Cortical demyelinated lesions are frequent and widespread in chronic multiple sclerosis (MS) patients, and may contribute to disease progression. Inflammation and related oxidative stress have been proposed as central mediators of cortical damage, yet meningeal and cortical inflammation is not specific to MS, but also occurs in other diseases. The first aim of this study was to test whether cortical demyelination was specific for demyelinating CNS diseases compared to other CNS disorders with prominent meningeal and cortical inflammation. The second aim was to assess whether oxidative tissue damage was associated with the extent of neuroaxonal damage. We studied a large cohort of patients diagnosed with demyelinating CNS diseases and non-demyelinating diseases of autoimmune, infectious, neoplastic or metabolic origin affecting the meninges and the cortex. Included were patients with MS, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO), viral and bacterial meningoencephalitis, progressive multifocal leukoencephalopathy (PML), subacute sclerosing panencephalitis (SSPE), carcinomatous and lymphomatous meningitis and metabolic disorders such as extrapontine myelinolysis, thus encompassing a wide range of adaptive and innate cytokine signatures. Using myelin protein immunohistochemistry, we found cortical demyelination in MS, ADEM, PML and extrapontine myelinolysis, whereby each condition showed a disease-specific histopathological pattern. Remarkably, extensive ribbon-like subpial demyelination was only observed in MS, thus providing an important pathogenetic and diagnostic cue. Cortical oxidative injury was detected in both demyelinating and non-demyelinating CNS disorders. Our data demonstrate that meningeal and cortical inflammation alone accompanied by oxidative stress are not sufficient to generate the extensive subpial cortical demyelination found in MS, but require other MS-specific factors.

中文翻译：

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广泛的软膜下皮质脱髓鞘是多发性硬化症特有的。

皮质脱髓鞘病变在慢性多发性硬化症 (MS) 患者中常见且广泛，并且可能会导致疾病进展。炎症和相关的氧化应激被认为是皮层损伤的中枢介质，但脑膜和皮层炎症并非 MS 特有，也发生在其他疾病中。本研究的第一个目的是测试与其他具有明显脑膜和皮质炎症的中枢神经系统疾病相比，皮质脱髓鞘是否对中枢神经系统疾病具有特异性。第二个目的是评估氧化性组织损伤是否与神经轴突损伤的程度有关。我们研究了大量诊断为中枢神经系统脱髓鞘疾病和自身免疫性、感染性、影响脑膜和皮质的肿瘤或代谢起源。包括多发性硬化症、急性播散性脑脊髓炎 (ADEM)、视神经脊髓炎 (NMO)、病毒性和细菌性脑膜脑炎、进行性多灶性白质脑病 (PML)、亚急性硬化性全脑炎 (SSPE)、癌性和脑桥性脑膜炎以及代谢性疾病（如髓鞘外溶解）的患者因此涵盖了广泛的适应性和先天性细胞因子特征。使用髓鞘蛋白免疫组织化学，我们发现 MS、ADEM、PML 和桥外髓鞘溶解症中的皮质脱髓鞘，其中每种情况都显示出疾病特异性的组织病理学模式。值得注意的是，广泛的带状软膜下脱髓鞘仅在 MS 中观察到，因此提供了重要的发病机制和诊断线索。在脱髓鞘和非脱髓鞘中枢神经系统疾病中均检测到皮质氧化损伤。我们的数据表明，单独伴有氧化应激的脑膜和皮质炎症不足以产生 MS 中发现的广泛的软膜下皮质脱髓鞘，但需要其他 MS 特异性因素。