Journal Article Ahead of print
PubMed: 42860886 DOI: 10.1002/mdc3.70813
Disease Duration Differentiates Freezing of Gait Response to Subthalamic and Nigral Stimulation for Parkinson's Disease in an Exploratory Multicenter Controlled Trial.
Mov Disord Clin Pract
Authors: Daniel Weiss, Idil Cebi, Marion Schütt, Imma Fischer, Lukas Pavelka, Pierre Kolber, Monika Pötter-Nerger, Wolfgang Hamel, Andrea A Kühn, Christian J Hartmann, Kai Bötzel, Thomas Köglsperger, Michael T Barbe, Zacharias Kohl, Steffen Paschen, Markus A Hobert, Sergiu Groppa, Tobias Warnecke, Inga Claus, Rejko Krüger, Alireza Gharabaghi
Affiliations
- Centre for Neurology, Department for Neurodegenerative Diseases, and Hertie-Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.
- Institute for Clinical Epidemiology and Applied Biometry, University of Tübingen, Hamburg, Germany.
- Parkinson Research Clinic, Centre Hospitalier de Luxembourg, Luxembourg; and Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg; and Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- Translational Neuroscience, Luxembourg Centre for Systems Biomedicine (LCSB), University of Luxembourg, Esch-sur-Alzette, Luxembourg.
- Department of Neurology, and Neurosurgery, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
- Department of Neurology, Charité-Universitätsmedizin Berlin, Berlin, Germany.
- Institute of Clinical Neuroscience and Medical Psychology, and Department of Neurology, Medical Faculty, Heinrich-Heine University Düsseldorf, Düsseldorf, Germany.
- Department of Neurology, University Hospital of the LMU Munich, Munich, Germany.
- Department of Neurology, Faculty of Medicine and University Hospital Cologne, University of Cologne, Jülich, Germany.
- Cognitive Neuroscience, Institute of Neuroscience and Medicine, Research Centre Jülich, Jülich, Germany.
- Department of Neurology, University of Regensburg, Regensburg, Germany.
- Department of Neurology, UKSH, Campus Kiel Christian-Albrechts-University, Kiel, Germany.
- Department of Neurology, UKSH, Campus Luebeck, University of Luebeck, Luebeck, Germany.
- Imaging and Neurostimulation, Department of Neurology, University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
- Department of Neurology, University of Münster, Münster, Germany.
- Department of Neurology and Neurorehabilitation, Klinikum Osnabrück-Academic Teaching Hospital of the University of Münster, Münster, Germany.
- Institute for Neuromodulation and Neurotechnology, Tübingen, Germany.
- Center for Bionic Intelligence Tübingen Stuttgart, University of Tübingen, Tübingen, Germany.
- German Center for Mental Health (DZPG), Tübingen, Germany.
- Max Planck-University of Toronto Centre for Neural Science & Technology (MPUTC), Toronto, Ontario, Canada.
Abstract
BACKGROUND
Freezing of gait (FoG) belongs to most pressing unmet symptoms in the treatment of Parkinson's disease.
OBJECTIVES
To explore whether combined subthalamic and nigral (STN + SNr) deep brain stimulation improves FoG compared with optimized STN stimulation alone; to identify clinical variables associated with therapeutic response.
METHODS
In this exploratory multicenter randomized controlled double-blind trial, we recruited patients from our existing cohorts and randomized them 1:1 to STN or STN + SNr. After baseline, patients were followed with close interim visits (visits 1-5) for 90 days (visit 6). The Freezing of Gait Assessment Course (FoG-AC) was the primary endpoint and was evaluated at P < 0.2 with exploratory intent. Secondary endpoints assessed responder rates, treatment dynamics, predictors of response, and patient preferences.
RESULTS
At V6, STN (n = 23) and STN + SNr (n = 22) FoG-AC outcomes did not differ significantly. We identified responders with clinically meaningful FoG improvement in both the STN (n = 7) and STN + SNr (n = 8) groups. In STN + SNr responders, mean disease duration was ~12 years, which was ~4.5 years shorter than in non-responders, but there were no differences in motor and cognitive functions. Treatment dynamics suggested that FoG responders improved slowly and gradually. The STN + SNr responder group showed numerically stronger FoG improvement compared with STN responders. Additionally, 15 STN compared to 10 STN + SNr patients wished to change treatment after the RCT phase and before unblinding. Both STN and STN + SNr treatment was safe.
CONCLUSIONS
Future trials evaluating adjunctive STN + SNr stimulation should stratify patients by disease duration to optimize outcomes.
MeSH
Parkinson Disease, Gait, Deep Brain Stimulation, Therapeutics, Substantia Nigra, Subthalamic Nucleus