Multidimensional Biomechanics-Based Score to Assess Disease Progression in Duchenne Muscular Dystrophy

Abstract

(1) Background: Duchenne (DMD) is a rare neuromuscular disease that progressively weakens muscles, which severely impairs gait capacity. The Six Minute-Walk Test (6MWT), which is commonly used to evaluate and monitor the disease’s evolution, presents significant variability due to extrinsic factors such as patient motivation, fatigue, and learning effects. Therefore, there is a clear need for the establishment of precise clinical endpoints to measure patient mobility. (2) Methods: A novel score (6M+ and 2M+) is proposed, which is derived from the use of a new portable monitoring system capable of carrying out a complete gait analysis. The system includes several biomechanical sensors: a heart rate band, inertial measurement units, electromyography shorts, and plantar pressure insoles. The scores were obtained by processing the sensor signals and via gaussian-mixture clustering. (3) Results: The 6M+ and 2M+ scores were evaluated against the North Star Ambulatory Assessment (NSAA), the gold-standard for measuring DMD, and six- and two-minute distances. The 6M+ and 2M+ tests led to superior distances when tested against the NSAA. The 6M+ test and the 2M+ test in particular were the most correlated with age, suggesting that these scores better characterize the gait regressions in DMD. Additionally, the 2M+ test demonstrated an accuracy and stability similar to the 6M+ test. (4) Conclusions: The novel monitoring system described herein exhibited good usability with respect to functional testing in a clinical environment and demonstrated an improvement in the objectivity and reliability of monitoring the evolution of neuromuscular diseases.

Extracellular Matrix Proteomics: The mdx-4cv Mouse Diaphragm as a Surrogate for Studying Myofibrosis in Dystrophinopathy

“…The most severe form of dystrophinopathy, Duchenne muscular dystrophy, is a primary-muscle-wasting disorder of early childhood [179] with a prevalence of approximately 1 in 5000 live male births [180], which is triggered by a variety of genetic abnormalities in the X-chromosomal DMD gene [181]. Initial clinical signs include developmental delays in Duchenne patients with proximal muscle weakness, temporal and spatial gait variations, decreased walking speed, and Gower's sign [182][183][184]. Characteristic patterns of toe walking and difficulties with climbing stairs progress at more advanced stages of the disease towards respiratory insufficiency, cardiomyopathy, scoliosis, and severe limitations in general mobility [185][186][187][188][189][190], which eventually results in the loss of unassisted ambulation and upper body weakness [191].…”