间充质干细胞移植治疗多发性硬化的研究进展

背景：多发性硬化是中枢神经系统白质脱髓鞘性疾病,其确切的病因和发病机制尚不清楚。其临床表现复杂多变,传统治疗均不能延缓疾病的进程。目的：综述间充质干细胞移植治疗多发性硬化的研究进展,并提出目前间充质干细胞使用方面许多亟待解决的问题。方法：以＂mesenchymal stem cells,encephalomyelitis,autoimmune,experimental,multiple sclerosis＂为英文检索词,检索Kjmed数据库中2000/2011发表的相关文章。纳入与间充质干细胞治疗多发性硬化研究相关的文献。结果与结论：共检索到104篇文献,排除无关重复的文献,保留33篇进行综述。目前研究证实间充质干细胞是一种具有免疫调节及神经修复功能的多能干细胞,同时间充质干细胞在治疗多发性硬化方面显示了初步的治疗效果。     

急性脊髓炎脑诱发电位的研究

目的;探讨脑诱发电位(BEP)在诊断急性脊髓炎阿多发性硬化关系中的作用。方法：对28例急性脊髓炎患进行了3种BEP检查,对其结果同正常对照值比较。结果：sEP异常率为90％,VEP异常率为52％．AEP异常率20％。其潜伏期值同正常对照值比较显延长(P<0．02)。结论：对急性脊髓炎患做BEP检查有助于多发性硬化的早期诊断,     

多发性硬化研究的动物模型制备

目的：探索实验性变应性脑脊髓炎（experimental allergic encephalomyelitis,EAE)动物模型的制备，了解其病理改变，为多发性硬化免疫病理机制及实验性治疗的研究提供实验依据。方法：采用免疫诱导方法制备EAE模型，利用光镜，电镜观察豚鼠EAE模型的组织学改变。结果：至免疫后18d，全部豚鼠均出现EAE临床症状，光镜下见脑实质及蛛网膜下腔小血管充血，血管周围炎性细胞浸润，呈“袖套”状改变，电镜下见髓鞘明显分层，水肿甚至断裂，轴突细胞器消失，结论：EAE模型建立方法稳定，可靠，其病理改变为血管周围炎性浸润，白质脱髓鞘。     

多发性硬化动物模型系列MRI与病理对照研究

目的研究多发性硬化(MS)动物模型—恒河猴实验性变态反应性脑脊髓炎(EAE)在MRI上显示病变的组织病理学基础。方法建立EAE的动物模型,系列MRI并与病理及临床进行对照研究。结果实验组9只动物全部发病,常规MRI在显示其病理结构上无特异性,强化扫描有助于区别活动性斑块和非活动性斑块,并可做为脱髓鞘病变的定位参考。磁化转移成像(MTI)提高了小病变的检出率。对应病变区病理可见袖状结构、轴突损伤、脱髓鞘改变。结论MR系列成像对于准确评价恒河猴EAECNS病变、推测其组织病理学改变有潜在的应用价值。     

基因治疗人类多发性硬化症的可能性研究:腺病毒转染CTLA-4Ig对动物实验性自身免疫性脑脊髓炎病理过程的抑制或阻断作用

背景实验性自身免疫性脑脊髓炎(experimental autoimmune encephalomyelitis,EAE)同人类的多发性硬化症(multiple sclerosis,MS)的病理机制相类似,因此认识和阻断EAE的病理过程是攻克MS的关键.目的寻求一种可能抑制或阻断EAE病理过程,加速神经功能恢复进程的方法.设计随机对照的实验研究.单位解放军第三军医大学附属西南医院神经内科和烧伤研究所.材料实验在解放军第三军医大学动物实验室完成.实验材料豚鼠4只(雌雄不限,体质量300～400 g),Wistar大鼠40只(雌雄不限,体质量180～200 g).方法用所构建的CTLA-4Ig腺病毒通过侧脑室注射到Wistar大鼠EAE模型体内观察其疗效,用冷冻切片观察CTLA-4Ig在脑组织中的表达,观察发病情况、病理改变.主要观察指标①两组大鼠致敏后的发病天数、发病只数及潜伏期及神经功能评分情况.②光镜下观察两组大鼠病理学改变情况.结果发病情况生理盐水对照组大鼠于致敏后第10天开始发病.于第16天全部发病,平均发病天数为12.2 d,临床评分平均为3.1;腺病毒介导的CTLA-4Ig组于致敏后第14天开始发病,第18天共发病6只,平均发病天数为14.1 d,临床评分平均为2.4.病理结果侧脑室注射AdCTLA-4Ig后24,48,72 h取脑组织做冷冻切片在荧光显微镜下观察侧脑室周围和脊髓有荧光.在光镜下可见对照组大鼠的脑和脊髓组织中有大量炎性细胞浸润,炎性细胞聚集在血管周围呈现袖套样改变,髓鞘染色(Loyez染色)可见髓鞘脱失;腺病毒介导的CTLA-4Ig组的脑脊髓组织炎性细胞浸润明显减轻,形成的血管套样改变也减少,髓鞘脱失也减少.结论CTLA-4Ig可诱导T细胞失活化,有效地抑制细胞及体液免疫,能阻断以T细胞过度活化为主要原因的自身免疫性疾病EAE的病理过程,可以提高大鼠的神经功能评分,有效地改善神经功能症状.     

多发性硬化症患者抑郁的研究进展

大量研究已证实大部分多发性硬化症（muhipesclerosis,MS）患者存在心理问题,其中抑郁是此类患者最常见的心理问题,发病率约为15％,且未经过系统治疗的抑郁症状与患者的自杀意念、认知功能损害和免疫调节治疗依从性差等有关,同时也是降低此类脱髓鞘性神经疾病患者生活质量的最主要因素。但目前国内外的研究更多注重对此类患者神经系统功能的恢复,对患者精神方面的康复关注较少。然而,医学发展到今天,其目的不再单纯是生命的保存与延长,而是要重视患者生命质量的提高。因此,对所有诊断为MS患者的抑郁症状应给予足够的监测和管理。本文就国内外MS患者抑郁的研究现状作一综述。     

他汀类药物对多发性硬化的治疗作用

多发性硬化（multiple sclerosis,MS）是一种中枢神经系统（central nervous system,CNS）自身免疫性疾病．在过去的几十年里,对其的治疗取得了巨大的进步。     

急性脊髓炎脑诱发电位的研究

目的：探讨脑诱发电位（ＢＥＰ） 在诊断急性脊髓炎同多发性硬化关系中的作用。方法：对２８ 例急性脊髓炎患者进行了３ 种ＢＥＰ检查, 对其结果同正常对照值比较。结果： ＳＥＰ异常率为９０％ , ＶＥＰ异常率为５２％ ,ＡＥＰ异常率２０％ 。其潜伏期值同正常对照值比较显著延长（Ｐ＜ ０．０１）。结论：对急性脊髓炎患者做ＢＥＰ检查有助于多发性硬化的早期诊断。     

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。     

多发性硬化动物模型系列MRI与病理对照研究

目的：研究多发性硬化（MS）动物模型－恒河猴实验性变态反应性脑脊髓炎（EAE）在MRI上显示病变的组织病理学基础。方法：建立EAE的动物模型，系列MRI并与病理及临床进行对照研究，结果：实验组9只动物全部发病，常规MRI在显示其病理结构上无特异性，强化扫描有助于区别活动性斑块和非活动性斑块，并可脱髓鞘病变的定位参考，磁化转移成像（MTI）提高了小病变的检出率，对应病变区病理可见袖状结构，轴突损伤，脱髓鞘改变，结论：MR系列成像对于准确评价恒河猴EAE在CNS病变，推测其组织病理学改变有潜在的应用价值。     

Factors predisposing to the development of multiple sclerosis

Multiple sclerosis (MS) is a chronic neurological disease, which is known to be more common in UK than many countries. While there are multiple genetic factors affecting risk of developing MS and disease severity within the condition, evidence on the rising worldwide prevalence and the increasing female to male preponderance has focused interest on environmental factors influencing MS risk. Data on several of these factors are reviewed, with particular focus on those such as vitamin intake, smoking and obesity, which may be influenced at a personal and population level by medical advice.     

多发性硬化弥散加权成像

目的研究脑部多发性硬化(multiple sclerosis,MS)病灶、表现正常脑白质及正常志愿者脑白质表观弥散系数(apparent diffusion coefficient,ADC)值的差异.方法对37例正常志愿者和46例MS患者进行弥散加权成像检查,分别测量T1WI低信号病灶、T1WI等信号病灶、额叶表现正常脑白质及正常志愿者额叶白质平均ADC值,比较其有无统计学差异.结果各感兴趣区平均ADC值分别为T1加权像低信号病灶1.384×10-3 mm2/s;T1加权像等信号病灶0.977×10-3 mm2/s;额叶表现正常脑白质0.762×10-3 mm2/s;正常志愿者额叶白质0.744×10-3 mm2/s.上述各组两两比较均存在显著性差异(P＜0.01).结论弥散加权成像可以分辨出MS病灶,并能够检测出MS患者表现正常脑白质的弥散异常.     

Sexuality and multiple sclerosis

The individual with multiple sclerosis (MS) experiences a severe alteration in lifestyle both physiologically and emotionally. Sexuality is an integral part of life. However, discussion of alterations in sexuality by health care workers has traditionally been viewed as taboo. Specifically, the sexual concerns in chronic debilitating disorders such as MS have been neglected. This paper will explore physical and psychological aspects of MS on a patient's sexuality. Implications for nursing practice will also be considered.     

Interferons and multiple sclerosis

Interferons (IFNs) are a family of proteins with antiviral, antitumoral and immunomodulating properties. Multiple Sclerosis (MS) is a CNS disease in which the immune reaction (IR) is the cause of the inflammatory demyelinating lesions. IFNs have been demonstrated in active lesions. The location of IFN gamma on astrocytes suggests an enhancing activity on IR by inducing Ia antigen expression on these cells. In contrast, IFN alpha/beta located on microglial cells and astrocytes might limit the growing lesion. MS patients frequently present a defective response of NK cell activity and an abnormally low production of IFNs reflecting immune dysregulation. The therapeutic trials available to date are discussed: IFN gamma possesses a severe deleterious effect but IFN alpha/beta are still under consideration due to a possible beneficial activity.     

Intimacy and multiple sclerosis

Persons with multiple sclerosis require extensive management of the physiologic and psychologic sequelae of their chronic disease process. Sexual intimacy is affected by many of these disease effects, which impacts them in diverse ways. Many persons with multiple sclerosis do not discuss sexual intimacy with their health care provider because they assume it is an expected part of the disease and nothing can help, or they are too embarrassed to admit to problems at a very young age. Since this is a disease that usually occurs between 20 and 40 years of age, sexual intimacy is affected from many perspectives. Collaboration is essential in the plan of care between the client, family, and the health care provider.     

OnabotulinumtoxinA and multiple sclerosis

Lower urinary tract dysfunction is present in two of three patients with multiple sclerosis five years after the diagnosis. Most frequent symptoms are related to neurogenic detrusor overactivity, often associated with detrusor-sphincter dyssynergia. From the end of the 1990s, there is growing evidence that neurogenic detrusor overactivity can be effectively managed by intradetrusorial injections of botulinum toxin type A. This treatment has shown, in different randomised placebo-controlled trials, to be safe and effective on clinical and urodynamic parameters with significant improvement in quality of life. The median duration of effect is in mean nine months. The vast majority of studies have been conducted with onabotulinumtoxinA. The dose of onabotulinumtoxinA commonly used to treat neurogenic detrusor overactivity in patients with multiple sclerosis is 200 UI, even if in selected patients lower doses can be preferred. To be considered eligible for treatment, all patients should accept and be instructed to perform clean intermittent self-catheterisation, since the risk of increased post-void residual volume and/or urinary retention after injection is high, especially with 200 UI of onabotulinumtoxinA. However, quality of life and patient satisfaction seem not to be affected by the need of intermittent catheterisation. The risk of urinary infection after the procedure is to be kept in mind, mainly in patients with multiple sclerosis, so that adequate antibiotic prophylaxis is highly recommended.     

Cannabinoids and multiple sclerosis

There is a growing amount of evidence to suggest that cannabis and individual cannabinoids may be effective in suppressing certain symptoms of multiple sclerosis and spinal cord injury, including spasticity and pain. Anecdotal evidence is to be found in newspaper reports and also in responses to questionnaires. Clinical evidence comes from trials, albeit with rather small numbers of patients. These trials have shown that cannabis, Delta(9)-tetrahydrocannabinol, and nabilone can produce objective and/or subjective relief from spasticity, pain, tremor, and nocturia in patients with multiple sclerosis (8 trials) or spinal cord injury (1 trial). The clinical evidence is supported by results from experiments with animal models of multiple sclerosis. Some of these experiments, performed with mice with chronic relapsing experimental allergic encephalomyelitis (CREAE), have provided strong evidence that cannabinoid-induced reductions in tremor and spasticity are mediated by cannabinoid receptors, both CB(1) and CB(2). Endocannabinoid concentrations are elevated in the brains and spinal cords of CREAE mice with spasticity, and in line with this observation, spasticity exhibited by CREAE mice can be ameliorated by inhibitors of endocannabinoid membrane transport or enzymic hydrolysis. Research is now needed to establish whether increased endocannabinoid production occurs in multiple sclerosis. Future research should also be directed at obtaining more conclusive evidence about the efficacy of cannabis or individual cannabinoids against the signs and symptoms of these disorders, at devising better modes of administration for cannabinoids and at exploring strategies that maximize separation between the sought-after therapeutic effects and the unwanted effects of these drugs.     

Diet and multiple sclerosis

The question of the role of diet in multiple sclerosis is far from settled, but some interesting theories have been advanced. The most promising one is inhibition of lymphocytic responsiveness by dietary linoleic acid. Manipulations of the diets of patients with this disease are not yet justified.