Migraine With Aura: A Vicious Cycle Perpetuated by Potassium‐lnduced Vasoconstriction

Abstract

Two hypotheses have dominated attempts to understand the etiology of migraine with aura or classic migraine; the vascular spasm model proposed by Wolff and colleagues, and the spreading cortical depression hypothesis. Neither can provide a fully satisfactory explanation for the syndrome, however. We propose that classic migraine is both spreading cortical depression and localized ischemia linked in a vicious cycle by potassium induced vasoconstriction. The cycle can be initiated by any event which raises the local cortical ECF potassium concentration to approximately 20 mM. Such an event could be a localized burst of activity of a group of cells, localized metabolic impairment, or a transient reduction in blood flow to a region of the cortex. Once this level of potassium concentration is reached, it may result in localized depolarization of neurons, releasing more potassium into the ECF. Glial siphoning can distribute the potassium preferentially toward the blood vessels in the area, leading to an elevation in potassium concentration in the ECF surrounding the vascular smooth muscle of the arterioles. Above approximately 15 mM, vascular smooth muscle increases its tension in response to elevations in potassium. Therefore, as cortical ECF potassium concentration rises above 15 to 20 mM, localized vasoconstriction occurs, thereby reducing both the supply of oxygen for aerobic metabolism and the removal of potassium in the blood. Under these conditions, the effectiveness of the mechanisms which control potassium concentration is impaired and unable to prevent additional elevations in potassium. As the concentration continues to rise, vasoconstriction becomes more intense, perpetuating the cycle that results in localized depression of cortical neuronal activity and ischemia. The condition is propagated to adjacent regions of the cortex by diffusion and glial-mediated spread of potassium. In many respects, the hypothesis unites the vascular spasm and spreading depression models. If verified, it may provide insight into the causes of classic migraine as well as give direction toward development of effective therapies.

Pathophysiology of the migraine aura

“…Propagation of CSD is totally independent of the vascular reaction: cortical, hippocampal, cerebellar and retinal nervous tissue support CSD perfectly well in vitro (BureS et al, 1974;Martins-Ferreira, 1984;Do Carmo, 1992). Therefore, it is questionable whether or not CSD sets up a cycle of potassium-induced vasoconstriction of importance for its propagation (Young and Van Vliet, 1992). During return to normal of ionic changes, rCBF increases by ~ 100% in anaesthetized animals (Leao, 1944ft;Lauritzen, 1987a), simultaneously with the release of lactate to the brain interstitial fluid (Scheller et al, 1992).…”

Perceived Scintillation Rate of Migraine Aura

“…Because scintillation or flicker is such a constant aspect of migraine aura reports, any satisfactory neural network model of the aura process will have to include a mechanism to account for this temporal oscillation. Yet to date, the few models in the literature have not attempted to incorporate this aspect of the aura phenomenology 13,14 . A prerequisite for doing so is a reliable objective measure of perceived flicker rate assessed in a broad sample of migraineurs.…”

“…Yet to date, the few models in the literature have not attempted to incorporate this aspect of the aura phenomenology. 13,14 A prerequisite for doing so is a reliable objective measure of perceived flicker rate assessed in a broad sample of migraineurs.…”