DBS and RNS were effective for treatment of pediatric DRE, with equivalent 12-month seizure outcomes but different temporal trajectories.
Abstract
Objective
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.
Methods
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).
Results
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.
Significance
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.
Thalamic neuromodulation using DBS and RNS was safe and well tolerated in pediatric patients with DRE, including multifocal and generalized seizure onsets, with a trend toward greater benefit in the DBS group.
Dominic Nistal, Benjamin D. Edmonds, Adriel Barrios-Anderson et al.· Journal of Neurosurgery: Ped...· 0 citations
Responsive neurostimulation (RNS) is a neuromodulation option for treatment of drug-resistant epilepsy (DRE). There is limited data reviewing bilateral thalamic and corticothalamic RNS therapy response. We performed a retrospective analysis of 21 patients undergoing RNS implantation with either bilateral thalamic (n = 17) or corticothalamic (n = 4) leads and ≥6 months of follow-up. Patients were classified as responders (≥50% seizure frequency reduction) vs. non-responders (<50% seizure frequency reduction). Among the bilateral thalamic cohort, 12/17 (70.6%) patients were responders, and 15/17 (88.2%) patients reported reduction in seizure severity. Pre-RNS seizure frequency was higher in bilateral thalamic nonresponders, although not found to be significant (median 13 vs. 30 seizures per month, p = 0.20). Among the corticothalamic cohort, 3/4 (75.0%) patients were responders, and all patients demonstrated improvement in seizure severity. These findings suggest that although bilateral thalamic targets were selected at our center more often, both bilateral thalamic and corticothalamic RNS approaches provided seizure frequency reduction. The majority of patients, including non-responders, reported seizure severity alleviation.
Ramya Krothapally, Ghazala Perven, D. Veerapaneni et al.· The Neuroscientist· 0 citations
Background Deep brain stimulation (DBS) has emerged as a palliative neurosurgical treatment option for drug-resistant epilepsy (DRE), particularly in patients who are not candidates for resective surgery or who continue to experience seizures after surgical intervention. Multiple thalamic and extrathalamic targets have been investigated; however, optimal target selection remains challenging and requires a comprehensive understanding of epileptogenic networks. Objective To provide a comprehensive overview of current evidence on DBS for DRE and refractory status epilepticus, with a focus on anatomical targets, mechanisms of action, clinical outcomes, and considerations for target selection. Methods We reviewed the existing literature on DBS in epilepsy, including randomized controlled trials, observational studies, meta-analyses, and relevant experimental data. Major targets—including the anterior nucleus of the thalamus (ANT), centromedian nucleus (CM), pulvinar, mediodorsal nucleus (DM), subthalamic nucleus (STN), and other emerging targets—were examined in terms of connectivity, proposed mechanisms, and clinical efficacy. Results Among available targets, ANT-DBS has the strongest clinical evidence, demonstrating sustained seizure reduction in randomized trials and long-term follow-up studies. CM-DBS shows particular promise in generalized epilepsy, especially Lennox–Gastaut syndrome, likely through modulation of thalamocortical and reticular networks. The pulvinar has emerged as a potential target for temporal and posterior quadrant epilepsies, reflecting its extensive cortical connectivity. Other targets, including the DM, STN, hippocampus, hypothalamus, nucleus accumbens, and cerebellum, have shown variable efficacy in smaller studies and may be relevant for specific epilepsy subtypes or network configurations. Across targets, therapeutic effects are likely mediated by modulation of distributed epileptogenic networks involving limbic, sensorimotor, and arousal systems. Conclusion DBS represents an important therapeutic option for DRE, expanding the scope of neuromodulation beyond traditional surgical approaches. Optimal outcomes depend on individualized target selection based on seizure semiology, network characteristics, and anatomical considerations. As clinical experience and technological advances continue to evolve, further studies are required to refine patient selection, improve targeting strategies, and optimize stimulation paradigms.
Ryota Sasaki, Masako Kinoshita, Abbas F. Sadikot et al.· Frontiers in Neurology· 0 citations
Neuromodulation for drug-resistant epilepsy is associated with modest improvements in depression and quality of life without meaningful cognitive deterioration over follow-up durations of 6 months to 14 years.
Margil Ranpariya, Gurleen Kaur, H. Shallwani et al.· Acta Neurologica Belgica· 0 citations
OBJECTIVE
Anterior nucleus of the thalamus (ANT) deep brain stimulation (DBS) is an effective therapy for frontotemporal and limbic drug-resistant focal epilepsies. The pulvinar nucleus (PUL) is an emerging neuromodulation target for seizure networks involving the posterior quadrant and temporal lobe. This study evaluates the safety and effectiveness of combined bilateral ANT plus PUL DBS for posterior quadrant and temporal lobe epilepsies.
METHODS
We conducted a single-center retrospective cohort study of patients receiving combined ANT/PUL DBS between 2021 and 2025. Outcomes included median seizure rate reduction (MSR), responder rate (RR; >50% seizure frequency reduction), and stimulation-related side effects, assessed across ANT, PUL, and concurrent ANT/PUL stimulation settings. Acute surgical complications were evaluated. Statistical significance was assessed using two-sided Wilcoxon signed-rank tests with Holm-Bonferroni correction.
RESULTS
Nine patients with combined ANT/PUL DBS were identified, and eight patients had sufficient follow-up for inclusion (median follow-up = 20 months). Posterior predominant structural abnormalities were present in eight of nine patients. There were no acute surgical complications. Three instances of transient stimulation-related side effects resolved with parameter adjustments, whereas one patient required rescue antiseizure medication in addition to programming changes. Eight patients received periods of ANT stimulation, six PUL stimulation, and seven combined ANT/PUL stimulation. Regarding overall outcome, at last follow-up, there was a significant 80.8% MSR (p = .0078) and 87.5% RR, with two patients receiving ANT and six ANT/PUL stimulation. Regarding target-specific MSR, concurrent ANT/PUL DBS (68.8% MSR) showed a trend toward superior performance relative to ANT (43.3%) and PUL DBS (17.5%) alone, although subgroup analysis of target-specific performance did not reach statistical significance.
SIGNIFICANCE
Combined four-lead ANT/PUL DBS appears safe and effective for patients with drug-resistant posterior quadrant and temporal lobe epilepsies. Dual-network neuromodulation may provide greater flexibility to individually optimize neuromodulation for complex seizure networks.
To characterize invasive neuromodulation for insular drug-resistant epilepsy, we retrospectively evaluated 22 patients treated with responsive neurostimulation (RNS; n = 14) or chronic subthreshold stimulation (CSS; n = 8). Stereoelectroencephalography was performed in 20 cases (91%). Median baseline seizure frequency was 10.5/month. Forty-one percent had prior epilepsy surgery. At year 3, median seizure reduction (MSR) was 83% (p = .01, Wilcoxon signed-rank test), with a responder rate (RR) of 77%; MSR was 92% for CSS and 75% for RNS. There were no significant differences in MSR (p ≥ .4) or RR (p > .9) when comparing RNS versus CSS. Three patients achieved seizure freedom by year 3. Patients undergoing combined insular-thalamic stimulation (n = 5) demonstrated an MSR of 84%, 86%, and 88% at 1, 2, and 3 years; seizure reduction in thalamocortical versus cortical-only stimulation was not different (p ≥ .1). Parasagittal lead trajectories achieved closer insular proximity than transopercular trajectories (p < .0001, Mann-Whitney U-test). Median charge density at last follow-up was 1.3 μC/cm2. There were no acute surgical complications and all stimulation-related side effects resolved with programming adjustments. This study expands the limited literature on insular neuromodulation by demonstrating effectiveness of RNS and CSS, suggesting potential benefit from combined thalamocortical targeting, and defining parasagittal trajectories as a surgical approach for optimal lead proximity.
Raunak Singh, N. Gregg, K. Starnes et al.· Epilepsia· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
