Lessons for future clinical trials in adults with Becker muscular dystrophy: Disease progression detected by muscle magnetic resonance imaging, clinical and patient-reported outcome measures.

BACKGROUND AND PURPOSE: Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials. METHODS: Muscle magnetic resonance imaging, patient-reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed-function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow-up. RESULTS: Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32-item Motor Function Measurement (MFM-32) scale (-1.3%, p = 0.017), North Star Ambulatory Assessment (-1.3 points, p = 0.010) and patient-reported activity limitations scale (-0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6-min walk distance (-28.7 m, p = 0.042), 10-m walking test (-0.1 m/s, p = 0.032), time to climb four stairs test (-0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (-4.6 N m, p = 0.014) and hamstrings (-5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM-32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15). DISCUSSION: It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow-up. Finally, significant changes are reported in a wide range of clinical and patient-reported outcome measures, of which the MFM-32 appeared to be the most sensitive to change in adults with BMD.

What can we learn from the relationship between gait deviations and clinical impairments when comparing two databases?

BACKGROUND: Several previous studies have tried to determine the relationship between gait and clinical impairments in children with Cerebral Palsy (CP). The heterogeneity of the population and the methodology used could explain the discrepancy within the results. Recently, Papageorgiou et al. (2019) used a Statistical Parametric Mapping (SPM) analysis to investigate this relationship, allowing to test across the kinematic waveforms parameters. RESEARCH QUESTION: Are we able to replicate the results of Papageorgiou et al. (2019) on a population of children with CP from another center? METHODS: Retrospectively, youth with spastic unilateral (uCP) or bilateral (bCP) CP (3-18 years of age) who underwent a clinical gait analysis at the Geneva University Hospitals (HUG) were screened. Following Papageorgiou et al. 2019, the same inclusion and exclusion criteria as well as the same methodology were applied. Mann-Whitney-U test was used to compare the impairments score between the two centers. A Student T-Test using SPM was applied to compare the kinematic waveforms from the two centers. A canonical correlation analysis using SPM was realized to assess the relationship between clinical impairments and the combined sagittal motion of the pelvis, hip, knee and ankle. RESULTS AND SIGNIFICANCE: A total of 211 patients were included with 131 uCP (10 [8-14] years old) and 80 bCP (11 [7-14] years old). The distribution of the Gross Motor Function Classification System levels and the proportion of previous treatment differs between centers. In both CP groups, significant differences were observed in the composite score and lower limb kinematics, reflecting less impaired patients with CP at HUG compared to Papagergiou et al. (2019). While similar associations between spasticity and kinematic were observed in both centers, the association with muscle weakness, selectivity, and range of motion differed.