脑脊液MOG抗体阳性的视神经脊髓炎谱系疾病患者的临床特征

目的探讨MOG抗体阳性的NMOSD患者的临床特点。方法选择29例NMOSD患者,根据血清AQP-4抗体以及脑脊液MOG抗体检测结果,分为MOG抗体阳性、AQP4抗体阳性的NMOSD(剔除双阳性者),同时选择13例MS患者作为对照。回顾性分析上述三组患者临床信息,统计归纳其临床特点。结果 29例NMOSD患者中血清AQP4抗体阳性者11例,脑脊液MOG抗体阳性者8例。36.4%(4例/11例)AQP4抗体阳性、62.5%(5例/8例)MOG抗体阳性NMOSD患者,以及7.7%(1例/13例)MS患者合并脊髓炎与视神经炎,三组间差异有统计学意义(χ~2=7.128,P=0.028),其中MOG抗体阳性NMOSD患者较MS患者更易合并视神经炎(χ~2=7.289,P=0.014)。MOG抗体阳性NMOSD患者缓解期EDSS分数低于AQP4抗体阳性NMOSD患者[3.50(2.50,4.00),4.00(3.50,6.00),Z=-2.379,P=0.020]。MOG抗体阳性NMOSD脊髓病灶多表现为多发的长节段脊髓病灶,50%(4例/8例)MOG抗体阳性脊髓病灶个数大于1个,与MS组无明显差异,而AQP4抗体阳性组均为单个病灶。MOG抗体阳性NMOSD脊髓病灶长度较AQP4抗体阳性组短[分别(3(2,3)个椎体、4(3,5)个椎体,Z=-2.499,P=0.012],较MS组[(1.25(1,1.5)个椎体]长(Z=-3.447,P0.001)。8例MOG抗体阳性患者中5例存在颅内病灶,3例表现为NMOSD样颅内病灶,余2例表现为MS样颅内病灶,其病灶形态及部位与AQP4抗体阳性组无明显差异,而与MS组存在差异。结论 MOG抗体阳性NMOSD合并视神经炎的患者较多,临床残障程度较轻,预后较好,脊髓病灶为多发的长节段脊髓病灶;颅内病灶的形态及部位与MS无明显差异。     

MOG抗体阳性和AQP4抗体阳性NMOSD患者的临床及影像学分析

目的比较髓鞘少突胶质细胞糖蛋白抗体(MOG-IgG)阳性和水通道蛋白4抗体(AQP4-IgG)阳性的视神经脊髓炎谱系疾病(NMOSD)患者临床表现和影像学特征,以提高对MOG-IgG阳性NMOSD的认识。方法对12例MOG-IgG阳性、98例AQP4-IgG阳性患者的性别、发病年龄、病程复发、EDSS评分、脑脊液蛋白、视觉诱发电位及磁共振(MRI)表现等进行回顾性分析。结果 MOG-IgG阳性与AQP4-IgG阳性相比,男性多见(χ~2=11. 270,P=0. 001),视神经和脊髓多同时受累(83. 3%),并常累及双侧视神经(χ~2=6. 050,P=0. 014),多呈单次病程(χ~2=11. 270,P=0. 001),表现出更好的预后(t=-4. 673,P=0. 001)。影像学上MOG-IgG组未发现典型的颅内病灶,AQP4-IgG组43例存在典型的颅内病灶(χ~2=8. 645,P=0. 003)。延髓极后区受累MOG-IgG组1例,AQP4-Ig G组37例(χ~2=4. 039,P=0. 043)。MOG-IgG与AQP4-IgG患者累及腰髓分别为6例、8例(χ~2=16. 847,P=0. 001);累及颈髓分别为4例、67例(χ~2=5. 734,P=0. 017)。结论 NMOSD患者中MOG-IgG阳性与AQP4-IgG阳性患者相比男性多见,多累及双侧视神经及腰髓,典型颅内病灶及延髓极后区病灶较少,呈单次病程,预后较好。     

血清MOG抗体阳性炎性脱髓鞘疾病患者临床特征分析

目的探讨MOG抗体阳性炎性脱髓鞘疾病患者的临床特征。方法回顾性分析36例血清MOG抗体阳性炎性脱髓鞘疾病患者(MOG抗体阳性组)与87例血清AQP4抗体阳性NMOSD患者(AQP4抗体阳性组)的临床信息,分析比较两组患者的临床特征。结果 MOG抗体阳性组与AQP4抗体阳性组患者相比,患病男女比例(1︰1.77 vs.1︰6.25,P=0.005)及发病年龄[(23.17±14.37)岁vs.(35.91±12.91)岁,P=0.000]差异存在统计学意义,两组患者均以女性为多,MOG抗体阳性组患者以儿童和青年为主。MOG抗体阳性组首发脱髓鞘事件中ADEM患者比例高于AQP4抗体阳性组[7例(19.4%)vs.0例(0%),P=0.000],脊髓炎[11例(30.6%)vs.47例(50.4%),P=0.018)]和脑干综合征[5例(13.9%)vs.25例(28.7%),P=0.049)]患者比例低于AQP4抗体阳性组。MOG抗体阳性组患者出现肢体抽搐症状患者比例高于AQP4抗体阳性组[5例(13.9%)vs.0(0%),P=0.002]。影像学表现上,MOG抗体阳性组头部总病灶[27例(75.0%)vs.33例(37.9%)]及NMO非典型病灶[23例(85.2%)vs.4例(12.1%)]患者比例高于AQP4抗体阳性组,头部NMO典型病灶[4例(14.8%)vs.29例(87.9%)]患者比例低于AQP4抗体阳性组(均P=0.000),仅14.8%MOG抗体阳性炎性脱髓鞘疾病患者存在典型NMO头部病灶。MOG抗体阳性组患者截访时EDSS评分低于AQP4抗体阳性组[(2.36±1.66)分vs.(3.83±1.66)分,P=0.000]。结论 MOG抗体阳性炎性脱髓鞘疾病患者男女比例差异较小,与AQP4抗体阳性NMOSD患者相比发病年龄小,首次发作以ADEM、视神经炎及脊髓炎为主,易出现肢体抽搐症状,少见NMO典型头部病灶,倾向于累及下段脊髓,预后较好。     

视神经脊髓炎谱系疾病复发相关因素的临床研究

目的研究视神经脊髓炎谱系疾病(NMOSD)的复发率及其临床特征,分析多因素与NMOSD复发的相关性。方法分析2009年7月29日~2015年12月31日就诊于本院神经内科确诊73例NMOSD患者的临床、实验室检查及扩展残疾状态量表(EDSS)评分等资料。运用卡方检验、Logistic回归分析等统计学方法分析影响NMOSD复发的危险因素。结果 73例NMSOD患者中,男性12例,女性61例,男女比例约1∶5,首次发病中位年龄38岁。血清水通道蛋白-4抗体(AQP4-Ab)阳性检出率84.9%(62/73),血清其他自身免疫抗体阳性72.6%(53/73),脑脊液(CSF)AQP4-Ab阳性检出率45.1%(23/51),CSF蛋白升高率43.9%(25/57)。有序Logistic回归分析结果显示血清AQP4-Ab(OR=14.5561,95%CI 0.120~2.809)、自身免疫抗体(OR=4.3281,95%CI 0.684~4.673)阳性可能是NMOSD发病3 y内复发的独立危险因素。结论血清AQP4-Ab及其他自身免疫抗体阳性可能与NMOSD发病3 y内复发频次呈正相关。     

120例视神经脊髓炎谱系疾病临床特点分析

目的基于2015年诊断标准分析视神经脊髓炎谱系疾病(NMOSD)患者的临床特点和影像学特征。方法回顾性分析120例NMOSD患者的临床特点、影像学特征、以及对比水通道蛋白4(AQP4)抗体阳性和阴性患者的临床异同点。结果女性∶男性=2.75∶1,平均发病年龄37.1岁,平均病程21个月,80%患者为复发病程。起病症状视神经炎和脊髓炎分别占41.7%和40%。15.8%患者伴有自身免疫病;5.8%患者伴有内分泌疾病。78.1%的患者AQP4抗体阳性,抗体阳性组疾病严重程度评分显著高于抗体阴性组(P=0.026)。长节段横贯性脊髓炎占83.7%。头部MRI异常见于36.7%(44/120)患者。28.3%(34/120)患者脑脊液白细胞升高(5×10~6/L),脑脊液蛋白49.5 mg/dl(正常值:15~45 mg/dl);30.8%(37/120)患者寡克隆区带阳性;52.2%(24/46)患者髓鞘碱性蛋白阳性;40%(48/120)患者脑脊液免疫球蛋白G升高。结论 2015年诊断标准有助于NMOSD诊断,NMOSD长节段脊髓炎多见,短节段脊髓炎不能排除NMOSD,AQP4抗体阳性患者病情更重,应重视早期诊断。     

视神经脊髓炎谱系疾病1例报道并文献复习

目的提高对视神经脊髓炎谱系疾病(NMOSD)的认识。方法报道1例以脑干症状为首发、继以急性横贯性脊髓炎的NMOSD患者,结合文献复习进行分析。结果青年女性患者,发病时表现为左侧味觉减退以及左侧面部瘙痒,继以出现急性横贯性脊髓炎。MRI显示延髓右侧和左侧桥脑被盖部、中脑导水管周围长T1、长T2信号病灶,脊髓MRI显示颈1~5长T2信号病灶;血清水通道蛋白4(AQP4)抗体阳性。患者符合AQP4抗体阳性NMOSD的诊断标准。结论 NMOSD常有脑部症状,尤其是脑干症状。部分患者可以脑干症状为首发临床表现,对此类患者应及早行AQP4抗体检测,以明确诊断及早干预。     

MOG抗体阳性视神经脊髓炎谱系疾病临床和影像学特点

目的探讨血清髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte glycoprotein, MOG)抗体阳性的视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorder, NMOSD)患者的临床和影像学特点。方法收集NMOSD患者57例、多发性硬化(multiple sclerosis, MS)患者29例,回顾性分析MOG抗体阳性的NMOSD患者的临床和影像学特点。结果 9/57(15.8%)NMOSD患者血清MOG抗体阳性,其中1例患者血清MOG与水通道蛋白-4(aquaporin-4, AQP4)抗体双阳性,2/29(6.9%)MS患者血清MOG抗体阳性,两组患者MOG抗体阳性率差异无统计学意义(P0.05)。MOG抗体阳性NMOSD患者男女比例为1:7,平均起病年龄为(41.4±11.5)岁,与MOG抗体阴性组以及AQP4抗体阳性组相比差异无统计学意义(P0.05)。MOG抗体阳性NMOSD组、MOG抗体阴性NMOSD组的病程均比AQP4抗体阳性NMOSD组短,差异有统计学意义(P均0.05),但MOG抗体阳性NMOSD组与MOG抗体阴性NMOSD组比较差异无统计学意义(P0.05)。三组患者均以复发为主,平均复发次数比较差异无统计学意义(P0.05)。MOG抗体阳性NMOSD患者出现视神经炎比例为62.5%,AQP4抗体阳性组比例为43.5%,两者差异无统计学意义(P0.05)。三组患者颅内病灶的形态以及部位均无统计学差异(P0.05)。MOG抗体阳性NMOSD患者多为单发长节段脊髓病灶,脊髓病灶数量比MOG抗体阴性组和AQP4抗体阳性组更少,但三组单个脊髓病灶所对应的中位椎体数相近,差异无统计学意义(P0.05)。结论 MOG抗体阳性的NMOSD患者女性比例更高,以复发为主,病程较短,易合并视神经炎,影像学表现与AQP4抗体阳性的NMOSD相比无明显特异性。     

滤泡辅助性T细胞与特发性视神经炎和视神经脊髓炎谱系疾病关系的研究

目的探讨滤泡辅助性T细胞(T follicular helper,Tfh)在特发性视神经炎(ON)和视神经炎谱系疾病(NMOSD)的体液免疫过程中的作用及其临床意义。方法选择2015-03—2017-04期间在作者科室住院的急性特发性ON患者41例(ON组)、NMOSD急性期患者55例(NMOSD组),患者均予甲基泼尼松龙冲击及序贯治疗,并行脑和脊髓MRI检查。于甲基泼尼松龙治疗前后进行扩展的神经功能障碍评分(EDSS)和视觉功能评分(VOS)检查;采用流式细胞术测定两组患者甲基泼尼松龙治疗前外周血和部分脑脊液Tfh标志物:包括辅助性T细胞(CD4)、趋化因子受体5(CXCR5)双阳性(CD4+CXCR5+)T细胞以及CD4、CXCR5、程序性死亡因子-1(PD-1)三阳性(CD4+CXCR5+PD-1+)T细胞占CD4+细胞的百分比(以下简称"比例");以ELISA法检测甲基泼尼松龙治疗前AQP-4抗体水平。以26名健康人为对照,检测其外周血CD4+CXCR5+、CD4+CXCR5+PD-1+T细胞比例。比较ON组和NMOSD组患者CD4+-CXCR5+及CD4+-CXCR5+-PD-1+T细胞比例、AQP4抗体水平及甲基泼尼松龙治疗前后EDSS和VOS功能评分变化,比较两患者组与健康对照组CD4+-CXCR5+和CD4+-CXCR5+-PD-1+T细胞比例,并分析患者血和脑脊液Tfh细胞比例的相关性,患者Tfh细胞比例与病程、年复发率、EDSS及VOS评分相关性,患者AQP4抗体水平与Tfh比例、病程和EDSS评分的相关性。结果ON组和NMOSD组外周血CD4+CXCR5+T细胞比例[分别为(16.69±4.78)%、(16.88±5.22%)]及CD4+CXCR5+PD-1+T细胞比例[分别为(10.61±3.44)%、(10.78±3.63)%]均显著高于健康对照组[分别为(12.60±4.57)%、(6.86±2.87)%,均P0.01],两患者组间外周血和脑脊液Tfh细胞比例差异均无统计学意义(均P0.05)。NMOSD组病程显著长于ON组[分别(27.23±37.78)、(12.06±32.02)个月,F=4.305,P0.05],治疗前后EDSS评分均高于ON组(分别为治疗前3.94±1.03、3.06±1.15,F=15.11,P0.01;治疗后3.43±1.47、2.50±1.58,F=8.836,P0.01)。两组甲基泼尼松龙治疗后VOS评分(分别为5.17±4.42、6.13±3.68)和EDSS评分(分别为2.50±1.58、3.43±1.47)均显著低于治疗前评分(VOS分别为6.63±4.25、7.44±3.66;EDSS分别为3.06±1.15、3.94±1.03,均P0.01)。相关分析显示,ON组及NMOSD组外周血及脑脊液中CD4+CXCR5+与CD4+CXCR5+PD-1+T细胞两种不同细胞比例均呈正相关(ON组分别r=0.822、P=0.000,r=0.714、P=0.047;NMOSD组分别r=0.826、P=0.000,r=0.917、P=0.001)),NMOSD组脑脊液CD4+CXCR5+T细胞比例与外周血中该细胞比例呈显著正相关(r=0.717、P=0.030),而ON组两者无相关性(r=0.321、P=0.482)。NMOSD患者血清AQP4抗体水平与病程和EDSS评分均呈正相关(r=0.418、P=0.000,r=0.351、P=0.001)。两组患者外周血和脑脊液CD4+CXCR5+PD-1+T细胞比例与EDSS评分、VOS评分及年均复发次数均无相关性(均P0.05)。结论Tfh可能参与了ON和/NMOSD的体液免疫过程,NMOSD患者血清AQP4抗体与病情相关。     

视神经脊髓炎水通道蛋白4抗体分布特征及其与脑脊液寡克隆区带间关系的临床研究

目的观察视神经脊髓炎患者水通道蛋白4(AQP4)抗体在血清和脑脊液的分布特征,探讨血清AQP4抗体与脑脊液寡克隆区带之间的关系。方法采用酶联免疫吸附试验和间接免疫荧光法检测视神经脊髓炎和多发性硬化患者血清和脑脊液AQP4抗体,动态定时散射比浊法检测白蛋白和IgG,等电聚焦电泳联合免疫固定法检测脑脊液寡克隆区带,免疫印迹法检测寡克隆区带阳性视神经脊髓炎患者脑脊液电泳条带中AQP4抗体。结果视神经脊髓炎组患者血清AQP4抗体滴度[8.94(5.41,11.93)ng/ml]与多发性硬化组[7.34(4.76,12.00)ng/ml]相近(Z=-0.510,P=0.610),脑脊液AQP4抗体滴度[0.45(0.42,0.47)ng/ml]高于多发性硬化组[0.41(0.40,0.41)ng/ml;Z=-2.359,P=0.018],而且血清水平高于脑脊液(Z=-3.702,P=0.000)。视神经脊髓炎组患者脑脊液AQP4抗体阳性检出率高于多发性硬化组(5/7对1/5),但差异未达到统计学意义(Fisher确切概率法:P=0.242);复发期血清AQP4抗体滴度[8.54(5.32,11.42)ng/ml]与缓解期[9.97(5.41,13.28)ng/ml]相近(Z=-0.347,P=0.728);寡克隆区带阳性检出率低于多发性硬化组(3/13对10/14)且差异有统计学意义(Fisher确切概率法:P=0.021)。未在寡克隆区带阳性视神经脊髓炎患者的IgG电泳条带中检出AQP4抗体。结论视神经脊髓炎患者血清AQP4抗体滴度高于脑脊液,行脑脊液AQP4抗体检测具有一定临床意义。视神经脊髓炎患者鞘内合成IgG能力低于多发性硬化患者,且无针对AQP4抗原的成分。     

客观认识水通道蛋白4抗体及其他胶质细胞抗体与视神经脊髓炎谱系疾病的关系

正视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)是在临床、影像等方面存在高度异质性的一组神经系统自身免疫性脱髓鞘疾病。尽管AQP4抗体被认为是NMOSD的特异性生物标志物,但仍有部分患者无法检测出此抗体。研究发现,在一些AQP4抗体阴性患者体内可检测到抗体如髓鞘少突胶质细胞糖蛋白(myelin oligodendrocyte glycoproeein,MOG)抗体等胶质细胞抗体,其致病性尚不明确。因此,关注和     

甲泼尼龙冲击治疗对视神经脊髓炎谱系病患者外周血滤泡辅助性T细胞百分率的影响

目的探究视神经脊髓炎谱系病(NMOSD)患者外周血滤泡辅助性T细胞(Tfh)百分率在甲泼尼龙冲击治疗前、后的变化。方法收集AQP-4抗体阳性的急性期NMOSD患者(NMOSD组)23例,采用流式细胞术检测甲泼尼龙冲击前、后外周血CXCR5~+ICOS~+的CD4~+T细胞(Tfh细胞),记录NMOSD组的EDSS评分,分析NMOSD组患者Tfh细胞百分率与患者AQP-4抗体滴度及EDSS评分的相关性。结果 NMOSD组患者甲泼尼龙冲击治疗前外周血Tfh细胞百分率[(1.77±0.74)%]显著高于甲泼尼龙冲击治疗后[(1.26±0.45)%](t=2.284,P=0.032)。首次发病NMOSD患者甲泼尼龙冲击治疗前Tfh细胞百分率与EDSS评分呈正相关(r=0.625,P=0.040),甲泼尼龙冲击治疗前、后Tfh细胞百分率与AQP-4抗体滴度无相关性(r=--0.02,P=0.928)。结论经甲泼尼龙冲击治疗后,NMOSD患者急性期外周血Tfh细胞百分率降低,首次发病NMOSD患者Tfh细胞百分率水平与EDSS评分有关。Tfh细胞百分率水平可能与NMOSD的复发有关。     

What proportion of AQP4-IgG-negative NMO spectrum disorder patients are MOG-IgG positive? A cross sectional study of 132 patients

Antibodies to myelin oligodendrocyte glycoprotein (MOG-IgG) have been described in patients with neuromyelitis optica spectrum disorders (NMOSD) without aquaporin-4 antibodies (AQP4-IgG). We aimed to identify the proportion of AQP4-IgG-negative NMOSD patients who are seropositive for MOG-IgG. In a cross sectional study, we reviewed all patients seen in the National NMO clinic over the last 4 years (after the availability of MOG-IgG testing), including clinical information, MRI, and antibody tests. 261 unique patients were identified. 132 cases satisfied the 2015 NMOSD diagnostic criteria. Of these, 96 (73%) were AQP4-IgG positive and 36 (27%) were AQP4-IgG negative. These 36 patients were tested for MOG-IgG and 15/36 (42%) tested positive. 20% (25/125) of the patients who did not satisfy NMOSD criteria had MOG-IgG. Approximately half of seronegative NMOSD is MOG-Ig seropositive and one in five of non-NMOSD/non-MS demyelination is MOG-IgG positive. Since MOG-associated demyelinating disease is likely different from AQP4-IgG disease in terms of underlying disease mechanisms, relapse risk and possibly treatment, testing for MOG-IgG in patients with AQP4-IgG-negative NMOSD and other non-MS demyelination may have significant implications to management and clinical trials.     

Prognostic factors and disease course in aquaporin-4 antibody-positive Chinese patients with acute optic neuritis

The objective is to assess the frequency of AQP4-Ab in Chinese patients with optic neuritis (ON) and to investigate the prognostic implications of AQP4-Ab seropositivity in such patients. The presence of aquaporin-4 (AQP4) antibodies in human AQP4-transfected cells was determined by indirect immunofluorescence, and the diagnostic and prognostic relevance of AQP4 antibodies in 215 Chinese patients with optic neuritis was evaluated. The patients were enrolled from the Chinese People’s Liberation Army General Hospital (PLAGH) and followed up to 1–228 months. Kaplan–Meier survival analysis was used to investigate the visual outcomes and prognostic characteristics of 70 patients who were aquaporin-4 antibody seropositive, and altogether 115 eyes were involved. AQP4-Ab was detectable in 70/215 (32.6%) patients with acute monosymptomatic optic neuritis. These AQP4-Ab seropositive patients were diagnosed as sufferers of neuromyelitis optica (NMO) (n = 10), NMO spectrum disease (NMOSD) (n = 41), multiple sclerosis (MS) (n = 1), and acute optic neuritis (AON) (n = 18). Moreover, AQP4-Ab levels did not vary between seropositive AON and NMO-ON and did not correlate with disease severity. Finally, the male gender, older age at onset, number of relapses, concomitant autoimmune antibodies, and optic lesions in magnetic resonance imaging (MRI) were associated with the AQP4-Ab seropositive status and the risk of developing permanent visual disability. Acute optic neuritis has a higher incidence of anti-aquaporin-4 antibody in China than in Western countries, and AQP4 antibody is a sensitive and specific biomarker for discriminating NMO-ON from other types of optic neuritis during the early stage of the disease course.     

视神经脊髓炎谱系病患者疼痛的初步研究

目的初步探讨视神经脊髓炎谱系病(NMOSD)患者相关的疼痛问题。方法收集57例NMOSD患者和51例多发性硬化(MS)患者的临床资料,采用数字疼痛强度量表(NRS)对患者疼痛程度及部位进行评估,对比分析两组疼痛发生情况、严重程度、部位及治疗情况。结果 NMOSD组患者疼痛发生率明显高于MS组患者(63.16%vs.35.29%,χ2=8.359,P=0.004)。NMOSD组患者痛性痉挛发生率与MS组差异无统计学意义(24.56%vs.11.76%,χ2=2.921,P=0.087)。NMOSD组患者的疼痛评分在0~8分,以中度疼痛为主[20例(55.56%)],MS组患者的疼痛评分在0~7分,以轻度疼痛为主[11例(61.11%)],但两组间轻度疼痛与中重度疼痛患者比例差异无统计学意义(36.11%vs.61.11%,63.89%vs.38.89%,χ2=3.038,P=0.081)。NMOSD组[16例/36例(44.44%)]及MS组[6例/18例(33.33%)]患者的疼痛部位均以躯干部位最常见。Logistic逐步回归分析显示NMOSD患者的疼痛程度与患者的性别、年龄、病程、发作次数、NMO-IgG及EDSS评分无相关性。结论疼痛在NMOSD患者中十分常见,其疼痛应受到重视,并应积极对症治疗。     

脑脊液BAFF、VEGF水平在视神经 脊髓炎患者中的变化及其意义

目的 探讨脑脊液B淋巴细胞活化因子(BAFF)、血管内皮生长因子(VEGF)水平在视神经脊髓炎(NMO)患者中的变化及其意义。方法 选取2015年1月-2018年1月本院收治的NMO患者50例作为NMO组,选取同期多发性硬化症(MS)患者50例作为MS组及非炎性神经系统疾病患者50例作为对照组,所有患者均检测脑脊液BAFF、VEGF水平、急性期扩展残疾状态量表(EDSS)评分、水通道蛋白4抗体(AQP4-Ab)滴度,分析BAFF、VEGF与EDSS评分、AQP4-Ab滴度的关系。结果 NMO组和MS组脑脊液BAFF、VEGF水平明显高于对照组,NMO组脑脊液BAFF、VEGF水平和EDSS评分、AQP4-Ab滴度阳性率明显高于对照组(P<0.05); Pearson相关性分析显示,脑脊液BAFF、VEGF水平均与EDSS评分呈正相关(r=0.695,0.668,P<0.05),但均与AQP4-Ab滴度无关(r=0.121,0.116,P>0.05)。结论 脑脊液BAFF、VEGF水平与NMO的发生发展有关,检测二者水平可作为鉴别NMO、MS及评估NMO病情的重要参考指标。     

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。     

Pruritus in neuromyelitis optica spectrum disorders and multiple sclerosis

PurposeDifferential diagnosis between neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) at early stage remains challenging at present. Pruritus is reported as a common or specific feature in NMOSD with serum aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). We aim to verify whether pruritus can help in distinguishing NMOSD from MS.MethodsWe retrospectively reviewed the medical records of consecutive cases of NMOSD and MS patients, demographic data, clinical features, whether or not had pruritus, serum AQP4-IgG status and magnetic resonance imaging (MRI) results.Results21.0% (22/105) of NMOSD patients and 2.1% (2/96) of MS patients reported pruritus during disease course (p < 0.01). 20.5% (18/88) of AQP4-IgG positive and 23.5% (4/17) of AQP4-IgG negative NMOSD patients reported pruritus during disease course (p = 0.775). 12.4% (13/105) of NMOSD and 1.0% (1/96) of MS patients reported pruritus at the first attack episode of disease (p < 0.01). 20.0% (21/105) of NMOSD and 1.0% (1/96) of MS patients reported pruritus at the first and second attack episodes of disease (p < 0.01).ConclusionPruritus is a common and relatively specific feature in either AQP4-IgG positive or negative NMOSD. Pruritus occurs more frequently in NMOSD than MS, which may help in distinguishing NMOSD from MS, especially at early stage.     

Neuromyelitis optica spectrum disorders: Features of aquaporin-4, myelin oligodendrocyte glycoprotein and double-seronegative-mediated subtypes

The new diagnostic classification of neuromyelitis optica spectrum disorder (NMOSD) in 2015 highlights the central role of biomarkers, such as antibodies against aquaporin-4 (AQP4-Ab), in diagnosis. Also, in approximately 20–25% of patients without AQP4-Ab (NMOSD^AQP4?) the presence of an antibody directed against myelin oligodendrocyte glycoprotein (MOG) characterizes a specific population of NMOSD patients (NMOSD^MOG+), according to their demographic and clinical data and prognoses. While double-seronegative cases (NMOSD^NEG) have not been fully described, they may correspond to the very first patients with opticospinal demyelination reported by Devic and Gault in 1894. The present report reviews the current knowledge of the pathophysiology and clinical features of NMOSD^AQP4+, NMOSD^MOG+ and NMOSD^NEG patients, and also discusses the relationship between the extended spectrum of MOG disease and NMOSD^MOG+. Finally, the current treatments for acute relapses and relapse prevention are described, with a focus on serological-based therapeutic responses and the promising new therapeutic targets.     

Antibodies to CV2/CRMP5 in neuromyelitis optica-like disease: case report and review of the literature

Neuromyelitis optica (NMO) is associated with antibodies to aquaporin-4 (termed NMO-IgG or AQP4-Ab) in 60-90% of cases. Little is known about the aetiology of NMO in NMO-IgG/AQP4-Ab negative patients. Here we report on CV2/CRMP5 antibodies in a 69-year-old male patient with NMO-IgG/AQP4-Ab negative NMO. The association of CV2/CRMP5-Ab with prostate cancer suggests a paraneoplastic aetiology of NMO in our patient. Our report strengthens the case of antibodies other than AQP4-Ab being involved in the immunopathogenesis in a subset of patients with NMO. We conclude that CV2/CRMP5-Ab should be included in the differential diagnosis of NMO, in particular if AQP4-Ab are negative and irrespective of whether a tumour is known or not. We recommend that recombinant tests, which are increasingly used because of their higher sensitivity and specificity, should always be accompanied by standard indirect immunofluorescence employing brain tissue sections in order to avoid CV2/CRMP5-Ab or other paraneoplastic antibodies being overlooked. In addition, we provide a comprehensive review of all patients with CV2/CRMP5-Ab and NMO-like disease published in the English literature so far.