Migraine Headache: Clinical Association With PFO and Observational Studies

Abstract Migraine, according to the International Headache Society, is a primary headache disorder and is classified as migraine with (MWA) or without aura (MWoA). Rarely migraine aura, with or without headache, can be secondary and may occur as the first manifestation of cerebral ischemia or repeatedly as a symptom of several neurological disorders. For both primary and secondary aura, cortical spreading depolarization has been shown to be the neurophysiological substrate that explains the phenotypic similarities. MWA has also been shown to double the risk of stroke though rare in absolute terms. A potential mechanism may be a link with patent foramen ovale (PFO) that is frequently present in stroke without other identifiable causes or in migraine stroke. Case control studies have demonstrated a higher prevalence of migraine in individuals with PFO compared to controls, and a higher prevalence of PFO in individuals with migraine, indicating an association of migraine and PFO. Furthermore, PFO closure may reduce MWA attacks according to some case control studies. This supports the hypothesis that microemboli may trigger cortical spreading depolarization and migraine aura, while PFO closure may reduce MWA attacks. Another observational study indicated that PFO closure reduces migraine headaches in PFO migraine patients who respond favorably to P2Y12 platelet inhibitors. However, both hypotheses have yet to be proven by randomized controlled trials focusing, unlike previous trials, on migraine patients who suffer an aura in most or all of their attacks or those who experience headache reduction with P2Y12 platelet inhibitors.