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     

家族性肌萎缩侧索硬化症的病因研究进展

肌萎缩侧索硬化症 (ａｍｙｏｔｒｏｐｈｉｃｌａｔｅｒａｌｓｃｌｅｒｏｓｉｓ,ＡＬＳ)是选择性侵犯上、下运动神经元的慢性进行性变性疾病 ,可分为散发性ＡＬＳ和家族性ＡＬＳ(ＦＡＬＳ)。ＦＡＬＳ约占 10 % ,表现为常染色体显性遗传或常染色体隐性遗传。ＦＡＬＳ病因尚未完全明确。随着分子遗传学的研究发展 ,目前 ,ＦＡＬＳ分为 5种类型[1,2 ] :ＡＬＳ1、ＡＬＳ2、ＡＬＳ3、ＡＬＳ4、ＡＬＳ5。ＡＬＳ1为常染色体显性遗传 ,基因定位于 2 1ｑ2 2 1,是由于铜锌超氧化物岐化酶(ＣｕＺｎｓｕｐｅｒｏｘｉｄｅｄｉｓｍｕｔａｓｅ ,ＳＯＤ1)基…     

肌萎缩侧索硬化患者肌电图与ALS-FRS-R的研究

目的研究肌萎缩侧索硬化(ALS)患者肌电图(EMG)相关肌肉小力收缩时运动单位动作电位(MUAP)的波幅(Amp)和时限(Lat)与肌萎缩侧索硬化功能评分(ALS-FRS-R)之间的相关性。方法 25例ALS患者分别进行ALS-FRS-R和EMG检查,分别记录并分析左右胫骨前肌、左右伸指总肌、腹直肌及胸锁乳突肌小力收缩时MUAP的Amp和Lat与ALS-FRS-R的相关性。结果 23例ALS患者右胫骨前肌小力收缩时Amp与ALS-FRS-R存在相关性,R2=0.173,P=0.043。左胫骨前肌、左右伸指总肌、腹直肌及胸锁乳突肌小力收缩时的Amp及左右胫骨前肌、左右伸指总肌、腹直肌及胸锁乳突肌小力收缩时的Lat与ALS-FRS-R不存在相关性(P>0.05)。结论 EMG中仅个别相关肌肉小力收缩时MUAP的Amp与ALS-FRS-R相关,因此EMG相关肌肉小力收缩时的Amp和Lat对ALS仅具有定性意义,不能反映ALS患者病情的严重程度。     

家族性肌萎缩侧索硬化一家系报道

我们最近在梁平县发现一肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)家系并进行了家系调查,报告如下. 1 临床资料 先证者Ⅲ4男性,现年21岁,农民.因四肢进行性无力1年,加重伴饮水呛咳5个月,于2007-06-28来我院门诊就诊.患者2006-05起无明显诱因出现四肢无力,以双下肢明显,无肢体疼痛及麻木,未诊治,无力渐加重,不能干农活,生活尚能自理,自今年1月以来,患者无力明显加重,行走拖拽,双手不能提重物,说话口齿不清,饮水呛咳,自觉睡觉时双侧肩部及大腿部肌肉跳动.     

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。     

Lack of cervical paraspinal muscle involvement in juvenile distal spinal muscular atrophy: an electromyographic study on 15 cases

Electromyography (EMG) of the lower cervical paraspinal muscles was performed in 15 young Chinese males with distal spinal muscular atrophy of the upper extremities. The lack of fibrillation and positive sharp waves in all patients, both in early or active and chronic or steady stages, did not correlate with the EMG status in the affected upper extremity on the same side. This finding is in striking contrast with that in amyotrophic lateral sclerosis.     

The electrophysiology of the motor neuron diseases

The motor neuron diseases are a set of disorders associated with the selective degeneration of motor neurons. Amyotrophic lateral sclerosis (ALS) is the most common and confers the gravest prognosis. Although ALS occurs with known genetic causes in a small minority, other motor neuron disorders have well-defined genetic mutations. Electrodiagnostic testing is important to distinguish these various disorders. Electrodiagnostic testing is also crucial for distinguishing potential mimic syndromes, such as multifocal motor neuropathy and inclusion body myositis. Newer neurophysiology techniques have been developed in the past several years. What role these techniques will play in clinical practice is currently unknown.     

Amyotrophic lateral sclerosis in an adult following acute paralytic poliomyelitis in early childhood

About 30% of polio survivors develop a post-polio syndrome. Some of these patients develop slowly progressive muscle weakness known as post-poliomyelitis muscular atrophy (PPMA). We describe an unusual form of amyotrophic lateral sclerosis (ALS) in a patient with acute poliomyelitis in childhood. An 80-year-old woman had acute poliomyelitis at 2 years of age and developed weakness limited to the lower extremities. Residual weakness was stable until the age of 75 when she developed rapidly progressive weakness that first affected her left arm and subsequently the right arm. Neurological examination revealed both upper and lower motor neuron signs. These clinical features were more consistent with ALS than PPMA. At autopsy, there was marked atrophy of the precentral gyrus. Microscopic examination revealed a severe loss of all nerve cells and pronounced fibrillary astrocytosis of the lumbar ventral horns in the spinal cord, presumably a result of poliomyelitis. Superimposed on these spinal cord alterations were the pathological features of ALS, consisting of loss of Betz cells, corticospinal tract degeneration and loss of motor neurons of other levels of the spinal cord. The findings included some atypical features for ALS, namely, sparing of the hypoglossal nucleus, absence of Bunina bodies and absence of ubiquitin-immunoreactive inclusions. Although poliomyelitis and ALS may be coincidental, the unusual pathological expression of ALS raise the possibility that it is related to the antecedent poliomyelitis. Received: 19 November 1997 / Revised: 24 April 1998, 6 September 1998 / Accepted: 14 September 1998     

Infantile neurodegenerative disease with neuronal accumulation of phosphorylated neurofilaments

Summary A caucasian male with a history of mental retardation and intractable epilepsy since birth, developed progressive wasting and weakness of skeletal muscles, leading to death at 4 years of age. A biopsy of gastrocnemius muscle at 2 years of age revealed severe neurogenic atrophy. Sural nerve biopsies at 2 and 3 years showed progressive atrophy and loss of large myelinated nerve fibers with a paucity of neurofilaments in remaining nerve fibers. Postmortem immunohistochemical and ultrastructural examination showed that neurons were markedly distended by phosphorylated neurofilaments. Whereas large lower motor neurons were most severely involved, dorsal root ganglia and neurons in the cerebral cortex and deep gray nuclei were also affected. It is suggested that this disease is caused by a disorder of neurofilament phosphorylation and transport.Supported by Aging Grant AG 04342 and by a Public Health Service International Research fellowship TW 03560 (SL). C. A. Wiley is a TIDA recipient NS 00928-01     

A survival analysis of 155 cases of progressive muscular atrophy

We performed a survival analysis of 155 cases of progressive muscular atrophy (PMA). In about half the cases, hands were involved first, the lower limbs in 30% and the shoulder girdle in 23%. The lifetables of PMA, adjusted to the expected mortality, showed a survival rate of 61.3% and 56.4% at three and five years, respectively. The location of onset symptoms did not modify the life expectancy, whereas the age of the patients at the moment of first diagnosis had a great influence on the course of the disease. The patients were further subdivided in two groups on the basis of the diffusion of the neuromuscular damage at the moment of the diagnosis. The course of the patients with a localized disease was markedly better than that of subjects with widespread disease. Some hypotheses are made about the latter group of cases.     

Detection of an Amadori product, 1-hexitol-lysine, in the anterior horn of the amyotrophic lateral sclerosis and spinobulbar muscular atrophy spinal cord: evidence for early involvement of glycation in motoneuron diseases

Glycation is a series of non-enzymatic reactions initiated by addition of reducing sugars to ɛ-amino group of lysine residues and α-amino group of the N terminus of proteins, leading to the formation of advanced glycation end products (AGE). It is thought to be involved in aging and various neurodegenerative conditions. In the present study using anti-1-hexitol-lysine (1-HL) antibody, Amadori product, an early glycation product, was detected in axonal spheroids in the anterior horn of amyotrophic lateral sclerosis and in atrophic neurons of spinobulbar muscular atrophy (SBMA, Kennedy disease with abnormally expanded triplet repeats in androgen receptor gene) but not in other regions of the central nervous system. Furthermore, Amadori product was undetectable in the tissues from age-matched controls. Thus, 1-HL formation could not reflect physiological aging. Received: 13 October 1998 / Revised: 31 March 1999     

Magnetic resonance imaging in motor neuron disease

Summary Magnetic resonance imaging (MRI) of the brain was evaluated in 20 patients with motor neuron disease (MND) and in a control group of 11 healthy people. Bilateral increased signal areas of various sizes in the centrum semiovale, corona radiata, internal capsule, pedunculi of midbrain, pons, medulla and even in the frontal lobe, topographically related with the corticospinal tract, were found in 8 out of 20 patients. Three out of 4 patients with progressive bulbar paralisis and 5 out of 11 cases of amyotrophic lateral sclerosis had abnormal MRI. Such MRI abnormalities have neither been found in patients with progressive muscular atrophy nor in controls, suggesting that they may be the hallmark of pyramidal tract degeneration in motor neuron disease.     

慢性脊髓性肌萎缩症的临床和肌活检

文章报道２４例慢性脊髓性肌萎缩症，其中婴儿型、少年型、成年型慢性近端型分别为５例、２例及１３例，面肩肱型２例，远端型和肩腓型各１例。本病主要临床表现为肌无力、肌萎缩和不同程度的肌束震颤，锥体束和周围神经一般不受累。各型肌萎缩的部位不同。３例患者伴有ＣＰＫ浓度增高。除２例肌电图正常外，其余表现为失神经性改变。光镜提示神经原性萎缩。电镜下见肌原纤维数量减少，Ｚ线变粗或波浪状以及线粒体和内质网肿胀。     

甲基汞引发的大鼠脊髓前角大型运动神经元的脱落

目的研究有机汞中毒大鼠脊髓前角的病理学改变。方法使用每日１０ｍｇ／ｋｇ甲基汞，给成熟大鼠连续灌胃１０日，观察其脊髓、前根及肌肉的病理学所见。结果首次投药１４日起，脊髓前角大型运动神经元胞质内出现空胞及尼氏小体脱失；在１６日观察到噬节现象；到１８日，前角大型运动神经元高度脱落，而中、小型神经元则无明显减少。使用醋酸银金属自显影技术亦检测到脊髓前角大型运动神经元有汞的特异性沉积。结论以往报道的汞中毒性类肌萎缩侧索硬化综合征的主要病理学基础为脊髓前角运动神经元的变性、脱落，本实验动物模型可以作为研究运动神经元疾病病理生理学改变的有用模型。