title: A trial of scheduled deep brain stimulation for Tourette syndrome: moving away from continuous deep brain stimulation paradigms.
abstract: OBJECTIVE
  To collect the information necessary to design the methods and outcome variables for a larger trial of scheduled deep brain stimulation (DBS) for Tourette syndrome.
  
  
  METHODS
  We performed a small National Institutes of Health-sponsored clinical trials planning study of the safety and preliminary efficacy of implanted DBS in the bilateral centromedian thalamic region. The study used a cranially contained constant-current device and a scheduled, rather than the classic continuous, DBS paradigm. Baseline vs 6-month outcomes were collected and analyzed. In addition, we compared acute scheduled vs acute continuous vs off DBS.
  
  
  METHODS
  A university movement disorders center.
  
  
  METHODS
  Five patients with implanted DBS.
  
  
  METHODS
  A 50% improvement in the Yale Global Tic Severity Scale (YGTSS) total score. RESULTS Participating subjects had a mean age of 34.4 (range, 28-39) years and a mean disease duration of 28.8 years. No significant adverse events or hardware-related issues occurred. Baseline vs 6-month data revealed that reductions in the YGTSS total score did not achieve the prestudy criterion of a 50% improvement in the YGTSS total score on scheduled stimulation settings. However, statistically significant improvements were observed in the YGTSS total score (mean [SD] change, -17.8 [9.4]; P=.01), impairment score (-11.3 [5.0]; P=.007), and motor score (-2.8 [2.2]; P=.045); the Modified Rush Tic Rating Scale Score total score (-5.8 [2.9]; P=.01); and the phonic tic severity score (-2.2 [2.6]; P=.04). Continuous, off, and scheduled stimulation conditions were assessed blindly in an acute experiment at 6 months after implantation. The scores in all 3 conditions showed a trend for improvement. Trends for improvement also occurred with continuous and scheduled conditions performing better than the off condition. Tic suppression was commonly seen at ventral (deep) contacts, and programming settings resulting in tic suppression were commonly associated with a subjective feeling of calmness.
  
  
  CONCLUSIONS
  This study provides safety and proof of concept that a scheduled DBS approach could improve motor and vocal tics in Tourette syndrome. Refinements in neurostimulator battery life, outcome measure selection, and flexibility in programming settings can be used to enhance outcomes in a future larger study. Scheduled stimulation holds promise as a potential first step for shifting movement and neuropsychiatric disorders toward more responsive neuromodulation approaches.
  
  
  BACKGROUND
  clinicaltrials.gov Identifier: NCT01329198.
authors.affiliation: Department of Neurology, University of Florida Center for Movement Disorders and Neurorestoration, Gainesville, FL, USA. okun@neurology.ufl.edu
authors.forename: Michael S
authors.initials: MS
authors.lastname: Okun
authors.forename: Kelly D
authors.initials: KD
authors.lastname: Foote
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Wu
authors.forename: Herbert E
authors.initials: HE
authors.lastname: Ward
authors.forename: Dawn
authors.initials: D
authors.lastname: Bowers
authors.forename: Ramon L
authors.initials: RL
authors.lastname: Rodriguez
authors.forename: Irene A
authors.initials: IA
authors.lastname: Malaty
authors.forename: Wayne K
authors.initials: WK
authors.lastname: Goodman
authors.forename: Donald M
authors.initials: DM
authors.lastname: Gilbert
authors.forename: Harrison C
authors.initials: HC
authors.lastname: Walker
authors.forename: Jonathan W
authors.initials: JW
authors.lastname: Mink
authors.forename: Stacy
authors.initials: S
authors.lastname: Merritt
authors.forename: Takashi
authors.initials: T
authors.lastname: Morishita
authors.forename: Justin C
authors.initials: JC
authors.lastname: Sanchez
mesh_terms: D000328:Adult; D015331:Cohort Studies; D046690:Deep Brain Stimulation / Q000295:instrumentation / Q000379:methods* / Q000592:standards; D004567:Electrodes, Implanted / Q000592:standards; D005260:Female; D006801:Humans; D008297:Male; D013788:Thalamus / Q000503:physiopathology* / Q000601:surgery; D005879:Tourette Syndrome / Q000503:physiopathology / Q000628:therapy*; D016896:Treatment Outcome