3D-Microscopic Muscle Architecture in Cerebral Palsy

The focus of this study is to understand and define the mechanisms of the altered muscle development and growth on a microscopic level within a long-term perspective in children with cerebral palsy and to relate these findings to muscle macroscopic properties defined by muscle imaging, to neuromuscular symptoms and to treatment. This study aims to (1) evaluate intrinsic microscopic muscle properties of young growing children with CP, and (2) to evaluate these muscle properties in relation to macroscopic properties, neuromuscular symptoms and to treatment. Improved understanding of changes in microscopic muscle properties, and how they relate to macroscopic properties and to the neuromuscular symptoms as well as how they are influenced by treatment, has the potential to delineate CP phenotypes prone to intervention and to optimize treatment protocols or develop new treatments, leading to new avenues for improving function in CP. The method to study microscopic muscle properties involves analysis of muscle biopsies (histological / immunohistochemistry analysis, SC and IC culture, gene expression). Biopsies will be collected using the minimally invasive percutaneous needle microbiopsy technique, suitable for collecting repeated samples over time in the same individual while still leading to sufficient tissue of good quality for subsequent analysis1,2. For the children with CP, the local hospital's tradition of applying general anesthesia for delivering BTX injections will be exploited to collect the muscle samples prior to the BTX session and the one-year follow-up, or general anesthesia planned for orthopedic surgery or diagnostic imaging such as MRI, etc. For the collection of the samples 3 months before the BTX session, as well as 3 months and 6 months after BTX injections, the common approach for microbiospy collection will be applied, with local sedation on the skin (Rapydan©) and fascia (Xylocaine©) and local anesthesia by using Kalinox© (nitrous oxide in oxygen) under supervision of the University Hospital PROSA team. Biopsies of TD muscles will be collected in children with no history of neurological disorder, nor musculoskeletal problems at the level of the gastrocnemius or semitendinosus, at the time of upper limb orthopedic or trauma surgery and thus always under general anesthesia. Ultrasound guided percutaneous muscle biopsy has been performed in children (2 months-18 years)3,4 and has proven to be safe and well-tolerated. A pilot study (S61110) was conducted to confirm that the microbiopsy technique is suitable for the analysis of microscopic muscle properties and is well-tolerated in children with CP. Two specific research goals are planned, with hypotheses emerging from literature.