番茄社区

Deep brain stimulation (DBS) may slow rest tremor progression in early-stage Parkinson's disease (PD), a small prospective suggested.

Over 24 months, early PD patients treated with drug therapy alone were more likely to develop new rest tremor compared with those treated with DBS plus medication, reported David Charles, MD, of Vanderbilt University Medical Center study in Nashville, and co-authors in

Four DBS patients had rest tremor improvement and, in one DBS patient, rest tremor completely disappeared from all affected limbs.

"This represents the first therapy that's been shown to slow the progression of tremor, a cardinal feature of Parkinson's disease," Charles told 番茄社区. "There's no therapy today -- medication, surgery, or any therapy -- that slows the progression of any element of the disease."

DBS can be an effective adjunctive therapy for mid-stage and advanced-stage PD, but rarely has been studied in early-stage patients. The EARLYSTIM trial previously showed that DBS led to improved outcomes in relatively young (average age of 52) PD patients who had the condition for an average of 7.5 years.

The Vanderbilt study looked at older, more typical, Parkinson's patients earlier in the disease, Charles explained. DBS in early-stage patients was controversial when the researchers first presented the trial to the FDA, "but we argued that if you want to slow the progression of the disease, you need to apply it early, before the neurons have completely degenerated and died off."

In this study, the team enrolled 28 early-stage PD patients with no history of dyskinesia or other motor fluctuations, randomizing them to receive medication alone or DBS plus drug therapy. Participants underwent a weeklong inpatient washout at baseline and every 6 months during the 2-year trial. At baseline, patients were an average of 61 years old and had an average disease duration of about 2 years.

Motor scores after the washout periods in the DBS group trended better than those in the medicine group throughout the study. Over 2 years, more medication-only patients (86%; 12/14 patients) developed new rest tremor in previously unaffected limbs than those receiving DBS with drugs (46%; 6/13 patients).

Seven patients who received adjunctive DBS did not develop rest tremor in any previously unaffected limb; four of those patients had rest tremor present in a limb at baseline that resolved by 24 months. Rest tremor disappeared from all affected limbs for one patient treated with both DBS and medication.

"Taken together, these findings suggest that DBS in early PD not only improves rest tremor in the treated state but that early subthalamic nucleus stimulation may also slow rest tremor progression," the researchers wrote.

The mechanisms underlying the effects of DBS in PD are not well understood, but suggest that synaptic plasticity is involved, Charles noted.

This trial did not assess rigidity, and the results should be interpreted with caution due to the study's post-hoc comparisons, small sample sizes, and open-label design, he added, noting that a larger-scale clinical trial across multiple investigational centers is needed to confirm the findings. The FDA has approved a pivotal phase III DBS clinical trial of 280 people with early-stage Parkinson's disease in 18 medical centers to start in 2019.