Congenital myopathies: general and ryr1
We received the thigh muscle biopsy of a 55 month old boy diagnosed with congenital hyporegenerative microcytic anemia of unknown origin to investigate for a possible mitochondrial cytopathy. He is the second child from a non-consanguineous couple born in the 32+2 week of pregnancy via cesarean section due to pathological CTG after receiving 7 erythrocyte transfusions in utero. His brother is healthy as are his parents. Hypertelorism, low-set ears and cryptorchidism were described at birth as were muscular hypotonia, truncal ataxia and global developmental delay in the following months. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. Reimann, C. Scholtes, K. Cremer, S. Schoenberger, W. Kunz Source Type: research

Congenital myopathies: general and ryr1
Cytoplasmic bodies (CB) in skeletal muscle biopsies typically appear as discrete, small sarcoplasmic inclusions that are eosinophilic and stain red with Gomori Trichrome (GT). The first description of CB as structural Z-disc anomalies was in 1969, and their association with desmin-related neuromuscular diseases (NMD) was recognised in the 1980s. Since then CB have been reported in association with a range of unrelated neuromuscular disorders, many of these in the pre-molecular era. The aim of our study was to look at the prevalence of CB in paediatric-onset NMD (0-16 years) and any particular genotypic correlation. (Source...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Aizpurua, F. Cepas, A. Sarkozy, A. Manzur, F. Muntoni, C. Sewry, R. Phadke Source Type: research

Congenital myopathies: general and ryr1
We describe three siblings with CFZS who are compound heterozygous for a recurrent variant in MYMK, p.(Pro91Thr) and a novel variant p.(Trp79Arg). (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: C. Hedberg-Oldfors, C. Lindberg, A. Oldfors Source Type: research

Congenital myopathies: general and ryr1
Congenital myopathies are a heterogeneous group of inherited muscle disorders characterised by the presence of distinctive morphological features on skeletal muscle biopsy. Cores myopathies show the presence of cores, corresponding to well-delimited rounded areas devoid of oxidative staining. AD RYR1 and MYH7 gene mutations have been found in central core and eccentric cores disease patients. Nevertheless, several cores myopathy patients remain genetically unsolved. Our patient was the third child born to healthy non-consanguineous parents. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: E. Malfatti, X. Lornage, J. B öhm, G. Brochier, R. Carlier, J. Laporte, M. Fardeau, N. Romero Source Type: research

Congenital myopathies: general and ryr1
Congenital myopathies affect children and adults in all populations. They are genetically and clinically heterogeneous with a marked variability in severity and disease progression, and patients can manifest additional non-muscle features affecting different tissues. We established a clinically homogeneous cohort of patients with a severe condition characterized by fetal hypokinesia, neonatal hypotonia, respiratory distress, arthrogryposis, and congenital bone fractures, and all deceased shortly after birth. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. B öhm, E. Malfatti, E. Oates, K. Jones, N. Romero, J. Laporte Source Type: research

Congenital myopathies: general and ryr1
We recently reported that mutations leading to absence of the poorly characterized transcriptional coactivator ASC-1 (Activating Signal Cointegrator –1), never previously associated with muscle function, cause a novel form of autosomal recessive congenital muscle disease. In 4 patients from a consanguineous family, we identified a homozygous nonsense mutation of the TRIP4 gene, encoding the ubiquitous ASC-1 protein. Patients presented with con genital muscle weakness predominantly involving axial muscles, lethal respiratory failure, skin abnormalities and joint hyperlaxity without contractures. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: I. Duband-Goulet, F. Catervi, E. Cabet, L. Davignon, C. Genetti, T. Gidaro, A. Koparir, S. Coppen, E. Pierce-Hoffman, A. Beggs, L. Servais, A. Ferreiro Source Type: research

Congenital myopathies: general and ryr1
Tropomyosin 3 encoded by the TPM3 gene is a member of the acting binding tropomyosin family, a component of the sarcomeric thin filaments troponin/ tropomyosin complex that is essential in muscle contraction by regulating the calcium dependent binding of the myosin head to the actin filament. Mutations in TPM3 cause a clinical and histopathological heterogeneous group of neuromuscular disorders characterized by congenital hypotonia and weakness that includes cap myopathy, congenital fiber type disproportion and nemaline myopathy. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: C. Camelo, A. Da Silva, U. Reed, C. B önnemann, E. Zanoteli Source Type: research

Congenital myopathies: general and ryr1
We present a monocentric revision of muscle biopsies from more than 50 genetically confirmed RYR1 recessive patients. We performed histological, immunohistochemical and ultrastructural analysis of 58 muscle biopsies from 53 patients. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Garibaldi, J. Rendu, J. Brocard, E. lacene, M. Beuvin, G. Brochier, C. Labasse, A. Madelaine, E. Malfatti, J. Bevilacqua, F. Lubieniecki, S. Monges, A. Taratuto, I. Marty, N. Romero Source Type: research

Congenital myopathies: general and ryr1
Ryanodine receptor 1-related congenital myopathies (RYR1-RM) are heterogenous, rare, slowly-progressive neuromuscular disorders for which there is no FDA-approved therapy. Estimated to affect 1:90,000 children in the US, causative RYR1 variants lead to dysfunctional RYR1-mediated Ca2+ release, elevated oxidative stress and deleterious post-translational modifications. RYR1 activity is modulated by several interacting molecules, including FKBP12 which binds to RYR1 at the cytosolic shell (4:1 ratio) and stabilizes the channel in the closed state. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. Todd, J. Witherspoon, A. Kushnir, S. Reiken, M. Razaqyar, M. Shelton, I. Chrismer, C. Grunseich, A. Mankodi, C. B önnemann, K. Meilleur Source Type: research

Congenital myopathies: general and ryr1
Lately, a syndrome with myalgia and rhabdomyolysis and variants in the ryanodine receptor 1 gene (RYR1) has been described. Index patients typically present with rhabdomyolysis induced by exercise, however, we and others have observed pronounced variability of symptoms among index patients with different variants in RYR1. RYR1 is a large gene and many different variants have been related to the myalgia-rhabdomyolysis syndrome. Some of these variants have a surprisingly high allele frequency in the background population. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: N. Witting, T. Solheim, J. Dahlqvist, N. Poulsen, M. Duno, J. Vissing Source Type: research

Congenital myopathies: general and ryr1
Mutations in RYR1 are associated with a wide spectrum of clinical muscle disorders, ranging from early-onset congenital myopathies, to late-onset axial myopathy, malignant hyperthermia susceptibility trait, exceptional myalgia and rhabdomyolysis and a rare bleeding disorder. The morphological changes on muscle biopsy vary from central cores to multi ‐minicores, central nuclei with or without myofibrillar disorganization and congenital fiber type disproportion. CK levels are usually normal or slightly elevated. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: L. Gonzalez-Quereda, A. Pellis é, N. Vidal, M. Rodriguez, P. Gallano, M. Olivé Source Type: research

Congenital myopathies: general and ryr1
RYR1 gene mutations cause heterogeneous myopathies, including dominantly inherited central core disease (CCD), recessive multi-minicore and centronuclear myopathies, rhabdomyolysis and susceptibility to malignant hyperthermia (MH). RYR1-related myopathy (RRM) is the most common congenital myopathy in the UK, and is characterized by a wide range of clinical presentations. Here we present a retrospective study on a large paediatric cohort of RRM patients regularly seen at the Dubowitz Neuromuscular Centre in London. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Sa, M. DiStefano, R. Mein, R. Phadke, L. Feng, P. Munot, R. Quinlivan, A. Manzur, S. Robb, M. Main, C. Sewry, A. Sarkozy, F. Muntoni Source Type: research

Congenital myopathies: general and ryr1
The more common symptoms of RYR1-related myopathies (RYR1-RM) include proximal, facial, bulbar, and/or respiratory muscle weakness, hypotonia, scoliosis, and fatigue. In many cases, respiratory muscle weakness results in respiratory insufficiency, which places individuals at risk of early mortality. To gain a better understanding of respiratory function in RYR1-RM, we assessed pulmonary function using forced and slow vital capacities (FVC, SVC) in this population. Thirty-four individuals (> 7 years, ambulatory) with RYR1-RM completed a 6-month natural history study. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: I. Chrismer, J. Witherspoon, B. Drinkard, M. Stockman, M. Shelton, A. Kuo, C. Allen, J. Todd, M. Jain, M. Meilleur Source Type: research

Congenital myopathies: general and ryr1
Identification of the skeletal muscle calcium release channel protein, ryanodine receptor-1 (RYR1), in 1988 and causative variations in its gene, RYR1, in 1991 led to the association of impaired calcium homeostasis with muscle dysfunction. Ryanodine receptor 1-related congenital myopathies (RYR1-RM) are histopathologically and clinically heterogeneous, rare, slowly-progressive neuromuscular disorders. Estimated to affect 1:90,000 children in the US, causative RYR1 variants lead to dysfunctional RyR1-mediated Ca2+ release, elevated oxidative stress and deleterious post-translational modifications. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: T. Lawal, J. Todd, J. Witherspoon, C. Bonnemann, S. Hamilton, J. Dowling, K. Meilleur Source Type: research

Congenital myasthenic syndromes and myasthenia
Juvenile acquired autoimmune myasthenia gravis (JMG) is a rare disorder of childhood. To further characterize this disorder in pediatric population, we conducted a retrospective study of 21 patients with childhood onset ( (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: P. Karachunski Source Type: research

Congenital myasthenic syndromes and myasthenia
Juvenile myasthenia gravis (JMG) is an acquired autoimmune condition of the neuromuscular junction, caused by an antibody-mediated attack on the nicotinic acetylcholine receptor (AChR) and in a small minority associated with muscle-specific kinase (MuSK) antibodies. To determine the clinical and evolution related features of JMG in a 240 argentinian pediatric cohort. Cross sectional study of patients with JMG at three argentinian hospital, from January 1993 to January 2018. We included 240 patients by the symptoms, electrophysiology, AChR or MuSK antibody levels and a positive response to pharmacological treatment. (Source...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Garc ía Erro, E. Cavassa, J. Muntadas, M. Pauni, G. Vázquez Source Type: research

Congenital myasthenic syndromes and myasthenia
We present our experience in the treatment of 27 patients with Myasthenia Gravis anti-MuSK. We evaluated the treatments received, and the therapeutic response according to clinical and post-interventional status (PIS) of the Myasthenia Gravis Foundation of America (MGFA) at 6, 12, 24 months and current in a cohort of Musk-MG patient. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Rugiero, V. Salutto, V. Alvarez, M. Bettini, N. Genco, C. Mazia Source Type: research

Congenital myasthenic syndromes and myasthenia
Myasthenia gravis (MG) is a neuromuscular disease characterized by fatigability and fluctuating muscle weakness that predominantly involves ocular muscles. The aim of the current study is to study the diagnostic value of the oVEMP test for the diagnosis of MG. oVEMPs were elicited by delivering a vibration to the forehead with a handheld mini-shaker, resulting in bilateral vestibular stimulation via bone-conduction. The oVEMP was recorded by electrodes below the eyes measuring the activity of the inferior oblique muscles. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: R. de Meel, K. Keene, M. Tannemaat, J. Verschuuren Source Type: research

Congenital myasthenic syndromes and myasthenia
Prevalence of respiratory dysfunction in pediatric myasthenia is unknown. The only available reports are from the few published pediatric series describing respiratory failure associated with myasthenic crisis. In a recent survey of 52 Canadian patients published in Pediatrics in 2013, two patients with myasthenia developed respiratory failure and another four reported respiratory dysfunction. This current two years long prospective study reports data obtained from patients with pediatric myasthenia at the Hospital for Sick Children in Toronto. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. Vajsar, H. Katzberg, H. Qashqari, N. Chrestian, I. Narang Source Type: research

Congenital myasthenic syndromes and myasthenia
We report a case of generalized myasthenia gravis and necrotizing myopathy induced by pembrolizumab. We describe a 71-year-old man with metastasic melanoma who started with MG symptoms after de second infusion of pembrolizumab and then developed severe bulbar symptoms and respiratory failure. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Rugiero, M. Bettini, F. Silveira, F. Sosa Albacete, S. Christiansen Source Type: research

Congenital myasthenic syndromes and myasthenia
A 38-year-old woman was referred to our hospital for an incidental thymic cyst. The chest CT demonstrated a 7cm sized cystic and mass lesion in the anterior mediastinum. She had no symptoms of myasthenia gravis(MG). The tumor was completely resected by thymectomy. Histological examination of the tumor identified it as a thymic cyst with fibrous tissue, cystic structure, cholesterol clefts, calcification, necrotic material, and chronic inflammatory lymphohistiocytic infiltrate. Two months after the surgery, she experienced post-thymectomy generalized MG. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: S. Ho, J. So, D. Bae Source Type: research

Congenital myasthenic syndromes and myasthenia
Botulinum toxin type A (BTA) is widely used for both medical treatment and cosmetic purposes. Botulinum toxin type A is a potent neurotoxin and produced by the anaerobic bacterium Clostridium botulinum: It paralyzes the injected muscle by inhibiting acetylcholine release from synapses of neuromuscular junctions and consequently, a dose dependent, reversible denervation develops in muscles. With increasing numbers of people receiving cosmetic botulinum toxin, we should consider the side effects of botulinum toxin type A carefully. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. So, S. Ho, D. Bae Source Type: research

Congenital myasthenic syndromes and myasthenia
Prevalence of depression and anxiety was observed in patients with myasthenia gravis (MG) as an effect of the unpredictable progression of the disease. Increase knowledge about the psychological and psychopathological disorders in patients with MG. We focused on the analysis of the psychological assessment realized at a point before randomization of patients included in the MGEX Study. Qualitative and quantitative methods: self-report questionnaires to evaluate: anxiety (STAI A-B), depression (Beck depression inventory, BDI-13), psychiatric disorders (MINI, French Version 5.0.0), self-esteem (Self- esteem inventory scale, ...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: E. Louet, S. Misdrahi, C. Orblin Bedos, S. Birnbaum, JR. Hogrel, P. Portero, B. Clair, B. Eymard, S. Demeret, G. Bassez, S. Berrih-Aknin, A. Jobic, P. Aegerter, P. Thoumie, T. Sharshar, M. Gargiulo, M. MGEX Study group Source Type: research

Congenital myasthenic syndromes and myasthenia
Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune-mediated disorder of neuromuscular transmission. Voltage-gated calcium channel antibodies (VGCC-Ab) impair calcium influx and acetylcholine release at motor nerve terminals, resulting in the failure of neuromuscular transmission. Patients present with skeletal muscle fluctuating weakness and paralysis in the clinical. Due to LEMS is often misdiagnosed as a peripheral nerve disease or a myopathy, so electromyography (EMG) and muscle biopsy are necessary. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: Y. Zhang, R. Ban, H. Liu, C. Pu, Q. Shi Source Type: research

Congenital myasthenic syndromes and myasthenia
CMS diagnosis often remains difficult, due to: 1) age at onset: (a) in neonates, congenital myopathy (CM) is suspected first; (b) if age at onset is> 2 years, seronegative autoimmune MG is hypothesized; 2) clinical expression differing from a common myasthenic syndrome, with atypical features such as (a) atrophy, scoliosis, contractures, prominent permanent muscle weakness overshadowing motor fluctuations, and myogenic pattern shown by electrophysiology (eg: DOK7), (b) unresponsiveness to/negative effect of AChE inhibitors (e.g.: COLQ); (c) atypical phenotypes initially orientating towards other neuromuscular diseases: ...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: B. Eymard, D. Sternberg, M. Mayer, T. Stojkovic, E. Fournier, S. Nicole, A. Behin, P. Lafor êt, L. Servais, S. Bauché, B. Fontaine, D. Hantaï, M. Fardeau, N. Romero Source Type: research

Congenital myasthenic syndromes and myasthenia
Mechanistic analyses of CMS caused by mutations in acetylcholine receptor (AChR) have guided therapy and yielded insights into structure-function relationships. AChR is a Cys-loop receptor formed by two α, and one β, δ and ε subunits surrounding an ion channel whose opening is triggered by agonist binding to α/δ and α/ε binding sites. A principal pathway that transduces agonist binding to channel opening was identified in the α-subunit: an invariant Arg residue (αR209) in the pre-M1 domai n couples with three nearby negatively charged residues (αE45, &alp...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: X. Shen, D. Selcen, J. Brengman, S. Shen, H. Durmus, V. Preethish-Kumar, A. Yuceyar, S. Vengalil, A. Nalini, F. Deymeer, S. Sine, A. Engel Source Type: research

Congenital myasthenic syndromes and myasthenia
The p.N88K RAPSN variant is a common variation found in European patients, but not in South Americans. Patients with p.N88K variant in compound heterozygosis with another pathogenic variant might present different phenotypes, seeming that the heteroallelic p.N88K-rapsyn is an important determinant of phenotype. In order to verify the presence of p.N88K in our population, 61 Brazilian CMS patients were tested for RAPSN p.N88K (Sanger sequencing). Three patients, 5%, were shown to harbor the p.N88K mutation, two in homozygosis (case 1 and 2) and one in compound heterozygosis (case 3) with the previously reported pathogenic v...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: E. Estephan, A. Zambon, P. Marchiori, A. Silva, C. Moreno, U. Reed, A. T öpf, H. Lochmüller, E. Zanoteli Source Type: research

Congenital myasthenic syndromes and myasthenia
Limb-girdle congenital myasthenic syndromes (LG-CMS) are a group of genetic disorders of the neuromuscular junction that have already been associated with mutations in 10 different genes. Our patient is a 17 years-old young woman from Polish origin who was referred to the neurology clinic at the age of 8 for walking and running difficulties. Walking was acquired between the age of 18 and 24 months. She always had difficulties for running and her walking perimeter was reduced to a few hundreds of meters. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: S. Coppens, G. Glibert, N. Deconinck Source Type: research

Congenital myasthenic syndromes and myasthenia
We describe the case of a 13-year-old-girl presenting with a limb-girdle congenital myasthenic syndrome (LG-CMS) due to a new homozygous missense mutation in DPAGT1. The patient from Guadeloupe was born to consanguineous parents as they share a great-grandmother. She was able to stay sit at 7 months and walked aided at 16 months. She had speech delay with first words at the age of 27 months. At clinical examination at the age of 10, she presented with axial and shoulder girdle muscle weakness, and abduction of the arms was limited to 45. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: T. Gidaro, L. Vandenbrande, E. Malfatti, C. Labasse, P. Carlier, N. Romero, L. Servais, J. B öhm Source Type: research

Congenital myasthenic syndromes and myasthenia
Neuromuscular disorders (NMDs) contain a broad group of disorders with overlapping symptoms and is therefore difficult to differentiate clinically. A subgroup is a plethora of rare and different congenital myasthenic syndromes (CMS) with different inheritance patterns, severity and possible treatments. Since May 2017, we have offered an expanded gene panel based on Next-generation Sequencing (NGS) to patients with NMDs, including CMS. We performed a NGS-analysis with a gene list of 328 genes on almost 150 patients where standard ``gene by gene testing'' had not yielded a diagnosis. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: C. Jonsrud, P. Aden, G. Hansen, M. Mork, B. Nyg ård, T. Popperud, M. Rasmussen, N. Songstad, K. Ørstavik, T. Fagerheim Source Type: research

Congenital myasthenic syndromes and myasthenia
COL13A1 is a membrane protein expressed at the human neuromuscular junction and cleaved via ectodomain shedding into a soluble form that is part of the synaptic basal lamina. In recent years, we have identified that mutations in COL13A1 underlay a novel subtype of congenital myasthenic syndrome highlighting the importance of collagen XIII in the muscle endplate cytoarchitecture and neurotransmission, and the crucial role of extra-cellular matrix proteins, other than those in the agrin pathway, in the formation and maintenance of the synapse. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: P. Rodriguez Cruz, J. Palace, D. Beeson Source Type: research

Congenital myasthenic syndromes and myasthenia
Congenital myasthenic syndromes (CMS) are caused by mutations in genes coding for proteins involved in the maintenance of the neuromuscular junction (NMJ). The patients can be effectively treated and prognosis can be improved when the precise genetic cause is known. In addition, the frequency of the different CMS-causing genes varies with ethnic and geographic origin. There are only few reports from India describing the occurrence of DOK7, RAPSN and COLQ mutations based on selective or limited genetic testing, but the prevalence of various gene mutations in the Indian CMS population is unknown, hence, limiting the effectiv...
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: S. Balaraju, A. T öpf, P. Veeramani, S. Vengalil, K. Polavarapu, S. Nashi, J. Kirschner, R. Horvath, N. Atchayaram, H. Lochmüller Source Type: research

Congenital myasthenic syndromes and myasthenia
We present a 22 year-old girl who presented at birth with signs of CMS. She was born from consanguineous parents, whose two-year-old first son had been previously diagnosed with a syndrome of congenital insensitivity to pain with anhidrosis, due to a homozygous mutation in the NTRK1 gene (c.C2011T, p.R643W). Prenatal screening showed that the female fetus carried the mutation in heterozygosity. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: F. Munell, D. Gomez-Andr és, L. Costa Comellas, A. Macaya, M. Gratacós, M. Dusl, J. Senderek, H. Lochmüller Source Type: research

Congenital myasthenic syndromes and myasthenia
This study aims to develop a home based assessment to enable people with myasthenic syndromes to self-monitor fluctuations in symptoms between clinical appointments. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: V. Selby, G. Ramdharry, M. Hanna, F. Muntoni Source Type: research

Sma clinical data, outcome measures and registries
Spinal muscular atrophy (SMA) refers to a group of autosomal recessive disorders characterized by degeneration of anterior horn cells in the spinal cord resulting in a progressive muscular weakness and atrophy. Our study is focused on the assessment of clinical course in patients with SMA types. To characterize the natural history of SMA 2 patients to gain further insight into the clinical course, we conducted a prospective observational cohort study of children and young adults with SMA 2. Patients were evaluated every 6 months over an 18 moth period. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: D. Natera - de Benito, A. Frongia, M. Alarc ón, A. Borras, J. Armas, J. Exposito, L. Carrera, L. Martorell, D. Moya, N. Padros, S. Roca, M. Vigo, J. Medina, J. Colomer, C. Ortez, A. Nascimento Source Type: research

Sma clinical data, outcome measures and registries
Spinal muscular atrophy (SMA) is caused by mutations in the survival motor neuron 1 gene. Clinically, SMA manifests in various ranges of severity including progressive muscle weakness and loss of motor function. SMA types are characterized based on clinical severity. Several therapeutic strategies are currently under clinical investigation and the first drug was approved in 2016. Given the variable clinical phenotype of SMA, it is essential to determine the best outcome measures and identify prognostic factors to inform clinical trial design. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: A. Chabanon, M. Annoussamy, A. Daron, Y. P éréon, C. Cances, C. Vuillerot, N. Goemans, J. Cuisset, V. Laugel, U. Schara, T. Gidaro, A. Seferian, L. Lowes, P. Carlier, JR. Hogrel, C. Czech, R. Hermosilla, O. Kwaja, L. Servais Source Type: research

Sma clinical data, outcome measures and registries
Proximal spinal muscle atrophy (SMA) is an autosomal recessive disorder caused by deletions or mutations in the SMN1 gene, being characterized by lower motor neuron degeneration in the brainstem and spinal cord with subsequent weakness and muscle atrophy. We aimed to raise awareness of phenotypic and genotypic features of alive SMA patients in Portugal. A multicentre, retrospective study was performed in Portuguese tertiary centres from January 2015 to December 2017. SMA patients were categorized into four phenotypic groups according to the age of onset and highest motor milestones. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Oliveira Santos, C. Falc ão de Campos, C. Garrido, I. Conceição, F. Palavra, L. Negrão, J. Pedro Vieira, C. Mendonça, T. Coelho, I. Fineza, M. Santos, T. Moreno Source Type: research

Sma clinical data, outcome measures and registries
The upper limb (UL) function in SMA patients has been studied using different functional scales and assessment tools but there are limited data on hand function and endurance. The purpose of this study was to determine what are the relationships between UL function and the muscle strength and fatigability of the hand in children with SMA type II and III. Data were collected at one baseline evaluation when 6 girls and 4 boys (mean age 8 years, range 5. 2 – 10. 9), five with SMA II and five with SMA III (3 ambulant) took part in the study. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: E. Milev, V. Selby, J. Reznik, R. Tillmann, M. Iodice, M. Scoto, JR. Hogrel, F. Muntoni Source Type: research

Sma clinical data, outcome measures and registries
In 2017, Cure SMA initiated a yearly membership survey. Surveys were completed for 214 unique individuals with type I spinal muscular atrophy (SMA). Most surveys were completed by parents (97.2%), followed by affected individuals (2.3%), and grandparents (0.5%). At the time of the survey, 50.0% of affected individuals were deceased and the median age of living type I individuals was 8.1 years [range:0-52 years]. Factors associated with death or requiring more than 16 hours of ventilation (an event) are described. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: L. Belter, J. Jarecki, C. Jones, A. Paradis, M. Jhaveri, S. Reyna, K. Hobby Source Type: research

Sma clinical data, outcome measures and registries
Spinal muscular atrophy (SMA) is a hereditary neuromuscular disease marked by the progressive weakness and muscle loss, with obesity as well as malnutrition, gastrointestinal dysmotility, and osteoporosis. Many patients exhibit metabolic abnormalities, such as insulin resistance, diabetes and fatty acid oxidation disorder. This observational study consisted of a nutritional and medical history survey of children with SMA type II and III collected between 2008-2015. We evaluated 109 patients, 55% of them were males, which 78% SMAII and 22% SMAIII. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: C. Saure, F. de Castro Perez, S. Monges Source Type: research

Sma clinical data, outcome measures and registries
This study aimed to measure levels of vitamin D in SMA-patients and investigate their association with SMA type, fractures, and supplementation with vitamin D. We conducted a descriptive observational study of the natural history of SMA in Chile between September 2017 and March 2018. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Mart ínez-Jalile, A. Lozano-Arango, C. Diemer, B. Suárez, K. Alvarez, C. Castiglioni Source Type: research

Sma clinical data, outcome measures and registries
We aim to evaluate the pattern of bone mass acquisition and fracture determinants in type 2/3 patients. DXA measurements of total body less head bone mineral density (TB-BMD and Z-score), bone mineral content (TB-BMC), fat mass (FM) and fat free mass (FFM) were obtained in 19 subjects with SMA (10 SMA2, 9 SMA3) and 19 controls, at baseline and every 12 months for 36 months. At baseline, the median age was 9.4 years. All patients underwent anthropometric (HT SDS, BMI SDS) and biochemical bone turnover evaluations. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: N. DiIorgi, E. Medone, G. Brigati, S. Notarnicola, C. Panicucci, C. Fiorillo, M. Pedemonte, C. Minetti, M. Maghnie, C. Bruno Source Type: research

Sma clinical data, outcome measures and registries
Spinal muscular atrophy (SMA) is an autosomal recessive neuromuscular disorder caused by mutations in SMN1 gene, characterized by degeneration and loss of motor neurons in the anterior horn of the spinal cord. SMN2, a homologous copy of SMN1, is considered a phenotypic modifier of the disease. However, unrelated SMA patients with the same SMN2 copy number but different phenotypes and intrafamilial phenotype discordance in haploidentical siblings have been extensively described. The aim of this study was to provide a phenotypic comparison in a series of Argentinean siblings with SMA. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: S. Monges, J. Mozzoni, M. Franchi, S. Medrano, L. Gravina, H. Ar áoz, F. de Castro, V. Aguerre, L. Alías, L. Chertkoff, E. Tizzano, S. Bernal Source Type: research

Sma clinical data, outcome measures and registries
This study aimed to evaluate the evidence about cognitive outcomes in children with spinal muscular atrophy. This study was registered in the international prospective register of systematic reviews. We performed electronic searches on PUBMED/Medline, Web of Knowledge and Scielo data sources (1992 to 2017) with the descriptors ``spinal muscular atrophy'' and ``cognition''. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: G. Polido, M. Miranda, N. Carvas Junior, F. Caromano, U. Reed, E. Zanoteli, M. Voos Source Type: research

Sma clinical data, outcome measures and registries
Spinal muscular atrophy (SMA) is a devastating inherited disorder caused by ubiquitous deficiency in the SMN protein. SMA main feature is the progressive loss of motor activity caused by motor neurons degeneration leading to muscle atrophy. Recent evidence suggests that SMA is a systemic disease. In the brain SMN is expressed in many cell types in addition to motoneurons. Brain morphology changes have been described, and circadian dysregulation, abnormal fatty acid metabolism have been observed. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: L. Paternoster, S. Baijot, G. Deliens, N. Goemans, L. Servais, N. Deconinck Source Type: research

Sma clinical data, outcome measures and registries
Clinical trials in the SMA I population could be advanced by using a motor tracking system that could quantify change in movement while minimizing the burden of testing on fragile children with SMA. ACTIVE-mini uses color tracking to quantify movement characteristics of the extremities such as quantity, velocity and complexity. The reliability and validity of the ACTIVE-mini has not been established for children with SMA. The purpose of this study was to establish the reliability and validity of ACTIVE-mini for children with SMA. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: L. Nelson, L. Alfano, D. Chen, N. Miller, M. Dugan, S. Rust, E. Lin, S. Lin, S. Wang-Price, C. Swank, M. Thompson, L. Lowes Source Type: research

Sma clinical data, outcome measures and registries
We present here the analyses on the relationships between skeletal muscle NMR imaging, electrophysiological, strength and function variables on this population of patients during a two-year follow-up. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. Hogrel, M. Annoussamy, A. Chabanon, A. Daron, Y. P éréon, C. Cances, C. Vuillerot, N. Goemans, J. Cuisset, V. Laugel, U. Schara, E. Gargaun, T. Gidaro, A. Seferian, S. Turk, R. Hermosilla, E. Fournier, P. Baudin, P. Carlier, L. Servais, Study Group Source Type: research

Sma clinical data, outcome measures and registries
This study explored the utility of ACTIVE scaled workspace volume scores to quantify meaningful change in individuals with spinal muscular atrophy (SMA) due to disease progression or treatment. ACTIVE, a 65-second custom designed video game, uses a skeletal tracking algorithm to quantify the volume of space (m3) the player can interact with while reaching in three dimensions to squish spiders or dig for jewels. Sixty-two individuals with SMA type 2 or 3 (age 10.5y +/-5y) and 362 age-matched controls (age 10.7y +/-3.5y) participated. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: L. Alfano, N. Miller, M. Iammarino, M. Moore-Clingenpeel, S. Lowes, M. Dugan, M. Waldrop, K. Flanigan, G. Noritz, C. Tsao, S. Al Zaidy, J. Kissel, L. Lowes Source Type: research

Sma clinical data, outcome measures and registries
Spinal muscular atrophy (SMA) is a devastating neuromuscular disorder characterized by paralysis and muscle weakness and can affect both children and adults. The first FDA approved SMA therapeutic, Spinraza, improves SMA patients' symptoms and motor function. It is expected that increased lifespan will lead to a shift from the severe infantile SMA population to a milder SMA adult population. It is unknown whether such lifespan extension will reveal new, previously unknown defects that could arise with age, as mild mouse models of SMA are currently lacking. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: M. Deguise, A. Beauvais, A. Tiernay, B. Paul, E. McFall, Y. De Repentigny, R. Kothary Source Type: research

Sma clinical data, outcome measures and registries
In this study, we investigated phenotypic features, with emphasis on muscle, in 40 patients with SBMA using MRI, stationary dynamometry, questionnaires and functional tests. Patients with a genetically confirmed diagnosis of SBMA were included. (Source: Neuromuscular Disorders)
Source: Neuromuscular Disorders - September 6, 2018 Category: Neurology Authors: J. Dahlqvist, S. Oestergaard, N. Poulsen, J. Vissing Source Type: research