Migraine and Ischemic Stroke in Women. A Narrative Review

Gretchen E. Tietjen, MD; Emily F. Maly, MSBS

Disclosures

Headache. 2020;60(5):843-863. 

In This Article

Abstract and Introduction

Abstract

Objective/Background: Migraine is associated with ischemic stroke. Women are 3-fold as likely as men to have migraine, and high estrogen states increase the risk of migraine with aura (MWA), venous thromboembolism (VTE), and of stroke. We review the epidemiological and mechanistic evidence of the migraine-stroke relationship and its risk factors, with a focus on women and conditions that exclusively or predominantly affect them.

Methods: We performed a search of MEDLINE/PubMed database, then a narrative review of the epidemiological evidence of the migraine-stroke relationship as well as the evidence for arterial, thrombophilic, and cardiac mechanisms to explain this connection. We examine the implications of this evidence for the diagnostic evaluation and treatment of MWA.

Results: MWA is associated with multiple stroke risk factors, such as hypertension, hyperlipidemia, diabetes mellitus, cigarette smoking, atrial fibrillation, and patent foramen ovale. In women, MWA is also associated with biomarkers of endothelial activation, hormonal contraceptive use, pregnancy, and VTE. This suggests that a subset of auras may be secondary, that is, induced by ischemia related to microemboli or in situ thrombosis. MWA-associated ischemic stroke is more common in young (<45 years old) women with high frequency of migraine attacks, hormonal contraception use, and with pregnancy and preeclampsia. There is increasing evidence that cardioembolism, often in conjunction with thrombophilia, plays a prominent role in MWA-associated cerebral infarction.

Conclusion: The commonality of factors associated with MWA and with MWA-associated stroke suggest that persons with secondary, ischemia-induced aura may be at elevated risk of stroke. Although further research is needed, we recommend consideration of a diagnostic evaluation of MWA that mirrors the evaluation of transient ischemic attack, given that prophylactic treatment targeting the ischemic origin of secondary aura may prevent migraine as well as stroke.

Introduction

Migraine and ischemic stroke are both highly prevalent and disabling conditions, affecting women more commonly than men, although with a 3:1 ratio, female predominance is more striking in migraine.[1,2] Only 10% of ischemic strokes occur in persons under 50 years,[1] the age group most commonly affected by migraine, yet, numerous case-control and cohort studies have demonstrated an independent association between these 2 conditions in the young.[3–7] Migrainous infarction, defined by ischemic stroke occurring during a typical aura, is relatively rare.[8–11] More commonly, ischemic stroke occurs in persons with active migraine, but remote from the attack. Examination of the multi-faceted migraine-stroke relationship suggests there may be several pathophysiological mechanisms, often acting in concert, connecting these 2 disorders. In this paper, we review the epidemiology of the link between migraine and ischemic stroke, including as it relates to combined hormonal contraceptive use and pregnancy. We describe potential mechanisms of the association of migraine and stroke, and discuss the diagnostic and treatment implications thereof.

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