视神经脊髓炎与多发性硬化的临床表现和视神经脊髓炎IgG抗体阳性率的对比

目的 比较视神经脊髓炎(NMO)和多发性硬化(MS)在临床表现、辅助检查等方面的不同;比较NMO和MS等脱髓鞘疾病患者血清NMO-IgG抗体的阳性率,判断该抗体能否作为鉴别诊断的一项实验室依据.方法 对34例NMO、22例MS、24例高危综合征、5例临床孤立综合征以及35例其他神经科疾病患者进行NMO-IgG检测,并对其中NMO、MS患者的人口学、临床表现、免疫学指标、脑脊液、头颅MRI等资料进行对比.结果 NMO的起病年龄较MS大且年龄跨度更广;从年复发率和进展指数来看,NMO更为严重,预后更差;NMO长节段脊髓损害者比MS多.NMO-IgG在NMO组和高危综合征组的阳性率分别为58.8%(20/34)和45.8%(11/24),高于MS组(1/22)、临床孤立综合征组(1/5)和其他疾病组(1/35;X2=37.2,P<0.01).NMO-IgG阳性率与脊髓病变长度相关.结论 NMO和MS在临床表现、辅助检查等方面都有所不同,提示NMO与MS可能是2种不同的疾病.NMO-IgG在NMO患者中的阳性率高于MS患者,可以作为鉴别诊断的一项实验室依据.     

视神经脊髓炎与多发性硬化的临床表现和视神经脊髓炎IgG抗体阳性率的对比

目的 比较视神经脊髓炎(NMO)和多发性硬化(MS)在临床表现、辅助检查等方面的不同;比较NMO和MS等脱髓鞘疾病患者血清NMO-IgG抗体的阳性率,判断该抗体能否作为鉴别诊断的一项实验室依据.方法 对34例NMO、22例MS、24例高危综合征、5例临床孤立综合征以及35例其他神经科疾病患者进行NMO-IgG检测,并对其中NMO、MS患者的人口学、临床表现、免疫学指标、脑脊液、头颅MRI等资料进行对比.结果 NMO的起病年龄较MS大且年龄跨度更广;从年复发率和进展指数来看,NMO更为严重,预后更差;NMO长节段脊髓损害者比MS多.NMO-IgG在NMO组和高危综合征组的阳性率分别为58.8%(20/34)和45.8%(11/24),高于MS组(1/22)、临床孤立综合征组(1/5)和其他疾病组(1/35;X2=37.2,P<0.01).NMO-IgG阳性率与脊髓病变长度相关.结论 NMO和MS在临床表现、辅助检查等方面都有所不同,提示NMO与MS可能是2种不同的疾病.NMO-IgG在NMO患者中的阳性率高于MS患者,可以作为鉴别诊断的一项实验室依据.     

早期多发性硬化和视神经脊髓炎高危综合征临床特点的比较

目的 比较早期多发性硬化(MS)和视神经脊髓炎(NMO)高危综合征患者的临床特点差异. 方法 回顾性收集广州医科大学附属第二医院神经内科自2004年1月至2013年8月收治的早期MS患者49例和NMO高危综合征患者30例(包括长节段的横贯性脊髓炎22例、复发性视神经炎8例)的临床资料、影像学检查结果、血清中NMO-IgG抗体情况等进行分析和比较. 结果 早期MS患者和NMO高危综合征患者的EDSS评分、病程以及感觉症状、脑干症状比例比较差异均有统计学意义(P＜0.05).早期MS组患者中病灶数＞9个的比例(77.6％)高于NMO高危综合征组患者,差异有统计学意义(P＜0.05).NMO高危综合征组患者在脑脊液蛋白异常率(19例,63.3％)、蛋白水平[(0.57±0.45) g/L]以及脑脊液白细胞计数异常率(19例,63.3％)、白细胞计数[中位数为24.317个/mm3 (0～274个)]方面与早期MS患者组比较差异有统计学意义(P＜0.05).10例NMO高危综合征患者中6例长节段横贯性脊髓炎患者NMO-IgG阳性,13例早期MS患者中2例出现阳性反应,阳性率比较差异有统计学意义(P＜0.05). 结论 早期MS患者和NMO高危综合症的临床特点明显不同,这些差异对早期鉴别MS与NMO具有一定意义.     

视神经脊髓炎患者血清 NMO-IgG 检测及其诊断价值

目的 检测神经脊髓炎(neuromyelitis optica,NMO)患者血清NMO-IgG的表达,并探讨其在NMO诊断中的价值.方法 收集北京、辽宁丹东、山西大同三家医疗机构临床诊断为NMO患者26例、多发性硬化(multiple sclerosis,MS)患者32例、神经科其他疾病患者77例;以稳定表达人源水通道蛋白-4(aquaporin-4,AQP4)的人胚肾293(HEK293)细胞株为底物,应用间接免疫荧光法检测患者血清NMO-IgG水平.结果 16例(61.5%)NMO患者血清NMO-IgG阳性,其阳性检出率显著高于MS患者(9.4 %)和MS+神经科其他疾病患者(4.6 %)(P<0.01).NMO-IgG对NMO诊断的灵敏度为61.5%,以MS作为对照时,该抗体对NMO诊断特异度为90.6%,以MS+神经科其他疾病作对照时,其特异度为95.4%.结论 NMO患者血清中普遍存在NMO-IgG,其可作为国内NMO诊断的重要生物学指标.     

视神经脊髓炎的研究进展

视神经脊髓炎(NMO)是一种主要累及视神经和脊髓的原发性中枢神经系统炎性脱髓鞘疾病,既往被认为是多发性硬化(MS)的亚型,但近年发现NMO在免疫机制、临床和影像学表现、病理改变及治疗等方面均与MS不同.NMO-IgG,即中枢神经系统水通道蛋白4(AQP4)抗体是NMO较为特异的一项免疫标志物,它的发现将NMO与MS独立开来.本文对NMO的免疫机制、病理、临床和影像学及治疗等方面进行综述.     

水通道蛋白4抗体检测对视神经脊髓炎的诊断价值

目的:探讨水通道蛋白4(AQP4)抗体检测对视神经脊髓炎(NMO)的诊断价值.方法:采用表达人AQP4基因的人胚肾(HEK)293细胞株分别对35例NMO患者(NMO组)、14例NMO高危综合征患者(HRS组)、37例多发性硬化患者(MS组)、23例其他脱髓鞘疾病患者(ODD组)及75例其他神经系统疾病患者(MD组)的血标本进行AQP4抗体检测,比较各组抗体的阳性率.结果:NMO组中31例患者(88.6%)及HRS组中6例患者(42.9%n)AQP4抗体检测为阳性;MS组、ODD组和MD组患者AQP4抗体检测均为阴性.NMO组AQP4抗体检测阳性的敏感性为88.6%,95%CI,73.11%-96.79%;HRS组AQP4抗体检测阳性的敏感性为42.9%,95%CI:16.97%-68.83%;NMO患者AQP4抗体检测阳性的特异性为100%.结论:AQP4抗体检测对NMO及其疾病谱早期确诊有重要意义,且具有较高的敏感性和特异性.     

血清抗核抗体在视神经脊髓炎谱系疾病和多发性硬化中的分布

目的 研究血清抗核抗体(ANAs)在视神经脊髓炎谱系疾病(NMOSDs)和多发性硬化(MS)中的分布.方法 收集2009-01-2011-03间在作者医院神经内科门诊和住院诊治并行血清ANAs筛查的NMOSDs患者74例,包括视神经脊髓炎(NMO)53例、复发长节段横贯性脊髓炎(rLETM)20例和复发性视神经炎(RON)1例,以及MS患者49例,统计其血清ANAs阳性率并进行分析.结果 NMOSDs患者血清ANAs阳性率为45.9%(34/74),其中ANA(本文中特指用间接免疫荧光法检测的抗核抗体)、抗dsDNA、抗着丝粒抗体(ACA)、抗SSA抗体、抗SSB抗体阳性率分别为36.5%(27/74)、5.4%(4/74)、1.4%(1/74)、27.0%(20/74)、9.5%(7/74),MS组仅1例ANAs阳性,阳性率为2.0%(1/49),两组间差异有统计学意义(P<0.01).血清ANAs诊断NMOSDs的灵敏度为45.9%,特异度达98.0%;NMO和rLETM患者血清ANAs阳性率分别为47.2%和40.0%,两者无统计学差异(P=0.635).结论 NMO和rLETM患者血清ANAs阳性率高于MS组,支持NMO和rLETM同属于NMOSDs的观点.ANAs有可能是NMOSDs和MS两组疾病的鉴别指标之一.     

水通道蛋白4与视神经脊髓炎的发病机制

视神经脊髓炎(neuromyelitis optica,NMO)是视神经和脊髓主要受累的中枢神经系统脱髓鞘疾病.特异性NMO-IgG抗体~([1])[也称抗水通道蛋白4(AQP4)抗体]的发现支持NMO是一独立疾病,而非多发性硬化(multiple sclerosis,MS)的亚型,开辟了NMO研究的新领域.NMO-IgG诊断NMO的敏感度为50%～91%,特异度85%～99%~([2]),2006年已被纳入NMO修订的诊断标准.     

视神经脊髓炎脊髓损害的磁共振研究

目的分析视神经脊髓炎(NMO)和多发性硬化(MS)患者脊髓MRI特点,以及血清抗水通道蛋白4(AQP4)IgG抗体阳性与阴性NMO患者脊髓MRI特点。方法回顾分析贵州省中枢神经系统脱髓鞘疾病数据库中42例NMO和32例有脊髓损害的MS患者的脊髓MRI资料。结果与MS组比较,NMO患者脊髓病灶累及更长的椎体节段(P0.05),在脊髓MRI矢状位上表现为线样征和纵向延展的脊髓损害(LESCL)(P0.05)。轴位T2WI上亮斑状损害(BSLs)以及中心性、横贯性脊髓损害更常见(P0.05);在病灶部位及强化病灶上,NMO和MS组间比较差异无统计学意义。与血清抗AQP4-IgG抗体阴性NMO患者比较,阳性患者线样征、BSLs、中心性损害更常见(P0.05),在脊髓病灶部位、受累椎体节段数、LESCL、横贯性损害及强化病灶方面,抗AQP4-IgG抗体阳性组和阴性组间比较差异无统计学意义。结论除LESCL、线样征、横贯性损害和中心性损害特点外,BSLs可能是另一个有助于鉴别NMO与MS的脊髓病灶MRI特征。BSLs、线样征、中心性损害特点可能与NMO患者抗AQP4-IgG抗体的血清学状态有关。     

临床孤立综合征转归为视神经脊髓炎的相关因素分析

目的探讨临床孤立综合征(CIS)转归为视神经脊髓炎(NMO)的影响因素。方法收集2004-09-2011-09就诊于作者医院神经内科CIS患者109例。回顾性分析所有患者首次发病时头颅和脊髓MRI特点及临床表现。采用酶联免疫吸附法(ELISA)检测血清水通道蛋白4抗体(AQP4-Ab)水平,另备30份健康者血清作为健康对照组,以高于健康对照组血清AQP4-Ab浓度的均值+3倍标准差者为阳性。结果 (1)随访0.5～7年,中位数为3.0年,四分位数间距为4.6年,转归为NMO 46例,转归为多发性硬化(MS)29例,其余仍是CIS,包括24例脊髓炎,10例视神经炎(ON)。(2)转归为NMO组血清AQP4-Ab水平明显高于MS组、脊髓炎组、ON组和健康对照组(P<0.05)。(3)转归为NMO组AQP4-Ab阳性率为63.03%(29/46),高于转归为MS组的13.79%(4/29)、脊髓炎组的29.17%(7/24)、ON组的20.00%(2/10),差异均有统计学意义(P<0.05)。(4)多因素分析结果提示:AQP4-Ab阳性、NMO颅内典型病灶、脊髓损伤>3个节段、扩展残疾状态量表(EDSS)与CIS转归为NMO有关。结论 AQP4-Ab阳性、NMO颅内典型病灶或者脊髓损伤>3个节段、EDSS评分对预测CIS转归为NMO有临床价值。     

Prevalence of neuromyelitis optica spectrum disorder and phenotype distribution

Neuromyelitis optica spectrum disorder (NMOsd) is a group of demyelinating disorders recently redefined and associated with NMO-IgG/anti-aquaporin 4 antibodies. Because NMOsd is of unknown prevalence worldwide, we conducted a retrospective, cross-sectional study of 850 patients with demyelinating disorders hospitalized in North East Tuscany from 1998 to 2006 to examine the prevalence of NMO and related disorders among unselected consecutive neurological patients with inflammatory CNS diseases and to evaluate the clinical phenotype spectrum of identified cases. Clinical data were updated after at least 2 years of follow-up. An immunofluorescence technique was used to detect NMO-IgG on rat brain tissue. Sera from other 828 neurological patients, 65 non-neurological patients and 50 healthy donors served as controls. The prevalence of NMOsd was 1.5%, with a MS:NMOsd ratio of 42.7. Among 13 NMOsd patients, 77% had long spinal cord lesions, 38% had severe optic neuritis and 23% had brain or brainstem lesions. Only 56% had clinically definite NMO at follow-up. The final EDSS score ranged from 1 to 10, mainly depending on brainstem involvement occurrence. Our findings confirm a low prevalence of NMO and related disorders among demyelinating inflammatory diseases in a Caucasian population. Moreover, this study demonstrates an unexpectedly high prevalence of limited and atypical variants of this disease, not previously documented.     

Autoimmunity in neuromyelitis optica and opticospinal multiple sclerosis: astrocytopathy as a common denominator in demyelinating disorders

Neuromyelitis optica (NMO) selectively affects the optic nerves and spinal cord. In Asians, multiple sclerosis (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 multiple sclerosis (OSMS), has similar features to the relapsing form of NMO in Westerners. The discovery that NMO-IgG, an NMO-specific IgG, targets aquaporin-4 (AQP4), suggested that NMO is a distinct disease entity with a fundamentally different etiology from MS. Because NMO-IgG is present in 30-60% of OSMS patients, OSMS in Asians is suggested to be the same entity as NMO. Pathologically, perivascular immune complex (IgM, IgG and C9neo) deposition and extensive loss of AQP4 in active lesions are reported hallmarks of NMO. However, we found that some autopsied NMO cases showed selective AQP4 loss while others showed preservation of AQP4, despite extensive tissue destruction. Vasculocentric deposition of complement and immunoglobulin was detected only in NMO patients, with less than 30% of actively demyelinating lesions showing AQP4 loss. Such heterogeneity of AQP4 expression and immunoglobulin deposition suggests a heterogeneous disease process in NMO. We recently reported that AQP4 was extensively lost in glial fibrillary acidic protein-positive hypertrophic astrocytes, both in demyelinated and myelinated layers of actively demyelinating lesions in Baló's disease, a variant of MS. We also found that in some acute MS lesions, AQP4 was lost extensively far beyond the areas of myelin loss. Active demyelinating lesions involved perivascular lymphocyte cuffings, consisting mainly of T cells in Baló's disease and MS, while the same was true for approximately half of the active lesions in NMO. This review proposes that anti-AQP4 antibody-dependent AQP4 loss occurs in some NMO patients while antibody-independent AQP4 astrocytopathy can occur in heterogeneous demyelinating conditions, including Baló's disease, NMO and MS. The latter may be mediated by T cells and other cell-mediated mechanisms, and should be tested in future experimental studies.     

Neuromyelitis optica-IgG testing in an Indian cohort with neuromyelitis optica and related demyelinating disorders: Our experience

Background:

Neuromyelitis optica (NMO) is an immune-mediated inflammatory demyelinating disorder of the central nervous system with a predilection for the optic nerves and the spinal cord. Immunopathological evidence suggests that the target antigen of the disease is aquaporin-4. An IgG antibody against this protein has been explored as a molecular marker for the disease and as a diagnostic tool due to its high sensitivity and specificity in various populations.

Objective:

To assess the value of NMO-IgG testing in Indian patients with clinical and magnetic resonance imaging features consistent with NMO and longitudinally extensive transverse myelitis (LETM).

Materials and Methods:

Forty-five patients with clinical and magnetic resonance imaging features consistent with NMO, LETM, and MS were tested for serum NMO-IgG. Of these patients, 22 patients satisfied revised (2006) Wingerchuk criteria for NMO (excluding NMO-IgG status) and 11 patients had LETM. Twelve patients satisfied the revised (2010) McDonald criteria for multiple sclerosis (MS).

Results:

Of the 21 patients, satisfying the criteria for NMO and for whom the test results were available, 17 were positive for NMO-IgG (80.9%), and of the 11 patients having LETM, 6 (54.5%) were positive for NMO-IgG. In one patient with NMO, the test result was not available. None of the 12 patients satisfying McDonald criteria for MS showed NMO-IgG seropositivity.

Conclusion:

Our study suggests that it is worthwhile to pursue NMO-IgG testing as a diagnostic tool for patients with clinical and Magnetic Resonance Imaging (MRI) features consistent with NMO and LETM in the Indian population.     

Devic's neuromyelitis optica: a critical review

Devic's neuromyelitis optica (NMO) is an idiopathic inflammatory demyelinating and necrotizing disease characterized by predominant involvement of the optic nerves and spinal cord. In Asian countries relapsing NMO has been known as opticospinal multiple sclerosis. It has long been debated if NMO is a variant of multiple sclerosis (MS) or a distinct disease. Recent studies have shown that NMO has more frequently a relapsing course, and results from attack to aquaporin-4 which is the dominant water channel in the central nervous system, located in foot processes of the astrocytes. Distinctive pathological features of NMO include perivascular deposition of IgG and complement in the perivascular space, granulocyte and eosinophil infiltrates and hyalinization of the vascular walls. These features distinguish NMO from other demyelinating diseases such as MS and acute demyelinating encephalomyelopathy. An IgG-antibody that binds to aquaporin-4, named NMO-IgG has high sensitivity and specificity. Magnetic resonance imaging (MRI) studies have revealed that more frequently there is a long spinal cord lesion that extends through three or more vertebral segments in length. Brain MRI lesions atypical for MS are found in the majority of cases. Treatment in the acute phase includes intravenous steroids and plasma exchange therapy. Immunosupressive agents are recommended for prophylaxis of relapses.     

Clinical and laboratory features of neuromyelitis optica with oligoclonal IgG bands

Of 23 neuromyelitis optica (NMO) cases, we found two cases with oligoclonal IgG bands (OBs). Both patients were positive for NMO-IgG. Their common features were long disease duration and co-existing autoimmune diseases (myasthenia gravis and sicca syndrome). Although OBs are mostly negative in NMO, which distinguishes it from multiple sclerosis (MS), they can be positive by long-standing autoimmunity, which may not be directly related to NMO.     

Seroprevalence of NMO-IgG among patients with neuromyelitis optica and opticospinal multiple sclerosis

Objectives

In this study we sought to compare the seropositivity of NMO-IgG in patients presenting with demyelinative involvement of optic nerve and spinal cord with and without longitudinally extensive spinal cord lesion (LESCL).

Methods

Patients who were referred to Isfahan Multiple Sclerosis Clinic and Isfahan Devic's Disease Clinic at Al-Zahra Hospital in Iran were screened for this study. Patients with signs and symptoms indicating the demyelinating involvement of optic nerve(s) and spinal cord were included. Patients were evaluated by a neurologist and spinal cord and brain magnetic resonance imaging (MRI) were obtained. Patients with normal first brain MRI and with spinal cord demyelinative lesions visible on spinal MRI were included. Patients were then put into two groups: (i) patients with LESCL [neuromyelitis optica (NMO)] and (ii) patients with spinal plaques which do not extend over three vertebrae [opticospinal multiple sclerosis (OSMS)]. NMO-IgG was measured in the serum of the included patients.

Results

Totally we recruited 33 patients with LESCL and 32 patients without LESCL. The mean age of patients without LESCL was 34.61 ± 10.98 and it was 33.48 ± 11.93 for the NMO patients. In both groups there were 24 females and the rest were males. Among the NMO patients 16 (48.5%) were positive for NMO-IgG, while in the OSMS group there were none.

Conclusion

The results of this study are in line with previous observations, and imply that the presence of LESCL is associated with the presence of NMO-IgG and thus an indicator of NMO.     

视神经脊髓炎与多发性硬化的临床症状、脊髓MRI表现的对比分析

目的 结合视神经脊髓炎(NMO)与多发性硬化(MS)患者的临床症状和脊髓MRI特点探讨两者之间差异发生的机制.方法 回顾性分析中山大学附属第三医院自2004年1月至2007年1月收治的23例NMO患者及21例MS患者的临床资料,比较其临床症状及脊髓MRI上受损部位MRI上的差异.结果 NMO患者多为女性,且首次发病年龄、扩展病残状况评分(EDSS)评分均高于MS患者;双侧深感觉障碍、束带感、直肠或膀胱括约肌功能障碍3种临床症状在NMO、MS患者中的发生率不同,差异均有统计学意义(P<0.05);上述各临床症状基本能在脊髓MRI找到相应受损病灶.结论 NMO是不同于MS的脱髓鞘疾病,其特殊的发病机制导致其临床症状与脊髓MRI均有自己的特点.