粒细胞集落刺激因子治疗肌萎缩侧索硬化：增加细胞外谷氨酸摄取和抗自由基的作用

兴奋性氨基酸毒性和自由基氧化损伤在肌萎缩侧索硬化的发生发展中起到重要的作用。一种新的神经保护类药物粒细胞集落刺激因子（Granulocyte colony stimulating factor,G-CSF）被认为具有抗兴奋性氨基酸毒性、抗氧化应激、抗凋亡等作用。既往研究发现G-CSF可以对暴露于高浓度谷氨酸盐的神经细胞起到保护作用,并且拮抗脑缺血再灌注后的氧化应激反应。由此,在慢性谷氨酸中毒诱导的运动神经元损伤的体外模型中,我们（1）使用生物化学方法测定G-CSF对体外模型细胞外谷氨酸浓度的影响;（2）测定G-CSF对运动神经元胞内超氧化物歧化酶、谷胱甘肽过氧化物酶活性以及组织内丙二醛、一氧化氮含量的影响;（3）免疫组织化学染色方法测定G-CSF对体外模型运动神经元存活的影响。结果显示G-CSF有显著的抗自由基和抗兴奋性毒性作用并明显减少脊髓前角运动神经元的凋亡和缺失,可以为肌萎缩侧索硬化提供新的治疗方向。     

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     

肌萎缩侧索硬化患者血浆和脑脊液谷氨酸改变及利鲁唑对血浆谷氨酸的影响

目的 :了解肌萎缩侧索硬化 (ALS)患者血浆和脑脊液谷氨酸浓度改变 ,以及药物干预对谷氨酸水平的影响。方法 :应用HPLC方法对ALS患者进行血浆和脑脊液谷氨酸测定。结果 :①患者血浆中存在兴奋性谷氨酸显著增高 ,谷氨酸浓度与性别、年龄、病程均无关。②力鲁唑 (力如太 )治疗 1个月后 ,血浆谷氨酸浓度下降 ,而环磷酰胺治疗变化不明显。③脑脊液中谷氨酸浓度未见明显变化。结论 :ALS患者存在谷氨酸代谢异常 ,但谷氨酸可能不是ALS致病的惟一途径。     

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...     

肌萎缩侧索硬化的昨天、今天和明天

肌萎缩侧索硬化(amyotrophic lateral sclero-sis,ALS)是运动神经元病中最为常见的一种类型,迄今已有140余年历史。早在1865年,著名的神经病学家Charcot教授即描绘了对ALS患者最初的印象———"一位肌肉痉挛的患者,在其死后病理中发现了位于皮质脊髓束的多发性硬化斑块"。在此后的100余年时间里,ALS的临床和病理特     

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.     

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.     

The roles of free radicals in amyotrophic lateral sclerosis

The mutations of the Cu,Zn superoxide dismutase (Cu,Zn-SOD) gene observed in amyotrophic lateral sclerosis (ALS) patients suggest that free radicals play a role in this fatal disease. Free radicals trigger oxidative damage to proteins, membrane lipids, and DNA, thereby destroying neurons. Mutations of the SOD gene may reduce its superoxide dismutase activity, thereby elevating free radical levels. In addition, the mutant SOD protein may function as a peroxidase to oxidize cellular components, and it may also react with peroxynitrite—a product of the reaction between superoxide and nitric oxide—to ultimately form nitrate proteins. The selective degeneration of motor neurons in ALS may be caused by the high level of Cu,Zn-SOD present in and the large number of glutamatergic synapses projecting to these neurons. Free radical-triggered and age-accumulated oxidation may modify the program controlling motor neuron death, thereby initiating apoptosis of motor neurons in young adults.     

兴奋毒性在肌萎缩侧索硬化的发病机制中具有重要作用

目的:分析比较肌萎缩侧索硬化病人和神经系统正常的受试者脑脊液中的谷氨酸水平,以明确由谷氨酸介导的“兴奋毒性”是否在ALS的发病机制中具有作用。方法:肌萎缩侧索硬化病人15例,神经系统正常的外科手术腰麻病人20例,采集脑脊液后用氨基酸自动分析仪进行检测。结果:肌萎缩侧索硬化病人脑脊液中谷氨酸水平与对照比较增高有极显著差异(两组分别为48.81±31.67μmol/L和15.85±6.70μmol/L)(P(0.01)。结论:由谷氨酸介导的“兴奋毒性”在肌萎缩侧索硬化的发病过程具有重要作用。     

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.     

Effect of birthplace on the development of amyotrophic lateral sclerosis and multiple sclerosis

After World War II the southeastern part of Finland was ceded to the Soviet Union and its entire population evacuated to other areas of the country. The prevalences of amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS) were studied among the evacuees and compared to the corresponding data among the nonevacuated population. The prevalence of ALS among the war evacuees was two times higher than among the nonevacuated population (18.0 and 8.8 per 100,000, respectively). The prevalence of MS among the evacuees was only half of that found among the nonevacuated population, 38.3 and 73.0 per 100,000, respectively. The findings for ALS indicate that birthplace may have an effect on the later development of the disease and that there may have existed some environmental factor(s) which have made the evacuees more liable to contract the disease later in their lives. The low figure of MS for evacuees supports our previous results of an uneven geographic distribution of MS in Finland with the high-risk areas in the western and southwestern parts of the country. No accumulation of MS was found among the evacuees living in the high-risk areas.     

Plasma glutamate and glycine levels in patients with amyotrophic lateral sclerosis: the effect of riluzole treatment

OBJECTIVES: Defective glutamate (glu) metabolism and excitotoxicity have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Moreover, glycine (gly) has been shown to potentiate excitatory transmission. The "antiglutamatergic" agent riluzole has been shown to prolong survival in ALS. The aim of the study was to investigate a possible effect of riluzole on plasma glu and gly levels, correlating with clinical response to treatment. PATIENTS AND METHODS: Plasma concentrations of glu and gly were measured in 20 healthy volunteers and 22 ALS patients before treatment and after 6 months on riluzole. RESULTS: At baseline, increased plasma glu correlated with spinal onset and male gender whereas gly levels did not differ between patients and controls. No significant change was observed for both amino acids post-treatment, despite a lower rate of disease progression. CONCLUSION: These results suggest that riluzole may affect disease progression without a significant impact on plasma glu and gly levels, possibly indicating different mechanisms of drug action.     

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]).     

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 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.