Fujihara Kazuo
Department of Multiple Sclerosis Therapeutics, Tohoku University Graduate School of Medicine.
Nihon Rinsho Meneki Gakkai Kaishi. 2012;35(2):129-35. doi: 10.2177/jsci.35.129.
Neuromyelitis optica (NMO) or Devic's disease is an inflammatory neurologic disease characterized by severe optic neuritis and transverse myelitis. Other features of NMO include female preponderance, higher onset age, severe functional disability, longitudinally extensive spinal cord lesions (longer than 3 vertebral segments), and oligoclonal IgG bands negativity. Brain lesions are not uncommon in NMO. The relation between NMO and multiple sclerosis (MS) has long been a matter of controversy, but since the discovery of anti-aquaporin 4 (AQP4) antibody (NMO-IgG), an NMO-specific autoantibody, the clinical, MRI, and laboratory features that distinguish NMO from MS have been clarified. Anti-AQP4 antibody binds to the extracellular domain of AQP4, which is highly expressed in endfeet of astrocytes. Recent neuropathological studies, analysis of CSF-GFAP levels during relapse and experimental studies strongly suggest that NMO is an anti-AQP4 antibody-mediated astrocytopathic disease and that T cell-mediated CNS inflammation is necessary to develop NMO. Also, IL-6 is remarkably elevated in the CSF and appears to regulate plasmablasts to produce anti-AQP4 antibody. Therefore, from the therapeutic point of view, depletion of anti-AQP4 antibody, suppression of T cell response to trigger relapse and anti-IL-6 therapy seem to be pivotal. High-dose intravenous methylprednisolone is the first-line therapy for acute exacerbations of NMO. But plasma exchange should be started soon if corticosteroid is not efficacious. If untreated, AQP4 antibody-positive patients are highly likely to experience relapses within a year. Thus, immunosuppressive therapy (corticosteroids, immunosuppressants, rituximab) should be initiated without delay. Preliminary results suggest that eculizumab, an anti-C5 monoclonal antibody, can also prevent relapse in NMO, Meanwhile, interferon-beta, a first-line disease modifying drug of MS, is not effective in NMO. Symptomatic therapy for pain, paresthesia, spasticity, dysuria and constipation which commonly occur in the chronic stage of NMO is also important to improve patients' quality of life.
视神经脊髓炎（NMO）或德维克病是一种炎症性神经系统疾病，其特征为严重的视神经炎和横贯性脊髓炎。NMO的其他特征包括女性居多、发病年龄较大、严重的功能残疾、纵向广泛的脊髓病变（长于3个椎体节段）以及寡克隆IgG带阴性。脑病变在NMO中并不罕见。NMO与多发性硬化症（MS）之间的关系长期以来一直存在争议，但自从发现抗水通道蛋白4（AQP4）抗体（NMO-IgG），一种NMO特异性自身抗体以来，区分NMO与MS的临床、MRI和实验室特征已得到明确。抗AQP4抗体与AQP4的细胞外结构域结合，AQP4在星形胶质细胞的终足中高度表达。最近的神经病理学研究、复发期间脑脊液GFAP水平分析以及实验研究强烈表明，NMO是一种抗AQP4抗体介导的星形细胞病，并且T细胞介导的中枢神经系统炎症对于NMO的发生发展是必要的。此外，脑脊液中的白细胞介素-6显著升高，似乎调节浆母细胞产生抗AQP4抗体。因此，从治疗角度来看，抗AQP4抗体的清除、抑制引发复发的T细胞反应以及抗白细胞介素-6治疗似乎至关重要。大剂量静脉注射甲基强的松龙是NMO急性加重期的一线治疗方法。但如果皮质类固醇无效，应尽快开始血浆置换。如果不进行治疗，AQP4抗体阳性患者很可能在一年内复发。因此，应立即开始免疫抑制治疗（皮质类固醇、免疫抑制剂、利妥昔单抗）。初步结果表明，抗C5单克隆抗体依库珠单抗也可预防NMO复发。同时，MS的一线疾病修正药物干扰素-β对NMO无效。对NMO慢性期常见的疼痛、感觉异常、痉挛、排尿困难和便秘进行对症治疗对于提高患者生活质量也很重要。
