Diagnostic usefulness of triple biopsies (Skin, Muscle and Nerve) in clinically suspected cases of vasculitis in a tertiary care hospital in Gujarat

Introduction: The term vasculitis refers to a heterogeneous group of diseases, all characterized by inflammation and destruction of blood vessel walls leading to ischemic, thrombotic, and hemorrhagic damage to tissues of central and peripheral nervous system. The main indication for triple biopsy (skin, muscle and nerve) is to rule out peripheral vasculitis neuropathy. However, the drawback is that any systemic inflammatory process may show changes in a skin biopsy and hence these changes need to be interpreted with caution. The aim of this study is to establish the diagnostic yield and the usefulness of the triple biopsies in clinically suspected cases of vasculitis. Material and Methods: The present study was conducted in the Department of General Pathology, SBKS MI & RC, Vadodara over a period of one year (1/1/2022 to 31/12/2022). All the clinically suspected cases of vasculitis received at OPD were included in the study. Any case with either muscle, nerve or skin biopsy reported as inadequate were excluded from the study. Results: On evaluation the usefulness of triple biopsies for vasculitis, we found a very low diagnostic yield with only 3.3% of peripheral nerve biopsy and 0.8% of muscle and nerve biopsy showed definite vasculitis. In case of suspected peripheral/systemic vasculitic neuropathy, nerve biopsy was sufficient in the majority of case and has the diagnostic armamentarium for the evaluation of vasculitis. Conclusion: In conclusion, nerve biopsies provide the best yield for the diagnosis of vasculitis, as opposed to muscle and skin biopsies. The role of triple biopsies as a routine protocol for the evaluation of vasculitis is questionable.

Genetics and muscle pathology in the diagnosis of muscular dystrophies: An update

Muscular dystrophies are a clinically and genetically heterogeneous group of disorders involving the skeletal muscles. They have a progressive clinical course and are characterized by muscle fiber degeneration. Congenital muscular dystrophies (CMD) include dystroglycanopathies, merosin-deficient CMD, collagen VI-deficient CMD, SELENON-related rigid spine muscular dystrophy, and LMNA-related CMD. Childhood and adult-onset muscular dystrophies include dystrophinopathies, limb-girdle muscular dystrophies, Emery-Dreifuss muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy. Traditionally, muscle biopsy and histopathology along with special pathology techniques such as immunohistochemistry or immunoblotting were used for the diagnosis of muscular dystrophies. However, recent advances in molecular genetic testing, especially the next-generation sequencing technology, have revolutionized the diagnosis of muscular dystrophies. Identification of the underlying genetic basis helps in appropriate management and prognostication of the affected individual and genetic counseling of the family. In addition, identification of the exact disease-causing mutations is necessary for accurate prenatal genetic testing and carrier testing, to prevent recurrence in the family. Mutation identification is also essential for initiating mutation-specific therapies (which have been developed recently, especially for Duchenne muscular dystrophy) and for enrolment of patients into ongoing therapeutic clinical trials. The 'genetic testing first' approach has now become the norm in most centers. Nonetheless, muscle biopsy-based testing still has an important role to play, especially for cases where genetic testing is negative or inconclusive for the etiology.

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.

Basic requirements to establish a neuromuscular laboratory

Histopathological analysis of muscle biopsy is a prerequisite in the evaluation of neuromuscular disorders, particularly inflammatory myopathies, metabolic myopathies, congenital myopathies, muscular dystrophies and differentiating myopathies and neurogenic disorders with overlapping clinically features. It not only provides useful information that helps in the diagnosis but also treatment and management. Fundamental skills and basic knowledge regarding handling, processing and analyzing a muscle biopsy are required in any specialized or a general pathology lab supporting neuromuscular clinical services. Care during transport of the muscle biopsy, sample receipt in the laboratory and grossing is very important. Standard operating procedure should be followed for the preanalytical steps (freezing and cryomicrotomy), routine and special staining (enzyme and non enzymatic) and immunohistochemistry. A well organized neuromuscular laboratory with good quality management system is necessary for the practice of myopathology. This article gives an overview of establishing such a laboratory.

New insights about myofibrillar myopathies: the role of metalloproteinases 2 and 9 in the pathogenesis

Backgroung: There are few reports suggesting that gene expression and activation of various matrix metalloproteinases (MMPs) are deregulated. MMP-2 and MMP-9 represent the two MMPs, which degrade type IV collagen, the component of basement membrane. Methods: We analysed the involvement of gelatinases, MMP-2 and MMP-9, in the pathogenesis of myofibrillar myopathy (MFM). Muscle specimens from 23 patients well diagnosed with MFM, were immunostained by MMP-2 and MMP-9. We analysed qualitatively the immunoexpression in three compartments: subsarcolemmal (SSC), intracytoplasmic (ICC) and perinuclear (PNC).Results: 95,7% and 100% samples showed MMP-2 and MMP-9 upregulation ICC, respectively. PNC showed MMP-2 (82,6%) and MMP-9 (8,7%) regulation (p<0.001). SSC and ICC did not present statistical significance. There was no correlation between mutated gene and immunohistochemical pattern distribution.Conclusion: Our results suggest that MMP-2 and/or MMP-9 could participate in the pathomechanism of MFM, causing damage of sarcomere and deposition of protein aggregates.

Introdução: Existem poucos relatos sugerindo que a expressão gênica e a ativação de várias metaloproteinases de matriz (MMPs) estão desreguladas. MMP-2 e MMP-9 representam as duas MMPs, que degradam o colágeno tipo IV, o componente da membrana basal.Método: Analisamos o envolvimento das gelatinases, MMP-2 e MMP-9, na patogênese da miopatia miofibrilar (MFM). Amostras de músculos de 23 pacientes bem diagnosticados com MFM foram imunocoradas por MMP-2 e MMP-9. Analisamos qualitativamente a imunoexpressão em três compartimentos: subsarcolemal (SSC), intracitoplasmático (ICC) e perinuclear (PNC).Resultados: 95,7% e 100% das amostras apresentaram ICC de regulação positiva de MMP-2 e MMP-9, respectivamente. PNC mostrou regulação MMP-2 (82,6%) e MMP-9 (8,7%) (p <0,001). SSC e ICC não apresentaram significância estatística. Não houve correlação entre o gene mutado e a distribuição do padrão imunohistoquímico.Conclusão: Nossos resultados sugerem que MMP-2 e / ou MMP-9 podem participar do patomecanismo da MFM, causando dano ao sarcômero e deposição de agregados proteicos.

Vacuoles in muscle fiber: pathological differences in various diseases / 中华神经科杂志

The vacuole in muscle fibers is a non-specific myopathological change. As a myopathological term, it occurs in several rare disorders. The vacuoles are mostly related to the autophagy of glycogen, lipids, abnormal proteins, and organelles, and a few are caused by glycogen or lipids deposition or sarcoplasmic reticulum luminal vacuolization. The vacuoles impair the structure of muscle fibers, being one of the myopathological features in various diseases. In this review, clinical features and myopathological changes of various diseases with vacuolar muscle fibers were introduced and the diagnostic value of intrafibral vacuoles was focused on. Knowing the underlying pathogenesis is required to understand these myopathological changes.

Clinical, muscle pathology and gene mutation characteristics of nemaline myopathy caused by mutations in NEB gene / 中华神经科杂志

Objective:To investigate the clinical, muscle biopsy and gene mutation characteristics of nemaline myopathy caused by the NEB gene variants.Methods:A retrospective analysis of the clinical manifestations, auxiliary examinations, muscle biopsies and genetic analysis of 3 nemaline myopathy patients carrying NEB gene mutations diagnosed in the Neuromuscular Pathology Laboratory of Qilu Hospital of Shandong University during 2019-2021 was done. And the related literature was reviewed.Results:All of the 3 patients were congenital onset. The onset symptoms of the 3 patients were weakness of bilateral lower limbs. Physical examinations showed high palatine arches and long narrow faces. Electromyography showed myogenic impairment. Muscle biopsies of the 3 patients revealed myodystrophic changes and nemaline bodies. The ATPase staining of patient 1 showed the predominance and grouping of type 1 muscle fibers. Genetic tests revealed patient 1 carried c.21522+3A>G and c.3471dupC (p.N1158Qfs *5) mutations in the NEB gene, patient 2 carried c.21522+3A>G and c.18991_18992delAG (p.Q6332Afs *8) compound heterozygous mutations and patient 3 carried c.21522+3A>G and c.3448A>T (p.K1150 *) compound heterozygous mutations. All the 3 patients carried the c.21522+3A>G mutation in the NEB gene, which had only been reported in Chinese population. The c.3471dupC (p.N1158Qfs *5), c.18991_18992delAG (p.Q6332Afs *8) and c.3448A>T (p.K1150 *) mutations have not been reported yet. According to American College of Medical Genetics and Genomics guideline, c.21522+3A>G, c.3471dupC (p.N1158Qfs *5), c.3448A>T (p.K1150 *) and c.18991_18992delAG (p.Q6332Afs *8) mutations were all rated pathogenic. Conclusions:The onset age and clinical symptoms of nemaline myopathy are heterogeneous. Muscle biopsy and genetic analysis are important for diagnosis of nemaline myopathy. The c.21522+3A>G mutation in the NEB gene may be more common in Chinese population.

High YKL-40 serum levels and its expression in the muscle tissues of patients with antisynthetase syndrome

Abstract Background: The protein chitinase-3-like-1 (YKL-40) is rarely analyzed in patients with myositis. Therefore, we aimed to evaluate YKL-40 serum levels; correlate them with laboratory and clinical parameters, disease status, and treatment schemes; and analyze the YKL-40 expression in the muscle tissues of patients with antisynthetase syndrome (ASSD). Methods: This cross-sectional single-center study included 64 adult patients with ASSD who were age-, gender-, and ethnicity-matched to 64 healthy control individuals. Their YKL-40 serum levels were analyzed using the Enzyme-Linked Immunosorbent Assay (ELISA) kit method, while YKL-40 expression in muscle tissues was analyzed using an immunohistochemical technique. Disease status was assessed using the International Myositis Assessment and Clinical Studies Group (IMACS) set scores. Results: The patients' mean age was 44.8 ± 11.8 years, and median disease duration was 1.5 (0.0-4.0) years. These patients were predominantly female (82.8%) and Caucasian (73.4%). Most patients had stable disease. The median YKL-40 serum level was significantly higher in patients with ASSD when compared to the healthy individuals: 538.4 (363.4-853.1) pg/mL versus 270.0 (201.8-451.9) pg/mL, respectively; P < 0.001. However, YKL-40 serum levels did not correlate with any clinical, laboratory, disease status, or therapeutic parameters (P > 0.050), except tumor necrosis factor alpha (TNF-α) serum levels (Spearman's correlation, rho = 0.382; P = 0.007). YKL-40 was highly expressed by inflammatory cells found in muscle biopsy specimens. Conclusions: High YKL-40 serum levels were observed in patients with ASSD and correlated positively with TNF-α serum levels. Moreover, YKL-40 was expressed by the inflammatory cells of the muscle tissue.

Métodos de diagnóstico en el estudio de las Miopatías Inflamatorias Autoinmunes: Datos del Registro Argentino de Miopatías Inflamatorias de la Sociedad Argentina de Reumatología / Diagnostic methods in the study of Inflammatory Myopathies. Data from the Argentine Register: Argentine Rheumatology Society

Las Miopatías Inflamatorias Autoinmunes (MI) comprenden un grupo de enfermedades heterogéneas con presentación y características clínicas variables. Se distinguen subtipos clínicos como Polimiositis (PM), Dermatomiositis (DM), Miositis por cuerpos de Inclusión (MCI), Miopatía Necrotizante Inmunomediada (MNIM), Miositis de los Síndromes de Superposición, formas juveniles de MI (DMJ), Síndrome Antisintetasa (SAS) y Miopatía Asociada a Cáncer (MAC). La presencia de anticuerpos séricos y el infiltrado inflamatorio en la biopsia de músculo sugiere que se trata de una condición autoinmune. Realizar el diagnóstico de las MI suele ser un desafío y las herramientas diagnósticas no siempre están disponibles en la práctica diaria. Se obtuvo información sobre la disponibilidad de estos métodos del Registro Argentino de Miopatías Inflamatorias. El estudio de enzimas musculares, Anticuerpos Antinucleares (ANA), anticuerpo anti-Jo-1 y la tomografía computada de tórax, estuvieron disponibles para la mayoría de los pacientes mientras que la Resonancia Magnética de musculo (RM), el estudio de difusión de monóxido de carbono (DLco) y la biopsia muscular se realizaron en menos del 50% de los casos. La determinación de otros anticuerpos específicos de miositis, de importancia en el diagnóstico y pronóstico de la enfermedad se realizó, en mayor parte, a través de un subsidio de la SAR.

The Idiopathic Inflammatory Myopathies (IIM) comprise a heterogeneous group of acquired muscle diseases classified as polymyositis (PM), dermatomyositis (DM), Inclusion Body Myositis (IBM), Immuno Mediated Necrotizing Myopathies (IMNM), Overlap Myositis (OM), juvenile myositis, Antisynthethase Syndrome (ASS) and cancer related myositis (CAM). The presence of myositis specific antibodies in the serum and autoantibodies against target antigens and inflammatory infiltrates in muscle tissue suggests the autoimmune condition of the disease. The diagnosis of inflammatory myopathies is often a challenge and the disposal of diagnostic tools are not always available in daily practice. Information on the accessibility of these methods was obtained from the Argentine Register of Myopathies. The study of muscle enzymes, ANA, anti-Jo-1 antibodies and chest tomography were easy to get to most patients while muscle MRI, lung diffusion capacity for carbon monoxide (DLco) and muscle biopsy were performed in less than 50% of cases. Other myositis specific antibodies, necessary for disease diagnosis and prognosis, were mostly done through a subsidy from the Argentine Rheumatology Society.

Métodos de diagnóstico en el estudio de las Miopatías Inflamatorias Autoinmunes: Datos del Registro Argentino de Miopatías Inflamatorias de la Sociedad Argentina de Reumatología / Diagnostic methods in the study of myopathies Inflammatory Autoimmune: Data from the Argentine Registry of Inflammatory Myopathies of the Argentine Society of Rheumatology

Las Miopatías Inflamatorias Autoinmunes (MI) comprenden un grupo de enfermedades heterogéneas con presentación y características clínicas variables. Se distinguen subtipos clínicos como Polimiositis (PM), Dermatomiositis (DM), Miositis por cuerpos de Inclusión (MCI), Miopatía Necrotizante Inmunomediada (MNIM), Miositis de los Síndromes de Superposición, formas juveniles de MI (DMJ), Síndrome Antisintetasa (SAS) y Miopatía Asociada a Cáncer (MAC).La presencia de anticuerpos séricos y el infiltrado inflamatorio en la biopsia de músculo sugiere que se trata de una condición autoinmune. Realizar el diagnóstico de las MI suele ser un desafío y las herramientas diagnósticas no siempre están disponibles en la práctica diaria. Se obtuvo información sobre la disponibilidad de estos métodos del Registro Argentino de Miopatías Inflamatorias. El estudio de enzimas musculares, Anticuerpos Antinucleares (ANA), anticuerpo anti-Jo-1 y la tomografía computada de tórax, estuvieron disponibles para la mayoría de los pacientes mientras que la Resonancia Magnética de musculo (RM), el estudio de difusión de monóxido de carbono (DLco) y la biopsia muscular se realizaron en menos del 50% de los casos. La determinación de otros anticuerpos específicos de miositis, de importancia en el diagnóstico y pronóstico de la enfermedad se realizó, en mayor parte, a través de un subsidio de la SAR.

The Idiopathic Inflammatory Myopathies (IIM) comprise a heterogeneous group of acquired muscle diseases classified as polymyositis (PM), dermatomyositis (DM), Inclusion Body Myositis(IBM), ImmunoMediated Necrotizing Myopathies, (IMNM), Overlap Myositis(OM), juvenile myositis, Antisynthethase Syndrome (ASS) and cancer related myositis(CAM).The presence of myositis specific antibodies in the serum and autoantibodies against target antigens and inflammatory infiltrates in muscle tissue suggests the autoimmune condition of the disease. The diagnosis of inflammatory myopathies is often a challenge and the disposal of diagnostic tools are not always available in daily practice. Information on the accessibility of these methods was obtained from the Argentine Register of Myopathies. The study of muscle enzymes, ANA, anti-Jo-1 antibodies and chest tomography were easy to get to most patients while muscle MRI, lung diffusion capacity for carbon monoxide (DLco%) and muscle biopsy were performed in less than 50% of cases. Other myositis specific antibodies, necessary for disease diagnosis and prognosis, were mostly done through a subsidy from the Argentine Rheumatology Society.

Profile of various idiopathic inflammatory myopathies at two university hospitals in Yangon, Myanmar

@#Objective: to determine the distribution of various idiopathic inflammatory myopathies (IIM) and their profile at the largest university hospitals in Yangon, Myanmar. Method: It was a hospital based prospective study recruiting IIM patients admitted to Neurology and Rheumatology ward over a 1.5 year period from September 2017 to February 2019. Results: Among total 51 IIM patients recruited, 62.7% presented to Neurology ward and 37.3% to Rheumatology ward. Overlap myositis (OM) was the commonest (43%), followed by immune-mediated necrotizing myopathy (IMNM) 27%, dermatomyositis (DM) 24%, polymyositis (PM) 6%. Among OM, anti-synthetase syndrome (ASS) was 23%, and among IMNM, anti-SRP positive was 79%. IMNM and PM patients presented more to neurologists while OM/ASS and DM more to rheumatologists; 82% were females (F:M= 4.6:1). Mean age of onset of myositis was 40.2 + 17.8 years, and duration of symptoms before presentation was 10-3,600 days (shortest in anti-SRP and longest in anti-HMGCR myopathy). Myositis antibodies were positive in 67%. CK range was 40-25,690 U/l, highest in IMNM and lowest in DM. Associated connective tissue diseases among OM in order of descending frequency were 47% systemic lupus erythematosus, 24% Sjogren syndrome, 41% scleroderma and 12% rheumatoid arthritis. Associated cancer identified were one lung cancer in DM, one breast cancer in OM, one buccal cancer in IMNM cases. Conclusions: With recent availability of myositis antibody panel and MHC staining in Myanmar, we have applied current updated classification to describe the first Myanmar data on IIM cases.

Miastenia gravis adquirida generalizada en caninos y su presentación con miositis de músculos masticatorios / Generalized Acquired Myasthenia Gravis in Canine and the Presentation with Masticatory Muscle Myositis / Miastenia gravis adquirida generalizada em caninos e apresentação com miosite de músculos mastigatórios

Resumen Cinco caninos de 4 a 9 años de edad fueron diagnosticados con miastenia gravis adquirida en asociación con miositis de músculos masticatorios, en el Hospital Escuela de la Facultad de Ciencias Veterinarias de Buenos Aires, durante el periodo 2013-2016. El diagnóstico se confirmó mediante la realización de pruebas serológicas específicas, electromiografías y biopsias musculares de los músculos masticatorios. Se realizó el tratamiento con bromuro de piridostigmina y prednisolona, por el origen inmunomediado de ambas enfermedades.

Abstract Five canines from 4 to 9 years of age were diagnosed with acquired myasthenia gravis in association with masticatory muscle myositis, in the Hospital School of the Faculty of Veterinary Sciences of Buenos Aires, during the 2013-2016 period. The diagnosis was confirmed by performing specific serological tests, electromyography, and muscle biopsies of the masticatory muscles. The treatment used pyridostigmine bromide and prednisolone, due to the immune-mediated origin of both diseases.

Resumo Cinco caninos de 4 a 9 anos foram diagnosticados com miastenia gravis adquirida em associação com miosite de músculos mastigatórios, no Hospital Escola da Faculdade de Ciências Veterinárias de Buenos Aires, durante o período 2013-2016. O diagnóstico foi confirmado pela realização de testes serológicos específicos, eletromiografias e biópsias musculares dos músculos mastigatórios. Realizou-se o tratamento com brometo de piridostigmina e prednisolona, devido à origem imunomediada de ambas as doenças.

Juvenile idiopathic inflammatory myopathies: A clinicopathological study with emphasis on muscle histology

Background: Juvenile idiopathic inflammatory myopathies (JIIM) are rare and heterogeneous. Subtype identification is important for treatment. Materials and Methods: Patients below 18 years diagnosed as idiopathic inflammatory myopathy (IIM) according to the Bohan and Peter criteria between January 2010 and May 2015 were evaluated with muscle biopsy in the four domains: muscle fiber, inflammation, connective tissue, and vascular, with basic panel of histochemical stains as per recommendations of the European Neuromuscular center (ENMC) workshop 2015. Immunohistochemistry with CD 31 was done to assess capillary density. Results: JIIM constituted 15.25% of IIM with juvenile dermatomyositis (JDM) being the most common subgroup (24/27) followed by juvenile overlap myositis (JOM) (3/27) in association with systemic lupus erythematosus (2) and systemic sclerosis (1). Muscle biopsy in JDM was characterized by perifascicular atrophy, necrosis, degeneration, and regeneration in all and the other features included perivascular inflammation (21), lymphoid aggregates (2), mitochondrial abnormalities (9), sarcoplasmic vacuoles (6), capillary dropout (5), capillary dilatation (6), and perimysial fibrosis (14). JOM was characterized by auto-antibodies and perivascular inflammation. Conclusion: JIIMs were rare and JDM was the most common subtype. Muscle biopsy evaluation as per ENMC criteria characterized the subgroups.

The Brazilian Society of Rheumatology recommendations on investigation and diagnosis of systemic autoimmune myopathies

Abstract Background: This research is recommended by the Myopathy Committee of the Brazilian Society of Rheumatology for the investigation and diagnosis of systemic autoimmune myopathies. Body: A systematic literature review was performed in the Embase, Medline (PubMed) and Cochrane databases, including studies published until October 2018. PRISMA was used for the review, and the articles were evaluated, based on the Oxford levels of evidence. Ten recommendations were developed addressing different aspects of systemic autoimmune myopathy investigation and diagnosis. Conclusions: The European League Against Rheumatism/ American College of Rheumatology (EULAR/ACR) classification stands out for the diagnosis of systemic autoimmune myopathies. Muscular biopsy is essential, aided by muscular magnetic resonance images and electroneuromyography in complementary research. Analysis of the factors related to prognosis with the evaluation of extramuscular manifestations, and comorbidities and intense investigation regarding differential diagnoses are mandatory.

The value of muscle biopsy in rhabdomyolysis / 中华内科杂志

Objective@#To analyze the diagnostic value of skeletal muscle biopsy in patients with rhabdomyolysis.@*Methods@#Clinical and pathological data of 26 patients with rhabdomyolysis from January 2002 to December 2018 undergoing muscle biopsy were collected.@*Results@#Eighteen males and 8 females were finally recruited with median age of 6-73 (37.3±19.6) years. The average time from onset to biopsy was 44 days (median course was 30 days). All patients had acute manifestations with muscle pain and/or weakness. Serum creatine kinase was between 1 648-92 660 U/L. Muscle biopsies showed nonspecific changes in 12 cases (a few with type 2 muscle fiber atrophy, slight deposition of lipid droplets), 10 cases with necrotizing myopathy (muscle fiber necrosis and regeneration). Toxic neurogenic damages were seen in 2 cases (type 1 and type 2 angular atrophic muscle fibers with group change), lipid storage disease in 1 case (lipid droplets deposit significantly) and idiopathic inflammatory myopathy in 1 case (muscle fiber necrosis and regeneration, with lymphocyte infiltration). The etiology of non-specific pathological changes included short-term strenuous exercise in 6 patients, poisoning in two, chronic kidney disease in one, viral infection in one, hypothyroidism in one and unknown reason in one. As to patients with necrotizing myopathy, seven were poisoning or drug-related, one with hyperthyroidism, two with unknown reason.@*Conclusions@#Among the numerous causes of rhabdomyolysis, exercise usually links nonspecific skeletal muscle changes and poisoning or drug-related disorders are commonly associated with necrotic myopathy. Rhabdomyolysis induced by primary myopathy is rare.

Chondroid metaplasia of paraspinal connective tissue in the degenerative spine / 대한해부학회지

A 51-year-old male was routinely biopsied during a paraspinal muscle study. The biopsy sample was taken from the right erector spinae muscle at the fourth lumbar vertebra. The patient had no history of (diagnosed) major back trauma. The obtained sample was histologically analyzed (hematoxylin and eosin, safranin O), and complementary magnetic resonance imaging was performed. The biopsied sample contained chondroid tissue. Based on its location, the biopsy sample was appointed as chondroid metaplasia. Although chondroid metaplasia is not uncommon in humans, this is the first report of chondroid metaplasia within the paraspinal connective tissue. We propose a novel mechanism to explain the paraspinal chrondrogenic changes, related to spinal degeneration.

The Usefulness of Muscle Biopsy in Initial Diagnostic Evaluation of Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-Like Episodes

PURPOSE: The disease entity mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is characterized by an early onset of stroke-like episodes. MELAS is the most dominant subtype of mitochondrial disease. Molecular genetic testing is important in the diagnosis of MELAS. The mitochondrial DNA (mtDNA) 3243A>G mutation is found in 80% of MELAS patients. Nevertheless, molecular analysis alone may be insufficient to diagnose MELAS because of mtDNA heteroplasmy. This study aimed to evaluate whether muscle biopsy is useful in MELAS patients as an initial diagnostic evaluation method. MATERIALS AND METHODS: The medical records of patients who were diagnosed with MELAS at the Department of Pediatrics of Gangnam Severance Hospital between January 2006 and January 2017 were reviewed. The study population included 12 patients. They were divided into two subgroups according to whether the results of muscle pathology were in accordance with mitochondrial diseases. Clinical variables, diagnostic evaluations, and clinical outcomes were compared between the two groups. RESULTS: Of the 12 patients, seven were muscle pathology-positive for mitochondrial disease. No statistically significant difference in clinical data was observed between the groups that were muscle pathology-positive and muscle pathology-negative for mtDNA 3243A>G mutation. Additionally, the patients with weakness as the initial symptom were all muscle pathology-positive. CONCLUSION: The usefulness of muscle biopsy appears to be limited to an initial confirmative diagnostic evaluation of MELAS. Muscle biopsy can provide some information in MELAS patients with weakness not confirmed by genetic testing.

Avaliações funcionais e morfométrica de modelo de lesão muscular por agulha de biópsia em gastrocnêmio de ratos / Functional and morphometric evaluations of model of muscle lesion with biopsy needle in gastrocnemius of rats

Introdução: Dentre os modelos experimentais, o uso de agulha de biópsia mostrou ser eficaz para reproduzir as lesões em atletas. Objetivo: Avaliar a força de preensão, a nocicepção e as alterações morfológicas do músculo gastrocnêmio de animais submetidos à lesão muscular. Métodos: Foram utilizados seis ratos Wistar. A lesão foi realizada na junção miotendínea do músculo gastrocnêmio direito, utilizando agulha de biópsia. Para avaliação funcional utilizou-se o teste de força de preensão e avaliação nociceptiva em três momentos: 24 horas antes da lesão (AV1); no segundo dia pós-lesão (AV2) e no sexto dia pós-lesão (AV3). Ao final do experimento o músculo foi retirado para análise morfológica. Resultados: Houve redução da força de preensão entre AV1 e AV2 (p=0,0031). Para a nocicepção os valores de AV2 (p<0,001) e AV3 (p=0,0109) foram maiores que AV1. Na região das fibras musculares observou-se desarranjo do padrão fascicular, aumento do calibre de vasos sanguíneos, da quantidade de tecido conjuntivo, de fibroblastos e de células inflamatórias. Conclusão: A lesão muscular por agulha de biópsia provocou redução da força de preensão e da nocicepção do membro lesado, como também evidenciou as etapas características do processo de degeneração muscular e início do processo de regeneração.

Introduction: Among the experimental models, the use of a biopsy needle was shown to be effective to reproduce lesions that occur with athletes. Objective: To evaluate the grip strength, nociception and morphological alterations of the gastrocnemius muscle of animals submitted to muscle injury. Methods: Six Wistar rats were used. The lesion was performed at the myotendinous junction of the right gastrocnemius muscle using a biopsy needle. For functional evaluation, the grip strength test and nociceptive evaluation were used at three moments: 24 hours before the injury (AV1); on the second postoperative day (AV2) and on the sixth postoperative day (AV3). At the end of the experiment the muscle was removed for morphological analysis. Results: There was a reduction in grip strength between AV1 and AV2 (p = 0.0031). For the nociception the values of AV2 (p < 0.001) and AV3 (p = 0.0109) were higher than AV1. In the muscle fibers region, there was disarrangement of the fascicular pattern, increased blood vessel size, the amount of connective tissue, fibroblasts and inflammatory cells. Conclusion: Muscle lesion by biopsy needle caused reduction of grip strength and nociception of the damaged limb, as well as the characteristic stages of the muscular degeneration process and the beginning of the regeneration process.

The expression and significance of Th17 cell/regulatory T cells in peripheral blood of patients with idiopathic inflammatory myopathy / 中华风湿病学杂志

Objective To explore the expression and their significance of peripheral Th17 cells and regulatory T cells (Tregs) in idiopathic inflammatory myopathy,and analyze the relationship between the expression and clinical indicators,imaging and pathological changes.Methods Clinical data,laboratory tests,imaging and pathological changes of IIM cases (n=85) and healthy controls (n=70) were enrolled.Clinical data included the classification,age,gender,course of the disease;laboratory tests including erythrocyte sedimentation rate (ESR),C-reactive protein (CRP),creatine kinase (CK),creatine kinase isoenzyme-MB (CKMB),lactate dehydrogenase (LDH),hydroxybutyrate dehydrogenase (HBDH).The level of peripheral Th17,Treg cells and clinical indicators,laboratory tests,imaging and pathological changes were analyzed retrospectively.Since the data was disregarded from the normal distribution,the median four quantile method was used for statistical description.Two samples were compared with Mann-Whitney U test,and the correlation between variables was Spearman rank correlation analysis.Results ①) The levels of Th17 cells in the case group was not significantly different from that in the control group [6.18(3.42,13.65) cell/μl vs 7.42(5.02,11.13) cell/μl,P＞0.05],the levels of Treg cells in patients was significantly lower than that in the control group [21.25(12.48,35.67) cell/μl vs 36.95(30.37,47.12) cell/μl,P＜0.05],the ratio of Th17/Treg was also significantly higher than that in the control group [0.31(0.21,0.47) vs 0.18(0.14,0.31),P＜0.05].② Peripheral Treg cells levels were not correlated with ESR,CRP,CK-MB,LDH and HBDH (P＞0.05).Peripheral Treg cells levels were negatively correlated with CRP (r=-0.279,P＜0.05),but no correlated with ESR,CK-MB,LDH and HBDH (P＞0.05).③ According to the involvement of important organs,patients were classified into two groups:organ involvement group and non-organ involvement group.The levels of Treg cells in the organ involvement group was fewer than that in non-organ involvement group [16.54(8.84,27.34) cell/ul vs 24.87(14.44,43.37) cell/ul,P＜0.05],and the ratio of Th17/Treg in the organ involvement group was significantly higher than that in non-organ involvement group [0.41(0.29,0.68) vs 0.29(0.19,0.39),P＜0.05].④) Peripheral Th17 cells levels in patients with skeletal muscle inflammatory edema was significantly higher than that of non-inflammatory edema patients [10.70 (4.11,14.51) cell/μl vs 3.10 (1.27,5.15) cell/μl,Z=-2.460,P＜0.05].⑤ The levels of Th17,Treg cells and ratio of Th17/Treg did not correlate with pathological features of inflammatory infiltration (P＞0.05).Conclusion The absolute number of peripheral Treg cells decreases significantly in IIM,and correlates with CRP.Patients with organ involvement have fewer Treg cells,and there is imbalance between Th17 and Treg.When muscle MRI presents with inflammatory edema,patients may have high level of Th17 cells.Our results suggest that Treg cells may play an important role in the pathogenesis of IIM.

Activation of the wnt/β-Catenin Signaling Pathway in Polymyositis, Dermatomyositis and Duchenne Muscular Dystrophy

BACKGROUND AND PURPOSE: The wnt/β-catenin signaling pathway plays a critical role in embryonic development and adult-tissue homeostasis. Recent investigations implicate the importance of wnt/β-catenin signaling in normal wound healing and its sustained activation being associated with fibrogenesis. We investigated the immunolocalization and activation of wnt/β-catenin in polymyositis (PM), dermatomyositis (DM), and Duchenne muscular dystrophy (DMD). METHODS: Immunofluorescence staining and Western blot analysis of β-catenin were performed in muscle specimens from 6 PM, 8 DM, and 6 DMD subjects. The β-catenin/Tcf4 DNA-binding activity in muscle was studied using an electrophoretic mobility shift assay (EMSA), and serum wnt/β-catenin/Tcf transcriptional activity was measured using a luciferase reporter gene assay. RESULTS: Immunoreactivity for β-catenin was found in the cytoplasm and nuclei of muscle fibers in PM, DM, and DMD. The protein level of β-catenin was elevated, and EMSA analysis confirmed the activation of wnt/β-catenin signaling. The transcriptional activities of β-catenin/Tcf in the circulation were increased in patients with PM, DM, and DMD, especially in those with interstitial lung disease, and these transcriptional activities decreased when PM or DM patients exhibited obvious clinical improvements. CONCLUSIONS: Our findings indicate that wnt/β-catenin signaling is activated in PM, DM, and DMD. Its activation in muscle tissue and the circulation may play a role in modulating muscle regeneration and be at least partly involved in the process of muscle and pulmonary fibrosis.