Scientific Advances in the Understanding of Contracture Pathogenesis in Brachial Plexus Birth Injury

Pediatric orthopedic surgeons are frequently confronted with musculoskeletal contractures caused by pediatric neuromuscular conditions, including brachial plexus birth injury (BPBI). These contractures substantially limit function and quality of life in affected children, and frequently lead to skeletal dysplasia and dislocations. However, existing orthopedic treatments for these contractures do not restore normal function as they fail to address the underlying contracture pathophysiology, which remains largely unknown. Over the past decade, a wealth of scientific and clinical research has contributed to a deeper understanding of the pathogenesis of contractures in BPBI. This review summarizes this research, describing a journey of discovery that intertwines clinical observations and scientific investigations in animal models. This research comprehensively highlights the role of impaired longitudinal muscle growth in contracture pathogenesis, shifting the paradigm of contracture pathogenesis from a problem of muscle strength to a problem of muscle length, and from a mechanical to biological realm. Moreover, these research efforts have elucidated mechanisms governing longitudinal muscle growth and how they are perturbed by neonatal denervation. Most recently, this work has led to the proof of concept discovery that muscle contractures following BPBI can be pharmacologically prevented by targeting the underlying biological perturbations in neonatally denervated muscles. Although much work must be done before such a pharmacologic strategy can be translated to children, these discoveries hold promise for a new era in the pediatric orthopedic care of BPBI in which contractures are medically prevented rather than surgically treated.