Microembolism and Other Links Between Migraine and Stroke: Clinical and Pathophysiologic Update

Overview

Journal Neurology

Specialty Neurology

Date 2022 Dec 15

PMID 36522158

Authors

Simona Sacco

Andrea M Harriott

Cenk Ayata

Raffaele Ornello

Rodrigo Bagur

Amado Jimenez-Ruiz

Luciano A Sposato

Affiliations

Soon will be listed here.

Abstract

Migraine and stroke are highly prevalent diseases with a high effect on quality of life, with multiple epidemiologic, pathophysiologic, clinical, and prognostic areas of overlap. Migraine is a risk factor for stroke. This risk is explained by common risk factors, migraine-specific mechanisms, and non-migraine-specific mechanisms that have a relevant role in patients with migraine with aura (e.g., atrial fibrillation and paradoxical embolism through a patent foramen ovale). Another important link between migraine aura and ischemic stroke is cardiac embolism. Cardioembolism is the most frequent cause of ischemic stroke, and increasing evidence suggests that microembolism, predominantly but not exclusively originating in the heart, is a contributing mechanism to the development of migraine aura. In this review, we discuss epidemiologic aspects of the association between migraine and ischemic stroke, the clinical presentation of ischemic strokes in patients with migraine, and the differentiation between migrainous and nonmigrainous infarctions. After that, we review migraine-specific and non-migraine-specific stroke mechanisms. We then review updated preclinical and clinical data on microembolism as a cause of migraine aura. In the last section, we summarize knowledge gaps and important areas to explore in future research. The review includes a clinical vignette with a discussion of the most relevant topics addressed.

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References

Wammes-van der Heijden E, Rahimtoola H, Leufkens H, Tijssen C, Egberts A . Risk of ischemic complications related to the intensity of triptan and ergotamine use. Neurology. 2006; 67(7):1128-34. DOI: 10.1212/01.wnl.0000240128.76399.fa. View

Daghlas I, Sargurupremraj M, Danning R, Gormley P, Malik R, Amouyel P . Migraine, Stroke, and Cervical Arterial Dissection: Shared Genetics for a Triad of Brain Disorders With Vascular Involvement. Neurol Genet. 2022; 8(1):e653. PMC: 8808356. DOI: 10.1212/NXG.0000000000000653. View

Pezzini A, Busto G, Zedde M, Gamba M, Zini A, Poli L . Vulnerability to Infarction During Cerebral Ischemia in Migraine Sufferers. Stroke. 2018; 49(3):573-578. DOI: 10.1161/STROKEAHA.118.020554. View

Hu X, Zhou Y, Zhao H, Peng C . Migraine and the risk of stroke: an updated meta-analysis of prospective cohort studies. Neurol Sci. 2016; 38(1):33-40. DOI: 10.1007/s10072-016-2746-z. View

Donmez-Demir B, Yemisci M, Kilic K, Gursoy-Ozdemir Y, Soylemezoglu F, Moskowitz M . Microembolism of single cortical arterioles can induce spreading depression and ischemic injury; a potential trigger for migraine and related MRI lesions. Brain Res. 2017; 1679:84-90. DOI: 10.1016/j.brainres.2017.11.023. View

Eikermann-Haerter K, Lee J, Yalcin N, Yu E, Daneshmand A, Wei Y . Migraine prophylaxis, ischemic depolarizations, and stroke outcomes in mice. Stroke. 2014; 46(1):229-36. PMC: 4276468. DOI: 10.1161/STROKEAHA.114.006982. View

Eikermann-Haerter K, Yuzawa I, Dilekoz E, Joutel A, Moskowitz M, Ayata C . Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy syndrome mutations increase susceptibility to spreading depression. Ann Neurol. 2011; 69(2):413-8. PMC: 3058390. DOI: 10.1002/ana.22281. View

Fridman S, Sposato L . Migraine with visual aura, incident AF, and stroke risk: Is migraine with aura an embolic TIA?. Neurology. 2018; 91(24):1077-1078. DOI: 10.1212/WNL.0000000000006637. View

Macclellan L, Giles W, Cole J, Wozniak M, Stern B, Mitchell B . Probable migraine with visual aura and risk of ischemic stroke: the stroke prevention in young women study. Stroke. 2007; 38(9):2438-45. DOI: 10.1161/STROKEAHA.107.488395. View

10.

. Headache Classification Committee of the International Headache Society (IHS) The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38(1):1-211. DOI: 10.1177/0333102417738202. View

11.

Couch J, Hassanein R . Platelet aggregability in migraine. Neurology. 1977; 27(9):843-8. DOI: 10.1212/wnl.27.9.843. View

12.

Metso T, Tatlisumak T, Debette S, Dallongeville J, Engelter S, Lyrer P . Migraine in cervical artery dissection and ischemic stroke patients. Neurology. 2012; 78(16):1221-8. DOI: 10.1212/WNL.0b013e318251595f. View

13.

De Giuli V, Grassi M, Locatelli M, Gamba M, Morotti A, Bonacina S . Cardiac sources of cerebral embolism in people with migraine. Eur J Neurol. 2020; 28(2):516-524. DOI: 10.1111/ene.14556. View

14.

Xu Z, Li Y, Tang S, Huang X, Chen T . Current use of oral contraceptives and the risk of first-ever ischemic stroke: A meta-analysis of observational studies. Thromb Res. 2015; 136(1):52-60. DOI: 10.1016/j.thromres.2015.04.021. View

15.

Vinciguerra L, Cantone M, Lanza G, Bramanti A, Santalucia P, Puglisi V . Migrainous Infarction And Cerebral Vasospasm: Case Report And Literature Review. J Pain Res. 2019; 12:2941-2950. PMC: 6814312. DOI: 10.2147/JPR.S209485. View

16.

Tietjen G, Khubchandani J . Vascular biomarkers in migraine. Cephalalgia. 2014; 35(2):95-117. DOI: 10.1177/0333102414544976. View

17.

Celikbilek A . Migraine symptoms and the role of autonomic dysfunction. Eur J Neurol. 2020; 27(12):e97. DOI: 10.1111/ene.14504. View

18.

Eikermann-Haerter K, Ayata C . Cortical spreading depression and migraine. Curr Neurol Neurosci Rep. 2010; 10(3):167-73. DOI: 10.1007/s11910-010-0099-1. View

19.

Sacquegna T, Andreoli A, Baldrati A, LAMIERI C, Guttmann S, De Carolis P . Ischemic stroke in young adults: the relevance of migrainous infarction. Cephalalgia. 1989; 9(4):255-8. DOI: 10.1046/j.1468-2982.1989.0904255.x. View

20.

Martinez-Majander N, Artto V, Ylikotila P, Von Sarnowski B, Waje-Andreassen U, Yesilot N . Association between Migraine and Cryptogenic Ischemic Stroke in Young Adults. Ann Neurol. 2020; 89(2):242-253. DOI: 10.1002/ana.25937. View