Jul 2026· Journal of Neurosurgery: Pediatrics· pp.
1-9
· 0 citations· 35 references
Medicine
TL;DR
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.
Abstract
Objective
Children with generalized or multifocal drug-resistant epilepsy (DRE) without a clearly localizable and safely resectable seizure focus present a significant clinical challenge, as traditional resective interventions are often not viable. Emerging evidence supports the use of neuromodulation-particularly deep brain stimulation (DBS) and responsive neurostimulation (RNS)-for generalized and multifocal epilepsy in adults. However, safety and efficacy data for thalamic neuromodulation in pediatric populations remain limited. This single-institution case series describes, to our knowledge, the largest pediatric cohort treated with thalamic DBS or RNS for generalized or multifocal DRE, providing descriptive data on safety and seizure burden.
Methods
The authors performed a retrospective chart review of pediatric patients with DRE who underwent thalamic neuromodulation using RNS or DBS at Seattle Children's Hospital between January 2020 and July 2025 with at least 6 months of follow-up. Clinical, surgical, and seizure outcome data were collected, including seizure frequency and complications. Seizure outcomes were stratified into categorical frequency bins, and a trend analysis was performed to evaluate postoperative shifts in seizure burden.
Results
Twenty-six patients (mean age 14.5, range 6-20 years) underwent thalamic neuromodulation with DBS (n = 12) or RNS (n = 14). The centromedian nucleus was the target in 24 cases; 1 patient each underwent targeting of the anterior nucleus and pulvinar nucleus. At the last follow-up (median 30.2 months), 65.4% of patients met the responder criteria (≥ 50% seizure reduction), with a higher response in the DBS group (83.3%) compared with the RNS group (50.0%). The median seizure reduction was 75.7% for DBS and 37.5% for RNS. A significant downward shift in seizure frequency was observed postoperatively across the entire cohort (p = 0.031), including among patients with the highest baseline seizure burden. No intraoperative complications occurred. Two patients (7.7%) required device explantation, 1 due to infection and 1 due to behavioral side effects, and 1 patient discontinued therapy without explantation. No instances of sudden unexpected death in epilepsy or hardware malfunction were observed.
Conclusions
Thalamic neuromodulation using DBS and RNS was safe and well tolerated in pediatric patients with DRE, including multifocal and generalized seizure onsets. Meaningful seizure reduction was observed across a range of epilepsy phenotypes, with a trend toward greater benefit in the DBS group. These findings support thalamic neuromodulation as a promising treatment option in children with nonlesional DRE and highlight the need for prospective multicenter studies with extended follow-up.
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
Complete resection of the epileptogenic zone offers the best chance of seizure control in patients with drug-resistant epilepsy. However, surgical management remains challenging when the epileptogenic zone is located within or adjacent to eloquent brain regions. Awake craniotomy (AC), combined with intraoperative functional mapping, has the potential to maximize resection while preserving neurological function. Despite its increasing use, evidence regarding its safety and efficacy in epilepsy surgery remains limited. This study aimed to systematically evaluate the feasibility, reported safety, and reported seizure outcomes of awake craniotomy in patients undergoing surgery for drug-resistant non-oncological epilepsy.
A systematic literature search was conducted in PubMed, Scopus, and Web of Science databases in accordance with PRISMA guidelines.
Seven retrospective studies comprising 231 patients from six countries were included; 120 patients underwent AC. Four studies (57.1%) included mixed adult and pediatric populations and three (42.9%) included adults only; however, none provided age-stratified seizure or complication outcomes, precluding separate pediatric analysis. Reported seizure duration ranged from 2 to 39 years. The frontal lobe was the most frequently involved region (
n
= 52; 43.3%), followed by the temporal lobe (
n
= 27; 22.5%), and cortical dysplasia was the most common underlying pathology (
n
= 30; 25.0%). Language and sensorimotor functions were the most commonly mapped eloquent areas, each reported in five studies (71.4%). Seizure outcomes were predominantly assessed using the Engel classification. Complete seizure freedom (Engel class I) was reported in 69 of 120 AC patients (57.5%); a random-effects single-arm synthesis estimated an Engel I proportion of 59.3% (95% CI: 46.3–71.2%; I2 = 31.9%). Comparisons with surgery under general anesthesia (GA) were available in only two non-randomized studies and should be interpreted cautiously. No study reported conversion from AC to GA. Postoperative neurological deficits were largely transient, with a low reported incidence of permanent morbidity. Owing to substantial differences in patient selection, surgical indications, and study design, these findings should be considered exploratory and should not be interpreted as demonstrating comparable seizure outcomes or treatment effectiveness.
In carefully selected patients with drug-resistant non-tumor epilepsy involving or adjacent to eloquent cortex, AC with intraoperative functional mapping appears feasible and may help preserve neurological function while enabling tailored resection. The current evidence base remains limited by retrospective designs, heterogeneous populations and techniques, inconsistent outcome reporting, and sparse comparative data; therefore, efficacy and equivalence with surgery under general anesthesia should not be inferred.
M. Mofatteh, M. Mashayekhi, Sho Giersztein et al.· BMC Surgery· 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
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
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