Feasibility Nutritional Supplements for Muscle Growth in CP

Cerebral palsy (CP) is the largest cause of childhood physical disability, with a prevalence of 2 to 3 per 1000 live births. While the disorder is caused by a non-progressive lesion in the developing brain, musculoskeletal alterations progress with age. The observed neuromuscular symptoms mainly involve spasticity and muscle weakness. Macroscopic lower limb muscle properties in CP, i.e. reduced muscle volume, length, anatomical cross-sectional area (CSA), and fiber CSA, have been reported, providing convincing evidence for impaired muscle growth in children with CP, already at young ages. Nutritional supplements may improve muscle strength and cause muscle hypertrophy. Within the muscle, protein synthesis depends on the availability of the branched chain amino acids (BCAA), and mainly on the presence of leucine. This stimulatory effect is thought to be primarily mediated by the upregulation of mRNA translation via enhanced signaling through the mTOR pathway. BCAA or leucine supplements have been widely used to improve muscle strength and achieve hypertrophy. In paediatric CP groups, such muscular effect of nutritional supplementation on macroscopic intrinsic muscle properties (i.e. muscle volume, anatomical CSA and muscle belly length) has not yet been studied. Therefore, a feasibility study will be carried out to investigate the feasibility of a 10-week plan with a nutritional supplement (leucine) and to perform pilot analyses on the effect of leucine on macroscopic muscle morphology in five children with cerebral palsy. This feasibility study will provide proof of concept of the administration plan of the leucine supplement and of the study design. Additionally, it will provide data for power analyses, that will be used in a future comprehensive study, investigating the effect of leucine on macroscopic muscle properties in children with cerebral palsy. To cover safety issues blood and urine sampling will be performed to objectify the patient's nutritional state and to exclude underlying disorders that would contraindicate the use of protein supplements.

Inclusion criteria

Spastic Cerebral Palsy (diagnosed by a neuro-pediatrician from the CP Reference Centre of the University Hospital Leuven)

• Uni- of bilateral involvement
• Level II or III on the Gross Motor Function Classification System (GMFCS)
• Muscle volume for the medial gastrocnemius (target muscle) of at least 20% compared to the expected muscle volume in age-matched typically developing children

Exclusion criteria

• Presence of dyskinesia or ataxia
• Severe co-morbidities
• Botulinum toxin treatment ten months prior to assessment
• Previous orthopedic or neurosurgery
• Severe ankle deformities preventing fitting in test positions
• Ankle range of motion (ROM) <30% of normal values