成人近端型脊肌萎缩症(附3个家系分析和电生理以及肌肉病理组化观察)

成人近端型脊肌萎缩症(adult spinal muscular a-trophy,Ⅳ型SMA)是一种神经系统遗传性疾病,其主要病理表现为脊髓前角运动神经神经元丢失,临床上以四肢近端肌萎缩无力为主要表现。目前对其临床、病理及基因研究较少,现将3个成年人近端型脊肌萎缩症家系及患者肌电图、肌活检标本的病理组化结果报告如下:     

6例脂质沉积性肌病的临床及病理特点

目的探讨脂质沉积性肌病（碍脚的临床和肌肉病理特点。方法分析6例LSM患者的临床资料,并观察其活检肌肉的常规组织学和组织化学病理。结果LSM的主要临床特点为四肢近端肌无力和对运动不耐受,肌萎缩多不明显,血清肌酶轻中度升高,肌电图多呈肌源性损害;肌肉病理显示Ⅰ型肌纤维为主的空泡变性．油红“O”染色示脂滴明显增多。皮质激素、内毒碱或维生索B2等治疗效果明显。结论LSM是一种少见的肌病类型,以肢体近端肌无力和肌疲劳现象为主要表现,临床上多长期误诊。目前LSM诊断需依赖症状、体征、酶学、肉毒碱检查、肌电图和肌肉活检等,其中肌肉活检发现肌纤维内脂肪滴增多是目前诊断此病的重要方法。     

罕见病脊髓性肌萎缩症治疗新药利司扑兰的临床药理与应用

脊髓性肌萎缩症(SMA)是一种主要发生在婴幼儿时期的致残致死的罕见神经肌肉疾病,目前治疗仍是个难题。2021年6月,全球首个治疗SMA口服药物利司扑兰(Risdiplam)经国家药监局批准上市,它是一种小分子运动神经元2(SMN2)前体mRNA剪接修饰剂,通过提高患者体内的功能SMN蛋白水平达到治疗脊髓性肌萎缩症的作用,适用于治疗2月龄及以上患者的脊髓性肌萎缩症。本文主要针对新药利司扑兰的作用机制、药理学、安全性和经济性以及临床应用开展简要的介绍。     

脂质沉积性肌病神经电生理及肌肉病理分析

目的：分析脂质沉积性肌病（LSM）的神经电生理及肌肉病理特点，旨为LSM早期诊断提供帮助。方法回顾性分析14例LSM确诊的患者的神经电生理及肌肉病理。结果肌电图表现正常占21.4％；神经源性损害占57.1％；源性损害占14.3％；既有神经源性又有为肌源性损害占7.1％；检测72条神经纤维表现为波幅下降占55.6％％，表现为传导速度和或潜伏期延长占27.8％，F波异常7.1％。肌肉病理表现为大量含有筛孔样空泡的肌纤维并脂质沉积。结论 LSM肌电图表现并非如肌炎及其他类型肌病以肌源性损害多见，而多表现为正常或神经源性损害，临床容易误诊，肌肉活检可明确诊断。     

《骨骼肌疾病肌肉酶组化病理学幻灯片》介绍

福建医学院病理解剖学副教授陈碧芬编著的《骨骼肌疾病肌肉酶组化病理学幻灯片》,最近已由北京科技声象服务中心发行。该套幻灯片收集国内外二千余例各种类型肌肉疾病的活检病理切片和电镜照片资料,选出其中经国内外专家确诊的典型病例摄制成彩色幻灯片154幅,内容包括进行肌营养不良症、运动神经原性肌肉疾病、先天性肌病、炎症性肌病、代谢性肌病及其它肌病等八个章节,附有临床病例摘要及详细病理组     

左卡尼汀治疗脂质沉积性肌病2例

目的 研究左卡尼汀（L-carnitine, L-CN）治疗有效的脂质沉积性肌病（lipid storage myopathy, LSM）患者的临床表现、神经电生理、病理学特点、治疗经过和病情转归. 方法 分析2例LSM患者的临床表现、神经电生理及病理学资料与治疗过程, 并复习相关文献. 结果 2例LSM患者以肌肉疼痛、近端肌无力和运动不耐受为主要临床症状, 神经电生理表现为肌源性损害和（或）周围神经损害, 肌肉活检超微病理确诊LSM, 但经激素治疗临床症状和体征改善不显著. 静脉注射左卡尼定后半月内临床患者症状和体征缓解, 但是肌酶谱升高, 左卡尼汀治疗4个月时肌酶谱、病理和电生理指标好转. 结论 脂质沉积性肌病是青少年肌肉无力的重要原因, 是可以临床治愈的疾病, 左卡尼汀治疗可以使LSM达到临床和病理缓解.     

连枷臂综合征及其与桶人综合征和运动神经元病的鉴别诊断

<正>运动神经元病(motor neuron disease,MND)是一组病因未明的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慢性进行性神经变性疾病,发病率约为每年1～3/10万,患病率为每年4～8/10万。临床根据肌无力、肌萎缩、肌肉纤颤和锥体束损害等症状的不同组合将经典的MND分为肌萎缩侧索硬化(amyotrophic lateral sclerosis,ALS)、脊肌萎缩症(spinal muscular atrophy,SMA)、     

慢性甲状腺亢进性肌病32例的诊治体会

目的通过对慢性甲状腺机能亢进性肌病(CTM)患者的肌电图检测和神经传导速度的测定,探讨慢性甲状腺机能亢进性肌病的临床表现及肌电图(EMG)特点,避免临床误诊。方法本组病例来自本院2004—2011年非选择性住院32例慢性甲状腺亢进性肌病患者,对其进行神经系统病史询问及体格检查,对其生化、肌酸激酶测定、肌电图检查及神经传导测定进行分析。结果 32位患者均有甲亢临床表现:甲状腺激素或自身免疫抗体升高;进行性肌无力和萎缩,以骨盆带肌最为严重;新斯的明试验阴性;肌肉变性与甲亢病情程度及病程呈正相关;肌电图动作电位时间显著缩短;肌活检提示肌源性损害。结论甲亢的病程及严重程度与慢性肌病的发生相关,一旦甲亢控制后,肌无力和肌萎缩等肌病症状可好转。     

婴儿型脊髓性肌萎缩症1例

脊髓性肌萎缩症（SMA）是一种常染色体隐性遗传病,累及脊髓前角运动神经元细胞,导致进行性、对称性肌萎缩和肌张力减低。本症早期发现和诊断较困难,容易误诊。笔者现就临床工作中诊治的1例脊髓性肌萎缩患儿进行分析和讨论。1病历摘要患儿男,61天,因咳嗽、气促4天,呼吸停止复苏后20分钟入院。系G1P1足月自然分娩,无产伤窒息史,人工喂养至今,既往体健。父母体健。     

小儿脊髓性肌萎缩32例临床分析

小儿脊髓性肌萎缩是儿童最常见的致死性常染色体隐性遗传病之一 ,临床表现为进行性对称性肌肉萎缩和肌无力。现将 1981～ 2 0 0 0年在我院诊断的 32例患者进行临床分析如下。1　临床资料1.1　纳入标准　具备以下 3条以上。①以进行性肌松驰为特征伴有反复呼吸道感染 ;②双侧对称性肌萎缩、肌张力减弱、腱反射消失或明显减弱 ,以双下肢为重 ;③血清肌酸磷酸肌酶正常 ;④肌电图提示神经源性肌损害 ,肌活检纤维结构模糊不清 ,缺乏横纹。1.2　一般资料　多在 1岁前发病 ,6月前发病共 19例 ,其中有胎动减少 7例 ,均生后发现肢体无力 ;6月至 1岁半…     

Histone deacetylase inhibitors: therapeutic agents and research tools for deciphering motor neuron diseases

Histone deacetylase (HDAC) inhibition as a therapeutic regimen in motor neuron diseases (MND) is generating intense interest in both the scientific and medical areas, with a number of potent compounds having demonstrated good safety profiles and hints of clinical activity on animal models. In this review, we discuss recent developments in dissecting the mechanism of action of HDAC inhibitors (HDACi) as a new group of mechanism-based drugs for motor neuron diseases, together with current progress in understanding their clinical application. We also discuss how the use of HDACi on animal models with motor neuron defects has allowed critical advances in the understanding of the pathophysiology of motor neuron diseases. The use of HDACi and possible mechanisms of action will be reviewed in three MND, i.e. amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA) and spinal and bulbar muscular atrophy (SBMA), diseases among which clinical trials with HDACi are currently perfomed (ALS, SMA).     

Developments in the discovery of drugs for spinal muscular atrophy: successful beginnings and future prospects

Introduction: Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in a gene that produces a protein called survival motor neuron (SMN). SMN has an important role in snRNP assembly in all cells but that may not be its only role; the reasons for SMN deficiency resulting in neuromuscular dysfunction and motor neuron degeneration remain active areas of research. Besides increasing SMN, compensating for SMN deficiencies or neuroprotection may be therapeutic options for SMA. Age of onset and the rate of disease progression are variable and therapeutic strategies should be appropriate to subtypes of SMA patients. Areas covered: The article discusses SMA, their targets and where these targets can be found. Additionally, the article reviews small molecules identified as disease modifiers and how these small molecules were discovered. The article also describes and discusses emerging concepts regarding the disease mechanisms. The author compiled this review using scientific literature, patent databases, company and patient association and government websites. Expert opinion: Small molecules targeting various processes implicated in SMA are reaching the clinic. These molecules and targets, although not yet validated, are providing insight into the complexity of a 'simple' genetic disease such as SMA. SMA is not a single disease and so various therapeutic strategies are needed. Biomarkers and regulatory guidelines are required to select patients for clinical trials, decide when to initiate treatment and how to develop combinations of investigational drugs.     

慢性炎症性脱髓鞘性多发性神经根神经病的误诊分析

目的：分析慢性炎症性脱髓鞘性多发性神经根神经病(CIDP)的误诊原因。方法：对误诊的18例CIDP患者进行回顾性分析。结果：早期误诊率81.81％(18／22)，平均误诊时间10个月，误诊为MDP3例，末梢神经炎4例，脊髓病变1例，腰椎间盘突出症2例，颈椎病3例，肌病2例，进行性脊肌萎缩症2例，共济失调症1例。其误诊原因有起病隐袭、症状不典型、查体不全面及缺乏特殊检查等。结论：对CIDP认识不足是误诊的主要原因。加强对本病的了解及认识，详尽的体格检查，腰穿脑脊液有无蛋白一细胞分离以及电生理检查，必要时行神经活检是提高CIDP检出率的关键。     

Valproic acid promotes neurite outgrowth in PC12 cells independent from regulation of the survival of motoneuron protein

Spinal muscular atrophy (SMA) is a neurodegenerative disorder of motoneurons. The disease is caused by deletions or mutations of the survival of motoneuron gene 1 (SMN1). The amount of protein expressed from the second gene, SMN2, correlated with the severity of the clinical phenotype. The histone deacetylase inhibitor valproic acid (VPA) has been shown to increase the total cellular amount of functional SMN protein and is therefore considered as a drug candidate for treatment of SMA. In this study, we analyzed the effects of VPA in PC12 cells, a model system for neuronal differentiation, with regard to neurite outgrowth and SMN expression. VPA promoted neurite outgrowth in PC12 cells. However, this effect did not correlate with upregulation of SMN protein levels, suggesting a SMN-independent mechanism for VPA regulation of neurite outgrowth.     

New treatments in spinal muscular atrophy: an overview of currently available data

ABSTRACT

Introduction: Spinal muscular atrophy (SMA) is one of the most common inherited neuromuscular disorders. It causes progressive muscle weakness and results in significant disability. Until recently, there were no drugs available for the treatment of SMA. Several phase 1–3 studies, including three double-blind randomized placebo-controlled studies have demonstrated the efficacy of disease-modifying approaches including gene replacement therapy, antisense oligonucleotides, and splicing modifiers.

Areas covered: This article covers the publically available data on therapeutic strategies that address the underlying cause of SMA and clinical data available on approved treatments and drugs in the pipeline.

Expert opinion: The newer therapeutic options in SMA have a good safety profile and deliver a therapeutic benefit in most patients. It is essential that the recommended standards of care are delivered along with the drugs for the best outcomes. No biomarkers to distinguish responders from non-responders are available; it is important that biomarkers be identified. Early treatment is essential for the maximum efficacy of the newly available treatments.     

New pharmacotherapies for genetic neuromuscular disorders: opportunities and challenges

ABSTRACT

Introduction: Genetic neuromuscular diseases (NMDs) constitute a heterogeneous group of rare conditions, including some of the most disabling conditions in childhood. Recently, advanced technologies have greatly expanded preclinical and clinical research, and specific therapies have been developed.

Area covered: We provide an overview of novel pharmacological approaches to the main NMDs, including Duchenne muscular dystrophy (DMD), spina muscular atrophy (SMA), X-linked myotubular myopathy, Pompe disease (PD), and myotonic dystrophy type 1, with attention to both achievements and unresolved therapeutic challenges. We conducted a selected review of relevant publications in the last five years identified through PubMed and Scopus. Additional information was derived from the website of clinicaltrials.gov and from the authors’ direct knowledge of research activities.

Expert Opinion: For the first time, targeted therapies have received conditional regulatory approval and have been introduced into clinical care: enzyme replacement therapy for PD, gene expression modulation for DMD and SMA, and gene therapy for SMA. Though not curative, these treatments can improve functioning and increase survival. Issues still to be addressed include: early recognition, definition of new emerging phenotypes, development of more sensitive outcome measures, long-term risk-benefit estimates, high costs sustainability, and criteria for therapy initiation and discontinuation.     

Developments in the discovery of drugs for spinal muscular atrophy: successful beginnings and future prospects

Introduction: Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by mutations in a gene that produces a protein called survival motor neuron (SMN). SMN has an important role in snRNP assembly in all cells but that may not be its only role; the reasons for SMN deficiency resulting in neuromuscular dysfunction and motor neuron degeneration remain active areas of research. Besides increasing SMN, compensating for SMN deficiencies or neuroprotection may be therapeutic options for SMA. Age of onset and the rate of disease progression are variable and therapeutic strategies should be appropriate to subtypes of SMA patients.

Areas covered: The article discusses SMA, their targets and where these targets can be found. Additionally, the article reviews small molecules identified as disease modifiers and how these small molecules were discovered. The article also describes and discusses emerging concepts regarding the disease mechanisms. The author compiled this review using scientific literature, patent databases, company and patient association and government websites.

Expert opinion: Small molecules targeting various processes implicated in SMA are reaching the clinic. These molecules and targets, although not yet validated, are providing insight into the complexity of a ‘simple’ genetic disease such as SMA. SMA is not a single disease and so various therapeutic strategies are needed. Biomarkers and regulatory guidelines are required to select patients for clinical trials, decide when to initiate treatment and how to develop combinations of investigational drugs.     

诺西那生钠注射液治疗儿童脊髓性肌萎缩症疗效观察

目的:探讨脊髓性肌萎缩症(SMA)患儿应用诺西那生钠注射液的临床疗效及安全性。 方法:选取 2022 年 1-6 月于我院 接受诺西那生钠鞘内注射治疗的 SMA 患儿 26 例,于治疗当天(T0)、第 14 天(T1)、第 28 天(T2)及第 63 天(T3)评估并比较 Hammersmith 扩展功能运动量表(HFMSE)、上肢模块修订版(RULM)、6 分钟步行试验(6MWT)及不良反应发生情况。 结果:与 T0 比较,T3 时 HFMSE 评分升高[(20. 69± 14. 64 ) 分 vs. ( 23. 38± 15. 69) 分, P< 0. 01]。 与 T0 比较,T3 时 RULM 评分升高 [(18. 27±10. 15)分 vs. (19. 88±10. 21)分,P<0. 05]。 结论:SMA 患儿应用诺西那生钠注射液治疗后,HFMSE 和 RULM 评分显 著提高,近端肢体运动功能明显改善,且无明显不良反应发生