Journal of multiple sclerosis最新文献

英文中文

Multiple Sclerosis and Gene Polymorphisms: are we Groping in the Dark? 多发性硬化症和基因多态性:我们是在黑暗中摸索吗?

Journal of multiple sclerosis

Pub Date : 2015-12-17 DOI: 10.4172/2376-0389.1000162

E. Haq

Copyright: © 2015 Haq E, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Till date, the etiology of multiple sclerosis (MS) remains convoluted and many recent studies have added some startling findings to the existing literature on MS. There have been some noticeable developments in dissecting genetics of MS, but the results remain controversial due to divergence in geographic prevalence of MS across different populations. By and large this may be attributed to the enigmatic genetic and environmental background in its etiopathogenesis. By unlocking the missing link between these two components, some advancement can be achieved in devising better treatment options for MS management. This commentary highlights the outcome of our recent study aimed at exploring the association between MS susceptibility and EIF2B5 Ile587Val polymorphism in a subset of Indian population [1].

版权所有:©2015 Haq E, et al。这是一篇根据知识共享署名许可协议发布的开放获取文章，该协议允许在任何媒体上不受限制地使用、分发和复制，前提是要注明原作者和来源。迄今为止，多发性硬化症(MS)的病因仍然很复杂，最近的许多研究为MS的现有文献增加了一些惊人的发现。MS的解剖遗传学有了一些显著的进展，但由于MS在不同人群中的地理患病率存在差异，结果仍然存在争议。总的来说，这可能归因于其发病机制中神秘的遗传和环境背景。通过解开这两个组成部分之间缺失的联系，可以在为MS管理设计更好的治疗方案方面取得一些进展。这篇评论强调了我们最近研究的结果，该研究旨在探索印度人群中一个亚群中MS易感性与EIF2B5 Ile587Val多态性之间的关系[1]。

引用次数: 2

Immune Tolerance Induction against Experimental Autoimmune Encephalomyelitis (EAE) Using A New PLP-B7AP Conjugate that Simultaneously Targets B7/CD28 Costimulatory Signal and TCR/MHC-II Signal. 利用同时针对 B7/CD28 Costimulatory 信号和 TCR/MHC-II 信号的新型 PLP-B7AP 共轭物诱导免疫耐受，对抗实验性自身免疫性脑脊髓炎 (EAE)

Journal of multiple sclerosis

Pub Date : 2015-12-01 DOI: 10.4172/2376-0389.1000131

Ahmed H Badawi, Paul Kiptoo, Teruna J Siahaan

Most of the current therapies used in the treatment of multiple sclerosis (MS) are either ineffective or have adverse side effects. As such, there is a need to develop better therapies that specifically target myelin-specific aberrant immune cells involved in CNS inflammation without compromising the general immune system. In the present study, we developed a new bifunctional peptide inhibitor (BPI) that is effective and specific. Our BPI (PLP-B7AP) is composed of an antigenic peptide from myelin proteolipid protein (PLP_139-151) and a B7 antisense peptide (B7AP) derived from CD28 receptor. The main hypothesis is that PLP-B7AP simultaneously targets MHC-II and B7-costimulatory molecules on the surface of antigen presenting cells (APC) and possibly alters the differentiation of naïve T cells from inflammatory to regulatory phenotypes. Results showed that PLP-B7AP was very effective in suppressing experimental autoimmune encephalomyelitis (EAE) compared to various controls in a mouse model. PLP-B7AP was effective when administered both before and after disease induction. Secreted cytokines from splenocytes isolated during periods of high disease severity and remission indicated that PLP-B7AP treatment induced an increased production of anti-inflammatory cytokines and inhibited the production of pro-inflammatory cytokines. Further, analysis of cortical brain tissue sections showed that PLP-B7AP treated mice had significantly lower demyelination compared to the control group. All these taken together indicate that the T cell receptor (TCR) and the CD28 receptor can be targeted simultaneously to improve efficacy and specificity of potential MS therapeutics.

目前用于治疗多发性硬化症（MS）的大多数疗法要么无效，要么有不良副作用。因此，有必要开发更好的疗法，在不损害一般免疫系统的情况下，专门针对参与中枢神经系统炎症的髓鞘特异性异常免疫细胞。在本研究中，我们开发了一种有效且特异的新型双功能肽抑制剂（BPI）。我们的 BPI（PLP-B7AP）由来自髓鞘蛋白脂质的抗原肽（PLP139-151）和来自 CD28 受体的 B7 反义肽（B7AP）组成。主要假设是 PLP-B7AP 同时靶向抗原呈递细胞（APC）表面的 MHC-II 和 B7-刺激分子，并可能改变幼稚 T 细胞从炎症型向调节型的分化。研究结果表明，在小鼠模型中，与各种对照组相比，PLP-B7AP能非常有效地抑制实验性自身免疫性脑脊髓炎（EAE）。PLP-B7AP 在疾病诱导前后给药均有效。从疾病严重期和缓解期分离的脾脏细胞分泌的细胞因子表明，PLP-B7AP 治疗可诱导抗炎细胞因子的产生，并抑制促炎细胞因子的产生。此外，对大脑皮层组织切片的分析表明，与对照组相比，PLP-B7AP 治疗组小鼠的脱髓鞘程度明显较低。所有这些都表明，T细胞受体（TCR）和CD28受体可以同时作为靶点，以提高潜在多发性硬化症疗法的疗效和特异性。

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引用次数: 0

The Pathology of the Internal Jugular Vein in Multiple Sclerosis 多发性硬化症颈内静脉的病理

Journal of multiple sclerosis

Pub Date : 2015-11-30 DOI: 10.4172/2376-0389.1000160

M. Pedriali, P. Zamboni

Abstract In the last years it has been described a condition named Chronic Cerebrospinal Venous Insufficiency (CCSVI), frequently but not exclusively associated to Multiple Sclerosis (MS), which generated a strong scientific controversy about the epidemiological prevalence and the possible role in the complex, multi-factorial MS ethio-pathogenesis. However, CCSVI description also stimulated a considerable research activity on the extracranial veins. Among the fields of interest, the pathology of the Internal Jugular Veins (IJVs) was deeply investigated by some groups, so improving our knowledge in an underestimated field of MS research. Currently, the available papers clearly show the presence of abnormalities in the IJV wall of MS patient’s respect to control tissue. In the tunica intima a significant derangement and loss of the endothelial cells have been described. Interestingly scanning electronic microscopy showed absence of endothelium in the defective jugular valves. In the adventitia it has been described an inverted ratio between type I and type III collagen, with prevalence of the latter. Finally, in the adventitia layer it has been found the presence of calcifications arranged around the vena venarum. Assessment of immune cells in the three IJV layers did not demonstrate increased infiltration. Current studies do not clarify the origin of the pathology of the IJV in patients with MS. Congenital, infectious, or even post thrombotic ethiology have been advocated. Finally, the review summarizes studies which link the CCSVI pathophysiology to the complex MS pathogenesis, and particularly to the impact of restricted brain outflow on the cerebral spinal fluid dynamics and cerebral perfusion.

近年来，慢性脑脊髓静脉功能不全(CCSVI)常与多发性硬化症(MS)相关，引起了关于其流行病学患病率及其在复杂的多因素MS发病机制中的可能作用的强烈科学争议。然而，CCSVI的描述也激发了大量关于颅外静脉的研究活动。在感兴趣的领域中，一些小组对颈内静脉(IJVs)的病理进行了深入的研究，从而提高了我们对MS研究中一个被低估的领域的认识。目前，现有文献清楚地显示MS患者相对于对照组织的IJV壁存在异常。在内膜中，内皮细胞有明显的紊乱和丢失。有趣的是，扫描电镜显示在缺陷的颈静脉瓣膜中内皮细胞的缺失。在外膜中，已经描述了I型和III型胶原蛋白之间的反向比例，后者的患病率。最后，在外膜层，发现在小静脉周围有钙化。对三层IJV中的免疫细胞的评估未显示浸润增加。目前的研究并没有明确ms患者IJV的病理起源，先天性的、传染性的，甚至血栓形成后的病理学都被提倡。最后，综述了将CCSVI病理生理与MS复杂发病机制联系起来的研究，特别是限制性脑流出对脑脊液动力学和脑灌注的影响。

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引用次数: 7

A Cohort Study of Cognitive Impairment in Patients of Multiple Sclerosis 多发性硬化患者认知功能障碍的队列研究

Journal of multiple sclerosis

Pub Date : 2015-11-29 DOI: 10.4172/2376-0389.1000161

Rumpaul Rima

Abstract Introduction:Multiple sclerosis (MS) is an inflammatory disease which disrupts the ability of nervous system to communicate, resulting in a wide range of signs and symptoms including physical, cognitive and psychiatric. Cognitive dysfunction is increasingly recognized as a critical factor in the quality of life of patients with MS. Remission of cognitive symptoms is uncommon, and cognitive decline may indicate progressive disease despite stable physical symptoms. Methods: A total of 30 patients of MS diagnosed by modified Mc Donald criterion 2010 had undergone MACFINS battery of Cognitive testing twice, first at the time of initial recruitement and then after a period of 6 months. Results: No significant cognitive decline was observed in patients after a mean follow up of 11 months. There was mild but not significant impairment in EDSS. There appears a strong direct correlation between all neuropsychological tests and physical disability. Most significant correlation of EDSS is seen with PASAT (P=0.002), BVMT1(P= 0.008), BVMT2(P=0.007), COWAT(P=0.0002) and Stroop B(P=0.009). Conclusion: Cognitive deterioration occurs probably insidiously and inconsistently in patients with MS. EDSS has significant direct correlation with cognitive impairment in these patients. A larger sample size study is required to conclusively establish cognitive performance in MS patients.

摘要简介:多发性硬化症(MS)是一种炎症性疾病，它破坏了神经系统的沟通能力，导致广泛的体征和症状，包括身体，认知和精神。认知功能障碍越来越被认为是ms患者生活质量的一个关键因素，认知症状的缓解并不常见，尽管身体症状稳定，但认知能力下降可能表明疾病的进展。方法:对30例经改良Mc - Donald标准诊断为MS的患者，在入组时和入组6个月后分别进行两次MACFINS认知测试。结果:平均随访11个月后，患者的认知能力未见明显下降。EDSS有轻微但不显著的损害。所有的神经心理测试和身体残疾之间都有很强的直接联系。EDSS与PASAT (P=0.002)、BVMT1(P= 0.008)、BVMT2(P=0.007)、COWAT(P=0.0002)和Stroop B(P=0.009)相关性最显著。结论:多发性硬化症患者的认知功能恶化可能是隐性和不一致的，EDSS与这些患者的认知功能障碍有显著的直接关系。需要更大样本量的研究来最终确定MS患者的认知表现。

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引用次数: 3

Useless Hand Syndrome and Astereognosis in Multiple Sclerosis 多发性硬化症的残手综合征与立体诊断

Journal of multiple sclerosis

Pub Date : 2015-11-20 DOI: 10.4172/2376-0389.1000159

B. Okuda

Useless hand syndrome (UHS) by Oppenheim, comprising clumsiness of complex finger movements and loss of manual dexterity, arises from cervical cord lesions in multiple sclerosis (MS) [1]. From Oppenheim’s report, UHS has been attributed to impaired proprioception, resembling the nature of sensory ataxia [1,2]. In fact, T2 MRI showed high cervical lesions (C2-C4), consistently involving the posterior cord at the C3 to C4 level, in all of our patients with MS and UHS. However, I do not necessarily support the above-mentioned mechanism underlying UHS, because UHS was not associated with disturbance of deep sensations in some cases. As reported previously, UHS might be attributable to astereognosis rather than sensory ataxia, suggesting a disorder of sensorimotor integration [3]. While posterior cord lesions cause both of UHS and sensory ataxia, the underlying mechanism appears to differ, at least in part. In this regard, concurrent sensory disturbances may be helpful in elucidating the underlying mechanism of UHS. In all of our patients, stereognosis was most severely disturbed, whereas disturbance of other combined sensations such as two-point discrimination and graphesthesia ranged from severe to moderate. Combined sense was not necessarily impaired in parallel with deep sense.

Oppenheim定义的无用手综合征(UHS)是由多发性硬化症(MS)的颈脊髓病变引起的，包括复杂手指运动的笨拙和手部灵巧性的丧失[1]。根据Oppenheim的报告，UHS被归因于本体感觉受损，类似于感觉性共济失调的性质[1,2]。事实上，在我们所有的MS和UHS患者中，T2 MRI显示高颈椎病变(C2-C4)，一贯累及C3至C4水平的后脊髓。然而，我并不一定支持上述UHS的机制，因为UHS在某些情况下与深层感觉的干扰无关。如先前报道，UHS可能是由立体认知而非感觉共济失调引起的，提示感觉运动整合障碍[3]。虽然后脊髓损伤可引起UHS和感觉性共济失调，但其潜在机制似乎有所不同，至少部分不同。在这方面，并发感觉障碍可能有助于阐明UHS的潜在机制。在我们所有的患者中，立体知觉受到最严重的干扰，而其他组合感觉如两点辨别和图形感觉的干扰从严重到中度不等。综合感觉并不一定与深层感觉同时受损。

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引用次数: 0

Multiple Sclerosis and Work: An Interpretative Phenomenological Analysis of the Perspective of Persons with Early Stage MS 多发性硬化症与工作:早期多发性硬化症患者视角的解释性现象学分析

Journal of multiple sclerosis

Pub Date : 2015-10-31 DOI: 10.4172/2376-0389.1000158

A. Capelle, L. Visser, Frans Vosman

Abstract Objective:This study explores the lived experience in their working lives of people with early stage multiple sclerosis (MS). Method: Ten people at various stages in their careers (applying, employed, recently retired) who had been diagnosed with early stage MS were interviewed in open, in depth interviews. Transcriptions were analysed following a phenomenological approach. Results: Six themes were found: the tiresome process of adjustment, inventing ways to do your work, feeling hurt about how others see your illness avoiding applying for jobs, embracing retirement, and mourning over lost work. Instead of relating these findings to mainstream theories that presuppose rather than investigate subjectivity (coping, selfmanagement, skills), we generalize these findings by relating them to the psychodynamic model of work of Christophe Dejours. This model is a clinical theory that offers an account of the relations between subjectivity, work, and action. Conclusion: Current models of management and vocational rehabilitation maintain individual/group and body/mind dichotomies that don’t exist in the lived experience of work and rehabilitation of people with MS. It is recommended that professionals offering supervision or vocational services to employees with early stage MS or other chronic conditions relativize these models while offering professional help, and that they revitalize the art of listening as an act of inclusion and acknowledgement.

摘要目的:探讨早期多发性硬化症(MS)患者在工作生活中的生活体验。方法:对10名处于职业生涯不同阶段(求职、在职、刚退休)的早期多发性硬化症患者进行公开、深度访谈。转录分析遵循现象学的方法。结果:发现了六个主题:令人厌烦的调整过程，发明工作方式，为别人对你的疾病的看法感到伤心，避免申请工作，接受退休，为失去工作而哀悼。我们没有将这些发现与预设而不是调查主体性(应对、自我管理、技能)的主流理论联系起来，而是通过将这些发现与Christophe Dejours的工作心理动力学模型联系起来来概括这些发现。这个模型是一种临床理论，它提供了主观性、工作和行动之间关系的解释。结论:目前的管理和职业康复模式维持了MS患者工作和康复生活经验中不存在的个人/群体和身体/心灵的二元对立。建议专业人员在提供专业帮助的同时，对早期MS或其他慢性疾病的员工提供监督或职业服务，并将这些模型相对化，并将倾听艺术作为一种包容和承认的行为重新激活。

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引用次数: 7

Short Commentary for “Features of anti-aquaporin 4 Antibody-Seronegative Thai Patients with Neuromyelitis Optica Spectrum Disorders: A Comparison with Seropositive Cases” 《抗水通道蛋白4抗体血清阴性的泰国视神经脊髓炎患者的特点:与血清阳性病例的比较》

Journal of multiple sclerosis

Pub Date : 2015-10-26 DOI: 10.4172/2376-0389.1000157

N. Prayoonwiwat, S. Siritho

Copyright: © 2015 Prayoonwiwat N, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Neuromyelitis optica (NMO) is an inflammatory CNS syndrome distinct from multiple sclerosis (MS) in their pathogenesis, clinical manifestations and neuroimaging findings [1]. According to the recent international consensus on diagnostic criteria for neuromyelitis optica spectrum disorders (NMOSD) 2015, the new criteria combine “definite NMO” and “NMOSD” into one term “NMOSD”. NMOSD was stratified further by serologic testing into NMOSD with or without presence of AQP4-antibody together with the 6 core clinical symptoms including clinical syndromes or MRI findings associated with optic nerve, spinal cord, area postrema, other brainstem, diencephalic, or cerebral manifestations. More stringent clinical criteria with MRI findings compatible with those seen in NMOSD are required for a diagnosis of seronegative NMOSD [2].

版权所有:©2015 Prayoonwiwat N, et al。这是一篇根据知识共享署名许可协议发布的开放获取文章，该协议允许在任何媒体上不受限制地使用、分发和复制，前提是要注明原作者和来源。视神经脊髓炎(Neuromyelitis optica, NMO)是一种炎症性中枢神经系统综合征，其发病机制、临床表现和神经影像学表现均不同于多发性硬化症(MS)[1]。根据近期国际共识的《神经脊髓炎视谱障碍诊断标准(NMOSD) 2015》，新标准将“明确的NMO”和“NMOSD”合并为一个术语“NMOSD”。通过血清学检测将NMOSD进一步分层，分为是否存在aqp4抗体以及6种核心临床症状，包括视神经、脊髓、后脑区、其他脑干、间脑或大脑表现相关的临床综合征或MRI表现。诊断血清阴性的NMOSD需要更严格的临床标准，且MRI表现与NMOSD一致[2]。

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引用次数: 0

Treatment of Multiple Sclerosis in Switzerland and the United States:What can be Learned from our Differences? 瑞士和美国多发性硬化症的治疗:从我们的差异中可以学到什么?

Journal of multiple sclerosis

Pub Date : 2015-10-22 DOI: 10.4172/2376-0389.1000E107

Elisabeth B. Lucassen

引用次数: 1

Introduction of Planaria as a New Model for Multiple Sclerosis Research:Evidence from Behavioural Differences in Cuprizone Treated PlanariaExposed to Patterned Magnetic Fields 引入涡虫作为多发性硬化症研究的新模型:来自暴露于图案磁场的铜处理涡虫行为差异的证据

Journal of multiple sclerosis

Pub Date : 2015-10-19 DOI: 10.4172/2376-0389.1000156

Mekers Wft, M. Nj, Persinger Ma

Abstract There has been a substantial history of correlative associations between subtle changes in geomagnetic intensity and the prevalence of multiple sclerosis. Several experiments have shown that rats in which experimental allergic encephalomyelitis had been induced respond to naturally-patterned weak magnetic fields. Exposures of only 6 min once per hour during the scotophase to a ~ 50 nT, 7 Hz magnetic field whose amplitude modulations simulated a sudden geomagnetic storm commencement markedly reduced both the behavioural symptoms and mononuclear cell infiltrations. In the present study planarian were exposed for only 6 min per day for three days to this same field pattern and intensities but with or without the presence of the demyelinating agent cuprizone. Behavioural analysis indicated a strong interaction after one day of exposure between cuprizone and field conditions for the numbers of “head whips” and an indicator of “unusual behaviours.” The 6 min exposures to the patterned magnetic field on the second and third days eliminated the effects of cuprizone upon the numbers of head whips and related anomalous behaviours. General activity was not affected. The specificity of the simultaneous exposure to the magnetic field and cuprizone for normalizing the planaria is consistent with the results of rodent studies involving one model of multiple sclerosis and suggests that this paradigm might be useful for examining the potential mechanisms for the correlation between prevalence of MS and geomagnetic variables.

地磁强度的细微变化与多发性硬化症的患病率之间存在着大量的相关关系。几项实验表明，实验性过敏性脑脊髓炎诱导的大鼠对自然模式的弱磁场有反应。在风暴期，每小时暴露一次~ 50 nT, 7 Hz的磁场，其振幅调制模拟了突然的地磁风暴的开始，仅6分钟即可显着减少行为症状和单个核细胞浸润。在本研究中，涡虫每天仅暴露6分钟，连续三天暴露在相同的野外模式和强度下，但有或没有脱髓鞘剂铜锌的存在。行为分析表明，暴露一天后，铜区和野外条件之间的“头鞭”数量和“异常行为”指标之间存在强烈的相互作用。在第二天和第三天，6分钟暴露在有图案的磁场中，消除了铜对鞭子数量和相关异常行为的影响。一般活动不受影响。同时暴露于磁场和铜钠使涡虫正常化的特异性与涉及一种多发性硬化症模型的啮齿动物研究结果一致，并表明该范式可能有助于研究多发性硬化症患病率与地磁变量之间相关性的潜在机制。

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引用次数: 1

Animal Models of Multiple Sclerosis: Imperfect but Imperative 多发性硬化症的动物模型:不完善但势在必行

Journal of multiple sclerosis

Pub Date : 2015-10-19 DOI: 10.4172/2376-0389.1000e106

R. Aharoni

Multiple sclerosis (MS) is a complex multifaceted disease involving autoimmune inflammation, demyelination and degeneration processes. The disease is heterogeneous in its clinical manifestation and progression, as well as in its pathological mechanisms [1]. Animal models have been indispensable for MS research. There is however, an ongoing controversy in regard to their true relevance to the human disease.

多发性硬化症(MS)是一种复杂的多方面疾病，涉及自身免疫性炎症、脱髓鞘和变性过程。本病临床表现、进展及病理机制均具有异质性[1]。动物模型在多发性硬化症的研究中是不可或缺的。然而，关于它们与人类疾病的真正相关性，目前仍存在争议。

引用次数: 1

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