Meningeal inflammation and cortical demyelination in acute multiple sclerosis
Meningeal inflammation and cortical demyelination in acute multiple sclerosis
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DOI：
10.1002/ana.25365
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发表时间：
2018-12-01
影响因子：
11.2
通讯作者：
Howell, Owain W.
中科院分区：
文献类型：
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作者：
Bevan, Ryan J.;Evans, Rhian;Howell, Owain W.
目的：皮质灰质（GM）病理，包括脱髓鞘和神经退行性变，与脑膜炎症相关，可能是确定多发性硬化症（MS）残疾进展的重要因素。然而，我们需要更多地了解皮质脱髓鞘、神经退行性变和脑膜炎症如何在MS早期病理中起作用，以更好地预测长期预后。方法采用免疫组化、免疫荧光和原位杂交的方法，定量分析来自病程短的MS （n = 12，中位病程2年）、进展性MS （n = 21，病程25年）、非发病对照（n = 11）和其他神经炎性疾病对照（n = 6）的组织阻滞。结果部分急性多发性硬化症患者皮质GM脱髓鞘广泛（占皮质GM总量的1 ~ 48%），其中最常见的是颅底下病变（62%）。与对照组相比，脑膜下病变组活化的（CD68(+)）小胶质细胞/巨噬细胞数量增加，急性MS正常表现组和病变GM组神经元密度显著降低（p < 0.005）。12例急性多发性硬化症中有4例可见明显的脑膜炎症和淋巴样结构。脑膜炎症程度与小胶质细胞/巨噬细胞激活相关（p < 0.05），但与皮质脱髓鞘面积无关，这反映了在GM病变附近以及部分脱髓鞘/再髓鞘皮质GM区域可见淋巴样结构。和脑膜炎症是急性多发性硬化症的显著病理标志，因此需要识别这种病理的早期生物标志物，以更好地预测预后。
Objective Cortical gray matter (GM) pathology, involving demyelination and neurodegeneration, associated with meningeal inflammation, could be important in determining disability progression in multiple sclerosis (MS). However, we need to know more about how cortical demyelination, neurodegeneration, and meningeal inflammation contribute to pathology at early stages of MS to better predict long-term outcome. Methods Tissue blocks from short disease duration MS (n = 12, median disease duration = 2 years), progressive MS (n = 21, disease duration = 25 years), non-diseased controls (n = 11), and other neurological inflammatory disease controls (n = 6) were quantitatively analyzed by immunohistochemistry, immunofluorescence, and in situ hybridization. Results Cortical GM demyelination was extensive in some cases of acute MS (range = 1-48% of total cortical GM), and subpial lesions were the most common type (62%). The numbers of activated (CD68(+)) microglia/macrophages were increased in cases with subpial lesions, and the density of neurons was significantly reduced in acute MS normal appearing and lesion GM, compared to controls (p < 0.005). Significant meningeal inflammation and lymphoid-like structures were seen in 4 of 12 acute MS cases. The extent of meningeal inflammation correlated with microglial/macrophage activation (p < 0.05), but not the area of cortical demyelination, reflecting the finding that lymphoid-like structures were seen adjacent to GM lesions as well as areas of partially demyelinated/remyelinated, cortical GM. Interpretation Our findings demonstrate that cortical demyelination, neuronal loss, and meningeal inflammation are notable pathological hallmarks of acute MS and support the need to identify early biomarkers of this pathology to better predict outcome.