Patterns of Cerebral Integration Indicated by the Scotomas of Migraine

Role of cortical spreading depression in the pathophysiology of migraine

“…Most common is a visual aura, a scintillating scotoma, in which a spot of fl ickering light appears near the center of the visual fi eld and then gradually expands outward [8][9][10] .…”

“…In 1941, Karl Spencer Lashley [10] , a psychologist at Harvard University, described his own experience of a visual aura, where a scotoma started as a small area, then gradually enlarged, and spread toward the periphery of the visual fi eld, and the propagation rate was estimated to be 3 mm/min or less. Three years later, Aristides Leao [1] reported the phenomenon of cortical SD, characterized by a self-propagating wave of depolarization that begins in the neuronal/glial cells of local areas of the brain and subsequently spreads in all directions at a rate of ~3 mm/ min.…”

“…The similarity of Lashley's migraine aura and Leao's cortical SD was first picked up by Milner in 1958 [7] , and further investigated by Olesen in the 1980s, as described above. Based on both Lashley's description of a spreading scotoma [10] and Leao's findings of cortical SD [1] , the pathogenic theories changed from primary vascular to primary neural mechanisms.…”

“…The rate of spreading correlates with the observed spread of the aura of a classical migraine [7] , which is characterized by a spot of fl ickering light that appears near the center of the visual field and then gradually expands outward [8][9][10] . Recently, cortical SD has been hypothesized to be the initial event involved in migraine headaches.…”

“…The similarity of Lashley's migraine aura and Leao's cortical SD was first picked up by Milner in 1958 [7] , and further investigated by Olesen in the 1980s, as described above. Based on both Lashley's description of a spreading scotoma [10] and Leao's findings of cortical SD [1] , the pathogenic theories changed from primary vascular to primary neural mechanisms.In the 1980s, Moskowitz and colleagues reconciled the primary vascular and primary neural views and proposed the trigeminovascular theory [11,12] . They hypothesized that some unknown stimulation, probably the cortical SD, depolarizes the trigeminocervical nerve terminals innervating the meninges, and pro-inflammatory peptides such as substance P and CGRP are released from the primary meningeal afferents, which further induce vasodilation and plasma protein extravasation.…”