UNASSIGNED: Idiopathic inflammatory myopathies (IIM) are a heterogeneous group of autoimmune diseases affecting primarily proximal muscles. Major subtypes include dermatomyositis, polymyositis, inclusion body myositis, immune-mediated necrotizing myopathy and antisynthetase syndrome. Overexpression of sarcoplasmic myxovirus-resistance protein A (MxA) has been observed in muscle biopsy specimens of dermatomyositis but is rarely seen in other subtypes of IIM and other myopathies.
UNASSIGNED: We evaluate the expression of sarcoplasmic MxA and its diagnostic value in IIM and other myopathies.
UNASSIGNED: One hundred and thirty-eight muscle biopsy specimens with the diagnosis of IIM and other myopathies from 2011 to 2020 were reviewed and stained for MxA by immunohistochemistry. The difference of the expression of MxA between IIM and other myopathies was analyzed by Fisher\'s exact test, and the sensitivity and specificity of MxA immunohistochemistry in the diagnosis of IIM were assessed.
UNASSIGNED: MxA protein was positive in 16/138 (11.6%) specimens. All 12 dermatomyositis specimens positive for MxA protein were positive in perifascicular area pattern. Only dermatomyositis specimens had a significantly higher percentage of positive sarcoplasmic MxA expression than specimens of other subtypes of IIM (p<0.001). Sarcoplasmic MxA expression for dermatomyositis diagnosis had a sensitivity of 46.15% (95% CI 26.59-66.63%) and a specificity of 94.44% (95% CI 81.34-99.32%) with the positive and negative likelihood ratio of 8.31 (95% CI 2.03-34.01) and 0.57 (95% CI 0.40-0.82), respectively.
UNASSIGNED: The MxA immunohistochemistry is highly specific for dermatomyositis and should be added to a routine inflammatory panel of muscle biopsy. MxA expression should be cautiously interpreted to avoid pitfalls.

UNASSIGNED: Myoadenylate deaminase (MAD) deficiency is a form of metabolic myopathy, which generally causes only mild symptoms in the primary inherited form. Inflammatory myopathies are a group of autoimmune diseases which result in skeletal muscle weakness. In addition to inflammatory pathology, it has been speculated that non-inflammatory mechanisms, and possibly secondary MAD-deficiency, may potentially contribute to weakness in these conditions.
UNASSIGNED: We investigated for an association between these two myopathic processes through two complementary methods. Firstly, muscle biopsy records in South Australia over a 17-year period were retrospectively reviewed for diagnosis of myositis or MAD-deficiency, as well as associated clinical features. Secondly, a prospective arm histochemically tested all incident biopsy specimens over a 12-month period for MAD-deficiency.
UNASSIGNED: In the retrospective arm, 30 MAD-deficient cases were identified (1.3% of all biopsies), with no significant difference observed in overall rates of myositis diagnosis between patients with intact and deficient MAD activity (21.3% vs 26.7%, P = 0.47). No cases of MAD-deficiency were detected in the prospective arm, despite 39 cases of myositis being identified over this period.
UNASSIGNED: Secondary MAD deficiency is unlikely to be a major driver of symptoms in inflammatory myopathies.

The goal of the study was to retrospectively evaluate a cohort of children and adults with mitochondrial diseases (MDs) in a single-center experience. Neurological clinical examination, brain magnetic resonance imaging (MRI) and spectroscopy, muscle biopsy, metabolic and molecular-genetic analysis were evaluated in 26 children and 36 adult patients with MD in Slovenia from 2004 to 2018. Nijmegen MD criteria (MDC) were applied to all patients and the need for a muscle biopsy was estimated. Exome-sequencing was used in half of the patients. Twenty children (77.0%) and 12 adults (35.0%) scored a total of ≥8 on MDC, a result that is compatible with the diagnosis of definite MD. Yield of exome-sequencing was 7/22 (31.0%), but the method was not applied systematically in all patients from the beginning of diagnostics. Brain MRI morphological changes, which can be an imaging clue for the diagnosis of MD, were found in 17/24 children (71.0%). In 7/26 (29.0%) children, and in 20/30 (67.0%) adults, abnormal mitochondria were found on electron microscopy (EM) and ragged-red fibers were found in 16/30 (53.0%) adults. Respiratory chain enzymes (RCEs) and/or pyruvate dehydrogenase complex (PDHc) activities were abnormal in all the children and six adult cases. First, our data revealed that MDC was useful in the clinical diagnosis of MD, and second, until the use of NGS methods, extensive, laborious and invasive diagnostic procedures were performed to reach a final diagnosis. In patients with suspected MD, there is a need to prioritize molecular diagnosis with the more modern next-generation sequencing (NGS) method.

UNASSIGNED: Congenital myopathies (CMs) are rare neuromuscular disorders. Through this article, authors want to present a clinicopathological study of 10 cases of CM.
UNASSIGNED: The study included patients with histopathologically confirmed CM attending the neurology services at the Institute of Human Behavior and Allied Sciences for 2 years. After collecting the demographic data, all patients were subjected to comprehensive workup including a detailed neurological examination and investigations, including muscle biopsy from representative involved muscle.
UNASSIGNED: Ten patients diagnosed with CM. The most common CM type was congenital fiber-type disproportion (CFTD) seen in four cases followed by centronuclear myopathy in two cases and one each in desmin-related myopathy, central core disease, nemaline myopathy, CM with type II fiber hypoplasia. Clinically, they have variable features.
UNASSIGNED: This study from India highlights the importance of specific clinical features to look for when suspecting a CM coupled with specific features in histopathology. However, studies with longer duration are needed to find out the true prevalence and various spectra of CMs.

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Sedentary lifestyle, chronic disease, or microgravity can cause muscle deconditioning that then has an impact on other physiological systems. An example is the nervous system, which is adversely affected by decreased physical activity resulting in increased incidence of neurological problems such as chronic pain. We sought to better understand how this might occur by conducting RNA sequencing experiments on muscle biopsies from human volunteers in a 5-week bed-rest study with an exercise intervention arm. We also used a computational method for examining ligand-receptor interactions between muscle and human dorsal root ganglion (DRG) neurons, the latter of which play a key role in nociception and are generators of signals responsible for chronic pain. We identified 1352 differentially expressed genes (DEGs) in bed rest subjects without an exercise intervention but only 132 DEGs in subjects with the intervention. Among 591 upregulated muscle genes in the no intervention arm, 26 of these were ligands that have receptors that are expressed by human DRG neurons. We detected a specific splice variant of one of these ligands, placental growth factor (PGF), in deconditioned muscle that binds to neuropilin 1, a receptor that is highly expressed in DRG neurons and known to promote neuropathic pain. We conclude that exercise intervention protects muscle from deconditioning transcriptomic changes, and prevents changes in the expression of ligands that might sensitize DRG neurons, or act on other cell types throughout the body. Our work creates a set of actionable hypotheses to better understand how deconditioned muscle may influence the function of sensory neurons that innervate the entire body.

Background  Duchene muscular dystrophy (DMD) is an X-linked progressive muscle disorder that is characterized by proximal muscle weakness followed by a premature death in young boys. There is a low index of reports on diagnosis ratio and clinical features in Southern India. Objective  The present study aimed to conduct an observational survey on preliminary analysis, family history, associated complaints, and diagnosis ratio of DMD in southern regions of India. Materials and Methods  A systematic observation and survey were conducted on clinically confirmed DMD patients registered between 2019 and 2021 through the questionnaire. The questionnaire and pattern of study were identified by exploring published and unpublished studies available from electronic databases and critical assessment criteria considered by physicians. Preliminary analysis such as onset criteria, motor difficulties, milestone delay; family history and consanguinity analysis; chief complaints (ambulatory status, lordosis, respiratory, and cardiac outcomes), associated complaints such as enlarged tongue, oral hygiene, behavioral problems; and other similar parameters were studied. An assessment of the diagnosis rate and pattern was performed. Statistical analysis  The data were reviewed and interpreted through statistical methods mean ± standard deviation represented as a percentage. Results  In total, 400 DMD patients were included and 250 participated in the study. The onset age group was 2 to 5 years in 37% of the population. Milestone delay was seen in 86%; consanguinity marriage of parents was reported in 39%. Frequent falls were reported in 62% in 5 to 8 years old group. Wheelchair status was reported in 65% in 9 to 12 years old. Cervical and lumbar lordoses were seen in 57 and 69%, respectively, in above 13 years old. Respiratory and cardiac complications were 88 and 78% reported in above 13 years old, respectively. Other major associated complaints such as enlarged tongue were reported in 79%. Fifty-one percent underwent genetic diagnosis and 79% of the population underwent serum creatine phosphokinase (CPK) analysis for the confirmation of DMD. Conclusion  In this study population of South India, milestone delay was a major observation. Although there was a slight margin, family history shows \"no blood relation among parents\" in the majority of the study population. Chief complaints were predominantly severe above 13-year age group population. Serum CPK was the first choice for the first investigation, which is followed by a genetic diagnosis.

Mitochondrial diseases (MDs) are a large group of genetically determined multisystem disorders, characterized by extreme phenotypic heterogeneity, attributable in part to the dual genomic control (nuclear and mitochondrial DNA) of the mitochondrial proteome. Advances in next-generation sequencing technologies over the past two decades have presented clinicians with a challenge: to select the candidate disease-causing variants among the huge number of data provided. Unfortunately, the clinical tools available to support genetic interpretations still lack specificity and sensitivity. For this reason, the diagnosis of MDs continues to be difficult, with the new \"genotype first\" approach still failing to diagnose a large group of patients. With the aim of investigating possible relationships between clinical and/or biochemical phenotypes and definitive molecular diagnoses, we performed a retrospective multicenter study of 111 pediatric patients with clinical suspicion of MD. In this cohort, the strongest predictor of a molecular (in particular an mtDNA-related) diagnosis of MD was neuroimaging evidence of basal ganglia (BG) involvement. Regression analysis confirmed that normal BG imaging predicted negative genetic studies for MD. Psychomotor regression was confirmed as an independent predictor of a definitive diagnosis of MD. The findings of this study corroborate previous data supporting a role for neuroimaging in the diagnostic approach to MDs and reinforce the idea that mtDNA sequencing should be considered for first-line testing, at least in specific groups of children.

UNASSIGNED: Sporadic inclusion body myositis (s-IBM) is rare in India.
UNASSIGNED: The aim of this study was to diagnose s-IBM according to the European Neuromuscular Center (ENMC) IBM research diagnostic criteria 2011.
UNASSIGNED: A retrospective review of patient records diagnosed as s-IBM according to the above criteria during the period from January 2010 to May 2015 was done with an emphasis on pattern of muscle weakness.Serumcreatine kinase (CK) andelectromyography (EMG) were noted. Muscle biopsy was evaluated with basic panel of histochemical stains including Congo red stain. Immunohistochemistry (IHC) with ubiquitin was done in 10 biopsies. IHC for major histocompatibility complex-1 and electron microscopy studies were not performed.
UNASSIGNED: The diagnosis of s-IBM constituted 5 clinicopathologically defined, 12 clinically defined, and 10 probable IBM in the study period. There was male predominance with median age at 51 and duration of disease varying from 1-5 years. All the patients presented with insidious onset of muscle weakness of quadriceps and/or forearm flexors. CK varied from 57-2939 IU/L. EMG was myopathic in 22, mixed in 2, and neuropathic in 3. Endomysial inflammation was seen in 23 (85.19%) and rimmed vacuoles in 24 (88.89%). Amyloid was demonstrated in only 5 (18.52%) and ubiquitin in 2 biopsies. Mitochondrial abnormalities were seen in 92.59% biopsies.
UNASSIGNED: Application of the ENMC IBM research diagnostic criteria allowed diagnosis of clinically-defined and probable IBM in the absence of all pathology criteria. Rimmed vacuoles in 88.89% of biopsies indicate presentation at a late stage. Use of ancillary techniques can improve diagnostic yield.

UNASSIGNED: The role of muscle magnetic resonance imaging (MRI) in the diagnostic procedures of myopathies is still controversially discussed. The current study was designed to analyze the status of qualitative muscle MRI, electromyography (EMG), and muscle biopsy in different cases of clinically suspected myopathy.
UNASSIGNED: A total of 191 patients (male: n = 112, female: n = 79) with suspected myopathy who all received muscle MRI, EMG, and muscle biopsy for diagnostic reasons were studied, with the same location of biopsy and muscle MRI (either upper or lower extremities or paravertebral muscles). Muscle MRIs were analyzed using standard rating protocols by two different raters independently.
UNASSIGNED: Diagnostic findings according to biopsy results and genetic testing were as follow: non-inflammatory myopathy: n = 65, inflammatory myopathy (myositis): n = 51, neurogenic: n = 18, unspecific: n = 23, and normal: n = 34. The majority of patients showed myopathic changes in the EMG. Edema, atrophy, muscle fatty replacement, and contrast medium enhancement (CM uptake) in MRI were observed across all final diagnostic groups. Only 30% of patients from the myositis group (n = 15) showed CM uptake.
UNASSIGNED: The study provides guidance in the definition of the impact of muscle MRI in suspected myopathy: despite being an important diagnostic tool, qualitative MRI findings could not distinguish different types of neuromuscular diagnostic groups in comparison with the gold standard histopathologic diagnosis and/or genetic testing. The results suggest that neither muscle edema nor gadolinium enhancement are able to secure a diagnosis of myositis. The current results do not support qualitative MRI as aiding in the diagnostic distinction of various myopathies. Quantitative muscle MRI is, however, useful in the diagnostic procedure of a suspected neuromuscular disease, especially with regard to assessing progression of a chronic myopathy by quantification of the degree of atrophy and fatty replacement and in exploring patterns of muscle group involvements in certain genetic myopathies.