Muscle metabolism and mechanical efficiency in cerebral palsy

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DESCRIPTION (provided by applicant): Cerebral Palsy (CP) affects more than 750,000 children and adults, with an additional 11,000 children added every year. There are dramatic lifelong consequences on a child's functional and endurance capacity, leading to increasing physical inactivity and limited mobility necessitating the use of assistive devices such as wheelchairs. There is an increase in energy expenditure even during submaximal activities such as during walking for activities of daily living, the reasons for which are not well understood. Muscular metabolic factors of oxidative potential and mitochondrial function and mechanical efficiency of activity are critical for energy expenditure and endurance capacity. Surprisingly, while there is some evidence of abnormalities of factors related to muscle metabolism, no direct measurements of muscle metabolism have been made in these children, nor is their relationship to increased energy expenditure known. The objective of this proposal is to define the relationship between muscle tissue metabolism, mechanical efficiency and energy expenditure of walking in children with CP. We hypothesize that increased energy expenditure during walking and decreased mechanical efficiency during cycling in children with CP is in part due to impaired skeletal muscle metabolism. Secondarily, we hypothesize that mechanical efficiency will be lower in children with reduced functional capabilities and this could be correlated with reductions in metabolic activity. 50 children with Typical Development (TD) and CP between 4‑17 years of age will be recruited for this study. The first aim will quantify the relationship between muscle oxidative capacity, mitochondrial function and energy expenditure during walking in children with TD and CP. We predict that the children with lower muscle metabolic activity will have higher energy expenditure during walking, which will be further reduced with age and across functional levels. The second complementary aim will quantify mechanical efficiency during graded submaximal exercise and measure its association with muscle metabolism in children with CP and TD. We predict that the children with CP will have lower mechanical efficiency and metabolic function compared to the children with TD and this does not change with age to the same extent as in children with TD. The results of this proposal will lead to targeted therapeutic interventions for improving daily function in children with CP, in particular in those identified as being most at risk for being unable to continue active participation in society.