Marburg型多发性硬化

Marburg型多发性硬化是一种临床少见、发病突然、病程“凶险”、发病机制独特、诊断和治疗困难的神经系统脱髓鞘疾病。该文就Marburg型多发性硬化的发病机制、病理、临床表现及治疗进展进行综述。     

多发性硬化中的脂代谢障碍和多不饱和脂肪酸的治疗

复习与多发性硬化相关的细胞膜脂蛋白的研究,及其生化和临床研究的资料,发现多不饱和脂肪酸,主要是n-6脂肪酸在多发性硬化的发病和治疗中具有重要意义。有研究发现高剂量γ-亚油酸[GIA(18:3n-6)oil]能减少复发性多发性硬化的复发率和疾病的进展。     

多发性硬化和尿酸

多发性硬化(multiple sclerosis，MS)是自身免疫反应所致的中枢神经脱髓鞘性疾病，病变晚期轴索亦可受到破坏。过氧化物是其病理机制中一个重要因素。自从在多发性硬化发病机制的研究中发现内源性过氧化物清除剂尿酸对多发性硬化有抑制作用后，该机制得到深入研究，并发现尿酸是反映多发性硬化病情活动性的重要指标。采用尿酸前体治疗多发性硬化也取得了重要进展。     

多发性硬化治疗的现状与前景

多发性硬化治疗的现状与前景董为伟一、多发性硬化（ＭＳ）治疗的现状多发性硬化（ＭＳ）是一种中枢神经系统（ＣＮＳ）的炎症性脱髓鞘疾病，在ＣＮＳ，主要是由激活的Ｔ淋巴细胞与巨噬细胞所组成的炎症反应，并有白介素分泌的局部免疫反应，导致浆细胞合成寡克隆ＩｇＧ。...     

多发性硬化的认知障碍研究进展

认知障碍是多发性硬化患者重要的临床表现之一,影响患者远期生活质量,及时采取相应的治疗措施早期干预对减缓认知障碍病程进展具有重要意义。近年来,多发性硬化的神经心理学测试及影像学检查不断发展。本文对多发性硬化认知障碍的相关研究进展做一综述。     

多发性硬化20例临床分析

目的：探讨多发性硬化的临床症状及MRI对其诊断的价值和意义。方法：综合分析20例多发性硬化患者一般资料、MRI、脑脊液检查及治疗转归。结果：多发性硬化好发于10－40岁，女性多见，起病形式及临床症状多样，病程呈复发与缓解，MRI对多发性硬化病灶的发现率可达100％。糖皮质激素治疗有效，但随着病程的延长，复发次数的增多，激素治疗欠佳。结论：根据临床特点、影像学检查、脑脊液及神经电生理检查可提高多发性硬化的确诊率。     

多发性硬化40例临床分析

多发性硬化(MS)是中枢神经系统的脱髓鞘疾病，近十年来，对MS的诊断和治疗有很大的进展．本文对临床已确诊的MS患者进行临床分析，并与国内外有关文献对比，从而对MS的诊断和治疗方面某些问题给以探讨。     

多发性硬化的诊断与早期治疗

多发性硬化（Ms）早期的炎症反应可造成髓鞘和轴索损害，引起复发和功能障碍进展。于Ms早期采用免疫调节剂治疗有助于减少复发和延缓疾病进展。McDonald标准有助于其尽早诊断。Ms的早期治疗需要个体化，并明确哪些患者可得益于早期治疗。     

多发性硬化研究进展(述评)

扼要概述了多发性硬化近年在病因、免疫学发病机制、治疗、方法学等方面的进展 ,并展望了未来研究方向     

2010年修订版多发性硬化诊断标准解读

介绍了多发性硬化诊断国际专家小组对多发性硬化临床诊断标准的最新修订。基于近年来在影像及实验室等相关领域关于多发性硬化诊断的最新研究结果及专家意见,重点在阐述时空多发性的客观证据以及原发进展型多发性硬化的诊断方面进行了修订,在保持敏感性和特异性的基础上一定程度简化了多发性硬化的诊断过程。该修订标准有可能应用于儿童、亚洲人群及拉丁美洲人群,但存在局限性。     

Immunologic therapy for secondary and primary progressive multiple sclerosis

Multiple sclerosis (MS) is generally considered an immunemediated demyelinating disease, and treatments designed to modify the course of MS are immunosuppressive or immunomodulatory. Although most people with MS have a relapsing-remitting course initially, the majority will eventually experience a more gradual decline in neurologic function, termed secondary progressive MS. Some patients have gradual worsening from the beginning, termed primary progressive MS. Recent pathologic studies have revealed that axonal injury and neuronal degeneration are much more prominent in MS than previously recognized, and may be the explanation for the gradual decline in neurologic function that characterizes progressive MS. The results of several clinical trials in MS indicate that suppression of the immune-mediated inflammation may decrease the relapse rate in MS, but not stop the progressive loss of neurologic function. There are many promising approaches to this clinical dilemma, but none has been proven to be effective in stopping or retarding progressive MS. More well-designed, controlled, blinded, randomized clinical trials are needed to test these putative therapies. In the mean time, we should avoid subjecting patients to potentially dangerous and unproven regimens.     

Contemporary immunomodulatory therapy for multiple sclerosis.

Multiple sclerosis (MS) is no longer considered an unmanageable disease. Five drugs have obtained regulatory approval to safely and effectively modify the course of MS. Three preparations of interferon beta-Avonex (interferon beta-1a), Betaseron (interferon beta-1b), and Rebif (interferon beta 1a)-have shown efficacy in relapsing-remitting MS and show promise in slowing the course of secondary progressive MS. Glatiramir acetate (Copaxone) has demonstrated efficacy in relapsing-remitting MS, and is being tested for the management of primary progressive disease. Mitoxantrone (Novantrone) has been approved for secondary progressive and progressive relapsing MS. There is a tendency toward early diagnosis and treatment based on the hypothesis that treatment effectiveness declines with advancing disease.     

Autonomic dysfunction in multiple sclerosis: cervical spinal cord atrophy correlates

Autonomic dysfunction has rarely been studied in patients suffering from multiple sclerosis (MS). Some hypotheses have concerned the pathophysiology, especially with regard to a possible spinal cord origin. However, there have been no previous studies on autonomic dysfunction in MS and spinal cord lesions. This study assessed the frequency of autonomic dysfunction (AD) in MS and the correlation to spinal cord magnetic resonance imaging (MRI) findings. We prospectively studied 75 MS patients (25 with relapsing-remitting forms, 25 with secondary progressive forms and 25 with primary progressive forms). We performed sympathetic skin response, R-R interval variability and orthostatic hypotension testing. Spinal cord MRI was performed to detect demyelinating lesions (sagittal and axial plane) or spinal cord atrophy. Clinical and laboratory evidence of AD was found in 84 % and 56 % of MS patients, respectively. The correlation of the latter with disability was evaluated using the Extended Disability Status Scale. AD was more frequent in primary progressive MS than in the other two forms. AD was correlated with spinal cord cross-sectional area reduction but not with spinal cord hyperintensities. This study confirms that the frequency of AD in MS, especially in primary progressive forms, has until now been underestimated. Furthermore, AD appears to be more closely related to axonal loss, as demonstrated by spinal cord atrophy, than to demyelinating lesions. Received: 20 March 2000, Received in revised form: 13 October 2000, Accepted: 29 October 2000     

Early recognition and diagnosis of multiple sclerosis

Multiple sclerosis (MS) is an autoimmune disorder associated with inflammation and demyelination in the brain, optic nerve, and spinal cord. Patients with MS may present with a wide range of clinical symptoms, either monofocal or multifocal, all of which are related to the central nervous system. Although several strategies for the early recognition of MS are available, diagnostic criteria call for MRI of the brain and spinal cord due to its specificity in identifying white matter lesions disseminated in time and space. The course of MS is unpredictable, but 4 clinical subtypes have been described: relapsing-remitting, secondary progressive, primary progressive, and progressive relapsing. Prevalence rates for MS vary depending on geography, and susceptibility for MS appears to be influenced by both environmental and genetic risk factors.     

Recent progress in the diagnosis and treatment of multiple sclerosis

Magnetic resonance imaging (MRI) now provides valuable diagnostic and prognostic information for the management of multiple sclerosis (MS) but the diagnosis still largely rests on the clinical features of central nervous system (CNS) lesions disseminated in time and place. Recent histological and MRI studies indicate that extensive axonal damage can occur in MS, even early in the disease course, and is likely to be an important cause of accumulating disability. Several immunomodulating agents have now been shown to have beneficial effects in MS. High dose intravenous or high dose oral methylprednisolone therapy accelerates recovery from attacks of relapsing-remitting MS, but at present there is no convincing evidence that standard dose (intermediate dose) oral corticosteroid therapy is beneficial for such attacks. Interferon beta, copolymer 1 (glatiramer acetate) and i.v. immunoglobulin therapy each significantly reduce the frequency of attacks of relapsing-remitting MS. Interferon beta also inhibits the progression of disability in relapsing-remitting MS and secondary progressive MS, but its effect on primary progressive MS is unknown. Oral low dose methotrexate therapy slows the progression of disability in secondary progressive MS and possibly in primary progressive MS, but it is likely that the currently used dosage (7.5 mg weekly) is suboptimal. Further research is needed to determine the optimal doses and combinations of the above therapies in MS and to develop better therapies, particularly for primary progressive MS.     

Management of multiple sclerosis: current trials and future options

PURPOSE OF THE REVIEW: The present review of multiple sclerosis (MS) therapeutic trials published in 2002 is intended to assist the reader in understanding the most current advances in the care of their patients. RECENT FINDINGS: A substantial number of pivotal and preliminary reports continue to demonstrate encouraging new evidence that advances are being made in the care of patients with MS. Several short-term studies in relapsing/remitting MS have demonstrated that it is possible to complete head-to-head comparison trials of active agents in MS (e.g. without a placebo control group). The findings of these trials remain open to interpretation and have generated considerable controversy, as expected. A phase 3 trial [the International MS Secondary Progressive Avonex Controlled Trial (IMPACT)] became the fourth study of the beta interferons (interferon-beta-1a, in this case) to demonstrate a partial effect on disease activity in secondary progressive MS. Two trials demonstrated apparent partial efficacy for the anthrecenedione mitoxantrone in active and progressive MS. Disappointing results were announced for a number of large pivotal trials, although those results have not yet been published (e.g. oral glatiramer acetate in relapsing/remitting MS, glatiramer acetate in primary progressive MS, and intravenous immunoglobulin in secondary progressive MS). SUMMARY: The MS research community needs to determine how best to address two key unanswered questions. Is late clinical deterioration often or invariably tied to the initial inflammatory/demyelinating phase of the disease? What is the optimal research design to address whether current and future experimental strategies affect the later phases of MS (e.g. does early treatment delay or prevent clinical disability)?     

Increased circulating T cell reactivity to GM3 and GQ1b gangliosides in primary progressive multiple sclerosis.

We have previously shown that patients with primary progressive multiple sclerosis (MS) have significantly elevated plasma levels of antibody to GM3 ganglioside compared to patients with relapsing-remitting MS, healthy subjects and patients with other neurological diseases. Anti-GM3 antibody levels were elevated also in patients with secondary progressive MS but to a lesser extent than in primary progressive MS. As gangliosides are particularly enriched in the axonal membrane, these findings suggested that antiganglioside immune responses might contribute to the axonal damage in progressive forms of MS. The present study was performed to determine whether peripheral blood T cell responses to GM3 are also increased in progressive MS. Blood was collected from 98 untreated patients with MS (40 with relapsing-remitting, 27 with secondary progressive and 31 with primary progressive MS), 50 healthy subjects and 24 patients with other disorders of the CNS, and reactivity to GM1, GM3, GD1a, GD1b, GD3, GT1b, GQ1b and sulphatide was assessed by 6-day T cell proliferation assays. Increased T cell reactivity to GM3 and GQ1b occurred significantly more often in patients with primary progressive MS than in healthy subjects and patients with other CNS diseases. These findings suggest that ganglioside-specific T cells may contribute to the axonal damage in primary progressive MS.     

Secondary progressive multiple sclerosis: current knowledge and future challenges

The secondary progressive phase of multiple sclerosis (MS), which is characterised by a steady accrual of fixed disability after an initial relapsing remitting course, is not clearly understood. Although there is no consensus on the mechanisms underlying such a transition to the progressive phase, epidemiological and neuroimaging studies indicate that it is probably driven by the high prevalence of neurodegenerative compared with inflammatory pathological changes. This notion is lent support by the limited efficacy of available immunomodulating and immunosuppressive treatment strategies, which seems to be further decreased in the late stages of secondary progressive MS. No established clinical or paraclinical predictors of the transition from relapsing remitting to secondary progressive MS have been described. However, the use of quantitative MRI-derived measures is warranted to monitor natural history studies and therapeutic trials of secondary progressive MS with increased reliability. In view of the small effects of immunomodulating and immunosuppressive treatments in preventing the transition to secondary progression, the development of treatments promoting neuroaxonal repair remains an important goal in this disease.     

Role of Immunosuppressive Therapy for the Treatment of Multiple Sclerosis

Immunosuppressives have been used in multiple sclerosis (MS) since 1966. Today, we have many treatments for the relapsing forms of the disease, including 8 US Food and Drug Administration-approved therapies, with more soon to be introduced. Given the current treatment landscape what place do immunosuppressants have in combating MS? Trial work and our experience suggest that immunosuppressives still have an important role in treating MS. Cyclophosphamide finds use in treating patients with severe, inflammatory relapsing remitting MS or those suffering from a fulminant attack. We tend to employ mycophenolate mofetil as an add-on to injectable therapy for patients experiencing breakthrough activity. Some progressive (primary progressive multiple sclerosis or secondary progressive multiple sclerosis) patients may stabilize after treatment with either cyclophosphamide or mycophenolate. We rarely employ mitoxantrone because of potential cardiac or carcinogenic effects. We prefer to use cyclophosphamide or mycophenolate mofetil in preference to methotrexate because evidence of efficacy is limited for this drug. We have less experience with azathioprine, but it may be an alternative for patients with limited options who are unable to tolerate conventional therapies.     

Progressive multiple sclerosis: characteristics and management

Progressive multiple sclerosis (MS) consists of 3 phenotypic subtypes: secondary progressive MS, primary progressive MS, and progressive relapsing MS. There has been a paucity of approved treatments for these subtypes possibly driven by irreversible neurodegeneration within the central nervous system and not amenable to drugs that target inflammation. This article reviews magnetic resonance imaging and clinical data that show that progression may occur early in the course of MS and specific subsets of progressive patients may respond to disease modifying drugs.