Hinson Shannon R, Lennon Vanda A, Pittock Sean J
Departments of Laboratory Medicine/Pathology and Neurology, Mayo Clinic, College of Medicine, Rochester, MN, USA.
Departments of Laboratory Medicine/Pathology and Neurology, Mayo Clinic, College of Medicine, Rochester, MN, USA.
Handb Clin Neurol. 2016;133:377-403. doi: 10.1016/B978-0-444-63432-0.00021-9.
Neuromyelitis optica (NMO) spectrum disorders (SD) represent an evolving group of central nervous system (CNS)-inflammatory autoimmune demyelinating diseases unified by a pathogenic autoantibody specific for the aquaporin-4 (AQP4) water channel. It was historically misdiagnosed as multiple sclerosis (MS), which lacks a distinguishing biomarker. The discovery of AQP4-IgG moved the focus of CNS demyelinating disease research from emphasis on the oligodendrocyte and myelin to the astrocyte. NMO is recognized today as a relapsing disease, extending beyond the optic nerves and spinal cord to include brain (especially in children) and skeletal muscle. Brain magnetic resonance imaging abnormalities, identifiable in 60% of patients at the second attack, are consistent with MS in 10% of cases. NMOSD-typical lesions (another 10%) occur in AQP4-enriched regions: circumventricular organs (causing intractable nausea and vomiting) and the diencephalon (causing sleep disorders, endocrinopathies, and syndrome of inappropriate antidiuresis). Advances in understanding the immunobiology of AQP4 autoimmunity have necessitated continuing revision of NMOSD clinical diagnostic criteria. Assays that selectively detect pathogenic AQP4-IgG targeting extracellular epitopes of AQP4 are promising prognostically. When referring to AQP4 autoimmunity, we suggest substituting the term "autoimmune aquaporin-4 channelopathy" for the term "NMO spectrum disorders." Randomized clinical trials are currently assessing the efficacy and safety of newer immunotherapies. Increasing therapeutic options based on understanding the molecular pathogenesis is anticipated to improve the outcome for patients with AQP4 channelopathy.
视神经脊髓炎谱系障碍（NMOSD）是一组不断演变的中枢神经系统（CNS）炎性自身免疫性脱髓鞘疾病，由针对水通道蛋白4（AQP4）水通道的致病性自身抗体统一起来。在历史上，它曾被误诊为多发性硬化症（MS），后者缺乏特异性生物标志物。AQP4-IgG的发现将CNS脱髓鞘疾病研究的重点从少突胶质细胞和髓鞘转移到了星形胶质细胞。如今，视神经脊髓炎被认为是一种复发疾病，其病变范围超出视神经和脊髓，还包括大脑（尤其是儿童）和骨骼肌。脑部磁共振成像异常在第二次发作的患者中60%可被识别，其中10%与MS一致。NMOSD典型病变（另外10%）发生在富含AQP4的区域：室周器官（导致顽固性恶心和呕吐）和间脑（导致睡眠障碍、内分泌疾病和抗利尿激素分泌失调综合征）。对AQP4自身免疫免疫生物学认识的进展使得对视神经脊髓炎谱系障碍临床诊断标准的持续修订成为必要。选择性检测靶向AQP4细胞外表位的致病性AQP4-IgG的检测方法在预后方面很有前景。在提及AQP4自身免疫时，我们建议用“自身免疫性水通道蛋白4通道病”取代“视神经脊髓炎谱系障碍”这一术语。随机临床试验目前正在评估新型免疫疗法的疗效和安全性。基于对分子发病机制的理解而增加的治疗选择有望改善AQP4通道病患者的预后。
