New Insights on Deep Brain Stimulation and Early Parkinson Disease

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A new study has found that deep brain stimulation (DBS), normally used as adjunctive treatment in moderate to advanced Parkinson disease (PD), may improve and potentially slow the progression of motor symptoms even in early PD.¹

Results showed that patients with early PD who were prescribed medication alone were seven times more likely to develop new resting tremor over two years, compared with DBS plus medication. Patients prescribed DBS plus medication also showed improvement in existing resting tremor, while those treated with drug therapy alone experienced worsening of symptoms.

“Taken together, these findings suggest that DBS in early PD not only improves rest tremor in the treated state but that early substantia nigra stimulation may also slow rest tremor progression,” wrote first author Mallory Hacker, PhD, of Vanderbilt University Medical Center, Nashville, Tennessee.

To see whether DBS could improve motor symptoms in early PD, researchers conducted a prospective RCT in 28 patients with PD aged 50 to 75 years. Participants received treatment for PD for 6 months-4 years and had no history of motor fluctuations. Researchers randomized patients to optimal medication alone or DBS plus optimal medication. At baseline, 6, 12, 18, and 24 months, participants underwent a one-week washout period during which they stopped all PD medication. The intention of the washout period was to capture early motor symptoms. Researchers assessed motor symptoms both “on” and “off” medication using the standardized Unified Parkinson’s Disease Rating Scale (UPDRS) part III.

Results showed that change in UPDRS-III score from baseline favored DBS plus medication, both “off” and “on” medication.

Key results over two years:

•“off” score: 2.6 times greater risk of 2-point worsening with medication alone vs DBS plus medication (HR 2.6; p = 0.07)

•“on” score: Improvement with DBS plus medication vs worsening with medication alone (difference = −0.74 points/year; p = 0.003)

•7 times higher odds of developing a new resting tremor with medication alone vs DBS plus medication (OR 7.0, p =0.046):

     -86% of the medication alone group developed new resting tremor

     -46% of the DBS plus medication group did so

The FDA limited enrollment in the trial to 30 participants, and two were excluded after enrollment. After meeting its safety endpoint, the FDA approved a multicenter trial of DBS in early PD.

The authors concluded: “The DBS in early PD pilot trial suggests that STN stimulation may slow resting tremor progression. More investigation is needed in a larger cohort, and the FDA has approved the conduct of a multicenter, pivotal clinical trial testing substantia nigra DBS in early PD.”

Take home points

•Small, pilot study suggests that DBS plus medication improves and prevents the progression of resting tremor in early PD better than medication alone

•Improvements were seen both “off” and “on” medication

•The FDA has approved a larger, multicenter trial of DBS in early PD

References:

1. Hacker ML, DeLong MR, Turchan M, et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018;91:e463-e471.