[Cortical spreading depression and molecular genetics in migraine].

Cortical spreading depression (CSD) is a slowly propagated wave of depolarization of neurons and glial cells, followed by a subsequent sustained suppression of spontaneous neuronal activity. Functional imaging studies of migraine patients have shown dramatic changes in blood flow and brain activity whose characteristics are similar to those of CSD, implicated in migraine visual aura. Although the trigeminal nerve innervates the meninges and participates in the genesis of migraine headaches, triggering mechanisms remain controversial and poorly understood. It is demonstrated by animal models that CSD activates trigeminovascular afferents and evokes a series of cortical meningeal and brainstem events consistent with the development of headache. Three familial hemiplegic migraine, a rare monogenic subtype of migraine with aura, genes have been identified, which all encode ion transporters, suggesting that disturbances in ion and neurotransmitter balances in the brain are responsible for this migraine type. Additional molecular insight into the pathophysiology of migraine may come from other monogenic syndromes such as CADASIL, RVCL. Several genetic associations with candidate migraine genes like ESR1, MTHFR, and INSR, have been convincingly replicated. The genome-wide association studies may be a successful strategy toward identification of migraine susceptibility genes.