Major Findings: Seizures declined by a mean of 29% during active stimulation with the device over the first 12 weeks, compared with a 14% reduction during sham activation.
Source of Data: Multicenter, randomized, sham-controlled clinical trial of 191 patients with medically intractable partial onset seizures.
Disclosures: Dr. Morrell is the chief medical officer of NeuroPace, which developed the system and funded the trial.
BOSTON — Patients with treatment-resistant epilepsy can significantly reduce their frequency of seizures with the use of an implantable device that detects pre-seizure electrical activity and preemptively aborts seizures, the results of a multicenter randomized controlled trial suggest.
In 191 patients with medically intractable partial onset seizures who were implanted with the neurostimulator, seizures declined by a mean of 29% during active stimulation with the device, compared with a 14% reduction during sham activation, Dr. Martha J. Morrell reported at the annual meeting of the American Epilepsy Society.
In the later, open-label phase of the study in which all of the patients received the active stimulation, nearly half of the 171 patients for whom 12 weeks of data were available experienced at least a 50% reduction in seizure frequency relative to baseline, said Dr. Morrell, clinical professor of neurology at Stanford (Calif.) University and chief medical officer of NeuroPace, developer of the Responsive Neurostimulator System (RNS).
The cranially implanted RNS device differs from conventional, “open loop” brain stimulation technologies that involve the scheduled delivery of electrical stimulation to specific brain regions independent of brain activity.
The responsive neurostimulation system comprises electrodes that are surgically implanted in epileptic regions of the brain and connected to the computerized, battery-powered neurostimulator, which is embedded in the patient's skull. The device is programmed to detect and disrupt significant electrical events.
“The programming is done wirelessly by the physician via a laptop computer,” Dr. Morrell said. “It's highly modifiable in that the physician can view the patient's electrocorticographic activity in real-time and change the [signal-detection] criteria at any time based on individual patient characteristics.”
Because the neurostimulation occurs in response to aberrant electrical activity in the patient's brain, fewer electrical impulses are being delivered to the brain than would occur with continuous stimulation. This in turn diminishes the possibility of treatment-related adverse events, Dr. Morrell explained.
In an initial feasibility study of 65 patients, the responsive neurostimulation system demonstrated excellent safety, tolerability, and preliminary evidence of efficacy, Dr. Morrell said.
The preliminary efficacy evidence from that study showed that a minimum 50% reduction in seizure frequency was experienced by 43% of the patients with complex partial seizures and 35% of those with total disabling seizures (Neurotherapeutics 2008;5:68–74).
In the double-blind pivotal trial, the 191 patients were randomized to active or sham therapy. All of the patients were 18–70 years of age (median age 35 years), and all had partial onset epilepsy localized to one or two foci and had failed at least two antiepileptic medications.
The patients were taking an average of three antiepileptic medications to attempt seizure control, and approximately 34% of the patients had been treated previously with vagus nerve stimulation, 33% had prior surgical resection, and 16% had been treated with both.
Of the 191 patients implanted with the responsive neurostimulator device, 50% had mesial temporal seizure onset, 42% had neocortical seizure onset, and 8% had both, Dr. Morrell said in a press briefing at the meeting.
The trial consisted of an initial 12-week period prior to system implantation during which baseline seizure activity was collected, followed by a 12-week blinded period when participants were randomly assigned to have the responsive stimulation activated or left inactive, she said.
At each of the 31 trial sites, the patients and one neurologist were blinded to the stimulation status, while a separate neurologist programmed the devices to maintain the study blinding. The responsive stimulation was optimized in the treatment over the next four weeks, followed by 84 days of data collection, Dr. Morrell said.
The responsive neurostimulation system has not yet received Food and Drug Administration approval, but NeuroPace plans to submit a premarket approval application early this year, she said.
My Take
Devices Likely to Improve Over Time
The development and use of stimulation devices for medically refractory epilepsy represents an altogether new approach when surgery is not possible and pharmacology is ineffective. Open loop devices that deliver electrical stimulation on a duty cycle include the vagal nerve stimulator (Cyberonics) and the thalamic deep brain stimulator (Medtronic).
The Responsive Neurostimulator device (NeuroPace), the first closed loop stimulator, is distinctly different than the other devices. Once it is permanently implanted using depth or surface leads, the RNS device detects and analyzes EEG/electrocorticography on a continuous basis. The device is programmed to “recognize” an individual's unique ictal onset through various algorithms. Once the abnormal signal is detected, the device responds quickly to deliver a small electrical potential in an attempt to abort the abnormal EEG activity before it can spread and become a clinical seizure.