Allison Gandey

December 15, 2009

December 15, 2009 (Boston, Massachusetts) — The investigational neurostimulator known as the RNS System appears to decrease partial-onset seizures with a low rate of serious adverse events. Presenting here at the American Epilepsy Society 63rd Annual Scientific Conference, investigators unveiled positive results for their double-blind, randomized, sham-stimulation controlled trial.

"The RNS System is safe and effective as adjunctive therapy in medically intractable partial epilepsy," lead investigator Martha Morrell, MD, from Stanford University in Palo Alto, California, presented.

The RNS System is battery powered and connected to 2 leads.

Dr. Morrell is also the chief medical officer for NeuroPace, the maker of the new device. The company plans to submit a premarket approval application to the US Food and Drug Administration in early 2010.

Investigators studied 191 subjects in the multicenter trial. Patients were 18 to 70 years of age and had not responded to 2 or more antiepileptic drugs. "Subjects were very ill, many of them with epilepsy for 20 years," Dr. Morrell said.

About a third of patients had also tried a vagus nerve stimulator, and another third had been treated surgically. Patients were having a median of 9.7 seizures per month. Dr. Morrell pointed out that two thirds of patients did not qualify for surgery because of the location of seizure onset.

Unlike continuous stimulation devices already on the market for vagus nerve and deep brain stimulation for Parkinson's disease and essential tremor, the RNS System intervenes in response to detected epileptiform activity. Responsive stimulation differs from other stimulators that intervene continuously or on a preset schedule.

The system is designed to detect abnormal electrical activity in the brain and deliver small amounts of electrical stimulation to suppress the abnormal activity before any seizure symptoms occur. "Almost without exception, patients could not perceive stimulation and most didn't require a high charge density," Dr. Morrell explained during a media briefing.

A clinical engineer from the trial using the system.

The system stores time- and date-stamped records of all detections and stimulations that clinicians can later access. The battery life on the system depends on how it is programmed, but typically it lasts 2 to 4 years. Dr. Morrell says that replacement is a quick and straightforward process, often as an outpatient procedure.

Investigators found that subjects in the treatment group experienced a mean percentage reduction of 29% compared with 14% in the sham stimulation group. In the long-term, open-label period of the trial, at least 12 weeks of data were available for 171 study participants. Researchers found that 47% of these patients experienced a 50% or greater reduction in their seizure frequency.

The overall infection rate in the study was 7.8%, and the overall hemorrhage rate was 4.7%. There were 2 deaths in the trial. The investigators suggest that the first death was due to sudden, unexpected death in epilepsy and the second was from suicide.

Table 1. Implant Site Infections and Intracranial Hemorrhage

Adverse Event and Location Percentage Severity
Infection    
Implant site 5.2 9 Serious
(2 due to seizure-related trauma)
and 7 resolved
Incision site 2.6 Mild and resolved
Hemorrhage    
Extradural 1.6 2 Serious, all resolved
Subdural 2.1 4 Serious
(3 due to seizure-related trauma)
and 3 resolved
Cerebral 1.0 1 Serious and resolved

 

Table 2. Psychiatric-Related Events

Adverse Event Percentage Severity
Panic attack 3.7 All mild, 6 of 7 resolved
Anxiety 6.3 All mild, 9 resolved
Depression 11.0 All mild, 10 resolved
Suicidal and depression ideation 3.7 3 serious, 6 resolved
Suicide attempt 1.0 All serious, 2 resolved
Completed suicide 0.5 Serious
Self-injury 0.5 Mild and resolved

 

During the discussion period at the meeting, attendees were generally enthusiastic about the trial findings. The results mirror those of another recent deep brain stimulation trial from Medtronic.

That study, known as SANTE (Stimulation of the Anterior Nucleus of the Thalamus in Epilepsy), is a prospective, randomized, double-blind trial. It evaluated deep brain stimulation in patients with medically intractable partial epilepsy.

The stimulator differs from the RNS System and instead of skull surgery uses a system similar to a cardiac pacemaker. The Medtronic device stimulates the left and right anterior nucleus of the thalamus. The company has already submitted a premarket approval to the US Food and Drug Administration.

SANTE lead investigator Robert Fisher, MD, from Stanford University, congratulated the investigators at the meeting. "These results reinforce the positive effects of stimulation," he said. "I feel like we have a newborn baby, but now it's twins," he laughed.

"There's nobody else I'd rather be a twin with, Bob," Dr. Morrell joked.

Jacqueline French, MD, from New York University's Comprehensive Epilepsy Center in New York City, also congratulated the researchers on their positive trial. "It is clearly having an effect," she said. But Dr. French also encouraged caution. "Long-term data suggest that some patients do achieve seizure freedom without intervention," she noted.

Steep Learning Curve

Dr. French is commission cochair of the International League Against Epilepsy task force, which is developing a consensus definition of drug-resistant epilepsy. "After a 1-year period, about 5% of even severely refractory patients will achieve seizure freedom," she said.

Asked by Medscape Neurology to comment, platform session moderator Thomas Henry, MD, from the University of Minnesota in Minneapolis, said the therapy appears to be well tolerated with a low complication rate.

Dr. Henry said that he does not agree with Dr. French's point. "I don't think this is a commonly expressed concern," he said.

Dr. Morrell acknowledged that these are early days for this new intervention and much work remains to be done. "We are just opening the door," she said, "and one day we will remember when we didn't know how best to implement this treatment. It is a very steep learning curve."

This study was funded by NeuroPace. Dr. Morrell is the chief medical officer of NeuroPace.

American Epilepsy Society (AES) 63rd Annual Scientific Conference: Platform session B.09. Presented December 7, 2009.

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