Myopathies

2001 ◽  
Vol 11 (2) ◽  
pp. 131-147
Author(s):  
David Hilton-Jones
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Family Members ◽  
The Elderly ◽  
Pathological Process ◽  
Muscle Disease ◽  
Muscle Fibres ◽  
Inappropriate Use ◽  
Incorrect Diagnosis ◽  
Symptoms And Signs

Myopathy is a convenient shorthand term meaning muscle disease or dysfunction. In other words, the myopathies are those conditions in which the patient’s symptoms and signs can be attributed to a pathological process affecting either the structure of muscle fibres or their associated interstitial tissues, or to disturbance of the biochemical or electrophysiological function of those fibres. Myopathies are rare in all age ranges. They may be inherited or acquired. Onset of inherited myopathies in the elderly, not surprisingly, is uncommon, but some of these diseases are asymptomatic or cause such minor symptoms that their significance is not appreciated by the patient, and thus they may not be recognized until late on in life. Their recognition may have implications for other, younger, family members. Many of the acquired myopathies afflicting the elderly are treatable, but the commonest, inclusion body myositis, is not, and incorrect diagnosis and inappropriate use of steroids may compound morbidity.

Coexistence of TDP-43 and C5b-9 staining of muscle in a patient with inclusion body myositis

2021 ◽  
Vol 14 (2) ◽  
pp. e238312
Author(s):  
Christina Law ◽  
Huili Li ◽  
Sankar Bandyopadhyay
Keyword(s):  
Inclusion Body ◽  
Transcriptional Repression ◽  
Inclusion Body Myositis ◽  
Inflammatory Myopathy ◽  
Membrane Attack Complex ◽  
Muscle Fibres ◽  
Rimmed Vacuoles ◽  
Histocompatibility Complex ◽  
Immune Mediated ◽  
Sporadic Inclusion Body Myositis

While sporadic inclusion body myositis (sIBM) is the most commonly acquired inflammatory myopathy above 50 years of age, its refractory response to conventional immunosuppressive treatments raises questions about its perplexing pathogenesis. Muscle biopsy typically reveals major histocompatibility complex I antigens and CD8+ T cell endomysial infiltrates invading non-necrotic muscle fibres early in the disease course with rimmed vacuoles, protein aggregates and amyloid inclusions later in the disease. Transactive response DNA-binding protein-43 (TDP-43), a protein implicated in transcriptional repression in neurodegenerative diseases, is also found in sIBM. C5b-9 membrane attack complex, an effector protein involved in the complement cascade of the immune response, is commonly found in dermatomyositis, but has rarely been reported in IBM. We describe a novel case of IBM with simultaneous C5b-9 and TDP-43 staining on quadriceps biopsy, raising the question of a possibility of concurrent immune-mediated inflammatory and myodegenerative pathogenesis.

Presence of BACE1 and BACE2 in muscle fibres of patients with sporadic inclusion-body myositis

The Lancet ◽  
2001 ◽  
Vol 358 (9297) ◽  
pp. 1962-1964 ◽  
Author(s):  
Gaetano Vattemi ◽  
W King Engel ◽  
Janis McFerrin ◽  
Joseph D Buxbaum ◽  
Lucia Pastorino ◽  
...  
Keyword(s):  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Muscle Fibres ◽  
Sporadic Inclusion Body Myositis

Highly differentiated cytotoxic T cells in inclusion body myositis

Brain ◽  
2019 ◽  
Vol 142 (9) ◽  
pp. 2590-2604 ◽  
Author(s):  
Steven A Greenberg ◽  
Jack L Pinkus ◽  
Sek Won Kong ◽  
Clare Baecher-Allan ◽  
Anthony A Amato ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Cytotoxic T Cells ◽  
Killer Cell ◽  
Cd8 T Cell ◽  
Muscle Disease ◽  
Effector Memory ◽  
Muscle Pathology

Abstract Inclusion body myositis is a late onset treatment-refractory autoimmune disease of skeletal muscle associated with a blood autoantibody (anti-cN1A), an HLA autoimmune haplotype, and muscle pathology characterized by cytotoxic CD8+ T cell destruction of myofibres. Here, we report on translational studies of inclusion body myositis patient muscle compared with a diverse set of other muscle disease samples. Using available microarray data on 411 muscle samples from patients with inclusion body myositis (n = 40), other muscle diseases (n = 265), and without neuromuscular disease (normal, n = 106), we identified a signature of T-cell cytotoxicity in inclusion body myositis muscle coupled with a signature of highly differentiated CD8 T-cell effector memory and terminally differentiated effector cells. Further, we examined killer cell lectin-like receptor G1 (KLRG1) as a marker of this population of cells, demonstrated the correlation of KLRG1 gene expression with lymphocyte cytotoxicity across 28 870 human tissue samples, and identified the presence of KLRG1 on pathogenic inclusion body myositis muscle invading T cells and an increase in KLRG1 expressing T cells in inclusion body myositis blood. We examined inclusion body myositis muscle T-cell proliferation by Ki67 immunohistochemistry demonstrating that diseased muscle-invading T cells are minimally or non-proliferative, in accordance with known properties of highly differentiated or terminally differentiated T cells. We found low expression of KLRG1 on infection-protective human lymphoid tissue central memory T cells and autoimmune-protective human blood regulatory T cells. Targeting highly differentiated cytotoxic T cells could be a favourable approach to treatment of inclusion body myositis.

scholarly journals Injection of Botulinum Toxin a to Upper Esophageal Sphincter for Oropharyngeal Dysphagia in Two Patients with Inclusion Body Myositis

2004 ◽  
Vol 18 (6) ◽  
pp. 397-399 ◽  
Author(s):  
Louis WC Liu ◽  
Mark Tarnopolsky ◽  
David Armstrong
Keyword(s):  
Botulinum Toxin ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Botulinum Toxin A ◽  
Oropharyngeal Dysphagia ◽  
Upper Esophageal Sphincter ◽  
Muscle Disease ◽  
Sphincter Pressure ◽  
Toxin A ◽  
Esophageal Sphincter

Inclusion body myositis (IBM) is a progressive degenerative skeletal muscle disease leading to weakening and atrophy of both proximal and distal muscles. Dysphagia is reported in up to 86% of IBM patients. Surgical cricopharyngeal myotomy may be effective for cricopharyngeal dysphagia and there is one published report that botulinum toxin A, injected into the cricopharyngeus muscle using a hypopharyngoscope under general anesthesia, relieved IBM-associated dysphagia. This report presents the first documentation of botulinum toxin A injection into the upper esophageal sphincter using a flexible esophagogastroduodenoscope under conscious sedation, to reduce upper esophageal sphincter pressure and successfully alleviate oropharyngeal dysphagia in two IBM patients.

scholarly journals 024 Resistance exercises with blood flow restriction in patients with sporadic inclusion body myositis

2019 ◽  
Vol 90 (e7) ◽  
pp. A9.1-A9
Author(s):  
Christina Liang ◽  
Melanie Burk ◽  
Abby Wall ◽  
Ryan Davis ◽  
Libby Augustine ◽  
...  
Keyword(s):  
Blood Flow ◽  
Resistance Training ◽  
Muscle Strength ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Muscle Disease ◽  
Blood Flow Restriction ◽  
Flow Restriction ◽  
Resistance Exercises ◽  
Sporadic Inclusion Body Myositis

IntroductionSporadic inclusion body myositis (sIBM) is the most common muscle disease affecting older adults with no disease-modifying treatment. Resistance exercises increase muscle hypertrophy, but weakness prevents exercising with higher resistance. In healthy subjects, augmentation of light-load training with blood flow restriction improved muscle strength1; and similar exercises were safe in the elderly.2 We therefore investigate whether resistance exercises with blood flow restriction is safe and helpful in sIBM patients. We explored methods for exercising weak leg muscles, and options for better outcome measures.MethodsA matched-control pilot study, with 12-week treatment and 4-week follow-up periods, where participants concentrated on lower limbs resistance exercises with 50% blood flow restriction 3 times/week, at 20%-30% of their repetition maximum. Patients are reviewed 4-weekly for muscle strength, blood biomarkers, 2-minute walk test (2MWT), timed up-and-go (TUG) test, minimal chair height standing ability test (MCHSAT), thigh girths, and quality of life scales.Results4 patients with varying abilities were on the exercise arm, and 3 acted as controls. Muscle groups with MRC score ≥2 were able to be exercised. We found strength testing by hand-held dynamometer was unreliable, whereas the 2MWT, TUG test and MCHSAT showed less variability. All patients could perform their exercises at significantly increased repetitions or weights by week 4, without concerning adverse events, with trend towards continued improvement over the 4-month period.ConclusionResistance exercises with blood flow restriction appear safe, and may be helpful in sIBM patients, even in weakened muscles, enabling improvement in muscle strength and endurance.ReferencesHughes L, Paton B, Rosenblatt B, Gissane C, Patterson SD. Blood flow restriction training in clinical musculoskeletal rehabilitation: a systematic review and meta-analysis. Br J Sports 2017.Vechin FC, Libardi CA, Conceicao MS, et al. Comparisons between low-intensity resistance training with blood flow restriction and high-intensity resistance training on quadriceps muscle mass and strength in elderly. J Strength Cond Res 2015.

Rabbits fed cholesterol-enriched diets exhibit pathological features of inclusion body myositis

2008 ◽  
Vol 294 (3) ◽  
pp. R829-R835 ◽  
Author(s):  
Xuesong Chen ◽  
Othman Ghribi ◽  
Jonathan D. Geiger
Keyword(s):  
Alzheimer’S Disease ◽  
Skeletal Muscle ◽  
Alzheimer's Disease ◽  
Inclusion Body ◽  
Inclusion Body Myositis ◽  
Muscle Fibers ◽  
Muscle Disease ◽  
Amyloid Β Protein ◽  
Pathological Features ◽  
Protein Levels

Sporadic inclusion body myositis (IBM) is the most common age-related muscle disease in humans; however, its etiology is unknown, there are few animal models for this disease, and effective treatments have not been identified. Similarities between pathological findings in Alzheimer's disease brain and IBM skeletal muscle include increased levels of amyloid precursor protein (APP) and amyloid β-protein (Aβ). Moreover, there have been suggestions that elevated levels of free cholesterol might participate in the pathogenesis of Alzheimer's disease and IBM due, in part, to its role in Aβ generation. Here, we tested the hypothesis that rabbits fed cholesterol-enriched diets might faithfully exhibit human-like IBM pathological features. In skeletal muscle of one-third of the female rabbits fed cholesterol-enriched diet but not control diet, we found features of IBM, including vacuolated muscle fibers, increased numbers of mononuclear inflammatory cells, increased intramuscular deposition of Aβ, hyperphosphorylated tau, and increased numbers of muscle fibers immunopositive for ubiquitin. The cholesterol-enriched diet increased mRNA and protein levels of APP, increased the protein levels of βAPP cleaving enzyme, and shifted APP processing in favor of Aβ production. Our study has demonstrated that increased ingestion of high levels of dietary cholesterol can result in pathological features that resemble IBM closely and thus may serve as an important new model with which to study this debilitating disorder.

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