Kooi Evert-Jan, Geurts Jeroen J G, van Horssen Jack, Bø Lars, van der Valk Paul
Departments of Pathology (Neuropathology) University Medical Center, Amsterdam, The Netherlands.
J Neuropathol Exp Neurol. 2009 Sep;68(9):1021-8. doi: 10.1097/NEN.0b013e3181b4bf8f.
Cortical demyelination can be extensive in chronic multiple sclerosis (MS) patients. Cortical lesions are not associated with lymphocyte infiltration, blood-brain barrier disruption, or complement deposition; therefore, their pathogenesis is unclear. We analyzed the extent and cellular composition of leptomeningeal inflammatory infiltrates and their relationship with cortical demyelinated lesions in brain autopsy samples from 28 chronic MS patients; samples from 6 nonneurological disease control patients were also studied. Immunohistochemistry was used to detect meningeal T cells, B cells, macrophages, mature and immature dendritic cells, T-helper cells, (activated) cytotoxic T cells, and plasma cells. Quantitative analysis revealed significant meningeal inflammation in chronic MS patients; T cells were the predominant inflammatory cells. Morphometric analysis was performed on coronal hemisphere sections of the MS cases to assess subpial demyelination; no correlation between the extent of subpial demyelination and extent of meningeal inflammation was identified. Moreover, no differences were observed in the degree or cellular composition of meningeal infiltrates in areas directly adjacent to subpial lesions compared with areas adjacent to normal-appearing gray matter in the MS cases. In addition, no follicle-like structures were found in the MS samples. Our data suggest that the occurrence of cortical lesions is not related to the presence of meningeal inflammation in a large number of chronic MS patients.
在慢性多发性硬化症(MS)患者中,皮质脱髓鞘可能广泛存在。皮质病变与淋巴细胞浸润、血脑屏障破坏或补体沉积无关;因此,其发病机制尚不清楚。我们分析了28例慢性MS患者脑尸检样本中软脑膜炎性浸润的程度和细胞组成,以及它们与皮质脱髓鞘病变的关系;还研究了6例非神经疾病对照患者的样本。采用免疫组织化学方法检测软脑膜T细胞、B细胞、巨噬细胞、成熟和未成熟树突状细胞、辅助性T细胞、(活化的)细胞毒性T细胞和浆细胞。定量分析显示慢性MS患者存在明显的软脑膜炎症;T细胞是主要的炎性细胞。对MS病例的冠状半球切片进行形态计量分析,以评估软脑膜下脱髓鞘情况;未发现软脑膜下脱髓鞘程度与软脑膜炎症程度之间存在相关性。此外,与MS病例中正常外观灰质相邻区域相比,软脑膜下病变直接相邻区域的软脑膜浸润程度或细胞组成未观察到差异。此外,在MS样本中未发现滤泡样结构。我们的数据表明,在大量慢性MS患者中,皮质病变的发生与软脑膜炎症的存在无关。