Progressive Muscular Dystrophy in Infancy

Clinical features of 11 cases of muscular dystrophy in infancy were discussed. From the detailed symptomatological analysis of the 11 patients we reported here, we found two subgroups of infantile muscular dystrophy. There were 6 cases of congenital cerebro-muscular dystrophy (Fukuyama) and 5 cases characterized by comparatively late onset, no sexual preference, proximally dominant muscle wasting, infrequence of associated joint contractures, normal facial muscle and no mental deficiency. The characteristics of this latter group in infantile muscular dystrophy are similar to those of limb-girdle muscular dystrophy. It is suggested that some of the patients with limb-girdle type of muscular dystrophy may have its onset in infancy.     

Progressive Muscular Dystrophy in Denmark

ABSTRACT. Prevalence of progressive muscular dystrophy in 1965 and incidence in Denmark for the period 1965 to 1975 was studied by collection of data from hospital departments, nursery homes and general practitioners. This material was supplemented with information from death certificates and disablement pension records. Total patient group included 445 patients with progressive muscular dystrophy alive January 1st 1965. Prevalence was 69.4 per 10⁶ male inhabitants in the Duchenne type, whereas the prevalences in the limb-girdle and facioscapulohumeral types were 36.5 and 18.6 per 10⁶ inhabitants, respectively. Incidence was 222 per 10⁶ male newborns in the Duchenne type, 66 and 26 per 10⁶ newborns for the limb-girdle and the facioscapulohumeral types, respectively. Figures for the Duchenne type are in agreement with previous results. Both prevalence and incidence rates for the limb-girdle and the facioscapulohumeral types exceed published figures by a factor 3 to 6. These high Danish rates seem to reflect the true prevalence and incidence in the less serious types of progressive muscular dystrophy, probably because the Danish health system with free medical care and easy access to specialized hospital departments makes it possible to identify all cases of progressive muscular dystrophy.     

Fukuyama Type Congenital Progressive Muscular Dystrophy

Clincopathological features of Fukuyama type congenital muscular dystrophy (FCMD), a combination of brain malformation and muscular dystrophy with facial muscle and CNS involvement and high prevalence in Japan, are reviewed. Evidence of progressive dystrophy, negative correlations between muscle enzyme levels and age and CT numbers of muscle and age, are presented. Skeletal muscle histopathology is reviewed. Febrile illness-induced transient exacerbation of muscle weakness is reported. Characteristic brain malformations, e.g. micropolygyria, other dysgenesis, are reviewed. Their severity correlated with maximal mental and motor function. The etiology and significance of low density areas (LDA) in white matter on CT, possibly reflecting delayed or abnormal myelination, and ventricular dilatation are discussed. Spontaneous LDA improvement makes hydrocephaly unlikely. Ophthalmological differential diagnosis from Santavouri disease and Walker-Warburg syndrome, characterized by visual disturbance/glaucoma and microphthalmia/anterior chamber defects, respectively, is discussed. A single defective gene, manifesting as a metabolic error, may produce CNS and ocular defects as well as muscle degeneration in FCMD.     

Progressive Muscular Dystrophy with Particular Reference to Muscle Regeneration

In various progressive muscular dystrophies (PMD), there were a number of fibers with histological and histochemical characteristics of regenerating fibers. With a morphometric analysis in diseased muscles, an identification of type 2C fiber on ATPase stain was the most simple and reliable method for fiber type evaluation. The type 2C fiber comprised 16.5% in Duchenne and 27.5% in Fukuyama type congenital MD, suggesting an active regenerating process taking place in both diseases. Regenerative capacity of muscle fibers after experimental damage to dystrophic chicken and mdx mouse muscles was similar to those seen in nondystrophic control muscles. From the above results, we speculate that a certain environmental factor such as interstitial fibrosis seems to play a major role in delaying regeneration in dystrophic muscles.     

进行性肌营养不良的神经电生理检测

目的探讨神经电生理检测对小儿进行性肌营养不良(PMD)的诊断价值。方法对32例PMD患儿的临床特征及实验室资料进行分析,并作针极肌电图(EMG)及神经传导(NCV)检测。观察静息状态时自发电位,测定轻收缩时运动单位电位(MUP)的时限、波幅,大力收缩时的幕集相。测定运动、感觉神经的传导速度(MCV、SCV)及动作电位的末端潜伏期(ML)、波幅(AMP)。结果PMD患儿32例自发电位的异常率为49.2%,胫前肌达80.9%,MUP时限缩短了29.7%～62.4%,大力收缩时波幅降低,与正常值比较有显著差异(P<0.01)。动作电位的ML轻度延长3.70%,AMP降低5.56%。结论神经电生理检测在PMD患儿的诊断、鉴别诊断及早期诊断中有重要意义。     

Plasma Levels of Natriuretic Peptide and Echocardiographic Parameters in Patients with Duchenne's Progressive Muscular Dystrophy

We investigated the relationship between plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels and systolic and diastolic cardiac function, determined by echocardiography, in 63 patients with Duchenne's progressive muscular dystrophy (DMD) (age range 8-21 years). The relationship between shortening fraction of the left ventricle and ANP and BNP levels was curvilinear rather than linear: When the shortening fraction was >15%, increases in ANP and BNP levels were minimal. However, if the shortening fraction was <15%, both natriuretic peptide levels increased dramatically. Stepwise regression analysis revealed that only the deceleration time of the early diastolic filling wave predicted plasma BNP concentration among various diastolic echocardiographic parameters determined by mitral flow. Three patients died of cardiac dysfunction during a 2-year follow-up period. These patients had a severely decreased deceleration time (<65% of normal) in association with increases in both natriuretic peptide levels. In conclusion, plasma ANP and BNP levels are not sensitive markers for the early detection of cardiac systolic dysfunction in patients with DMD. However, in patients with systolic dysfunction, an increase in the concentrations of these peptides, associated with a decrease in the deceleration time of early diastolic filling, suggests poor prognosis.     

Selenium Supplementation in X-linked Muscular Dystrophy

ABSTRACT. The selenium concentrations in serum and erythrocytes and the erythrocyte glutathione peroxidase activity were determined in 15 boys with the Duchenne type and in 5 boys with the Becker type of X-linked muscular dystrophy before and during long-term selenium and α-tocopherol supplementation and compared with values in unsupplemented controls. The purpose of the treatment was to improve the muscular strength. Twelve of the 20 patients had pretreatment levels of selenium in serum that were within the 95 % confidence limit of the unsupplemented control children. The values in 2 patients, both with the Duchenne type of muscular dystrophy, fell below this level. Selenium supplementation in a daily dose of 6 μg/kg/day for 6 months caused a substantial rise in both serum and erythrocyte selenium, suggesting suboptimal pretreatment body contents of selenium. The greatest increases in both serum and erythrocyte selenium were observed in subjects with initially low selenium levels. Only in 4 of the 20 patients did the selenium supplementation result in a significant rise in erythrocyte glutathione peroxidase activity. As no sure improvement was noted in muscular strength during this treatment period, the Se dose was increased to 20 μg/kg/day. This resulted in a further rise in both serum and erythrocyte selenium, but not in erythrocyte glutathione peroxidase activity.     

Myocardial Cell Damage in Duchenne Muscular Dystrophy

We report two cases of Duchenne muscular dystrophy that presented with laboratory evidence of acute transient myocardial cell damage. The mechanism for development of cardiomyopathy associated with Duchenne muscular dystrophy is not well understood, and this report raises the possibility that the progressive deterioration of cardiac function is punctuated by acute episodes of cell damage.     

非典型性肌营养不良1例

患儿,男,3岁。因反复咳嗽2个月余,发现肝功能异常5 d入院。患儿2个月前无明显诱因下出现咳嗽,呈单声咳,无咳痰及咯血,无发热及气促。在家服用感冒药(具体用药不详)咳嗽仍时有时无。5 d前在当地就诊时发现ALT 80 U/L,1d前复查ALT 305 U/L。既往史及个人史无殊。其祖父有肝病史。     

非典型性营养不良1例

患儿，男，3岁，因反复咳嗽2个月余，发现肝功能异常5d入院，患儿2个月前无明显诱因下出现咳嗽，呈单声咳，无咳痰及咯血，无发热及气促。在家服用感冒药（具体用药不详）咳嗽仍时有时无。5d前在当地就诊时发现ALT80U/L，1d前复查ALT 305U/L。     

Myoblast Transfer Therapy for Duchenne Muscular Dystrophy

A randomly selected extensor digitorum brevis (EDB) muscle in each of three Duchenne muscular dystrophy (DMD) boys aged 9 to 10 was injected with approximately 8 times 10₆ myoblasts. The contralateral EDBs were sham-injected with carrier solution. Donor myoblasts were derived from cell culture of muscle biopsies from the normal ward or normal brothers of the recipients. Cyclosporine (CsA) treatment began two days before myoblast injection and continued for three months. Three days prior to myoblast injection and three months after, the isometric twitch and maximum voluntary contraction of the left and the right EDBs were measured. Myoblast-injected EDBs showed increases in tensions whereas sham-injected EDBs showed reductions. Both immunocytochemical staining and immunoblot revealed dystrophin in the myoblast-injected EDBs. Dystrophic characteristics such as fiber splitting, central nucleation, phagocytic necrosis, variation in fiber shape and size, and infiltration of fat and connective tissues were less frequently observed in these muscles. Sham-injected EDBs exhibited significant structural and functional degeneration and no dystrophin. Throughout the study, there was no sign of erythema, swelling or tenderness at the injection sites. Serial laboratory evaluation including electrolytes, creatinine, and urea did not reveal any significant changes before or after myoblast transfer. We conclude that myoblast transfer therapy is a safe and efficacious procedure to improve the biochemistry, structure, and function of degenerative EDB muscles in DMD.     

Duchenne Muscular Dystrophy: A Practice Update

Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disorder caused by a deficient or defective synthesis of dystrophin protein. DMD is the most common form of muscular dystrophy with an incidence of about 1 in 5000 live boys. Though primarily resulting in progressive muscle weakness, it affects various other organs as well. Heart, brain and smooth muscles are commonly involved, because of expression of dystrophin in these organs. The management of DMD requires a multidisciplinary liaison, anticipatory management and prevention of the complications. Consensus based international recommendation for management of DMD have been published in the year 2010, recognizing DMD as a multi-systemic and progressive disease. The proper management of a boy with DMD can improve ambulation, independence, quality of life and delay disease – related complications. A lot can be done to comfort affected children and their care givers even in a resource limited setting. This review discusses these options and also the current understanding of the disease.