Responsive Neurostimulation. Another direct brain neurostimulating technology under FDA review is the Responsive Neurostimulator System (RNS) by NeuroPace. The system detects and aborts spontaneously occurring abnormal discharges* to prevent seizures, explained Dr. Lawrence J. Hirsch of Columbia University in New York. "It is designed to respond within seconds to abnormal activity in the brain by delivering a series of up to five stimuli to terminate the abnormal discharge."
The RNS device is implanted in a recess of the skull, and is connected to up to two four-contact electrodes that are placed within the brain or on the brain surface, depending on where the seizures begin. The device collects and stores seizure information, which the patient subsequently downloads to a laptop using a wand. Physicians can access the stored electrocorticograms via a secure Web page through which they can adjust detection and stimulation parameters specific to the individual patient, Dr. Hirsch said during the neurostimulation plenary session.
In the pivotal clinical trial of the RNS system, 191 patients with medically intractable, partial-onset seizures localized to one or two foci received the cranial implant. During a blinded period, patients received active or sham stimulation, followed by an open-label phase in which all the patients received active stimulation. During the entire blinded evaluation period, active stimulation was associated with a mean 37.9% reduction in seizure frequency, compared with a mean 17% reduction during the sham activation, Dr. Hirsch said.
"In the final month of the blinded period – month 4 to 5 – the respective reduction in seizure frequency was 42% and 9%." During the last 3 months of the open-label period, "47% of the patients had a greater than 50% seizure reduction," he said. "And at 4 years post implant, more than 50% of the patients had at least a 50% reduction in seizure frequency."
A subset analysis showed that neither prior surgery nor the number of seizure foci had an effect on treatment response, Dr. Hirsch noted. "It also showed that [RNS] is possibly more effective with medial temporal onset."
With respect to adverse events, implant site infections were reported in 5% of the patients, and led to explantation in 2%. The combined rate of status epilepticus reported in all trials of the device (256 patients) was 3.5%, and included episodes occurring between 5 months and 5 years post implant. Intracranial hemorrhage was reported in 4% of the patients, and included only one patient with neurological sequelae, which was chronic headache, he said.
The chronic, intracranial EEG recordings provided by the RNS technology have other potentially valuable uses, including seizure prediction/warning; seizure awareness and counting as a way to assess treatment efficacy; identification of circadian, catamenial, and other ictal and interictal patterns; and the lateralization of bitemporal seizures, Dr. Hirsch said.
Dr. Bergey disclosed financial relationships with Pfizer, UCB, and Eli Lilly. Dr. Ben-Menachem disclosed financial relationships with UCB, Eisai, Janssen, Cilag, Cyberonics, Lundbeck, and Sunovion. Dr. Wennberg disclosed a financial relationship with Medtronic. Dr. Hirsch reported having no financial disclosures.
Medtronic's DBS system (top left) stimulates the anterior nucleus of the thalamus, whereas NeuroPace's RNS device (bottom left) responds to abnormal activity in targeted areas and Cyberonics' VNS Therapy System (right) periodically stimulates the left vagus nerve. (Photo Credit: top left: (c) Medtronic Inc., bottom left: (c) NeuroPace Inc., right: (c) Cyberonics Inc.)
* CORRECTION, 12/16/2010: The original version of this article misstated the function of the Responsive Neurostimulator System (RNS) by NeuroPace Inc. The system detects and aborts spontaneously occurring abnormal discharges. Also, the programmed deep brain stimulation device manufactured by Medtronic uses two leads that are placed bilaterally into the anterior thalamus. Each lead contains four electrodes. This version has been updated.