Seizure outcomes after VNS therapy in children with drug-resistant epilepsy due to monogenic etiologies versus malformations of cortical development

OBJECTIVE Vagus nerve stimulation (VNS) is an established adjunctive therapy for drug-resistant epilepsy (DRE). However, evidence regarding its efficacy in children with structural and nonstructural etiologies of epilepsy remains limited. Herein, the authors aimed to explore the effectiveness of VNS in patients with either etiology. METHODS In this retrospective single-center study, authors evaluated children (ages 2–18 years) with DRE due to nonlesional monogenic epilepsies (MEs) or malformations of cortical development (MCDs) who had undergone VNS device implantation between 2008 and 2024 and had ≥ 6 months of follow-up. Patients with tuberous sclerosis complex were excluded. Clinical, genetic, neuroimaging, VNS programming, and outcome data were extracted from medical records. The primary outcome was the responder rate, defined as > 50% seizure reduction from baseline at 6 months, 12 months, and the last follow-up, in the two groups. RESULTS Of 336 VNS device recipients, 64 children with ME (n = 44) or MCD (n = 20) met the study inclusion criteria. The median follow-up was 3.5–4.0 years. The responder rate in the ME versus MCD group at 6 months, 1 year, and the last follow-up was 38.6% versus 42.1% (p = 0.77), 45.7% versus 44.4% (p = 0.46), and 47.6% versus 63.2% (p = 0.64), respectively. The SCN1A-related Dravet syndrome (SCN1A-DS) subgroup (n = 12) had a responder rate (50.0%) comparable to that of the non–SCN1A-DS ME group (43.7%) at the last follow-up. The frequency of status epilepticus decreased significantly in both groups (p = 0.03). VNS was well tolerated, with mild to moderate side effects reported in < 5% patients. No clinical variable, including age at seizure onset, epilepsy duration, or age at VNS device implantation predicted seizure outcomes. CONCLUSIONS VNS therapy was noted to have a similar responder rate in children with DRE due to MEs or MCDs. Both groups experienced meaningful benefits, with a small proportion of patients experiencing mild side effects.