Evolution of the Vagus Nerve Stimulation (VNS) Therapy System Technology for Drug-Resistant Epilepsy

Abstract

The vagus nerve stimulation (VNS) Therapy® System is the first FDA-approved medical device therapy for the treatment of drug-resistant epilepsy. Over the past two decades, the technology has evolved through multiple iterations resulting in software-related updates and implantable lead and generator hardware improvements. Healthcare providers today commonly encounter a range of single- and dual-pin generators (models 100, 101, 102, 102R, 103, 104, 105, 106, 1000) and related programming systems (models 250, 3000), all of which have their own subtle, but practical differences. It can therefore be a daunting task to go through the manuals of these implant models for comparison, some of which are not readily available. In this review, we highlight the technological evolution of the VNS Therapy System with respect to device approval milestones and provide a comparison of conventional open-loop vs. the latest closed-loop generator models. Battery longevity projections and an in-depth examination of stimulation mode interactions are also presented to further differentiate amongst generator models.

Dogs as a Natural Animal Model of Epilepsy

“…In line with this suggestion, the results of VNS in dogs were confirmed in a monkey model and shortly thereafter in the first VNS implant in an adult patient with DRE (341). After positive data from two RCTs, the VNS Therapy R System received FDA approval in 1997 for use as adjunctive therapy in reducing the frequency of focal-onset seizures which are refractory to ASMs (341). The first clinical trial using this device in dogs with DRE was published in 2002 (342), reporting up to a 50% reduction in seizure frequency in four of nine dogs.…”

“…Vagal stimulation terminated seizures in 0.5-5 s. Zabara (280) suggested that these results may form the basis of a new therapeutic approach to epilepsy. In line with this suggestion, the results of VNS in dogs were confirmed in a monkey model and shortly thereafter in the first VNS implant in an adult patient with DRE (341). After positive data from two RCTs, the VNS Therapy R System received FDA approval in 1997 for use as adjunctive therapy in reducing the frequency of focal-onset seizures which are refractory to ASMs (341).…”

Clinical Benefit of Vagus Nerve Stimulation for Epilepsy: Assessment of Randomized Controlled Trials and Prospective Non-Randomized Studies

“…Newer generation implantable pulse generators now provide the option for cardiac-triggered stimulation, automatic changes in planned changes in stimulation parameters, and the integration of event detection monitoring which aids in therapeutic optimization. 37 In parallel with these advances, latest generation implantable pulse generators are physically smaller than the original device and have significantly longer battery life. Our analysis of the literature raised several key questions that await future investigations, including development of biomarkers for identification of seizure patients who are most likely to benefit from VNS as well as resolving the discrepancy between efficacy of VNS in RCTs when compared to “real world” experiences.…”

The Neuromodulator Effect of Vagal Nerve Stimulation as the Treatment of Medically Refractory Epilepsy in Comparison with Surgical Approach: A Systematic Review

“…analyzed patients to predict the outcome with>90% seizure reduction after VNS. [5] Villarreal et al researched the predictor for seizure-free after VNS in follow-up. There was no randomized controlled trial among the included studies, and most were retrospective studies.…”