Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial

Daniel Weiss*, Margarete Walach, Christoph Meisner, Melanie Fritz, Marlieke Scholten, Sorin Breit, Christian Plewnia, Benjamin Bender, Alireza Gharabaghi, Tobias Wächter, Rejko Krüger

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

166 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2098-2108
Number of pages11
JournalBrain
Volume136
Issue number7
DOIs
Publication statusPublished - Jul 2013
Externally publishedYes

Keywords

  • DBS
  • Parkinson's disease
  • freezing
  • gait
  • subthalamic nucleus

Fingerprint

Dive into the research topics of 'Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial'. Together they form a unique fingerprint.

Cite this