Department of Psychology, University of California, Los Angeles, Los Angeles, CA.
Coma Science Group, Cyclotron Research Center and Neurology Department, University and University Hospital of Liège, Liège, Belgium.
Ann Neurol. 2015 Jul;78(1):68-76. doi: 10.1002/ana.24423. Epub 2015 May 4.
What mechanisms underlie the loss and recovery of consciousness after severe brain injury? We sought to establish, in the largest cohort of patients with disorders of consciousness (DOC) to date, the link between gold standard clinical measures of awareness and wakefulness, and specific patterns of local brain pathology-thereby possibly providing a mechanistic framework for patient diagnosis, prognosis, and treatment development.
Structural T1-weighted magnetic resonance images were collected, in a continuous sample of 143 severely brain-injured patients with DOC (and 96 volunteers), across 2 tertiary expert centers. Brain atrophy in subcortical regions (bilateral thalamus, basal ganglia, hippocampus, basal forebrain, and brainstem) was assessed across (1) healthy volunteers and patients, (2) clinical entities (eg, vegetative state, minimally conscious state), (3) clinical measures of consciousness (Coma Recovery Scale-Revised), and (4) injury etiology.
Compared to volunteers, patients exhibited significant atrophy across all structures (p < 0.05, corrected). Strikingly, we found almost no significant differences across clinical entities. Nonetheless, the clinical measures of awareness and wakefulness upon which differential diagnosis rely were systematically associated with tissue atrophy within thalamic and basal ganglia nuclei, respectively; the basal forebrain was atrophied in proportion to patients' response to sensory stimulation. In addition, nontraumatic injuries exhibited more extensive thalamic atrophy.
These findings provide, for the first time, a grounding in pathology for gold standard behavior-based clinical measures of consciousness, and reframe our current models of DOC by stressing the different links tying thalamic mechanisms to willful behavior and extrathalamic mechanisms to behavioral (and electrocortical) arousal.
严重脑损伤后意识丧失和恢复的机制是什么？我们试图在迄今为止最大的意识障碍（DOC）患者队列中建立联系，将意识和觉醒的金标准临床测量与特定的局部脑病理模式联系起来，从而为患者的诊断、预后和治疗发展提供一个机制框架。
在两个三级专家中心，连续收集了 143 名严重脑损伤伴有 DOC 的患者（和 96 名志愿者）的结构 T1 加权磁共振图像。在（1）健康志愿者和患者、（2）临床实体（如植物状态、最小意识状态）、（3）意识的临床测量（修订后的昏迷恢复量表）和（4）损伤病因学方面，评估了皮质下区域（双侧丘脑、基底节、海马体、基底前脑和脑干）的脑萎缩。
与志愿者相比，患者在所有结构上都表现出明显的萎缩（p < 0.05，校正后）。引人注目的是，我们发现临床实体之间几乎没有显著差异。尽管如此，依赖于差异诊断的意识和觉醒的临床测量与丘脑和基底节核内的组织萎缩分别系统相关；基底前脑的萎缩与患者对感觉刺激的反应成正比。此外，非创伤性损伤表现出更广泛的丘脑萎缩。
这些发现首次为意识的金标准行为临床测量提供了病理学基础，并通过强调将丘脑机制与意志行为联系起来的不同联系以及将外丘脑机制与行为（和脑电图）唤醒联系起来的不同联系，重新构建了我们当前的 DOC 模型。
