Edited by Ashraf Zaher NEUROMUSCULAR DISORDERS Edited by Ashraf Zaher Neuromuscular Disorders Edited by Ashraf Zaher Published by InTech Janeza Trdine 9, 51000 Rijeka, Croatia Copyright © 2012 InTech All chapters are Open Access distributed under the Creative Commons Attribution 3.0 license, which allows users to download, copy and build upon published articles even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. After this work has been published by InTech, authors have the right to republish it, in whole or part, in any publication of which they are the author, and to make other personal use of the work. Any republication, referencing or personal use of the work must explicitly identify the original source. As for readers, this license allows users to download, copy and build upon published chapters even for commercial purposes, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. Notice Statements and opinions expressed in the chapters are these of the individual contributors and not necessarily those of the editors or publisher. No responsibility is accepted for the accuracy of information contained in the published chapters. The publisher assumes no responsibility for any damage or injury to persons or property arising out of the use of any materials, instructions, methods or ideas contained in the book. Publishing Process Manager Oliver Kurelic Technical Editor Teodora Smiljanic Cover Designer InTech Design Team First published July, 2012 Printed in Croatia A free online edition of this book is available at www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Neuromuscular Disorders, Edited by Ashraf Zaher p. cm. ISBN 978-953-51-0696-8 Contents Preface IX Chapter 1 Integrins in the Development and Pathology of Skeletal Muscle 1 Susan C. Brown, Ulrich Mueller and Francesco J. Conti Chapter 2 Facioscapulohumeral Muscular Dystrophy: From Clinical Data to Molecular Genetics and Return 21 Monica Salani, Elisabetta Morini, Isabella Scionti and Rossella Tupler Chapter 3 AON-Mediated Exon Skipping for Duchenne Muscular Dystrophy 55 Ingrid E. C. Verhaart and Annemieke Aartsma-Rus Chapter 4 Psychosocial Support Needs of Families of Boys with Duchenne Muscular Dystrophy 81 Jean K. Mah and Doug Biggar Chapter 5 Comparison Between Courses of Home and Inpatients Mechanical Ventilation in Patients with Muscular Dystrophy in Japan 105 Toshio Saito and Katsunori Tatara Chapter 6 Myopathy in Autoimmune Diseases – Primary Sjögren’s Syndrome and Dermatomyositis 117 Fumio Kaneko, Ari Togashi, Erika Nomura, Teiji Yamamoto and Hideo Sakuma Chapter 7 Dermatomyositis 129 Fred van Gelderen Chapter 8 Interstitial Pneumonia in Dermatomyositis 143 Tohru Takeuchi, Takuya Kotani and Shigeki Makino VI Contents Chapter 9 IBMPFD and p97, the Structural and Molecular Basis for Functional Disruption 155 Wai-Kwan Tang and Di Xia Chapter 10 Congenital Myasthenic Syndromes – Molecular Bases of Congenital Defects of Proteins at the Neuromuscular Junction 175 Kinji Ohno, Mikako Ito and Andrew G. Engel Chapter 11 Motor Neuron Disease 201 Hamdy N. El Tallawy Chapter 12 Spinal Muscular Atrophy 221 Yasser Salem Chapter 13 Respiratory Muscle Aids in the Management of Neuromuscular Respiratory Impairment to Prevent Respiratory Failure and Need for Tracheostomy 235 A. J. Hon and J. R. Bach Chapter 14 Neuromuscular Diseases in the Context of Psychology and Educational Science 253 Andrea Pieter and Michael Fröhlich Preface Recent advances in the understanding of the genetics and basic mechanisms of neuromuscular diseases have been both rapid and spectacular. Furthermore, these advances have resulted in an expansion of the methods used for diagnosis—from routine clinical histologic and electrophysiologic tests to more specific techniques, such as biochemical and Western Blot analysis, and, most important, molecular genetic testing. These modern techniques have begun to replace more costly and painful procedures for some patients . Although the goal of our specialty is to find cures or effective treatments for neuromuscular disorders, the management of symptoms to improve quality of life is still paramount. Ambulation and survival can be prolonged with well-planned rehabilitation programs, orthopaedic surgery, and proper early management of cardiac, respiratory, and gastrointestinal complications, particularly in patients with motor neuron diseases and muscular dystrophy. Prolonged survival has changed the care of these patients. For example, in the past patients with Duchenne muscular dystrophy generally died of respiratory failure before they developed symptomatic cardiac disease; now they are living longer and require aggressive treatment of their cardiac complications to further prolong their lives . Many excellent textbooks and treatises dedicated to the understanding of the basic mechanisms of clinical and laboratory diagnoses of neuromuscular diseases also include discussions of treatment but this information is not comprehensive. In this text we aim to cover the current treatment and management of these subjects and to discuss promising experimental therapies . The introductory chapter is a brief overview of the Integrins in the development and pathology of skeletal muscle—information that we hope will be helpful to young clinicians. The next several chapters discuss neuromuscular disorders and their general management, such as rehabilitation, orthopaedic surgery, and cardiac, gastrointestinal, and respiratory care. The balance of the chapters covers specific diseases as well as the basic mechanisms of these disorders . The information in each chapter is intended to complement that in others, although occasionally there are minor repetitions. When possible, evidence-based treatment X Preface recommendations are given, particularly for the more common conditions, though we emphasize that the treatment of all patients should be individualized. For less common disorders, for which controlled trials have not yet been published, recommendations are based on published information and the authors’ experience . I am honored and grateful for the collaboration of an excellent group of renowned specialists. They have generously contributed their time and expertise to make what we hope is a textbook that is useful for all physicians who care for patients with neuromuscular disorders . Ashraf Zaher, MD Lecturer and Consultant of Neurology, University of Mansoura, Mansoura, Egypt [...]... adult, and mutant muscle: selective association of alpha1, alpha7A, and alpha7B integrins with the neuromuscular junction', Developmental biology 174(1): 125-39 Mayer, U (2003) 'Integrins: redundant or important players in skeletal muscle?', The Journal of biological chemistry 278(17): 14587-90 18 Neuromuscular Disorders Mayer, U., Saher, G., Fassler, R., Bornemann, A., Echtermeyer, F., von der Mark, H.,... development Fusion of myoblasts is essential for the formation of a syncytial myofibre, and it occurs in distinct steps: (i) migration of myoblasts to achieve cell proximity; (ii) contact between 4 Neuromuscular Disorders myoblasts and alignment of the plasma membranes; (iii) breakdown of the plasma membrane at the site of fusion, leading to the formation of fusion pores (iv) merging of the cytoplasmic... muscle, where it localizes to the sarcolemma and to the Z-disk, and interacts with several proteins associated with muscular dystrophies, including calpain-3and sarcoglycans (Zhou et al., 2010) 6 Neuromuscular Disorders Downregulation of filamin C in C2C12 myoblasts via siRNA causes an impairment of cellcell fusion, defective elongation of myotubes, and impaired gene expression during myoblast differentiation,... rare 4.2 Talin Of the proteins that bind to the cytoplasmic domain of integrins, studies have revealed important functions for talin in mediating the connection to myofilaments at the MTJ In 8 Neuromuscular Disorders Drosophila, ablation of the talin gene (mys), induces detachment of actin filaments from the integrin cytoplasmic domain at muscle termini (Brown et al., 2002) Two talin isoforms are expressed... (ILK) ILK is closely associated to 1 and 3-integrins (Hannigan et al., 1996; Zervas et al., 2001; Wickstrom et al., 2010), and binds to several proteins that relay biochemical signals and 10 Neuromuscular Disorders regulate actin dynamics, including paxillin, -and -parvins and PKB Ablation of ILK in invertebrates leads to detachment of myofibres at the MTJ, a phenotype similar to that obtained... FAK ablation in cardiomyocytes These mice developed defects that included thinner ventricular walls, ventricular septal defects and reduced cell numbers (DiMichele et al., 2006; Hakim et al., 12 Neuromuscular Disorders 2007; Peng et al., 2008) However, the function of FAK in the postnatal heart is still unclear, as studies provide contrasting data on its function in cardiac hypertrophy, reporting either... biology 139(6): 1583-95 Bendig, G., Grimmler, M., Huttner, I G., Wessels, G., Dahme, T., Just, S., Trano, N., Katus, H A., Fishman, M C and Rottbauer, W (2006) 'Integrin-linked kinase, a novel 14 Neuromuscular Disorders component of the cardiac mechanical stretch sensor, controls contractility in the zebrafish heart', Genes & development 20(17): 2361-72 Bitoun, M., Maugenre, S., Jeannet, P Y., Lacene,... hypertrophy and failure', Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas / Sociedade Brasileira de Biofisica [et al.] 42(1): 44-52 16 Neuromuscular Disorders Franchini, K G., Torsoni, A S., Soares, P H and Saad, M J (2000) 'Early activation of the multicomponent signaling complex associated with focal adhesion kinase induced by pressure overload... The two main adhesion systems recognised in striated muscle are the dystrophin-associated protein complex (DPC) and the integrins Each system is composed of transmembrane * Corresponding Author 2 Neuromuscular Disorders proteins that bind to the ECM, and of cytoplasmic proteins that connect to the cytoskeleton and transmit biochemical signals The DPC is composed of several proteins, which include - and... Anatomists 210(4): 472-86 Vasile, V C., Will, M L., Ommen, S R., Edwards, W D., Olson, T M and Ackerman, M J (2006) 'Identification of a metavinculin missense mutation, R975W, associated with 20 Neuromuscular Disorders both hypertrophic and dilated cardiomyopathy', Molecular genetics and metabolism 87(2): 169-74 Vasyutina, E., Martarelli, B., Brakebusch, C., Wende, H and Birchmeier, C (2009) 'The small . Edited by Ashraf Zaher NEUROMUSCULAR DISORDERS Edited by Ashraf Zaher Neuromuscular Disorders Edited by Ashraf Zaher Published by. www.intechopen.com Additional hard copies can be obtained from orders@intechopen.com Neuromuscular Disorders, Edited by Ashraf Zaher p. cm. ISBN 978-953-51-0696-8 Contents. Aids in the Management of Neuromuscular Respiratory Impairment to Prevent Respiratory Failure and Need for Tracheostomy 235 A. J. Hon and J. R. Bach Chapter 14 Neuromuscular Diseases in the