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 >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). RESULTS: 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. 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.
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 >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). RESULTS: 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. 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.
Authors: Judith C van Deutekom; Anneke A Janson; Ieke B Ginjaar; Wendy S Frankhuizen; Annemieke Aartsma-Rus; Mattie Bremmer-Bout; Johan T den Dunnen; Klaas Koop; Anneke J van der Kooi; Nathalie M Goemans; Sjef J de Kimpe; Peter F Ekhart; Edna H Venneker; Gerard J Platenburg; Jan J Verschuuren; Gert-Jan B van Ommen Journal: N Engl J Med Date: 2007-12-27 Impact factor: 91.245
Authors: Leo H Wang; Seth D Friedman; Dennis Shaw; Lauren Snider; Chao-Jen Wong; Chris B Budech; Sandra L Poliachik; Nancy E Gove; Leann M Lewis; Amy E Campbell; Richard J F L Lemmers; Silvère M Maarel; Stephen J Tapscott; Rabi N Tawil Journal: Hum Mol Genet Date: 2019-02-01 Impact factor: 6.150
Authors: Ke Li; Richard D Dortch; E Brian Welch; Nathan D Bryant; Amanda K W Buck; Theodore F Towse; Daniel F Gochberg; Mark D Does; Bruce M Damon; Jane H Park Journal: NMR Biomed Date: 2014-07-26 Impact factor: 4.044
Authors: Jerry R Mendell; Zarife Sahenk; Samiah Al-Zaidy; Louise R Rodino-Klapac; Linda P Lowes; Lindsay N Alfano; Katherine Berry; Natalie Miller; Mehmet Yalvac; Igor Dvorchik; Melissa Moore-Clingenpeel; Kevin M Flanigan; Kathleen Church; Kim Shontz; Choumpree Curry; Sarah Lewis; Markus McColly; Mark J Hogan; Brian K Kaspar Journal: Mol Ther Date: 2017-03-06 Impact factor: 11.454
Authors: Ishu Arpan; Sean C Forbes; Donovan J Lott; Claudia R Senesac; Michael J Daniels; William T Triplett; Jasjit K Deol; H Lee Sweeney; Glenn A Walter; Krista Vandenborne Journal: NMR Biomed Date: 2012-10-09 Impact factor: 4.044