Cognitive Neurorehabilitation Sciences Laboratory, Research Department, Toronto Rehabilitation Institute Toronto, ON, Canada ; Department of Psychiatry, Faculty of Medicine, University of Toronto Toronto, ON, Canada.
Cognitive Neurorehabilitation Sciences Laboratory, Research Department, Toronto Rehabilitation Institute Toronto, ON, Canada.
Front Hum Neurosci. 2014 Mar 31;8:67. doi: 10.3389/fnhum.2014.00067. eCollection 2014.
Moderate-severe traumatic brain injury (TBI) is increasingly being understood as a progressive disorder, with growing evidence of reduced brain volume and white matter (WM) integrity as well as lesion expansion in the chronic phases of injury. The scale of these losses has yet to be investigated, and pattern of change across structures has received limited attention.
(1) To measure the percentage of patients in our TBI sample showing atrophy from 5 to 20 months post-injury in the whole brain and in structures with known vulnerability to acute TBI, and (2) To examine relative vulnerability and patterns of volume loss across structures.
Fifty-six TBI patients [complicated mild to severe, with mean Glasgow Coma Scale (GCS) in severe range] underwent MRI at, on average, 5 and 20 months post-injury; 12 healthy controls underwent MRI twice, with a mean gap between scans of 25.4 months. Mean monthly percent volume change was computed for whole brain (ventricle-to-brain ratio; VBR), corpus callosum (CC), and right and left hippocampi (HPC).
(1) Using a threshold of 2 z-scores below controls, 96% of patients showed atrophy across time points in at least one region; 75% showed atrophy in at least 3 of the 4 regions measured. (2) There were no significant differences in the proportion of patients who showed atrophy across structures. For those showing decline in VBR, there was a significant association with both the CC and the right HPC (P < 0.05 for both comparisons). There were also significant associations between those showing decline in (i) right and left HPC (P < 0.05); (ii) all combinations of genu, body and splenium of the CC (P < 0.05), and (iii) head and tail of the right HPC (P < 0.05 all sub-structure comparisons).
Atrophy in chronic TBI is robust, and the CC, right HPC and left HPC appear equally vulnerable. Significant associations between the right and left HPC, and within substructures of the CC and right HPC, raise the possibility of common mechanisms for these regions, including transneuronal degeneration. Given the 96% incidence rate of atrophy, a genetic explanation is unlikely to explain all findings. Multiple and possibly synergistic mechanisms may explain findings. Atrophy has been associated with poorer functional outcomes, but recent findings suggest there is potential to offset this. A better, understanding of the underlying mechanisms could permit targeted therapy enabling better long-term outcomes.
中度至重度创伤性脑损伤（TBI）越来越被认为是一种进行性疾病，越来越多的证据表明，在损伤的慢性阶段，脑体积和白质（WM）的完整性以及病变的扩大。这些损失的规模尚未得到调查，而且结构之间的变化模式也受到了有限的关注。
（1）测量我们的 TBI 样本中，在损伤后 5 至 20 个月期间，整个大脑以及已知对急性 TBI 易受影响的结构中出现萎缩的患者比例；（2）检查相对易损性和结构间的体积损失模式。
56 名 TBI 患者[复杂轻度至重度，平均格拉斯哥昏迷量表（GCS）在重度范围内]在损伤后平均 5 个月和 20 个月进行 MRI 检查；12 名健康对照者两次进行 MRI 检查，两次扫描的平均间隔时间为 25.4 个月。计算整个大脑（脑室与大脑比率；VBR）、胼胝体（CC）以及右侧和左侧海马体（HPC）的平均每月体积百分比变化。
（1）使用低于对照组 2 个 z 分数的阈值，96%的患者在至少一个区域显示出跨时间点的萎缩；75%的患者在测量的 4 个区域中至少有 3 个区域显示出萎缩。（2）在显示出 VBR 下降的患者中，在结构之间显示出萎缩的比例没有显著差异。对于 VBR 下降的患者，与 CC 和右侧 HPC 都有显著关联（两种比较的 P 值均 < 0.05）。在以下情况下也存在显著关联：（i）右侧和左侧 HPC（P < 0.05）；（ii）CC 的所有结合体、体部和压部（P < 0.05），以及（iii）右侧 HPC 的头部和尾部（所有亚结构比较的 P < 0.05）。
慢性 TBI 中的萎缩是可靠的，胼胝体、右侧 HPC 和左侧 HPC 似乎同样容易受到影响。右侧和左侧 HPC 之间，以及 CC 和右侧 HPC 的亚结构之间的显著关联，提出了这些区域存在共同机制的可能性，包括跨神经元变性。鉴于萎缩的发生率为 96%，遗传解释不太可能解释所有发现。多种可能的协同机制可能解释这些发现。萎缩与较差的功能结局相关，但最近的发现表明有可能抵消这种情况。更好地了解潜在机制可以实现靶向治疗，从而获得更好的长期结局。
