Arguments against the role of cortical spreading depression in migraine.

Cortical spreading depression (CSD) is a wave of increased electrocortical activity and vasodilation, followed by sustained decreased activity and prolonged vasoconstriction. Although the discovery of CSD has been ascribed to Leão, rather than vasoconstriction, he only observed a depression of neural activity combined with vasodilation, with much weaker stimulation than used by his followers. There is a longstanding belief that CSD underlies migraine aura, with its positive symptoms such as mosaic patterns and its negative symptoms such as scotoma, and a similar propagation speed and vasoreaction pattern. However, there are many arguments against this theory. CSD is difficult to evoke in man, and electroencephalography (EEG) readings are not flattened during migraine (as opposed to EEG during CSD). Moreover, in contrast to CSD, migraine can occur bilaterally, and is not accompanied by a disrupted blood-brain barrier, increased cerebral metabolism, or cerebral cell swelling. Calcitonin gene-related peptide, which is thought to be characteristic of migraine pain, is increased in the blood from the external jugular vein during migraine in humans, but not during CSD in cats or rats. Moreover, CSD does not explain the appearance of premonitory symptoms or allodynia, long before the actual onset of aura. In addition, there is a variation in the pain mechanisms of migraine and CSD, and in their reaction to transcranial magnetic stimulation and several pharmacologic interventions. Finally, the origin of putative CSD in migraine is currently unknown.