多发性硬化患者血清维生素D水平变化及与临床相关性研究

目的观察多发性硬化(MS)患者体内维生素D水平,探讨维生素D水平与MS临床表型的关系。方法收集MS患者72例,包括复发缓解型MS(RRMS)62例、继发进展型MS(SPMS)7例及原发进展型MS(PPMS)3例;视神经脊髓炎(NMO)患者24例;以32名健康体检者为健康对照组(NC组)。采用电化学发光法对血清25-羟维生素D_3[25-hydroxyvitamin D_3,25(OH)D_3]进行检测,所有MS患者在留取血标本的同时进行扩展残疾状态量表(EDSS)评分,对其中15例急性复发期RRMS患者在缓解期再次行血清25(OH)D_3检测和EDSS评分。结果 MS组、NC组及NMO组间血清25(OH)D_3水平比较差异有统计学意义(F=10.55,P0.01),MS组及NMO组均低于NC组(分别P0.01,P0.05),但MS组与NMO组相比差异无统计学意义(P0.05);SPMS患者血清25(OH)D_3水平低于NC组(P0.01),但与RRMS患者比较无统计学差异(P0.05);RRMS患者血清25(OH)D_3水平缓解期高于急性复发期(t=2.92,P0.05),但仍低于NC组(P0.01)。结论 MS及NMO患者体内维生素D不足,且维生素D不足贯穿于MS的不同病程阶段,RRMS患者急性复发期维生素D不足更为明显。     

多发性硬化患者外周血T淋巴细胞受体β链可变区多态性研究

目的探讨多发性硬化(MS)不同阶段外周血T淋巴细胞受体β链可变区(TCRVβ)多态性的特点。方法收集首都医科大学宣武医院神经内科临床孤立综合征(CIS)患者30例、复发-缓解型多发性硬化(RRMS)患者40例、继发-进展型多发性硬化(SPMS)患者10例、健康对照者30名,经TCRVβ单克隆抗体标记后采用流式细胞仪分析各组外周血TCRVβ扩增程度以及TCRVβ24个亚家族扩增患者百分比、扩增片段所占百分比的差异。结果 CIS、RRMS及SPMS组TCRVβ存在扩增患者比例、扩增个数和扩增分数均高于对照组(P0.01),而CIS、RRMS及SPMS组间比较无统计学差异(P0.05)。CIS、RRMS及SPMS组CD4+TCRVβ2扩增频率均高于对照组(P0.008),CIS组、RRMS及SPMS组CD8+TCRVβ11表达水平均低于对照组(P0.05),SPMS组CD4+TCRVβ21.3表达水平低于CIS组(P0.05)。ROC曲线分析提示CD8+TCRVβ11的扩增片段所占百分比对MS诊断具有一定价值,对MS分型无诊断价值;CD4+TCRVβ21.3的扩增片段所占百分比对SPMS诊断具有一定价值。结论可通过检测部分TCRVβ片段对MS及SPMS的早期诊断提供相关依据。     

多发性硬化与认知功能障碍

多发性硬化(multiple Sclerosis, MS)是中枢神经系统最常见的脱髓鞘疾病,常分为复发-缓解型(RRMS)、原发进展型(PPMS)及继发进展型(SPMS)三种类型.MS不仅可以导致患者躯体残疾,还常常造成不同程度认知功能损害.提高临床医师对MS认知障碍的认识,并及早采取有效的干预措施,可有效改善MS患者的预后.     

多发性硬化患者糖皮质激素受体蛋白和mRNA表达与激素疗效的相关性

目的 检测多发性硬化(MS)患者外周血单个核细胞(PBMC)中糖皮质激素受体(GR)蛋白与mRNA亚型:GRα mRNA、GRβ mRNA的表达,探讨GR蛋白和GRα mRNA、GRβ mRNA的表达与甲泼尼龙静脉冲击治疗(IVMP)疗效间的关系.方法 采用放射配体结合法测定20例缓解复发型MS(RRMS)、6例继发进展型MS(SPMS)及26名健康对照GR蛋白数量;采用半定量逆转录聚合酶链反应法测定GRα mRNA、GRβ mRNA的表达,使用扩展残疾状态量表(EDSS)评价IVMP疗效.结果 (1)IVMP前RRMS和SPMS患者GR蛋白数量分别为(3.8±0.2)×103位点/细胞和(1.6±0.2)×103位点/细胞,均显著低于健康对照组[(4.2±0.8)×103位点/细胞,P＜0.05].RRMS患者IVMP前GR蛋白数量与EDSS呈线性负相关(r=-0.441,P=0.015).(2)以磷酸甘油醛脱氢酶的表达作为内参照,RRMS患者GRα mRNA的表达水平(0.792±0.177)与健康对照组(0.805±0.158)差异无统计学意义,而SPMS患者的表达水平(0.315±0.129)明显低于健康对照(P＜0.05).(3)RRMS和SPMS患者PBMC中均有GRβ mRNA的表达,健康对照组未检出GRβ mRNA表达.(4)RRMS、SPMS患者GRβ mRNA的表达分别占各自GRα mRNA的43.98%±2.40%和140.01%±78.75%.结论 RRMS患者GRβ mRNA的低水平表达不影响IVMP疗效.SPMS患者GRα mRNA表达水平显著降低和(或)GRβ mRNA表达水平显著升高导致GC抵抗.     

吸烟对多发性硬化病人病情进展影响

目的探讨吸烟对多发性硬化(MS)病人病情进展的影响。方法从2005-01～2010-12,随访三所医院364例临床诊断为MS的病人,分为吸烟组、戒烟组和非吸烟组,根据临床和磁共振成像(MRI)特点,比较各组转化为继发进展型MS的比例、脑实质分数(BPF)和T2高密度病灶体积变化。结果吸烟组与非吸烟组相比,扩展残疾状态量表评分(EDSS)和多发性硬化严重程度评分(MSSS)增加,从复发缓解型MS(RRMS)向继发进展型MS(SPMS)的转化较快,T2加权病灶体积增加,BPF减少。结论研究提示吸烟对MS进展有不利影响,吸烟可加速RRMS向SPMS的转化。     

多发性硬化病人脑脊液中肥大细胞类胰蛋白酶升高

肥大细胞在调节血管通透性方面起了关键作用。被确定为人体肥大细胞特异性介质的有组织胺(其代谢产物为甲基组胺)、蛋白水解酶、类胰蛋白酶等。本文实验证明MS病人CSF类胰蛋白酶升高。 55例临床确诊的MS,其中缓解复发型MS(RRMS)31例、慢性进行性MS(CPMS)24例。年龄18～62岁,男21、女34例;43例其它脑疾病如脑血管病、脑肿瘤病人作为对照组。常规腰穿、取CSF,以     

多发性硬化与慢性脑脊髓静脉功能不全

多发性硬化(Multiple sclerosis, MS)是病因未明的中枢神经系统炎性脱髓鞘疾病,通常把MS分为4种亚型:即复发缓解型MS(Relapsing-remitting MS,RRMS)、继发进展型MS(Secondary-progressive MS,SPMS)、原发进展型MS(Primary-progressive MS,PPMS)及进展复发型MS(Progressive-relapsing MS,PRMS),其中RRMS最为常见约占80%～85%.核磁共振静脉成像[1]和尸体解剖研究[2]发现MS病灶分布与颅内静脉系统相关.Zamboni等提出慢性脑脊髓静脉功能不全(Chronic cerebrospinal venous insufficiency, CCSVI)可能参与了多发性硬化的发生发展[3～5],对传统MS的病因提出了挑战,为治疗提供了新途径,本文将对其观点进行综述.     

多发性硬化血清麻疹、风疹和水痘-带状疱疹病毒IgG抗体水平及临床意义

目的通过检测多发性硬化(Multiple sclerosis,MS)患者血清中麻疹病毒、风疹病毒和水痘-带状疱疹病毒的免疫球蛋白G(Immunoglobulin G,IgG)抗体浓度,并进行扩展残疾状态量表(Expanded disability status scale,EDSS)评分,探讨上述病毒在MS发病中的临床意义及其与临床神经功能缺失的相关性。方法收集2013年9月-2015年2月郑州大学第一附属医院神经内科收治的50例MS患者急性期(复发期)的血清标本,其中临床孤立综合征(CIS亚组)22例,复发-缓解型MS(RRMS亚组)28例,对照组收集同一时期我院体检结果正常的37例健康志愿者的血清标本。采用双抗体夹心酶联免疫吸附方法(Enzyme linked immunosorbent assay,ELISA)测定并比较血清中3种病毒IgG抗体的浓度,分析血清中各病毒抗体水平与EDSS评分的相关性。结果 (1)MS病例组麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体的血清浓度高于对照组,差异具有统计学意义(P0.05);(2)CIS亚组患者血清中麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体水平低于RRMS亚组,EDSS评分亦低于RRMS亚组,差异均具有统计学意义(P0.05);(3)MS病例组血清中麻疹病毒、风疹病毒、水痘-带状疱疹病毒IgG抗体与EDSS评分无相关性(P0.05)。结论 MS患者血清中的麻疹病毒、风疹病毒和水痘-带状疱疹病毒可能不仅与MS的发病相关,而且与疾病的复发有关。     

多发性硬化患者生活质量评估及其影响因素探讨

目的评估多发性硬化患者生活质量水平,并探讨其影响因素。方法收集2012年7月~2016年12月就诊于河南省人民医院复发缓解型多发性硬化患者(relapsing-remitting MS,RRMS)36例,继发进展性多发性硬化患者(secondary progressive MS,SPMS)21例作为研究对象。采用多发性硬化生活质量54项评分(Multiple Sclerosis Quality of Life-54 instrument,MSQo L-54)测试MS患者的生活质量;对所有研究对象进行认知功能、抑郁状态、疲劳、睡眠质量及日常生活能力评估。结果 (1)RRMS组及SPMS组患者躯体生活质量(RRMS组58.62±16.32;SPMS组28.77±15.99,P=0.000)、精神生活质量(RRMS组57.33±16.72;SPMS组36.27±23.50,P=0.000)均有下降,SPMS组下降更明显。多元逐步回归法分析,与MS生活质量相关因素中,Hamilton抑郁量表评分处于第一位(β=-0.516,P<0.001),其次为反应躯体化残疾程度的EDSS评分(β=-0.372,P<0.001),第三位为疲劳评分(β=-0.250,P=0.002)。结论 MS患者有不同程度的生活质量下降,SPMS患者更明显。EDSS评分、抑郁、疲劳影响患者生活质量,早期干预抑郁及疲劳,对于改善MS患者生活质量有益。     

多发性硬化患者糖皮质激素受体和甲基强的松龙疗效的关系

目的比较复发-缓解型多发性硬化(RRMS)、继发-进展型多发性硬化(SPMS)患者激素冲击治疗前、中、后外周血单核细胞(PBMC)中糖皮质激素受体(GR)蛋白含量和健康对照组的差异及其与甲基强的松龙(MP)疗效的关系。方法采用放射配体结合法测定45例健康成人、30例RRMS和6例SPMS患者PBMC中GR蛋白含量;使用扩展残疾状态量表(EDSS)评价MP疗效。结果(1)治疗前RRMS和SPMS患者的GR蛋白含量分别为(3765.83±1053.24)位点/细胞和(1599.67±448.79)位点/细胞,均低于健康对照组[(4249.09±616.10)位点/细胞](P<0.05);治疗中,RRMS和SPMS患者的GR蛋白含量分别为(3127.57±970.06)位点/细胞和(1219.67±346.27)位点/细胞,两者较治疗前均有下调(P<0.05);治疗后RRMS患者的GR蛋白含量上升至(4487.20±1473.18)位点/细胞,与健康对照组差异无统计学意义(P>0.05),而SPMS患者的GR蛋白含量上升至(3115.50±868.83)位点/细胞,但仍低于健康对照组(P<0.05)。(2)RRMS患者治疗后EDSS降至(2.70±1.80)分,与治疗前的(3.97±1.76)分相比差异有统计学意义(P<0.05);SPMS患者治疗后EDSS为(6.25±2.73)分与治疗前的(6.92±1.93)分之间差异无统计学意义(P>0.05)。(3)RRMS患者治疗前、后GR蛋白含量与同时期EDSS评分之间呈明显线性负相关(P<0.05)。结论GR蛋白含量的降低可能与MS的发生和发展有关,MP冲击治疗中症状一过性加重与GR蛋白含量下降相关,RRMS患者GR蛋白含量与MP的疗效相关。     

Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis

Verbeek MM, Notting EA, Faas B, Claessens‐Linskens R, Jongen PJH. Increased cerebrospinal fluid chitotriosidase index in patients with multiple sclerosis.
Acta Neurol Scand: 2010: 121: 309–314.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – To investigate chitotriosidase (CTTS) activity in serum and cerebrospinal fluid (CSF) in multiple sclerosis (MS) patients in relation to disease course and CSF markers for immune activation or inflammation. Materials and methods – We studied 80 patients with relapsing–remitting MS (RRMS), 24 with secondary progressive MS (SPMS), 20 with primary progressive MS (PPMS) and 29 patients with other neurological disorders (OND). We measured CTTS activity and studied the correlation with CSF mononuclear cell count (MNC) and intrathecal IgG production. Results – CTTS activity was significantly higher in CSF, but not in serum, from the total MS group compared with OND and controls. In RRMS and SPMS CTTS, index was increased compared with controls (RRMS, 0.10 ± 0.21; SPMS, 0.10 ± 0.15; controls, 0.021 ± 0.020), but not in PPMS (0.061 ± 0.052). CTTS index was higher in MS patients with elevated MNC or CSF‐restricted oligoclonal IgG bands than in MS patients without these CSF findings. Conclusions – CTTS index is elevated in RRMS and SPMS. The CTTS index is related to CSF markers of inflammation or immune activation.     

Evaluation of the clinical utility of cerebrospinal fluid (CSF) indices of inflammatory markers in multiple sclerosis

OBJECTIVES: Accumulating evidence indicates significant heterogeneity in MS and soluble (s) adhesion molecules are postulated as markers of disease activity. We sought to evaluate intrathecal production of these and other molecules across the clinical spectrum of MS. METHODS: CSF indices of IgG, sICAM-1, sVCAM-1, sE-selectin and sCD30 were calculated in 17 primary progressive (PPMS) patients, 15 secondary progressive patients (SPMS), 28 relapsing-remitting patients in relapse (RRMSR) and 14 RRMS patients in remission (RRMSNR) using commercially available ELISA kits. Patients had not received any immunomodulating therapy within the previous 6 months. MS patients were compared with 44 patients with non-inflammatory neurological diseases (NINDs). RESULTS: The most sensitive CSF index at a 90% level of specificity was for IgG which had 93% sensitivity in RRMSR and 92% sensitivity in RRMSNR. Corresponding sensitivity in PPMS and SPMS was 71% and 73% respectively. None of the other indices had sensitivity >50% apart from sVCAM-1 (64% in RRMSR and 52% RRMSNR) and sCD30 (53% in PPMS). CONCLUSIONS: Unsurprisingly the strongest association in MS was with the intrathecal production of IgG. Similar results in PPMS and SPMS may reflect comparable rates of progression in these 2 groups. Of the other molecules only intrathecal sVCAM-1 production is significantly associated with MS and only in relapsing-remitting disease.     

Antibodies to sulfatide in cerebrospinal fluid of patients with multiple sclerosis

The identity of target antigen(s) in multiple sclerosis (MS) remains elusive despite much effort to identify it. We analyzed cerebrospinal fluid (CSF) from patients with MS, other neurological diseases (OND), other diseases (OD) and healthy controls for antibodies against purified sulfatide, a major glycosphingolipid of human myelin, by an enzyme-linked immunosorbent assay (ELISA) and a thin-layer chromatogram (TLC)-immunostaining technique. Elevated anti-sulfatide antibodies were significantly higher in MS patients as compared with the OND group (p<0.05) and all controls combined (P<0.025). Binding of high titer antibodies to sulfatide was confirmed with TLC-immunostaining. Anti-sulfatide antibodies were detected in all subtypes of MS although the frequency was higher in patients with secondary progressive MS (SPMS) than in patients with primary progressive (PPMS) and relapsing-remitting MS (RRMS). The data demonstrate a humoral response to sulfatide in the CSF of patients with MS.     

Patients with progressive multiple sclerosis have elevated antibodies to neurofilament subunit

OBJECTIVE: The cause of axonal loss, an important contributor to disability in MS, is poorly understood. This study investigated whether progression in MS is associated with CSF antibodies to the 68-kd light neurofilament subunit (NF-L), an axonal cytoskeletal protein, and compared this with antibodies against tubulin and the heavy neurofilament subunit (NF-H). METHODS: IgG to NF-L, tubulin, and NF-H was measured by immunoassay in matched CSF and serum samples from patients with relapsing-remitting MS (RRMS; n = 39), primary progressive MS (PPMS; n = 10), and secondary progressive MS (SPMS; n = 18); patients with other inflammatory (n = 21) and noninflammatory (n = 40) neurologic diseases; and healthy controls (n = 12). Immunocytochemistry was performed to assess antibody binding to human brain sections, and isoelectric focusing with immunoblotting was performed to assess oligoclonal anti-NF-L production. RESULTS: Intrathecal production of anti-NF-L antibodies was significantly elevated in PPMS and SPMS. In contrast, there were no significant differences in CSF levels of antibodies to tubulin or NF-H between the groups. Anti-NF-L, antitubulin, and anti-NF-H levels correlated with the duration of disease before lumbar puncture and Expanded Disability Status Scale levels. Immunocytochemistry demonstrated binding of CSF or serum antibodies to axonal or neuronal components in six of seven RRMS patients, seven of seven PPMS patients, and eight of 10 SPMS patients tested. Isoelectric focusing demonstrated independent CSF oligoclonal bands reactive with NF-L in six of 13 specimens tested. CONCLUSIONS: Anti-NF-L antibodies seem to be raised in progressive MS and may serve as a marker for axonal loss and disease progression. They may contribute to axonal loss and the accumulation of disability.     

Adhesion molecules in multiple sclerosis: relation to subtypes of disease and methylprednisolone therapy

OBJECTIVES: To determine levels of adhesion molecules in blood and cerebrospinal fluid (CSF) samples from patients with different subtypes and activities of multiple sclerosis (MS) and to assess the effect of intravenous methylprednisolone sodium succinate treatment on the levels of soluble adhesion molecules. DESIGN: The expressions of very late activation antigen 4 (VLA-4), lymphocyte function associated antigen 1 (LFA-1), vascular cell adhesion molecule 1 (VCAM-1), and intercellular adhesion molecule 1 (ICAM-1) were determined immunocytochemically, and levels of soluble VCAM-1, ICAM-1, and E-selectin, by means of enzyme immunoassay technique. The volumes of T2- and T1-weighted MS plaques and brain atrophy were determined by means of the semiautomatic magnetic resonance imaging (MRI) segmentation technique. SETTING: A university hospital in Finland. PATIENTS: One hundred subjects (71 patients with MS and 29 healthy control subjects). The subtypes of MS were relapsing-remitting (RRMS [n = 26]), secondary progressive (SPMS [n = 20]), and primary progressive (PPMS [n = 25]). RESULTS: In patients with RRMS and SPMS, the expressions of VLA-4 and LFA-1 on immune cells from blood were at least 1.5- to 3-fold higher than in controls (RRMS, P = .002 and P<.001, respectively; SPMS, P = .03 and P =.001, respectively). In RRMS, LFA-1 and ICAM-1 expression in blood was more up-regulated than in SPMS (P = .03 and P = .01, respectively). The expressions of adhesion molecules on CSF lymphocytes in RRMS and SPMS were of similar magnitude, but the proportions of CSF VLA-4- and LFA-1-expressing lymphocytes were 3- to 4-fold higher than in controls (P = .04 and P = .008, respectively). The levels of serum soluble VCAM-1 were higher in SPMS than in RRMS (P = .005) or PPMS (P = .04). Intravenous methylprednisolone treatment of patients with RRMS in exacerbation caused a significant reduction in the serum levels of soluble VCAM-1 and E-selectin (P<.001). In SPMS, the volumes of T2-weighted plaques correlated with the serum level of soluble ICAM-1 (r = 0.64; P = .03). CONCLUSIONS: Up-regulated adhesion molecules in blood and CSF indicate sustained potential for inflammation in the CNS throughout the clinical spectrum of MS. Therapies interfering with cell adhesion may be of key importance in suppressing MS.     

N-acetylaspartic acid in cerebrospinal fluid of multiple sclerosis patients determined by gas-chromatography-mass spectrometry

Abstract Background Axonal degeneration is considered to play a major role in the development of clinical disability in multiple sclerosis (MS). N-AcetylAspartic Acid (NAA) is a neuron-specific marker constantly identified in MR-spectroscopy studies of the normal and MS brain. To our knowledge there are no studies available that evaluated NAA in cerebrospinal fluid (CSF) as a possible marker for disease severity. Objective To evaluate CSF concentrations of NAA in MS in relation to disease phenotype, clinical measures of disability and MRI markers of disease burden. Methods NAA concentrations were determined in CSF of 46 patients with MS (26 relapsing remitting (RRMS), 12 secondary progressive (SPMS) and 8 primary progressive (PPMS)). Prior to lumbar puncture, MS-patients underwent MRI and clinical examination, including the Expanded Disability Status Scale (EDSS) and the MS Functional Composite (MSFC). Additionally, CSF concentrations of NAA were determined in 12 patients with other neurological diseases (OND). Results Median CSF NAA concentration was 0.74 (IQR: 0.59–0.94) in RRMS , 0.54 (IQR: 0.35–0.73) in SPMS and 0.83 μmol/l (IQR: 0.56–1.03) in PPMS patients. SPMS patients had a significantly lower NAA concentration than RRMS patients. NAA concentrations correlated with EDSS (r = )0.37, p = 0.016), MSFC (r = 0.41, p = 0.010), normalised brain volume (r = 0.49, p = 0.001), T2 lesion load (r = )0.35, p = 0.021) and black hole lesion load (r = )0.47, p = 0.002). No differences were observed between OND (median: 0.57 IQR: 0.28–0.73) and MS patients. Conclusion CSF NAA concentration in MS patients is related to clinical performance and MRI measures of disease burden and may therefore be an important neuron specific marker of disease severity and possibly progression.     

Interferon-gamma activated calcium influx in peripheral blood lymphocytes from patients with primary and secondary progressive multiple sclerosis.

Interferon-gamma (IFN-gamma) contributes to the early events leading to T cell activation in relapsing-remitting (RR) multiple sclerosis (MS) by activating a transplasmalemma calcium influx, the detection of which is closely associated with clinical and MRI evidence of disease activity. The appearance of this influx represents one of the earliest peripheral events in the pathogenesis of RRMS. It is still questioned whether the same immune mediated mechanisms also operate in primary progressive (PP)MS. Fluorimetric evidence of the IFN-gamma activated calcium influx was sought in 16 patients with PPMS and 39 patients with secondary progressive (SP)MS. To compare peripheral versus CNS evidence of immune activation 11 of the patients with PPMS and 27 of the patients with SPMS underwent gadolinium enhanced brain MRI. The IFN-gamma activated influx was detected in peripheral blood lymphocytes from eight of 16 (50%) patients with PPMS, and 20 of 39 (51%) patients with SPMS, a frequency similar to that previously reported in patients with RRMS during phases of disease stability. Gadolinium enhancing brain MRI lesions were found in only one of 11 (9%) patients with PPMS and 12 of 27 (41%) with SPMS. Our study shows that peripheral blood lymphocytes from patients with PPMS and patients with SPMS express with the same frequency as patients with RRMS, an IFN-gamma dependent intracellular process leading to T cell activation able to trigger disease activity.     

Clinical, MRI, CSF and electrophysiological findings in different stages of multiple sclerosis

Effective therapy in the earliest stages of multiple sclerosis (MS) demands early correct diagnosis. Retrospective analysis included 130 patients (90 women) with a median age of 35.5 years, median duration of the disease of 2 years and median EDSS score of 3.0. Twenty-seven patients had clinically isolated syndrome (CIS) suggestive of MS, 66 relapsing-remitting (RR) MS, 19 secondary progressive (SP) MS and 18 primary progressive (PP) MS. The predominant symptoms were sensory in 52% of the patients with CIS compared to 27% in patients with RRMS, whereas they were more often motor in patients with PPMS. Patients with CIS had higher CSF cell counts than patients diagnosed in later stages of the disease and oligoclonal bands were found in 89% of all patients without statistically significant differences between the subgroups. Prolonged latencies of visual evoked potentials (VEP) were found in only 29% of patients with CIS compared to 66% in RRMS, 75% in SPMS and 65% of PPMS patients. Fifty-six percent of patients with CIS, 88% with RRMS, 74% with SPMS and 78% of patients with PPMS fulfilled modified the Barkhof et al. MRI criteria at the time of diagnosis. Patients in early MS often present with sensory symptoms. Brain MRI can be inconclusive in over 40% of patients with CIS but the elevated CSF cell count and positive oligoclonal bands are helpful in establishing the diagnosis of CIS suggestive of MS. In later stages of the disease the combination of clinical features, MRI, prolonged VEP latencies and positive CSF oligoclonal bands secures the correct diagnosis.     

Serum soluble adhesion molecules in multiple sclerosis: raised sVCAM-1, sICAM-1 and sE-selectin in primary progressive disease

Leucocyte invasion into the central nervous system in multiple sclerosis (MS) is complex, involving T-cell/endothelium interaction dependent upon initial adhesion mediated by molecules such as E-selectin, L-selectin, intracellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Circulating levels of these can be measured by sensitive enzyme-linked immunoassay (ELISA) techniques. To assess whether serum concentrations of soluble adhesion molecules vary across the spectrum of patients with relapsing-remitting (RR), secondary progressive (SP) and primary progressive (PP) MS, we measured circulating levels of soluble (s)E-selectin, sL-selectin, sICAM-1 and sVCAM-1 in serum obtained from 78 PPMS patients, 71 patients with RRMS, 65 patients with SPMS and 66 patients with other neurological disease using commercially available ELISA systems. Levels of serum sVCAM-1 were significantly elevated in PPMS compared with RRMS in remission (P = 0.0001) and in relapse (P = 0.0001), whilst sICAM-1 was significantly elevated in PPMS compared with all other MS groups (vs SPMS, P = 0.006; vs RRMS in relapse, P = 0.003; vs RRMS in remission, P = 0.0001). Serum sE-selectin levels were significantly higher in PPMS compared with all other groups except inflammatory neurological disease (IND) [vs SPMS, P = 0.029; vs RRMS in relapse, P = 0.002; vs RRMS in remission, P = 0.001; vs non-inflammatory neurological disease (NIND), P = 0.002; vs IND, P = 0.076]. In PPMS there was no correlation between levels of any adhesion molecule and disability or disease duration. These results provide evidence for significant immunological heterogeneity in MS and suggest that different leucocyte/endothelial cell interactions may be active in various MS subgroups. It also challenges the hypothesis that PPMS is a less inflammatory form of the disease. Received: 12 January 1998 Received in revised form: 2 June 1998 Accepted: 8 June 1998     

Defective T cell fas function in patients with multiple sclerosis

BACKGROUND: Fas (CD95) triggers programmed cell death and is involved in shutting off the immune response. Inherited deleterious mutations hitting Fas or its signaling pathway cause autoimmune/lymphoproliferative syndrome (ALPS). OBJECTIVE: To assess the possibility that decreased Fas function plays a role in development of MS. METHODS: The authors evaluated Fas function in long-term T cell lines (21 days of culture) from 32 patients with relapsing-remitting MS (RRMS), 15 with secondary progressive MS (SPMS), and 15 with primary progressive MS (PPMS) by assessing cell survival upon Fas triggering by monoclonal antibodies (Mab). RESULTS: Fas-induced cell death was significantly lower in all patient groups than in controls, and lower in SPMS than in RRMS. Moreover, 8/15 patients with PPMS, 10/15 with SPMS, and 8/32 with RRMS were frankly resistant to Fas. Frequency of resistance to Fas-induced cell death was significantly higher in all patient groups than in controls (2/75), and higher in SPMS than in RRMS. The findings that the parents of two Fas-resistant patients were Fas-resistant and that fusion of T cells from two Fas-resistant patients with Fas-sensitive HUT78 cells gave rise to Fas-resistant hybrid lines suggest that Fas-resistance is due to inherited alterations of the Fas signaling pathway, with production of molecules exerting a dominant negative effect on a normal Fas system. CONCLUSIONS: Defects of the immune response shutting-off system may be involved in the pathogenesis of MS, particularly in its progressive evolution.