Repetitive transcranial magnetic stimulation for the treatment of focal drug-resistant epilepsy: A crossover, randomized, single-blinded, sham-controlled clinical trial.

Objective: To evaluate the efficacy and safety of low-frequency repetitive transcranial magnetic stimulation (LF rTMS) in patients with focal drug-resistant epilepsy (DRE) using a randomized, single-blinded, crossover design (NCT06681480 on ClinicalTrials.gov).

Methods: Eighteen patients with focal DRE completed two 5-day treatment phases with either active or sham LF rTMS (0.5 Hz, 90 % rMT, 3000 pulses/session), separated by a 3-month washout period. The epileptogenic focus was targeted using MRI-guided neuronavigation. Primary outcomes included monthly seizure frequency, responder and seizure-free rates, and duration of seizure freedom. Secondary outcomes included weekly seizure frequency, interictal epileptiform discharges (IEDs), seizure severity, and quality of life. Crossover-specific analyses were performed with baseline correction.

Results: Active rTMS resulted in a significant reduction in monthly seizure frequency compared to sham (p = 0.0399), with 50 % of patients classified as responders and 16.7 % achieving seizure freedom. The seizure reduction was most prominent during the first two weeks after stimulation. Active rTMS also significantly reduced seizure severity (p < 0.0001) and improved quality of life (p = 0.0212). Although a trend toward reduction in IEDs was observed, this did not reach statistical significance. No serious adverse events occurred, and treatment was well tolerated.

Significance: LF rTMS targeting the epileptogenic focus appears to be a safe and potentially effective non-invasive adjunctive therapy for focal DRE. Its short-term efficacy and favorable safety profile support further investigation, including studies incorporating maintenance stimulation protocols and biomarker-guided treatment strategies.