Neurostimulation as a Treatment Option for Epilepsy
Neurostimulation as a Treatment Option for Epilepsy
European Neurological Review 2010; 5(1): 92–6
Abstract
Although neurostimulation is not a new treatment modality, it is an emerging treatment for various neurological diseases. Currently available pharmacological and surgical treatments leave about 30% of patients not seizure-free. Electrical stimulation of the 10th cranial nerve or vagus nerve stimulation (VNS) is an extracranial type of stimulation that is currently routinely available. Through an implanted device and electrode, electrical pulses are administered to the afferent fibres of the left vagus nerve in the neck. VNS is indicated in patients with refractory epilepsy who are unsuitable candidates for epilepsy surgery or who have had insufficient benefit from such a treatment. Intracerebral neurostimulation requires accessing the intracranial nervous system as stimulation electrodes are inserted into intracerebral targets for deep brain stimulation (DBS) or placed over the cortical convexity for cortical stimulation (CS). Recently, trials with DBS in different intracerebral structures such as the thalamus, the subthalamic nucleus and medial temporal lobe structures have been performed. CS ± DBS in a closed-loop system (responsive neurostimulator system [RNS]) is currently being investigated in a multicentre trial. It is likely that neurostimulation for epilepsy will become a more practical and more widely used treatment modality for patients with refractory epilepsy.
Keywords
Neurostimulation, seizures, refractory epilepsy, therapeutic stimulation
Disclosure: Paul Boon and Kristl Vonck are supported by grants from the Ghent University Research Fund (BOF), the Fund for Scientific Research Flanders and the Clinical Epilepsy Research Grant of Ghent University Hospital. Both authors have received speaker and consultancy fees and travel grants from Cyberonics. Paul Boon has received speaker and consultancy fees and free devices for deep brain stimulation studies from Medtronic.
Received: 6 June 2010 Accepted: 29 June 2010 Citation: European Neurological Review, 2010;5(1):92–96
Correspondence: Paul Boon, Department of Neurology, Ghent University Hospital, De Pintelaan 185, 9000 Gent, Belgium. E: Paul.Boon@UGent.be
Vagus Nerve Stimulation
Electrical stimulation of the 10th cranial nerve or vagus nerve stimulation (VNS) has become a valuable option in the therapeutic armamentarium of adults and children with refractory epilepsy. Since its introduction in 1989 over 50,000 patients have been treated with VNS worldwide. Efficacy, side effects and tolerability have been extensively studied. The precise mechanism of action remains to be elucidated, but some essential intracerebral pathways have been identified.1
Clinical Efficacy
In the early 1990s, initial results from two single-blinded pilot clinical trials (phase I trials EO1 and EO2) in a small group of patients with refractory complex partial seizures from three epilepsy centres in the US were reported.2–5 In nine out of 14 patients treated for three to 22 months, a reduction in seizure frequency of at least 50% was observed.6 Complex partial seizures, simple partial seizures and secondary generalised seizures were affected. It was noticed that reduction in the frequency, duration and intensity of seizures lagged four to eight weeks after the initiation of treatment.2 In the meantime, two prospective multicentre (n=17) double-blind randomised studies (EO3 and EO5) were started including patients from centres in the US (n=12), Canada (n=1) and Europe (n=4).7–11 The results of EO3 in 113 patients showed a 24% decrease in seizures in the treatment group versus 6% in the control group after three months of treatment. The number of patients was insufficient to achieve US Food and Drug Administration (FDA) approval, leading to the EO5 study of 198 patients in the US. Ninety-four patients in the treatment group had a 28% decrease in seizure frequency versus 15% of patients in the control group.11
The controlled EO3 and EO5 studies had their primary efficacy end-point after 12 weeks of VNS. Increased efficacy with longer treatment was found in all published reports on long-term results.12–16 The mean reduction in seizure frequency increased up to 35% at one year and up to 44% at two years of follow-up. After that, improved seizure controlreached a plateau.
Neurostimulation, seizures, refractory epilepsy, therapeutic stimulation
