Translational research to unravel the mechanism of action of vagus nerve stimulation

Abstract

Abstract Vagus nerve stimulation (VNS) is a neurophysiological treatment for patients with drug resistant epilepsy. To date the precise mechanism of action remains to be elucidated. Better insight in the mechanism of action may identify seizure types or syndromes that respond better to VNS, may guide the search for optimal stimulation parameters and finally improve clinical efficacy. In the field of the search for mechanisms of action animal experiments can provide essential clues such as crucial neuranatomical structures that are involved in the seizure-suppressing effect of VNS. The nucleus of the solitary tract as well as the locus coeruleus have been identified to play such a role. With the development of animal models that mimic human refractory epilepsy more reliably such as the kindling model, the status epilepeticus model and genetic models more valuable and usable information for human applicability may become available. In the past ten years some progress has been made through neurophysiological, neuroanatomical, neurochemical and cerebral blood flow studies in patients and animals undergoing VNS. Interesting results have been found in VNS-treated patients that underwent evoked potential measurements, cerebrospinal fluid investigation, neuropsychological testing and PET, SPECT and fMRI testing. Desynchronisation of abnormal synchronous epileptic activity is one of the hypotheses on the mode of action that might primarily be responsible for an anti-seizure effect. There is however increasing evidence from research and clinical observation that VNS might establish a true and long-term anti-epileptic effect. It has been shown that VNS influences neurotransmission in the brain and provokes long-term changes in cerebral blood flow in areas crucial for epileptogenesis such as the thalamus and medial temporal lobe structures. Further elucidation of the mechanism of action may increase the clinical efficacy of VNS and provide inspiration for the development of new therapeutic modalities in the field of neurostimulation and epilepsy. Keywords: vagus nerve stimulation, mechanism of action, epilepsy