Miositis por cuerpos de inclusión esporádica / Sporadic inclusion body myositis

A pesar de ser la miopatía primaria más frecuente en hombres mayores de 50 años de edad, la miositis por cuerpos de inclusión (MCI) esporádica es una enfermedad rara. En muchas ocasiones su diagnóstico es retrasado por lo que se refuerza la importancia de una adecuada valoración clínica e indicación oportuna de estudios complementarios. En el presente artículo se presenta un caso que tiene la distinción de presentarse en un paciente mestizo, sin afectación demostrada en flexores profundos de las manos y con elementos de gravedad, determinadas por la presencia de disfagia alta funcional y disnea a la posición de decúbito supino. En la revisión realizada no se recogen hasta el presente reportes en publicaciones de esta enfermedad en Cuba. Clínicamente, la afección se caracteriza por debilidad muscular combinada distal y proximal, electromiografía (EMG) con alteración mixta neuropática y miopática, y escasa respuesta a la terapia inmunosupresora. La biopsia de músculo ayuda a establecer el diagnóstico definitivo al demostrar la presencia de inclusiones distintivas en las fibras musculares. El pronóstico es sombrío al mostrar un comportamiento progresivo con afectación de la calidad de vida y llevar a una discapacidad física avanzada(AU)

Despite being the most common primary myopathy in men over 50 years of age, sporadic inclusion body myositis (ICM) is a rare disease. On many occasions its diagnosis is delayed, which is why the importance of an adequate clinical assessment and timely indication of complementary studies is reinforced. This article reports a case that has the peculiarity of affecting a mestizo patient, with no established involvement in the deep flexors of his hands and with elements of severity, determined by the presence of high functional dysphagia and dyspnea in the supine position. There have not been publication reports on this disease in Cuba. Clinically, the condition is characterized by combined distal and proximal muscle weakness, electromyography (EMG) with mixed neuropathic and myopathic impairment, and poor response to immunosuppressive therapy. Muscle biopsy helps establish the definitive diagnosis by demonstrating the presence of distinctive inclusions in the muscle fibers. The prognosis is bleak, showing progressive behavior affecting quality of life and leading to advanced physical disability(AU)

Role of noninvasive ventilation in perioperative patients with neuromuscular disease: a clinical case / Papel da ventilação não invasiva no período perioperatório de doentes com patologia neuromuscular: caso clínico

The inclusion body myositis is an inflammatory myopathy that leads to chronic muscle inflammation associated with muscle weakness. It is characterized by a restrictive ventilatory syndrome requiring ventilatory support under non-invasive ventilation. The authors describe a clinical case and the anaesthetic management of a patient with inclusion body myopathy candidate for vertebroplasty, which highlights the importance of locoregional anaesthesia and of noninvasive ventilation and includes assisted cough techniques, maintained throughout the perioperative period.

A miosite por corpos de inclusão é uma miopatia inflamatória que cursa com inflamação crônica muscular associada à fraqueza muscular. Caracteriza-se por uma síndrome ventilatória restritiva com necessidade de suporte ventilatório sob ventilação não invasiva. Os autores descrevem caso clínico e respectivo manuseio anestésico de paciente com miopatia por corpos de inclusão proposta para vertebroplastia que realça a importância da anestesia locorregional e da ventilação não invasiva e inclui as técnicas de tosse assistida, mantidas durante todo o período perioperatório.

Estudo clínico, histológico, imunoistoquímico e da função lisossomal na miosite por corpos de inclusão / Clinical, histological, immunohistochemical and lysosomal function study in inclusion body myositis

A miosite por corpos de inclusão (inclusion body myositis - IBM), na sua forma esporádica, é considerada a miopatia adquirida mais comum após os 50 anos de idade. Embora seja incluída no grupo das miopatias inflamatórias, estudos recentes mostram um processo particular de degeneração muscular caracterizado por deposição anormal de agregados de proteínas nas fibras musculares e funcionamento anormal dos principais sistemas de degradação proteica. O objetivo deste estudo foi o de avaliar os aspectos clínicos, histológicos e imunoistoquímicos de pacientes com IBM. Avaliamos 18 casos com diagnóstico de IBM de dois dos principais centros de doenças neuromusculares do Brasil (25 biópsias musculares). Na tentativa de diferenciar os casos de IBM das outras miopatias inflamatórias, determinamos o padrão de expressão tecidual da p-tau (p62), alfa-sinucleína e TDP-43. Também foi avaliada a função lisossomal através da reação da fosfatase ácida (marcação da atividade lisossomal global) e determinação da marcação para LC3B (marcador de autofagia). Foi observado que a IBM predominou no sexo masculino (61% dos casos), da cor branca, com início das manifestações clínicas ao redor dos 59 anos de idade e os sintomas mais frequentes foram fraqueza muscular, instabilidade postural com quedas da própria altura, disfagia e perda ponderal, podendo ainda apresentar dispneia. O diagnóstico demorou em média 7,4 anos após o início dos sintomas e frequentemente esteve associada às seguintes comorbidades: hipertensão arterial sistêmica, diabetes mellitus tipo 2, osteopenia / osteoporose, dislipidemia e hiperuricemia / gota. O padrão de comprometimento muscular na IBM foi caracterizado por tetraparesia de predomínio proximal em membros inferiores e distal em membros superiores. Os valores séricos da creatinofosfoquinase em pelo menos uma das medições foram elevados em todos os pacientes, porém sem ultrapassar 10 vezes o limite superior da normalidade. O uso de...

Sporadic inclusion body myositis (sIBM) is considered the most common acquired myopathy affecting adults aged over 50 years. Although included in the group of inflammatory myopathies, recent studies show a particular process of muscle degeneration characterized by abnormal deposit of protein aggregates in muscle fibers and abnormal operation of the main protein degradation systems. The aim of this study was to evaluate the clinical, histological and immunohistochemical patients with IBM. We evaluated 18 cases with IBM diagnostic of two of the main centers of neuromuscular diseases in Brazil (25 muscle biopsies). In an attempt to differentiate the IBM cases of other inflammatory myopathies, we determined the pattern of tissue expression of p-tau (p62), alfa-synuclein and TDP-43. Also evaluated the lysosomal function by acid phosphatase reaction (marking global lysosomal activity) and determining the markup for LC3B (autophagy marker). It was observed that IBM was predominant in males (61% of cases), white colored, with onset of clinical manifestations around 59 years old and the most common symptoms are muscle weakness, postural instability with high falls, dysphagia and weight loss, and may also present dyspnea. The diagnosis took an average of 7.4 years after the onset of symptoms and was often associated with the following comorbidities: hypertension, type 2 diabetes mellitus, osteopenia / osteoporosis, dyslipidemia and hyperuricemia / gout. The muscular damage pattern at IBM was characterized by tetraparesis predominantly proximal lower limbs and distal upper limbs. Serum creatine kinase levels in at least one of the measurements were elevated in all patients, but not exceeding 10 times normal. Immunosuppression was not effective in patients with IBM. The IBM histological findings included diversify dystrophic changes, endomysial inflammation, as well as the occurrence of rimmed vacuoles, in addition to high frequency of mitochondrial changes. Other...

Hypokalemia-Induced Rhabdomyolysis by Primary Aldosteronism Coexistent With Sporadic Inclusion Body Myositis

We describes a patient with hypokalemia-induced rhabdomyolysis due to primary aldosteronism (PA), who suffered from slowly progressive muscle weakness after laparoscopic adrenalectomy, and was later diagnosed with coexisting sporadic inclusion body myositis (sIBM). A 54-year-old Asian male presented with severe muscle weakness of both lower extremities. Laboratory findings showed profound hypokalemia, and extreme elevation of the serum creatine phosphokinase levels, suggestive of hypokalemia-induced rhabdomyolysis. Further evaluation strongly suggested PA by an aldosterone-producing adenoma, which was successfully removed surgically. However, muscle weakness slowly progressed one year after the operation and a muscle biopsy demonstrated findings consistent with sIBM. This case is the first report of hypokalemia-induced rhabdomyolysis by PA coexistent with sIBM, to the best of our knowledge.

A Brazilian family with hereditary inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia

Inclusion body myopathy associated with Paget disease and frontotemporal dementia (IBMPFD) is a progressive and usually misdiagnosed autosomal dominant disorder. It is clinically characterized by a triad of features: proximal and distal myopathy, early onset Paget disease of bone (PDB), and frontotemporal dementia (FTD). It is caused by missense mutations in the valosin-containing protein (VCP) gene. We describe here the clinical and molecular findings of the first Brazilian family identified with IBMPFD. Progressive myopathy affecting the limb girdles was detected by clinical examination followed by muscle biopsy and creatine kinase measurement. PDB was suggested after anatomopathological bone examination and FTD was diagnosed by clinical, neuropsychological and language evaluations. Brain magnetic resonance revealed severe atrophy of the anterior temporal lobes, including the hippocampi. A R93C mutation in VCP was detected by direct sequencing screening in subject W (age 62) and in his mother. Four more individuals diagnosed with "dementia" were reported in this family. We also present a comprehensive genotype-phenotype correlation analysis of mutations in VCP in 182 patients from 29 families described in the literature and show that while IBM is a conspicuously penetrant symptom, PDB has a lower penetrance when associated with mutations in the AAAD1 domain and FTD has a lower penetrance when associated with mutations in the Junction (L1-D1) domain. Furthermore, the R93C mutation is likely to be associated with the penetrance of all the clinical symptoms of the triad.

update on inflammatory myopathies

Inflammatory myopathies are heterogeneous groups of immune mediated myopathies that present as pure form or in association with other auto-immune diseases or malignancy. There are three major subsets: dermatomyositis, polymyositis and sporadic inclusion body myositis. This review highlights our understanding of these disorders, their clinical aspects, diagnosis, pathogenesis and treatment. The idiopathic inflammatory myopathies occurring alone or in association with auto-immune disease and / or cancer have an overlapping clinical presentation with an overall incidence of 3.0 to 7.8 per million and a prevalence from 10 to 60 per million. Because of the variability in epidemiological studies, the interpretation of these results cannot be conclusive. Recent evidence indicates that polymyositis is over diagnosed and many reported cases are likely to be some other disorders. Decreasing the incidence of true polymyositis is due to reliance not only on clinical criteria but also on immunopathological changes in muscle biopsies. Polymyositis and inclusion body myositis occur primarily in adults, whereas dermatomyositis occurs in adults and children between five and fifteen years of age. Sporadic inclusion body myositis affects almost exclusively men over the age of 50 years

Miopatia por corpos esferóides: relato de caso / Spheroid body myopathy: case report

A miopatia por corpos esferóides é doença rara, classificada no grupo das miopatias congênitas relacionadas aos distúrbios da desmina; apresenta, em geral, origem autossômica dominante e com início dos sintomas na fase adulta. Relatamos o caso de menina de sete anos, com diparesia facial, hipotrofia e hipotonia muscular generalizadas, arreflexia profunda generalizada, força muscular proximal nos membros superiores e inferiores e distal dos membros superiores grau 3 e distal nos membros inferiores grau 1. A eletromiografia de agulha evidenciou recrutamento aumentado e potenciais de unidade motora de curta duração e baixa amplitude, caracterizando um padrão miopático. A biópsia muscular revelou padrão misto para miopatia e desinervação e presença de corpos esferóides intracitoplasmáticos compatíveis com a miopatia por corpos esferóides. No presente caso, a paciente apresentou precocemente o início dos sintomas e não há relatos de casos semelhantes na família.

Miositis por cuerpos de inclusion: comunicacion de cuatro casos / Inclusion body myositis. Report of 4 cases

Inclusion body myositis (IBM) is a primary inflammatory myopathy characterized by an older age at presentation. We describe four IBM cases fulfilling Mendell's diagnostic criteria. All patients were older than 60 years at diagnosis and the mean length of time from onset to diagnosis was 5.7 years. Two of them complained of leg weakness with unsteady gait and the other two, of upper limb weakness. Three patients had dysphagia, one of them had diaphragmatic paralysis and another had bilateral blepharoptosis. Histological sections of the muscle biopsy showed mononuclear cell invasion of nonnecrotic muscle fibers, rimmed vacuoles, intracellular amyloid deposits and 16-21 nm tubulofilaments by electron microscopy. Mitochondrial anomalies were found in two cases. Only one patient had transient response to steroid therapy. Our serie shows that clinical presentation of inclusion body myositis includes a broader spectrum than the classical description.

Effect of beta-amyloid Peptide on Fine Structure of Cardiac Myocytes in Culture / 대한해부학회지

Several predetermined concentrations of beta-amyloid peptide, (betaA) were administered to the rat cardiac myocyte cultures for three days to determine the effects of betaA. Stainings with congo red and crystal violet were used to evaluate the deposition of betaA in the cardiac myocytes and MTT assay was used to elucidate the cytotoxic effects of betaA by anlaysis of cell viability. Beating rates and morphological changes were investigated with inverted microscope and TEM was used to study the fine structures. Administration of 0.5 microgram/ml of betaA to cardiac myocytes induced the reduction of beating rate, however, it did neither affect the viability nor fine structures. No significant differences in cell viability or fine structures were noted in the experimental groups which were exposed to 5 microgram/ml or higher concentration of betaA. Deposition of betaA was confirmed in the cytoplasm of betaA treated cardiac myocytes with congo red and crystal violet amyloid stains. The viability of cardiac myocytes exposed to betaA was found to be reduced significantly (19%) compared to control cultures with the MTT assay. Cardiac myocytes treated with betaA presented a reduced cytoplasmic area that appeared very condensed under inverted microscope. Mitochondrial abnormalities in betaA treated cardiac myocytes included their significant enlargement, vacuolization, disorganization or paucity of cristae, paracrystalline inclusion, and accumulation of amorphous material in mitochondrial space. Mitochondrial abnormalities were present sometimes in betaA treated cardiac myocytes without disorganization of myofibils or degeneration of other cell organelles. To understand the mechanism involved in amyloid deposit and its role in pathogenesis of the diseases such as Alzheimer and inclusion body myositis (IBM), a need for in vitro model is imperative. This model of betaA treated cultured cardiac myocytes represent a amyloidosis model, and it offers several advantages for future studies of betaA to help elucidate the pathogenesis of amyloid diseases. For example, cardiac myocytes can be easily accessible, and since cardiac myocytes can be cultured for quite a long time, it is possible to study morphological and physiological changes consequent to amyloid deposits.

Inclusion Body Myositis: A case report

In 1971 inclusion body myositis was reported by Yunis and Samaha. This disease is similar with chronic multiple myositis clinically. Pathologically, inclusion body myositis is characterized by intracytoplasmic vacuole with degenerating fibers and accompanied with inclusion body in internal nucleus and cytoplasm. Since then 240 cases of inclusion body myositis have been reported in the world including 3 cases in Korea. A 27 years-old lady had inclusion body myositis, which show slowly progressive muscular weakness. We confirmed this with clinical symptom, muscle biopsy, and electrophysiologic study. We report the typical manifestation of inclusion body myositis in a 27 years-old lady with the brief review of literature.

A Case of Mumps Virus Infection Associated with Severe Myositis / 감염

Myositis caused by mumps virus is very rare. Mumps virus has been suggested as a causative agent of inclusion body myositis, but there has been no definite evidence. We experienced a case of severe myositis associated with mumps virus infection. A 21-year old man was admitted because of myalgia, headache, fever, and chill for 2 months. The cerebrospinal fluid analysis performed at a local clinic showed findings compatible with viral meningitis. His blood chemistry results revealed elevated levels of serum creatine kinase, lactate dehydrogenase, and serum myoglobin. On the 5th day of admission, the patient showed pain and swelling of parotid gland and scrotum. Electromyography was compatible with inflammatory myopathy. Muscle biopsy of his calf muscle revealed necrotizing (leukocytoclastic) vasculitis and multifocal myolysis with multinucleation. We suspected mumps virus infection because of his symptoms of meningitis, epididymo-orchitis and parotitis. Mumps virus was isolated in throat culture. The past medical history of the patient's mumps virus vaccination was unclear. After 2 weeks of supportive treatment, the patient's condition was improved.

A Case of Polymyositis Treated with Intravenous Immunoglobulin

Inflammatory myopathies are comprised of three major subsets, polymyositis, dermatomyositis and inclusion body myositis. Although their etiology is unclear, each group retains its characteristic clinical, immunopathologic features. In polymyositis, a CD8+ T-cell mediated cytotoxicity against muscle fibers has emerged as the main pathologic event, whereas in dermatomyositis complement-mediated injury by antibody may be the primary pathology. There has been several reports on polymyositis internationally but we could find only a few reports in Korea. We report here a 8-year old female patient admitted with a stuporous mentality. After coughing and fever for 3 days, she got myalgia, abruptly developed gross hematuria and dyspnea. After admission, she showed weak self respiration and exclussively elevated muscle enzyme in blood chemistry. In muscle biopsy, lymphocytic infiltrations were found in the fascicles without endomysial fibrosis and these lymphocytes were composed of T lymphocytes on immunohistochemical stain. She received two infusions of intravenous immunoglobulin(1g/kg/day), and showed dramatic improvement in symptoms and signs.

A Case of Polymyositis Treated with Intravenous Immunoglobulin

Inflammatory myopathies are comprised of three major subsets, polymyositis, dermatomyositis and inclusion body myositis. Although their etiology is unclear, each group retains its characteristic clinical, immunopathologic features. In polymyositis, a CD8+ T-cell mediated cytotoxicity against muscle fibers has emerged as the main pathologic event, whereas in dermatomyositis complement-mediated injury by antibody may be the primary pathology. There has been several reports on polymyositis internationally but we could find only a few reports in Korea. We report here a 8-year old female patient admitted with a stuporous mentality. After coughing and fever for 3 days, she got myalgia, abruptly developed gross hematuria and dyspnea. After admission, she showed weak self respiration and exclussively elevated muscle enzyme in blood chemistry. In muscle biopsy, lymphocytic infiltrations were found in the fascicles without endomysial fibrosis and these lymphocytes were composed of T lymphocytes on immunohistochemical stain. She received two infusions of intravenous immunoglobulin(1g/kg/day), and showed dramatic improvement in symptoms and signs.

Análise imunocitoquímica do infiltrado inflamatório na miosite com corpo de inclusäo citoplasmática e em outras doenças neuromusculares com vacúolos marginados / Immunocytochemical analysis of the inflammatory infiltrate in inclusion body myositis and other neuromuscular disorders rimmed vacuoles

Encontramos 16 casos com vacúolos marginados entre 1400 biópsias musculares cujo diagnóstico final foi miosite com corpos de inclusao citoplasmática esporádica (MCIC) (4 casos), atrofia muscular espinhal juvenil (6 casos), miopatias distais (3 casos), distrofia das cinturas pélvica e escapular (2 casos) e neuropatia periférica (1 caso). Foram utilizados anticorpos monoclonais contra linfócitos T totais e subpopulaçoes (CD4+ e CD8+), linfócitos B, macrófagos, células exterminadoras naturais (NK), imunoglobulinas e porçao C3 do complemento. A análise foi quantitativa e de acordo com o local de acúmulo (interstício, intra-fibra e perivascular). Linfócitos CD8+ foram encontrados no interstício na maioria dos casos, sendo menos comuns dentro das fibras musculares e raros no espaço perivascular. Os casos de MCIC apresentaram maior número de linfócitos CD8+ se comparados às outras doenças. A proporçao de células CD8+/CD4+ foi maior na MCIC do que nas outras doenças. Existiam macrófagos em grande proporçao na MCIC, miopatias distais e em um dos casos de distrofia das cinturas pélvica e escapular. Células NK foram frequentes no interstício nos casos de MCIC e mais raras nas outras doenças. Houve maior depósito de imunoglobulinas e complemento nos casos de MCIC do que nas demais doenças. O grande número de células CD8+ e a relaçao CD8+/CD4+ podem auxiliar no diagnóstico diferencial da MCIC de outras doenças neuromusculares com vacúolos marginados.

A Case of Incontinentia Pigmenti with Destructive Encephalopathy

Becker muscular dystrophy is a X-linked recessive disease with the affected gene at locus Xp21, characterized by progressive muscular weakness. Without the definite family history, it has been known that the diagnosis of this disease is almost impossible on clinical grounds alone. We reviewed the muscle pathology of two casses of genetically confirmed Becker muscular dystrophy to know the diagnositc significances of this study. The first case, a 20 year old man, is the classical one with definite family history of X-linked recessive heredity. The muscle pathology of the biceps showed dystrophic muscular changes, including increased internal nuclei, marked variation of fiber sizes and mild endomysial fibrosis. The dystrophin stain of the muscle was also confirmative for the diagnosis. The second case was a 32 year old man who has been biopsied his left vastus lateralis 5 years before this genetic diagnosis. This case is a sporadic one without the family history. The diagnosis at the time of muscle biopsy was limb-girdle muscular dystorphy or inclusion body myositis because of the typical rimmed vacuoles and marked variation of fiber sizes. The dystophin stain was not available at that time. Our conclusion is that the molecular genetic study and/or dystrophin protein test of muscle biopsy should be done in every clinically suspected patient, including limb-girdle muscular dystorphy, inclusion body myositis or rimmed vacuolar myopathies.

A case of rigid spine syndrome with rimmed vacuolar myopathy

Rigid spine syndrome (RSS) is a childhood onset muscle disorder characterized by: marked limitation of motility of cervical and lumbar spine with severe lordosis, contracture of limb joints, mild and nonprogressive proximal muscle weakness, moderately elevated muscle enzymes, myopathic electromyographic patterns, and histological features of nonspecific myopathies. Here we present a 14-year-old girl with distinctive clinical features of rigid spine syndrome. She developed slowly progressive difficulty on walking because of joint contracture and rigid spine with severe lordosis since 4 years of age. There was mild but generalized muscle weakness. The serum creatine kinase was increased up to 743 IU/ml and the EMG studies showed combined features of myopathy and neuropathy. The muscle biopsy of vastus lateralis revealed the typical findings of rimmed vacuolar myopathy with perivascular inflammatory cell infiltration, which were consistent with the inclusion body myositis.

Miositis a cuerpos de inclusion: a proposito de dos casos / Inclusion-body myositis: apropos of two cases

La miositis a cuerpos de inclusion es una entidad actualmente incluida dentro del grupo de las Miopatias inflamatorias idiopaticas, conjuntamente con la poliomiositis y dermatomiositis. Constituye la afeccion muscular adquirida mas frecuente de inicio en pacientes mayores de 50 años y se la considera una entidad sub-diagnosticada en varios paises. Es una miopatia cronica, lentamente progresiva, muy invalidante y en general refractaria al tratamiento inmunosupresor. En el presente trabajo se reportan los dos primeros casos diagnosticados en nuestro medio, mediante biopsia muscular, destacandose la importancia del adecuado procesamiento de la biopsia por un equipo especializado a efectos de un diagnostico preciso. Se revisan brevemente los ultimos avances en el estudio de esta enfermedad, con implicancias en la comprension de su etiopatogenia

Anticardiolipin antibodies in inclusion body myositis and the other inflammatory myopathies

In an attempt to address a possible immunologic mechanism in the inflammatory myopathies, we studied sera from patients with a variety of neuromuscular disorders [N = 55] for the presence of anticardiolipin antibodies [ACA] by use of an enzyme-linked immunosorbant assay [ELISA]. High titres of ACA [IgG] were detected in two of five [40%] patients with inclusion body myositis [IBM]. The findings of ACA in IBM, but not in other neuromuscular disorders including other inflammatory myopathies, suggest a possible role for ACA in the pathogenesis of this disorder

Inclusion body myositis: a case report

Inclusion body myositis is a rare myopathy that clinically resembles a chronic polymyositis and histopathologically is characterized by the presence of rimmed vacuoles containing ultrastructural cytoplasmic degradation products with filamentous intranuclear and cytoplasmic inclusions. Since clinical features are not uniform, histopathologic and ultrastructural studies are necessary to confirm the diagnosis. We report a typical case of inclusion body myositis with histopathologic and ultrastructural study. The patient was a 31 year old male who presented with progressive weakness of both forearms, hands and lower extremities for 10 years.