Vitello Marie M, Rosenfelder Martin J, Cardone Paolo, Niimi Masachika, Willacker Lina, Thibaut Aurore, Lejeune Nicolas, Laureys Steven, Bender Andreas, Gosseries Olivia
Coma Science Group, GIGA Consciousness, University of Liège, Liège, Belgium.
Centre du Cerveau2, University Hospital of Liège, Liège, Belgium.
Front Neurol. 2023 Jul 21;14:1216468. doi: 10.3389/fneur.2023.1216468. eCollection 2023.
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.
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.
https://clinicaltrials.gov/ct2/show/NCT04401319, Clinicaltrials.gov, n° NCT04401319.
改善慢性意识障碍（DoC）患者的功能恢复仍然是该领域最大的挑战之一。关于大脑前部（前额叶区域）和后部（顶叶区域）作为意识恢复热点的作用，存在不同的理论。重复经颅磁刺激（rTMS）是一种用于治疗DoC的强大非侵入性脑刺激技术。然而，尚未对TMS治疗大脑前部和后部的效果进行直接比较。在本研究中，我们旨在评估额叶和顶叶rTMS对DoC恢复的短期和长期影响，并对反应者进行表型特征分析。
方法/设计：90例亚急性和持续性DoC患者将纳入一项两部分的多中心前瞻性研究。在第一阶段（随机对照试验，RCT），患者将在10天内采用交叉设计接受4次rTMS治疗，靶点为（i）左侧背外侧前额叶皮质（DLPFC）和（ii）左侧角回（AG），以及（iii和iv）它们的假刺激对照部位。在第二阶段（纵向个性化试验），患者将接受针对在RCT中显示最佳效果的脑区进行20个工作日的个性化刺激，并将被随机分配到主动或假刺激干预组。将使用反应性临床生物标志物（即昏迷恢复量表修订版；CRS-R）和电生理生物标志物（如功率谱、功能和有效连接性、干预前后的微扰复杂性指数）评估rTMS对DoC患者神经行为和神经生理功能的影响。将在干预后3个月和6个月评估功能长期结果。在治疗阶段将记录不良事件。
本研究旨在确定使用rTMS治疗DoC患者时，刺激哪个脑区（前部或后部）最佳，并描述其在意识恢复和功能结果方面作用的神经相关性。此外，我们将根据患者特征和功能障碍定义反应者的特征；并根据对治疗的临床反应，利用脑电图分析开发反应性生物标志物。
https://clinicaltrials.gov/ct2/show/NCT04401319，Clinicaltrials.gov，编号NCT04401319。
