神经肌肉病研究新亮点

为方便临床医师了解神经肌肉病的最新进展,笔者对2013年1月-2014年2月美国国立医学图书馆(PubMed)收录的神经肌肉病相关文章进行筛选并整理,从临床诊断和治疗角度提纲挈领地介绍糖原贮积病Ⅱ型、Duchenne型肌营养不良症、肌萎缩侧索硬化症和脊髓性肌萎缩症的研究背景和最新研究亮点,并附相应参考文献供读者参考。     

青年上肢远端肌萎缩症的临床肌电图及肌肉病理的研究

对２２例青年上肢远端肌萎缩症的临床，肌电图及肌肉病理进行了研究。肌电图显示神经源性损害，主要分布于病侧手肌，对侧手肌也可有亚临床电生理异常，提示受损节段多在颈７、８－胸１脊髓前角，肌肉组织病理，酶组织化学及电镜检查显示神经源性肌萎缩，为下颈髓前角细胞受损的结果有别于运动神经元病，其病因可能与局部脊髓血循环境障碍有关。     

一种罕见的运动神经元病:远端型脊肌萎缩症（附1例报道）

目的 探讨远端型脊肌萎缩症(Distal spinal muscular atrophy,dSMA)的临床特征及诊断。方法 对1例双下肢远端肌无力伴萎缩的患者进行临床、实验室、电生理、影像学检查。结果 患者幼年起病,表现为对称性双下肢无力,病情缓慢进行性加重,逐渐出现双下肢远端对称性肌肉萎缩,血清肌酶基本正常,电生理检查提示四肢神经源性损害,感觉、运动神经传导正常。结论 远端型脊肌萎缩症的临床特征与腓骨肌萎缩症、运动神经元病极为类似,实验室、电生理检查及基因检测有助于疾病的诊断。     

青年上肢远端肌萎缩症的临床、肌电图及肌肉病理的研究

对２２例青年上肢远端肌萎缩症的临床、肌电图及肌肉病理进行了研究。肌电图显示神经源性损害，主要分布于病侧手肌，对侧手肌也可有亚临床电生理异常，提示受损节段多在颈＿（７、８）～胸＿１脊髓前角。肌肉组织病理、酶组织化学及电镜检查显示神经源性肌萎缩，为下颈髓前角细胞受损的结果，有别于运动神经元病。其病因可能与局部脊髓血循环障碍有关。     

广泛神经源性损害患者的临床分析

目的进一步研究肌萎缩性侧索硬化(ALS)的诊断及预后。方法2008年2月～2010年1月间因缓慢起病、逐渐进展的肌肉无力、萎缩、痉挛、束颤就诊,且针肌电图呈广泛神经源性损害者均纳入登记建档;记录首发起病部位、修订肌萎缩侧索硬化功能评分(ALSFRS-R)以及病程,并分析临床特点。结果(1)广泛神经源性损害患者共80例,19例(23.75%、19/80)为下运动神经元综合征(LMNS)患者,61例(76.25%、61/80)为不同诊断级别的ALS(Awaji-shi ma标准);其中临床肯定型24例(30%、24/80),临床拟诊型22例(27.5%、22/80),临床可能型15例(18.75%、15/80)(χ2=0.067,P=0.381);(2)在不同诊断级别的ALS中,首发起病部位在延髓者,临床肯定型的例数多于拟诊型和可能型(P0.05);(3)ALSFRS-R平均35.35±6.17,平均病程(27.7±22.2)年;与临床拟诊型和可能型患者组比较,肯定型组ALSFRS-R分值(31.00)更小,病程(1.64年)更短。结论广泛神经源性损害的患者中虽然不同诊断级别的ALS患者占大部分,但临床肯定型仅1/3;预后不良的因素为延髓起病、评分低和病程短。     

中华医学会第五届全国神经肌肉病学术会议征文通知

中华医学会第五届全国神经肌肉病学术会议 ,拟于 2 0 0 2年 9月 15～ 17日在北京召开 ,除了交流近 5年来国内神经肌肉病取得的进展外 ,还邀请国外学者进行专题讲座 ,现开始征文。征文内容 :进行性肌营养不良症的分子生物学研究、线粒体肌病和代谢性肌病的诊断、先天性肌病的临床和病理学研究、中毒和药物性肌病、重症肌无力及肌无力综合征、吉兰 巴雷综合征的免疫学、病理学、生理学、流行病学 ,各类遗传及代谢性周围神经病、肌萎缩侧索硬化和进性行脊髓性肌萎缩。凡与上述内容有关未在公开刊物上发表的论文均可投稿 ,来稿请寄 10 0 0字左右…     

二代测序在遗传性神经肌肉病分子生物学中的应用

<正>遗传性神经肌肉病(inherited neuromuscular disorders,NMDs)是一组少见的累及神经(遗传性运动感觉周围神经病、肌萎缩侧索硬化、遗传性脊肌萎缩症等)、肌肉(各型肌病/肌营养不良、离子通道病等)及神经-肌肉接头疾病的单基因遗传性疾病,多以肌无力、肌萎缩,伴/不伴肌张力低下及感觉障碍为主要临床表现,可于新生儿、儿童或成年期发病,为患者及其家庭以及公共卫生造成极大负担。该类疾病     

4例原发性甲旁亢伴肌萎缩临床分析

目的:探讨原发性甲旁亢伴肌萎缩临床特点,提高临床医师对本病认识,降低误诊率和漏诊率。方法:回顾性分析1990年至今在我科诊治的以肌萎缩和肌无力为首发症状的甲旁亢病例共4例,就其临床表现、实验室检查、电生理特点、组织学变化以及治疗预后结合文献进行分析。结果:4例均以双下肢无力起病,逐渐进展为四肢对称性以近端为主的肌无力和肌肉萎缩,下肢重于上肢,其中2例同时有上运动神经元损害表现。4例肌酶均正常,血钙浓度和血清甲状旁腺激素测定都明显升高。肌电图和肌活检结果可表现为肌源性或神经源性。3例患者采用手术治疗,切除甲状旁腺腺瘤后肌无力症状有所改善。结论:原发性甲旁亢对神经肌肉系统的影响错综复杂,肌电图和肌肉活检结果缺乏特异性,血钙浓度测定对疾病诊断有较大帮助．手术是治疗的重要手段。本病存在类似肌萎缩侧索硬化症状的少见类型。     

下期内容预告

正本刊2021年第6期报道专题为神经系统遗传性疾病,重点内容包括:再论重视可治性罕见病的早期诊断与治疗;脊髓性肌萎缩症治疗进展;定量磁共振成像在遗传性肌肉病中的应用;转甲状腺素蛋白淀粉样变性多发性神经病诊断与治疗进展;治疗脊髓性肌萎缩症2型患儿疗效评估及长期随访;糖原贮积病Ⅱ型酶替代治疗及长期随访;肌肉磁共振成像在遗传性肌肉病诊断中的应用研究;常染色体隐性遗传性帕金森病的临床、影像、基因分析及疗效评价;PARK2基因突变致早发型帕金森病一例     

良性局限性下肢肌萎缩

良性局限性下肢肌萎缩是一隐匿起病,缓慢进展,继之以3年以上稳定期的局限性肌萎缩疾病。该病肌萎缩与肌无力不成比例,无感觉障碍,锥体束损害和延髓麻痹。病例都呈散发性,无脊髓灰质炎病史。患者血肌酸磷酸激酶正常,抗神经节苷脂抗体阴性,肌电图上运动和感觉传导速度正常。肌电图和肌活检检查除萎缩肌肉外,在其他肢体上也可见到广泛前角细胞损害。肌肉CT显示肌萎缩呈不对称性,主要或选择性损害下肢后组肌群和股二头肌长头。该病是脊肌萎缩症的一种变异类型,预后良好。     

脊髓性肌萎缩症临床诊断研究进展

脊髓性肌萎缩症系由脊髓前角运动神经元退行性变而导致的进行性、对称性肌无力和肌萎缩的一类常染色体隐性遗传性疾病,其致病基因为运动神经元生存(SMN1)基因。临床上共分为4种类型即脊髓性肌萎缩症Ⅰ、Ⅱ、Ⅲ和Ⅳ型,其临床诊断主要依赖于临床表现、家族遗传史、实验室检查及基因检测。目前尚无有效治疗方法,因此产前诊断和对基因携带者的筛查为有效预防措施。     

Neuromuscular disorders in pregnancy

Preexisting and coincident neuromuscular disorders in pregnancy are challenging for clinicians because of the heterogeneity of disease and the limited data in the literature. Many questions arise regarding the effect of disease on the pregnancy, delivery, and newborn in addition to the effect of pregnancy on the course of disease. Each disorder has particular considerations and possible complications. An interdisciplinary team of physicians is essential. This article discusses the most recent literature on neuromuscular disorders in pregnancy including acquired root, plexus, and peripheral nerve lesions; acquired and inherited neuropathies and myopathies; disorders of the neuromuscular junction; and motor neuron diseases.     

Subsarcolemmal expression of utrophin in neuromuscular disorders: an immunohistochemical study of 80 cases

The immunohistochemical expression of utrophin in 80 muscle biopsies from patients with dystrophinopathies and other neuromuscular disorders is reported. All biopsy specimens were routinely studied by a battery of 12 histoenzymatic techniques, and immunohistochemistry was performed for spectrin, three domains of dystrophin and two domains of utrophin. Abnormal utrophin expression was observed in all dystrophinopathic muscles compared with normal controls or biopsy samples from several other muscular diseases. Inflammatory myopathies presented abnormal overexpression of utrophin and an abnormal dystrophin immunolabeling pattern. This overexpression of utrophin appears to be directly related to the decrease in dystrophin. We conclude that the study of utrophin is important for the histological interpretation and differential diagnosis of dystrophin-related muscular disorders. Received: 13 November 1997 / Revised: 6 February 1998, 20 May 1998 / Accepted: 22 May 1998     

Recommendations for the diagnosis and management of typical childhood spinal muscular atrophy

Typical childhood spinal muscular atrophy is a disease that affects the anterior horn of the spinal cord related to SMN1 gene defects. Since no etiological treatment is currently available, its management is necessarily symptomatic and involves multidisciplinary care. The national plan on rare diseases for 2005–2008 developed by the French Ministry of Health resulted in the creation of 12 reference centres for neuromuscular diseases, mainly to improve their diagnosis and management. During the first one-day clinical research meeting on neuromuscular disorders, organized by the French Association to fight myopathies (AFM) in May 2007, clinicians from the 12 national reference centers led workshops for each of the main neuromuscular diseases. Concerning spinal muscular atrophy, discussions involving specialists from medical and allied professions were led by clinicians in charge of the workshop sessions. This paper reports the final version of their recommendation regarding the diagnosis, monitoring and management of typical infantile spinal muscular atrophy, which is necessarily multidisciplinary, including orthopedic, pulmonary, gastroenterology and nutrition care.     

肢带型肌营养不良症临床特点及诊断与治疗进展

肢带型肌营养不良症是一组基因突变导致的以近端肌无力为主要表现的遗传性肌病。尽管其临床表现具有共性特征,但不同亚型之间仍存在差异,且遗传缺陷具有异质性,故应结合临床表现、影像学、肌肉病理学和基因检测等综合判断。目前主要采取综合治疗方法。近年来,国内外对此类疾病的诊断与治疗取得新的进展。本文拟就肢带型肌营养不良症各亚型临床特点以及诊断与治疗进展进行概述。     

Clinical outcome assessments in Duchenne muscular dystrophy and spinal muscular atrophy: past,present and future

Scores and scales used in pediatric motor development for neuromuscular disorders have evolved greatly since the beginning of their development. In this review we provide a brief history of scales used in pediatric patients with neuromuscular disorders and an update regarding the advancement of the scales commonly used in patients with spinal muscular atrophy and Duchenne muscular dystrophy. We focus on the collaborative effort that has led to the development of outcomes and speak to the possible future of Clinical Outcome Assessments.     

What we do not know about pregnancy in hereditary neuromuscular disorders

Only sparse information is available concerning the relationship between pregnancy and hereditary neuromuscular disorders. This review deals with several issues like the effects of such conditions on female fertility (myotonic dystrophy type 1 and mitochondrial disorders), on the risk to the fetus (myotonic dystrophy type 1 and Charcot-Marie-Tooth disease), on the ability to carry pregnancy and its complications (markedly increased preterm labor in myotonic dystrophies and spinal muscular atrophy), on the labor and its possible need for interventions (myotonic dystrophy type 1, facioscapulohumeral dystrophy and Charcot-Marie-Tooth disease). It also discusses the question of pregnancy effects on the course of the inherited neuromuscular disorders (myotonic dystrophies, spinal muscular atrophy, facioscapulohumeral dystrophy, Charcot-Marie-Tooth disease, congenital myopathy and limb-girdle muscular dystrophy). The aim of this critical review is to point at pregnancy-related problems that need further research.     

Differential and quantitative neuroimaging characteristics of inclusion body myositis

In clinical settings, it is often difficult to distinguish inclusion body myositis (IBM) from other neuromuscular diseases. In order to clarify clinically useful characteristics for making the differential diagnosis of IBM, we performed clinical, epidemiological, and neuroimaging analyses in patients with various types of neuromuscular disorders. We enrolled 333 patients with myopathy and 12 patients with amyotrophic lateral sclerosis (ALS) who had been hospitalized in our department from January 1, 1979, to December 31, 2018. Among them, 18 patients with IBM, 16 patients with polymyositis (PM), and 12 patients with ALS who showed equivalent severity of muscle weakness in their lower limbs underwent the quantitative neuroimaging analysis using lower limb CT and clinical assessment. Patients with IBM exhibited significantly greater muscular degeneration in the rectus femoris, vastus, sartorius, adductor, anterior calf, and medial gastrocnemius muscles than those with PM or ALS. The ratio of the remaining muscle area of the quadriceps relative to that of the hamstrings and the duration from onset to CT imaging were negatively correlated in patients with IBM, indicating that the anterior thigh muscles were preferentially affected over the posterior muscles. Characteristic muscular degeneration in the lower limbs on CT imaging may aid for making the diagnosis of IBM.     

Cognitive impairment in neuromuscular disorders

Several studies have suggested the presence of central nervous system involvement manifesting as cognitive impairment in diseases traditionally confined to the peripheral nervous system. The aim of this review is to highlight the character of clinical, genetic, neurofunctional, cognitive, and psychiatric deficits in neuromuscular disorders. A high correlation between cognitive features and cerebral protein expression or function is evident in Duchenne muscular dystrophy, myotonic dystrophy (Steinert disease), and mitochondrial encephalomyopathies; direct correlation between tissue-specific protein expression and cognitive deficits is still elusive in certain neuromuscular disorders presenting with or without a cerebral abnormality, such as congenital muscular dystrophies, congenital myopathies, amyotrophic lateral sclerosis, adult polyglucosan body disease, and limb-girdle muscular dystrophies. No clear cognitive deficits have been found in spinal muscular atrophy and facioscapulohumeral dystrophy.     

炎症性肌病247例临床与病理研究

目的探讨多发性肌炎（PM）、间质性肌炎（IM）与神经肌炎（NM）的临床特点及神经肌肉活检的诊断价值。方法回顾分析247例炎症性肌病的临床表现及神经肌肉活检结果。结果3组临床表现相似,为近端肌无力、肌痛等;均有不同程度的肌酶增高,但PM组增高明显;IM和NM具有PM的病理改变,但炎性程度不及PM,又各有其特异性,IM组为炎性细胞浸润间质,NM组神经活检多有髓鞘脱失、炎性细胞浸润。结论PM、IM、NM炎性肌病的临床表现相似,诊断困难,需结合神经肌肉活检等辅助检查才能作出正确的诊断。