Approximately one-third of the 3 million people in the United States with epilepsy continue to have seizures despite taking anti-epileptic medications. Surgery is an option for some but not all of these people. Trials of therapeutic brain stimulation have shown reductions in seizures, but rarely provide seizure-free outcomes. In addition to coping with the side effects of medications and the actual seizure, patients spend much of their lives dreading when the next seizure will strike.
Researchers at Mayo Clinic in Rochester, Minnesota, are at the forefront of developing the next generation of epilepsy treatments. "We've embarked over the past decade on building a program of basic science, translational research and clinical trial infrastructure focused on developing new therapies for patients with difficult-to-treat epilepsy," says Gregory A. Worrell, M.D., Ph.D., a consultant in Neurology at Mayo Clinic in Rochester, Minnesota.
The fruits of that research will be incorporated into the next generation of epilepsy devices that Mayo Clinic is developing in collaboration with Medtronic, the University of Minnesota and the University of Pennsylvania, using a $6.8 million grant from the National Institutes of Health (NIH).
The grant — part of the first wave of funding from the NIH Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative — is one of only three BRAIN Initiative awards for implantable devices, and the only one of the three directed at epilepsy.
Under the grant's time frame, implantation of the new device in patients is expected to occur in fall 2018. "We have a clear path to this goal. All the engineering is in place and initial studies are underway," says Squire (Matt) M. Stead, M.D., Ph.D., a pediatric neurologist at Mayo Clinic with expertise in the use of brain stimulation to treat children with epilepsy and movement disorders.
A fresh look at patients
The path from basic science through clinical trials to new treatments begins with assessing patients' needs. Mayo Clinic has a large, active clinical practice that offers several options for people with drug-resistant epilepsy.
Two of these options involve devices approved by the Food and Drug Administration (FDA) for treatment of drug-resistant epilepsy:
- The first is responsive neurostimulation, in which a pacemaker-like device is implanted in the patient's skull. The device detects abnormal electrical activity and delivers electrical stimulation to normalize brain activity before the patient experiences a seizure.
- The second FDA-approved device stimulates the vagus nerve in the neck and has been available for more than a decade.
As described in the June 2015 issue of Neurosurgical Focus, Mayo Clinic has an investigational device exemption from the FDA for an experimental device capable of combined hippocampus and anterior nucleus of the thalamus stimulation and sensing. Mayo Clinic is also able to offer deep brain stimulation for drug-resistant epilepsy, a treatment approved in many other countries but not in the United States.
Through research and clinical trials, Mayo Clinic has more than a decade of experience using neurostimulation devices. Mayo Clinic is also one of the few centers in the United States utilizing a wide range of these devices — including deep brain, cortical, and hippocampal stimulation — in an effort to individualize brain stimulation.
"When patients come to Mayo Clinic, we look at them freshly and consider the options for those who haven't responded to medication," Dr. Worrell says. "Are these patients candidates for epilepsy surgery, or for an approved device? Or would they be better served with one of the experimental protocols that we're able to do?"
It isn't uncommon for patients to find treatment options at Mayo Clinic that aren't available elsewhere. Jamie J. Van Gompel, M.D., a consultant in Neurosurgery at Mayo Clinic, cites the case of a patient who had reflex epilepsy for more than 20 years, causing seizures when he moved his right foot. The patient's semiology suggested a problem originating in the left motor cortex.
After being told that nothing could be done, he came to Mayo Clinic. "For this type of patient, we consider subthreshold stimulation," Dr. Van Gompel says. "Just because the seizure focus is in eloquent tissue, it doesn't mean we can't design an implant that may help the patient."
After evaluating the patient, Dr. Van Gompel implanted a device that delivers electrical stimulation to the precentral gyrus. The patient's seizures have eased to the point that, for the first time in years, he is able to put a shoe on his right foot and stand. "We are able to stop a lot of seizures," Dr. Van Gompel says. "Some patients aren't seizure-free, but they can certainly see huge improvement."
Seizure prediction in dogs and humans
Helping patients to become seizure-free is the motivation behind Mayo Clinic's BRAIN Initiative efforts to develop an improved implantable device for epilepsy. Based on Mayo Clinic's earlier work, novel devices have already been implanted in patients as well as in dogs with epilepsy.
Canine epilepsy is common and often resistant to medication, similar to human epilepsy. The devices being developed and tested provide continuous monitoring of brain activity, and will allow data to be uploaded continuously to the cloud and accessed by researchers.
"We are learning a lot from the dogs," Dr. Worrell says. "We have good evidence that we can forecast when seizures are going to occur." Preliminary results of this work were published in the Aug. 4, 2015, issue of PLOS One; further results will be published in Brain.
In addition to seizure prediction, the next generation of devices will provide automated seizure detection, accurate seizure diaries, programmable brain stimulation and treatment algorithms that learn from patients' brain activity. The ability to stream data from an implanted device to a hand-held device and then via the cloud to the patient's physician will facilitate communication and treatment.
"The next-generation device will be transformative because we'll be working with real data," Dr. Worrell says. "It will provide quantitative information about brain health, just as heart rhythm or blood pressure can be tracked now. We will be able to stimulate the brain based on real information."
Eventually, Dr. Worrell hopes that devices will help neurologists address common comorbidities of epilepsy, such as mood disorders and problems with memory and sleep. It might be possible someday to stimulate the brain of a patient with epilepsy in ways that ease these problems.
"We imagine a future," Dr. Worrell says, "where seizures are stopped before they occur, therapies are given at the right place in the right way at the right time, and patients who currently would have had surgeries that might leave them with some functional deficits would be treated with stimulation that can modulate those regions of the brain."
For more information
Van Gompel JJ, et al. Anterior nuclear deep brain stimulation guided by concordant hippocampal recording. Neurosurgical Focus. 2015;38:E9.
Brinkmann BH, et al. Forecasting seizures using intracranial EEG measures and SVM in naturally occurring canine epilepsy. PLOS One. 2015;10:e1.
Brinkmann BH, et al. Crowdsourcing reproducible seizure forecasting in human and canine epilepsy. Brain. 2016;139:1713.