title: Combined STN/SNr-DBS for the treatment of refractory gait disturbances in Parkinson's disease: study protocol for a randomized controlled trial.
abstract: BACKGROUND
  Severe gait disturbances in idiopathic Parkinson's disease (PD) are observed in up to 80% of all patients in advanced disease stages with important impact on quality of life. There is an unmet need for further symptomatic therapeutic strategies, particularly as gait disturbances generally respond unfavourably to dopaminergic medication and conventional deep brain stimulation of the subthalamic nucleus in advanced disease stages. Recent pathophysiological research pointed to nigro-pontine networks entrained to locomotor integration. Stimulation of the pedunculopontine nucleus is currently under investigation, however, hitherto remains controversial. The substantia nigra pars reticulata (SNr)--entrained into integrative locomotor networks--is pathologically overactive in PD. High-frequent stimulation of the substantia nigra pars reticulata preferentially modulated axial symptoms and therefore is suggested as a novel therapeutic candidate target for neuromodulation of refractory gait disturbances in PD.
  
  
  METHODS
  12 patients with idiopathic Parkinson's disease and refractory gait disturbances under best individual subthalamic nucleus stimulation and dopaminergic medication will be enroled into this double-blind 2 × 2 cross-over clinical trial. The treatment consists of two different stimulation settings using (i) conventional stimulation of the subthalamic nucleus [STNmono] and (ii) combined stimulation of distant electrode contacts located in the subthalamic nucleus and caudal border zone of STN and substantia nigra pars reticulata [STN+SNr]. The primary outcome measure is the change of the cumulative 'axial score' (UPDRS II items '13-15' and UPRDS III items '27-31') at three weeks of constant stimulation in either condition. Secondary outcome measures include specific scores on freezing of gait, balance function, quality of life, non-motor symptoms, and neuropsychiatric symptoms. The aim of the present trial is to investigate the efficacy and safety of a three week constant combined stimulation on [STN+SNr] compared to [STNmono]. The results will clarify, whether stimulation on nigral contacts additional to subthalamic stimulation will improve therapeutic response of otherwise refractory gait disturbances in PD.
  
  
  BACKGROUND
  The trial was registered with the clinical trials register of http://www.clinicaltrials.gov (NCT01355835).
authors: German Centre of Neurodegenerative Diseases, Tübingen, Germany.
authors: Daniel
authors: D
authors: Weiss
authors: Tobias
authors: T
authors: Wächter
authors: Christoph
authors: C
authors: Meisner
authors: Melanie
authors: M
authors: Fritz
authors: Alireza
authors: A
authors: Gharabaghi
authors: Christian
authors: C
authors: Plewnia
authors: Sorin
authors: S
authors: Breit
authors: Rejko
authors: R
authors: Krüger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002985:Clinical Protocols; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D046690:Deep Brain Stimulation / Q000379:methods*; D004311:Double-Blind Method; D005684:Gait; D006801:Humans; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000628:therapy*; D018401:Sample Size; D013378:Substantia Nigra / Q000502:physiology*; D020531:Subthalamic Nucleus / Q000502:physiology*