Inflammatory cortical demyelination in early multiple sclerosis.
Inflammatory cortical demyelination in early multiple sclerosis.
复制标题
DOI：
10.1056/nejmoa1100648
复制
发表时间：
2011-12-08
期刊：
影响因子：
--
通讯作者：
Ransohoff RM
中科院分区：
文献类型：
--
作者：
Lucchinetti CF;Popescu BF;Bunyan RF;Moll NM;Roemer SF;Lassmann H;Brück W;Parisi JE;Scheithauer BW;Giannini C;Weigand SD;Mandrekar J;Ransohoff RM
皮质疾病已成为多发性硬化症发病机制的一个重要方面，与疾病进展和认知障碍有关。大多数皮质病变的研究集中在长期的，慢性的，进行性多发性硬化症患者的尸检结果，并强调这些病变的非炎症性质。磁共振成像研究表明，皮质损伤发生在疾病的早期。我们评估了多发性硬化患者脱髓鞘皮质病变的患病率和特征。在白质病变的活检取样过程中获得皮质组织。在大多数情况下，使用立体定向程序进行活检以诊断可疑肿瘤。对有足够皮质的患者（筛选的563例患者中的138例）进行皮质脱髓鞘评价。使用免疫组化，我们的特点是皮质病变的脱髓鞘活动，炎性浸润，脑膜炎的存在，以及皮质脱髓鞘和脑膜炎之间的地形关联。在末次随访访视（中位时间为3.5年）时，在77例患者（56%）的亚组中确定了诊断。53例患者（38%）（104处病变和222个组织块）存在皮质脱髓鞘，85例患者（121个组织块）不存在皮质脱髓鞘。25例皮质脱髓鞘患者有明确的多发性硬化（81%的31例患者进行了长期随访），33例无皮质脱髓鞘患者（72%的46例患者进行了长期随访）。在代表性组织中，58/71处病变（82%）显示CD 3 + T细胞浸润，32/78处病变（41%）显示巨噬细胞相关脱髓鞘。在有足够脑膜组织的患者中，脑膜炎症与皮质脱髓鞘在地形学上相关。在这组早期多发性硬化患者中，皮质脱髓鞘病变是常见的炎性病变，与脑膜炎症密切相关。（由国家多发性硬化症协会和国立卫生研究院资助。
Cortical disease has emerged as a critical aspect of the pathogenesis of multiple sclerosis, being associated with disease progression and cognitive impairment. Most studies of cortical lesions have focused on autopsy findings in patients with long-standing, chronic, progressive multiple sclerosis, and the noninflammatory nature of these lesions has been emphasized. Magnetic resonance imaging studies indicate that cortical damage occurs early in the disease. We evaluated the prevalence and character of demyelinating cortical lesions in patients with multiple sclerosis. Cortical tissues were obtained in passing during biopsy sampling of white-matter lesions. In most cases, biopsy was done with the use of stereotactic procedures to diagnose suspected tumors. Patients with sufficient cortex (138 of 563 patients screened) were evaluated for cortical demyelination. Using immunohistochemistry, we characterized cortical lesions with respect to demyelinating activity, inflammatory infiltrates, the presence of meningeal inflammation, and a topographic association between cortical demyelination and meningeal inflammation. Diagnoses were ascertained in a subgroup of 77 patients (56%) at the last follow-up visit (at a median of 3.5 years). Cortical demyelination was present in 53 patients (38%) (104 lesions and 222 tissue blocks) and was absent in 85 patients (121 tissue blocks). Twenty-five patients with cortical demyelination had definite multiple sclerosis (81% of 31 patients who underwent long-term follow-up), as did 33 patients without cortical demyelination (72% of 46 patients who underwent long-term follow-up). In representative tissues, 58 of 71 lesions (82%) showed CD3+ T-cell infiltrates, and 32 of 78 lesions (41%) showed macrophage-associated demyelination. Meningeal inflammation was topographically associated with cortical demyelination in patients who had sufficient meningeal tissue for study. In this cohort of patients with early-stage multiple sclerosis, cortical demyelinating lesions were frequent, inflammatory, and strongly associated with meningeal inflammation. (Funded by the National Multiple Sclerosis Society and the National Institutes of Health.)