“One such mutation disrupts the resting membrane potential and increases excitability of membranes; other implicated genes control glutamate release or cycling,” said Dr. Moskowitz. “Most patients expressing these mutations live normally, but some unknown paroxysmal event reduces the threshold to evoke cortical spreading depression and causes the mutation to express itself clinically. We don’t know what or where that switch is. But we probably will find out within the next decade.”
Experiments on mice expressing migraine mutations also indicate that female hormones play a role in modulating susceptibility to cortical spreading depression. “Animal experiments suggest that ovarian hormones determine why females, as opposed to males, have a higher susceptibility to migraine with aura,” Dr. Moskowitz said. “Remove the ovarian hormones and females show the same cortical spreading depression susceptibility as males.”
—Jack Baney