More than two decades ago, I elucidated a fundamental clinico theoretical principle for the understanding of migraine linked physiologic mechanisms that has well stood the test of time, technology and biologic commonsense: “No systemic influence can explain the characteristic lateralizing headache of migraine, unilateral, bilateral, side shifting or side locked”.3 Over the last fifty years, some of the “systemic” influences believed to play key pathogenetic roles in migraine include serotonin, platelets, catecholamines, calcitonin gene related peptide, magnesium depletion, stress, post stress state, and recurrent micro thrombo embolisms across the patent foramen ovale at the level of the cardiac inter atrial septum. 4,5,6 https://www.newnfljerseysusa.com Little vertical and biologically plausible robust generalizable progress, however, has been made in gestalt understanding of the disorder well into the 21st century.7 Trait linked genetic association is also a “systemic” influence. Ion transporters as well as the three main causative genes CACNA1A, ATP1A2 and SCN1A which encode for ion transporters1 do not offer clues to the mechanistic physiological basis of lateralizing headache.8.
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