Assessment of left ventricular dyssynchrony by speckle tracking echocardiography in children with duchenne muscular dystrophy

The International Journal of Cardiovascular Imaging - Prognosis of Duchenne muscular dystrophy (DMD) is related to cardiac dysfunction. Two dimensional-speckle tracking echocardiography (2D-STE)...     

Serum pyruvate kinase in carriers of duchenne muscular dystrophy

Independent studies by two different groups (Madras and Edinburgh) have failed to confirm the suggestion that measurement of the serum level of pyruvate kinase (EC 2.7.1.40, PK) may be superior to measurement of the serum level of creatine kinase (EC 2.7.3.2, CK) for detecting female carriers of X-linked Duchenne muscular dystrophy (DMD). At present the serum level of creatine kinase remains the best test for this purpose.     

A stress model for parents of children with duchenne muscular dystrophy

This study explored the problems encountered by parents in caring for children with Duchenne muscular dystrophy (DMD). Open questionnaires (N=21) designed to identify and gauge stress factors were used to collect study data. Results showed that key elements of the care stress model in parents of DMD children prior to joining a support group included: (1) recognition of the factors underlying the changes in their child's health condition (incomprehension, inference, rationalization, and acceptance of mutation and sexual heredity); (2) special assistance needs such as barrier-free facilities, government/social assistance (role substitution, coordination, and long-term care) and medical information (on treating disease causes, psychological adjustment, rehabilitation, and the welfare system); and (3) strains (physical, psychological, sleep disturbances, and feelings of powerlessness). Once families of DMD children began participating in DMD support groups, it is important to note the information exchanged, particularly with regard to medical, rehabilitation, psychological adjustment, role substitution, and welfare benefit information.     

Brain and heart magnetic resonance imaging/spectroscopy in duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is an X‐linked muscle disorder characterized by progressive and irreversible loss of muscular function. As muscular disease progresses, the repair mechanisms cannot compensate for cellular damage, leading inevitably to necrosis and progressive replacement by fibrous and fatty tissue. Cardiomyopathy and respiratory failure are the main causes of death in DMD. In addition to the well‐described muscle and heart disease, cognitive dysfunction affects around 30% of DMD boys. Myocardial fibrosis, assessed by late gadolinium enhancement (LGE), using cardiovascular magnetic resonance imaging (CMR), is an early marker of heart involvement in both DMD patients and female carriers. In parallel, brain MRI identifies smaller total brain volume, smaller grey matter volume, lower white matter fractional anisotropy and higher white matter radial diffusivity in DMD patients. The in vivo brain evaluation of mdx mice, a surrogate animal model of DMD, showed an increased inorganic phosphate (P(i))/phosphocreatine (PCr) and pH. In this paper, we propose a holistic approach using techniques of magnetic resonance imaging, spectroscopy and diffusion tensor imaging as a tool to create a “heart and brain imaging map” in DMD patients that could potentially facilitate the patients’ risk stratification and also future research studies in the field.     

血流多普勒Tei指数对进行性肌营养不良患者左心功能的探讨

目的应用血流多普勒Tei指数探讨早期进行性肌营养不良症(duchenne muscular dystrophy,DMD)患者心功能的情况。方法28例进行性肌营养不良患者和15例正常对照者分别进行常规二维及M型超声心动图检查,脉冲多普勒二尖瓣及Tei指数血流的测定,测量左室射血分数(LVEF%)、E/A、Tei指数。结果与正常对照组比较,DMD组Tei指数及IRT明显升高(P<0.05)。LVEF及E/A在两组间差别则无显著性意义(P>0.05)结论多普勒血流Tei指数可以早期发现DMD患者心脏功能受损。     

Optimal classification for the diagnosis of duchenne muscular dystrophy images using support vector machines

Background

This study aimed to investigate the optimal support vector machines (SVM)-based classifier of duchenne muscular dystrophy (DMD) magnetic resonance imaging (MRI) images.

Methods

T1-weighted (T1W) and T2-weighted (T2W) images of the 15 boys with DMD and 15 normal controls were obtained. Textural features of the images were extracted and wavelet decomposed, and then, principal features were selected. Scale transform was then performed for MRI images. Afterward, SVM-based classifiers of MRI images were analyzed based on the radical basis function and decomposition levels. The cost (C) parameter and kernel parameter \(\gamma \) were used for classification. Then, the optimal SVM-based classifier, expressed as \((C,\gamma \)), was identified by performance evaluation (sensitivity, specificity and accuracy).

Results

Eight of 12 textural features were selected as principal features (eigenvalues \(\lambda _{\mathrm{c}}\ge 1\)). The 16 SVM-based classifiers were obtained using combination of (C, \(\gamma \)), and those with lower C and \(\gamma \) values showed higher performances, especially classifier of \((C = 1,\gamma = 0.083)\,(p<0.05\)). The SVM-based classifiers of T1W images showed higher performance than T1W images at the same decomposition level. The T1W images in classifier of \((C = 1,\gamma = 0.083\)) at level 2 decomposition showed the highest performance of all, and its overall correct sensitivity, specificity, and accuracy reached 96.9, 97.3, and 97.1 %, respectively.

Conclusion

The T1W images in SVM-based classifier \((C =1, \gamma = 0.083)\) at level 2 decomposition showed the highest performance of all, demonstrating that it was the optimal classification for the diagnosis of DMD.

     

Protein kinase and adenylate cyclase of erythrocyte membrane from patients with duchenne muscular dystrophy

In freshly prepared erythrocyte membranes from normal individuals and from patients with Duchenne progressive muscular dystrophy the endogenous protein kinase and the cAMP stimulated phosphorylation was identical for the three main ³²P proteins including spectrin (protein band II). Another enzyme, adenylate cyclase, was found unchanged. Altered protein kinase and adenylate cyclase has been reported in this disorder. We have no explanation for these discrepancies.     

MLPA及测序技术在DMD/BMD家系分析中的应用

目的运用MLPA技术和DNA及cDNA测序技术对DMD/BMD进行家系分析,对患者、可能携带者基因诊断并探讨诊断流程的临床可行性。方法对2个DMD/BMD家系中6例患者、13例女性可能携带者、6例男性家系成员,6例女性和男性健康对照共31例采集外周血提取DNA,运用MLPA技术分析对以上31例的DMD基因79个外显子;患者取右侧腓肠肌10～30mg肌肉提取RNA,逆转录cDNA;分别进行DNA及cDNA序列测定,测序结果与MLPA结果进行比较。结果经MLPA检测,家系1的4例患者均缺失DMD基因Exon50,家系2中2例患者均缺失Exon43。以上结果经肌肉cDNA测序证实了相应外显子缺失。结论 MLPA技术结合DNA及cDNA测序技术进行DMD家系分析具有可靠的临床应用价值。     

A simplified immune suppression scheme leads to persistent micro-dystrophin expression in duchenne muscular dystrophy dogs

Highly abbreviated micro-dystrophin genes have been intensively studied for Duchenne muscular dystrophy (DMD) gene therapy. Following adeno-associated virus (AAV) gene transfer, robust microgene expression is achieved in murine DMD models in the absence of immune suppression. Interestingly, a recent study suggests that AAV gene transfer in dystrophic dogs may require up to 18 weeks' immune suppression using a combination of three different immune-suppressive drugs (cyclosporine, mycophenolate mofetil, and anti-dog thymocyte globulin). Continued immune suppression is not only costly but also may cause untoward reactions. Further, some of the drugs (such as anti-dog thymocyte globulin) are not readily available. To overcome these limitations, we developed a novel 5-week immune suppression scheme using only cyclosporine and mycophenolate mofetil. AAV vectors (either AV.RSV.AP that expresses the heat-resistant human alkaline phosphatase gene, or AV.CMV.μDys that expresses the canine R16-17/H3/ΔC microgene) at 2.85×10(12) vg particles were injected into adult dystrophic dog limb muscles under the new immune suppression protocol. Sustained transduction was observed for nearly half year (the end of the study). The simplified immune suppression strategy described here may facilitate preclinical studies in the dog model.     

Effect of intrapulmonary percussive ventilation on mucus clearance in duchenne muscular dystrophy patients: a preliminary report

OBJECTIVE: To determine the effects of intrapulmonary percussive ventilation (IPV) on mucus clearance in tracheostomized Duchenne muscular dystrophy patients. METHODS: We studied 8 patients, 5 of whom had mucus hypersecretion (> 30 mL/d). In a randomized, cross-over study we compared assisted mucus clearance techniques with and without IPV. There were 2 treatment sequences and each patient received 5 consecutive days of each treatment sequence, delivered 3 times a day. One sequence consisted of (1) assisted mucus clearance technique (AMCT, which involves forced expiratory technique and manual assisted cough), (2) endotracheal suctioning, (3) nebulizer administration of 5 mL of 0.9% sodium chloride solution for 5 min, (4) a second AMCT session, (5) endotracheal suctioning, (6) 45 min after the end of the nebulizer treatment a third AMCT session, (7) endotracheal suctioning. The other treatment sequence was the same except that it included IPV during the 5-min nebulizer treatment. The collected secretions were weighed. Vital capacity was measured once, before the treatments. Heart rate, respiratory rate, oxyhemoglobin saturation, end-tidal carbon dioxide, airway resistance, and peak expiratory flow were measured before and at 45 min after the treatments. Mean values were compared using analysis of variance with repeated measures. RESULTS: In patients with hypersecretion the mean +/- SD weight of the collected secretions was significantly higher with IPV (6.53 +/- 4.77 g vs 4.57 +/- 3.50 g, p = 0.01). Heart rate, respiratory rate, oxyhemoglobin saturation, end-tidal carbon dioxide, airway resistance, and peak expiratory flow did not differ statistically between the 2 treatments. CONCLUSIONS: IPV is a safe airway clearance method for tracheostomized Duchenne muscular dystrophy patients, and this preliminary study suggests that IPV increases the effectiveness of assisted mucus clearance techniques.     

Sensitive ultrasonic detection of dystrophic skeletal muscle in patients with duchenne muscular dystrophy using an entropy-based signal receiver

The dystrophinopathies comprise a group of X-linked genetic diseases that feature dystrophin deficiency. Duchenne and Becker muscular dystrophy are characterized by progressive weakness and wasting of skeletal, smooth, and/or cardiac muscle. Duchenne muscular dystrophy (DMD) is the most severe dystrophinopathy, with an incidence of 1:3500 male births. Despite understanding the structural and genetic basis for DMD, the pathogenesis and clinical basis for more severe involvement in specific skeletal muscle groups and the heart are poorly understood. Current techniques, such as strength testing for monitoring progress of disease and therapy in DMD patients, are imprecise and physically demanding for test subjects. Ultrasound is well-suited to detect changes in structure and organization in muscle tissue in a manner that makes low demands on the patient. Therefore, we investigated the use of ultrasound to quantitatively phenotype the remodeling process in patients with DMD. Beam-formed radio-frequency (RF) data were acquired from the skeletal muscles of nine DMD and five normal subjects imaged with a clinical imaging system (HDI5000 w/7 MHz probe applied above left biceps muscle). From these data, images were reconstructed using B-mode (log of analytic signal magnitude) and information-theoretic receivers (H(f)-receiver). H(f) images obtained from dystrophic muscle contained extensive "mottled" regions (i.e., areas with heterogeneous image contrast) that were not readily apparent from the B-Mode images. The 2-D autocorrelation of DMD H(f) images have broader peaks than those of normal subjects, which is indicative of larger scatterer sizes, consistent with pathologic changes of fibers, edema and fatty infiltration. Comparison of the relative peak widths (full width measured at 60% maximum) of the autocorrelation of the DMD and normal H(f) images shows a quantitative difference between the two groups (p < 0.005, student two-tailed paired t-test). Consequently, these imaging techniques may prove useful for longitudinal monitoring of disease progression and therapy.     

Intraarterial delivery of naked plasmid DNA expressing full-length mouse dystrophin in the mdx mouse model of duchenne muscular dystrophy

Our previous studies have demonstrated that the intraarterial delivery of naked plasmid DNA leads to high levels of foreign gene expression throughout the muscles of the targeted limb. Although the procedure was first developed in rats and then extended to nonhuman primates, the present study has successfully implemented the procedure in normal mice and the mdx mouse model for Duchenne muscular dystrophy. After intraarterial delivery of plasmid DNA expressing the normal, full-length mouse dystrophin from either the cytomegalovirus promoter or a muscle-specific human desmin gene control region, mdx mouse muscle stably expressed dystrophin in 1-5% of the myofibers of the injected hind limb for at least 6 months. This expression generated an antibody response but no apparent cellular response.