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  • Observations on the classification of the inflammatory myopathies

    20 November 2017

    This brief review considers historical approaches to the classification of the inflammatory myopathies. The last 25. years have seen advances in our knowledge of the underlying immune mechanism but the initial trigger for the idiopathic inflammatory myopathies remains unknown. Existing classifications have their limitations, but with the absence of a "gold standard" a definitive classification is not yet possible. Despite these problems, a working classification is possible that is valuable for everyday clinical practice. In this issue. Inflammatory or necrotizing myopathies, myositides and other acquired myopathies, new insight in 2011.O. Benveniste et al., Paris, FranceObservations on the classification of the inflammatory myopathiesD. Hilton-Jones, Oxford, United KingdomPathogenic aspects of dermatomyositis, polymyositis and overlap myositis R.K. Gherardi, Créteil, FranceSporadic inclusion-body myositis: conformational multifactorial aging-related degenerative muscle disease associated with proteasomal and lysosomal inhibition, endoplasmic reticulum stress, and accumulation of amyloid-β42 oligomers and phosphorylated tauV. Askanas et al., Los Angeles, USAPathophysiology of inflammatory and autoimmune myopathiesM.C. Dalakas, Philadelphia, USAMyositis or dystrophy? Traps and pitfallsO. Benveniste et al., Paris, FranceTherapy of polymyositis and dermatomyositisI. Marie, Rouen, France. © 2011 Elsevier Masson SAS.

  • Observations on the classification of the inflammatory myopathies.

    15 March 2018

    This brief review considers historical approaches to the classification of the inflammatory myopathies. The last 25 years have seen advances in our knowledge of the underlying immune mechanism but the initial trigger for the idiopathic inflammatory myopathies remains unknown. Existing classifications have their limitations, but with the absence of a "gold standard" a definitive classification is not yet possible. Despite these problems, a working classification is possible that is valuable for everyday clinical practice.

  • The myotonic dystrophies: diagnosis and management.

    8 June 2018

    There are currently two clinically and molecularly defined forms of myotonic dystrophy: (1) myotonic dystrophy type 1 (DM1), also known as 'Steinert's disease'; and (2) myotonic dystrophy type 2 (DM2), also known as proximal myotonic myopathy. DM1 and DM2 are progressive multisystem genetic disorders with several clinical and genetic features in common. DM1 is the most common form of adult onset muscular dystrophy whereas DM2 tends to have a milder phenotype with later onset of symptoms and is rarer than DM1. This review will focus on the clinical features, diagnosis and management of DM1 and DM2 and will briefly discuss the recent advances in the understanding of the molecular pathogenesis of these diseases with particular reference to new treatments using gene therapy.

  • The study of human organs by phosphorus-31 topical magnetic resonance spectroscopy.

    8 June 2018

    The potential clinical use of topical magnetic resonance spectroscopy (volume selection by static magnetic field gradients) was tested in 50 studies in volunteers. Topical magnetic resonance spectroscopy (MRS) was shown to be a straightforward method for localising 31P spectra of brain and liver. However, the spherical shape and fixed position of the selected volume posed serious limitations to the study of heart and transplanted kidney by topical MRS. Phosphorus-31 spectra of approximately 30 cm-3 of brain or liver could be obtained in 8 min. Ratios of metabolite concentrations could be determined with a coefficient of variation ranging from 10% to 30%. The ratios of phosphocreatine/ATP and inorganic phosphate/ATP in brain were 1.8 and 0.3, respectively. The ratio of inorganic phosphate/ATP in liver was 0.9. Intracellular pH was 7.03 in brain and 7.24 in liver. The T1 relaxation times of phosphocreatine, inorganic phosphate and gamma-ATP in brain were 4.8 s, 2.5 s and 1.0 s, respectively.

  • Cardiac abnormalities and skeletal muscle weakness in carriers of Duchenne and Becker muscular dystrophies and controls.

    14 May 2018

    Cardiac abnormalities, cardiomyopathy and skeletal muscle weakness have been described in female carriers of the Xp21 (Duchenne and Becker) muscular dystrophies (J Neurol 1975;209(4):279-285; Br Med J 1969;2:418-420; J AmMed Assoc 1996;275(17):1335-1338; Neurology 1980;30(5):497-501; Neuromusc Disord 1999;9:347-351; Arch Neurol 1989;46:673-675). We have screened volunteers from our Xp21 genetics register and found the prevalence of previously unrecognized, clinically relevant, abnormalities in this group to be less than previously reported. We studied 91 women (56 carriers and 35 controls), aged between 18 and 69 years, from our local population known to the Oxford Regional Genetics Register. Our study included controls, with the investigators being blind to the subject's genetic status. The prevalence of previously unrecognised cardiac abnormalities on echocardiogram and ECG was 18% (10/56). Seven percent (4/56) of carriers had cardiomyopathy, defined by significant LV dilatation and decreased shortening fraction. In most cases, subjects with abnormal cardiac findings were asymptomatic. Echocardiography was more frequently abnormal than electrocardiography, but in many subjects the measurements of left ventricular dimensions were only just outside the normal ranges. The prevalence of skeletal muscle weakness was 12% (7/56). It was usually recognized by the individual, although not previously volunteered, but was mild and did not substantially affect activities of daily living.

  • Oculopharyngeal muscular dystrophy: phenotypic and genotypic studies in a UK population.

    11 May 2018

    Oculopharyngeal muscular dystrophy (OPMD) is an autosomal dominant disorder of late onset that commonly presents with ptosis and dysphagia. The genetic basis of the condition has been identified recently as a stable trinucleotide repeat expansion in exon 1 of the poly(A) binding protein 2 gene (PABP2), in which (GCG)(6) is the normal repeat length. The prevalence of OPMD is greatest in patients of French-Canadian origin. It is not clear if expansion repeat length is a reliable test in other populations. In this study, we analysed the phenotypic and genotypic characteristics of 31 patients with OPMD in the UK. Ptosis was the first reported symptom in two-thirds of the patients, and half of the subjects studied had evidence of ophthalmoplegia. All but one family had a pathological expansion in the PABP2 gene, ranging from (GCG)(8) to (GCG)(13). In contrast to the French-Canadian population, (GCG)(10) was almost as common as (GCG)(9), evidence against a strong founder effect in the UK population. There was a weak association between repeat length and age of disease onset. Patients with longer repeat lengths, such as (GCG)(13), developed severe limb weakness early in the disease. We were unable to detect the (GCG)(7) polymorphism in over 200 normal controls, suggesting that the frequency of this expansion is lower than that found in the French-Canadian population. One family was negative for the expansion. Affected members presented with the classical features of OPMD, namely ptosis, dysphagia and cytoplasmic inclusions on muscle biopsy, although with some atypical features, such as early age of onset, high serum levels of creatine kinase and a profound ophthalmoplegia. This family is an example of a GCG expansion-negative oculopharyngeal syndrome requiring further genetic investigation. We conclude that PABP2 analysis is a reliable non-invasive diagnostic test for OPMD in the UK population.

  • Motor neuron disease in England and Wales, 1959-1979.

    4 April 2018

    Mortality rates from motor neuron disease in England and Wales for the years 1959-1979 were studied through death certification data supplied by the Office of Population Censuses and Surveys. The age- and sex-adjusted mortality rate increased over the period from 1.2 per 100 000 per year in 1959-61 to 1.6 in 1977-79, the increase being most apparent in women over age 45 years and men over 60 years. The ratio of the sex-specific mortality rates remained fairly constant at 1.6:1 (male to female). The distribution of motor neuron disease deaths within England and Wales showed more variation between counties and between Hospital Regions than expected, and areas of high motor neuron disease mortality along the south coast and low mortality in the Midlands could be identified. The variation was most marked in those aged over 65 years at death. Examination of occupation, as listed on the death certificates, showed an excess of motor neuron disease deaths in leather workers in all three periods for which data were available (1959-63, 1970-72 and 1975). A small study of the certified cause of death of 56 motor neuron disease patients showed that a high percentage (88%) had motor neuron disease given as the cause of death.

  • Fracture rate in patients with myasthenia gravis: the general practice research database.

    14 March 2018

    SUMMARY: The aim of this study was to evaluate fracture risk after onset of myasthenia gravis using the UK General Practice Research Database. Overall fracture risk is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use, but was increased in those using antidepressants, anxiolytics or anticonvulsants. INTRODUCTION: Myasthenia gravis (MG) is a neuromuscular disease which has been associated with an increased falls risk and glucocorticoid-induced osteoporosis, recognized determinants of increased fracture risk. The aim of this study was to evaluate the risk of fracture after onset of MG. METHODS: We conducted a retrospective cohort study using the UK General Practice Research Database (1987-2009). Each MG patient was matched by age, sex, calendar time and practice to up to six patients without a history of MG and we identified all fractures and those associated with osteoporosis. RESULTS: Compared to the control cohort, there was no statistically significant increased risk observed in patients with MG for any fracture (adjusted hazard ratio [AHR] 1.11; 95 % confidence interval [CI], 0.84-1.47) or osteoporotic fractures (AHR 0.98 [95 % CI 0.67-1.41]). Further, use of oral glucocorticoids up to a cumulative dose exceeding 5 g prednisolone equivalents did not increase risk of osteoporotic fracture (AHR 0.99 [95 % CI, 0.31-3.14]) compared with MG patients without glucocorticoid exposure. However, fracture risk was higher in patients with MG prescribed antidepressants (AHR 3.27 [95 % CI, 1.63-6.55]), anxiolytics (AHR 2.18 [95 % CI, 1.04-4.57]) and anticonvulsants (AHR 6.88 [95 % CI, 2.91-16.27]). CONCLUSION: Overall risk of fracture in patients with MG is not statistically increased compared with age- and gender-matched controls irrespective of glucocorticoid use but was increased in those using antidepressants, anxiolytics or anticonvulsants. These findings have implications in strategies preserving bone health in patients with MG.