We searched PubMed without language restrictions up to October, 2011, with the following search terms: “migraine AND (stroke OR cerebrovascular disease OR brain infarct OR ischaemia OR transient ischaemic attack)” and “migraine AND cortical spreading depression”. Furthermore, the reference lists of identified articles were cross-examined for relevant papers. The quality of the identified studies was judged on the basis of the study design (randomised trial, systematic review, prospective study,
ReviewMigraine and stroke: a complex association with clinical implications
Introduction
The existence of a link between migraine and stroke has long been suspected. Since the report by Féré, one of Charcot's residents, of a patient with migraine who died after 2 months of headache, visual disturbances, and hemiplegia,1 multiple cases of “migrainous stroke” or even “fatal migraine” have been reported, pointing to a unidirectional causal relation, whereby migraine increases risk of stroke.2 However, over the past 20 years, this association has increasingly been shown to be far more complex than previously recognised. For example, evidence has accumulated that a number of vascular disorders can cause both migraine with aura and ischaemic stroke3, 4, 5, 6 and that cerebral ischaemia can trigger migraine aura.7 Furthermore, MRI studies have shown an association between migraine and various types of subclinical ischaemic brain lesion,8, 9, 10, 11, 12 and epidemiological studies have reported an association of migraine, mostly with aura, not only with ischaemic stroke,13, 14, 15 but also with haemorrhagic stroke,16, 17 coronary events,18, 19 and even all-cause mortality.20
Migraine and stroke differ widely with regard to sex preponderance, age of onset, clinical presentation, outcome, and treatment. Another major difference is that the diagnosis of migraine remains entirely clinical whereas that of stroke is based on both clinical symptoms and neuroimaging. The International Headache Society (IHS)21 has proposed strict diagnostic criteria for migraine and its two main types: migraine without aura (MO), in patients who have had only migraine without aura; and migraine with aura (MA), in patients who have had at least two migraine attacks with aura, regardless of how many attacks they have had without aura. MA occurs in about a third of people with migraine, and of those with MA up to 33% have both types of attack.22 Neuroimaging allows the diagnosis of the two main types of stroke: ischaemic stroke, which accounts for 80% of cases; and haemorrhagic stroke, which occurs in 20% of cases. However, extensive investigations are necessary to establish the cause of stroke, which remains unidentified in up to 40% of cases, particularly in young patients.23 Despite these differences, a relation between migraine and stroke seems likely because they both involve the neuronal and vascular systems of the brain, which are physiologically linked by the mechanisms of neurovascular coupling.24
In this Review, we describe the evidence linking migraine and stroke, discuss how our understanding of the pathophysiology of migraine relates to the risk of ischaemic stroke, and highlight the importance of distinguishing between migraine as a primary disorder and migraine as a consequence of other disorders that could, by themselves, lead to ischaemic stroke. We also discuss the diagnostic and therapeutic implications of the association between migraine and stroke.
Section snippets
Epidemiological studies
Over the past 40 years, many clinic-based and population-based studies13, 14, 15, 25, 26, 27 and three meta-analyses28, 29, 30 have been undertaken to assess the association of migraine and migraine characteristics with the risk of ischaemic stroke. These studies consistently show that migraine roughly doubles the risk of ischaemic stroke (table). In most studies, particularly those with a prospective design, the association is apparent mainly in patients with MA, with a relative risk of
Cortical spreading depression and aura
The migrainous aura is central to the association between migraine and stroke since the increased risk of ischaemic stroke is doubled only in MA. There is now clinical and experimental evidence that the biological substrate for aura is cortical spreading depression (CSD). Lashley, who described his own migraine aura, was the first to suspect a slow cortical phenomenon underlying the symptoms of aura in human beings.50 The link between migraine aura and CSD was proposed a few years later, in
Practical implications of the migraine–stroke association
The complex relations between migraine and stroke, together with the purely clinical diagnosis of migraine and the potentially severe consequences of a stroke event, have important diagnostic and therapeutic implications in clinical practice. The first implication relates to diagnostic issues. Clinicians should be very careful not to overdiagnose migraine in patients who have other types of headache, which can also carry a risk of stroke and require different investigations and treatment. This
Conclusions
Migraine and stroke share common and complex underlying physiological processes, which might explain the association between these common, heterogeneous neurovascular disorders that has emerged in many studies of patients with migraine. The strongest available evidence and pathophysiological considerations show that MO—the most common type of migraine—is not a risk factor for stroke. By contrast, the risk of ischaemic stroke is doubled in MA, particularly in young women, but whether this
Search strategy and selection criteria
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