Interrupting Progression to Bilateral Tonic-Clonic Seizures with Exogenous Rhythmic Stimulation: A Safety and Efficacy Study

Background: Drug-resistant epilepsy remains a major therapeutic challenge, especially in preventing the progression of focal seizures to bilateral tonic-clonic seizures (BTCS). Previous studies demonstrated that exogenous rhythmic stimulation at 1.13 Hz syn-chronized with wrist tapping enhances prefrontal cortex activity in epilepsy patients. Methods: We conducted a randomized controlled study involving 60 adult patients with drug-resistant structural focal epilepsy (SFE). Participants were assigned to either an in-tervention group (n = 30), using the EpiTapp™ smartphone application during aura and/or focal onset of BTCS in out-of-hospital settings, or a control group (n = 30) receiving standard care. The study lasted six months. Primary outcomes were BTCS frequency and quality of life measured by the QOLIE-31 scale. Results: Use of EpiTapp™ significantly reduced BTCS frequency by interrupting seizure progression at the focal onset stage. Additionally, 22.6% of patients in the intervention group reported improved quality of life after six months. Conclusions: Exogenous rhythmic stimulation via the EpiTapp™ ap-plication is a promising non-invasive intervention for preventing seizure generalization in patients with drug-resistant structural focal epilepsy. Larger-scale studies are warranted to confirm these findings.