P.192 - Muscle fiber dysfunction contributes to clinical muscle weakness in inclusion body myositis

Abstract

Inclusion body myositis (IBM) is the most common acquired muscle disorder in adults over 50 years old. It is characterized by progressive muscle weakness and marked muscle atrophy, most prominent in the finger flexors and quadriceps muscle. In addition to atrophy, fatty replacement of muscle tissue contributes to clinical muscle weakness and functional decline. This study aims to investigate the contractile performance of residual muscle tissue. We included 8 participants with IBM and 12 healthy controls. We measured individual health related quality of life, functional performance and muscle strength. In all participants, muscle contractile capacity was measured both in vivo, using quantitative muscle testing and MRI imaging, and ex vivo, using single fiber studies of the vastus lateralis as well as tibialis anterior muscle biopsies. Quadriceps specific force was calculated by correcting the voluntary maximum force (N) for the contractile cross-sectional area (CCSA). CCSA was calculated by multiplying the total cross-sectional area by the muscle fraction on MRI. Voluntary maximum force generation of the quadriceps muscle was significantly reduced in IBM participants (216.9 ± 57.6 N vs. 572.1 ± 53.1 N, p < .001). Quadriceps specific force was reduced in IBM participants. Muscle fiber specific force was also reduced in IBM patients compared to healthy controls (type 1 fibers: 158.3 ± 4.1 mN/mm2 in IBM vs. 178.9 ± 3.4 in controls, type 2 fibers: 180.3 ± 7.2 mN/mm2 in IBM vs. 213.7 ± 4.2 in controls, p = .036). Reduced muscle fiber specific force was equally present in vastus lateralis and tibialis anterior muscles. Contractile performance of residual muscle tissue is impaired in IBM patients, both in vivo and ex vivo. We conclude that sarcomeric dysfunction contributes to clinical muscle weakness in IBM.