STIMULATING: A new generation of implantable "closed-loop" devices are designed to monitor the seizure focus, detect patterns of electrical activity that indicate a seizure is beginning, and quickly respond without external intervention. Image: Courtesy of Henrik Jonsson, via iStockphoto.com
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Epilepsy affects some 2.7 million Americans—more than Parkinson’s disease, multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease) combined. More than half of patients can achieve seizure control with treatment, yet almost a third of people with epilepsy have a refractory form of the disease that does not respond well to existing antiepileptic drugs. Nor are these patients typically helped by the one implanted device—Cyberonics' Vagus Nerve Stimulator (VNS)—that has had U.S. Food and Drug Administration approval for treatment of epilepsy since 1997.
Because epilepsy causes repeated, sudden seizures, people with the condition would benefit greatly from a therapy that can detect seizures just as they are starting or, eventually, predict them before they begin and prevent them from happening. A new generation of implantable devices is looking to pick up where medications—and even the VNS—often leave off, at least for people whose seizures routinely begin in one part of the brain (the seizure focus). "Closed-loop" devices are designed to monitor the seizure focus, detect patterns of electrical activity that indicate a seizure is beginning, and quickly respond without external intervention. Such responses could include electrical stimulation, cooling or focused drug delivery—all meant to interrupt the activity and stop the seizure.
Closed-loop devices are considered a new frontier in epilepsy treatment because of their responsiveness. By comparison, the VNS is an open-loop device that stimulates the vagus nerve—a pair of nerves running from the brain stem to the abdomen—to deliver mild electrical pulses (which mitigate the electrical activity of seizures) to the brain on a consistent schedule rather than in response to detected seizure activity. The concept of a closed-loop device for epilepsy comes out of the cardiac world, jumping off from implanted defibrillators that monitor the heart and deliver stimulation in response to an event.
So far, only one closed-loop device has reached human trials: NeuroPace's Responsive Neurostimulation System (RNS), an electrical-stimulation implant with two leads, each containing four electrodes, placed in the brain at the seizure focus. The RNS detects electrical activity that denotes the start of a seizure and delivers direct electrical stimulation to interrupt the activity and normalize the area. The device is surgically positioned in a section of the skull, can be accessed via outpatient surgery when the battery has to be changed, and is imperceptible to the patient and others—all strong design advantages for patients and doctors. The implant, which is now seeking FDA approval, also records information on electrical activity in the brain throughout the day for later review. The RNS has a laptop-based wand interface for remote patient monitoring.
Results of the RNS trials, which tested the implant in conjunction with medications, have been mixed: seizure frequency was reduced by about half in approximately 50 percent of patients. "For a patient to go though permanent implanting of the device on the skull, and electrodes over the brain, which is what is needed for RNS, you'd want it to eliminate most or all seizures, which isn't the result in most patients," says John Miller, director of the University of Washington School of Medicine's Regional Epilepsy Center at Harborview in Seattle. Possible ways to improve the device's effectiveness, Miller says, could include refining patient selection, improving electrode placement or honing the RNS's detection process so that it can pick up seizure activity earlier.
Work in closed-loop electrical stimulation is also happening at Boston’s Center for Integration of Medicine and Innovative Technology, where researchers are effectively attempting to turn the VNS into a closed-loop device by developing a nonimplanted add-on system to detect early seizure activity and automatically fire the VNS in response. The VNS comes with a therapy magnet wristband that allows wearers to stimulate the device if they feel a seizure coming on (a sensation called an aura), but not everyone is physically able to do so once the aura begins. The CIMIT system automates the process, activating the VNS once the start of a seizure is detected through electroencephalogram and electrocardiogram readings.
Another key area of closed-loop research is focal cooling. Here, an implant—after detecting the onset of a seizure by sensing a rise in brain temperature at the seizure focus, which may slightly precede the start of abnormal electrical activity—rapidly cools the involved region to halt the event. The warming associated with the seizure focus makes thermal detection and cooling a potentially promising technique. One center of focal cooling research is the University of Kansas Medical Center, where Ivan Osorio, professor of neurology, has collaborated with an international research partnership to design a prototype implant with funding from the U.S. Department of Energy. Work on cooling is also in progress at other sites, including Yale University and the University of Minnesota.