Perhaps the most heavily investigated potential mecha- nistic link between migraine and stroke is the association of migraine and PFO. Initial studies found that PFOs are more common in young patients with cryptogenic stroke and those particularly migraine with aura.608 The speculated relationship between PFO and migraine includes microemboli that flow through the PFO, causing brain isch- emia and thereby triggering migraine.609 The Migraine Intervention with STARFlex Technology (MIST) trial, a randomized, double-blind, sham-controlled trial, showed no benefit of PFO closure on the cessation of migraine headaches There is much controversy concerning the results of this trial,611 and it was not designed to evaluate the primary prevention of stroke in patients with migraines with aura. Furthermore, recent studies have found a lack of association between migraine and PFO in a large population-based study among elderly indi- in a hospital-based case-control study,613 and in a placing some doubt on whether PFO has a causal role in migraines. In terms of primary prevention of stroke in patients with migraine, aspirin reduced risk of ischemic stroke (RR, 0.76; 95% CI, 0.63 0.93) but not other clinical atherothrombotic end points in the WHS group.615 In subgroup analyses, the pro- tective effect of aspirin on ischemic stroke was similar among women with or without migraines.615 However, women with migraine with aura on aspirin had an increased risk of MI (RR, 3.72; 95% CI, 1.39 9.95), primarily women with history of smoking or hypertension.615 The clinical significance of this increased risk for this subgroup is unclear because of small numbers. Migraine: Summary and Gaps Migraine headache, particularly migraine with aura, appears to be associated with stroke in women <55 years of age, but the mechanisms linking these 2 conditions remain unclear. The stroke risk of migraine in men appears to be less estab- lished. 