COMMENTARY

Thalamic Stimulation: New Approach to Treatment of Epilepsy

Andrew N. Wilner, MD

Disclosures

April 22, 2010

Epilepsy Treatment: Introduction

The treatment of epilepsy relies primarily on antiepileptic medications, which control seizures in approximately two thirds of patients. Other proven therapeutic modalities include epilepsy surgery, vagus nerve stimulation, and the ketogenic and modified Atkins diets. Scientific evidence for benefit from alternative therapies, such as Yoga, biofeedback, or herbal therapy, remains minimal. The effectiveness of a dramatic new approach, bilateral stimulation of the anterior nucleus of the thalamus, has recently been reported.[1]

Thalamic Stimulation

A double-blind, randomized trial of bilateral stimulation of the anterior nucleus of the thalamus for epilepsy (SANTE) demonstrated a reduction in seizures among a majority of patients with medically refractory partial seizures.[1]The multicenter trial was sponsored by medical device manufacturer Medtronic.

Background

Wide experience in deep-brain stimulation (DBS) in the treatment of Parkinson’s disease has paved the way for the use of this technique for the treatment of refractory epilepsy. Advances in magnetic resonance imaging, stereotactic devices, and microelectrodes allow more precise targeting and electrode placement.

The authors selected the anterior nucleus of the thalamus for stimulation on the basis of the knowledge that it projects to the superior frontal and temporal lobes and previous observations that its stimulation can reduce seizures and produce changes on the electroencephalogram. Stimulation of a relatively small anatomic site in the thalamus can affect widespread areas of cortex.[2]

Results

The SANTE study, led by Robert Fisher, MD, PhD, Professor of Neurology and Director of the Stanford Comprehensive Epilepsy Center, Stanford, California, randomly assigned 110 adults with medically refractory partial seizures to 3 months of blinded stimulation or no stimulation, followed by unblinded stimulation for all participants. In all patients, at least 3 antiepileptic drugs had failed. Although seizures decreased in both groups, stimulated patients had an unadjusted median decline at the end of the blinded phase of 40.4% compared with a decrease of only 14.5% in the nonstimulated group. Stimulated patients with temporal lobe seizures improved compared with the control group, whereas those with extratemporal (frontal, parietal, occipital) seizures did not.

At the end of 2 years, 91 patients remained active in the study; 54% had a seizure reduction of at least 50%, and 14 patients were seizure free for at least 6 months. In addition, seizure-related injuries occurred in only 7% of the treatment group compared with 26% of the control group during the blinded phase (P = .01).

Mechanism of Action

The thalamus has long been implicated in epilepsy[3] but is more often discussed in terms of idiopathic generalized epilepsy rather than localization-related epilepsy. The mechanism of action of seizure reduction by anterior thalamic DBS has not been elucidated but is under investigation.

Advantages

Unlike brain surgery, DBS is nondestructive. The stimulator can be turned off and removed if necessary, leaving the brain essentially intact.

Adverse Events

Device-related adverse events included paresthesias (18.2%), implant site infections (12.7%), and implant site pain (10.9%). Five hemorrhages (4.5%) were observed on neuroimaging but were not symptomatic. One patient had a meningeal reaction. Patients who received stimulation were significantly more likely to report depression or memory problems. Cognitive and mood scores from neuropsychological testing were similar between the groups. Eighteen patients (16.4%) withdrew from the study because of adverse events.

Conclusions

The SANTE study results are under review by the Food and Drug Administration for possible approval for the treatment of medically refractory partial seizures. It is too early to determine the role that DBS may have in the treatment of epilepsy. The risk/benefit ratio of this procedure needs to be further clarified, with more attention to the long-term effects of repeated stimulation on epileptic brain circuitry, depression, and memory. For patients who are not surgical candidates, DBS may become an additional alternative. Even for those who are candidates for surgery, a trial of DBS may be warranted before surgical resection. A comparison of DBS with the vagus nerve stimulator would be of interest. If approved, DBS will be a very important option for seizure control in people with refractory partial seizures.

*Dr. Wilner also writes NeuroNotes and is the author of Epilepsy:199 Answers (3rd ed).

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