Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis
Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis
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DOI：
10.1093/brain/awr182
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发表时间：
2011-09-01
期刊：
影响因子：
14.5
通讯作者：
Reynolds, Richard
中科院分区：
文献类型：
--
作者：
Howell, Owain W.;Reeves, Cheryl A.;Reynolds, Richard
异位淋巴样结构形式的脑膜炎症已被认为在多发性硬化症大脑皮层灰质病理的发展中起着重要作用。本研究的目的是分析广泛年龄范围的继发性进展性多发性硬化病例中B细胞滤泡样结构的发生率和分布，并确定它们与弥漫性脑膜炎症、白质血管周围浸润和小胶质细胞激活的关系。我们检查了123例继发性进行性多发性硬化症患者的脑膜和血管周围免疫细胞浸润的组织块和/或整个冠状大切片，包括广泛的脑区。大的，致密的，富含B细胞的淋巴细胞聚集体被筛选滤泡树突状细胞，增殖的B细胞和浆细胞的存在。49例（40%）发现异位B细胞滤泡样结构，频率不同，分布于整个前脑，最常见于颞叶、扣带回、岛叶和额叶皮层的深沟。枕下灰质脱髓鞘病变位于这些结构的邻近和一定距离。B细胞滤泡样结构的存在与弥漫性脑膜炎症的定量增加相关，而弥漫性脑膜炎症与小胶质细胞激活程度和灰质皮质脱髓鞘有关。与没有B细胞滤泡样结构的患者相比，这些病例的中位发病年龄、疾病进展时间、轮椅依赖时间和死亡年龄均有显著差异。我们的研究结果表明，脑膜浸润可能在潜在的枕下灰质病理和加速临床过程中起作用，在很大比例的病例中，B细胞滤泡样结构的存在加重了临床过程。
Meningeal inflammation in the form of ectopic lymphoid-like structures has been suggested to play a prominent role in the development of cerebral cortical grey matter pathology in multiple sclerosis. The aim of this study was to analyse the incidence and distribution of B cell follicle-like structures in an extensive collection of cases with secondary progressive multiple sclerosis with a wide age range and to determine their relationship to diffuse meningeal inflammation, white matter perivascular infiltrates and microglial activation. One hundred and twenty three cases with secondary progressive multiple sclerosis were examined for the presence of meningeal and perivascular immune cell infiltrates in tissue blocks and/or whole coronal macrosections encompassing a wide array of brain areas. Large, dense, B cell-rich lymphocytic aggregates were screened for the presence of follicular dendritic cells, proliferating B cells and plasma cells. Ectopic B cell follicle-like structures were found, with variable frequency, in 49 cases (40%) and were distributed throughout the forebrain, where they were most frequently located in the deep sulci of the temporal, cingulate, insula and frontal cortex. Subpial grey matter demyelinated lesions were located both adjacent to, and some distance from such structures. The presence of B cell follicle-like structures was associated with an accompanying quantitative increase in diffuse meningeal inflammation that correlated with the degree of microglial activation and grey matter cortical demyelination. The median age of disease onset, time to disease progression, time to wheelchair dependence and age at death all differed significantly in these cases when compared with those without B cell follicle-like structures. Our findings suggest that meningeal infiltrates may play a contributory role in the underlying subpial grey matter pathology and accelerated clinical course, which is exacerbated in a significant proportion of cases by the presence of B cell follicle-like structures.