Stimulating New Therapy for Epilepsy

Electric pulses delivered to the forehead by external electrodes could cut many epilepsy sufferers’ seizure rates in half, according to the results of a recent trial. Unlike other nerve-stimulation approaches that require surgical implants, this temporary device could allow physicians to ascertain whether their patients would benefit from more permanent invasive approaches.

Epilepsy affects about two million people in the U.S., and medications can help keep seizures to a minimum in a majority of patients. However, as many as 30 percent of people with the disorder are drug resistant. Because seizures occur when the brain’s electrical impulses go awry, a number of devices that stimulate the brain electrically are currently under testing, based on the theory that external stimulation can disrupt those abnormal impulses and interrupt or even prevent the aberrant signals.

The vagus nerve stimulator (VNS), an implant in the chest that sends electric pulses to an electrode wrapped around a nerve in the left side of the neck, has already been approved by the U.S. Food and Drug Administration. But VNS is expensive (costing $20,000 or more), and it’s only effective in about 40 percent of patients—and there’s no presurgical way to predict who will benefit. The new, external device uses the same basic principle but exploits the more superficial trigeminal nerve—a large cranial nerve that emerges from deep in the brain and branches to run down both sides of the face.

“The trigeminal nerve projects to key parts of the brain that modulate seizure and mood,” says Christopher DeGiorgio, a neurologist at the University of California at Los Angeles and the inventor of the device. “I started to think about using it because it can be stimulated noninvasively.”

With the trigeminal neural stimulator (TNS), a long, butterfly-shaped sticker electrode is affixed to the forehead. Small wires, which can be tucked behind the ears, lead from the electrodes to a small pulse generator that can be worn in a back pocket for 12 to 16 hours each day. According to the results of a 50-person, placebo-controlled study that DeGiorgio presented in April, the TNS device showed similar efficacy to the implantable VNS; about 40 percent of those in the test group experienced at least 50 percent fewer seizures.

“The preliminary results and open-label studies appear promising,” says Robert Fischer, a neurologist at Stanford University’s epilepsy center who was not involved in the research. “We put VNS devices into the chest and neck of people and ultimately find that it’s substantially helpful in no more than 50 percent. That means the other 50 percent have had a surgical procedure without benefit. The ability to do a trial run would be helpful.”

For epilepsy patients experiencing success on TNS, the device has been life-changing. “I was getting 20 seizures a month when I started using it, and now I’m down to eight,” says Walter Cortes, 29, of Reseda, California, who participated in the study. When Cortes was hospitalized for a case of pancreatitis caused by one of his epilepsy medications, he suspended his use of the device, and the seizures returned in full force. “That’s when I realized that machine was something special.”

Beyond suppression of seizures, many in the TNS trial reported an improvement in mood. (Epilepsy patients commonly suffer from depression.) “The trigeminal nerve projects to a brain-stem structure that produces norepinephrine, which regulates mood, attention, and anxiety,” DeGiorgio says. When the TNS device was tested in a small trial on treatment-resistant depression, it showed such promising results—with four out of five patients going into remission after eight weeks of nightly TNS treatment—that a larger 20-person study is now under way. “The technology is so elegant and simple that it’s almost hard to believe,” says Ian Cook, the psychiatrist and neuroscience researcher at UCLA who’s heading the depression trials.  

The current trials use an off-the-shelf stimulator, but startup NeuroSigma has licensed the approach. The company is now developing a proprietary device, working with researchers on clinical trials for epilepsy, depression, and PTSD, and developing an implantable version for patients who find relief with the temporary one.