[en] [en] BACKGROUND: Improving the functional recovery of patients with DoC remains one of the greatest challenges of the field. Different theories exist about the role of the anterior (prefrontal areas) versus posterior (parietal areas) parts of the brain as hotspots for the recovery of consciousness. Repetitive transcranial magnetic stimulation (rTMS) is a powerful non-invasive brain stimulation technique for the treatment of DoC. However, a direct comparison of the effect of TMS treatment on the front versus the back of the brain has yet to be performed. In this study, we aim to assess the short- and long-term effects of frontal and parietal rTMS on DoC recovery and characterize responders phenotypically.
METHODS/DESIGN: Ninety patients with subacute and prolonged DoC will be included in a two-part multicenter prospective study. In the first phase (randomized controlled trial, RCT), patients will undergo four rTMS sessions in a crossover design over 10 days, targeting (i) the left dorsolateral prefrontal cortex (DLPFC) and (ii) the left angular gyrus (AG), as well as (iii & iv) their sham alternatives. In the second phase (longitudinal personalized trial), patients will receive personalized stimulations for 20 working days targeting the brain area that showed the best results in the RCT and will be randomly assigned to either active or sham intervention. The effects of rTMS on neurobehavioral and neurophysiological functioning in patients with DoC will be evaluated using clinical biomarkers of responsiveness (i.e., the Coma Recovery Scale-Revised; CRS-R), and electrophysiological biomarkers (e.g., power spectra, functional and effective connectivity, perturbational complexity index before and after intervention). Functional long-term outcomes will be assessed at 3 and 6 months post-intervention. Adverse events will be recorded during the treatment phase.
DISCUSSION: This study seeks to identify which brain region (front or back) is best to stimulate for the treatment of patients with DoC using rTMS, and to characterize the neural correlates of its action regarding recovery of consciousness and functional outcome. In addition, we will define the responders' profile based on patients' characteristics and functional impairments; and develop biomarkers of responsiveness using EEG analysis according to the clinical responsiveness to the treatment.
CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ct2/show/NCT04401319, Clinicaltrials.gov, n° NCT04401319.
Rosenfelder, Martin J; Department of Neurology, Therapiezentrum Burgau, Burgau, Germany ; Clinical and Biological Psychology, Institute of Psychology and Education, Ulm University, Ulm, Germany
Cardone, Paolo ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group
Niimi, Masachika ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; Department of Rehabilitation Medicine, Nihon University School of Medicine, Tokyo, Japan
Willacker, Lina; Department of Neurology, Ludwig-Maximilians University Hospital of Munich, University of Munich, Munich, Germany
Thibaut, Aurore ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group
Lejeune, Nicolas ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group ; William Lennox Neurological Hospital, Ottignies-Louvain-la-Neuve, Belgium
Laureys, Steven ; Centre Hospitalier Universitaire de Liège - CHU > > Centre du Cerveau² ; CERVO Research Center, Laval University, Québec, QC, Canada
Bender, Andreas; Department of Neurology, Therapiezentrum Burgau, Burgau, Germany ; Department of Neurology, Ludwig-Maximilians University Hospital of Munich, University of Munich, Munich, Germany
Gosseries, Olivia ; Université de Liège - ULiège > GIGA > GIGA Consciousness - Coma Science Group
Language :
English
Title :
A protocol for a multicenter randomized and personalized controlled trial using rTMS in patients with disorders of consciousness.
BMBF - Federal Ministry of Education and Research ESA - European Space Agency BELSPO - Belgian Federal Science Policy Office Bial Foundation MSF - Mind Science Foundation FRB - King Baudouin Foundation
Funding text :
This work was supported by the ZNS Hannelore-Kohl Stiftung and the Federal Ministry of Education and Research (BMBF), the Belgian National Funds for Scientific Research (FRS-FNRS), FNRS project No PDR/BEJ T.0134.21, the University of Liège Conseil Sectoriel de la Recherche, the European Union’s Horizon 2020 Framework Programme for Research and Innovation under the Specific Grant Agreement No. 945539 (Human Brain Project SGA3), the ERA-Net FLAG-ERA JTC2021 project ModelDXConsciousness (Human Brain Project Partnering Project), the European Space Agency (ESA) and the Belgian Federal Science Policy Office (BELSPO) in the framework of the PRODEX Programme, the GIGA Doctoral School for Health Science, the BIAL Foundation, the Mind Science Foundation, the fund Generet of the King Baudouin Foundation, the Mind Care International foundation and AstraZeneca Foundation. SL is FNRS Research Director, OG and AT are FNRS Research Associates, NL is FNRS Post Doctorate Fellow, and MV and PC are FNRS Research Fellows.We would like to express our gratitude to the University and University Hospital of Liège, the patients and their families and the staff from the neurological center William Lennox (Belgium), the Therapiezentrum Burgau (Germany) and the Schön Klinik Bad Aibling-Harthausen (Germany) for their precious collaboration.
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