More Good News for Deep Brain Stimulation in Epilepsy

Pauline Anderson

December 03, 2012

San Diego, California — The positive effects of bilateral stimulation of the anterior nuclei of the thalamus appear to be long-lasting, with a 69% median reduction in seizure frequency at 5 years, according to updated data.

Importantly, the latest results from the ongoing Stimulation of the Anterior Nucleus of Thalamus for Epilepsy (SANTE) trial also showed that patients had improved quality of life.

"Despite the fact that these patients were so refractory, they showed a significant decrease in frequency of seizures," Vicenta Salanova, MD, professor of neurology and director of the Indiana University School of Medicine Comprehensive Epilepsy Program told Medscape Medical News.

On the basis of earlier positive SANTE trial results, the deep brain stimulation (DBS) device, manufactured by Medtronic Inc, has been approved in Europe and in Canada. However, it's still considered investigational in the United States after the US Food and Drug Administration voted against approving it in 2010, despite a positive recommendation from an advisory panel. At that time, there was some concern that the 3-month blinded phase may not have been long enough, said Dr. Salanova. She emphasized that there are no safety issues related to the device.

"We hope that based on the results we have shown — that there is continuous improvement — that the device will eventually be approved in the US," said Dr. Salanova.

The 5-year SANTE trial results were presented here at the American Epilepsy Society (AES) 66th Annual Meeting. The trial was funded by Medtronic Inc.

Still Investigational

The SANTE trial enrolled 110 adult patients who had at least 6 partial or secondarily generalized seizures per month and in whom at least 3 antiepileptic drugs had failed.

"These patients were very, very refractory to treatment," said Dr. Salanova. Study patients had not responded to numerous drug, and many had not responded to resection surgery (a standard epilepsy treatment) or neurostimulation, she said.

The trial used a prospective randomized, double-blind, parallel-group design. After a 3-month baseline, researchers implanted DBS electrodes in the anterior nuclei of the thalamus bilaterally. One month later, they randomly assigned patients to stimulation at 5 V or to no stimulation. After 3 months of blinded treatment, all patients received stimulation.

The primary analysis was performed on patients with at least 70 days of diary data.

The study found a median reduction in seizure frequency of 40% by the end of the blinded phase in patients receiving the stimulation compared with 14.5% for controls.

The improvement continued over time: The median reduction from baseline was 41% at 1 year, 56% at 2 years, and 69% at 5 years.

As well, the rate of responders, defined as a 50% or greater reduction in seizure frequency, was also 69% at 5 years, said Dr. Salanova.

The new SANTE results also showed that patients had improvements on measures of quality of life compared with baseline. No unanticipated adverse device effects and no symptomatic intracranial hemorrhages occurred, the authors report.

Hippocampal DBS

Commenting on these results, Paul Boon, MD, head, Department of Neurology, Ghent University Hospital, Belgium, said they are "encouraging" and contribute to "accumulating evidence that stimulating the anterior nucleus actually affects epileptogenic networks."

However, further work is needed to widen the eligible patient population, he said. "I can't foresee that in 10 years all patients will have an anterior nucleus deep brain stimulation as we perform it right now, but I can foresee that there will be optimization in terms of stimulation," and other measures used in DBS.

Dr. Boon was part of another research team that reported that DBS is effective in treating temporal lobe epilepsy in an animal model and causes no damage to the hippocampus.

The team found that rats induced into status epilepticus and stimulated for 10 weeks had significantly fewer seizures in week 14 compared with a control group receiving sham stimulation and another group receiving shorter DBS whose seizures increased at relatively similar rates.

This approach appears to be an appropriate one for patients, too, according to an open-label study of 11 patients with temporal lobe epilepsy. These patients, who were not eligible for surgery and received hippocampal DBS, were followed for up to 86 months. Dr. Boon reported that the responder rate in these patients was a relatively high 70% and that these patients have had no negative cognitive effects.

A randomized controlled trial is being organized in 2 European centers to test hippocampal DBS in patients with refractory unilateral temporal lobe epilepsy, said Dr. Boon. Researchers aim to recruit 45 patients in 3 groups: surgery, immediate stimulation, or delayed stimulation.

American Epilepsy Society (AES) 66th Annual Meeting. Abstract 1.272, Platform A.04. Presented December 2, 2012.