A new Japanese study has demonstrated promising results for transcatheter patent foramen ovale (PFO) closure in treating drug-resistant migraine, with 81% of patients showing significant improvement or complete resolution at 12 months follow-up. The findings, published in Cardiovascular Intervention and Therapeutics, offer hope for patients who have exhausted conventional treatment options.
Study Design and Patient Population
The single-center study included 27 patients with a mean age of 36.4 years, comprising 15 females and 21 patients with migraine with aura. All participants experienced more than two migraine attacks per month despite medication and had confirmed PFO through transesophageal echocardiography. The inclusion criteria required patients to be between 16-69 years old, have resistance to conventional migraine medications including triptans, and show no history of ischemic stroke.
Procedure and Safety Outcomes
All procedures were performed under general anesthesia with transesophageal echocardiographic monitoring using the Amplatzer PFO Occluder. In 26 of 27 cases, a 25-mm device was successfully implanted, with one patient requiring a larger 35-mm occluder due to PFO size. The procedure was completed successfully without complications in all cases, with no observed atrial arrhythmias or cardiac erosion during the 12-month follow-up period.
Efficacy Results Show Strong Response in Aura Patients
The study revealed striking differences in treatment response based on migraine subtype. Among the 21 patients with migraine with aura, 10 (48%) experienced complete resolution of migraine symptoms at one year. In contrast, patients without aura showed a markedly lower response rate, with only one case achieving complete resolution.
The overall success rate of 22 out of 27 patients (81%) experiencing either complete resolution or improvement represents a substantial clinical benefit for this treatment-resistant population. The researchers categorized outcomes into four levels: no change, reduced frequency, improvement with rare attacks not requiring medication, and complete resolution with medication discontinuation.
Clinical Context and Limitations
The study acknowledges several important limitations, including the lack of a control group, small sample size, and potential patient selection bias. The willingness of patients to undergo the procedure and bear the associated costs may have influenced their psychological state and perceived treatment outcomes. Additionally, the temporary use of clopidogrel, which may reduce migraines, could have affected early assessments.
Despite these limitations, the researchers note that transcatheter PFO closure offers a distinct advantage as a single procedure with potential to eliminate migraines, contrasting with ongoing medical treatments that provide symptom relief but require continuous medication.
Broader Implications for Migraine Treatment
Migraine affects 8-13% of adults aged 15 years and older and causes an estimated economic loss of approximately 300 billion yen annually in Japan. While recent advances in CGRP-targeting monoclonal antibodies have revolutionized migraine treatment, cost, administration route, and long-term effects remain important considerations.
The Japanese Headache Society has issued a statement noting that while there is a suspected association between migraine with aura and PFO, the effectiveness of transcatheter closure has not been confirmed through large-scale trials, and the procedure is not currently recommended or covered by health insurance in Japan.
Future Research Directions
The study's findings contrast with three randomized controlled trials conducted in Europe and the United States that failed to demonstrate efficacy as a primary endpoint. The researchers suggest that previous trials may have been limited by factors including inclusion of patients resistant to medical therapy, insufficient sample sizes, and inadequate morphological assessments of PFO.
The emergence of high-risk PFO concepts, including those with atrial septal aneurysm, long tunnel, and large shunt, may provide new insights for patient selection. The study could not conclude whether high-risk PFOs are more common in patients with migraine with aura, but this represents an important area for future investigation.
The researchers emphasize that medical treatment should remain the first choice for migraine management, particularly given recent improvements in CGRP inhibitors. However, for carefully selected patients with drug-resistant migraine, particularly those with aura, transcatheter PFO closure may offer a viable treatment option warranting further investigation through larger, controlled studies.
