Diagnosis Of Myopathy Research Articles

Objective Evaluation of Clinical Actionability for Genes Involved in Myopathies: 63 Genes with a Medical Value for Patient Care.

The implementation of high-throughput diagnostic sequencing has led to the generation of large amounts of mutational data, making their interpretation more complex and responsible for long delays. It has been important to prioritize certain analyses, particularly those of “actionable” genes in diagnostic situations, involving specific treatment and/or management. In our project, we carried out an objective assessment of the clinical actionability of genes involved in myopathies, for which only few data obtained methodologically exist to date. Using the ClinGen Actionability criteria, we scored the clinical actionability of all 199 genes implicated in myopathies published by FILNEMUS for the “National French consensus on gene Lists for the diagnosis of myopathies using next generation sequencing”. We objectified that 63 myopathy genes were actionable with the currently available data. Among the 36 myopathy genes with the highest actionability scores, only 8 had been scored to date by ClinGen. The data obtained through these methodological tools are an important resource for strategic choices in diagnostic approaches and the management of genetic myopathies. The clinical actionability of genes has to be considered as an evolving concept, in relation to progresses in disease knowledge and therapeutic approaches.

Process and reflections on the development of expert consensus on diagnosis and treatment of idiopathic inflammatory myopathy associated interstitial lung disease

This paper introduced the following information on the purpose of the consensus, process, writing format, formation of expert opinions, and the issues that remain to be solved and reflections, hoping to provide reference for readers to understand the content of this consensus and rational choice of application.

Chinese expert-based consensus statement on diagnosis and treatment of idiopathic inflammatory myopathy associated interstitial lung disease

Idiopathic inflammatory myopathies (IIM), a group of heterogenous autoimmune diseases, are characterized by proximal, skeletal muscle involvement of chronic immunological pathogenesis. IIM associated interstitial lung diseases (IIM-ILDs) are the most important causes of morbidity or mortality for IIM patients. Patients with IIM-ILDs always exhibit diversity of diseases manifestations including onset pattern, diseases progress, therapeutic respond and prognosis. Hence, the diagnosis and evaluation of IIM-ILDs usually need multidisciplinary consultations. And we have to face some dilemmas, such as sophisticated choice of immunosuppressants due to limited prospective research data, and personnel and different responses to therapeutic remedy. It is an urgent task to develop a consensus on the diagnosis and treatment of IIM-ILDs for guiding the routine practice of clinicians. Experts from pulmonology, rheumatology, and radiology were organized by Respiratory Council of Chinese Research Hospital Association, and developed a consensus based on previous studies and the experts' experiences. This consensus mainly illustrated the epidemiology, clinical characteristics, diagnosis and evaluation, therapeutic remedy for IIM-ILDs. After full discussion and voting by the expert group, a total of 18 recommendations were formed, including 7 recommendations on diagnosis and evaluation, and 11 recommendations on the choice of therapeutic strategies. This consensus is intended to facilitate the standardization of diagnosis and treatment of patients with IIM-ILD and promote the development of relevant clinical and basic research in China.

Diagnosis of Statin-Induced Necrotizing Myopathy: Contribution of Anti-HMGCR Antibodies

Over the last few years, several cases of statin-induced necrotizing myopathy have been described. This myopathy is characterized by the necrosis of muscle fibers and the presence of anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies. Although the diagnosis of myopathies relies on muscle biopsy, which is considered the gold-standard, the search for autoantibodies has proved to be an essential contribution to the diagnosis of immune-mediated myopathies. The detection of anti-HMGCR antibodies in the patient's serum can be performed by enzyme immunoassays, and more recently, by imunofluorescence. As for the latter, the detection of anti-HMGCR antibodies is performed on tissue sections by indirect immunofluorescence and is characterized by a typical fluorescence pattern called "HMGCR Associated Liver IFL Pattern". The authors present two case reports that show the importance of diagnosing statin-induced necrotizing myopathy as quickly as possible and the contribution of anti-HMGCR antibody detection for the diagnosis.

Accuracy of power Doppler ultrasonography in the diagnosis and monitoring of idiopathic inflammatory myopathies.

No clear-cut guidelines exist for the use of imaging procedures for the diagnosis of idiopathic inflammatory myopathies (IIM). The aim of the present study was to assess the diagnostic accuracy of power Doppler ultrasonography (PDUS) score in IIM patients compared with a control group and its usefulness during follow-up. All patients evaluated in the Vasculitis and Myositis Clinic, Rheumatology Unit, University of Siena were prospectively collected. All patients underwent US examination of both thighs in axial and longitudinal scans, which were also performed twice (T1) or three times (T2). Forty-five patients with IIM (median [interquartile range] age 55 [45-66] years; 35 female) were enrolled. Receiver operating characteristic curves distinguished patients and controls based on ∑power Doppler (PD), ∑oedema, ∑atrophy and CRP. The best cut-off value for ∑PD was 0.5, ∑oedema 1.5, ∑atrophy 0.5 and CRP 0.22 mg/dl. In a logistic regression analysis, the variables that most influenced diagnosis of IIM were ∑PD and ∑oedema (P = 0.017 and P = 0.013, respectively). ∑Oedema was lower at T1 (P = 0.0108) and T2 (P = 0.0012) than at T0. Likewise, ∑PD was lower at T1 (P = 0.0294) and T2 (P = 0.0420) than at T0. Physician global assessment was lower at T1 (P = 0.0349) and T2 (P = 0.0035) than at baseline. Our findings show that PDUS is a reliable diagnostic tool in the differential diagnosis between inflammatory and non-inflammatory myopathies. Moreover, PDUS can be employed also during the follow-up of patients with IIM. A reduction in disease activity, measured by physician global assessment, led to a concomitant decrease in both oedema and PD, which was directly correlated with their rate of change. This underlines the close link between clinical assessment and PDUS findings, not only at diagnosis but also during monitoring.

REFERENCE VALUES AND COMPARISON OF BLOOD CHEMISTRY AND PLASMA PROTEIN VALUES BETWEEN GOLD STANDARD ANALYZERS AND FOUR POINT-OF-CARE DEVICES IN FREE-RANGING CANVASBACKS (AYTHYA VALISINERIA).

Accurate, timely, and cost-effective blood chemistry analysis is an essential tool for directing emergency treatment, monitoring the health status of captive and free-ranging individuals and flocks, and improving the efficacy of conservation actions. Blood samples were obtained from 52 canvasbacks (Aythya valisineria) that were captured on San Francisco Bay, California, during December 2017 as part of a long-term study. Reference values and clinical agreement were determined for blood chemistry and plasma protein parameters among four commonly used point-of-care devices (VetScan® VS2, i-STAT®, AlphaTRAK®2 glucometer, refractometer) and two gold standard laboratory analyzers (Roche cobas® c501, Helena SPIFE 3000 system). Canvasback reference values were generally within expected ranges for Anatidae species with the exception of higher upper limits for sodium and chloride. Creatine kinase and aspartate transaminase values exceeded a published threshold for diagnosis of capture myopathy even though study birds were captured using low-stress techniques and successfully released. With the exception of higher alkaline phosphatase in hatch-year canvasbacks, no age or sex differences were observed for any analyte in this population that was captured during a nonbreeding period. Analysis of analyzer agreement found raw VetScan aspartate transaminase, calcium, glucose, and uric acid values; corrected VetScan albumin, potassium, sodium, and total protein values; raw i-STAT glucose and potassium values; and corrected i-STAT sodium and chloride values were clinically interchangeable with Roche cobas values. Raw VetScan and i-STAT glucose values were also interchangeable. However, none of the Roche or point-of-care analyzer plasma protein values were in clinical agreement with gold standard electrophoresis values. The findings of this study highlight the need for analyzer- or technique-specific reference values and provide biologists and veterinarians quantitative reference values using currently available analyzers to better assess and respond to the health of individuals and populations.

Immune Checkpoint Inhibitor-Associated Myositis: A Distinct Form of Inflammatory Myopathy.

Research on the relationship between inflammatory myopathy and malignancy has grown considerably within the last century. Now, the burgeoning field of inflammatory myopathy has yet another player in the mix: immune checkpoint inhibitor-associated myositis (ICI myositis). Immune checkpoint inhibitor-associated myositis is indicated by clinical diagnosis of inflammatory myopathy after initiation of immune checkpoint inhibitor for cancer management. Current literature reflects low prevalence but high mortality associated with ICI myositis, especially when involving myasthenia gravis and myocarditis. Immune checkpoint inhibitor-associated myositis tends to have muscle pain along with weakness, infrequent presentation with dermatitis, or interstitial lung disease and is typically seronegative with scattered, endomysial inflammatory infiltrates on biopsy. The differential diagnosis of ICI myositis includes myasthenia gravis and other neurological immune-related adverse events. Therapeutic approach involves high doses of corticosteroids with a choice of steroid-sparing immunomodulating agent(s) that is primarily driven by expert opinion due to lack of robust research to support one agent over another. There is wide variation in the inclusion criteria for ICI myositis used in previous studies. We review previously used inclusion criteria and suggest an expertise-based classification criterion to provide a standardized definition and allow comparability between studies. There is a critical need for prospective translational and clinical studies that elucidate the pathophysiology of ICI myositis in order to improve evaluation and management of these patients.

Differential diagnosis of myopathy and multiple epiphysal dysplasia caused by mutations in the <i>COMP</i> gene in children

Background. Multiple epiphysal dysplasia (MED) type 1 (OMIM: 132400) is one of 7 genetic variants of this group of skeletal dysplasias described to date. The disease is caused by mutations in the COMP gene located on chromosome 19p13.1. The presence of muscle hypotonia and ligamentous laxity, as well as a moderate increase in the level of creatinephosphokinase activity, can lead to misdiagnosis of myopathy.Objective: to analyze the clinical and genetic characteristics of type 1 MED caused by mutations in the COMP gene in a series of Russian patients. Differential diagnosis was focused on the distinctive features of the disorder and hereditary myopathies.Materials and methods. We observed 8 patients from 7 families aged 7 to 15 years with MED type 1 caused by heterozygous mutations in the COMP gene. To confirm the diagnosis, the following methods were used: genealogical analysis, clinical examination, neurological examination with psycho-emotional testing, radiography and targeted sequencing of a panel consisting of 166 genes responsible for the development of inherited skeletal pathology.Results. Case history, clinical, radiological and genetic characteristics of 8 patients with MED type 1 caused by mutations in the COMP gene were analyzed. The first clinical manifestations of the disease were recorded from the age of 2–3 years and were characterized by gait disturbances, muscle weakness, difficulties with climbing stairs, frequent falls when walking, the inability to get up from the floor and from a squatting position and hypermobility of the joints. Electroneuromyographic study did not reveal the signs of miopathy. In two patients, a moderate increase in the creatinekinase level of up to 250–360 u / l was found. All patients were surveyed by neurologists for several years with a clinical diagnosis of congenital myopathy. At the age of 5–6 years patients COMPlained knee and ankle pain, which was assumed as rheumatic arthropathy. X-ray examination revealed typical signs of deficient ossification of the epiphyses. The next-generation sequencing analysis revealed seven single nucleotide variants in the COMP gene that lead to MED type 1. Three of the found variants here identified for the first time. As previously described, the majority of nucleotide variants (six out of seven) were localized in the 8–14 exons of the COMP gene and led to amino acid substitutions in calmodulin-like protein domain repeats, and only one substitution was localized in the C-terminal region of the protein molecule.Conclusion. In most patients with MED caused by mutations in the COMP gene, the first symptoms of the disease are gait disturbance, muscle weakness, and Gowers» maneuvers. The presence of these symptoms, along with a moderate increase in the level of creatinephosphokinase activity, often precedes the onset of clinical manifestations of skeletal dysplasia, leading to a misdiagnosis with myopathies. Accession of expressive arthralgias to these symptoms was mistakenly identified as reactive arthritis. X-ray examination of patients’ long bones helps to suspect the presence of MED. This X-ray imaging shows specific signs of epiphyses damage. A molecular-genetic analysis needs to be done to diagnose the genetic variant, caused by mutations in gene COMP.

081 Ultrasound-guided muscle biopsy: a practical alternative for investigation of myopathy

ObjectiveWe propose the use of ultrasound-guided muscle biopsy as a viable method of obtaining muscle specimen to aid the diagnosis of myopathy. We retrospectively review the diagnostic accuracy and patient feedback of ultrasound-guided muscle biopsies in our neuromuscular service.MethodMul- tidisciplinary team meeting reviewed select patients and agreed on those suitable for ultrasound-guided muscle biopsy. They underwent biopsy using direct ultrasound guidance and a modified Bergström needle. The specimens were sent for histopathological analysis and patients were given a feedback form.Results10 patients underwent 11 ultrasound-guided muscle biopsies. Of these 11, 1 was processed incorrectly, but all others were suitable for analysis. All of those processed correctly aided diagnosis. All patient feedback was rated good or excellent. In 4 patients with a previous unsuccessful surgical biopsy, ultrasound-guided biopsy was successful in obtaining suitable muscle. Of those 4 patients, 2 preferred ultrasound-guided biopsy and 2 did not state a preference.DiscussionOur ultrasound-guided muscle biopsy technique offers an alternative to surgical biopsy. It yields high quality specimens that aids diagnosis and receives good patient feedback. It can be performed as a day-case and does not require theatre space. Fur- thermore, direct visualization of structures minimizes complications and allows biopsy of otherwise difficult targets.ConclusionUtilisation of ultrasound-guided modified Bergström needle technique for muscle biopsy provides comparable success rates to other techniques, and has several benefits compared to alternative techniques.m.ashraghi@nhs.net

POS0911 DIAGNOSTIC VALUE AND CLINICAL RELEVANCE OF MUSCLE BIOPSY IN PATIENTS WITH SUSPECTED MYOSITIS

BackgroundDiagnosis of idiopathic inflammatory myopathies (IIM) represents a clinical challenge and muscle biopsy itself is regarded as the cornerstone for confirming diagnosis of IIM. However, the significance of muscle biopsy as diagnostical tool remains inconclusiveObjectivesTo determine the diagnostic accuracy and clinical relevance of muscle biopsy in patients with suspected myositis.MethodsIn this retrospective cohort study, histopathological findings of muscle biopsy specimens of adult (≥ 18 years of age) patients with clinically suspected or differential diagnosis of myositis referred from all over Austria to the Medical University of Vienna through the period of 01.01.2007-31.10.2021 were analyzed. Following information were extracted from handwritten assignment sheets: referral department, suspected diagnosis (inflammatory and/or non-inflammatory myopathy), sampling location, demographic, clinical, laboratory and serologic data, and imaging results.Histological findings were grouped in: 1) inflammatory, 2) non-inflammatory (neurogenic, metabolic etc.), 3) inflammatory and non-inflammatory mixed, and 4) normal. Clinical information on start of immunosuppressive treatment after muscle biopsy could be partly retrieved form electronical medical records (EMR). Sensitivity, specificity, positive (PPV) and negative predictive values (NPV) of histological results were calculated using clinical diagnosis (defined as initiation of immunosuppressive therapy) as gold standard.Results778 muscle biopsy specimens of 762 patients with suspected myositis (49.6% female, mean age of 56 years) were analyzed. Cohort descriptives are displayed in Table 1.Overall, 373/778 (47.9%) muscle biopsies revealed inflammatory features only or had mixed results with non-inflammatory characteristics. Out of 541 samples with suspected diagnosis of myositis, diagnosis was confirmed histologically in 300 (55.5%) cases; 46 (8.5%) specimens additionally showed co-features of non-inflammatory myopathy, whereas 221 (40.3%) were non-inflammatory at all and 15 (2.8%) were normal. Proportion of myositis was more pronounced, when CK was elevated at time of biopsy (Figure 1).Figure 1.From suspicion to histological verification depending on CK-levelsOut of 237 samples with differential diagnosis of non-inflammatory myopathy in addition to myositis, 53 (22.4%) were histology. confirmed as inflammatory only and 20 (8.4%) showed mixed features. 153 (64.6%) biopsies were non-inflammatory only and 8 (3.4%) normal. Samples with no pathological features were observed in 24/778 (2.3%) of the cases, with 0.8% sampling error (no muscle tissue).Of 421/778 (54.1%) patients, clinical data could be extracted from EMR of which 209/421 (49.6%) had histological features of inflammation. In 287/421 (68%) cases, information regarding initiation of immunosuppressive treatment were available on EMR. 224/287 (78%) patients received immunosuppression (steroids and/or disease-modifying anti-rheumatic drug [DMARD]), thus fulfilled clinical diagnosis of myositis. In 155/224 (69.2%) cases, muscle biopsy confirmed histology. features of inflammation. Tests on diagnostic accuracy of muscle biopsy using initiation of any immunosuppressive treatment as gold standard were performed. The sensitivity of the test (biopsy) for diagnosing IIM was 71.4% with a specificity of 79.6%. PPV was high (92.8%), whereas NPV low (43.1%).ConclusionLess than 50% of biopsy samples with suspected diagnosis of myositis histologically revealed an inflammatory myopathy. The percentage increased when CK levels were elevated. Sensitivity and specificity of muscle biopsy was moderate, when using start of immunosuppressive therapy as gold standard for IIM diagnosis.

Long-Reads Sequencing Strategy to Localize Variants in TTN Repeated Domains

Titin protein is responsible for muscle elasticity. The TTN gene, composed of 364 exons, is subjected to extensive alternative splicing and leads to different isoforms expressed in skeletal and cardiac muscle. Variants in TTN are responsible for myopathies with a wide phenotypic spectrum and autosomal dominant or recessive transmission. The I-band coding domain, highly subject to alternative splicing, contains a three-zone block of repeated sequences with 99% homology. Sequencing and localization of variants in these areas are complex when using short-reads sequencing, a second-generation sequencing technique. We have implemented a protocol based on the third-generation sequencing technology (long-reads sequencing). This new method allows us to localize variants in these repeated areas to improve the diagnosis of TTN-related myopathies and offer the analysis of relatives in postnatal or in prenatal screening.

Evolving classification and role of muscle biopsy in diagnosis of inflammatory myopathies.

Idiopathic inflammatory myopathy (IIM) is a broad term that includes dermatomyositis, polymyositis, overlap myositis, sporadic inclusion body myositis, and immune-mediated necrotizing myopathy. The understanding of the pathogenesis of IIM is ever-evolving with regular updates in the classification schema. With the recognition of autoantibodies and their detection, the diagnostic algorithms are changing in favor of non-invasive diagnoses. However, muscle biopsy has immensely contributed to our understanding of the pathogenesis of inflammatory myopathies, and the pathologic features of different subtypes are well established. The biopsy also aids in distinguishing myopathies with overlapping clinical features, particularly dystrophies, which can show inflammation on biopsy in some cases. In this article, the various classification schemes of the IIM are reviewed. Also, the pathogenesis and pathology of each type of IIM have been highlighted. This article emphasizes the role of muscle biopsy in the diagnosis of inflammatory myopathies.

Approach to the diagnosis of metabolic myopathies.

Metabolic myopathies are a diverse group of genetic disorders that result in impaired energy production. They are individually rare and several have received the 'orphan disorder' status. However, collectively they constitute a relatively common group of disorders that affect not only the skeletal muscle but also the heart, liver, and brain among others. Mitochondrial disorders, with a frequency of 1/8000 population, are the commonest cause of metabolic myopathies. Three main groups that cause metabolic myopathy are glycogen storage disorders (GSD), fatty acid oxidation defects (FAOD), and mitochondrial myopathies. Clinically, patients present with varied ages at onset and neuromuscular features. While newborns and infants typically present with hypotonia and multisystem involvement chiefly affecting the liver, heart, kidney, and brain, patients with onset later in life present with exercise intolerance with or without progressive muscle weakness and myoglobinuria. In general, GSDs result in high-intensity exercise intolerance while, FAODs, and mitochondrial myopathies predominantly manifest during endurance-type activity, fasting, or metabolically stressful conditions. Evaluation of these patients comprises a meticulous clinical examination and a battery of investigations which includes- exercise stress testing, metabolic and biochemical screening, electrophysiological studies, neuro-imaging, muscle biopsy, and molecular genetics. Accurate and early detection of metabolic myopathies allows timely counseling to prevent metabolic crises and helps in therapeutic interventions. This review summarizes the clinical features, diagnostic tests, pathological features, treatment and presents an algorithm to diagnose these three main groups of disorders.

Current approach to diagnosis of inflammatory myopathies: Clinical features and myositis antibody profiles.

Diagnosis of inflammatory myositis has been made easier with the availability of commercial assays for myositis-specific and myositis-associated antibodies. Clinico-serological association studies have permitted a better definition of clinical subsets. Myositis-specific auto-antibodies are highly specific and non-overlapping, whereas myositis-associated antibodies are those seen also in other connective tissue disorders such as systemic lupus erythematosus, primary Sjogren's syndrome, and idiopathic pulmonary auto-immune fibrosis. Their value is pronounced when clinical features are subtle or non-specific or when the muscle is not the primary organ involved. Overall, the muscle-specific and myositis-associated antibodies have changed the landscape in terms of diagnostic utility, prognostication, and the approach to organ-specific evaluation and management of idiopathic inflammatory myopathies (IIMs).

Weakness After an Intraarticular Steroid Injection: A Case Report of Acute Steroid-Induced Myopathy

Introduction: Weakness is a common chief complaint in the emergency department, and the use of glucocorticoids is pervasive in medicine. Muscle weakness, or myopathy, is a well documented side effect of chronic glucocorticoid use. However, acute myopathy, with an onset shortly after initiation of glucocorticoids, is much rarer. Case Report: We present a case of acute steroid-induced myopathy after a single intra-articular dose of triamcinolone in a young, healthy, active male. To our knowledge, this is the first case described in the medical literature of acute steroid-induced myopathy following a single intra-articular injection. Conclusion: In a patient who presents with proximal muscle weakness and has a history of glucocorticoid use, the diagnosis of steroid-induced myopathy should be considered. Acute steroid-induced myopathy should be high on the differential in a patient who presents with typical symptoms and has been prescribed glucocorticoids for less than 14 days or, in rare cases, may have recently received a single dose of glucocorticoids. Treatment is supportive and outpatient management is typically indicated, as respiratory muscle involvement is rare.

Weakness After an Intra-articular Steroid Injection: A Case Report of Acute Steroid-induced Myopathy.

IntroductionWeakness is a common chief complaint in the emergency department, and the use of glucocorticoids is pervasive in medicine. Muscle weakness, or myopathy, is a well documented side effect of chronic glucocorticoid use. However, acute myopathy, with an onset shortly after initiation of glucocorticoids, is much rarer.Case ReportWe present a case of acute steroid-induced myopathy after a single intra-articular dose of triamcinolone in a young, healthy, active male. To our knowledge, this is the first case described in the medical literature of acute steroid-induced myopathy following a single intra-articular injection.ConclusionIn a patient who presents with proximal muscle weakness and has a history of glucocorticoid use, the diagnosis of steroid-induced myopathy should be considered. Acute steroid-induced myopathy should be high on the differential in a patient who presents with typical symptoms and has been prescribed glucocorticoids for less than 14 days or, in rare cases, may have recently received a single dose of glucocorticoids. Treatment is supportive and outpatient management is typically indicated, as respiratory muscle involvement is rare.

P067 Covid- 19 infection as a trigger for immune inflammatory myositis

Abstract Background/Aims Increasing experience in managing patients with COVID-19 infection has demonstrated the development of autoimmune phenomena following infection. We describe a patient with preceding COVID-19 infection who presented with inflammatory immune myositis, positive myositis antibodies and a normal creatine kinase. Methods N/A Results A 61-year-old Caucasian female presented feeling generally unwell and with weakness. She had COVID-19 infection 4 months prior, which necessitated admission to the Intensive Care Unit (ITU), treatment with dexamethasone and oxygen and subsequent discharge with home continuous positive airway pressure (CPAP). Other co-morbidities included atrial fibrillation, chronic kidney disease stage three, hypertension, obesity, recent pulmonary embolism, obstructive sleep apnoea, chronic lymphoedema and hypercholesterolaemia on atorvastatin. Her mobility had been gradually reducing over the previous months to now requiring a wheelchair. Neurological examination demonstrated bilateral proximal lower limb weakness, power 3/5 and an unsafe swallow, for which a naso-gastric tube was inserted. A non-specific erythematous pruritic rash was noted on the arms. Full body Computerised tomography (CT) and Magnetic Resonance Imaging (MRI) of the brain and spine were unremarkable. Creatinine kinase (CK) was within normal limits at 81, and C-reactive protein (CRP) was mildly raised at 36. C3 was low at 0.67 and C4 low at 0.03. Cryoglobulins were not detected. She was positive for antinuclear antibody (ANA) (1:320 titre), Ro-52, PM-Scl75, and anti-La. Anti-dsDNA was negative. Electromyography could not be performed due to the presence of chronic lymphoedema. MRI showed symmetrical STIR hyperintense signal changes in the quadriceps muscles bilaterally. A muscle biopsy showed a small focus of mild lymphocyte infiltration in the endomysial connective tissue, mild increase in acid phosphatase expression in many fibres in dotlike pattern, overexpression of HLA-ABC with deposits of complement found in in endomysial capillaries, consistent with a diagnosis of inflammatory myopathy. Following commenced of 60 mg prednisolone daily, there was a marked improvement in swallowing and the NG tube was removed. A positron emission tomography (PET) scan showed non-specific marrow, splenic and adrenal hyperplasia. The patient was then started on mycophenolate mofetil (MMF), but was switched to azathioprine due to side effects. On review following discharge, the patient continues to require a wheelchair to mobilise, but there has been improvement in her swallow and she reports feeling better within herself. Conclusion Inflammatory myositis is a rare sequela of COVID-19 infection. The development of myositis-specific antibodies post infection has previously been described. This case highlights the significant dysphagia and debility despite a normal CK and the need for a high index of suspicion. Possible triggers of an inflammatory response predisposing to autoimmune phenomena include molecular mimicry, bystander activation, exposure of previously hidden epitopes to activated T cells, activation of Toll-like receptors and activation of the complement system. Disclosure G. Bartminski: None. A. Vijayan: None. K. Beharry: None. D. De Lord: None.

Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study

Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype–phenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect.

Statin-associated immune-mediated necrotizing myositis in Native Americans.

Statin-associated immune-mediated necrotizing myopathy (IMNM) and idiopathic inflammatory myositis (IIM) are myopathies with overlapping features. This study compared the manifestations of IMNM to IIM in Native Americans. Twenty-one Native American patients with inflammatory myopathy (IM) were characterized as to diabetes mellitus, hyperlipidaemia, statin exposure, myopathy diagnosis, muscle histology, autoimmune and myositis-specific autoantibodies, therapy and outcome. IM consisted of 52.4% IMNM, 42.9% IIM and 4.8% metabolic myopathy. IMNM vs IIM patients were older [61.6 years (s.d. 9.8) vs 39.8 (14.3)], diabetes mellitus (100% vs 55.6%), hyperlipidaemia (100% vs 33.3%), statin-exposure (100% vs 22.2%), creatine kinase [CK; 11 780 IU (s.d. 7064) vs 1707 (1658)], anti-3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) antibodies (85.7% vs 11.1%) and necrotizing IM (81.8% vs 11.1%), but shorter disease duration [26.2 months (s.d. 395) vs 78.4 (47.9)], RP (9.1% vs 55.6%), cutaneous manifestations (0% vs 55.6%), ANA (18.2% vs 66.7%) or any autoantibody (18.2% vs 88.9%) (all P < 0.05). MRI abnormalities, histologic IM, myositis-specific autoantibodies, pulmonary hypertension, oesophageal dysfunction, interstitial lung disease, disability and persistently elevated CK were similar. IMNM vs IIM was treated more with IVIG (72.7% vs 11.1%; P = 0.009) and less with antimetabolites (45.5% vs 88.9%; P = 0.05) and rituximab (18.2% vs 55.6%; P = 0.09). IMNM may occur in Native Americans and is associated with diabetes mellitus, hyperlipidaemia, statin use and older age and is characterized by marked CK elevation, necrotizing myopathy and anti-HMGCR antibodies with few cutaneous or vascular manifestations.

Muscle Biopsy: A Requirement for Precision Medicine in Adult-Onset Myopathy.

Muscle biopsy is a fundamental procedure to assist the final diagnosis of myopathy. With the recent advances in molecular diagnosis, serology tests, and mechanism-based classification in myopathy, the précised diagnosis for myopathy required the applications of multiple tools. This study intends to reappraise the benefit of muscle biopsy in adult-onset myopathy under the setting of an optimized muscle biopsy protocol and comprehensive serology tests. A one-group pretest-posttest study design was used. The pre- and post-biopsy diagnoses and treatments in 69 adult patients were compared. Muscle biopsy yielded 85.5% of definitive diagnoses, including changes in pre-biopsy diagnoses (40.6%) and narrowing down the suspicious myopathies (49.3%). The demographic data and clinical parameters between the group “with change” and “without change” after biopsy were not different. Among those with changes in diagnosis, 39.3% also had a corresponding shift in treatment, which benefits the patients significantly. Regarding the most common adult-onset myopathy, idiopathic inflammatory myopathy (IIM), 41% of patients with pre-biopsy diagnosis as IIM had changes in their IIM subtype diagnosis, and 53% was finally not IIM after muscle biopsy. Although there have been advances in molecular diagnosis recently, muscle biopsy still undoubtedly critically guided the diagnosis and treatment of adult-onset myopathy in the era of precision medicine.