Riluzole治疗肌萎缩侧索硬化

Riluzole是谷氨酸受体拮抗剂。现介绍Riluzole治疗ALS的作用机制和临床疗效。     

肌萎缩侧索硬化发病机制的研究进展

肌萎缩侧索硬化为慢性变性疾病,其发病机制尚不明确,可能为多种因素参与其发病,本文试从兴奋性氨基酸毒性、基因、免疫及神经营养因子等方面进行综述,以期说明各种因素在肌萎缩侧索硬化发病机制中的可能作用。     

肌萎缩侧索硬化研究进展

<正>肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是一种主要累及大脑皮质、脑干和脊髓运动神经元的慢性致死性神经系统变性疾病,临床表现为骨骼肌无力和萎缩,进行性加重。其病因、发病机制均不明确,迄今为止还未发现特效治疗方法,患者平均生存期仅3～5 y。其中5%～10%为家族性ALS(fA LS),90%～95%为散发性ALS(sA LS)。本文综述ALS在临床表现及相关生物标记物等方面的发展历程,重点介绍ALS神经电生理及神经影像等技术的应用,利于临床     

肌萎缩侧索硬化发病机制的研究进展

肌萎缩侧索硬化(ALS)发现至今已有一百余年, 但其发病机制尚未阐明, 曾提出过多种学说. 近年来在基因遗传学和分子生物学方面的研究取得了长足的进步, 现已确定该病是一种基因病. 下面从基因遗传学、自由基、兴奋毒性、神经微丝等方面综述了与ALS发病机制有关的研究进展, 试图为其治疗提供依据.     

肌萎缩侧索硬化的研究进展

<正>肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)属于严重致死性神经系统变性疾病,目前还未有明确的发病机制,主要是由于运动神经病变导致,ALS在该类疾病中发病最为严重且发病率最高。1临床表现ALS大多数为获得性,少数为家族性。起病隐匿,发病年龄多在30～60岁之间。男性多于女性,5%的患者以躯干肌或呼吸肌无力起病~([1])。发病初期多表现为一侧或两侧手指灵活度下降、无力,慢慢手部小肌肉开始出现萎缩,蚓状肌、大小鱼际肌及骨间肌萎缩程度较重,从手部肌肉开始蔓     

肌萎缩侧索硬化免疫学研究进展

肌萎缩侧索硬化免疫学研究进展李晓光郭玉璞肌萎缩侧索硬化（ＡＬＳ）是一种神经系统变性病，至今病因及发病机理尚不清楚。有许多证据说明本病的发病可能是多源性的或异质性的。已提出的病因涉及遗传因素、环境因素、病毒感染及免疫因素等。过去数十年临床及病理研究缺乏...     

肌萎缩侧索硬化实验模型及发病机制研究进展

肌萎缩侧索硬化（ALS）病因及发病机制的研究一直是神经科较棘手的问题。本文介绍最近对ALS研究较多的几种模型:免疫介导的动物模型、体外细胞培养模型及转基因动物模型,并介绍各自的优、缺点,适应研究的方向及由此而阐明的发病机制。为今后研究ALS的发病机制及治疗方案奠定基础。     

肌萎缩侧索硬化分裂手现象研究进展

<正>肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是一种以皮质脊髓束、皮质脑干束和脊髓运动神经元变性为特征的进行性神经退行性疾病~([1])。常表现为肌肉无力和萎缩,尤其是手部小肌肉。在ALS患者中,常优先累及手内肌的大鱼际肌肌群包括拇短展肌(Abductor pollicis brevis,APB)和第一骨间肌(first dorsal interosseous muscle,FDI),而包括小指展肌(Abductor digiti minimi,ADM)在内的小鱼际肌群则相对豁免,这一独特的手内肌分裂萎缩模式称为"分裂手"。近年     

肌萎缩侧索硬化叠加帕金森综合征临床分析

本文报道了广东省人民医院2例肌萎缩侧索硬化叠加帕金森综合征(ALS-PS)患者的诊断过程,通过文献复习分析了肌萎缩侧索硬化叠加综合征(ALS-Plus)的临床特征、发病率、预后以及可能的发病机制。例1患者表现出运动迟缓和铅管样肌强直的帕金森综合征,左旋多巴冲击试验阴性,无嗅觉减退和痴呆,我们诊断为未分化的ALS-PS。例2患者不仅表现出运动迟缓和铅管样肌强直,同时还有小脑、自主神经功能受累的表现,可以归结到MSA的诊断,故诊断为ALS-MSA。ALS-Plus约占所有ALS患者的13. 6%,并且较单纯ALS患者有更短的生存时间。尽管相关研究尝试为ALSPlus提供合理的解释,但目前具体发病机制仍不完全清楚,有待进一步的研究。ALS-Plus在ALS中并不罕见,但在临床上容易被忽略,一方面因为ALS-Plus对其他系统特别是锥体外系的损伤常常被严重的肌萎缩、肌无力症状所掩盖;另一方面在于神经科医生仍对其缺乏充分的认识。因此,我们认为神经科医生应该加强对ALS-Plus的认识,详细的病史和体格检查有助于避免误诊及漏诊。     

肌萎缩侧索硬化的免疫学研究进展

肌萎缩侧索硬化（AmyotrophicLateralSclerosis,ALS）由Charot于1869年首先报道以来,至令其病因和发病机制尚不清楚。已提出的病因有遗传因素、环境因素、病毒感染及无疾因素等。近年来随着免疫学及分子生物学的迅速发展,ALS免疫学资料越来越多。现就本病的免疫学研究情况作一综述。     

Ceftriaxone in amyotrophic lateral sclerosis

One hundred and eight patients with amyotrophic lateral sclerosis (ALS) received ceftriaxone 2 g daily i.v. (62) or i.m. (34) or by both routes (12), for 21-day cycles on an open basis. Baseline MRC and Norris scores were similar to those at the end of the first 21-day cycle of therapy. Seven patients showed remarkable clinical improvement, mostly segmental, which started during the first week of treatment and lasted up to 2 months after its completion. Improvement was also noted in seven out of 21 cases given a subsequent cycle of treatment. Based on these findings, the drug is supposed to act by altering the neurochemical transmission at the neuromuscular junction and/or by facilitating the presynaptic uptake of glutamate at the synaptic junction. This hypothesis positively correlates with the results of in vitro experiments showing that ceftriaxone increases ³H-glutamate uptake in rat spinal cord synaptosomes.     

Branched-chain amino acids in the treatment of amyotrophic lateral sclerosis

Summary Thirty-two patients affected by amyotrophic lateral sclerosis (ALS) were included in a controlled, open therapeutic trial with branched chain amino acids (BCAA). Patients with bulbar muscle involvement were evaluated separately. No statistically significant differences were found in the clinical outcome between the patients treated and the control groups. Blood l-glutamate levels measured in eight patients were normal. The failure of BCAA in the treatment of the patients could be due to different disorders with unpredictable outcome included under the diagnosis of ALS.     

The ratio of N-acetyl aspartate to glutamate correlates with disease duration of amyotrophic lateral sclerosis

Glutamate (Glu)-induced excitotoxicity has been implicated in the neuronal loss of amyotrophic lateral sclerosis. To test the hypothesis that Glu in the primary motor cortex contributes to disease severity and/or duration, the Glu level was investigated using MR spectroscopy. Seventeen patients with amyotrophic lateral sclerosis were diagnosed according to the El Escorial criteria for suspected, possible, probable or definite amyotrophic lateral sclerosis, and enrolled in this cross-sectional study. We measured metabolite concentrations, including N-acetyl aspartate (NAA), creatine, choline, inositol, Glu and glutamine, and performed partial correlation between each metabolite concentration or NAA/Glu ratio and disease severity or duration using age as a covariate. Considering our hypothesis that Glu is associated with neuronal cell death in amyotrophic lateral sclerosis, we investigated the ratio of NAA to Glu, and found a significant correlation between NAA/Glu and disease duration (r = −0.574, p = 0.02). The “suspected” amyotrophic lateral sclerosis patients showed the same tendency as possible, probable and definite amyotrophic lateral sclerosis patients in regard to correlation of NAA/Glu ratio with disease duration. The other metabolites showed no significant correlation. Our findings suggested that glutamatergic neurons are less vulnerable compared to other neurons and this may be because inhibitory receptors are mainly located presynaptically, which supports the notion of Glu-induced excitotoxicity.     

Respiratory function in amyotrophic lateral sclerosis

Abstract. The aim of this study was to examine the vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1) in relation to the site of amyotrophic lateral sclerosis (ALS) onset and the duration of the disease. Respiratory involvement is the principal cause of death in ALS patients. The study was conducted at the Department of Neurology, University School of Medicine in Lublin. The study comprised 18 ALS patients. The average duration of ALS was 12 months. The patients were divided into two groups according to the site of ALS onset and into two groups according to the duration of the disease. FVC was significantly higher in the group of patients with a limb onset than in the group of patients with a bulbar onset of the disease. The study has shown respiratory function disturbances in ALS patients. FVC significantly depends on the site of ALS onset but not on the duration of the disease.     

The physician-patient relationship in amyotrophic lateral sclerosis

The principal models of the physician-patient relationship are analysed in terms of their historical development. An outline is given of the clinical, psychological and ethical particularities of the approach to patients with amyotrophic lateral sclerosis. The peculiarities of this disease are so exclusive that they do not resemble other progressive diseases with a negative prognosis, and therefore require an equally exclusive approach to the physician-patient relationship. This approach should not only be informative, scientific and interpretative-deliberative, but most simultaneously be founded on a solid therapeutic alliance aimed at seeking the best interests of the patients while respecting their autonomy as well as their “good” (not only in the sense of physical well-being, but also in terms of respect for their personal values). This is the only way to confront the conflicts that inevitably arise (especially in advanced stages of the disease) without the risks associated with a desire to escape or to adopt extreme solutions (such as euthanasia and therapeutic insistence) and without the risk of burn-out. Received: 5 May 2000 / Accepted in revised form: 6 December 2000     

Creatine kinase activity in amyotrophic lateral sclerosis patients

Abstract. The aim of this study was to investigate creatine kinase (CK) in the serum of amyotrophic lateral sclerosis (ALS) patients. Previous investigations have shown an increased CK activity in ALS patients and this has been suggested to be an indicator of patients survival. The study was conducted at the Department of Neurology, University School of Medicine in Lublin. Thirty ALS patients took part in the study. The average duration of the disease was 17 months. Serum CK levels were measured by the enzymatic method with N-acethylcysteine. CK was elevated in 43.3% of the ALS patients. There were no significant differences in the serum CK level between the groups of the ALS patients depending on age, sex, duration of the disease, or clinical condition of patients. The CK level was significantly higher in the serum of the patients with a limb onset than in patients with a bulbar onset of ALS. Our study confirmed the increase in the serum CK activity in ALS patients. CK activity depends on a limb onset or a bulbar onset of ALS, but not on the duration of the disease and the severity of the clinical condition.     

Novel drug development for amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) has become an increasingly attractive area for the pharmaceutical industry, the most experimentally tractable of the neurodegenerative diseases. Mechanisms underlying cell death in ALS are likely to be important in more common but more complex disorders. Riluzole, the only drug launched for treatment ALS is currently undergoing industrial trials for Alzheimer’s, Parkinson’s, Huntington disease, stroke and head injury. Other compounds in Phase III testing for ALS (mecamserin, xaliproden, gabapentin) are also in trials for other neurodegenerative disorders. Mechanisms of action of these advanced compounds are limited to glutamate antagonism, direct or indirect growth factor activity, as well as GABA agonism and interaction with calcium channels. A broader range of mechanisms is represented by compounds in Phase I trials: glutamate antagonism (dextramethorphan/p450 inhibitor; talampanel), growth factors (leukemia inhibiting factor; IL-1 receptor; encapsulated cells secreting CNTF) and antioxidants (TR500, a glutathione-repleting agent; recombinant superoxide dismutase; procysteine.) An even broader range of mechanisms is being explored in preclinical discovery programs. Recognition of the difficulties associated with delivery of protein therapeutics to the CNS has led to development of small molecules interacting either with neurotrophin receptors or with downstream intracellular signalling pathways. Other novel drug targets include caspaces, protein kinases and other molecules influencing apoptosis. High-throughput screens of large libraries of small molecules yield lead compounds that are subsequently optimized by chemists, screened for toxicity, and validated before a candidate is selected for clinical trials. The net is cast wide in early discovery efforts, only about 1% of which result in useful drugs at the end of a decade-long process. Successful discovery and development of novel drugs will increasingly depend on collaborative efforts between the academy and industry.     

Six important themes in amyotrophic lateral sclerosis (ALS) research, 1999

My assignment was to identify the 6 most important ALS papers published in 1999 but, great to relate, there were too many excellent candidates. Rather than confining the search to individual papers, six major themes seemed appropriate for discussion: 1) The study of transgenic mice that carry a mutated human gene for superoxide dismutase-1 (SOD1) has led to many far-reaching advances in ALS research. The mice are regarded as the best test system to evaluate potential therapies, including creatine. Inconsistencies between efficacy in mice and people are noted, however. 2) Transgenic mice have also been used to evaluate the role of glutamate toxicity in the pathogenesis of ALS, a dominant theory. 3) The role of mitochondria in the pathogenesis of ALS is gathering increasing attention. 4) The role of neurofilaments in the pathogenesis of ALS has provided new twists in mice and people. 5) Motor neuropathy is the most important differential diagnosis of ALS. 6) Gene therapy, as exemplified by the use of stem cells, has been applied successfully to animal models of other inherited diseases of the central nervous system.     

肌萎缩侧索硬化症临床诊断进展

肌萎缩侧索硬化症为致命性神经系统变性疾病,主要累及锥体束、脑干和脊髓前角细胞,临床表现呈进行性加重的肌肉萎缩、无力及痉挛,以及认知损害等,与额颞叶痴呆的临床表现存在部分重叠。约有5%的患者为家族遗传性,临床表现与散发型相似。诊断主要基于患者临床表现、世界神经病学联盟公布的共识,同时排除临床表现相似的疾病。基因检测为加速诊断进程、早期干预提供了新的途径,部分基因突变与特异性表型相关,可据此进行预后评价和遗传学咨询。     

肌萎缩侧索硬化的病毒病因学研究进展

运动神经元病(motor neuron disease,MND)是一组由于上、下运动神经元丢失导致延髓部、四肢、胸部肌肉逐渐无力和萎缩的进展性神经系统退行性疾病.MND多于45～60岁发病,发病率为1～2/100 000,患病率为4～6/100 000,生存期为1～5年~([1]).