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     

肌萎缩侧索硬化研究进展

肌萎缩侧索硬化症（ALS）是运动神经元（MN）系统的变性疾病,其病因、发病机制均不明确;因此也无有效治疗措施。本文将主要回顾近年来有关ALS病因、病理生理和发病机制研究方面的进展,并简要概述临床相关问题。     

肌萎缩侧索硬化的自主神经功能障碍

长久以来,肌萎缩侧索硬化一直被认为是一种仅选择性累及运动神经元的疾病,现在发现其还可能出现自主神经系统、锥体外系和认知功能障碍等症状,提示可能是一个多系统累及的变性疾病.本文就近年来关于肌萎缩侧索硬化的自主神经功能紊乱的研究作一综述,内容涉及心血管自主神经系统、腺体分泌和胃肠道自主神经系统等,包括临床症状、辅助检查、治疗手段以及可能的病生机制等方面的研究进展.越来越多的证据表明,ALS患者存在自主神经功能紊乱,往往是交感神经活动增强,但是,许多时候血压和肌肉交感神经活动的反应则提示交感神经功能较低,可能是静息状态下对交感神经过度活跃的一种高限效应.     

肌萎缩侧索硬化的动物模型

肌萎缩侧索硬化的动物模型对研究该病的细胞与分子机制及评估治疗药物的有效性具关键作用。本文介绍5种自发性动物模型及3种实验诱发性模型,后者包括兴奋性氨基酸模型,自身免疫性模型及当今研究与使用较多的转基因模型。最后介绍38种用于实验模型的治疗药物。     

肌萎缩侧索硬化与氧化应激

肌萎缩侧索硬化（amyotrophic lateral sclerosis,ALS）是中枢神经系统常见的一种慢性进行性变性疾病,以脑和脊髓中选择性运动神经元变性为特征。根据其发病和遗传特点分为家族型肌萎缩侧索硬化（familial amyotrophic lateral sclerosis,fALS）和散发型肌萎缩侧索硬化（sporadic amyotrophic lateral sclerosis,sALS）。从临床和病理诊断标准上不能区分fALS和sALS,说明散发型和家族型可能具有相同的或共同的发病机制。目前的证据提示ALS运动神经元的丢失是由于一些复杂的相互作用的机制所致,     

家族性肌萎缩侧索硬化

多数肌萎缩侧索硬化(ALS)病人是散发或典型类型的,但家族性变异也已众所周知.在关岛,家族性ALS非常多见,已构成另一类型.成人ALS病例组的研究有家族史者占5～10%.多数家族报告属常染色体显性遗传,两性分布相等,但在散发病例中,平均男性占优势,为1.6∶1.迄今在许多家族中所描述的临床及病理所见,     

肌萎缩侧索硬化的治疗

肌萎缩侧索硬化 (ＡＬＳ)是一种病因未明的选择性侵犯脊髓前角细胞、脑干运动神经核及锥体束的慢性进行性变性疾病。临床表现为上下运动神经元合并受损的体征 ,是慢性运动神经元病 (ＭＮＤ)的最常见类型 ,已为大家所熟知。下面主要讨论治疗研究进展 ,供临床参考。1　一般治疗〔1～ 3〕ＭＮＤ是一种慢性致残性神经变性病 ,目前无特殊治疗 ,主要为对症支持治疗 ,保证足够营养 ,改善全身状况。有研究证实营养不良是缩短ＡＬＳ病人生存的独立预后因素 ,16%～ 5 0 %ＡＬＳ病人有不同程度的营养不良 ,主要由吞咽困难所致 ,代谢过高也可引起 ,因此…     

肌萎缩侧索硬化中医药研究进展

以肌无力、肌萎缩为主证的肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)属中医"痿病""脾痹"范畴;以延髓麻痹为主证的ALS属中医"风痱""暗痱"范畴。中医认为ALS的主要病因病机为本虚标实,五脏皆能致痿;病位最常责于脾胃,多从脾胃补益论治施治,有助于延缓肌萎缩、延髓麻痹等症状的进展,延长患者生存期。本文通过查阅重订版古籍及国内近年来发表的相关文献,从中医学角度探讨ALS的历史沿革,归纳总结ALS的病因病机、诊断和治疗及其研究进展。     

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     

EGCG与肌萎缩侧索硬化

<正>肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是一种选择性侵犯皮层、脊髓和脑干运动神经元的进行性神经变性疾病。目前病因不清,发病机制不明,大量证据提示ALS运动神经元的选择性丢失并不是单一因素造成,而是由于多种因素复杂的相互作用所致,包括氧化应激、谷氨酸兴奋毒性、遗传因素、自身免疫异常、细胞骨架异常以及蛋白质异常聚积等。目     

大蒜素和肌萎缩侧索硬化

蒜是人们日常生活中常见的百合科葱属植物的鳞茎,含有复杂的化学成分,具有多方面的药理作用。大蒜素是大蒜中主要生物活性成分的总称,为多种烯丙基有机硫化物复合体。肌萎缩侧索硬化（amyotrophic lateral sclerosis,ALS）是一种选择性累及上、下运动神经元的慢性进行性神经系统变性疾病。成年发病,患者多在首次出现症状后的3～5年内死于呼吸衰竭,多数国家ALS的患病率为5／10万～7／10万,并且近年有上升的趋势 ,目前尚无有效治疗方法。近年来大蒜素中的烯丙基硫化物的抗氧化作用成为人们关注的热点,提示其在神经系统变性疾病方面有利用的可能。此篇综述就大蒜素中的活性成分在ALS方面的研究进展进行讨论。     

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...     

肌萎缩侧索硬化的研究进展

肌萎缩侧索硬化(ALS)是最常见的运动神经元病,表现为上下运动神经元同时受累症状、体征.继SOD1之后,又发现多个ALS相关基因,新近的C9orf72六核苷酸重复突变考虑影响RNA加工过程致病.该病诊断依赖临床表现及神经电生理结果,Criteria认为束颤电位与纤颤电位、正尖波有同等价值,增加了诊断灵敏性,且特异性不受影响.利鲁唑是目前唯一一个国际公认的可延缓病情进展的药物,对症治疗可改善患者生存质量.     

肌萎缩侧索硬化患者轻度认知功能损害

目的 探讨肌萎缩侧索硬化(ALS)患者认知功能状态、ALS轻度认知功能损害(ALS-MCI)的受累领域和各种亚型及其可能的危险因素.方法 收集ALS患者29例,健康对照者58名,选用改良Norris量表评价ALS患者的延髓功能及肢体功能.根据美国精神病学会精神障碍诊断和统计手册(DSM-Ⅳ-R)痴呆的诊断标准,将ALS患者分为痴呆和非痴呆;对于非痴呆的ALS患者,通过常用的认知功能(包括精神状态、记忆力、执行功能、注意力、视空间功能)量表、汉密尔顿焦虑量表(HAMA)、汉密尔顿抑郁量表(HAMD)进行评分,按照Petersen等修订的MCI诊断标准,将其分为认知功能正常(ALS-CogNL)组和ALS-MCI组,分析ALS-MCI受累的领域及其亚型;比较2组在年龄、起病年龄、病程、起病部位、延髓性麻痹症状、肢体运动功能损害等方面的差异,分析ALS患者出现MCI的相关危险因素.结果 29例ALS患者中,认知功能正常14例(48.3%),MCI有15例(51.7%),未发现痴呆患者.15例ALS-MCI患者中,执行功能损害12例,注意力损害9例,记忆力损害8例,未发现视空间功能损害;其中遗忘型(ALS-aMCI)1例,非记忆单一领域损害型(ALS-sdMCI)6例,多领域受损型(ALS-mdMCI)8例.ALS-MCI组与ALS-CogNL组的教育年限[(8.7±2.8)年与(11.3 ±3.0)年]、Norris量表延髓功能评分[(28.4±7.7)分与(34.0±3.4)分]差异有统计学意义(t=-2.435、-2.576,均P＜0.05),性别、年龄、起病年龄、病程、起病部位、HAMA及HAMD评分、Norris量表肢体功能评分差异无统计学意义.结论 ALS患者常出现MCI,其中以执行功能损害最常见,记忆力、注意力亦有损害,未发现视空间功能损害,ALS-mdMCI是最常见的亚型.文化程度低、严重延髓性麻痹症状是ALS患者出现认知功能损害的危险因素.

Abstract：

Objective To explore the cognitive status of amyotrophic lateral sclerosis (ALS) patients, and to explore the involved cognitive domains, subtypes and risk factors of mild cognitive impairment in ALS ( ALS-MCI).Methods Twenty-nine cases of ALS and 58 healthy volunteers were included.The severity of the bulbar and spinal functions of the patients was evaluated by the Improved Norris Scale.According to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition-Revised( DSM-Ⅳ-R) criteria of dementia, ALS cases were classified as demented and non-demented.For non-demented ALS cases, the common cognitive batteries evaluating mental state, verbal memory, executive, attentional and visuospatial abilities were performed.Hamilton Anxiety Scale ( HAMA) and Hamilton Depression Scale (HAMD) were evaluated too.They were further classified into ALS-cognitively normal (ALS-CogNL) and ALS-MCI groups according to Petersen criteria of MCI.Risk factors possibly correlated with ALS-MCI were analyzed by comparing the differences in age, age of onset, duration of the disease, sites of onset, symptoms of bulbar and limb function between ALS-CogNL and ALS-MCI groups.Results Among 29 ALS cases, 14 (48.3% ) cases with cognitively normal( ALS-CogNL), 15 cases (51.7% ) with ALS-MCI,and none with dementia were identified.Among 15 ALS-MCI cases, 12 cases with executive dysfunction, 8 cases with memory deficits,9 cases with attention impairment and none with visuospatial impairment were found.ALSMCI cases could be further classified into three subtypes; 1 case with amnestic MCI (aMCI) ,6 cases with single domain non-memory MCI ( sdMCI), and 8 cases with multiple domains slightly impaired MCI (mdMCI).Between ALS-MCI and ALS-CogNL groups, there were significant differences (t = -2.435,- 2.576, both P ＜ 0.05) in education ((8.7 ± 2.8) years vs (11.3 ± 3.0) years) and Improved Norrisscale (bulbar score: (28.4 ± 7.7) scores vs ( 34.0 ± 3.4) scores) , however, no significant differences in sex, age, age of onset, duration,site of onset,HAMA or HAMD scores,and Improved Norris scale( spinal score) were found.Conclusions Cognitive deficits commonly exist in ALS patients.For the involved domains, executive dysfunction is the most common, deficits of attention and memory are also common, and deficit in visuospatial function is not found.The most common subtype of ALS-MCI is mdMCI.Severe bulbar symptoms and lower education may be the risk factors of ALS-MCI.     

肌萎缩侧索硬化患者轻度认知功能损害

Objective To explore the cognitive status of amyotrophic lateral sclerosis (ALS) patients, and to explore the involved cognitive domains, subtypes and risk factors of mild cognitive impairment in ALS ( ALS-MCI).Methods Twenty-nine cases of ALS and 58 healthy volunteers were included.The severity of the bulbar and spinal functions of the patients was evaluated by the Improved Norris Scale.According to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition-Revised( DSM-Ⅳ-R) criteria of dementia, ALS cases were classified as demented and non-demented.For non-demented ALS cases, the common cognitive batteries evaluating mental state, verbal memory, executive, attentional and visuospatial abilities were performed.Hamilton Anxiety Scale ( HAMA) and Hamilton Depression Scale (HAMD) were evaluated too.They were further classified into ALS-cognitively normal (ALS-CogNL) and ALS-MCI groups according to Petersen criteria of MCI.Risk factors possibly correlated with ALS-MCI were analyzed by comparing the differences in age, age of onset, duration of the disease, sites of onset, symptoms of bulbar and limb function between ALS-CogNL and ALS-MCI groups.Results Among 29 ALS cases, 14 (48.3% ) cases with cognitively normal( ALS-CogNL), 15 cases (51.7% ) with ALS-MCI,and none with dementia were identified.Among 15 ALS-MCI cases, 12 cases with executive dysfunction, 8 cases with memory deficits,9 cases with attention impairment and none with visuospatial impairment were found.ALSMCI cases could be further classified into three subtypes; 1 case with amnestic MCI (aMCI) ,6 cases with single domain non-memory MCI ( sdMCI), and 8 cases with multiple domains slightly impaired MCI (mdMCI).Between ALS-MCI and ALS-CogNL groups, there were significant differences (t = -2.435,- 2.576, both P ＜ 0.05) in education ((8.7 ± 2.8) years vs (11.3 ± 3.0) years) and Improved Norrisscale (bulbar score: (28.4 ± 7.7) scores vs ( 34.0 ± 3.4) scores) , however, no significant differences in sex, age, age of onset, duration,site of onset,HAMA or HAMD scores,and Improved Norris scale( spinal score) were found.Conclusions Cognitive deficits commonly exist in ALS patients.For the involved domains, executive dysfunction is the most common, deficits of attention and memory are also common, and deficit in visuospatial function is not found.The most common subtype of ALS-MCI is mdMCI.Severe bulbar symptoms and lower education may be the risk factors of ALS-MCI.     

肌萎缩侧索硬化患者轻度认知功能损害

Objective To explore the cognitive status of amyotrophic lateral sclerosis (ALS) patients, and to explore the involved cognitive domains, subtypes and risk factors of mild cognitive impairment in ALS ( ALS-MCI).Methods Twenty-nine cases of ALS and 58 healthy volunteers were included.The severity of the bulbar and spinal functions of the patients was evaluated by the Improved Norris Scale.According to the Diagnostic and Statistical Manual of Mental Disorders 4th Edition-Revised( DSM-Ⅳ-R) criteria of dementia, ALS cases were classified as demented and non-demented.For non-demented ALS cases, the common cognitive batteries evaluating mental state, verbal memory, executive, attentional and visuospatial abilities were performed.Hamilton Anxiety Scale ( HAMA) and Hamilton Depression Scale (HAMD) were evaluated too.They were further classified into ALS-cognitively normal (ALS-CogNL) and ALS-MCI groups according to Petersen criteria of MCI.Risk factors possibly correlated with ALS-MCI were analyzed by comparing the differences in age, age of onset, duration of the disease, sites of onset, symptoms of bulbar and limb function between ALS-CogNL and ALS-MCI groups.Results Among 29 ALS cases, 14 (48.3% ) cases with cognitively normal( ALS-CogNL), 15 cases (51.7% ) with ALS-MCI,and none with dementia were identified.Among 15 ALS-MCI cases, 12 cases with executive dysfunction, 8 cases with memory deficits,9 cases with attention impairment and none with visuospatial impairment were found.ALSMCI cases could be further classified into three subtypes; 1 case with amnestic MCI (aMCI) ,6 cases with single domain non-memory MCI ( sdMCI), and 8 cases with multiple domains slightly impaired MCI (mdMCI).Between ALS-MCI and ALS-CogNL groups, there were significant differences (t = -2.435,- 2.576, both P ＜ 0.05) in education ((8.7 ± 2.8) years vs (11.3 ± 3.0) years) and Improved Norrisscale (bulbar score: (28.4 ± 7.7) scores vs ( 34.0 ± 3.4) scores) , however, no significant differences in sex, age, age of onset, duration,site of onset,HAMA or HAMD scores,and Improved Norris scale( spinal score) were found.Conclusions Cognitive deficits commonly exist in ALS patients.For the involved domains, executive dysfunction is the most common, deficits of attention and memory are also common, and deficit in visuospatial function is not found.The most common subtype of ALS-MCI is mdMCI.Severe bulbar symptoms and lower education may be the risk factors of ALS-MCI.     

肌萎缩侧索硬化认知功能及行为障碍的研究进展

正肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是累及上下运动神经元的神经退行性疾病,以进行性肌萎缩、肌无力、延髓麻痹及锥体束征为主要特征。既往认为ALS是一种仅影响运动系统的运动神经元病,近年来越来越多的国内外研究显示ALS可能是一种以运动系统变性为核心的累及多个系统的神经变性疾病,不仅有运动症状,部分还有非运动症状,其中认知及行为障碍是ALS最     

肌萎缩侧索硬化患者的呼吸功能评价进展

肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是一种选择性侵犯脊髓前角细胞、脑干运动神经元、皮质锥体细胞及锥体束的神经系统变性病,最早由Charcot于1869年发现并报道,平均生存期仅3～5年[1],迄今尚无有效治愈方法,因此对呼吸困难、延髓性麻痹等并发症的治疗显得尤为重要[2].呼吸功能是影响ALS患者生存期及生存质量的重要因素,流行病学调查及尸检证实70%以上患者死于呼吸衰竭[1,3],一旦确诊ALS就应警惕呼吸衰竭的发生.