Neuromuscular disorders : NMD
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Animal models in biomedical research are important for understanding the pathological mechanisms of human diseases at a molecular and cellular level. Several aspects of mammalian animals, however, may limit their use in modelling neuromuscular disorders. ⋯ This review focuses on a number of key studies using the zebrafish to model hereditary muscle diseases with additional emphasis on recent advances in zebrafish functional genomics and drug discovery. Increasing research in zebrafish disease models, combined with knowledge from mammalian models, will bring novel insights into the disease pathogenesis of neuromuscular disorders, as well as facilitate the development of effective therapeutic strategies.
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Neuromuscul. Disord. · Jul 2012
Single deletions in mitochondrial DNA--molecular mechanisms and disease phenotypes in clinical practice.
Over 20 years ago single clonal deletions were the first mitochondrial DNA (mtDNA) genetic defects described in association with human disease. Since then very large numbers of children and adults harbouring such deletions have been described and it is clear they are an important cause of human mitochondrial disease. However, there still remain many important challenges in relation to our understanding of mechanisms leading to deletion formation and propagation and in relation to the factors determining the complex and varying relationship between genotype and clinical phenotype. ⋯ Single mtDNA deletions may enter into the differential diagnosis of many different paediatric and adult presentations across a wide range of medical specialties, although neurological presentations are amongst the most common. In this review, we examine the molecular mechanisms underpinning mtDNA replication and we consider the hypotheses proposed to explain the formation and propagation of single large-scale mtDNA deletions. We also describe the range of clinical features associated with single mtDNA deletions, outline a molecular diagnostic approach and discuss current management including the role of aerobic and resistance exercise training programmes.
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There have been suggestions from previous studies that patients with Charcot-Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. ⋯ Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.
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Neuromuscul. Disord. · Jul 2012
Case ReportsUltrasonography of MADSAM neuropathy: focal nerve enlargements at sites of existing and resolved conduction blocks.
Using the emerging technique of peripheral nerve ultrasonography, multiple focal nerve swellings corresponding to sites of existing conduction blocks have been described in demyelinating polyneuropathies. We report two cases of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). ⋯ In the second case, existing proximal conduction blocks could be localized by ultrasound. Our cases highlight the importance of nerve ultrasound in identifying conduction blocks and demonstrate that ultrasonographic morphological changes may outlast functional recovery in demyelinating neuropathies.