Neuromuscular Disorders RSS feed: Current Issue. This international, multidisciplinary journal covers all aspects of neuromuscular disorders in childhood and adult life (including the muscular dystrophies, spinal muscular atrophies, hereditary neuropathies, congenital myopathies, myasthenias, myotonic syndromes, metabolic myopathies and inflammatory myopathies). The Editors welcome original articles from all areas of the field: • Clinical aspects , such as new clinical entities, case studies of interest, treatment, management and rehabilitation (including biomechanics, orthotic design and surgery). • Basic scientific studies of relevance to the clinical syndromes, including advances in the fields of molecular biology and genetics. • Studies of animal models relevant to the human diseases. The journal is aimed at a wide range of clinicians, pathologists, associated paramedical professionals and clinical and basic scientists with an interest in the study of neuromuscular disorders. In addition to original research papers , the journal also publishes reviews and mini-reviews, preliminary short communications and book reviews, and has editorial, correspondence and news sections. Reports on congresses and workshops, taking the form of a digested or very comprehensive commentary, pointing out some of the particular highlights in relation to the contributors and giving some detail of the area covered, important contributions and a list of participants, are also welcome. The journal is published monthly and aims at rapid publication of high quality papers of scientific merit as well as general interest to a wide readership. There is also a fast track for rapid publication of new material of outstanding scientific merit and importance. Neuromuscular Disorders is the official journal of the World Muscle Society an international, multidisciplinary, scientific society, dedicated to the advancement and dissemination of knowledge in the field of neuromuscular disorders. http://www.nmd-journal.com/?rss=yesElsevier Inc.en © 2010 Published by Elsevier Inc. All rights reserved. Neuromuscular Disorders0960-8966202February 2010 © 2010 Published by Elsevier Inc. All rights reserved. healthpermissions@elsevier.comhttp://www.nmd-journal.com/article/PIIS0960896610000337/abstract?rss=yesEditorial Board10.1016/S0960-8966(10)00033-7Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7IFCIFChttp://www.nmd-journal.com/article/PIIS096089661000043X/abstract?rss=yesOn Friday December 4th 2009, the Network of Excellence, TREAT-NMD, issued a press release (by E-mail), drawing attention to a major review article published simultaneously online in Lancet Neurology, providing guidelines on clinical care in Duchenne muscular dystrophy.Clinical myology at the crossroads; the gospel truth10.1016/j.nmd.2010.01.007Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Editorials9596http://www.nmd-journal.com/article/PIIS0960896610000441/abstract?rss=yesFrom time to time we have had contributions submitted to the Journal, which are of potential interest to our readership but do not quite conform to any existing section of the Journal, either as an original scientific paper or a case report. They are also not appropriate for our correspondence columns, which are focussed mainly on commentary on papers published in the Journal. Some of these have been by scientists or clinicians who personally have a neuromuscular disorder, and are comparable to the personal experience documented by physicians from time to time in general medical journals. Other contributions that are equally difficult to place are from patient advocacy groups. I recalled how revealing and educational it was for the clinicians some years ago when I was Therapeutics Director of the ENMC (European Neuromuscular Centre) and we decided for the first time, at the request of an advocacy group, to include patient representatives at a workshop discussing therapy in myotonic dystrophy. It was a great success for both sides, and the forerunner of involvement of patient advocacy groups in many subsequent workshops and discussion groups on treatment. A third group of potential interest within this new umbrella would be studies by sociologists, which often do not conform to a strict scientific constraint, yet may have data of potential interest and importance.A new section for Neuromuscular Disorders: Patients’ Forum10.1016/j.nmd.2010.01.008Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Editorials9797http://www.nmd-journal.com/article/PIIS0960896609006920/abstract?rss=yesAbstract: Ca2+ ions are key regulators of skeletal muscle contraction. By binding to contractile proteins, they initiate a cascade of molecular events leading to cross-bridge formation and ultimately, muscle shortening and force production. The ability of contractile proteins to respond to Ca2+ attachment, also known as Ca2+ sensitivity, is often compromised in acquired and congenital skeletal muscle disorders. It constitutes, undoubtedly, a major physiological cause of weakness for patients. In this review, we discuss recent studies giving strong molecular and cellular evidence that pharmacological modulators of some of the contractile proteins, also termed Ca2+ sensitizers, are efficient agents to improve Ca2+ sensitivity and function in diseased skeletal muscle cells. In fact, they compensate for the impaired contractile proteins response to Ca2+ binding. Currently, such Ca2+ sensitizing compounds are successfully used for reducing problems in cardiac disorders. Therefore, in the future, under certain conditions, these agents may represent an emerging class of agents to enhance the quality of life of patients suffering from skeletal muscle weakness.Ca2+ sensitizers: An emerging class of agents for counterbalancing weakness in skeletal muscle diseases?Julien Ochala10.1016/j.nmd.2009.11.010Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Review98101http://www.nmd-journal.com/article/PIIS096089660900666X/abstract?rss=yesAbstract: Duchenne muscular dystrophy (DMD) is caused by the lack of functional dystrophin protein, most commonly as a result of a range of out-of-frame mutations in the DMD gene. Modulation of pre-mRNA splicing with antisense oligonucleotides (AOs) to restore the reading frame has been demonstrated in vitro and in vivo, such that truncated but functional dystrophin is expressed. AO-induced skipping of exon 51 of the DMD gene, which could treat 13% of DMD patients, has now progressed to clinical trials. We describe here the methodical, cooperative comparison, in vitro (in DMD cells) and in vivo (in a transgenic mouse expressing human dystrophin), of 24 AOs of the phosphorodiamidate morpholino oligomer (PMO) chemistry designed to target exon 53 of the DMD gene, skipping of which could be potentially applicable to 8% of patients. A number of the PMOs tested should be considered worthy of development for clinical trial.Comparative analysis of antisense oligonucleotide sequences targeting exon 53 of the human DMD gene: Implications for future clinical trialsLinda J. Popplewell, Carl Adkin, Virginia Arechavala-Gomeza, Annemieke Aartsma-Rus, Christa L. de Winter, Steve D. Wilton, Jennifer E. Morgan, Francesco Muntoni, Ian R. Graham, George Dickson10.1016/j.nmd.2009.10.013Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers102110http://www.nmd-journal.com/article/PIIS0960896609007007/abstract?rss=yesAbstract: Glucocorticoids are beneficial in many muscular dystrophies but they are ineffective in treating dysferlinopathy, a rare muscular dystrophy caused by loss of dysferlin. We sought to understand the molecular basis for this disparity by studying the effects of a glucocorticoid on differentiation of the myoblast cell line, C2C12, and dysferlin-deficient C2C12s. We found that pharmacologic doses of dexamethasone enhanced the myogenic fusion efficiency of C2C12s and increased the induction of dysferlin, along with specific myogenic transcription factors, sarcolemmal and structural proteins. In contrast, the dysferlin-deficient C2C12 cell line demonstrated a reduction in long myotubes and early induction of particular muscle differentiation proteins, most notably, myosin heavy chain. Dexamethasone partially reversed the defect in myogenic fusion in the dysferlin-deficient C2C12 cells. We hypothesize that a key therapeutic benefit of glucocorticoids may be the up-regulation of dysferlin as an important component of glucocorticoid-enhanced myogenic differentiation.Dexamethasone induces dysferlin in myoblasts and enhances their myogenic differentiationJoseph J. Belanto, Silvia V. Diaz-Perez, Clara E. Magyar, Michele M. Maxwell, Yasemin Yilmaz, Kasey Topp, Guney Boso, Catriona H. Jamieson, Nicholas A. Cacalano, Christina A.M. Jamieson10.1016/j.nmd.2009.12.003Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers111121http://www.nmd-journal.com/article/PIIS0960896609006877/abstract?rss=yesAbstract: Two siblings were evaluated for progressive proximal weakness and elevated creatine kinase. Immunohistochemical staining in the brother’s muscle biopsy showed near absence of all four sarcoglycan subunits. Clinical progression prompted a trial of deflazacort in both siblings. At 22months of drug therapy, both patients have stable or improved strength testing. Further analysis on the muscle biopsy revealed homozygous β-sarcoglycan gene mutation (S114F), consistent with the limb-girdle muscular dystrophy type 2E (LGME 2E). Despite the severe phenotype, deflazacort has a beneficial effect on slowing disease progression in LGME 2E similar to that seen in Duchenne muscular dystrophy.Two siblings with limb-girdle muscular dystrophy type 2E responsive to deflazacortLily C. Wong-Kisiel, Nancy L. Kuntz10.1016/j.nmd.2009.11.005Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers122124http://www.nmd-journal.com/article/PIIS0960896609006865/abstract?rss=yesAbstract: Muscle phosphorylase b kinase (PHK) deficiency (glycogenosis type VIII) is a rare disorder caused by mutations in the PHKA1 gene encoding the αM subunit of PHK. Only 5 patients with molecular defects in the X-linked PHKA1 gene have been described until now, and they all presented with exercise intolerance. Here, we report a patient with a new mutation in the PHKA1 gene who presented with PHK deficiency, cognitive impairment, but no overt myopathy. This report supports the concept that PHK deficiency is a mild metabolic myopathy and suggests that PHK mutations may interfere with normal brain function.Muscle phosphorylase b kinase deficiency revisitedAndoni Echaniz-Laguna, Hasan O. Akman, Michel Mohr, Christine Tranchant, Violaine Talmant-Verbist, Marie-Odile Rolland, Salvatore Dimauro10.1016/j.nmd.2009.11.004Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers125127http://www.nmd-journal.com/article/PIIS0960896609006889/abstract?rss=yesAbstract: The authors describe a 50-year-old man who was evaluated for a rigid spine syndrome with onset at age 15, and subsequent walking difficulties. Cardiac and pulmonary functions were normal. Deltoid biopsy revealed the presence of small vacuoles and increased glycogen with Periodic Acid Schiff staining in a limited number of fibers. Acid α-glucosidase staining was decreased in leucocytes, and genetic analysis identified the presence of two mutations in that gene. This observation suggests that Pompe disease should be considered in the differential diagnosis of rigid spine syndrome, even in patients without respiratory involvement or with a muscle biopsy showing only mild histopathological changes.Rigid spine syndrome revealing late-onset Pompe diseasePascal Laforêt, Valérie Doppler, Catherine Caillaud, Kenza Laloui, Kristl G. Claeys, Pascale Richard, Ana Ferreiro, Bruno Eymard10.1016/j.nmd.2009.11.006Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers128130http://www.nmd-journal.com/article/PIIS0960896609006634/abstract?rss=yesAbstract: Isolated complex I deficiency is the most commonly reported enzyme defect in paediatric mitochondrial disorders, and may arise due to mutations in nuclear-encoded structural or assembly genes, or the mitochondrial genome. We present the clinical, biochemical and molecular genetic data in a young girl whose clinical picture is dominated by chronic renal failure, myopathy and persistent lactic acidosis. An isolated complex I deficiency in muscle was identified due to a novel mutation (m.12425delA) in the MTND5 gene. This single nucleotide deletion is heteroplasmic and detectable in several tissues from the proband but not her mother, suggesting a de novo mutation event. The description of the first frameshift mutation in a mitochondrial complex I gene affirms mitochondrial DNA mutations as an important cause of isolated complex I deficiency in children and the importance of whole mitochondrial genome sequencing in the diagnostic work-up to elucidate the underlying molecular genetic abnormality and provide important genetic advice.A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathyCharlotte L. Alston, Monika Morak, Christopher Reid, Iain P. Hargreaves, Simon A.S. Pope, John M. Land, Simon J. Heales, Rita Horvath, Helen Mundy, Robert W. Taylor10.1016/j.nmd.2009.10.010Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers131135http://www.nmd-journal.com/article/PIIS0960896609006919/abstract?rss=yesAbstract: Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle involvement should be considered in patients with hemophagocytic syndrome to ensure proper treatment.Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantationAlfred Peter Born, Klaus Müller, Hanne Vibeke Marquart, Carsten Heilmann, Lone Schejbel, John Vissing10.1016/j.nmd.2009.11.009Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers136138http://www.nmd-journal.com/article/PIIS0960896609007172/abstract?rss=yesAbstract: Incontinentia pigmenti is an X-linked dominant or sporadic multisystemic disorder with involvement of skin, eyes and central nervous system which results from mutations in the gene for NF-kappaB essential modulator (NEMO). We report on a patient with genetically confirmed Bloch–Sulzberger syndrome, who presented with a progressive myopathy and cardiomyopathy. Genetic analyses revealed an intragenic deletion (Intron3 and Exon10) of the NEMO/IKKγ/IKKAP/IKBKG gene. Further complete sequencing of genes encoding for desmin, lamin A/C, emerin, and FHL1 showed no evidence of pathogenic mutations. A pathological expansion of CCTG repeats of the ZNF9 gene (PROMM) was ruled out by PCR amplification analysis. MLPA-analysis showed no evidence for duplications or deletions of the dystrophin gene. This report highlights the unusual combination of a genetically confirmed incontinentia pigmenti and a proximal myopathy and dilatative cardiomyopathy of unknown origin. We discuss that the striated muscle involvement (i) might be based on the observed intragenic deletion of the NEMO gene, or (ii) on an additional gene defect leading to an adult onset myopathy. Further studies on neuromuscular involvement in patients with incontinentia pigmenti are needed to clarify this issue.Incontinetia pigmenti-related myopathy or unsolved “double trouble”?H.B. Huttner, G. Richter, A. Jünemann, W. Kress, J. Weis, J.M. Schröder, A. Gal, A. Doerfler, B. Udd, R. Schröder10.1016/j.nmd.2009.12.006Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Research papers139141http://www.nmd-journal.com/article/PIIS0960896609006853/abstract?rss=yesThis first MRC workshop on inclusion body myositis assembled 29 clinicians and scientists. The workshop sought to establish a platform upon which an organised international network of neuromuscular specialists could consider a range of important unresolved issues in relation to IBM. The aims of the workshop were as follows: to review current practice regarding clinical and histopathological diagnostic criteria, to assess recent advances in relation to aetiology and basic science with potential for translation into clinical trials, to review current evidence for IBM treatments and lessons applicable to future trial design, to review genetic advances in IBM and to consider an IBM disease-specific prospective database in an electronic network.Inclusion body myositis: MRC Centre for Neuromuscular Diseases, IBM workshop, London, 13 June 2008D. Hilton-Jones, A. Miller, M. Parton, J. Holton, C. Sewry, M.G. Hanna10.1016/j.nmd.2009.11.003Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Workshop report142147http://www.nmd-journal.com/article/PIIS0960896609006658/abstract?rss=yesAbstract: This article investigates to what extent patient advocacy organisations play a role in influencing R&D and policymaking for rare neuromuscular diseases. The Dutch neuromuscular disease organisation VSN is studied in depth. A brief history of the VSN is sketched along with the international embedding of the organisation. Then, a more general perspective is provided on the reasons and extent of the involvement of patient organisations (and especially the VSN) in innovation processes. Lastly, internal mechanisms are presented that can best be applied by these organisations. The VSN adheres to a rare, long-term vision on drug innovation that requires long-term planning and policy and vision creation and steering the direction of science and technology. At the same time, other actors like scientific organisations and science policymakers and managers can benefit from these lessons to learn how to deal with patients and patient organisations in the future.The role of patient advocacy organisations in neuromuscular disease R&D – The case of the Dutch neuromuscular disease association VSNWouter Boon, Ria Broekgaarden10.1016/j.nmd.2009.10.012Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Patient's forum148151http://www.nmd-journal.com/article/PIIS0960896609006932/abstract?rss=yesWith the growing interest in day-to-day measures of value to patients, it may be of help to understand what goes through the minds of those who live with dystrophy every day. We don’t think about 6MWT or the density on an MRI. It is much more practical than that. It is falling, broken bones, struggling to breathe, watching one ability after another vanish. As a scientist, I think in equations, models, variables, and predictability. I want to, and can, describe dystrophy in this sort of sterile way. I do think about dystrophy that way. But, I feel it very differently as I watch one muscle after the other decay and vanish.Living with muscular dystrophy: Personal reflectionsMichael W. Munn10.1016/j.nmd.2009.11.011Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7Patient's forum152153http://www.nmd-journal.com/article/PIIS0960896610000362/abstract?rss=yesWMS 201010.1016/S0960-8966(10)00036-2Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7IIhttp://www.nmd-journal.com/article/PIIS0960896610000374/abstract?rss=yesWMS online application form10.1016/S0960-8966(10)00037-4Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7IIIIhttp://www.nmd-journal.com/article/PIIS0960896610000386/abstract?rss=yesWMS News10.1016/S0960-8966(10)00038-6Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7IIIIVhttp://www.nmd-journal.com/article/PIIS0960896610000416/abstract?rss=yesENMC Assessment10.1016/S0960-8966(10)00041-6Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7VVhttp://www.nmd-journal.com/article/PIIS0960896610000428/abstract?rss=yesParent project10.1016/S0960-8966(10)00042-8Neuromuscular Disorders 20, 2 (2010)2010-02-01Neuromuscular Disorders2010-02-01202S0960-8966(10)X0003-7VIVI