Patent foramen ovale and migraine

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-In-Chief: Priyamvada Singh, M.B.B.S. [2]; Assistant Editor-In-Chief: Kristin Feeney, B.S. [3]

Overview

Patent foramen ovale has been associated with migraine headaches, particularly those with an aura. However, patent foramen ovale's role as a causative factor for migraine headaches is still not clear. The beneficial effect of patent foramen ovale closure in patients with migraine is controversial. Some smaller studies have shown some benefits of these closure, however, the large randomized double blinded 'MIST' trial failed to show any difference in cessation of migraines, between the percutaneous and the sham group.

Trial supportive data for Supporting the Association Between a Patent foramen ovale and migraine

  • A recent metanalysis including 18 studies and comprising 2636 patients, found a low-grade positive association between migraines in patients with patent foramen ovale (PFO) [1]. However, the results of this study should be interpreted with cautions, as the individual studies included for the metanalysis were quite heterogeneous. There was some positive association seen in patients of migraine with aura {odds ratio of 3.21(95% CI 2.38–4.70)} but no such relation was seen for patients of migraine without aura
  • Similar results were shown in a large (1101 subjects) multiethnic, elderly, population-based cohort as no increased association was seen between patent foramen ovale (PFO) and migraine [3].

Genetics

A study of 71 relatives of 20 probands, found a dominant inheritance pattern in atrial shunts (patent foramen ovale and atrial septal defects). This was found to be linked to inheritance of migraine with aura in some families [4].

Impact of percutaneous closure of patent foramen ovale on migraine

The famous and controversial MIST trial (Migraine intervention with STARFlex Technology trial), was a large, randomized, prospective, double-blinded trial that intended to compare the impact of percutaneous closure of patent foramen ovale to a sham procedure, on the episodes of migraine [5], [6]. The primary end point of the study was complete cessation of migraines headache 91 to 180 days after the procedure. (i.e. cure) and the secondary end point was a 50% reduction in migraine days. The study came out to be negative (primary end-point was not achieved i.e. total cessation of migraine episodes at 91-180 days was not different in the two study arms). Nevertheless, the secondary end-point was achieved and 50% reduction in migraine days, was seen in 42% of patients in the device arm versus 23% in the sham arm (P=0.038). Despite, the fact that the study was negative, it helped the future studies in deciding their endpoints as reduction in migraine frequency rather than complete cessation. Also, the statistically significant secondary end-point suggested that patent foramen ovale (PFO) closure could be beneficial in migraine patients refractory to medications.

References

  1. Schwedt TJ, Demaerschalk BM, Dodick DW (2008). "Patent foramen ovale and migraine: a quantitative systematic review". Cephalalgia. 28 (5): 531–40. doi:10.1111/j.1468-2982.2008.01554.x. PMID 18355348.
  2. Garg P, Servoss SJ, Wu JC, Bajwa ZH, Selim MH, Dineen A; et al. (2010). "Lack of association between migraine headache and patent foramen ovale: results of a case-control study". Circulation. 121 (12): 1406–12. doi:10.1161/CIRCULATIONAHA.109.895110. PMID 20231534.
  3. Rundek T, Elkind MS, Di Tullio MR, Carrera E, Jin Z, Sacco RL; et al. (2008). "Patent foramen ovale and migraine: a cross-sectional study from the Northern Manhattan Study (NOMAS)". Circulation. 118 (14): 1419–24. doi:10.1161/CIRCULATIONAHA.108.771303. PMC 2737546. PMID 18794393.
  4. Wilmshurst PT, Pearson MJ, Nightingale S, Walsh KP, Morrison WL (2004). "Inheritance of persistent foramen ovale and atrial septal defects and the relation to familial migraine with aura". Heart. 90 (11): 1315–20. doi:10.1136/hrt.2003.025700. PMC 1768524. PMID 15486131.
  5. Carroll JD (2008). "Migraine Intervention With STARFlex Technology trial: a controversial trial of migraine and patent foramen ovale closure". Circulation. 117 (11): 1358–60. doi:10.1161/CIRCULATIONAHA.107.758748. PMID 18332260.
  6. Dowson A, Mullen MJ, Peatfield R, Muir K, Khan AA, Wells C; et al. (2008). "Migraine Intervention With STARFlex Technology (MIST) trial: a prospective, multicenter, double-blind, sham-controlled trial to evaluate the effectiveness of patent foramen ovale closure with STARFlex septal repair implant to resolve refractory migraine headache". Circulation. 117 (11): 1397–404. doi:10.1161/CIRCULATIONAHA.107.727271. PMID 18316488.

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