Migraine and epilepsy are episodic disorders that share many
clinical features and underlying pathophysiological mechanisms. Cortical
spreading depression (CSD), a wave of profound cellular depolarization, is
believed to underlie migraine aura and to be a trigger for the headache pain in
migraine. However, the initial event preceding CSD is cellular
hyperexcitability associated with localized epileptiform discharges. Glutamate
is a critical mediator of the hyperexcitability in both focal seizures and
migraine. In focal epilepsy, seizure generation and spread is mediated by
synaptically released glutamate acting on AMPA receptors, whereas triggering of
CSD depends on NMDA receptors and spread does not require synaptic
transmission. Some antiepileptic drugs prevent the occurrence of migraine
attacks, supporting the view that neuronal hyperexcitability is an initiating
event.