Résumé :
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In DMD, repeated cycles of acute myofiber necrosis and regeneration progressively lead to severe terminal myofiber degeneration and extensive fibrosis. A preliminary analysis of 39 muscle biopsies from DMD patients at different ages allowed rough time-course characterization of both interstitial and cellular alterations in DMD. It includes initial prominence of edema and fiber hypercontraction (2-4 years), followed by prominence of myonecrosis and regeneration (5-7 years), and then by fibrosis and fatty degeneration (8-10 years). However, there were marked inter-individual variations at both the myopathological and clinical level in patients of similar age. As DMD is more clinically heterogeneous than classically described and may involve fibrosis as a central pathogenic player (see the other abstracts by the same group), we carried out a mulpiparametric analysis of myopathological alterations and all available clinical variables in a series of 35 DMD steroid-free patients with both quadriceps muscle biopsy performed from 3 to 6 years and a long term follow-up (>10 years). Seven myopathological alterations (endomysial and perimysial fibrosis, myofiber size, myonecrosis, hypercontraction, endomysial oedema, and fatty degeneration) were assessed using Gomori trichrome and Collagen-1 immunostaining, stereological methods and color image segmentation applied to digitized images. Analysis was done with the Categories module of SPSS 11.0 software using non linear Categorical Principal Component Analysis, an approach allowing one to handle together nominal, ordinal, and interval variables, and suitable for data recorded with uncertain units (e.g. MMT scores). Plotting of myopathologic variables detected in the quadriceps muscle with motor scores obtained in the same muscle group (mean score, minimal score, score at 10 years, deterioration score), allowed us to point out endomysial fibrosis as the sole myopathologic alteration correlated with motor scores. We conclude that early muscle fibrosis represents a sign of poor future motor outcome.
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