Examination of effects of corticosteroids on skeletal muscles of boys with DMD using MRI and MRS

Abstract

Objective: To evaluate the effects of corticosteroids on the lower extremity muscles in boys with Duchenne muscular dystrophy (DMD) using MRI and magnetic resonance spectroscopy (MRS).Methods: Transverse relaxation time (T2) and fat fraction were measured by MRI/MRS in lower extremity muscles of 15 boys with DMD (age 5.0-6.9 years) taking corticosteroids and 15 corticosteroid-naive boys. Subsequently, fat fraction was measured in a subset of these boys at 1 year. Finally, MRI/MRS data were collected from 16 corticosteroid-naive boys with DMD (age 5-8.9 years) at baseline, 3 months, and 6 months. Five boys were treated with corticosteroids after baseline and the remaining 11 served as corticosteroid-naive controls. Results:Cross-sectional comparisons demonstrated lower muscle T2 and less intramuscular (IM) fat deposition in boys with DMD on corticosteroids, suggesting reduced inflammation/damage and fat infiltration with treatment. Boys on corticosteroids demonstrated less increase in IM fat infiltration at 1 year. Finally, T2 by MRI/MRS detected effects of corticosteroids on leg muscles as early as 3 months after drug initiation.Conclusions: These results demonstrate the ability of MRI/MRS to detect therapeutic effects of corticosteroids in reducing inflammatory processes in skeletal muscles of boys with DMD. Our work highlights the potential of MRI/MRS as a biomarker in evaluating therapeutic interventions in DMD. Duchenne muscular dystrophy (DMD) is a devastating form of muscular dystrophy caused by the absence of dystrophin, making muscle cell membranes fragile and susceptible to mechanical damage.1,2 Currently, there is no cure for the disease. Corticosteroids have been reported to slow disease progression in DMD.3-7 However, the mechanism by which corticosteroids preserve muscle function in DMD is not fully understood.Among several proposed mechanisms, corticosteroids are thought to reduce inflammation in dystrophic muscles. 8,9 MRI, in particular T2-weighted MRI, is sensitive to alterations in muscle chemistry and structure induced by processes like damage/inflammation and fat infiltration, [10][11][12][13][14][15][16][17] and therefore may have the potential to detect the effects of corticosteroid treatment on dystrophic muscles. Magnetic resonance spectroscopy (MRS) allows quantification of chemical compounds and can separate lipid and water components, allowing a more targeted investigation of skeletal muscles in DMD. 18-21The overall goal of this study was to examine the ability of MRI/MRS to detect the effects of corticosteroids on skeletal muscles in boys with DMD. The specific aims of the study were to (1) perform a cross-sectional comparison between the lower extremity muscles of 5-to 6.9-year-old

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

“…31,[34][35][36] It does not follow the same disease progression as fat infiltration 13,34 ; instead, T2 of muscle water appears to be highest in earlier stages of the disease. 15 In a study on corticosteroid therapy followup in young patients with DMD with very low fat infiltration, 35 investigators used NMRI and 1 H NMRS to measure fat fraction and T2 of water with the 6MWT, timed tests, and quantitative force measurements of the lower limb. Though no direct comparison was given, the 6MWT did not discriminate between treated and untreated patients, nor did plantar flexion strength.…”

Longitudinal 2-point dixon muscle magnetic resonance imaging in becker muscular dystrophy

“…17,18 This also corresponds to the rate of clinical disease progression in BMD, which is slower than that of DMD and faster than that of OPMD.…”

Skeletal muscle quantitative nuclear magnetic resonance imaging and spectroscopy as an outcome measure for clinical trials (part II)

“…Обнару-жено, что уровень сигнала Т2 является предиктором скорости прогрессирования хронических дегенератив-ных изменений. У юношей с ПМД Дюшенна после начала лечения стероидами сигнал Т2 от мышц ног быстро уменьшался на несколько миллисекунд и на-блюдаемое понижение поддерживалось в течение не-которого времени и было связано с приостановкой жирового инфильтративного процесса [46]. У взрослых пациентов с болезнью Помпе в 1/3 всех исследованных мышц ног было получено от легкой до умеренной степени повышение сигнала Т2 от воды, по меньшей мере на 1 из 2 сканирований в течение года.…”