DeLuca G C, Ebers G C, Esiri M M
Department of Clinical Neurology, University of Oxford, Oxford, UK.
Brain. 2004 May;127(Pt 5):1009-18. doi: 10.1093/brain/awh118. Epub 2004 Mar 26.
Clinical, imaging, and pathological studies in multiple sclerosis have generally emphasized the relative preservation of axons in comparison with myelin. Recent evidence, however, demonstrates that axonal loss is also significant, affects long tracts such as the corticospinal and sensory tracts and relates closely to functional disability. Accordingly, the distribution and extent of this axonal loss is the focus of the current investigation. Post-mortem material of 55 multiple sclerosis patients and 32 matched controls was used to examine quantitatively the population of axons in the corticospinal tracts from the medulla to the lumbar spinal cord and the sensory tracts from the lumbar to the upper cervical spinal cord. Myelin- and axon-stained sections have been prepared to estimate the notional area and axon density, respectively of both tracts. Our results indicate that in the corticospinal tracts there is a significant reduction of the area and axon density at all levels investigated in multiple sclerosis cases when compared with controls. In contrast, the sensory tracts in multiple sclerosis cases showed a significant reduction in area and axon density only in the upper regions of the spinal cord. As has been found with MRI plaque load and T2 burden, correlations of axonal loss with duration of disease were not strong. Of the fibres lost in multiple sclerosis, we have found that small fibres (<3 microm2) seem to be particularly affected, with large fibres remaining relatively preserved in both the corticospinal and sensory tracts. In multiple sclerosis, axonal loss is widespread, and its extent is tract specific and size selective.
多发性硬化症的临床、影像学和病理学研究通常强调与髓鞘相比轴突相对保留。然而，最近的证据表明，轴突损失也很显著，影响皮质脊髓束和感觉束等长束，并与功能残疾密切相关。因此，这种轴突损失的分布和程度是当前研究的重点。使用55例多发性硬化症患者和32例匹配对照的尸检材料，定量检查从延髓到腰髓的皮质脊髓束以及从腰髓到颈髓上段的感觉束中的轴突数量。已制备髓鞘和轴突染色切片，分别估计这两条束的理论面积和轴突密度。我们的结果表明，与对照相比，在多发性硬化症病例中，在所研究的所有水平上，皮质脊髓束的面积和轴突密度均显著降低。相比之下，多发性硬化症病例中的感觉束仅在脊髓上部区域显示面积和轴突密度显著降低。正如在MRI斑块负荷和T2负荷研究中所发现的那样，轴突损失与疾病持续时间的相关性不强。在多发性硬化症中丢失的纤维中，我们发现小纤维（<3平方微米）似乎特别受影响，而大纤维在皮质脊髓束和感觉束中相对保留。在多发性硬化症中，轴突损失广泛存在，其程度具有束特异性和大小选择性。
