ARTICLE IN BRIEF
Investigators reported that five years after patients with intractable epilepsy first enrolled in a trial of deep brain stimulation, they experienced a 69 percent reduction in the frequency of the seizures.
Five years after the first patients with intractable epilepsy signed on to a multicenter study of deep brain stimulation (DBS) to control their seizures, they continue to get better, investigators reported at last month's annual meeting of the American Epilepsy Society.
The patients experienced a 69 percent reduction in the frequency of their seizures five years later.
The investigators have been following 95 of the initial 110 patients in the original three-month double-blind study of DBS, the SANTE (Stimulation of the Anterior Nucleus of the Thalamus for Epilepsy) trial.
The investigators had previously reported a 41 percent median reduction in seizure frequency at one-year post-baseline and a 56 percent reduction at two-years. The latest data show a steady increase in improvement, Robert S. Fisher, MD, PhD, professor of neurology at Stanford University and the SANTE principal investigator, told Neurology Today.
Vicenta Salanova, MD, an epilepsy specialist at Indiana University and one of the lead investigators in the study, presented the results of the most recent analysis at the meeting.
“Most of us would not have been interested in the technique if the effects wore off,” said Dr. Fisher. “But patients are still improving.”
After the three-month blinded study, during which 14.5 percent of the patients in the placebo arm of the study had some reduction in the frequency of their seizures, the stimulators were turned on in all study patients. Over the course of the follow-up period, Dr. Fisher and his colleagues reported that 16 percent of patients were seizure free for at least six months. (These were patients with at least six partial or secondarily generalized seizures a month despite having tried at least three anti-epileptic drugs.) The severity of the seizures was also reduced throughout the five-year follow-up period. Quality of life was also improved, according to the researchers.
There were no unanticipated adverse device effects, and no symptomatic intracranial hemorrhages. Dr. Fisher said that a few of the patients experienced seizures linked to the five volts of stimulation. This problem stopped when the voltage was turned down. The high frequency stimulation is intermittent, one minute on and 5 minutes off.
Dr. Fisher and his colleagues also reported new information on changes in depression and mood over the course of the treatment. Neuropsychometric testing did not find differences in the rates of depression and mood problems in people on or off stimulation during the blinded phase of the study, although more people receiving active stimulation subjectively reported depression or memory side effects. These emergent subjective problems in memory or mood that did occur usually resolved over time or with adjustment of stimulation parameters. There was one suicide in the study a few years ago that was associated with the circumstances in the patient's life, Dr. Fisher added.
“For many people, this has been a life-changing experience,” said Dr. Fisher. “Their epilepsy remained refractory even after a number of medicines failed to help. Half had had vagal nerve stimulation and 25 percent had brain surgery. We wish we could figure out a way to know who will benefit from DBS, but we have no idea yet.”
EXPERTS WEIGH IN
Gregory K. Bergey, MD, professor of neurology and vice chair for research in the department of neurology at Johns Hopkins University School of Medicine and director of the John Hopkins Epilepsy Center, said that alternatives to resection are attractive for those patients who seizures can't be medically controlled and are not candidates for neurosurgical resection. “These are very refractory patients” and studies on neuromodulation suggests “there is a gradual increase in efficacy that occurs over time. That is very important because sometimes techniques lose their effectiveness. This is reassuring.”
Dennis Spencer, MD, chairman of neurosurgery at Yale University School of Medicine and director of the Yale epilepsy neurosurgery program, said that there is “definitely a need to think about DBS” as a choice in patients who can't be resected. Surgery is not an option for medication refractory patients whose seizures are diffuse or in those whose seizures are hard to reach or near functionally active tissue.
“Most of us in the field are disappointed that DBS has not been approved for refractory epilepsy patients,” said Dr. Spencer. “We have people who would benefit and we have nothing to offer them.”
Both Drs. Bergey and Spencer have been involved in a trial of the NeuroPace responsive stimulation technology, which works differently than the current study's technique: the DBS device in the current study involves ongoing anterior thalamic stimulation to reduce seizure frequency, while the NeuroPace device is a closed-loop system that responds to early seizure activity and provides stimulation near the site of the seizure focus to stop the seizure. Both treatments involve placement of electrodes in brain structures, but once implanted, the patient is not aware of the stimulation.
An advisory committee at the Food and Drug Administration (FDA) is scheduled to meet in February to discuss the findings regarding the NeuroPace device. An advisory panel commissioned by the FDA to weigh the results of the SANTE trial submitted its recommendations to approve the device in 2010. It was a close vote at seven to five and the FDA has yet to make its final decision. The device is being used off-label in patients with diffuse onset seizures who are not candidates for surgical resection.
The DBS device, manufactured by Medtronic, has been approved for use in epilepsy patients in 31 countries in Europe and several countries in South America, Asia and Canada.