BIOchemical, DEnsitometric, TEChnological and Imaging Tools to Evaluate the Bone/muscle in Children with Cerebral Palsy

Overview

Cerebral palsy (CP) is the most common chronic disability in childhood, burden by motor, sensation, cognition, feeding and communication impairment. A serious concern in children with CP is bone/muscle health deterioration, which negatively impacts the already reduced quality of life (QoL). Children with CP show low bone density, vitamin D deficiency, sarcopenia and high risk of fragility fractures, with heavy effects on what is already limited home, school and community life. The causes for muscle-bone impairment are low weight-bearing deambulation during skeletal formation with low bone mineralization, poor nutrition and low calcium intake, low sun exposure, use of anticonvulsant medications with a negative profile on bone. Understanding the causes affecting bone quality and setting up interventions to reduce the impact of physical disability are essential in young subjects with CP. This project combines complementary expertise and resources in the fields of Endocrinological Biochemistry, Paediatric Neurological Disorders and Neuroimaging, to allow an innovative, technology-assisted workup for bone/muscle health evaluation in young subjects with CP, which could drive novel therapeutics, nutritional and rehabilitation programs. The first aim of this project is to evaluate bone/muscle health in young subjects with CP compared with sex-age matched healthy subjects, providing i) serum biomarkers of mineral metabolism and the metabolome of Vitamin D, assessed with last generation Mass Spectrometry, ii) muscle sarcopenia markers like Irisin and other myokines, depicting the response of the muscle to exercise iii) neuronal damage and inflammatory markers, iv) densitometric data by the low-cost and safe Quantitative ultrasound (QUS) at phalanges of the hand, plus the novel and very promising Radiofrequency Echographic Multi Spectrometry (REMS) served by the software for fragility fractures risk. We also aim to correlate the previous mentioned markers of bone/muscle health with a combination of demographic, clinical, cognitive and technological parameters, the last obtained by an innovative use of wearable sensors or actigraphs, positioned at the wrists, which depicts movements, physical activity (PA), energy expenditures (EE) and, together with heart-rate monitors, metabolic data during a normal like week in subjects with CP and healthy controls. Finally, a newly validated scoring for brain lesions in subjects with CP and the production of imaging "biomarkers" of neuronal damage, will be correlated with their bone/muscle health data, PA and EE to understand the impact of brain damage on functional performance and bone metabolism.

This study investigates the correlation between brain lesions, physical ability, and bone/muscle health in young patients with cerebral palsy (CP). It posits that: Bone and muscle health in young individuals with CP is compromised, affecting their quality of life and development. The study aims to utilize biomarkers related to bone fragility, sarcopenia, and neuronal damage, alongside advanced imaging techniques (quantitative ultrasound and Radiofrequency Echographic Multi Spectrometry) to assess bone/muscle unit health accurately. Physical activity limitations and reduced energy expenditure negatively impact bone/muscle health in CP patients. The researchers plan to leverage wearable sensors to provide precise measurements of physical activity and correlate these with the established biomarkers and imaging results, aiding in customized treatment approaches. Brain MR imaging could reveal structural changes in the brain, which may correlate with physical activity and bone/muscle health data, helping to understand the implications of brain damage on overall functionality. The objectives include comparing bone/muscle health between children with CP and healthy peers, assessing physical activity's impact on bone/muscle health, and analyzing brain imaging results in relation to those health metrics. The study anticipates enrolling 50 participants with CP and 50 age-matched controls, utilizing various biochemical and imaging techniques to gather and compare data on bone and muscle health, physical activity, and brain lesions.