T lymphocyte populations in multiple sclerosis

Summary In 36 patients representing different clinical stages of multiple sclerosis (MS) (9 patients with acute exacerbations; 21 patients in remission; 5 patients with chronic progressive MS) determinations of T lymphocyte populations using monoclonal antibodies against surface antigens (OKT3 (pan T cells), OKT4 (helper T cells), OKT8 (cytotoxic/suppressor T cells)) were performed. Compared to the control group (40 healthy individuals) a clear elevation of the T4/T8 ratio was found in acute exacerbations and to a lesser degree in patients with inactive phases of MS. Patients with chronic progressive disease did not show increased T4/T8 ratios. Serial determination of lymphocyte populations after corticosteroid therapy in 10 selected patients revealed no significant changes which could be attribted to this therapeutic modality.Pathogenetic and clinical implications of the shifts in surface antigen expression of T lymphocyte populations mirroring the clinical course of MS are discussed.Deceased in July 1985     

HLA antigens in Italian multiple sclerosis patients

We analyzed HLA-A,-C,-B,-DR and-DQ specificities in 104 Italian multiple sclerosis patients and in 905 healthy controls. The frequencies of HLA-A23, A26, Cw4, DR3 and, especially DR5 antigens were significantly higher in multiple sclerosis patients than in controls. Patients with progressive course were characterized by high frequencies of B7, B8 and DR3 antigens: Cw1 and DRw11 show a negative correlation with the extent of intrathecal IgG production. These data confirm that the HLA system may influence the clinical expression and the immune responses to the disease.

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Sommario Abbiamo analizzato le specificità HLA del locus A, C, B, DR e DQ in 104 pazienti italiani affetti da Sclerosi Multipla e in 905 controlli sani. La frequenza degli antigeni A23, A26, Cw4, DR3 e soprattutto DR5 era aumentata in maniera significativa nei pazienti rispetto ai controlli. I pazienti con decorso progressivo erano caratterizzati da un'alta frequenza degli antigeni B7, B8 e DR3; Cw1 e DRw11 mostravano una correlazione negativa con l'estensione della produzione intratecale di IgG. Questi dati confermano che il sistema HLA può influenzare l'espressione clinica e le risposte immunitarie nella malattia.

     

Disease activity markers in multiple sclerosis. Another look at suppressor cells defined by monoclonal antibodies OKT4, OKT5, and OKT8

Here we report our experience in profiling peripheral blood T-cell subsets with the monoclonal antibodies OKT4, OKT5 , and OKT8. Lymphocyte surface phenotype was measured by automated cytofluorometry. In a population survey, we were unable to detect differences between patients with multiple sclerosis (MS) and control subjects when we compared ratios of lymphocytes of helper cell phenotype (OKT4) to those with suppressor cell phenotype ( OKT5 and OKT8). No differences could be established between patients with stable disease, chronic progressive disease, or those with active disease. In a study of 10 patients followed through an exacerbation, we were also unable to define perturbations in these lymphocyte ratios that correlated with disease activity. Detailed analysis of the fluorescence histogram, which examines the entire spectrum of cell surface fluorescence intensity in a population of lymphocytes, was also not useful in predicting disease activity in these patients. The discrepancies between these data and other reports in the literature are discussed. We propose that these reagents are inadequate indices of disease activity, and that until other monoclonal reagents are developed and studied, the suppressor cell compartment is best assessed by assays of function.     

多发性硬化患者外周血和脑脊液淋巴细胞亚群的观察

用碱性磷酸酶抗酸酶法检查了４６例多发性硬化活动期患者外周血和脑脊液的淋巴细胞亚群。结果显示：活动期ＭＳ者外周血ＣＤ＾＋４，ＣＤ＾＋９细胞较对照组减少，ＣＤ＾＋２５细胞，ＣＤ＾＋４／ＣＤ＾＋８比值较对照组升高。ＣＳＦ中ＣＤ＾４，ＣＤ＾＋２５细胞，ＣＤ＾＋４／ＣＤ＾＋８比值较对照组升高，ＣＤ＾＋８细胞降低，且ＣＳＦ中淋巴亚群均高于自身外周血中的相应细胞。     

Membrane protein antigens in multiple sclerosis

Rabbits were immunized with white matter (WM) membrane fractions isolated from autopsy brain specimens of three patients with multiple sclerosis (MS), and three controls. All the rabbits developed high serum antibody titers to the MS and control WM fractions, as tested by enzyme immunoassay. Antibodies against WM membrane components were analyzed further by immunoprecipitation of radiolabeled WM proteins and subsequent polyacrylamide gradient gel electrophoresis. Antigenic membrane components with molecular weights of 138 000, 111 000, 86 500, 79 600, 69 000, 63 000, 58 000, 53 400, 45 700, 24 500 and 22 300 were found in both MS and control WM. Although there may have been some quantitative differences in these immunogenic proteins of MS and normal WM, no multiple sclerosis-specific membrane antigen could be demonstrated.The hyperimmune anti-WM sera did not precipitate ³⁵S-labeled polypeptides from cells infected with herpes simplex type 1, adeno type 5, measles, mumps, rubella, respiratory syncytial, parainfluenza type 2 or cytomegaloviruses, which suggests that the MS brain WM membrane proteins do not share common antigenic determinants with the viral polypeptides.     

Immunological monitoring of azathioprine treatment in multiple sclerosis patients

Despite the longstanding clinical use of azathioprine as an immunosuppressive agent in multiple sclerosis, little is known about the action of this drug on a number of parameters of putative pathogenic relevance in the disease. Eleven patients with multiple sclerosis, treated with azathioprine 2.5–3 mg/kg per day, and six untreated patients were studied with serial blood sampling for 1 year. The following immunological parameters were investigated: peripheral blood lymphocyte subsets, natural killer activity, serum IgG, IgM, ICAM-1 and tumour necrosis factor alpha (TNF-α). The most relevant changes included a decrease in CD3^–CD56⁺ cells, an increase in CD4⁺CD45RA⁺ cells and a decrease in TNF-α levels only in treated patients, while no changes occurred in untreated patients over a 1-year period. The decrease in TNF-α levels and the increase in “suppressor-inducer” lymphocytes could reduce chronic inflammation in multiple sclerosis, and paralleled an overall favourable clinical response to azathioprine treatment in our patients. Received: 9 July 1996 Received in revised form: 21 October 1996 Accepted: 22 November 1996     

Fas和FasL在多发性硬化患者表达的意义

目的　探讨多发性硬化 (MS)患者外周血淋巴细胞Fas和FasL的表达及其与病情严重程度的关系。方法　采用流式细胞术 (FCM)检测 2 2例复发缓解型MS患者外周血淋巴细胞Fas和FasL的表达情况 ,并选择 1 6例同期住院的非免疫相关性疾病患者作为对照。结果　 (1 )复发期MS患者Fas表达 (1 8 2 5 %± 1 0 69% )均高于缓解期MS患者和对照组 (分别为 1 1 43 %± 6 83 % ,9 68%±5 2 4 % ) ;复发期MS患者FasL表达 (2 79%± 2 47% )亦均高于缓解期MS患者和对照组 (分别为1 0 6 %± 0 58% ,0 76 %± 0 61 % )。 (2 )病损程度为重度的MS患者Fas和FasL的表达 (分别为2 1 63 %± 1 2 74% ,3 51 %± 2 0 6 % )均高于中度的MS患者 (分别为 1 2 82 %± 6 1 5 % ,1 94%±1 1 3 % )。 (3)反复发病的MS患者Fas和FasL的表达 (分别为 1 9 56 %± 8 78% ,3 2 8%± 1 82 % )均高于首次发病的MS患者 (分别为 1 3 63 %± 5 36 % ,2 0 6 %± 0 68% )。 (4)MS患者Fas与FasL表达之间呈正相关 (r=0 51 8,P =0 0 0 3)。结论　Fas和FasL与MS的临床复发、复发次数和病情的严重程度有关 ;Fas和FasL可能参与MS的发病机制     

Hypermetabolism in multiple sclerosis patients

Hypermetabolism, which can lead to wasting syndrome, is well recognized in diseases such as AIDS, cancer, rheumatoid arthritis, sepsis and burns. In these conditions proinflammatory cytokines are thought to be essentially involved. In experimental allergic encephalitis (EAE), which is regarded as an animal model of multiple sclerosis (MS), wasting syndrome and elevated levels of cytokines have also been reported. The aim of this study was to investigate whether hypermetabolism does occur in MS patients. After a 3-day standard diet the basal metabolic rate (BMR) was measured by indirect calorimetry in 20 MS patients and 10 healthy controls. Body composition was assessed using an impedance analyser and lean body mass (LBM) was calculated. Other metabolic disturbances and infectious disease were ruled out by clinical examination and various laboratory tests. Tested by analysis of variance (ANOVA), the BMR corrected for LBM was increased by an average of 6% in the patients group (p < 0.05) as compared to the controls. As far as we know this is the first study demonstrating the presence of hypermetabolism in MS.     

A two-label microfluorometric analysis of the expression of OKT5 and Leu 2a antigens on peripheral blood lymphocytes in patients with multiple sclerosis

Four patients with relapsing-remitting multiple sclerosis (MS) and one control were evaluated serially over a 10-week interval. Peripheral blood lymphocyte (PBL) subsets were enumerated using a double labelling technique, OKT5 and anti-Leu 2a monoclonal antibodies, and FACS IV analysis. Results were correlated with clinically assessed disease activity. Two subsets were identified. Subset 1 is characterized by cells positive for Leu 2a and either weakly positive or negative for OKT5 . Subset 2 was positive for both. Subset 1 was constantly present in both patients and controls while subset 2 was variable in presence and in size. No associations between these subsets and disease activity were made in this preliminary study, however, no acute relapses occurred in this interval. It is postulated that the reason for the differences in results of studies attempting to correlate disease activity with PBL phenotypes as assessed by different monoclonal antibodies may be the result of the suppressor/cytotoxic cell subpopulation being nonhomogeneous for the expression of various cell surface antigens. The technique of multiple labelling of lymphocytes may be useful in defining subsets which correlate more closely with disease activity.     

Rehabilitation for patients with multiple sclerosis?

Summary In the epidemiological area of Southern Lower Saxony 92 patients with clinically definite or probable diagnosis of multiple sclerosis (MS) were interviewed and examined. This group contained a remarkably high percentage of benign cases (52%) in comparison with a sample of hospitalized patients. Neurological examination revealed spasticity and pareses to be the most important disturbances followed by ataxia and bladder/bowel problems.After a mean duration of 18.4 years, 52% received a pension and about 30% were still working full time. The pension was granted too early to 11 patients and vocational rehabilitation services would be required for 13 men.Although only half of the patients had an acceptable income, the socioeconomic situation of the families was adequate in 71%; 80% lived with their own families and could stay there in case more ambulant services were offered. Psychotherapeutic measures are required among these to relieve the stress within the families (present in 42%) and to improve the coping behavior (unsatisfactory in 60%).

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Zusammenfassung Im epidemiologischen Areal Südniedersachsens (1121 km², 256195 Einwohner) waren zum Zeitpunkt der Untersuchung 200 Patienten mit Multipler Sklerose (MS) bekannt. Von den 148 mit klinisch sicherer oder wahrscheinlicher Diagnose konnten 92 zu Hause von einer medizinsoziologischen Arbeitsgruppe interviewt werden. Ein halb standardisierter Fragebogen erfaßte die psychosoziale Lage der Patienten und ihrer Familien. Alle Patienten wurden im selben Zeitraum neurologisch untersucht.Die Hälfte der Patienten hatte einen gutartigen Verlauf (Zunahme des Schweregrades nach Kurtzke um höchstens eine Stufe in 5 Jahren). Spastische Paresen standen bei 70% der Patienten ganz im Vordergrund des Krankheitsbildes, an zweiter Stelle folgte die Ataxie, an dritter die Blasen-/Mastdarmstörungen. Nach einer mittleren Erkrankungsdauer von 18,4 Jahren war etwa noch ein Drittel der Patienten voll berufstätig bzw. konnten ihren Haushalt voll versorgen. 52% der Patienten bezogen Rente. Bei 13 männlichen Kranken wären berufliche Rehabilitationsmaßnahmen sinnvoll.Nur die Hälfte der Patienten hatte ein ausreichendes eigenes Einkommen, aber bei 71% war die finanzielle Lage der Familie zufriedenstellend. In 22 Fällen wäre eine Haushaltshilfe und/oder eine Pflegekraft erforderlich. 80% der Patienten leben in der eigenen Familie und könnten mit entsprechender Hilfe auch dort bleiben.Die familiäre Situation war bei 51 Kranken intakt, bei 27 konfliktbelastet und bei 12 zerrüttet. 7 Patienten waren geschieden. Der Umgang mit der Krankheit konnte bei 37 Patienten als angemessen bezeichnet werden, bei 32 lagen Störungen vor, entweder im Sinne einer zunehmenden Isolierung oder einer resignierten Haltung der Krankheit gegenüber.23 Patienten waren isoliert und resigniert. Es bestand keine Korrelation zwischen dem Schweregrad der Krankheit und der familiären Situation bzw. der Verarbeitung der Krankheit.Aus den Ergebnissen wird ein Bedarfsspektrum abgeleitet, das ambulante Hilfeleistungen für Haushalt und Pflege am wichtigsten erscheinen läßt.

     

多发性硬化患者的认知功能损害

目的研究多发性硬化(multiplesclerosis,MS)患者认知功能损害的形式、特点及相关影响因素,了解认知功能损害对患者生活功能的影响。方法将66例MS患者分为脊髓型和脑/脑脊髓型两组,另外选择健康对照30名,采用神经心理学测验的方法系统评价记忆、语言、信息处理速度、执行功能及整体认知功能,并进行生活功能评定,所有MS患者同时接受头颅及脊髓磁共振成像(MRI)检查。结果神经心理学测试发现,与健康对照组相比,脑/脑脊髓型MS组瞬时记忆和长延迟记忆受损明显(P<0.05),执行功能损害显著(P<0.01),信息处理速度下降(P<0.01)。单纯脊髓型也存在认知功能损害,以执行功能损害及信息处理速度下降为主(P<0.05)。记忆、执行功能等认知功能测验成绩与头颅MRI所见病变相关(r=-0.319～-0.543,P<0.05)。认知功能测验成绩与病程长短、复发次数无明显相关。执行性画钟作业(CLOX)及Stroop测验反应错误数与扩展功能障碍状态量表(EDSS)有相关性(r=-0.325及0.372,P<0.05)。操作性日常生活能力(IADL)及MS生活影响量表(MSIS29)得分与记忆、执行功能等认知测验成绩呈负相关(r=-0.325～-0.537,P<0.05)。结论MS的认知功能损害以记忆、信息处理速度、执行功能为主,整体认知功能及语言功能相对保存。认知功能损害影响患者的生活功能,与病程长短、复发次数无明显相关。     

Problems in diagnosing cranial base meningioma in patients with multiple sclerosis

Abstract. A 49-year-old patient had been suffering from the relapsing-remitting form of multiple sclerosis since the age of 23. Attacks of the disease appeared every 2 years in the form of right-sided hemiparesis, vertigo, and problems in maintaining balance. The symptoms disappeared after treatment. At the age 32 retrobulbar inflammation of the second cranial nerve appeared with visual acuity weakness. The symptoms disappeared after treatment. At the age of 42, bilateral weakness of visual acuity appeared and then epileptic attacks occurred. After surgical treatment of meningioma the symptoms disappeared. Only the features of a psychoorganic syndrome remained. The following attack of MS appeared 2 years after surgical intervention. MRI of the head disclosed numerous demyelinating foci.     

Plasma copeptin levels in patients with multiple sclerosis

We compared copeptin levels in relapsing-remitting multiple sclerosis (RRMS) patients with controls and investigated how plasma copeptin levels were changed with the disease period.Thirty patients with RRMS without a prior attack in the last twelve months, and 19 RRMS patients with a clinical acute attack and 30 healthy individuals were included into the study.Copeptin levels were significantly higher in all RRMS patient groups than healthy controls. Plasma copeptin levels were higher in patients in remission period compared with relapse period of 19 RRMS patients with an acute attack.We consider copeptin can be used as a potential biomarker for RRMS.     

多发性硬化患者外周血单个核细胞转录因子Sp3基因的缺陷表达

目的：研究我国多发性硬化（MS）病人外周血单个核细胞（PBMC）转录因子Sp3基因表达情况及其与临床相关性。方法：采用反转录－聚合酶链反应（RT－PCR）技术，经2对引物扩增，检测了33例MS、30例非免疫 性其他神经系统疾病对照、30例神经系统其他自身免疫性疾病对照和30名健康对照组者PBMC的Sp3基因表达。结果：Sp3基因表达缺如，MS患者组（45％，15／33）明显高于其他3组（依次为16％，5／30，6％，2／30；10％，3／10，P均（＜0．01），可自Sp3表达阴性MS患者的DNA中扩增出相应Sp3片段。Sp3表达阴性MS患者改良的伤残状态量表（EDSS）评分显著高于表达阳性者。脑脊液的IgG24h合成率和血清可溶性白细胞介素－2受全稍高，4例MS患者治疗前病情重和治疗后病情轻时相比，未见其Sp3基因表达有明显变化。结果：汉 MS病人PBMC中有Sp3表达缺陷，Sp3阴性患者残疾程度和免疫功能紊乱程度明显高于阳性者，作 为转录调节因子Sp3的表达缺乏可能与免疫控制的异常启动有关。     

Anomalous lymphocyte-antigen reaction in relatives of multiple sclerosis patients

Summary A combined familial study of multiple sclerosis (MS) in England and in the Rostock area of the GDR using the macrophage electrophoretic mobility (MEM)-LAD test embracing 132 relatives has revealed a closely similar pattern of distribution of anomalous LAD (LInoleic Acid Depression) values in relatives (77% type of reaction) to that originally reported in the British study. The anomaly is predominantly associated with females—all mothers of MS patients being affected, whilst daughters and sisters are also represented. In addition unusual full MS type of reaction (90% reduction) has been found in some children related to patients. There is clearly a genetic element in the development of MS probably manifested in the inborn mishandling of unsaturated fatty acids suggested by Thompson; no recognizable pattern of inheritance is noticeable even within the combined material. There is evidence that the metabolic anomaly alone does not inevitably lead to MS, and the full abnormality may be present at an early age. A survey about the examinations and a selection of characteristic family trees of MS are given, illustrating the manner in which the 77% type anomaly is distributed with occasional omission of a generation.

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Zusammenfassung Bei der Multiplen Sklerose (MS) ergaben Untersuchungen mit dem Makrophagen-Elektrophorese-Mobilitäts-(MEM-)LAD-Test an 132 Familienmitgliedern (kombiniert aus England und dem Rostocker Bereich der DDR) ein gleichartiges Muster der Verteilung eines anomalen LAD(linoleic acid depression)- Wertes (Typ der 77%-Reaktion) bei Angehörigen, wie in der vorangegangenen britischen Studie. Die Anomalie erwies sich als vorwiegend an das weibliche Geschlecht gebunden: alle Mütter der MS-Patienten waren betroffen, jedoch auch eine große Anzahl der Töchter und Schwestern boten derartige Werte. Außerdem konnte bei Kindern einiger Patienten ein MS-Typ der Reaktion (über 90% Reduktion) ermittelt werden. Im ganzen muß ein deutlicher genetischer Faktor für die Entstehung der MS angenommen werden — möglicherweise basierend auf der von Thompson erörterten angeborenen Störung im Bereich der ungesättigten Fettsäuren. Insgesamt war zwischen dem vorliegenden kombinierten Untersuchungsmaterial kein weiterer Unterschied der Erblichkeit feststellbar. Es bestanden fernerhin Anzeichen für eine nicht allein durch die metabolische Abweichung bedingte unvermeidliche Entwicklung einer MS sowie dafür, daß die Anomalie bereits im frühen Lebensalter voll ausgeprägt sein kann. In einer Übersicht wurden die Ergebnisse angeführt, des weiteren erfolgte die Darlegung einiger charakteristischer Stammbäume, welche die Form der Verteilung der Anomalie vom 77%-Typ (mit gelegentlichem Überspringen einer Generation) in den Familien mit einer MS zeigt.

     

Cell-mediated immunity to viral antigens and tuberculin in multiple sclerosis

Lymphocyte transformation responses to measles, mumps, herpes simplex and parainfluenza virus antigens and purified protein derivative of tuberculin were determined in both 78 normal controls and 40 patients with multiple sclerosis, 16 of whom were studied serially.
Patients with multiple sclerosis showed significantly reduced responses to all antigens except herpes simplex. Impaired responses occurred at all stages of clinical activity, but were lowest during recovery from an acute exacerbation or in patients with chronic disease. The transformation responses to measles, mumps and parainfluenza virus antigens correlated significantly with the numbers of circulating T cells, which, similarly, showed parallel fluctuations with disease activity.     

Autoantibodies against pituitary peptides in sera from patients with multiple sclerosis

Autoantibodies against pituitary peptides were demonstrated in sera from multiple sclerosis (MS) patients. Ten patients with lupus erythematosus disseminatus (SLE) and 97 healthy blood donors served as controls. The sera were used as primary antibodies in the indirect immuno-enzyme cytochemical (IEC) method, with fixed, paraffin-embedded rat brains and rat and hog pituitaries as antigen substrates. Eleven of the 33 MS sera reacted with peptides in the neural lobe/hypothalamic nuclei or distal lobe. The MS had a significantly higher incidence of peptide antibodies than sera from controls (11/33 vs 9/97). The mean antibody titers were significantly different (1577 vs 333). Comparison with rabbit reference antibodies specific to each of the 6 distal lobe hormones showed that the 9 distal lobe-positive MS sera reacted with cells harboring peptides of the somatotropin family. The presence of peptide autoantibodies was not related to clinical status or medical treatment. No antibodies against pituitary peptides were found in the SLE sera. One of the 11 positive MS sera showed antibodies against gastric parietal cells. None of the 11 sera showed antibodies against muscle, mitochondria, thyroid, adrenal, or parotid antigens. We propose that in a proportion of patients with MS, these autoantibodies might be involved in the demyelinization process by interfering with the peptide/receptor interplay, thus placing MS as a disease in analogy with myasthenia gravis. Alternatively, these autoantibodies might be involved in the altered immunoregulation of MS or be secondary to the disease.     

多发性硬化患者CD8+记忆性T细胞亚群穿孔素和颗粒酶-B表达的研究

目的 测定多发性硬化(MS)患者外周血中CD8+记忆性T细胞亚群效应细胞因子的表达,并将其与MS病情严重程度进行相关分析.方法 利用四色-流式细胞术检测未经治疗的MS患者、其他神经系统疾病(OND)患者和正常对照(NC)成员组外周血表达穿孔素和颗粒酶-B的CD8+记忆性T细胞亚群数量,并利用扩展的残疾状况量表(EDSS)对MS患者病情严重程度做评分.结果 与NC组比较,MS患者外周血表达颗粒酶-B的CD8+效应记忆性T细胞(TEM)和终末效应记忆性T细胞(TerTEM)均明显减少,比较差异有统计学意义(P＜0.05);表达穿孔素和颗粒酶-B的TEM数量与EDSS呈负相关(r=-0.493,P=0.027;r=-0.594,P=0.009).结论 CD8+TEM参与MS相关的CNS内炎性免疫应答,外周血穿孔素和颗粒酶-B表达阳性的CD8+TEM数量可在一定程度上反映MS患者CNS的病损程度.     

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.     

Choreoathetosis in multiple sclerosis

Extrapyramidal symptoms are extremely rare in multiple sclerosis. We examined a patient with a ten year history of multiple sclerosis, who developed choreoathetoid movements of both upper extremities. To our knowledge this is the second case report of this association.