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.