Intraoperative and Laboratory Studies of Spastic Human Skeletal Muscle

Friday, May 28, 2010 - 2:00pm
Richard L. Lieber, Ph.D.

Departments of Orthopaedic Surgery and Bioengineering

Intraoperative and Laboratory Studies of Spastic Human Skeletal Muscle

Abstract: 
Spasticity, secondary to upper motor neuron lesion, can result in muscle contractures. We have studied the mechanics and biology of muscle from children with wrist flexion contractures secondary to Cerebral Palsy (CP).Dramatic architectural changes are observed in these children whereby sarcomere lengths are dramatically altered relative to patients without upper motor neuron lesions. This suggests dramatic alterations in the regulation of muscle growth in these children. Biomechanical studies of isolated single muscle cells reveal an increased passive modulus and decreased resting sarcomere length suggesting alterations in the cellular cytoskeleton. Similar studies on small bundles of muscle fiber reveal an increase in the compliance of the extracellular matrix and a proliferation of endomysial connective tissue. Thus, passive biomechanical properties of muscle from children with CP are dramatically altered in ways that are unparalleled by other altered use models. A recent expression profiling study revealed a number of “conflicting” biological pathways in spastic muscle. Specifically, this muscle adapts by altering processes related to extracellular matrix production, fiber type determination, fiber hypertrophy and myogenesis. We also obtained evidence that calcium handling is altered secondary to cerebral palsy and may be a significant component of this disease. These transcriptional adaptations were not characteristic of muscle adaptations observed in Duchenne muscular dystrophy or limb immobilization. Taken together, these results support the notion that, while spasticity is multifactorial and neural in origin, significant structural alterations in muscle also occur. An understanding of the specific changes that occur in the muscle and extracellular matrix may facilitate the development of new conservative or surgical therapies for this devastating problem.