血清抗幽门螺旋杆菌抗体和抗AQP4 抗体在中枢神经系统脱髓鞘病中的相关性研究

目的：探讨血清抗幽门螺旋杆菌抗体（HP-IgG）和抗AQP4抗体在多发性硬化（MS）、视神经脊髓炎（NMO）中的相关性。方法：对33例MS患者、7例NMO患者和35例健康体检者采用间接酶联免疫吸附法（ELISA法）检测血清中抗HP的IgG抗体,采用细胞间接免疫荧光法（CBA）检测血清标本抗AQP4抗体;分析MS、NMO患者中HP-IgG及抗AQP4抗体的阳性率,并对比抗AQP4抗体阳性与抗AQP4抗体阴性患者间HP-IgG阳性率的差别。结果：MS组、NMO组和正常对照组血清中抗血清HP-IgG抗体阳性率分别为69.70%、85.71%、42.86%,差别有统计学意义（P＜0.05）,其中MS组、NMO组与正常对照组血清中抗HP-IgG抗体阳性率差别均有统计学意义（P＜0.05）;但MS组与NMO组血清中抗HP-IgG抗体阳性率差别无统计学意义（P＞0.05）。MS组、NMO组和正常对照组血清中抗AQP4抗体阳性率分别为4.2%、85.71%、0%,差别有统计学意义（P＜0.05）。MS组和NMO患者组中抗AQP4抗体阳性患者与抗AQP4抗体阴性患者抗HP-IgG抗体阳性率分别为72.73%、79.31%,差别无统计学意义（P＞0.05）。结论：HP感染是引起MS及NMO疾病发生的危险因素,而与MS及NMO患者是否含有抗AQP4抗体无关。     

视神经脊髓炎特异性自身抗体NMO-IgG的诊断价值研究

目的:初步探讨视神经脊髓炎特异性自身抗体NMO-IgG的诊断价值。方法:入选患者共120例,视神经脊髓炎患者(Neuromyelitis optica,NMO)45例,包括高危NMO(High-risk NMO,HR-NMO)患者9例,多发性硬化(Multiple sclerosis,MS)患者65例,其他神经系统疾病患者10例,采用细胞间接免疫荧光法检测所有患者血清NMO-IgG水平,比较NMO与MS患者临床特点及NMO-IgG水平,初步评估HR-NMO的预后。结果:血清NMO-IgG诊断NMO的灵敏度达67%,特异性达92%;NMO组与MS组患者男女比例、发生严重视神经炎、横贯性脊髓炎、颅脑MRI正常表现、脊髓病灶超过3个椎体节段、合并其他免疫性疾病及血清NMO-IgG水平均有统计学差异(P0.05)。HR-NMO组中血清NMO-IgG阳性的4例中有3例在一年后的随访中有横贯性脊髓炎的再次发作。结论:血清NMO-IgG的检测对视神经脊髓炎的诊断、鉴别诊断及预后评估有一定的价值。     

抗水通道蛋白4抗体与中枢神经脱髓鞘性神经免疫性疾病

<正>2004年Lennon等[1]首次发现视神经脊髓炎(NMO)患者血清中存在一种能与小鼠血脑屏障及其附近组织结合的抗体——NMO-IgG,随后的研究证实NMO-IgG的靶抗原为水通道蛋白4(AQP4)[2]。由于NMO特异性抗体AQP4-IgG的发现,使NMO也由原来归类为MS的严重变异型重新定义为有别于MS的中枢神经系统脱髓鞘性疾病[3]。然而,研究显示NMO患者AQP4-IgG血清阳性率并非100%,其敏感性在42%~97%之间[4],此     

细胞免疫荧光法在视神经脊髓炎患者血清及脑脊液中水通道蛋白4抗体检测中的运用价值

目的 探讨细胞免疫荧光法(CBA)在视神经脊髓炎患者血清与脑脊液水通道蛋白4抗体(AQP4-Ab)检测中的运用价值.方法 选择多发性硬化患者52例为硬化组,视神经脊髓炎患者54例为脊髓炎组,体检正常的自愿者50例为正常组.分别采用组织间接免疫荧光检测(IIF)、细胞免疫荧光法(CBA)和酶联免疫吸附法(ELISA)检测血清和脑脊液标本(正常组未提取)的AQP4-Ab,比较各方法AQP4-Ab的阳性检出率、特异性和灵敏度.结果 CBA、IIF和ELISA对脊髓炎组血清标本和脑脊液标本的AQP4-Ab阳性检出率显著高于硬化组和正常组(P<0.05).CBA对脊髓炎组患者脑脊液标本和血清标本的AQP4-Ab阳性检出率分别为87.04%、70.37%,显著高于其他两种方法(P<0.05).不同方法对脊髓炎组患者血清和脑脊液标本AQP4-Ab检测的敏感性为:CBA>IIF>ELISA,且有统计学差异(χ2=7.394、14.687,P<0.05),但是不同方法的特异性无差异(P>0.05).结论 AQP4-Ab阳性表达与视神经脊髓炎的发生有一定关系.在CBA、IIF和ELISA等检测方法中,CBA的阳性检出率和灵敏度最高,适宜视神经脊髓炎的早期诊断.     

通过测定78例视神经脊髓炎患者血清中NMO-IgG水平判断其临床诊断价值

目的 通过测定视神经脊髓炎(NMO)患者血清中的NMO-IgG水平,判断NMO-IgG对视神经脊髓炎的临床诊断价值.方法 选取本院2006年9月至2014年6月NMO患者78例,长节段横惯性脊髓炎(LETM)患者32例,多发性硬化(MS)患者54例,以及40名健康志愿者,收集其血清,采用ELISA法检测血清NMO-IgG水平.结果 NMO组NMO-IgG阳性率为61.5％ (48/78),LETM组阳性率为43.8％ (14/32),MS组阳性率为9.3％(5/54),对照组阳性率为0(0/40).NMO组与LETM组的血清NMO-IgG阳性率均显著高于MS组(P＜0.05),支持两者都属于视神经脊髓炎疾病谱(NMOSD).其中男性患者NMO-IgG阳性率为14.5％ (9/62),女性患者NMO-IgG阳性率为56.9％ (58/102),女性患者的NMO-IgG阳性率显著高于男性患者.单相病程组血清NMO-IgG阳性率为26.3％ (5/19),多相病程组血清NMO-IgG阳性率为72.9％ (43/59),多相病程与NMO-IgG呈正相关,单相病程与NMO-IgG呈负相关.血清NMO-IgG诊断NMO的灵敏度为61.5％ (48/78),以MS为对照,其诊断NMO的特异度为90.7％ (49/54),以MS同对照组一起为对照,其诊断特异度为94.7％ (89/94).结论 利用血清NMO-IgG检测来诊断NMO具有较高的敏感性及很强的特异性,可以有效的鉴别NMO与MS,从而有助于病人的确诊及临床合理用药,应该在临床上推广使用.     

模拟抗原ELISA检测视神经脊髓炎患者血清水通道蛋白-4抗体

目的 初步探讨以人工合成多肽模拟抗原酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测视神经脊髓炎(neuromyelitis optica,NMO)患者血清水通道蛋白-4(aquaporin-4,AQP4)抗体.方法根据AQP4蛋白的分子构成和三级结构,应用生物信息学和结构生物学的方法设计3段AQP4蛋白膜外段多肽片段,分别为AQP456-69、AQP4135-155、AQP4209-230;以其为抗原ELISA检测9例NMO及神经科其他疾病7例患者血清,并与免疫荧光法检测结果进行对比分析.结果 以AQP4135-155、AQP4209-230为抗原ELISA检测结果显示,9例NMO患者中,7例经免疫荧光法证实AQP4抗体阳性患者吸光度A值平均值比阴性对照患者显著提高(P＜0.05);当血清稀释4倍和8倍时具有较高的A值,与对照组相比差异具有统计学意义(P＜0.05).结论 AQP4蛋白2段膜外段多肽,即AQP4135-155和AQP4209-230可能是NMO患者血清中AQP4抗体所针对的主要抗原表位或抗原表位的主要部分,初步表明模拟抗原ELISA检测NMO患者血清AQP4抗体的可行性.     

重症肌无力患者抗Ryanodine受体抗体检测及其意义

本实验应用Westernblot分析 4 4例伴不同胸腺病理类型重症肌无力 (MG )患者血清中Ryanodine受体 (RyR )抗体特异性 ,同时应用ELISA法检测 1 6 9例伴不同胸腺病理类型MG血清中RyR抗体水平。结果显示在Westernblot法分析中 ,2 4例伴胸腺瘤重症肌无力 (MGT )患者血清中有 1 9例可见到RyR抗体阳性条带 ,2 0例非胸腺瘤重症肌无力 (NTMG )患者血清中仅1例可见RyR抗体阳性条带 ,2 5例非MG个体 (NMG )均未见RyR抗体阳性条带。MGT患者血清中RyR抗体阳性条带检出率明显高于NTMG和NMG组 (P <0 0 1 )。在ELISA法检测中 ,MGT组患者血清中RyR抗体水平明显高于NTMG组、其他神经系统疾病 (OND )组、正常对照 (NC )组 (P <0 0 1 ) ;5 9例MGT患者血清中 4 6例RyR抗体阳性 ,2 83例NTMG、OND、NC组检测血清中 1 9例RyR抗体阳性 ,ELISA法检测MGT患者血清中RyR抗体敏感性为 78% ,特异性为 93 3%。结果表明RyR抗体检测是诊断MGT特异性较高的实验室指标 ,具有重要的临床意义     

稳定表达水通道蛋白-4 HEK293细胞株的建立及应用

目的:建立稳定表达水通道蛋白-4(AQP4)的HEK293细胞株,并以其检测12例视神经脊髓炎患者血清中是否存在AQP4抗体。方法:从颞叶癫痫患者脑组织提取总RNA,RT-PCR扩增AQP4的cDNA,构建AQP4-绿色荧光蛋白(GFP)融合表达重组体pEGFP-N1-AQP4,转染HEK293细胞,抗生素筛选联合流式细胞仪分选筛选稳定表达细胞株,RT-PCR和间接免疫荧光法鉴定AQP4的表达,激光共聚焦显微镜观察AQP4在细胞中的定位,并以已建立的细胞为底物间接免疫荧光法检测12例视神经脊髓炎患者血清中是否存在AQP4抗体。结果:经PCR、双酶切、测序鉴定证实成功获取AQP4的cDNA,AQP4-GFP融合表达重组质粒pEGFP-N1-AQP4构建成功,抗生素筛选联合流式细胞仪分选筛选稳定表达细胞株,稳定表达率达90%以上,RT-PCR和间接免疫荧光法鉴定存在AQP4的表达,激光共聚焦显微镜进一步确认AQP4-GFP融合蛋白主要表达于细胞膜上,11例典型视神经脊髓炎患者血清中检出AQP4抗体,对视神经脊髓炎诊断敏感性为91.7%,特异性为94.7%。结论:成功建立稳定表达AQP4的HEK293细胞株,以其作为检测底物检出视神经脊髓炎患者血清中存在AQP4自身抗体。     

血清水通道蛋白4-IgG 抗体相关骨骼肌损害

<正>视神经脊髓炎(Neuromyelitis optica,NMO)是一种体液免疫介导为主的中枢神经系统(Central nervous system,CNS)炎性脱髓鞘疾病,其特异性抗体标志物血清抗水通道蛋白4(Aquaporin-4,AQP4)-IgG抗体的发现~([1]),将NMO与多发性硬化Multiple sclerosis,MS)区别开,并拓宽了NMO疾病     

CD1d~(hi)CD~(5+)CD19~+调节性B细胞在视神经脊髓炎患者外周血中的数量及意义

目的检测视神经脊髓炎(NMO)患者外周血中CD1dhiCD5+CD19+调节性B细胞的比例,探讨CD1dhiCD5+CD19+调节性B细胞能否作为NMO和多发性硬化(MS)鉴别诊断的生物标志物。方法采用流式细胞术检测44例NMO患者,38例MS患者和30例健康正常人外周血中CD1dhiCD5+CD19+调节性B细胞的比例。采用间接免疫荧光法检测NMO患者水通道蛋白4抗体(AQP4-Ab)的表达情况。结果 NMO患者外周血中CD1dhiCD5+CD19+调节性B细胞占CD19+B细胞及淋巴细胞的比例较MS患者和健康正常人明显减低,而MS患者与健康正常人比较,差异无统计学意义。AQP4-Ab阳性NMO患者较AQP4-Ab阴性NMO患者CD1dhiCD5+CD19+调节性B细胞占CD19+B细胞及淋巴细胞的比例明显减低。结论外周血中CD1dhiCD5+CD19+调节性B细胞数量是NMO和MS鉴别诊断的一种生物标志物。     

Aquaporin‐4 Antibodies (NMO‐IgG) as a Serological Marker of Neuromyelitis Optica: A Critical Review of the Literature

Antibodies to aquaporin‐4 (called NMO‐IgG or AQP4‐Ab) constitute a sensitive and highly specific serum marker of neuromyelitis optica (NMO) that can facilitate the differential diagnosis of NMO and classic multiple sclerosis. NMO‐IgG/AQP4‐Ab seropositive status has also important prognostic and therapeutic implications in patients with isolated longitudinally extensive myelitis (LETM) or optic neuritis (ON). In this article, we comprehensively review and critically appraise the existing literature on NMO‐IgG/AQP4‐Ab testing. All available immunoassays—including tissue‐based (IHC), cell‐based (ICC, FACS) and protein‐based (RIPA, FIPA, ELISA, Western blotting) assays—and their differential advantages and disadvantages are discussed. Estimates for sensitivity, specificity, and positive and negative likelihood ratios are calculated for all published studies and accuracies of the various immunoassay techniques compared. Subgroup analyses are provided for NMO, LETM and ON, for relapsing vs. monophasic disease, and for various control groups (eg, MS vs. other controls). Numerous aspects of NMO‐IgG/AQP4‐Ab testing relevant for clinicians (eg, impact of antibody titers and longitudinal testing, indications for repeat testing, relevance of CSF testing and subclass analysis, NMO‐IgG/AQP4‐Ab in patients with rheumatic diseases) as well as technical aspects (eg, AQP4‐M1 vs. AQP4‐M23‐based assays, intact AQP4 vs. peptide substrates, effect of storage conditions and freeze/thaw cycles) and pitfalls are discussed. Finally, recommendations for the clinical application of NMO‐IgG/AQP4‐Ab serology are given.     

Marked potentiation of cell swelling by cytokines in ammonia-sensitized cultured astrocytes

Background

In 70-80% of cases, neuromyelitis optica (NMO) is associated with highly specific serum auto-antibodies to aquaporin-4 (termed AQP4-Ab or NMO-IgG). Recent evidence strongly suggests that AQP4-Ab are directly involved in the immunopathogenesis of NMO.

Objective

To assess the frequency, syndrome specificity, diagnostic relevance, and origin of cerebrospinal fluid (CSF) AQP4-Ab in patients with NMO spectrum disorders (NMOSD).

Methods

87 CSF samples from 37 patients with NMOSD and 42 controls with other neurological diseases were tested for AQP4-Ab in a cell based assay using recombinant human AQP4. Twenty-three paired CSF and serum samples from AQP4-Ab seropositive NMOSD patients were further analysed for intrathecal IgG synthesis to AQP4.

Results

AQP4-Ab were detectable in 68% of CSF samples from AQP4-Ab seropositive patients with NMOSD, but in none of the CSF samples from AQP4-Ab seronegative patients with NMOSD and in none of the control samples. Acute disease relapse within 30 days prior to lumbar puncture, AQP4-Ab serum titres >1:250, and blood-CSF barrier dysfunction, but not treatment status, predicted CSF AQP4-Ab positivity. A positive AQP4-specific antibody index was present in 1/23 samples analysed.

Conclusions

AQP4-Ab are detectable in the CSF of most patients with NMOSD, mainly during relapse, and are highly specific for this condition. In the cohort analysed in this study, testing for CSF AQP4-Ab did not improve the sensitivity and specificity of the current diagnostic criteria for NMO. The substantial lack of intrathecal AQP4-Ab synthesis in patients with NMOSD may reflect the unique localisation of the target antigen at the blood brain barrier, and is important for our understanding of the immunopathogenesis of the disease.     

Neuromyelitis optica and opticospinal multiple sclerosis: Mechanisms and pathogenesis

Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) while neuromyelitis optica (NMO) is an inflammatory disease of the CNS that selectively affects the optic nerves and spinal cord. In Asians, MS is rare; however, when it appears, the selective and severe involvement of the optic nerves and spinal cord is characteristic. This form, termed opticospinal MS (OSMS), has similar features to the relapsing form of NMO in Western populations. Recently, a specific IgG against NMO, designated NMO-IgG, was discovered, and the relevant antigen was found to be aquaporin-4 (AQP4), one of the major water channel proteins in the CNS. Because NMO-IgG has been reported to be present in 30-60% of OSMS patients, OSMS in Asians has been suggested to be the same entity as NMO.The sensitivity of NMO-IgG/anti-AQP4 antibody for NMO varies from 30% to 80%, while the specificity is 90-100%. Pathological studies on NMO have revealed perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions, where myelin basic protein (MBP) staining was relatively preserved. IgG from NMO-IgG-seropositive NMO patients induces astrocyte death in culture in the presence of complements, and reproduces astrocyte loss in vivo when MBP-specific T cells are co-transferred to cause experimental autoimmune encephalomyelitis. It is thus postulated that the complement-activating anti-AQP4 antibody plays a pivotal role in the development of NMO lesions through astrocyte necrosis, and that demyelination is a secondary event.However, in autopsied cases of NMO, we and others found that some demonstrated selective AQP4 loss while others showed preservation of AQP4, even in the acute lesions. We also found that, in some MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. In the CSF, proinflammatory cytokines such as IL-17, IL-8, IFNγ, and G-CSF are markedly elevated in OSMS patients, irrespective of the presence or absence of anti-AQP4 antibody. In OSMS and NMO patients, T cells reactive to myelin proteins show intra- and inter-molecular epitope spreading, suggesting that T cells are already stimulated with myelin antigens in vivo. These findings suggest that mechanism of NMO and OSMS in Asians is heterogeneous, anti-AQP4 antibody-related and -unrelated, and that not only anti-AQP4 antibody but also myelin-autoreactive Th17 or Th1 cells may also play a role in triggering CNS inflammation. Possible mechanisms for NMO and OSMS are discussed in this review.     

Reappraisal of aquaporin-4 astrocytopathy in Asian neuromyelitis optica and multiple sclerosis patients

Selective aquaporin‐4 (AQP4) loss and vasculocentric complement and immunoglobulin deposition are characteristic of neuromyelitis optica (NMO). We recently reported extensive AQP4 loss in demyelinated and myelinated layers of Baló's lesions without perivascular immunoglobulin and complement deposition. We aimed to reappraise AQP4 expression patterns in NMO and multiple sclerosis (MS). We evaluated AQP4 expression relative to glial fibrillary acidic protein, extent of demyelination, lesion staging (CD68 staining for macrophages), and perivascular deposition of complement and immunoglobulin in 11 cases with NMO and NMO spectrum disorders (NMOSD), five with MS and 30 with other neurological diseases. The lesions were classified as actively demyelinating (n = 66), chronic active (n = 86), chronic inactive (n = 48) and unclassified (n = 12). Six NMO/NMOSD and two MS cases showed preferential AQP4 loss beyond the demyelinated areas, irrespective of lesion staging. Five NMO and three MS cases showed AQP4 preservation even in actively demyelinating lesions, despite grave tissue destruction. Vasculocentric deposition of complement and immunoglobulin was detected only in NMO/NMOSD patients, with less than 30% of actively demyelinating lesions showing AQP4 loss. Our present and previous findings suggest that antibody‐independent AQP4 loss can occur in heterogeneous demyelinating conditions, including NMO, Baló's disease and MS.     

Usefulness of serum S100B as a marker for the acute phase of aquaporin-4 autoimmune syndrome

The aquaporin-4 (AQP4) water channel antibody is used in the diagnosis of neuromyelitis optica (NMO) due to its high sensitivity and high specificity. However, some patients are reported to have neither optic neuritis nor myelitis despite being positive for the AQP4-autoantibody (AQP4-Ab). Therefore, recent reports suggest that such patients should be diagnosed as having 'AQP4-autoimmune syndrome'. In this study, we quantified the levels of glial fibrillar acidic protein (GFAP) and S100B by enzyme-linked immunosorbent assay (ELISA) in CSF and serum samples simultaneously obtained in the acute phase of ten AQP4-autoantibody (AQP4Ab)-positive and seven AQP4Ab-negative patients. Serum levels of S100B were significantly higher in the acute phase of the AQP4Ab-positive patients (2.92±1.22pg/ml) than in the AQP4Ab-negative patients (0.559±0.180pg/ml, p=0.0250), while serum levels of GFAP were not different between the two groups (AQP4Ab-positive vs. AQP4Ab-negative: 0.120±0.113ng/ml vs. 0.00609±0.00609ng/ml, p=0.193). Furthermore, the CSF and serum levels of S100B had a significant positive correlation in AQP4Ab-positive patients (n=10, r=0.673, p=0.0390). Our results raise the possibility that serum levels of S100B, but not GFAP, examined in the acute phase of the disease might be a useful biomarker for the relapse of AQP4 autoimmune syndrome.     

Astrocytic autoantibody of neuromyelitis optica (NMO-IgG) binds to aquaporin-4 extracellular loops,monomers, tetramers and high order arrays

The principal central nervous system (CNS) water channel, aquaporin-4 (AQP4), is confined to astrocytic and ependymal membranes and is the target of a pathogenic autoantibody, neuromyelitis optica (NMO)-IgG. This disease-specific autoantibody unifies a spectrum of relapsing CNS autoimmune inflammatory disorders of which NMO exemplifies the classic phenotype. Multiple sclerosis and other immune-mediated demyelinating disorders of the CNS lack a distinctive biomarker. Two AQP4 isoforms, M1 and M23, exist as homotetrameric and heterotetrameric intramembranous particles (IMPs). Orthogonal arrays of predominantly M23 particles (OAPs) are an ultrastructural characteristic of astrocytic membranes. We used high-titered serum from 32 AQP4-IgG-seropositive patients and 85 controls to investigate the nature and molecular location of AQP4 epitopes that bind NMO-IgG, and the influence of supramolecular structure. NMO-IgG bound to denatured AQP4 monomers (68% of cases), to native tetramers and high order arrays (90% of cases), and to AQP4 in live cell membranes (100% of cases). Disease-specific epitopes reside in extracellular loop C more than in loops A or E. IgG binding to intracellular epitopes lacks disease specificity. These observations predict greater disease sensitivity and specificity for tissue-based and cell-based serological assays employing “native” AQP4 than assays employing denatured AQP4 and fragments. NMO-IgG binds most avidly to plasma membrane surface AQP4 epitopes formed by loop interactions within tetramers and by intermolecular interactions within high order structures. The relative abundance and localization of AQP4 high order arrays in distinct CNS regions may explain the variability in clinical phenotype of NMO spectrum disorders.     

Treatment of neuromyelitis optica

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.