Development of Contractures in DMD in Relation to MRI-Determined Muscle Quality and Ambulatory Function

Abstract

Background: Joint contractures are common in boys and men with Duchenne muscular dystrophy (DMD), and management of contractures is an important part of care. The optimal methods to prevent and treat contractures are controversial, and the natural history of contracture development is understudied in glucocorticoid treated individuals at joints beyond the ankle.

Objective: To describe the development of contractures over time in a large cohort of individuals with DMD in relation to ambulatory ability, functional performance, and muscle quality measured using magnetic resonance imaging (MRI) and spectroscopy (MRS).

Methods: In this longitudinal study, range of motion (ROM) was measured annually at the hip, knee, and ankle, and at the elbow, forearm, and wrist at a subset of visits. Ambulatory function (10 meter walk/run and 6 minute walk test) and MR-determined muscle quality (transverse relaxation time (T2) and fat fraction) were measured at each visit.

Results: In 178 boys with DMD, contracture prevalence and severity increased with age. Among ambulatory participants, more severe contractures (defined as greater loss of ROM) were significantly associated with worse ambulatory function, and across all participants, more severe contractures significantly associated with higher MRI T2 or MRS FF (ρ: 0.40-0.61 in the lower extremity; 0.20-0.47 in the upper extremity). Agonist/antagonist differences in MRI T2 were not strong predictors of ROM.

Conclusions: Contracture severity increases with disease progression (increasing age and muscle involvement and decreasing functional ability), but is only moderately predicted by muscle fatty infiltration and MRI T2, suggesting that other changes in the muscle, tendon, or joint contribute meaningfully to contracture formation in DMD.

Keywords: 10 m walk/run; 6 minute walk test; Range of motion; heel cord; magnetic resonance imaging; transverse relaxation time.

Fig. 1.

Frequency of contractures equal to or exceeding 5°, and of contractures equal to or exceeding 20°, in boys with DMD across age groups. Age groups are collapsed into 2 year bins in the upper extremity because fewer upper extremity measurements are available; upper extremity measurements began 5 years after lower extremity measurements. Contractures were most prevalent at the ankle (E) and hip (A) in younger boys, and at the hip (A), knee (B), ankle (C) and forearm (D) in the teenage years.

Fig. 2.

Contractures were more prevalent, and more severe, in nonambulatory boys and young men (B, D, F, H, J, L) compared with ambulatory boys and men (A, C, E, G, I, K). The dashed line represents the median control value. Age was weakly correlated with knee, elbow, wrist, and forearm ROM and moderately correlated with ankle ROM in ambulatory subjects but was only weakly correlated with wrist ROM in nonambulatory boys and men.

Fig. 3.

ROM was significantly decreased from normal from 5 years prior to the first nonambulatory visit at the ankle (C), 2 years prior to the first nonambulatory visit at the knee (B) and 4 years prior to the first nonambulatory visit at the hip (A). Contractures progressed rapidly following loss of ambulation. (*significantly different from control subjects, p < 0.05).

Fig. 4.

Boys with greater ROM had better performance on the 6MWT and 10 m walk/run across all 3 lower extremity joints measured. However, there was a wide range of function in boys with full ROM. Notably, no boys were able to walk with 20 degree or greater contractures at the knee, while many boys maintained fairly good functional performance with 20 degree or greater contractures at the ankle. *Bonferroni-corrected bootstrap confidence intervals for the mean difference between groups exclude 0.

Fig. 5.

Example T₁-weighted gradient echo images of the calves in individuals with similar ROM and different muscle quality. MRI T₂ values: Subject A: TA = 39.8 ms, SOL = 45.4 ms, ratio = 0.88; Subject B: TA = 71.7 ms, SOL = 78.8 ms, ratio = 0.91; TA = 33.4 ms, SOL = 38.7 ms, ratio = 0.86; D: TA = 57.3 ms, SOL = 60.9 ms, ratio = 0.94). The presence of pronounced contractures in individuals with relatively healthy muscle, and absence of contractures in individuals with substantial fatty infiltration in the lower leg muscles, point to the important role factors other than muscle fibrofatty infiltration may play in contracture development.

Fig. 6.

ROM was moderately correlated with MRI T₂ in a flexor and an extensor muscle at both the knee and ankle (A-D). However, the ratio of the MRI T₂ from an agonist and an antagonist muscle was not strongly correlated with maximum ROM at either the knee (E: no significant correlation) or the ankle (F: SOL: rho = 0.18; bootstrap 95%CI = 0.05 to 0.30; G: MG: rho = 0.18, bootstrap 95%CI = 0.06 to 0.30). Bootstrap 95% CI for panels A-D can be found in Table 2. For panels E-F, higher ratios indicate greater involvement in the anterior compartment; lower ratios indicate greater involvement in the posterior compartment.