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Background: Migraine is a highly prevalent and complex neurovascular disease. However, the currently available therapeutic drugs often fall to adequately meet clinical needs due to limited effectiveness and numerous undesirable side effects. This study aims to identify putative novel targets for migraine treatment through proteome-wide Mendelian randomization (MR)., Methods: We utilized MR to estimate the causal effects of plasma proteins on migraine and its two subtypes, migraine with aura (MA) and without aura (MO). This analysis integrated plasma protein quantitative trait loci (pQTL) data with genome-wide association studies (GWAS) findings for these migraine phenotypes. Moreover, we conducted a phenome-wide MR assessment, enrichment analysis, protein-protein interaction networks construction, and mediation MR analysis to further validate the pharmaceutical potential of the identified protein targets., Results: We identified 35 protein targets for migraine and its subtypes (p < 8.04 × 10 -6 ), with prioritized targets showing minimal side effects. Phenome-wide MR identified novel protein targets-FCAR, UBE2L6, LATS1, PDCD1LG2, and MMP3-that have no major disease side effects and interacted with current acute migraine medication targets. Additionally, MMP3, PDCD1LG2, and HBQ1 interacted with current preventive migraine medication targets. The causal effects of plasma protein on migraine were partly mediated by plasma metabolites (proportion of mediation from 3.8% to 21.0%)., Conclusions: A set of potential protein targets for migraine and its subtypes were identified. These proteins showed rare side effects and were responsible for biological mechanisms involved in migraine pathogenesis, indicating priority for the development of migraine treatments., (© 2024. The Author(s).)

Background/hypothesis: Levcromakalim has previously been shown to induce attacks of migraine with aura in certain individuals. In this study, we tested the migraine-inducing effect of levcromakalim in a cohort of participants with migraine aura without headache., Methods: In a double-blind, randomized, placebo-controlled cross-over study, eight adult participants with migraine with aura received intravenous infusions of levcromakalim and saline. Headache, aura and associated symptoms were evaluated for 24 h following administration of the study drug. The primary endpoint was occurrence of migraine-like attacks with or without aura in the 24-h observation period., Results: Five participants (62.5%) developed migraine of any type following levcromakalim compared with three participants (37.5%) following placebo. No participants developed aura following levcromakalim., Conclusion/interpretation: Our findings suggest that the aura-inducing effect of levcromakalim is likely not based on direct induction of cortical spreading depression but may involve activation of the trigeminovascular system. This hypothesis should be further explored in future studies., Clinicaltrials.gov Identifier: NCT04905654., 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: A.V.T., M.M.A-K., and S.R.O. declare no competing interests. A.H. reports receiving personal fees from AbbVie, Eli Lilly, Lundbeck, Novartis, Teva and Pfizer. A.H. also serves as an associate editor of Headache. M.A reports receiving personal fees from AbbVie, Amgen, Astra Zeneca, Eli Lilly, GlaxoSmithKline, Lundbeck, Novartis, Pfizer, and Teva Pharmaceuticals outside of the submitted work. MA also serves as an associate editor of The Journal of Headache and Pain, and an associate editor of Brain.

Familial hemiplegic migraine (FHM), an autosomal dominant subtype of hemiplegic migraine, is a channelopathy presenting with severe headache, visual field defect, paresthesia, unilateral motor deficit, encephalopathy, seizures and aphasia. This cross-sectional study was conducted over 10 months in children aged 1-18 years suspected of hemiplegic migraine at a tertiary care pediatric hospital. Fourteen children were screened and five children with genetically confirmed FHM were included. The symptoms in the study population were paroxysmal hemiparesis (5/5), headache (5/5) and focal seizures (1/5). The hemiplegia episodes lasted from 4 h to 7 days. The mean age at the onset of neurological symptoms was 6.8 ± 0.7 years and the mean age at diagnosis was 12.8 ± 1.7 years, with a mean delay of 6.1 ± 1.9 years for the diagnosis. Neuroimaging during acute episodes revealed accentuated gray, white differentiation in the contralateral cerebral hemisphere with mild effacement of sulcal spaces in T2/fluid-attenuated inversion recovery (FLAIR) images. Genetic testing revealed ATP1A2 mutations (FHM2) in 4/5 and SCN1A (FHM3) in 1/5 patients. All of them (5/5) were initiated on oral topiramate and had favorable treatment responses with a mean follow-up duration of 7 ± 1.4 months. Diagnosis of FHM is mainly clinical and can be confirmed by genetic analysis. Perfusion and diffusion-weighted MRI should be considered during acute headache episodes, as it is mostly normal in symptom-free periods. Routine MRI sequences like T1 weighted, T2 weighted, FLAIR and contrast remain normal even during acute attacks., (© The Author(s) [2024]. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Limited clinical evidence is available regarding the potential effectiveness of anti-CGRP monoclonal antibodies for the preventive treatment of migraine with aura., Aim of the Study: This observational study involved a series of migraine patients affected by either migraine with or without aura, who were investigated for any changes in their frequencies and their migraine aura attack characteristics observed during treatment with anti-CGRP Mabs over a 1-year period., Patients and Methods: Twelve migraine patients were included, seven of whom were treated with erenumab, 2 with fremanezumab, and 3 with galcanezumab. Clinical data were collected at baseline, which were defined as 3 months prior to the initiation of treatment, and thereafter at each trimester, over the 1-year treatment period. The parameters included the number of headache and migraine days/month, the frequency of aura episodes, the number of days with acute drug intakes/month, and the scores from the migraine disability status scale (MIDAS), and the Headache Impact Test 6 (HIT-6)., Results: Anti-CGRP Mbs antibodies induced significant decreases in mean headache and migraine without aura days per month, the number of days with medication intake, as well as MIDAS and HIT-6 scores (p < 0.0001). In contrast, the anti-CGRP Mab treatment did not appear to impact the frequency of migraine with aura attacks but seemed to reduce both the intensity and the duration of headache phases of migraine aura. Furthermore, some migraine patients referred to having aura attacks without headache over the course of the treatment period., Conclusions: Based on the above findings, we hypothesize that anti-CGRP Mabs did not influence neuronal and vascular events related to cortical spreading depression (CSD) which is considered the pathophysiological substrate of aura. Conversely, these antibodies are able to counteract, via their peripheral mechanisms of action, the sensitization of the trigemino-vascular pathway which is triggered by CSD. This aforementioned might explain why in our patients, migraine aura attacks remained unchanged in their frequencies, but the headache phases were either reduced or absent., (© 2024 The Authors. CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Targeting CGRP-pathways has substantially expanded our options for treating individuals with migraine. Although the efficacy of these drugs on migraine aura is yet to be fully revealed, it seems from existing studies that CGRP antagonism reduces the number of migraine auras. The present perspective summarizes the evidence linking CGRP to the migraine aura and proposes a model by which targeting the CGRP-pathways and, thus, inhibition the interaction between C- and Aδ-trigeminal fibers might reverse a possible high cortical glutamate level leading to a reduced number of migraine auras., 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.

Familial hemiplegic migraine type-1 (FHM-1) is a form of migraine with aura caused by mutations in the P/Q-type (Cav2.1) voltage-gated calcium channel. Pregabalin, used clinically in the treatment of chronic pain and epilepsy, inhibits P/Q-type calcium channel activity and recent studies suggest that it may have potential for the treatment of migraine. Spreading Depolarization (SD) is a neurophysiological phenomenon that can occur during migraine with aura by propagating a wave of silenced neuronal function through cortex and sometimes subcortical brain structures. Here, utilizing an optogenetic stimulation technique optimized to allow for non-invasive initiation of cortical SD, we demonstrate that chronic pregabalin administration [12 mg/kg/day (s.c.)] in vivo increased the threshold for cortical spreading depolarization in transgenic mice harboring the clinically-relevant Ca v 2.1 S218L mutation (S218L). In addition, chronic pregabalin treatment limited subcortical propagation of recurrent spreading depolarization events to the striatum and hippocampus in both wild-type and S218L mice. To examine contributing underlying mechanisms of action of chronic pregabalin, we performed whole-cell patch-clamp electrophysiology in CA1 neurons in ex vivo brain slices from mice treated with chronic pregabalin vs vehicle. In WT mice, chronic pregabalin produced a decrease in spontaneous excitatory postsynaptic current (sEPSC) amplitude with no effect on frequency. In contrast, in S218L mice chronic pregabalin produced an increase in sEPSC amplitude and decreased frequency. These electrophysiological findings suggest that in FHM-1 mice chronic pregabalin acts through both pre- and post-synaptic mechanisms in CA1 hippocampal neurons to elicit FHM-1 genotype-specific inhibitory action. The results highlight the potential of chronic pregabalin to limit recurrent SD to subcortical brain structures during pathophysiological events in both the genetically-normal and FHM-1 brain. The work further provides insights into FHM-1 pathophysiology and the potential for chronic pregabalin treatment to prevent SD in migraineurs., (© 2023. The Author(s).)

Migraine or migraine-like symptoms can contribute to a delayed stroke diagnosis. However, migraine with aura is a common stroke mimic and often the basis for acute thrombolytic therapy. It is probably also the reason why many patients are misdiagnosed with a transient ischemic attack. In this clinical review, we explain the factors that could differentiate a transient ischemic attack from a migraine with aura.

Introduction: Multiple medications have been related to triggering headache attacks or worsening headache frequency or severity in patients with migraine disease. However, the impact of direct oral anticoagulants on headache frequency and severity in patients with migraine disease is unclear. Current literature is scarce and controversial., Case Report: A 45-year-old male with a history of migraine with aura for the last 20 years underwent percutaneous transcatheter closure of an atrial septal defect due to right ventricular enlargement and systolic dysfunction. The intervention was complicated by postprocedural atrial fibrillation, for which he was started on apixaban. Shortly after starting the apixaban, the patient experienced an increase in the frequency and severity of his migraine with aura episodes that were persistent until he discontinued this medication 7 months later. Following the discontinuation of apixaban, the patient's frequency and severity of migraine episodes returned to baseline almost immediately., Conclusion: Novel oral anticoagulants, including apixaban, may be associated with an increase in the frequency and severity of migraine attacks in patients with migraine disease. Larger observational studies are required to investigate further the impact of direct oral anticoagulants on migraine disease., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Migraine is an extremely disabling, common neurological disorder characterized by a complex neurobiology, involving a series of central and peripheral nervous system areas and networks. A growing increase in the understanding of migraine pathophysiology in recent years has facilitated translation of that knowledge into novel treatments, which are currently becoming available to patients in many parts of the world and are substantially changing the clinical approach to the disease. In the first part of this review, we will provide an up to date overview of migraine pathophysiology by analyzing the anatomy and function of the main regions involved in the disease, focusing on how these give rise to the plethora of symptoms characterizing the attacks and overall disease. The second part of the paper will discuss the novel therapeutic agents that have emerged for the treatment of migraine, including molecules targeting calcitonin gene-related peptide (gepants and monoclonal antibodies), serotonin 5-HT 1F receptor agonists (ditans) and non-invasive neuromodulation, as well as providing a brief overview of new evidence for classic migraine treatments., (© 2023. The Author(s).)

Hemiplegic migraine (HM) is a subtype of migraine with aura that includes motor weakness; such headaches can be excruciating. The presence of not only headache but also aura symptoms of HM increase the burden on patients, and the treatment of HM is sometimes challenging. Monoclonal antibodies (mAbs) targeting the calcitonin gene-related peptide (CGRP) pathway are novel migraine preventive treatments that have shown promising efficacy in patients with migraine; however, there have been no reports regarding their efficacy in HM to date. Six patients with HM were treated with galcanezumab in a tertiary-care headache center. After 3 months of treatment, the number of monthly days with headache of at least moderate severity was reduced in three patients. The number of days each month with weakness was also reduced in four patients. Furthermore, the Patient's Global Impression of Change and change in Migraine Disability Assessment total score, were improved in five of the six patients after the treatment; however, the change from baseline in days with bothersome symptoms did not show any specific trends in our patients. Notably, no adverse events were reported during the treatments. The mechanism underlying the improvement in aura symptoms in our patients is not clear; however, we speculate that a small amount of CGRP mAbs have a direct mode of action in the central nervous system; alternatively, blocking the CGRP pathway in the periphery may secondarily inhibit cortical spreading depression. While prudence must be practiced, galcanezumab was still generally effective in HM and well tolerated. Further prospective clinical studies will more clearly elucidate the effects of CGRP mAbs in patients with HM., (© 2023 American Headache Society.)

Introduction: This MONONOFU trial subgroup analysis evaluates the efficacy of lasmiditan across patient and migraine characteristics in Japanese patients with migraine., Methods: MONONOFU trial was a multicenter, randomized, double-blind, placebo-controlled study. The patients were randomly assigned in a 3:7:6:7 ratio to receive lasmiditan 50 mg, 100 mg, 200 mg, or placebo for a single migraine attack within 4 h of pain onset. Efficacy of lasmiditan vs placebo was evaluated at 2 h post dose for proportion of patients with headache pain freedom. Efficacy was assessed across patient characteristics (age, sex, body weight, cardiovascular risk factors (CVRF), and comorbidity of tension-type headache), migraine disease characteristics (history of migraine with aura, migraine prevention therapy, triptan response, and triptan use or nonuse), and migraine attack characteristics (headache severity, aggressive headache, attack during perimenstrual period, time to dosing, time of dosing, experienced treatment-emergent adverse event (TEAE) of dizziness, and experienced TEAE of somnolence). Logistic regression was used; all subgroup analyses were not analyzed with multiplicity-adjusted statistical tests., Results: Treatment-by-subgroup interactions (by each arm) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups and lasmiditan doses, except for CVRF (100 mg and 200 mg), migraine with aura (50 mg), triptan response (50 mg), and time to dosing (200 mg). Treatment-by-subgroup interactions (by overall) were not significant (p ≥ 0.05) for pain freedom at 2 h post dose across all patient subgroups, except for CVRFs. Higher proportions of patients were pain free at 2 h post dose when treated with lasmiditan (50 mg, 100 mg, and 200 mg) versus placebo, irrespective of most patient characteristics, migraine disease characteristics, and migraine attack characteristics., Conclusion: Although few interactions were observed, lasmiditan could be a promising acute treatment option in a wide range of Japanese patients with migraine, as efficacy is not generally influenced by patient and migraine characteristics., (© 2022. The Author(s).)

Background: The prophylactic treatment of migraine includes anticonvulsant drugs such as valproic acid and topiramate. However, these substances are often poorly tolerated by migraine patients. So far levetiracetam has hardly been studied as an episodic migraine prophylactic agent in adults., Objective: To perform a prospective pilot study for the evaluation of the efficacy and tolerability of levetiracetam in the prophylactic treatment of episodic migraine., Methods: Fifty patients with episodic migraine were enrolled in this prospective, open label study. After a baseline period of four weeks, patients received 1,000 mg (starting dose 500 mg) bid levetiracetam for 12 weeks. Migraine frequency and accompanying symptoms were recorded in a headache diary. The primary endpoint was the comparison of attack frequency during the baseline with attack frequency during the last four weeks of treatment (treatment period 3)., Results: In the Intent-To-Treat analysis, 46% of the patients had a migraine reduction of more than 50% in the third period as compared to the baseline period. The mean number of migraine attacks decreased from 5.2 +/- 2.1 (baseline) to 3.4 +/- 2.7 (period 3). The most frequently reported side effects were somnolence, nausea, and weight gain; all were mild and transient. In a post-hoc comparison, responders to levetiracetam had significantly less migraine attacks at baseline and had significantly more often migraine with aura., Conclusion: The data suggest that levetiracetam has some potential in the prophylactic treatment of episodic migraine which seems, however, to be not superior to that of other anticonvulsant drugs. Levetiracetam was well tolerated and showed better efficacy in patients with migraine with aura and in less affected migraine patients. A larger placebo-controlled, double-blind study in adults seems justified on the basis of these data.

Introduction: It has not been established if migraine headache and migraine aura share common pathophysiological mechanisms. Sildenafil, a phosphodiesterase-5 inhibitor, causes cGMP accumulation and provokes migraine-like headache in patients with migraine without aura. We investigated if sildenafil induced aura and migraine-like headache in patients with migraine with aura., Methods: In a randomized, double-blinded, placebo-controlled crossover study, 16 patients with migraine with aura (of whom 11 patients exclusively had attacks of migraine with aura) received 100 mg sildenafil or placebo on two separate days. The development, duration, and characteristics of aura and headache were recorded using a questionnaire. The primary outcome was the incidence of migraine aura., Results: Aura symptoms were induced in three patients (19%) after sildenafil and none after placebo (P < 0.001). After administration of sildenafil, 12 patients (75%) developed headache compared with two patients (12.5%) after placebo (Fisher's exact test, P < 0.001). The headache in nine patients (56%) after sildenafil and one patient (6%) after placebo fulfilled the criteria for migraine-like attacks (Fisher's exact test, P = 0.002). All patients, who fulfilled the criteria for migraine-like attacks, reported that the attack mimicked the headache phase during their usual migraine attacks., Discussion: Sildenafil have a moderate migraine headache-inducing and a modest aura-inducing effect in patients with migraine with aura, even in those who exclusively experienced attacks of migraine with aura in their spontaneous attacks. These findings suggest that accumulation of cGMP by PDE5-inhibition do not play any significant role in the initiation of migraine aura and refute the hypothesis of sildenafil being a tool for pharmacological provocation of this phenomenon. These findings further support dissociation between the aura and the headache phase. Trial registration: ClinicalTrials.gov - NCT02795351.

Importance: Migraine with aura may respond differently to therapies than migraine without aura. Individuals with migraine with aura have an elevated vascular risk, necessitating a safety assessment of migraine preventive treatments in this patient subgroup., Objective: To assess the efficacy and safety profiles of erenumab in patients with migraine with aura., Design, Setting, and Participants: This post hoc secondary analysis evaluated 4 double-blind, placebo-controlled randomized clinical trials that were conducted in treatment centers in North America, Europe, Russia, and Turkey between August 6, 2013, and November 12, 2019. Participants were adults aged 18 to 65 years with episodic migraine or chronic migraine and were randomized to receive either erenumab or placebo., Interventions: One or more dose of erenumab (70 mg or 140 mg once per month) or placebo was administered by subcutaneous injection in the double-blind treatment phase and open-label or dose-blinded active treatment, and erenumab, 70 mg or 140 mg, was administered once per month by subcutaneous injection during extension phases., Main Outcomes and Measures: Efficacy assessments included change from baseline monthly migraine days (MMDs) and monthly acute migraine-specific medication (AMSM) days. Safety end points included patient incidences of adverse events. Subgroups of patients were categorized according to their history of aura., Results: Of the 2682 patients who were randomized in the 4 trials, 1400 (52.2%) received 1 or more dose of erenumab, 70 mg or 140 mg, and 1043 (38.9%) received placebo. Patients had a mean (SD) age of 41.7 (11.2) years and were predominantly women (n = 2055 [84.1%]). Reductions from baseline MMDs and AMSM days were greater in the erenumab than placebo groups in patients with and without a history of aura during the double-blind treatment phase, and these reductions were maintained throughout the extension phases. In patients with episodic migraine and a history of aura, least-squares mean differences in change from baseline MMDs at week 12 were -1.1 (95% CI, -1.7 to -0.6) in those who received erenumab, 70 mg, and -0.9 (95% CI, -1.6 to -0.2) in those who received erenumab, 140 mg, compared with placebo. In patients with chronic migraine with a history of aura, the least-squares mean differences from placebo treatment were -2.1 (95% CI, -3.8 to -0.5) in those who received erenumab, 70 mg, and -3.1 (95% CI, -4.8 to -1.4) in those who received erenumab, 140 mg. Overall safety profiles were similar across treatment groups regardless of aura history and were comparable to that of placebo over 12 weeks, with no increased emergence of adverse events over time., Conclusions and Relevance: Results of this secondary analysis of 4 randomized clinical trials showed reduced migraine frequency and AMSM days with erenumab treatment in patients with migraine with and without a history of aura. The findings support the efficacy and safety of using erenumab in this patient population., Trial Registration: ClinicalTrials.gov Identifiers: NCT01952574, NCT02456740, NCT02483585, NTCT02066415, and NCT02174861.

Persistent migraine aura without infarction is a rare but debilitating condition. Treatment options are mostly anecdotal and limited due to inefficacy and side effects. We present a 16-year-old female patient with triple X syndrome, having persistent aura symptoms for over 2 years, consisting of continuous visual and sensory sensations. Previous treatments with seven different migraine preventatives were not successful. The patient successfully responded to zonisamide against refractory prolonged aura and remained symptom-free under the ongoing treatment without any relevant side effects. Zonisamide may be considered a new and safe treatment option for patients with persistent migraine aura., Competing Interests: Competing interests: KK received travel grants from Novartis and Eli Lilly. FF received travel grants from Novartis, Teva and Eli Lilly, and is a recipient of a grant from the Austrian Academy of Sciences (ÖAW). GB received unrestricted grants, honoraria, personal fees and travel grants from Allergan, Amgen, Menarini, Pfizer, Linde AG, AstraZeneca, St Jude Medical, Reckitt Benckiser, Novartis, Teva, Fresenius, Janssen-Cilag, Eli Lilly, Österreichische Gesellschaft für Neurologie, European Headache Federation, Österreichische Kopfschmerzgesellschaft, ÖAW and European FP7 framework programme., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Migraine auras typically last for 5-60 min. An aura that persists for more than a week without evidence of infarction on neuroimaging is called persistent aura without infarction. Persistent migraine aura without infarction is usually described with visual auras. Herein, we are reporting a 24-year-old man who had an attack of a headache with diplopia, vertigo and tinnitus. Tinnitus and vertigo disappeared within 30 min. The headache also disappeared within 6 hours. However, diplopia and ophthalmoplegia persisted for 4 weeks. Secondary causes of bilateral ophthalmoplegia were ruled out by a proper history, clinical examinations and appropriate investigations. A trial with lamotrigine and sodium valproate led to the complete improvement in ophthalmoplegia within 2 weeks. We considered ophthalmoplegia in this patient as 'persistent brainstem aura without infarction'. We suggest that a possibility of persistent migraine aura without infarction should be considered in all migraineurs who have unexplained and persistent neurological symptoms., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To evaluate the pharmacokinetics, safety, and tolerability of a single 50-mg oral dose of diclofenac potassium for oral solution (OS) in a pediatric cohort with a diagnosis of episodic migraine; the 3-month safety trial following an outpatient dosing period was also evaluated., Background: Children and adolescents often experience migraine pain that is poorly controlled, which may affect their emotional and psychological well-being. Diclofenac potassium for OS is approved for the treatment of migraine with aura (MWA) or migraine without aura (MWoA) in adults 18 years of age or older. It is formulated in a soluble buffered powder that provides more rapid absorption than the tablet formulations of diclofenac potassium. In a randomized, double-blind, crossover trial, more adult patients were pain-free at 2 hours post-dose following treatment with diclofenac potassium for OS than those who received the diclofenac tablet formulation or placebo., Methods: This was a Phase 4 open-label study that took place at 2 US sites. Participants 12-17 years of age with a diagnosis of episodic MWA or MWoA for ≥3 months and ≤14 headaches per month were enrolled in the study. Participants received one 50-mg dose of diclofenac potassium for OS under fasted conditions on day 1. Blood samples were collected for PK analysis within 15 minutes pre-dose and at 5, 10, 15, 20, 30, 40, and 60 minutes post-dose, and at 2, 4, and 6 hours post-dose. Safety evaluations were performed after the initial dose and at the end of study on day 90; adverse events were monitored throughout the study. After completing the PK assessments, participants were given a 3-month supply (27 packets) of diclofenac potassium for OS (50-mg doses) for their migraine attacks. Participants were advised to take diclofenac potassium for OS at the onset of a migraine. They were told to take no more than 2 doses daily and not to use it more than 3 days/week., Results: Twenty-five participants completed the study; 84% were females and 96% were white or Caucasian, with a mean age of 15.5 years and a mean weight of 63.1 kg. Diclofenac was rapidly absorbed with a median time to maximum concentration of 15 minutes and a mean peak plasma concentration of 1412 (±846.2) ng/mL. Diclofenac had a half-life of 66.8 (±9.2) minutes. The mean area under the concentration-time curve from zero to the last measurable time point was 82,920.0 (±25,327.6) minutes × ng/mL, and the mean area under the concentration-time curve from time zero to infinity was 84,388.8 (±25,993.6) minutes × ng/mL. Participants took the study drug an average of 10 times over 79 days, with an overall total drug exposure of 506 mg. No deaths or discontinuations due to an AE were reported during the study. The most frequently reported treatment emergent adverse events were arthralgia and motion sickness, each of which occurred in 2 (8%) of the participants., Conclusions: Diclofenac potassium for OS exhibited a favorable pharmacokinetic and safety profile in 12- to 17-year-old patients with a diagnosis of episodic MWA or MWoA., (© 2020 American Headache Society.)

Cortical spreading depolarisation (CSD), the neural mechanism underlying migraine aura, may cause headache by sensitising the trigeminal system. Photophobia, the most bothersome accompanying symptom during migraine attacks, is more prevalent in migraine with aura than in migraine without aura. Whether CSD plays a role in developing photophobia remains unknown. Moreover, migraine-induced physical hypoactivity contributes to loss of productivity. We aimed to investigate the development of trigeminal sensitisation, photophobia and locomotive abnormality after KCl-induced CSD using 86 male C57BL/6 mice. Sham-operated mice were used as controls. We confirmed the presence of trigeminal sensitisation and photophobia at 24 h after CSD. CSD-subjected mice also exhibited significantly reduced locomotive activity in both light and dark zones. Hence, the CSD-induced hypomobility was likely to be independent of photophobia. The 5-HT 1B/1D agonist, sumatriptan, corrected all these CSD-induced abnormalities. Moreover, dose dependency was demonstrated in the ameliorating effect of the calcitonin gene-related peptide (CGRP) receptor antagonist, olcegepant, on these abnormalities. Sumatriptan and olcegepant improved mouse locomotion with therapeutic lags ranging from 20 to 30 min. Collectively, CSD caused trigeminal sensitisation, photophobia and hypomobility that persisted for at least 24 h by a mechanism involving the 5-HT 1B/1D and CGRP activity.

Disruption of blood-brain barrier integrity and dramatic failure of brain ion homeostasis including fluctuations of pH occurs during cortical spreading depression (CSD) events associated with several neurological disorders, including migraine with aura, traumatic brain injury and stroke. NHE1 is the primary regulator of pH in the central nervous system. The goal of the current study was to investigate the role of sodium-hydrogen exchanger type 1 (NHE1) in blood brain barrier (BBB) integrity during CSD events and the contributions of this antiporter on xenobiotic uptake. Using immortalized cell lines, pharmacologic inhibition and genetic knockdown of NHE1 mitigated the paracellular uptake of radiolabeled sucrose implicating functional NHE1 in BBB maintenance. In contrast, loss of functional NHE1 in endothelial cells facilitated uptake of the anti-migraine therapeutic, sumatriptan. In female rats, cortical KCl but not aCSF selectively reduced total expression of NHE1 in cortex and PAG but increased expression in trigeminal ganglia; no changes were seen in trigeminal nucleus caudalis. Thus, in vitro observations may have a significance in vivo to increase brain sumatriptan levels. Pharmacological inhibition of NHE1 prior to cortical manipulations enhanced the efficacy of sumatriptan at early time-points but induced facial sensitivity alone. Overall, our results suggest that dysregulation of NHE1 contributes to breaches in BBB integrity, drug penetrance, and the behavioral sensitivity to the antimigraine agent, sumatriptan., Competing Interests: The authors have declared that no competing interests exist.

Background: Visual snow syndrome is a debilitating disorder characterized by tiny flickering dots (like TV static) in the entire visual field and a set of accompanying visual (palinopsia, enhanced entoptic phenomena, photophobia, nyctalopia), nonvisual (e.g. tinnitus) and nonperceptional (e.g. concentration problems, irritability) symptoms. Its pathophysiology is enigmatic and therapy is often frustrating., Objectives: To summarize our current understanding of pathophysiology and treatment of visual snow syndrome., Methods: A systematic search of PubMed database was performed using the key word "visual snow" and predefined in- and exclusion criteria. The results were stratified into "treatment" and "pathophysiology." Additionally, we conducted a search with the key words "persistent migraine aura" and "persistent visual aura" and screened for mis-diagnosed patients actually fulfilling the criteria for visual snow syndrome. The reference lists of most publications and any other relevant articles known to the authors were also reviewed and added if applicable., Results: From the 50 original papers found by searching for "visual snow," 21 were included according to the inclusion and exclusion criteria. Additional four publications came searching for "persistent migraine aura" or "persistent visual aura." Further publications derived from literature references resulting in a total of 20 articles for pathophysiology and 15 for treatment with some overlaps. Regarding pathophysiology, hyperexcitability of the visual cortex and a processing problem of higher order visual function are assumed, but the location is still in discussion. In particular, it is unclear if the primary visual cortex, the visual association cortex or the thalamocortical pathway is involved. Regarding treatment, data is available on a total of 153 VSS patients with medication mentioned for 54 resulting in a total of 136 trials. From the 44 different medications tried, only eight were effective at least once. The best data is available for lamotrigine being effective in 8/36 (22.2%, including one total response and no worsening), followed by topiramate being effective in 2/13 (15.4%, no total response and one worsening). The only other medication resulting in worsening of VSS was amitriptyline according to our literature review. The others reported to be effective at least once were valproate, propranolol, verapamil, baclofen, naproxen and sertraline. The nonpharmacological approach using color filters of the yellow-blue color spectrum might also be helpful in some patients., Conclusions: Visual snow syndrome is still far from being fully understood. In respect of pathophysiology, a disorder of visual processing is likely. The best pharmacological evidence exists for lamotrigine, which can be discussed off-label. As nonpharmacological option, patients might benefit from tinted glasses for everyday use., Competing Interests: Competing interests O Eren has received honoraria for consulting within the past 3 years from Novartis Pharma. CJ Schankin has received travel grants and honoraria for consulting, advisory boards and presentations within the past 3 years from Novartis, Eli Lilly, TEVA Pharmaceuticals, Allergan, Almirall, Amgen, MindMed and Grünenthal., (© 2020 Elsevier B.V. All rights reserved.)

Introduction: The typical aura without headache is a type of migraine with aura regularly assessed by ophthalmology. It is defined as at least two recurrent attacks, lasting from 5 to 60 minutes, of reversible, visual, sensorial and / or language unilateral neurological symptoms., Methods: We present a case report of a male with typical aura without headache., Results: Male with a history of migraine without aura in adolescence and without vascular risk factors. Referred from ophthalmology by biweekly episodes characterized by central teicopsia that progressively covers the entire visual field in 20 minutes, without being influenced by opening or closing eyes, which disappears after 40 minutes from the beginning. The episodes are not stereotyped, they are not followed by headache, nor do they associate other neurological symptoms. Neurological examination and complementary tests were normal. It is concluded in favor of typical aura without headache and after six months of starting treatment with Lamotrigine there were no recurrences., Final Conclusion: The diagnosis of typical aura without headache begins with an adequate anamnesis. Due to the nature of its manifestations it is necessary to differentiate it from other etiologies such as transient ischemic attacks and focal seizures due to the diagnostic, therapeutic and prognostic implications. It may appear, as in this case, in patients with migraine without aura. Lamotrigine is an excellent therapeutic option in the typical aura without headache., (Universidad Nacional de Córdoba)

The most common type of migraine aura is multifaceted visual aura, such as scintillating scotoma or geometrical patterns, visual hallucinations in which a physical body is extremely rare. We report a paediatric case of migraine in which visual hallucinations appeared as auras in the form of a human body. The patient was an 11-year-old girl suffering from migraine with curious visual aura. The auras were atypical visual hallucinations that were sometimes accompanied by auditory hallucinations. Approximately 5-20 min before the headache, the patient would see a middle-aged man wearing sunglasses in her field of vision. Acetaminophen (10 mg/kg) and Japanese herbal medicine administered when necessary effectively treated the headaches. Finally, the patient was no longer complaining of her hallucination auras. Although the pathophysiology of migraines accompanied by auras is unclear, it appears that cerebral blood flow and cortical spreading depression are involved in auras., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Recent insights into the clinical presentation and pathophysiology of migraine aura have paved the way for new treatments for this common but frequently debilitating condition. Marked efflux of cellular potassium and glutamate contributes to the cortical spreading depression that forms the electrophysiological basis of migraine aura phenomena. Secondary vascular perturbations also contribute to the various symptoms of a migraine attack. Calcitonin gene-related peptide (CGRP) plays a key role in many of these steps, and a growing class of CGRP-antagonists have emerged as a novel, efficacious preventative therapy. It is still not fully understood why a preponderance of migraine aura symptoms is visual, and this issue is an active area of research. In addition, the pathophysiological changes responsible for visual snow syndrome are under investigation. Before diagnosing a patient with migraine aura, it is important to consider the differential diagnosis of transient visual phenomena, with attention to clinical features that may suggest conditions such as retinal disorders, transient ischemic attack, or occipital epilepsy., Competing Interests: None., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

None of the clinical trials on migraine conducted thus far have focused on the possibility to modulate the phenomenon of aura. Furthermore, whether proper management of aura results in a better control of the headache phase has been poorly investigated. In the setting of a single-center, pilot, clinical trial, we aimed at comparing the effects of Aurastop (a combination of tanacetum parthenium (150 mg extracted at 0.8% = 1.2 mg di of active parthenolide), griffonia simplicifoila (20 mg of 5-hydroxy tryptophan), and magnesium (185 mg of magnesium pidolatum)) with those of magnesium alone (2.25 grams/tablet, corresponding to 184 mg of Mg++) in the treatment of acute attacks of migraine with aura. Between June 2017 and June 2018, 50 consecutive patients (27/23 male/female; mean age, 31 [18-57] years) with at least 3 episodes of aura per year were included ( t 0 ). Participants were instructed to keep track of the following 4 episodes of migraine with aura ( t 1 ) and invited to assume (1) a tablet of Aurastop at the beginning of the following 2 episodes of aura and (2) a magnesium tablet alone at the occurrence of the third and fourth aura attacks. Forty-eight patients (96.0%) had >50% reduction in aura duration when treated with Aurastop vs. 7 patients (14.0%) when treated with magnesium alone ( p < 0.001); 48 patients (96.0%) had >50% reduction of aura-related disability when receiving Aurastop vs. 5 patients (10.0%) when treated with magnesium alone ( p < 0.001); however, patients receiving Aurastop did not need to take pain killers in 35% of aura attacks vs. 3% when assuming magnesium ( p < 0.001). These results support the hypothesis that Aurastop might be effective in interfering with the phenomenon of aura and provide evidence that the clinical benefit attributable to this combination of molecules might be greater than that obtained with single compounds of proven effect on the biology of migraine., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this paper., (Copyright © 2019 Giorgio Dalla Volta et al.)

Patent Foramen Ovale and impaired cerebral hemodynamics were proposed among the pathophysiological mechanisms explaining the increased risk for stroke in patients with Migraine with Aura (MA). Our study aimed at comparing the vasomotor reactivity (VMR) of the anterior and the posterior cerebral circulation in patients with Migraine with Aura, in patients with acute vascular ischemic accidents, and in controls. We hypothesized that VMR in MA patients is preserved in the anterior circulation and reduced in the posterior circulation. We prospectively assessed with Transcranial Doppler the vasomotor reactivity to breath holding of the Middle and Posterior Cerebral Arteries (MCA, PCA) in MA patients, in acute vascular patients and healthy controls. We also evaluated the possible effect of clinical characteristics of MA (attack frequency, aura length or type, disease history), vascular factors and the presence of right-to-left shunt on VMR. Diverging from our hypothesis, MA patients displayed a higher breath-holding index (BHI) than controls in the MCA (1.84±0.47%/s vs 1.53±0.47%/s, p = .001) as well as in the PCA (1.87±0.65%/s vs 1.47±0.44%/s, p < .001). In MA patients, MCA BHI was higher in those with large right-to-left shunts (2.09±0.42 vs 1.79±0.47, p = .046) and lower in those taking estrogens (1.30±0.30%/s vs 1.9±0.45%/s, p = .009). We did not observe an effect of MA characteristics on BHI. The increased BHI in MA patients with large right-to-left shunts could be explained by the vasoactive effect in the cerebral circulation of substances bypassing the deactivating pulmonary filters or by a constitutional trait of the vascular system associating persistent right-to-left shunts and hyper-reactive hemodynamics. Our results discourage the hypothesis that altered hemodynamics contribute to increasing the stroke risk in all MA patients. However, estrogens can lower VMR, curtailing the hemodynamic resources of MA patients., Competing Interests: The authors have declared that no competing interests exist.

Background: In this work, we describe an association of brainstem headache with aura (BHA) and Alice in Wonderland syndrome (AIWS) in a 17-year-old male, suffering from crises of vertigo, weakness, dysarthria, and diplopia, in half-hour duration, followed by diffuse or occipital headache, lasting several hours., Methods: The frequency of the attacks was monthly, and once there was short loss of consciousness. The last episodes were accompanied by symptoms such as deformation of figures and objects, small or large in shape., Results: Diagnostic examinations were performed, mainly neuroimaging tests such as brain MRI and brain angio-MRI, all resulting normal; and treatment with flunarizine was followed by improvement of both BHA and AIWS symptoms., Conclusions: There would be a correlation between BHA and AIWS, presumably represented by dysfunction of temporo-parieto-occipital carrefour.

Cortical spreading depression (CSD) is a wave of neuronal depolarization thought to underlie migraine aura. Calcitonin gene-related peptide (CGRP) is a potent vasodilator involved in migraine pathophysiology. Evidence for functional connectivity between CSD and CGRP has triggered scientific interest in the possibility that CGRP antagonism may disrupt vascular responses to CSD and the ensuing plasma protein extravasation (PPE). Using imaging tools that allow us to generate continuous, live, high-resolution views of spatial and temporal changes that affect arteries and veins in the dura and pia, we determined the extent to which CGRP contributes to the induction of arterial dilatation or PPE by CSD in female rats, and how these events are affected by the anti-CGRP monoclonal antibody (anti-CGRP-mAb) fremanezumab. We found that the CSD-induced brief dilatation and prolonged constriction of pial arteries, prolonged dilatation of dural arteries and PPE are all unaffected by fremanezumab, whereas the brief constriction and prolonged dilatation of pial veins are affected. In comparison, although CGRP infusion gave rise to the expected dilatation of dural arteries, which was effectively blocked by fremanezumab, it did not induce dilatation in pial arteries, pial veins, or dural veins. It also failed to induce PPE. Regardless of whether the nociceptors become active before or after the induction of arterial dilatation or PPE by CSD, the inability of fremanezumab to prevent them suggests that these events are not mediated by CGRP, a conclusion with important implications for our understanding of the mechanism of action of anti-CGRP-mAbs in migraine prevention. SIGNIFICANCE STATEMENT The current study identifies fundamental differences between two commonly used models of migraine, CSD induction and systemic CGRP infusion. It raises the possibility that conclusions drawn from one model may not be true or relevant to the other. It sharpens the need to accept the view that there is more than one truth to migraine pathophysiology and that it is unlikely that one theory will explain all types of migraine headache or the mechanisms of action of drugs that prevent it. Regarding the latter, it is concluded that not all vascular responses in the meninges are born alike and, consequently, that drugs that prevent vascular dilatation through different molecular pathways may have different therapeutic outcomes in different types of migraine., (Copyright © 2019 the authors.)

Objective: In contrast with combined hormonal contraception, progestin-only contraception is not associated with an increase in venous thromboembolism or stroke. Women with migraine are at increased risk of ischaemic stroke. Several studies have reported a reduction in migraine frequency and intensity with desogestrel 75 µg, a progestin-only pill. At present the quality of data is limited by retrospective study designs, lack of control groups and small sample sizes. We present the first prospective nonrandomised controlled trial. Methods: A total of 150 women with migraine visiting our clinic for contraceptive counselling were screened. The intervention group comprised women who opted for contraception with desogestrel ( n  = 98); the control group comprised women who continued their usual contraceptive ( n  = 36). Participants completed daily diaries for 90 days before the intervention and 180 days after the intervention. Results: In the intervention group, we found improvements in migraine frequency ( p  < .001), migraine intensity ( p  < .001) and the number of triptans used ( p  < .001). These improvements were already significant after 90 days of desogestrel use ( p  < .001). Disability scores also decreased significantly. No improvement was seen in the nonintervention group. Conclusion: These data demonstrate for the first time in a prospective controlled setting that daily use of the progestin desogestrel is associated with a decrease in migraine frequency, migraine intensity and pain medication use in women with migraine, with and without aura, who had previously been experiencing at least three days of migraine per month. Trial registration: The study is registered in the University of Zürich database ( www.research-projects.uzh.ch/unizh.htm ).

Background: OnabotulinumtoxinA has been demonstrated to be effective for the preventive treatment of headache in individuals with chronic migraine and has been approved and recommended for this patient population. While the therapeutic effect of onabotulinumtoxinA on migraine headache is well documented, there is limited information on the effect of onabotulinumtoxinA on migraine aura., Objective: Given the prolonged and often debilitating nature of aura in patients with hemiplegic migraine, our group sought to examine the effect of onabotulinumtoxinA on aura frequency and severity in this specific subset of migraine patients., Methods: All clinical notes from July 1, 1994 to December 1, 2017 at our institution were retrospectively reviewed to identify patients diagnosed with hemiplegic migraine who received at least one set of onabotulinumtoxinA injections. Thirty-four patients were identified; and of those, 23 were excluded due to incomplete documentation regarding aura symptoms at follow-up visits. The clinical notes of the remaining 11 patients (4 with familial hemiplegic migraine [FHM] and 7 with sporadic hemiplegic migraine [SHM]) were reviewed, and the frequency and description of their headaches and aura before and after receiving onabotulinumtoxinA were recorded., Results: Nine of the 11 patients in our series noted a decrease in the frequency, severity, and/or duration of their aura after receiving onabotulinumtoxinA. Of the 2 non-responders, one was FHM and one was SHM. Of the 9 that noticed improved aura symptoms, 6 described a "wearing off" effect of onabotulinumtoxinA around week 9 or 10 of the 12-week cycle, with subsequent improvement after the next round., Conclusion: For 9 of 11 patients with hemiplegic migraine, onabotulinumtoxinA was helpful not only in reducing the frequency and severity of headaches but also in reducing the frequency and severity of the aura. In this manuscript, we speculate on potential pathophysiologic mechanisms that could have contributed to this effect., (© 2018 American Headache Society.)

This article reports a case of exploding head syndrome (EHS) as an aura of migraine with brainstem aura (MBA). A middle-aged man presented with intermittent episodes of a brief sensation of explosion in the head, visual flashing, vertigo, hearing loss, tinnitus, confusion, ataxia, dysarthria, and bilateral visual impairment followed by migraine headache. The condition was diagnosed as MBA. Explosive head sensation, sensory phenomena, and headaches improved over time with nortriptyline. This case shows that EHS can present as a primary aura symptom in patients with MBA.

Competing Interests: Competing interests: We have read and understood the BMJ policy on declaration of interests and have no relevant interests to declare.

Background: Polypharmacology is a design or use of pharmaceutical agents in which single drug is used to treat multiple diseases. Aquaporin proteins are identified to treat migraine with aura and brain edema. This study focuses on Aquaporin-1 and Aquaporin-4. AQP-1 is expressed in small afferent sensory nerve fibers. Over-expression of peripheral nervous system causes migraine., Methods: AQP-4 is an abundant channel water protein in brain that regulates water transport to prevent homeostasis. Over-expression of AQP-4 contributes to water imbalance in ischemic pathology resulting in cerebral edema. Purpose of this study is to identify a potent inhibitor for the treatment of migraine with aura and brain edema., Results: As in the recent studies, no conventional methodologies have been focused through the approach of polypharmacology. Structures of AQP-1 and AQP- 4 proteins were retrieved from PDB (Protein Data Bank). PyRx software was used to perform molecular docking., Conclusion: Analogues of ligands were analyzed which contained significant similarities of associated proteins to get efficient inhibitor. Toxicity of lead compound was measured through admetSAR. A lead compound was predicted to treat these diseases., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

We review the published literature on migraine with prolonged aura (PA), specifically with regards to the phenotype and treatment options. PA is not uncommon. A recent study found that about 17% of migraine auras are prolonged and that 26% of patients with migraine with aura have experienced at least one PA. The characteristics of PA are similar to most typical auras with the exception of a higher number of aura symptoms (in particular sensory and/or dysphasic). There are no well-established treatments at present which target the aura component of migraine. Other than case reports, there have been open-label studies of lamotrigine and greater occipital nerve blocks. The only randomised, blinded, controlled trial to date has been of nasal ketamine showing some reduction in aura severity but not duration. A small open-labelled pilot study of amiloride was also promising. Larger randomised, controlled trials are needed to establish whether any of the existing or novel compounds mentioned are significantly effective and safe.

Differential diagnosis of migraine, can be difficult, especially of migraine with aura. On the one hand, some diseases can produce symptoms similar to migraine (cerebral aneurysm before rupture, reversible cerebral vasoconstriction syndrome). On the other hand, migraine with aura and some other disorders are conditions that have common pathophysiological mechanisms (e.g., CADASIL and MELAS syndrome, antiphospholipid syndrome). Thirdly, clinical presentations of migraine are often difficult to distinguish from features of other headache conditions (migraine with aura - transient ischemic attack, migraine with visual aura - occipital epilepsy). The author discusses the differential diagnosis of acute headache, especially thunderclap headache, and main strategies of effective treatment of migraine attacks.

Several case reports have associated anticoagulants such as heparin and vitamin K antagonists with reduced symptoms in migraine, but no data exist for direct acting oral factor Xa inhibitors. We report the case of a 55-year-old female who experienced complete remission of migraine with aura for 12 years while on warfarin, with return of symptoms within 3 weeks of switching to apixaban, and resolution of symptoms once again within days of warfarin resumption. Our case suggests that anticoagulation alone is not sufficient to improve migraine symptoms. Further study of vitamin K-dependent proteins not involved in anticoagulation, such as the relatively novel growth arrest-specific gene 6, may clarify the link between warfarin and migraine symptoms., (© 2017 American Headache Society.)

Several data indicate that migraine, especially migraine with aura, is associated with an increased risk of ischemic stroke and other vascular events. Of concern is whether the risk of ischemic stroke in migraineurs is magnified by the use of hormonal contraceptives. As migraine prevalence is high in women of reproductive age, it is common to face the issue of migraine and hormonal contraceptive use in clinical practice. In this document, we systematically reviewed data about the association between migraine, ischemic stroke and hormonal contraceptive use. Thereafter a consensus procedure among international experts was done to develop statements to support clinical decision making, in terms of cardiovascular safety, for prescription of hormonal contraceptives to women with migraine. Overall, quality of current evidence regarding the risk of ischemic stroke in migraineurs associated with the use of hormonal contraceptives is low. Available data suggest that combined hormonal contraceptive may further increase the risk of ischemic stroke in those who have migraine, specifically migraine with aura. Thus, our current statements privilege safety and provide several suggestions to try to avoid possible risks. As the quality of available data is poor further research is needed on this topic to increase safe use of hormonal contraceptives in women with migraine.

Introduction Variants in the CACNA1A gene on chromosome 19p13 result in a spectrum of neurological phenotypes ranging from familial or sporadic hemiplegic migraine to congenital or progressive encephalopathies. Patients with CACNA1A variants often show acute attacks with ataxia or hemiplegia till coma, sometimes related to unilateral brain oedema. No guidelines for the medical management of these attacks are available since treatment is empiric, and many cases do not respond to common antimigraine drugs. Case description We report on the emergency personalized treatment protocol used in an 11 year-old girl with CACNA1A-related encephalopathy for the management of acute attacks of headache, hemiconvulsions and hemiplegia with coma. Discussion Combined corticosteroid pulses and hypertonic solution led to a reduction in severity and duration of acute attacks when administered in the early stages, characterized by migraine, seizure, fever, vomiting and impairment of consciousness associated to hemispheric slowing on the EEG.

Hemodialysis headache (HDH) is an infrequent new-onset symptom, occurring mainly in old uremic patients. Type of pain is nonspecific, occurs during hemodialysis treatment, assuming features similar to tension-type headache and representing a problem, also as regards the therapy to be taken. International Headache Society (IHS) has placed this form of headache among the headaches disorders of homeostasis. We found a case of new-onset HDH in old uremic man, presenting with migraine aura features. A similar case has not been reported in literature, placing us some questions: why and how does this happen? What are the mechanisms involved? Role of trigeminal-vascular system and cortical spreading depression as regards the aura could be considered, through the activation of neuroinflammatory events, lastly causing migraine aura. Moreover, the administration of flunarizine strongly improved migraine symptoms in our patient, as happens in migraine syndromes. Definitely, this case leads us to think that some mechanisms involved in headaches will need to be further clarified., (Copyright © 2017 Polish Neurological Society. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.)

Background Presently, there is no evidence to guide the acute treatment of migraine aura. We aimed to describe the effect of greater occipital nerve (GON) anaesthetic block as a symptomatic treatment for long-lasting (prolonged or persistent) migraine aura. Methods Patients who presented with migraine aura lasting > 2 hours were consecutively recruited during one year at the Headache Unit and the Emergency Department of a tertiary hospital. All patients underwent a bilateral GON block with bupivacaine 0.5%. Patients were followed up for 24 hours. Results A total of 22 auras were treated in 18 patients. Auras consisted of visual ( n = 13), visual and sensory ( n = 4) or sensory symptoms alone ( n = 5). Eleven episodes met diagnostic criteria for persistent aura (>1 week) without infarction. The response was complete without early recurrence in 11 cases (50%), complete with recurrence in < 24 hours in two cases (9.1%), and partial with ≥ 50% improvement in six cases (27.3%). Complete responses without recurrence were more common in cases with prolonged auras lasting < 1 week than in those with persistent auras (72.7% vs. 27.3%; p = 0.033). Conclusions GON block could be an effective symptomatic treatment for prolonged or persistent migraine aura. Randomised controlled trials are still required to confirm these results.