Longitudinal Alterations in Gait Features in Growing Children With Duchenne Muscular Dystrophy

Abstract

Prolonging ambulation is an important treatment goal in children with Duchenne muscular dystrophy (DMD). Three-dimensional gait analysis (3DGA) could provide sensitive parameters to study the efficacy of clinical trials aiming to preserve ambulation. However, quantitative descriptions of the natural history of gait features in DMD are first required. The overall goal was to provide a full delineation of the progressive gait pathology in children with DMD, covering the entire period of ambulation, by performing a so-called mixed cross-sectional longitudinal study. Firstly, to make our results comparable with previous literature, we aimed to cross-sectionally compare 31 predefined gait features between children with DMD and a typically developing (TD) database (1). Secondly, we aimed to explore the longitudinal changes in the 31 predefined gait features in growing boys with DMD using follow-up 3DGA sessions (2). 3DGA-sessions (n = 124) at self-selected speed were collected in 27 boys with DMD (baseline age: 4.6-15 years). They were repeatedly measured over a varying follow-up period (range: 6 months-5 years). The TD group consisted of 27 children (age: 5.4-15.6 years). Per measurement session, the spatiotemporal parameters, and the kinematic and kinetic waveforms were averaged over the selected gait cycles. From the averaged waveforms, discrete gait features (e.g., maxima and minima) were extracted. Mann-Whitney U tests were performed to cross-sectionally analyze the differences between DMD at baseline and TD (1). Linear mixed effect models were performed to assess the changes in gait features in the same group of children with DMD from both a longitudinal (i.e., increasing time) as well as a cross-sectional perspective (i.e., increasing baseline age) (2). At baseline, the boys with DMD differed from the TD children in 17 gait features. Additionally, 21 gait features evolved longitudinally when following-up the same boys with DMD and 25 gait features presented a significant cross-sectional baseline age-effect. The current study quantitatively described the longitudinal alterations in gait features in boys with DMD, thereby providing detailed insight into how DMD gait deteriorates. Additionally, our results highlight that gait features extracted from 3DGA are promising outcome measures for future clinical trials to quantify the efficacy of novel therapeutic strategies.

Keywords: Duchenne muscular dystrophy; gait pattern; longitudinal study; mixed models for repeated measures; three-dimensional gait analysis; typically developing children.

FIGURE 1

Mixed cross-sectional longitudinal dataset. Overview of the ages at the included measurements for the children with DMD (A) and for the TD database (B). Each color represents one patient. DMD, Duchenne muscular dystrophy; TD, typically developing.

FIGURE 2

Schematic overview of statistical analyses to achieve the first (A) and the second aim (B).

FIGURE 3

The individual predicted profiles (dashed lines) for cadence (A), normalized walking velocity (B), normalized step length (C), and normalized step width (D). The actual observed values are visualized by the symbols. Each color represents one patient with DMD. The regression coefficients of the fixed effects are given in Table 3. DMD, Duchenne muscular dystrophy.

FIGURE 4

The individual predicted profiles (dashed lines) for the GPS (A), the maximal anterior pelvic tilt (B), range of motion pelvic obliquity (C), and range of motion pelvic rotation (D). The actual observed values are visualized by the symbols. Each color represents one patient with DMD. The regression coefficients of the fixed effects are given in Table 4. DMD, Duchenne muscular dystrophy; GPS, Gait Profile Score.

FIGURE 5

The individual predicted profiles (dashed lines) for the minimal hip flexion angle during stance (A), maximal hip flexion angle during swing (B), range of hip motion in the sagittal plane (C), maximal hip extension moment (D), maximal hip power generation during stance (E), minimal hip adduction angle during stance (F), minimal hip adduction angle during swing (G), and maximal hip abduction moment during stance (H). The actual observed values are visualized by the symbols. Each color represents one patient with DMD. The regression coefficients of the fixed effects are given in Table 5. DMD, Duchenne muscular dystrophy.

FIGURE 6

The individual predicted profiles (dashed lines) for the maximal knee flexion angle during stance (A), minimal knee flexion angle during stance (B), range of knee motion in sagittal plane during stance (C), maximal knee flexion angle during swing (D), maximal knee extension moment (E), and minimal knee extension moment (F). The actual observed values are visualized by the symbols. Each color represents one patient with DMD. The regression coefficients of the fixed effects are given in Table 6. DMD, Duchenne muscular dystrophy.

FIGURE 7

The individual predicted profiles (dashed lines) for the dorsiflexion angle at initial contact (A), maximal dorsiflexion angle during swing (B), maximal dorsiflexion angle during stance (C), minimal plantar flexion moment during loading response (D), maximal plantar flexion moment during push-off (E), minimal ankle power during loading response (F), maximal ankle power generation during push-off (G), and maximal internal foot progression angle during stance (H). The actual observed values are visualized by the symbols. Each color represents one patient with DMD. The regression coefficients of the fixed effects are given in Table 7. DMD, Duchenne muscular dystrophy.