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Deep brain stimulation reduces epileptic seizures

Reuters Health • The Doctor's Channel Daily Newscast

NEW YORK (Reuters Health) – Bilateral thalamic stimulation reduces seizure frequency and severity in medically refractory epilepsy, new study findings show.

About a third of people with epilepsy continue to have seizures despite treatment. “We revived deep brain stimulation for epilepsy partly because it was having such great success with Parkinson’s patients,” lead investigator Dr. Robert Fisher, from Stanford University School of Medicine, California, told Reuters Health.

“We chose the thalamus, which is connected to wide regions of cortex, as a way to favorably influence electrical activity in wide regions of the brain,” Dr. Fisher said. “An advantage is patients can have multiple sites of seizure origin, and even if we do not know exactly where all of them are, stimulation here may still be beneficial.”

The randomized multicenter study involved 110 adults with refractory partial seizures, including secondarily generalized seizures, at least six times per month. Patients were taking up to four antiepileptic drugs at baseline, which they continued for at least a year.

All subjects had electrodes implanted into the anterior nuclei of the thalamus. A month later they entered a 3-month blinded phase in which half of them received stimulation and half did not. In the stimulation group patients, the devices delivered 5 volts using 90 microsecond pulses, 145 pulses/second, “on” 1 minute, “off” 5 minutes.

Then, in a 9-month unblinded phase, all subjects received stimulation, after which the investigators continued to follow everyone long term. Through all phases, participants received 325 subject-years of active stimulation for a mean duration of 3.0 (maximum 5.0) years.

Forty-nine patients already had vagal nerve stimulators, which the investigators swapped out for the thalamic stimulators. Twenty-seven had previously undergone epilepsy surgery, but this factor did not affect their outcomes in this study.

In a March 18 online report in Epilepsia, the authors report that one subject had 210 brief partial seizures corresponding to the 1 minute on/5 minutes off cycle of stimulation in the first 3 days of activation. Seizures stopped when stimulation was turned off and did not return when stimulation was restored at 4 volts instead of 5. This outlier was excluded from the analyses.

By the end of the blinded phase, seizure frequency had declined significantly by a median of 40.4% in the stimulation group versus 14.5% in controls. Complex partial seizures improved more in the stimulated group (36.3% vs 12.1% improvement, p = 0.041). Also, the stimulation group had fewer injuries produced by seizures (7% vs 26%, p = 0.01).

Treatment was most effective for seizures originating in the temporal regions and among subjects with multifocal or diffuse seizure origin.

When “everybody’s stimulator was turned on, those randomized to the control group started improving right away and caught up with stimulated group, so that by the end of the second year there was a 56% overall reduction in seizures,” Dr. Fisher said.

Those still in the trial by the end of the third year had a 67% improvement, he added.

Quality of life also improved, with some patients able to start working. In fact, the patient whose initial response to stimulation was increased seizure activity ended up “able to coach his kids’ sports team, and able to work at his hotel resort with his wife. Another indicated she was able to take and pass a licensing exam that she was never able to do before,” Dr. Fisher said.

“That change takes time,” he added. “The majority were not seizure free, but about 13% were seizure free for 6 months or more.”

During the two study phases, the authors recorded 238 device-related adverse events, including paresthesias, implant site pain, and implant site infection — all of which decreased in frequency over time. Five patients had asymptomatic hemorrhages detected incidentally by neuroimaging. Five patients died, but the deaths were not related to the device.

During the blinded phase, more patients in the stimulation group reported problems with depression and memory impairment. Neuropsychological testing for cognition and mood showed no difference between groups, however.

“I think those are things to watch for, but I didn’t see any unexpected serious side effects related to the device or stimulation,” Dr. Fisher said. “Still, it is brain surgery, not a treatment that should be used with mild or controllable epilepsy. It’s for patients for whom little else is available.”

Dr. Fisher noted that based on this study, a U.S. Food and Drug Administration advisory panel recently recommended that deep brain stimulation in the anterior nuclei of the thalamus be approved for patients with severe and refractory partial seizures with or without secondary generalization.

Reference:

Epilepsia 2010.