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.     

Antibodies target microvessels in neuromyelitis optica and multiple sclerosis patients

Abstract

Objective: This study investigated the presence of serum antibodies targeting microvessels in Chinese patients with multiple sclerosis (MS) and neuromyelitis optica (NMO).

Methods: Serum samples were collected from 50 patients with NMO, 10 with longitudinally extensive transverse myelitis (LETM), 4 with recurrent optic neuritis, 42 with MS and 27 controls. Serum antibodies binding to microvessels were measured by indirect immunofluorescence (IIF) assay of tissue sections from the brain, stomach and pancreas, and human umbilical vein endothelial cells (HUVEC). Aquaporin-4 (AQP4) antibodies were detected using a cell-based assay.

Results: Indirect immunofluorescence assay of tissue sections from 42 samples (30·4%, 42/138) were positive for microvessel antibodies, where microvessel antibody positivity was 38% (19/50) in patients with NMO, 57·1% (8/14) in high-risk NMO (hrNMO), 26·2% (11/42) in MS, and 14·8% (4/27) in controls. Based on HUVEC analysis, 14 patients with NMO (28%, 14/50), 5 with hrNMO (35·7%, 5/14), 15 with MS (35·7%, 15/42), and 5 controls (18·5%, 5/27) had (AECA). Sixteen patients (32%, 16/50) with NMO, four with hrNMO (28·6%, 4/14), two with MS (4·8%, 2/42), and 0% of controls were positive for antinuclear antibodies (ANA). In MS patients, seropositive AECA MS patients had higher numbers of relapse events and increased spinal lesions than seronegative MS patients (P < 0·05).

Conclusions: Serum microvessel antibodies were present in patients with NMO and MS and the role of microvessel antibodies in diseases may be heterogeneous. This study suggests that AECA may have some significance in MS patients.     

应早期鉴别和区别治疗视神经脊髓炎与多发性硬化

视神经脊髓炎(NMO)是主要累及视神经和脊髓的中枢神经系统炎性脱髓鞘疾病。1884年首先由Devic报告,故又称为Devic’s病。在中枢神经系统炎性脱髓鞘疾病中,视神经脊髓炎在亚洲人群较为多见,而欧美人群则以经典型多发性硬化(MS)更常见。近年研究发现,中枢神经系统水通道蛋白aquaporin4(AQP4)抗体(NMOIgG)为视神经脊髓     

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.     

视神经脊髓炎和多发性硬化患者颈髓扩散张量成像研究

目的通过扩散张量成像(DTI)比较视神经脊髓炎和多发性硬化患者与正常对照者常规MRI表现正常脊髓的扩散性差异,并探讨其临床应用价值。方法采用平面回波成像技术对10例视神经脊髓炎、14例多发性硬化患者和13例正常对照者进行颈髓DTI检查,分别测量颈椎C2~5水平前索、侧索、后索和灰质兴趣区的部分各向异性(FA)和平均扩散率(MD)。结果与正常对照组相比,视神经脊髓炎组患者前索、侧索、后索FA值降低(均P0.05),左侧侧索、后索、灰质MD值升高(均P≤0.05);多发性硬化组患者右侧侧索、后索FA值降低(均P0.05)。与多发性硬化患者相比,视神经脊髓炎患者侧索FA值更低,左侧侧索和右侧后索MD值更高(均P0.05)。结论 DTI可以检出视神经脊髓炎和多发性硬化患者常规MRI表现正常脊髓的水分子扩散异常,进而发现二者脊髓扩散指标的差异性,为早期诊断与鉴别诊断提供重要信息。     

Treatment of multiple sclerosis and neuromyelitis optica in children and adolescents

Paediatric multiple sclerosis (MS) accounts for up to 5% of all MS cases. No therapies have been formally approved for paediatric patients with MS. However, there is published experience on the use of disease modifying therapies in children and adolescents with MS.Neuromyelitis optica (NMO) is an autoimmune inflammatory disease preferentially targeting the optic nerves and spinal cord. This devastating disease usually requires preventive therapy with a range of immunosuppressive medications. There are limited studies informing the use of these medications in children with NMO. This review provides a comprehensive analysis of the published literature on therapeutic interventions in children and adolescents with MS and 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.     

水通道蛋白4启动子基因多态性与多发性硬化、视神经脊髓炎遗传易患性的关系

目的 探讨水通道蛋白4(AQP4)启动子区基因多态性与我国南方多发性硬化(MS)、视神经脊髓炎(NMO)患者血清抗AQP4抗体水平及遗传易患性的关系.方法 收集18例NMO、38例MS、13例复发性脊髓炎(RM)、6例复发性视神经炎(RON)患者及39名对照,PCR扩增AQP4外显子0及外显子1启动子基因(即AQP4-promoter0和AQP4-promoter 1),并行DNA测序.结果 共发现14个AQP4-promoter0及6个AQP4-promoter 1基因多态性位点.血清抗AQP4抗体阳性患者AQP4-promoter 0中-1003 bp多态性位点(A突变为G)发生率比血清抗AQP4抗体阴性患者(13/18与20/45,P=0.046)及对照组(13/18与10/39,P=0.001)高,差异有统计学意义.血清抗AQP4抗体阳性患者及血清抗AQP4抗体阴性患者AQP4-promoter 1中- 401 bp与-400 bp之间多态性位点(插入1个C)发生率均比对照组高(5/16与0/28,P=0.008; 8/38与0/28,P=0.027),差异有统计学意义.NMO及MS患者-1003bp多态性位点及-401 bp与-400 bp之间多态性位点发生率均比对照组高,差异有统计学意义(NMO:11/18与10/39,P=0.010;4/15与0/28,P=0.020;MS:19/38与10/39,P=0.027;8/34与0/28,P=0.018).结论 AQP4启动子区基因存在多态性位点,且与NMO、MS易患性有一定的关系;AQP4外显子0启动子中- 1003 bp多态性位点可能与血清抗AQP4抗体的出现有关.     

Comparison of olfactory function between neuromyelitis optica and multiple sclerosis

Objectives: Olfactory dysfunction (ODF) has been reported in patients with neuromyelitis optica (NMO) and multiple sclerosis (MS). However, the comparison of olfactory function and olfactory-related gray matter (GM) between patients with NMO and MS needed to be further elucidated.

Materials and methods: Thirty-seven patients with NMO and 37 with MS were enrolled. Olfactory function was evaluated with a Japanese T&T olfactometer test kit, and the neuroanatomical features of olfactory-related GM were assessed using voxel-based morphometry.

Results: Olfactory deficits were found in 51.4% of patients with NMO and 40.5% of patients with MS. Patients with NMO with ODF had significantly smaller olfactory bulbs than patients with MS with ODF (p = 0.031). Olfactory-related GM atrophy was found in patients with NMO in several regions of the right orbitofrontal cortex and right superior frontal gyrus; in patients with MS, reduced GM volume was found in the right parahippocampal gyrus and piriform cortex (p < 0.05, cluster size > 200 voxels).

Conclusions: Olfactory deficits are common in both NMO and MS. However, the neuroanatomical features related to olfactory deficits differ greatly between the two diseases.     

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.     

视神经脊髓炎患者33例脑部磁共振分析

目的 探讨视神经脊髓炎(neuromyelitis optica,NMO)患者脑部MRI影像学表现.方法 收集满足最新NMO诊断标准且脑部MRI表现不符合多发性硬化诊断标准的患者33例,均行脑部和脊髓MRI检查,分析其MRI影像学特点.结果 33例NMO中,脑部正常表现者5例(15.2%),异常表现28例(84.8%),其中脑内实质有明确病灶22例(66.7%),另6例(18.2%)脑内虽未见明确病灶,但深部脑白质显示了肉眼可视的对称性弥漫性脱髓鞘高信号影.22例明确病灶中,15例病灶数≥2个,7例为单个病灶.幕上近皮质、皮质下和深部脑白质区的点状非特异性病灶最多,少数为非典型的斑片状融合病灶.幕下脑干是易受累的部位(14/33,42.4%),特别是延髓(7/33,21.2%).结论 NMO患者出现脑内异常较为常见,有脑部的异常不能排除NMO的诊断.认识NMO脑内病灶对完善NMO诊断标准有帮助.     

急性播散性脑脊髓炎、多发性硬化及视神经脊髓炎脑深部灰质病灶MRI影像比较

目的 探讨并比较急性播散性脑脊髓炎(ADEM)、多发性硬化(MS)及视神经脊髓炎(NMO)脑深部灰质病灶的MRI影像学特征. 方法 自2004年8月至2012年10月在中山大学附属第三医院神经内科住院的ADEM、MS、NMO患者共353例,筛选出其中MRI显示有脑深部灰质病灶者95例(包括ADEM 12例,MS 60例,NMO 23例),对这些病灶的大小、数量、部位等特征进行分析. 结果 3组患者丘脑、尾状核、苍白球受累的病例数比例比较差异均无统计学意义(P=0.154,P=0.438,P=0.697).ADEM组壳核受累的病例数比例明显高于MS组、NMO组,差异有统计学意义(P=0.002,P=0.013).NMO组下丘脑受累的病例数比例则明显高于ADEM组、MS组,差异有统计学意义(P=0.033,P=0.001).ADEM组丘脑的病灶直径明显大于NMO组,差异有统计学意义(P=0.027),但和MS组相比差异无统计学意义(P=0.116),而MS组和NMO组丘脑的病灶直径比较差异亦无统计学意义(P=0.209).3组尾状核、壳核、苍白球、下丘脑的病灶直径比较差异均无统计学意义(P＞0.05).3组的病灶分布对称性比较差异无统计学意义(P=0.335). 结论 丘脑受累对于ADEM和MS的鉴别诊断可能意义不大,壳核受累可能是将ADEM区别于MS和NMO的一个鉴别点,下丘脑受累是NMO的特异性表现.病灶直径大小在这三种疾病的鉴别诊断中价值不大.     

视神经脊髓炎脊髓磁共振成像特征

目的 比较视神经脊髓炎(NMO)与多发性硬化(MS)的脊髓MRI特点,从MBI的角度重新认识NMO.方法 对20例MS患者和23例NMO患者的脊髓MRI进行同顾性分析.结果 NMO患者脊髓MRI多表现为线样延髓征、线样延髓脊髓征、线样脊髓征、脊髓横贯性或次横贯性损伤,且常超过3个节段(23例),而MS患者脊髓MRI病变节段短(≥3个节段者8例,χ2=19.142,P<0.01),常呈偏心性分布(17例,与NMO组比较,χ2=25.256,P<0.01).结论 NMO不同于MS,在MRI方面,病灶的分布有其自身特征,而MS的脊髓病灶与髓鞘走向一致.因此,我们从影像学角度进一步证实NMO是有异于MS的一种独立的疾病.     

Audiological evidence of therapeutic effect of steroid treatment in neuromyelitis optica with hearing loss

Neuromyelitis optica (NMO) is an autoimmune astrocytopathy caused by anti-aquaporin 4 antibody. Only two patients with NMO have been reported presenting with hearing disorders to our knowledge. We recently treated a 40-year-old woman with NMO complaining of right hearing loss. Audiometry showed minimal asymmetry, but the auditory brainstem responses (ABR) were severely attenuated on the right. The attenuated ABR and her aural symptoms (hearing loss and fullness) improved after steroid treatment. The present case shows that the retrocochlear-type hearing loss may be associated with NMO.     

Differentiation between multiple sclerosis and neuromyelitis optica spectrum disorders by multiparametric quantitative MRI using convolutional neural network

Multiple sclerosis and neuromyelitis optica spectrum disorders are both neuroinflammatory diseases and have overlapping clinical manifestations. We developed a convolutional neural network model that differentiates between the two based on magnetic resonance imaging data. Thirty-five patients with relapsing-remitting multiple sclerosis and eighteen age-, sex-, disease duration-, and Expanded Disease Status Scale-matched patients with anti-aquaporin-4 antibody-positive neuromyelitis optica spectrum disorders were included in this study. All patients were scanned on a 3-T scanner using a multi-dynamic multi-echo sequence that simultaneously measures R1 and R2 relaxation rates and proton density. R1, R2, and proton density maps were analyzed using our convolutional neural network model. To avoid overfitting on a small dataset, we aimed to separate features of images into those specific to an image and those common to the group, based on SqueezeNet. We used only common features for classification. Leave-one-out cross validation was performed to evaluate the performance of the model. The area under the receiver operating characteristic curve of the developed convolutional neural network model for differentiating between the two disorders was 0.859. The sensitivity to multiple sclerosis and neuromyelitis optica spectrum disorders, and accuracy were 80.0%, 83.3%, and 81.1%, respectively. In conclusion, we developed a convolutional neural network model that differentiates between multiple sclerosis and neuromyelitis optica spectrum disorders, and which is designed to avoid overfitting on small training datasets. Our proposed algorithm may facilitate a differential diagnosis of these diseases in clinical practice.     

Serum lipoprotein levels in patients with neuromyelitis optica elevated but had little correlation with clinical presentations

Objective

To explore the relationship between serum lipoproteins and clinical presentations of NMO patients. To investigate the differences of serum lipoprotein levels between NMO and MS patients.

Patients and methods

Serum lipoprotein levels were measured in 56 NMO patients, 53 MS patients and 54 health subjects. Serum lipoprotein levels in all participants and relevant clinical parameters of NMO patients were investigated. Statistical analyses were performed using the SPSS statistical software.

Results

NMO patients had significantly higher serum cholesterol (TC), triglyceride, low-density lipoprotein cholesterol, apolipoprotein B (apoB), lipoprotein (a) levels and TC/HDL-C, apoB/apoA-1 ratios than health control group. NMO patients had significantly higher serum apoB level and apoB/apoA-1 ratio than MS patients. There was little correlation between serum lipoproteins and NMO presentations.

Conclusion

The elevated lipoprotein levels in NMO patients could be just secondary changes with limited value in clinical prediction. However, elevated apoB level and apoB/apoA-1 ratio in NMO might indicate severer disability and might provide some useful information in the differential diagnosis with MS.     

水通道蛋白4抗体检测的方法学比较及其临床意义

目的 比较经典分析法和水通道蛋白4(AQP4)抗体分析法对AQP4抗体检测率的异同,并探讨该抗体对区分中国视神经脊髓炎(NMO)和多发性硬化(MS)患者的诊断准确度.方法 选择44例NMO和46例MS患者的血清,采用经典分析法检测血清中的NMO-IgG(AQP4),AQP4抗体分析法检测血清中AQP4抗体.结果 90份血清中,两种方法检测结果均为阳性的36份,两种方法检测结果均为阴性的45份,经典分析法阳性但AQP4抗体分析法阴性血清4份,AQP4抗体分析法阳性但经典分析法阴性血清5份,2种方法的阳性率、阴性率差异无统计学意义(P=1.000).2种方法一致性检验Kappa=0.798,P=0.000.经典分析法检测NMO患者NMO-IgG的灵敏度为77.3%,阳性预测值85.0%,特异度87.0%,阴性预测值87.0%,诊断正确率为82.2%,Youden指数74.3%.AQP4抗体分析法检测NMO患者AQP4抗体的灵敏度为88.6%,阳性预测值95.1%,特异度95.7%,阴性预测值89.8%,诊断正确率为92.2%,Youden指数84.3%.结论 两种AQP4抗体检测方法对区分MS与NMO都具有高灵敏度与特异度,但是抗AQP4抗体分析法对NMO诊断具有更高的诊断准确性,值得推广.     

多发性硬化、视神经脊髓炎患者血清及脑脊液中脑源性神经营养因子与胶质细胞源性神经营养因子水平

目的 探讨多发性硬化(MS)、视神经脊髓炎(NMO)患者血清及脑脊液中脑源性神经营养因子(BDNF)、胶质细胞源性神经营养因子(GDNF)水平及其神经保护作用.方法 对62例MS、NMO患者及21例对照者进行研究,患者组复发期进行扩展残疾状态量表(EDSS)评分、MRI检查及寡克隆带测定,液相芯片分析技术检测血清及脑脊液BDNF、GDNF浓度.结果 MS、NMO患者复发期血清及脑脊液BDNF(μg/L,MS患者:5.616±0.650、0.186±0.012;NMO患者6.584±0.929、0.176±0.006)、GDNF浓度(μg/L,MS患者:0.039、0.080;NMO患者0.029、0.050)与对照组(μg/L,血清:4.374±0.501、0.040;脑脊液:0.152±0.011、0.065)比较差异无统计学意义;脑脊液BDNF与GDNF浓度水平呈正相关(r=0.756,P=0.000),血清BDNF与GDNF浓度水平呈负相关(r=-0.329,P=0.018).血清及脑脊液BDNF、GDNF浓度与EDSS评分、血脑屏障指数、Delpech指数及Tourtellotte合成率无明显相关性.有或无脑萎缩的MS、NMO患者血清及腩脊液BDNF、GDNF浓度差异无统计学意义.结论 MS、NMO患者体内BDNF与GDNF水平相关,二者可能具有协同的神经保护作用.BDNF及GDNF与NMO、MS患者血脑屏障破坏及中枢神经系统内IgG合成无关,与神经功能残疾及脑萎缩的关系仍需研究.     

视神经脊髓炎脑脊液改变的特点

目的　分析视神经脊髓炎 (NMO)患者的脑脊液 (CSF)改变特征。方法　对 56例NMO患者的临床资料 ,66次腰穿CSF检查结果进行分析。结果　①NMO分为单纯型和复发型 ;CSF细胞数在两型都有轻度增高 ,但单纯型同时多伴有全身炎症反应 ,复发型多不伴发急性炎症 ;②两型均有蛋白轻中度增高 ;③CSF中IgG在复发型增高 ,尤其以发展为多发性硬化 (MS)者显著 ;④蛋白 细胞分离现象仅见于NMO两型患者 ,MS者无此现象 ;⑤CSF细胞学检查两型均无特异性。结论　利用CSF特点对NMO两型患者及发展为MS者可进行诊断、鉴别诊断和治疗指导