A brain implant designed to detect and block the onset of seizures can significantly reduce their frequency in people with difficult-to-treat epilepsy, according to results revealed on Monday. Neuropace, a startup in Mountain View, CA, that developed the device, plans to seek regulatory approval for it next year.
“It sounds extremely promising,” says Jaimie Henderson, a neurosurgeon at Stanford University who is not involved with Neuropace or with the clinical trials. “The demonstration that a system like this can be effective is a big step forward.”
Some 30 to 50 percent of epilepsy patients cannot adequately control their seizures with medication, a figure that amounts to hundreds of thousands of patients in the United States. Some resort to surgery, in which the part of the brain where the seizure originates is removed. But not everyone has this option–the abnormal activity may start in brain areas responsible for language or vision and thus cannot be surgically destroyed without serious consequences.
The Neuropace system, called the Responsive Neurostimulator, is one of a handful of electrical stimulation devices that are available or in development for epilepsy patients. These devices are designed to counter the uncontrolled electrical storm of a seizure with an externally delivered current.
While other devices stimulate the nervous system continuously or in a predetermined pattern, the Neuropace implant is unique in that it monitors the brain, delivering jolts of electricity only when it detects the abnormal electrical activity that signals the onset of a seizure. “It’s like dousing a spark before it becomes a flame,” said Martha Morrell, Neuropace’s chief medical officer, at a press conference at the American Epilepsy Society’s annual meeting in Boston on Monday.
The device consists of a neurostimulator that’s smaller than a deck of cards. It’s surgically implanted into a hollowed out part of the skull, along with a set of electrical leads that can both record electrical activity and dispense jolts of electricity. The leads are placed either on the surface of the brain or deep in the brain tissue, depending on where a patient’s seizures begin. Surgeons locate this spot, known as the “seizure focus,” prior to surgery using a combination of brain imaging and electroencephalogram (EEG) recordings, which measure brain activity from surface electrodes on the skull, or electrocorticography (ECoG), in which activity is recorded directly from the surface of the brain.
The device, which contains a battery and a small computer, continuously monitors electrical activity. “As the [electrical activity] becomes higher in amplitude, the device is programmed to identify that as a significant event and deliver a stimulus,” said Morrell at the conference. “The system then reevaluates the EEG and determines if further stimulus is needed.”
According to the results of a clinical trial of nearly 200 epilepsy patients who had failed to respond to at least two medications, the device reduced the frequency of seizures by 29 percent, compared to a 14 percent reduction in those who had a placebo treatment (they were implanted with the device but it was not turned on). Nearly half of the patients given the treatment saw a 50 percent or greater reduction in seizure frequency.
Experts say the response is similar to two other implanted devices: the vagus nerve stimulator, an FDA-approved device that indirectly stimulates the brain by delivering electrical jolts to a part of the peripheral nervous system called the vagus nerve; and an experimental deep-brain stimulation device from Medtronic that targets a highly connected part of the brain called the anterior thalamus. Deep-brain stimulation is currently approved to treat Parkinson’s disease.
While the results of the trial may seem modest, the neurosurgeons who ran the clinical studies emphasize that the patients in the trial had severe epilepsy. “These patients tended to have frequent seizures, at least three per 28-day period, and many had three times that many,” says Gregory Bergey, a neurologist and director of the Johns Hopkins Epilepsy Center at Johns Hopkins University in Baltimore, who led one part of the Neuropace trial.Most of the patients had suffered from epilepsy for 20 years or more and were taking an average of three drugs to control their seizures. A third had already tried vagus nerve stimulation, and a third had already had epilepsy surgery.
“Itsounds incredibly invasive, but these patients have a form of the disease that is so terrible that they are almost willing to try anything we can do to stop there seizures,” says Kenneth Vives, a neurosurgeon at Yale who also ran part of the clinical trial. “We would have been happier to see a better effect, but these patients had tried everything. So these gains are quite significant.”
According to the study, both the procedure and device appear relatively safe. A few patients suffered infections or bleeding, but at rates lower than for comparable procedures. And those who were treated with the device didn’t show any differences in signs of depression or memory impairment compared to those given the sham treatment. While invasive, one of the benefits of the device is that it doesn’t carry the side effects of many epilepsy medications, such as sleepiness or double-vision, says Bergey.
A drawback is that the device is fairly complex to use. After surgery, patients go through an optimization period, during which doctors program it to recognize a typical pattern that precedes the seizure and deliver a particular pattern of electrical activity. Patients wave a wand over the device to download data recorded before and after stimulation, so that physicians can monitor how well these parameters are working and adjust them accordingly. “There is a steep learning curve,” says Vives. “But as we gained experience, it was not so difficult.”
Because the device is so new, researchers believe that its effectiveness will improve as they learn more about what works best in individual patients. For example, since starting the trial, researchers have learned that the most effective pattern of stimulation is predicted in part by the spot in the brain where the seizure originates. Most patients in the study have seizures originating in the hippocampus, though some had abnormal activity originating in parts of the cortex, or in both areas. “We learned that people with hippocampal origins tend to respond better to high-frequency stimulus,” said Morrell, while those whose seizures originate in the neocortex respond better to somewhat lower frequencies.
Neurosurgeons are also excited about the device’s potential to help them better understand epilepsy. “We have, in some cases, four to five years of continuous activity,” says Bergey, recorded as people go about their everyday lives.
“There are all sorts of interesting phenomena we can start to look at and understand,” adds Vives. For example, researchers can determine if the patterns indicating the onset of a seizure change over time, or if there are certain factors that predict the outcome of a seizure. “These are questions we could never answer before,” says Vives.