多发性硬化患者血清和脑脊液Epstein-Barr病毒抗体检测的意义

目的探讨多发性硬化(MS)患者血清和脑脊液(CSF)中EpsteinBarr(EB)病毒IgG抗体检测的意义。方法采用酶联免疫吸附法检测MS患者65例、其他神经科疾病(OND组)患者71例、非神经科疾病(NND组)患者42例的血清和CSF中EB病毒核抗原、壳抗原和早期抗原的IgG抗体,并进行分析比较。根据血清抗体检测结果的组合,分析各组中病毒初次感染、既往感染和病毒重新激活的情况。结果3组患者血清EB病毒核抗原、壳抗原IgG抗体阳性率均>90%,差异无显著性(均P>0.05)。MS组EB病毒早期抗原IgG抗体阳性率(46.2%)明显高于其他两组(18.3%,9.5%,均P<0.05)。MS组病毒感染重新激活的比率(46.2%)明显高于其他两组(18.3%,9.5%,均P<0.05)。3组CSF病毒抗体阳性率差异无显著性(均P>0.05)。结论MS患者活动性的EB病毒感染较多,EB病毒感染重新激活的比例很高。     

皮质类固醇对多发性硬化IgG指数和IgG合成率的影响

采用Beckman免疫化学仪(ICS—Ⅱ),对21例经皮质类固醇(激素)治疗的多发性硬化(MS)患者(治疗组)和19例未经激素治疗的MS患者(未治疗组)进行IgG指数和IgG合成率测定。结果发现:治疗组IgG指数和IgG合成率均明显低于未治疗组,差异有极显著性意义(P<0.01)。用于MS诊断时,治疗组IgG指数和IgG合成率的敏感性亦明显低于未治疗组(P<0.01)。提示激素可降低中枢神经系统内IgG自身合成量,并可降低IgG指数和IgG合成率诊断MS的敏感性。     

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。     

多发性硬化患者头颅磁共振、诱发电位和IgG指数的对比研究

报道43例多发性硬化(MS)患者头颅磁共振成像(MRI)、诱发电位(EP)和IgG指数(IgGIndex)的对比研究结果。发现MRI的检测异常率为81.4％,而VEP仅53.7％、BAEP47.5％、IgGIndex57.5％。MRI在显示空间脱髓鞘方面是最敏感的方法,但VEP、BAEP只要有一项异常即判断为EP异常则其异常率高达79.5％,接近MRI。作者认为三者同时检查可以提高诊断的准确性。     

多发性硬化患者血清及脑脊液的神经节苷酯抗体检测

目的 观察多发性硬化（MS）患者血清及脑脊液（CSF）中神经节苷抗体的分布，研究其在MS发病过程中的作用。方法 采用改良Marcus法检测20例MS患者血清和CSF神经节苷酯抗体的水平。结果 20例MS患者CSF和血清神经节苷酯抗体阳性率分别为75％，65％；和对照组比较均有显著性差异（P＜0．01）。结论 神经节苷酯抗体与参与了MS的发病过程。     

抗心磷脂抗体与多发性硬化

目的　探讨抗心磷脂抗体 ( ACA)与多发性硬化 ( MS)的关系。方法　采用 ELISA方法检测 3 5例活动期MS、45例对照组血清中 ACA-Ig G、ACA-Ig M、ACA-Ig A结合指数 ( BI)。结果　活动期 MS的 ACA-Ig G BI、ACA-Ig M BI、ACA-Ig A BI的均数与对照组相比差异无统计学意义。 MS组中 4例 ACA-Ig G BI、1例 ACA-Ig MBI阳性 ,对照组无一例阳性。MS组阳性率 ( 5 /3 5 ,1 4.2 9% )与对照组 ( 0 /4 5 ,0 % )比较差异有显著性 ( P <0 .0 5 )。视神经脊髓型 MS ACA阳性率 ( 3 /1 3 ,2 3 .0 8% )与非视神经脊髓型 ( 2 /2 2 ,9.0 9% )差异无显著性 ( P >0 .0 5 )。结论　ACA与部分 MS可能存在某种联系 ,但确切的关系尚不清楚 ,尚待积累更多资料进一步探讨。     

多发性硬化患者IgG指数、24 h合成率、组分区带检测的比较

目的 研究IgG指数，24h合成率，组分区带对多发性硬化（MS）患者的临床意义。方法 应用免疫比浊法，等电点聚焦及银染色法进行检测。结果 103例经临床诊断为MS患者中IgG组分区带阳性占90.3%，IgG24h合成率异常占19.4%,IgG指数异常占17.5%。结论 MS患者IgG组分区带阳性率比IgG指数，IgG24h合成率高，对MS有辅助性诊断意义。     

多发性硬化脑苷酯抗体检测

<正> 脑苷酯是一种髓鞘成分,存在于神经元表面,调节多种神经过程。在脱髓鞘的情况下,CSF中各种抗体增加,也包括脑苷酯抗体。为了进一步探讨MS的自身免疫机制,我们检测了MS患者血清和CSF脑苷酯抗体。     

寡克隆区带和IgG指数对多发性硬化的诊断价值

目的　探讨寡克隆区带 (OCB)和IgG指数对多发性硬化 (MS)诊断的敏感性及特异性。方法　收集 4 8例MS、6 8例神经系统炎性疾病 (NID)及 110例非炎性疾病 (NNID) 3组患者的脑脊液 (CSF)和血清标本 ,分别进行OCB的检测 (等电聚焦 )和IgG指数的计算。并对其阳性结果似然比 (PRLR)进行分析。结果　MS组与NID组比较 ,CSF中OCB阳性率和IgG指数异常率的差异均没有显著性 (均P >0 0 5 ) ;但MS组、NID组与NNID组比较 ,差异均有极显著性 (均P <0 0 0 0 1)。MS组CSF中OCB和IgG指数的敏感性分别为 39 6 %、6 0 4 % ;特异性分别为 80 3%、72 1% ;PRLR分别为 2 0、2 2。当用于判断有无IgG鞘内合成时 ,特异性分别为 97 2 %、92 7% ;PRLR分别为 13 5、7 3。结论　CSF中OCB阳性和IgG指数升高强烈提示有中枢神经系统局部IgG合成 ,对MS有一定的辅助诊断价值     

多发性硬化患者血清瘦素水平的变化及其临床意义

目的探讨多发性硬化(MS)患者血清瘦素(leptileptinn)水平的变化及其临床意义。方法采用放射免疫法对31例活动期MS患者、22例缓解期MS患者和40名健康对照者的血清leptin水平进行检测。结果活动期MS患者血清leptin水平显著高于缓解期MS患者和对照组(P<0·01);经过糖皮质激素治疗后活动期MS患者血清leptin水平明显降低(P<0·01),但治疗前血清leptin越高则疗效越差(P<0·01,P<0·01)。结论活动期MS患者血清leptin水平升高,且与MS的疗效及性别具有相关性。leptin水平升高可能与MS的活动性相关,降低血清leptin水平可能是激素治疗MS的一个作用机制。     

Prevalence of antibodies to a human papova virus (BK virus) in subacute sclerosing panencephalitis and multiple sclerosis patients

Summary Sera and cerebrospinal fluids (CSF) from 10 patients with subacute sclerosing panencephalitis (SSPE) were tested for antibodies to the BK virus, a new tentative member of the papovavirus group, in an effort to determine any relationships between BK virus and SSPE and the papova-like virus seen in glial cells of SSPE patients. Serum specimens from a group of 50 multiple sclerosis (MS) patients and from corresponding control groups were also included in the tests. All the CSF samples were antibody negative. The prevalence of antibodies in the SSPE and the MS groups, 70% and 60% respectively, and the distributions of individual titers were similar to those in the corresponding control groups. These results suggest that BK virus probably has no connection with SSPE. Further studies of the etiological role of the BK virus in human diseases and the role of the papova-like virus seen in SSPE patients' brains are needed.

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Zusammenfassung Serum- und Liquorproben von 10 Patienten mit subakuter sklerosierenden Panencephalitis (SSPE) wurden auf Antikörper gegen das BK-Virus, ein neues Glied der Papovavirusgruppe, untersucht, um die mögliche Verbindung des BK-Virus' zu der SSPE und zu dem papovaähnlichen Virus, das in Gliazellen der SSPE-Patienten gesehen worden ist, zu finden. Eine Gruppe von 50 Patienten mit Multipler Sklerose (MS) und ihre Kontrollen wurden auch in die Untersuchungen einbezogen. Keine Antikörper waren in den Liquorproben nachweisbar. In den Seren war es möglich, in 70% in der SSPE-Gruppe und in 60% in der MS-Gruppe beziehungsweise in 70 und 46% in den Kontrollgruppen Antikörper gegen das BK-Virus zu finden. Auch die Verteilung von individuellen Titern in den verschiedenen Gruppen war sehr ähnlich. Diese Untersuchungsergebnisse zeigen, daß das BK-Virus kaum eine Verbindung zu der SSPE hat. Weitere Untersuchungen über die ätiologische Rolle des BK-Virus' in menschlichen Krankheiten und über die Rolle des papovaähnlichen Virus', das im Gehirn der Patienten mit SSPE gesehen worden ist, werden diskutiert.

     

Antibodies against viruses and structural brain components in oligoclonal IgG obtained from multiple sclerosis brain

Summary Immunoglobulin G (IgG) was isolated from three multiple sclerosis (MS) and two control brains by Protein A Sepharose affinity chromatography and was characterized by thin-layer polyacrylamide gel isoelectric focusing (PAG IEF) and antiserum immunofixation. The three MS brains contained oligoclonal IgG. Immunofixation with measles, herpes simplex, varicella, rubella, mumps and cytomegalovirus as antigens and autoradiography revealed that some of the oligoclonal IgG bands separated by PAG IEF contained antibodies against herpes simplex in one, measles in two and varicella virus in all three MS brains. No antibodies were detected with this technique against structural human (crude saline, lipid-proteolipid, ganglioside, and myelin basic protein extracts of MS and normal human brain) and bovine (purified myelin, myelin basic protein and oligodendrocytes of bovine brain) brain components. The finding of viral antibodies and the absence of antibodies against structural brain proteins in oligoclonal MS brain IgG is similar to that previously recorded in MS cerebrospinal fluid (CSF).

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Zusammenfassung Immunoglobulin G, IgG, wurde aus der Gehirnsubstanz von drei Fällen mit multipler Sklerose (MS) und zwei Kontrollen mittels Affinitätschromatographie mit Protein A-Sepharose isoliert. Das IgG wurde mit isoelektrischer Fokussierung in Polyacrylamidgelplatten (PAG IEF) und anschließender Antiserum-Immunofixation charakterisiert. Bei MS wurde oligoklonales IgG gefunden. Mit Hilfe von Antigen-Immunofixation mit Masern, Herpes simplex, Varizellen, Rubella, Parotitis und Zytomegalievirus und nachfolgender Autoradiographie (radioaktive Zweitantikörper gegen die genannten Antigene) konnte gezeigt werden, daß die oligoklonalen Bande in den drei MS-Gehirnen Antikörper gegen Herpes simplex in einem, Masern in zwei und Varizellen-Virus in allen drei Fällen enthielten. Keine solchen Antikörper wurden entdeckt, wenn die Technik für strukturelle Gehirn-Komponenten vom Menschen (einfache physiologische Salz-, Lipid-Proteolipid-, Gangliosid- und basische Myelo-Protein-Extrakte von MS und normalem Gehirn) und vom Rind (gereinigtes Myelin, basisches Myelo-Protein und Oligo-Dendrozyten aus Gehirnrinde) verwendet wurde.

     

IgG ratios and oligoclonal IgG in multiple sclerosis and other neurological disorders

The findings are reported of various CSF abnormalities, including IgG indices and oligoclonal IgG, in 160 patients with multiple sclerosis of differing diagnostic certainty and 146 patients with other neurological disorders.

An abnormal IgG index, defined as the ratio of IgG/albumin in CSF to that in serum, has been found in 77.7% of definite MS cases, falling to a figure of 32.1% in the single lesion group. A tendency, reported previously, for IgG levels to be higher in disabled patients, particularly those with a short history or early onset, has been confirmed.

Oligoclonal IgG, on the other hand, has been found in 56% of definite MS cases, less frequently than in most other reported series. Analysis of the literature suggests considerable variability in the finding of oligoclonal IgG in other than definite MS, and in other neurological disorders. The possibility that subjective factors are partly responsible for this variability, rather than discrepancies in patient selection requires consideration, and suggests that CSF electrophoresis and IgG estimations are complementary aids in the diagnosis of multiple sclerosis.

Differences have been expressed regarding the relationship of oligoclonal IgG to clinical parameters of the disease. Further sequential analysis of the development and variability of the oligoclonal pattern in MS is required.     

The diagnosis of multiple sclerosis and the clinical subtypes

The diagnosis of multiple sclerosis (MS) requires objective findings referable to the central nervous system. A wide differential diagnosis often has to be considered. Magnetic resonance imaging and electrophysiologic and cerebrospinal fluid studies can all contribute to an early definitive diagnosis. The McDonald diagnostic criteria for MS (2005) are the currently recognized MS diagnostic criteria. The clinical subtypes of MS and their diagnosis are discussed in this article. Being informed of the diagnosis may be a stressful experience for the patient and this is also dealt with.     

Isoelectric point restriction of cerebrospinal fluid and serum IgG antibodies to measles virus polypeptides in multiple sclerosis

Thirty consecutive isoelectric point (pI)-discrete IgG fractions were isolated from multiple sclerosis (MS) cerebrospinal fluid (CSF) and used to immune precipitate measles virus (MV) polypeptides. Most basic fractions were enriched in activity against nucleocapsid protein (NP), and to a lesser extent against hemagglutinin (H) protein; intermediate fractions were enriched in activity against H and fusion (F) proteins; and more anodic pI fractions were almost exclusively enriched in activity against the large (L) protein of MV. In MS there are marked differences between CSF and autologous serum in regard to antibody activity to MV. In contrast, there were similar profiles of antibody response to MV proteins in SSPE CSF and serum.     

Complement dependent cytotoxic antibody activity against measles virus in multiple sclerosis

Summary The presence of measles cytotoxic (CT) and hemagglutination inhibiton (HI) antibodies in 195 multiple sclerosis (MS) patients and 251 controls was tested. The measles virus Lu carrier cells labeled with ⁵¹Cr were exposed to serum specimens in the presence of complement in order to test the presence of CT antibody. The analysis of complement dependent CT antibodies against measles virus revealed significantly (P<0.01) higher titers in MS patients than in the control group. However, the measles HI test failed to show this difference. Measles CT titers 1:32 among MS patients occured in 54.9% and in 35.5% among the controls. In comparison with this the HI method revealed measles titers 1:128 more often in the control group than in MS cases (27.9 and 17.9%, respectively). The presence of CT antibodies against measles virus in MS proves that these patients have a functional defence mechanism to eliminate virus infected cells. The high measles antibody titer among MS patients could be due to recurrent antigenic stimulation caused by measles virus persistency. Whether this virus persistency plays a role in MS can not be decided on the available data.Supported by Deutsche Forschungsgemeinschaft (Schwerpunkt Ätiologie und Pathogenese der multiplen Sklerose und verwandter Erkrankungen)     

Physiopathology and treatment of fatigue in multiple sclerosis

Fatigue is a common symptom of patients with multiple sclerosis (MS). It is reported by about one-third of patients, and for many fatigue is the most disabling symptom. Fatigue may be associated with motor disturbances and/or mood disorders, which makes it very difficult to determine whether the fatigue is an aspect of these features or a result per se of the disease. Although peripheral mechanisms have some role in the pathogenesis of fatigue, in MS there are clear indications that the more important role is played by “central” abnormalities. Neurophysiological studies have shown that fatigue does not depend on involvement of the pyramidal tracts and implicate impairment of volitional drive of the descending motor pathways as a physiopathological mechanism. Metabolic abnormalities of the frontal cortex and basal ganglia revealed by positronemission tomography and correlations between fatigue and magnetic resonance imaging lesion burden support this hypothesis. Some recent studies also suggest that pro-inflammatory cytokines contribute to the sense of tiredness. No specific treatments are available. Management strategies include medications, exercise, and behavioural therapy; in most cases a combined approach is appropritate. Received: 26 September 2000, Accepted: 28 September 2000     

Antinuclear antibodies positivity is not rare during multiple sclerosis and is associated with relapsing status and IgG oligoclonal bands positivity

IntroductionAs an immune-mediated disease of the central nervous system, multifaceted aspects of a humoral immune response are widely described during multiple sclerosis (MS). However, the prevalence of different auto-antibodies, such as antinuclear antibodies (ANA), during MS is very variable and their clinical relevance remains controversial. Our aim was to evaluate the prevalence and clinical correlations of ANA positivity in South Tunisian MS patients.Material and methodsWe performed ANA screening using indirect immunofluorescence (IIF) on HEp-2 cells (Biosystems®) in 82 MS patients. For ANA positive samples (titer ≥1/160), anti-ds-DNA detection (IIF on Crithidia luciliae (Biosystems®)) and extractable nuclear antigen typing (immunodot (Euroimmun®)) were performed.ResultsANA were positive in 35/82 MS patients (42.7%). The titer was ≥ 1/320 in 16/35 patients. The antigenic specificity of ANA was identified in 7/35 patients. None of the patients had extra-neurological manifestations. No correlation was found between ANA and age, gender, MS course, disease duration, disability, annual relapse rate nor IgG index. ANA positivity was more frequent in patients with IgG oligoclonal bands (OCB) (47.1%) than in patients without IgG OCB (16,6%) (p = 0.049). Regarding disease activity, ANA positivity was significantly more frequent in patients with relapse (52.6%) than in patients in remission (25.9%) (p = 0.031).ConclusionOur results showed that ANA positivity in MS disease is not rare. This positivity was not associated with clinical expression of any connective tissue disease. ANA occurrence in MS was associated with IgG OCB+ profile and relapsing status, probably reflecting an ongoing immune dysregulation.