Migraine with aura and persistent foramen ovale.

The association between migraine with aura and persistent foramen ovale (PFO), as well as other right-to-left shunts, is described. A hypothesis that might explain this association is discussed. Observational studies suggested that when a PFO is closed patients who have migraine with aura are usually improved. The Migraine Intervention with STARFlex Technology (MIST) Trial was a randomised double-blind trial in patients with severe intractable migraine with aura and a moderate-large PFO that compared implantation of STARFlex devices with the intention of closing their PFO versus a sham procedure. It was hoped that the trial would demonstrate whether PFO closure would cure migraine. A series of problems in design and execution of the trial are discussed.