Muscle architecture, growth, and biological Remodelling in cerebral palsy: a narrative review

Abstract

Cerebral palsy (CP) is caused by a static lesion to the brain occurring in utero or up to the first 2 years of life; it often manifests as musculoskeletal impairments and movement disorders including spasticity and contractures. Variable manifestation of the pathology across individuals, coupled with differing mechanics and treatments, leads to a heterogeneous collection of clinical phenotypes that affect muscles and individuals differently. Growth of muscles in CP deviates from typical development, evident as early as 15 months of age. Muscles in CP may be reduced in volume by as much as 40%, may be shorter in length, present longer tendons, and may have fewer sarcomeres in series that are overstretched compared to typical. Macroscale and functional deficits are likely mediated by dysfunction at the cellular level, which manifests as impaired growth. Within muscle fibres, satellite cells are decreased by as much as 40–70% and the regenerative capacity of remaining satellite cells appears compromised. Impaired muscle regeneration in CP is coupled with extracellular matrix expansion and increased pro-inflammatory gene expression; resultant muscles are smaller, stiffer, and weaker than typical muscle. These differences may contribute to individuals with CP participating in less physical activity, thus decreasing opportunities for mechanical loading, commencing a vicious cycle of muscle disuse and secondary sarcopenia. This narrative review describes the effects of CP on skeletal muscles encompassing substantive changes from whole muscle function to cell-level effects and the effects of common treatments. We discuss growth and mechanics of skeletal muscles in CP and propose areas where future work is needed to understand these interactions, particularly the link between neural insult and cell-level manifestation of CP.

Progressive resistance training for children with cerebral palsy: A randomized controlled trial evaluating the effects on muscle strength and morphology

“…In SCP muscles, a decreased number of satellite cells has been observed in comparison to typically developing muscles ( Smith et al, 2013 ; von Walden et al, 2018 ). The influence of altered cytokine expression and extracellular matrix remodeling by fibroblasts on the complex process of muscle repair and growth, together with the alterations in satellite cell concentration and efficacy, are to be further explored in SCP muscles ( Handsfield et al, 2022 ).…”

Adult stem cell characterization from theMedial GastrocnemiusandSemitendinosusmuscles in early development of cerebral palsy pathology

“…To address the second study objective, we assessed multiple factors potentially leading to heterogeneity in reported results on the CP muscle pathology 19,20,42 . Firstly, to address objective 2.1, we have uniquely cultured and extracted cells from two different muscles of the same young patients with CP, as well as from aged matched TD children.…”

Plastic Spinal Motor Circuits in Health and Disease

“…Spastic muscles show variable macroscopic and microscopic changes, including reduced muscle volumes, fascicle lengths and pennation angles, stretched tendons, and fewer sarcomeres in series that are stretched out (Handsfield et al 2022). In part these changes are caused by reduced neural innervation, in part by accompanying circumstances.…”