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News from the American Neurological Association Annual Meeting
Deep Brain Stimulation Results Encouraging After Five Years of Follow up, Study Finds

ARTICLE IN BRIEF

Patients with early-stage Parkinson's disease who received deep brain stimulation continued to have better motor scores five years later than those who only received medical treatment.

BALTIMORE — Patients with early-stage Parkinson's disease (PD) who received deep brain stimulation (DBS) continued to have better motor scores five years later than those who only received medical treatment, according to new pilot-study data reported by Vanderbilt University investigators here in October at the annual meeting of the American Neurological Association.

The researchers said the evidence supports the need for a larger phase 3 trial of DBS in patients with very early disease. The FDA has approved such a trial, planned for 280 patients enrolled across 18 US centers, for which researchers are now pursuing funding.

Subthalamic nucleus DBS is already approved for patients with mid- and advanced stage PD, but its efficacy in early PD is still being investigated. Medical therapy is better at controlling symptoms in early PD than in later stages. Other researchers have tried to demonstrate a disease-modifying effect, but no therapy has been definitively shown to halt or slow the progression of disease.

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DR. MALLORY HACKER: “Whats distinct about this population is that these are very early stage Parkinsons disease patients. Patients couldnt have any signs or history of dyskinesias or motor fluctuations when they enrolled.”

In this study, patients were eligible if they had a stable response to dopaminergic therapy and had been on levodopa or dopamine-agonist therapy for six months to four years. The average duration for medication use before enrollment was just over two years.

“What's distinct about this population is that these are very early stage Parkinson's disease patients,” said Mallory Hacker, PhD, assistant professor of neurology at Vanderbilt. “Patients couldn't have any signs or history of dyskinesias or motor fluctuations when they enrolled.”

STUDY METHODOLOGY

Thirty patients were randomized to receive either optimal drug therapy alone or deep-brain stimulation plus optimal drug therapy. In this study, DBS therapy was applied to the bilateral subthalamaic nucleus to deliver electrical stimulation to modify the brain circuits responsible for Parkinson's disease symptoms.

After the initial study period of two years, four out of 14 total patients in the optimal drug therapy group elected to receive DBS. Feedback received during peer review also led investigators to narrow the inclusion criteria for medication duration for the future pivotal trial to one to four years.

Patients who had DBS and optimal drug therapy — who had been on medical therapy for one to four years — experienced improvements in motor scores on the United Parkinson's Disease Rating Scale Part III that were an average of 8.9 points better than the group that only received medical therapy five years after baseline (p<.03). That represented more than three times the minimal clinically meaningful change for this measure, researchers noted.

“In this study, the medication group progressively worsens over five years as you would expect in early stage Parkinson's,” Dr. Hacker said. “And these results show that average scores were improved over years for the DBS and optimal drug therapy group.”

Patients on medical therapy for six months to four years at the beginning of the study also showed a trend of greater improvement in motor scores; the DBS and optimal drug therapy group improved by an average of 4.6 points more than the group on medical therapy alone — but the difference wasn't statistically significant.

Dr. Hacker acknowledged the small study size of the pilot trial, but said the results reinforce the rationale for studying DBS further to determine whether the DBS should be offered for patients with very early stage PD.

“This is further evidence to support why a multicenter, pivotal study should be done,” she said.

David Charles, MD, FAAN, professor and vice chairman of neurology, chief medical officer of the Vanderbilt Neuroscience Institute and principal investigator of the study, said: “Our team's overarching goal is to determine if very early DBS will dramatically slow the progression of Parkinson's disease. If that were proven true, it would be a landmark achievement in the battle against this devastating disease.”

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DR. CHARLES H. ADLER: “This is a very small study so the results need to be interpreted with great caution. But the fact that there were statistically significant differences between these groups is promising.”

EXPERTS COMMENT

Charles H. Adler, MD, PhD, FAAN, professor of neurology at the Mayo Clinic in Phoenix, AZ, who conducts research on Parkinson's, said: “This is a very small study so the results need to be interpreted with great caution. But the fact that there were statistically significant differences between these groups is promising.”

Commenting on the abstract, he said he would like to know what medications the patients were taking, and how many of the patients in each group developed motor fluctuations or dyskinesias. As this therapy moves to phase 3, there will be more questions that need to be answered, he said.

“I would like to know more than just the effect on motor score,” he said. “It will be important to know how early DBS might affect activities of daily living, non-motor symptoms, development of motor fluctuations or dyskinesias, overall medication needs, quality of life, etc.”

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• Hacker ML, Currie AD, Molinari AL, et al. Subthalamic nucleus deep brain stimulation may reduce medication costs in early stage Parkinson's disease http://content.iospress.com/articles/journal-of-parkinsons-disease/jpd150712. J Parkinson's Dis 2016;6(1):125–131.