OBJECTIVE
The NeuroPace responsive neurostimulation (RNS) System effectively treats focal drug-resistant epilepsy (DRE) in adults but lacks pediatric regulatory approval. Despite effective off-label pediatric use, systemic device-trial challenges have impeded label expansion. The prospective RESPONSE Study (NCT04839601), evaluating RNS in children with focal DRE, terminated prematurely after enrolling nine of 200 planned participants. We aimed to identify barriers to pediatric device-trial participation and evaluate whether anticipated ethical concerns about insurance-based access disparities materialized in practice.
METHODS
We conducted a mixed-methods study: a multi-site cross-sectional survey of barriers to RESPONSE participation, and a retrospective single-site case study at Massachusetts General Hospital (MGH) analyzing insurance distribution against state benchmarks in 96 RNS patients (73 adults and 23 pediatric), with denial rates and time to first reimbursement in a 62-patient subset (2020-2025).
RESULTS
Survey respondents comprised 8 of 9 RESPONSE sites plus MGH (which declined): 2 active, 6 withdrawn, and 1 declined. Study-design and enrolment feasibility were the dominant barriers (89%), followed by financial (44%), resource (33%), ethical (22%), and regulatory concerns (11%). The narrow eligible population reflected a mismatch between regulatory-aligned criteria (≤ 2 seizure-onset zones; exclusion of generalized or multifocal epilepsy; ages 12-17) and the heterogeneous presentations of real-world pediatric DRE, limiting recruitment. Insurance distributions did not differ from statewide benchmarks (p = .13) or between pre- and post-evaluation periods (p = .15). Denial occurred in 2/26 off-label pediatric (7.7%) and 1/36 focal adult (2.8%) RNS indications, all upheld on appeal and resolved by institutional subsidy; time to reimbursement did not differ (p = .31).
SIGNIFICANCE
The RESPONSE Study's premature termination reflected systemic barriers to pediatric device trials rather than isolated site failures. Anticipated insurance-based access disparities did not materialize locally. Advancing pediatric neuromodulation will require practice-aligned protocol design, alternative evidence pathways including registry-based real-world evidence, and leadership from well-resourced centers in collaborative evidence generation.
M. C. Hasner, F. Robertson, Nathaniel D. Sisterson et al.· Epileptic disorders· 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
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.
