多发性硬化患者外周血白细胞粘附分子的表达

目的 :探讨多发性硬化 (MS)患者外周血白细胞粘附分子表达的水平及予甲基强的松龙 (MP)治疗后的变化。方法 :流式细胞仪测定 2 8例缓解复发型MS患者及 12例复发期MS予静脉MP治疗后外围血淋巴细胞和单核细胞细胞间粘附分子 3(CD5 0 )、细胞间粘附分子 1(CD5 4 )、整合素LFA 1β亚单位 (CD18)、非常晚抗原 4 (VLA 4 )α、β亚单位 (CD4 9d、CD2 9)和 (- )选择素 (CD6 2L)的阳性百分率。结果 :复发期MSCD4 9d和CD2 9在淋巴细胞和单核细胞、CD5 4和CD6 2L在单核细胞的阳性百分率高于缓解期MS和对照组 ,复发和缓解期MSCD5 4在淋巴细胞的阳性百分率高于对照组 ;MP治疗后 ,CD5 4和CD4 9d在淋巴细胞和单核细胞、CD6 2L在单核细胞的阳性百分率下降。结论 :MS患者外周血白细胞粘附分子的表达升高并可作为MS活动期的指标     

Total knee replacement in patients with multiple sclerosis

Total knee replacement was performed on two patients with Multiple sclerosis. Severe hamstring spasticity was encountered in both patients in the immediate post-operative period requiring further surgery. Both patients remain ambulatory at follow-up. The disease, and its implications in patients warranting total joint replacement are discussed.     

Glucocorticoid treatment reduces T-bet and pSTAT1 expression in mononuclear cells from relapsing remitting multiple sclerosis patients

High dose glucocorticoid (GC) treatment has been demonstrated to have a short-term beneficial effect on functional recovery in relapsing multiple sclerosis (MS) patients but the exact mechanism of action of GCs in MS is unclear. We found that high dose intravenous GCs strongly reduced T-bet and pSTAT1 expression in CD4+, CD8+, CD14+ circulating cells in RRMS patients in relapse. pSTAT1and T-bet reduction was associated with the decline of IFNgamma production by PBMCs. A significant increase of AV-positive CD4+ and CD8+ T cells was detectable after GC treatment without any variation in the percentage of annexin V-positive monocytes. By in vitro analysis, patients during relapse, either before or after GC treatment, exhibited a lower proportion of apoptotic lymphocytes than remitting patients and controls. Our study suggests that GCs can modulate T-bet and STAT1 expression and that IFNgamma signalling inhibition contributes to anti-inflammatory action of GCs in the treatment of relapses of MS patients.     

Cerebrospinal fluid progranulin levels in patients with different multiple sclerosis subtypes

Progranulin has recently attracted attention due to the discovery of mutations in its encoding gene (GRN) in several cases of frontotemporal lobar degeneration, but also for a possible role in inflammatory processes. In adult central nervous system, GRN mRNA is expressed in forebrain, olfactory bulbs and spinal cord. Progranulin cerebrospinal fluid (CSF) levels were evaluated in 55 patients with multiple sclerosis (MS) as well as in 35 subjects with non-inflammatory neurological diseases (NIND), 7 individuals with other inflammatory neurological disease (OIND) and 8 controls (CON), matched for ethnic background, gender and age. No statistically significant differences were found in patients compared with either NIND, OIND or CON (P > 0.05), even stratifying according to disease subtype or gender. A positive correlation between progranulin CSF levels and age was observed in patients (ρ = 0.29, P = 0.03). According to these data, progranulin does not likely play a major role in the pathogenesis of MS.     

Immunopathogenesis of multiple sclerosis

Multiple sclerosis (MS) is a chronic disorder of the central nervous system characterized by autoimmune inflammation, demyelination, and axonal damage. MS etiology remains unknown, but disease phenotype is most likely the result of an interaction between complex genetic factors and environmental influences. The better understanding of the mechanisms involved in the immunopathogenesis of MS has led to the development of promising new therapeutic strategies for the disease. This review will discuss the key pathogenic steps implicated in the disease and the role of the main cellular populations that drive the immune responses in MS.     

Quality of life in Polish patients with multiple sclerosis

PurposeThis study is a pilot evaluation of the quality of life (QoL) in Polish patients with multiple sclerosis (MS).Material/methodsData from 21 centers in Poland were collected from May 2008 to January 2009. QoL was assessed using the questionnaire Euro Quality of Life (EQ-5D), with Polish population norms. Demographic profile of patients, duration/form/relapsing activity of the disease, disability and comorbidity were also analyzed.ResultsData from 3521 patients (F/M ratio 2.4:1) were collected. The average EQ-5D index was 0.8 ± 0.27 and the mean score in a visual analog scale (EQ-VAS) was 65.6 ± 21.5. There was a highly significant positive correlation between both indices (r = 0.7334, p < 0.0001). The mean patient age was 40.7 years (11.2–92.3 years) and disease duration was 10.3 ± 8.8 years (0.04–53 years). 74.2% of subjects had relapsing-remitting form of MS, while 17.2% were classified as secondary progressive and 8.6% as primary progressive. In the group of relapsing-remitting MS subjects there were 2.5% patients with “benign MS”. The average degree of disability on EDSS scale was 3.6 ± 2.2, while disability ≥6 was observed in 20.3% of patients. Most patients did not have other diseases besides MS.ConclusionsThis is the first large study of QoL in patients with MS in Poland (approximately 18% of all patients). Our results confirm a reduction in QoL compared with the general population. Further studies are indicated to identify the modifiable risk factors (e.g. type of treatment) that may affect QoL.     

多发性硬化患者淋巴细胞激活的临床意义

目的：探讨多发性硬化(MS)患者淋巴细胞的激活状态及临床意义。方法：流式细胞仪测定28例缓解复发型MS患者(复发期20例，缓解期8例)外周血(PB)、12例复发期脑脊液(CSF)及11例复发期MS患者予糖皮质激素治疗后淋巴细胞CD69和HLA-DR表达的阳性百分率。结果：复发期MS患者阳淋巴细胞HLA-DR 和CD3 ／HAL-DR 的百分率高于对照组和缓解期MS，缓解期MS患者CD3 /HLA-DR 的百分率高于对照组3复发期MS患者CSF中CD69 、HLA-DR 和CD3 ／HLA-DR 的百分率均高于PB；复发期MS患者CSF中CD69 的百分率与血脑屏障受损呈正相关；激素治疗降低复发期MS PB淋巴细胞HLA-DR 的百分率。结论：MS患者淋巴细胞激活涉及MS的发病机制并可作为MS活动期的一个指标。     

The incubation period of multiple sclerosis

Movement of myelin through the spiral laminar arrangement of the myelin sheaths of neurones might act as a biological clock in determining the prolonged incubation period of multiple sclerosis. A defect incorporated peripherally in the myelin sheath as a result of neonatal virus infection might be revealed years later when the defective myelin reaches the axolemma and provokes an immunological reaction. This process could, directly or indirectly, be prevented by the effects of solar radiation, thus accounting for the geographical distribution of the disease.     

多发性硬化外周全血mRNA差异表达的来源及其特异性分析

目的 探究多发性硬化外周全血mRNA差异表达的来源及其特异性.方法 利用外周全血mRNA表达谱数据,分别筛选多发性硬化和炎症性疾病(感染性休克、肺结核)患者相对正常人群的差异表达基因并进行比较.筛选正常外周血中髓系相对淋巴系细胞的差异表达基因,并与多发性硬化患者相对正常人群的差异表达基因作比较.结果 比较多发性硬化患者与两种炎症性疾病(感染性休克、肺结核)患者相对正常人群的差异表达基因,发现交叠基因上/下调方向的一致性分别为91.32%(P<0.05),93.23%(P<0.05).比较多发性硬化患者相对正常人群的差异表达基因及正常人群髓系相对淋巴系细胞的差异表达基因,发现交叠基因上/下调方向的一致性为96.82%(P<0.05).结论 多发性硬化患者相对于正常人群的差异表达基因与炎症性疾病患者相对正常人群的差异表达基因高度一致,同时与髓系相对淋巴系细胞的差异表达基因同样高度一致.上述结果表明多发性硬化患者外周全血中观察到的基因表达的改变可能是由于髓系/淋巴系细胞构成比例改变所致,是非特异的炎症性改变.     

多发性硬化患者抗髓鞘碱性蛋白抗体的检测及其意义

目的 检测多发性硬化(MS)患者抗髓鞘碱性蛋白(MBP)抗体并探讨其意义.方法 采用ELISA方法测定56例多发性硬化患者急性期血清和脑脊液配对标本的抗髓鞘碱性蛋白抗体,30例其它神经疾病(OND)患者及36例正常人(NC)为对照.结果 以OND组患者OD值为标准,测得MS患者脑脊液抗MBP抗体,其阳性率为26.8%,与OND组比较有显著性意义;以NC组OD值为对照,MS患者血清抗MBP抗体阳性率为78.6%,OND组抗MBP抗体阳性率为50%,与NC组均有显著性意义,MS患者与OND组患者抗MBP抗体阳性率比较亦有显著性意义.结论 多发性硬化患者脑脊液和血液中均可检测到抗MBP抗体,可为临床诊断和治疗提供指导.     

APOE genotypes in African American female multiple sclerosis patients

Multiple sclerosis (MS) is a chronic inflammatory CNS disorder, resulting in progressive neurological dysfunction. The disease has a higher incidence in Caucasian Americans (CA) than African Americans (AA); however, the latter may have a more aggressive disease course. We used cluster analysis to determine whether there is a difference in disease progression between the races and whether the APOE AND APOC1 genotypes influence the disease progression. AA female patients were younger and had a higher progression index and MS severity score than CA female MS patients. AA females who were APOE 4/4, 2/4, or 2/3 and APOC1 AA had a younger age-of-onset, had primarily a relapsing remitting disease course, with a higher progression index and MS severity score, as assessed by cluster analysis. Cluster analysis also indicated that CA female patients were of two groups. One group was younger, had the APOE 3/3 genotype with relapsing remitting less severe disease. The second CA group was older, had the APOE 3/4 or 2/3 genotypes with more of the secondary progressive more severe disease phenotype. Thus, the AA MS female patients who were APOE 4 carriers had an earlier age-of-onset and more severe disease course than CA MS female patients.     

Cognitive impairment in three subtypes of multiple sclerosis

Patients with relapsing, primary progressive, and secondary progressive MS were administered the Tower of London and the Stroop Color-Word Interference Test, yielding several measures of executive function and speeded information processing. MS patients' performance was compared with healthy controls and with a clinical control group consisting of patients with rheumatoid arthritis. The MS patients performed the tests more slowly, but did not differ from either group of controls on measures of executive function. Slowing in the speed of information processing was characteristic of MS patients across two basic tasks differing in terms of controlled versus automatic processing and in terms of whether or not rapid responding was an explicit feature of successful performance. Although evident in all subtypes, this slowing was more pronounced in secondary progressive patients and somewhat less pronounced in primary progressive patients. Furthermore, the slowing was unrelated to patients' disability status or level of depression.     

Lymphocytes from multiple sclerosis patients produce elevated levels of gamma interferonin vitro

The production of gamma interferon (IFN) by mononuclear cells (MNC) from patients with exacerbating/remitting multiple sclerosis (MS) and controls was evaluated. After 3 days of culture with concanavalin A, the amount of gamma IFN in supernatant fluids was determined by radioimmunoassay. MNC from MS patients produced significantly (P<0.001) more gamma IFN than MNC from either normal controls or patients with other neurologic diseases. Levels of gamma IFN in the serum and CSF were also measured. Despite the relative absence of gamma IFN in serum (4 positive of 30), all CSF samples tested had low, but detectable, levels of gamma IFN (0.3 to 1.4 U/ml). These studies suggest that some of the autoimmune features and immunologic abnormalities in MS may be related to elevated gamma IFN production.     

诱发电位在多发性硬化诊断中的价值

目的：评价诱发电位在多发性硬化(MS)诊断中的价值，并为临床提供MS的诱发电位(EP)资料。方法：本课题采用临床病例分析统计方法，对164例MS患者的3项EP资料进行分析。结果：MS患者的3项EP中，视觉诱发电位(VEP)的异常率最高，其次为体感诱发电位(SEP)，脑干听觉诱发电位(BAEP)最低；这3项EP联合检查可使异常率提高，EP发现病灶的敏感性较临床检查高，其不仅可以发现中枢神经系统的病灶，而且还能够发现外周神经系统的病灶。结论：联合应用3项EP检查有助于MS诊断以及亚临床病灶的发现。     

Immunological mechanisms in multiple sclerosis

Multiple sclerosis (MS) remains a leading cause of neurologic disability among young adults. Clinical manifestations of the disease result from immune-mediated demyelination of the central nervous system. Most patients experience new symptoms in a relapsing-remitting pattern, although the course is highly variable from person to person and even in the same individual over time.Recent neuropathological studies reveal that in addition to the surrounding myelin sheath, nerve axons themselves are targets of injury in MS lesions. Characterization of the inflammatory infiltrates present in MS brain and spinal cord tissue shows that active lesions can be segregated into 1 of 4 subtypes, with each individual having only a single pattern of involvement. Studies in animal models demonstrate that a number of myelin proteins can become immune system targets resulting in demyelination, and these models have also served to define multiple immunological mechanisms of disease. Translational studies using peripheral blood samples have characterized differences in the various myelin protein-reactive immune responses of MS patients and controls, and these investigations have validated some, but not all, of the disease mechanisms uncovered in animals. Adaptive and innate immunity both appear to contribute to disease pathogenesis within the target tissue of the central nervous system.Immunomodulatory therapies have been developed that partially arrest disease relapses and progression. Studies to dissect how these agents work have shed light on underlying disease mechanisms in MS. More effective interventions in the future will need to target multiple points in disease pathways.     

Anticipatory postural adjustments in individuals with multiple sclerosis

Individuals with multiple sclerosis (MS) frequently exhibit difficulties in balance maintenance. It is known that anticipatory postural adjustments (APAs) play an important role in postural control. However, no information exists on how people living with MS utilize APAs for control of posture. A group of individuals with MS and a group of healthy control subjects performed rapid arm flexion and extension movements while standing on a force platform. Electromyographic (EMG) activity of six trunk and leg muscles and displacement of center of pressure (COP) were recorded and quantified within the time intervals typical of APAs. Individuals with MS demonstrated diminished ability to produce directional specific patterns of anticipatory EMGs as compared to control subjects. In addition, individuals with MS demonstrated smaller magnitudes of anticipatory muscle activation. This was associated with larger displacements of the COP during the balance restoration phase. These results suggest the importance of anticipatory postural control in maintenance of vertical posture in individuals with MS. The outcome of the study could be used while developing rehabilitation strategies focused on balance restoration in individuals with MS.     

视觉、脑干听觉诱发电位对多发性硬化的诊断价值

目的 :探讨视觉诱发电位 (VEP)、听觉诱发电位 (BAEP)对多发性硬化 (MS)的诊断价值。方法 :对 30例临床诊断为MS的患者进行VEP、BAEP检测 ,并与正常对照组进行比较分析。结果 :MS患者VEP和BAEP的异常率分别为 73%和 6 0 %。异常中VEP有 6 8% ,BAEP有 78%的患者 ,临床有相应的症状 ;VEP 32 % ,BAEP 2 2 %的患者临床无相应症状。 5例MS患者在临床缓解期复查VEP、BAEP ,1例VEP、BAEP恢复正常 ,4例仍异常。结论 :VEP、BAEP检测对MS的诊断具有重要意义。