People with epilepsy whose seizures are not controlled by any of the currently available medications may soon have another treatment option. Called “responsive cortical stimulation,” it's one of a growing number of different techniques now being studied that directly stimulate the brain in an effort to short-circuit seizure activity.
Responsive cortical stimulation requires that doctors first use advanced imaging, such as magnetic resonance imaging (MRI) or positron emission tomography (PET), to identify one or two areas in the brain where the seizures originate, known as a “seizure focus.”
Surgeons then implant a device, called the responsive neurostimulator, into the person's skull (it replaces a small piece of the skull) and connect it to the areas of seizure focus using electrodes. The device continuously monitors the person's brain-wave activity. It can be programmed to identify the earliest sign of each individual patient's seizure pattern and stimulate the brain to interrupt the seizure in response. The person doesn't feel the stimulation.
In a study that appeared in the American Academy of Neurology's medical journal Neurology in September 2011, 191 people with medically intractable partial epilepsy who experienced an average of at least three seizures a month were all given the implant. (“Medically intractable partial epilepsy” involves seizures that can be localized to specific areas within a person's brain, but those seizures have not responded to multiple medications.)
Half of the people—the “treatment group”—received responsive stimulation, which means stimulation in response to detected seizure activity. The other half—the “placebo group”—initially received no stimulation (“sham treatment”). None of the participants knew whether they were receiving stimulation or not. After three months, seizures decreased in the treatment group by nearly 38 percent, while they declined in the placebo group by only 17.3 percent. (Even though placebos are not active treatment, many studies have shown that even the perception of treatment can have some effect on patients.)
After the three-month initial period, everyone in the study was given responsive stimulation. Nearly half of the participants who completed two years of the study with the implant achieved a 50 percent or greater reduction in seizures—something that was particularly impressive given how many other treatments had not been able to help this same group of people.
DEEP BRAIN STIMULATION
In 2010, another trial—the SANTE trial—had similarly encouraging results using a related technique, deep brain stimulation, to reduce seizure frequency. Deep brain stimulation has been used for years to treat Parkinson's disease. Unlike responsive cortical stimulation, which only sends its signals when it detects possible seizure activity, the deep brain stimulation device sends electrical pulses on an automatic schedule (usually “on” for one minute and “off” for five minutes) to disrupt and prevent the seizure process. Most people do not feel the stimulation as it reduces their symptoms, but some do experience a tingling sensation when the stimulation is first activated.
In SANTE, patients who were treated with deep brain stimulation also experienced a 40 percent reduction in seizures, compared with about 14 percent in the placebo group. The entire patient group continued to improve when the device was turned on for all of them following the initial study period. By the end of two years, they reported a 56 percent median reduction in seizures, and 14 percent of them became seizure-free for six months or more. (The entire patient group had the device turned on after the blinded phase, so there was no long-term effect in the placebo group.)
“Brain stimulation doesn't completely obliterate a seizure focus, but it may stop the spread of seizures through the brain, which may result in seizures that are less intense and cause less injuries,” says Robert Fisher, M.D., Ph.D., the Maslah Saul M.D. professor of neurology at Stanford University School of Medicine, director of the Stanford Epilepsy Center, Fellow of the American Academy of Neurology (AAN), and a lead investigator in the SANTE trial. “Our trial also showed a statistically significant reduction in injuries caused by seizures,” he says.
The outcomes may even get better in the future, says Jacqueline French, M.D., professor of neurology at the New York University Langone Medical Center, co-director of epilepsy research and epilepsy clinical trials at the NYU Comprehensive Epilepsy Center, and Fellow of the AAN. “I think that as we learn how to manipulate frequencies and which patients are the best candidates for these treatments, results will improve,” she says.
STILL WAITING APPROVAL
Both the deep brain and cortical stimulation devices have been approved by European authorities and are available in European countries. So far, however, neither device is available in the United States. The U.S. Food and Drug Administration (FDA) is still deliberating on whether to approve them.
Of course, the devices have drawbacks. Both techniques involve brain surgery, which is invasive and involves risks of bleeding and infection, although the complication rates in both trials were low. In the NeuroPace trial, 2 percent of the patients had significant bleeding, although none had long-term neurologic consequences. About 5 percent had infections at their surgical sites. During the SANTE trial, no patients had noticeable symptoms of bleeding; five instances of bleeding did occur but were only seen on brain imaging studies. About 13 percent of the SANTE patients developed infections at the site of their brain surgery.
Dr. Fisher thinks that these studies represent only the beginning for brain stimulation in epilepsy. “In time, new devices besides these will be developed, including ones that have various sensors and different ways of stimulating,” he says. “This is engineering and electronics linked with neuroscience. It's a fast-moving field.” But since it is the job of the FDA and other regulatory agencies to assure the safety of new devices, they must move with caution.
“We're hopeful that this will become available to patients in the near future, but don't know when that might be,” Dr. Fisher says.