Migraine and Ischaemic Heart Disease and Stroke: Potential Mechanisms and Treatment Implications

Abstract

The migraine-ischemia relationship is best understood in the context of the pathophysiology of migraine. Potential mechanisms of migrainous infarction (stroke occurring during migraine) include vasospasm, hypercoagulability, and vascular changes related to cortical spreading depression. Stroke occurring remote for the migraine attack may be related to arterial dissection, cardioembolism, and endothelial dysfunction. Endothelial dysfunction, a process mediated by oxidative stress, may be a cause or a consequence of migraine, and explain the relationship of migraine to vascular factors and ischemic heart disease. It remains uncertain whether stroke or myocardial infarction can be prevented by migraine prophylaxis, endothelial repair, platelet inhibition, or a combination of these strategies. Although triptans are generally considered safe for use in migraine, caution is warranted in those with multiple vascular risk factors. Known vascular disease is a contraindication to triptan use.

Migraine and Stroke: What’s the Link? What to Do?

“…Also, it plays a role in the pathogenesis of ischemic stroke, intracranial hemorrhage, subarachnoid hemorrhage, traumatic brain injury, transient global amnesia, and some other diseases [45–47]. CSD is a potent, self- propagating, short-lasting depolarization wave that moves across the cortex at a rate of 3–5 mm/min [48]. By activation of metalloproteinases, CSD changes the permeability of the blood–brain barrier [49].…”

Genetics of migraine in the age of genome-wide association studies

“…For example, migraineurs carry an approximately twofold increased risk for ischemic stroke compared to non-migraineurs [38], some vasculopathies are frequently observed among migraineurs such as livedo reticularis [39] and Sneddon’s syndrome [40], and altered vascular reactivity can be found among young migraineurs even in the absence of other disorders [41]. These findings may be linked to oxidative stress causing endothelial dysfunction [42]. Specifically, certain gene variants in the methylenetetrahydrofolate reductase gene ( MTHFR 677C>T polymorphism) and angiotensin-converting enzyme gene ( ACE D/I polymorphism) appear to importantly contribute to the vascular oxidative stress response [42].…”

“…These findings may be linked to oxidative stress causing endothelial dysfunction [42]. Specifically, certain gene variants in the methylenetetrahydrofolate reductase gene ( MTHFR 677C>T polymorphism) and angiotensin-converting enzyme gene ( ACE D/I polymorphism) appear to importantly contribute to the vascular oxidative stress response [42]. Consequently, an association between the MTHFR 677C>T and ACE D/I polymorphisms with migraine has been suggested [42].…”

Migraine and Coronary Artery Disease: An Open Study on the Genetic Polymorphism of the 5, 10 Methylenetetrahydrofolate (MTHFR) and Angiotensin I-Converting Enzyme (ACE) Genes

“…In addition, migrainous infarcts provoked by a severe hypoperfusion during a migraine attack with aura are very rare and likely to be over-diagnosed [2]. Finally, most ischaemic strokes occur between attacks and not during or shortly after a migraine attack with aura [2,5].…”

“…This process induces an efflux of excitatory amino acids from nerve cells, enhanced energy metabolism, and changes in genes, growth factors, neurotransmitters, neuromodulators and inflammatory mediators. Microvascular changes, marked by a brief cortical spreading hyperemia, followed by a longer lasting cortical spreading oligemia, have been observed during the phase of cortical neurons depression [5,6].…”