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.
Keywords: endothelial dysfunction; ischemic stroke; migraine with aura; patent foramen ovale; reproductive hormones; women.
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[Migraine with aura and patent foramen ovale. A different clinical entity].Neurologia. 2008 Oct;23(8):503-10. Neurologia. 2008. PMID: 18770055 Spanish.
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Patent foramen ovale, stroke, and cardiovascular disease in migraine.Curr Opin Neurol. 2007 Jun;20(3):310-9. doi: 10.1097/WCO.0b013e328136c22d. Curr Opin Neurol. 2007. PMID: 17495626 Review.
Use of combined hormonal contraceptives among women with migraines and risk of ischemic stroke.Am J Obstet Gynecol. 2017 May;216(5):489.e1-489.e7. doi: 10.1016/j.ajog.2016.12.019. Epub 2016 Dec 26. Am J Obstet Gynecol. 2017. PMID: 28034652
- Benjamin EJ, Virani SS, Callaway CW, et al. Heart disease and stroke statistics-2018 update: A report from the American Heart Association. Circulation. 2018;137:e67-e492.
- Buse DC, Loder EW, Gorman JA, et al. Sex differences in the prevalence, symptoms, and associated features of migraine, probable migraine and other severe headache: Results of the American Migraine Prevalence and Prevention (AMPP) Study. Headache. 2013;53:1278-1279.
- Etminan M, Takkouche B, Isorna FC, Samii A. Risk of ischaemic stroke in people with migraine: Systematic review and meta-analysis of observational studies. BMJ. 2005;330:63.
- Schürks M, Rist PM, Bigal ME, Buring JE, Lipton RB, Kurth T. Migraine and cardiovascular disease: Systematic review and meta-analysis. BMJ. 2009;339:b3914.
- Spector JT, Kahn SR, Jones MR, Jayakumar M, Dalal D, Nazarian S. Migraine headache and ischemic stroke risk: An updated meta-analysis. Am J Med. 2010;123:612-624.