Subthreshold cortical stimulation for epilepsy

For patients with drug-resistant focal epilepsy, surgery is the most effective treatment. However, surgery isn't feasible when seizures originate from the eloquent cortex. Focal brain stimulation has been shown to be efficacious, but typical approaches — such as vagal nerve stimulation or responsive nerve stimulation — rarely yield seizure-free outcomes.

Neurologists at Mayo Clinic in Rochester, Minnesota, have successfully suppressed seizures in patients treated with chronic subthreshold stimulation of the cortex. In a research letter published in JAMA Neurology, Mayo Clinic neurologists reported that 10 of 13 patients (76.9 percent) had improvement for epilepsy severity and quality of life after chronic subthreshold stimulation. The majority of patients experienced a reduction in seizure frequency of more than 50 percent and a pronounced reduction in interictal epileptiform discharges that occurred within minutes of initiating stimulation.

"This option will provide us with a plan B if we can't do a surgical resection for a patient with focal epilepsy," says Jeffrey W. Britton, M.D., a consultant in Neurology at Mayo Clinic's campus in Minnesota. "Subthreshold cortical stimulation shows promise in allowing us to stop seizures in critical brain regions without affecting function."

"Historically, we've thought about stimulation as a secondary alternative when surgery isn't possible. But improving stimulation technology opens up a new therapeutic approach," says Gregory A. Worrell, M.D., Ph.D., a consultant in Neurology at Mayo Clinic's campus in Minnesota.

Stopping seizures before they start

Existing responsive neurostimulation devices detect abnormal electrical activity and then deliver electrical stimulation to normalize brain activity before the patient experiences a seizure. "By the time the responsive device detects abnormal electrical activity, it might be too late to prevent a seizure," Dr. Britton says. "In contrast, subthreshold cortical stimulation tries to stun the brain before it goes into seizure — instead of catching the snowball, subthreshold stimulation can prevent it from ever starting down the hill."

The subthreshold stimulation used at Mayo Clinic is a repurposed device approved for treatment of other neurological disorders. Initially, patients undergo several days of electroencephalographic monitoring with surgically implanted electrodes. Once the seizure focus is pinpointed, patients are given a therapeutic trial of continuous subthreshold cortical stimulation. If the stimulation is clinically beneficial, the recording electrodes are replaced with permanent electrical contacts. Electrodes can be placed on or in the brain — at the precise location of seizure onset — and are connected to a generator implanted in the chest.

"The entire process can take a week or two, with patients usually in the hospital for seven to 20 days," says Jamie J. Van Gompel, M.D., a consultant in Neurologic Surgery at Mayo Clinic's campus in Minnesota.

None of the patients in the Mayo Clinic research has experienced adverse effects from the treatment. Four patients achieved cessation of their disabling seizures. Ten patients overall reported significant improvement in seizure intensity and duration.

On his feet again

Although patients treated with chronic subthreshold cortical stimulation aren't always seizure-free, the impact of treatment can be life-changing. Dr. Van Gompel cites the case — described in the April 2016 issue of the Journal of Neurology, Neurosurgery & Psychiatry — of a man in his 20s who came to Mayo Clinic after being told elsewhere there were no options for treatment. The patient had previously undergone cortical resection, which stopped his day-to-day seizures. But he could no longer stand because doing so triggered seizures. As a result, he hadn't walked in five years.

"We placed a grid in the appropriate brain area because we knew the seizures were happening in the legs," Dr. Van Gompel says. "Then we asked him to stand, and we recorded the seizures. After proving that subthreshold stimulation allowed him to stand, we implanted chronic stimulation. A week later, he walked out of the hospital and went down to the mall."

Another patient, who came to Mayo Clinic with epilepsia partialis continua, had experienced continued facial movements for four years. After treatment with chronic subthreshold stimulation, the patient has facial movements only when she becomes nervous. "Her seizures are not entirely controlled, but she's no longer having continual facial movements. It has been very helpful for her quality of life," Dr. Van Gompel says.

Unlike anti-seizure medications, which have widespread effects on the brain, subthreshold cortical stimulation directs treatment at the precise area of seizure focus. "We're bringing electricity right to the problem," Dr. Van Gompel says.

"This therapy provides levels of electrical stimulation low enough to kind of stun part of the brain so it cannot generate a seizure, yet does not cause that part of the brain to be completely nonfunctional," Dr. Britton adds. "We are cautiously optimistic we may have a long-term solution for these patients."

For more information

Lundstrom BN, et al. Chronic subthreshold cortical stimulation to treat focal epilepsy. JAMA Neurology. 2016;73:1370.

Feyissa AM, et al. I cannot stand this anymore! Journal of Neurology, Neurosurgery & Psychiatry. 2016;87:441.