Migraine mechanisms are discussed in relation to familial hemiplegic migraine (FHM) genotypes by investigators from the Massachusetts General Hospital, Boston, and Universities in Ankara, Turkey. FHM, a dominantly inherited disease, is characterized by sustained attacks of visual, somatosensory, and aphasic auras followed by motor weakness or paralysis. FHM type 1 mutation exhibits cerebellar signs, but otherwise types 1 and 2 FHM cannot be easily distinguished phenotypically. Cortical spreading depression (CSD) causes migraine aura, and glutamate triggers CSD. FHM mutations render the brain more susceptible to prolonged CSD by excessive synaptic glutamate release (type 1) or decreased removal of glutamate and K from the synaptic cleft (type 2). [1]

COMMENT. Migraine pathogenesis and possible mechanisms of action of preventive therapies are reviewed by Welch KMA. [2]. A cerebral cortical origin of migraine aura, cortical hyperexcitability and CSD, and the trigeminovascular system and its central projections are involved in the migraine attack. Progressive damage to the periaqueductal gray matter (PAG) by iron deposition may explain change in phenotypic expression and why episodic migraine becomes chronic over time in some patients. Antimigraine mechanisms include Na channel blockade (amitryptyline), intracellular Ca modulation (gabapentin), blockade of NMDA receptors (magnesium), aminergic-mediated modulation (propranolol), GABA inhibition potentiation (topiramate), and GABA-mediated inhibition of cell excitation (valproate).