Muscle histology vs MRI in Duchenne muscular dystrophy

Abstract

Objective: 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. Methods:We studied the degree of muscle involvement in the lower leg muscles of 34 patients with DMD Ͼ8 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). Results:In all patients we documented a gradient of involvement of the lower leg muscles: the posterior compartment (gastrocnemius Ͼ 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 ϭ 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. Conclusion: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. Neurology ® 2011;76:346-353 GLOSSARY AO ϭ antisense oligonucleotide; DMD ϭ Duchenne muscular dystrophy; EDB ϭ extensor digitorum brevis; KAFO ϭ knee-ankle-foot orthosis; NSA ϭ number of signal averages; TE ϭ echo time; TR ϭ repetition time.The progressive loss of muscle fibers and their replacement by fat and connective tissue is part of the disease course of DMD.1 Despite several exhaustive natural history studies on the clinical course of DMD, the progression of pathology in individual muscle groups is poorly defined. 2Information on muscle pathology in DMD is limited to the muscles that are biopsied at the time of diagnosis (often quadriceps femoris), 2 the mean age at diagnosis being ϳ4.5 years. 3,4 There are now early clinical trials using novel genetic-based techniques in boys with DMD with the aim to restore dystrophin expression. These include the drug PTC124, 5 which allows

Longitudinal functional and NMR assessment of upper limbs in Duchenne muscular dystrophy

“…Despite pioneering NMRS work in forearm muscles of patients with DMD, 7 NMR data have since been primarily acquired in pelvic muscles or lower limbs in ambulant patients. [8][9][10][11][12][13][14][15][16][17][18][19][20] We recently reported the feasibility of using NMR for assessing the upper limb in nonambulatory patients. 21 Our main objective in the present study was to establish the baseline values for NMR and functional variables and at a 1-year follow-up time point period for ambulatory and nonambulatory patients with DMD.…”

Effect of Cellular Therapy seen on Musculoskeletal Magnetic Resonance Imaging in a Case of Becker’s Muscular Dystrophy

“…Advanced non-invasive radio-imaging techniques have been found to be accurate in diagnosing and monitoring MD [25]. MRI has several advantages over other imaging techniques used in BMD.…”

Biomarkers in Rare Diseases

“…In muscle diseases, MRI scans may be used to correlate the clinical phenotype with the muscle biopsy morphology and immunocytochemistry. Kinali et al [25] have demonstrated that MRI scanning can be a reliable tool to inform the choice of muscles to be assessed during clinical trials. In this paper, reporting data on a clinical trial based on antisense oligonucleotide in DMD, the results of the MRI scan serve as biomarkers of disease progression, in particular muscles, by identifying which ones are sufficiently preserved.…”