Quadriceps muscle strength in Duchenne muscular dystrophy and effect of corticosteroid treatment

Abstract

Objectives: In Duchenne muscular dystrophy, quadriceps weakness is recognized as a key factor in gait deterioration. The objective of this work was three-fold: first, to document the strength of the quadriceps in corticosteroid-naïve DMD boys; second, to measure the effect of corticosteroids on quadriceps strength; and third, to evaluate the correlation between baseline quadriceps strength and the age when starting corticosteroids with the loss of ambulation.

Methods: Quadriceps muscle strength using hand-held dynamometry was measured in 12 ambulant DMD boys who had never taken corticosteroids and during corticosteroid treatment until the loss of ambulation.

Results: Baseline quadriceps muscle strength at 6 years of age was 28% that of normal children of the same age; it decreased to 15% at 8 years and to 6% at 10 years. The increase in quadriceps muscle strength obtained after 1 year of corticosteroid treatment had a strong direct correlation with the baseline strength (R = 0.96). With corticosteroid treatment, the age of ambulation loss showed a very strong direct relationship (R = 0.92) with baseline quadriceps muscle strength but only a very weak inverse relationship (R = -0.73) with the age of starting treatment. Age of loss of ambulation was 10.3 ± 0.5 vs 19.1 ± 4.7 (P < 0.05) in children with baseline quadriceps muscle strength less than or greater than 40 N, respectively.

Conclusions: Corticosteroid-naïve DMD boys have a quantifiable severe progressive quadriceps weakness. This long-term study, for the first time, shows that both of the positive effects obtained with CS treatment, i.e. increasing quadriceps strength and delaying the loss of ambulation, have a strong and direct correlation with baseline quadriceps muscle strength. As such, hand-held dynamometry may be a useful tool in the routine physical examination and during clinical trial assessment.

Keywords: Duchenne muscular dystrophy; corticosteroid treatment; hand-held dynamometry; prolongation of walking; quadriceps muscle strength.

Figure 1.

Regression lines between age and quadriceps/knee extension (KE) muscle strength in normal boys (aged 6-11 years, green line) , in 61 corticosteroid-naïve DMD boys (aged 5-11 years, red line) , and in 12 DMD boys before starting CS (aged 2-10 years, blue line). The differences between the regression lines y = -6.679x + 84.57 by Scott et al. and y = -6.686x + 81.65 of the 12 DMD boys were not significant (p = 0.65). The linear equation for normal boys aged 6-11 years was y = 21.543x + 16.55.

Figure 2.

Linear trend of quadriceps strength for each of the 12 DMD boys from the age of initiation of corticosteroid treatment until the age of ambulation loss. The patients had 1-4 strength measurements each year and each line shows the maximum force value expressed during each year. The increase in knee extension muscle strength started in the first year of treatment in most patients and continued for 4-7 years in patients who at the beginning of the treatment had a force greater than 60 N (P1, P2, P4, P5). The 6 patients with baseline knee extension strength below 40 N (P3, P7, P9-P11) had a limited increase or only stabilization (P6) in KE muscle strength. For each of the 12 patients, the age of onset of CS and the age of loss of ambulation are shown in parentheses.

Figure 3.

Increase in KE muscle strength with CS treatment in 12 DMD boys. (A) Regression line between baseline KE (X) and 1-year KE (Y): R² = 0.9281. This means that 92.8% of the variability in Y is explained by X. R = 0.9634. This means that there is a very strong direct relationship between X and Y. P-value = 4.879e-7. Y = -11.413 + 1.53X. (B) Regression line between baseline KE (X) and peak KE (Y): R² = 0.9050. This means that 90.5% of the variability in Y is explained by X. R = 0.9513. This means that there is a very strong direct relationship between X and Y. P-value = 0.000001987. Y = -33.0743 + 2.4230X.

Figure 4.

Regression lines in 12 CS treated DMD boys between (A) age of CS initiation (X) and age WCB (Y) and (B) baseline KE (X) and age wheelchair-bound (WCB) (Y). (A) R² = 0.5347. This means that 53.5% of the variability in Y is explained by X. R = -0.7313. This means that there is a very weak inverse relationship between X and Y. P-value = 0.006884. Y = 24.736-1.80X. (B) R² = 0.8489. This means that 84.9% of the variability in Y is explained by X. R = 0.9214. This means that there is a very strong direct relationship between X and Y. P-value = 0.00002072. Y = 2.6012 + 0.2719X.