贝氏肌营养不良症与杜氏肌营养不良症患者骨骼肌脂肪浸润程度的对比研究

目的分析贝氏肌营养不良症（BMD）患者大腿骨骼肌在磁共振成像（MRI）上所显示的骨骼肌脂肪浸润规律,探讨其与杜氏肌营养不良症（DMD）患者之间的差异,为针对性康复治疗提供指导依据。 方法纳入23例BMD患者和47例DMD患者,所有患者均未经糖皮质激素治疗,均行双侧大腿骨骼肌MRI检查,并通过T1加权成像和应用改良的Mercuri分级评分法,对骨骼肌脂肪浸润程度进行0～5分的6级评分。采用描述性统计分析BMD的骨骼肌脂肪浸润进展程度,采用秩合检验分析BMD和DMD的组间差异。 结果BMD患者大收肌的重度脂肪浸润所占百分比最高,而后受累的依次为股二头肌、股四头肌、半膜肌和半腱肌,缝匠肌、股薄肌和长收肌的重度脂肪浸润所占百分比最低。BMD患者的大收肌、股二头肌和股四头肌在8～9岁可见中到重度脂肪浸润,半膜肌和半腱肌在10～11岁可见中到重度脂肪浸润,缝匠肌、股薄肌和长收肌在15岁以后可见轻到中度脂肪浸润。BMD组骨骼肌脂肪浸润程度评分总和的中位数在8、9、10和11岁依次为10、22、28和25分,DMD组依次为29、34、34和30分。BMD与DMD相比,8岁患者的脂肪浸润程度评分在大收肌（P=0.017）、股二头肌（P=0.013）、股外侧肌（P=0.021）、股直肌（P=0.007）、股内侧肌（P=0.008）、股中间肌（P=0.009）及评分总和（P=0.011）之间的差异均有统计学意义;9岁患者的脂肪浸润程度评分在大收肌（P=0.007）、股直肌（P=0.013）、股内侧肌（P=0.028）、股中间肌（P=0.028）及评分总和（P=0.020）之间的差异具有统计学意义。 结论BMD患者的大腿骨骼肌脂肪浸润存在一个特定受累模式,相同年龄的BMD与DMD患者骨骼肌脂肪浸润程度存在差异,可以协助指导BMD及DMD患者的康复治疗。     

肢带型肌营养不良的MRI表现

目的 观察肢带型肌营养不良的MRI表现。方法 回顾性分析7例经临床及病理检查确诊为肢带型肌营养不良患者的MRI资料,观察双侧大腿肌群脂肪沉积与炎性水肿情况,采用4分法进行评价。并进行统计学分析。结果 肢带型肌营养不良患者大腿肌群MRI均可见脂质沉积和炎性水肿性改变。不同肌肉间脂肪沉积(χ²=75.596,P<0.01)与炎性水肿差异均有统计学意义(χ²=41.368,P<0.01),双侧大腿肌群间脂肪沉积与炎性水肿差异均无统计学意义(P均>0.05)。结论 肢带型肌营养不良患者大腿肌群MRI信号特点及分布具有一定特征,MR检查有助于疾病的诊断。     

MRI测量对坐骨股骨撞击综合征的诊断价值

目的 探讨MRI对坐骨股骨撞击综合征（IFIS）患者的诊断价值。方法 回顾性分析70例IFIS患者（IFIS组）和40名健康志愿者（对照组）的MRI资料。于轴位脂肪抑制T2WI测量坐骨股骨间隙（IFS）宽度、股方肌间隙（QFS）宽度,于轴位T1WI测量坐骨角,于冠状位T2WI测量股骨颈干角,比较2组间的差异,分析IFS宽度与其他3个指标的相关性,绘制ROC曲线,评价其对IFIS的诊断效能。对IFIS组患者股方肌水肿和脂肪浸润程度进行分级,比较不同级别间IFS宽度的差异。结果 IFIS组患者IFS宽度、QFS宽度、坐骨角及股骨颈干角分别为（11.76±2.22）mm、（8.33±2.20）mm、（132.59±1.39）°和132.70（131.18,134.13）°,与对照组比较差异均有统计学意义（P均<0.001）。IFS宽度、QFS宽度、坐骨角度及股骨颈干角诊断IFIS的ROC曲线下面积分别为1.000、0.999、0.996和0.975（P均<0.001）。IFS宽度与QFS宽度呈正相关（r=0.743,P<0.001）,与坐骨角度及股骨颈干角呈负相关（r=-0.273,P=0.022;r=-0.332,P=0.005）。IFIS组患者不同股方肌水肿、脂肪浸润分级间IFS宽度总体差异均有统计学意义（P均<0.05）。结论 IFIS患者IFS、QFS均明显狭窄;股方肌水肿及脂肪浸润是IFIS常见MRI表现。     

小剂量激素治疗Duchenne型肌营养不良的疗效

  目的  评估短期应用小剂量糖皮质激素是否具有提高Duchenne型肌营养不良(Duchenne muscular dystrophy, DMD)患儿肌力和运动功能的作用。  方法  纳入2005年9月至2008年12月北京协和医院明确诊断的5~10岁DMD患儿。试验采取随机、双盲、对照的原则, 分为治疗组和对照组。治疗组患儿给予泼尼松0.75 mg/(kg·d), 对照组给予维生素C 0.3 mg/d。治疗时间为3个月, 每隔1个月随访1次, 随访3个月, 评估4次就诊时的肌力、运动功能、肺功能和肌酸激酶。  结果  共31例DMD患儿纳入研究, 其中治疗组17例, 对照组14例。对照组患儿4次就诊的平均肌力评分依次为38.2±7.5、37.0±8.0、36.2±7.6、36.6±7.7, 治疗组为37.7±6.1、39.1±6.4、40.3±5.9、40.0±5.6, 两组治疗1、2、3个月后与治疗前肌力的差值比较, 差异均有统计学意义(P=0.024, P=0.000, P=0.002)。对照组4次就诊行走9 m的平均时间依次为(7.7±2.5)、(7.6±2.8)、(8.1±2.4)、(7.6±2.8)s, 治疗组为(8.5±3.4)、(7.2±3.3)、(7.6±3.1)、(7.1±2.8)s, 两组治疗2、3个月后与治疗前行走9 m所用时间的差值比较, 差异均有统计学意义(P=0.013, P=0.003)。对照组4次就诊的平均用力肺活量(forced vital capacity, FVC)依次为(1.24±0.28)、(1.13±0.26)、(1.21±0.31)、(1.16±0.26)L, 治疗组为(1.14±0.37)、(1.40±0.35)、(1.42±0.36)、(1.52±0.37)L, 两组治疗1、2、3个月后与治疗前FVC的差值比较, 差异均有统计学意义(P=0.000, P=0.006, P=0.000)。两组治疗1个月后与治疗前的肌酸激酶的差值比较, 差异亦有统计学意义(P=0.035)。3个月后治疗组激素不良反应仅表现为体重增加, 无其他严重不良反应。  结论  短期应用小剂量泼尼松治疗DMD可以增加患儿肌力, 改善患儿运动及肺功能。     

肌营养不良蛋白表达在萎缩性肌病鉴别诊断中的意义

目的探讨肌营养不良蛋白(Dystrophin蛋白)在萎缩性肌病中的表达及其临床意义。方法对均表现为双下肢近端肌肉萎缩的43例肌营养不良患者、3例其他神经肌肉疾病患者(包括1例脂质沉积性肌病、2例运动神经元病)及5例正常对照者的骨骼肌标本进行Dystrophin蛋白免疫组化染色。结果 Duchenne型肌营养不良(DMD)患者肌细胞膜上无显色,Becker型肌营养不良(BMD)患者全部为弱阳性,BMD/LGMD(肢带型肌营养不良)患者中6例肌细胞膜上显色浅淡、不连续或呈斑片状,其余15例患者肌细胞膜上染色正常;2例运动神经元病患者中1例肌细胞膜显色浅淡、呈斑片状,另1例染色正常。脂质沉积性肌病患者和正常对照肌细胞膜上染色均正常。结论对于存在双下肢近端肌肉萎缩的临床表现相似的肌病患者,Dystrophin免疫组化染色可以将其大致区分,对早期预测肢体功能影响程度及正确地进行遗传咨询具有重要意义。     

血清VEGF的表达与肌营养不良症的关系

目的检测肌营养不良症患者的血清血管生长因子（VEGF）水平,鉴定其是否与肌营养不良症的疾病发展有关。方法对46例肌营养不良患者,其中32例Duchenne肌营养不良症（DMD）、9例Becker肌营养不良症（BMD）、5例强直性肌营养不良症（DM）患者的血清VEGF水平进行检测。15例健康人和8例疾病患者为对照组。结果DMD患者血清VEGF为（274．7±2．52）pg／ml,BMD患者的为（358．8±9．64）pg／ml,DM患者为（165．0±6．34）pg／ml,而健康对照组为（148．3±2．91）pg/ml,疾病对照组为（153．7±5．42）pg／ml。与DM组和对照组相比,BMD的VEGF水平显著提高。而DMD组中卧床的患者相对于坐轮椅的DMD、DM组和对照组则VEGF水平显著升高。结论VEGF可以反映肌肉组织低氧和／或缺血状况,并且与DMD和BMD患者的疾病发展过程有关。     

灰阶超声联合剪切波弹性成像评估肌筋膜疼痛综合征患者肌筋膜疼痛触发点

目的 探讨灰阶超声联合剪切波弹性成像（SWE）技术评估肌筋膜疼痛综合征（MPS）患者肌筋膜疼痛触发点（MTrPs）处肌肉形态及组织学特性的价值。方法 以28例MPS患者（36个MTrPs）为病例组,33名健康志愿者（33个正常肌肉点）为对照组。由2名检查者分别测量病例组MTrPs （上斜方肌）厚度、剪切波传播速度（SWV）及杨氏模量值（E）,1名检查者测量对照组上述参数,1周后2组均重复测量。采用组内相关系数（ICC）评价2名检查者检测结果的一致性,以Pearson检验分析MPS患者疼痛视觉模拟量表（VAS）评分与上斜方肌厚度、SWV及E的相关性。结果 2名检查者重复测量一致性、时间一致性及检查者间一致性均好或优（ICC 0.73~0.98）。病例组MPS患者上斜方肌厚度、SWV及E均高于对照组,差异均有统计学意义（P均<0.05）。MPS患者VAS评分与上斜方肌厚度无相关性（r=0.016,P=0.945）,与SWV （r=0.709,P<0.001）、E （r=0.653,P=0.002）均呈正相关。结论 灰阶超声联合SWE可定量评估MPS患者MTrPs处肌肉形态及组织学特性。     

假肥大型肌营养不良治疗进展

假肥大型肌营养不良是一组严重性进行性遗传性肌病,有假肥大型肌营养不良(duchenne muscular dystrophy,DMD)和良性Duchenne肌营养不良(BMD)两种类型.由于DMD/BMD是X连锁隐性遗传性疾病,男性多发,且DMD最常见,全世界每3500～5000个新生儿中就会有一名患者,女性携带者大多...     

假肥大型肌营养不良患儿的肌肉病理及dystrophin免疫组化SP法检测的临床意义

目的探讨肌肉病理及抗肌萎缩蛋白（dystrophin）免疫组化SP法检测在假肥大型肌营养不良诊断中的临床价值。方法通过组织学观察和免疫组化SP法检测方法,对50例假肥大型肌营养不良患儿[40例Duchenne型营养不良（DMD组）,10例Becker型营养不良（BMD组）]肌纤维膜dystrophin的表达、肌肉病理改变及临床表现进行观察,并与30例其他疾病（多发性肌炎3例、皮肌炎6例、糖元累积病1例、脂质累积病15例、周围神经病2例、脊肌萎缩症3例）对照组患儿进行对比分析。结果肌肉病理显示：DMD组中有30例肌肉病理改变较重,10例较轻;BMD组的肌肉病理改变较轻,这些均与年龄有关。免疫组化显示：DMD组肌肌纤维膜均有严重的dystro-phin缺失,BMD组肌纤维膜有50%~70%的dystrophin缺失;对照组无dystrophin缺失。结论肌肉病理及dys-trophin SP免疫组化检测对假肥大型肌营养不良具有较大的临床意义。     

腰大肌及侧腹肌相关CT参数评价肝硬化肌少症

目的 观察腰大肌及侧腹肌相关CT参数评价肝硬化肌少症的价值。方法 采集210例临床诊断肝硬化患者腹部CT,获得L3水平骨骼肌总横截面积,计算相应骨骼肌指数（SMI）。根据SMI结果将患者分为肌少症组（n=105）与非肌少症组（n=105）,测量相同层面右侧腰大肌轴径及横径、右侧腹肌厚度,计算腰大肌轴径指数（APMI）、腰大肌横径指数（TPDI）及侧腹肌厚度指数（LWMI）;比较组间差异。以SMI结果为标准,绘制TPDI、APMI及LWMI鉴别肝硬化肌少症的受试者工作特征（ROC）曲线,计算曲线下面积（AUC）,并分析TPDI、APMI及LWMI与SMI的相关性及肌少症的影响因素。结果 组间体质量指数、胆固醇、NRS2002评分、APMI、TPDI和LWMI差异均有统计学意义（P均<0.05）。TPDI（r=0.71）、APMI（r=0.59）和LWMI（r=0.61）均与SMI呈正相关（P均<0.01）。APMI、TPDI及LWMI鉴别肝硬化肌少症的AUC分别为0.61、0.71及0.72（P均<0.05）。男性、三酰甘油为肌少症的危险因素,TPDI、LWMI为肌少症的保护因素（P均<0.05）。结论 腰大肌及侧腹肌相关CT参数可用于评估肝硬化肌少症,并有望成为临床评估肌少症的新方法。     

MR IDEAL-IQ脂肪定量技术评价进行性假肥大性肌营养不良患儿骨骼肌脂肪浸润程度

目的 采用MR基于最小二乘估算法和不对称回波迭代分解的水脂分离(IDEAL-IQ)脂肪定量技术评估进行性假肥大性肌营养不良(DMD)患儿臀部及大腿骨骼肌脂肪浸润程度,观察脂肪分数(FF)与临床资料的相关性.方法 纳入89例经病理学和/或基因检测确诊的DMD患儿,记录其臀部及双侧大腿MR T1WI及IDEAL-IQ数据....     

A comparison of swallowing dysfunction in Becker muscular dystrophy and Duchenne muscular dystrophy

Purpose: Swallowing dysfunction has been reported in Duchenne muscular dystrophy (DMD), but has not been studied in Becker muscular dystrophy (BMD). The aims of this study were to report the characteristics of swallowing dysfunction in BMD compared with DMD.

Materials and methods: The study participants were 18 patients with BMD and 18 patients with DMD. All the patients were examined using videofluorography during swallowing of 5?mL of fluid. The penetration–aspiration scale (P–A scale) and the videofluorographic dysphagia scale (VDS) were used to evaluate dysphagia.

Results: Swinyard functional ability stage was not significantly different between the BMD and DMD groups. Rate of aspiration, P–A scale score, and total VDS score did not differ across groups, but the VDS item score for laryngeal elevation was lower in the BMD group than in the DMD group (median scores 4.5 and 9, respectively; p?r?=?0.78, p?Conclusion: Patients with BMD have swallowing problems similar to those observed in patients with DMD when matched according to physical functional status. These patients should be evaluated and followed-up for the duration of their disease.

• Implications for rehabiliation

• Dysphagia is one of the most critical problems in patients with progressive neuromuscular disease but dysphagia in patients with Becker muscular dystrophy (BMD) was not well known.

• Eighteen patients with BMD and 18 patients with Duchenne muscular dystrophy were examined with videofluorography.

• Patients with BMD have swallowing problems similar to those observed in patients with DMD.

     

Sonoelastography of the trunk and lower extremity muscles in a case of Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a rare genetic disorder typically presenting with muscle weakness and reduced tone of trunk and lower extremities. The sonoelastographic properties of DMD are poorly understood. We describe sonoelastographic characteristics of a patient’s trunk and lower extremity musculature. An 8-year-old male presented with a 5-year history of DMD. Sonoelastographic measures of the gluteus maximus and medius, lumbar erector spinae, rectus abdominis, rectus femoris, biceps femoris, tibialis anterior, medial and lateral gastrocnemius muscles were obtained. Sonoelastography demonstrated increased elasticity by elevated kiloPascals (kPa) across all muscles, except the lumbar erector spinae. Patient values were compared to an age-matched healthy control. These abnormal sonoelastographic findings reflected the pathological mechanical properties of DMD. Sonoelastography was valuable for characterizing the mechanical properties of normal and abnormal muscle tissue. There is limited information on the sonoelastography application to DMD. Sonoelastography may serve as a useful measure for diagnosis and monitoring clinical outcomes for DMD.     

高频超声对Duchenne型肌营养不良症的诊断价值

目的　探讨Duchenne进行性肌营养不良症肌肉声像图的特点及其诊断价值。方法　应用高频超声检测 81例Duchenne进行性肌营养不良症患者下肢肌肉。按照年龄分为 4组 :3～ <7岁 13例 ,7～ <10岁 3 0例 ,10～ <13岁 3 0例 ,13～ 14岁 8例。选择 1～ 11岁健康儿童 2 0例作为对照组。依次对臀部、大腿部、小腿部肌肉行纵横切位超声扫查。结果　患者 3岁时 ,臀肌萎缩 ,皮下脂肪增厚 ;随着年龄的增长 ,臀肌、大腿部位肌肉、小腿肌肉和背肌萎缩呈现进行性加重 ,皮下脂肪增厚 ,各年龄组差异有显著性意义 (P <0 .0 1)。结论　高频超声可为Duchenne进行性肌营养不良症的诊断、病情随访和临床病理活检提供客观依据。     

Quality of life of patients with Duchenne muscular dystrophy: from adolescence to young men

Purpose: This study investigated quality of life (QOL) in adolescent and young men with Duchenne muscular dystrophy (DMD).

Methods: Health-related QOL and global QOL were assessed with the Short Form 36 (SF-36) and World Health Organization Quality of Life-BREF (WHOQOL-BREF). Associations between functional status and QOL were assessed.

Results: All domains of the SF-36 were below Taiwan norms (effect size: ?14.2 to ?0.5), especially Physical Function, Role Physical, and Social Function. Three of the four domains of the WHOQOL-BREF were below Taiwan norms (effect size: ?2.0 to ?0.7). The Physical Function of the SF-36 was moderately correlated with functional status (mobility, basic activities of daily living, and arm function). The Social Function of the SF-36 and Social Relationships of the WHOQOL-BREF were also moderately correlated with functional status (impairment, basic activities of daily living, and arm function).

Conclusion: The adolescent and young men with DMD had poor health-related and global QOL. Poor QOL was related to both physical condition and social health. We suggest that rehabilitation programs focus on using assistive devices to facilitate arm function and encouraging participation in social activities to improve the QOL of patients with DMD.

• Implications for rehabilitation

• Duchenne muscular dystrophy (DMD) is a progressive muscle weakness disease that not only impacts physical health but also leads to poor quality of life in many domains.

• A valuable rehabilitation goal for patients with DMD is to encourage participation in social activities. Medical care and educational programs should plan a formal transition processes for patients with DMD from pediatric to adult care to maximum their quality of life.

• Arm function is associated with many domains of global quality of life, so a key element in improving quality of life may be to improve arm function.

     

Gene therapy for muscular dystrophy: current progress and future prospects

Muscular dystrophies refer to a group of inherited disorders characterized by progressive muscle weakness, wasting and degeneration. So far, there is no effective treatment but new gene-based therapies are currently being developed with particular noted advances in using conventional gene replacement strategies, RNA-based approaches, or cell-based gene therapy with a main focus on Duchenne muscular dystrophy (DMD). DMD is the most common and severe form of muscular dystrophy and current treatments are far from adequate. However, genetic and cell-based therapies, in particular exon skipping induced by antisense strategies, and corrective gene therapy via functionally engineered dystrophin genes hold great promise, with several clinical trials ongoing. Proof-of-concept of exon skipping has been obtained in animal models, and most recently in clinical trials; this approach represents a promising therapy for a subset of patients. In addition, gene-delivery-based strategies exist both for antisense-induced reading frame restoration, and for highly efficient delivery of functional dystrophin mini- and micro-genes to muscle fibres in vivo and muscle stem cells ex-vivo. In particular, AAV-based vectors show efficient systemic gene delivery to skeletal muscle directly in vivo, and lentivirus-based vectors show promise of combining ex vivo gene modification strategies with cell-mediated therapies.     

New developments in exon skipping and splice modulation therapies for neuromuscular diseases

Introduction: Antisense oligonucleotide (AON) therapy is a form of treatment for genetic or infectious diseases using small, synthetic DNA-like molecules called AONs. Recent advances in the development of AONs that show improved stability and increased sequence specificity have led to clinical trials for several neuromuscular diseases. Impressive preclinical and clinical data are published regarding the usage of AONs in exon-skipping and splice modulation strategies to increase dystrophin production in Duchenne muscular dystrophy (DMD) and survival of motor neuron (SMN) production in spinal muscular atrophy (SMA).

Areas covered: In this review, we focus on the current progress and challenges of exon-skipping and splice modulation therapies. In addition, we discuss the recent failure of the Phase III clinical trials of exon 51 skipping (drisapersen) for DMD.

Expert opinion: The main approach of AON therapy in DMD and SMA is to rescue (‘knock up’ or increase) target proteins through exon skipping or exon inclusion; conversely, most conventional antisense drugs are designed to knock down (inhibit) the target. Encouraging preclinical data using this ‘knock up’ approach are also reported to rescue dysferlinopathies, including limb-girdle muscular dystrophy type 2B, Miyoshi myopathy, distal myopathy with anterior tibial onset and Fukuyama congenital muscular dystrophy.     

Anesthesia management in a pediatric patient with Becker muscular dystrophy undergoing laparoscopic surgery: A case report

BACKGROUNDPatients with Becker muscular dystrophy (BMD) have a high risk of developing hyperkalemia, rhabdomyolysis, and malignant hyperthermia when exposed to volatile anesthetics and depolarizing muscle relaxants. Patients with BMD are also prone to respiratory depression after general anesthesia. Thus, it is extremely challenging for anesthesiologists to manage anesthesia in BMD patients, particularly in pediatric BMD patients. Here, we present successful anesthesia management using transversus abdominis plane block (TAPB) combined with total intravenous anesthesia (TIVA) in a pediatric BMD patient undergoing laparoscopic inguinal hernia repair.CASE SUMMARYA 2-year-old boy, weighing 15 kg, with BMD, was scheduled for laparoscopic inguinal hernia repair. TIVA was used for induction, and continuous infusions of short-acting intravenous anesthetics combined with TAPB were performed for anesthesia maintenance. Moreover, TAPB provided good postoperative analgesia. The patient underwent uneventful surgery and anesthesia, and over the 17 mo follow-up period showed no anesthesia-induced complications.CONCLUSIONTAPB combined with TIVA, using short-acting intravenous anesthetic agents, can provide safe and effective anesthesia management in pediatric BMD patients undergoing short-term abdominal surgery.