Efficacy of repetitive transcranial magnetic stimulation (rTMS) therapy in children with drug refractory focal epilepsy – A randomized trial

BACKGROUND: Low frequency repetitive transcranial magnetic stimulation (rTMS) can suppress local neural circuits beyond the stimulation period and can be a potential treatment option for focal epilepsy. This study analysed the short-term effect of rTMS on seizure frequency, EEG, behavior, and cognition in children with drug refractory focal epilepsy (DRFE). METHODS: This is a single center, randomized double-blind sham controlled clinical trial (CTRI/2019/02/017,440). Children aged 5 to 18 years with DRFE with ≥ four focal seizures per month despite on ≥ two appropriately chosen antiseizure medications (ASMs) randomly received active or sham rTMS treatment along with the ongoing ASMs. Intervention comprised of 45 min rTMS sessions of 0.5 Hz (1200 pulses at 110 % of resting motor threshold (RMT) targeted over seizure focus using figure-of-8 coil for 10 consecutive days. The primary outcome was to compare the proportion of children who achieved >50 % seizure reduction in active and sham arm at 8-week post-therapy. RESULTS: Forty-nine children were enrolled in the trial (25 active and 24 sham). All randomized participants received the allocated treatment. No attrition occurred. Active rTMS therapy led to >50 % seizure reduction in 76 % (19/25) children versus 12.5 % (03/24) in sham arm (p < 0.0001) with absolute risk difference (95 % CI) between the groups was 0.68 (0.52, 0.84). Mean (SD) reduction in spike wave index (SWI) in sleep EEG was 34.4(29.9) with rTMS vs -1.89(22.5) in sham arm with absolute risk difference (95 % CI) -36.4(-51.7, -21.1). Between active and sham group mean (SD) change in Intelligence quotient (IQ) was 3.7(2.8) vs -0.91(3.1), p value 0.001; Child Behavior Checklist (CBCL) scores improved in behavioral domains of inattention (-5.5(3.8) vs 0.41(2.7), p < 0.001; hyperactivity -3.8(4.1) vs -0.5(2.8), p < 0.006 and aggression -4.1(2.4) vs 0.40(2.8), p < 0.001. Adverse effects were primarily limited to headache and scalp discomfort. CONCLUSION: Adjunctive low frequency rTMS may induce better short-term seizure control and electrographic improvement compared to sham stimulation in children with DRFE. These results will serve as a basis for a larger multicentric clinical trial.