Upper extremity outcome measures for collagen VI-related myopathy and LAMA2-related muscular dystrophy.

Congenital muscular dystrophy (CMD) comprises a rare group of genetic muscle diseases that present at birth or early during infancy. Two common subtypes of CMD are collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). Traditional outcome measures in CMD include gross motor and mobility assessments, yet significant motor declines underscore the need for valid upper extremity motor assessments as a clinical endpoint. This study validated a battery of upper extremity measures in these two CMD subtypes for future clinical trials. For this cross-sectional study, 42 participants were assessed over the same 2-5 day period at the National Institutes of Health Clinical Center. All upper extremity measures were correlated with the Motor Function Measure 32 (MFM32). The battery of upper extremity assessments included the Jebsen Taylor Hand Function Test, Quality of Upper Extremity Skills Test (QUEST), hand held dynamometry, goniometry, and MyoSet Tools. Spearman Rho was used for correlations to the MFM32. Pearson was performed to correlate the Jebsen, QUEST, hand-held dynamometry, goniometry and the MyoSet Tools. Correlations were considered significant at the 0.01 level (2-tailed). Significant correlations were found between both the MFM32 and MFM Dimension 3 only (Distal Motor function) and the Jebsen, QUEST, MyoGrip and MyoPinch, elbow flexion/extension ROM and myometry. Additional correlations between the assessments are reported. The Jebsen, the Grasp and Dissociated Movements domains of the QUEST, the MyoGrip and the MyoPinch tools, as well as elbow ROM and myometry were determined to be valid and feasible in this population, provided variation in test items, and assessed a range of difficulty in CMD. To move forward, it will be of utmost importance to determine whether these upper extremity measures are reproducible and sensitive to change over time.

Results of a two-year pilot study of clinical outcome measures in collagen VI- and laminin alpha2-related congenital muscular dystrophies.

Potential therapies are currently under development for two congenital muscular dystrophy (CMD) subtypes: collagen VI-related muscular dystrophy (COL6-RD) and laminin alpha 2-related dystrophy (LAMA2-RD). However, appropriate clinical outcome measures to be used in clinical trials have not been validated in CMDs. We conducted a two-year pilot study to evaluate feasibility, reliability, and validity of various outcome measures, particularly the Motor Function Measure 32, in 33 subjects with COL6-RD and LAMA2-RD. In the first year, outcome measures tested included: Motor Function Measure 32 (MFM32), forced vital capacity (FVC) percent predicted sitting, myometry, goniometry, 10-meter walk, Egen Klassification 2, and PedsQL(TM) Generic and Neuromuscular Cores. In the second year, we added the North Star Ambulatory Assessment (NSAA), Hammersmith Functional Motor Scale (HFMS), timed functional tests, Measure of Activity Limitations (ACTIVLIM), Quality of Upper Extremity Skills Test (QUEST), and Patient-Reported Outcomes Measurement Information System (PROMIS) fatigue subscale. The MFM32 showed strong inter-rater (0.92) and internal consistency (0.96) reliabilities. Concurrent validity for the MFM32 was supported by large correlations (range 0.623-0.936) with the following: FVC, NSAA, HFMS, timed functional tests, ACTIVLIM, and QUEST. Significant correlations of the MFM32 were also found with select myometry measurements, mainly of the proximal extremities and domains of the PedsQL(TM) scales focusing on physical health and neuromuscular disease. Goniometry measurements were less reliable. The Motor Function Measure is reliable and valid in the two specific subtypes of CMD evaluated, COL6-RD and LAMA2-RD. The NSAA is useful as a complementary outcome measure in ambulatory individuals. Preliminary concurrent validity of several other clinical outcome measures was also demonstrated for these subtypes.