Muscle histology vs MRI in Duchenne muscular dystrophy

TLDR

Duchenne muscular dystrophy lacks effective treatments, and clinical trials rely on restoring dystrophin, necessitating well‑preserved muscle in participants. The study aimed to evaluate lower‑leg muscle involvement in DMD patients over 8 years using MRI to guide muscle selection for trials. MRI grading (0–4) of 34 patients’ lower‑leg muscles, with a subgroup of 15 biopsied for EDB histology, revealed a posterior‑to‑anterior involvement gradient and enabled correlation with tissue pathology. MRI grades correlated with age, with grades 3–4 indicating severe fibro‑adipose replacement, and the EDB remained sufficiently preserved in most wheelchair users, confirming MRI as a reliable tool for muscle selection in trials.

Abstract

There are currently no effective treatments to halt the muscle breakdown in Duchenne muscular dystrophy (DMD), although genetic-based clinical trials are being piloted. Most of these trials have as an endpoint the restoration of dystrophin in muscle fibers, hence requiring sufficiently well-preserved muscle of recruited patients. The choice of the muscles to be studied and the role of noninvasive methods to assess muscle preservation therefore require further evaluation.We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD >8 years, using muscle MRI. In a subgroup of 15 patients we correlated the muscle MRI findings with the histology of open extensor digitorum brevis (EDB) muscle biopsies. Muscle MRI involvement was assigned using a scale 0-4 (normal-severe).In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius > soleus) was most severely affected; the anterior compartment (tibialis anterior/posterior, popliteus, extensor digitorum longus) least affected. Muscle MRI showed EDB involvement that correlated with the patient's age (p = 0.055). We show a correlation between the MRI and EDB histopathologic changes, with MRI 3-4 grades associated with a more severe fibro-adipose tissue replacement. The EDB was sufficiently preserved for bulk and signal intensity in 18/22 wheelchair users aged 10-16.6 years.This study provides a detailed correlation between muscle histology and MRI changes in DMD and demonstrates the value of this imaging technique as a reliable tool for the selection of muscles in patients recruited into clinical trials.