Vagus nerve stimulation – Mechanism of action and usefulness of its combination with corpus callosotomy for palliation of refractory epilepsy

Vagus nerve stimulation (VNS) is indicated as an adjunctive therapy for refractory epilepsy patients who are not suitable for resective surgery (adults: grade A; children: grade C recommendation). It is effective to various seizure types regardless of their pathology both acutely and chronically. Early studies revealed a mean seizure frequency reduction of 24–31% over 3 months of follow-up. And its effects are enhanced over time (median seizure reduction of 45% at one year, with 20% of patients achieving a greater than 75% reduction).

Its mechanism of action (MOA) is not established yet. Theories include direct activation, neurotransmitter and neuropeptide modulation influencing ictal discharge, preictal changes and arousal. VNS is thought to have an effect on EEG synchronization which may prevent establishing epileptic discharge in the neural circuits and act as the acute effect. In VNS effective patients, PET scanning showed increased blood flow in the thalamus, hypothalamus, and the insular cortex with decreased blood flow in the amygdala, hippocampus, and posterior cingulate. Animal studies have looked into various possible mechanisms. In a maximal electroshock rat epilepsy model, VNS therapy was no longer effective when noradrenergic pathways were depleted by lesioning of the locus coeruleus. These data suggest complex MOA of VNS in both acute and chronic phases.

In recent years, we have studied the combination of VNS and corpus callosotomy, and found the combination of both techniques in selected patients achieves better results than both techniques separately. In this paper we would discuss our tentative experience and indications.