The cerebrospinal fluid proteins in multiple sclerosis

A specific and reliable diagnostic test for MS does not currently exist. However, most patients afflicted with this disorder demonstrate both qualitative and quantitative changes in CSF proteins. An abnormal immunoglobulin fraction synthesized within the CNS is frequently found to be electrophoretically distinct from other proteins of the CSF and quantifiable according to different formulas. Although an etiologic antigen has not been implicated as yet, these findings provide compelling evidence to support an immunopathologic basis for MS.     

Therapeutic role of beta-interferons in multiple sclerosis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system (CNS). In the last 12 years, there has been a proliferation of studies elucidating the immune mechanisms that mediate tissue damage in MS. Interferons (IFNs) have an important role in regulating innate and adaptive immune responses. They decrease pro-inflammatory responses such as the autoimmunity in MS, but other autoimmune responses such as systemic lupus erythematosus (SLE) may be exacerbated. This review offers a general overview of the biological properties of IFNs, effects on immune cells, and clinical effectiveness in MS treatment. IFN signaling is complex, from receptor binding events to the generation of effector mechanisms that dampen inflammation. Immune cell function is altered in MS. IFN treatment of MS patients ameliorates immune dysfunction, but not completely. The incomplete resolution of immune dysfunction by IFNs partly explains their significant, but modest therapeutic effects. This observation also suggests that there are immune mechanisms in MS that are resistant to IFN therapy. In MS, abnormalities may exist at several points along the IFN signaling pathway, including molecular defects in the IFN second messenger system. Currently, several studies are ongoing evaluating ways of potentiating IFN effects. IFNs were the first agents to show clinical efficacy in treatment of MS. More than a decade of experience with IFNs has showed continued clinical efficacy over time. In the near future, IFNs will continue to play a major role in MS.     

Therapeutic role of mitoxantrone in multiple sclerosis

Mitoxantrone is approved by several health authorities for treatment of active forms of relapsing-remitting or secondary progressive multiple sclerosis (SPMS). This review provides an outline on relevant preclinical as well as clinical studies, places mitoxantrone in the context of other therapeutic approaches against multiple sclerosis (MS), and discusses relevant side effects. The current knowledge of the putative mechanisms of action of the compound is discussed.     

Involvement of NK and NKT cells in the pathogenesis of multiple sclerosis

We have previously demonstrated that NK cells and CD1d-restricted NKT cells regulate clinical and pathological manifestations of experimental autoimmune encephalomyelitis(EAE), an animal model for multiple sclerosis(MS). It is important to address whether NK and NKT cells are also involved in the pathogenesis of human MS. Our laboratory has recently showed that NK cells as well as CD4+ NKT cells are biased for secreting type 2 cytokines in the remission phase of MS. However, CD4- CD8- NKT cells, that mainly secrete TNF-alpha and IFN-gamma, are reduced in number and attenuated in cytokine secretion. These results support our postulate that NK and NKT cells are involved in the regulation of MS.     

Diagnosing multiple sclerosis and its imitators

The diagnosis of MS requires central nervous system symptoms that are disseminated in time and space, and that have no better explanation.Dissemination in time and space may be demonstrated clinically or by MRI imaging. The differential diagnosis is broad, and requires the exclusion of several diseases that are described in the text. Following the new guidelines for the diagnosis of MS allows an early and accurate diagnosis of the disease.     

The role of vitamin D in multiple sclerosis

OBJECTIVE: To evaluate the literature about the role of vitamin D in the prevention and treatment of multiple sclerosis (MS). DATA SOURCES: MEDLINE (1966-April 2006) and International Pharmaceutical Abstracts (1970-April 2006) searches were performed. In addition, pertinent references from identified articles were obtained. Key search terms included vitamin D, 25-hydroxyvitamin D, vitamin D deficiency, and multiple sclerosis. DATA SYNTHESIS: Vitamin D supplementation prevented the development and progression of experimental autoimmune encephalitis, an animal model of MS, in mice. A large, prospective, cohort study found that vitamin D supplementation was associated with a 40% reduction in the risk of developing MS. Four small, noncontrolled studies suggested that vitamin D supplementation may decrease exacerbation of MS symptoms. CONCLUSIONS: Vitamin D supplementation may help prevent the development of MS and may be a useful addition to therapy. However, current studies are in small populations and are confounded by other variables, such as additional vitamin and mineral supplementation.     

多发性硬化的轴索损害及其机制

目的:回顾多发性硬化轴索损害及其发病机制的研究结果,以便在此基础上对多发性硬化轴索损害更全面深入的了解和对该病的临床监测和治疗提供有效的理论指导。资料来源:应用计算机检索Medline1998-01/2005-01与多发性硬化轴索损害相关的文章,检索词为“multiplesclerosis,axonaldamageoraxonalinjury”,并限定文章语言种类为“English”,同时应用中国期刊全文数据CNKI检索1998-01/2005-01相关文章,检索词为“多发性硬化”和“轴索损害”,限定语言种类为中文。资料选择:选择与多发性硬化的轴索损害相关性强的文献46篇。资料提炼:在46篇文献中,选择32篇文献进行分类整理用于综述,其中20篇选用为参考文献,其余14篇因与入选文献内容呈不同程度重复给予删除。资料综合:对检索的文章进行分析综合显示,越来越多的证据表明多发性硬化的轴索损害出现在疾病早期,呈现出一种亚临床状态,在没有明显炎性活动的部位(如外观正常的白质组织)也存在轴索病变,而且在急性发作后缓解期和慢性期仍有进行性轴索损害,这可能是疾病进展的决定性因素。多发性硬化时轴索损害可由多种因素引起,但目前认为主要与炎症反应有关。结论:在多发性硬化的不同病程阶段均存在轴索损害,并且它是造成多发性硬化神经功能障碍的主要原因,轴索损害可由多种因素引起,但主要与炎症反应有关。     

多发性硬化的轴索损害及其机制

目的：回顾多发性硬化轴索损害及其发病机制的研究结果，以便在此基础上对多发性硬化轴索损害更全面深入的了解和对该病的临床监测和治疗提供有效的理论指导。 资料来源：应用计算机检索Medline 1998—01／2005-01与多发性硬化轴索损害相关的文章，检索词为“multiple sclerosis，axonal damage or axonal injury”，并限定文章语言种类为“English”，同时应用中国期刊全文数据CNKI检索1998—01／2005—01相关文章，检索词为“多发性硬化”和“轴索损害”，限定语言种类为中文。 资料选择：选择与多发性硬化的轴索损害相关性强的文献46篇。 资料提炼：在46篇文献中，选择32篇文献进行分类整理用于综述，其中20篇选用为参考文献，其余14篇因与人选文献内容呈不同程度重复给予删除。 资料综合：对检索的文章进行分析综合显示，越来越多的证据表明多发性硬化的轴索损害出现在疾病早期，呈现出一种亚临床状态，在没有明显炎性活动的部位（如外观正常的白质组织）也存在轴索病变，而且在急性发作后缓解期和慢性期仍有进行性轴索损害，这可能是疾病进展的决定性因素。多发性硬化时轴索损害可由多种因素引起，但目前认为主要与炎症反应有关。 结论：在多发性硬化的不同病程阶段均存在轴索损害，并且它是造成多发性硬化神经功能障碍的主要原因，轴索损害可由多种因索引起，但主要与炎症反应有关。     

铁及氧化应激在多发性硬化中的作用机制及其MRI研究进展

多发性硬化(multiple sclerosis,MS)是中枢神经系统最常见的一种炎性脱髓鞘疾病,其发病机制迄今不明。近年来研究表明铁和氧化应激均参与到MS的发病机制中,但其具体的时间空间动态变化规律尚未完全被阐明。因此,借助多参数MRI进行在体无创性定量评估MS病灶内的铁及氧化应激水平,对揭示MS各期不同病理特征具有重要意义。作者就铁及氧化应激在多发性硬化中的潜在致病机制和相应MRI研究进展进行综述。     

Update on the etiology and pathogenesis of multiple sclerosis and neuromyelitis optica

Recent findings on the etiology and pathogenesis of multiple sclerosis (MS) and neuromyelitis optica (NMO) were reviewed. As new MS-susceptibility genes, IL-7Ralpha and IL-2Ralpha genes were identified. Among environmental factors, Epstein-Barr virus, vitamin D and smoking appear to play a role in developing MS. As opposed to previous reports on the lesion heterogeneity, a recent study showed antibody-, complement-mediated myelin phagocytosis is the dominant mechanism of demyelination in MS. Clinical trials of monoclonal antibodies demonstrated that targeting such immune molecules as CD52, CD25, VLA-4 and CD20, is therapeutically effective. Aquaporin-4 (AQP4) antibody is a diagnostically useful biomarker of NMO, and a recent study revealed severe astrocytic damage in NMO probably caused by AQP4-targeting is a pathological finding distinct from that in MS.     

Abnormalities of serum and plasma components in patients with multiple sclerosis

Qualitative and quantitative abnormalities in protein and non-protein components of serum and plasma in patients with multiple sclerosis have been the subjects of numerous reports. In this review many of the more recent observations are documented and evaluated. It is concluded that at present the welter of information that has been gathered does not contribute in any major, coherent way to our understanding of the etiology or pathogenesis of the disorder. Several of the abnormalities that have been observed may be future candidates for biochemical markers for multiple sclerosis; at present none is sufficiently reliable, distinctive or easily performed to warrant the status of a useful diagnostic or prognostic test.     

The role of psychologists in the treatment of multiple sclerosis

Multiple sclerosis (MS) is the most common progressive neurological disorder affecting individuals between 15 and 50 years of age. Because of its neuropathological process, MS causes multiple symptoms that impact the physical, social, vocational, and psychological well-being of patients. Within the comprehensive care approach to treatment of these patients, psychologists provide multiple services. In the present paper, we summarize current research on psychological treatments of symptoms common to patients with MS. Investigators have advocated use of many types of individual and group psychotherapeutic approaches to treat psychiatric symptoms caused by MS, but there are few controlled outcome studies. The existing controlled outcome studies indicate that cognitive behavioral, insight-oriented, and stress management group therapies are effective, as are individual approaches utilizing stress inoculation training and pharmacotherapy. Reports concerning biofeedback have used single case designs and provide initial evidence that this technique is useful for treating fecal incontinence and retention, postural instability, and weaning from a respirator. MS symptoms that may also be amenable to psychological treatments include chronic pain, weight management, and sexual dysfunctions, although there are currently no outcome studies that verify the efficacy of these treatments when used with MS patients. Because of the multiple symptoms produced by MS, clinicians often need to modify delivery of services. In this paper, we provide specific recommendations to help clinicians tailor their treatments to the special needs of patients with MS. Finally, we provide suggestions for future research.     

Molecular pathogenesis of multiple myeloma and its premalignant precursor

Multiple myeloma is a monoclonal tumor of plasma cells, and its development is preceded by a premalignant tumor with which it shares genetic abnormalities, including universal dysregulation of the cyclin D/retinoblastoma (cyclin D/RB) pathway. A complex interaction with the BM microenvironment, characterized by activation of osteoclasts and suppression of osteoblasts, leads to lytic bone disease. Intratumor genetic heterogeneity, which occurs in addition to intertumor heterogeneity, contributes to the rapid emergence of drug resistance in high-risk disease. Despite recent therapeutic advances, which have doubled the median survival time, myeloma continues to be a mostly incurable disease. Here we review the current understanding of myeloma pathogenesis and insight into new therapeutic strategies provided by animal models and genetic screens.     

Lactoferrin and its role in the pathogenesis of tick-borne encephalitis

The content of lactoferrin (LF) was studied in the liquor and blood of patients with tick-borne encephalitis (TBE) of the meningeal and focal types; additionally, the information density of the discussed parameter was assessed for evaluating the severity and degree of the inflammation process in the central nervous system (CNS). The LF level was determined in liquor of 37 samples obtained from TBE patients (main group) and of 10 persons with osteochondrosis (controls); it was also determined in the serum taken from 21 TBE patients and from 40 healthy donors by using the immune-enzyme analysis. The LF concentration in TBE patients was found to exceed the normal value by 1.5-3 times during the whole observation period. As for the liquor, it was high, by the onset of the disease, by more than 20 times, however, after the 7th day it was higher 6-fold. A direct dependence of a concentration of the studied protein on a form and severity of the disease was established. The LF level in the liquor of TBE patients alongside with clinical signs can be an objective indicator of a severity and activity of the inflammation process in the CNS; it can also be a criteria of how much the conducted therapy effective is.     

Magnetic resonance spectroscopy and its clinical applications in multiple sclerosis

Proton magnetic resonance spectroscopy(1H-MRS), which provides biochemical information in not only visible lesions on conventional MR imaging but also normal appearing white matter(NAWM), has extended the genesis of multiple sclerosis(MS) in several important directions. First, serial 1H-MRS studies reveal dynamic regional biochemical alterations in plaques during the course of the illness. Second, axonal damage may occur at early stage. Third, neuronal loss can be substantial in the gray matter. Fourth, NAWM shows widespread biochemical involvement prior to detection on MRI. Fifth, severities of neuroaxonal involvement significantly correlate with neurological dysfunction. 1H-MRS will provide more detailed information than conventional MRI, and could be beneficial in monitoring effects of therapeutic interventions in MS.