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July 31, 2018; 91 (5) Article

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease

Mallory L. Hacker, Mahlon R. DeLong, Maxim Turchan, Lauren E. Heusinkveld, Jill L. Ostrem, Anna L. Molinari, Amanda D. Currie, Peter E. Konrad, Thomas L. Davis, Fenna T. Phibbs, Peter Hedera, Kevin R. Cannard, Lea T. Drye, Alice L. Sternberg, David M. Shade, James Tonascia, David Charles
First published June 29, 2018, DOI: https://doi.org/10.1212/WNL.0000000000005903
Mallory L. Hacker
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.
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Mahlon R. DeLong
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.
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Maxim Turchan
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.
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Lauren E. Heusinkveld
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.
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Jill L. Ostrem
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.
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Anna L. Molinari
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.
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Amanda D. Currie
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.
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Peter E. Konrad
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.
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Thomas L. Davis
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.
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Fenna T. Phibbs
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.
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Peter Hedera
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.
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Kevin R. Cannard
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.
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Lea T. Drye
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.
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Alice L. Sternberg
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.
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David M. Shade
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.
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James Tonascia
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.
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David Charles
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.
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Citation
Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease
Mallory L. Hacker, Mahlon R. DeLong, Maxim Turchan, Lauren E. Heusinkveld, Jill L. Ostrem, Anna L. Molinari, Amanda D. Currie, Peter E. Konrad, Thomas L. Davis, Fenna T. Phibbs, Peter Hedera, Kevin R. Cannard, Lea T. Drye, Alice L. Sternberg, David M. Shade, James Tonascia, David Charles
Neurology Jul 2018, 91 (5) e463-e471; DOI: 10.1212/WNL.0000000000005903

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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.

Glossary

CI=
confidence interval;
DBS=
deep brain stimulation;
FDA=
Food and Drug Administration;
HR=
hazard ratio;
LEDD=
levodopa equivalent daily dose;
ODT=
optimal drug therapy;
PD=
Parkinson disease;
STN=
subthalamic nucleus;
UPDRS-III=
Unified Parkinson's Disease Rating Scale, part III

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • The views expressed in this article are those of the authors and do not reflect the official policy of the Department of Army/Navy/Air Force, Department of Defense, or US Government.

  • See page e495

  • CME Course: NPub.org/cmelist

  • Received October 19, 2017.
  • Accepted in final form April 5, 2018.
  • © 2018 American Academy of Neurology
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