5 Questions: Robert Fisher on deep-brain stimulation for drug-resistant epilepsy

Devices that administer deep-brain stimulation, or DBS, are now in widespread use for the treatment of Parkinson’s disease and other movement disorders. They also are used for the treatment of obsessive-compulsive disorder. In April, the Food and Drug Administration approved such a device for the treatment of patients with recurring epileptic seizures that don’t respond to existing drugs. That approval was based largely on clinical trial results published in 2010 in Epilepsia and led by Robert Fisher, MD, PhD, professor of neurology at the School of Medicine.

Fisher, who holds the Maslah Saul, MD, Professorship, has been studying the use of deep-brain stimulation for epilepsy since 1990. Science writer Bruce Goldman interviewed him about the trial’s findings and the FDA’s action.

1. What is epilepsy and how common is it?

Fisher: Epilepsy is a brain disease characterized by vulnerability to spontaneous, recurrent seizures. It affects about 1 percent of all people in the world. A seizure, in simple terms, is an electrical storm in the brain arising from excessive or abnormally synchronous neuronal activity. Different types of seizures can produce symptoms ranging from mild tingling or twitching to loss of awareness to falling and shaking. Epilepsy can result either from brain injury or from a genetic predisposition. More than half of adults with the condition have so-called focal-onset seizures, meaning these seizures originate in a particular spot in the brain — although they can spread throughout the brain. Anti-seizure medications work well for only about 2 of 3 people with epilepsy. The number left with seizures is very large, and their epilepsy can seriously interfere with their health and quality of life.

2. What is deep-brain stimulation, and how can it be used to treat seizures?

Fisher: DBS entails sending electrical signals to a location in the brain. This is done by implanting electrodes in the brain and supplying power to these electrodes via fine wires threaded to a pulse-generating device placed under the skin of the chest. For this therapy, the wires are placed in the part of brain called the anterior thalamus, which can influence widespread regions of brain.

I led a trial in 2010 that showed DBS in the anterior thalamus can reduce seizures in epilepsy patients for whom other therapies have failed. Compared with surgery to remove parts of the brain, which can also eliminate or reduce the frequency of recurrent, drug-refractory seizures, DBS is adjustable and reversible. And it spares brain tissue. However, surgery may be more effective in some cases.

3. Can you briefly discuss the clinical trial you led in 2010?

Fisher: The trial was performed at 17 centers on 110 patients with medication-resistant focal-onset seizures that occurred, on average, about 20 times per month. Half of these patients were randomized to active stimulation and half to placebo stimulation. Patients could not feel the stimulation so could not tell which group they were in. Active stimulation reduced seizures by 40 percent, whereas placebo reduced seizures by 15 percent — a significant difference. There were fewer seizure injuries in the active group. This was the first proof in a large, controlled trial that electrical brain stimulation could reduce seizures.

In 2015, another study I led showed that the long-term results of this procedure were very favorable. Over time, numbers continued to improve, reaching a 70 percent reduction of seizures. About 15 percent of the participants receiving active stimulation became seizure-free for at least six months. And a study assessing the cognitive and psychological outcomes confirmed the positive findings. In April of this year, the FDA approved the device’s use for epilepsy. Exactly how DBS works is only partially understood.

4. Now that the FDA has approved this device for this indication, is it commercially available?

Fisher: It’s marketed by Medtronic but is not yet approved for reimbursement by American insurance companies. It should be available at experienced epilepsy centers by early 2019. About 30 other countries have already been using DBS to treat uncontrolled seizures for several years.

5. How would you categorize Stanford’s academic and clinical strengths regarding the application of DBS for treating neurological disease?

Fisher: Stanford is the world leader in neurostimulation for epilepsy, and one of the leaders for neurostimulation in a variety of other neurologic and psychiatric diseases. Martha Morrell in the Stanford Comprehensive Epilepsy Program led the successful trial for the FDA-approved responsive neurostimulation therapy for epilepsy, which stimulates by a different method from DBS that is applicable to some epilepsy patients. I led the U.S. trial of the latest generation of vagus nerve stimulators for epilepsy at Stanford. Our neurosurgeons Jaimie Henderson, Casey Halpern and Lawrence Shuer have developed important techniques for stimulation. Peter Tass, a research neurosurgeon at Stanford, is pioneering a better method to deliver stimulation. Helen Bronte-Stewart, a neurologist here, is a leader in using DBS to treat movement disorders such as Parkinson’s disease.

Until we find definitive cures for epilepsy, neurostimulation is an important new option, and Stanford stands at the forefront of its development.