Clinical and Pathological Features of Immune-Mediated Necrotising Myopathies in a Single-Centre Muscle Biopsy Cohort

Objective Immune-mediated necrotising myopathy (IMNM) is a recently entitled novel subset of idiopathic inflammatory myopathies (IIM) characterized by significant elevated creatine kinase (CK) level, muscle weakness and predominant muscle fibre necrosis in muscle biopsy. This study aimed to investigate the clinical and pathological characteristics of patients with IMNM in our single-centre muscle biopsy cohort. Methods A total of 860 patients who had muscle biopsy reports in our centre from May 2008 to December 2017 were enrolled in this study. IMNM was diagnosed in according with 2018 European Neuromuscular Centre (ENMC) clinicopathological diagnostic criteria for IMNM. Results The muscle biopsy cohort consisted of 531 patients with IIM (61.7%), 253 patients with non-IIM (29.4%), and 76 undiagnosed patients (8.8%). Among IIM patients, polymyositis (PM), dermatomyositis(DM), amyopathic dermatomyositis, juvenile DM, and inclusion body myositis were 182(21.2%), 236(27.4%), 83(9.7%), 18(2.1%) and 3(0.3%), respectively. In PM subgroup, 59 patients met serological and pathological characteristics of IMNM according to 2018 ENMC criteria including 29 anti-SRP-positive patients,10 anti-HMGCR-positive patients and 20 MSA-negative patients. Limb girdle muscular dystrophy (LGMD) 2B and lipid storage myopathy (LSM) were 29 and 16 respectively, which present similar manifestations of IMNM with elevated CK levels and muscle weakness among non-IIM group. IMNM patients had older age of onset (mean: 42.25 vs 21.66 and 24.56, p<0.0001), shorter duration of diseases (mean: 22.56 vs 66.69 and 48.94, p<0.0001) and more frequent of dysphagia (33.9% vs 3.4% and 6.3%, p<0.0001) compare to patients with LGMD 2B and LSM. Muscle biopsy from IMNM patients showed frequent muscle fibre necrosis (96.6% vs 72.4% and 56.3%, p<0.0001), overexpression of MHC-I on sarcolemma (81.4% vs 37.9% and 12.9%, p<0.0001) and CD4+ T cell endomysial infiltration (89.9% vs 53.6% and 50%, p<0.0001) compared with LGMD 2B and LSM patients. Conclusions It is easy to distinguish IMNM from other subtype of IIM according to clinical symptoms and MSAs profiles. However, distinguishing IMNM from disorders clinically similar non-IIM need to combine with clinical, serological and pathological features.

Histology of Muscle Development in Pigs, Epigenetics from Myotubes to Tapered Fibres

Pre-natal muscle development in pigs starts with myotubes (axial nuclei in a tube of myofibrils) and secondary fibres (peripheral nuclei on an axial strand of myofibrils). By the time of birth, the nuclei of myotubes move to a peripheral position like secondary fibres. As pre-natal secondary fibres grow in length, the number of fibres in a transverse section may appear to increase. This stereology may also occur in post-natal muscles that have tapered fibres anchored in endomysial connective tissue around adjacent fibres and with one or both ends not reaching the end of their fasciculus. Up to 100 days gestation, Peroneus longus (no tapered fibres) had larger (P < 0.001) diameter secondary fibres than Longissimus thoracis (with tapered fibres). Up to 100 days gestation, no radial growth of secondary fibres was detected, but myotubes decreased in diameter (P < 0.001). From a curve showing the relative numbers of myotubes and secondary fibres, it was deduced that approximately 80% of muscle fibres in pigs are derived from secondary fibres. In post-natal Sartorius muscle there was an increase (P < 0.005) in the apparent number of muscle fibres attributed to longitudinal growth of tapered fibres. Myotubes located centrally within their fasciculi had the same position as slow-contracting fibres with a high myoglobin content in adult muscle. Post-natal changes in muscle fibre histochemistry were achieved through transitional types, probably neurally regulated rather than by differential longitudinal growth of tapered endings. Secondary fibres are important – they give rise to both the majority of muscle fibres in adult pigs and affect subsurface optical pathways and pork colourimetry.

Type II muscle fibre properties are not associated with balance recovery following large perturbations during walking in young and older adults

Falls among older adults are often attributed to declining muscle strength with ageing. Associations between muscle strength and balance control have been reported, but the evidence for, and key mechanisms of resistance exercise in fall prevention are unclear. No studies have directly examined the relationship between muscle fibre characteristics and reactive balance control. Here, we address whether or not Type II muscle fibre characteristics associate with reactive balance during walking in young and older adults with varying muscle fibre type composition. We analyse muscle biopsy-derived fibre characteristics and stability during a treadmill-based walking perturbation (trip-like) task of healthy young adults, healthy, normally active older adults, trained older adults and physically impaired older adults. We find no significant associations between Type II muscle fibre properties and reactive balance during walking, indicating that practitioners and researchers should consider more than just the muscle tissue properties when assessing and intervening on fall risk.

A new framework for analysis of three-dimensional shape and architecture of human skeletal muscles

A new framework is presented for comprehensive analysis of the three-dimensional shape and architecture of human skeletal muscles from magnetic resonance and diffusion tensor imaging data. The framework comprises three key features: (1) identification of points on the surface of and inside a muscle that have a correspondence to points on and inside another muscle, (2) reconstruction of average muscle shape and average muscle fibre orientations, and (3) utilization of data on between-muscle variation to visualize and make statistical inferences about changes or differences in muscle shape and architecture. The general use of the framework is demonstrated by its application to three datasets. Analysis of data obtained before and after eight weeks of strength training revealed there was little regional variation in hypertrophy of the vastus medialis and vastus lateralis, and no systematic change in pennation angle. Analysis of passive muscle lengthening revealed heterogeneous changes in shape of the medial gastrocnemius, and confirmed the ability of the methods to detect subtle changes in muscle fibre orientation. Analysis of the medial gastrocnemius of children with unilateral cerebral palsy showed that muscles in the more-affected limb were shorter, thinner and less wide than muscles in the less-affected limb, and had slightly more pennate muscle fibres in the central and proximal part of the muscle. Amongst other applications, the framework can be used to explore the mechanics of muscle contraction, investigate adaptations of muscle architecture, build anatomically realistic computational models of skeletal muscles, and compare muscle shape and architecture between species.