Longitudinal trajectories of muscle impairments in growing boys with Duchenne muscular dystrophy

Abstract

Background Insights into the progression of muscle impairments in growing boys with Duchenne muscular dystrophy (DMD) remains incomplete due to the frequent oversight of normal maturation as confounding factor, thereby restricting the delineation of sole pathological processes. Objective To establish longitudinal trajectories for a comprehensive integrated set of muscle impairments, including muscle weakness, contractures and muscle size alterations, whilst correcting for normal maturation, in DMD. Methods Thirty-five boys with DMD (aged 4.3-17 years) were included. Fixed dynamometry, goniometry and 3D freehand ultrasound were used to repeatedly asses lower limb muscle strength, passive range of motion (ROM) and muscle size, resulting in 165, 182 and 67 assessments for the strength, ROM and ultrasound dataset, respectively. To account for natural strength development, ROM reduction and muscle growth in growing children, muscle impairments were converted to unit-less z-scores calculated in reference to typically developing (TD) peers. This allows the interpretation of the muscle impairments as deficits or alterations with respect to TD. Mixed-effect models estimated the longitudinal change in muscle impairments. Results The pathological trajectories of most muscle impairments with age followed a similar non-linear, piecewise pattern, characterized by an initial phase of improvement or stability lasting until 6.6-9.5 years, and a subsequent decline after these ages. The muscle strength outcomes and several ROMs showed already initial deficits at young ages. General muscle weakness and plantar flexion contractures exhibited the steepest declines, resulting in large deficits at older ages. The muscle size alterations with age were muscle-specific. Conclusions The established longitudinal trajectories of muscle impairments will serve as the basis to enhance understanding of their relationship with the progressive gait pathology in DMD. Our study provides outcome measures, which will be useful for future clinical trials that assess the efficacy of novel therapeutic strategies.