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.

© 2014 American Academy of Neurology.

Figures

Figure 1. Cross-sectional comparisons of MRI T2 between corticosteroid-treated and corticosteroid-naive boys with Duchenne muscular dystrophy

Comparison of T2 by imaging in the lower leg muscles (A) and thigh muscles (B) of boys with Duchenne muscular dystrophy (DMD) on corticosteroid treatment (CS) and corticosteroid-naive boys (CS-naive). T2 values were lower in all the muscles examined in boys with DMD on corticosteroid therapy except for the gracilis (Gra) muscle. Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05. BFLH = biceps femoris long head; MG = medial gastrocnemius; Per = peroneals; Sol = soleus; TA = tibialis anterior; TP = tibialis posterior; VL = vastus lateralis.

Figure 2. Cross-sectional comparisons of MRS T2 between corticosteroid-treated and corticosteroid-naive boys with Duchenne muscular dystrophy

An example gradient echo image of the lower leg with voxel placement in the soleus (Sol) muscle is depicted with the corresponding spectra acquired during the spectroscopic relaxometry scan. (A) Cross-sectional comparisons of T2 by spectroscopy between corticosteroid-treated boys (CS) and corticosteroid-naive boys (CS-naive) with Duchenne muscular dystrophy. (B) T2 values for both the Sol and vastus lateralis (VL) muscles were lower in CS boys compared to CS-naive boys, indicating less damage in the muscles of boys on corticosteroid treatment. Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05. MRS = magnetic resonance spectroscopy; TE = echo time.

Figure 3. Cross-sectional and longitudinal comparisons of fat fraction between corticosteroid-treated and corticosteroid-naive boys with Duchenne muscular dystrophy

(A) 1H–magnetic resonance spectroscopy spectrum from the soleus (Sol) muscle of a boy with Duchenne muscular dystrophy (DMD) depicts water and lipid peaks. (B) Cross-sectional comparisons of fat fraction in the Sol and vastus lateralis (VL) muscles between corticosteroid-treated (CS) and corticosteroid-naive boys (CS-naive) with DMD. (C) Longitudinal changes in fat fraction over 1 year in the Sol and VL muscles of boys in 2 groups. Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05.

Figure 4. Effects of corticosteroid initiation on MRI T2 of lower leg muscles in boys with Duchenne muscular dystrophy

Comparison of absolute change in MRI T2 with respect to baseline in lower leg muscles of corticosteroid-treated boys with Duchenne muscular dystrophy (CS) and corticosteroid-naive boys (CS-naive) at 3 months (A) and 6 months (B). Values are represented as mean ± SEM; **p ≤ 0.01 and *p ≤ 0.05. MG = medial gastrocnemius; Per = peroneals; Sol = soleus; TA = tibialis anterior; TP = tibialis posterior.