The Role of Vagus Nerve Stimulation in the Treatment of Epilepsy

The Role of Vagus Nerve Stimulation in the Treatment of Epilepsy

Montavont Alexandra, Ryvlin Philippe
Published: European Neurological Review - Volume 3 - Issue I
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Following the first encouraging human trials in 1988,1,2 several controlled studies have demonstrated the antiepileptic efficacy of adjunctive vagus nerve stimulation (VNS) in patients suffering from refractory seizures.3–7 Accordingly, VNS was approved in Europe in 1994 as an antiepileptic treatment for patients with generalised or focal drug-resistant epilepsy. In 1997, the US Food and Drug Administration (FDA) approved VNS as an adjunctive antiepileptic treatment for patients over 12 years of age suffering from drug-resistant partial epilepsy.

Following the first encouraging human trials in 1988, 1,2 several controlled studies have demonstrated the antiepileptic efficacy of adjunctive vagus nerve stimulation (VNS) in patients suffering from refractory seizures.3–7 Accordingly, VNS was approved in Europe in 1994 as an antiepileptic treatment for patients with generalised or focal drug-resistant epilepsy. In 1997, the US Food and Drug Administration (FDA) approved VNS as an adjunctive antiepileptic treatment for patients over 12 years of age suffering from drug-resistant partial epilepsy.

At present, more than 50,000 patients from 24 countries have been treated with VNS, a widely used non-pharmacological treatment for epilepsy. The antiepileptic efficacy of VNS is remarkably consistent among series, with an average decrease in seizure frequency of 40%, a 50% responder rate (i.e. the proportion of patients whose seizure frequency declined by at least 50%) usually ranging between 40 and 50% and a proportion of seizure-free patients below 5%. These figures appear stable over time, with no obvious indication of tolerance, although only a few long-term studies, with a follow-up period of more than three years, have been carried out in adults8–13 or in children.14–16 One puzzling limitation to the optimal use of VNS is the lack of a factor that reliably predicts its effectiveness.17,18

Whatever the type of epilepsy being considered, VNS is offered only to patients who continue to suffer from refractory seizures despite wellconducted medical treatments. The number of antiepileptic drugs (AEDs) that must be tested before concluding that the epilepsy is drugresistant remains debatable, but a minimum of two is required. In practice, the majority of patients treated with VNS have previously received numerous AEDs as both monotherapy and polytherapy. Often, these patients have exhausted all other therapeutic options, including surgery, before VNS is proposed. In terms of the advantages and disadvantages of the various antiepileptic treatments, this strategy is not necessarily the most appropriate.

In this article, we aim to pragmatically address the current indications for VNS against the range of therapeutic, medical and surgical alternatives available for the treatment of refractory epilepsies.

Indications for Vagus Nerve Stimulation in Drug-resistant Partial Epilepsy

Vagus Nerve Stimulation versus Antiepileptic Drugs
No controlled study has directly compared the impact of adjunctive VNS versus AEDs alone in patients with drug-resistant partial epilepsy. Indirect comparison of the 50% responder and seizure-freedom rates observed during placebo-controlled trials suggests that the average efficacy of new-generation AEDs is comparable to that of VNS.19 However, numerous factors complicate the interpretation of such indirect comparisons, including significant differences in terms of tolerability profile, ease of use, interruption of treatment and delay of efficacy. Globally, VNS offers the advantage of more favourable central nervous system tolerability than AEDs, but at the price of possible aesthetic concerns or intermittent vocal disturbances, with a delay in efficacy that can often be deferred for several months.

It is for this reason that a direct and global comparison of the effects of VNS and AEDs, incorporating quality of life measurements, is needed to assess the respective benefits of these two therapeutic approaches. This is currently being undertaken as part of an international randomised controlled trial, the PuLse study. The rationale for this study rests on the one hand on the observation that, following the failure of three successive AEDs, the addition of a new drug has very little chance of achieving a seizure-free outcome while often being responsible for disturbing side effects,20 and on the other hand on the notion that VNS might allow a reduction in the number of concomitant AEDs and related side effects.9,21–23 However, recent studies suggest that only a minority of VNS-treated patients experience a significant reduction in their AED load.11,13,24 It is therefore too early to answer the question of whether VNS should be proposed after the failure of only a few AEDs, or instead after all available drugs have been tested.

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