Comparative Seizure Outcomes of Vagus Nerve Stimulation, Deep Brain Stimulation, and Their Combination in Lennox-Gastaut Syndrome.

Abstract

Lennox-Gastaut syndrome (LGS) is a severe treatment-resistant epilepsy. Although vagus nerve stimulation (VNS) and deep brain stimulation (DBS) are established therapies, comparative data and the impact of dual neuromodulation remain limited. We compared seizure outcomes across VNS, DBS, and combined DBS + VNS therapy in LGS. This retrospective cohort study at Mayo Clinic (2005-2024) included LGS patients treated with VNS and/or DBS. Seizure frequency was assessed at 6, 12, and 24 months post-stimulation. Responder was defined as 50% or more seizure reduction. Forty patients were included (42% female, median, 150 seizures/month). Eleven patients underwent sequential VNS followed by DBS and contributed data to 2 treatment epochs, yielding 3 treatment groups: VNS alone (n = 29), DBS alone (n = 12), and DBS + VNS (n = 10). At 24 months, median seizure reduction rate was comparable between VNS (50%; 95% confidence interval [CI], 44-75%) and the overall DBS cohort (59%, 95% CI, 33-86%) (p = 0.54). However, a significant difference emerged when comparing the 3 treatment arms (p = 0.027). Specifically, DBS + VNS therapy yielded significantly greater median reduction rate (81%, 95% CI, 60-99%) than DBS alone (43%, 95% CI, 0-58%) (p_adj = 0.027) or VNS alone (50%, 95% CI, 44.4-75.0%) (p_adj = 0.048). Four patients attained sustained seizure freedom above 1 year at last follow-up. VNS and DBS provide comparable seizure reduction in LGS over a 2-year follow-up period. DBS + VNS was associated with further improvements in seizure reduction in this small, retrospective dataset. This possibility warrants further investigation. ANN NEUROL 2026.