Outcomes Following Thalamic Neuromodulation for Pediatric Generalized Drug-resistant Epilepsy: A Systematic Review and Individual Participant Data Meta-analysis

Introduction: Therapeutic stimulation to thalamic targets for treatment drug-resistant epilepsy (DRE) is a well-studied and proven therapy, yet is not approved in patients under age 18. We sought to perform a systematic review and individual participant data meta-analysis of the current literature to compare outcomes between deep brain stimulation (DBS) and responsive neurostimulation (RNS).

Methods: Electronic databases (PubMed, Ovid, Embase, Cochrane) were searched with no language or data restriction to identify studies that reported seizure outcomes in pediatric populations following DBS or RNS implantation of thalamic nuclei. Studies that included individual participant data on patients with primary or secondary generalized drug resistant epilepsy were included. Response to therapy was defined as greater than 50% reduction in seizure frequency from baseline.

Results: Of 488 citations, 22 articles reporting on 94 participants were eligible. Mean age at implantation was 13 +/-3.5 years. 56 (60%) of patients underwent DBS and 38 (40%) RNS. 60 (64%) patients were implanted in CMT, 29 (31%) in ANT, and 5 (5%) had both targets implanted. 80 (85%) patients were implanted bilaterally. The median time to last follow up was 12 month (IQR 6.75-26.25. 69% of patient achieved response to treatment. Age, modality of stimulation, target, and laterality showed no significant association with response in univariate analysis. Multivariate analysis using logistic regression revealed an only increased likelihood of treatment response with use of RNS compared to DBS (OR 3.36, 95%-CI 1.25-9.06, P=0.02).

Conclusion : This study demonstrates that thalamic neuromodulation is a safe and effective means of treatment for generalized pediatric drug-resistant epilepsy. This is the first study to compare RNS and DBS in pediatric populations via meta-analysis. RNS systems may show more therapeutic promise in pediatric populations compared to DBS.