Relationship of inflammatory factors with migraine in patients with patent foramen ovale undergoing percutaneous closure

Abstract Background Observational studies have reported the incidental reduction of the frequency and severity of migraine attacks following transcatheter patent foramn ovale (PFO) for established indications. Possible physiologic mechanisms for a relationship between PFO and migraine, if such a link does exist, have been the subject of much speculation, with some researchers suggesting the possible role of PFO as a conduit for the passage of various migraine-inducing inflammatory, vasoactive triggers in cerebral circulation. Purpose The aim of this study was to compare the levels of inflammatory mediators between migraineurs and non –migraineurs and to investigate the impact of PFO closure on the inflammatory state of individuals with migraine and alleviation of migraine symptoms. Methods Forty-five patients (mean age 48.2 ± 10.8 years, 48% male) undergoing percutaneous PFO closure were enrolled in the study. Among them, 15 patients reported recurrent migraine episodes (mean age 46.4 ± 8.90 years, 86% female) while 30 individuals (mean age 49 ± 12.32 years, 70% male) were non-migraineurs. White blood cell count, C-reactive protein (CRP), ferritin and d-dimers levels, as well as the erythrocyte sedimentation rate (ESR) were compared between migraineurs and non-migraineurs. We additionally analyzed the inflammatory levels before and after the percutaneous PFO closure in migraineurs, correlating these changes with migraine relief assessed using the Migraine Disability Assessment Questionnaire (MIDAS) over a 6-month follow-up period. Results White blood cell count, d-dimers levels and ESR were similar in migraineurs and non-migraineurs (6,583 ± 2,251 Χ1 0.e3/uL vs 6,115 ± 1,958 Χ10.e3/uL; p-value = 0.48; 0.54 ± 0.49 μg/L vs 0.45 ± 0.29 μg/L; p- value= 0.49; 23.08 ± 16.68 mm vs 18.51 ± 14.98 mm; p- value 0.402; respectively). However, CRP and ferritin levels were significantly greater in patients with migraine compared to non- migraineurs (3.82 ± 1.87 mg/L vs 1.34 ± 1.52 mg/L; p- value =0.037 and 111.21 ± 82.70 ng/ml vs 50.12 ± 47.9 ng/ml; p- value = 0.023, respectively). Moreover, there was no significant difference between pre- and post-procedural inflammatory levels in migraineurs undergoing percutaneous PFO closure. Of note, following the procedure a reduction in CRP levels was observed without, however, reaching statistical significance. Finally, all patients observed a cessation in the occurrence of migraine attacks after closure. Conclusions Our study revealed significantly higher baseline levels of CRP and ferritin in migraineurs compared to non-migrainers with PFO. Although no alteration in inflammatory factors was observed following the procedure in migraineurs with PFO, all individuals experienced relief from migraine symptoms. Given the limitation of our study due to the small sample size, future studies may provide more insights into the potential benefits of PFO closure in specific migraine patient phenotypes.