Efficient gene transfer into primary muscle cells to analyse nerve-independent postsynaptic organization in vitro
The establishment, maturation and maintenance of functional contacts between motor neurons and skeletal muscles at the neuromuscular junction (NMJ) are essential events for the coordinated movement of many organisms. The main morphological features leading to embryonic NMJ formation have been well described; axonal growth cones differentiate into presynaptic terminals, whereas the innervated portion of the muscle membrane aggregates acetylcholine receptors (AChRs) on its surface. At the mature NMJ, the postsynaptic terminal becomes drastically re-arranged to organize unique pretzel-like structures, which alternate domains ...
Source: Neuromuscular Disorders - June 20, 2019 Category: Neurology Authors: Jessica Mella, Viviana P érez, Diego Zelada, Nicolás Moreno, Ariel Ionescu, Eran Perlson, Juan Pablo Henríquez Source Type: research

X-linked Emery-Dreifuss muscle dystrophy manifesting with adult onset axial weakness, camptocormia, and minimal joint contractures
Emery-Dreifuss muscular dystrophy (EDMD) is an early-onset, usually in the first decade, slowly progressive myopathy [1]. EDMD is mainly caused either by mutations in EMD gene encoding emerin in X-linked EDMD (X-EDMD) [2], or mutations in LMNA gene encoding lamins A and C in autosomal dominant and recessive forms [3]. EDMD clinical presentation includes the classical triad of symptoms with early joint contractures involving Achilles, elbows and the neck tendons, progressive muscle weakness and wasting beginning in the humero and peroneal regions, and cardiac disease combining cardiac arrhythmias, conduction defects and car...
Source: Neuromuscular Disorders - June 19, 2019 Category: Neurology Authors: Marion Brisset, Rabah Ben Yaou, Robert-Yves Carlier, Anais Chanut, Guillaume Nicolas, Norma B. Romero, Karim Wahbi, Camille Decrocq, France Leturcq, Pascal Lafor êt, Edoardo Malfatti Tags: Case report Source Type: research

Chronic inflammatory demyelinating polyneuropathy: Plasmapheresis or cyclosporine can be good treatment options in refractory cases
Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is an acquired immune-mediated disease of the peripheral nervous system. CIDP is traditionally described as progressive symmetric weakness of all limbs over the course of at least 8 weeks [1]. It is observed in patients of all ages but is much rarer in pediatric patients, with a prevalence of less than 0.5 per 100,000 [2,3]. CIDP is a clinical diagnosis, and there are many proposed diagnostic criteria [4]. Thus, CIDP can be seen as a group of heterogeneous polyneuropathies with a spectrum of clinical findings and numerous variants [5]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 19, 2019 Category: Neurology Authors: WooJoong Kim, Young Kyu Shim, Sun Ah Choi, Soo Yeon Kim, Hunmin Kim, Byung Chan Lim, Hee Hwang, Jieun Choi, Ki Joong Kim, Jong-Hee Chae Source Type: research

Clinical spectrum and gene mutations in a Chinese cohort with Anoctaminopathy
Recessive mutations in anoctamin-5 (ANO5) are responsible for limb girdle muscular dystrophy(LGMD) 2L, the most prevalent forms of muscular dystrophy in Europe [1], as well as the non-dysferlin Miyoshi-like distal myopathy(MMD3) [2].The clinical manifestations of anoctaminopathy include presymptomatic hyperCKemia, myalgia, muscle stiffness [3], recurrent rhabdomyolysis and limb girdle muscle weakness. Suspected cardiomyopathy was also reported [4]. Muscle involvement in patients with anoctaminopathy was usually asymmetric and selective at early stage with preferential involvement of quadriceps, hamstrings and calves [5,6]....
Source: Neuromuscular Disorders - June 11, 2019 Category: Neurology Authors: Shuang Cai, Mingshi Gao, Jianying Xi, Zhuo Liu, Dongyue Yue, Hui Wu, Haixia Bi, Jing Li, Zonghui Liang, Chongbo Zhao, Bjarne Udd, Sushan Luo, Jiahong Lu Source Type: research

Muscle biopsies in clinical trials for Duchenne muscular dystrophy – patients’ and caregivers’ perspective
Duchenne muscular dystrophy (DMD) is a devastating disorder hallmarked by progressive muscle weakness leading to loss of ambulation in childhood, respiratory insufficiency, cardiomyopathy and early death [1]. Mutations in the DMD gene lead to absence of the dystrophin protein that normally links the extracellular matrix to the contractile elements in the sarcolemma, which is thought to protect skeletal muscle fibres from contraction induced damage [2]. Muscle pathology consists of inflammation, failed muscle regeneration and a progressive replacement of muscle by fibrotic tissue and fat [3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 11, 2019 Category: Neurology Authors: Ingrid E.C. Verhaart, Alex Johnson, Sejal Thakrar, Elizabeth Vroom, Fernanda De Angelis, Francesco Muntoni, Annemieke M. Aartsma-Rus, Erik H. Niks Source Type: research

European regulators ’ views on a wearable-derived performance measurement of Ambulation for Duchenne Muscular Dystrophy regulatory trials
Before new medicines can be placed on the market, medicines ’ developers have to generate and submit evidence to regulators that the benefits outweigh the risks of the new medicine in the targeted indication. A critical part of such evidence is the design of the pivotal clinical trial and the choice of endpoints. For regulators, a primary endpoint in a piv otal trial needs to be accurate, reliable, sensitive to change, reflect the objectives of the trial, and be relevant to patients and clinicians. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 7, 2019 Category: Neurology Authors: Marion Haberkamp, Jane Moseley, Dimitrios Athanasiou, Fernando de Andres-Trelles, Andr é Elferink, Mário Miguel Rosa, Armando Magrelli Tags: Short communication Source Type: research

The prevalence of faecal incontinence in myotonic dystrophy type 1
Myotonic dystrophy type 1 (DM1) [1] is an autosomal dominant multi-system disorder. The range of clinical features is well described [2,3,4]. The clinical picture is dominated by the consequences of muscle involvement, with associated risks of respiratory failure and cardiac arrhythmias. More recently the major impact of brain involvement on individuals and families has been recognised [5,6]. However, in addition, a major feature causing distress for patients and families relate to symptoms of bowel dysfunction. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 6, 2019 Category: Neurology Authors: R.K.H. Petty, M.P. Eugenicos, M.J. Hamilton, M.E. Farrugia, Y. Robb, R. Ballantyne, H. Gregory, C. McWilliam, C. Longman Source Type: research

Stopping Oral Steroid-Sparing Agents at Initiation of Rituximab in Myasthenia Gravis
Myasthenia Gravis is an autoimmune disorder in which antibodies develop against components of the post-synaptic neuromuscular junction membrane [1]. Patients present with skeletal muscle weakness involving extraocular, bulbar and appendicular muscles and, less commonly, the diaphragm. The two most common antigens are the acetylcholine receptor [2] in 85% of patients and muscle specific kinase [3 –6] in 10% of patients. Other newly discovered rarer antigens include low-density lipoprotein receptor-related protein 4 (Lrp4) [7–9] and agrin [10–12]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 6, 2019 Category: Neurology Authors: Ricardo H. Roda, Leana Doherty, Andrea M. Corse Source Type: research

Evolution of bone mineral density, bone metabolism and fragility fractures in Spinal Muscular Atrophy (SMA) types 2 and 3.
Spinal muscular atrophy (SMA) is caused by homozygous deletion and/or mutation of the survival motor neuron 1 (SMN1) gene on chromosome 5q13, leading to degeneration of lower motor neurons [1]. An increasing body of preclinical and anecdotal clinical studies suggest that SMA can be considered as a multi-system disorder, due to the ubiquity of the SMN protein [2 –4]. Four types of SMA are currently recognized, with types 1 to 3 having a childhood onset. Infants with SMA type 1 are most severely affected, showing generalized muscle weakness, hypotonia, and inability to sit unsupported since early infancy, with death oc...
Source: Neuromuscular Disorders - June 6, 2019 Category: Neurology Authors: Giovanni Baranello, Silvia Vai, Francesca Broggi, Riccardo Masson, Maria Teresa Arnoldi, Riccardo Zanin, Chiara Mastella, Maria Luisa Bianchi Source Type: research

The World Wide Web (WWW): For better or for worse
Since the launch of Neuromuscular Disorders in 1990, there have been a series of cataclysmic events, which have turned the traditional approach to scientific publishing completely on its head. The meticulous search of the literature to acknowledge earlier publications is now a thing of the past and references are often restricted to recently published on-line papers. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 1, 2019 Category: Neurology Authors: Victor Dubowitz Tags: Commentary Source Type: research

Critical Review Ahead of Publication
In a recent commentary in the online website of the Support Group of SMA, it was claimed that scientists had been able to replicate all the Types of human SMA, including Type 4, in a drosophila model of SMA [1]. This sounded bizarre as the different “Types” of SMA are based on the achievement of various motor milestones, such as ability to sit unsupported (“Type 2”) and the ability to stand and walk (“Type 3”.) There is no “Type 4” but it was an effort of the clinicians to separate the classical ambulant cases with onset in adol escence, as described by Kugelberg and Welander...
Source: Neuromuscular Disorders - June 1, 2019 Category: Neurology Authors: Victor Dubowitz Tags: Editorial Source Type: research

Spinal Muscular Atrophy Revisited
The mills of God grind slowly ...... but they are no patch on the medical profession. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 1, 2019 Category: Neurology Authors: Victor Dubowitz Tags: Editorial Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - June 1, 2019 Category: Neurology Source Type: research

Novel compound heterozygous GFPT1 mutations in a family with limb-girdle myasthenia with tubular aggregates
Congenital myasthenic syndrome (CMS) is a clinically and genetically heterogeneous group of inherited disorders characterized by defects in neuromuscular transmission resulting from mutations in numbers of genes [1 –3]. CMS is clinically similar to the autoimmune disorder myasthenia gravis, leading to transient muscle weakness and fatigue [4,5]. Herein, we described the clinical features of two siblings in a Chinese family, who presented with transient weakness of the limb-girdle and fatigue, but the result of anti-acetylcholine receptor antibodies assay was negative and the facial or extraocular muscles were not inv...
Source: Neuromuscular Disorders - May 28, 2019 Category: Neurology Authors: Hai-yang Luo, Lu Zhao, Cheng-yuan Mao, Zhi-hua Yang, Jing Yang, Yan-lin Wang, Hui-xia Niu, Yu-tao Liu, Chang-he Shi, Yu-ming Xu Source Type: research

Concurrent positive anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase antibody with reducing body myopathy: possible double trouble
Immune mediated necrotizing myopathy (IMNM), a recently recognized but a common entity among the heterogenous group of inflammatory myopathies, has been classified by the ENMC Immune-Mediated Necrotizing Myopathies Working Group into 1) anti-signal recognition particle (anti-SRP) positive IMNM or anti-SRP myopathy, 2) anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) positive IMNM or anti-HMGCR myopathy, and 3) antibody negative IMNM using integrated clinical, serological, and pathological criteria [1]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 23, 2019 Category: Neurology Authors: Jantima Tanboon, Oranee Sanmaneechai, Sirirat Charuvanij, Tumtip Sangruchi, Angeles S. Galindo-Feria, Ingrid E. Lundberg, Yuko Ohnuki, Takashi Shiina, Shigeaki Suzuki, Ichizo Nishino Tags: Case report Source Type: research

Dilated cardiomyopathy and limb-girdle muscular dystrophy-dystroglycanopathy due to novel pathogenic variants in the DPM3 gene
Abnormalities of the N-glycosylation and O-mannosylation pathways are respectively involved in congenital disorders of glycosylation (CDG) and alpha-dystroglycanopathies [1 –4]. Dolichol-P-mannose (DPM) is produced by the DPM synthase and plays an important role, as a mannosyl donor, in four different glycosylation pathways (N-glycosylation, C-mannosylation, glycosyl-phosphatidylinositol anchor assembly, and O-mannosylation) [1]. DPM synthase is composed of three sub units; DPM3 anchors the cytoplasmic catalytic subunit DPM1 to the endoplasmic reticulum membrane, and DPM2 stabilizes the complex [5–7]. (Source: ...
Source: Neuromuscular Disorders - May 9, 2019 Category: Neurology Authors: J. Svahn, P. Lafor êt, C. Vial, N. Streichenberger, N. Romero, C. Bouchet-Séraphin, A. Bruneel, T. Dupré, N. Seta, R. Menassa, L. Michel-Calemard, T. Stojkovic Tags: Case report Source Type: research

Inflammation-induced fibrosis in skeletal muscle of female carriers of Duchenne muscular dystrophy
Duchenne muscular dystrophy (DMD) is an X-chromosomal recessively inherited disease, which affects boys from early childhood on. Loss or severe reduction of dystrophin protein induces a plethora of different physiological mechanisms finally leading to myofibre necrosis, atrophy, structural abnormalities, loss of homeostatic functions, and exhaustion of satellite cells. Over time, skeletal and cardiac muscles undergo structural remodelling with development of fibrosis and fatty tissue replacement. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 9, 2019 Category: Neurology Authors: Corinna Preu ße, Arpad von Moers, Heike Kölbel, Debora Pehl, Hans-Hilmar Goebel, Ulrike Schara, Werner Stenzel Source Type: research

Rhabdomyolysis and myoglobinuria following bisphosphonate infusion in patients with Duchenne muscular dystrophy
We read with interest the recent article by Ivanyuk et al. [1] who presented two cases of suspected Zoledronate induced rhabdomyolysis with myoglobinuria in boys with Duchenne Muscular Dystophy (DMD). Since 2014, 13 patients affected by DMD and steroid induced osteoporosis have been treated at our centre with intravenous Zoledronate. All had a BMD Z-score of −2.0 standard deviations or less with severe or symptomatic vertebral compression fractures and were treated in line with recent guidelines [2]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 8, 2019 Category: Neurology Authors: Jennifer Lemon, Lucy Turner, Poonam Dharmaraj, Stefan Spinty Tags: Letter to the Editor Source Type: research

Further reports of rhabdomyolysis and myoglobinuria following bisphosphonate infusion in patients with Duchenne Muscular Dystrophy
We read with interest the recent article by Ivanyuk and colleagues [1] who presented two cases of suspected Zoledronate induced rhabdomyolysis with myoglobinuria in boys with Duchenne Muscular Dystophy (DMD). Since 2014, 13 patients affected by DMD and steroid induced osteoporosis have been treated at our centre with intravenous Zoledronate. All had a BMD Z- score of -2.0 standard deviations or less with severe or symptomatic vertebral compression fractures and were treated in line with recent guidelines [2]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 8, 2019 Category: Neurology Authors: Dr Jennifer Lemon, Dr Lucy Turner, Dr Poonam Dhamaraj, Dr Stefan Spinty Tags: Letter to the Editor – Journal of Neuromuscular Disorders Source Type: research

Autosomal recessive axonal neuropathy caused by HINT1 mutation: new association of a psychiatric disorder to the neurologic phenotype
In a recent paper Meng et al. [1] described three Chinese patients with autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM), caused by mutations in the histidine triad nucleotide binding protein (HINT1) gene. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 4, 2019 Category: Neurology Authors: Gaia Scarpini, Carlotta Spagnoli, Grazia Gabriella Salerno, Susanna Rizzi, Daniele Frattini, Carlo Fusco Tags: Letter to the Editor Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - May 1, 2019 Category: Neurology Source Type: research

Surgical outcomes of cavovarus foot deformity in children with Charcot-Marie-Tooth disease
Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of inherited peripheral neuropathies affecting 3 to 82 per 100,000 individuals of both sexes and all backgrounds [1]. CMT is characterised by demyelination and/or axonal degeneration of the peripheral nerves, with typical onset in the first two decades of life [2,3]. More than 90 causative genes have been identified so far, and CMT type 1A is the most common subtype [4]. Most patients exhibit a length-dependent progression of symptoms and impairments, with symptoms initially distal at the feet and hands, progressing proximally. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 26, 2019 Category: Neurology Authors: Ting Lin, Paul Gibbons, Anita J. Mudge, Kayla M.D. Cornett, Manoj P. Menezes, Joshua Burns Source Type: research

Salbutamol Tolerability and Efficacy in Patients with Spinal Muscular Atrophy type II
Spinal muscular atrophy (SMA) is an autosomal recessive disease caused by homozygous deletions or loss-of-function mutations in the gene encoding survival motor neuron 1 (SMN1), which result in a degeneration of motor neurons in the spinal cord and brain stem [1]. It is the most common genetic cause of childhood mortality [2, 3], with an estimated incidence of 1 in 11,000 live births [4] and a carrier frequency of 1 in 40 –60 adults [5]. It is classified in several major phenotypes based on the age of onset and maximal motor capacity achieved [6-8]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 18, 2019 Category: Neurology Authors: A.L. Frongia, D. Natera-de Benito, C. Ortez, M. Alarc ón, A. Borrás, J. Medina, M. Vigo, N. Padrós, O. Moya, J. Armas, L. Carrera-García, J. Expósito-Escudero, D. Cuadras, S. Bernal, L. Martorell, J. Colomer, A. Nascimento Source Type: research

Recessive MYH7-related myopathy in two families
Mutations in MYH7 cause a wide range of cardiac and skeletal muscle diseases, including both dilated and hypertrophic cardiomyopathy (MIM 613426, MIM192600), left ventricular non-compaction (MIM 613426), dominant and recessive myosin storage myopathy (MSM, MIM 608358, MIM 255160), Laing distal myopathy (MIM 160500), scapuloperoneal myopathy (MIM 181430) [1,2], and subgroups of congenital myopathies with characteristic histopathological features such as multi-minicores [3] and myofiber type disproportion with small type I myofibers [4]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 12, 2019 Category: Neurology Authors: Sarah J. Beecroft, Martijn van de Locht, Josine M. de Winter, Coen A. Ottenheijm, Caroline A. Sewry, Shehla Mohammed, Monique M. Ryan, Ian R. Woodcock, Lauren Sanders, Rebecca Gooding, Mark R. Davis, Emily C. Oates, Nigel G. Laing, Gianina Ravenscroft, Ca Source Type: research

Exome sequencing detects compound heterozygous nonsense LAMA2 mutations in two siblings with atypical phenotype and nearly normal brain MRI.
The autosomal recessive congenital muscular dystrophy type 1A (MDC1A) results from a variety of mutations, either missense, nonsense, deletions or splice site variants, in the LAMA2 gene [1]. The LAMA2 gene, comprising 65 exons, encodes the α2 chain subunit of laminin-2 (merosin). Generally, complete absence of the laminin α2 chain leads to a very severe disease course, while partial deficiency results in a variety of milder phenotypes [2,3]. Accordingly, skeletal muscles of MDC1A patients show, depending on complete or partial absen ce of the laminin-α2 chain, either severe dystrophic features such as mu...
Source: Neuromuscular Disorders - April 10, 2019 Category: Neurology Authors: Simona Saredi, Sara Gibertini, Leslie Matalonga, Laura Farina, Anna Ardissone, Isabella Moroni, Marina Mora Tags: Case report Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - April 1, 2019 Category: Neurology Source Type: research

Mutation spectrum of 260 dystrophinopathy patients from Turkey and important highlights for genetic counseling
Dystrophinopathy is a group of X linked muscle diseases caused by pathogenic DMD variants that manifest in a clinical spectrum ranging from asymptomatic hyperCKemia and muscle cramps with myoglobinuria at the mild end to Becker muscular dystrophy (BMD, MIM 300376), DMD-associated dilated cardiomyopathy (XL-DCM, MIM 302045) and Duchenne muscular dystrophy (DMD, MIM 310200) at the severe end. Establishing precise identification of those pathogenic DMD variants not only expatiate our understanding of the molecular pathology underlying dystrophinopathies, but also helps with clarifying phenotype-genotype correlation, which is ...
Source: Neuromuscular Disorders - March 27, 2019 Category: Neurology Authors: G Toksoy, H Durmus Tekce, A Aghayev, G Bagirova, B Sevinc Rustemoglu, S Basaran, S Avc ı, B Karaman, Y Parman, U Altunoglu, Z Yapici, P Tekturk, F Deymeer, H Topaloglu, H Kayserili, P Oflazer-Serdaroglu, ZO Uyguner Source Type: research

PMP22-related disease: a Novel Splice Site Acceptor Variant and Intrafamilial Phenotype Variability
PMP22 is the most frequent mutated gene in Charcot-Marie-Tooth disease (CMT) type 1A. Another phenotype, hereditary neuropathy with pressure palsies (HNPP), could be caused by PMP22 mutations. PMP22 encodes a peripheral myelin protein with molecular weight 22-kDa. Various pathomechanisms have been postulated in PMP22-related disease, including dysfunction due to missense mutations, and alteration of a gene dose due to duplication/deletion mutations. We identified a novel PMP22 splice site acceptor variant, c.179-1G>A, in a patient with adult-onset chronic generalized polyneuropathy and two asymptomatic family members. (...
Source: Neuromuscular Disorders - March 27, 2019 Category: Neurology Authors: Toshitaka Kawarai, Hiroki Yamazaki, Ryosuke Miyamoto, Naoko Takamatsu, Atsuko Mori, Yusuke Osaki, Antonio Orlacchio, Hiroyuki Nodera, Akihiro Hashiguchi, Yujiro Higuchi, Akiko Yoshimura, Hiroshi Takashima, Ryuji Kaji Tags: Case report Source Type: research

A novel case of MSTO1 gene related congenital muscular dystrophy with progressive neurological involvement
Congenital muscular dystrophies (CMDs) and congenital myopathies (CMs) are individually rare and highly heterogeneous conditions, characterized by congenital/early onset muscle weakness and characteristic muscle biopsy findings compatible with a dystrophic or myopathic process, respectively. The clinical complexity of CMDs and CMs is mirrored by their wide genetic heterogeneity. With advances in novel diagnostic genetic technologies such as the introduction of next generation sequencing (NGS), the number of genes and disease-causing variants associated with CMDs and CMs has rapidly increased in recent years [1]. (Source: N...
Source: Neuromuscular Disorders - March 27, 2019 Category: Neurology Authors: Didem Ardicli, Anna Sarkozy, Irina Zaharieva, Charu Deshpande, Istvan Bodi, Ata Siddiqui, Jean Marie U-King-Im, Amy Selfe, Rahul Phadke, Heinz Jungbluth, Francesco Muntoni Source Type: research

A review of the histopathological findings in myasthenia gravis: clues to the pathogenesis of treatment-resistance in extraocular muscles
Pathogenic autoantibodies in myasthenia gravis (MG) target the nicotinic acetylcholine receptor (AChR) or other muscle endplate proteins such as muscle-specific kinase (MuSK) resulting in AChR loss or reduced clustering of AChRs at the endplate, respectively [1]. The first clinical manifestation of MG is often fatigable weakness of the extraocular muscles (EOMs) and /or levator palpebrae superioris resulting in fatigable diplopia and/or ptosis [2]. The disease may progress to involve the limb, bulbar and respiratory muscles resulting in variable weakness, which usually responds to cholinesterase inhibitors (CHEI) and/or im...
Source: Neuromuscular Disorders - March 26, 2019 Category: Neurology Authors: Tarin A. Europa, Melissa Nel, Jeannine M. Heckmann Tags: Review Source Type: research

Central drive and ventilatory failure in late-onset Pompe disease: At the gates of a new phenotype
Pompe disease (PD) is an infrequent metabolic autosomal recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Late-onset Pompe disease (LOPD) is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders (NMD) [1]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 21, 2019 Category: Neurology Authors: EL De Vito, SC Arce, SG Monteiro, GA Vaca Ruiz Source Type: research

Central drive and ventilatory failure in Pompe disease: At the gates of a new phenotype
Pompe disease (PD) is an infrequent metabolic autosomal recessive disorder produced by the lack or deficiency of the acid alpha-glucosidase lysosomal enzyme in tissues of involved individuals. Late-onset Pompe disease (LOPD) is a multisystem condition, with a heterogeneous clinical presentation that mimics other neuromuscular disorders (NMD) [1]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 21, 2019 Category: Neurology Authors: EL De Vito, SC Arce, SG Monteiro, GA Vaca Ruiz Tags: Short communication Source Type: research

Polyradiculoneuropathy in dourine-affected horses
Dourine is a contagious equine disease caused by the protozoan organism, Trypanosoma equiperdum [1, 2]. Depending on the virulence of the T. equiperdum strain involved, there are 3 clinical stages associated with the disease [1, 2]. The first is the genital stage, characterized by genital swelling [1, 2]. The second is the cutaneous stage, characterized by cutaneous plaques; cutaneous plaques constitute pathognomonic lesions in dourine, but may not occur depending the immunological status of the host and the virulence of the infecting T. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 18, 2019 Category: Neurology Authors: Bayasgalan Mungun-Ochir, Noriyuki Horiuchi, Adilbish Altanchimeg, Kenji Koyama, Keisuke Suganuma, Uranbileg Nyamdolgor, Ken-ichi Watanabe, Purevdorj Baatarjargal, Daiki Mizushima, Banzragch Battur, Naoaki Yokoyama, Badgar Battsetseg, Noboru Inoue, Yoshiya Tags: Veterinary Myology Source Type: research

Thoracic circumference: a new outcome measure in spinal muscular atrophy Type 1?
Proximal Spinal Muscular Atrophy (SMA) is one of the most common neuromuscular diseases, with an incidence of about one in 10,000 live births [1]. It is a progressive motor neuron disorder caused by deletion of exon 7 or other mutations in the survival motor neuron (SMN) 1 gene, resulting in SMN protein deficiency [2]. The almost identical SMN2 gene produces a small amount of functional SMN protein, and SMN2 copy number is recognized as a major modulator of the SMA phenotype. Although the role of SMN protein in motor neurons is incompletely understood, the phenotype of spinal muscular atrophy is largely related to the numb...
Source: Neuromuscular Disorders - March 14, 2019 Category: Neurology Authors: Juliette Ropars, Christine Barnerias, Marie Hully, Delphine Chabalier, Sylviane Peudenier, Audrey Barzic, Pierrick Cros, Isabelle Desguerre Source Type: research

Unraveling upper extremity performance in Duchenne Muscular Dystrophy: a biophysical model
Duchenne Muscular Dystrophy (DMD) is an x-linked neuromuscular disorder that affects 1 in 5000 live-born boys [1]. DMD is characterized by progressive muscle weakening. First the pelvic girdle is affected and later on, all muscles become affected. Boys with DMD lose the ability to walk around the age of 13 when using corticosteroids [2] and their arm function also weakens around that age [3]. Consequently, DMD patients are in a wheelchair for the largest parts of their lives, and the ability to perform activities with their upper extremities (UE) becomes more and more difficult. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 14, 2019 Category: Neurology Authors: Mariska M.H.P. Janssen, Jaap Harlaar, Bart Koopman, Imelda J.M. de Groot Source Type: research

Severe distal muscle involvement and mild sensory neuropathy in a boy with infantile onset Pompe disease treated with enzyme replacement therapy for 6 years
Infantile onset Pompe disease (IOPD) is caused by virtually complete deficiency of the lysosomal enzyme acid alpha glucosidase (GAA) and abnormal storage of glycogen, leading to hypertrophic cardiomyopathy (HCM), a myopathy with profound axial muscle weakness, and early death usually within the first year of life before enzyme replacement therapy (ERT) became available. ERT with recombinant human GAA has enabled long-term survival and achievement of motor milestones such as free walking for some of the affected. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 14, 2019 Category: Neurology Authors: Anne Sch änzer, Jonas Görlach, Kerstin Claudi, Andreas Hahn Tags: Case report Source Type: research

Recessive mutations in proximal I-band of TTN gene cause severe congenital multi-minicore disease without cardiac involvement
Titin, encoded by the 364-exon TTN gene [OMIM #188840], is the largest protein in nature [1]. It acts as one of the main sarcomere components, each titin molecule bridges half of the entire sarcomere to form a continuous elastic myofilament. These myofilaments provide a scaffold for sarcomere assembly during muscle development, maintain sarcomeric structural integrity, generate passive tension, and serve as key mechanosensing and signaling hubs [2,3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 14, 2019 Category: Neurology Authors: Lin Ge, Xiaona Fu, Wei Zhang, Dong Wang, Zhaoxia Wang, Yun Yuan, Ikuya Nonaka, Hui Xiong Source Type: research

1st ENMC European meeting: THE EURO-NMD Pathology Working Group Recommended Standards for Muscle Pathology 7 December 2018, Amsterdam, the Netherlands
European Reference Networks, ERNs, were established by the EU commission in December 2016 in order to enhance the access to accurate diagnostics and disease management for patients with rare disorders. EURO-NMD is the dedicated ERN for neuromuscular patients since all the hundreds of different neuromuscular disorders are rare diseases. EURO-NMD has an established structure with 61 centres currently members of the EURO-NMD organisation and with10 different working groups (WG) on different areas of the clinical aspects of neuromuscular diseases. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 14, 2019 Category: Neurology Authors: Bjarne Udd, Werner Stenzel, Anders Oldfors, Montse Olive, Norma Romero, Martin Lammens, Benno Kusters, Caroline Sewry, Hans-Hilmar Goebel, Teresinha Evangelista Tags: Workshop report Source Type: research

Muscle fiber dysfunction contributes to weakness in inclusion body myositis
Sporadic inclusion body myositis (IBM) is one of the most common acquired muscle disorders in adults over 50 years old [1,2]. Progressive disease is characterized by atrophy and fatty infiltration of muscle tissue, resulting in muscle weakness [3 –5]. In early disease, the quadriceps, deep finger flexors and the pharyngeal muscles are most frequently affected, restricting functional ability and quality of life [6–8]. IBM is the result of a complex and only partially understood interplay between muscle inflammation, degeneration and impai red proteostasis which results in the accumulation of proteins in rimmed v...
Source: Neuromuscular Disorders - March 6, 2019 Category: Neurology Authors: Saskia Lassche, Anke Rietveld, Arend Heerschap, Hieronymus W van Hees, Maria TE Hopman, Nicol C Voermans, Christiaan GJ Saris, Baziel GM van Engelen, Coen AC Ottenheijm Source Type: research

Participation and mental well-being of mothers of home-living patients with spinal muscular atrophy
Proximal spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disease caused by homozygous loss of function of the survival motor neuron (SMN) 1 gene. SMA displays significant variability in severity, mainly due to copy number variation of the nearly homologous SMN2 gene. The clinical classification that distinguishes SMA types (i.e. types 1, 2, 3, and 4), based on age at onset and motor milestones achieved, captures the severity spectrum. Despite recent successes in the development of SMN augmenting therapies [1], SMA is in essence a disorder of developmental arrest followed by progressive weakness [2]. (...
Source: Neuromuscular Disorders - March 2, 2019 Category: Neurology Authors: C.H. Cremers, M.J. Fischer, E.T. Kruitwagen-van Reenen, R.I. Wadman, J.J. Vervoordeldonk, M. Verhoef, J.M. Visser-Meily, W.L. van der Pol, C.D. Schr öder Source Type: research

237th ENMC International Workshop: GNE myopathy – current and future research Hoofddorp, The Netherlands, 14–16 September 2018
Clinicians, researchers, industry and patient group representatives (in total 25 members of the study group from 12 countries) gathered in Hoofddorp in September 2018 to discuss current knowledge and perspective research in GNE myopathy (previously known as Nonaka disease, Quadriceps Sparing Myopathy, Distal Myopathy with Rimmed Vacuoles or Hereditary inclusion body myopathy type 2). GNE myopathy is an -rare autosomal recessive disease caused by bi-allelic mutations in the GNE gene (UDP-N-acetyl) −2-epimerase/N-acetylmannosamine kinase). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 1, 2019 Category: Neurology Authors: Oksana Pogoryelova, J. Andoni Urtizberea, Zohar Argov, Ichizo Nishino, Hanns Lochm üller, ENMC workshop study group Tags: Workshop report Source Type: research

Editorial Board
(Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 1, 2019 Category: Neurology Source Type: research

ACTA1-myopathy With Prominent Finger Flexor Weakness and Rimmed Vacuoles
Mutations in the skeletal muscle sarcomeric α-actin 1-encoding gene (ACTA1) cause autosomal dominant or less commonly recessive congenital myopathies with a wide range of clinical phenotypes and pathological findings [1]. Weakness generally occurs prior to teenage years, but adult-onset weakness has been reported [1]. The pattern of weakness varies from limb-girdle, scapuloperoneal [2] to the recently described distal phenotype [3]. Muscle biopsy may show classic nemaline rods or less commonly actin filament aggregates, caps, cores, fiber type disproportion, myofibrillar pathology, or zebra bodies [3]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 1, 2019 Category: Neurology Authors: Teerin Liewluck, Zhiyv Niu, Steven A. Moore, Mohammad Alsharabati, Margherita Milone Tags: CASE REPORTS Source Type: research

237th ENMC International Workshop: GNE myopathy current and future research Hoofdorp, The Netherlands, 14 – 16 September 2018
Clinicians, researchers, industry and patient group representatives (in total 25 members of the study group from 12 countries) gathered in Hooffdorp in September 2018 to discuss current knowledge and perspective research in GNE myopathy (previously known as Nonaka disease, Quadriceps Sparing Myopathy, Distal Myopathy with Rimmed Vacuoles or Hereditary inclusion body myopathy type 2). GNE myopathy is an -rare autosomal recessive disease caused by bi-allelic mutations in the GNE gene (UDP-N-acetyl)-2-epimerase/N-acetylmannosamine kinase). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - March 1, 2019 Category: Neurology Authors: Oksana Pogoryelova, J. Andoni Urtizberea, Zohar Argov, Ichizo Nishino, Hanns Lochm üller, ENMC workshop study group Tags: Workshop report Source Type: research

Distinct segregation of the pathogenic m.5667G > A mitochondrial tRNAAsn mutation in extraocular and skeletal muscle in chronic progressive external ophthalmoplegia
Chronic progressive external ophthalmoplegia (CPEO) is the most frequent mitochondrial myopathy [1], which is characterised by a slowly progressive paresis of extraocular muscles leading to ptosis and restriction of eye movements with subsequent strabism and – less frequently – diplopia. CPEO is caused by mutations either in the mitochondrial (mt) or the nuclear genome both resulting in a perturbance of mitochondrial oxidative phosphorylation. Sporadically occurring single large-scale mtDNA rearrangements (deletions or duplications) as well as spora dically or maternally inherited mtDNA point mutations are attr...
Source: Neuromuscular Disorders - February 25, 2019 Category: Neurology Authors: Elena Schlapakow, Viktoriya Peeva, G ábor Zsurka, Monika Jeub, Bettina Wabbels, Cornelia Kornblum, Wolfram S. Kunz Source Type: research

Charcot-Marie-Tooth Disease Type 2CC due to a frameshift mutation of the neurofilament heavy polypeptide gene in an Austrian family
Neurofilaments are components of the neuronal cytoskeleton and are composed of three subunits: the neurofilament heavy chain (NFEH), the medium chain (NEFM), and the light chain (NEFL). They are crucial for the growth of axons, the maintenance of axon caliber and the transmission of electrical impulses along axons.[1] Abnormal accumulation of neurofilament occurs in pathological conditions such as neurofilament inclusion disease (NFID), giant axonal neuropathy (GAN), diabetic neuropathy, spinal muscular atrophy (SMA), spastic paraplegia, Alzheimer's disease (AD) and Parkinson's disease (PD). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 20, 2019 Category: Neurology Authors: Elena Ikenberg, Peter Reilich, Angela Abicht, Corina Heller, Benedikt Schoser, Maggie C. Walter Tags: Case report Source Type: research

Fractures and bone health in Duchenne dystrophy in Scotland
Response (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 20, 2019 Category: Neurology Authors: M. Di Marco, S. Joseph, I. Horrocks, S.F. Ahmed, S.C. Wong Tags: Letter to the Editor Source Type: research

Fractures and bone health in Duchenne muscular dystrophy in Scotland
We thank Professor Topalo ǧlu for his comment on our retrospective study of radiologically confirmed fractures in all boys with Duchenne muscular dystrophy (DMD) managed in the Scottish Muscle Network [1]. Professor Topaloglu has three main queries which we will address. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 20, 2019 Category: Neurology Authors: M. Di Marco, S. Joseph, I. Horrocks, S.F. Ahmed, S.C. Wong Tags: Letter to the Editor Source Type: research

Cardiac Autonomic Function Evaluation in Pediatric and Adult Patients with Congenital Myasthenic Syndromes
Congenital myasthenic syndromes (CMS) are genetically inherited defects of the neuromuscular junction (NMJ) resulting in weakness and fatigability in skeletal, extraocular or bulbar muscles [1, 2]. They are divided into three groups according to the site of the defect: presynaptic, synaptic, or postsynaptic, the latter being the most common. The nicotinic acetylcholine receptor (nAChR) in the human NMJ is a pentameric complex composed of four subunits: two alpha, one beta, and one epsilon ( ε) or delta subunit [1, 2]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 19, 2019 Category: Neurology Authors: Ceren G ünbey, Kutay Sel, Çağrı Mesut Temuçin, Hayrettin Hakan Aykan, Bahadır Konuşkan, Tevfik Karagöz, Banu Anlar Source Type: research

Sleep-disordered breathing and effects of non-invasive ventilation on objective sleep and nocturnal respiration in patients with myotonic dystrophy type I
Myotonic dystrophy type I (DM1; Online Mendelian Inheritance in Man ® ID 160900) is a hereditary multi-system disorder characterized by myopathic facies, distal muscle wasting, myotonia, bilateral cataract, endocrine and cardiac conduction abnormalities. The prevalence of DM1 in industrialized countries is 3-15/100,000. DM1 follows an autosomal dominant trait and i s caused by an expansion of a trinucleotide CTG-repeat in the 3’-untranslated region of the DMPK gene on chromosome 19 [1]. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - February 19, 2019 Category: Neurology Authors: Jens Spiesshoefer, Maya Runte, Anna Heidbreder, Michael Dreher, Peter Young, Tobias Brix, Matthias Boentert Source Type: research