Spreading Depolarization May Link Migraine and Stroke

Abstract

Migraine increases the risk of stroke, particularly in young and otherwise healthy adults. Being the most frequent neurological condition, migraine prevalence is on a par with that of other common stroke risk factors, such as diabetes or hypertension. Several patterns of association have emerged: (1) migraine and stroke share a common association (eg, vasculopathies, patent foramen ovale, or pulmonary A-V malformations); (2) injury to the arterial wall such as acute arterial dissections can present as migraine aura attacks or stroke; (3) strokes rarely develop during a migraine attack, as described for "migrainous stroke." Increasing experimental evidence suggests that cerebral hyperexcitability and enhanced susceptibility to spreading depolarization, the electrophysiologic event underlying migraine, may serve as a mechanism underlying the migraine-stroke association. Mice carrying human vascular or neuronal migraine mutations exhibit an enhanced susceptibility to spreading depolarization while being particularly vulnerable to cerebral ischemia. The severe stroke phenotype in migraine mutant mice can be prevented by suppressing spreading depolarization. If confirmed in the clinical setting, inhibiting spreading depolarization might protect migraineurs at stroke risk as well as decrease attacks of migraine.

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

“…Among suggested theories of migraine–stroke relation are cortical spreading depression, vasoconstriction, endovascular dysfunction, increased prevalence of vascular risk factors, shared genetic defects, cervical artery dissection, cardiac abnormalities including patent foramen ovale (PFO), neurogenic inflammation, and hypercoagulability [11, 19, 37–43]. …”

“…In addition, in vulnerable tissue, severe hypoperfusion may follow CSD, consequently leading to enlargement of ischemic lesion [54]. Mice with human migraine mutations represent an increased vulnerability to CSD and cerebral ischemia [37, 53]. It may be speculated that CSD could be the mechanism causing the ischemic lesion in the vulnerable brain.…”

Spreading Depolarization May Link Migraine, Stroke, and Other Cardiovascular Disease

“…The mechanisms underlying the relationship between migraine and stroke are still unclear, and their elucidation may provide the basis to explain the vascular risk associated with migraine. Dr. Eikermann‐Haerter proposes that cortical hyperexcitability may be a mechanism common to migraine pathogenesis and to the increased risk of cerebral ischemia in migraineurs . As reported by the author, the genetic mouse models expressing migraine mutations (eg, familial hemiplegic migraine 1 and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) show a faster onset of ischemia‐triggered spreading depolarization; an increased frequency of ischemic depolarization; enlarged infarcts with worse neurological outcomes (which could be prevented by anti‐excitatory treatment); and more severe spreading of depolarization‐induced oligemia .…”

“…Dr. Eikermann‐Haerter proposes that cortical hyperexcitability may be a mechanism common to migraine pathogenesis and to the increased risk of cerebral ischemia in migraineurs . As reported by the author, the genetic mouse models expressing migraine mutations (eg, familial hemiplegic migraine 1 and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) show a faster onset of ischemia‐triggered spreading depolarization; an increased frequency of ischemic depolarization; enlarged infarcts with worse neurological outcomes (which could be prevented by anti‐excitatory treatment); and more severe spreading of depolarization‐induced oligemia . While it is known that brain ischemia can induce spreading depression, triggers for the spontaneously occurring spreading depression in migraine remain uncertain.…”

“…We read with interest the paper by Katharina Eikermann‐Haerter about spreading depolarization as the possible link between migraine and stroke . The mechanisms underlying the relationship between migraine and stroke are still unclear, and their elucidation may provide the basis to explain the vascular risk associated with migraine.…”