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Mehdi Khan, Jaber Paktiawal, Rory J. Piper, Aswin Chari, and Martin M. Tisdall

OBJECTIVE

In children with drug-resistant epilepsy (DRE), resective, ablative, and disconnective surgery may not be feasible or may fail. Neuromodulation in the form of deep brain stimulation (DBS) and responsive neurostimulation (RNS) may be viable treatment options, however evidence for their efficacies in children is currently limited. This systematic review aimed to summarize the literature on DBS and RNS for the treatment of DRE in the pediatric population. Specifically, the authors focused on currently available data for reported indications, neuromodulation targets, clinical efficacy, and safety outcomes.

METHODS

PRISMA guidelines were followed throughout this systematic review (PROSPERO no. CRD42020180669). Electronic databases, including PubMed, Embase, Cochrane Library, OpenGrey, and CINAHL Plus, were searched from their inception to February 19, 2021. Inclusion criteria were 1) studies with at least 1 pediatric patient (age < 19 years) who underwent DBS and/or RNS for DRE; and 2) retrospective, prospective, randomized, or nonrandomized controlled studies, case series, and case reports. Exclusion criteria were 1) letters, commentaries, conference abstracts, and reviews; and 2) studies without full text available. Risk of bias of the included studies was assessed using the Cochrane ROBINS-I (Risk of Bias in Non-randomised Studies - of Interventions) tool.

RESULTS

A total of 35 studies were selected that identified 72 and 46 patients who underwent DBS and RNS, respectively (age range 4–18 years). Various epilepsy etiologies and seizure types were described in both cohorts. Overall, 75% of patients had seizure reduction > 50% after DBS (among whom 6 were seizure free) at a median (range) follow-up of 14 (1–100) months. In an exploratory univariate analysis of factors associated with favorable response, the follow-up duration was shorter in those patients with a favorable response (18 vs 33 months, p < 0.05). In the RNS cohort, 73.2% of patients had seizure reduction > 50% after RNS at a median (range) follow-up of 22 (5–39) months. On closer inspection, 83.3% of patients who had > 50% reduction in seizures actually had > 75% reduction, with 4 patients being seizure free.

CONCLUSIONS

Overall, both DBS and RNS showed favorable response rates, indicating that both techniques should be considered for pediatric patients with DRE. However, serious risks of overall bias were found in all included studies. Many research needs in this area would be addressed by conducting high-quality clinical trials and establishing an international registry of patients who have undergone pediatric neuromodulation, thereby ensuring robust prospective collection of predictive variables and outcomes.