Title: Responsive Neurostimulation Targeting Thalamic Nuclei in Lennox-Gastaut Syndrome: A Systematic Review of Clinical Outcomes and Programming Parameters (P1-10.002)
Authors: Ana Leticia Fornari Caprara, Jamir Pitton Rissardo, Salman Assad, Evren Burakgazi-Dalkilic, and Eric P. Nagele
Conference: 2026 AAN, Chicago, IL
Objective
To summarize clinical outcomes, stimulation parameters, and safety of thalamic responsive neurostimulation (RNS) in patients with Lennox-Gastaut syndrome (LGS).
Background
LGS is a severe developmental and epileptic encephalopathy often refractory to medications and vagus nerve stimulation. Deep brain stimulation of the centromedian (CM) nucleus has shown promise, but data on closed-loop RNS targeting thalamic nuclei remain limited. Understanding programming strategies and outcomes is critical for optimizing therapy.
Design/Methods
We performed a structured review of PubMed and clinical trial registries through September 2025 for studies reporting RNS in LGS or LGS phenotype. Extracted variables included demographics, seizure outcomes (≥50% responder rate), stimulation parameters, lead configuration, follow-up duration, and adverse events.
Results
Nine studies (n=30 LGS patients) were identified: 2 case reports, 4 case series, 1 multicenter cohort, and 2 feasibility trials. Mean age at implant ranged from 12–17 years; follow-up ranged 5–24 months. Targets included CM (most common), anterior nucleus, and pulvinar. Reported programming typically used high-frequency stimulation (100–200 Hz), pulse width 160 μs, and current 1–3 mA, with individualized titration. ≥50% responder rates varied widely across studies (0%–100%), with a pooled weighted estimate of 56.7% (95% CI: 38.9%–74.4%). Adverse events were rare; one case of myasthenia gravis and two infections requiring intervention were reported. Concurrent neuromodulation (e.g., active VNS) was feasible without device interference. Ongoing IDE trials (NCT05339126) aim to clarify long-term efficacy and biomarker-driven programming.
Conclusions
Thalamic RNS is a promising adjunctive therapy for LGS, offering individualized, closed-loop modulation with favorable safety. Early evidence suggests clinically meaningful seizure reduction in most patients, though heterogeneity in targets and programming underscores the need for prospective trials and standardized protocols.
Citation
Caprara AL, Rissardo JP, Assad S, Burakgazi-Dalkilic E, Nagele EP. Responsive Neurostimulation Targeting Thalamic Nuclei in Lennox-Gastaut Syndrome: A Systematic Review of Clinical Outcomes and Programming Parameters (P1-10.002). Neurology 2026;106(11_suppl_1):689. doi: 10.1212/WNL.0000000000213061.
Figure 1. Summary of included studies on thalamic responsive neurostimulation in Lennox–Gastaut syndrome, detailing targets, stimulation parameters, responder rates, and safety outcomes across reported cohorts.