This study aimed to systematically review and meta-analyze the available literature on the efficacy and tolerability of non-invasive brain stimulation (NIBS) in pediatric refractory epilepsy.

Pediatric refractory epilepsy presents significant treatment challenges, with approximately 30% of children remaining unresponsive to pharmacologic therapies. NIBS, including repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS), has emerged as a potential adjunctive treatment.

A systematic search of PubMed, Embase, and the Cochrane Library was conducted from inception till August 2025. We included RCTs and single-arm intervention studies assessing the effects of rTMS or tDCS in patients aged ≤18 years with refractory epilepsy. The primary outcome was the change in seizure frequency (SF) from baseline at 4-8 weeks post-intervention. Secondary outcomes included the change in interictal epileptiform discharges (IEDs), the proportion of patients achieving >50% seizure reduction, and the incidence of reported side effects.

Eight studies were included with a total of 229 patients: four RCTs (n=125; 76 in intervention group, 49 in sham group) and four single-arm studies (n=104). A random-effects meta-analysis of the RCTs showed that rTMS/tDCS significantly reduced seizure frequency compared to sham (SMD: –0.422; 95% CI: –0.839 to –0.004; p = 0.048, I² = 16%). IEDs were also significantly reduced at 4-8 weeks post intervention (MD: –14.31; 95% CI: –27.57 to –1.05; p = 0.034). In the pooled analysis of single-arm studies, 41.1% of patients (95% CI: 27.5% to 56.2%, I² = 38%) achieved >50% seizure reduction. Adverse events were generally mild and transient, including transient skin erythema, itching, mild headache, and scalp discomfort. No serious complications were reported.

NIBS appears to be a safe and promising adjunctive treatment for children with refractory epilepsy, demonstrating significant short-term reductions in SF and IEDs. Larger, high-quality RCTs with standardized protocols are needed to validate these findings and inform clinical practice.