TY - JOUR
T1 - Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial
AU - Weiss, Daniel
AU - Walach, Margarete
AU - Meisner, Christoph
AU - Fritz, Melanie
AU - Scholten, Marlieke
AU - Breit, Sorin
AU - Plewnia, Christian
AU - Bender, Benjamin
AU - Gharabaghi, Alireza
AU - Wächter, Tobias
AU - Krüger, Rejko
N1 - Funding Information:
The study was supported by a Research Grant (AKF 259-0-0) of the Eberhard Karls University Tübingen and by Medtronic Europe Sarl. Daniel Weiss is supported by a research grant of the German Research Council (DFG) WE5375/1-1 and was supported by a Research Grant of the Medical Faculty of the University of Tübingen (AKF 259-0-0). Daniel Weiss received speaker’s honoraria and a travel grant from Medtronic, Abott Pharmaceutical, UCB, and the Movement Disorder Society. Margarete Walach received a travel grant from GlaxoSmithKline. Christoph Meisner received reimbursement from the Department of Neurodegenerative Diseases as provided by Medtronic study support. Melanie Fritz received a travel grant from Ipsen Pharmaceuticals.
Funding Information:
Christian Plewnia received resarch grants from the German Research Council (DFG; PL 525/1–1), the University of Tübingen (AKF #238-0-0) and the Werner Reichardt Centre for Integrative Neuroscience (CIN, PP2011_11). He received speaker’s honoraria by Inomed Medizintechnik GmbH. Sorin Breit was supported by a Research Grant of the Medical Faculty of the University of Tübingen (AKF 246-0-1). Benjamin Bender received a travel grant by Bayer Vital and was supported by research grants of the German Research Council (DFG) BE4609/1-1 and the Wilhelm-Schuler-Stiftung. Alireza Gharabaghi is supported by grants from the German Research Council [DFG GH 94/2-1, DFG EC 307], Federal Ministry for Education and Research [BFNT 01GQ0761, BMBF 16SV3783, BMBF 03160064B, BMBF V4UKF014, and European Union [ERC 2276329]. Alireza Gharabaghi received speaker’s honoraria and travel grants from Medtronic. Tobias Wächter: received speaker‘s honoraria and travel reimbursement for scientific meetings from Medtronic, Solvay, Abbott Pharma, Cephalon, Merz Pharmaceuticals, Ipsen Pharma and Schwarz Pharma. He has also received financial support for research from and conducted commissioned research for Medtronic, Abbott Pharma, Merz Pharmaceuticals, Ipsen Pharma and Pharm-Allergan and worked on advisory boards for Ipsen Pharma and Merz Pharmaceuticals. Rejko Krüger serves as Editor of European Journal of Clinical Investigation, Journal of Neural Transmission and Associate Editor of BMC Neurology; has received research grants of the German Research Council (DFG; KR2219/ 2-3 and KR2119/8-1), the Michael J Fox Foundation, the Fritz Thyssen foundation (10.11.2.153) and the Federal Ministry for Education and Research [BMBF, NGFNplus; 01GS08134], as well as speaker’s honoraria and/or travel grants from UCB Pharma, Cephalon, Abott Pharmaceutical, Takeda Pharmaceuticals and Medtronic.
PY - 2013/7
Y1 - 2013/7
N2 - 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.
AB - 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.
KW - DBS
KW - Parkinson's disease
KW - freezing
KW - gait
KW - subthalamic nucleus
UR - http://www.scopus.com/inward/record.url?scp=84879948179&partnerID=8YFLogxK
U2 - 10.1093/brain/awt122
DO - 10.1093/brain/awt122
M3 - Article
AN - SCOPUS:84879948179
SN - 0006-8950
VL - 136
SP - 2098
EP - 2108
JO - Brain
JF - Brain
IS - 7
ER -