Klaver Roel, Popescu Veronica, Voorn Pieter, Galis-de Graaf Yvonne, van der Valk Paul, de Vries Helga E, Schenk Geert J, Geurts Jeroen J G
From the Departments of Anatomy and Neurosciences (RK, PV, YGdG, GJS, JJGG), Radiology and Nuclear Medicine (VP), Pathology (PvdV), and Molecular Cell Biology and Immunology (HEdV), VU University Medical Center, Neuroscience Campus, Amsterdam, the Netherlands.
J Neuropathol Exp Neurol. 2015 May;74(5):453-8. doi: 10.1097/NEN.0000000000000189.
Multiple sclerosis (MS) is a demyelinating and neurodegenerative disease of the CNS. Multiple sclerosis lesions include significant demyelination of the gray matter, which is thought to be a major contributor to both physical and cognitive impairment. Subpial (Type III) lesions are the most common demyelinated cortical lesions. We investigated neurodegenerative features of subpial lesions in cerebral cortex samples from 11 patients with MS and 6 nondemented non-MS controls. There were no significant differences in neuron and axon density between normally myelinated normal-appearing gray matter (NAGM) and Type III MS lesions. Neurons were 11.2% smaller in Type III lesions than in NAGM in the cingulate cortex only; Type III lesions contained 25.4% fewer NeuN-positive neurons compared with control cortex. Neurons in MS NAGM were 13.6% smaller than those in control cortex. Finally, the same regions, immunostained with anti-SMI312 antibodies, showed reduced axon densities in Type III lesions (-31.4%) and NAGM (-33.0%) compared with controls. In conclusion, both NAGM and Type III lesions showed neurodegenerative changes, but they had no consistent differences in neuronal and axonal alterations. This suggests that neurodegeneration in the cerebral cortex of patients with MS may be independent of cortical demyelination.
多发性硬化症（MS）是一种中枢神经系统的脱髓鞘和神经退行性疾病。多发性硬化症病变包括灰质的显著脱髓鞘，这被认为是导致身体和认知障碍的主要因素。软脑膜下（III型）病变是最常见的脱髓鞘皮质病变。我们研究了11例多发性硬化症患者和6例无痴呆的非多发性硬化症对照者大脑皮质样本中软脑膜下病变的神经退行性特征。正常髓鞘化的正常外观灰质（NAGM）和III型多发性硬化症病变之间的神经元和轴突密度没有显著差异。仅在扣带回皮质中，III型病变中的神经元比NAGM中的神经元小11.2%；与对照皮质相比，III型病变中NeuN阳性神经元减少25.4%。多发性硬化症NAGM中的神经元比对照皮质中的神经元小13.6%。最后，用抗SMI312抗体免疫染色的相同区域显示，与对照相比，III型病变（-31.4%）和NAGM（-33.0%）中的轴突密度降低。总之，NAGM和III型病变均显示神经退行性变化，但它们在神经元和轴突改变方面没有一致的差异。这表明多发性硬化症患者大脑皮质中的神经退行性变可能与皮质脱髓鞘无关。
