Migraine and Vascular Disorders

Migraine is a highly prevalent disorder, affecting 10% of the population, and 20-40% of persons with migraine experience aura. Migraine, especially migraine with aura (MWA), is independently associated with vascular disease, including stroke, myocardial infarction, and venous thromboembolism. Migraine is also associated with arterial dissection, as well as other non-atherosclerotic vasculopathies, such as fibromuscular dysplasia (FMD), endothelial activation, and endotheliopathies (including as reversible cerebral vasoconstriction syndrome, vasospastic angina, retinal vasculopathy, Raynaud’s, pre-eclampsia, and livedo reticularis). The most studied of the migraine-associated vascular disorders, ischemic stroke, may occur in conjunction with aura, i.e. migrainous infarction, but it is usually remote from the migraine attack. There are multiple potential mechanisms of the migraine aura-stroke association. Cortical spreading depression (SD), the electrophysiological correlate of aura, leads to transient cerebral hypoperfusion, although this is usually of a severity insufficient to cause infarction. In experimental models, ischemia from thrombi or micro emboli may induce CSD, but still be below the level of infarction. Identification of right-to-left interatrial shunt, thrombophilia, and biomarkers of endothelial activation in persons with migraine and in MWA-associated ischemic stroke raises the possibility that in a sizable MWA subset, CSD/aura is a secondary phenomenon, i.e. induced by ischemia. If aura is a potential harbinger of stroke in a MWA subset, diagnosis, evaluation, and treatment in this subset may result in improved control of migraine and prevention of stroke.

This Research Topic focuses on the relationship between vascular disorders and migraine including the pathophysiology and genetics of aura, features of the population most likely to experience migraine-associated cerebral and cardiac ischemia, mechanisms putatively linking migraine with stroke, heart disorders and dissection, utility of a diagnostic evaluation after aura to identify vascular event risk, and the role of therapeutic strategies to prevent both migraine and vascular events.

We welcome submissions of review papers, meta-analyses and original research submissions addressing, but not limited to, the following subtopics:

• Epidemiology
- Association of migraine and ischemic stroke, including i) migrainous infarction, and ii) migraine remote from stroke
- Association of migraine and subclinical vascular brain lesions
- Association of migraine and other vascular conditions

• Genetics
- polygenic: gene variants associated with stroke/vascular conditions also associated with migraine with aura and migraine without aura
- monogenic disorders associated with migraine with aura and with stroke, including CADASIL, Col4A1 mutations, AD-RVCL, hereditary vascular retinopathy, familial hemiplegic migraine

• Brain Lesions in migraine with and without aura: etiology, pathophysiology (including as possible hallmark of microembolism), & natural history
- White matter hyperintensities, infarct-like lesions, and loss of grey matter

• Potential mechanisms of the association of migraine and other vascular conditions
- Cortical spreading depression (CSD)-related ischemia
- Ischemia-related CSD (due to hypoperfusion from micro emboli, thrombosis, vasospasm)
- Cardiac disorders: including right-to-left shunt, mitral valve prolapse, atrial fibrillation, angina, myocardial infarction
- Thrombosis, including platelet disorders, hypercoagulability (acquired, hereditary, due to exogenous [e.g. CHC] or endogenous [e.g. pregnancy] reproductive hormones), hemostatic/vascular biomarkers
- Vascular conditions, such as arterial dissection and other non-atherosclerotic vasculopathies (e.g. fibromuscular dysplasia ([FMD]), atherosclerosis, endothelial perturbation (e.g. activation, dysfunction, endothelial microparticles, endothelial progenitor cells), and association with endotheliopathies, including vasospastic angina, retinal vasculopathy, Raynaud’s, pre-eclampsia, and livedo reticularis
- Mechanisms of surgery-related stroke in persons with migraine

• Evaluation considerations in persons with migraine with aura, or migraine associated vascular conditions
- Evaluation of aura (i.e. role of neuroimaging, cardiac testing, hypercoagulability profile, neurophysiological testing, and identification of other stroke risk factors) in order to identify stroke or other vascular disease risk
- Evaluation of stroke (or other vascular conditions) in persons with migraine

• Therapeutic considerations in persons with migraine with aura, or migraine- associated stroke or other vascular conditions
- Use of Anti-thrombotic medications
- Closure Patent foramen ovale (PFO)
- Avoidance of combined hormonal contraceptives
- Avoidance of migraine-specific medications (e.g.CGRP blockers, triptans)