Vagus Nerve Stimulation for Intractable Seizures

Abstract

Vagus nerve stimulation (VNS) is the most widely used non-pharmacological treatment for pharmacoresistant epilepsy since 1988 based on experimental and clinical observations over several decades. In 1997, the FDA approved VNS “as an adjunctive treatment for partial refractory epilepsy in adults and adolescents over 12 years of age”. Considering that polytherapy seldom contributes to seizure control after monotherapy has failed, the need for options—even if only palliative—to address the devastating health, psychosocial, and economic consequences of refractory epilepsy in selected groups and the increasing concern about adverse effects of medications on neurological development, VNS usage has been extended to younger age groups and patients with generalized seizures, who are not candidates for resective surgery. VNS therapy involves implantation of a battery-operated device in the upper chest with two subcutaneously placed wires with electrodes attached to the left vagus nerve in the carotid sheath. The generator is programmed by a telemetry wand attached to a laptop computer. Stimulation is usually initiated 15 days alter implantation and adjusted over time on the basis of patient tolerance and response. The safety, tolerability, and efficacy of the procedure and therapy have been repeatedly demonstrated in prospective randomized clinical trials, uncontrolled retrospective series and long-term follow-up series. Complications of surgery are rare with infection being the most often reported, while stimulation related side effects are usually mild and in most cases decrease over time or can be resolved by changing stimulation parameters. Series have shown a remarkably consistent average reduction in seizure frequency of 40–50% responder rate (i.e., the proportion of patients whose seizure frequency is reduced by at least 50%) with no obvious indication of tolerance and generally a long-term increase of efficacy. The number of patients who become seizure free is relatively small. The use of on-demand stimulation triggered by a handheld magnet that may help to prevent or abort seizures has also been cited as a substantial benefit. Other positive outcome measures include improvement in mood, alertness, memory and postictal recovery period, which have been collectively seen as improvement in quality of life. Cost-benefit of the therapy has also been documented, although in many countries the deterrent to the use of VNS is currently the initial cost of the device. However, despite extensive clinical studies and studies on experimental animal models, three aspects of VNS remain elusive (a) the exact mechanisms of action, (b) the definition of stimulation parameters for optimal seizure control, and (c) the precision of factors that can predict which patients will respond and to what extent. Given these evidences, VNS should be considered within a comprehensive epilepsy surgery center on a patient to patient basis, following a detailed bio-psycho-social workup and review of expenses ands risks weighted against expectations, and potential improvements in seizures and quality of life.