Depression in parents of children with Duchenne muscular dystrophy

This study examined depression, self-esteem, and mastery in the family caretakers of a group of males with Duchenne muscular dystrophy in comparison to a control group. A questionnaire based on the National Population Health Survey from Statistics Canada, a survey to collect information on the health of the Canadian population and related sociodemographic information, was conducted by telephone with 42 parents. The results were compared with the national data from the National Population Health Survey (1994 and 1999), matched for province of residence, number of children in the household, age, and marital status of the respondents. Parents of children with Duchenne muscular dystrophy had a higher probability of going through a major depressive episode and had significantly lower self-esteem and mastery scores than the national control group. None of the variables investigated (age, intelligence quotient, and ambulatory status of child or sex, age, and marital status of parent) could predict the depressive episode, with two exceptions. Parents without a partner had lower scores on the mastery scale, and parents of males older than 13 years of age were more likely to experience distress that interfered with life. It is incumbent on those caring for patients with Duchenne muscular dystrophy to counsel families regarding their potential to suffer a major depressive episode and to advise on appropriate therapy.     

Clinical study on cognitive impairment in Duchenne muscular dystrophy

Our study aimed to explore the intellectual function of patients with Duchenne muscular dystrophy (DMD) in China and examine the correlation of full-scale intelligence quotient (FSIQ) with age, mutation locations, mutation class, and dystrophin isoforms. We assessed 64 boys with DMD using The Wechsler Intelligence Scales for Children-Fourth Edition and compared intellectual function at enrollment and follow-up in the 15 patients who completed the follow-up. Our findings confirm that boys with DMD may exhibit cognitive impairment, with the Working Memory Index being the most impaired. There was no significant correlation between FSIQ and age; however, a positive correlation was noted between age and the Verbal Comprehension Index. FSIQ was not associated with mutation class, the number of affected mutated exons, or mutation locations. However, there was a significant difference in FSIQ between the groups with intact and deficient Dp140. Fifteen participants adhered to glucocorticoid therapy throughout the two-year follow-up period, and eleven of them showed an improvement in FSIQ compared to their initial scores, with improvement ranging from 2 to 20. In conclusion, patients with the cumulative loss of isoforms in the brain are at a higher risk of cognitive deficits and may require early cognitive interventions.     

Reactions of families to children with Duchenne muscular dystrophy

Twenty-five families were interviewed to examine their adjustments to having a child with Duchenne muscular dystrophy (DMD). Chronic emotional stress experienced by families of DMD children was found to be a significant problem in the overall management of the illness. Based on information obtained from the assessment of families' adaptation to their child's illness, recommendations are made concerning parent education, school placement, facilitation of marital harmony, informing the child about his illness, and sensitivity to the responses of other family members.     

Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD), an X-linked disorder, is the most common muscular dystrophy in children, presenting in early childhood and characterized by proximal muscle weakness and calf hypertrophy in affected boys. Patients usually become wheelchair-bound by the age of 12 years, and die of cardiorespiratory complications in their late teens to early twenties. Advances in the management of DMD, including treatment with corticosteroids and the use of intermittent positive pressure ventilation have provided improvements in function, ambulation, quality of life and life expectancy, although novel therapies still aim to provide a cure for this devastating disorder. The clinical features, investigations, and management of DMD are reviewed, as well as the latest in some of the novel therapies.     

Motor development in children with muscular dystrophy of the Duchenne type

For determination of the age of onset and the age of immobilization in Duchenne's progressive muscular dystrophy the motor development was studied in 129 affected children. It was demonstrated that motor development was delayed and abnormal in 58% of the cases. On the average the affected children started to walk in the 19th month of life. According to the history data in 83% of the cases the age of onset of the disease was 1 year; in 10% of the cases the onset was placed before and in 7% after the 5th year of life. It was observed that earlier age of onset was not associated with a more rapid development of the disease and independently of the onset the age of immobilization was about 10 years. The results of investigation were compared with reports in the literature.     

Therapeutics in Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is a fatal disorder affecting approximately 1 in 3500 live born males, characterized by progressive muscle weakness. Several different strategies are being investigated in developing a cure for this disorder. Until a cure is found, therapeutic and supportive care is essential in preventing complications and improving the afflicted child’s quality of life. Currently, corticosteroids are the only class of drug that has been extensively studied in this condition, with controversy existing over the use of these drugs, especially in light of the multiple side effects that may occur. The use of nutritional supplements has expanded in recent years as researchers improve our abilities to use gene and stem cell therapies, which will hopefully lead to a cure soon. This article discusses the importance of therapeutic interventions in children with DMD, the current debate over the use of corticosteroids to treat this disease, the growing use of natural supplements as a new means of treating these boys and provides an update on the current state of gene and stem cell therapies.     

Dystrophin deletions and cognitive impairment in Duchenne/Becker muscular dystrophy

Analyses of deletions in the dystrophin gene and of cognitive status were performed on patients with Duchenne (DMD) or Becker (BMD) muscular dystrophy in order to find a correlation between both features. Molecular study by multiplex and simplex PCR of dystrophin exons led to the identification of 51 deletions in 126 unrelated patients. Most of them were frameshift, in full agreement with severe clinical symptoms, three patients with a BMD-like phenotype had in-frame mutations. Deletions were localized with reference to the different dystrophin isoform sequences and were clustered in two main areas, 5' and central+ 3' end of the gene. Cognitive abilities were tested in 47 out of 51 patients with identified mutations, 23 of them being mentally impaired. Comparison of molecular and neuropsychological features showed that deletions localized in central and 3' parts of the gene (18 out of 23) are preferentially associated with mental impairment. Fourteen of them were found in the regulatory and coding sequences for the three CNS specific carboxy terminal isoforms. Therefore, though mutations with variable locations may lead to cognitive impairment, our results show that deletions in the distal portion of the gene are basically related to mental retardation.     

Prevalence of smooth muscle dysfunction among children with Duchenne muscular dystrophy

Smooth muscle dysfunction in Duchenne muscular dystrophy (DMD) has been rarely studied. A cross-sectional study was conducted to estimate the prevalence of smooth muscle dysfunction (vascular, upper gastrointestinal, and bladder smooth muscle) in children with DMD using questionnaires (Pediatric Bleeding Questionnaire, Pediatric Gastroesophageal Symptom Questionnaire, and Dysfunctional Voiding Symptom Score). Investigations included bleeding time estimation, nuclear scintigraphy for gastroesophageal reflux, and uroflowmetry for urodynamic abnormalities. Ninety-nine subjects were included in the study. The prevalence of vascular, upper gastrointestinal, and bladder smooth muscle dysfunction was 27.2%. Mean bleeding time was prolonged by 117.5 seconds. The prevalence of gastroesophageal reflux was 21%. Voided volume/estimated bladder capacity over 15% and abnormal flow curves on uroflowmetry were seen in 18.2% and 9.7% of the subjects, respectively. Our study highlights the need for addressing issues related to smooth muscle dysfunction in the routine clinical care of patients with DMD.     

Duchenne型进行性肌营养不良30例临床与病理分析

目的 探讨Duehenne型进行性肌营养不良(DMD)的临床与病理特征,为其早期诊断与治疗提供帮助.方法 对30例经免疫组化测定Dystrophin蛋白而确诊的患者的临床与病理资料进行回顾性分析.结果 本组患者平均年龄6.9岁,5例有家族史,2例伴有智力障碍.25例患者可见典型双下肢腓肠肌肥大,Cower征阳性25例,鸭步21例,翼状肩胛18例.30例患者血清肌酶升高,以肌酸激酶(CK)升高为主.28例行肌电图检查提示肌源性损害,肌肉活检示典型肌营养不良病理表现,其中5例可见肌纤维分裂及漩涡状肌纤维,4例NADH染色可见虫噬状肌纤维,ATP染色2例Ⅰ型肌纤维优势,1例Ⅱ型肌纤维优势,ORO染色部分肌纤维脂肪成分轻度增高9例.结论 DMD起病年龄较早,肌无力为其主要临床症状,血清酶学与肌电图检查有助于诊断,结合肌肉活检可明确诊断.     

Pain and activity limitations in children with Duchenne or Becker muscular dystrophy

The purpose of this study was to examine the prevalence and characteristics of pain in children with Duchenne (DMD) or Becker (BMD) muscular dystrophy, including the nature of disagreements concerning pain symptoms among children, parents, and physicians, and limitations in daily activities. Male children (age 8-18 y, n=53) and parents (n=53) completed questionnaires assessing pain intensity (visual analogue scale), pain frequency (Likert scale [LS]), pain duration (LS), emotional distress due to pain (LS), and pain location (body outline markings). The Child Activity Limitations Interview was also completed by both raters to assess daily activities that are limited by recurrent pain. Physicians completed a form indicating medical history and pain symptoms. The majority of children with DMD (mean age 13 y 11 mo [SD 3.38]; range 8-18 y) or BMD (mean 14 y 10 mo [SD 1.48]; range 12-17 y) were non-ambulatory (79 and 50% respectively) and experienced pain according to self (54-80%) and parent reports (70-90%). Pain typically occurred at least once per week and was of mild to moderate intensity. Most children experienced pain for less than a few hours and little to moderate levels of emotional distress due to pain. Pain occurred in the lower back, spine, and legs, and was described as 'aching'. Children and parents indicated significantly more intense pain than the physician. Actual agreement between parent and child report on pain symptoms was poor to fair. Pain is a common occurrence in children with DMD or BMD, yet may be under-recognized. Pain assessment needs to be a standard part of care and may identify difficulties faced by these children to be targeted by interventions.     

Muscle ultrasound elastography and MRI in preschool children with Duchenne muscular dystrophy

The aim of this study was to determine muscle tissue elasticity, measured with shear-wave elastography, in selected lower limb muscles of patients affected by Duchenne muscular dystrophy (DMD) and to correlate the values obtained with those recorded in healthy children and with muscle magnetic resonance imaging (MRI) data from the same DMD children, specifically the pattern on T1-weighted (w) and short-tau inversion recovery (STIR) sequences. Five preschool DMD children and five age-matched healthy children were studied with shear-wave elastography. In the DMD children, muscle stiffness was moderately higher compared with the muscle stiffness in HC, in the rectus femoris, vastus lateralis, adductor magnus and gluteus maximus muscles. On muscle MRI T1-w images showed fatty replacement in 3/5 patients at the level of the GM, while thigh and leg muscles were affected in 2/5; hyperintensity on STIR images was identified in 4/5 patients. No significant correlation was observed between stiffness values and MRI scoring. Our study demonstrated that lower limb muscles of preschool DMD patients show fatty replacement and patchy edema on muscle MRI and increased stiffness on shear-wave elastography. In conclusion, although further studies in larger cohorts are needed, shear-wave elastography could be considered a useful non-invasive tool to easily monitor muscle changes in early stages of the disease.     

Database for patients with Duchenne muscular dystrophy

We had a plan to arrange database for patients with Duchenne muscular dystrophy in Japan. The purpose of this projects will make it possible to design accurate and serial evaluation of patients and conduct therapeutic trial. The items of input are composed of two cards. One card is basic card which fills out mainly patients' basic and genetic informations, the other is course card which records symptoms, muscle strength, joint range of motion, laboratory studies including pulmonary function testing and therapeutic trials. These cards are written by physicians of dystrophic wards in national hospital twice a year and are sent to the statistical coordinating center of database. On the other hand outputs include annual report and optional output which are requested by each investigator. Now 519 basic cards and 1026 course cards have completed. In this paper we tried to output about some results of the data obtained. These outputs include the age of initial gait and difficulty in walking, mean muscle strength by functional grade and the change of muscle strength during the administration of some drugs.     

Management of patients with Duchenne muscular dystrophy

As there is no cure in Duchenne muscular dystrophy (DMD), we must pay attention to the management of its cardiopulmonary complications. In 1984, DMD patients died at the mean age of 18.2 years in my hospital. From autopsy findings, the cause of death was respiratory failure in 75% of them, and left-sided heart failure 12.5%. First, we had to know the relationship between cardiac and respiratory systems. Based on the findings of right-sided heart catheterization, patients with respiratory failure were classified into Forrester's subset 1' normal left ventricular function. These results showed that these patients require treatment with a respirator, but not with digitalis and/or diuretics. Since 1984, we tried cuirass ventilation, which prolonged their lives by about 3 years. Since 1991, NIPPV was introduced in Japan, and prolonged their lives by about 5.5 years. Nowadays TIPPV with tracheostomy is not the first choice of treatment, but we do not hesitate to select this treatment any more. As for left-sided heart failure, brain natriuretic peptide (BNP) is now considered a useful parameter of left ventricular function. Japanese clinical researcher proposed treatment based on values of BNP in left-sided heart failure. In 1980s, the mean interval from the onset of heart failure to death was only 16 months. Recently we feel that better results have already been accomplished. In 2002 Kawai reported that average age at death in Japan was 26.8 years old. More efforts must be made until cure of this disease is found.     

Treatment of Duchenne muscular dystrophy with gentamicin

This article reviews the clinical application of gentamicin treatment for nonsense mutations. Since gentamicin is applied only for Duchenne muscular dystrophy caused by a nonsense mutation, genetic diagnosis of DMD is reviewed. Of the two reports describing gentamicin treatment of DMD, one concluded it to be effective, and the other to be ineffective.     

Oral kinesthesia in patients with Duchenne muscular dystrophy

In trials on normal subjects and patients with Duchenne muscular dystrophy (DMD), interdental dimension discrimination (IDD) was tested by assessing the ability of subjects to discriminate between pairs of sticks of different dimensions held between the upper and lower teeth. The IDD ability of the DMD patients was significantly inferior to that of the normal subjects. Further, DMD patients tended to overestimate the dimension of the first stick of each pair even more than did normal subjects. Vibration applied to the mandible seemed to lessen such inaccuracies of oral kinesthesia in the DMD patients. These results are compatible with the idea that muscle receptors, especially muscle spindles in jaw closing muscles, are mainly responsible for IDD.