The mechanism of action of vagus nerve stimulation for refractory epilepsy- The current status

Vagus nerve stimulation (VNS) is a neurophysiologic treatment for patients with medically or surgically refractory epilepsy. Since the first human imp lant in 1989, more than 10,000 patients have been treated with VNS. The pre cise mechanism of action remains to be elucidated. Animal experiments with VNS were initially performed to demonstrate efficacy and safety preceding t he clinical trials in human patients. Mechanism of action research involvin g animal experiments can provide essential clues. Animal experiments are of ten labor-intensive even in the hands of experienced researchers, however, and the results remain only a reflection of the complicated pathophysiologi c systems of the human brain. Mechanism of action research in human patient s treated with VNS is particularly challenging because of safety concerns, the large number of patients required, and the heterogenous nature of vario us small patient series. This study provides an overview of the progress th at has been made in the past 10 years through neurophysiologic, neuroanatom ic, neurochemical, and cerebral blood flow studies in animals and patients treated with VNS. Further elucidation of the mechanism of action of VNS may increase its clinical efficacy. It may also provide inspiration for the de velopment of new therapeutic modalities for refractory epilepsy.