title: Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial.
abstract: Gait and balance disturbances typically emerge in advanced Parkinson's disease with generally limited response to dopaminergic medication and subthalamic nucleus deep brain stimulation. Therefore, advanced programming with interleaved pulses was put forward to introduce concomittant nigral stimulation on caudal contacts of a subthalamic lead. Here, we hypothesized that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata improves axial symptoms compared with standard subthalamic nucleus stimulation. Twelve patients were enrolled in this 2 × 2 cross-over double-blind randomized controlled clinical trial and both the safety and efficacy of combined subthalamic nucleus and substantia nigra pars reticulata stimulation were evaluated compared with standard subthalamic nucleus stimulation. The primary outcome measure was the change of a broad-scaled cumulative axial Unified Parkinson's Disease Rating Scale score (Scale II items 13-15, Scale III items 27-31) at '3-week follow-up'. Secondary outcome measures specifically addressed freezing of gait, balance, quality of life, non-motor symptoms and neuropsychiatric symptoms. For the primary outcome measure no statistically significant improvement was observed for combined subthalamic nucleus and substantia nigra pars reticulata stimulation at the '3-week follow-up'. The secondary endpoints, however, revealed that the combined stimulation of subthalamic nucleus and substantia nigra pars reticulata might specifically improve freezing of gait, whereas balance impairment remained unchanged. The combined stimulation of subthalamic nucleus and substantia nigra pars reticulata was safe, and of note, no clinically relevant neuropsychiatric adverse effect was observed. Patients treated with subthalamic nucleus and substantia nigra pars reticulata stimulation revealed no 'global' effect on axial motor domains. However, this study opens the perspective that concomittant stimulation of the substantia nigra pars reticulata possibly improves otherwise resistant freezing of gait and, therefore, highly warrants a subsequent phase III randomized controlled trial.
authors.affiliation: German Centre for Neurodegenerative Diseases (DZNE), Tübingen, Germany. daniel.weiss@uni-tuebingen.de
authors.forename: Daniel
authors.initials: D
authors.lastname: Weiss
authors.forename: Margarete
authors.initials: M
authors.lastname: Walach
authors.forename: Christoph
authors.initials: C
authors.lastname: Meisner
authors.forename: Melanie
authors.initials: M
authors.lastname: Fritz
authors.forename: Marlieke
authors.initials: M
authors.lastname: Scholten
authors.forename: Sorin
authors.initials: S
authors.lastname: Breit
authors.forename: Christian
authors.initials: C
authors.lastname: Plewnia
authors.forename: Benjamin
authors.initials: B
authors.lastname: Bender
authors.forename: Alireza
authors.initials: A
authors.lastname: Gharabaghi
authors.forename: Tobias
authors.initials: T
authors.lastname: Wächter
authors.forename: Rejko
authors.initials: R
authors.lastname: Krüger
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018592:Cross-Over Studies; D046690:Deep Brain Stimulation / Q000379:methods*; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D020233:Gait Disorders, Neurologic / Q000209:etiology / Q000628:therapy*; D006801:Humans; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D010300:Parkinson Disease / Q000150:complications / Q000628:therapy*; D004856:Postural Balance / Q000502:physiology*; D011788:Quality of Life; D012678:Sensation Disorders / Q000209:etiology / Q000628:therapy*; D012720:Severity of Illness Index; D013378:Substantia Nigra / Q000502:physiology*; D055815:Young Adult
keywords: DBS; Parkinson’s disease; freezing; gait; subthalamic nucleus