多发性硬化治疗中值得关注的问题

近年来 ,关于多发性硬化 (ｍｕｌｔｉｐｌｅｓｃｌｅｒｏｓｉｓ,ＭＳ)的治疗研究已取得令人瞩目的进展 ,合理治疗能改善患者的残障程度 ,降低复发率。但目前在临床治疗ＭＳ中存在的一些问题值得商榷。一、以循证医学为依据 ,并结合个人经验治疗ＭＳ应以最新的有充分证据的临床研究作为依据 ,结合个人的经验进行 ,二者缺一不可。仅凭个人经验对某些个体可能有效 ,但总体评价不一定有效。例如 ,临床上有的医生长期用肾上腺糖皮质激素治疗和预防ＭＳ,这种方法缺乏可靠证据。只有将循证医学证据与个人经验完美地结合 ,才有可能获得最佳的疗效和…     

糖皮质激素治疗多发性硬化不同方案的临床应用

目的探讨糖皮质激素治疗多发性硬化(MS)的不同方案的疗效、住院费用、住院时间、复发情况及不良反应等。方法 97例MS急性期患者随机分为鞘内注射甲泼尼龙(MPS)组(30例)、MPS冲击治疗组(36例)及地塞米松治疗组(31例),比较各组治疗后不同时间的Kurtzke扩展致残量表(EDSS)评分减少值、住院费用、费用中药品比例、住院时间、复发情况及不良反应等。结果鞘内注射MPS组治疗后5 d起,MPS冲击治疗组治疗后10 d起EDSS评分减少值明显高于地塞米松治疗组(均P<0.05)。治疗后5 d时鞘内注射MPS组EDSS评分减少值明显高于MPS冲击治疗组(P<0.05)。3组间鞘内注射MPS组总住院费用最少,费用中药品比例最低,日均住院费用较少,住院时间较短(均P<0.05);MPS冲击治疗组日均住院费用最高,地塞米松治疗组住院时间最长(均P<0.05)。MPS冲击治疗组复发率最高,复发时间最短(均P<0.05);地塞米松治疗组和鞘内注射MPS组复发率及复发时间比较差异无统计学意义。各组均无严重不良反应发生。结论鞘内注射MPS治疗MS起效较快,近期疗效显著,住院费用较低,复发率较低,复发时间较长,无严重不良反应,宜在临床推广应用。     

定期糖皮质激素治疗复发-缓解型多发性硬化临床试验

<正> 2009年第6期Lancet Neurology发表了复发-缓解型多发性硬化(RRMS)患者口服甲强龙作为干扰素β1a添加治疗的北欧研究(NORdic trial of oral methylprednisoloneas add-on therapy to interferon beta-1a for treatment ofrelapsing-remitting multiple sclerosis,NORMIMS study)结果。该研究采用双盲评价法,对使用干扰素治疗期间仍有复发的RRMS患者添加口服大剂量甲强龙或安慰剂,经96周的治疗发现,定期添加大剂量糖皮质激素(以下简称激素)组患者复发率显著低于安慰剂组,而严重不良反应并     

多发性硬化患者白细胞糖皮质激素受体改变的研究

目的明确多发性硬化患者白细胞糖皮质激素受体改变,阐明其改变与病因学的联系及在治疗中的作用。方法应用放射免疫法和放射配体结合法测定了１５例多发性硬化患者血浆皮质醇和外周血白细胞ＣＲ。结果ＭＳ患者的Ｆ和ＧＲ分别为３９０．３３±２８２.０３ｎｍｏｌ／Ｌ和１０００±７８０位点／细胞。Ｆ与对照组比较无显著性差异（４７８．６０±９６．８１ｎｍｏｌ／Ｌ,Ｐ＞０．０５）;ＧＲ明显低于对照组（５４２０±７７５位点／细胞,Ｐ＜０．００１）。ＭＳ患者ＧＲ与Ｆ无相关性（ｒ＝０．２５８,Ｐ＞０．０５）。结论提示ＭＳ存在有ＧＣ－ＧＲ系统的紊乱,与ＭＳ疾病有关联。ＧＲ含量低,ＧＣ治疗仍有效,提出ＭＳ患者白细胞上可能存在低亲和力受体。     

肌萎缩侧索硬化症治疗措施的临床证据评价

目的 评价不同治疗方案对肌萎缩侧索硬化症的作用及药物不良反应,以为循证制定最佳治疗方案.方法 以肌萎缩侧索硬化症、利鲁唑、加巴喷丁、拉莫三嗪、神经营养因子、抗氧化和氧自由基清除药、基凶治疗、神经十细胞治疗、治疗等词组作为检索词,分别检索MEDLINE、Cochrane图书馆、万方数据知识服务平台学术期刊库和中国知网中国期刊全文数据库,按照相应的纳入标准和排除标准,获取临床指南.系统评价、随机对照临床试验、临床对照试验、回顾性病例分析及病例观察研究的相关文献.并采用Jadad量表对文献质量进行评价,判断研究结论的真实性和可靠性.同时手工榆索有关会议资料和中英文原著、教科书,并与该研究领域从事此方面研究的学者联系,以便对在线检索不到全文者直接Email联系以获取全文.结果 经筛选纳入与肌萎缩侧索硬化症治疗相关的系统评价4篇、随机对照临床试验18篇、临床对照试验11篇、病例观察研究6篇.其中27篇为高质量文献(Jadad量表评价:11篇4分、13篇5分、3篇7分),12篇为低质量文献(评分3分).对各种治疗方法或药物疗效及安全性进行评价显示:利鲁唑为目前唯一被美幽食晶与药晶管理局批准应用于临床的药物,缺乏其他更有效的治疗药物;利鲁唑无效时口r采用多药联合方案及对症治疗.结论 借助循证医学评价方法可为肌萎缩侧索硬化症患者的治疗提供最佳临床证据.     

多发性硬化患者血清尿酸水平变化的研究

目的　探讨多发性硬化 (MS)患者血清尿酸 (UA)水平的变化及其临床意义。方法　采用酶定量分析法对 4 3例MS患者和 4 5名正常对照者的血清UA水平进行检测。结果　MS组血清UA水平明显低于对照组 (P <0 0 1)。MS组中病程越长 (P <0 0 1)、神经伤残程度越重 (DSS评分越高 ) (P <0 0 5 ) ,血清UA水平越低 ;女性患者UA水平明显低于男性患者 (P <0 0 0 1) ;经过糖皮质激素治疗后血清UA水平明显回升 (P <0 0 0 1) ,但治疗前血清UA水平越低则疗效越差 (P <0 0 1、P <0 0 5 )。结论　MS患者血清UA水平降低 ,且与MS的病程、伤残程度、疗效及性别密切相关。UA水平升高可能为激素治疗MS的一个作用机制     

多发性硬化的治疗进展

传统观点认为多发性硬化（MS）是一种中枢神经系统的自身免疫性炎性脱髓鞘疾病,常采用免疫抑制和抗炎治疗。随着对MS发病机制研究的深入,许多新的治疗策略被用于MS的治疗。MS疾病修正治疗已尝试进行MS发病的特异性靶点治疗,而对进展性MS则采用神经保护和神经修复治疗。与当前的治疗措施相比,新的治疗方案对控制MS复发更有效,但也带来一定的风险。目前仍在积极寻找进展性MS的有效治疗手段。     

多发性硬化临床特征分析及治疗

目的 探讨多发性硬化(multiple sclerosis,MS) 的临床特征及治疗方法.方法 回顾分析42例MS患者的临床资料.结果 MS 好发于青年女性(29例),常见症状为肢体无力(29例)、视力障碍(22例)和感觉障碍(21例).病变累及大脑半球30例,视神经28例,脊髓23例,脑干9例,小脑4例,所有病例MRI检查均有阳性改变,CSF检查IgG鞘内合成率阳性16例,寡克隆区带阳性19例,抗髓鞘碱性蛋白(MBP)抗体阳性15例.视觉诱发电位(VEP)异常28例,脑干听觉诱发电位(BAEP)阳性16例,体感诱发电位(SEP)异常20例,急性期甲强龙冲击治疗患者临床症状均有改善,缓慢激素减量及小剂量激素长期维持治疗,随访至2008-01仅有7例复发.结论 结合临床特点、MRI、脑脊液免疫学、诱发电位检查能明显提高临床确诊率.急性期甲强龙冲击治疗可改善临床症状,缩短急性期病程,缓慢激素减量及小剂量激素长期维持可能有助于降低复发率.     

多发性硬化的临床特点与预后的分析

目的分析多发性硬化(MS)的临床特点与预后。方法回顾性分析117例MS患者的临床资料,从临床、影像学等方面对视神经脊髓型(OSMS)和经典MS型(CMS)进行比较。结果117例MS患者中,OSMS型42例(35.9%),CMS型75例(64.1%)。临床表现中,OSMS患者出现肢体无力(88.1%)、感觉缺失(85.7%)、感觉异常(57.1%)、视物模糊(76.2%)、尿便障碍(73.8%)明显多于CMS患者(70.7%、56.0%、20.0%、45.3%及26.7%)(均P<0.05);出现共济失调(7.1%)、复视(0)及构音不清(0)明显少于CMS患者(42.7%、10.7%及16.0%)(P<0.05～0.01)。OSMS患者出现长节段融合性脊髓病变的比例(94.1%)显著多于CMS患者(48.2%)(P<0.01)。脑脊液检查和诱发电位检查结果OSMS组和CMS组差异无统计学意义。发病5年后扩大的残疾状态量表(EDSS)评分OSMS组(2.42±0.90)显著高于CMS组(1.50±0.88)(P<0.05)。在发病的第1年和第3年,年平均复发次数复发缓解型OSMS[(1.92±1.05)次、(1...     

The therapy of multiple sclerosis with immune-modulating or immunosuppressive drug. A critical evaluation based upon evidence based parameters and published systematic reviews

Today many different drugs are available for treatment of multiple sclerosis (MS). Interferons, glatiramer acetate, mitoxantrone, and natalizumab have been approved by the regulatory authorities of many countries for the treatment of MS. Evidence based medicine (EBM) principles allow physicians to better address the correct treatment for patients. This article aimed to review all the clinical trials on immune-modulating and immunosuppressive drugs on the basis of the EBM principles. Based on the evidence to date interferon beta represents the best therapeutic option, particularly if given at high doses and with multiple injections per week. Due to its lower efficacy, glatiramer acetate should be used as a second choice in case of intolerable side effects or toxicity of interferon beta. Great efficacy has been demonstrated for mitoxantrone and natalizumab. These drugs should be, however, used with particular attention for their potential toxic effects.     

EFNS guideline on treatment of multiple sclerosis relapses: report of an EFNS task force on treatment of multiple sclerosis relapses.

Relapses, exacerbations or attacks of multiple sclerosis are the dominating feature of relapsing-remitting multiple sclerosis (MS), but are also observed in patients with secondary progressive MS. High-dose methylprednisolone is the routine therapy for relapses at present, but other treatments are also in current use. The objective of the task force was to review the literature on treatment of MS relapses to provide evidence-based treatment recommendations. Review was carried out on the literature with classification of evidence according to the EFNS guidelines for scientific task forces. Short-term, high-dose methylprednisolone treatment should be considered for the treatment of relapses of MS (level A recommendation). The optimal glucocorticoid treatment regimen, in terms of clinical efficacy and adverse events, remains to be established. A more intense, interdisciplinary rehabilitation programme should be considered as this probably further improves recovery after treatment with methylprednisolone (level B recommendation). Plasma exchange is probably efficacious in a subgroup of patients with severe relapses not responding to methylprednisolone therapy, and should be considered in this patient subgroup (level B recommendation). There is a need for further randomized, controlled trials in order to establish the optimal treatment regimen for relapses of MS.     

糖皮质激素不同给药方式治疗急性期多发性硬化的疗效观察

目的探讨糖皮质激素3种不同给药方式治疗急性期多发性硬化(multiple sclerosis，MS)的疗效及安全性。方法将1998～2002年于我科治疗的48例MS患者按主要治疗方法的不同分为鞘内注入地塞米松(DXM)组、甲基强的松龙(MPS)冲击组及常规使用激素组。比较治疗后各组不同时间的Kurtzke扩充致残量表(Kurtzke expanded disability status scale，EDSS)评分减少数及副作用的发生率。结果鞘内注入DXM组治疗早期EDSS评分减少较其它两组显著，尤其对于脊髓受累为主的MSEDSS评分改善更为明显。结论鞘内注入DXM与两种常规方法比较见效快，建议用于脊髓受累为主的急性期MS。     

Teriflunomide for the treatment of multiple sclerosis

Teriflunomide is a new active drug which has recently been approved as a first-line treatment of relapsing forms of MS in the US, Australia, Argentina, and the European Union. It is characterized by a once-daily oral application and a well-established long-term safety profile. The main therapeutic effect is considered to be mediated via the inhibition of the de novo synthesis of pyrimidine in proliferating immune cells. Two phase III clinical trials (TEMSO, TOWER) tested teriflunomide in patients with relapsing forms of MS: efficacy was shown, with positive effects on relapse rates and disease progression for 14 mg/day. Overall, the safety profile in these studies was favorable. In patients treated with teriflunomide, the regular monitoring of blood cell counts and liver enzymes is required. Teriflunomide must not be used during pregnancy. In this article, we review recent phase II and phase III clinical trial data, and discuss the potential of teriflunomide for the treatment of relapsing forms of MS.     

Evoked potentials for evaluation of multiple sclerosis

The role of evoked potentials (EP) in the assessment of multiple sclerosis (MS) has changed over the last decade. This is largely due to progress in imaging techniques. But while MRI has a greater diagnostic sensitivity, EP remain a useful diagnostic tool in many clinical situations. Moreover, recent studies demonstrate the utility of EP for monitoring and predicting the course of the disease in patient groups, although not yet in individuals. For these purposes, EP show better results than conventional MRI. In the near future, new developments in electrophysiology, immunology and imaging may allow to differentiate between different subtypes of MS early in the course, and consequently to tailor therapeutic measures more precisely to the individual patients.     

Targeting remyelination treatment for multiple sclerosis

Since disability in multiple sclerosis (MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/ß-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.     

Immunosuppressive treatment in multiple sclerosis

Immunosuppressive therapy has been used to treat multiple sclerosis (MS) for over 30 years based on the hypothesis that MS is a T cell-mediated autoimmune disease. The most commonly used immunosuppressive agents in MS are azathioprine, cyclophosphamide, methotrexate, and mitoxantrone. Since the interferons and glatiramer acetate have become widely used in MS, immunosuppressive agents have found a role given as combination therapy or as monotherapy in instances where the interferons and glatiramer acetate are not effective in controlling the disease. Like the interferons and glatiramer acetate, immunosuppressive drugs are most efficacious in stages of MS that have an inflammatory component as evidenced by relapses and/or gadolinium-enhancing lesions on MRI or in patients in earlier stages of disease where inflammation predominates over degenerative processes in the CNS. There is no evidence of efficacy in primary progressive MS or later stages of secondary progressive MS. In our studies of cyclophosphamide, we have found that although it is a general immunosuppressant that affects both T cell and B cell functions, cyclophosphamide has selective immune effects in MS by suppressing IL-12- and Th1-type responses and enhancing Th2/Th3 responses (IL-4, IL-10, TGF-beta; eosinophils in peripheral blood). Cyclophosphamide and mitoxantrone are the most common immunosuppressive drugs used in patients with rapidly worsening MS whose disease is not controlled by beta-interferon or glatiramer acetate.     

The spectrum of multiple sclerosis and treatment decisions

An increasing number of patients referred for neuroimaging studies unrelated to multiple sclerosis (MS) are found to have incidental lesions suggestive of MS in their nervous systems but many such patients do not develop clinical symptoms and signs and remain as "subclinical MS" (SCMS). MRI and cerebrospinal fluid (CSF) studies in monozygotic twins and siblings of MS patients, as well as necropsy studies in asymptomatic persons also reveal findings consistent with SCMS. Clinically isolated syndromes (CIS), acute disseminated encephalomyelitis (ADEM), benign MS, relapsing-remitting MS, primary and secondary progressive MS, optico-spinal MS, Balo's and Marburg's diseases, are considered different forms of MS by many because of their heterogeneous clinical, imaging and pathological features. Studies of disease susceptibility, type, course and severity have given different results in different populations, consistent with "genetic heterogeneity". The various forms of the disease may change from one to another, and their clinical and imaging features became similar after a number of years. The current data support the concept that MS, whether it is a single disease or a group of disorders, is an immune-mediated disease of the CNS, with both inflammatory and degenerative features with available therapies being only partially and temporarily effective for the inflammatory phase of the disease. Making the diagnosis of MS may not be an absolute indication for early treatment with disease modifying agents. The use of new technology such as microarray and other techniques in diagnosing and understanding the MS spectrum may make it possible to recognize the different molecular subtypes of these diseases and develop better therapies.     

α-硫辛酸改善多发性硬化患者认知功能障碍作用观察

目的观察α-硫辛酸(α-LA)对多发性硬化(MS)认知障碍的疗效,探讨α-LA对MS的可能治疗机制。方法收集30例MS患者和30例健康体检者,采用神经心理学测试的方法评价患者治疗前的认知功能;MS组患者根据治疗情况分为两组,MS对照组,给予激素冲击治疗;α-LA治疗组,给予激素冲击和硫辛酸联合治疗。治疗后继续应用神经心理学测试的方法评价患者认知功能;比较治疗前后的认知功能改善情况。结果临床功能障碍评价表明MS患者存在明显的认知功能下降(P<0.05),治疗后MS对照组认知功能改善无明显变化(P>0.05),α-LA治疗组认知功能改善明显(P<0.05)。结论α-LA通过多种作用机制对MS具有保护作用,能明显改善患者认知功能。