Migraña

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Lancet Neurol. Author manuscript; available in PMC 2010 August 16.

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Published in final edited form as:
Lancet Neurol. 2010 March ; 9(3): 309–317. doi:10.1016/S1474-4422(09)70358-8.

Migraine aura pathophysiology: the role of blood vessels and
microembolisation
Turgay Dalkara, MD, Ala Nozari, MD, and Michael A Moskowitz, MDStroke and Neurovascular Regulation Laboratory, Department of Radiology (T Dalkara MD, A
Nozari MD, M A Moskowitz MD) and Department of Anesthesia and Critical Care (A Nozari),
Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA; and
Department of Neurology, Faculty of Medicine, Hacettepe University, 06100, Ankara, Turkey (T
Dalkara)

Abstract
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Migraine attacks with auras are sometimes associated with underlying hereditary or acquired
cerebrovascular disorders. A unifying pathophysiological explanation linking migraine to these
conditions has been diffcult to identify. On the basis of genetic and epidemiological evidence, we
suggest that changes in blood vessels, hypoperfusion disorders, and microembolisation can causeneurovascular dysfunction and evoke cortical spreading depression, an event that is widely
thought to underlie aura symptoms. In fact, recent experimental data have indicated that focal,
mild, and transient ischaemia can trigger cortical spreading depression without an enduring tissue
signature. Although migraine with aura has many causes (eg, neuronal network excitability), it
seems thatmigraine and stroke might both be triggered by hypoperfusion and could therefore exist
on a continuum of vascular complications in a subset of patients who have these hereditary or
acquired comorbid vascular conditions.

Introduction

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Migraine headache can occur as a comorbidity of ischaemic stroke, carotid or vertebral
artery dissection, arteriovenous malformations,cerebral auto somal dominant arteriopathy
with subcortical infarcts and leukoencephalopathy (CADASIL syndrome), or platelet
disorders (eg, thrombocytosis) among other disorders (panel).1–5 Although diffcult to
identify a unifying hypothesis linking these disorders to migraine pathogenesis, a
disturbance within brain vessels might be common to a subset of patients who have migraine
with aura.Migraine with aura has been identified as an independent risk factor for ischaemic
stroke6 and possibly for white matter hyperintensities, suggesting common
pathophysiological mechanisms that implicate the neurovascular unit.7,8 Although several
possibilities can explain the comorbidity of migraine and vascular diseases (eg, shared
mutations or a consequence of repeated migraine attacks), anemerging hypothesis, which
we find persuasive, places stroke and migraine on a continuum of vascular complications
caused by, for example, focal and transient hypoperfusion. Recent experimental data in mice
indicate that cerebral microembolism triggers cortical spreading depression (CSD), a
biological substrate for migraine aura, without causing requisite tissue injury.9 Although theCorrespondence to: Michael A Moskowitz, Stroke and Neurovascular Regulation Laboratory, Massachusetts General Hospital, 149
13th Street, Room 6403, Charlestown, MA 02129, USA moskowitz@helix.mgh. harvard.edu.
Contributors All authors contributed to the concept and design of this paper, acquisition, analysis, and interpretation of data, drafting
of the paper, critical revision, and administrative,technical, and material support. TD prepared the first draft and MAM supervised the
preparation of this paper.
Conflicts of interest We have no conflicts of interest.

Dalkara et al.

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brain’s vulnerability to injury is well recognised, it is only with the help of emerging data
from experiments in animals that we are now able to examine the possibility that...