Closure of a patent foramen ovale is associated with a decrease in prevalence of migraine
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A patent foramen ovale (PFO) is one of the major causes of right-to-left shunt, and a causal relationship between migraine and a PFO has been suggested.1 We evaluated whether percutaneous closure of a PFO was associated with changes in the prevalence of migraine.
Methods.
Patient selection.
Patients with a PFO who had a paradoxical embolic event or systemic desaturation and who underwent a percutaneous closure in our center between February 1999 and September 2002 were included. The medical files were reviewed. The ethical committee approved the study.
Evaluation of migraine.
A questionnaire was composed in such a way that a neurologist could diagnose migraine with or without aura (MA+ and MA−) according to the criteria of the International Headache Society. The questionnaire was sent to all patients and focused on three periods: 1 year before and 2 months and at least 6 months after percutaneous closure. Two neurologists blinded to the patients’ files diagnosed MA+ and MA−.
Statistical analysis.
Within-patient comparisons of the absence or presence of migraine were performed with the McNemar’s paired χ2 test. Interobserver reliability was evaluated by measuring the kappa coefficient. p Value < 0.05 was considered significant. All statistical analyses were performed with GB Stat software (version 8.0; Dynamic Microsystems, Inc., Silver Spring, MD).
Results.
Patient characteristics.
Seventy-six patients (mean age, 50.7 ± 12.9 years) were selected, and 66 completed the questionnaire. In 57 patients, the period between PFO closure and completing the questionnaire was >6 months. The characteristics of patients who completed the questionnaire are summarized in the table.
Table Characteristics of patients who completed the questionnaire
Prevalence of migraine.
The median time interval between the occurrence of a paradoxical embolic event and the closing procedure was 162 days (range, 0 to 3,613 days). The time between PFO closure and administration of the questionnaire was 579 days (range, 110 to 1,419 days).
Migraine was present in 26 of 66 patients (9 men and 17 women; 39.4%). Twelve (18.2%) had MA+, and 14 (21.2%) had MA−. Two months after closure, the prevalence of MA+ and MA− decreased to 6.1% (4/66) and 6.1% (4/66; p < 0.05 vs before closure). At 6 months or more, the overall prevalence of migraine was 15.8% (9/57; p < 0.05 vs before closure). The prevalences of MA+ and MA− were 5.3% (3/57; p < 0.05 vs before closure) and 10.5% (6/57; p = 0.11 vs before closure). The frequency of migraine attacks also decreased (p < 0.05). Seven patients were taking potential prophylactic migraine drugs 6 months after closure (six, β-blockers; one, calcium antagonists). The kappa coefficient for interobserver reliability for migraine was 0.8 (p < 0.05).
Discussion.
Patients with migraine have a high prevalence of PFO.2 An increased rate of MA+ among stroke patients with PFO was found compared with patients with PFO.2 A causal relationship between PFO and migraine has been proposed. In individuals with a right-to-left shunt, a lower dose of venous trigger substances may be needed to induce migraine because the shunt permits the pulmonary filter to be bypassed.1 Moreover, the prevalence of migraine seems to decrease subsequent to PFO closure in patients with decompression illness.3
We evaluated whether PFO closure in patients who mainly had cryptogenic stroke would be associated with changes in the prevalence of migraine. We found a high rate of migraine in patients with PFO (39.4%) and documented a significant and persistent decrease in prevalence of MA+ ≥6 months after PFO closure. The frequency of migraine attacks also decreased significantly. Our data might fit with the recently reported experience that MA+ decreased after PFO closure.4
The prevalence of migraine also decreases with age; however, we believe that the changes in our study are too pronounced to be explained by the natural history of migraine.5 Most of our patients were treated with low-dose aspirin, which could also influence migraine prophylaxis. The effect of low-dose aspirin, if any, seems to be modest.6 The placebo effect in migraine therapy is potent, but the decrease in prevalence of migraine in our study seems to be larger than reported placebo effect rates of 20 to 40%.7
Nevertheless, this study has important limitations. It is a retrospective, nonrandomized trial of patients selected from a hospital-based database. The questionnaire may be influenced by recall bias.
The prevalence of migraine in patients with a PFO is high. After ≥6 months, percutaneous PFO closure is associated with a decrease in the prevalence of MA+. Whether percutaneous PFO closure has the potential to manage migraine needs to be determined in a prospective randomized trial.
Footnotes
See also page 1399
- Received September 15, 2003.
- Accepted in final form November 13, 2003.
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