To summarize clinical outcomes, stimulation parameters, and safety of thalamic responsive neurostimulation (RNS) in patients with Lennox-Gastaut syndrome (LGS).

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.

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.

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.