Invasive Neuromodulation of Drug-Resistant Epilepsy in Pediatric Populations: A Comprehensive Systematic Review and...

To evaluate the efficacy and safety of vagus nerve stimulation (VNS), responsive neurostimulation (RNS), and deep brain stimulation (DBS) in pediatric drug-resistant epilepsy (DRE).

A systematic review and meta-analysis following Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 guidelines searched PubMed/MEDLINE, Embase, Scopus, and Cochrane Central through August 2025 for studies evaluating VNS, RNS, or DBS in pediatric DRE (aged <18 years). The primary outcome was responder rate (≥50% seizure reduction). The secondary outcomes included seizure freedom and complication rates. Pooled proportions with 95% confidence intervals (CI) were calculated using DerSimonian-Laird random-effects models.

A total of 88 studies involving 3068 pediatric patients met inclusion criteria, comprising 2784 VNS (73 studies), 182 RNS (11 studies), and 102 DBS (seven studies). DBS exclusively targeted thalamic structures, including the centromedian nucleus (61.8%), anterior thalamic nucleus (25.5%), dual centromedian/anterior thalamic nucleus targeting (11.8%), and pulvinar targeting (1.0%), reflecting a network neuromodulation approach. RNS predominantly used focal stimulation at seizure onset zones, with extratemporal targets (45%) more common than temporal-only targets (32%) in the largest cohort. VNS showed a pooled responder rate of 54% (95% CI, 51%-58%), seizure freedom of 6% (95% CI, 4%-8%), and complication rate of 4% (95% CI, 2%-5%). RNS showed responder rate of 71% (95% CI, 59%-82%), seizure freedom of 6% (95% CI, 2%-12%), and complication rate of 6% (95% CI, 2%-11%). DBS yielded a responder rate of 65% (95% CI, 48%-81%) and a complication rate of 15% (95% CI, 7%-26%); seizure freedom was rare, reported in only one study, with no seizure freedom observed in remaining DBS studies. No procedure-related deaths were reported.

VNS, RNS, and DBS provide meaningful seizure reduction with favorable safety profiles in pediatric DRE, though seizure freedom remains uncommon. Treatment selection should be individualized on the basis of epilepsy characteristics, age, and practical considerations.