Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease

Mallory L. Hacker, James Tonascia, Maxim Turchan, Amanda Currie, Lauren Heusinkveld, Peter E. Konrad, Thomas L. Davis, Joseph S. Neimat, Fenna T. Phibbs, Peter Hedera, Lily Wang, Yaping Shi, David M. Shade, Alice L. Sternberg, Lea T. Drye, David Charles

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

Background: The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. Methods: A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. Results: DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. Conclusions: DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD.

Original languageEnglish (US)
Article number2731
Pages (from-to)1177-1183
Number of pages7
JournalParkinsonism and Related Disorders
Volume21
Issue number10
DOIs
StatePublished - Oct 1 2015
Externally publishedYes

Fingerprint

Deep Brain Stimulation
Parkinson Disease
Drug Therapy
Dyskinesias
Quality of Life
Clinical Trials
Therapeutics

Keywords

  • Deep brain stimulation
  • Parkinson's disease
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Neurology
  • Geriatrics and Gerontology
  • Clinical Neurology

Cite this

Hacker, M. L., Tonascia, J., Turchan, M., Currie, A., Heusinkveld, L., Konrad, P. E., ... Charles, D. (2015). Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease. Parkinsonism and Related Disorders, 21(10), 1177-1183. [2731]. https://doi.org/10.1016/j.parkreldis.2015.08.008

Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease. / Hacker, Mallory L.; Tonascia, James; Turchan, Maxim; Currie, Amanda; Heusinkveld, Lauren; Konrad, Peter E.; Davis, Thomas L.; Neimat, Joseph S.; Phibbs, Fenna T.; Hedera, Peter; Wang, Lily; Shi, Yaping; Shade, David M.; Sternberg, Alice L.; Drye, Lea T.; Charles, David.

In: Parkinsonism and Related Disorders, Vol. 21, No. 10, 2731, 01.10.2015, p. 1177-1183.

Research output: Contribution to journalArticle

Hacker, ML, Tonascia, J, Turchan, M, Currie, A, Heusinkveld, L, Konrad, PE, Davis, TL, Neimat, JS, Phibbs, FT, Hedera, P, Wang, L, Shi, Y, Shade, DM, Sternberg, AL, Drye, LT & Charles, D 2015, 'Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease', Parkinsonism and Related Disorders, vol. 21, no. 10, 2731, pp. 1177-1183. https://doi.org/10.1016/j.parkreldis.2015.08.008
Hacker, Mallory L. ; Tonascia, James ; Turchan, Maxim ; Currie, Amanda ; Heusinkveld, Lauren ; Konrad, Peter E. ; Davis, Thomas L. ; Neimat, Joseph S. ; Phibbs, Fenna T. ; Hedera, Peter ; Wang, Lily ; Shi, Yaping ; Shade, David M. ; Sternberg, Alice L. ; Drye, Lea T. ; Charles, David. / Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease. In: Parkinsonism and Related Disorders. 2015 ; Vol. 21, No. 10. pp. 1177-1183.
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abstract = "Background: The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. Methods: A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. Results: DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80{\%} reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. Conclusions: DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD.",
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AU - Tonascia, James

AU - Turchan, Maxim

AU - Currie, Amanda

AU - Heusinkveld, Lauren

AU - Konrad, Peter E.

AU - Davis, Thomas L.

AU - Neimat, Joseph S.

AU - Phibbs, Fenna T.

AU - Hedera, Peter

AU - Wang, Lily

AU - Shi, Yaping

AU - Shade, David M.

AU - Sternberg, Alice L.

AU - Drye, Lea T.

AU - Charles, David

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N2 - Background: The Vanderbilt pilot trial of deep brain stimulation (DBS) in early Parkinson's disease (PD) enrolled patients on medications six months to four years without motor fluctuations or dyskinesias. We conducted a patient-centered analysis based on clinically important worsening of motor symptoms and complications of medical therapy for all subjects and a subset of subjects with a more focused medication duration. Continuous outcomes were also analyzed for this focused cohort. Methods: A post hoc analysis was conducted on all subjects from the pilot and a subset of subjects taking PD medications 1-4 years at enrollment. Clinically important worsening is defined as both a ≥ 3 point increase in UPDRS Part III and a ≥ 1 point increase in Part IV. Results: DBS plus optimal drug therapy (DBS + ODT) subjects experienced a 50-80% reduction in the relative risk of worsening after two years. The DBS + ODT group was improved compared to optimal drug therapy (ODT) at each time point on Total UPDRS and Part III (p = 0.04, p = 0.02, respectively, at 24 months). Total UPDRS, Part IV, and PDQ-39 scores significantly worsened in the ODT group after two years (p < 0.003), with no significant change in the DBS + ODT group. Conclusions: DBS + ODT in early PD may reduce the risk of clinically important worsening. These findings further confirm the need to determine if DBS + ODT is superior to medical therapy for managing symptoms, reducing the complications of medications, and improving quality of life. The FDA has approved the conduct of a large-scale, pivotal clinical trial of DBS in early stage PD.

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