Microscopic and molecular aspects of skeletal muscle alterations in cerebral palsy

Cerebral palsy (CP), the most prevalent childhood-onset motor disability, frequently entails progressive musculoskeletal complications. This comprehensive review synthesizes existing knowledge of microscopic and molecular alterations in CP skeletal muscle. Considerable methodological variability, heterogeneous patient cohorts, and inconsistent control groups significantly complicate comparative interpretations across studies. Nonetheless, some structural abnormalities consistently emerge, including increased variability in muscle fibre size, altered fibre type distribution, long sarcomeres at standardized joint positions, increased collagen content, disrupted neuromuscular junction integrity, reduced capillary density, and mitochondrial and satellite cell impairments. Investigations of satellite cell function in vitro further underscore potential mechanistic alterations, although findings remain inconsistent. Remarkably, few studies have systematically explored the cellular and molecular consequences of standard clinical interventions, revealing a notable research gap. In conclusion, the overall literature reveals considerable divergence in reported outcomes, reflecting the profound complexity of CP muscle biology. We believe that resolving this complexity will require more coordinated and collaborative research approaches.