Patent Foramen Ovale Closure Alleviates Long-Term Drug-Refractory Epilepsy: A Case Report

Background: Drug-refractory epilepsy (DRE) poses a persistent clinical burden, and the identification of reversible extracranial contributing factors represents a promising strategy to improve seizure control. Patent foramen ovale (PFO) with right-to-left shunt (RLS) has been recognized as a potential modifiable driver of epileptic seizures, yet clinical data on patients with extremely long-standing DRE exceeding 40 years remain exceedingly scarce. Methods: We report a 46-year-old female patient with a 44-year history of DRE, who experienced daily secondarily generalized tonic-clonic seizures (GTCSs) despite sequential treatment with six mechanistically distinct antiseizure medications. Systematic workup was performed and the patient underwent percutaneous transcatheter PFO closure, with a follow-up period of 14 months. Results: Systematic workup confirmed severe PFO-related RLS (grade III by contrast transthoracic echocardiography, grade IV by contrast transcranial Doppler), while brain MRI revealed no definite structural epileptogenic lesions other than an old ischemic infarct in the right corona radiata. At the latest follow-up, the patient had achieved complete freedom from GTCS with a markedly reduced antiseizure medication burden, retaining only infrequent mild focal absence-like seizures. Follow-up video electroencephalography unmasked previously occult focal epileptiform discharges in the left temporal region. Conclusions: This case suggests that severe PFO-related RLS may serve as a reversible aggravating factor even in decades-long refractory epilepsy, and provides electroclinical evidence supporting a hypothetical two-hit model of seizure generalization. PFO screening may be considered in selected patients with cryptogenic drug-refractory epilepsy, particularly those with non-lesional MRI, non-localizing EEG, and morning-predominant seizures.