Migraine with brainstem aura.

Migraine with brainstem aura has been long described but remains poorly understood. Previously known as "basilar" or "basilar artery" migraine, it is an uncommon subtype of migraine with aura, one seen primarily in children, adolescents, and younger adults. The condition is characterized by migraine headache accompanied by several neurological symptoms conventionally assigned to dysfunction of brainstem structures. Initially felt to be vascular in origin, partly due to prevailing concepts of migraine pathophysiology at the time, most now believe the aura symptoms of migraine with brainstem aura are secondary to neural circuitry dysfunction. The differential diagnosis is reasonably broad, and most patients warrant investigation to exclude conditions bearing high degrees of morbidity and mortality. Neuroimaging, specifically brain MRI without contrast, is recommended for migraine with brainstem aura. Depending on the clinical presentation certain cases may require consideration of contrasted or vascular imaging, EEG, or lumbar puncture with cerebrospinal fluid analysis. Migraine prophylaxis should involve lifestyle adjustments and preventive medical therapies shown to be effective in clinical trials of migraine, following evidence-based guidelines. The acute pharmacological management of attacks of migraine with brainstem aura remains a matter of controversy. The prognosis is generally favorable. Future refinements in the diagnostic criteria might possibly enhance diagnostic specificity and improved clinical research.

Hemiplegic migraine.

Hemiplegic migraine (HM) is a rare subtype of migraine with aura in which the aura phase includes transient motor weakness. Diagnosis is based on the International Classification of Headache Disorders criteria (ICHD-3). The most important diagnostic tools remain a patient interview, neurological examination during attacks, and exclusion of other disorders, such as epilepsy, stroke, encephalitis and secondary headache syndromes. Hemiplegic migraine can occur either familial or sporadic. Three genes, CACNA1A, ATP1A2, and SCN1A have been identified. Taken together, mutations in these three genes predict increased neurotransmitter and potassium ion levels at the synaptic cleft, which facilitates cortical spreading depolarization, the phenomenon underlying the migraine aura. The presence of several symptoms, including extensive weakness and brainstem manifestations increase the likelihood of finding a monogenic cause. While the diagnosis can be confirmed by genetic testing, it cannot be excluded if one of the known (F)HM genes is not implicated. Most patients with hemiplegic migraine without a mutation in CACNA1A, ATP1A2, or SCN1A display a mild phenotype that is more akin to that of common (nonhemiplegic) migraine. Additional diagnostics such as brain imaging, cerebrospinal fluid analysis or an electroencephalography are mainly performed to exclude other causes of focal neurologic symptoms associated with hemiparesis and headache. Due to the rarity of the disorder, current treatment recommendations are based on small, unblinded studies and empirical data.

Migraine with aura.

This chapter describes the different types of aura including rare aura subtypes such as retinal aura. In addition, aura manifestations not classified in the International Classification of Headache Disorders and auras in headache disorders others than migraine are also described. The differential diagnosis of migraine aura comprises several neurological disorders which should be known to specialists. Migraine aura also has impact on the choice of migraine treatment; recommendations for the treatment of the migraine aura itself are also presented in this chapter.

Impact of a 12-week olfactory training programme in women with migraine with aura: protocol for a double-blind, randomised, placebo-controlled trial.

INTRODUCTION: Migraine is a leading cause of disability and suffering worldwide. However, conventional pharmacological migraine preventive therapies are often challenging and accompanied by adverse effects. Recently, structured odour exposure has shown to successfully increase pain thresholds in patients with chronic back pain. Despite the importance of the olfactory system in migraine, there are no studies investigating the impact of structured odour exposure in patients with migraine. METHODS AND ANALYSIS: This double-blind randomised placebo-controlled trial will be conducted at the Headache Clinic of the University Pain Center at TU Dresden, Germany and aims at investigating the impact of a 12-week structured exposure to odours in women with migraine. Fifty-four women between 18 and 55 years with migraine with aura will be recruited and randomised to training with odours and odourless training. The primary outcomes are mechanical and electrical pain thresholds. Secondary outcomes comprise olfactory threshold and the number of headache days. Other exploratory measurements are headache associated pain intensity, acute analgesic intake, symptoms of anxiety and depression, and quality of life. Additionally, this protocol assesses neuroanatomical and neurofunctional changes associated with the 12-week olfactory training. Data analysis will be executed on the basis of the general linear model considering repeated measurements. ETHICS AND DISSEMINATION: Ethical approvals were obtained from the Ethics Board of the TU Dresden (Protocol No. BO-EK-353082020). Participation will only be possible after written informed consent is provided. Findings will be disseminated through peer-reviewed journals and scientific conferences. TRIAL REGISTRATION NUMBER: DRKS00027399.

Migraine aura-like episodes following sclerotherapy for varicose veins of the lower extremities-A systematic review.

OBJECTIVE: This systematic review provides a summary and evaluation of cases of migraine aura-like episodes elicited by sclerotherapy of veins of the lower extremities and discusses possible underlying mechanisms. BACKGROUND: Sclerotherapy is a commonly used treatment for varicose veins. Symptoms resembling migraine aura have been reported during and following sclerotherapy of the lower extremities, suggesting that sclerotherapy may elicit migraine aura. METHODS: We searched PubMed for articles reporting neurological complications that were transient and fully reversible following sclerotherapy treatment for varicose veins in the lower limbs. There were no restrictions regarding article language or publication date. Only original studies and case reports were included. Two authors independently reviewed included articles in detail. Data were extracted from each article, including details on symptoms, previous migraine history, sclerotherapy method, and the presence of a right-to-left cardiac shunt in patients. We evaluated whether episodes fulfilled modified International Classification of Headache Disorders, 3rd edition, criteria for 1.2 Migraine with aura or 1.5.2 Probable migraine with aura. RESULTS: The search yielded 777 articles, 28 of which were included. Twenty-six articles reported 119 episodes of transient neurological symptoms in 34,500 sclerotherapy sessions. Two additional articles reported six episodes of transient neurological symptoms with no specification of the number of sessions. Of the 125 episodes, 119 involved transient visual disturbances, and eight met the modified criteria for Probable migraine with aura. In most episodes (98%), clinical information was insufficient to determine if the criteria were fulfilled. CONCLUSIONS: Symptoms that are clinically indistinguishable from migraine with aura attacks may occur following sclerotherapy, although this likely is rare. Microembolization through a right-to-left shunt triggering cortical spreading depolarization is a possible mechanism. Our findings are limited by infrequent specific assessments for neurological complications and a low level of detail in the description of symptoms in the available literature. Future prospective studies are needed to determine this phenomenon's incidence and underlying mechanisms.

Applications of transcranial magnetic stimulation in migraine: evidence from a scoping review.

Transcranial magnetic stimulation (TMS), a non-invasive brain stimulation method, is trying to emerge as a migraine management strategy for both attack treatment and prevention. This scoping review presents 16 among single-pulse (to manage episodic and chronic migraine) and repetitive TMS randomized clinical trials (to manage chronic migraine). The works we reviewed suggest that TMS may be adopted as add-on therapy in those patients who are refractory to pharmacological therapy only with special arrangements for individualized treatment strategies or research. There are still limited clinical research programs and metaanalysis to promote routinely TMS employment, as TMS has been shown either to have no significant effects for any outcome or to be effective for migraine. These diverging conclusions depend on several biasing factors, including the lack of reliable, large, sham-controlled clinical trials, the dyshomogeneity in study designs (including the area of stimulation, the frequency of stimulation, the number of pulses, pulse intensity, and the number of sessions), patient selection criteria (migraine w/o aura, episodic and chronic migraine; TMS contraindication), and the lack of outcomes homogeneity and long-term real-world efficacy data. Therefore, in the future, it will be important to conduct larger randomized trials to confirm TMS usefulness in migraine management (acute attack and prophylactic treatment), identify those patients who may benefit from TMS, maybe independently of pharmacological treatments (i.e., using TMS as an alternative and not only as an add-on treatment). Otherwise, TMS will play a role in treating migraine only with special arrangements for individualized management strategies or research.

Case Report: Visual Snow Syndrome after Repetitive Mild Traumatic Brain Injury.

SIGNIFICANCE: Visual snow syndrome is a recently recognized condition with its own diagnostic criteria, evolving pathophysiologic research, and potential treatment options. PURPOSE: This report documents a rare but likely underdiagnosed condition called visual snow syndrome. A review of the current literature on pathophysiology and treatments is discussed. CASE REPORT: A 40-year-old Whiteman started experiencing symptoms of constant pulsating pixels throughout his entire visual field approximately 3 weeks after a series of mild concussions. In addition, he experienced a persistence of images and photosensitivity. The patient had normal eye examination results, visual fields, and retinal imaging result. Brain MRI, magnetic resonance angiography, electroencephalography, and cerebrospinal fluid analysis were unremarkable. A positron emission tomography scan demonstrated hypometabolism in the posterior parietal lobes and left posterior cingulate gyrus. Pharmacological treatment with antiepileptic and migraine medications was unsuccessful. Tinted lenses were essentially ineffective with a 10% reduction in symptoms reported with the use of a custom blue-tinted lens.Vision rehabilitation aids with optical character recognition were used for prolonged reading needs. CONCLUSIONS: Although rare, visual snow syndrome should be considered in all patients reporting continuous pixelations in their vision for more than 3 months, especially when accompanied by at least two of the following: photosensitivity, palinopsia, enhanced entopic phenomena, or nyctalopia. The pathophysiology is still unclear at this point, with evidence suggesting a link to the secondary visual cortex, specifically the lingual gyrus. More studies are needed to determine the exact cause, especially studies that separate visual snow syndrome patients with and without comorbid migraine. Because the pathophysiology is unclear, the treatment course is also unclear. Anecdotal evidence may suggest that tinted lenses may be of some value.

Migraine and cardiovascular risk factors: A clinic-based study.

OBJECTIVE: The relation between migraine and vascular risk factors is an unclear issue. Furthermore, the reasons for chronification are still unknown. Probably, the age-related risk and other factors leading to migraine progression will also change in the future. Under these questions, we aimed to investigate whether or not there is a specific association with vascular risk factors between several age groups and subtypes of migraine and also in their families. METHODS: A dataset (the Turkish Headache Database) from four tertiary headache centres in Turkey was used. This database included headache-defining features according to ICHD criteria based on face-to-face interviews and examinations by a Neurologist. Vascular risk factors of migraine without aura (MwoA), migraine with aura (MwA) and chronic migraine (CM) were compared between three age groups (under 30 years, 30-50 years and over 50 years) and in first-degree relatives of the patients. Our study included 2712 patients comprising 1868 (68.9 %), 246 (9.1 %) and 598 (22.1 %) subjects with MwoA, MwA and CH, respectively. RESULTS: This study showed that both the patients and the first-degree relatives were more frequently associated with vascular risk factors in CM than episodic MwA and MwoA. MwoA showed a weaker association with vascular risk factors than MwA and CM. CONCLUSION: Chronic migraine was associated with vascular risk factors at all ages and first-degree relatives as well. Vascular risk factors should be investigated with greater focus on chronic migraine.

Tratamento homeopático de um caso de enxaqueca: relato de caso

A enxaqueca é uma doença de alta prevalência, com importantes repercussões nas atividades diárias dos indivíduos e de difícil tratamento na prática médica hegemônica. OBJETIVO: esta monografia visa relatar o caso de uma paciente do sexo feminino de 55 anos de idade portadora de enxaqueca há mais de 40 anos, que foi tratada sem sucesso pela terapêutica alopática. MÉTODO: as informações foram obtidas por meio de revisão do prontuário, entrevista com a paciente, pesquisa na Matéria Médica Homeopática e Repertório de Sintomas e revisão da literatura. CONSIDERAÇÕES FINAIS: o caso relatado e publicações levantadas trazem à luz a discussão da terapêutica homeopática de uma doença complexa como a enxaqueca. O presente estudo, apesar de relatar um caso ainda em andamento, mostra que a terapêutica homeopática é capaz de proporcionar resultados satisfatórios e duradouros no que diz respeito ao alívio sintomático e melhoria da qualidade de vida, quando comparado com a terapêutica hegemônica. (AU)

The objective of this paper is. Migraine is a highly prevalent disease, with important repercussions on individuals' daily activities and difficult to treat in hegemonic medical practice. OBJECTIVE: This monograph aims to report the case of a 55-year-old female patient with migraine for over 40 years, who was unsuccessfully treated by allopathic therapy. METHOD: the information was obtained through a review of the medical record, interview with the patient, research in the Homeopathic Materia Medica and Repertoire of Symptoms and literature review. FINAL CONSIDERATIONS: the case reported and publications raised bring to light the discussion of homeopathic therapy for a complex disease such as migraine. The present study, despite reporting a case still in progress, shows that homeopathic therapy is capable of providing satisfactory and lasting results with regard to symptomatic relief and improvement in quality of life, when compared to hegemonic therapy. (AU)

Insights into pathophysiology and treatment of visual snow syndrome: A systematic review.

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.

Migraine Aura: Updates in Pathophysiology and Management.

PURPOSE OF REVIEW: To provide an updated review of the pathophysiology, diagnosis, and management of migraine with aura. RECENT FINDINGS: Thalamic and other subcortical regions may play a role in the pathophysiology of migraine. There is inter-patient and intra-patient attack variability in the characteristics of typical aura especially visual aura symptoms. Migraine with brainstem aura may originate cortically. Migraine with retinal aura may be associated with structural and functional changes in the retina. Although cortical spreading depression (CSD) continues to be the predominant theory surrounding the pathophysiology of migraine with aura, the exact mechanism of action of CSD and its role in relation of all phases of migraine including features of aura are not fully understood. Novel experimental models and newer diagnostic tools including neuroimaging are currently being used to enhance of understanding of migraine with and without aura. Transient ischemia attacks, stroke, and epilepsy should be considered in your differential diagnosis of migraine with aura. There are no specific therapies for migraine with aura.

Manual acupuncture versus sham acupuncture and usual care for prophylaxis of episodic migraine without aura: multicentre, randomised clinical trial.

OBJECTIVE: To assess the efficacy of manual acupuncture as prophylactic treatment for acupuncture naive patients with episodic migraine without aura. DESIGN: Multicentre, randomised, controlled clinical trial with blinded participants, outcome assessment, and statistician. SETTING: Seven hospitals in China, 5 June 2016 to 15 November 2018. PARTICIPANTS: 150 acupuncture naive patients with episodic migraine without aura. INTERVENTIONS: 20 sessions of manual acupuncture at true acupuncture points plus usual care, 20 sessions of non-penetrating sham acupuncture at heterosegmental non-acupuncture points plus usual care, or usual care alone over 8 weeks. MAIN OUTCOME MEASURES: Change in migraine days and migraine attacks per four weeks during weeks 1-20 after randomisation compared with baseline (four weeks before randomisation). RESULTS: Among 150 randomised patients (mean age 36.5 (SD 11.4) years; 123 (82%) women), 147 were included in the full analysis set. Compared with sham acupuncture, manual acupuncture resulted in a significantly greater reduction in migraine days at weeks 13 to 20 and a significantly greater reduction in migraine attacks at weeks 17 to 20. The reduction in mean number of migraine days was 3.5 (SD 2.5) for manual versus 2.4 (3.4) for sham (adjusted difference -1.4, 95% confidence interval -2.4 to -0.3; P=0.005) at weeks 13 to 16 and 3.9 (3.0) for manual versus 2.2 (3.2) for sham (adjusted difference -2.1, -2.9 to -1.2; P<0.001) at weeks 17 to 20. At weeks 17 to 20, the reduction in mean number of attacks was 2.3 (1.7) for manual versus 1.6 (2.5) for sham (adjusted difference -1.0, -1.5 to -0.5; P<0.001). No severe adverse events were reported. No significant difference was seen in the proportion of patients perceiving needle penetration between manual acupuncture and sham acupuncture (79% v 75%; P=0.891). CONCLUSIONS: Twenty sessions of manual acupuncture was superior to sham acupuncture and usual care for the prophylaxis of episodic migraine without aura. These results support the use of manual acupuncture in patients who are reluctant to use prophylactic drugs or when prophylactic drugs are ineffective, and it should be considered in future guidelines. TRIAL REGISTRATION: Clinicaltrials.gov NCT02765581.

The American Registry for Migraine Research: Research Methods and Baseline Data for an Initial Patient Cohort.

BACKGROUND: The American Registry for Migraine Research (ARMR) is a multicenter, prospective, longitudinal patient registry, biorepository, and neuroimaging repository that collects clinical data, electronic health record (EHR) data, blood samples, and brain imaging data from individuals with migraine or other headache types. In this manuscript, we outline ARMR research methods and report baseline data describing an initial cohort of ARMR participants. METHODS: Adults with any International Classification of Headache Disorders (ICHD) diagnosis were prospectively enrolled from one of the 8 participating headache specialty centers. At baseline, ARMR participants complete web-based questionnaires, clinicians enter the participant's ICHD diagnoses, an optional blood specimen is collected, and neuroimaging data are uploaded to the ARMR neuroimaging repository. Participants maintain the ARMR daily headache diary longitudinally and follow-up questionnaires are completed by participants every 3 months. EHR data are integrated into the ARMR database from a subset of ARMR sites. Herein, we describe the ARMR methodology and report the summary data from ARMR participants who had, from February 2016 to May 2019, completed at least 1 baseline questionnaire from which data are reported in this manuscript. Descriptive statistics are used to provide an overview of patient's sociodemographics, headache diagnoses, headache characteristics, most bothersome symptoms other than headache, headache-related disability, comorbidities, and treatments. RESULTS: Data were available from 996 ARMR participants, enrolled from Mayo Clinic Arizona, Dartmouth-Hitchcock Medical Center, University of Utah, University of Colorado, Thomas Jefferson University, University of Texas Health Science Center at Houston, Georgetown University Medical Center, and DENT Neurological Institute. Among ARMR participants, 86.7% (n = 864) were female and the mean age at the time of enrollment was 48.6 years (±13.9; range 18-84). The most common provider-reported diagnosis was chronic migraine (n = 622), followed by migraine without aura (n = 327), migraine with aura (n = 196), and medication overuse headache (n = 65). Average headache frequency was 19.1 ± 9.2 days per month (n = 751), with 68% reporting at least 15 headache days per month. Sensitivity to light was the most frequent (n = 222) most bothersome symptom overall, other than headache, but when present, cognitive dysfunction was most frequently (n = 157) the most bothersome symptom other than headache. Average migraine disability assessment (MIDAS) score was 52 ± 49 (n = 760), (very severe headache-related disability); however, 17% of the ARMR population had MIDAS scores suggesting "no" or "mild" disability. The most common non-headache health issues were allergies (n = 364), back pain (n = 296), neck pain (n = 296), depression (n = 292), and anxiety (n = 278). Nearly 85% (n = 695) of patients were using preventive medications and 24.7% were using non-medication preventive therapy (eg, vitamins and neuromodulation). The most common preventive medication classes were neurotoxins, anticonvulsants, antidepressants, vitamins/supplements, and anticalcitonin gene-related peptide ligand or receptor-targeted monoclonal antibodies. Nearly 90% (n = 734) of ARMR participants was taking medications to treat migraine attacks, with the most common classes being triptans, non-steroidal anti-inflammatory drugs, antiemetics, acetaminophen, and combination analgesics. CONCLUSIONS: ARMR is a source of real-world patient data, biospecimens, and brain neuroimaging data that provides comprehensive insight into patients with migraine and other headache types being seen in headache specialty clinics in the United States. ARMR data will allow for longitudinal and advanced analytics that are expected to lead to a better characterization of patient heterogeneity, healthcare resource utilization, identification of endophenotypes, factors that predict treatment outcomes and clinical course, and ultimately advance the field toward precision headache medicine.

Migraine headache: Is it only a neurological disorder? Links between migraine and cardiovascular disorders.

Migraine headache (MH) is a common disorder affecting millions of people in the United States. MH is substantially more prevalent in women compared to men. An association between migraine with or without aura and risk of cardiovascular disease (CVD) has been extensively reported. There are several proposed theories that may explain the pathophysiologic relationship between MH and CVD. This review will summarize the recent literature on this topic and provide an evidence-based perspective regarding the current knowledge and controversies regarding association of MH and CVD.

Differences in treatment response between migraine with aura and migraine without aura: lessons from clinical practice and RCTs.

Migraine is a major public health problem afflicting approximately 10% of the general population and is a leading cause of disability worldwide, yet our understanding of the basis mechanisms of migraine remains incomplete. About a third of migraine patients have attacks with aura, consisting of transient neurological symptoms that precede or accompany headache, or occur without headache. For patients, aura symptoms are alarming and may be transiently disabling. For clinicians and scientists, aura represents an intriguing neurophysiological event that may provide important insight into basic mechanisms of migraine. Several observations point toward important differences between migraine with and without aura. Compared with migraine without aura, migraine with aura has different heritability, greater association with different conditions including stroke, different alterations of brain structure and function as revealed by imaging studies. A number of studies also indicate that migraine with aura may respond differently to acute and preventive therapies as compared to migraine without aura. The purpose of this review is to provide an overview of these differences in treatment responses, and to discuss the possibility of different therapeutic strategies for migraine with vs. without aura.

Episodic Migraine With and Without Aura: Key Differences and Implications for Pathophysiology, Management, and Assessing Risks.

PURPOSE OF REVIEW: To review the pathophysiologic, epidemiologic, and clinical evidence for similarities and differences between migraine with and without aura. RECENT FINDINGS: The ICHD-3 has recently refined the diagnostic criteria for aura to include positive symptomatology, which better differentiates aura from TIA. Although substantial evidence supports cortical spreading depression as the cause of visual aura, the role (if any) of CSD in headache pain is not well understood. Recent imaging evidence suggests a possible hypothalamic origin for a headache attack, but further research is needed. Migraine with aura is associated with a modest increase in the risk of ischemic stroke. The etiology for this association remains unclear. There is a paucity of evidence regarding treatments specifically aimed at the migraine with aura subtype, or whether migraine with vs without aura responds to treatment differently. Migraine with typical aura is therefore often treated similarly to migraine without aura. Lamotrigine, daily aspirin, and flunarizine have evidence for efficacy in prevention of migraine with aura, and magnesium, ketamine, furosemide, and single-pulse transcranial magnetic stimulation have evidence for use as acute treatments. Although triptans have traditionally been contraindicated in hemiplegic migraine and migraine with brainstem aura, this prohibition is being reconsidered in the face of evidence suggesting that use may be safe. The debate as to whether migraine with and without aura are different entities is ongoing. In an era of sophisticated imaging, genetic advancement, and ongoing clinical trials, efforts to answer this question are likely to yield important and clinically meaningful results.

Migraine Aura Without Headache [corrected].

PURPOSE OF REVIEW: This review evaluates and explains our current understanding of a rare subtype of migraine, typical aura without headache, also known as migraine aura without headache or acephalgic migraine. RECENT FINDINGS: Typical aura without headache is a known entity within the spectrum of migraine. Its pathophysiology is suggested to be similar to classic migraines, with cortical spreading depression leading to aura formation but without an associated headache. No clinical trials have been performed to evaluate treatment options, but case reports suggest that most patients will respond to the traditional treatments for migraine with aura. Bilateral greater occipital nerve blocks may be helpful in aborting migraine with prolonged aura. Transcranial magnetic stimulation has shown efficacy in aborting attacks of migraine with aura but has not been specifically tested in isolated aura. Typical aura without headache occurs exclusively in 4% patients with migraine, and may take place at some point in 38% of patients with migraine with aura. Typical aura without headache commonly presents with visual aura without headache, brainstem aura without headache, and can also develop later in life, known as late-onset migraine accompaniment.

Treatment of acute migraine by a partial rebreathing device: A randomized controlled pilot study.

Background Impaired brain oxygen delivery can trigger and exacerbate migraine attacks. Normoxic hypercapnia increases brain oxygen delivery markedly by vasodilation of the cerebral vasculature, and hypercapnia has been shown to abort migraine attacks. Stable normoxic hypercapnia can be induced by a compact partial rebreathing device. This pilot study aimed to provide initial data on the device's efficacy and safety. Methods Using a double-blinded, randomized, cross-over study design, adult migraine-with-aura patients self-administered the partial rebreathing device or a sham device for 20 minutes at the onset of aura symptoms. Results Eleven participants (mean age 35.5, three men) self-treated 41 migraine attacks (20 with the partial rebreathing device, 21 with sham). The partial rebreathing device increased mean End Tidal CO2 by 24%, while retaining mean oxygen saturation above 97%. The primary end point (headache intensity difference between first aura symptoms and two hours after treatment (0-3 scale) - active/sham difference) did not reach statistical significance (-0.55 (95% CI: -1.13-0.04), p = 0.096), whereas the difference in percentage of attacks with pain relief at two hours was significant ( p = 0.043), as was user satisfaction ( p = 0.022). A marked efficacy increase was seen from first to second time use of the partial rebreathing device. No adverse events occurred, and side effects were absent or mild. Conclusion Normoxic hypercapnia shows promise as an adjunctive/alternative migraine treatment, meriting further investigation in a larger population. Clinical study registered at ClinicalTrials.gov with identifier NCT03472417.

Active role of capillary pericytes during stimulation-induced activity and spreading depolarization.

Spreading depolarization is assumed to be the mechanism of migraine with aura, which is accompanied by an initial predominant hyperaemic response followed by persistent vasoconstriction. Cerebral blood flow responses are impaired in patients and in experimental animals after spreading depolarization. Understanding the regulation of cortical blood vessels during and after spreading depolarization could help patients with migraine attacks, but our knowledge of these vascular mechanisms is still incomplete. Recent findings show that control of cerebral blood flow does not only occur at the arteriole level but also at capillaries. Pericytes are vascular mural cells that can constrict or relax around capillaries, mediating local cerebral blood flow control. They participate in the constriction observed during brain ischaemia and might be involved the disruption of the microcirculation during spreading depolarization. To further understand the regulation of cerebral blood flow in spreading depolarization, we examined penetrating arterioles and capillaries with respect to vascular branching order, pericyte location and pericyte calcium responses during somatosensory stimulation and spreading depolarization. Mice expressing a red fluorescent indicator and intravenous injections of FITC-dextran were used to visualize pericytes and vessels, respectively, under two-photon microscopy. By engineering a genetically encoded calcium indicator we could record calcium changes in both pericytes around capillaries and vascular smooth muscle cells around arterioles. We show that somatosensory stimulation evoked a decrease in cytosolic calcium in pericytes located on dilating capillaries, up to the second order capillaries. Furthermore, we show that prolonged vasoconstriction following spreading depolarization is strongest in first order capillaries, with a persistent increase in pericyte calcium. We suggest that the persistence of the 'spreading cortical oligaemia' in migraine could be caused by this constriction of cortical capillaries. After spreading depolarization, somatosensory stimulation no longer evoked changes in capillary diameter and pericyte calcium. Thus, calcium changes in pericytes located on first order capillaries may be a key determinant in local blood flow control and a novel vascular mechanism in migraine. We suggest that prevention or treatment of capillary constriction in migraine with aura, which is an independent risk factor for stroke, may be clinically useful.