Familial Hemiplegic Migraine - Causes

Causes

See the equivalent section in the main migraine article.

It is believed that FHM mutations lead to migraine susceptibility by lowering the threshold for cortical-spreading-depression generation. The FHM1 and FHM3 mutations occur in ion channels expressed in neurons. These mutations may lead to both the hyper and hypoexcitable neurons that might underlie cortical-spreading-depression. It is even less clear how the mutations seen in FHM2 patients might lead to FHM symptoms as the gene mutated in FHM2 is expressed primarily in astrocytes. One proposal states that the depolarization of astrocytes caused by haploinsufficiency of the ATP1A2 Na+/K+-ATPase causes increased release of compounds such as adenosine from astrocytes. These compounds then interact with neighboring neurons, altering their excitability and leading to cortical-spreading-depression and migraine.