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, Dave Shade, James A Tonascia, David Charles

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)e463-e471
JournalNeurology
Volume91
Issue number5
DOIs
StatePublished - Jul 31 2018

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Deep Brain Stimulation
Tremor
Parkinson Disease
Drug Therapy
Dyskinesias
United States Food and Drug Administration
Multicenter Studies
Extremities
Clinical Trials

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Hacker, M. L., DeLong, M. R., Turchan, M., Heusinkveld, L. E., Ostrem, J. L., Molinari, A. L., ... Charles, D. (2018). Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology, 91(5), e463-e471. https://doi.org/10.1212/WNL.0000000000005903

Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. / Hacker, Mallory L.; DeLong, Mahlon R.; Turchan, Maxim; Heusinkveld, Lauren E.; Ostrem, Jill L.; Molinari, Anna L.; Currie, Amanda D.; Konrad, Peter E.; Davis, Thomas L.; Phibbs, Fenna T.; Hedera, Peter; Cannard, Kevin R.; Drye, Lea T.; Sternberg, Alice L; Shade, Dave; Tonascia, James A; Charles, David.

In: Neurology, Vol. 91, No. 5, 31.07.2018, p. e463-e471.

Research output: Contribution to journalArticle

Hacker, ML, DeLong, MR, Turchan, M, Heusinkveld, LE, Ostrem, JL, Molinari, AL, Currie, AD, Konrad, PE, Davis, TL, Phibbs, FT, Hedera, P, Cannard, KR, Drye, LT, Sternberg, AL, Shade, D, Tonascia, JA & Charles, D 2018, 'Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease', Neurology, vol. 91, no. 5, pp. e463-e471. https://doi.org/10.1212/WNL.0000000000005903
Hacker ML, DeLong MR, Turchan M, Heusinkveld LE, Ostrem JL, Molinari AL et al. Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. Neurology. 2018 Jul 31;91(5):e463-e471. https://doi.org/10.1212/WNL.0000000000005903
Hacker, Mallory L. ; DeLong, Mahlon R. ; Turchan, Maxim ; Heusinkveld, Lauren E. ; Ostrem, Jill L. ; Molinari, Anna L. ; Currie, Amanda D. ; Konrad, Peter E. ; Davis, Thomas L. ; Phibbs, Fenna T. ; Hedera, Peter ; Cannard, Kevin R. ; Drye, Lea T. ; Sternberg, Alice L ; Shade, Dave ; Tonascia, James A ; Charles, David. / Effects of deep brain stimulation on rest tremor progression in early stage Parkinson disease. In: Neurology. 2018 ; Vol. 91, No. 5. pp. e463-e471.
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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.",
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AU - Hacker, Mallory L.

AU - DeLong, Mahlon R.

AU - Turchan, Maxim

AU - Heusinkveld, Lauren E.

AU - Ostrem, Jill L.

AU - Molinari, Anna L.

AU - Currie, Amanda D.

AU - Konrad, Peter E.

AU - Davis, Thomas L.

AU - Phibbs, Fenna T.

AU - Hedera, Peter

AU - Cannard, Kevin R.

AU - Drye, Lea T.

AU - Sternberg, Alice L

AU - Shade, Dave

AU - Tonascia, James A

AU - Charles, David

PY - 2018/7/31

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N2 - 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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