Comparative multicenter evaluation of thalamic neuromodulation for treatment-resistant epilepsy in children

Use of neuromodulation strategies targeting thalamic nuclei, including deep brain stimulation (DBS) and responsive neurostimulation (RNS), for treatment of pediatric drug-resistant epilepsy (DRE) is increasing, despite limited evidence for efficacy and safety. We present the initial results from the Comparative Multicenter Evaluation of Thalamic Neuromodulation for Treatment-Resistant Epilepsy in Children consortium, which was created to study thalamic modulation in children with DRE.

We performed a retrospective cohort study of children who underwent thalamic DBS or RNS for DRE between January 2015 and December 2024 across 12 centers. Primary outcomes were percent seizure reduction, Engel class, and responder rates (>50% seizure reduction) at 3, 6, and 12 months postoperatively. Secondary outcomes included antiseizure medications and surgical complications. Differences were quantified using ordinal logistic regression, generalized estimating equations with center clustering, and mixed-effects models. Stratified analyses were performed by thalamic target (centromedian vs. anterior nucleus) and epilepsy diagnosis (Lennox-Gastaut syndrome, generalized, focal, and multifocal).

Among the 221 included patients (111 DBS, 110 RNS) included, DBS and RNS achieved comparable Engel scores and 12-month responder rates, but different temporal trajectories were observed. There was a significant device × time interaction (odds ratio = 1.10/month, 95% confidence interval = 1.01-1.20, p = .04), with RNS response rates increasing from 26.9% at 3 months to 55.6% at 12 months (paired p < .001) but with DBS response rates reaching 41.7% at 3 months and remaining comparatively stable over time. DBS achieved significantly higher 12-month seizure freedom (9.5% vs. 1.2%, p = .03). Neither thalamic target selection nor diagnosis predicted seizure outcome. Safety profiles were equivalent.

This multicenter analysis provides pediatric-specific data to inform surgical indications, device selection, and preoperative counseling. DBS and RNS were effective for treatment of pediatric DRE, with equivalent 12-month seizure outcomes but different temporal trajectories. DBS provided earlier seizure control and higher rates of overall seizure freedom.