环孢菌素治疗用激素类药无效的多发性硬化

目的探讨环孢菌素（ＣｓＡ）治疗用激素类无效的多发性硬化（ＭＳ）的效果。方法对激素等治疗５个月以上病情无明显好转或仍在加重的１０例ＭＳ，用ＣｓＡ５ｍｇ·ｋｇ－１·ｄ－１，疗程至少２个月，然后根据病情逐渐减量，最后小剂量维持用药。统计各个治疗期及最后随访（６～３２个月后）的扩充致残量表（ＥＤＳＳ）评分和脑ＭＲＩ病灶数。结果激素治疗前后ＥＤＳＳ差异无显著性意义（Ｐ＞０．２０）；ＣｓＡ足量治疗使ＥＤＳＳ评分下降及脑ＭＲＩ病灶数减少（Ｐ＜０．０５）；最后随访ＥＤＳＳ评分进一步下降（Ｐ＜０．０１），其中４例复查了ＭＲＩ，３例病灶数进一步减少。ＣｓＡ治疗未见严重毒副作用。结论ＣｓＡ可治疗用激素类无效的ＭＳ。     

肿瘤坏死因子α基因多态性与多发性硬化的相关性研究

目的:研究肿瘤坏死因子α(TNFα)基因多态性与多发性硬化(MS)的相关性。方法:①采用聚合酶链式反应-限制性片段长度多态性(PCR-RFLP)技术对58例MS患者和79名健康人进行TNFα基因多态性分析。②对MS组患者分别进行扩展病残状态评分(expanded disability status scale,EDSS)、首次发病年龄、病程、发病次数临床资料收集。结果:①MS组TNFα基因型分布及等位基因频率与正常对照组比较均无明显差异(χ2=0.466,P=0.495;χ2=0.229,P=0.632)。②基因型为TNFα1/1、TNFα1/2、TNFα2/2的EDSS评分、首次发病年龄、病程及发病次数各组间比较差异均无统计学意义(F=0.53,P=0.5914;F=1.34,P=0.2699;F=0.37,P=0.6914;F=0.49,P=0.6182)。结论:TNFα等位基因多态性与MS的易患性、EDSS评分、首次发病年龄、病程及发病次数均无显著相关性。     

Predictors for Employment Status in People With Multiple Sclerosis: A 10-Year Longitudinal Observational Study

Objective

To identify predictors for employment status after 10 years in a cohort of people with multiple sclerosis (MS), with the aim to increase knowledge concerning factors present at an early stage that are important for working life and work-life balance.

Information processing characteristics in subtypes of multiple sclerosis

The purpose of this study was to evaluate information processing characteristics in patients with multiple sclerosis (MS). We selected 53 patients with MS and 58 matched healthy controls. Using computerized tests, we investigated focused, divided, sustained attention, and executive function, and attempted to pinpoint deficits in attentional control to peripheral or central processing stages. The results substantiate the hypothesis that the slowing of attention-demanding (controlled) information processing underlying more complex cognitive skills is general, i.e. irrespective of type of controlled processing, with MS patients being 40% slower than controls. MS patients may suffer from focused, and divided and sustained attention deficits, as well as from compromised central processing stages, with secondary progressive (SP) patients showing the most extensive range of deficits, closely followed by primary progressive (PP) patients, while relapsing-remitting (RR) patients appear to be much less affected. General slowing appears to be highest in PP and SP type MS patients (50% slower) versus relapsing-remitting MS (24% slower). In contrast to most previous results, (complex) processing speed appeared to be robustly correlated with severity of MS as measured by the expanded disability status scale and with disease duration. Patients did much less differ in accuracy of processing from controls, suggesting the importance of using time strategies in planning everyday life and job activities to compensate for or alleviate MS-related speed handicaps.     

Natural interferon-β treatment of relapsing—remitting and secondary-progressive multiple sclerosis patients. A two-year study

OBJECTIVES: To evaluate clinical and MRI effects of natural interferon beta treatment in both relapsing-remitting (RR) and secondary-progressive (SP) multiple sclerosis patients. MATERIAL AND METHODS: A double-blind, randomized trial of natural interferon beta (nIFN-beta) in 58 ambulatory patients with RR and 40 with SP multiple sclerosis. Forty-nine patients (29 RR and 20 SP) were treated with intramuscular nIFN-beta6 MIU three times a week for 24 months and 49 control patients were treated with placebo. RESULTS: Primary clinical endpoints were differences in exacerbation rates and proportion of patients remaining exacerbation-free. There were no significant baseline differences between the treated and placebo groups. In the treated RR group a significant reduction in exacerbation rate, an increase in the probability of remaining exacerbation-free, and an improvement in mean EDSS were found at 24 months. MRI activity and total lesion burden were significantly reduced in treated RR patients. In the SP group, nIFN-beta produced a significant reduction in EDSS score, a significant reduction in active lesion number, a marginally significant favourable difference in total lesion burden but no significant effect on the number of gadolinium-enhancing lesions. Side effects were transient and mild in treated patients. CONCLUSIONS: These observations confirm that nIFN-beta is a promising and well-tolerated treatment for either RR or SP MS patients.     

Combined therapies to treat complex diseases: The role of the gut microbiota in multiple sclerosis

The commensal microbiota has emerged as an environmental risk factor for multiple sclerosis (MS). Studies in experimental autoimmune encephalomyelitis (EAE) models have shown that the commensal microbiota is an essential player in triggering autoimmune demyelination. Likewise, the commensal microbiota modulates the host immune system, alters the integrity and function of biological barriers and has a direct effect on several types of central nervous system (CNS)-resident cells. Moreover, a characteristic gut dysbiosis has been recognized as a consistent feature during the clinical course of MS, and the MS-related microbiota is gradually being elucidated. This review highlights animal studies in which commensal microbiota modulation was tested in EAE, as well as the mechanisms of action and influence of the commensal microbiota not only in the local milieu but also in the innate and adaptive immune system and the CNS. Regarding human research, this review focuses on studies that show how the commensal microbiota might act as a pathogenic environmental risk factor by directing immune responses towards characteristic pathogenic profiles of MS. We speculate how specific microbiome signatures could be obtained and used as potential pathogenic events and biomarkers for the clinical course of MS. Finally, we review recently published and ongoing clinical trials in MS patients regarding the immunomodulatory properties exerted by some microorganisms. Because MS is a complex disease with a large variety of associated environmental risk factors, we suggest that current treatments combined with strategies that modulate the commensal microbiota would constitute a broader immunotherapeutic approach and improve the clinical outcome for MS patients.     

Investigation of quantitative magnetisation transfer parameters of lesions and normal appearing white matter in multiple sclerosis

The aim of this study was to use quantitative magnetisation transfer (MT) imaging to assess the different pathological substrates of tissue damage in multiple sclerosis (MS) and examine whether the MT parameters may be used to explain the disability in relapsing remitting (RR) MS. Thirteen patients with RRMS and 14 healthy controls were prescribed conventional MRI and quantitative MT imaging at 3.0 T. A two‐pool model of MT (where A refers to the free pool and B to the macromolecular pool) was fitted to the data yielding a longitudinal relaxation rate R_A, a relative size F of macromolecular pool, transverse relaxation times T and T for the two pools and a forward exchange rate RM. The MT ratio (MTR) was also computed. The mean MT parameters of the normal appearing white matter (NAWM) and of lesions in patients, and of white matter in controls were estimated. MT parameters were significantly different between lesions and NAWM in patients, and between the NAWM and the white matter of controls (with the exception of T and the MTR). Two models were investigated using ordered logistic regression, with the expanded disability status scale (EDSS) as the dependent variable. In the first one, mean NAWM MT parameters and lesion load were entered as explanatory variables; in the second one, mean MT variables within lesions and lesion load were entered as explanatory variables. Unexpectedly, T was the parameter most significantly associated with EDSS in NAWM. This parameter might represent a weighted average of the relaxation times of spins with different molecular environments, and therefore its variation could indicate a change in the balance between subpopulations of macromolecular spins. Conversely, in lesions, RM, T, F, R_A, and lesion load significantly predicted disability only when combined together. This might reflect the complex interaction between demyelination, remyelination, gliosis, inflammation and axonal loss taking place within lesions. Copyright © 2009 John Wiley & Sons, Ltd.     

Correlation between disability and transcranial magnetic stimulation abnormalities in patients with multiple sclerosis

Multiple sclerosis (MS) is an idiopathic inflammatory demyelinating disorder of the central nervous system. Clinical evaluation, MRI, cerebrospinal fluid testing and evoked potentials (EP) are among the available methods utilized for disease diagnosis and monitoring. To date, no surrogate markers have been established to assess disease evolution and progression. The aim of this study is to assess motor evoked potentials (MEP) of MS patients by transcranial magnetic stimulation (TMS) and investigate the possible correlations between TMS abnormalities and disability in the patient group, which includes a subgroup with no apparent pyramidal tract dysfunction. A total of 131 clinically definite MS patients were included in the study. Motor responses to TMS stimulation were recorded. Absent values, decreases in amplitude, prolongation of latency and central motor conduction time (CMCT) were considered as abnormal. A total of 109 (83%) patients displayed abnormal MEP amplitude, 68 (52%) displayed MEP latency, and 64 (49%) displayed CMCT abnormalities. Abnormal CMCT, latency and amplitude results were correlated with Expanded Disability Status Scale scores (p < 0.001). Our results indicate that TMS-EP in MS patients is correlated with disability, and that these findings may support the role of EPs in predicting disability even in subclinical presentations.