Brain Stimulation an Option for Epilepsy Market

by Warren Grill, senior technical editor

Approximately one third of the 2.3 million Americans with epilepsy are refractory to medical treatment. This has led to substantial efforts to develop neural stimulation devices to treat epilepsy. Cyberonics’ VNS system for stimulation of the vagus nerve is the only device on the market to treat epilepsy, and last year had 18 percent growth in international sales. A recent series of reports provides updates on the prospects for control of epilepsy by direct stimulation of brain targets.

In a follow-up to their earlier report, Andrade and colleagues from the University of Toronto report in Neurology on the effects of deep brain stimulation (DBS) for control of epilepsy. The effects of DBS in either the anterior nucleus (AN) or the centromedian nucleus (CMS) of the thalamus was assessed in eight subjects. The seizure frequency was reduced in all subjects following implantation of the electrodes, but subsequent application and removal of stimulation did not result in any apparent further changes in seizure frequency. The reduction in seizures was attributed to the lesion associated with implantation of the electrode.

While the lack of clear effect of stimulation may be the result of inappropriate stimulation parameters, these were explored over a wide range in several subjects. Adverse events related to stimulation included eye movements, possible auditory hallucinations and anorexia, and feelings of numbness or tingling. Medtronic Inc. is continuing their SANTE trial (Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy) to determine the safety and efficacy of their Intercept Epilepsy Control System.

Alternative brain targets are also being pursued, and Tellez-Zenteno and colleagues from the University of Western Ontario report in Neurology on the effect of hippocampal DBS in four subjects with mesial temporal lobe epilepsy. Seizure frequency was measured during one-month stimulation ON and stimulation OFF periods in a double-blind multiple crossover design. Seizure frequency decreased in three subjects, and across all subjects there was a median 15 percent reduction in seizure frequency. However, it appeared that, similar to the case with thalamic electrodes, implantation of the DBS electrode resulted itself in a substantial degree of seizure reduction.

A recent review of cortical stimulation for control of epilepsy was more optimistic. Martha Morrell, Chief Medical Officer at NeuroPace, Inc. (Mountain View, CA) writing in Current Opinion in Neurobiology, stated that “responsive neural stimulation may be effective in terminating human spontaneous seizures.” Results from NeuroPace’s multi-center feasibility investigation were presented by Gregory Bergey from Johns Hopkins, and colleagues at the 58th Annual Meeting of the American Academy of Neurology held in April in San Diego. Following seizure detection, the Responsive Neurostimulator System delivered stimulation to the seizure focus through either cortical surface or depth electrodes. Between 29 percent and 64 percent of the 38 subjects had greater than a 50 percent reduction in seizure frequency, depending on the seizure type. NeuroPace is continuing a clinical trial to determine the safety and efficacy of their RNS to reduce seizure frequency.

Epilepsy is a complex disease, and seizure frequency is often highly variable, may be influenced by changes in medications, and placebo effects can be quite strong. Further, there is still a lack of understanding of the mechanisms of action whereby brain stimulation can suppress seizures, and this makes selection of appropriate stimulation parameters challenging. However, epilepsy remains a substantial opportunity for neurotech devices.