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.     

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     

High serum neurofilament levels among Chinese patients with aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders

BackgroundSerum neurofilament light chain (sNfL) is a promising biomarker for neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS), but there is limited validation data in specific ethnic and disease groups.ObjectiveTo investigate the levels of sNfL in a cohort of Chinese patients with NMOSD and compare sNfL levels in patients with different disease courses and treatments.MethodsWe analysed sNfL levels in 153 Chinese patients with NMOSD (n = 51) and MS (n = 102) using single-molecule array (Simoa) technology. The sNfL levels were compared with those of 71 healthy controls from two centres in southern China. For each disease, we assessed correlations between sNfL and disease phases and treatments.ResultsHigher levels of sNfL were found in the patients with NMOSD [17.97 (10.55–27.94) pg/mL] and MS [15.83 (8.92–25.67) pg/mL] compared to healthy controls [10.09 (7.19–13.29) pg/mL, p < 0.001]. No significant differences were found between the AQP4-IgG-positive NMOSD group and OCB-positive MS group.ConclusionssNfL measured by Simoa technology is a potential candidate blood biomarker for the diagnosis and disease monitoring of NMOSD in Chinese patients, warranting further prospective and multicentre studies.     

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.     

Prominent brainstem symptoms/signs in patients with neuromyelitis optica in a Taiwanese population

Neuromyelitis optica (NMO) is a severe demyelinating disease defined principally by its selective effect on the optic nerves and spinal cord. Contemporary diagnostic criteria require an absence of any clinical disease outside the optic nerve or spinal cord. However, we frequently encounter patients with NMO who have previously undetected symptomatic brainstem lesions. We investigated the brainstem symptoms/signs in patients with NMO and their corresponding MRI findings in a Taiwanese population. We evaluated the clinical symptoms/signs, anti-aquaporin-4 antibody titer and corresponding brain MRI of 49 patients with NMO; results were obtained from chart reviews and during clinical visits. A total of 18 (37%) patients with NMO had brainstem symptoms/signs, including diplopia (n = 9, 50%), prolonged hiccup and poor appetite (n = 9, 50%). For these patients, most of their brainstem events occurred during the first demyelinating attack in their NMO course. A higher percentage (77.8%) of patients with brainstem NMO had brain lesions with specific NMO patterns, including lesions involving the hypothalamus (n = 6, 33.3%), midbrain or pons (n = 8, 44.4%), periaqueductal regions (n = 5, 27.7%), and medulla (n = 10, 55.6%). Brainstem symptoms/signs and characteristic NMO imaging findings are common in Taiwanese patients with NMO, and should be considered a part of the illness in addition to optic neuritis and myelitis.     

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.     

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。     

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。     

吸烟与多发性硬化和视神经脊髓炎谱系疾病发病风险关联性研究

研究背景既往研究提示吸烟可以增加多发性硬化发病风险,但与视神经脊髓炎谱系疾病发病风险的关联性研究少见,本研究探讨吸烟与多发性硬化和视神经脊髓炎谱系疾病发病风险的关联性,以探讨吸烟是否增加上述两种疾病的发病风险。方法采用调查问卷和电话随访方式记录53例多发性硬化患者、62例视神经脊髓炎患者和85例正常对照者的吸烟暴露情况,包括开始吸烟年龄、吸烟持续时间、每日吸烟量和累积吸烟量,以及受试者配偶、父母是否吸烟,是否存在职业暴露。结果最终获得有效调查问卷和电话随访者156例(包括39例多发性硬化患者、43例视神经脊髓炎谱系疾病患者和74例正常对照者),与不主动吸烟者(被动吸烟和不吸烟)相比,主动吸烟者发生多发性硬化(OR=10.800,95%CI:2.202~52.975;P=0.001)和视神经脊髓炎谱系疾病(OR=5.838,95%CI:1.123~30.357;P=0.050)的风险增加;与不吸烟者相比,吸烟者(主动吸烟和被动吸烟)发生多发性硬化(OR=3.444,95%CI:1.491~7.953;P=0.003)和视神经脊髓炎谱系疾病(OR=2.370,95%CI:1.039~5.407;P=0.038)的风险增加;与男性不吸烟者相比,男性吸烟者仅多发性硬化的发病风险增加(OR=15.000,95%CI:2.239~100.483;P=0.005)。结论吸烟可以增加多发性硬化的发病风险,但是否增加视神经脊髓炎谱系疾病的发病风险尚不明确。     

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.     

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.     

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.     

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.     

Recent insights into the pathology of multiple sclerosis and neuromyelitis optica

Multiple sclerosis (MS) is the most common inflammatory demyelinating disease of the central nervous system. Traditionally, demyelinating lesions in the white matter have been regarded as the most important pathological feature in MS, but recent pathological and imaging studies confirmed substantial changes in grey matter and normal-appearing white matter. MS lesions are characterized by inflammation, demyelination, axonal damage and astrogliosis. During early MS lesion formation acute axonal injury is extensive and correlates with inflammation. In addition to focal lesions, diffuse wide-spread changes including neuroaxonal degeneration and compartmentalized inflammation are likely to contribute to increasing disability in progressive MS. Neuromyelitis optica (NMO) is classically characterized by severe transverse myelitis and optic neuritis, but brain lesions are also present in the majority of NMO patients. The discovery of the NMO-specific antibody demonstrated that NMO is a disease entity distinct from MS. This antibody binds to aquaporin-4 expressed in astrocytes and ependymal cells. NMO lesions are characterized by inflammation, demyelination, axonal damage and a marked loss of aquaporin-4. Early NMO lesions demonstrate a pronounced humoral inflammatory response and astrocytic cell death with loss of aquaporin-4, followed by inflammatory demyelination and axonal damage. These recent findings contribute to a better understanding of different mechanisms leading to inflammatory demyelination.     

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。     

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.     

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     

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.     

NMO-IgG检测及其临床意义

视神经脊髓炎是主要累及视神经和脊髓的自身免疫性炎性脱髓鞘疾病。自2004年在视神经脊髓炎患者血清中发现特异性抗体NMO-IgG以来,相继发现其作用靶点是广泛分布于视神经、脊髓、脑室周围区域的水通道蛋白4(AQP4),故亦称之为AQP4抗体。NMO-IgG对视神经脊髓炎的诊断与鉴别诊断,以及对疾病活动性、药物疗效和预后评价均具有重要临床意义。近年基于组织、细胞和蛋白质测定的多种方法应用于血清或脑脊液NMO-IgG检测,本文拟对不同检测方法之进展和临床意义进行概述。