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ALS-Plus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。     

以胸髓前角先受累的肌萎缩侧索硬化的临床特点

目的探讨胸髓前角先受累的肌萎缩侧索硬化(ALS)患者的临床特征。方法回顾性分析3例以胸髓前角先受累的ALS患者的临床资料。结果3例患者均为男性,发病年龄分别为52岁、66岁、62岁;均以呼吸困难为首发表现,有明显的肋间肌和腹直肌萎缩,而肢体肌无力及肌萎缩的出现相对较轻、较迟;肌电图显示上肢及椎旁肌的神经源性损害。结论以胸髓前角先受累的ALS患者以男性多见,起病年龄晚于ALS的平均发病年龄,呼吸困难明显,呼吸肌萎缩早于肢体肌无力及肌萎缩,肌电图检查可以确诊。     

肌萎缩侧索硬化三例误诊分析

目的掌握肌萎缩侧索硬化(ALS)的诊断标准,以便早期准确诊断,避免误诊。方法分析3例ALS患者早期被误诊的临床资料。结果 3例患者均以下肢无力发病,逐渐波及上肢或对侧肢体,脊柱MR I示颈部或腰部椎间盘突出压迫硬膜囊,手术治疗后,症状无缓解,病情仍进行性加重,经肌电图检查证实为ALS。结论临床医师应熟知ALS的诊断标准,对患者详细询问病史、认真查体和电生理检查是减少ALS误诊的关键。     

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。     

139例肌萎缩侧索硬化临床及肌电图表现特点

目的 探讨肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)的临床及电生理特征,为早期准确诊断ALS提供依据.方法 回顾性研究近5年来收治的门诊及住院139例肌萎缩侧索硬化患者的临床及电生理表现,对其发病特点、症状、体征及实验室检查进行统计分析.结果 ALS在临床上慢性隐袭起病,逐渐进展,50岁前后发病,平均年龄49.1岁,平均病程2.4年.男性明显多于女性.首发症状为单侧上肢肌肉无力和肌肉萎缩最常见,其次为肌束震颤、延髓麻痹、锥体束征等,少数患者可出现肢体麻木、疼痛或发凉等感觉异常.临床主要症状是肢体无力、肢体和舌肌肌肉萎缩、锥体束征、肢体和舌肌肌束震颤.所有ALS侵害的部位均表现神经源性损害,胸锁乳突肌肌电图检查、胸脊旁肌肌电图、头部/颈/腰椎CT及MRI等辅助检查具有重要的确诊及鉴别诊断意义.结论 目前ALS的诊断仍然依靠临床表现.肌电图、CT/MRI是ALS诊断和鉴别诊断的重要辅助手段.     

肌萎缩侧索硬化26例临床分析

<正>肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)是成年运动神经元病中最常见的形式,其发病机制不清楚,诊断仍处于临床水平,无特效治疗,存活期为3~5年,预后不良。本文对我科近几年收治的肌萎缩侧索硬化病例的临床特征进行分析如下:     

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。     

Considerations on the concept,definition, and diagnosis of amyotrophic lateral sclerosis

The concept, definition, and diagnosis of amyotrophic lateral sclerosis(ALS) currently present some problems. This article systematically reviews the literature on the history, current concepts, definition, and diagnosis of ALS, and discloses the present problems based on the retrieved literature and the authors' clinical experience. The current concepts and definitions of ALS have not yet been unified or standardized in clinical practice, and are sometimes vague or inaccurate, which can cause difficulties for neurologists in the clinical treatment of ALS. The concept and definition of ALS need to be further ascertained, and the current diagnostic criteria for ALS require further development. The identification of effective and objective biomarkers may be a feasible method for the early and accurate diagnosis of ALS. Therefore, future research should focus on the identification of reliable biomarkers—especially neuroimaging biomarkers—through autopsy. Standardizing the concept and definition of ALS and formulating clear diagnostic criteria will largely avoid many uncertainties in the future clinical research and treatment of ALS, which will greatly benefit patients.     

Dissociated small hand muscle atrophy in amyotrophic lateral sclerosis: frequency, extent, and specificity

Previous studies suggest that in amyotrophic lateral sclerosis (ALS) the abductor pollicis brevis (APB) and first dorsal interosseous (FDI) are more severely involved than abductor digiti minimi (ADM). To elucidate the pattern, frequency, extent, and specificity of such dissociated muscle atrophy in ALS, compound muscle action potentials recorded from APB, FDI, and ADM were analyzed in 77 ALS patients, 171 normal controls, and 196 disease controls. Compared with normal controls, ALS patients had a reduced APB/ADM amplitude ratio (P < 0.001) and FDI/ADM ratio (P < 0.001), whereas patients with other anterior horn diseases showed similar APB/ADM and FDI/ADM ratios to normal values. Decreased APB/ADM ratio was found in 41% of ALS patients, 5% of normal controls, and 4% of disease controls. Prominent muscle atrophy in APB and FDI, with relatively preserved ADM, appears to be specific to ALS. Dissociated hand muscle atrophy presumably reflects part of the pathophysiology and supports the diagnosis of ALS.     

肌萎缩侧索硬化患者的重复神经电刺激特点

目的探讨肌萎缩侧索硬化(ALS)患者重复神经电刺激(RNS)特点,及其在ALS诊断和鉴别诊断中的应用价值。方法收集2008-05-2009-04在北京协和医院神经科门诊或住院确诊或拟诊的ALS患者101例,另选择同期门诊就诊的非ALS肌肉萎缩患者40例为对照。记录患者的临床资料。所有患者行肌电图和RNS检查。比较ALS患者和非ALS肌萎缩患者RNS阳性率的差异。比较ALS患者不同神经RNS阳性率及递减幅度差异,并分析性别、年龄、病程、尺神经波幅、临床疾病分级对RNS阳性率的影响。结果 (1)ALS患者和非ALS肌萎缩无力患者RNS检查低频递减阳性率分别为53.5%和7.5%,两组间比较差异有统计意义(P0.05),未出现高频递增患者。(2)所检测神经低频递减阳性率从高至低依次为腋神经(30.6%)副神经(25%)桡神经(15.5%)尺神经(7.8%)面神经(1.0%)胫神经(0%)。(3)ALS患者RNS检测低频递减阳性率与性别、年龄、病程、临床疾病分级无关(均P0.05),肢体起病者较球部起病者RNS低频递减阳性率高(P0.05)。结论 ALS患者RNS检测低频递减阳性率较非ALS肌无力萎缩患者高,RNS检测有助于ALS的诊断和鉴别诊断。ALS患者RNS检测低频递减阳性与性别、年龄、病程、临床疾病分级均无关。     

Utility of trapezius EMG for diagnosis of amyotrophic lateral sclerosis

Needle electromyography (EMG) of the tongue is traditionally used as a key to the diagnosis of amyotrophic lateral sclerosis (ALS), although relaxation of the tongue is often difficult to achieve. Recently, frequent abnormalities in the EMGs of the sternocleidomastoid (SCM) and upper trapezius muscles in ALS have been reported. To elucidate the diagnostic utility of these muscles we performed a multicenter prospective study to examine EMGs of the tongue (genioglossus), SCM, and trapezius in 104 ALS or suspected ALS patients. We also examined EMGs of the SCM and trapezius in 32 cervical spondylosis (CS) patients. We mainly evaluated fibrillation potentials/positive sharp waves (Fib/PSWs) and fasciculation potentials. Complete relaxation was achieved in 85% of ALS patients in the trapezius, but in only 6% of patients in the tongue. Fib/PSWs were observed in 8%, 13%, and 45% of ALS patients in the tongue, SCM, and trapezius, respectively, whereas fasciculation potentials were observed in 1%, 7%, and 39%, respectively. Abnormal spontaneous activity of any type was found in 9%, 17%, and 63% of patients, respectively. The high frequency of abnormal spontaneous activity in the trapezius was similar among the different diagnostic categories, and even 72% of clinically suspected ALS (progressive muscular atrophy) patients showed them in their trapezius. We did not observe Fib/PSWs or fasciculation potentials in any of our CS patients, thus these findings have excellent specificity. Tongue EMG added little utility over the clinical sign of tongue atrophy. Abnormal spontaneous activity in the trapezius would be more useful for the early diagnosis of ALS. Muscle Nerve 39: 63–70, 2009     

肌萎缩侧索硬化患者骨骼肌线粒体功能的改变及其临床意义

目的 研究肌萎缩侧索硬化(ALS)患者骨骼肌线粒体功能的改变及其临床意义.方法 对80例ALS患者应用ALS功能等级量表(FRS)评价病情;应用改良Gomori三色(MGT)及线粒体酶细胞色素C氧化酶(COX)染色方法检测肌肉标本不整边红纤维(RRF)的百分比及COX活性;分析其与FRS评分的相关性.结果 本组患者骨骼肌出现RRF 13例(16.3％),其中9例RRF为1％、3例RRF为4％、1例RRF＞4％;COX活性缺失21例(26.3％),其中完全缺失6例,部分缺失15例.肌肉RRF百分比和COX染色缺失程度与FRS评分呈负相关(r=-0.234,P＜0.05;r=-0.285,P＜0.01).结论 ALS患者骨骼肌线粒体功能异常,其异常越明显的患者病情越重.     

ULTRASOUND IN THE DIAGNOSIS AND MONITORING OF AMYOTROPHIC LATERAL SCLEROSIS: A REVIEW

Neuromuscular ultrasound is complementary to electrodiagnostic (EDx) testing and is useful in enhancing the diagnosis of mononeuropathies, peripheral nerve trauma, and demyelinating polyneuropathies. There is increasing interest in using ultrasound both to aid in the diagnosis of amyotrophic lateral sclerosis (ALS) and to monitor its progression. In this article we review the relevant literature on ultrasound in ALS. Ultrasound is more sensitive than EDx in identifying fasciculations in patients with ALS. It can detect decreased muscle thickness, increased muscle echointensity and echovariance, and reduced peripheral nerve size in these patients. Ultrasound is also a helpful tool in assessment of diaphragm function. Although additional studies are required to define the exact role of ultrasound in the evaluation and monitoring of ALS, it can improve the diagnostic yield in patients when ALS is suspected, but insufficiently supported, by clinical and EDx examinations. Muscle Nerve 60 : 114–123, 2019     

Diagnostic problems and delay of diagnosis in amyotrophic lateral sclerosis

Objective

Initial symptoms of amyotrophic lateral sclerosis (ALS) mimic several neurological syndromes that may decelerate a correct diagnosis. The aim of our study was to investigate if diagnostic and therapeutic parameters have influence on the time of diagnosis.

Methods

We retrospectively reviewed the medical records of 100 consecutive ALS patients focusing on clinical and diagnostic data, the timing of diagnosis and treatments attributed to the onset of symptoms of ALS.

Results

Among 100 consecutive patients with ALS, 12% underwent surgery due to symptoms retrospectively attributable to ALS. The comparison of duration from first symptoms to correct diagnosis showed a significant difference between operated and non-operated patients. 35% of all ALS patients had bulbar onset symptoms. The mean time from first symptoms to diagnosis was 9 months in this group. In patients without bulbar onset it was 16.4 months which also represents a significant difference. In 44% of patients other diagnoses were considered and medically treated previous to correct diagnosis, but there was no significant delay of diagnosis.

Conclusion

Our study confirms that diagnosis of ALS is still a common clinical problem and shows the need of sensitive and specific diagnostic tests.     

Muscle ultrasound quantifies the rate of reduction of muscle thickness in amyotrophic lateral sclerosis

Sensitive biomarkers are lacking in amyotrophic lateral sclerosis (ALS). Muscle ultrasound (MUS) can quantify muscle thickness and echointensity (EI). We evaluated the rate of muscle atrophy in ALS using MUS. Ten patients had serial unilateral MUS examination of biceps, wrist flexors, and tibialis anterior over 6 months. The rates of change of muscle thickness and EI were determined. Muscle thickness declined at a mean rate of -0.663 mm/month (P = 0.0014), greatest in biceps. Muscle thickness correlated moderately with ALSFRS-R, grip dynamometry, and body weight. There was no change in EI. MUS can quantify the rate of reduction in muscle thickness in ALS patients. The lack of strong correlation between muscle thickness and standard ALS measures may reflect limited sensitivity in these conventional measures. The rate of change of muscle thickness merits further study as a potential biomarker in ALS, particularly when considering biceps brachii as a candidate.