Electromyographic pattern in Duchenne and Becker muscular dystrophy. Part II. Electromyographic pattern in Becker muscular dystrophy in comparison with Duchenne muscular dystrophy

BACKGROUND: The aim of this study was to compare the electromyographic pattern in Becker muscular dystrophy (BMD) with that found in Duchenne muscular dystrophy (DMD). MATERIAL AND METHOD: Fourteen men with BMD and 51 boys with DMD were investigated. Proximal muscles were examined: m. biceps brachii (BB) and m. rectus femoris (RF). They were divided according to the clinical criteria in two groups: of those with slight changes (group AB) and of those with severe abnormalities (CD). As in the Part I of the paper our own method of Functional-QEMG was applied in the CNEMG examination. RESULTS AND CONCLUSIONS: Spontaneous activity (fibrillations, complex repetitive discharges) was equally frequent in BMD and DMD. Linked potentials were rather frequent in either group. Myopathic features such as MUAPs low amplitude and area, polyphasic shape were seen in either condition, but more marked in DMD than in BMD. Evaluation of IP recordings revealed that IP amplitude (amplitude size) is low in DMD already at the early stage of lesion but normal or only slightly diminished in BMD. It might perhaps suggest different degrees of lesion in type II MUs between the compared types of muscular dystrophy.     

Carrier detection in Duchenne muscular dystrophy.

Serum creatine kinase, myoglobin, and percentage lymphocyte capping was determined in ten patients with Duchenne muscular dystrophy, 12 carriers (nine definite and three probable), 16 other female relatives, and eight normal controls. There was no detectable difference in lymphocyte capping ability between any of these clinical groups. Significant myoglobinaemia was present in all the affected males, but the difference in levels between carriers and controls suggested that this test has no advantage over creatine kinase estimations in carrier detection.     

Carrier detection in Duchenne muscular dystrophy.

We measured endogenous phosphorylation of peak II (apparent molecular weight of 220,000 daltons) of the erythrocyte membrane in 21 mothers of patients with Duchenne muscular dystrophy. The mean values of mothers with affected sons were significantly increased over those of matched controls (77.0 and 55.8 pmoles per milligram of 15-minute incubation; P less than 0.01). Detailed testing of mothers of affected sons revealed proximal muscle weakness. Seven mothers of isolated patients who had normal levels of creatine phosphokinase and no daughters with elevated levels were identified as carriers, because their mean value of peak II phosphorylation was increased (75.9 pmoles per milligram per 15 minutes) and equivalent to the level demonstrated in the 14 acknowledged carriers. Our results suggest that cases of Duchenne muscular dystrophy previously considered to be new mutations are much less common than estimated.     

Molecular deletion analysis in Duchenne muscular dystrophy.

Study of 165 unrelated patients with X linked muscular dystrophy (117 with Duchenne and 48 with Becker dystrophy) has shown nine Duchenne cases (8% of the total) where a molecular deletion was detected using probes pERT87 or XJ1.1. No cytogenetic abnormalities were detectable in this unselected series of patients and no clear clinical or other differences were found between deletion and non-deletion cases. No deletions were found in the 48 Becker patients. Analysis of the families allowed unequivocal identification carrier status in females hemizygous for the deleted allele. Since some of the deletions were detected with only one of the two probes, it is important that both pERT87 and XJ1.1 are used when studying patients for molecular deletions.     

Echinocytes in families with Duchenne muscular dystrophy.

The results of the present investigation have failed to confirm the suggestion that there is a significant increase in the proportion of echinocytes in preparation of fresh erythrocytes in patients with Duchenne muscular dystrophy and heterozygous carriers of this disorder.     

Motor unit changes in inflammatory myopathy and progressive muscular dystrophy

The aim of present study was to analyse the motor unit (MU) changes in progressive muscle dystrophy (PMD) and in inflammatory myopathy (IM) and to evaluate eventual neurogenic factors in MU reorganisation. The material consisted of 20 patients with (PMD), 20 patients with (IM) and 20 healthy age-matched volunteers. The shape of concentric needle motor unit potentials (cn MUPs), including their duration, amplitude, area, size index and number of phases, the interference pattern and the amplitude and area of macro MUPs were evaluated. The cn emg data satisfied the classical criteria for myopathy in all examined patients, at least in one of the tested muscles. A decreased amplitude and/or area of macro MUPs, compatible with myopathy, were observed in 32 of the 40 patients. In some cases of chronic IM and PDM the long duration polyphasic potentials were recorded. The size index (SI) value of long polyphasic MUPs was usually decreased or normal. This feature indicated that desynchronisation of "myopathic" MUPs results from a reduced number of muscle fibers and their degeneration and regeneration. The results indicated no difference in MU reorganization between PMD and IM and no evidence of neurogenic factors in MU changes.     

Duchenne型肌营养不良症的细胞治疗

Duchenne型肌营养不良症（Duchenne muscular dystrophy，DMD）表现为进行性肌肉萎缩，是一种致死性、遗传性神经肌肉疾病。尽管对肌肉萎缩的分子机理的研究取得了很大进展，但是仍然不能治愈，细胞治疗是很有前景的一种治疗方法。成肌细胞移植面临的主要限制是注射后细胞分布差，免疫排斥和细胞存活率低；骨髓干细胞移植需要解决横向分化的低效率问题；而肌源性干细胞看来能更有效地再生表达dystrophin的肌纤维。     

The manifesting carrier in Duchenne muscular dystrophy

Twenty-two female carriers of Duchenne muscular dystrophy (DMD) presenting with myopathic symptoms have been examined. Eleven were definite carriers, aged 29 to 79 years, and 11 were possible carriers, aged 4 to 57 years. There was considerable variation in the clinical manifestations and the course of the myopathy, which in many cases resembled the autosomal recessive limb girdle type of muscular dystrophy (LGMD). Serum levels of creatine kinase were significantly greater in manifesting carriers than in non-manifesting carriers of DMD and female patients with LGMD. Ten out of the 22 manifesting carriers were familial cases, being either sisters or mother and daughter(s). The frequency of clinical manifestations among female first degree relatives of myopathic DMD carriers is significantly greater than would be expected from the observed prevalence of manifestations among definite carriers (7.8 %). The prevalence of manifesting DMD carriers in the general female population was estimated to be 22.4 × 10^-6, which is comparable to the 19.9 × 10^-6 prevalence for LGMD. The differential diagnosis between the two conditions and the pathogenetic aspects with regard to Lyon's hypothesis and to additional, possibly genetic regulatory mechanisms, are discussed.     

Clinically manifesting carriers in Duchenne muscular dystrophy

Three manifesting carriers of Duchenne muscular dystrophy were examined clinically and histologically. All had muscle weakness in the upper and lower limbs without facial muscle involvement, onset being at the ages of 35, 19 and 25 years, respectively. Pseudohypertrophy of calves was evident in all cases. Biochemical, electrocardiographic and histological observations revealed the presence of myopathy in all cases. Sex chromatin patterns were normal. Compared with the manifesting carriers previously reported by others, at least one case showed more severe histological findings which were typical of the advanced stage of Duchenne muscular dystrophy. The cardiac involvement in three cases was moderate. A possible involvement of other factors besides Lyonization influencing the development of myopathy in the carriers is suggested.     

Progress in therapy for Duchenne muscular dystrophy

Duchenne muscular dystrophy is a devastating muscular dystrophy of childhood. Mutations in the dystrophin gene destroy the link between the internal muscle filaments and the extracellular matrix, resulting in severe muscle weakness and progressive muscle wasting. There is currently no cure and, whilst palliative treatment has improved, affected boys are normally confined to a wheelchair by 12 years of age and die from respiratory or cardiac complications in their twenties or thirties. Therapies currently being developed include mutation-specific treatments, DNA- and cell-based therapies, and drugs which aim to modulate cellular pathways or gene expression. This review aims to provide an overview of the different therapeutic approaches aimed at reconstructing the dystrophin-associated protein complex, including restoration of dystrophin expression and upregulation of the functional homologue, utrophin.