Managing pregnancy and anaesthetics in patients with skeletal muscle channelopathies
The skeletal muscle channelopathies are a rare group of inherited diseases which result from the abnormal functioning of voltage-gated ion channels expressed in skeletal muscle. They are made up of non-dystrophic myotonia (NDM) and periodic paralysis (PP). In the UK the prevalence is at least 1.12/100,000 and increasing as our use of next generation sequencing and our rapidly evolving knowledge extends the number of genetically confirmed cases [1]. These diseases are not normally life limiting and therefore the management of these patients during pregnancy and anaesthesia is even more pertinent, especially given the role o...
Source: Neuromuscular Disorders - May 28, 2020 Category: Neurology Authors: Dipa L Raja Rayan, Michael G Hanna Source Type: research

Transportin 3 (TNPO3) and related proteins in limb girdle muscle dystrophy D2 muscle biopsies: a morphological confocal microscopy study and pathogenetic hypothesis.
1. Introduction (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 26, 2020 Category: Neurology Authors: Roberta Costa, Maria Teresa Rodia, Sara Vianello, Spartaco Santi, Giovanna Lattanzi, Corrado Angelini, Elena Pegoraro, Giovanna Cenacchi Source Type: research

Mutations in the SIGMAR1 gene cause a distal hereditary motor neuropathy phenotype mimicking ALS: Report of two novel variants
Introduction: (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 22, 2020 Category: Neurology Authors: Maxwell T. Ma, Dong-Hui Chen, Wendy H. Raskind, Thomas D. Bird Tags: Case report Source Type: research

Spontaneous Symptomatic Improvement in a Pediatric Patient with Anti-3-Hydroxy-3-Methylglutraryl-Coenzyme A Reductase Myopathy
Immune-mediated necrotizing myopathy (IMNM) is a subcategory of idiopathic inflammatory myopathies characterized by proximal limb weakness, high creatine kinase (CK) plasma levels, myopathic EMG and histopathological findings of manifest muscle fiber necrosis and regeneration with minimum or no inflammation [1]. IMNM may be associated with anti-signal recognition particle (SRP) and anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), both myositis-specific autoantibodies [1]. A subgroup of seronegative patients has also been described. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 21, 2020 Category: Neurology Authors: Bernardita Su árez, Javiera Jofré, Andres Lozano-Arango, Ximena Ortega, Jorge Diaz, Giancarlo Calcagno, Jorge A. Bevilacqua, Claudia Castiglioni Tags: Case report Source Type: research

First presentation of LPIN1 acute rhabdomyolysis in adolescence and adulthood
Lipin-1 (LPIN1) is an 890 aminoacid intracellular protein involved in different pathways of fatty acid metabolism (1). It belongs to the family of phosphatidate phosphatase (PAP) enzymes and its main role is to catalyse the conversion of phosphatidate to diacylglycerol, the penultimate step of triglyceride synthesis which constitute the major energy storage in our body (2). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 21, 2020 Category: Neurology Authors: Chiara Pizzamiglio, Nayana Lahiri, Niranjanan Nirmalananthan, Bhrigu Sood, Subash Somalanka, Philip Ostrowski, Rahul Phadke, Dominic Gerard O'Donovan, Francesco Muntoni, Rosaline Quinlivan Tags: Case report Source Type: research

Randomized phase 2 trial and open-label extension of domagrozumab in Duchenne muscular dystrophy
1 ntroduction (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 18, 2020 Category: Neurology Authors: Kathryn R. Wagner, Hoda Z. Abdel-Hamid, Jean K. Mah, Craig Campbell, Michela Guglieri, Francesco Muntoni, Yasuhiro Takeshima, Craig M. McDonald, Anna Kostera-Pruszczyk, Peter Karachunski, Russell J. Butterfield, Eugenio Mercuri, Chiara Fiorillo, Enrico S. Source Type: research

Combining genetics, neuropsychology and neuroimaging to improve understanding of brain involvement in Duchenne muscular dystrophy – a narrative review
Studies have shown that learning and behavioural difficulties are not seen in all Duchenne muscular dystrophy (DMD) patients, and when they are reported the severity varies greatly [1 –4]; this is in contrast to the condition of progressive muscle wasting which is universal. To people living with DMD, brain comorbidities can in fact have a greater impact on the family than limited mobility [5]. There is an acute need for a better understanding of the origin of the cognitive phe notype so that better advice can be provided, learning aids can to be developed or made available, and to determine where appropriate neurops...
Source: Neuromuscular Disorders - May 16, 2020 Category: Neurology Authors: Nathalie Doorenweerd Tags: Review Source Type: research

Confounding clinical presentation and different disease progression in CMT4B1
Charcot-Marie-Tooth (CMT) is the most frequent hereditary sensory and motor neuropathy (10-30/1000,000)[1]. Genetic testing is guided by clinical signs, nerve conduction studies and mode of inheritance. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 16, 2020 Category: Neurology Authors: Raquel Guimar ães-Costa, Rocio-Nur Villar-Quiles, Philippe Latour, Guilhem Sole, Isabelle Husson, Arnaud Lacour, Sarah Leonard-Louis, Tanya Stojkovic Tags: Case Report Source Type: research

Results of an open label feasibility study of Sodium Valproate in people with McArdle disease
1. INTRODUCTION: (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 15, 2020 Category: Neurology Authors: Renata S Scalco, Mads Stemmerik, Nicoline L økken, Christoffer R. Vissing, Karen L. Madsen, Zuzanna Michalak, Jatin Pattni, Richard Godfrey, George Samandouras, Paul Bassett, Janice L. Holton, Ronald G Haller, John Vissing, Ros Quinlivan Source Type: research

VAMP1-Related Congenital Myasthenic Syndrome with Partial Electrophysiological Recovery After Pyridostigmine Therapy
INTRODUCTION (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 14, 2020 Category: Neurology Authors: Mohammad A. Al-Muhaizea, Laila AlQuait, Afnan AlRasheed, Shoug AlHarbi, Anoud Abdulmalik Albader, Rawan AlMass, Albandary Albakheet, Abdullah Alhumaidan, Maha M. AlRasheed, Dilek Colak, Namik Kaya Source Type: research

Double seropositivity for AChR and MuSK autoantibodies in myasthenia gravis
Autoimmune myasthenia gravis (MG) is an acquired, IgG-mediated disorder of neuromuscular transmission that targets the postsynaptic nicotinic acetylcholine receptor (AChR) ion channel in 90% of cases with generalized weakness. An alternative target, in 4 percent of cases, is the muscle-specific tyrosine kinase (MuSK) protein, a component of the functional postsynaptic AChR-complex. Rare double seropositive cases have been reported, both pediatric and adult (1-5), and other synaptic proteins have been implicated, even more rarely. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 13, 2020 Category: Neurology Authors: Mingqin Zhu, Vanda A. Lennon Tags: Commentary Source Type: research

Characterizing cognitive-motor impairments in patients with myotonic dystrophy type 1
Introduction (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 13, 2020 Category: Neurology Authors: Linard Filli, Selina Schwegler, Christian Meyer, Tim Killeen, Christopher S. Easthope, Sarah D. Broicher, Armin Curt, Bj örn Zörner, Marc Bolliger, Hans H. Jung, Jens A. Petersen Source Type: research

Non-dystrophic myotonia Chilean cohort with predominance of the SCN4A Gly1306Glu variant
Non-dystrophic myotonias are muscle channelopathies caused by pathogenic variants in CLCN1 or SCN4A. The specific phenotype or subtype, treatment, and inheritance pattern of non-dystrophic myotonias depend on the involved gene and pathogenic variant of the same gene [1 –3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 13, 2020 Category: Neurology Authors: Daniela Avila-Smirnow, Carmen Paz Vargas Leal, Mar ía de Los Angeles Beytía Reyes, Rocío Cortés Zepeda, Raúl G. Escobar, Karin Kleinsteuber Saa, Marcela Lagos Lucero, María de los Angeles Avaria Benapres, Oslando Padilla Pérez, Juan Carlos Casar Le Source Type: research

MRI findings in SANDO variety of the ataxia-neuropathy spectrum with a novel mutation in POLG (c.3287G > T): A case report.
1. Introduction (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 13, 2020 Category: Neurology Authors: Parada-Garza Juan Didier, L ópez-Valencia German, Miranda-García Luis Adrián, Pérez-García Guillermo, Ruiz-Sandoval José Luis Source Type: research

Muscle cell differentiation and development pathway defects in Emery-Dreifuss muscular dystrophy
Emery-Dreifuss muscular dystrophy (EDMD) is a rare genetic neuromuscular disorder with an estimated world-wide incidence of 1 in 100,000 [1]. The disease is characterised in the early stages by muscle contractures that usually become noticeable during childhood or adolescence[2], accompanied by muscle weakness and wasting that worsens over time. Almost all people with EDMD develop heart abnormalities by adolescence [3]. These typically present as atrioventricular conduction block [2,4,5], but in some cases, dilated cardiomyopathy may gradually develop, which can be further complicated by ventricular tachydysrhythmias [3,5]...
Source: Neuromuscular Disorders - May 11, 2020 Category: Neurology Authors: Emily C Storey, Ian Holt, Glenn E Morris, Heidi R Fuller Source Type: research

1st Sitting Workshop for Neuromuscular disorders. Denmark 30 September – 1 October 2019
From 30th September till 1st October 2019 a workshop was organized on sitting of persons with neuromuscular disorders, specifically focusing on Duchenne muscular dystrophy (DMD), Spinal muscular atrophy (SMA), congenital muscular dystrophy (CMD) and myopathy (CM), in Musholm Ferie-Sport- Konference in Kors ør, Denmark. Recruitment for occupational therapists was done in western European countries, participating countries were Denmark, Norway, Sweden, Belgium, France and the Netherlands. A pre-workshop questionnaire was send around concerning the use of standard evaluating methods and possible interve ntions. (Source...
Source: Neuromuscular Disorders - May 7, 2020 Category: Neurology Authors: Imelda JM de Groot, Ulla Werlauff, Working group sitting in NMD Tags: Workshop report Source Type: research

Hereditary polyneuropathy with optic atrophy due to PDXK variant leading to impaired Vitamin B6 metabolism
Pyridoxal 5 ’-phosphate (PLP) is an essential co-factor involved in vital metabolic pathways, including neurotransmitter production and amino acid biosynthesis [1,2]. Like all other mammals, humans cannot synthesize PLP de novo and therefore require the dietary uptake of the inactive B6 vitamers pyridoxine (P N), pyridoxal (PL), and pyridoxamine (PM) which are subsequently converted into catalytically active PLP [3]. Bioregulation of PLP involves three enzymes namely, pyridoxal kinase (PDXK), pyridoxamine 5’-phosphate oxidase (PNPO) and pyridoxal phosphatase (PDXP). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 28, 2020 Category: Neurology Authors: Natalie Keller, Natalia Mendoza-Ferreira, Reza Maroofian, Viorica Chelban, Youssef Khalil, Philippa B. Mills, Reza Boostani, Paria Najarzadeh Torbati, Ehsan Ghayoor Karimiani, Holger Thiele, Henry Houlden, Brunhilde Wirth, Mert Karakaya Source Type: research

Book review
This smaller size book, edited by two renowned experts in paediatric neuromuscular disorders (NMD), aims to gather in one place extensive knowledge on these rare, ultra-complex conditions from international experts including clinicians, geneticists, physiotherapists, psychologists, surgeons and parents as well. The book is organised in eight sections on clinical assessment and investigations, the most frequent conditions and the main management aspects. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 23, 2020 Category: Neurology Authors: Anna Sarkozy Tags: Book review Source Type: research

Collagen VI-related limb-girdle syndrome caused by frequent mutation in COL6A3 gene with conflicting reports of pathogenicity
Bethlem myopathy 1 and the more severe Ullrich congenital muscular dystrophy 1 are both associated with mutations in one of the three collagen VI genes —COL6A1, COL6A2 and COL6A3. Since the same genes are involved, these two diseases are now often viewed as the two extremes of a spectrum of collagen VI-related myopathies. Lately, however, there has been also data on involvement of the COL12A1 gene, with mutations in it being associated with Bethl em myopathy 2 [1–3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 18, 2020 Category: Neurology Authors: Janis Stavusis, Ieva Micule, Nathan T. Wright, Volker Straub, Ana Topf, Lu ísa Panadés-de Oliveira, Cristina Domínguez-González, Inna Inashkina, Dita Kidere, Nicolas Chrestian, Baiba Lace Source Type: research

Pathogenic variants in COL6A3 cause Ullrich-like congenital muscular dystrophy in young Labrador Retriever dogs
The collagen VI-related muscular dystrophies in people include a broad spectrum of severities ranging from the severe Ullrich congenital muscular dystrophy to the mild type Bethlem [1]. Ullrich congenital muscular dystrophy is rare but is among the most common type of congenital muscular dystrophies in several populations [1,2]. In northern England, the collagen VI-related myopathies have a point prevalence of 0.9 patients for 100,000 individuals [3]. These diseases are caused by both dominantly and recessively acting variants in the three major α-chains encoded by the collagen VI genes COL6A1, COL6A2 and COL6A3, whi...
Source: Neuromuscular Disorders - April 16, 2020 Category: Neurology Authors: V éronique Bolduc, Katie M. Minor, Ying Hu, Rupleen Kaur, Steven G. Friedenberg, Samantha Van Buren, Ling T Guo, Joseph Glennon, Katia Marioni-Henry, James R Mickelson, Carsten G Bönnemann, G. Diane Shelton Source Type: research

Randomisation versus prioritisation in a managed access programme: lessons from spinal muscular atrophy
Over the last few years, spinal muscular atrophy (SMA) has transitioned from being an untreatable, inexorably progressive disease to a condition for which there is now an approved therapeutic option, Nusinersen. Two additional therapeutic options are likely to become available in the very near future in Europe. Published [1] and emerging data from treated, pre-symptomatic patients indicate that a large majority of these individuals have, so far, a normal motor development. This has resulted in a resurgence of the efforts to initiate newborn screening programmes [2]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 16, 2020 Category: Neurology Authors: Laurent Servais, Janbernd Kirschner, Francesco Muntoni Tags: Editorial Source Type: research

Is it Pompe Disease? Australian Diagnostic Considerations
Pompe Disease is a spectrum disorder with an evolving phenotype in which diagnostic delay is common. Contributing factors include the rarity of the disorder, its wide clinical spectrum, signs and symptoms that overlap with those of other neuromuscular disorders, variable diagnostic approaches, lack of awareness of the clinical manifestations and difficulties in completing the diagnostic inventory. International updates and recommendations have been published providing diagnostic guidelines and management criteria. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 16, 2020 Category: Neurology Authors: Michel Tchan, Robert Henderson, Andrew Kornberg, Kristina Kairaitis, Maria Fuller, Mark Davis, Carolyn Ellaway, Katrina Reardon, Alastair Corbett, Merrilee Needham, Penny McKelvie Source Type: research

Clinical and Genomic characteristics of LAMA2 Related congenital Muscular Dystrophy in a Patients ’ Cohort from Qatar. A population Specific Founder Variant
This study aimed to reveal the prevalence, clinical and genomic characteristics of congenital LAMA2-RD in a patient's cohort of 17 families (21 patients) from the Gulf and Middle East.Affected subjects exhibited the classic phenotype of generalized hypotonia, developmental delay, and progressive muscular weakness. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 16, 2020 Category: Neurology Authors: Alice Abdel Aleem, Mahmoud F. Elsaid, Nader Chalhoub, Almahdi Chakroun, Khalid A.S. Mohamed, Rana AlShami, Omer Kuzu, Reem Mohamed, Khalid Ibrahim, Noora AlMudheki, Omar Osman, M. Elizabeth Ross, Osama ELalamy Source Type: research

AChR myasthenia gravis switching to MuSK or double antibody positive myasthenia gravis in two children and literature review
Myasthenia gravis (MG) is an autoantibody-mediated autoimmune disease that affects the neuromuscular junction. In southern China, children and adolescents accounts for approximately 50% of MG cases [1]. Most pediatric MG cases initially manifest extraocular muscle paresis. Muscle tyrosine-specific kinase antibody (MuSK-Ab), discovered in 2001 by Hoch [2], is the second most frequent antibody detected in MG after acetylcholine receptor antibody (AChR-Ab) [3]. AChR-Ab and MuSK-Ab coexistence in the same patient is rare, and only a few double antibody positive MG cases (DP-MG) have been reported [4 –9]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 13, 2020 Category: Neurology Authors: Yaru Lu, Hao Ran, Wenhao Yang, Qian Ma, Li Qiu, Changyi Ou, Pei Chen, Zhongqiang Lin, Weibin Liu Source Type: research

248th ENMC international workshop: Myotonic dystrophies: molecular approaches for clinical purposes, framing a European molecular research network Hoofddorp, The Netherlands, 11 –13 October 2019
A total of 27 participants including molecular biologists, clinicians, geneticists, and patient advocates from 13 countries convened from the October 11 –13, 2019 in Hoofdorp, The Netherlands, for the 248th ENMC International Workshop, on the topic Myotonic dystrophies: molecular approaches for clinical purposes, framing a European molecular research network. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 11, 2020 Category: Neurology Authors: Derick G. Wansink, Genevi ève Gourdon, Baziel G.M. van Engelen, Benedikt Schoser, DM workshop study group Tags: Workshop report Source Type: research

Early pathological signs in young dysf −/− mice are improved by halofuginone
Muscular dystrophies (MDs) are genetically inherited myogenic disorders characterized by progressive muscle wasting and weakness of variable distribution and severity [1]. These symptoms are caused by cycles of myofiber degeneration –regeneration, myofiber necrosis, and the initiation of the dystrophy, resulting in the general pathologies of MDs, such as increased fibrosis, appearance of smaller and split myofibers, and reduced muscle mass [2–5]. The dysferlinopathies are a group of non-lethal MDs (e.g., limb girdle MDs and Myioshi myopathy) [6–8], differing in the muscle group in which the disease phenot...
Source: Neuromuscular Disorders - April 11, 2020 Category: Neurology Authors: Hila Barzilai-Tutsch, Olga Genin, Mark Pines, Orna Halevy Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 1, 2020 Category: Neurology Source Type: research

The Association of Methylprednisolone Dosing to Cessation of Myotonia in a Patient with Myotonic Dystrophy Type 1
We report the case of a patient suffering from duplicity of DM1 and ulcerative colitis (UC) whose treatment for UC included, among other drugs, repeated administrations of descending doses of methylprednisolone and in whom we found an association between initiation of methylprednisolone dosage and cessation of myotonia. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 18, 2020 Category: Neurology Authors: Magda Hor áková, Tomáš Horák, Prof. Josef Bednařík, Stanislav Voháňka Tags: Case Report Source Type: research

Language, speech, and oromotor function in children with Pompe disease
Pompe disease is a rare progressive muscle disease that results in significant muscle weakness, including the involvement of respiratory and oral-facial muscles. The effects on speech and swallowing can be devastating. Two subtypes of the disease are recognized, based on onset and progression. Infantile-onset Pompe disease (IOPD) is associated with symptoms prior to one year of age, severe muscle weakness, hypertrophic cardiomyopathy, difficulty breathing, and failure to thrive. Late-onset Pompe disease (LOPD) is usually diagnosed later in life and presents with milder, more slowly progressive myopathy and respiratory prob...
Source: Neuromuscular Disorders - March 13, 2020 Category: Neurology Authors: Hsiao-Ting Su, Li-Mei Wang, Chia-Feng Yang, Li-Hong Lee, Fran çois-Xavier Brajot Source Type: research

Facioscapulohumeral muscular dystrophy 1 patients participating in the UK FSHD registry can be subdivided into 4 patterns of self-reported symptoms
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant skeletal muscle disease with an estimated prevalence of 12/100,000 [1] for which there is currently no cure. The condition is linked to epigenetic derepression of the subtelomeric D4Z4 macrosatellite region at chromosome 4q35, alongside a permissive 4qA haplotype in cis encoding a polyadenylation signal [2]. Epigenetic deregulation occurs either via truncation of the D4Z4 region to between 1-10 repeats (FSHD1) [3] or by mutation in chromatin remodelling genes (FSHD2), mainly SMCHD1 [4], with DNMT3B [5] also recently identified. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 12, 2020 Category: Neurology Authors: Christopher R.S. Banerji, Phillip Cammish, Teresinha Evangelista, Peter S. Zammit, Volker Straub, Chiara Marini-Bettolo Source Type: research

“Status myotonicus” in Nav1.4-M1592V channelopathy
The gene SCN4A codes for the voltage-gated muscle sodium channel Nav1.4. Muscle channelopathies due to SCN4A mutations can present with varying degrees of muscle pain, stiffness and myotonia as well as with episodic attacks of myotonia (potassium-aggravated myotonia) or flaccid muscle weakness (potassium-sensitive periodic paralysis) triggered by fluctuation in the potassium level [1,2]. Here we report a case of potassium-aggravated myotonia due to Nav1.4-M1592V channelopathy with severe and long-lasting focal attacks of myotonia resembling dystonic posturing. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 12, 2020 Category: Neurology Authors: Torge Rempe, S.H. Subramony Tags: Case report Source Type: research

Patient and parent oriented tools to assess health-related quality of life, activity of daily living and caregiver burden in SMA. Rome, 13 July 2019
Twenty-five participants from Italy, United States, United Kingdom, Germany, Spain and Switzerland met to discuss Patient Reported Outcome Measures (PROM) in Spinal Muscular atrophy (SMA). The group included physicians and physical therapists with a specific experience in developing or validating PROMS in neuromuscular disorders, advocacy groups and representatives from pharmaceutical companies. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 6, 2020 Category: Neurology Authors: Eugenio Mercuri, Sonia Messina, Jacqueline Montes, Amy Pasternak, Erik Henricson, Anna Lia Frongia, Mencia de Lemus, Nicole Gusset, Mary Schroth, Ksenija Gorni, Marcus Droege, Ivana Rubino, Francesco Muntoni, Valeria A Sansone, SMA PROM working group Tags: Workshop report Source Type: research

A Mutation in MTM1 Causes X-Linked Myotubular Myopathy in Boykin Spaniels
Centronuclear myopathies are rare but devastating causes of congenital myopathy grouped together based on their characteristic histopathological findings [1]. Within this group of myopathies, X-linked myotubular myopathy (XLMTM, OMIM 310400) caused by mutations within the myotubularin (MTM1) gene form a particularly severe subset [2]. In the classic form of XLMTM, affected infant boys show signs of facial, axial and proximal muscular weakness, hypotonia and areflexia leading to respiratory insufficiency and death soon after birth. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 5, 2020 Category: Neurology Authors: Natasha J. Olby, Steven Friedenberg, Kathryn Meurs, Dylan DeProspero, Julien Guevar, Jeanie Lau, Oriana Yost, Ling T. Guo, G. Diane Shelton Source Type: research

Progressive external ophthalmoplegia due to a recurrent de novo m.15990C > T MT-TP (mt-tRNAPro) gene variant
Mitochondrial diseases are a group of inherited, metabolic disorders with heterogeneous, systemic or organ-specific symptoms, often showing poor phenotype –genotype correlation. As a direct consequence, the presence of heterogeneous clinical symptoms associated with a unique genetic variant is a classical trait of mitochondrial disorders [1]. Progressive external ophthalmoplegia (PEO) is a common mitochondrial clinical feature that presents with gra dually worsening bilateral ptosis and ophthalmoparesis. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 4, 2020 Category: Neurology Authors: Pushpa Raj Joshi, Karen Baty, Sila Hopton, Isabell Cordts, Gavin Falkous, Benedikt Schoser, Emma L. Blakely, Robert W. Taylor, Marcus Deschauer Source Type: research

Cognitive impairment appears progressive in the mdx mouse
Duchenne muscular dystrophy (DMD) is an X-linked recessive disease, occurring at an incidence of 1 in 3,600-10,000 live male births [1,2]. DMD is characterised by a severe pathology of the skeletal musculature causing progressive loss of muscle, with premature death frequently occurring in the third decade of life as a result of cardiac and respiratory complications [3]. This fatal disease arises from mutations in the DMD gene; the largest gene in the human genome, with 79 exons spanning 2.4 Mb [4], and coding for a 427 kDa intracellular protein named dystrophin [5]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 3, 2020 Category: Neurology Authors: Emine Bagdatlioglu, Paola Porcari, Elizabeth Greally, Andrew M. Blamire, Volker W. Straub Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 1, 2020 Category: Neurology Source Type: research

Chronic pain is common in mitochondrial disease
Mitochondrial diseases are genetic disorders caused by mutations in the mitochondrial and nuclear genomes that cause dysfunction of oxidative phosphorylation and affect approximately 1 in 5,000 people in the UK [1]. Curative treatments are currently lacking and management is largely based on symptomatic therapies and maximizing quality of life [2,3]. Pain has been reported in series of patients with mitochondrial disease, related to myopathy [4], neuropathy [5] and headache [6]. However, the prevalence, severity, impact on the quality of life and the genetic predisposition of chronic pain in this population is not fully kn...
Source: Neuromuscular Disorders - February 29, 2020 Category: Neurology Authors: Jelle van den Ameele, Joshua Fuge, Robert D.S. Pitceathly, Sarah Berry, Zoe McIntyre, Michael G. Hanna, Michael Lee, Patrick F. Chinnery Source Type: research

Screening for early symptoms of respiratory involvement in myotonic dystrophy type 1 using the respicheck questionnaire
Patients with Myotonic Dystrophy type 1 (DM1) have a reduced life expectancy, death occurring from cardiac and respiratory causes, including pneumonia [1 –5]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 28, 2020 Category: Neurology Authors: Elisa De Mattia, Andrea Lizio, Elisa Falcier, Giulia Sannicol ò, Marco Gualandris, Gabriella Rossi, Alice Zanolini, Susanna Pozzi, Sonia Messina, Maria Sframeli, Christian Lunetta, Fabrizio Rao, Valeria A. Sansone Source Type: research

Strength-training effectively alleviates skeletal muscle impairments in myotonic dystrophy type 1
Myotonic dystrophy type 1 (DM1) is the most prevalent neuromuscular disease in adults [1,2]. It is nevertheless a rare disease with an average prevalence of 1 out of 20 000 worldwide [1] that reaches 1 out of 475 in the Saguenay —Lac-St-Jean region of Québec (Canada) [3]. DM1 is a progressive and multisystemic disease caused by abnormal cytosine, thymine and guanine (CTG) repetitions on the Dystrophy Myotonic Protein Kinase (DMPK) gene [4], which in turn leads to the accumulation of toxic RNA within cells causing RNA-bin ding proteins sequestration and related dysregulation in alternative splicing [5]. (Source...
Source: Neuromuscular Disorders - February 27, 2020 Category: Neurology Authors: Marie-Pier Roussel, Luc J. H ébert, Elise Duchesne Source Type: research

Immune checkpoint inhibitors (ICIs)-related ocular myositis
Immune check point inhibitors (ICIs) are a novel class of anti-tumor agents which have been linked to several neurological adverse event (irAE) including myositis (irMyositis), myocarditis and myasthenia.[1,2] Overlapping irMyositis with myocarditis or myasthenia has been reported in approximately 32% and 5% of cases respectively.[3] Conversely, while ocular involvement has been frequently observed in patients with generalized irMyositis and/or myasthenia, [4 –6] only few cases have been reported with isolated ocular myositis. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 26, 2020 Category: Neurology Authors: Matteo Garibaldi, Fabio Calabr ò, Gioia Merlonghi, Silvia Pugliese, Marco Ceccanti, Lara Cristiano, Tommaso Tartaglione, Antonio Petrucci Tags: Case report Source Type: research

No Effect of Oral Sucrose or IV Glucose During Exercise in Phosphorylase b Kinase Deficiency
Muscle phosphorylase kinase deficiency, also called Glycogen Storage Disease IXd (GSD IXd, OMIM #300559), is an X-linked recessive disorder affecting muscle glycogen breakdown in men. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 24, 2020 Category: Neurology Authors: A.G. Andersen, M.C. Ørngreen, D.E.T. Raaschou-Pedersen, J. de Stricker Borch, N. Løkken, T.O. Krag, M.B. Petersen, J. Vissing Tags: Case report Source Type: research

Exploring the efficacy of the Expiratory Muscle Strength Trainer to improve swallowing in Inclusion Body Myositis: A pilot study
Inclusion Body Myositis (IBM) is the most common acquired myopathy in patients over 50 years of age [1]. Dysphagia, defined as difficulty or discomfort in swallowing, is a common symptom of the disease and occurs in 40-80% of IBM patients [2 –4]. Swallowing is an essential biological function and a major contributor to quality of life; dysphagia is linked to life-threatening medical complications such as dehydration, malnutrition and recurrent aspiration pneumonia [5]. Any intervention that improves swallowing function therefore has t he capacity to significantly reduce morbidity and mortality in IBM patients and imp...
Source: Neuromuscular Disorders - February 24, 2020 Category: Neurology Authors: Nika Mohannak, Gemma Pattison, Bronwyn Radich, Kathryn Hird, Erin Godecke, Frank Mastaglia, Merrilee Needham Source Type: research

The endocrine manifestations of Spinal Muscular Atrophy, a real-life observational study
Spinal muscular atrophy (SMA) is a rare, autosomal recessive inherited disease caused by a homozygote deletion of exon 7 in the SMN1 (survival motor neuron) gene. SMA is characterized by degeneration of anterior horn cells of the spinal cord and brainstem resulting in muscular atrophy and proximal muscle weakness [1, 2]. The disease is classified into five subtypes according to age of presentation and severity of symptoms. There is no clear delineation between subtypes in many cases, and SMA is regarded as a spectrum [3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 24, 2020 Category: Neurology Authors: Avivit Brener, Yael Lebenthal, Anna Shtamler, Sigal Levy, Ronnie Stein, Aviva Fattal-Valevski, Liora Sagi Source Type: research

Severe congenital myasthenic syndrome associated with novel biallelic mutation of the CHRND gene
Congenital myasthenic syndromes (CMS) are a group of heterogeneous inherited disorders caused by mutations in genes encoding proteins essential for the integrity of the neuromuscular transmission. Although clinical manifestations vary by subtype, CMS are usually characterized by fatigable muscle weakness (ocular, bulbar, limb muscles) with onset at birth or in early childhood; rarely, symptoms may present later. The main proteins involved in the pathogenesis of CMS are: choline acetyltransferase (ChAT), the endplate species of acetylcholinesterase (AChE), β2-laminin, the acetylcholine receptor subunits (CHRNA, CHRNB, ...
Source: Neuromuscular Disorders - February 24, 2020 Category: Neurology Authors: Carmen Bonanno, Carmelo Rodolico, Ana T öpf, Francesca Maria Foti, Wei-Wei Liu, David Beeson, Antonio Toscano, Hanns Lochmüller Tags: Case report Source Type: research

A late-onset congenital myasthenic syndrome due to a heterozygous DOK7 mutation
Myasthenia Gravis (MG) is an autoimmune disease of the neuromuscular junction (NMJ), with autoantibodies binding proteins in the NMJ detected in ∼85% of the patients. However, 10-15% of MG patients present with no known antibodies [1,2]. Congenital myasthenic syndromes (CMS), in turn, are disorders of the NMJ due to various genetic defects in components essential for NMJ structure and function. Symptoms in CMS patients typically start shor tly after birth or during childhood, with an adult onset being rarer. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 23, 2020 Category: Neurology Authors: Paulo Bastos, Raquel Barbosa, Marco Fernandes, Isabel Alonso Tags: Case report Source Type: research

Beyond Ambulation: Measuring Physical Activity in Youth with Duchenne Muscular Dystrophy
Duchenne Muscular Dystrophy (DMD) is an X-linked recessive disease affecting 1 in 4700 male births [1]. A mutation in the dystrophin gene leads to progressive skeletal and cardiac muscle dysfunction [2]. Most patients lose the ability to ambulate between ages 10 and 13 years and subsequently develop progressive cardiac disease in late teenage years [3,4]. Life has been prolonged for patients with DMD with noninvasive ventilatory support [5]. Current standard of care includes corticosteroids, which have been shown to improve strength and pulmonary function [6,7]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 20, 2020 Category: Neurology Authors: Mary Killian, Maciej S. Buchowski, Thomas Donnelly, W. Bryan Burnette, Larry W. Markham, James C. Slaughter, Meng Xu, Kimberly Crum, Bruce M. Damon, Jonathan H. Soslow Source Type: research

Clinical and histological features of immune-mediated necrotising myopathy: a multi-centre South Australian cohort study
The idiopathic inflammatory myopathies (IIMs) are a group of systemic autoimmune diseases characterised primarily by muscle inflammation but also potentially accompanied by a range of extra-muscular manifestations. Dermatomyositis (DM), polymyositis (PM) and inclusion body myositis (IBM) constitute well-characterised subtypes of IIM, with the entity of non-specific idiopathic inflammatory myopathy (NSIIM) being more recently described [1]. Whilst these IIM subtypes are distinguished on clinical, serological and histological grounds, they are unified by the presence of a typically prominent intramuscular lymphocytic infiltr...
Source: Neuromuscular Disorders - February 18, 2020 Category: Neurology Authors: Jessica Day, Sophia Otto, Kathy Cash, Vidya Limaye Source Type: research

Expanding the disease phenotype of ADSSL1-associated myopathy in non-Korean patients
Distal myopathies are a heterogeneous group of rare genetic disorders that are characterised by progressive, distal skeletal muscle wasting and weakness. They are inherited in both an autosomal dominant and an autosomal recessive manner [1]. Variants in the ADSSL1 gene, encoding for adenylosuccinate synthase, are a very rare cause of adult onset distal myopathy with only nine individuals from six families of Korean origin reported [2, 3]. All affected individuals presented with adult onset, distal myopathy and facial weakness (myopathy, distal 5 (MPD5), MIM# 617030) [2, 3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 14, 2020 Category: Neurology Authors: Magdalena Mroczek, Hacer Durmus, Sunita Bijarnia-Mahay, Ana T öpf, Roula Ghaoui, Samantha Bryen, Jennifer Duff, Eleina England, Sandra T. Cooper, Daniel G. MacArthur, Volker Straub Tags: Case report Source Type: research

Obstructive sleep apnea in late-onset Pompe disease treated by enzyme replacement therapy
Pompe disease (PD), also known as glycogen-storage disease type II or acid-maltase deficiency, is an orphan disease characterized by deficient acid alfa-glucosidase (GAA) enzyme activity, resulting in a metabolic myopathy from the accumulation of intracellular glycogen [1]. The estimated incidence ranges from 1 in 40,000 to 1 in 300,000 live births and varies with region and race [2]. Of the many complications of the late-onset form of PD (LOPD), obstructive sleep apnea (OSA) is relatively common with studies showing prevalence rates of approximately 20% [3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 11, 2020 Category: Neurology Authors: Raj Bhui, Andrew R. Spector Tags: Case report Source Type: research

A novel heterozygous mutation in the C-terminal region of HSPB8 leads to limb-girdle rimmed vacuolar myopathy
Heat shock protein B8 (HspB8) is a small heat shock protein that plays a key role in preventing protein aggregation and facilitating turnover of damaged proteins in mechanically-strained tissues [1, 2]. Mutations in HSPB8 were initially found in distal hereditary motor neuropathy type IIa and Charcot-Marie-Tooth disease type 2L [3, 4]. More recently, HSPB8 variants were identified in rare myopathies with myofibrillar and rimmed vacuolar pathology, with or without an associated neuropathy [5 –8]. The discovery of such a phenotype was not surprising, as HspB8 is an integral player in chaperone-assisted selective autoph...
Source: Neuromuscular Disorders - February 11, 2020 Category: Neurology Authors: Stefan Nicolau, Teerin Liewluck, Jeffrey L Elliott, Andrew G Engel, Margherita Milone Source Type: research