Wolfson Neuroscience Laboratories, Centre for Neuroscience, Imperial College Faculty of Medicine, Hammersmith Hospital, London W12 0NN, UK.
Brain. 2012 Oct;135(Pt 10):2925-37. doi: 10.1093/brain/aws189. Epub 2012 Aug 20.
The primary progressive form of multiple sclerosis is characterized by accrual of neurological dysfunction from disease onset without remission and it is still a matter of debate whether this disease course results from different pathogenetic mechanisms compared with secondary progressive multiple sclerosis. Inflammation in the leptomeninges has been identified as a key feature of secondary progressive multiple sclerosis and may contribute to the extensive cortical pathology that accompanies progressive disease. Our aim was to investigate the extent of perivascular and meningeal inflammation in primary progressive multiple sclerosis in order to understand their contribution to the pathogenetic mechanisms associated with cortical pathology. A comprehensive immunohistochemical analysis was performed on post-mortem brain tissue from 26 cases with primary progressive multiple sclerosis. A variable extent of meningeal immune cell infiltration was detected and more extensive demyelination and neurite loss in the cortical grey matter was found in cases exhibiting an increased level of meningeal inflammation. However, no tertiary lymphoid-like structures were found. Profound microglial activation and reduction in neuronal density was observed in both the lesions and normal appearing grey matter compared with control cortex. Furthermore, cases with primary progressive multiple sclerosis with extensive meningeal immune cell infiltration exhibited a more severe clinical course, including a shorter disease duration and younger age at death. Our data suggest that generalized diffuse meningeal inflammation and the associated inflammatory milieu in the subarachnoid compartment plays a role in the pathogenesis of cortical grey matter lesions and an increased rate of clinical progression in primary progressive multiple sclerosis.
原发性进行性多发性硬化症的特征是从疾病发作开始就出现神经功能障碍，且没有缓解，并且与继发性进行性多发性硬化症相比，这种疾病过程是否是由不同的发病机制引起的仍存在争议。软脑膜中的炎症已被确定为继发性进行性多发性硬化症的一个关键特征，并且可能导致伴随进行性疾病的广泛皮质病理学。我们的目的是研究原发性进行性多发性硬化症中血管周围和脑膜炎症的程度，以便了解其对与皮质病理学相关的发病机制的贡献。对 26 例原发性进行性多发性硬化症的尸检脑组织进行了全面的免疫组织化学分析。检测到脑膜免疫细胞浸润程度不同，并且在脑膜炎症水平升高的情况下，发现皮质灰质中有更广泛的脱髓鞘和神经突丢失。然而，没有发现三级淋巴样结构。与对照皮质相比，在病变和正常外观的灰质中观察到明显的小胶质细胞激活和神经元密度降低。此外，原发性进行性多发性硬化症患者中脑膜免疫细胞浸润广泛的病例表现出更严重的临床病程，包括疾病持续时间更短和死亡时年龄更小。我们的数据表明，广泛弥漫性脑膜炎症以及蛛网膜下腔间隙中的相关炎症环境在皮质灰质病变的发病机制中发挥作用，并导致原发性进行性多发性硬化症的临床进展速度加快。
