Muscle imaging in laminopathies: Synthesis study identifies meaningful muscles for follow-up

Introduction: Particular fibroadipose infiltration patterns have been recently described by muscle imaging in congenital and later onset forms of LMNA-related muscular dystrophies (LMNA-RD). Methods: Scores for fibroadipose infiltration of 23 lower limb muscles in 34 patients with LMNA-RD were collected from heat maps of 2 previous studies. Scoring systems were homogenized. Relationships between muscle infiltration and disease duration and age of onset were modeled with random forests. Results: The pattern of infiltration differs according to disease duration but not to age of disease onset. The muscles whose progression best predicts disease duration were semitendinosus, biceps femoris long head, gluteus medius, and semimembranosus. Discussion: In LMNA-RD, our synthetic analysis of lower limb muscle infiltration did not find major differences between forms with different ages of onset but allowed the identification of muscles with characteristic infiltration during disease progression. Monitoring of these specific muscles by quantitative MRI may provide useful imaging biomarkers in LMNA-RD. Muscle Nerve 58:812-817, 201

Nurses' perceptions of online continuing education

<p>Abstract</p> <p>Background</p> <p>There is increasing attention to online learning as a convenient way of getting professional training. The number and popularity of online nursing continuing education programs are increasing rapidly in many countries. Understanding these may contribute to designing these programs to maximize success. Also, knowing the perceptions and preferences in online learning aids development and orientation of online programs. The aims of this study are to show nurses' perceptions of online continuing education and to determine perceptions of various groups; area groups, working companies, frequency of computer usage and age.</p> <p>Methods</p> <p>The survey method was used in this quantitative study to reveal perception levels and relationship with related variables. Data were collected through an online instrument from a convenience sample of 1041 Registered Nurses (RNs) at an online bachelor's degree program. Descriptive and inferential analysis techniques were performed.</p> <p>Results</p> <p>Nurses generally have positive perceptions about online learning (<it>X </it>= 3.86; SD = 0.48). A significant difference was seen between nurses who used computers least and those with the highest computer usage [<it>F </it>(3, 1033) = 3.040; <it>P </it>< .05]. Neither nurses' ages nor lengths of working experience are significantly related to perceptions of online programs (<it>r </it>= -.013; <it>P </it>> .05 and <it>r </it>= -.036; <it>P </it>> .05, respectively). Nurses' perceptions are significantly different depending on the settings where they work [<it>F </it>(3,989) = 3.193; <it>P </it>< .05]. The difference between perceptions of nurses living in urban areas (<it>X </it>= 3.82; SD = .51) and those living in rural areas (<it>X </it>= 3.88; SD = .47) was not significant [<it>t </it>(994) = -1.570, <it>P </it>> .05].</p> <p>Conclusions</p> <p>We found that nurses regard online learning opportunities as suitable for their working conditions and needs. Nurses should be provided with continued training through online learning alternatives, regardless of age, working experience or area of residence.</p

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency

INTRODUCTION: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of β-galactosidase (β-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). METHODS: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. RESULTS: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. CONCLUSION: This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management

Dihydropyridine receptor (DHPR, CACNA1S) congenital myopathy

Muscle contraction upon nerve stimulation relies on excitation–contraction coupling (ECC) to promote the rapid and generalized release of calcium within myofibers. In skeletal muscle, ECC is performed by the direct coupling of a voltage-gated L-type Ca2+ channel (dihydropyridine receptor; DHPR) located on the T-tubule with a Ca2+ release channel (ryanodine receptor; RYR1) on the sarcoplasmic reticulum (SR) component of the triad. Here, we characterize a novel class of congenital myopathy at the morphological, molecular, and functional levels. We describe a cohort of 11 patients from 7 families presenting with perinatal hypotonia, severe axial and generalized weakness. Ophthalmoplegia is present in four patients. The analysis of muscle biopsies demonstrated a characteristic intermyofibrillar network due to SR dilatation, internal nuclei, and areas of myofibrillar disorganization in some samples. Exome sequencing revealed ten recessive or dominant mutations in CACNA1S (Cav1.1), the pore-forming subunit of DHPR in skeletal muscle. Both recessive and dominant mutations correlated with a consistent phenotype, a decrease in protein level, and with a major impairment of Ca2+ release induced by depolarization in cultured myotubes. While dominant CACNA1S mutations were previously linked to malignant hyperthermia susceptibility or hypokalemic periodic paralysis, our findings strengthen the importance of DHPR for perinatal muscle function in human. These data also highlight CACNA1S and ECC as therapeutic targets for the development of treatments that may be facilitated by the previous knowledge accumulated on DHPR

Antiepileptic treatment in Dravet syndrome : an additional complexity for the families

Antiepileptic treatment in Dravet syndrome : an additional complexity for the families. 12. European Paediatric Neurology Society Congres

P431 Steroid treatment may change natural history in congenital laminopathies

Mutations in LMNA gene lead to a broad spectrum of muscle disorders from congenital (L-CMD) to later onset muscular dystrophies (Emery Dreifuss type, EDMD). Patients with congenital laminopathies start before the age of 2 years and show a poor motor development or a rapidly progressive course after initial sitting or walking acquisition. A recognizable cervico-axial weakness (Dropped Head Syndrome, DHS) is observed, followed by constant loss of function of the extremities and respiratory muscles. Lordo-scoliosis and cardiac involvement (arrhythmias, heart failure) are later complications. Treatment with corticosteroids has been suggested as a potential therapy because of inflammatory changes observed on muscle biopsy. We describe the experience treating with corticosteroids children with L-CMD in three French Neuromuscular Paediatric Centers (FILNEMUS). A retrospective study was performed in all the children with genetically confirmed skeletal muscle laminopathies with onset at the paediatric age and treated by oral corticosteroids, at least during one year, in three paediatric neuromuscular centers. Collected data included molecular, clinical features and respiratory, motor, and heart functions, and ancillary tests (biopsy, muscle imaging, spinal X -rays, CK and Pro-BNP levels). Seven children (6 DHS, 1 EDMD), all carrying de novo LMNA mutations, were treated with prednisone (0.75 mg/Kg/day) at a mean age of 4 years (2-8) during an average of 3 years (1-7). Six of the patients were males. Inflammatory signs were observed in all, either on biopsy (2) or in the whole body muscle MRI pre-therapeutic examinations (5). Three boys younger than 2 years, who had never walked unsupported and were losing head, trunk and limb function, improved significantly after prednisone and were able to walk several weeks or months after treatment onset (2 weeks-1 year). A 4-year-old boy who lost walking, recovered this ability 2 years after starting prednisone. Both ambulant patients with DHS phenotype (a boy and a girl) remained ambulant (1-3 years). The girl showed a decrease of leg pain, significant decrease of CK levels and normalisation of Pro-BNP and Troponin blood results after treatment. Joint contractures were milder than expected in follow-up, except for the ankles. Spine did not show the typical stiffness but rather a hyperlordotic deformity, leading to an unexpected new phenotype. Corticosteroid treatment was discontinued in the only EDMD patient, a 12-year-old boy after 3 years of treatment, due to worsening of motor and cardiac status. Treatment with corticosteroids seems to stop progression of muscle weakness and contractures in congenital skeletal laminopathies when inflammation is present on muscle biopsy or imaging. Moreover, acquisition of new motor functions and striking improvement of axial and head support is observed in the weeks or months after onset of treatment. We observed only a clear beneficial effect in young children with de novo LMNA mutations treated before the age of 4 years. Muscle MRI may be useful to assess the presence of inflammation before treatment and as a potential biomarker during follow-up of the patients

Muscular MRI-based algorithm to differentiate inherited myopathies presenting with spinal rigidity

International audienceObjectives Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each inherited myopathy long before the genetically confirmed diagnosis.MethodsThis multicentre retrospective study enrolled 79 patients from referral centres in France, Brazil and Chile. The patients underwent 1.5-T or 3-T mWB-MRI. The protocol comprised STIR and T1 sequences in axial and coronal planes, from head to toe. All images were analyzed manually by multiple raters. Fatty muscle replacement was evaluated on mWB-MRI using both the Mercuri scale and statistical comparison based on the percentage of affected muscle.ResultsBetween February 2005 and December 2015, 76 patients with genetically confirmed inherited myopathy were included. They were affected by Pompe disease or harbored mutations in RYR1, Collagen VI, LMNA, SEPN1, LAMA2 and MYH7 genes. Each myopathy had a specific pattern of affected muscles recognizable on mWB-MRI. This allowed us to create a novel decision algorithm for patients with rigid spine syndrome by segregating these signs. This algorithm was validated by five external evaluators on a cohort of seven patients with a diagnostic accuracy of 94.3% compared with the genetic diagnosis.ConclusionWe provide a novel decision algorithm based on muscle fat replacement graded on mWB-MRI that allows diagnosis and differentiation of inherited myopathies presenting with spinal rigidity.Key Points center dot Inherited myopathies are rare, diagnosis is challenging and genetic tests require specialized centres and often take years.center dot Inherited myopathies are often characterized by spinal rigidity.center dot Whole body magnetic resonance imaging is a unique tool to orientate the diagnosis of each inherited myopathy presenting with spinal rigidity.center dot Each inherited myopathy in this study has a specific pattern of affected muscles that orientate diagnosis.center dot A novel MRI-based algorithm, usable by every radiologist, can help the early diagnosis of these myopathies