The patent foramen ovale-migraine connection: a new perspective to demonstrate a causal relation

In the last ten years a considerable bulk of evidence has accumulated on the relationship between migraine, particularly migraine with aura, and atrial septal defects, particularly patent foramen ovale (PFO). The increased frequency of PFO in migraine with aura, which almost parallels that found in stroke of unknown cause, the fact that in migraine patients PFO tends to be larger than in non-migraine controls and some positive results on migraine severity obtained after PFO closure have spurred speculation on a possible causal relationship. By applying the criteria proposed by Bradford-Hill to establish causality between associated phenomena, we try to demonstrate that PFO is not just a further example of migraine comorbidity but exerts a causal effect at least in the triggering of aura.