP2022-I-4/2022; TKP2021-EGA-25; OTKA (K143391); ERA PerMed (2019-2.1.7-ERA-NET-2020- 00005). associated with EKÖP-2024-164, LP079 Brain activation patterns of painful thermal stimulation in patients with Thalamic post-stroke pain P. Zuber1, K. Schönholzer2,3,4,5, K. A. Ebner2,3,4,5, L. Gaetano6, G. Sanabria Diaz4,5, L. Melie-Garcia4,5, K. Berati3, S. Sellathurai2,3,4,5, A. Cagol4,5, K. Parmar7, L. Kappos2,3,4,5, S. Magon8, C. Granziera2,4,5, T. Sprenger9, A. Papadopoulou2,3,4,5 1Institute of Psychology, Faculty of Behavioural Sciences, Leiden University, Health, Medical and Neuropsychology, Leiden, Netherlands 2University Hospital Basel, Department of Neurology, Basel, Switzerland 3University of Basel, Department of Clinical Research, Basel, Switzerland 4University Hospital Basel and University of Basel, Translational Imaging in Neurology (ThINk) Basel, Department of Medicine and Biomedical Engineering, Basel, Switzerland 5University Hospital Basel and University of Basel, Research Center for Clinical Neuroimmunology and Neuroscience Basel (RC2NB), Departments of Medicine, Clinical Research and Biomedical Engineering, Basel, Switzerland 6Novartis Pharma AG, Basel, Switzerland 7Reha Rheinfelden, Rheinfelden, Switzerland 8F. Hoffmann-La Roche Ltd, Roche Pharma Research and Early Development, Roche Innovation Center Basel,, Basel, Switzerland 9University Hospital Zürich, Zürich, Switzerland Objective: Thalamic post-stroke pain (TPSP) is a rare neuropathic pain syndrome, frequently accompanied by allodynia. We aimed to compare functional brain activation patterns after painful heat- and cold stimulation in TPSP patients vs. stroke controls (SC), who had thalamic stroke without pain. Methods: Ten TPSP patients (prospectively recruited and diagnosed according to the Klit et al. criteria) and 13 SC underwent 3T magnetic resonance imaging (MRI) of the brain including painful cold (4°C) and heat (45°C) stimulation on the arm affected by stroke. Preprocessing of functional MRI (fMRI) data and a two-sample unpaired t-test comparing the two groups were performed using FSL v.5.0, with a cluster threshold of Z > 2.3 and a cluster extent significance threshold of p < 0.01. Results: There was no group-difference in age (TPSP, 69.4±12.4 years; SC, 63.5±15.4 years old), sex (TPSP, 60%; SC, 46% male) and time since stroke (TPSP, 66.1±75.4 months; SC, 80.9 ±19.3 months). In TPSP, mean spontaneous pain intensity was 5.4/10 (numeric rating scale), involving the arm in 100% and the head/face in 50%. Reported pain after heat and cold stimulation did not differ between TPSP and SC. However, during heat stimulation, TPSP patients showed more activation contralateral cerebellum and less activation in the precuneus and inferior frontal gyrus contralaterally as well as middle frontal gyrus, paracingulate gyrus and insula, ipsilaterally. During cold stimulation, TPSP patients showed more activation in the ipsilateral primary and secondary somatosensory cortices and less activation in the bilateral frontal pole, ipsilateral middle frontal gyrus and inferior frontal gyrus. Conclusion: TPSP patients showed greater sensory- and less activation in frontal areas after painful thermal stimulation than SC. These distinct brain activation patterns suggest an association between TPSP and altered responses to painful stimulation, involving bilateral cortical regions. inferior parietal lobule and in the LP080 Headache as a frequent neurologic manifestation of rare syndromes M. Xhelili1,2, J. Kruja2,3, Z. Ilirjana2,3 1Regional Hospital Center “Shefqet Ndroqi”, Neurology, Tirana, Albania 2University of Medicine, Faculty of Medicine, Tirana, Albania 3UHC “Mother Teresa”, Head of Neurology Service, Tirana, Albania Background: Headache is one of the most common neurological disorders, affecting approximately 40% of the population1. Crouzon first syndrome (CS),

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by congenital hypertelorism, strabismus, hydrocephalus, described in 19122, is a rare autosomal dominant syndrome caused by mutations in the FGFRII gene located on chromosome 10q3. CS has a neuro- ophthalmologic clinical picture characterized by headache, craniosynostosis, exophthalmos, sleep apnea, and epileptic seizures. Escobar Syndrome (ES), also known as nonfatal multiple pterygium syndrome (MPS)4, is a very rare autosomal recessive disorder characterized pterygium, arthrogryposis, and spinal malformations. Mutations in the gamma subunit of the acetylcholine receptor (AChR) gene CHRNG, are found in this disorder. Escobar syndrome was first described by Bussiere et al. in 1902 and again by Escobar et al. in 19785. Langerhans cell histiocytosis (LCH) is a localized form of histiocytosis X6, characterized by osteolytic lesions and involvement of many organs, including the lungs, spleen, liver, lymph nodes, gastrointestinal tract, and pituitary gland. Langerhans cell histiocytosis infiltrates the hypothalamic-pituitary axis in 5–50% of cases, causing diabetes insipidus7. Aims and objectives: To present three clinical cases in which headache was the symptom leading to a neurological consultion. Case report (s): 1. Crouson Syndrome~ We present the case of a 30-year-old female patient who presented with a seven- year history of daily moderate frontal headache and vertigo. Eight months later, she developed blurred vision and significant hearing loss on both sides. The patient complained of nocturnal dyspnea consistent with sleep apnea. Recurrent episodes of keratoconjunctivitis were also noted. Neurological examination revealed no motor increased or sensory deficits or clinical signs of intracranial psychomotor development. Examination: multiple malformations of the dental arches without facial dysmorphism, exophthalmos and syndactyly. General metabolic and Normal hematological normal. electroencephalography. Panoramex has identified numerous orthodontic abnormalities. MRI of the head shows scaphocephalic prominence of the skull and enlargement of the optic nerve sheath without signs of hydrocephalus. 2. Escobar Syndrome~ A 26-year-old female patient presented with severe daily frontotemporal headache and anxiety. Examination revealed severe muscle wasting and hypotonia, cervical and popliteal pterygium, hypertrichosis, severe scoliosis, and left upper syndactyly. The patient also had a flat face with micrognathia, hypertelorism, and mild bilateral ptosis. Clinically, Escobar syndrome was suspected, which has been genetically confirmed. 3. Langerhans cell histiocytosis~ A 33-year-old patient presented with a 3-month history with progressive moderate-intensity headaches and psychomotor pressure. Normal tests are a through In addition, and may be increased emotional agitation. she has memory and concentration difficulties, behavioral disturbances, and instability. She was consulted several times by her physician and was taking analgesic drugs. She has been reported to have had severe dysphagia since 10 weeks, drinking more than 10 liters of water per day. The patient was admitted and underwent the necessary laboratory and imaging tests. MRI of the skull showed an increase in the size of the pituitary infundibulum, which was homogeneously enlarged after the injection of contrast, suggesting an eosinophilic granuloma. Results: Headache is the most common neurological symptom spontaneous or physiopathological sign of many rare systemic diseases. For this reason, attention should be paid to all details of the patient's history and general examination, because routine patient complaints, we can diagnose rare syndromes. Conclusions: Headaches are often not something that can be addressed by a neurologist alone. An interdisciplinary approach is needed to identify these syndromes and provide the most appropriate treatment for the patient. Keywords: headache, general inspection, challenge, syndrome, further evaluation Abbreviations: CS- Crouzon Syndrome ES- Escobar Syndrome FGFRII- fibroblast growth factor receptor II LCH- Langerhans cell Histiocytosis MRI= Magnetic Resonance Imaging Figure 1. Crouson Syndrome~ We present the case of a 30-year-old female patient who presented with a seven- year history of daily moderate frontal exophthalmos, headache hypertelorism, proptosis b)multiple malformations of the dental arch, uvula bifida, hypoplastic maxilla, prognathia, high arched narrow palate c) panoramex: malocclusion d) skull x- ray, dolichocephaly e) Magnetic Resonace of the head shows scaphocephalic prominence of the skull and enlargement of the optic nerve sheath without signs of hydrocephalus Figure 2: a) b) Clinical features of Escobar syndrome (Reference: Escobar V. Bixler D. Gleise, Weaver DD. Multiple pterygium syndrome. American Journal of Diseases of Children 1978; 132. 609-611 c) Langerhans cell histiocytosis: MRI of the skull showed an increase in the size of the pituitary infundibulum, which was homogeneously enlarged after the injection of contrast, suggesting an eosinophilic granuloma. vertigo. and a)

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