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Rob C. G. van de Ven, MSc; Simon Kaja, PhD; Jaap J. Plomp, PhD; Rune R. Frants, PhD; Arn M. J. M. van den Maagdenberg, PhD; Michel D. Ferrari, MD, PhD

Arch Neurol. 2007;64(5):643-646.

Migraine is a common, disabling, complex brain disorder, presenting in attacks that may have up to 3 phases: a prodromal phase, the aura phase, and the headache phase. The pathogenesis of the aura and headache phases is reasonably well understood, but the mechanism by which migraine attacks are triggered is unknown. Most likely, migraineurs have a genetically determined reduced threshold for migraine triggers. Identifying "threshold genes" and deciphering their function will help to unravel the triggering mechanisms for migraine attacks. Familial hemiplegic migraine is a rare monogenic subtype of migraine with aura. Three genes have been identified for familial hemiplegic migraine. Recently, knock-in mice carrying human pathogenic FHM1 mutations were generated, which show behavioral, electrophysiological, and neurobiological characteristics in line with prevailing views of migraine physiological processes. Genetic migraine models will be useful in unraveling the triggering mechanisms for migraine attacks and in identifying novel migraine prophylactic targets and therapies.

Author Affiliations: Departments of Human Genetics (Mr van de Ven and Drs Frants and van den Maagdenberg), Neurology (Drs Kaja and Plomp, van den Maagdenberg, and Ferrari), and Neurophysiology (Drs Kaja and Plomp), Leiden University Medical Centre, Leiden, the Netherlands. Dr Kaja is now with Michael Smith Laboratories, The University of British Columbia, Vancouver.

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