Multifocal continuous theta burst stimulation in idiopathic generalized epilepsy: a cohort study

OBJECTIVE: Idiopathic generalized epilepsy (IGE) is a disorder of the cortico-subcortical networks. Continuous theta burst stimulation (cTBS) can target these networks to provide an innovative, noninvasive neuromodulation treatment. This study evaluated the safety and efficacy of multifocal cTBS in IGE. METHODS: This single-arm, open-label trial recruited adults with IGE. Following a four-week screening period, participants received one daily cTBS session for six days. Each session involved delivering three cTBS trains (600 pulses) at 80% of resting motor threshold over the vertex. The primary endpoint was a ≥ 50% reduction in seizures (responder rate) at 12 weeks. Secondary endpoints included seizure severity (SSQ), quality of life (QOLIE-31) and changes in cortical excitability. RESULTS: Among 13 participants (32.8 ± 7.3 years), the responder rate was 76.9% (p < 0.001). Median total seizure frequency decreased from 5 (range 2-22) to 1 (0-9) seizures at 12 weeks (p < 0.001). The greatest treatment effect was observed for tonic-clonic seizures (100% response), followed by myoclonic seizures (66.7% response) and absence seizures (33.3% response). Overall cohort SSQ score improved by 75%, QOLIE-31 by 25% (p < 0.05), with gains mainly in social, cognitive, energy/fatigue, and emotional domains. Post-cTBS, cortical excitability showed increased resting motor thresholds (p < 0.001) and decreased motor evoked potential amplitudes (p < 0.05). No serious adverse events occurred. CONCLUSIONS: Multifocal cTBS appeared to be a safe and effective treatment in our cohort of patients with IGE. SIGNIFICANCE: Further investigation of the applied cTBS paradigm is warranted in larger, sham-controlled trials in IGE.