Department of Neurology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Clinical Research Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Front Immunol. 2022 Sep 29;13:966781. doi: 10.3389/fimmu.2022.966781. eCollection 2022.
BACKGROUND AND OBJECTIVES: Cerebrospinal fluid (CSF) and interstitial fluid exchange along a brain-wide network of perivascular spaces (PVS) termed the 'glymphatic system'. The aquaporin-4 (AQP4) water channels abundantly expressed on astrocytic endfeet play a key role in the CSF circulation in the glymphatic system. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating autoimmune disease of the central nervous system (CNS) featured with a specific autoantibody directed against AQP4 in most of patients. Anti-AQP4 antibodies are likely resulting in the impairment of the brain glymphatic system and the enlargement of PVS in NMOSD patients. In the current study, we aimed to demonstrate the features of EPVS detected by MRI and its association with the CSF anti-AQP4 antibody titer, CNS inflammatory markers, and disease severity in NMOSD patients. METHODS: We conducted a retrospective review of a consecutive cohort of 110 patients with NMOSD who had brain MRI. We assessed the correlation of EPVS with markers of neuroinflammation, blood-brain barrier (BBB) function and severity of neurological dysfunction in patients. We used multivariate logistic regression analysis to determine the independent variables associated with disease severity. RESULTS: The median number of total-EPVS was 15.5 (IQR, 11-24.2) in NMOSD patients. The number of total-EPVS was significantly related to EDSS score after correcting for the effects of age and hypertension (r=0.353, p<0.001). The number of total-EPVS was also significantly associated with the titer of CSF anti-AQP4 antibody, the albumin rate (CSF/serum ratios of albumin), the CSF albumin, IgG and IgA levels. Logistic regression analysis showed that total-EPVS and serum albumin level were two independent factors to predict disease severity in NMOSD patients (OR=1.053, p=0.028; OR=0.858, p=0.009 respectively). Furthermore, ROC analysis achieved AUC of 0.736 (0.640-0.831, p<0.001) for total-EPVS to determine severe NMOSD (EDSS 4.5-9.5). DISCUSSION: In our cohort, we found a relationship between EPVS and neuroinflammation and BBB function in NMOSD. Moreover, EPVS might independently predict neurological dysfunction in patients with NMOSD.
背景与目的：脑脊髓液（CSF）和间质液沿着被称为“神经胶淋巴系统”的血管周围空间（PVS）的广泛网络进行交换。水通道蛋白-4（AQP4）在星形细胞终足上大量表达，在神经胶淋巴系统中的 CSF 循环中起着关键作用。视神经脊髓炎谱系障碍（NMOSD）是一种中枢神经系统（CNS）的炎症性脱髓鞘自身免疫性疾病，其特征是大多数患者存在针对 AQP4 的特异性自身抗体。抗 AQP4 抗体可能导致脑神经胶淋巴系统受损和 NMOSD 患者 PVS 增大。在本研究中，我们旨在证明 MRI 检测到的 EPVS 的特征及其与 CSF 抗 AQP4 抗体滴度、CNS 炎症标志物和 NMOSD 患者疾病严重程度的相关性。 方法：我们对 110 例连续 NMOSD 患者的脑 MRI 进行了回顾性分析。我们评估了 EPVS 与神经炎症标志物、血脑屏障（BBB）功能和患者神经功能障碍严重程度之间的相关性。我们使用多元逻辑回归分析确定与疾病严重程度相关的独立变量。 结果：NMOSD 患者的总 EPVS 中位数为 15.5（IQR，11-24.2）。在校正年龄和高血压的影响后，EPVS 的数量与 EDSS 评分显著相关（r=0.353，p<0.001）。总 EPVS 的数量也与 CSF 抗 AQP4 抗体滴度、CSF/血清白蛋白比值、CSF 白蛋白、IgG 和 IgA 水平显著相关。逻辑回归分析显示，总 EPVS 和血清白蛋白水平是预测 NMOSD 患者疾病严重程度的两个独立因素（OR=1.053，p=0.028；OR=0.858，p=0.009）。此外，ROC 分析得出总 EPVS 预测严重 NMOSD（EDSS 4.5-9.5）的 AUC 为 0.736（0.640-0.831，p<0.001）。 讨论：在我们的队列中，我们发现 NMOSD 中 EPVS 与神经炎症和 BBB 功能之间存在关系。此外，EPVS 可能独立预测 NMOSD 患者的神经功能障碍。
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