中文版北极星移动评价量表在Duchenne型肌营养不良症患儿的信度和效度研究

目的：确定中文版北极星移动评价量表（NSAA）应用在Duchenne型肌营养不良症（DMD）患儿的信度和效度。方法：纳入对象为2014年1月至2016年1月在复旦大学附属儿科医院康复科接受功能评估的DMD患儿,均经基因检测或肌肉活检明确诊断,能独立行走≥10 m,无严重认知障碍。2名物理治疗师同时对DMD患儿进行测试,检验不同测试者间的信度;同一评价者在第1次评价后3~7 d进行第2次评价,检测重测信度;采用《国际功能、残疾和健康分类》儿童和青少年版（ICF-CY）的类目编码与NSAA的项目概念进行关联,确定NSAA的内容效度;通过分析NSAA的分值与6 min步行距离的相关性进行关联效度分析。结果：2个治疗师对20名DMD男孩的不同测试结果间的信度分析显示,NSAA原始分和线性分信度ICC分别为0.96和0.97;1名治疗师前后3～7 d重测16名DMD男孩,NSAA的原始分和线性分具有很好的重测信度（ICC=0.96）;NSAA17个项目共与8个ICF-CY编码发生了20次关联,8个编码都属于d4（移动）下属,表明NSAA的评价内容主要聚焦于DMD患儿活动能力中的移动能力;143例DMD男孩的NSAA原始分和线性分与6min步行距离具有中等程度的相关性（r分别为0.40和0.38）。结论：中文版NSAA量表无论是原始分还是线性分都具有良好的心理测量学特性,结合其他的评价指标,NSAA可以有效地评价中国DMD男孩的活动能力。     

北极星移动评价量表在Duchenne型肌营养不良患儿中的信度研究

目的了解北极星移动评价量表(North Star Ambulatory Assessment,NSAA)应用在Duchenne型肌营养不良(Duchenne muscular dystrophy,DMD)患儿中的组间信度及组内信度,并探讨通过录像法评测运动功能的可行性。方法分析2017年7月至2017年11月北京大学第一医院使用NSAA对40例DMD患儿进行运动功能评估的资料。40例DMD患儿年龄4.3～13.4岁,均为男性;分为3个年龄亚组,5岁的10例,5～9岁的18例,9岁的12例。由3名治疗师A、B、C进行评估。在组间信度的研究中,评估者A应用NSAA对DMD患儿进行现场运动评估并摄像,评估者B、C分别通过录像进行独立评分,通过三者对同一患儿的评分计算组间信度。在组内信度的研究中,与第1次评估至少间隔1个月以上,评估者分别根据录像对每个患儿进行第2次评估,根据评估者B、C对同一患儿两次评估的评分计算组内信度。根据评估者A对同一患儿两次评估的评分,计算录像评分与现场评分的一致性。通过计算相关系数检测信度。结果在组间信度的研究中,总体相关系数为0.990,各年龄亚组相关系数为0.971～0.992;在组内信度的研究中,总体相关系数为0.987～0.988;录像评分与现场评分一致性相关系数为0.980。结论 NSAA在评估DMD患儿运动功能水平时具有较高的信度,且现场评分和对录像评分一致性好,可能适用于远程康复评估。     

Duchenne型肌营养不良患儿认知损害的研究进展北大核心CSCD

Duchenne型肌营养不良(DMD)是由于抗肌萎缩蛋白基因突变所致的X连锁隐性遗传性神经肌肉病,约1/3的患儿存在认知损害,早期发现认知损害并给予适当干预对改善患儿生存质量具有重要意义。现就近年来关于DMD患儿认知损害的临床特点、发病机制、脑结构改变和干预措施等方面的研究进展作一综述。     

Duchenne型进行性肌营养不良40例临床分析

目的 探讨Duchenne型进行性肌营养不良(DMD)的临床特点及肌酶、肌电图、肌肉活检的诊断价值.方法 对40例经dystrophin蛋白检测确诊的DMD患儿的临床特征及实验室检查资料进行分析.结果 40例患儿平均年龄7.2岁,平均发病年龄4.5岁,15%患儿有家族史.40例患儿均有典型的临床症状和体征,肌酶升高以肌酸磷酸激酶(CPK)升高为主,≤8岁年龄组CPK值高于＞8岁组.所有患儿肌肉活检均有肌纤维变性和坏死,12.5%的患儿尚伴炎性细胞浸润.在有肌源性损害同时,15%的患儿肌电图尚有神经源性损害.结论 血清肌酶、肌电图及肌活检是DMD重要的辅助诊断指标,对于肌电图有神经源性损害和肌活检病理检查有炎性细胞浸润者,应进行基因检测和(或)dystrophin蛋白检测.     

Duchenne型肌营养不良基因治疗研究进展

Duchenne型肌营养不良（DMD）是由编码抗肌萎缩蛋白的DMD基因突变导致的X连锁隐性遗传病。它的特点是进行性肌无力和因缺乏抗肌萎缩蛋白而导致的骨骼肌和心肌退化。患儿多于2~5岁起病,常在20岁左右死于心力衰竭或呼吸功能不全。目前,临床上多采用支持疗法改善疾病症状,但并不能改变疾病的最终结局。基因治疗的兴起为该病的治愈提供了希望。本文总结了DMD的基因替代疗法,包括腺相关病毒介导的DMD基因转导技术、肌营养不良蛋白相关蛋白（utrophin）上调技术和成簇规律间隔的短回文重复序列基因编辑技术的研究进展,并为解决腺相关病毒载量、转基因产物的长期有效表达、utrophin蛋白表达量问题提出的建议进行综述,为研究者们进一步研究提供参考。     

不同年龄阶段Duchenne型肌营养不良患儿肌细胞膜上DGC关联复合物蛋白的表达

目的 研究不同年龄阶段Duchenne型肌营养不良患儿肌细胞膜上DGC关联复合物蛋白的表达.方法 将24例已确诊的Duchenne型肌营养不良患儿根据儿童发育年龄分成3组,0.5～3岁为幼儿期组,～6岁为学龄前期组,～13岁为学龄期组.利用免疫组织化学方法对肌细胞膜上与抗肌萎缩蛋白(dystrophin)组成相关DGC复合体的蛋白进行分析.结果 dystrophin蛋白的缺失可引起不同年龄阶段的肌细胞膜上α-SG、β-SG、γ-SG、δ-SG、β-DG和dysferlin不同程度的缺乏或完全缺乏;肌细胞膜七的nNOS蛋白在3组中完全缺乏,而caveolin-3蛋白表达增加.结论 与dystrophin组成相关DGC复合体的蛋白在不同年龄阶段Duchenne型肌营养不良患儿均呈现不同程度的缺乏或完全缺乏,这些蛋白的缺乏可能发生在胚胎时期,而caveolin-3蛋白表达增高与肌纤维再生过程有关.     

Duchenne肌营养不良患儿的智力特点及与基因突变关系初步探讨

目的：了解国内Duchenne肌营养不良（DMD）患儿智力水平及智力低下的比例,初步探讨DMD患儿智力的结构特点及与基因突变类型的关系。方法：选择2009年1月至2011年3月的102例DMD患儿,其中84例患儿通过多重连接依赖式探针扩增（MLPA）方法进行DMD基因检测。102例DMD患儿中,选择≥6岁的50例DMD患儿作为DMD组;另选取50例年龄、性别与DMD组匹配的健康体检儿童作为对照组。采用韦氏智力量表对两组儿童进行智力及智力结构分析。结果：102例DMD患儿的平均智商为84±21,其中30例（29.4%）总智商低于70。DMD组患儿总智商、言语智商、操作智商及其11项分测验得分均显著低于对照组（P<0.01）。其中DMD基因56-79号外显子突变患儿的智商最低(59.3±11.9),另外,45-55号外显子突变患儿的智商(88.6±1.9) 明显低于1-29号(97.5±9.6)和30-44号(102.8±3.8)外显子突变的患儿（P<0.01）。结论：DMD患儿的总智商、言语智商、操作智商均显著低于正常儿童。DMD患儿智力低下与基因突变存在联系。     

Duchenne型假肥大肌营养不良症患儿的主要生活事件发生规律

目的分析Duchenne型假肥大肌营养不良症(DMD)患儿主要生活事件发生时间,了解DMD进展规律及主要临床特征。方法选取临床确诊436例DMD患者(经基因检测或肌肉活检证实),详细记录患者临床资料,分析患者的主要临床特点、进展情况、智力情况。检测其血清肌酸激酶(CK)水平,并分析CK的演变规律。结果 DMD患儿就诊时年龄为(6.37±2.88)岁,病程为(4.46±3.02)a,走路无力易摔倒和上楼困难是患者就诊的主要原因。学走路月龄在18个月以上的患儿约占59.86%。96.56%的患儿小腿腓肠肌假性肥大;5～7岁DMD患儿中93.59%存在Gower’s征阳性。血清CK水平在2～5岁逐渐升高,6～7岁达到高峰,其后逐年下降,15岁时仍然明显高于健康人。结论 DMD患者病程进展遵循一定规律,一般出生时正常,然后依次出现习步延迟、上楼困难和步行一小段距离的能力衰退,直至不能行走。     

Duchenne肌营养不良患儿的智力及与孤独症谱系障碍的关系研究

目的 探讨Duchenne肌营养不良(DMD)患儿的智力水平和智力结构特点,以及与孤独症谱系障碍(ASD)关系及其所占比例.方法 收集2006年1月-2010年5月诊断的DMD患儿118例(其中78例已经dystrophin基因确诊),应用修订的韦氏儿童智力量表-中国版(C-WISC)和美国精神疾病诊断统计手册(DSM-Ⅳ)结合儿童孤独症评定量表(CARS)对其进行智力及智力结构分析和孤独症谱系障碍评估.结果 118例DMD患儿中有39例进行了智力测定,其中有12例总智商(FIQ)低于70,占30.8%(12/39),轻度智力低下7例(50≤IQ<70),中、重度智力低下5例(IQ<50);DMD患儿总智商、言语智商(VIQ)、操作智商(PIQ)及其11项分测验得分中,除图形拼凑与对照组差异无统计学意义(P=0.237),其余均低于对照组(P<0.05);且言语智商低于操作智商(P<0.05).在118例DMD患儿中有3例(2.5%)同时合并孤独症谱系障碍,CARS评分均≥30分.结论 DMD合并孤独症谱系障碍可能并不是偶然事件,DMD与孤独症谱系障碍可能存在一定联系.     

肾病综合征合并Duchenne型肌营养不良症1例病例报告

【摘要】 目的 研究肾病综合征合并Duchenne型肌营养不良症患儿的临床特点,探讨肾病综合征与Duchenne型肌营养不良症的可能关系。方法 对2014年5月就诊于湖南省儿童医院肾内科的一例肾病综合征合并Duchenne型肌营养不良症患儿的临床特点、肾脏病理、基因诊断及对激素治疗的反应进行总结。结果 ①临床特点：6岁男孩,有1兄20岁,身体健康,家庭中两系3 代无类似疾病者。该患儿肾病综合征频繁复发,伴有谷草转氨酶、丙转氨酶、肌酸激酶、乳酸脱氢酶等肝酶及肌酶显著升高;肾脏病理为轻度系膜增生性肾小球肾炎。②遗传学检查：染色体核型分析无异常;dystrophy基因52号外显子缺失。结论 肾病综合征合并Duchenne型肌营养不良症患儿表现为难治性肾病,dystrophy基因52号外显子缺失与NS发病无直接联系,但有可能与NS频繁复发有关联,需要进一步研究。     

Evaluation of the North Star Ambulatory Assessment scale and cardiac abnormalities in ambulant boys with Duchenne muscular dystrophy

Aim We evaluated ambulatory patients with Duchenne muscular dystrophy from the cardiovascular standpoint and studied the correlation between the results of electrocardiographic (ECG) findings, left ventricular ejection fraction (LVEF), troponin T and N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels and patients' North Star Ambulatory Assessment scores. Methods: Fifty patients of ages 6–12 (8.9 ± 2.8) were enrolled in this cross‐sectional study. Cardiac evaluation included electrocardiography, echocardiography and cardiac enzyme tests. Results North Star scores ranged from 6/34 to 34/34. Twenty‐eight patients (56%) had ECG changes. The most frequently seen ECG abnormalities were short PR interval (14%, n= 7), right ventricular hypertrophy (16%, n= 8), prolonged QTc interval (10%, n= 5), prominent Q wave (10%, n= 5) and T wave inversion (44%, n= 22). In 10 patients (20%), LVEF was below 55%, troponin T and NT‐proBNP levels were significantly elevated (P= 0.003 and P < 0.001, respectively). When North Star scores were compared to patients' age, enzyme levels, ECG and echocardiographic results, we discovered negative correlation with age (P < 0.001) and troponin T levels (P= 0.02) and positive correlation with LVEF (P= 0.02). Conclusion Patients with North Star scores of ≤16 are more at risk of developing cardiomyopathies. Troponin T is a cardiac index that can be used for evaluating myopathic patients and it seems to be correlated with the proBNP levels and LVEF values.     

Cardiomyopathy of Duchenne muscular dystrophy

Summary A total of 18 male patients with Duchenne muscular dystrophy (DMD), aged 8–29 years (mean, 15.7 years), were prospectively studied to assess the cardiomyopathy associated with DMD, using clinical parameters and noninvasive cardiovascular investigations: electrocardiogram (ECG), Holter monitoring, and echocardiography. In addition, five clinical tests of cardiovascular autonomic function were used to assess the role of the autonomic nervous system in the pathogenesis of dysrhythmias.The majority of subjects were asymptomatic, but four had abnormal physical findings. All had abnormal ECG, the commonest abnormality (in 16) being tall R waves or increased R/S ratios in the right precordial leads; 14 had abnormal findings on echocardiography, including three with poor left ventricular function and five with mitral valve prolapse (MVP). Labile abrupt sinus tachycardia was present in 11, and four had high-grade ventricular ectopy. None had definite clinical evidence of autonomic dysfunction.The cardiomyopathy of DMD appears to be unrelated to disease severity. However, abnormal Q waves or Q/R ratios in ECG leads I, a V_L, and V₅–V₆ are significantly related to young age (p<0.05), and high-grade ventricular ectopy occurred significantly more frequently (p<0.05) in older subjects (>15 years). Dysrhythmias were not related to the presence of MVP, poor left ventricular function, or autonomic dysfunction.     

Autonomic function in patients with Duchenne muscular dystrophy

Background: Assessing autonomic function is important for patients with chronic heart failure, but the way that autonomic function changes in patients with Duchenne muscular dystrophy (DMD) and correlates with other clinical parameters during their young age is not clearly known. Methods: Heart rate variability (HRV) during ambulatory electrocardiogram (ECG) was performed in 57 DMD patients (130 recordings) who were not receiving medication (mean age 15.3 ± 4.5 years). The data were compared with the serum levels of brain natriuretic peptide (BNP), the shortening fraction (SF) of the left ventricle on echocardiography, and simple parameters of heart rate from 24 h ambulatory ECG. Results: Among four parameters of HRV measurements (high frequency [HF]; percentage of adjacent normal R‐R intervals that were >50 ms different for the entire 24 h recording [%RR50]; ratio of low to high frequency [LF/HF]; and standard deviation for all normal R‐R intervals for the entire 24 h recording [SDNN]), SDNN was most frequently abnormal. Even when SF was normal, a significant percentage of patients exhibited, abnormal parasympathetic activity (HF, %RR50: 74%, 78%, respectively), sympathetic activity (LF/HF, 43%), and SDNN (96%). Similarly, even if serum BNP levels were normal, 86%, 89%, 59%, and 97% of the patients displayed abnormal autonomic function on these measurements, respectively. Mean heart rate at night most accurately predicted abnormality of SDNN. When the cut‐off point for mean heart rate at night was 71 beats/min, the sensitivity and specificity of this parameter for predicting abnormal SDNN was 94% and 85%, respectively (P < 0.0001). Conclusion: In DMD, autonomic function, especially SDNN, was frequently abnormal, although conventional clinical examinations of cardiac function (BNP levels and SF) were normal. It is proposed that mean heart rate during night could be used as a simple measurement for evaluation of autonomic function.     

杜氏肌营养不良患儿的相关基因研究

目的　对确诊为杜氏肌营养不良 (DMD)患儿血清进行基因和肌酸磷酸激酶 (CPK)检测 ,以研究DMD的基因缺失情况以及与CPK的关系。方法　①采用多重引物PCR的方法检测基因缺失 ;②应用多功能全自动生化仪检测CPK。结果　① 30例患儿中基因缺失者 17例 (5 6 7% ) ,单一缺失者 8例 (47 1% ) ,多重缺失 9例(5 2 9% )。其中外显子 5 1缺失占 6 4 7% (11人次 ) ,其次为 4 8缺失占 5 2 9% (9人次 ) ;4 5缺失占 35 2 % (6人次 ) ;4 4缺失占 17 6 % (3人次 ) ;12缺失占 11 8% (2人次 ) ;外显子 8、17、19缺失各 1人次 ,各占 5 9%。②外显子缺失者CPK(1196 2 78± 6 30 5 6 5 )IU/L与无外显子缺失者CPK (95 37 6 9± 4 30 3 85 )IU/L相比 ,单一缺失者CPK(1170 4 6 5± 6 5 6 1 10 )IU/L与多重缺失者CPK(12 192 2 2± 6 0 96 80 )IU/L比较 ;单纯外显子 5 1缺失CPK(135 4 2 10± 5 5 73 93)IU/L与外显子 5 1缺失合并 4 8缺失者CPK(12 2 16 2 5± 6 833 75 )IU/L相比 ,三组均P >0 0 5 ,无显著性差异。结论　①应用PCR技术检测DMD基因缺失检出率较高 ,多重缺失占 4 7 1% ,其中以外显子 5 1、4 8、4 5缺失最多见 ;②外显子缺失与否或缺多少与CPK增高程度无相关性     

Communication regarding breathing support options for youth with Duchenne muscular dystrophy

BACKGROUND:

Ventilators for home use, manual and mechanically assisted coughing techniques, and the services of in-home respiratory therapists are options for youth with Duchenne muscular dystrophy (DMD). Evidence supports the use of these modalities, but there seems to be few youth who are receiving these therapies. Is there a knowledge transfer issue? Is there a lack of resources? What is the best way to discuss the issues? What do youth and parents want?

OBJECTIVE:

To determine practices, attitudes and beliefs regarding the timing and content of client/family communication related to ventilatory support decisions for individuals with DMD.

METHODS:

A questionnaire was sent to all 19 children’s treatment centres in Ontario. The lead clinician responded on behalf of his or her centre. Another questionnaire was given to 11 families who attended a parent support meeting.

RESULTS:

Respondents from the treatment centres who provide services for youth with DMD indicated that there are resources in terms of personnel and an obligation to provide information about ventilatory support, but provision of information is often late and/or inconsistent. The family respondents wanted more information and they wanted it earlier than they are currently receiving it.

CONCLUSIONS:

Parents and youth dealing with DMD have many resources at their disposal in Ontario. The evidence is clear that there are long-term health benefits to providing ventilatory support as well as instruction in coughing assistance. Due to the classical nature of disease progression in DMD, information should be provided within reasonable timelines.     

杜氏肌营养不良与骨骼肌纤维化

骨骼肌纤维化是杜氏肌营养不良杜氏肌营养不良的主要病理变化之一,可影响肌纤维的再生、收缩功能,加重病情,在骨骼肌纤维化的发生发展过程中,炎症细胞、成纤维细胞、成肌纤维细胞及其分泌的细胞因子起重要作用.该文对杜氏肌营养不良的骨骼肌纤维化研究进展进行综述.     

Spontaneous deep venous thrombosis in Duchenne muscular dystrophy

Deep venous thrombosis (DVT) is an uncommonly encountered condition in childhood and, as a consequence, the diagnosis may be overlooked. We describe the first two cases of DVT occurring in children with Duchenne muscular dystrophy. Both brothers were wheel-chair-bound for protracted periods. The first case occurred following spinal fusion for scoliosis. The second occurred spontaneously following immobilisation in hospital while undergoing investigation for a ureteric stone. Serological investigations to outrule an underlying thrombogenic cause showed no deficiency of protein C or antithrombin III nor the presence of lupus anticoagulant in either patient. The presence of flaccid lower extremities resulting in prolonged immobilisation combined with an ineffective muscle pump for venous return may have predisposed the patients in our series. The issue of prophylaxis should now be actively considered in such patients in high-risk circumstances. Correspondence to: R. Fitzgerald