Pediatric "Super Responders" to Vagus Nerve Stimulation Achieve Early Seizure Freedom With Low-Charge Density

Vagus nerve stimulation (VNS) is an established therapy for drug-resistant epilepsy, although complete seizure freedom is rare. Prognostic factors for seizure freedom remain unclear. Optimizing stimulation parameters remains a challenge, particularly in the later stages of treatment if efficacy is uncertain. This study investigated the clinical characteristics and stimulation settings of pediatric patients with VNS in whom complete seizure freedom was achieved, including the absence of auras. By investigating these exceptionally responsive individuals, referred to as "super responders" (SRs) in this study, we aim to identify key characteristics, including programming paradigms, that may predict strong VNS responsiveness in children.

A retrospective review was conducted in pediatric patients (aged <18 years) who underwent VNS implantation. Clinical and demographic characteristics of SRs were compared with non-SRs. Stimulation parameters, including output current and duty cycle, were analyzed.

Of 129 patients, ten were classified as SRs. Epilepsy duration before surgery was significantly shorter in SRs (mean: 5.7 years) than in non-SRs (mean: 8.3 years; p = 0.043). No significant differences were found in sex, age at epilepsy onset, age at surgery, epilepsy etiologies, epilepsy types, prior treatments including epilepsy surgeries, or imaging findings. Seizure freedom was achieved in SRs with significantly lower stimulation settings (mean output current: 0.84 mA; duty cycle: 12.3%) than in non-SRs (1.91 mA and 19.6%; p < 0.001 and p = 0.015, respectively). All SRs had seizure freedom within one year of therapy initiation, with six doing so within six months (mean follow-up: 3.8 years).

Complete seizure freedom after VNS in children was associated with shorter epilepsy duration, underscoring the importance of early neurosurgical referral. SRs showed early favorable responses within the first year despite lower charge density, suggesting potential intrinsic brain features that predispose them to benefit from VNS. Further research into predictive biomarkers is warranted.