脑脊液寡克隆区带在多发性硬化和视神经脊髓炎中的应用

目的探讨脑脊液寡克隆区带在多发性硬化和视神经脊髓炎2组疾病中的应用价值。方法通过等电聚焦电泳加免疫固定染色的实验室方法检测多发性硬化和视神经脊髓炎2组患者的脑脊液寡克隆区带,比较2组疾病的脑脊液寡克隆区带特点。结果多发性硬化患者共120例,其中脑脊液寡克隆区带阳性39例,阳性率为32.5%;视神经脊髓炎患者共45例,其中脑脊液寡克隆区带阳性4例,阳性率为8.9%。多发性硬化组脑脊液寡克隆区带阳性率明显高于视神经脊髓炎组,差异有统计学意义(P=0.002)。结论本结果对2组疾病的鉴别诊断具有一定的指导意义,且支持多发性硬化和视神经脊髓炎发病机制不同的观点。     

脑脊液寡克隆区带对多发性硬化的意义

目的探讨脑脊液寡克隆区带(oligoclonal bands,OCB)在多发性硬化(multiple sclerosis,MS)中的意义。方法收集神经系统疾病患者895例,其中MS患者151例,视神经脊髓炎(neuromyelitis optica,NMO)患者92例,其他神经系统脱髓鞘疾病(other demyelinating diseases,ODD)患者122例,其他神经系统炎性疾病(other inflammatory neurological diseases,IND)患者99例,神经系统非炎性疾病(noninflammatory neurologicaldiseases group,NIND)患者431例。检测所有患者的OCB、IgG指数及24hIgG合成率,比较各组OCB阳性、IgG指数及24hIgG合成率升高情况,并比较OCB阳性和阴性MS患者的主要临床特点。结果 OCB阳性率MS组为32.45%,NMO组为20.65%,ODD组为18.03%,IND组为16.16%,NIND组为2.09%;IgG指数升高比例MS组为29.8%,NMO组为17.39%,ODD组为16.39%,IND组为15.15%,NIND组为1.62%;24hIgG合成率升高比例MS组为30.46%,NMO组为18.48%,ODD组为18.85%,IND组为19.19%,NIND组为1.39%。OCB阳性率、IgG指数和24hIgG合成率升高比例MS组均高于其他各组(均P<0.05);NMO组与ODD组、IND组的OCB阳性率、IgG指数和24hIgG合成率升高比例无统计学差异(均P>0.05);MS组、NMO组、ODD组及IND组OCB阳性率均高于NIND组(均P=0.000)。OCB阳性MS患者的女性比例、EDSS评分、IgG指数和24hIgG合成率〔分别为女∶男2.5∶1、(4.10±1.49)、(0.81±0.31)、(4.98±3.35)〕均高于OCB阴性患者〔分别为女∶男1.17∶1、(3.47±1.39)、(0.51±0.17)、(3.37±3.20)〕(均P<0.05)。结论与其他中枢神经系统疾病相比,MS患者的OCB阳性率更高。OCB阳性MS患者的女性比例、EDSS评分、IgG指数和24hIgG合成率均高于OCB阴性患者。     

多发性硬化脑脊液寡克隆区带的研究进展

<正> 脑脊液(cerebrospinal fluid,CSF)寡克隆区带(oligoclonalbands,OB)的出现是诊断多发性硬化(multiple sclerosis,MS)的一项指标,提示中枢神经系统内存在体液免疫反应,是检测中枢神经系统亚急性、慢性炎性病变鞘内免疫球蛋白合成的最     

寡克隆区带和IgG指数在多发性硬化中的诊断意义

目的研究寡克隆区带（OCBs）和IgG指数（IgGI）对多发性硬化（MS）诊断的敏感性及其影响因素。方法用等电聚焦结合银染色法检测30例MS、40例神经系统炎性疾病（NID）和22例神经系统非炎性疾病（NNID）患者CSF中OCBs，并计算IgG I。结果MS组和NID组比较OCBs阳性率、IgG I异常率均无显著性差异（P〉0．05）；MS组、NID组与NNID组比较。差异均有显著性（P〈0．05）；传统型MS和脊髓型MS比较，差异均无显著性（P〉0．05）。OCBs对MS诊断的敏感性、特异性和阳性结果似然比分别为63．3％、77．7％和2．8；IgG I分别为40．0％、76．7％和1．7。结论本地区MSOCBs阳性率和IgG I异常率较低，可能与遗传背景、疾病类型和药物应用有关，OCBs和IgG I对MS诊断具有相对特异性。     

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。     

多发性硬化和格林巴利综合征脑脊液细胞学及寡克隆区带测定的临床意义

用改进的聚丙烯酰胺凝胶电泳法对９０例神经系统患者脑脊液行寡克隆区带测定同时行细胞学检查。出现寡克隆区带阳性率分别为多发性硬化症（ＭＳ）５２．９％（９例），格林巴利（ＧＢＳ）（５７％），明显高于脊髓病（６％）和其它病变组（７％）。用Ｘ２检验做各组间率的比较均有明显差异。脑脊液细胞学（ＣＳＦ—Ｃ）检查总阳性率为５１．１％（４６例），其中ＭＳ１１例（６４．７％），ＧＢＳ异常２０例（６６．７％）。细胞学检查异常改变与寡克隆区带阳性有密切关系，呈正相关性。揭示ＭＳ和ＧＢＳ患者中枢神经系统有免疫功能异常。笔者认为同时行脑脊液寡克隆区带和ＣＳＦ—Ｃ检查对ＭＳ和ＧＢＳ的早期诊断有一定价值。     

等电聚焦电泳联合免疫印迹法检测寡克隆区带诊断神经系统炎性脱髓鞘疾病

目的 探讨等电聚焦电泳(IEF)联合免疫印迹法检测寡克隆区带(OB)在神经系统炎性脱髓鞘疾病(IDD)中的应用.方法 IEF联合免疫印迹法检测112例IDD及24例神经系统非炎性疾病(NIND)患者血清和脑脊液中OB,并进行对比分析.结果 与视神经脊髓炎(5/21,23.8%,x2=32.679)、急性播散性脑脊髓炎(1/4,Fisher精确检验)、系统性自身免疫病继发中枢神经系统IDD(3/19,15.8%,x2=37.425)、周围神经系统IDD(0,x2=51.944)和NIND(0,x2=51.944)患者比较,多发性硬化(MS)患者脑脊液OB阳性率(44/46,91.7%)显著升高(P＜0.01).IEF联合免疫印迹法检测OB诊断MS的敏感度为91.7%,特异度为89.8%,高于其他检测方法.2例急性播散性脑脊髓炎患者和1例MS患者血清和脑脊液OB有相同条带,呈"镜像分布".结论 IEF联合免疫印迹法检测OB在MS诊断中具有一定的临床价值.

Abstract：

Objective To explore the diagnostic value of oligoclonal band (OB) detected by isoelectric focusing (IEF) with immunoblotting in inflammatory demyelinating diseases (IDD) in nervous system.Methods Serum and cerebrospinal fluid (CSF) OB was detected by IEF with immunoblotting in 112 patients with IDD ( multiple sclerosis ( MS):n = 48;neuromyelitis optica ( NMO):n = 21:acute disseminated encephalomyelitis ( ADEM):n = 4;secondary IDD from systemic autoimmune diseases:n = 19;peripheral nervous system IDD:n =20) and 24 patients with non-inflammatory neurological disease (NIND).Results CSF-restricted OB was detected in 91.7% (44/48) of MS patients,23.8% (5/21) of NMO patients(x2nmO vs MS= 32.679),1/4 of ADEM patients (Fisher' s excact test),15.8% (3/19) of secondary IDD patients (x2secondary IDD vs MS = 37.425 ),0 of peripheral nervous system IDD patients (x2peripheral nervous system IDD vs MS =37.425) and 0 of NIND patients (x2NIND vs MS =37.425).MS patients had significantly higher percentage of patients with CSF-restricted OB ( all P ＜0.01),compared with NIND and other IDD patients.The sensitivity and specificity of OB detected by IEF with immunoblotting for MS were 91.7% and 89.8%,which were higher than that of OB detected by other methods.Identical serum and CSF OB ( "mirror pattern" ) was detected in 2 of 4 ADEM patients and 1 of 48 MS patients.Conclusion IEF with immunoblotting to detect OB is a reliable method of diagnosis for MS.     

CSF寡克隆区带对多发性硬化的诊断意义

目的:琼脂糖等电聚焦结合双抗体过氧化物酶标记、亲和素-生物素放大技术检测CSF寡克隆区带,研究该方法的敏感性和特异性。方法:琼脂糖等电聚焦结合双抗体过氧化物酶标记、亲和素-生物素放大技术检测21例MS患者、42例神经系统炎性疾病(NID)患者和19例神经系统非炎性疾病(NNID)患者的CSF及对照血清。结果:MS患者寡克隆区带阳性率为47.6%,诊断特异性为98.4%,MS组与NID组、NNID组的差异均有统计学意义(P<0.0125)。结论:该方法敏感、特异,是MS临床诊断最有价值的免疫学指标。我国MS患者寡克隆区带的阳性率较欧美地区低,但与亚洲一些国家及我国的台湾和香港地区接近,阳性率差异可能与东西方MS患者的免疫遗传背景不同有关。     

等电聚焦结合双抗体过氧化物酶标记、亲和素-生物素放大技术检测CSF寡克隆区带

目的琼脂糖等电聚焦结合双抗体过氧化物酶标记、亲和素-生物素放大技术检测CSF寡克隆区带,研究该方法的敏感性和特异性。方法琼脂糖等电聚焦结合双抗体过氧化物酶标记、亲和素-生物素放大技术检测21例多发性硬化(MS)患者、42例神经系统炎性疾病(NID)患者和19例神经系统非炎性疾病(NNID)患者的CSF及对照血清。结果MS患者寡克隆区带阳性率为47．6％,MS组与NID组、NNID组的差异均有统计学意义(P<0．0125)。结论该方法敏感,是MS临床诊断有价值的免疫学指标。我国MS患者寡克隆区带的阳性率较欧美地区低,但与亚洲一些国家及我国的台湾和香港地区接近,阳性率差异可能与东西方MS患者的免疫遗传背景不同有关。     

脑脊液寡克隆区带和核磁共振检查对多发性硬化的临床诊断价值

目的：探讨脑脊液寡克隆区带CSFOB和头颅MRI的变化对诊断多发性硬化（MS）的临床价值。方法：对25例怀疑多发性硬化（MS）的患者进行脑脊液的寡克隆区带和头颅MRI的检查，研究两者和MS间的关系。结果：确诊多发性硬化的患者均有脑脊液的寡克隆带和头颅核磁共振（头MRI）异常。结论：脑脊液寡克隆带和头MRI两者结合对诊断发硬化（MS）有重要监床价值。     

Oligoclonal bands in cerebrospinal fluid: a comparative study of isoelectric focusing, agarose gel electrophoresis and IgG index

OBJECTIVE: To compare the sensitivity and specificity of isoelectric focusing (IEF) with immunofixation, agarose gel electrophoresis (AGE) and the IgG index in detecting intrathecally synthesized IgG in multiple sclerosis (MS) and in other nervous system disorders. MATERIALS AND METHODS: Cerebrospinal fluid (CSF) and serum from 147 patients with various nervous system diseases, 20 of whom had MS, were compared with IEF, AGE and the IgG index. RESULTS: CSF-restricted oligoclonal bands (OCB) were found in 20 of 20 patients with MS using IEF and in 9 of 20 using AGE. OCB were found in 12 patients with other nervous system disorders (OND) using IEF and 4 using AGE. The mean IgG index was 0.50 in OND and 0.96 in MS (P< 0.0001). Of 20 MS patients, 9 had an IgG index above the defined cut-off value of 0.72. CONCLUSIONS: IEF is about twice as sensitive as AGE in detecting OCB in MS. IEF is also far superior to the IgG index in determining intrathecal IgG synthesis.     

Two subtypes of optic-spinal form of multiple sclerosis in Japan: clinical and laboratory features

Abstract Seventy-seven cases of the optic-spinal form of multiple sclerosis (OSMS) were collected from 6 institutes in 3 cities of Japan, and the clinical and MRI features were analyzed. Two-thirds of the OSMS patients had longitudinally extensive spinal cord MRI lesions (LESL), and had clinical features similar to those of relapsing neuromyelitis optica which often causes severe disability. In contrast, OSMS patients without LESL tended to have milder disease and had some feature commonly seen in the conventional form of MS. The percentage of OSMS without LESL in total OSMS has recently been increasing. The present study suggests that LESL is crucially important for distinguishing the two subtypes of OSMS.     

Isoelectric focusing is superior to immunofixation electrophoresis in diagnosing CNS inflammation

BACKGROUND: A sensitive method to detect intrathecal IgG production is important in diagnosing inflammatory central nervous system (CNS) diseases, including multiple sclerosis (MS). OBJECTIVE: To compare cerebrospinal fluid (CSF) electrophoresis with isoelectric focusing (IEF), immunofixation-peroxidase electrophoresis (IFPE) and high-resolution agarose electrophoresis with protein-staining (HRAGE). METHODS: Paired serum and CSF samples from 307 consecutive patients attending a general neurology clinic were examined with IEF, IFPE and HRAGE. Clinical diagnosis was based on review of the patients' medical records after an average of 4 years. RESULTS: The sensitivity for detecting any inflammatory (autoimmune or infectious) CNS disease (52 patients) was 67% for IEF, 50% for IFPE and 29% for HRAGE. The sensitivity for detecting MS (14 patients) was 93%, 86% and 29% respectively. The sensitivity for detecting clinically isolated syndrome (eight patients) was 75%, 25% and 13% respectively. The number of oligoclonal bands in IEF was higher in inflammatory than in non-inflammatory neurological diseases or symptoms, but similar in MS and other inflammatory diseases. CONCLUSION: IEF is the method of choice in diagnosing intrathecal IgG synthesis.     

Bilateral and recurrent optic neuritis in multiple sclerosis

Burman J, Raininko R, Fagius J. Bilateral and recurrent optic neuritis in multiple sclerosis.
Acta Neurol Scand: 2011: 123: 207–210.
© 2010 John Wiley & Sons A/S. Objective – To assess the frequency of bilateral and recurrent optic neuritis (ON) in multiple sclerosis (MS) and to compare these results with epidemiological data of ON in neuromyelitis optica (NMO) and recurrent ON without other signs of disease. Methods – We identified 472 patients with diagnosis of MS from the Swedish Multiple Sclerosis Register. These patients were evaluated for the presence of ON and whether the ON was the presenting symptom of MS; unilateral or bilateral; monophasic or recurrent. Results – Twenty‐one percent presented with ON as their first manifestation of MS. The proportion of patients developing a second attack of ON before demonstration of other manifestations of MS was 5.5% and the frequency of recurrent bilateral ON as the presenting symptom was 3.8%. Only two patients presented with simultaneously appearing bilateral ON corresponding to 0.42%. Conclusion – Recurrent ON, whether unilateral or bilateral, is a common presentation of MS. As MS is a much more common disease than NMO, care must be taken when evaluating the work‐up of patients with recurrent ON. In some cases repeated MRI and lumbar punctures are warranted to improve diagnostic accuracy, even in the presence of the serological marker NMO‐IgG.     

Magnetization Transfer Magnetic Resonance Imaging in the Assessment of Neurological Diseases

In several white matter diseases of the central nervous system (CNS), and in particular in multiple sclerosis, conventional magnetic resonance imaging (MRI) has proved to be sensitive for detecting lesions and their changes over time. However, conventional MRI is not able to characterize and quantify the tissue damage within and outside such lesions. Magnetization transfer MRI (MT-MRI) is a quantitative MRI technique with the potential to overcome this limitation and, as a consequence, to provide additional information about the nature and the extent of tissue damage. Metrics derived from MT-MRI can quantify the structural changes occurring within and outside lesions visible on conventional MRI scans. The present review summarizes the major contributions given by MT-MRI to provide an accurate in vivo picture of the heterogeneity of CNS pathology and, ultimately, to improve our ability to monitor the evolution of various neurological conditions.     

视神经脊髓炎临床与病理

目的：分析视神经脊髓炎（NMO）的特征。方法：对114例NMO患者的临床资料,3例尸检结果,28例随访情况进行研究。结果：该病患者男女之比为1：2．5,发病年龄以12－50岁居多（85％）,急性和亚急性起病占大多数（74．84％）,视神经症状为首发占58．77％,视神经与脊髓症状的间隔时间在1年内者60例,占52．33％。脊髓以横贯性损害为主,有95例（83．33％）,以胸段损害最多（64．33％）,尸体解剖例2、3为NMO;病程中有缓解－复发者65例,其中有14例发展为多发性硬化,包括尸体解剖例1。结论：NMO有两种类型;复发型中有一小部分可发展成为MS,MRI,脑干视觉诱发电位和长期随访有利于NMO和MS的鉴别。     

Immunoperoxidase staining of cerebrospinal fluid IgG in isoelectric focusing gels: a sensitive new technique

An isoelectric focusing (IEF) technique using direct peroxidase or peroxidase-antiperoxidase (PAP) overlay staining for detection of cerebrospinal fluid (CSF) oligoclonal IgG is described. The method involves chemical fixation of all proteins in the gel followed by application of peroxidase coupled antiserum as a specific stain. The direct peroxidase system is 4 times and the PAP system 8 times as sensitive as Coomassie blue staining after standard IEF or Coomassie blue staining of immunofixed gels. As little as 0.5 microgram (direct peroxidase) or 0.3 microgram (PAP) of IgG can be detected. Direct peroxidase staining of IgG in IEF gels can be used to examine unconcentrated CSF, with banding patterns similar to those obtained by Coomassie blue staining after standard IEF of concentrated CSF.     

CSF proteins in neurological disorders analyzed by immobilized PH gradient isoelectric focusing using narrow PH gradients

We analyzed 352 paired CSF and serum samples with isoelectric focusing and immobilized pH gradients (IPG-IEF) using three different gradients. All MS patients (n = 35) had several (from 5 to 30) oligoclonal bands (OBs) in the CSF and most of them had few (from 1-8) OBs in serum. 54.5% patients with CNS infections (n = 12) had oligoclocal bands. OBs in these patients were fewer in number and located at the more acidic pH region compared with the MS samples. Also, corresponding serum bands were more often recognized. We suggest that IPG-IEF improves the diagnostic evaluation of the oligoclonal band pattern. The possibility of the use of extremely narrow gradients makes it a valuable tool for the analysis of selective proteins in various disorders.     

Silver staining of cerebrospinal fluid IgG in isoelectric focusing gels

A silver staining technique to be used on isoelectric focusing (IEF) gels for cerebrospinal fluid (CSF) oligoclonal IgG bands is described. The technique provides a sensitivity for detection of greater than 0.17 micrograms of IgG. The additional use of immunofixation with anti-human IgG antiserum rather than chemical fixation improves the sensitivity two-fold and permits identification of the oligoclonal bands as IgG. The technique enables one to focus small volumes of unconcentrated CSF (less than 40 microliters) and provides a powerful research tool.     

Intrathecal synthesis of free immunoglobulin light chains in multiple sclerosis

Objective – The detection of oligoclonal immunoglobulin free light chains (FLC) in the diagnosis of multiple sclerosis (MS) was compared to IgG isoelectric focusing. Material and methods – Cerebrospinal fluid and serum samples from 69 patients with possible first attacks of MS, 50 patients with clinically definite MS (CDMS), and 118 patients with other neurological diseases (OND) were analyzed. IgG and FLC oligoclonal bands were detected by isoelectric focusing and immunoperoxidase staining. Results – Intrathecal synthesis of IgG, kappa FLC, and lambda FLC oligoclonal bands, respectively, was seen in 92%, 92%, and 86% of MS patients; in 61%, 62%, and 64% of patients with possible first attacks of MS; and in 3%, 3%, and 8% of the patients with OND. In control patients without IgG synthesis intrathecal lambda FLC synthesis was more common than kappa FLC synthesis ( P =0.03). Conclusion – Kappa FLC detection proved as useful as IgG analysis for the laboratory diagnosis of MS whereas the presence of intrathecal lambda FLC synthesis was less specific.