Mallory L Hacker1, Mahlon R DeLong1, Maxim Turchan1, Lauren E Heusinkveld1, Jill L Ostrem1, Anna L Molinari1, Amanda D Currie1, Peter E Konrad1, Thomas L Davis1, Fenna T Phibbs1, Peter Hedera1, Kevin R Cannard1, Lea T Drye1, Alice L Sternberg1, David M Shade1, James Tonascia1, David Charles2. 1. From the Departments of Neurology (M.L.H., M.T., L.E.H., A.L.M., A.D.C., T.L.D., F.T.P., P.H., D.C.) and Neurosurgery (P.E.K.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (M.R.D.), Emory University School of Medicine, Atlanta, GA; Laboratory of Molecular Immunology (L.E.H.), National Institute of Allergy and Infectious Diseases, Bethesda, MD; Movement Disorders and Neuromodulation Center (J.L.O.), Department of Neurology, University of California San Francisco; Department of Neurology (K.R.C.), Walter Reed National Military Center, Bethesda; and Department of Epidemiology (L.T.D., A.L.S., D.M.S., J.T.), Johns Hopkins University, Baltimore, MD. 2. From the Departments of Neurology (M.L.H., M.T., L.E.H., A.L.M., A.D.C., T.L.D., F.T.P., P.H., D.C.) and Neurosurgery (P.E.K.), Vanderbilt University Medical Center, Nashville, TN; Department of Neurology (M.R.D.), Emory University School of Medicine, Atlanta, GA; Laboratory of Molecular Immunology (L.E.H.), National Institute of Allergy and Infectious Diseases, Bethesda, MD; Movement Disorders and Neuromodulation Center (J.L.O.), Department of Neurology, University of California San Francisco; Department of Neurology (K.R.C.), Walter Reed National Military Center, Bethesda; and Department of Epidemiology (L.T.D., A.L.S., D.M.S., J.T.), Johns Hopkins University, Baltimore, MD. david.charles@vanderbilt.edu.
Abstract
OBJECTIVE: To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. METHODS: The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. RESULTS: UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT (p = 0.001). CONCLUSIONS: These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.
OBJECTIVE: To evaluate whether the progression of individual motor features was influenced by early deep brain stimulation (DBS), a post hoc analysis of Unified Parkinson's Disease Rating Scale-III (UPDRS-III) score (after a 7-day washout) was conducted from the 2-year DBS in early Parkinson disease (PD) pilot trial dataset. METHODS: The prospective pilot trial enrolled patients with PD aged 50-75 years, treated with PD medications for 6 months-4 years, and no history of dyskinesia or other motor fluctuations, who were randomized to receive optimal drug therapy (ODT) or DBS plus ODT (DBS + ODT). At baseline and 6, 12, 18, and 24 months, all patients stopped all PD therapy for 1 week (medication and stimulation, if applicable). UPDRS-III "off" item scores were compared between the ODT and DBS + ODT groups (n = 28); items with significant between-group differences were analyzed further. RESULTS: UPDRS-III "off" rest tremor score change from baseline to 24 months was worse in patients receiving ODT vs DBS + ODT (p = 0.002). Rest tremor slopes from baseline to 24 months favored DBS + ODT both "off" and "on" therapy (p < 0.001, p = 0.003, respectively). More ODT patients developed new rest tremor in previously unaffected limbs than those receiving DBS + ODT (p = 0.001). CONCLUSIONS: These results suggest the possibility that DBS in early PD may slow rest tremor progression. Future investigation in a larger cohort is needed, and these findings will be tested in the Food and Drug Administration-approved, phase III, pivotal, multicenter clinical trial evaluating DBS in early PD. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with early PD, DBS may slow the progression of rest tremor.
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