Deep brain stimulation (DBS) in patients with early-stage Parkinson’s disease (PD) could slow the advance of resting tremor, according to a new study published in Neurology.
“The finding concerning tremor progression is truly exceptional,” stated senior author David Charles, MD, Department of Neurology, Vanderbilt University Medical Center, Nashville, TN. “It suggests that DBS applied in early-stage Parkinson’s disease may slow the progression of tremor, which is remarkable because there are no treatments for Parkinson’s that have been proven to slow the progression of any element of the disease.”
Experts recognize DBS as an effective additional therapy in patients with mid- and advanced stage PD. The application of DBS in patients with early-stage PD for added benefit needs to be further elucidated, with only preclinical data on the topic.
In 2006, Vanderbilt University researchers embarked on a 2-year pilot study examining the safety and tolerability of subthalamic nucleus (STN) DBS in patients aged 50-75 years with early PD. At enrollment, these patients were taking PD medications for 6 months to 4 years and had no history of movement disorders.
This prospective, randomized-control study was controversial at the time, and the FDA limited patient enrollment to 30 patients. In total, 28 patients were randomized to receive either optimal drug therapy (ODT) or DBS+ODT. Study results indicated that the intervention was safe.
A central facet of this pilot study was week-long wash-out periods in which PD medications were stopped. These washout periods occurred at baseline, 6, 12, 18, and 24 months, during which researchers determined UPDRS-III “off” item scores and compared ODT with DBS+ODT groups.
“A secondary analysis of the Unified Parkinson’s Disease Rating Scale, part III (UPDRS-III) total motor examination ‘off’ score favored DBS plus optimal drug therapy (ODT) over ODT but did not reach statistical significance,” the authors wrote. “This study’s objective was to evaluate whether progression of individual motor features was influenced by early DBS.”
The team found that the deterioration in UPDRS-III “off” rest tremor scores between baseline and 24 months was worse in patients receiving ODT versus those receiving DBS+ODT (P=0.002). They also found that rest tremor slopes from baseline to 24 months supported DBS+ODT, as indicated by both UPDRS-III “off” and “on” scores.
More patients in the ODT group (86%) manifested new resting tremor in previously unaffected limbs—a hallmark of PD—than did patients in the DBS+ODT group (46%). In other terms, patients with early PD who received ODT alone were seven times more likely to manifest resting tremor in unaffected limbs after 2 years of study compared with patients who received DBS+ODT.
On a related note, during a patient-satisfaction survey, 6 of 13 patients who received DBS+ODT cited tremor amelioration as the best benefit of DBS surgery.
The investigators suggest that cumulatively, these data indicate that DBS for early PD not only ameliorates resting tremor in the treated state but also that early STN stimulation attenuates resting tremor progression. Nevertheless, these results should be gingerly interpreted in light of the study’s limitations, such as the use of post hoc comparisons, small sample size, and open-label design.
“These results suggest the possibility that DBS in early PD may slow rest tremor progression,” the authors concluded. “Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration–approved, phase 3, pivotal, multicenter clinical trial evaluating DBS in early PD.”