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Cerebral palsy (CP), the most common cause of movement disorders and physical disability in children all over the world, is caused by an injury to the developing brain. Although this injury is not progressive, the manifestations of the disorder change as the child ages. Spasticity and altered viscoelastic properties of the muscle often enhance muscle resistance to stretch and the peak spasticity of the calf muscles in children with CP observed at four years of age declines thereafter until twelve years of age. The cause of muscle contractures, which appear early and progress throughout childhood and adolescence is unclear and needs to be elucidated further to help design more effective preventive measures. Therefore, the first aim of this thesis was to further characterize muscle pathophysiology in children with CP with fixed contractures. Treatment of patients with CP involves a wide variety of efforts. Standardized and objective follow-up, as well as cost effectiveness are of considerable importance. Therefore, the second aim here focused on novel tools for clinical evaluation, as well as assessment of the economics of switching between two botulinum toxins (BoNT-A) in treatment of children with CP. We developed further a three-dimensional test of arm reach in typically developing (TD) children and tested the feasibility of this test in young adults with CP. We also developed a new approach evaluating the effects of BoNT-A treatment involving monitoring the child ́s home and school environments with four accelerometers. Moreover, we made a controlled switch from one brand of BoNT-A to another in attempt to reduce the drug cost without reducing efficacy or duration or exacerbating side-effects. The major novel findings with respect to muscle pathophysiology are that impaired production of ribosomes probably explains, at least in part, the deficient growth of skeletal muscle observed in children with CP and that levels of pro-inflammatory cytokines are elevated in t

Introduction: Children with cerebral palsy (CP) and acquired brain injury (ABI) commonly develop muscle contractures with advancing age. An underlying growth defect contributing to skeletal muscle contracture formation in CP/ABI has been suggested. Methods: The biceps muscles of children and adolescents with CP/ABI (n=20) and typically developing controls (n=10) were investigated. We used immunohistochemistry, quantitative real-time polymerase chain reaction, and Western blotting to assess gene expression relevant to growth and size homeostasis. Results: Classical pro-inflammatory cytokines and genes involved in extracellular matrix (ECM) production were elevated in skeletal muscle of children with CP/ABI. Intramuscular collagen content was increased and satellite cell number decreased and this was associated with reduced levels of RNA polymerase I transcription factors, 45s pre-rRNA and 28S rRNA. Discussion: The present study provides novel data suggesting a role for pro-inflammatory cytokines and reduced ribosomal production in the development/maintenance of muscle contractures, possibly underlying stunted growth and perimysial ECM expansion.