Search

Focal myositis are inflammatory muscle diseases of unknown origin. At the opposite from the other idiopathic inflammatory myopathies, they are restricted to a single muscle or to a muscle group. They are not associated with extramuscular manifestations, and they have a good prognosis without any treatment. They are characterized by a localized swelling affecting mostly lower limbs. The pseudo-tumor can be painful, but is not associated with a muscle weakness. Creatine kinase level is normal. Muscle MRI shows an inflammation restricted to a muscle or a muscle group. Muscle biopsy and pathological analysis remain necessary for the diagnosis, showing inflammatory infiltrates composed by macrophages and lymphocytes without any specific distribution within the muscle. Focal overexpression of HLA-1 by the muscle fibers is frequently observed. The muscle biopsy permits to rule out differential diagnosis such a malignancy (sarcoma). Spontaneous remission occurs within weeks or months after the first symptoms, relapse is unusual., (Copyright © 2017. Published by Elsevier SAS.)

Extracellular vesicles (EVs) are composed of microvesicles and exosomes. Exosomes are small membrane vesicles (40-120 nm sized) of endosomal origin released in the extracellular medium from cells when multivesicular bodies fuse with the plasma membrane, whereas microvesicles (i.e., shedding vesicles, 100 nm to 1 μm sized) bud from the plasma membrane. Exosomes and microvesicles carry functional proteins and nucleic acids (especially mRNAs and microRNAs) that can be transferred to surrounding cells and tissues and can impact multiple dimensions of the cellular life. Most of the cells, if not all, from neuronal to immune cells, release exosomes and microvesicles in the extracellular medium, and all biological fluids including blood (serum/plasma), urine, cerebrospinal fluid, and saliva contain EVs.Prion-infected cultured cells are known to secrete infectivity into their environment. We characterized this cell-free form of prions and showed that infectivity was associated with exosomes. Since exosomes are produced by a variety of cells, including cells that actively accumulate prions, they could be a vehicle for infectivity in body fluids and could participate to the dissemination of prions in the organism. In addition, such infectious exosomes also represent a natural, simple, biological material to get key information on the abnormal PrP forms associated with infectivity.In this chapter, we describe first a method that allows exosomes and microvesicles isolation from prion-infected cell cultures and in a second time the strategies to characterize the prions containing exosomes and their ability to disseminate the prion agent.

Amongst the heterogeneous group of inflammatory myopathies, focal myositis stands as a rare and benign dysimmune disease. Although it can be associated with root and/or nerve lesions, traumatic muscle lesions and autoimmune diseases, its triggering factors remain poorly understood. Defined as an isolated inflammatory pseudotumour usually restricted to one skeletal muscle, clinical presentation of focal myositis is that of a rapidly growing solitary mass within a single muscle, usually in the lower limbs. Electromyography shows spontaneous activity associated with a myopathic pattern. MRI reveals a contrast enhanced enlarged muscle appearing hyper-intense on FAT-SAT T2 weighted images. Adjacent structures are spared and there are no calcifications. Serum creatine kinase (CK) levels are usually moderately augmented and biological markers of systemic inflammation are absent in most cases. Pathological histological features include marked variation in fibre size, inflammatory infiltrates mostly composed of T CD4+ lymphocytes and macrophages, degenerating/regenerating fibres and interstitial fibrosis. Differential diagnoses are numerous and include myositis of other origin with focal onset. Steroid treatment should be reserved for patients who present with major pain, nerve lesions, associated autoimmune disease, or elevated C reactive protein or CK., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Pompe disease is an inherited lysosomal disease in which there is a decrease or absence of acid alpha-glucosidase activity. This enzyme defect induces glycogen storage in different tissues, especially muscle and heart, resulting in muscle weakness, respiratory failure and heart disease. Substitutive enzyme replacement therapy (ERT) dispensed every two weeks is the only treatment that has shown benefits. However, this treatment induces hypersensitivity for half of the treated patients. Reactions range from mild to severe, sometimes requiring ERT suspension and anti-anaphylaxis drug administration. Understandably, high amount of acid alpha-glucosidase infusion seems to be identified by the immune system as a danger associated molecular pattern, and induce an immune reaction, involving sometimes, but not always, immunoglobulin E (IgE) production and activating mast and basophil polynuclear cells. Considering the lack of therapeutic alternatives and the proved benefit of ERT, desensitization finds its place here. We hereby report the case of a patient for whom a simplified desensitization protocol ("SWORD": Start With One Regular Drop) was successfully achieved, allowing ERT to be pursued, resulting eventually in clinical improvement., (Copyright © 2016. Published by Elsevier B.V.)

Sporadic inclusion-body myositis (sIBM) is the most frequent myopathy after 50 years of age. As the clinical presentation may often be typical, pathological confirmation by muscle biopsy appears necessary, but sometimes difficult. Further delineation of the framework of this particular disease, especially during its early-onset stage, appears to be challenging. New classification of diagnostic criteria as well as the identification of new diagnostic hallmarks appear to be the two main tools towards to achieve this purpose. sIBM pathophysiology has long been discussed and remains yet controversial. Since its initial description, there have been two major pathogenic hypotheses: inflammatory and degenerative. To date, the debate is still ongoing, as recent works support both pathophysiological mechanisms, although the inflammatory process seems to be slightly more preeminent in the recent literature. Treatment remains the most disappointing aspect of the disease as, despite various therapeutic attempts, no significant efficacy has been reported thus far. Nevertheless, advances in our pathophysiological understanding of the disease are paving the way for further therapeutic perspectives that might arise in the years to come. The objective of the present work was to summarize the most significant data published on sIBM during the past 2 years., (Copyright © 2016. Published by Elsevier Masson SAS.)