Surgically Induced Subacute Antiepileptic Effect of Vagus Nerve Stimulation before Stimulation Onset

Abstract

Objective: Vagus nerve stimulation (VNS) is an established adjunctive therapy for drug-resistant epilepsy (DRE). Although its long-term efficacy after electrical activation is well recognized, transient seizure reduction has occasionally been observed immediately after implantation, even before stimulation onset. This study aimed to investigate the early postoperative antiepileptic effect of VNS surgery itself during the stimulation-off period. Methods: We retrospectively analyzed 16 patients with DRE who underwent VNS implantation at a single institution between May 2019 and July 2024. Only patients whose stimulators remained off postoperatively were included. The latency to first postoperative seizure was compared with the expected interval estimated from preoperative seizure frequency using the Wilcoxon signed-rank test. Subgroup analysis was performed according to seizure type. Results: The median age was 43.0 years (interquartile range [IQR], 30.0-56.0), and the median latency to first seizure was 25.0 days (IQR, 18.0-48.5). The observed seizure-free interval was significantly longer than expected based on preoperative frequency (p=0.008), with no difference between patients with and without generalized tonic-clonic seizures (p=0.965). No serious postoperative complications were noted. Conclusion: VNS implantation was associated with a transient but significant postoperative seizure-free period even before stimulation onset, suggesting that surgery itself may induce short-term neuromodulatory modulation. This preliminary observation supports the presence of a surgically induced antiepileptic effect and warrants further prospective validation.