The Mind Research Network, Lovelace Biomedical and Environmental Research Institute, Albuquerque, NM 87106, USA.
Brain. 2012 Apr;135(Pt 4):1281-92. doi: 10.1093/brain/aws073.
Mild traumatic brain injury is the most prevalent neurological insult and frequently results in neurobehavioural sequelae. However, little is known about the pathophysiology underlying the injury and how these injuries change as a function of time. Although diffusion tensor imaging holds promise for in vivo characterization of white matter pathology, both the direction and magnitude of anisotropic water diffusion abnormalities in axonal tracts are actively debated. The current study therefore represents both an independent replication effort (n = 28) of our previous findings (n = 22) of increased fractional anisotropy during semi-acute injury, as well as a prospective study (n = 26) on the putative recovery of diffusion abnormalities. Moreover, new analytical strategies were applied to capture spatially heterogeneous white matter injuries, which minimize implicit assumptions of uniform injury across diverse clinical presentations. Results indicate that whereas a general pattern of high anisotropic diffusion/low radial diffusivity was present in various white matter tracts in both the replication and original cohorts, this pattern was only consistently observed in the genu of the corpus callosum across both samples. Evidence for a greater number of localized clusters with increased anisotropic diffusion was identified across both cohorts at trend levels, confirming heterogeneity in white matter injury. Pooled analyses (50 patients; 50 controls) suggested that measures of diffusion within the genu were predictive of patient classification, albeit at very modest levels (71% accuracy). Finally, we observed evidence of recovery in lesion load in returning patients across a 4-month interval, which was correlated with a reduction in self-reported post-concussive symptomatology. In summary, the corpus callosum may serve as a common point of injury in mild traumatic brain injury secondary to anatomical (high frequency of long unmyelinated fibres) and biomechanics factors. A spatially heterogeneous pattern of increased anisotropic diffusion exists in various other white matter tracts, and these white matter anomalies appear to diminish with recovery. This macroscopic pattern of diffusion abnormalities may be associated with cytotoxic oedema following mechanical forces, resulting in changes in ionic homeostasis, and alterations in the ratio of intracellular and extracellular water. Animal models more specific to the types of mild traumatic brain injury typically incurred by humans are needed to confirm the histological correlates of these macroscopic markers of white matter pathology.
轻度创伤性脑损伤是最常见的神经损伤，经常导致神经行为后遗症。然而，对于损伤的病理生理学以及这些损伤如何随时间变化知之甚少。尽管扩散张量成像有望对脑白质病变进行体内特征描述，但轴突束中各向异性水扩散异常的方向和幅度仍存在争议。因此，本研究既是对我们之前研究结果（n = 22）的独立复制（n = 28），也是对扩散异常可能恢复的前瞻性研究（n = 26）。此外，还应用了新的分析策略来捕捉空间异质性的脑白质损伤，从而最大限度地减少了对不同临床表现中均匀损伤的隐含假设。结果表明，尽管在复制和原始队列的各种脑白质束中均存在高各向异性扩散/低径向扩散率的一般模式，但这种模式仅在两个样本的胼胝体膝部一致观察到。在两个队列中，都在趋势水平上发现了更多具有高各向异性扩散的局部聚类的证据，证实了脑白质损伤的异质性。基于 50 名患者和 50 名对照的汇总分析表明，胼胝体膝部的扩散测量值可预测患者分类，尽管准确度非常低（71%）。最后，我们观察到在 4 个月的随访中，返回患者的病变负荷有恢复的证据，这与自我报告的脑震荡后症状减少有关。总之，胼胝体可能是由于解剖学（高频率的长未髓鞘纤维）和生物力学因素导致轻度创伤性脑损伤的共同损伤部位。在各种其他脑白质束中存在增加的各向异性扩散的空间异质模式，并且这些脑白质异常似乎随着恢复而减少。这种扩散异常的宏观模式可能与机械力引起的细胞毒性水肿有关，导致离子动态平衡变化，以及细胞内和细胞外水的比例改变。需要更具体针对人类常见的轻度创伤性脑损伤类型的动物模型来确认这些脑白质病理学宏观标志物的组织学相关性。
