Stiffness of knee extensors in Duchenne Muscular Dystrophy

The series elastic component (SEC) of Hill's muscle model is sensitive to a modification in muscle functional demand. In this study, SEC stiffness was quantified from quick-released movements in knee extensors of Duchenne muscular dystrophy (DMD) boys to look for possible modifications with the stage of disease. A SEC stiffness index (SI) was defined and was found significantly lower for controls than for DMD. Moreover, a linear relationship was established between mean SI and knee extensors involvement. This suggests a role for this parameter, together with other functional tests, for following patients with DMD. © 1998 John Wiley & Sons, Inc. Muscle Nerve 21: 1772–1774, 1998     

Corticosteroid Therapy for Duchenne Muscular Dystrophy: Improvement of Psychomotor Function

BackgroundOf the numerous clinical trials for Duchenne muscular dystrophy, only the corticosteroid prednisolone has shown potential for temporal improvement in motor ability. In this study, the effects of prednisolone on intellectual ability are examined in 29 cases of Duchenne muscular dystrophy because little information has been reported. And also, motor functions and cardiac functions were evaluated.MethodsThe treated group was administered prednisolone (0.75 mg/kg) orally on alternate days and the compared with the untreated control group. Gene mutations were investigated. The patients were examined for intelligence quotient adequate for age, brain natriuretic peptide, creatine kinase, and manual muscle testing before treatment and after the period 6 months to 2 years.ResultsIntelligence quotient scores of the treated increased to 6.5 ± 11.9 (mean ± standard deviation) were compared with the controls 2.1 ± 4.9 (P = 0.009). Intelligence quotient scores of the patients with nonsense point mutations improved significantly (21.0 ± 7.9) more than those with deletion or duplication (1.9 ± 9.0; P = 0.015). Motor function, such as time to stand up, of those treated improved significantly and brain natriuretic peptide level was reduced to a normal level after treatment in 15 patients (73%).ConclusionsOur results demonstrate the effectiveness of prednisolone in improving intellectual impairment as well as in preserving motor function and brain natriuretic peptide levels. We presume that prednisolone has a read-through effect on the stop codons in the central nervous systems of Duchenne muscular dystrophy because intelligence quotient of point mutation case was improved significantly.     

低年龄Duchenne型肌营养不良患儿心功能异常分析

目的探讨低年龄Duchenne型肌营养不良(DMD)患儿的心电图、心脏超声异常的特点和临床意义。方法采用统计学方法回顾性分析50例3.0~6.9岁DMD患儿的临床资料和检查结果。结果行心电图检查的DMD患儿中93%存在心电图异常表现,以Ⅲ或Ⅴ6导联Q波、PR间期缩短、Ⅴ1导联S波最为常见;所有患儿心脏超声均未出现心肌病表现,但与同年龄正常儿童相比,存在左室舒张末径升高,左室射血分数和左室缩短分数降低。结论 DMD患儿的心脏损害出现较早,早期开展低年龄DMD患儿常规心脏功能评估,有助于减少心源性猝死,延长患儿生命。     

Duchenne型肌营养不良症的冷冻断裂电镜观察

应用冷冻断裂电镜技术对Duchenne型肌营养不良症(DMD)的骨胳肌标本4例(异常组),正常标本2例(正常组)肌细胞质膜的蛋白颗粒进行电镜观察。结果表明,正常组和异常组的EF(extracellular face)面膜蛋白颗粒比PF(protoplasmic face)面少;异常组与正常组比较,其EF面和PF面的膜蛋白颗粒均明显减少,并具有显著的统计学意义。     

Genetic and Early Clinical Manifestations of Females Heterozygous for Duchenne/Becker Muscular Dystrophy

BackgroundFemale carriers of Duchenne muscular dystrophy (DMD), although usually asymptomatic, develop muscle weakness up to 17% of the time, and a third present cardiac abnormalities or cognitive impairment. Clinical features of DMD carriers during childhood are poorly known.PatientsWe describe a cohort of pediatric DMD carriers, providing clinical, genetic, and histopathologic features, with a mean follow-up of 7 years.ResultsFifteen females with a DMD mutation (age range 5 to 18 years) were included. Seven patients (46%) presented with clinically evident symptoms and signs such as limb girdle weakness, abnormal gait, and exercise intolerance. The other eight patients (53%) were evaluated because of an incidental finding of elevated level of creatine kinase. Creatine kinase level was elevated in all, ranging from 392 to 13,000 U/L. Calf hypertrophy was observed in eight patients (53%). No patient developed respiratory or cardiac involvement. The most frequent complication was scoliosis (46%). Four patients (29%) also presented minor learning disabilities or behavioral problems. We performed electromyography in half of patients, showing myopathic pattern in four (53%). Muscle biopsy revealed a mosaic reduction of dystrophin in nine available cases. DMD gene mutations were mostly deletions (71%), resulting in loss of reading frame in five patients (36%). The three patients who experienced the most severe disease course were affected either by a nonsense or frameshift mutation.ConclusionsOur analysis suggests that DMD gene mutations may be suspected in a female child with persistently elevated levels of creatine kinase. Evidence of scoliosis, calf hypertrophy, or myopathic pattern at electromyography may also be helpful, and muscle biopsy is always indicative. DMD carriers should be followed for subtle orthopedic and psychiatric complications during childhood.     

Poor Facial Affect Recognition Among Boys with Duchenne Muscular Dystrophy

Children with Duchenne or Becker muscular dystrophy (MD) have delayed language and poor social skills and some meet criteria for Pervasive Developmental Disorder, yet they are identified by molecular, rather than behavioral, characteristics. To determine whether comprehension of facial affect is compromised in boys with MD, children were given a matching-to-sample test with four types of visual recognition (Object, Face, Affect, and Situation matching) developed by Lucci and Fein. Within-group analyses on 50 boys with MD found decreased Affect matching relative to the other matching conditions. Between-group comparisons on 20 sibling pairs found the boys with Duchenne performed more poorly only on the Affect-matching condition. Thus, mildly impaired facial affect recognition may be part of the phenotype associated with Duchenne or Becker MD.     

Duchenne型肌营养不良的临床和病理及抗肌萎缩蛋白表达

目的：归纳总结Duchenne型肌营养不良（DMD）的临床表现,组织病理特点及抗肌萎缩蛋白表达情况。方法：通过临床、病理及免疫组化染色方法,对16例DMD患者的临床表现,肌肉病理改变和肌肉抗肌萎缩蛋白表达情况进行观察分析。结果：年龄〉4岁的14例患儿均有比较典型的DMD临床表现;而年龄〈4岁的2例患儿症状较轻。肌肉病理显示2例为早期改变、11例为中期改变、3例为晚期改变,病理改变严重程度与年龄相关。免疫组化染色显示16例患者的肌肉标本抗肌萎缩蛋白均完全缺失。结论：DMD患者的临床和病理表现的严重程度与年龄有关,检查抗肌萎缩蛋白在肌纤维膜上表达是诊断DMD的金标准。     

定量PCR法对缺失型DMD家系携带者诊断价值的研究

目的探讨紫外凝胶分析系统定量PCR方法对缺失型杜(氏)/贝(氏)进行性肌营养不良(DMD/BMD)携带者的诊断价值。方法采用紫外凝胶分析系统定量检测16个缺失型DMD/BMD家系中的19名女性亲属和15名健康对照的二重PCR产物,并计算计量系数DQ值。结果定量PCR方法将9名女性确定为携带者。结论定量PCR方法是一种准确、快速、简便的DMD携带者诊断方法。     

One Year Outcome of Boys With Duchenne Muscular Dystrophy Using the Bayley-III Scales of Infant and Toddler Development

BackgroundThe pathogenesis of Duchenne muscular dystrophy starts before birth. Despite this, clinical trials exclude young boys because traditional outcome measures rely on cooperation. We recently used the Bayley-III Scales of Infant and Toddler Development to study 24 infants and boys with Duchenne muscular dystrophy. Clinical evaluators at six centers were trained and certified to perform the Bayley-III. Here, we report 6- and 12-month follow-up of two subsets of these boys.PatientsNineteen boys (1.9 ± 0.8 years) were assessed at baseline and 6 months. Twelve boys (1.5 ± 0.8 years) were assessed at baseline, 6, and 12 months.ResultsGross motor scores were lower at baseline compared with published controls (6.2 ± 1.7; normal 10 ± 3; P < 0.0001) and revealed a further declining trend to 5.7 ± 1.7 (P = 0.20) at 6 months. Repeated measures analysis of the 12 boys monitored for 12 months revealed that gross motor scores, again low at baseline (6.6 ± 1.7; P < 0.0001), declined at 6 months (5.9 ± 1.8) and further at 12 months (5.3 ± 2.0) (P = 0.11). Cognitive and language scores were lower at baseline compared with normal children (range, P = 0.002-<0.0001) and did not change significantly at 6 or 12 months (range, P = 0.89-0.09). Fine motor skills, also low at baseline, improved >1 year (P = 0.05).ConclusionDevelopment can reliably be measured in infants and young boys with Duchenne muscular dystrophy across time using the Bayley-III. Power calculations using these data reveal that motor development may be used as an outcome measure.     

Clinical Follow‐Up for Duchenne Muscular Dystrophy Newborn Screening: A Proposal

New developments in the rapid diagnosis and treatment of boys with Duchenne muscular dystrophy (DMD) have led to growing enthusiasm for instituting DMD newborn screening (NBS) in the United States. Our group has been interested in developing clinical guidance to be implemented consistently in specialty care clinics charged with the care of presymptomatically identified newborns referred after DMD‐NBS. We reviewed the existing literature covering patient‐centered clinical follow‐up after NBS, educational material from public health and advocacy sites, and federal recommendations on effective NBS follow‐up. We discussed the review as a group and added our own experience to develop materials suitable for initial parent and primary care provider education. These materials and a series of templates for subspecialist encounters could be used to provide consistent care across centers and serve as the basis for ongoing quality improvement. Muscle Nerve 54 : 186–191, 2016     

Genitourinary health in a population‐based cohort of males with Duchenne and Becker Muscular dystrophies

Introduction: Genitourinary (GU) health among patients with Duchenne and Becker muscular dystrophies (DBMD) has not been explored using population‐based data. Methods: Medical records of 918 males ascertained by the Muscular Dystrophy Surveillance, Tracking, and Research Network were reviewed for documentation of GU‐related hospitalizations and prescribed medications. Percentages of males who received these medical interventions were calculated, and hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for associations with sociodemographics (study site, race/ethnicity), symptoms (early‐ vs. late‐onset, ambulation status, scoliosis), and treatments (respiratory support, steroids). Results: Among the 918 males, 81 (9%) had a GU condition, with voiding dysfunction (n = 40), GU tract infection (n = 19), and kidney/ureter calculus (n = 9) most frequently seen. The Kaplan‐Meier curve produced a cumulative probability of 27%. Cox regression showed GU conditions were more common when males were non‐ambulatory (HR 2.7, 95% CI 1.3–5.6). Conclusions: Our findings highlight the need for increased awareness of GU health and multidisciplinary care of DBMD patients. Muscle Nerve 52 : 22–27, 2015     

肌型肌酸激酶同工酶亚型在早期诊断假肥大型肌营养不良中的价值

目的 研究假肥大型肌营养不良（DMD）患者肌型肌酸激酶（CK－MM）亚型的变化,为早期诊断和正确评价病情提供依据。方法 采用不连续缓冲体系,在稳流低压条件下电泳分离CK－MM型亚,荧光扫描。结果 随着DMD患者病情的加重,其不同阶段的MM2／MM1均与对照组差异显著（P＜0．05）,DMD患者不同阶段的MM2／MM1值差异也显著（P＜0．05）,结论 CK－MM亚型的改变是DMD的早期诊断指标,是判断病情及科学评价治疗效果的依据。     

Being ambulatory does not secure respiratory functions of Duchenne patients

Aim:

The aim of this work was to assess the respiratory functions of ambulatory Duchenne patients and to propose an earlier time period for intervention.

Materials and Methods:

Lung functions and North Star Ambulatory Assessment (NSAA) scores of Duchenne patients were evaluated simultaneously.

Results:

Thirty ambulatory Duchenne patients were included in this study. NSAA scores of the patients were directly correlated with arm abduction, arm adduction, and shoulder flexion strengths. Forced expiratory volume in 1 second percent predicted and forced vital capacity (FVC) percent predicted correlated inversely to age and to the NSAA score. Twelve of 13 patients with FVC values lower than 80% of predicted had NSAA scores below 24 points. None of the patients who were younger than 7 years had FVC values lower than 80% of predicted.

Conclusion:

Annual spirometry is necessary for Duchenne patients older than 6 years regardless of the ambulatory status.     

Assessment of locomotor function in young boys with Duchenne muscular dystrophy

Thirty-three young boys (mean age 3.42 years) with Duchenne muscular dystrophy (DMD) and 21 normal control boys (mean age 3.51 years) were studied prospectively to determine whether it is possible to objectively assess locomotor function in young boys with DMD so that they can be included in treatment trials. An initial reproducibility study using a hand-held myometer demonstrated that this method was not useful. The Hammersmith Motor Ability Score demonstrated an increase in developmental abilities with age which was markedly different from normal. The locomotor quotient of the Griffiths' Scales demonstrated a deterioration of quotient scores and is a useful method of assessment that could be used in treatment trials involving young boys with DMD. Sample size planning for treatment trials is discussed.