MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Neuromuscular Disorders' source. Wed, 08 Feb 2012 20:43:30 +0100 http://www.medworm.com/index.php?rid=5650185&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896612000247%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650185 Wed, 01 Feb 2012 05:00:00 +0100 5650185 http://www.medworm.com/index.php?rid=5650184&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896612000120%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650184 Wed, 01 Feb 2012 05:00:00 +0100 5650184 http://www.medworm.com/index.php?rid=5650183&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896612000090%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650183 Wed, 01 Feb 2012 05:00:00 +0100 5650183 http://www.medworm.com/index.php?rid=5650178&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013332%2Fabstract%3Frss%3Dyes Abstract: Charcot–Marie–Tooth type 1B (CMT1B) is a demyelinating neuropathy caused by mutations in the myelin protein zero (MPZ) gene. Here, we describe a patient with CMT1B with focally folded myelin, a rarely reported phenotype of CMT1B, who initially presented with multiple entrapment neuropathies. She complained of palmar dysesthesia on both sides and on both soles of her feet in her 30’s. She underwent bilateral carpal and tarsal tunnel release at age 44, which provided transient relief from the symptoms. A sural nerve biopsy performed at age 49 revealed focally folded myelin. Molecular genetic analysis revealed a novel Asn131Ser mutation in MPZ. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650178 Wed, 01 Feb 2012 05:00:00 +0100 5650178 http://www.medworm.com/index.php?rid=5650168&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013307%2Fabstract%3Frss%3Dyes We report a case of 12 fast channel patients to highlight clinical features and management difficulties. Patients were diagnosed through genetic screening and identification of mutations shown to cause fast channel syndrome. Data was obtained from clinical notes, history, examination and follow up. Patterns of muscle weakness involved limb, trunk, bulbar, respiratory, facial and extraocular muscles. Patients responded to treatment with anticholinesterase medication and 3,4-diaminopyridine. Fast channel syndrome contrasted with AChR deficiency in the occurrence of severe respiratory crises in infancy and childhood. The death of two children even when on treatment and the family histories of sibling deaths re-inforces the need for accurate genetic diagnosis, optimised pharmacological treatme... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650168 Wed, 01 Feb 2012 05:00:00 +0100 5650168 http://www.medworm.com/index.php?rid=5650166&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896612000065%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650166 Wed, 01 Feb 2012 05:00:00 +0100 5650166 http://www.medworm.com/index.php?rid=5650174&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101337X%2Fabstract%3Frss%3Dyes We describe a 22-month-old girl with axial muscle and diaphragmatic weakness as well as motor developmental delay without mental retardation. The striking clinical feature was a dropped head, although she could walk unaided. T2/FLAIR brain MRI revealed a focal abnormality with high signal intensity in the white matter including U-fibers. A muscle biopsy showed active necrotic and regenerative processes. These distinct clinical findings prompted a mutational analysis of the lamin A (LMNA) gene, and we identified a novel heterozygous mutation in LMNA (c.1330_1338dup9). This is the first report of an Asian patient with LMNA-related congenital muscular dystrophy (L-CMD) and a dropped head. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650174 Fri, 13 Jan 2012 05:00:00 +0100 5650174 http://www.medworm.com/index.php?rid=5611241&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013137%2Fabstract%3Frss%3Dyes Abstract: An 80-year-old woman (PI) has been suffering of late onset progressive weakness and wasting of lower-limb muscles, accompanied by high creatine kinase levels in blood. A muscle biopsy, performed at 63years, showed myopathic features with partial deficiency of cytochrome c oxidase. A second biopsy taken 7years later confirmed the presence of a mitochondrial myopathy but also of vacuolar degeneration and other morphological features resembling inclusion body myopathy. Her 46-year-old daughter (PII) and 50-year-old son (PIII) are clinically normal, but the creatine kinase levels were moderately elevated and the EMG was consistently myopathic in both. Analysis of mitochondrial DNA sequence revealed in all three patients a novel, homoplasmic 15bp tandem duplication adjacent to the 5�... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611241 Mon, 09 Jan 2012 05:00:00 +0100 5611241 http://www.medworm.com/index.php?rid=5611249&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611014118%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611249 Sun, 01 Jan 2012 05:00:00 +0100 5611249 http://www.medworm.com/index.php?rid=5611234&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661200003X%2Fabstract%3Frss%3Dyes The 21st year of Neuromuscular Disorders ended with a crescendo of over 300 pdf pages of manuscripts past the proof stage, awaiting publication in the new year. Our anniversary was duly celebrated with a champagne luncheon at our annual editorial board meeting, at the WMS Congress in the Algarve, Portugal. Amongst those present, in addition to the founding editor, were Luciano Merlini, who originally recognised the need for a freestanding multi-disciplinary journal dedicated to neuromuscular disorders and was a founder Associate Editor. Another vintage Associate Editor who joined us for the celebration was Ikuya Nonaka, whilst a third, Fernando Tomé, who was tower of strength through the life of the Journal, was with us in spirit in Lisbon, although unable to join us in person. Another t... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611234 Sun, 01 Jan 2012 05:00:00 +0100 5611234 http://www.medworm.com/index.php?rid=5611233&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611014088%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611233 Sun, 01 Jan 2012 05:00:00 +0100 5611233 http://www.medworm.com/index.php?rid=5650172&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013411%2Fabstract%3Frss%3Dyes Abstract: Polymorphisms in PTPN22 are associated with many autoimmune diseases; while rs2476601 is supposed to play a major role, other experimental data suggest that rs2488457 may be even more important. Results in myasthenia gravis are controversial. In 356 Italian myasthenic patients and 439 controls genotyped for both polymorphisms, we found that rs2476601 was not associated with myasthenia, presence of autoantibodies, thymus pathology, sex or onset age unlike previous studies on other European populations (confirmed by the present meta-analysis). On the other hand, while rs2488457 was not associated with myasthenia or thymus pathology, we found a correlation of rs2488457 with low autoantibody titers and a trend of association with a less severe disease. Both polymorphisms were in tigh... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650172 Mon, 26 Dec 2011 05:00:00 +0100 5650172 http://www.medworm.com/index.php?rid=5611235&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013496%2Fabstract%3Frss%3Dyes Abstract: Distal myopathies are a group of muscle diseases which share the clinical pattern of predominant weakness in the feet and/or hands. Rapid advance in the understanding of underlying gene defects have to date separated more than 20 distinct disorders and many are yet without genetic characterisation. No definite diagnosis can be made on other grounds than identification of the final molecular genetic defect. Besides usual investigations including EMG and muscle biopsy, muscle imaging is very important in defining the precise pattern of muscle involvement. Based on the combination of age at onset, mode of inheritance, pathology and muscle imaging, the number of underlying candidate genes for a certain disease can be significantly reduced, which is of help for the molecular genetic a... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611235 Mon, 26 Dec 2011 05:00:00 +0100 5611235 http://www.medworm.com/index.php?rid=5611248&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013745%2Fabstract%3Frss%3Dyes The timing of this well merited second edition of so roundly presented a history of the evolution in our understanding of muscular dystrophy could scarcely be bettered, coming as it does in close juxtaposition with the very real hope of potentially effective treatment by means of targeted modification of gene behaviour for the X-linked hypertrophic disorder. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611248 Fri, 23 Dec 2011 05:00:00 +0100 5611248 http://www.medworm.com/index.php?rid=5611247&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013733%2Fabstract%3Frss%3Dyes The Editors suggest this book is suitable for laboratory medical staff and clinicians and should be seen as a supplement to other books on laboratory diagnosis and neurology. The book is presented in four sections: Basics, Analysis, Clinical Pictures and an Appendix and the bias is very much toward analytical methodology. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611247 Thu, 22 Dec 2011 05:00:00 +0100 5611247 http://www.medworm.com/index.php?rid=5611239&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013277%2Fabstract%3Frss%3Dyes Abstract: Loss of mobility influences the quality of life for patients with neuromuscular diseases. Common measures of mobility and chronic muscle damage are the six-minute walk test and serum creatine kinase. Despite extensive pre-clinical studies of therapeutic approaches, characterization of these measures is incomplete. To address this, a six-minute ambulation assay, serum creatine kinase, and myoglobinuria were investigated for the mdx mouse, a dystrophinopathy mouse model commonly used in pre-clinical studies. mdx mice ambulated shorter distances than normal controls, a disparity accentuated after mild exercise. An asymmetric pathophysiology in mdx mice was unmasked with exercise, and peak measurements of serum creatine kinase and myoglobinuria were identified. Our data highlights th... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611239 Mon, 12 Dec 2011 05:00:00 +0100 5611239 http://www.medworm.com/index.php?rid=5470307&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013794%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5470307 Thu, 01 Dec 2011 05:00:00 +0100 5470307 http://www.medworm.com/index.php?rid=5470302&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013769%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5470302 Thu, 01 Dec 2011 05:00:00 +0100 5470302 http://www.medworm.com/index.php?rid=5527063&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013666%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5527063 Thu, 24 Nov 2011 05:00:00 +0100 5527063 http://www.medworm.com/index.php?rid=5470306&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013666%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5470306 Thu, 24 Nov 2011 05:00:00 +0100 5470306 http://www.medworm.com/index.php?rid=5650167&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013678%2Fabstract%3Frss%3Dyes Abstract: Congenital myasthenic syndromes (CMS) are heterogeneous disorders in which the safety margin of neuromuscular transmission is compromised by one or more specific mechanisms. Clinical, electrophysiologic, and morphologic studies have paved the way for detecting CMS-related mutations in proteins residing in the nerve terminal, the synaptic basal lamina, and in the postsynaptic region of the motor endplate. The disease proteins identified to date include choline acetyltransferase (ChAT), the endplate species of acetylcholinesterase (AChE), β2-laminin, the acetylcholine receptor (AChR), rapsyn, plectin, Nav1.4, the muscle specific protein kinase (MuSK), agrin, downstream of tyrosine kinase 7 (Dok-7), and glutamine–fructose-6-phosphate transaminase 1 (GFPT1). Myasthenic syndromes a... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650167 Mon, 21 Nov 2011 05:00:00 +0100 5650167 http://www.medworm.com/index.php?rid=5650173&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013344%2Fabstract%3Frss%3Dyes Abstract: Mutations in COL6A1, COL6A2 and COL6A3 genes result in collagen VI myopathies: Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and intermediate phenotypes. At present, none of the existing diagnostic techniques for evaluating collagen VI expression is quantitative, and the detection of subtle changes in collagen VI expression remains challenging.We investigated flow cytometry analysis as a means of quantitatively measuring collagen VI in primary fibroblasts and compared this method with the standard method of fibroblast collagen VI immunohistochemical analysis. Eight UCMD and five BM molecularly confirmed patients were studied and compared to five controls.Flow cytometry analysis consistently detected a reduction of collagen VI of at least 60% in all UCMD case... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650173 Thu, 10 Nov 2011 05:00:00 +0100 5650173 http://www.medworm.com/index.php?rid=5349777&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013551%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349777 Thu, 27 Oct 2011 01:26:02 +0100 5349777 http://www.medworm.com/index.php?rid=5349768&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013526%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349768 Thu, 27 Oct 2011 01:26:02 +0100 5349768 http://www.medworm.com/index.php?rid=5650175&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013393%2Fabstract%3Frss%3Dyes Abstract: The following is a report on a large family with 5 males affected by the X-linked recessive form of Emery–Dreifuss muscular dystrophy with mutation in the STA gene. A detailed longitudinal cardiological evaluation and muscle imaging studies allowed for the assessment of intrafamilial variability of cardiac and muscle involvement.Long term cardiological follow up in the 5 affected males and in 7 female carriers revealed different degrees of severity, ranging from tachycardia–bradycardia syndrome and variable biatrial and left ventricle dilatation, to an episode of isolated symptomatic sustained ventricular tachycardia requiring a device implantation.Muscle imaging in the affected males showed involvement of the soleus and medial head of gastrocnemius on leg muscles and variabl... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650175 Wed, 12 Oct 2011 04:00:00 +0100 5650175 http://www.medworm.com/index.php?rid=5650177&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013368%2Fabstract%3Frss%3Dyes We report a new muscle GSD0 patient, a Japanese girl, who had been suffering from recurrent attacks of exertional syncope accompanied by muscle weakness and pain since age 5years until she died of cardiac arrest at age 12. Muscle biopsy at age 11years showed glycogen depletion in all muscle fibers. Her loss of consciousness was gradual and lasted for hours, suggesting that the syncope may not be simply caused by cardiac event but probably also contributed by metabolic distress. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650177 Wed, 28 Sep 2011 04:00:00 +0100 5650177 http://www.medworm.com/index.php?rid=5650182&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001702%2Fabstract%3Frss%3Dyes The 7th UK SMA researchers meeting at Lake Vyrnwy Hotel, Oswestry UK in October 2010, was focussed on two main aspects of current SMA research: (1) to understand the normal functions of SMN protein () and the mechanism of what goes seriously wrong when SMN levels are reduced to less than 10–15% of normal; and (2) to generate novel treatment options for current SMA patients and preventative options for future sufferers. Possible targets for treatment are shown in . (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650182 Thu, 22 Sep 2011 04:00:00 +0100 5650182 http://www.medworm.com/index.php?rid=5650181&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009199%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650181 Thu, 22 Sep 2011 04:00:00 +0100 5650181 http://www.medworm.com/index.php?rid=5650180&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001465%2Fabstract%3Frss%3Dyes Sixteen doctors and scientists met in Naarden, The Netherlands, from 5 to 7 November 2010 to review current knowledge in the field of pregnancy in women with neuromuscular disease. The group was joined by three patients and their families. Participants were from eight countries, namely Belgium, Finland, France, Germany, Italy, Norway, The Netherlands and the United Kingdom. A variety of disciplines were represented, including neurology, clinical genetics, cardiology, respiratory medicine, obstetrics and gynaecology, epidemiology, ethics, a nurse specialist, and a representative from the ENMC research committee. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650180 Thu, 22 Sep 2011 04:00:00 +0100 5650180 http://www.medworm.com/index.php?rid=5650179&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013125%2Fabstract%3Frss%3Dyes This study describes in detail two standardised protocols for the treadmill exercise of mdx mice and profiles changes in molecular and cellular events after a single 30min treadmill session (Protocol A) or after 4weeks of (twice weekly) treadmill exercise (Protocol B). Both treadmill protocols increased multiple markers of muscle damage. We conclude that a single 30min treadmill exercise session is a sufficient and conveniently fast screening test and could be used in ‘proof-of-concept’ studies to evaluate the benefits of pre-clinical drugs in vivo. Myofibre necrosis, blood serum CK and oxidative stress (specifically the ratio of oxidised to reduced protein thiols) are reliable markers of muscle damage after exercise; many parameters demonstrated high biological variation including cha... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650179 Thu, 22 Sep 2011 04:00:00 +0100 5650179 http://www.medworm.com/index.php?rid=5650176&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013320%2Fabstract%3Frss%3Dyes We report a case of a 37year-old male with multiple acyl-CoA dehydrogenation deficiency (MADD). The patient had suffered from exercise intolerance in his hip and thigh muscles for one year. Then, restriction of carbohydrates for a diet made his symptoms rapidly deteriorate. Blood test revealed compound heterozygosity for two novel missense mutations in the electron transfer flavoprotein dehydrogenase gene (ETFDH), and an abnormal LDH isoenzyme pattern: LDH-1 (60.0%) and LDH-2 (26.0%) predominated with abnormally elevated LDH-1/LDH-2 ratio (2.3), compared with muscle-derived LDH-5 (4.0%). Oral riboflavin treatment significantly improved his exercise intolerance and the LDH profile: LDH-1 (34.4%), LDH-2 (34.9%), LDH-5 (6.9%) and LDH-1/LDH-2 ratio (1.0). The abnormal LDH isoenzyme pattern may... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650176 Thu, 22 Sep 2011 04:00:00 +0100 5650176 http://www.medworm.com/index.php?rid=5650171&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013162%2Fabstract%3Frss%3Dyes Abstract: Autosomal recessive proximal spinal muscular atrophy is caused by deletions in the survival of motor neuron (SMN1) gene, while autoimmune myasthenia gravis is an acquired disorder. An association between these two diseases has not been reported. Our patient with intermediate spinal muscular atrophy (SMA type II) did not need alimentary or respiratory aid until age 51 when he suddenly developed bulbar weakness and respiratory insufficiency. Seropositive myasthenia gravis was confirmed and the corresponding symptoms resolved on treatment. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650171 Thu, 22 Sep 2011 04:00:00 +0100 5650171 http://www.medworm.com/index.php?rid=5650170&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009217%2Fabstract%3Frss%3Dyes We report two patients with facioscapulohumeral muscular dystrophy (FSHD) presenting with atypical clinical features. Both were found to have antibodies to acetylcholine receptor (AChR-abs) and improved with immunosuppression. AChR-abs have also been reported in patients with other genetic myopathies and it is unlikely that the association is coincidental. There is increasing evidence that muscle fibre degeneration can cause innate immune responses (autoinflammation) that may lead to the breaking of immune tolerance and the generation of autoantibodies to muscle proteins. We compare and contrast this process with the pathogenesis of archetypical myasthenia gravis. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650170 Thu, 22 Sep 2011 04:00:00 +0100 5650170 http://www.medworm.com/index.php?rid=5650169&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013356%2Fabstract%3Frss%3Dyes Abstract: Autoimmune myasthenia gravis is a rare condition in children. Identifying antibodies directed against the acetylcholine receptor is helpful in making the diagnosis. However, seronegative cases do exist and need to be distinguished from congenital forms of myasthenia. There is little published experience to inform the judicious management of autoimmune myasthenia gravis in children. In this article, we report our experience in the management of 12 cases of autoimmune myasthenia gravis in children in the modern era of medical immunotherapy and thymectomy. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5650169 Thu, 22 Sep 2011 04:00:00 +0100 5650169 http://www.medworm.com/index.php?rid=5611246&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009175%2Fabstract%3Frss%3Dyes The therapeutic strategies for myotonic dystrophy 2010 workshop was held in Banff, Alberta, Canada, from September 8–10, 2010. This meeting was the second, biennial therapeutic strategy workshop sponsored by the Marigold Foundation and was attended by 52 participants spanning academic and clinical investigators with an interest in myotonic dystrophy (DM), industry participants with an interest in neuromuscular disease and/or rare disorders, and representatives from regulatory and funding agencies. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611246 Thu, 22 Sep 2011 04:00:00 +0100 5611246 http://www.medworm.com/index.php?rid=5611245&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001386%2Fabstract%3Frss%3Dyes An ENMC meeting was held in Naarden, the Netherlands (July 9th–11th 2010) with 12 clinical and basic scientists and three industrial representatives from Europe (France, Belgium, Germany, Italy, Spain, Switzerland, the Netherlands and the UK) and the USA, to discuss their collective experience with the molecular underpinnings, diagnosis, and management of patients with deficiency of coenzyme Q10 (CoQ10). (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611245 Thu, 22 Sep 2011 04:00:00 +0100 5611245 http://www.medworm.com/index.php?rid=5611244&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013319%2Fabstract%3Frss%3Dyes We report an 11-year-old girl affected by sporadic juvenile ALS with a rapid course resulting in tracheostomy after 14months from the onset. Sequencing FUS gene revealed a de novo P525L mutation. Our findings, together with literature data, indicate that this mutation is consistently associated with a specific phenotype characterized by juvenile onset, severe course and high proportion of de novo mutations in sporadic cases. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611244 Thu, 22 Sep 2011 04:00:00 +0100 5611244 http://www.medworm.com/index.php?rid=5611243&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013083%2Fabstract%3Frss%3Dyes We report a novel CRYAB mutation, D109H, associated with posterior polar cataract, myofibrillar myopathy and cardiomyopathy in a two-generation family with five affected individuals. Age of onset, clinical presentation, and muscle abnormalities were very similar to those described in the R120G family. Alpha-B crystallin may form dimers and acts as a chaperone for a number of proteins. It has been suggested that the phenotypic diversity could be related to the various interactions between target proteins of individual mutant residues.Molecular modeling indicates that residues D109 and R120 interact with each other during dimerization of alpha-B crystallin; interestingly, the two substitutions affecting these residues (D109H and R120G) are associated with the same clinical phenotype, thus su... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611243 Thu, 22 Sep 2011 04:00:00 +0100 5611243 http://www.medworm.com/index.php?rid=5611242&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009382%2Fabstract%3Frss%3Dyes Abstract: Drug screening on sodium currents of native myofibers by means of voltage-clamp recordings is predictive of pre-clinical anti-myotonic activity in vivo and ex vivo. By this approach we identified the N-benzylated beta-proline derivative of tocainide (To10) as the most potent use-dependent blocker of Nav1.4 so far. We tested novel analogs with modifications on the pharmacophore groups of To10. The substitution of the proline cycle with less planar piperidine or piperazine rings disclosed the importance of a two carbon atom distance and/or an additional nitrogen atom for potency. Structural changes on the xylididic group corroborated the role of a proper electronic cloud for hydrophobic interactions with the binding site. The N-benzylated moiety lead to a stereoselective behavior o... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611242 Thu, 22 Sep 2011 04:00:00 +0100 5611242 http://www.medworm.com/index.php?rid=5611240&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001350%2Fabstract%3Frss%3Dyes Abstract: Duchenne Muscular Dystrophy is an X-linked disorder that affects boys and leads to muscle wasting and death due to cardiac involvement and respiratory complications. The cause is the absence of dystrophin, a large structural protein indispensable for muscle cell function and viability. The mdx mouse has become the standard animal model for pre-clinical evaluation of potential therapeutic treatments. Recent years have seen a rapid increase in the number of experimental compounds being evaluated in the mdx mouse. There is, however, much variability in the design of these pre-clinical experimental studies. This has made it difficult to interpret and compare published data from different laboratories and to evaluate the potential of a treatment for application to patients. The author... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611240 Thu, 22 Sep 2011 04:00:00 +0100 5611240 http://www.medworm.com/index.php?rid=5611238&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013113%2Fabstract%3Frss%3Dyes We examined the effects of chronic inflammation on the distribution of heat shock protein families 70 and 90 using immunofluorescence and Western blotting, in muscle biopsies from 33 idiopathic inflammatory myopathy patients [aged 26–66 (dermatomyositis), 17–78 (polymyositis) and 57–80 (sporadic inclusion body myositis) years], and seven Duchenne muscular dystrophy patients (aged 3–19years). Our results reveal the multifaceted role played by chaperones in inflammatory muscle tissue. On the one hand, regenerating, atrophic and vacuolated muscle fibers displayed upregulation of both protein families. Higher levels of chaperones in challenged fibers point to the myocyte’s attempt to restore and regenerate. On the other hand, heat shock proteins of the 90 family were strongly upregul... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611238 Thu, 22 Sep 2011 04:00:00 +0100 5611238 http://www.medworm.com/index.php?rid=5611237&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009205%2Fabstract%3Frss%3Dyes Abstract: The purpose of this study was to assess the contractile and non-contractile content in thigh muscles of patients with Duchenne muscular dystrophy (DMD) and determine the relationship with functional abilities. Magnetic resonance images of the thigh were acquired in 28 boys with DMD and 10 unaffected boys. Muscle strength, timed functional tests, and the Brookes Lower Extremity scale were also assessed. Non-contractile content in the DMD group was significantly greater than in the control group for six muscles, including rectus femoris, biceps femoris-long head and adductor magnus. Non-contractile content in the total thigh musculature assessed by MRI correlated with the Brookes scale (rs=0.75) and supine-up test (rs=0.68), as well as other functional measures. An age-related spec... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611237 Thu, 22 Sep 2011 04:00:00 +0100 5611237 http://www.medworm.com/index.php?rid=5611236&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013095%2Fabstract%3Frss%3Dyes We describe a 53-year-old woman with exercise intolerance since childhood, recurrent rhabdomyolysis and late-onset weakness. Muscle biopsy showed amyloid deposits within the blood vessel walls and around muscle fibers. Mutation analysis identified two pathogenic heterozygous mutations in anoctamin 5 and no mutations in dysferlin. To our knowledge this is the first report of muscle amyloidosis in anoctamin 5 muscular dystrophy. This finding suggests that patients with amyloid in muscle should be screened for anoctamin 5 muscular dystrophy. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5611236 Thu, 22 Sep 2011 04:00:00 +0100 5611236 http://www.medworm.com/index.php?rid=5470305&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013101%2Fabstract%3Frss%3Dyes We read with interest the letters of Dubowitz and Stern on their release from muscle cramps with abstinence of coffee . We have no personal experience to contribute, but would like to draw attention to a n=1 double blind study on caffeine intake and cramps we have performed previously . The results suggested that that caffeine can increase susceptibility to muscle cramps. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5470305 Thu, 22 Sep 2011 04:00:00 +0100 5470305 http://www.medworm.com/index.php?rid=5470304&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001726%2Fabstract%3Frss%3Dyes Highlights: ► GNE is the key enzyme of the sialic acid biosynthesis. ► The M712T mutation of the GNE is responsible for the hereditary inclusion body myopathy. ► GNE were localized in the water-soluble, cytosolic fraction. ► M712T GNE was also found in significant amounts in the water-insoluble fraction. ► GNE has an isoelectric point between 5.0 and 5.5. ► M712T GNE has an isoelectric point between 4.8 and 5.4. ► The M712T mutation of the GNE is not involved in the oligomerization of the GNE.Abstract: Hereditary inclusion body myopathy is a neuromuscular disorder characterized by muscle weakness with a late onset and slow progression. It is caused by mutations of the gene encoding UDP-N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase (GNE). One of the most frequent ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5470304 Thu, 22 Sep 2011 04:00:00 +0100 5470304 http://www.medworm.com/index.php?rid=5470303&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009394%2Fabstract%3Frss%3Dyes Abstract: McArdle’s disease is the most common muscle glycogenosis. It is caused by the deficiency of myophosphorylase, encoded by the PYGM gene. We studied 123 patients previously diagnosed with McArdle’s disease and we identified 20 novel mutations (10 missense and 3 nonsense mutations, 3 small deletions, 2 gross deletions and 2 small insertions). Most patients of this cohort belong to Spanish and French populations. This allowed us to determine the differences between the allelic frequencies of the common mutations R50X and G205S of these populations. The R50X has an allelic frequency in this cohort of about 61.7%, being 68.5% in French and 53.7% in Spanish patients. The G205S had a higher allelic frequency in the Spanish (10.2%) than in the French population (3.2%). Moreover, a cli... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5470303 Thu, 22 Sep 2011 04:00:00 +0100 5470303 http://www.medworm.com/index.php?rid=5349776&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001428%2Fabstract%3Frss%3Dyes We describe a patient with this uncommon myopathy, caused by a new p.K1784delK mutation in the MYH7 gene. The patient developed a severe thoracolumbar scoliosis and had scoliosis surgery. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349776 Thu, 22 Sep 2011 04:00:00 +0100 5349776 http://www.medworm.com/index.php?rid=5349775&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001714%2Fabstract%3Frss%3Dyes Abstract: Oculopharyngeal muscular dystrophy is a neuromuscular disease usually presenting in the 5th or 6th decades of life with a dominant inheritance pattern. In almost all cases the cause of the disease is the expansion of a DNA repeat sequence containing GCG and GCA codons in exon 1 of the PABPN1 gene from 10 to between 12 and 17 repeats. However one case has been previously reported without the gene expansion but instead with a c.35G>C missense mutation converting a glycine codon to an alanine and resulting in a sequence of 13 contiguous alanine codons, thus mimicking the effect of the common expansion mutation. Here we report two further cases of OPMD caused by the c.35G>C point mutation. Clinical and pedigree data indicate the usual OPMD dominant inheritance pattern. (Source: Neuro... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349775 Thu, 22 Sep 2011 04:00:00 +0100 5349775 http://www.medworm.com/index.php?rid=5349774&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001738%2Fabstract%3Frss%3Dyes Highlights: ► The mitochondrial phosphate carrier SLC25A3 is expressed in tissue specific isoforms by alternative splicing. ► We identified a novel mutation of the SLC25A3 in three children with a neonatal onset of cardiomyopathy and myopathy. ► The mutation affects the alternatively spliced exon 3A specific for heart and muscle. ► It broadens the clinical spectrum of this disease since patients may survive into adulthood.Abstract: In a family three children presented with severe neonatal lactic acidosis, hypertrophic cardiomyopathy and generalised muscular hypotonia. One child died in infancy, two survived a clinically severe neonatal period. At an age of 9 and 17years, respectively, they present with exercise intolerance, proximal muscle weakness, non-progressive hypertrophic car... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349774 Thu, 22 Sep 2011 04:00:00 +0100 5349774 http://www.medworm.com/index.php?rid=5349773&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661100174X%2Fabstract%3Frss%3Dyes We report the outcome of the ambulatory status of a patient with DMD treated with daily steroid therapy and orthoses. This male patient was diagnosed with DMD at age of 2. He has been treated with daily steroids since age 7years. He lost the ability to arise from the floor and walk up steps at age 14 and lost ambulation by age 16. He was fitted with orthoses at age 16 following surgical correction of his lower extremity contractures and regained independent ambulation. At age 20, he was able to stand independently in his orthoses and take steps with moderate support. We conclude that a combination of daily steroids and orthoses prolongs ambulation beyond that of the natural history DMD. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349773 Thu, 22 Sep 2011 04:00:00 +0100 5349773 http://www.medworm.com/index.php?rid=5349772&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611009187%2Fabstract%3Frss%3Dyes Abstract: To describe muscle involvement on whole-body MRI scans in adult patients at different stages of late-onset Pompe disease. Twenty patients aged 37 to 75 were examined. Five were bedridden and required ventilatory support. Axial and coronal T1 turbo-spin-echo sequences were performed on 1.5T or 3T systems. MRI was scored for 47 muscles using Mercuri’s classification. Whole-body scans were obtained with a mean in-room time of 29min. Muscle changes consisted of internal bright signals of fatty replacement without severe retraction of the muscles’ corpus. Findings were consistent with previous descriptions of spine extensors and pelvic girdle, but also provided new information on recurrent muscle changes particularly in the tongue and subscapularis muscle. Moreover thigh involveme... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349772 Thu, 22 Sep 2011 04:00:00 +0100 5349772 http://www.medworm.com/index.php?rid=5349771&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001696%2Fabstract%3Frss%3Dyes Abstract: Dystroglycanopathies are a heterogeneous group of muscular dystrophies with autosomal recessive inheritance characterized by abnormal glycosylation of alpha-dystroglycan. The most severe phenotypes are Walker-Warburg Syndrome (WWS) and muscle-eye-brain disease (MEB) presenting with lissencephaly type II (LIS II) and in which muscular dystrophy is associated with mental retardation and eye abnormalities. To date, six distinct genes, POMT1, POMT2, POMGNT1, FKTN, FKRP, LARGE and recently in one case DPM3, have been shown to be involved in dystroglycanopathies. Genomic sequencing alone is still frequently used for diagnosis purpose, not allowing detection of intragenic rearrangements at the heterozygous state contrarily to RNA analysis, quantitative PCR and CGH array analysis. These ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349771 Thu, 22 Sep 2011 04:00:00 +0100 5349771 http://www.medworm.com/index.php?rid=5349770&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001441%2Fabstract%3Frss%3Dyes In conclusion, we have excluded these five genes as common causes of muscular dystrophy in Australia. Patients with reducing body myopathy may be initially diagnosed as muscular dystrophy. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349770 Thu, 22 Sep 2011 04:00:00 +0100 5349770 http://www.medworm.com/index.php?rid=5349769&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001507%2Fabstract%3Frss%3Dyes Abstract: This review focuses on the “pure” hereditary peripheral neuropathies where peripheral nerve disease is the main manifestation and does not address neurodegenerative disorders associated with but not dominated by peripheral neuropathy. Aetiologies of childhood-onset peripheral neuropathies differ from those of adult-onset, with more inherited conditions, especially autosomal recessive. Charcot–Marie-Tooth disease is the commonest neuromuscular disorder. The genetic labels of CMT (Charcot–Marie-Tooth) disease types 1–4 are the preferred sub-type terms. Clinical presentations and molecular genetic heterogeneity of hereditary peripheral neuropathies are diverse. For most patients worldwide, diagnostic studies are limited to clinical assessment. Such markers which could be u... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5349769 Thu, 22 Sep 2011 04:00:00 +0100 5349769 http://www.medworm.com/index.php?rid=5211790&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101323X%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211790 Tue, 13 Sep 2011 03:40:12 +0100 5211790 http://www.medworm.com/index.php?rid=5211789&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013228%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211789 Tue, 13 Sep 2011 03:40:12 +0100 5211789 http://www.medworm.com/index.php?rid=5211788&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611001799%2Fabstract%3Frss%3Dyes (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211788 Tue, 13 Sep 2011 03:40:12 +0100 5211788 http://www.medworm.com/index.php?rid=5211787&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013071%2Fabstract%3Frss%3Dyes Mutations in the skeletal muscle α-actin gene (ACTA1) cause a range of pathologically-defined congenital myopathies. Most patients have dominant mutations and experience severe skeletal muscle weakness, dying within one year of birth. Transgenic mice expressing dominant mutant ACTA1(D286G) were created. These Tg(ACTA1)D286G mice were less active than wildtypes. Their skeletal muscles were significantly weaker and showed various pathological lesions reminiscent of human patients, however they had a normal lifespan. Mass spectrometry revealed that Tg(ACTA1)D286G skeletal muscle contained ∼25% mutant protein. Tg(ACTA1)D286G mice were crossed with hemizygous Acta1+/− knock-out mice to generate Tg(ACTA1)D286G+/+·Acta1+/− offspring: homozygous for the transgene and hemizygous for endogen... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211787 Tue, 13 Sep 2011 03:40:12 +0100 5211787 http://www.medworm.com/index.php?rid=5211786&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101306X%2Fabstract%3Frss%3Dyes Recessive mutations in ANO5 were recently found to cause LGMD2L (MIM 611307) and MMD3 (MIM613319) myopathies. LGMD2L is characterized by late-onset progressive weakness of proximal limb muscles with prominent quadriceps atrophy and high serum Creatine Kinase, while the MMD3 distal myopathy is characterize by initial asymmetrical distal weakness in particular of calves muscles. A total of 13 published and unpublished ANO5 mutations were uncovered to date, consisting of 7 missense mutations, 2 nonsense mutations, 1 splice site mutation, 1 single base pair duplication, 1 small insertion/deletion, and 1 large deletion of two exons. We demonstrated that one splice site mutation introduces a premature termination codon and consequently triggered nonsense-mediated mRNA decay (NMD), which supporte... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211786 Tue, 13 Sep 2011 03:40:12 +0100 5211786 http://www.medworm.com/index.php?rid=5211785&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013058%2Fabstract%3Frss%3Dyes In conclusion, we provide proof of a new pattern of inheritance of LGMD2A in four unrelated families. This dominantly inherited form of calpainopathy seems to be much milder, and presents later in life than patients with recessive LGMD2A. The disorder could be named as the seventh dominantly inherited LGMD, i.e. LGMD1G. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211785 Tue, 13 Sep 2011 03:40:12 +0100 5211785 http://www.medworm.com/index.php?rid=5211784&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013046%2Fabstract%3Frss%3Dyes Limb Girdle Muscular Dystrophy Type 2B (LGMD2B) and Miyoshi Myopathy (MM) are caused by mutations in the dysferlin gene, but the role of dysferlin in healthy muscle and the changes that occur when it is mutated or absent are poorly understood. Previous work supported a role for dysferlin in sarcolemmal repair following laser wounding or other in vitro injuries. We study the response of A/J mice, which lack dysferlin, to injury by large-strain lengthening contractions in vivo. We find that dysferlin promotes normal recovery from this physiological injury but is not necessary for sarcolemmal repair. Consistent with this, immunofluorescence microscopic studies of healthy muscle, that we fixed and treated in a hot, mildly acidic solution to expose dysferlin’s epitopes, show that dysferlin is... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211784 Tue, 13 Sep 2011 03:40:12 +0100 5211784 http://www.medworm.com/index.php?rid=5211783&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013034%2Fabstract%3Frss%3Dyes We report on the generation of a transgenic mouse model carrying D4Z4 units from a patient allele that expresses DUX4 and recapitulates all genetic, epigenetic and DUX4 expression attributes of FSHD, including high DUX4 expression levels in the germ line and the characteristic bursts of DUX4 expression in 1:1000 muscle nuclei. These transgenic mice therefore represent a faithful animal model for FSHD and will be a unique model to study the molecular mechanisms underlying FSHD and to test new therapeutic intervention strategies. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211783 Tue, 13 Sep 2011 03:40:12 +0100 5211783 http://www.medworm.com/index.php?rid=5211782&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013022%2Fabstract%3Frss%3Dyes Facioscapulohumeral muscular dystrophy (FSHD) is a common muscular dystrophy characterized by progressive and often asymmetric weakness and wasting of facial, shoulder girdle and upper arm muscles. FSHD is caused by a local the chromatin relaxation of the D4Z4 repeat array which results in the transcriptional derepression of the DUX4 retrogene. The chromatin relaxation can be initiated by contraction of the D4Z4 repeat array (FSHD1), or by a yet unknown chromatin modifier (FSHD2), but only leads to detectable levels of DUX4 when the repeat array is localized on a specific permissive genetic background of chromosome 4q. Chromatin relaxation on non-permissive 4q or 10q chromosomes does not cause FSHD. By detailed D4Z4 sequence analysis of permissive and non-permissive haplotypes we identifie... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211782 Tue, 13 Sep 2011 03:40:12 +0100 5211782 http://www.medworm.com/index.php?rid=5211781&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013010%2Fabstract%3Frss%3Dyes Hereditary inclusion body myopathy (HIBM) is a unique neuromuscular adult onset disease characterized by slowly progressive distal and proximal muscle weakness, caused by missense recessive mutations in GNE, the gene coding for UDP-GlcNAc 2-epimerase/ManNAc kinase. Recently zebrafish have been recognized as a potent tool for the study of development and of various human disorders, such as neuromuscular disease. In particular, the GNE gene and protein are well conserved between zebrafish and mammals, and especially with the human ortholog. In order to unravel new insights in the pathophysiology of HIBM we are using the zebrafish system towards the elucidation of the fundamental mechanisms of GNE in normal muscle and in disease. Through in situ hybridization of whole mounted embryos we have ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211781 Tue, 13 Sep 2011 03:40:12 +0100 5211781 http://www.medworm.com/index.php?rid=5211780&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611013009%2Fabstract%3Frss%3Dyes Autophagy is crucial in the turnover of cell components both in constitutive conditions and in response to starvation. Defects of this degradative system play a role in various diseases, but little is known about autophagy in muscular dystrophies. Mutations in any of the three genes coding for collagen VI cause several muscle diseases in humans, including Ullrich congenital muscular dystrophy (UCMD), Bethlem myopathy (BM) and Congenital myosclerosis. Collagen VI null (Col6a1−/−) mice display an early onset myopathic phenotype characterized by organelle defects, mitochondrial dysfunction and spontaneous apoptosis, leading to myofiber degeneration. We found that persistence of abnormal organelles and apoptosis are caused by defective autophagy. Indeed, skeletal muscles of Col6a1−/− m... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211780 Tue, 13 Sep 2011 03:40:12 +0100 5211780 http://www.medworm.com/index.php?rid=5211779&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012995%2Fabstract%3Frss%3Dyes Centronuclear myopathies (CNMs) are congenital muscle disorders, described for the first time in 1966 by Spiro, characterized morphologically by small fibers with centrally-positioned nuclei. Although, at present, mutations in at least three genes (Myotubularin I, Amphiphysin II/Bin1 and Dynamin-2) have been found in patients little is known about the detailed mechanism causing the pathology. In particular, the cytoskeletal anomalies leading to the mis-positiong of nuclei within the fibers remain elusive, even though no muscle degeneration is associated with these diseases. The relevance of a physiologic model, where it would be possible to follow the nuclear positioning process and manipulate protein expression and function, is glaring. Bearing this in mind, we set up a 3D-like cellular m... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211779 Tue, 13 Sep 2011 03:40:12 +0100 5211779 http://www.medworm.com/index.php?rid=5211778&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012983%2Fabstract%3Frss%3Dyes We report clinical, muscle MR imaging and histopathological findings of 5 patients from 4 families presenting with RYR1-related exertional myalgia and rhabdomyolysis. Patients (2 females, 3 males) are currently between 10 and 52years of age and presented from between 3 to 15years of age with recurrent episodes of exertional myalgia and/or rhabdomyolysis. During or immediately after those episodes, serum creatine kinase (CK) levels were markedly increased and ranged from 1551IU/l to 110200IU/l. Preceding motor development had been invariably normal. Except one case with mild proximal weakness, patients were normally strong or even particularly sporty with often prominent muscle bulk. Inconsistent additional features included increased tendency to sweat and muscle stiffness prompted by cold.... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211778 Tue, 13 Sep 2011 03:40:12 +0100 5211778 http://www.medworm.com/index.php?rid=5211777&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012971%2Fabstract%3Frss%3Dyes The aquaporin 4 (AQP-4) is homologous intrinsic membrane protein that functions as highly selective water channels. However its physiological function in skeletal muscle sarcolemma is unclear. To investigate the expression of AQP-4 by differentiation of C2C12 myoblasts into myotubes, we compared the expression of aquaporin 4 between C2C12 myoblasts and myotubes. Cultured myoblasts from the C2C12 mouse cell line were isolated at the different stages of myogenesis (myoblasts and myotubes). Immunocytochemical staining was performed using polyclonal rabbit antibodies against AQP-4 on C2C12 myoblasts and myotubes. The expression of AQP-4 by Western blot analysis was also determined on them. Immunocytochemical analysis did not reveal a significant difference of AQP-4 expression, but western blot... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211777 Tue, 13 Sep 2011 03:40:12 +0100 5211777 http://www.medworm.com/index.php?rid=5211776&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101296X%2Fabstract%3Frss%3Dyes A major limit of using myoblast transplantation in cell therapy for muscular dystrophies is a massive cell death and a differentiation of the remaining cells, shortly after transplantation into the recipient’s muscle. The reason for that remains largely unknown. Nevertheless, we recently showed that stimuli that delay differentiation improve efficacy of myoblast transfer therapy in vivo. Then, a better dissection of the myoblast differentiation process in terms of gene expression and microRNA could provide new clues for potential targets. This prompted us to study simultaneously gene expression, correlating with miRNA expression, comparing undifferentiated versus differentiated human myogenic cells. We used human myoblasts (CHQ cells) before and after in vitro differentiation. Total RNA ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211776 Tue, 13 Sep 2011 03:40:12 +0100 5211776 http://www.medworm.com/index.php?rid=5211775&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012958%2Fabstract%3Frss%3Dyes Duchenne muscular dystrophy (DMD) is a severe X-linked muscle-wasting disease which results from a mutation in the gene encoding dystrophin. Dystrophin absence in DMD patients causes sarcolemma inestability leading to frequent muscle fiber damage and repair. One strategy to prevent mechanical stress-induced damage in dystrophic muscle is to promote muscle fiber hypertrophy and regeneration, processes regulated by endogenous growth factors, most notably Insulin-like growth factor-1 (IGF-1) and myostatin. Previously we showed that IGF-1 induces calcium release from intracellular stores that activates calcium dependent signaling pathways and induces myostatin mRNA expression suggesting a negative feedback in the pathways that regulates myoblast proliferation and differentiation. MSTN, a membe... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211775 Tue, 13 Sep 2011 03:40:12 +0100 5211775 http://www.medworm.com/index.php?rid=5211774&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012946%2Fabstract%3Frss%3Dyes In this study, combined molecular and immunocytochemistry methods were used to investigate the expression profile of sarcomeric genes and proteins during myoblast proliferation and differentiation in human muscle cell line. We observed the expression of a panel of sarcomeric gene transcripts together with the early expression of a number of the investigated sarcomeric proteins at the proliferated myoblasts. In addition, after 6days of differentiation, the majority of cells expressed all the investigated sarcomeric proteins. The results presented here provide novel insights into the sequential onset of the sarcomeric genes and proteins and support the previous notion that non-committed stem cells exist in the adult muscle satellite cells during myogenesis in vitro. In addition, our study de... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211774 Tue, 13 Sep 2011 03:40:12 +0100 5211774 http://www.medworm.com/index.php?rid=5211773&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012934%2Fabstract%3Frss%3Dyes Muscular dystrophies and congenital myopathies often produce a similar clinical picture of muscle weakness and atrophy. Population studies that include muscular dystrophies and congenital myopathies are rare, it is not well studied how common these disorders are. The aim of the study was to identify all the patients diagnosed with muscular dystrophies and congenital myopathies in childhood over a thirty year period, between 1979 and 2009. The geographic area studied was the region of western Sweden. We analyzed registers from local and regional pediatric hospitals and local and regional child rehabilitations, registers of muscle biopsies, neurophysiologic examinations and genetic analyses. The total number of identified cases were 221 patients. 131 patients with muscular dystrophies that w... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211773 Tue, 13 Sep 2011 03:40:12 +0100 5211773 http://www.medworm.com/index.php?rid=5211772&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012922%2Fabstract%3Frss%3Dyes The University of Ferrara, partner in the European Project NMD CHIP, has been involved in the design and validation of the CGH array for 50 known NMD (neuromuscular disorders) disease genes. We hybridized on this chip samples from our cohort of patients with dystrophinopathies and all the dystrophin rearrangements (deletion and duplication) have been detected independently of the size and of the localization in the genomic region. Moreover we selected 19 patients with a clinical and immunohistochemical diagnosis of myofibrillar myopathy (MFMs) negative at the sequence analysis of ZASP, MYOT, DESMIN and CRYAB genes; we did not find gross rearrangements in the MFMs known genes present on the array (ZASP, MYOT, DESMIN, CRYAB, FHL1, FILAMIN C and BAG3). The analysis revealed several CNVs in ot... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211772 Tue, 13 Sep 2011 03:40:12 +0100 5211772 http://www.medworm.com/index.php?rid=5211771&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012910%2Fabstract%3Frss%3Dyes The peroxisome proliferator-activated receptor γ coactivator 1alpha or PGC-1alpha is a transcriptional coactivator of nuclear receptors which regulates mitochondrial function in many tissues, including the skeletal muscle. This factor mediates the response of muscle to motor neuron activity, and is able to stabilize the neuromuscular junction (NMJ) via increased expression of some post-synaptic genes. It also improves the dystrophic phenotype when over-expressed in mdx mice, the model for Duchenne muscular dystrophy. The aim of this project is to elucidate the exact mechanism of this phenomenon that still remains unclear. We have at our disposal transgenic mice that over-express PGC-1alpha only in the muscle. We compared those transgenic mice with the wild-type animals in terms of neuromu... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211771 Tue, 13 Sep 2011 03:40:12 +0100 5211771 http://www.medworm.com/index.php?rid=5211770&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012909%2Fabstract%3Frss%3Dyes The amyloid-beta (Abeta) peptide is derived from the sequential cleavage of amyloid-beta precursor protein (AbetaPP) by two enzymes, the β- and γ-secretases. The major β-secretase, identified as the novel transmembrane aspartic protease Beta site APP-cleaving enzyme 1 (BACE1), mediates the primary amyloidogenic cleavage of AbetaPP and initiates the production of Abeta. It has been implicated in the proteolytic processing of another substrate, namely β galactoside alpha 2,6 sialyltransferase 1 (ST6Gal1) which is the major α2,6-sialyltransferase responsible for the broad synthesis of glycoproteins and glycolipids. We analyzed the effect of overexpression of AbetaPP on expression and secretion of ST6Gal1 in skeletal muscle cells by inducing overexpression of wild-type full-length 751-Abe... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211770 Tue, 13 Sep 2011 03:40:12 +0100 5211770 http://www.medworm.com/index.php?rid=5211769&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012892%2Fabstract%3Frss%3Dyes Neck muscles of the horses used in the daily life of the horses, and the splenius muscle undergoes age-related changes associated with postural and phasic muscles. The sonographic documentation of these changes as well as their effect on the muscle activity remains unknown. Investigating muscle activity, size and volume as well as sonographic muscle characteristics and the area changes of the splenius muscle during flexion-extension neck exercises. Surface electromyography activity of the splenius muscle was measured in 6 horses (3-mature horse and 3 aged) without signs of neck pain during flexion and extension of the head/neck unit as well as in a neutral position. Electrodes were placed over both splenius muscles at the level of C2. The measurements were taken by use of an EMG telemetric... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211769 Tue, 13 Sep 2011 03:40:12 +0100 5211769 http://www.medworm.com/index.php?rid=5211768&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012880%2Fabstract%3Frss%3Dyes In this study age related changes of the splenius muscle during different neck exercises were investigated, as it is representative for spinal musculature. Investigating splenius muscle activity during stretching and flexing of the head/neck complex and comparing it to the neutral position in mature and aged horses. Kinematics and surface electromyography were measured in 6 horses (3-mature horse, 8–15years and 3 aged, >20years) without signs of neck pain or clinical neurological impairments. Electrodes were placed over both splenius muscles at the level of C2. The measurements were taken by use of an EMG telemetric system with a sample frequency 1.2kHz. Twenty-four reflective skin markers were attached to each horse using adhesive tape. Eighteen markers were placed on left and right sid... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211768 Tue, 13 Sep 2011 03:40:12 +0100 5211768 http://www.medworm.com/index.php?rid=5211767&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012879%2Fabstract%3Frss%3Dyes A 51year old woman presented with a four year history of slowly progressive dysphagia, dysarthria, mild facial and proximal muscle weakness. Her CK was elevated to >800U/l and EMG demonstrated pathological spontaneous activity in one iliopsoas muscle only, while other muscles were found normal. As work-up for motoneuron disease, amyloidosis and scleroderma did not provide a diagnosis, a deltoid muscle biopsy was taken to rule out myositis. Histology showed a marked, selective type II fibre atrophy without further relevant changes. Work-up for associated disorders revealed bilateral invasive ductal mammary carcinoma. After surgery, radio- and chemotherapy, dysphagia and dysarthria improved. The CK fell to about 400U/l. Serum screening for paraneoplasic diseases associated (’onconeural’)... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211767 Tue, 13 Sep 2011 03:40:12 +0100 5211767 http://www.medworm.com/index.php?rid=5211766&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012867%2Fabstract%3Frss%3Dyes In this study we investigated the effect of low-dose atorvastatin administration in vivo to get insight into the early steps of statin induced myopathy. Male Wistar rats were dosed daily with 10 mg/kg/day atorvastatin (n=26) or vehicle (n=12) by oral gavage for 12days. Total body weight and weight of M. biceps femoris (type IIB fibers), M. soleus (type I fibers) and M. extensor digitorum longus (mixed fiber type) did not change during statin administration; furthermore, histological differences could not be detected. Transcript levels of the investigated parameters representing protein degradation, inflammation, apoptosis, matrix metalloproteinases and their tissue inhibitors were unchanged when analyzed by qPCR in slow oxidative soleus and fast glycolytic biceps femoris muscles after ator... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211766 Tue, 13 Sep 2011 03:40:12 +0100 5211766 http://www.medworm.com/index.php?rid=5211765&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012855%2Fabstract%3Frss%3Dyes Critical illness myopathy (CIM) is a serious complication of critical illness without effective treatment and characterized by general paresis and respiratory failure. Recovery from the acute phase is slow and requires a long rehabilitation. Immobilization together with a disordered carbohydrate metabolism have been regarded as risk factors for CIM. We asked whether electrical muscle stimulation would be beneficial. In five critical ill patients (SAPS score>8) we performed two daily sessions of low frequency electrical muscle stimulation on one Vastus lateralis for 12days, while the other leg received routine care. Currents applied (Muskelaktiv®, Schwa-Medico) were adjusted to the point of visible or palpable muscle contraction. After 12days muscle biopsies were performed on both legs. Sp... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211765 Tue, 13 Sep 2011 03:40:12 +0100 5211765 http://www.medworm.com/index.php?rid=5211764&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012843%2Fabstract%3Frss%3Dyes Neuraminidase-1 (Neu1) regulates the catabolism of sialoglycoconjugates in lysosomes. Congenital Neu1 deficiency in children is the basis of sialidosis, a neurosomatic disorder whose symptoms include hypotonia, muscle weakness and osteoskeletal deformities. Mice with Neu1 deficiency develop an atypical form of muscle degeneration characterized by abnormal fibroblast proliferation and expanded extra cellular matrix (ECM), with invasion of muscle fibers by ECM components, cytosolic fragmentation, vacuolar formation and muscle atrophy. The aim of this study is to investigate the role of Neu1 on muscle regeneration process. Experimentally, inflammatory response, muscle fiber maturation and fibrosis development during the muscle regeneration process induced by intramuscular administration of ca... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211764 Tue, 13 Sep 2011 03:40:11 +0100 5211764 http://www.medworm.com/index.php?rid=5211763&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012831%2Fabstract%3Frss%3Dyes In conclusion, while the Omega-3 is known to be effective in attenuating the muscle atrophy induced by sepsis and cancer, we were unable to demonstrate the same beneficial effect on muscle atrophy induced by DEXA. The identification of nutritional supplements that are able to alleviate the side effects of steroids on skeletal muscle, i.e. muscle atrophy, and the potential molecular pathways involved in this process, would be very important in the medical practice. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211763 Tue, 13 Sep 2011 03:40:11 +0100 5211763 http://www.medworm.com/index.php?rid=5211762&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101282X%2Fabstract%3Frss%3Dyes In obesity, excess fat accumulates in ectopic tissues, such as skeletal muscle, which may lead to Insulin Resistance (IR) and type 2 Diabetes. The purpose of this study was to describe histological alterations and mitochondrial abnormalities in muscle biopsies of morbid obesity patients and to correlate them with the development of IR. Prospective recruitment of morbidly obese patients undergoing bariatric surgery, with deltoid muscle biopsies collection. IR was considered if HOMA ⩾3. We evaluated lipid and glycogen content, mitochondrial changes (presence of RRF and COX negative fibers) and the morphometry of muscle fibers by histochemistry and histoenzymatic techniques (HE, TG, PAS, Oil Red, COX-SDH and ATPase 9.4). Mitochondrial function (citrate synthase, and respiratory chain I-IV c... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211762 Tue, 13 Sep 2011 03:40:11 +0100 5211762 http://www.medworm.com/index.php?rid=5211761&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012818%2Fabstract%3Frss%3Dyes Many diagnostic tests and research protocols, such as sequencing large genes, require the analysis of tissue RNA, which is highly vulnerable to degradation. Extraction and analysis of RNA from frozen muscle is a specialised technique and it is often necessary to transport frozen tissue over large distances to access testing. Such transport is expensive and biopsies may be lost from thawing if there are transport delays. RNAlater® (Invitrogen Life Technologies, Carlsbad, CA) is a solution designed to preserve tissue RNA in freshly harvested tissue. Poor tissue penetration is an expected difficulty when using RNAlater® with tissues already frozen. We investigated whether an adapted RNAlater® protocol could adequately preserve mRNA in biopsies already frozen to allow transport of samples o... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211761 Tue, 13 Sep 2011 03:40:11 +0100 5211761 http://www.medworm.com/index.php?rid=5211760&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012806%2Fabstract%3Frss%3Dyes Muscle magnetic resonance imaging (MRI) is used in the diagnosis of inherited myopathies. Muscle weakness is often diffuse but data in the literature is mostly limited to lower limbs (sequential MRI). We evaluated the technical feasibility and diagnostic correlation of a paediatric/adult Whole-Body MRI (WB-MRI) protocols using a 1.5-Ts MRI system in 105 patients with known or suspected inherited neuromuscular disorder and 11 relatives. All 116 individuals were examined, even those with severe limb retractions, mechanically ventilated or with metallic implants. WB-MRI was abnormal in 67% of patients and in 27% of non complaining relatives. Pathogenic mutations were identified in 35% of patients, all of them with abnormal MRI findings: COL6A1–3 (14), RYR1 (4), LMNA (4), TPM2 (4), DNM2 (2),... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211760 Tue, 13 Sep 2011 03:40:11 +0100 5211760 http://www.medworm.com/index.php?rid=5211759&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101279X%2Fabstract%3Frss%3Dyes Selection for high protein content and body weight in the Technical University of Berlin resulted in a mouse strain, which showed a hypermuscular character similar to the KO mutant of myostatin, the growth inhibitor of skeletal muscle. The genetical mapping of the Hungarian subpopulation of the Compact strain revealed that the phenotype was not entirely monogenic. In addition to the 12bp deletion in the myostatin propeptide, several loci e.g. androgen receptor gene region were proposed to modulate the Compact phenotype. So far, no data have proven the effect of androgens, however, a glycolytic hyperplastic muscle phenotype with only a moderate hypertrophy was described for Compact mouse. Our aim was to investigate fiber type composition as well as fiber size distribution of the Compact hin... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211759 Tue, 13 Sep 2011 03:40:11 +0100 5211759 http://www.medworm.com/index.php?rid=5211758&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012788%2Fabstract%3Frss%3Dyes In our large neuromuscular outpatient clinic myalgia associated with weakness is a frequent complaint mostly not caused by neuromuscular diseases or statins. Myopathy associated with vitamin D deficient osteomalacia presents as a proximal weakness with pain and type II fibre atrophy. Further, eight patients with statin-induced myopathy being vitamin D deficient were reported. The mechanisms are unclear. There are conflicting results about the expression of vitamin D receptor (VDR) in skeletal muscle. In a cohort of 102 adult patients who presented with diffuse myalgia, mild proximal weakness, two- to fivefold elevated creatine kinase levels or a combination of those, we prospectively measured serum calcium, phosphate, alkaline phosphatase, and 25 (OH) vitamin D concentration. Patients were... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211758 Tue, 13 Sep 2011 03:40:11 +0100 5211758 http://www.medworm.com/index.php?rid=5211757&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012776%2Fabstract%3Frss%3Dyes This factsheet was produced after several requests from families and individuals affected by neuromuscular conditions. They wished to explore if organ and tissue donation was something they could do. With publicity regarding the lack of donor organs, this group wanted advice on their suitability to help others if their lives were shortened either by their disease or other causes. They also wished to know whether their neuromuscular condition specifically excluded them from donating organs. With the help of the local Donor Co-ordinator and UKT, the national transplant body based in Bristol, we devised this factsheet. The information in the factsheet tells patients and families that they can potentially donate, whatever the condition. It also provides information on who to ask for advice and... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211757 Tue, 13 Sep 2011 03:40:11 +0100 5211757 http://www.medworm.com/index.php?rid=5211756&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012764%2Fabstract%3Frss%3Dyes In recent years the number of clinical trials on neuromuscular diseases (NMD) has increased. Safely keeping patients data became necessary. We designed a study to assess the knowledge of the general population about NMD. People from three neighborhoods (H, M and L) of a city were interviewed. Phone calls were made by a trained medical student. (A) Do you know someone with a muscle disease? (B) If yes, what is his or her clinical condition? (C) Do you know the diagnosis? (D) Have you ever heard of Duchenne muscular dystrophy (DMD)? (E) Do you access internet? Among 124 individuals, 72% of H, 34% of M and 7% of L graduated from university; 12% of H, 12% of M and 13% of L know someone with a muscle disease (md); 80% of H, 60% of M and 17% of L know the diagnosis of the patients. Twenty-five p... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211756 Tue, 13 Sep 2011 03:40:11 +0100 5211756 http://www.medworm.com/index.php?rid=5211755&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012752%2Fabstract%3Frss%3Dyes Filaminopathy is a subtype of myofibrillar myopathies (MFM) caused by filamin C mutations. Massive protein aggregation in muscle fibres is a histopathological hallmark in this disease and seems to be important in pathogenesis. The aim of our study (funded by DFG FOR1228) was to unravel the composition of these aggregates by mass spectrometric-based proteomic analysis. Protein aggregates were collected from muscle biopsies of five filaminopathy patients by laser microdissection (Leica LMD 6500). Patients’ muscle fibres not showing aggregates and muscle fibres of healthy persons served as controls. Samples were solubilised, digested with trypsin and peptides analysed by nanoLC electrospray MS/MS using a Thermo LTQ Orbitrap Velos mass spectrometer. Identified proteins of interest were furth... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211755 Tue, 13 Sep 2011 03:40:11 +0100 5211755 http://www.medworm.com/index.php?rid=5211754&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012740%2Fabstract%3Frss%3Dyes Myofibrillar myopathies (MFM) are characterized by disintegration of myofibrils and abnormal protein aggregation in muscle fibres. Filaminopathy is a subtype of MFM associated with mutations in FLNC, encoding filamin C. The aims of our studies (funded by DFG FOR1228) were to refine the phenotype of filaminopathy, to get new insights in pathogenesis and to characterize the effects of filamin C mutations in murine myoblast cell lines. We evaluated 66 filaminopathy patients. Double immunofluorescence studies were performed to examine the expression and distribution of Hsp20, Hsp22, Hsp27, Hsp60, Hsp70, CHIP, BAG3, LC3, LAMP2, p53, p62, HDAC6, VCP, ubiquitin, UBB+1, 20S proteasome, UCHL1 and Urm1. Transfection studies (p.V933_T933del and p.W2710X mutation) were performed in C2 and C2C12 cells.... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211754 Tue, 13 Sep 2011 03:40:11 +0100 5211754 http://www.medworm.com/index.php?rid=5211753&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012739%2Fabstract%3Frss%3Dyes In this study, we firstly reproduced mutation dependent pathological changes in vivo mimicking to the skeletal muscle from patients with MYOT mutations. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211753 Tue, 13 Sep 2011 03:40:11 +0100 5211753 http://www.medworm.com/index.php?rid=5211752&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012727%2Fabstract%3Frss%3Dyes We report herein two unrelated patients with different novel BAG3 mutation. Patient 1 is a 7month-old boy with carrying a heterozygous p.Ala558Val mutation showed reduced fetal movement and was born at 38weeks of gestation with severe asphyxia. He manifested hypotonia, joint contractures and severe respiratory insufficiency which required artificial ventilation. Serum CK levels shifted 200 to 3000 U/L and transient ventricular enlargement were seen. Muscle biopsy showed many cytoplasmic bodies and disorganization of myofibrils. Patient 2 is a 67-year-old woman with a heterozygous p.261–265RAASP deletion. From 60years of age, photophobia, diplopia, ptosis, ophthalmoplesia and weakness of orbicularis oculi and lower limb muscles gradually appeared. Myasthenia gravis were excluded by electr... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211752 Tue, 13 Sep 2011 03:40:11 +0100 5211752 http://www.medworm.com/index.php?rid=5211751&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012715%2Fabstract%3Frss%3Dyes Currently, FHL1 gene mutations have been detected in reducing body myopathy, X-linked myopathy with postural muscle atrophy (XMPMA), Emery–Dreifuss muscular dystrophy, X-linked scapuloperoneal myopathy, rigid spine syndrome, and in a single family with contractures, rigid spine and cardiomyopathy. The C224W mutation is known to cause XMPMA, but up to now no protein aggregation in this disease is reported. Two brothers reporting first symptoms at 20 and 41years of age presenting with a scapuloperoneal phenotype, rigid spine, atrophy of shoulder girdle and distal leg muscle, and myalgia. CK was elevated 8 to 10-fold. Using genotyping and phenotyping (mutational analysis and muscle histopathology) we characterized two affected brothers. Both brothers displayed a more severe XMPMA phenotype.... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211751 Tue, 13 Sep 2011 03:40:11 +0100 5211751 http://www.medworm.com/index.php?rid=5211750&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012703%2Fabstract%3Frss%3Dyes Mutations in the FHL1 have been associated with diverse chronic myopathies including late onset X-linked axial and scapuloperoneal myopathy with bent spine syndrome, reducing body myopathy, X-linked dominant scapuloperoneal muscular dystrophy, rigid spine syndrome, and contractures and cardiomyopathy mimicking Emery-Dreifuss muscular dystrophy. Myofibrillar myopathies (MFMs) are morphologically distinct but genetically heterogeneous muscular dystrophies arising from mutations in Z-disk related proteins. Because some pathologic features of the FHL1 dystrophies and the MFMs overlap, we searched for mutations in FHL1 in our cohort of 50 genetically undiagnosed MFM patients. We detected two novel and one previously identified missense mutation in five. Two mutations are in the second LIM domai... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211750 Tue, 13 Sep 2011 03:40:11 +0100 5211750 http://www.medworm.com/index.php?rid=5211749&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012697%2Fabstract%3Frss%3Dyes Laser microdissection is used to isolate homogeneous subpopulations of single cells from tissue sections for subsequent proteomic analysis High specific protein profiling of skeletal muscle cells, overcoming the problem of tissue heterogeneity, can be ensured using this straightforward method. This work establishes a basis for research of pathological changes of the proteomic pattern observable in muscle disorders like myofibrillar myopathies. We combined UV laser based microdissection (LMD) with liquid chromatography–tandem mass spectrometry and iTRAQ to identify a general protein profile of normal skeletal muscle cells. To establish the minimal amount of tissue sample required for protein profiling, we used unstained control tissue sections from human biopsies cut at 10μm. To evaluate... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211749 Tue, 13 Sep 2011 03:40:11 +0100 5211749 http://www.medworm.com/index.php?rid=5211748&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012685%2Fabstract%3Frss%3Dyes A clinical and biochemical review of patients for systematic metabolic and molecular analyses with orphan neuromuscular diseases including lipid-storage-myopathies. Four subtypes of hereditary Lipid-Storage-Myopathies (LSM) are currently known. The clinical symptoms range from minimal muscular weakness to muscular pain and severe systemic deficits, often combined with very high plasma levels of creatinkinase. Validation of subtypes is essential, as therapy is achievable. In, e.g. primary carnitine-deficiency (PCD), clinical symptoms and disease progress can be improved by substitution of carnitine. In primary or secondary coenzyme-Q10-deficiency coenzyme Q-10 and riboflavin can be substituted and also improves muscular weakness, muscular pain and possibly progress of disease. To evaluate c... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211748 Tue, 13 Sep 2011 03:40:11 +0100 5211748 http://www.medworm.com/index.php?rid=5211747&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012673%2Fabstract%3Frss%3Dyes Deficiency of very-long-chain acyl-CoA dehydrogenase (VLCAD), which catalyzes the first step of mitochondrial fatty acid oxidation, is inherited as an autosomal recessive trait. The most common phenotypes occur in neonatal period or childhood, presenting with cardiomyopathy, hepatomegaly and hypoketogenic hypoglycemia. The juvenile/adult-onset is characterized by exercise intolerance and recurrent rhabdomyolysis triggered by prolonged exercise or fasting. Since VLCAD deficiency was included in neonatal screening, seven cases were diagnosed in Portugal, between 2004 and 31th August 2010 (incidence of 1:73.244 per 512.705 newborns). 51-year-old caucasian male, without consanguinity or relevant family history, presented in adolescence, with recurrent myalgia, weakness and muscle contractures ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211747 Tue, 13 Sep 2011 03:40:11 +0100 5211747 http://www.medworm.com/index.php?rid=5211746&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012661%2Fabstract%3Frss%3Dyes We report the case of a patient with progressive muscle weakness without rhabdomyolysis episodes or anemia. A 41years-old woman, originating from Morocco presented a progressive muscle weakness since the age of 7years, with difficulties for climbing stairs and raising from the floor or a chair. She also mentioned muscle fatigability since childhood, but never noticed muscle pain or dark urines. Clinical examination revealed a limb weakness predominating on deltoids and psoas (3/5 on MRC scale). Echocardiography was normal. Muscle biopsy revealed vacuoles in the majority of muscle fibers with considerable glycogen storage (a massive increase in PAS staining) and polysaccharide deposits resistant to diastase digestion. Electron microscopy revealed very high subsarcolemmal and intermyofibrill... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211746 Tue, 13 Sep 2011 03:40:11 +0100 5211746 http://www.medworm.com/index.php?rid=5211745&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101265X%2Fabstract%3Frss%3Dyes We present a patient with symptoms of cramps and myoglobinuria after dynamic exercise. Due to the nature of the metabolic block, we hypothesised that the patient with PGM deficiency could improve exercise tolerance with IV glucose infusion, similar to what is seen in McArdle disease (Myophosphorylase deficiency). One male patient (37years old), and five healthy male subjects were included (35±14years). Neurological examination of the patient showed mild pelvic weakness, but was otherwise normal. Peak oxidative capacity (VO2peak) was determined with an incremental cycle test. On separate days the subjects cycled at a constant load corresponding to 70% of their VO2peak for 32min, after which workload was increased gradually every other minute until exhaustion. This was done with either a pl... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211745 Tue, 13 Sep 2011 03:40:10 +0100 5211745 http://www.medworm.com/index.php?rid=5211744&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012648%2Fabstract%3Frss%3Dyes We report on two families in whom the previously healthy siblings of the indexpatients died unexpected in early infancy. Indexpatient P1 is the second child of healthy parents. At the age of eight years the girl developed a severe rhabdomyolysis following a mild upper airway respiratory infection and prolonged physical activity. Metabolic causes of acute rhabdomyolysis were excluded. Moleculargenetic analysis revealed a compound heterozygote mutation (c.2295-863_2410-27del/c.2401C>T) in the LPIN1 gene. The elder brother of P1 had a mild episode of rhabdomyolysis following an orchidopexia at the age of three years and died acute with generalised muscle hypotonia, myalgia, vomiting and somnolence at age four years. Urine was reported to be “dark” and “liver enzymes” were elevated. Au... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211744 Tue, 13 Sep 2011 03:40:10 +0100 5211744 http://www.medworm.com/index.php?rid=5211743&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012636%2Fabstract%3Frss%3Dyes Recently, LPIN1 gene mutation has being described as the main cause of recurrent episodes of rhabdomyolysis in early childhood. LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Herby we report a 9year old boy affected by this condition. He was born from non consanguineous healthy Caucasian parents. From the age of 2years, the patient presented tip-toe walking and pes cavus. At 5years, he suddenly presented headache, vomiting, myalgia, generalized weakness, stupurous and breathing difficulties requiring mechanical ventilation. Deep tendon reflex were abolished and Achilles tendon retraction was observed. Patient recovered in tree weeks normalising the plasma CK values. Tree years later he presented ano... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211743 Tue, 13 Sep 2011 03:40:10 +0100 5211743 http://www.medworm.com/index.php?rid=5211742&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012624%2Fabstract%3Frss%3Dyes We report a novel mutation in PNPLA2 gene causing distal asymmetrical myopathy, abnormal adipose tissue distribution and mild skin involvement. Our observations expand the clinical manifestations associated with PNPLA2 gene mutations. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211742 Tue, 13 Sep 2011 03:40:10 +0100 5211742 http://www.medworm.com/index.php?rid=5211741&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012612%2Fabstract%3Frss%3Dyes It is unclear to which extent skeletal muscle is affected in patients with Medium-chain acyl-CoA dehydrogenase deficiency (MCADD). L-carnitine is commonly used as a dietary supplement to MCADD-patients, though it has not been verified that they benefit from this. We investigated: (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211741 Tue, 13 Sep 2011 03:40:10 +0100 5211741 http://www.medworm.com/index.php?rid=5211740&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012600%2Fabstract%3Frss%3Dyes We examined 14 patients (58.6±10.8y; f/m:8/6) with suspected mitochondrial myopathy harbouring multiple deletions in skeletal muscle and 13 matched controls (54.1±13.2y; f/m:7/6). Patients and controls were compared with respect to clinical parameters, skeletal muscle histology, respiratory chain function, and skeletal muscle mtDNA rearrangements. Long-range and single-molecule (sm) PCR were used for deletion detection and quantification. The amount of COX-negative muscle fibers was significantly higher in patients younger than 55y compared to controls (0.54% vs. 0.01%). In patients older than 55y, the amount of COX-negative fibers did not differ from controls (0.43% vs. 0.48%). A positive correlation of COX-negative fibers with age was present in controls only. 8/13 controls showed mult... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211740 Tue, 13 Sep 2011 03:40:10 +0100 5211740 http://www.medworm.com/index.php?rid=5211739&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012594%2Fabstract%3Frss%3Dyes We report on a selection of complex V deficient patients harbouring pathogenic mutations in either the mtDNA or nuDNA. Patients with mtDNA alterations usually display a normal complex V activity measured by spectrophotometric analysis and show complex V subcomplexes in the BN-PAGE gel. Complex V deficiency due to nuDNA mutations results in a significant decrease in complex V activity using spectrophotometric techniques. The amount of detectable holocomplex V protein with BN-PAGE or western blotting is very low. Microscopic analysis in these patients shows aberrant mitochondrial morphology and severely decreased complex V immunoreactivities. Deficiencies of complex V either from mtDNA or nuDNA origin can be identified by the combined use of several diagnostic techniques. (Source: Neuromuscu... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211739 Tue, 13 Sep 2011 03:40:10 +0100 5211739 http://www.medworm.com/index.php?rid=5211738&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012582%2Fabstract%3Frss%3Dyes We present a patient with inflammatory changes (IC) in muscle and a new phenotype associated with the m.4317A>G mutation, first reported in a case of fatal infantile cardiomyopathy. A 33-year-old female was admitted to the intensive care unit (ICU) with global respiratory failure requiring mechanic ventilation, presumably due to benzodiazepine intoxication. Her past medical history included complains of fatigability and exercise intolerance since adolescence, yet medicated as depression. The hospitalization was complicated by pneumonia and rhabdomyolysis. She was extubated on the 14th day, requiring nocturnal non-invasive ventilation. Muscle histology showed fibre size variation, nuclear centralizations, degenerating fibres and an inflammatory cell infiltrate. It also revealed numerous rag... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211738 Tue, 13 Sep 2011 03:40:10 +0100 5211738 http://www.medworm.com/index.php?rid=5211737&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012570%2Fabstract%3Frss%3Dyes We report a 55-year-old man with adPEO and lung adenocarcinoma showing compound heterozygous mutations (T251I-P587L/P648R) in POLG1 gene. A 55-year-old male presented with progressive bilateral ptosis and dysphagia. Four years later he also noted muscle weakness and fluctuant dysphonia. His father and paternal grandfather also had bilateral ptosis and presumably died due to cancer. Neurological examination revealed bilateral ptosis, external ophthalmoparesis, pigmentary retinopathy and moderate weakness of the neck, distal upper limbs and proximal lower limbs. Muscle histology disclosed ragged red fibres and COX-deficient fibres. Southern blot analysis showed multiple mtDNA deletions in muscle. Sequence analysis of POLG1 gene revealed three compound heterozygous mutations T251I-P587L/P648R... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211737 Tue, 13 Sep 2011 03:40:10 +0100 5211737 http://www.medworm.com/index.php?rid=5211736&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012569%2Fabstract%3Frss%3Dyes Mutations in the PEO1 gene, which encodes for the twinkle mitochondrial helicase, are a cause of autosomal dominant progressive external ophtalmoplegia (PEO) with accumulation of multiple mitochondrial DNA (mtDNA) deletions. To characterize the clinical features and molecular anomalies in a cohort of patients with twinkle mutations. Ten patients were analyzed, originating from 6 different families. In all of them a PEO1 mutation was searched by DNA sequencing, either in peripheral blood (6 patients), or in muscle (1 patient), or in both of them (3 patients). A muscle biopsy was performed in 8 patients. In 6 of them a search for multiple deletions in mitochondrial DNA was performed using long range polymerase chained reaction (LR-PCR). The following analysis were performed: cardiological ex... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211736 Tue, 13 Sep 2011 03:40:10 +0100 5211736 http://www.medworm.com/index.php?rid=5211735&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012557%2Fabstract%3Frss%3Dyes Mitochondrial respiratory chain disorders (MRC), defined as primary diseases of the oxidative phosphorylation system are clinically, neuroradiologically, histologically, enzymatic and genetically heterogeneous. Then they are difficult to diagnose and classify. The aim of this study is to characterize the primary findings on histopathology of muscle biopsies performed in patients with definitive MRC. We include in this study the patients of our neurometabolic diseases consultation that fulfilled Walker’s criteria for definitive MRC and had performed a muscle biopsy. A total of 48 patients were assigned. The average age is 45.8years and mean age at onset of symptoms was 25.4years. 37.5% of the biopsies were considered normal. In the group of patients with clinically predominant muscle invo... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211735 Tue, 13 Sep 2011 03:40:10 +0100 5211735 http://www.medworm.com/index.php?rid=5211734&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012545%2Fabstract%3Frss%3Dyes Mitochondrial disorders result in impaired oxidative metabolism leading to lactate accumulation. Numerous studies have described physiologic responses to exercise, including blood lactate, in such patients. We devised a standardized protocol in order to differentiate children with mitochondrial myopathy who manifest abnormally high blood lactate concentrations at light and moderate levels of aerobic exercise from patients with non-mitochondrial myopathies and from healthy controls. The premise was that steady-state exercise done at power outputs of equivalent intensity across individual subjects would result in a blood lactate response which could then be related to measured oxygen uptake, the latter in turn reflecting tissue oxidative metabolism. We tested 6 patients with mitochondrial my... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211734 Tue, 13 Sep 2011 03:40:10 +0100 5211734 http://www.medworm.com/index.php?rid=5211733&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012533%2Fabstract%3Frss%3Dyes This study suggests that the ESCRT-pathway is implicated in formation of aggregates in sIBM. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211733 Tue, 13 Sep 2011 03:40:10 +0100 5211733 http://www.medworm.com/index.php?rid=5211732&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012521%2Fabstract%3Frss%3Dyes In this study we investigated whether there is age-dependent accumulation of progerin transcript in muscle biopsy samples from 13 healthy adults (37–71years of age). RNA was extracted from biopsy samples and reverse transcriptase polymerase chain reaction (RT-PCR) was performed. Lamin A was consistently found in all samples. In addition, a product 150bp smaller than lamin A, which was confirmed to be progerin by sequencing, was present in 7/13 samples. All individuals over 60years of age had a progerin band with the youngest individual being 44years. In view of the possibility that there is acceleration of the aging process in s-IBM muscle we also investigated biopsies from 7 s-IBM cases (aged 57–84years) to determine if progerin expression is increased. Progerin amplicons were present... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211732 Tue, 13 Sep 2011 03:40:10 +0100 5211732 http://www.medworm.com/index.php?rid=5211731&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101251X%2Fabstract%3Frss%3Dyes We report a rare case of BCIM which improved with corticosteroid treatment. The pattern of inflammatory infiltrates observed in BCIM has several consistent features and can be missed because the disease is often patchy and altered by steroid use. Idiopathic inflammatory myopathies, as BCIM syndrome, are very important to consider in the differential diagnosis in all patients with muscle weakness because they are treatable. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211731 Tue, 13 Sep 2011 03:40:10 +0100 5211731 http://www.medworm.com/index.php?rid=5211730&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012508%2Fabstract%3Frss%3Dyes In conclusion, our study of the MUAP parameters was not helpful to explain the mechanisms of importance for the evolvement of muscle weakness in sIBM. We discuss our findings in relation to previous studies. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211730 Tue, 13 Sep 2011 03:40:10 +0100 5211730 http://www.medworm.com/index.php?rid=5211729&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012491%2Fabstract%3Frss%3Dyes In sporadic inclusion body myositis (sIBM), there is in most cases a characteristic pattern of muscle weakness. The primary cause of muscle destruction is debated. We have investigated 20 patients with definite sIBM in order to describe what disease causing mechanisms may be of importance in early (strong muscles) and late stages (weaker muscles). The tibialis anterior (T), quadriceps (Q) and biceps brachii (B) were chosen. Muscle strength was measured by a hand-held dynamometer and related in percent of published normal values. Muscle MRI images were acquired covering these muscles and an open muscle biopsies were obtained from the same muscles at one occasion or within a short time-span ( (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211729 Tue, 13 Sep 2011 03:40:10 +0100 5211729 http://www.medworm.com/index.php?rid=5211728&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101248X%2Fabstract%3Frss%3Dyes The currently accepted diagnostic criteria for inclusion body myositis (IBM), first published in 1995, comprise pathological and clinical elements. The pathological features being endomysial inflammation with invasion of intact fibres, rimmed vacuoles and either amyloid or tubulofilamentous inclusions; all of these must be present for a definite diagnosis. However, these features are not specific to IBM and furthermore in many clinically typical cases one or more may be absent. Recently a variety of proteins more commonly associated with neurodegenerative diseases have been found to accumulate in muscle fibres in IBM. The benefit of immunohistochemical staining for these proteins in the diagnosis of IBM is unknown. We propose that these protein accumulations may assist in the diagnosis of ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211728 Tue, 13 Sep 2011 03:40:10 +0100 5211728 http://www.medworm.com/index.php?rid=5211727&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012478%2Fabstract%3Frss%3Dyes This study suggests that the quadriceps extensor strength is the most sensitive marker for disease progression in sIBM patients. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211727 Tue, 13 Sep 2011 03:40:10 +0100 5211727 http://www.medworm.com/index.php?rid=5211726&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012466%2Fabstract%3Frss%3Dyes Human T-cell lymphotropic virus type I (HTLV-1) is a human retrovirus and the etiologic agent for a progressive neurological disease called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), which primarily affects the thoracic spinal cord and is associated with inflammatory muscle diseases such as polymyositis. However, HTLV-1 virus is detected in infiltrating CD4+ lymphocytes but not in muscle fibers. Evidence in the literature supports the hypothesis that myositis is mediated by the release of cytokines and/or the viral Tax transactivator by HTLV-1 infected mononuclear cells that infiltrate the muscle. We investigated the gene expression of cultured human muscle cells in response to soluble factors secreted by infected HTLV-1 T cells, and if this modulation could induc... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211726 Tue, 13 Sep 2011 03:40:10 +0100 5211726 http://www.medworm.com/index.php?rid=5211725&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012454%2Fabstract%3Frss%3Dyes Sporadic Inclusion Body Myositis (sIBM) is an inflammatory myopathy characterized by CD8+ cytotoxic infiltrates and amyloid deposits. Regulatory T cells (Treg) are key regulators of immune response. We analysed 54 parameters of the immune response, in attempt to develop new therapeutic approaches. We included 22 definite sIBM patients (mean age; 70.1) and 22 controls (matched on age and sex). No sIBM patients nor controls received immunosuppressants. Peripheral blood mononuclear cells (PBMC) were analyzed using flow cytometry. Using a multiplex assay, the concentrations of 25 cytokines and chemokines was determined. Muscle biopsies of 8 patients were tested by immunohistochemistry for presence of Treg. In blood, mean percentage of activated CD4+ T cells (16.2±13% vs 8.7±4.6%; p=0.03) and... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211725 Tue, 13 Sep 2011 03:40:10 +0100 5211725 http://www.medworm.com/index.php?rid=5211724&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012442%2Fabstract%3Frss%3Dyes Different myopathies may be observed in HIV-infected patients. The most frequent are mitochondrial myopathies due to nucleoside analogs toxicity, and HIV-associated myositis like sporadic inclusion body myositis (sIBM) or polymyositis, which seem to be due to viral replication. More rarely described are myositis related to opportunistic infections in case of severe immunodepression or some sporadic late onset nemaline myopathies (SLONM). Nevertheless, the frequency and evolution of these different HIV associated myopathies are not precisely known. Our aim was thus to describe these myopathies from our reference center for neuromuscular disorders. On the database of the Department of pathology of our center, we crossed key words HIV and muscle biopsy for the period 2005–2010. For each mus... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211724 Tue, 13 Sep 2011 03:40:10 +0100 5211724 http://www.medworm.com/index.php?rid=5211723&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012430%2Fabstract%3Frss%3Dyes The inflammatory muscle diseases represent a group of rare autoimmune diseases of unknown etiology which can have an acute, subacute or chronic presentation. Polymyositis (PM), Dermatomyositis (DM) and Inclusion Body Myositis (IBM) are the largest group of acquired and potentially treatable inflammatory myopathies. Clinically these entities share the presence of symmetric proximal muscle weakness caused by muscle inflammation and necrosis, heralded by elevated serum muscle enzymes. Frequently there are extramuscular manifestations associated and the presence of myositis-specific auto-antibodies. Diagnosis is based on clinical findings, confirmed by laboratory examinations. The aim of the present study was to make a review of the demographic characteristics, main clinical features, laborato... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211723 Tue, 13 Sep 2011 03:40:10 +0100 5211723 http://www.medworm.com/index.php?rid=5211722&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012429%2Fabstract%3Frss%3Dyes We report a male and a female patients aged 58 and 78years old, who were on statin treatment for a period of 4 and 5years, respectively. They developed muscle weakness with a limb girdle distribution and respiratory and neck weakness in the female patient who were more affected. CK were highly elevated and EMG showed myopathic potentials with denervation at rest. Muscle biopsy showed necrosis without inflammtion Both patients met the following criteria for immune-mediated necrotizing myopathy: (1) proximal muscle weakness occurring during or after treatment with statins (2) elevated serum creatine kinase (CK) (3) persistence of weakness and elevated CK despite discontinuation of the statin; (4) improvement with immunosuppressive agents; and (5) muscle biopsy showing necrotizing myopathy wi... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211722 Tue, 13 Sep 2011 03:40:10 +0100 5211722 http://www.medworm.com/index.php?rid=5211721&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012417%2Fabstract%3Frss%3Dyes There is debate as to whether sIBM is a primary autoimmune muscle disease or a late-onset degenerative myopathy with inflammatory features. The reported occurrence of systemic autoantibodies (AAb) in 43% of sIBM cases in a previous study by Koffman et al. (1998) was considered to support the autoimmune hypothesis. However, the significance of this finding is uncertain as AAb frequencies were not compared with population control frequencies. In the present study the frequencies of myositis-associated AAb (antinuclear antibody (ANA), extractable nuclear antigen (ENA) and its subgroups, Thyroid peroxidase (TPO), and IgA-anti-tissue transglutaminase) were compared in a group of 54 patients with biopsy-proven sIBM and a control group of 198 sera from the Busselton Population Health Survey. Pati... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211721 Tue, 13 Sep 2011 03:40:10 +0100 5211721 http://www.medworm.com/index.php?rid=5211720&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012405%2Fabstract%3Frss%3Dyes A 54-year-old man diagnosed with hepatitis C presented muscle atrophy and progressive muscle weakness in the lower limbs, resulting in difficulties in walking, with frequent falls without pain or sensibility changes. He was treated with interferon and ribavirin, with improvement of the muscle symptoms. It was performed an electromyography and a muscle biopsy for neuromuscular disease research. Electromyography revealed a myopathic pattern. Muscle biopsy showed sarcoplasmic vacuoles and granulomas with epithelioid histiocytes, lymphocytes and occasional multinucleate giant cells of the Langerhans type within muscle parenchyma. Special histochemical stains for microorganisms detection were negative and we did not observe vasculitis using established histologic criteria. The presence of granu... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211720 Tue, 13 Sep 2011 03:40:10 +0100 5211720 http://www.medworm.com/index.php?rid=5211719&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012399%2Fabstract%3Frss%3Dyes To characterize the molecular basis of a congenital myasthenic syndrome (CMS). Deciphering the molecular basis of a CMS is required for correct diagnosis and appropriate therapy. After agonist binding, the extracellular AChR C-loop caps the binding site and initiates structural transitions ultimately resulting in opening the AChR-channel. No AChR-C-loop mutations have been detected to date. Mutation analysis; EM; expression studies in HEK cells; single-channel recordings from mutant AChRs expressed in HEK cells; thermodynamic mutant cycle analysis. A 40-year-old woman with severe myasthenic symptoms since birth and 66% EMG decrement is heterozygous for Gly74Cys in the main immunogenic region, and Val188Met in the C-loop, of the AChR α-subunit. Both mutations are absent in 200 normal contr... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211719 Tue, 13 Sep 2011 03:40:10 +0100 5211719 http://www.medworm.com/index.php?rid=5211718&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012387%2Fabstract%3Frss%3Dyes Recently a new form of congenital myasthenia has been associated with mutations in the gene encoding glutamine-fructuosa-6 phosphate transaminase (GFPT1). Patients usually present weakness in a limb girdle distribution and fatigue. Ocular and facial muscles are spared. Decremental response in repetitive stimulation is common and most patients benefit from anticholinestarase drugs. Many patients have tubular aggregates in conventional muscle biopsies. Hereby we report two patients affected with this condition. Patient 1: Is a 7year old black girl born from a consanguineous Senegalese family. Clinical symptoms began at 1year. Parents noticed falls and difficulties in getting up from the floor. Weakness and fatigue progressed and worsening with physical exercise was noted. Ptosis and ophtalmo... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211718 Tue, 13 Sep 2011 03:40:10 +0100 5211718 http://www.medworm.com/index.php?rid=5211717&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012375%2Fabstract%3Frss%3Dyes The investigation of nonverbal communication in clinical populations can illuminate brain-behavior relationships underlying emotional expression, as well as provide about social an interpersonal functioning. Assessment of facial expression is an important aspect of the clinical neurological examination, both as an indicator of a mood disorder and as a sign of neurological damage. To the date there are studies about some psychosocial aspects of myasthenia, such as quality of life, anxiety or about neuropsychological aspects like a memory. However, there is not a study which has assessed facial emotion recognition accuracy. To assess the facial emotion recognition accuracy (fear, surprise, sadness, happiness, anger and disgust) and reaction time of patients with myasthenia. 35 patients with ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211717 Tue, 13 Sep 2011 03:40:10 +0100 5211717 http://www.medworm.com/index.php?rid=5211716&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012363%2Fabstract%3Frss%3Dyes Myasthenia gravis (MG) is a paralytic disorder with autoantibodies against components of the neuromuscular junction (NMJ). The most prevalent form is caused by antibodies against the acetylcholine receptor (AChR), but some patients instead have antibodies against muscle-specific kinase (MuSK), a protein essential for AChR clustering. MuSK MG antibodies are generally IgG4 subclass, contrasting most autoimmune diseases including AChR MG, which are IgG1/3-mediated. IgG4 antibodies are considered anti-inflammatory, but in some autoimmune diseases a direct pathogenic role of IgG4 autoantibodies has been suggested. Interestingly, anti-MuSK IgG4 titers correlate with disease severity, suggesting specific myasthenogenic activity of these specific antibodies. However, direct evidence is lacking. We... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211716 Tue, 13 Sep 2011 03:40:10 +0100 5211716 http://www.medworm.com/index.php?rid=5211715&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012351%2Fabstract%3Frss%3Dyes In conclusion, patients diagnosed with unknown congenital myopathy should undergo an electrophysiological study of neuromuscular junction to identify ColQ-related CMS. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211715 Tue, 13 Sep 2011 03:40:10 +0100 5211715 http://www.medworm.com/index.php?rid=5211714&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101234X%2Fabstract%3Frss%3Dyes This study demonstrates that pregnancy constitutes a high risk period for women with CMS, and that they should be closely followed up in a centre specialized in neuromuscular disorders. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211714 Tue, 13 Sep 2011 03:40:10 +0100 5211714 http://www.medworm.com/index.php?rid=5211713&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012338%2Fabstract%3Frss%3Dyes We describe the first group of VLOMG in our country. Females and males were equally affected, 60.3% were AChR-MG,thymus pathology were uncommon and a good response to treatment according to PIS was seen. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211713 Tue, 13 Sep 2011 03:40:10 +0100 5211713 http://www.medworm.com/index.php?rid=5211712&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012326%2Fabstract%3Frss%3Dyes We describe a case of a girl born with congenital talipes that was hospitalized at 21days due to fever and dyspnea and soon required intensive care therapy. EMG showed myogenic changes but muscle biopsy had only minor abnormalities. Repetitive stimulation revealed significant decrement. Motor weakness partially improved with pyridostigmin but tracheostomy and gastrostomy were necessary at 4months. Volume-controlled ventilation with high volumes was required due to diaphragmatic failure. Outpatient management was possible only after 8months, Multi-fiber enteral nutrition, atropine and urecholine improved gastroesophageal reflux and secondary complications of pyridostigmin. Garches brace prevented spinal collapse and allowed verticalization, sitting position and head support. At 3years she s... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211712 Tue, 13 Sep 2011 03:40:10 +0100 5211712 http://www.medworm.com/index.php?rid=5211711&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012314%2Fabstract%3Frss%3Dyes The non-dystrophic myotonias are a heterogeneous group of skeletal muscle ion channel diseases that demonstrate myotonia as their common feature, in reference to a delayed muscle relaxation after voluntary or evoked muscle contraction. The non-dystrophic myotonias are caused by mutations in the genes coding the skeletal muscle chloride channel 1 (CLCN1) or the alpha subunit of voltage-gated sodium channel 4 (SCN4A). Mutations of the CLCN1 gene result in either autosomal dominant myotonia congenita (Thomsen type) or autosomal recessive myotonia congenita (Becker type). A subset of CLCN1 mutations have been found to cause both recessive and dominant myotonia. Mutations of the SCN4A gene are typically inherited as an autosomal dominant trait, regardless of the associated phenotype (paramyoton... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211711 Tue, 13 Sep 2011 03:40:09 +0100 5211711 http://www.medworm.com/index.php?rid=5211710&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012302%2Fabstract%3Frss%3Dyes Myotonia is known as a delayed relaxation of skeletal muscle following voluntary contraction which usually abates after repeated muscle activity. This phenomenon is caused by ion channel disorders on muscle membrane. Chloride channel (ClC1) is most frequently affected. The mutations in voltage-gated chloride channel gene ClCN1 cause the disease inherited either as an autosomal dominant (Thomsen’s myotonia) or recessive (Becker’s myotonia) manner. During 2008–2010 the mutations in the chloride channel gene were found in 10 unrelated patients with myotonia. It is the third most frequent cause of myotonia in our local registry (54 patients with myotonic dystrophy type 2, 18 with myotonic dystrophy type 1, and 7 suffering from mutations in the sodium channel). All persons revealed hypert... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211710 Tue, 13 Sep 2011 03:40:09 +0100 5211710 http://www.medworm.com/index.php?rid=5211709&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012296%2Fabstract%3Frss%3Dyes Thomsen’s disease is a dominant chloride-channel-associated myotonia free of extra-muscular systemic involvement. The implicated muscle chloride channel, hClC-1, is regulated by fast gates opening and closing each pore of the dimeric channel independently and a common gate operating on both pores simultaneously. Common gating is poorly understood. Typically, in Thomsen’s disease, it is drastically affected, not only in hClC-1 channels homodimeric for the causative mutation but also in mutant-wild-type heterodimers (a dominant negative effect). Its voltage dependence is so much altered that muscle cells can never, physiologically, depolarise sufficiently to allow effective opening. Using fluorescence resonance energy transfer (FRET), we studied lateral movements of the cytoplasmic C-ter... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211709 Tue, 13 Sep 2011 03:40:09 +0100 5211709 http://www.medworm.com/index.php?rid=5211708&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012284%2Fabstract%3Frss%3Dyes Myotonia congenita is the most common inherited skeletal muscle channelopathy, and is caused by mutations in the skeletal muscle voltage-gated chloride channel, encoded by the CLCN1 gene. Mutations may be either dominant, and associated with Thomsen disease, or recessive, and associated with Becker myotonia. A total of 126 apparently unrelated patients from around Australasia with a clinical suspicion of myotonia congenita were referred to the Neurogenetics Unit at Royal Perth Hospital for CLCN1 gene analysis. Thirty-eight mutations, of which seven are novel, were identified in 74 patients. Additionally, in a cohort of seven Japanese patients, six novel mutations were identified in five individuals. Of the 13 novel mutations, five are nonsense, splice site or frameshift and five are missen... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211708 Tue, 13 Sep 2011 03:40:09 +0100 5211708 http://www.medworm.com/index.php?rid=5211707&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012272%2Fabstract%3Frss%3Dyes Clinical, electrophysiological and genetic studies are the key instruments to characterize several muscle disorders affecting ion channels, called channelopathies, such as non-dystrophic myotonias (myotonia congenita, paramyotonia congenita and sodium channel myotonias) and periodic paralysis. The aim of this study was to clinically and genetically characterize a cohort of Italian patients, affected by suspected muscular channelopathies We recruited 31 patients with clinical and laboratory features compatible with muscle channellopathy The patients were phenotypically classified in four groups: Periodic Paralysis (3 pts.), Paramyotonia congenita (4), Sodium Channel Myotonia (4) and Myotonia congenita (20). Molecular genetic analysis was positive in 23 out of the 31 patients, revealing: 16 ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211707 Tue, 13 Sep 2011 03:40:09 +0100 5211707 http://www.medworm.com/index.php?rid=5211706&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012260%2Fabstract%3Frss%3Dyes A DM registry is essential to identify potential participants in clinical trials, to follow the natural history of the disease and to serve as an indicator of the effectiveness of the health care provided to the DM population. A Quebec DM population-based registry has been developed over the last 10 years. In December 2010, the Quebec DM population-based registry contained: 1183 individuals including 892 patients with DM1, 2 patients with DM2 and 145 non-affected subjects. Among these patients, 667 patients were clinically evaluated in a standardized manner. 44% of patients were male and 55% female. Patient’s distribution revealed that 3% were aged less than 18 years, 9% between 19 and 30 years, 44% between 31 and 50 years and 44% above 50 years. The congenital form represents 5% of the ... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211706 Tue, 13 Sep 2011 03:40:09 +0100 5211706 http://www.medworm.com/index.php?rid=5211705&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012259%2Fabstract%3Frss%3Dyes The progression of muscle damage was studied in the patients with myotonic dystrophy type1 (DM1) using CT. We calculated % muscle volume index (%MVI) by using the histogram-based prosedure. We applied this method to 115 CT scans of skeletal muscles retrospectively selected from 31 patients with DM1. %MVI was well correlated with the disability stage (p (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211705 Tue, 13 Sep 2011 03:40:09 +0100 5211705 http://www.medworm.com/index.php?rid=5211704&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012247%2Fabstract%3Frss%3Dyes Adipocytes represent a large pool of cells participating in glucose uptake, which depends on the presence and type of the insulin receptors (IR). The human IR is expressed in two isoforms: The A-isoform (IRA) lacks the exon 11 and binds both insulin and insulin-like growth factor-II, whereas the exon 11 containing isoform (IRB) only binds insulin. In adults, IRB is expressed predominantly in insulin-sensitive tissues: liver, muscle, adipocytes, and kidney. Altered expression of the two variants was recorded in adipocytes of patients with insulin independent diabetes mellitus that appears also in myotonic dystrophy type 1 (DM1). DM1 muscles contain lower levels of IR and display aberrant IR splicing associated with weaker metabolic response. Importantly, the primary determinant of pathogeni... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211704 Tue, 13 Sep 2011 03:40:09 +0100 5211704 http://www.medworm.com/index.php?rid=5211703&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012235%2Fabstract%3Frss%3Dyes The current model of myotonic dystrophy 2 (DM2) pathogenesis comprises interaction of CCUGexp pre-mRNAs of ZNF9 gene with CCUG-binding proteins, which leads to their sequestration at ribonuclear foci and, in turn, to deregulation of transcription and alternative splicing of target RNAs. To characterize the role of ZNF9 loss and the CCUG repeat expression, it is necessary to establish the identity of tissues and cell types in which the DMPK/ZNF9 protein and the ZNF9 mRNA are expressed. For this purpose, we have prepared an antibody against the ZNF9 protein and followed its immunohistochemical reactivity in human skeletal muscle, soft tissues and lymphocytes from the peripheral blood. Obtained reactivity was compared to the presence and localization of CCUGexp pre-mRNA foci and CUG/CCUG-bind... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211703 Tue, 13 Sep 2011 03:40:09 +0100 5211703 http://www.medworm.com/index.php?rid=5211702&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012223%2Fabstract%3Frss%3Dyes In this study, we assume that those living with DM1 are experts about their condition, and that Photovoice may be an appropriate research method to use to capture their experiences. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211702 Tue, 13 Sep 2011 03:40:09 +0100 5211702 http://www.medworm.com/index.php?rid=5211701&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012211%2Fabstract%3Frss%3Dyes In conclusion, this study addresses various measurement issues required to construct a clinically meaningful scale using Rasch analysis. The final combined fatigue and daytime sleepiness scale (FDSS) specifically developed for myotonic dystrophy type 1 patients provides interval measures on a single continuum. If its responsiveness can be demonstrated, we expect that the FDSS will be valuable for future clinical trials and therapeutic follow-up studies. (Source: Neuromuscular Disorders) Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211701 Tue, 13 Sep 2011 03:40:09 +0100 5211701 http://www.medworm.com/index.php?rid=5211700&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101220X%2Fabstract%3Frss%3Dyes Myotonic dystrophy (DM) is the commonest muscular dystrophy in adults and the most variable neuromuscular disorder. Such variability together with multisystemic involvement creates particular challenges for both clinical management and the design of therapeutic trial. We have therefore developed a unique database specifically dedicated to myotonic dystrophies summarizing the relevant informations from a large population of patients. The DM-scope registry collects in a standardized form the most relevant clinical and epidemiological data. The data management and the software are designed to both optimize the annual monitoring of patients and to promote DM clinical research. Specific software tools such as symptoms’ severity graphs and synopsis editing can assist clinicians in improving me... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211700 Tue, 13 Sep 2011 03:40:09 +0100 5211700 http://www.medworm.com/index.php?rid=5211699&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012193%2Fabstract%3Frss%3Dyes In this study, we compared the global gene expression profiles of muscle biopsies from DM2 patients versus control muscles and expression changes associated with individuals who are on statin medication, with the aim of distinguishing shared affected pathways in a common pathomechanism. The microarray expression profile leads were further analysed in multiple DM2 biopsies by RT-PCR, with the aim of identifying aberrantly spliced genes among the abnormally expressed genes. We identified a unique set of dysregulated genes. NEDD4, an ubiquitin ligase, was one of the dysregulated genes in DM2 patient muscles and in individuals with statin-induced changes. Our work demonstrates that NEDD4 is abnormally spliced in DM2, which leads to an aberrant isoform of NEDD4 protein being expressed in DM2 pa... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211699 Tue, 13 Sep 2011 03:40:09 +0100 5211699 http://www.medworm.com/index.php?rid=5211698&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012181%2Fabstract%3Frss%3Dyes Health services research identifies and measures the most effective ways to organize, manage, finance and deliver high-quality care. But for Duchenne Muscular Dystrophy this is very limited and approaches like using mortality rate as care indicator does not give a very detailed insight. In addition a correlation is impossible to make because ICD-10 code covers too many neuromuscular disorders. Also natural history data on DMD with references to steroid use and other treatment recommendations are limited. A different approach is needed. Using Patient registries can be a valuable tool for data collection even so there may be the limit of selection bias. The EU funded 3year project CARE-NMD (www.care-nmd.eu) will look on the degree of implementation of Care Standards for DMD (Bushby et al., 2... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211698 Tue, 13 Sep 2011 03:40:09 +0100 5211698 http://www.medworm.com/index.php?rid=5211697&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS096089661101217X%2Fabstract%3Frss%3Dyes The Muscular Dystrophy Association of New Zealand has set the establishment of a national registry for neuromuscular disease as one of their main priorities to advance the potential of enabling clinical trials to take place in New Zealand. New Zealand has a relatively small total population just in excess of four million and it is expected that approximately 4000 people have a neuromuscular condition. Standards of care for people with neuromuscular conditions in New Zealand are comparable to much of Europe and North America meaning that selected endpoints used in clinical trials are equally measurable in the NZ population. Most neuromuscular diseases are rare and any study of disease-modifying medication will require the enrolment of participants from many countries to achieve sufficient n... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211697 Tue, 13 Sep 2011 03:40:09 +0100 5211697 http://www.medworm.com/index.php?rid=5211696&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012168%2Fabstract%3Frss%3Dyes The Jain Foundation’s mission is to accelerate and develop a therapy for Limb Girdle Muscular Dystrophy 2B/Miyoshi Myopathy, a rare, autosomal recessive muscular dystrophy caused by mutations in the dysferlin gene. We accomplish this through funding, coordinating, and managing global research projects. Since 2005, we have awarded over $7.2 million USD in research support and currently fund 43 research projects in the following areas of study: dysferlin structure/function, ferlin proteins, membrane repair, reactive oxygen species, high-throughput drug screening, gene, protein and cell therapy, calcium and mitochondrial degeneration and other therapeutic strategies. Prior to the establishment of the Jain Foundation, LGMD2B/MM received little attention from researchers due to the lack of fu... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211696 Tue, 13 Sep 2011 03:40:09 +0100 5211696 http://www.medworm.com/index.php?rid=5211695&cid=s_38558_25_f&fid=38558&url=http%3A%2F%2Fwww.nmd-journal.com%2Farticle%2FPIIS0960896611012156%2Fabstract%3Frss%3Dyes In June 2010, it was held in Brazil an International Conference on Neuromuscular Diseases. Lecturers from several European countries, from the United States and Argentina were present. Brazilian neurologists and other health professionals working on the neuromuscular field attended the meeting. We had the support of TREAT-NMD and of muscular dystrophy and spinal atrophy associations. The Brazilian physicians were moved by the cosmopolitan atmosphere. In August of the same year, it was held the Brazilian Congress of Neurology in Rio de Janeiro. Once again physicians from all over the country interested in the attention of neuromuscular diseases patients met. They agreed with the creation of a national network. The main purposes of that association would be to train professionals to create r... Neuromuscular Disorders journals http://www.medworm.com/rss/comments.php?id=5211695 Tue, 13 Sep 2011 03:40:09 +0100 5211695