Direct electrophysiological evidence that spreading depolarization-induced spreading depression is the pathophysiological correlate of the migraine aura and a review of the spreading depolarization continuum of acute neuronal mass injury

Abstract

Spreading depolarization is observed as a large negative shift of the direct current potential, swelling of neuronal somas, and dendritic beading in the brain's gray matter and represents a state of a potentially reversible mass injury. Its hallmark is the abrupt, massive ion translocation between intraneuronal and extracellular compartment that causes water uptake (= cytotoxic edema) and massive glutamate release. Dependent on the tissue's energy status, spreading depolarization can co-occur with different depression or silencing patterns of spontaneous activity. In adequately supplied tissue, spreading depolarization induces spreading depression of activity. In severely ischemic tissue, nonspreading depression of activity precedes spreading depolarization. The depression pattern determines the neurological deficit which is either spreading such as in migraine aura or migraine stroke or nonspreading such as in transient ischemic attack or typical stroke. Although a clinical distinction between spreading and nonspreading focal neurological deficits is useful because they are associated with different probabilities of permanent damage, it is important to note that spreading depolarization, the neuronal injury potential, occurs in all of these conditions. Here, we first review the scientific basis of the continuum of spreading depolarizations. Second, we highlight the transition zone of the continuum from reversibility to irreversibility using clinical

Tracking the Migraine Cycle Using Visual Tasks

“…Consequently, adjacent regions of the visual field above and below the horizontal are no longer represented by adjacent areas of the cortex in V2 and V3, yet retinotopy is maintained within each separate quadrant [ 10 , 11 , 12 ]. The classic visual aura has long been attributed to a wave of activity followed by suppressed neuronal activity (spreading depression) that traverses the primary visual cortex, V1, if restricted to one hemifield [ 13 , 14 , 15 , 16 , 17 ]. By extension, if the aura is restricted to a quadrant, it may be attributed to a wave of activity and subsequent neuronal depression that is probably occurring in V2 or V3.…”

Lasting s-ketamine block of spreading depolarizations in subarachnoid hemorrhage: a retrospective cohort study

“…In the context of lesion progression, terminal SD was typically preceded by a temporal cluster of increasingly prolonged SDs that could start up to hours earlier, suggesting a spiraling trend toward increasing risk of injury [10]. By contrast, isolated SD in eloquent and metabolically intact tissue is the pathophysiological correlate of the harmless migraine aura [14, 15]. SD induces tone alterations in resistance vessels, causing either transient hyperemia (normal hemodynamic response) in healthy tissue or severe hypoperfusion (inverse hemodynamic response = spreading ischemia) in tissue at risk for injury [16–18].…”

White Matter Lesions in Migraine

“…77 In addition, a typical sequence of speech and motor deficits characteristic of migraine aura have been observed in a patient with subarachnoid hemorrhage and electrocorticographic evidence for the occurrence of SD and SD-induced spreading depression of activity. 78 Similarly, migraine aura symptoms have been described in patients with reversible cerebral vasoconstriction syndrome. SD is a self-propagating neuronal and glial depolarization wave that spreads at a speed of 2 to 9 mm per minute.…”