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Aim: Successful acute migraine treatment potentially prevents emergency room (ER) consultations but requires that the diagnosis of migraine was given earlier. The aim of this study is to quantify the problem of missed migraine diagnosis prior to ER visits., Methods: Inclusion criterion for this single-center prospective study was the presentation at the ER for acute headache. Patients with acute migraine attacks were assessed for previous migraine attacks, and whether they were given a diagnosis of migraine in the past., Results: Of 137 patients with migraine diagnosis at discharge, 108 (79%) had previous headache attacks fulfilling the criteria for migraine according to The International Classification of Headache Disorders 3rd edition (ICHD-3). Of those, 54 (50%) received the diagnosis for the first time., Conclusion: Half of the migraine patients (50%) presenting in the ER for headache could have been diagnosed earlier. This highlights the need for better detection and treatment of migraine by pre-hospital healthcare providers, as earlier diagnosis and specific acute treatment could have prevented the ER visit., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Drangova et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Patients with visual snow syndrome (VSS) experience uncountable flickering tiny dots in the entire visual field. Symptoms often persist over the years. Very little is known about altered perception in VSS. VSS is diagnosed based on subjective reports because there is no manual with objective measures. In this study, 20 patients with VSS and 17 healthy controls performed a battery of tests assessing visual acuity, contrast sensitivity, illusion perception, spatial-temporal vision, motion perception, visual attention, and selective attention. Surprisingly, except for one test, which is the honeycomb illusion, patients performed at the same level as controls. Patients reporting black and white visual snow performed better in the Stroop test compared to patients reporting other visual snow colours. In addition to a clinical visit, the 30-day clinical diary was administered to patients to broadly measure their symptom severity. We found that better performance in the tests, in particular in the contrast and coherent motion tests, was correlated with lower VSS symptoms, weaker VS characteristics (e.g. density and size) and lower VS severity. Our results suggest that, even if visual abilities are not deteriorated by VSS, they can determine how severe symptoms are, and show that VSS is an heterogenous disorder where symptoms and visual abilities vary between patients, for instance depending on the VS colour. The study was primarily designed to identify tests where performance differs between controls and patients. In addition, exploratory analyses were conducted to initiate an understanding of the overall pattern of relationships between patients' visual abilities and symptoms, which is of clinical relevance. Future studies with more power are necessary to validate our findings., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Identifying genetic risk factors for highly heterogeneous disorders like epilepsy remains challenging. Here, we present the largest whole-exome sequencing study of epilepsy to date, with >54,000 human exomes, comprising 20,979 deeply phenotyped patients from multiple genetic ancestry groups with diverse epilepsy subtypes and 33,444 controls, to investigate rare variants that confer disease risk. These analyses implicate seven individual genes, three gene sets, and four copy number variants at exome-wide significance. Genes encoding ion channels show strong association with multiple epilepsy subtypes, including epileptic encephalopathies, generalized and focal epilepsies, while most other gene discoveries are subtype-specific, highlighting distinct genetic contributions to different epilepsies. Combining results from rare single nucleotide/short indel-, copy number-, and common variants, we offer an expanded view of the genetic architecture of epilepsy, with growing evidence of convergence among different genetic risk loci on the same genes. Top candidate genes are enriched for roles in synaptic transmission and neuronal excitability, particularly postnatally and in the neocortex. We also identify shared rare variant risk between epilepsy and other neurodevelopmental disorders. Our data can be accessed via an interactive browser, hopefully facilitating diagnostic efforts and accelerating the development of follow-up studies., Competing Interests: Competing Interests B.M.N is a member of the scientific advisory board at Deep Genomics and Neumora. No other authors have competing interests to declare

Background: There are limited real-world data in Switzerland examining the impact of erenumab, a fully human IgG2 monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) receptor, on migraine-related quality of life., Objective: This 18-month interim analysis of 172 patients with episodic or chronic migraine from the SQUARE study provides first prospective insights on the impact of mandatory erenumab treatment interruption, following Swiss-reimbursement requirements, in a real-world clinical setting in Switzerland., Findings: Recruited patients receiving 70 or 140 mg erenumab underwent treatment interruption on average 11.2 months after therapy onset with a mean duration of 4 months. There were sustained improvements in mean monthly migraine days (MMD) and migraine disability (mMIDAS) during initial treatment with erenumab. Treatment interruption was associated with a temporary worsening of condition. Symptoms ameliorated upon therapy reuptake reaching improvements similar to pre-break within 3 months., Conclusions: Treatment interruption was associated with a temporary worsening of condition, which improved again after therapy restart., (© 2024. The Author(s).)

Introduction: Migraine and endometriosis are chronic disabling pain conditions. There is evidence for a shared genetic background. Migraine phenotype and course in patients with the comorbidity are insufficient investigated. Both conditions can be treated with progestins., Methods: For this observational study we included women with migraine and endometriosis, visiting our clinic from 2015 to 2021. We collected available information from charts and complemented these data by a structured phone interview to collect more specific information on migraine and the course of both diseases., Results: From 344 patients fulfilling the inclusion criteria, 94 suffered from both, endometriosis and migraine. Migraine with aura was reported by 41% of the patients and was associated with earlier onset of migraine (age < 17 years (OR 6.54) and with a history of medication overuse headache (OR 9.9, CI 1.6-59.4). Present monthly migraine frequency (1.5 ± 2.6) was significantly lower than five years before the interview (2.9 ± 4.64). There was a correlation between medication overuse headache and use of analgesics more than 3 days/months for dysmenorrhoea (p < 0.03). ASRM endometriosis score was not associated with migraine characteristics., Conclusions: We conclude that the comorbidity of endometriosis is highly linked to migraine with aura. Migraine onset in these patients was earlier. Further studies are needed to explore, if the observed decrease in migraine frequency can be attributed to recent endometriosis surgery and to understand if early diagnosis and treatment of both conditions may contribute to improve the course of both conditions. Trial registration BASEC Nr. 2021-00285., (© 2024. The Author(s).)

Objective: Spontaneous intracranial hypotension (SIH) is an important cause of orthostatic headaches caused by spinal CSF leaks. It has a strong negative impact on patients' socioeconomic status and health-related quality of life (HRQOL). This study aimed to analyze the impact of surgical and endovascular treatments on patients' HRQOL., Methods: The authors conducted a prospective, observational cohort study that included all patients treated for SIH with microsurgery or embolization, depending on the type of CSF leak, at their institution between April 2022 and May 2023. Patients were asked to complete a specifically designed questionnaire, as well as the 15D HRQOL questionnaire, before and 3 months after treatment., Results: A total of 21 patients (14 female; mean age 51.7 years) were treated in the study period. There were 12 (57%) type 1 leaks, 3 (14%) type 2, and 6 (29%) type 3. While 20 (95.2%) leaks were localized in the thoracic spine, only 1 (4.8%) was found in the lumbar spine. All patients completed the questionnaires. Fifteen (71.4%) patients underwent microsurgery and 6 (28.6%) endovascular embolization. The mean 15D score improved from 0.802 before to 0.889 after treatment (p = 0.013). Compared with an age- and sex-matched general population, HRQOL was significantly impaired in patients with SIH before treatment. After treatment, the authors found no significant difference in the overall HRQOL between patients and the healthy population. Mean headache intensity on a numeric rating scale improved from 8.1 before treatment to 2.3 after treatment (p = 0.003). Patients reported that SIH had a notable impact on their social and working life., Conclusions: SIH has a considerable negative impact on HRQOL. Microsurgery or embolization can dramatically improve HRQOL, subjective perception of health, and headache intensity. Therefore, surgical or endovascular treatment should be considered given the improvement observed in HRQOL for patients with SIH.

Purpose of Review: Visual snow syndrome (VSS) is a disorder characterized by persistent visual disturbances, including the visual snow phenomenon, palinopsia, heightened perception of entoptic phenomena, impaired night vision, and photophobia. The purpose of this review is to provide an update on recent findings over the past 18 months in VSS research and to summarize the current state of treatment approaches., Recent Findings: Electrophysiological studies have revealed cortical hyperresponsivity in visual brain areas, imaging studies demonstrated microstructural and functional connectivity alterations in multiple cortical and thalamic regions and investigated glutamatergic and serotoninergic neurotransmission. These findings suggest that VSS might be a network disorder.Only few treatment studies are currently available demonstrating limited response to medication and even worsening or triggering of visual symptoms by certain antidepressants. Promising nonpharmacological treatments include mindfulness-based cognitive therapy, the use of chromatic filters, and research on visual noise adaption and neuro-optometric visual rehabilitation therapy (NORT). However, the level of evidence is still low and further research is needed including larger trials and involving objective measures of individual dysfunction., Summary: Although there has been recent progress, we still have not fully understood the nature of VSS. Further research is needed on a clinical and pathophysiological level to successfully treat the condition., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Visual snow syndrome is a disorder characterized by the combination of typical perceptual disturbances. The clinical picture suggests an impairment of visual filtering mechanisms and might involve primary and secondary visual brain areas, as well as higher-order attentional networks. On the level of cortical oscillations, the alpha rhythm is a prominent EEG pattern that is involved in the prioritisation of visual information. It can be regarded as a correlate of inhibitory modulation within the visual network., Methods: Twenty-one patients with visual snow syndrome were compared to 21 controls matched for age, sex, and migraine. We analysed the resting-state alpha rhythm by identifying the individual alpha peak frequency using a Fast Fourier Transform and then calculating the power spectral density around the individual alpha peak (+/- 1 Hz). We anticipated a reduced power spectral density in the alpha band over the primary visual cortex in participants with visual snow syndrome., Results: There were no significant differences in the power spectral density in the alpha band over the occipital electrodes (O1 and O2), leading to the rejection of our primary hypothesis. However, the power spectral density in the alpha band was significantly reduced over temporal and parietal electrodes. There was also a trend towards increased individual alpha peak frequency in the subgroup of participants without comorbid migraine., Conclusions: Our main finding was a decreased power spectral density in the alpha band over parietal and temporal brain regions corresponding to areas of the secondary visual cortex. These findings complement previous functional and structural imaging data at a electrophysiological level. They underscore the involvement of higher-order visual brain areas, and potentially reflect a disturbance in inhibitory top-down modulation. The alpha rhythm alterations might represent a novel target for specific neuromodulation., Trial Registration: we preregistered the study before preprocessing and data analysis on the platform osf.org (DOI: https://doi.org/10.17605/OSF.IO/XPQHF , date of registration: November 19th 2022)., (© 2024. The Author(s).)

Background: Sometimes migraine aura changes from attack to attack, raising the question of whether the change is heralding an ischemic stroke or an unusual aura. Differentiating unusual migraine aura from the onset of an acute ischemic stroke in patients with migraine with aura (MwA) can be challenging., Objective: The aim of this cohort study was to assess clinical characteristics that help distinguish between MwA and minor stroke in patients with a previous history of MwA who presented with suspicion of stroke., Methods: We interviewed patients with MwA and ischemic stroke (MwA + IS) and patients with MwA and unusual aura, but without ischemic stroke (MwA - IS) from a tertiary hospital using a structured questionnaire. We assessed how symptoms of ischemic stroke or unusual aura differed from usual, that is, the typical aura in each patient. Stroke or exclusion of stroke was verified by multimodal magnetic resonance imaging., Results: Seventeen patients with MwA + IS and twelve patients with MwA - IS were included. New focal neurological symptoms (13/17 [76%] vs. 3/12 [25%]), change of the first symptom (10/17 [59%] vs. 1/12 [8%]), and absence of headache (6/15 [40%] vs. 2/10 [20%]) were more often reported during ischemic stroke. The physical examination was normal in 8/17 (47%) MwA + IS and in 6/12 (50%) MwA - IS patients. In 5/17 (29%) patients with MwA + IS, there were unequivocal physical signs suggestive of stroke such as persistent visual loss, ataxia, or paresis., Conclusion: There are clues from the history that might help identify stroke in patients with MwA with changed aura symptoms. These might be particularly useful in patients presenting without physical findings suggestive of stroke., (© 2024 The Authors. Headache: The Journal of Head and Face Pain published by Wiley Periodicals LLC on behalf of American Headache Society.)

Objective: Although orthostatic headache is the hallmark symptom of spontaneous intracranial hypotension (SIH), patients can present with a wide range of different complaints and thereby pose a diagnostic challenge for clinicians. Our aim was to describe and group the different symptoms associated with SIH and their course over time., Methods: We retrospectively surveyed consecutive patients diagnosed and treated for SIH at our institution from January 2013 to May 2020 with a specifically designed questionnaire to find out about their symptomatology and its course., Results: Of 112 eligible patients, 79 (70.5%) returned the questionnaire and were included in the analysis. Of those, 67 (84.8%) reported initial orthostatic headaches, whereas 12 (15.2%) denied having this initial symptom. All except one (98.7%) patients reported additional symptoms: most frequently cephalic pressure (69.6%), neck pain (68.4%), auditory disturbances (59.5%), nausea (57%), visual disturbances (40.5%), gait disturbance (20.3%), confusion (10.1%) or sensorimotor deficits (21.5%). Fifty-seven (72.2%) patients reported a development of the initial symptoms predominantly in the first three months after symptom onset. Age and sex were not associated with the symptomatology or its course (p > 0.1)., Conclusion: Although characteristic of SIH, a relevant amount of patients present without orthostatic headaches. In addition, SIH can manifest with non-orthostatic headaches at disease onset or during the course of the disease. Most patients report a wide range of associated complaints. A high degree of suspicion is crucial for an early diagnosis and targeted treatment., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Spontaneous intracranial hypotension (SIH) is a serious medical condition caused by loss of cerebrospinal fluid at the level of the spine, which, when not treated, may cause substantial long-term disability and increase morbidity. The following video summarizes the necessary steps for successful diagnosis and treatment of SIH, starting with a brain and spine magnetic resonance imaging, followed by dynamic myelography. Because an epidural bloodpatch did not provide a lasting relief, the patient underwent surgery which demonstrated a ventral dural slit caused by an osteodiscogenic microspur. In the 1-month follow up, the patient was symptom free. This video is meant to raise awareness of SIH among clinicians in order to increase general sensitivity for this diagnosis., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The ongoing Pan-European Real Life (PEARL) phase 4 study is evaluating fremanezumab effectiveness and safety for the prevention of episodic and chronic migraine. This interim analysis reports primary, secondary and exploratory endpoints from when 500 participants completed at least six months of treatment., Methods: Adults with episodic migraine or chronic migraine maintaining daily headache diaries were enrolled upon initiation of fremanezumab. Primary endpoint: proportion of participants with ≥50% reduction in monthly migraine days during the six-month period after fremanezumab initiation. Secondary endpoints: mean change from baseline across months 1-12 in monthly migraine days, acute migraine medication use, and headache-related disability. Exploratory endpoint: mean change in headache severity from baseline across months 1-12. Safety was assessed through adverse events reported., Results: Overall, 897 participants were enrolled and 574 included in the effectiveness analyses (episodic migraine, 25.8%; chronic migraine, 74.2%). Of participants with data available, 175/313 (55.9%) achieved ≥50% monthly migraine days reduction during the six-month period post-initiation. Across months 1-12, there were sustained reductions in mean monthly migraine days, acute medication use, disability scores, and headache severity. Few adverse events were reported., Conclusion: PEARL interim results support the effectiveness and safety of fremanezumab for migraine prevention in a real-world population across several European countries.Trial registration: encepp.eu: EUPAS35111., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: MA reports personal fees and PI in clinical trials for AbbVie, Amgen, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals; and research grants from Lundbeck Foundation, Novo Nordisk Foundation, and Novartis. DDM has received honoraria, research, and travel grants from Allergan/Abbvie, Amgen, Biogen, Cefaly, Genesis Pharma, Electrocore, Eli Lilly, Lundbeck, Merk-Serono, Mertz, Novartis, Roche, Sanofi, Specifar, and Teva Pharmaceuticals; participated in clinical trials for Amgen, Cefaly, Electrocore, Eli Lilly, Genesis Pharma, Lundbeck, Mertz, Novartis, Specifar, and Teva Pharmaceuticals as principal investigator; and is President of the board of the Hellenic Headache Society and Co-chairman of the management group of the Headache Panel at the European Academy of Neurology. FMA reports lectures, advisory boards, and/or PI in clinical trials for Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals. PK, VRC, and AHA are employees and/or shareholders of Teva Pharmaceuticals. LL is a former employee of Teva Pharmaceuticals. CJS reports consulting, advisory boards, presentations, and travel support from Novartis, Eli Lilly, Teva Pharmaceuticals, AbbVie, Allergan, Almirall, Amgen, Lundbeck, MindMed, and Grünenthal; is a part-time employee of Zynnon; and reports research support from the Swiss Heart Foundation, Eye on Vision Foundation, Baasch-Medicus Foundation, and German Migraine and Headache Society. GS reports advisory boards and/or PI in clinical trials for AbbVie, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals; and research support from Vinnova (Sweden’s innovation agency), Lund University, and the Swedish Neurological Association. PPR reports grant/research support from AbbVie, AGAUR, EraNet NEURON, Instituto Investigación Carlos III, MINECO, Novartis, RIS3CAT FEDER, and Teva Pharmaceuticals; and consultancy or education for AbbVie, Amgen, Biohaven, Chiesi, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals. PJD reports educational meetings and/or collaboration in clinical trials for Allergan/AbbVie, electroCore, Novartis, Teva Pharmaceuticals, and Lundbeck. TN reports consulting, speaking fees, and travel grants from Eli Lilly, Glenmark, Lundbeck, Novartis, Pfizer, St. Jude Medical, Teva Pharmaceuticals, and UCB; and advisory boards or PI in clinical trials for AbbVie, Amgen, Eli Lilly, Lundbeck, Neurocrine, Novartis, Teva Pharmaceuticals, and UCB. ACP reports lectures, advisory boards, and/or PI in clinical trials for Allergan, AbbVie, Pfizer, Teva Pharmaceuticals, Novartis, Lundbeck, Eli Lilly, and Roche. IPM reports lectures, advisory boards, and/or PI in clinical trials for Allergan-AbbVie, Teva Pharmaceuticals, Novartis, Lundbeck, and Eli Lilly. MLS reports lectures, advisory boards, and/or PI in clinical trials for Pfizer, Teva Pharmaceuticals, Novartis, Lundbeck, AbbVie, and Eli Lilly. CT reports personal fees for the participation in advisory boards or symposia for AbbVie, Dompé, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals; she reports institutional fees for conducting clinical trials for AbbVie, Dompé, Eli Lilly, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals; she received funding for research projects from the European Commission, the Italian Ministry of Health, the Migraine Research Foundation, and the Italian Multiple Sclerosis Foundation.

Roughly one-third of migraine patients suffer from migraine with aura, characterized by transient focal neurological symptoms or signs such as visual disturbance, sensory abnormalities, speech problems, or paresis in association with the headache attack. Migraine with aura is associated with an increased risk for stroke, epilepsy, and with anxiety disorder. Diagnosis of migraine with aura sometimes requires exclusion of secondary causes if neurological deficits present for the first time or are atypical. It was the aim of this review to summarize EEG an MRI findings during migraine aura in the context of pathophysiological concepts. This is a narrative review based on a systematic literature search. During visual auras, EEG showed no consistent abnormalities related to aura, although transient focal slowing in occipital regions has been observed in quantitative studies. In contrast, in familial hemiplegic migraine (FHM) and migraine with brain stem aura, significant EEG abnormalities have been described consistently, including slowing over the affected hemisphere or bilaterally or suppression of EEG activity. Epileptiform potentials in FHM are most likely attributable to associated epilepsy. The initial perfusion change during migraine aura is probably a short lasting hyperperfusion. Subsequently, perfusion MRI has consistently demonstrated cerebral hypoperfusion usually not restricted to one vascular territory, sometimes associated with vasoconstriction of peripheral arteries, particularly in pediatric patients, and rebound hyperperfusion in later phases. An emerging potential MRI signature of migraine aura is the appearance of dilated veins in susceptibility-weighted imaging, which may point towards the cortical regions related to aura symptoms ("index vein"). Conclusions: Cortical spreading depression (CSD) cannot be directly visualized but there are probable consequences thereof that can be captured Non-invasive detection of CSD is probably very challenging in migraine. Future perspectives will be elaborated based on the studies summarized.

Aim: Given the similar presentation of migraine aura and acute ischemic stroke, advancing patient age might change the characteristics of migraine with aura (MA) and be clinically important. Clinical data, however, are limited. Experimental studies indicate a decrease in the magnitude of cortical spreading depression (CSD), the pathophysiological correlate of migraine aura, with advancing age. Our study aimed to assess the influence of age on the clinical features of MA., Methods: Three hundred and forty-three patients were interviewed using a structured questionnaire. The questions covered the headache characteristics and symptom types including the characteristics of the C-criterion, as defined by the International Classification of Headache Disorders 3 rd Edition. The association of age with MA characteristics was assessed., Results: The median age was 29 (IQR 28-52) and 235 of the 343 patients were women (69%). Individual symptoms of the C-criterion such as gradual aura spreading over longer than 5 min (P < 0.001), two or more aura symptoms occurring in succession (P = 0.005), duration of at least one MA symptom for longer than 60 min (P = 0.004), and associated headache (P = 0.01) were more frequent in younger patients. The number of symptoms including the C-characteristics decreased with increasing age (P < 0.001). Patients with sensory (P < 0.001), motor (P = 0.004) and speech disturbance (P = 0.02) were younger, and older patients with headache had less photophobia (P = 0.04) and phonophobia (P = 0.03). Sensitivity analyses yielded similar results., Conclusion: The frequency of typical characteristics of migraine aura and migraine headache including photophobia and phonophobia decreases with advancing patient age. This might have potentially difficult implications for the diagnosis of MA in the elderly., (© 2023. The Author(s).)

Migraine is the most common neurological disorder and can be associated with a high degree of disability. In addition to non-pharmacological approaches to reduce migraine frequency, pharmacological migraine preventatives are available. Evidence-based guidelines from the German Migraine and Headache Society (DMKG), and German Society for Neurology (DGN), Austrian Headache Society (ÖKSG), and Swiss Headache Society (SKG) are available for indication and application. For therapy-relevant questions such as the duration of a pharmacological migraine prevention, no conclusions can be drawn from currently available study data. The aim of this review is to present a therapy consensus statement that integrates the current data situation and, where data are lacking, expert opinions. The resulting current recommendations on the duration of therapy for pharmacological migraine prophylaxis are shown here., (© 2022. The Author(s), under exclusive licence to Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Background and Purpose: Response predictors to erenumab (ERE) in migraine patients would benefit their clinical management. We investigate associations between patients' clinical characteristics and polymorphisms at calcitonin receptor-like receptor (CALCRL) and receptor activity-modifying protein 1 (RAMP1) genes and response to ERE treatment measured as clinically meaningful improvement on the Headache Impact Test-6 (HIT-6) score., Methods: This post hoc analysis of a prospective, multicenter, investigator-initiated study involves 110 migraine patients starting ERE 70 mg/month. Demographics, medical history, and migraine-related burden measured by HIT-6 score were collected during 3 months before and after ERE start. Selected polymorphic variants of CALCRL and RAMP1 genes were determined using real-time polymerase chain reaction. Logistic regression models identified independent predictors for response to ERE, defined as HIT-6 score improvement ≥ 8 points (HIT-6 responders [HIT-6 RESP] vs. HIT-6 nonresponders)., Results: At Month 3, 58 (52.7%) patients were HIT-6 RESP. Comorbid hypertension predicted a lower probability of being HIT-6 RESP (odds ratio [OR] = 0.160, 95% confidence interval [CI] = 0.047-0.548, p = 0.003). Compared to major alleles, minor alleles CALCRL rs6710852G and RAMP rs6431564G conferred an increased probability of being HIT-6 RESP (for each G allele: OR = 2.82, 95% CI = 1.03-7.73, p = 0.043; OR = 2.10, 95% CI = 1.05-4.22, p = 0.037). RAMP1 rs13386048A and RAMP1 rs12465864G decreased this probability (for each rs13386048A, OR = 0.53, 95% CI = 0.28-0.98, p = 0.042; for each rs12465864G, OR = 0.32, 95% CI = 0.13-0.75, p = 0.009). A genetic risk score based on the presence and number of identified risk alleles was independently associated with HIT-6 RESP (OR = 0.49, 95% CI = 0.33-0.72, p = 0.0003), surviving Bonferroni correction., Conclusions: Response to ERE was associated with comorbid hypertension and specific allelic variants in CALCRL and RAMP1 genes. Results require confirmation in future studies., (© 2023 European Academy of Neurology.)

Purpose: Epidural blood patch (EBP) is a minimally invasive treatment for spontaneous intracranial hypotension (SIH). Follow-up after EBP primarily relies on clinical presentation and data demonstrating successful sealing of the underlying spinal cerebrospinal fluid (CSF) leak are lacking. Our aim was to evaluate the rate of successfully sealed spinal CSF leaks in SIH patients after non-targeted EBP., Methods: Patients with SIH and a confirmed spinal CSF leak who had been treated with non-targeted EBP were retrospectively analyzed. Primary outcome was persistence of CSF leak on spine MRI or intraoperatively. Secondary outcome was change in clinical symptoms after EBP., Results: In this study 51 SIH patients (mean age, 47 ± 13 years; 33/51, 65% female) treated with non-targeted EBP (mean, 1.3 EBPs per person; range, 1-4) were analyzed. Overall, 36/51 (71%) patients had a persistent spinal CSF leak after EBP on postinterventional imaging and/or intraoperatively. In a best-case scenario accounting for missing data, the success rate of sealing a spinal CSF leak with an EBP was 29%. Complete or substantial symptom improvement in the short term was reported in 45/51 (88%), and in the long term in 17/51 (33%) patients., Conclusion: Non-targeted EBP is an effective symptomatic treatment providing short-term relief in a substantial number of SIH patients; however, successful sealing of the underlying spinal CSF leak by EBP is rare, which might explain the high rate of delayed symptom recurrence. The potentially irreversible and severe morbidity associated with long-standing intracranial hypotension supports permanent closure of the leak., (© 2022. The Author(s).)

Background and Objectives: Taking a detailed history of symptoms is important for differentiating incipient ischemic stroke and migraine aura. The aim of our study is to describe in detail symptom type and temporal pattern of symptom evolution (i.e., symptom succession and the time lapse between symptoms) and to identify differentiating clinical features in patients with ischemic stroke and migraine with aura., Methods: Consecutive patients with ischemic stroke and migraine with aura were interviewed using a structured questionnaire. Stroke diagnosis was confirmed by imaging and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Wake-up strokes and patients with severe cognitive deficits were excluded., Results: In stroke patients and migraine patients, respectively, 50/78 (64%) vs. 123/326 (37%) had one, 18 (23%) vs. 127 (38%) had two, 5 (6%) vs. 69 (21%) had three, 2 (2%) vs. 4 (1%) had four, and 3 (3%) vs. 3 (1%) had five visual symptoms. In respect of sensory symptoms, 76/145 (52.4%) vs. 116/175 (66%) reported paresthesia and 92/145 (63.4%) vs. 132 (75%) numbness. Looking at the beginning, visual symptoms were the first symptom more often in migraine aura than in ischemic stroke (72.1 vs 18.8%, P < 0.001; PPV 86.8%). Sensory (29 vs 13.9%, P = 0.001; PPV 54.8%) and motor symptoms (20.5 vs 1.4%, P < 0.001; PPV 88.9%) were the first symptom more frequently in ischemic stroke. Of patients with consecutive symptoms, 39 of 201 (19%) compared to 34 of 117 (29%) ( P = 0.02; PPV 46.6%) reported at least two simultaneous symptoms. A time lapse between symptoms of < 1 min (18.6 vs 6.3%, P < 0.001; PPV 57.1%) and > 360 min (15.8 vs 0%, χ 2 = 39.61, P < 0.001; PPV 100%) was more frequent in stroke whereas a time lapse between 5 and 60 min was more frequent in migraine aura (41.1 vs 68.7%, χ 2 = 23.52, P < 0.001; PPV 78.7%)., Conclusion: There is a significant overlap in the clinical presentation of stroke and migraine aura. In particular, a substantial proportion of patients in one group had symptoms that are traditionally attributed to the other group. This study highlights the similarities and differences between symptoms of ischemic stroke and migraine aura and challenges our reasoning in daily clinical practice., Competing Interests: AS and SJ report research support from the Swiss Heart Foundation. UF Consulting for Medtronic, Stryker, CSL Behring. Advisory boards for Portola/Alexion (money paid to institution). MA reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichy Sankyo, Medtronic, Novartis, Pfizer, and Amgen. HM grants from Abbott for the PC and PRIMA trials and from Cerenovus for the ARISE studies. Personal and speaker fees from Cerenovus, Bayer, Servier, Medtronic, and Stryker. CS Consulting, Advisory Boards, Speaker, Travel Support for/from Novartis, Eli Lilly, TEVA Pharmaceuticals, Allergan, Abbvie, Almirall, Amgen, Lundbeck, MindMed, Grünenthal. Part-time-employee at Zynnon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Scutelnic, Bracher, Kreis, Beyeler, Fischer, Arnold, Mattle, Jung and Schankin.)

Background and objectives To assess the usefulness of the "index vein" for making the diagnosis of migraine aura.Methods 400 patients were included when they: i) presented with an acute neurological deficit, ii) had a brain MRI, and iii) had a discharge diagnosis of migraine aura, ischemic stroke, epileptic seizure or controls (n = 100 per group).Results Compared to stroke (2%), epileptic seizure (4%) and controls (1%), the index vein is more prevalent in migraine aura (17%, p < 0.001). The index vein is highly specific for migraine aura (specificity 97%, 95% CI 95-99). The index vein has a positive predictive value for the diagnosis of migraine aura of 70% (95%CI 48-87). The index vein-score has the ability to diagnose migraine aura with a sensitivity of 94% (95%CI 87.4-97.8) and specificity of 73.5% (95%CI 66.8-79.5) at a cut-off of 4 points.Discussion The index vein serves as a good biomarker for migraine aura in the emergency setting.

Visual snow is the main symptom of visual snow syndrome, a disorder of predominantly visual disturbances initially described in patients without abnormalities on ancillary investigations. We present a case series of patients with visual snow in the setting of acute ischemic stroke. The first and second patient reported previous episodic visual snow with migraine attacks. The third patient experienced visual snow for the first time during the ischemic stroke. In the first patient, the ischemic stroke affected the right and left precuneus and the right lingual gyrus. In the second patient, the ischemic stroke was located in the left lingual gyrus, parts of the left fusiform and parahippocampal gyrus, left dorso-lateral thalamus, and left cerebellar hemisphere. In the third patient, occipital pole, trunk of the corpus callosum on the right, right paramedian pons, right cerebellar hemisphere, and vermis were affected. Our case series indicates that the symptom visual snow can be caused by vascular lesions in areas of visual processing. Because patients did not meet criteria for visual snow syndrome, dysfunction in the affected areas might only explain part of the complex pathophysiology of visual snow syndrome., (© 2023 American Headache Society.)

Background: The fully human monoclonal antibody erenumab, which targets the calcitonin gene-related peptide (CGRP) receptor, was licensed in Switzerland in July 2018 for the prophylactic treatment of migraine. To complement findings from the pivotal program, this observational study was designed to collect and evaluate clinical data on the impact of erenumab on several endpoints, such as quality of life, migraine-related impairment and treatment satisfaction in a real-world setting., Methods: An interim analysis was conducted after all patients completed 6 months of erenumab treatment. Patients kept a headache diary and completed questionnaires at follow up visits. The overall study duration comprises 24 months., Results: In total, 172 adults with chronic or episodic migraine from 19 different sites across Switzerland were enrolled to receive erenumab every 4 weeks. At baseline, patients had 16.6 ± 7.2 monthly migraine days (MMD) and 11.6 ± 7.0 acute migraine-specific medication days per month. After 6 months, erenumab treatment reduced Headache Impact Test (HIT-6™) scores by 7.7 ± 8.4 (p < 0.001), the modified Migraine Disability Assessment (mMIDAS) by 14.1 ± 17.8 (p < 0.001), MMD by 7.6 ± 7.0 (p < 0.001) and acute migraine-specific medication days per month by 6.6 ± 5.4 (p < 0.001). Erenumab also reduced the impact of migraine on social and family life, as evidenced by a reduction of Impact of Migraine on Partners and Adolescent Children (IMPAC) scores by 6.1 ± 6.7 (p < 0.001). Patients reported a mean effectiveness of 67.1, convenience of 82.4 and global satisfaction of 72.4 in the Treatment Satisfaction Questionnaire for Medication (TSQM-9). In total, 99 adverse events (AE) and 12 serious adverse events (SAE) were observed in 62 and 11 patients, respectively. All SAE were regarded as not related to the study medication., Conclusions: Overall quality of life improved and treatment satisfaction was rated high with erenumab treatment in real-world clinical practice. In addition, the reported impact of migraine on spouses and children of patients was reduced., Trial Registration: BASEC ID 2018-02,375 in the Register of All Projects in Switzerland (RAPS)., (© 2022. The Author(s).)

Background: Visual snow syndrome is a phenomenon for which no effective treatment is known. It is highly comorbid with migraine, therefore we performed a retrospective chart review of patients with visual snow syndrome treated with a monoclonal antibody against calcitonin gene related peptide or its receptor., Findings: We enrolled 15 patients with visual snow syndrome who received at least once a monoclonal antibody against calcitonin gene related peptide or its receptor. None of the patients reported relief of visual snow syndrome whereas those patients with comorbid migraine reported a very good efficacy of the antibody against the migraine headache but not against the migraine aura., Conclusion: The data suggest that visual snow syndrome is not mediated by calcitonin gene related peptide in a relevant way and that the calcitonin gene related peptide receptor is not involved in the network underlying the visual snow syndrome.

Background and Objectives: In general, suddenly occurring neurological deficits, i.e., negative neurological symptoms, are considered symptoms of focal cerebral ischemia, while positive irritative symptoms with gradual onset are viewed as the characteristics of migraine aura. Nevertheless, cortical spreading depolarization, the pathophysiological basis of migraine aura, has also been observed in acute ischemic stroke. The aim of our study was to determine the frequency of migraine aura-like symptoms at ischemic stroke onset and stroke-like symptoms in migraine with aura., Methods: We interviewed 350 consecutive patients with ischemic stroke and 343 with migraine with aura using a structured questionnaire. Stroke diagnosis was confirmed by imaging, and migraine with aura was diagnosed according to the current criteria of the International Headache Society. Patients with wake-up strokes or severe cognitive deficits that precluded a useful interview were excluded from the study., Results: Seventy-eight patients with stroke (22.3%) reported visual symptoms, 145 (41.4%) sensory symptoms, 197 (56.3%) a paresis, and 201 patients (57.4%) more than one symptom, compared to 326 migraine patients with aura (95%) with visual symptoms ( P < 0.001), 175 (51%) with sensory symptoms ( p = 0.011), 50 (14.6%) with paresis ( P < 0.001), and 211 (61.5%) with more than one symptom ( p = 0.27). Among patients with stroke, migraine-like symptoms were frequent: 36 patients (46.2%) with visual disturbance and 78 (53.8%) with sensory symptoms experienced irritative sensations. Paresis-onset in stroke lasted longer than 5 min in 43 patients (21.8%). Spreading of sensory and motor symptoms occurred in 37 (25.5%) and 37 (18.8%) patients, respectively. Stroke-like negative symptoms in migraine with aura occurred in 39 patients (12%) with visual symptoms, in 55 (31.4%) with sensory symptoms, and paresis appeared suddenly in 14 patients (28%). More than one symptom in succession occurred in 117 patients with stroke (58.2%) and in 201 migraine with aura patients (95.3%; P < 0.001)., Conclusion: Many patients with stroke experience migraine-like symptoms at stroke onset, and many migraine with aura patients have stroke-like symptoms. Though overall the symptom frequencies of the two groups are significantly different, clarifying the differential diagnosis in an individual patient requires additional history elements, physical findings, or results of ancillary investigations., Competing Interests: Authors AS and SJ report research support from the Swiss Heart Foundation. Author JK reports grants from the Swiss Academy of Medical Sciences/Bangerter Foundation, Swiss Stroke Society, and Clinical Trials Unit Bern during the conduct of the study. Author MRH has received grants from the Swiss Heart Foundation, the Bangerter Foundation, the Swiss National Science Foundation, the sitem-insel Support Funds, and personal fees for advisory board participation from Amgen. Author UF reports consulting for Medtronic, Stryker, CSL Behring. Advisory boards for Portola/Alexion (money paid to institution). Author MA reports personal fees from AstraZeneca, Bayer, Bristol Myers Squibb, Covidien, Daiichi Sankyo, Medtronic, Novartis, Pfizer, and Amgen. Author HPM grants from Abbott for the PC and PRIMA trials and from Cerenovus for the ARISE studies. Personal and speaker fees from Cerenovus, Bayer, Servier, Medtronic, and Stryker. Author CJS reports consulting, advisory boards, speaker, travel support for/from Novartis, Eli Lilly, TEVA Pharmaceuticals, Allergan, Almirall, Amgen, Lundbeck, MindMed, and Grünenthal. Part-time employee at Zynnon. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Scutelnic, Kreis, Beyeler, Heldner, Meinel, Kaesmacher, Hakim, Arnold, Fischer, Mattle, Schankin and Jung.)

Visual snow syndrome is characterized by a continuous visual disturbance resembling a badly tuned analogue television and additional visual and non-visual symptoms causing significant disability. The natural course of visual snow syndrome has not hitherto been studied. In this prospective longitudinal study, 78 patients with the diagnosis of visual snow syndrome made in 2011 were re-contacted in 2019 to assess symptom evolution using a semi-structured questionnaire. Forty patients (51% of 78) were interviewed after 84 ± 5 months (mean ± SD). In all patients, symptoms had persisted. Visual snow itself was less frequently rated as the most disturbing symptom (72 versus 42%, P = 0.007), whereas a higher proportion of patients suffered primarily from entopic phenomena (2 versus 17%, P = 0.024). New treatment was commenced in 14 (35%) patients, of whom in seven, visual snow syndrome was ameliorated somewhat. Three (7%) experienced new visual migraine aura without headache, and one (2%) had new migraine headache. There were no differences in the levels of anxiety and depression measured by the Patient Health Questionnaire 8 and the Generalized Anxiety Disorder Scale 7. Thirty-eight patients (49%) were lost to follow-up. In visual snow syndrome, symptoms can persist over 8 years without spontaneous resolution, although visual snow itself might become less bothersome., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background and Purpose: Patients with migraine are at increased risk of stroke. The aim was to systematically review the current literature on the association between migraine and atrial fibrillation, which is a relevant risk factor for stroke., Methods: PubMed was searched for 'migraine' AND 'atrial fibrillation' and selected original investigations on the association of migraine and atrial fibrillation for our analysis. Articles without original data, such as guidelines, narrative reviews, editorials and others, were excluded., Results: In all, 109 publications were found. Twenty-two were included and analysed for this review. The population-based Atherosclerosis Risk in Communities study showed a significant association of migraine with visual aura and incident atrial fibrillation (hazard ratio 1.30, 95% confidence interval 1.03-1.62, p = 0.02), but not for migraine without aura, compared to non-headache persons after multivariable adjustment for vascular risk factors. An even larger population-based study in Denmark confirmed this association (odds ratio 1.25, 95% confidence interval 1.16-1.36). Studies investigating patients with ischaemic stroke and migraine are methodologically insufficient and provide contradictory results. Ablation therapy for atrial fibrillation in patients with migraine might reduce migraine attacks, but transient post-ablation new-onset migraine-like headaches in persons without a history of migraine have also been reported., Conclusion: Population-based studies indicate a significant association of migraine with aura and atrial fibrillation. In practical terms, screening for atrial fibrillation in patients who have a long history of migraine might be reasonable, whereas in patients with stroke or other disorders and migraine extensive screening for atrial fibrillation should be performed as in all patients without migraine., (© 2021 European Academy of Neurology.)

Objective: Patients with visual snow syndrome (VSS) suffer from a debilitating continuous ("TV noise-like") visual disturbance. They report problems with vision at night and palinopsia despite normal visual acuity. The underlying pathophysiology of VSS is largely unknown. Currently, it is a clinical diagnosis based on the patient's history, an objective test is not available. Here, we tested the hypothesis that patients with VSS have an increased threshold for detecting visual contrasts at particular temporal frequencies by measuring dynamic contrast detection-thresholds., Methods: Twenty patients with VSS were compared to age-, gender-, migraine- and aura-matched controls in this case-control study. Subjects were shown bars randomly tilted to the left or right, flickering at six different frequencies (15 Hz, 20 Hz, 25 Hz, 30 Hz, 35 Hz, 40 Hz). The contrast threshold (CT) for detection of left or right tilt was measured in a two-alternative adaptive forced-choice procedure (QUEST). The threshold was defined as the Michelson contrast necessary to achieve the correct response in 75% of the cases., Results: The CT increased for higher flicker frequencies (ANOVA: main effect frequency: F (5,180) = 942; p < 0.001), with an additional significant frequency*diagnosis interaction (ANOVA: F (5,180) = 5.00; p < 0.001). This interaction effect was due to an increased CT at a flicker frequency of 15 Hz in the VSS cohort (VSS: MC = 1.17%; controls: MC = 0.77%). At the other frequencies, group comparisons revealed no differences. Furthermore, in the VSS cohort we observed an increase of CT with higher age (r = 0.69; p < 0.001), which was not seen in controls (r = 0.30; p = 0.20)., Conclusions: This study demonstrates a lower visual contrast sensitivity exclusively at 15 Hz in VSS patients and demonstrates frequency-dependent differences in dynamic contrast vision. The peak sensitivities of both parvo- and magnocellular visual pathways are close to a frequency of about 10 Hz. Therefore, this frequency seems to be of crucial importance in everyday life. Thus, it seems plausible that the impairment of contrast sensitivity at 15 Hz might be an important pathophysiological correlate of VSS. Furthermore, the overall age-related decrease in contrast sensitivity only in VSS patients underscores the vulnerability of dynamic contrast detection in VSS patients. Dynamic CT detection seems to be a promising neurophysiological test that may contribute to the diagnosis of VSS., (© 2021. The Author(s).)