Sustained Improvement After DBS
Regarding the overall results, the benefit of stimulation was detected early and continued to increase throughout the course of the trial. From the point when the stimulator was turned on during the blinded phase, an immediate separation of the control and stimulation groups was observed, Dr. Fisher noted. “By the end of the blinded phase—months 3 to 4—the stimulated patients had a median seizure improvement, compared to their individual baselines, of 37%, [versus] the 0-volt control patients, who had a median improvement, compared to their baselines, of 14.5%.”
The degree of improvement in seizure frequency was sustained into the open-label period, according to Dr. Fisher. “In the open-label part of the trial, which went from months 4 to 13, medications were kept constant,” he said. “This is not a free-form open-label kind of trial. There are just three kinds of stimulation changes allowed—increase from 5 to 7.5 volts, increase of frequency from 145 to 185 pulses per second, or change in the positive-negative polarity of the contacts.”
At the end of the blinded phase, when the investigators turned on the stimulator for control patients, who had received 0 volts before, their seizure frequency was reduced. “In contrast, turning on [the stimulator for] the patients who had already been at 5 volts shows no effect, which says something about the placebo effect at this point, because these patients turned from 0 to 5 volts didn’t know and started improving,” Dr. Fisher noted. At the end of the open-label phase, “there’s a 40% improvement in the seizure frequency. By the end of the long-term follow-up, the reduction in seizures has been 63.6%, which means that patients are almost at one-third of their baseline seizure levels.
“In the long-term follow-up phase, I want to emphasize that we’re not dropping out the patients who are doing badly at this point,” he said. “This is still complete capture with all patients still in the protocol, although in this part of the long-term follow-up, the medications and stimulation parameters are allowed to change.”
Even before the stimulator was turned on at the beginning of the blinded phase, the investigators observed a 20% improvement in seizure frequency for both groups—a result for which Dr. Fisher had no clear explanation. “It could be a placebo effect; it could be a regression to the mean,” he said. “People go into a trial like this when they’re doing badly. It could be a microlesion effect … of just placing the electrodes, or it could be some other reason.
“But I want to be very clear about this next point,” Dr. Fisher concluded. “Even though there was some improvement before we turned the stimulator on, there was significantly more improvement due to turning the stimulator on. So the effect of the trial is not a microlesion or a placebo effect—it’s an effect of stimulation.”
—Fred Balzac