Neuromuscular Disorders RSS feed: Articles in Press. 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//inpress?rss=yesElsevier Inc.en © 2012 Elsevier B.V. All rights reserved. Neuromuscular Disorders0960-89662012-05-18 © 2012 Elsevier B.V. All rights reserved. healthpermissions@elsevier.comhttp://www.nmd-journal.com/article/PIIS0960896612000466/abstract?rss=yesAbstract: Adult-onset acid maltase deficiency is a rare disorder characterized by progressive proximal muscle weakness and early respiratory insufficiency. We present a case of a 53-year-old woman who presented with several years of severe, diffuse myalgia and no evidence of weakness on examination. Further testing revealed a mildly elevated serum creatine kinase, a subtle vacuolar myopathy, decreased skeletal muscle α-glucosidase activity, and causative mutations in the responsible GAA gene. While likely very uncommon, adult-onset acid maltase deficiency may present with diffuse strength-sparing myalgia.Myalgic phenotype and preserved muscle strength in adult-onset acid maltase deficiency - Corrected ProofLyell K. Jones, Teerin Liewluck, Ralitza H. Gavrilova10.1016/j.nmd.2012.02.003Neuromuscular Disorders (2012)2012-05-18Neuromuscular Disorders2012-05-18CASE REPORThttp://www.nmd-journal.com/article/PIIS0960896612001009/abstract?rss=yesWe read with interest the manuscript by Ricci et al. about a patient with an overlapping muscular syndrome due to a heterozygous CAV3 T78M mutation and a partial D4Z4 mutation . Although caveolinopathies are usually transmitted as an autosomal dominant trait, the Authors concluded that this CAV3 mutation status maybe considered pathogenic as well, acting in tandem with the known D4Z4 deletion. As support of this hypothesis they offered the phenotype compatible with caveolinopathies, and the muscular biopsy in which caveolin-3 was found markedly reduced.CAV3 T78M mutation as polymorphic variant in South Italy - Corrected ProofPatrizia Spadafora, Maria Liguori, Virginia Andreoli, Aldo Quattrone, Antonio Gambardella10.1016/j.nmd.2012.03.007Neuromuscular Disorders (2012)2012-05-18Neuromuscular Disorders2012-05-18LETTERS TO THE EDITORhttp://www.nmd-journal.com/article/PIIS0960896612001228/abstract?rss=yesAbstract: Missense mutations in the small heat shock protein HSPB8 cause distal hereditary motor neuropathy (dHMN) and axonal Charcot-Marie-Tooth disease (CMT2L). We previously demonstrated that, despite the ubiquitous expression of HSPB8, motor neurons appear to be predominantly affected by HSPB8 mutations. Here, we studied the effect of mutant HSPB8 in primary fibroblast cultures derived from dHMN patients’ skin biopsy. In early passage cultures, we observed in all patients’ fibroblasts HSPB8 protein aggregates that were not detected in control cells. After applying heat shock stress on the patients’ early passage cultured cells, the protein aggregates coalesced into larger formations, while in control cells a homogenous upregulation of HSPB8 protein expression was seen. We also found a reduction in the mitochondrial membrane potential in the early passage cultures. After three months in culture, the number of cells with aggregates had become indistinguishable from that in controls and the mitochondrial membrane potential had returned to normal. These results emphasize the possible drawbacks of using patients’ non-neuronal cells to study neuropathological disease mechanisms.Mutant HSPB8 causes protein aggregates and a reduced mitochondrial membrane potential in dermal fibroblasts from distal hereditary motor neuropathy patients - Corrected ProofJoy Irobi, Anne Holmgren, Vicky De Winter, Bob Asselbergh, Jan Gettemans, Dirk Adriaensen, Chantal Ceuterick-de Groote, Rudy Van Coster, Peter De Jonghe, Vincent Timmerman10.1016/j.nmd.2012.04.005Neuromuscular Disorders (2012)2012-05-17Neuromuscular Disorders2012-05-17http://www.nmd-journal.com/article/PIIS0960896612001022/abstract?rss=yesAbstract: Over 20years ago single clonal deletions were the first mitochondrial DNA (mtDNA) genetic defects described in association with human disease. Since then very large numbers of children and adults harbouring such deletions have been described and it is clear they are an important cause of human mitochondrial disease. However, there still remain many important challenges in relation to our understanding of mechanisms leading to deletion formation and propagation and in relation to the factors determining the complex and varying relationship between genotype and clinical phenotype. Although multidisciplinary team care is essential and can improve quality of life and outcomes for patients, a definitive molecular treatment for single mtDNA deletions remains an important translational research goal. Patients with mtDNA deletions exhibit a very wide range of different clinical phenotypes with marked variation in age at onset and disease severity. Single mtDNA deletions may enter into the differential diagnosis of many different paediatric and adult presentations across a wide range of medical specialties, although neurological presentations are amongst the most common. In this review, we examine the molecular mechanisms underpinning mtDNA replication and we consider the hypotheses proposed to explain the formation and propagation of single large-scale mtDNA deletions. We also describe the range of clinical features associated with single mtDNA deletions, outline a molecular diagnostic approach and discuss current management including the role of aerobic and resistance exercise training programmes.Single deletions in mitochondrial DNA – Molecular mechanisms and disease phenotypes in clinical practice - Corrected ProofR.D.S. Pitceathly, S. Rahman, M.G. Hanna10.1016/j.nmd.2012.03.009Neuromuscular Disorders (2012)2012-05-11Neuromuscular Disorders2012-05-11REVIEWhttp://www.nmd-journal.com/article/PIIS0960896612000806/abstract?rss=yesAbstract: Limb-girdle muscular dystrophy type 2B results from mutations in dysferlin, a membrane-associated protein involved in cellular membrane repair. Primary myoblast cultures derived from dysferlinopathy patients show reduced myogenic potential, suggesting that dysferlin may regulate myotube fusion and be required for muscle regeneration. These observations contrast with the findings that muscle develops normally in pre-symptomatic dysferlinopathy patients. To better understand the role of dysferlin in myogenesis, we investigated this process in vitro using cells derived from two mouse models of dysferlinopathy: SJL/J and A/J mice. We observed that myotubes derived from dysferlin-deficient muscle were of significantly smaller diameters, contained fewer myonuclei, and displayed reduced myogenic gene expression compared to dysferlin-sufficient cells. Together, these findings suggest that the absence of dysferlin from myoblasts is detrimental to myogenesis. Pro-inflammatory NFκB signaling was upregulated in dysferlin-deficient myotubes; the anti-inflammatory agent celastrol reduced the NFκB activation and improved myogenesis in dysferlin-deficient cultures. The results suggest that decreased myotube fusion in dysferlin deficiency is attributable to intrinsic inflammatory activation and can be improved using anti-inflammatory mediators.Myogenesis in dysferlin-deficient myoblasts is inhibited by an intrinsic inflammatory response - Corrected ProofTatiana V. Cohen, Jonathan E. Cohen, Terence A. Partridge10.1016/j.nmd.2012.03.002Neuromuscular Disorders (2012)2012-05-07Neuromuscular Disorders2012-05-07http://www.nmd-journal.com/article/PIIS0960896612001010/abstract?rss=yesAbstract: Nemaline myopathy and myofibrillar myopathy are heterogeneous myopathies that both comprise early-onset forms. We present two sisters from a consanguineous Iraqi Kurdish family with predominant axial and limb girdle weakness. Muscle biopsies showed features of both nemaline myopathy and myofibrillar myopathy. We performed homozygosity mapping in both siblings using an Affymetrix 250K Nspl SNP array. One of the overlapping homozygous regions harbored the gene CFL2. Because a mutation in CFL2 was identified in a family with nemaline myopathy, we performed sequence analysis of the gene and a novel homozygous missense mutation in exon 2 (c.19G>A, p.Val7Met) of CFL2 was identified in both siblings. CFL2 encodes the protein cofilin-2, which plays an important role in regulation of sarcomeric actin filaments. To our knowledge, this is the second family in which a mutation in CFL2 causes an autosomal recessive form of congenital myopathy with features of both nemaline and myofibrillar myopathy. Given the clinical variability and the multitude of histological features of congenital myopathies, CFL2 sequence analysis should be considered in patients presenting with an autosomal recessive form of congenital myopathy.Congenital myopathy caused by a novel missense mutation in the CFL2 gene - Corrected ProofC.W. Ockeloen, H.J. Gilhuis, R. Pfundt, E.J. Kamsteeg, P.B. Agrawal, A.H. Beggs, A. Dara Hama-Amin, A. Diekstra, N.V.A.M. Knoers, M. Lammens, N. van Alfen10.1016/j.nmd.2012.03.008Neuromuscular Disorders (2012)2012-05-07Neuromuscular Disorders2012-05-07http://www.nmd-journal.com/article/PIIS0960896612001150/abstract?rss=yesAbstract: Inclusion body myositis is an inflammatory myopathy characterized pathologically by rimmed vacuoles and the accumulation of amyloid-related proteins. Autopsy studies in these patients, including histochemical examinations of multiple skeletal muscles, have not yet been published. In this paper, we describe the autopsy findings of a patient with inclusion body myositis and hypertrophic cardiomyopathy. A 69-year-old man, who was a human T lymphotropic virus type 1 carrier, exhibited slowly progressive muscle weakness and atrophy, predominantly affecting the scapular, quadriceps femoris, and forearm flexor muscles. His disease course was more rapidly progressive than that typically observed; the patient died suddenly of arrhythmia 5years after diagnosis. Autopsy findings revealed that multiple muscles, including the respiratory muscles, were involved. Longitudinal studies revealed an increased frequency of rimmed vacuoles and p62/sequestosome 1- and/or TAR DNA-binding protein 43-positive deposits in autopsied muscles, although the amount of inflammatory infiltrate appeared to be decreased. We speculated that muscle degeneration may be more closely involved in disease progression compared with autoimmunity. Genetic analysis revealed a myosin binding protein C3 mutation, which is reportedly responsible for familial hypertrophic cardiomyopathy. This mutation and human T lymphotropic virus type 1 infection may have affected the skeletal muscles of this patient.Inclusion body myositis coexisting with hypertrophic cardiomyopathy: An autopsy study - Corrected ProofYukie Inamori, Itsuro Higuchi, Teruhiko Inoue, Yusuke Sakiyama, Akihiro Hashiguchi, Keiko Higashi, Tadafumi Shiraishi, Ryuichi Okubo, Kimiyoshi Arimura, Yoshio Mitsuyama, Hiroshi Takashima10.1016/j.nmd.2012.03.011Neuromuscular Disorders (2012)2012-05-07Neuromuscular Disorders2012-05-07http://www.nmd-journal.com/article/PIIS0960896612001186/abstract?rss=yesAbstract: Either dominantly inherited mutations in MFN2 encoding mitofusin 2 or GDAP1 encoding ganglioside-induced differentiation associated protein 1 may be associated with mild neuropathy.The proband, a 41-year-old woman, and her daughter present a severe axonal form of Charcot–Marie–Tooth (CMT) disease. Both are heterozygous for the well-described mild variant p.R120W in GDAP1, which was transmitted by the pauci symptomatic proband’s mother. Given that they had an early onset in the first decade and delayed walking acquisition, the other genes implicated in axonal forms of CMT disease were analyzed. A second mutation truncating MFN2 (p.Val160fsX26) was found in the proband and her daughter. This mutation was transmitted by the proband’s father who has normal neurological examination. The proband underwent two nerve biopsies which showed an axonal degeneration, myelin modifications, and intra-axonal mitochondria with distorted cristae. Such abnormal mitochondria have been reported in cases with autosomal dominant MFN2 mutations and in one patient with an autosomal recessive GDAP1 mutation. Our two cases show that heterozygous truncation of MFN2, which is silent at least until the sixth decade, when combined with the mild p.R120W GDAP1 variant, leads to a severe neuropathy. This supports the emerging hypothesis of cumulative effects of MFN2 and GDAP1 mutation.A French family with Charcot–Marie–Tooth disease related to simultaneous heterozygous MFN2 and GDAP1 mutations - Corrected ProofAnne Vital, Philippe Latour, Guilhem Sole, Xavier Ferrer, Marie Rouanet, François Tison, Claude Vital, Cyril Goizet10.1016/j.nmd.2012.04.001Neuromuscular Disorders (2012)2012-04-30Neuromuscular Disorders2012-04-30http://www.nmd-journal.com/article/PIIS0960896612001198/abstract?rss=yesAbstract: Charcot–Marie–Tooth neuropathies (CMT) are a group of clinically and genetically heterogeneous disorders of the peripheral nervous system. Selection of candidate disease genes for mutation analysis is sometimes difficult since more than 40 genes and loci are known to be associated with CMT neuropathies. Hence a Czech family Cz-CMT with demyelinating type of autosomal dominant CMT disease was investigated by genome-wide linkage analysis by means of single-nucleotide polymorphism (SNP) arrays. Among 35 regions with linkage, five carried known CMT genes. In the final result a novel early growth response 2 – missense mutation c.1235 A>G, p.Glu412Gly was found. Surprisingly, the more severely affected proband carried an additional heterozygous myelin protein zero variant p.Asp246Asn detected previously, which may modify the phenotype. However, this MPZ variant is benign in heterozygous state alone, because it is also carried by the patient’s healthy father.Charcot–Marie–Tooth neuropathy due to a novel EGR2 gene mutation with mild phenotype – Usefulness of human mapping chip linkage analysis in a Czech family - Corrected ProofDana Šafka Brožková, Soňa Nevšímalová, Radim Mazanec, Bernd Rautenstrauss, Pavel Seeman10.1016/j.nmd.2012.04.002Neuromuscular Disorders (2012)2012-04-30Neuromuscular Disorders2012-04-30http://www.nmd-journal.com/article/PIIS0960896612000818/abstract?rss=yesAbstract: Laing distal myopathy is an autosomal dominant disease due to mutations in the gene encoding for the human slow-β myosin heavy chain, MYH7. Most reports describe it as a mild, early onset myopathy with involvement usually restricted to foot extensors, hand finger extensors and neck flexors, and unspecific findings on muscle biopsy. We identified the first two Italian families with Laing distal myopathy, harboring two novel mutations in the MYH7 gene and performed clinical, neurophysiological, pathological, muscle MRI and cardiological investigations on affected members from the two families. Subjects from one family presented a moderate-severe phenotype, with proximal together with distal involvement and even loss of ambulation at advanced age. One patient displayed atypical muscle biopsy findings including cytoplasmic bodies and myofibrillar myopathy-like features. Affected members from the second family shared a very mild phenotype, with weakness largely limited to long toe and foot extensors and/or late onset. No patient showed any sign of heart involvement. Our study significantly broadens the clinical and pathological spectrum of Laing distal myopathy. We suggest that MYH7 screening should be considered in undiagnosed late-onset distal myopathy or cytoplasmic body myopathy patients.New phenotype and pathology features in MYH7-related distal myopathy - Corrected ProofGiorgio Tasca, Enzo Ricci, Sini Penttilä, Mauro Monforte, Vincenzo Giglio, Pierfrancesco Ottaviani, Giovanni Camastra, Gabriella Silvestri, Bjarne Udd10.1016/j.nmd.2012.03.003Neuromuscular Disorders (2012)2012-04-23Neuromuscular Disorders2012-04-23http://www.nmd-journal.com/article/PIIS096089661200082X/abstract?rss=yesAbstract: The pathogenesis of myotonic dystrophy type 2 includes the sequestration of MBNL proteins by expanded CCUG transcripts, which leads to an abnormal splicing of their target pre-mRNAs. We have found CCUGexp RNA transcripts of the ZNF9 gene associated with the formation of ribonuclear foci in human skeletal muscle and some non-muscle tissues present in muscle biopsies and skin excisions from myotonic dystrophy type 2 patients. Using RNA-FISH and immunofluorescence-FISH methods in combination with a high-resolution confocal microscopy, we demonstrate a different frequency of nuclei containing the CCUGexp foci, a different expression pattern of MBNL1 protein and a different sequestration of MBNL1 by CCUGexp repeats in skeletal muscle, vascular smooth muscle and endothelia, Schwann cells, adipocytes, and ectodermal derivatives. The level of CCUGexp transcription in epidermal and hair sheath cells is lower compared with that in other tissues examined. We suppose that non-muscle tissues of myotonic dystrophy type 2 patients might be affected by a similar molecular mechanism as the skeletal muscle, as suggested by our observation of an aberrant insulin receptor splicing in myotonic dystrophy type 2 adipocytes.Sequestration of MBNL1 in tissues of patients with myotonic dystrophy type 2 - Corrected ProofZ. Lukáš, M. Falk, J. Feit, O. Souček, I. Falková, L. Štefančíková, E. Janoušová, L. Fajkusová, J. Zaorálková, R. Hrabálková10.1016/j.nmd.2012.03.004Neuromuscular Disorders (2012)2012-04-23Neuromuscular Disorders2012-04-23http://www.nmd-journal.com/article/PIIS096089661200079X/abstract?rss=yesAbstract: Although neuromuscular clinical features often dominate the clinical presentation of mitochondrial disease due to the m.3243A>G mitochondrial DNA (mtDNA) mutation, many patients develop cardiac failure, which is often overlooked until it reaches an advanced stage. We set out to determine whether cardiac complications are sufficiently common to warrant prospective screening in all mutation carriers. Routine clinical echocardiography and 3 Tesla cardiac MRI were performed on ten m.3243A>G mutation carriers and compared to age and gender matched controls, with contemporaneous quadriceps muscle biopsies to measure respiratory chain activity and mtDNA mutation levels. Despite normal echocardiography, all ten m.3243A>G mutation carriers had evidence of abnormal cardiac function on MRI. The degree of cardiac dysfunction correlated with the percentage level of mutant mtDNA in skeletal muscle. Sub-clinical cardiac dysfunction was a universal finding in this study, adding weight to the importance of screening for cardiac complications in patients with m.3243A>G. The early detection of cardiac dysfunction with MRI opens up opportunities to prevent heart failure in these patients through early intervention.Cardiomyopathy is common in patients with the mitochondrial DNA m.3243A>G mutation and correlates with mutation load - Corrected ProofKieren G. Hollingsworth, Grainne S. Gorman, Michael I. Trenell, Robert McFarland, Robert W. Taylor, Douglass M. Turnbull, Guy A. MacGowan, Andrew M. Blamire, Patrick F. Chinnery10.1016/j.nmd.2012.03.001Neuromuscular Disorders (2012)2012-04-18Neuromuscular Disorders2012-04-18http://www.nmd-journal.com/article/PIIS0960896612000831/abstract?rss=yesAbstract: Using the emerging technique of peripheral nerve ultrasonography, multiple focal nerve swellings corresponding to sites of existing conduction blocks have been described in demyelinating polyneuropathies. We report two cases of multifocal acquired demyelinating sensory and motor neuropathy (MADSAM). In the first, multiple focal nerve enlargements were detected by ultrasound at sites of previous conduction blocks, well after complete clinical and electrophysiological resolution. In the second case, existing proximal conduction blocks could be localized by ultrasound. Our cases highlight the importance of nerve ultrasound in identifying conduction blocks and demonstrate that ultrasonographic morphological changes may outlast functional recovery in demyelinating neuropathies.Ultrasonography of MADSAM neuropathy: Focal nerve enlargements at sites of existing and resolved conduction blocks - Corrected ProofErika Scheidl, Josef Böhm, Magdolna Simó, Csilla Rózsa, Benjamin Bereznai, Tibor Kovács, Zsuzsanna Arányi10.1016/j.nmd.2012.03.005Neuromuscular Disorders (2012)2012-04-18Neuromuscular Disorders2012-04-18CASE REPORThttp://www.nmd-journal.com/article/PIIS0960896612000995/abstract?rss=yesAbstract: Disorders of mitochondrial DNA (mtDNA) maintenance are clinically and genetically heterogeneous, embracing recessive mtDNA depletion syndromes affecting children and adult-onset multiple mtDNA deletion disorders. Here we show that mutation of MPV17 – a gene implicated in severe, infantile hepatocerebral mtDNA depletion disorders characterised by a loss of mtDNA copies – can also cause clonally-expanded mtDNA deletion and focal cytochrome c oxidase (COX) deficiency in skeletal muscle associated with an adult presentation of neuropathy and leukoencephalopathy. The mpv17 protein is therefore intimately involved in both the mtDNA replication and repair processes and associated with both quantitative and qualitative mtDNA abnormalities.MPV17 mutation causes neuropathy and leukoencephalopathy with multiple mtDNA deletions in muscle - Corrected ProofEmma L. Blakely, Anna Butterworth, Robert D.M. Hadden, Istvan Bodi, Langping He, Robert McFarland, Robert W. Taylor10.1016/j.nmd.2012.03.006Neuromuscular Disorders (2012)2012-04-16Neuromuscular Disorders2012-04-16http://www.nmd-journal.com/article/PIIS0960896612000788/abstract?rss=yesAbstract: X-linked Charcot–Marie–Tooth disease (CMT1X) is the second most common inherited neuropathy, caused by mutations in gap junction beta-1 (GJB1). Males have a uniformly moderately severe phenotype while females have a variable phenotype, suggested to be due to X inactivation. We aimed to assess X inactivation pattern in females with CMT1X and correlate this with phenotype using the CMT examination score to determine whether the X inactivation pattern accounted for the variable phenotype in females with CMT1X. We determined X inactivation pattern in 67 females with CMT1X and 24 controls using the androgen receptor assay. We were able to determine which X chromosome carried the GJB1 mutation in 30 females. There was no difference in X inactivation pattern between patients and controls. In addition, there was no correlation between X inactivation pattern in blood and phenotype. A possible explanation for these findings is that the X inactivation pattern in Schwann cells rather than in blood may explain the variable phenotype in females with CMT1X.X inactivation in females with X-linked Charcot–Marie–Tooth disease - Corrected ProofSinéad M. Murphy, Richard Ovens, James Polke, Carly E. Siskind, Matilde Laurà, Karen Bull, Gita Ramdharry, Henry Houlden, Raymond P.J. Murphy, Michael E. Shy, Mary M. Reilly10.1016/j.nmd.2012.02.009Neuromuscular Disorders (2012)2012-04-09Neuromuscular Disorders2012-04-09http://www.nmd-journal.com/article/PIIS0960896612000727/abstract?rss=yesAbstract: There have been suggestions from previous studies that patients with Charcot–Marie–Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.Hand weakness in Charcot-Marie-Tooth disease 1X - Corrected ProofP.J. Arthur-Farraj, S.M. Murphy, M. Laura, M.P. Lunn, H. Manji, J. Blake, G. Ramdharry, Z. Fox, M.M. Reilly10.1016/j.nmd.2012.02.008Neuromuscular Disorders (2012)2012-03-30Neuromuscular Disorders2012-03-30http://www.nmd-journal.com/article/PIIS0960896612000557/abstract?rss=yesThe 187th ENMC Workshop on dystroglycan and dystroglycanopathies in Naarden from 11th to 13th November 2011, brought together 20 researchers from seven different countries (Germany, Italy, The Netherlands, Sweden, Switzerland, UK and USA) working on the clinical and basic aspects of the post-translational modification of dystroglycan. Topics included the pathophysiology in patients, animal models of dystroglycanopathies, and cellular approaches addressing the effects of post-translational modification on dystroglycan function in a variety of systems. Specific issues which were addressed included factors that might determine the development of central nervous system involvement in patients, if current cell and animal models of the dystroglycanopathies are appropriate for the study of the disease and their utility for therapeutic screening and whether dystroglycan signalling pathways in the cytoskeleton, cancer and polarity can provide new insight into the dystroglycanopathies.Dystroglycan and dystroglycanopathies: Report of the 187th ENMC Workshop 11–13 November 2011, Naarden, The Netherlands - Corrected ProofSusan C. Brown, Steve J. Winder10.1016/j.nmd.2012.02.006Neuromuscular Disorders (2012)2012-03-21Neuromuscular Disorders2012-03-21WORKSHOP REPORThttp://www.nmd-journal.com/article/PIIS0960896612000545/abstract?rss=yesAbstract: Excessive daytime sleepiness (EDS), of very similar pattern to that seen in narcolepsy syndrome, is extremely common in myotonic dystrophy type 1 (DM1). In a significant minority it has a profound disabling effect on employment, social functioning and activities of daily living. Limited published studies have shown inconsistent results from use of the psychostimulant drug modafinil. A recent European Medicines Agency (EMA) review concluded that on current evidence regarding safety and efficacy, modafinil’s use should be restricted to the treatment of narcolepsy. In other conditions (although DM1 was not specifically considered) it was concluded that there was insufficient evidence of benefit to outweigh potentially serious side-effects, including severe skin reactions and cardiac arrhythmia. Clinicians with extensive experience in the management of DM1 have found modafinil to be extremely effective in appropriately selected patients with a very low incidence of serious side-effects. Given the recent EMA review, patients have expressed concern about the potential restriction of the use of modafinil in DM1. This brief review is an audit of the experience of a large group of patients and their clinicians concerning EDS and DM1 and concludes that despite the limited literature there is strong evidence to support the use of modafinil in carefully selected patients.Modafinil for excessive daytime sleepiness in myotonic dystrophy type 1 – The patients’ perspective - Corrected ProofD. Hilton-Jones, M. Bowler, H. Lochmueller, C. Longman, R. Petty, M. Roberts, M. Rogers, C. Turner, D. Wilcox10.1016/j.nmd.2012.02.005Neuromuscular Disorders (2012)2012-03-19Neuromuscular Disorders2012-03-19