Clinical effectiveness of vagus nerve stimulation in pediatric drug-resistant epilepsy: etiology-based comparison of genetic and non-genetic cohorts for seizure reduction and antiseizure medication burden

Introduction Drug-resistant epilepsy (DRE) affects up to 40% of pediatric patients and continues to be a major therapeutic challenge. Vagus nerve stimulation (VNS) is an established neuromodulatory therapy; however, the impact of genetic etiology on treatment efficacy and antiseizure medication (ASM) burden remains unclear. Conclusions: VNS provides clinically observable seizure reduction in pediatric DRE regardless of etiology, though responses appear more pronounced in non-genetic cases. Genetic etiology should not preclude VNS consideration, as it remains a safe and effective adjunctive therapy for refractory epilepsy. Aim To evaluate the clinical effectiveness of VNS in pediatric DRE, comparing seizure reduction and ASM burden between genetically and non-genetically determined epilepsies. Materials and methods We retrospectively analyzed 18 pediatric patients (aged 4–18 years) with DRE who underwent VNS implantation between 2021 and 2025. Patients were stratified into genetic (n = 8) and non-genetic (n = 10) cohorts. Seizure frequency and ASM exposure were in comparison to before and after implantation using nonparametric tests. The significance level was set at p < 0.05. Median duration of VNS therapy was 15 months (interquartile range [IQR] width: 16 months). Results Overall, 67% of individuals exhibited clinical improvement, and 61% achieved a ≥ 50% reduction in seizure frequency. Median seizure reduction appeared greater in the non-genetic cohort (60%) than in the genetic cohort (20%), although this difference did not reach statistical significance (p = 0.088). Reduction in ASM burden occurred in 50% of non-genetic cases versus 13% of genetic cases. Post-implantation exposure to calcium-channel modulators was significantly more frequent amongst non-genetic patients (p = 0.036). Conclusions VNS provides clinically observable seizure reduction in pediatric DRE regardless of etiology, though responses appear more pronounced in non-genetic cases. Genetic etiology should not preclude VNS consideration, as it remains a safe and effective adjunctive therapy for refractory epilepsy.