Neuromyelitis optica (NMO) is a chronic inflammatory autoimmune disease of the central nervous system (CNS) characterized by acute optic neuritis (ON) and transverse myelitis (TM). NMO is caused by a pathogenic serum IgG antibody against the water channel aquoporin 4 (AQP4) in the majority of patients. AQP4-antibody (AQP4-ab) presence is highly specific, and differentiates NMO from multiple sclerosis. It binds to AQP4 channels on astrocytes, triggering activation of the classical complement cascade, causing granulocyte, eosinophil, and lymphocyte infiltration, culminating in injury first to astrocyte, then oligodendrocytes followed by demyelination and neuronal loss. NMO spectrum disorder (NMOSD) has recently been defined and stratified based on AQP4-ab serology status. Most NMOSD patients experience severe relapses leading to permanent neurologic disability, making suppression of relapse frequency and severity, the primary objective in disease management. The most common treatments used for relapses are steroids and plasma exchange. Currently, long-term NMOSD relapse prevention includes off-label use of immunosuppressants, particularly rituximab. In the last 2 years however, three pivotal clinical trials have expanded the spectrum of drugs available for NMOSD patients. Phase III studies have shown significant relapse reduction compared to placebo in AQP4-ab-positive patients treated with satralizumab, an interleukin-6 receptor (IL-6R) inhibitor, inebilizumab, an antibody against CD19+ B cells; and eculizumab, an antibody blocking the C5 component of complement. In light of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs, we present this descriptive review, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.

中文翻译：

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视神经脊髓炎谱系障碍：从病理生理学到治疗策略

视神经脊髓炎（NMO）是一种以急性视神经炎（ON）和横贯性脊髓炎（TM）为特征的中枢神经系统（CNS）慢性炎症性自身免疫性疾病。在大多数患者中，NMO 是由针对水通道水通道蛋白 4 (AQP4) 的致病性血清 IgG 抗体引起的。AQP4 抗体 (AQP4-ab) 的存在具有高度特异性，可将 NMO 与多发性硬化症区分开来。它与星形胶质细胞上的 AQP4 通道结合，触发经典补体级联反应，导致粒细胞、嗜酸性粒细胞和淋巴细胞浸润，最终导致首先损伤星形胶质细胞，然后是少突胶质细胞，然后脱髓鞘和神经元丢失。NMO 谱系障碍 (NMOSD) 最近已根据 AQP4-ab 血清学状态进行定义和分层。大多数 NMOSD 患者经历严重复发，导致永久性神经功能障碍，因此抑制复发频率和严重程度是疾病管理的主要目标。用于复发的最常见治疗方法是类固醇和血浆置换。目前，长期 NMOSD 复发预防包括超说明书使用免疫抑制剂，尤其是利妥昔单抗。然而，在过去 2 年中，三项关键的临床试验扩大了 NMOSD 患者可用的药物范围。III 期研究表明，与安慰剂相比，使用 satralizumab（一种白细胞介素 6 受体 (IL-6R) 抑制剂）、inebilizumab（一种针对 CD19+ B 细胞的抗体）治疗的 AQP4-ab 阳性患者的复发率显着降低；和 eculizumab，一种阻断补体 C5 成分的抗体。