Inflammatory myopathies: an update for neurologists.

Idiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.

The Location of Disease-Causing DES Variants Determines the Severity of Phenotype and the Morphology of Sarcoplasmic Aggregates.

Desmin (DES) is the main intermediate muscle filament that connects myofibrils individually and with the nucleus, sarcolemma, and organelles. Pathogenic variants of DES cause desminopathy, a disorder affecting the heart and skeletal muscles. We aimed to analyze the clinical features, morphology, and distribution of desmin aggregates in skeletal muscle biopsies of patients with desminopathy and to correlate these findings with the type and location of disease-causing DES variants. This retrospective study included 30 patients from 20 families with molecularly confirmed desminopathy from 2 neuromuscular referral centers. We identified 2 distinct patterns of desmin aggregates: well-demarcated subsarcolemmal aggregates and diffuse aggregates with poorly delimited borders. Pathogenic variants located in the 1B segment and the tail domain of the desmin molecule are more likely to present with early-onset cardiomyopathy compared to patients with variants in other segments. All patients with mutations in the 1B segment had well-demarcated subsarcolemmal aggregates, but none of the patients with variants in other desmin segments showed such histological features. We suggest that variants located in the 1B segment lead to well-shaped subsarcolemmal desmin aggregation and cause disease with more frequent cardiac manifestations. These findings will facilitate early identification of patients with potentially severe cardiac syndromes.

Inflammatory myopathies: an update for neurologists / Miopatias inflamatórias: uma atualização para neurologistas

ABSTRACT Idiopathic inflammatory myopathies (IIM) are a heterogenous group of treatable myopathies. Patients present mainly to the rheumatologist and neurologists, complaining of acute or subacute onset of proximal weakness. Extramuscular manifestations may occur, including involvement of the lungs, skin, and joints. Classically, the diagnosis used to be made based on the creatine kinase level increase, abnormalities in electroneuromyography and presence of inflammatory infiltrates in the muscle biopsy. Recently, the importance of autoantibodies has increased, and now they may be identified in more than half of IIM patients. The continuous clinicoseropathological improvement in IIM knowledge has changed the way we see these patients and how we classify them. In the past, only polymyositis, dermatomyositis and inclusion body myopathy were described. Currently, immune-mediated necrotizing myopathy, overlap myositis and antisynthetase syndrome have been considered the most common forms of IIM in clinical practice, increasing the spectrum of classification. Patients previously considered to have polymyositis, in fact have these other forms of seropositive IIM. In this article, we reviewed the new concepts of classification, a practical way to make the diagnosis and how to plan the treatment of patients suffering from IIM.

RESUMO As miopatias inflamatórias idiopáticas (MII) são um grupo heterogêneo de miopatias tratáveis. Os pacientes procuram principalmente o reumatologista e o neurologista, queixando-se de início agudo ou subagudo de fraqueza proximal. Manifestações extramusculares podem ocorrer, incluindo envolvimento dos pulmões, pele e articulações. Classicamente, o diagnóstico era feito com base na elevação dos níveis de creatina quinase, anormalidades na eletroneuromiografia e presença de infiltrados inflamatórios na biópsia muscular. Recentemente, a importância dos autoanticorpos aumentou, e agora eles podem ser identificados em mais da metade dos pacientes com MII. A contínua melhora clínico-soropatológica no conhecimento do MII mudou a forma como vemos esses pacientes e como os classificamos. No passado, apenas polimiosite, dermatomiosite e miopatia por corpos de inclusão eram descritas. Atualmente, a miopatia necrosante imunomediada, a miosite de sobreposição e a síndrome antissintetase têm sido consideradas as formas mais comuns de MII na prática clínica, aumentando o espectro de classificação. Pacientes previamente considerados como portadores de polimiosite, na verdade, têm uma dessas outras formas de MII soropositivas. Neste artigo, revisamos os novos conceitos de classificação, uma forma prática de fazer o diagnóstico e como planejar o tratamento de pacientes que sofrem de MII.

Histological changes underlying bupivacaine's effect on extra ocular muscle.

To determine the changes in the cross-sectional area (CSA) of myofibers and their subtype distribution based on the myosin isoform expression after bupivacaine (BUP) injection in the EOM of rabbits and help the understanding of strabismus correction after BUP injection in the clinical practice. A total of 32 rabbits received 0.3 mL of 1.5% BUP in the superior rectus muscle (SR) of the right eye (OD) and were sacrificed at days 7, 28, 60, and 92. Additional eight untouched rabbits were included as controls. Hematoxylin and eosin staining was performed, and ImageJ software was used to measure CSA. Immunohistochemical analysis was performed to analyze the proportion of myofibers positive for myosin types 1 (slow), 2 (fast) and embryonic. Myofiber area measurement decreased 7 days after BUP injection [SR, 1271 ±â€¯412 µm2 (control) to 909 ±â€¯255 µm2 (day 7)] after BUP injection, followed by an increasing trend after 28 days and normalization after 92 days [SR; 1062 ±â€¯363 µm2 (day 28), 1492 ±â€¯404 µm2 (day 60), 1317 ±â€¯334 µm2 (day 92)]. The proportion of slow myosin-positive fibers increased in the 60-day group (88.5% ±â€¯16.2%). There was no statistically significant difference in fast myosin-positive fibers. The inferior rectus of both eyes showed an increase in CSA. No increase of endomysial fibrous tissue was observed after 60 and 92 days of BUP injection. Bupivacaine, when injected into the SR of rabbits, initially decreases the fiber area followed by a transient increasing trend and normalization. There is a transient increase in the proportion of slow myosin-positive fibers in the injected muscle. Muscle adaptation in untreated EOM was found with increased CSA. These findings help clarify the clinical effects of BUP in extraocular muscle.

Inclusion-body myositis: a difficult diagnosis? / Miosite por corpos de inclusão: um diagnóstico difícil?

Sporadic inclusion-body myositis (IBM) is the most common myopathy in individuals over 55 years of age. However, in many cases, the diagnosis is neglected. Its main findings include progressive muscle weakness, normal or low levels of serum creatine kinase, and the absence of a response to immunosuppression. Muscle biopsy shows inflammatory reaction in association with degenerative changes of the muscle fibers. We report a typical case of IBM, in which diagnosis was possible only after three muscle biopsies. The challenges to confirm histological diagnosis and the caution to avoid repeating tests are discussed.

A miosite por corpos de inclusão (MCI) esporádica é a miopatia mais comum acima dos 55 anos de idade. No entanto, em muitos casos, o diagnóstico é negligenciado. Os principais achados incluem fraqueza muscular progressiva, níveis séricos normais ou levemente elevados de creatinoquinase (CK) e ausência de resposta à imunossupressão. A biópsia muscular evidencia reação inflamatória associada com alterações degenerativas das fibras musculares. Apresentamos um caso típico de MCI cujo diagnóstico foi obtido após a realização de uma terceira biopsia muscular. Discutimos os desafios para a confirmação do diagnóstico histológico e os cuidados que podem evitar repetições do exame.