title: Deep brain stimulation may reduce the relative risk of clinically important worsening in early stage Parkinson's disease.
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.
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States. Electronic address: mallory.hacker@vanderbilt.edu.
authors: Mallory L
authors: ML
authors: Hacker
authors: Department of Epidemiology, Johns Hopkins University, 615 N Wolfe St., Baltimore, MD, 21205, United States.
authors: James
authors: J
authors: Tonascia
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: Maxim
authors: M
authors: Turchan
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: Amanda
authors: A
authors: Currie
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: Lauren
authors: L
authors: Heusinkveld
authors: Department of Neurosurgery, Vanderbilt University, 4340 Village at Vanderbilt, Nashville, TN, 37232-8618, United States.
authors: Peter E
authors: PE
authors: Konrad
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: Thomas L
authors: TL
authors: Davis
authors: Department of Neurosurgery, Vanderbilt University, 4340 Village at Vanderbilt, Nashville, TN, 37232-8618, United States.
authors: Joseph S
authors: JS
authors: Neimat
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: Fenna T
authors: FT
authors: Phibbs
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: Peter
authors: P
authors: Hedera
authors: Department of Biostatistics, Vanderbilt University, 2525 West End Avenue, Suite 11000, Nashville, TN, 37212, United States.
authors: Lily
authors: L
authors: Wang
authors: Department of Biostatistics, Vanderbilt University, 2525 West End Avenue, Suite 11000, Nashville, TN, 37212, United States.
authors: Yaping
authors: Y
authors: Shi
authors: Department of Epidemiology, Johns Hopkins University, 615 N Wolfe St., Baltimore, MD, 21205, United States.
authors: David M
authors: DM
authors: Shade
authors: Department of Epidemiology, Johns Hopkins University, 615 N Wolfe St., Baltimore, MD, 21205, United States.
authors: Alice L
authors: AL
authors: Sternberg
authors: Department of Epidemiology, Johns Hopkins University, 615 N Wolfe St., Baltimore, MD, 21205, United States.
authors: Lea T
authors: LT
authors: Drye
authors: Department of Neurology, Vanderbilt University, 1611 21st Ave S., A-0118 Medical Center North, Nashville, TN, 37232-2551, United States.
authors: David
authors: D
authors: Charles
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000008:administration & dosage*; D003131:Combined Modality Therapy; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000628:therapy*; D010865:Pilot Projects
chemical_list: D000978:Antiparkinson Agents
keywords: Deep brain stimulation; Parkinson's disease; Subthalamic nucleus