肌萎缩侧索硬化症肺通气功能改变与病情程度的相关性

目的:探讨肌萎缩侧索硬化症(ALS)患者病情轻重程度与肺功能受损的关系。方法:测定56例ALS患者的肺通气功能:肺活量(VC)、用力肺活量(FVC)、第1秒用力呼气量(FEV1)、第1秒用力呼气量/全部用力肺活量(FEV1/FVC)、最大通气量(MVV)、用力呼气高峰流量(PEF)并与对照组52名(健康人)进行比较,根据ALS患者病情轻重程度分为轻度患者组、中度患者组、重度患者组、终末患者组,对每位患者临床表现进行Norris评分。对每组Norris评分、肺功能指标进行相关性分析。结果:ALS患者通气功能明显减低(P<0.01,表现为限制性通气障碍。除轻度组患者:FEV1/FVC与Norris评分(r=-0.2718)无相关性外,各组指标与Norris评分均呈正相关(0≥r≤1),ALS患者病情的轻重程度与肺通气功能的改变呈正相关。结论:ALS患者肺功能损害表现为限制性通气障碍。病情的轻、重程度与肺功能下降程度呈正相关。     

肌萎缩侧索硬化患者肺功能及呼吸肌功能的临床研究

目的研究肌萎缩侧索硬化(ALS)患者肺功能及呼吸肌功能的特点。方法将130例ALS患者按临床起病方式分为球部起病组(36例)和肢体起病组(94例),并与健康对照组(30例)的肺功能进行比较;并比较球部起病组(35例)和肢体起病组(89例)的呼吸肌功能。结果与健康对照组比较,球部起病组及肢体起病组肺活量(VC)、用力肺活量(FVC)、第1 s用力呼气量(FEV1)、最大通气量(MVV)、用力呼气高峰流量(PEF)均显著下降(均P0.01)。球部起病组及肢体起病组FEV1/FVC均值(80%)在正常范围,但球部起病组FEV1/FVC显著低于健康对照组(P0.05)。与肢体起病组比较,球部起病组MVV显著降低(P0.05),其他肺功能指标差异无统计学意义(均P0.05)。与肢体起病组比较,球部起病组最大吸气压(MIP)、最大呼气压(MEP)显著降低(均P0.01),第0.1 s口腔闭合压(P0.1)差异无统计学意义(P0.05)。ALS患者呼吸肌功能异常率(87.90%)显著高于肺功能异常率(52.30%)(χ~2=38.07,P=0.000)。结论 ALS患者肺功能障碍以限制性通气功能障碍为主。球部起病患者呼吸肌功能损害较肢体起病患者更加严重。     

肌萎缩侧索硬化SOD1基因多态性与临床表型分析

肌萎缩侧索硬化(amyotrophic lateral sclerosis muscular atrophy,ALS)分为家族性 ALS (familial amyotrophiclateral sclerosis,FALS)和散发性 ALS (sporadic amyotrophic lateral sclerosi...     

肌萎缩侧索硬化与免疫(综述)

肌萎缩侧索硬化 (amyotrophic lateral sclerosis,ALS)是一种神经系统慢性变性疾病 ,其发病机制目前尚不明确。许多研究表明 ,其发病与免疫因素有关 ,ALS患者体内既存在着体液免疫异常 ,又有细胞免疫异常。这为免疫抑制剂治疗 ALS提供了新的依据。     

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     

额颞叶痴呆-肌萎缩侧索硬化症1例报告及文献复习

<正>额颞叶痴呆(frontotemporal dementia, FTD)和肌萎缩侧索硬化(amyotrophic lateral sclerosis, ALS)是成人发病的进行性神经退行性疾病。FTD是一种痴呆亚型，主要通过行为改变和语言缺陷来识别^[1]。ALS是最常见的运动神经元疾病，患者主要临床表现为运动功能障碍，但高达50%的患者会出现认知和(或)行为障碍。大约15%的FTD患者出现ALS症状，     

肌萎缩侧索硬化的基因及其分子机制研究进展

肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是最常见的成人运动神经元疾病,以进行性上、下运动神经元变性和死亡为主要特征。ALS平均发病年龄为55岁,临床表现为进行性骨骼肌无力和萎缩、延髓性麻痹及锥体束征,多数患者于发病后3～5年内死于呼吸衰竭。ALS按起病方式可分为散发性ALS(sporadic ALS,sALS)和家族性ALS(familialALS,fALS),二者具有相似的病理及临床特征。约5%～10%的ALS患者     

早期误诊为重症肌无力的肌萎缩侧索硬化1例报告并文献复习

肌萎缩侧索硬化( amyotrophic lateral sclerosis,ALS)是一种快速进展的神经退行性疾病,同时影响上、下运动神经元,并导致进行性肌肉萎缩和无力.ALS是一种高度异质性的疾病实体,上下运动神经元受累的程度在ALS中可变,其中进行性肌萎缩(progressive muscular atrophy...     

肌萎缩侧索硬化中的臂丛神经受累3例报告并文献复习

肌萎缩侧索硬化( amyotrophic lateral sclerosis,ALS)是一种快速进展的神经退行性疾病,临床特征同时影响上、下运动神经元( LMN、UMN) ,并导致进行性肌肉萎缩和无力.两种不同的过程可能同时或者相互独立的影响ALS的发生发展:"顺行死亡( dying-forward)"认为在ALS中谷...     

Riluzole-induced recurrent pancreatitis

Riluzole is the only drug approved for the treatment of patients with Amyotrophic Lateral Sclerosis (ALS). It is well tolerated, being the most frequent adverse effects asthenia, nausea and reversible increase of liver enzymes levels. Severe adverse effects are extremely rare. We report for the first time, two patients with sporadic limb-onset ALS who developed recurrent acute pancreatitis (AP), with portal vein thrombosis as complication, during treatment with riluzole. We suggest that AP should be considered as a probable rare and severe side effect of treatment with riluzole in patients with ALS. We believe that in patients who develop AP during treatment with riluzole, its withdrawn may prevent recurrent AP and should be discussed with patients.     

Innate and adaptive immunity in amyotrophic lateral sclerosis: evidence of complement activation

Increasing evidence suggests a role for the immune system in amyotrophic lateral sclerosis (ALS). To determine the extent of the immune activation in ALS we analyzed the expression and cellular distribution of components of innate and adaptive immunity in spinal cord (SC) and motor cortex (MCx) from patients with rapid and slow sporadic ALS and controls. High levels of mRNA and protein of classical complement pathway, C1q and C4, as well as the downstream complement components C3 and C5b-9 were found in all ALS samples. Furthermore, we found higher numbers of activated microglia, reactive astrocytes, dendritic cells (DCs) and CD8(+) T-cells in ALS than in control tissue. Rapid ALS cases had more dendritic cells than slow ALS cases, whereas slow ALS cases had more activated microglia than rapid cases. Our findings demonstrate a persistent and prominent activation of both innate and adaptive immunity in ALS. We propose a complement-driven immune response which may contribute to the progression of the inflammation and ultimately lead to even more motor neuron injury.     

Therapeutic news in ALS

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by death of motor neurons in the cortex and the spinal cord. This loss of motor neurons causes progressive weakness and amyotrophy. To date, the median duration of survival in patients with ALS, from first symptoms to death, is estimated to be 36 months. Currently the treatment is limited to two options: riluzole which prolongs survival for a few months and edaravone which is available in only a few countries and also has a small impact on disease progression. There is an urgent need for more effective drugs in this disease to significantly improve progression. Over the last 30 years, all trials have failed to find a curative drug for ALS. This is due, partially, to the heterogeneity of the clinical features and the pathophysiology of motor neuron death. We present in this review the various treatment options currently being developed for ALS, with an emphasis on the range of therapeutic approaches being explored, from old drugs tested in a new indication to innovative drugs obtained via biotechnology or gene therapy.     

Clinical Linguistics and Phonetics : an index to volumes 1-15

Two cases of amyotrophic lateral sclerosis (ALS) were investigated over time, from a point when speech intelligibility is still at a high level until oral communication becomes almost impossible. Speech intelligibility, speaking rate, and maximum repetition rate (MRR) were examined. Great declines in speaking rate and MRR were observed over time. In addition, both speaking rate and MRR were considerably slower when compared to the control group even when speech intelligibility was still high. The latter finding indicates these parameters are more sensitive in reflecting functional changes in articulators, rather than speech intelligibility, at the early stage of the disease. These results are discussed in terms of an assessment and management system for ALS speakers.     

Measuring the validation of assessing the non-dominant-hand function by ALSFRS-r in Chinese ALS patients

ALSFRS-r is a widely accepted rating scale for measuring the global function of Amyotrophic Lateral Sclerosis (ALS) patients, but we found some limitations of ALSFRS-r in assessing the function of non-dominant hand in Chinese ALS patients. We reviewed 95 ALS patients who expressed upper-limb symptoms at first visit and analyzed the ALSFRS-r score and subscale. In both upper limb involved patients, the ALSFRS-r had no difference between dominant-hand and non-dominant-hand onset groups (39.15 ± 5.55 vs 38.0 ± 5.91, p = 0.477). But in only one upper limb involved patients, the ALSFRS-r score in non-dominant-hand onset patients was higher than dominant-hand onset patients (43.94 ± 3.44 vs 40.87 ± 4.42, p < 0.05), especially in item of handwriting, cutting food and handing utensils (3.56 ± 0.89 vs 2.2 ± 1.27 p = 0.001, 3.44 ± 1.03 vs 1.8 ± 1.21 p = 0.000). When the item of cutting food and handing utensils was replaced by using food bowl and chopsticks to assess the function of non-dominant-hand, the modified ALSFRS-r score was significantly lower than original ALSFRS-r (43.94 ± 3.44 vs 42.88 ± 3.07 p = 0.001), the progression rate was slower (0.81 ± 0.63 vs 0.64 ± 0.63, p = 0.001). So, for Chinese ALS patients, using food bowl and chopsticks should replace the item of cutting food and handling utensils to assess the non-dominant-hand function, especially in non-dominant-hand onset patients.     

Impaired salivary gland function reveals autonomic dysfunction in amyotrophic lateral sclerosis

Recent studies have revealed autonomic dysfunction in amyotrophic lateral sclerosis (ALS). We studied salivary gland function by quantitative scintigraphy in ALS patients (n = 30) and healthy controls (n = 30). Uptake of ^99mTc-pertechnetate in the parotid and submandibular glands was significantly decreased in ALS patients. No correlation was found between radiotracer uptake and regions of onset (bulbar-limb), duration of disease, or functional scores. Our data show early subclinical autonomic involvement supporting the view that ALS is a multisystem degenerative disease. Received: 11 December 2001, Received in revised form: 5 March 2002, Accepted: 11 March 2002     

MOTOR UNIT NUMBER ESTIMATION (MUNE) AS A QUANTITATIVE MEASURE OF DISEASE PROGRESSION AND MOTOR UNIT REORGANIZATION IN AMYOTROPHIC LATERAL SCLEROSIS

Motor Unit Number Estimation (MUNE), a technique allowing to estimate the number of functioning Motor Units (MU) in single muscles, was used to score the disease's severity and progression rate in a group of 58 patients with Amyotrophic Lateral Sclerosis (ALS). All patients underwent MUNE in the abductor digiti minimi (ADM) muscle during the diagnostic work-up (T0), after three (T1) and six (T2) months. A significant loss [p < .001] of MU and a decrease [p < .001] of the maximal M wave area at T0 was found, whereas mean step area was increased [p < .001]. During the follow-up (T1 and T2), MU loss continued, maximal M wave decreased, and mean step area increased significantly. The results confirm that MUNE is a suitable tool to quantify the pathological changes in MU in patients with ALS.     

Challenges in diagnosis of motor neuron disease: A case series of ALS mimic syndromes

Amyotrophic lateral sclerosis (ALS) is most often a sporadic disorder that affects both upper and lower motor neurons. Because the prognosis of ALS is uniformly poor compared to other motor neuron disorders, defining the diagnosis can help guide appropriate clinical management and improve quality of life for patients. However, the diagnosis of ALS is often challenging and there may be overlapping clinical features with other rare diseases. We present four patients who were referred to our center because of the clinical suspicion of ALS, in whom more detailed assessments revealed an alternative diagnosis, and we discuss the limitations of the modified-El Escorial criteria.     

Glutamate levels in cerebrospinal fluid in amyotrophic lateral sclerosis: a reappraisal using a new HPLC method with coulometric detection in a large cohort of patients.

Glutamate is involved in the degeneration of motor neurons in amyotrophic lateral sclerosis (ALS). However, the aetiology of ALS appears heterogeneous, leading to the possibility that patient subgroups with different pathophysiology may exist. The concentration of glutamate in cerebrospinal fluid (CSF) is measured using a new HPLC method with coulometric detection in a large cohort of ALS patients and controls: 377 ALS patients, 88 neurological patients and 18 normal controls. In ALS patients, and only in these subjects, the existence of two groups was observed, one with normal glutamate concentrations and one (40.8% of ALS patients) with high glutamate concentrations. High glutamate concentrations were correlated with a spinal onset of the disease, more impaired limb function and a higher rate of muscle deterioration. These results suggest that elevations of CSF glutamate concentrations could reflect the intensity of cell insult in the spinal cord. It remains to be determined if the group of patients with high CSF glutamate concentrations represents a specific subgroup of patients in terms of mechanism of disease, or only in terms of the spatial extent of motor neuron insult.     

Endoplasmic reticulum stress and induction of the unfolded protein response in human sporadic amyotrophic lateral sclerosis

The unfolded protein response (UPR) is induced at symptom onset and disease end stage in rodent models of familial amyotrophic lateral sclerosis (ALS) that express superoxide dismutase (SOD1) mutations. However, ninety percent of human ALS is sporadic and mutations in SOD1 account for only 2% of total ALS. Here we show that a full UPR, including induction of stress sensor kinases, chaperones and apoptotic mediators, is also present in spinal cords of human patients with sporadic disease. Furthermore, the UPR chaperone protein disulphide isomerase (PDI) was present in CSF and was aggregated and widely distributed throughout the motor neurons of these patients. We also show up-regulation of UPR prior to the onset of symptoms in SOD1 rodents, implying an active role in disease. This study offers new insights into pathogenesis, placing ER stress onto a generic pathophysiology for ALS.