July 19, 2018
By Lorraine L. Janeczko
NEW YORK (Reuters Health) - Deep brain stimulation (DBS) may be able to slow the progression of rest tremor in early Parkinson's disease (PD), a post hoc analysis of data from a pilot trial suggests.
"We were surprised that the effect was so potent, even in this small pilot study," Dr. David Charles of Vanderbilt University in Nashville, Tennessee, told Reuters Health by phone. "This could be the first evidence of any therapy slowing the progression of Parkinson's."
"Therein lies our excitement," Dr. Charles added. "To date, there has been no treatment, no medication, no surgery, to slow the progression of any element of Parkinson's disease. We have symptomatic therapies but they don't slow the progression. The quest to slow this illness down has been a long time in coming."
Dr. Charles and his colleagues analyzed Unified Parkinson's Disease Rating Scale-III (UPDRS-III) scores from a previous two-year pilot randomized trial of subthalamic nucleus DBS in early PD (https://bit.ly/2LzMjUU). The new results appeared online June 29 in Neurology.
The trial, done at one academic treatment center, enrolled patients between 50 and 75 years of age who had been treated with PD medications for between six months and four years. In the study, 14 participants received optimal drug therapy (ODT) only and 13 received DBS plus ODT. Both groups were similar at baseline.
Patients' medication and stimulation were adjusted as needed during the trial by their treating neurologist. All patients in the DBS-plus-ODT group received monopolar stimulation with case positive and optimal contact negative (model 3389 leads from Medtronic, Inc.).
At baseline and at six, 12, 18 and 24 months, participants were taken off their PD medicine and those who were also receiving DBS had their stimulators turned off for seven-day "washouts."
A blinded outside evaluator scored the patients' motor features on the UPDRS-III, using de-identified videos that did not reveal whether they were on or off treatment or their treatment group.
The DBS-plus-ODT group averaged better overall motor scores than the group treated with ODT only. Between baseline and 24 months, the UPDRS-III off-treatment rest tremor scores worsened in patients receiving ODT only compared with those treated with DBS plus ODT (P=0.002).
Rest-tremor slopes were better for patients treated with DBS plus ODT, both off (P<0.001) and on treatment (P=0.003). From baseline to 24 months, 86% of the participants on ODT only developed rest tremor in previously unaffected limbs compared with 46% of patients who received DBS plus ODT (odds ratio, 7.0; P=0.046).
Seven patients on DBS plus ODT did not display rest tremor in any previously unaffected limb. In four of those patients, baseline limb rest tremor resolved by 24 months; and in one patient on DBT plus ODT, rest tremor disappeared from all affected limbs.
Dr. Alon Mogilner, director of the Center for Neuromodulation at NYU Langone Medical Center in New York City, told Reuters Health by phone, "This is the first conclusive evidence showing that DBS can cause permanent changes in the brain for the better."
"Turning the device off for a week shows that the medication and simulation have no residual effects," noted Dr. Mogilner. "The authors did a very rigorous comparison with these patients, and they showed that somehow the device causes permanent changes in the brain, so much so that even if you turn it off, the changes remain."
"The traditional thought over the past 25 years or so has been that surgery is a last resort for patients with more advanced Parkinson's disease," he said. "Surgery improves quality of life and makes symptoms better, but there has been no evidence to show that, when the device is off and not working, the patient is better than someone who does not have the device."
"There is increasing evidence that the surgery should be done sooner in patients to improve their quality of life," he added. "This study appears to confirm that."
Dr. Andrew D. Siderowf, who heads the Parkinson's Disease and Movement Disorders Center at Penn Medicine in Philadelphia, said, "These findings reflect the expert consensus that DBS surgery is particularly effective for tremor in PD. It is surprising that the effect of DBS seems to increase over time relative to medical therapy and persists even after the stimulator has been turned off."
"Although DBS has been part of standard treatment of PD for many years, there have been relatively few randomized studies with long-term follow-up," Dr. Siderowf, who also was not involved in the study, told Reuters Health by email. "The long-term effects of surgery, particularly if the stimulators are turned off, are not fully understood."
He added that the study had several notable strengths, including that it was conducted at a regional referral center for DBS. "It is important to have surgery performed by a center with the right resources and experience."
The research team plans to test their finding in a pivotal multicenter phase 3 trial and begin enrolling participants in that larger study next year.
Medtronic supported the study. Dr. Mogilner and Dr. Charles, as well as several of his coauthors, have financial relationships with Medtronic.
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