Safety profile of intracranial neuromodulation for drug-resistant epilepsy in children

Abstract

Objective: Children with drug-resistant epilepsy (DRE) in whom resection or disconnective surgeries are not recommended can still benefit from neurostimulation. Vagus nerve stimulation (VNS) is FDA approved for those aged 4 years and older, but intracranial stimulators, that is, responsive neurostimulation (RNS) and deep brain stimulation (DBS) devices, are only approved for those aged 18 years and older. Studies in adults and early experience in children suggest that intracranial stimulation may be more effective than VNS but with higher risk. This risk has not been examined in large pediatric cohorts. This study aimed to evaluate the safety profile of RNS and DBS for pediatric DRE as well as the possible risk factors for wound-related complications.

Methods: This retrospective study examined the records of DRE patients who underwent RNS or DBS at Children's Hospital of Philadelphia from November 2017 to March 2024 with at least 6 months of follow-up. DBS electrodes were placed in the anterior or centromedian nucleus of the thalamus. RNS electrodes were placed in seizure foci.

Results: A total of 54 patients, aged 6-22 years, underwent intracranial stimulator implantation for DRE (24 DBS, 30 RNS). The mean follow-up was 24.4 ± 15.3 months (median 21 months, range 6-69 months). Five (9.3%) patients returned to surgery, 3 (5.6%) of whom required explant and 1 (1.9%) of whom required explant and also had a surgical site infection (SSI). Prior craniotomy was a significant risk factor for wound-related complications (p = 0.0046 in all patients, p = 0.0375 in patients < 18 years). No patient experienced hemorrhage, lead malposition, device malfunction, or long-term stimulation-induced paresthesia, depression, or memory loss. The overall responder rates, defined by achieving 50% or greater reduction in seizure frequency, were 54% in the RNS cohort and 73% in the DBS cohort at the 12-month follow-up.

Conclusions: To the best of the authors' knowledge, this study represents the largest single-center series of intracranial stimulation for pediatric DRE. In comparison with established rates of SSI and explant in adults (12% and 7.0% in the RNS pivotal trial and 13% and 8.6% in the DBS SANTE [Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy] trial, respectively), the present cohort demonstrated favorable rates of 1.9% and 5.6%, respectively. Studies with larger pediatric DRE cohorts are needed with longer follow-up and seizure outcomes to elucidate the risk/benefit balance of intracranial stimulation in children.

Keywords: deep brain stimulation; drug-resistant epilepsy; pediatric; responsive neurostimulation.