Muscle Changes at the Cellular-Fiber Level in Cerebral Palsy

Abstract

Muscle changes are routinely observed in children with cerebral palsy. The natural progression of gait leads to a reduction in passive range of motion and muscle contractures. Here we discuss the physiological properties of skeletal muscle tissue and recent advances in the biological basis of contractures. Skeletal muscles are highly organized structures composed of muscle cells, i.e., myofibers, arranged in parallel and series. Myofibers in turn are made up of basic contractile proteins actin and myosin that interact to form sarcomeres. Sarcomere length and force production are intricately associated such that at very long and short sarcomere lengths, there is a reduction in force-generating capacity. During typical postnatal development, longitudinal skeletal muscle growth occurs by addition of sarcomeres secondary to stretch induced by bone growth. In children with cerebral palsy, sarcomere lengths are overstretched, and serial sarcomere number is lower, associated with a limitation in joint range of motion, suggesting reduced ability for muscle growth and weakness. Increase in muscle extracellular matrix content and increase in passive mechanical stiffness of fibers and fiber bundles are also observed in contractured muscles. Satellite cells are resident stem cells indispensable for postnatal development, repair, and regeneration of skeletal muscles. The satellite cell population is dramatically reduced in contractured muscles. Overall these findings suggest that impaired muscle growth and contractures in children with cerebral palsy are related to a reduced muscle stem cell number.