Buch, Vivek

Abstract Objectives Pivotal trials have established the effectiveness of the Responsive Neurostimulation System (RNS® System) in treating focal epilepsy. In clinical trials, depth leads were primarily used to treat mesial temporal seizure onsets while cortical strip leads were used to treat neocortical seizure onsets. Here, we systematically analyze the safety and efficacy of stereoelectroencephalography (sEEG)‐guided depth leads to provide responsive stimulation to neocortical gray matter. Methods Patients were stratified as strong responders (>median cohort seizure reduction %), weak responders (>0% and ≤median cohort seizure reduction %), and anti‐responders (≤0%) based on percent seizure reduction at 1 year post‐implant (1‐Y). Pre‐operative T1‐weighted magnetic resonance imaging and post‐operative computed tomography images were merged, and the Euclidean distance between the sEEG epileptic focus (sEEG‐EF) and the nearest RNS System depth lead contacts was calculated. Results A total of 87 depth leads were implanted in 55 patients across neocortical brain regions. The median reduction in clinical seizures improved from 66.7% at 1‐Y to 77.5% at long‐term follow‐up (LTFU: 2.35 ± 0.95 years), with 10 patients (18.2%) achieving complete seizure freedom. Seven patients (12.7%) experienced six serious adverse events. At 1‐Y, shorter Euclidean distance between the sEEG‐EF and RNS System depth leads predicted improved seizure outcome in strong responders ( β = −0.84, p = 0.008) but not in weak responders ( β = 0.21, p = 0.9) or anti‐responders ( β = −20.34, p = 0.11). At LTFU, there was no significant relationship between Euclidean distance and seizure reduction in strong responders ( β = 0.77, p = 0.18), weak responders ( β = 2.05, p = 0.54), or anti‐responders ( β = 0.24, p = 0.99). Exploratory analyses at 1‐Y showed nominal associations between older age ( ρ = 0.32), longer epilepsy duration ( ρ = 0.27), and non‐mesial temporal sEEG‐EFs and greater seizure reduction; however, none survived Bonferroni correction (adjusted α = 0.0027; all post‐correction p > 0.0027), and no associations were observed at LTFU. Significance In this series, neocortical depth leads for RNS therapy had favorable safety and efficacy and proximity to the sEEG‐EF drove initial outcomes for strong responders to RNS therapy. Plain Language Summary In this multi‐center study, patients with difficult‐to‐treat seizures received brain‐responsive stimulation using a device called responsive neurostimulation (RNS), which delivers small electrical pulses to reduce seizures. We focused on patients treated with electrodes placed in the brain's outer regions (the neocortex) and guided by a mapping procedure called sEEG. On average, patients had their seizures cut by two‐thirds after one year and by more than three‐quarters with longer follow‐up, with about one in five becoming seizure‐free. The treatment was safe, and closer electrode placement to the seizure source helped explain early—but not long‐term—improvements.

BACKGROUND Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by multiple seizure types, intellectual disability, and distinctive EEG findings. Deep brain stimulation of the centromedian nucleus (CM-DBS) is an emerging therapy for LGS, but pediatric experience remains limited. OBSERVATIONS The authors report a single-center experience with CM-DBS in 6 children and adolescents (ages 12–18 years) with LGS. One patient experienced infection-related device removal after 2 months. The remaining 5 received sustained stimulation for 2.5–5 years. All 5 showed caregiver-reported improvements in seizure burden and alertness, with corroborating Clinical Global Impression–Improvement scores. Three patients exhibited marked seizure reduction following targeted reprogramming toward a previously identified optimal target of stimulation in the anterolateral CM. Pre- and post-DBS scalp EEG recordings were available in 1 patient and showed a reduced burden of interictal discharges. LESSONS CM-DBS is a promising treatment for pediatric, medically refractory LGS when resective approaches are unsuitable. Benefits were sustained over years. Lead localization and direction of stimulation appear important to optimize clinical benefit. These findings support the feasibility and safety of pediatric CM-DBS and highlight the need for prospective trials incorporating EEG-based outcomes and patient-centered measures including comorbidities and quality of life. Early, network-targeted neuromodulation may improve long-term outcomes. https://thejns.org/doi/10.3171/CASE25478