From the Spinal Cord Injury Center (E.H., G.D., P.F.), Balgrist University Hospital, Zurich, Switzerland; Department of Brain Repair and Rehabilitation (A.J.T., P.F.) and Wellcome Trust Centre for Neuroimaging (N.W., S.M., P.F.), UCL Institute of Neurology, University College London, UK; Department of Neurophysics (N.W., P.F.), Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany; and Department of Systems Neuroscience (S.M.), University Medical Center Hamburg-Eppendorf, Germany.
Neurology. 2018 Apr 24;90(17):e1510-e1522. doi: 10.1212/WNL.0000000000005361. Epub 2018 Mar 28.
To investigate whether gray matter pathology above the level of injury, alongside white matter changes, also contributes to sensorimotor impairments after spinal cord injury.
A 3T MRI protocol was acquired in 17 tetraplegic patients and 21 controls. A sagittal T2-weighted sequence was used to characterize lesion severity. At the C2-3 level, a high-resolution T2*-weighted sequence was used to assess cross-sectional areas of gray and white matter, including their subcompartments; a diffusion-weighted sequence was used to compute voxel-based diffusion indices. Regression models determined associations between lesion severity and tissue-specific neurodegeneration and associations between the latter with neurophysiologic and clinical outcome.
Neurodegeneration was evident within the dorsal and ventral horns and white matter above the level of injury. Tract-specific neurodegeneration was associated with prolonged conduction of appropriate electrophysiologic recordings. Dorsal horn atrophy was associated with sensory outcome, while ventral horn atrophy was associated with motor outcome. White matter integrity of dorsal columns and corticospinal tracts was associated with daily-life independence.
Our results suggest that, next to anterograde and retrograde degeneration of white matter tracts, neuronal circuits within the spinal cord far above the level of injury undergo transsynaptic neurodegeneration, resulting in specific gray matter changes. Such improved understanding of tissue-specific cord pathology offers potential biomarkers with more efficient targeting and monitoring of neuroregenerative (i.e., white matter) and neuroprotective (i.e., gray matter) agents.
探讨损伤水平以上的灰质病理学是否与白质变化一起导致脊髓损伤后的感觉运动功能障碍。
在 17 名四肢瘫痪患者和 21 名对照者中采集了 3T MRI 方案。矢状 T2 加权序列用于描述损伤严重程度。在 C2-3 水平,使用高分辨率 T2*-加权序列评估灰质和白质的横截面积,包括它们的亚区;使用弥散加权序列计算基于体素的弥散指数。回归模型确定了损伤严重程度与组织特异性神经退行性变之间的关联,以及后者与神经生理和临床结果之间的关联。
损伤水平以上的背角和腹角以及白质内存在神经退行性变。特定于束的神经退行性变与适当电生理记录的延长传导有关。背角萎缩与感觉结果相关,而腹角萎缩与运动结果相关。背柱和皮质脊髓束的白质完整性与日常生活独立性相关。
我们的结果表明,除了白质束的顺行和逆行变性外,脊髓内远高于损伤水平的神经元回路也会发生突触后神经退行性变,导致特定的灰质变化。这种对组织特异性脊髓病理学的更好理解提供了潜在的生物标志物,可更有效地针对神经再生(即白质)和神经保护(即灰质)剂进行靶向和监测。