The effects of botulinum toxin injection frequency on calf muscle growth in young children with spastic cerebral palsy: A 12-month prospective study

Abstract

Purpose This study was a 12-month prospective investigation of changes in the medial gastrocnemius (MG) muscle morphology in children aged 2-5 years with spastic cerebral palsy (CP) who had received no previous intramuscular injections of botulinum neurotoxin type-A (BoNT-A) and were randomised to receive either single or multiple (three) BoNT-A injections to the gastrocsoleus. MG morphological changes were compared to age-matched typically developing (TD) peers. Methods Thirteen children with spastic CP with a mean age of 45 (15) months and 18 TD children with a mean age of 48 (14) months participated in the study. The principal outcome measures were MG muscle volume, fascicle length, pennation angle and physiological cross-sectional area (PCSA), which were obtained using 2D and 3D ultrasound.Results The single and multiple injection frequency groups significantly increased MG muscle volume at 12 months relative to the baseline by 13 and 15 %, respectively. There were no significant differences in the MG muscle volume 28.5 (12.3) versus 30.3 (3.8) ml, fascicle length 48.0 (10.4) versus 44.8 (1.2) mm or PCSA 7.0 (1.2) versus 6.6 (1.7) cm 2 between the single and multiple injection groups, respectively, at 12 months follow-up. The change in MG muscle volume in the single and multiple injection groups was significantly lower than the TD peers by 66 and 60 %, respectively. Interpretation In young children with spastic CP, naive to BoNT-A treatment, MG muscle growth over 12 months does not appear to be influenced by intramuscular BoNT-A injection frequency. However, MG muscle growth in the spastic CP groups was significantly lower than the agematched TD peers. It is unclear whether this is an effect of intramuscular BoNT-A injections or reduced growth rates in children with spastic CP in general. 123J Child Orthop (2013) 7:425-433 DOI 10.1007 investigations and longitudinal studies with multiple measurement time points are required in order to determine the influence of BoNT-A treatment on muscle physiological and mechanical growth factors in young children with spastic CP.

Medial gastrocnemius muscle volume in ambulant children with unilateral and bilateral cerebral palsy aged 2 to 9 years

“…5 Muscle development begins during gestation with maturation of skeletal muscle cells and growth in muscle fibre girth, length, and number continuing until shortly after birth. 11 The change in medial gastrocnemius muscle volume in the CP groups was significantly lower than the growth rate of CTD, at 0.9 mL/month. 9 In a review, Gough and Shortland 10 have outlined a number of possible factors that influence muscle fibre size and muscle protein synthesis and degradation in children with CP.…”

“…Intramuscular BoNT-A causes atrophy in animal and human muscle 31,32 and concerns about the possible adverse effect of BoNT-A on muscle development in children with CP have been previously expressed. 11 Smaller muscles in children with CP compared with CTD may be the result of a reduced number and/or size of muscle fibres that constitute the muscle and also influenced by muscle connective tissue and fat content. Our findings provide evidence that the calf muscles of children with CP experience growth during periods of intramuscular BoNT-A injections, however, the influence of number and timing of injections on muscle growth remains unknown and differences in recovery response of calf muscle volume in UCP and BCP cannot be discounted.…”

“…11,16 Freehand 3D ultrasound has been shown to demonstrate high accuracy (1.1% [3.8] difference in muscle volume compared with magnetic resonance imaging) and high reliability across repeated scans and segmentation (intraclass correlation coefficient>0.99) for the assessment of muscle volume. 11,16 Freehand 3D ultrasound has been shown to demonstrate high accuracy (1.1% [3.8] difference in muscle volume compared with magnetic resonance imaging) and high reliability across repeated scans and segmentation (intraclass correlation coefficient>0.99) for the assessment of muscle volume.…”

“…11,16 Freehand 3D ultrasound has been shown to demonstrate high accuracy (1.1% [3.8] difference in muscle volume compared with magnetic resonance imaging) and high reliability across repeated scans and segmentation (intraclass correlation coefficient>0.99) for the assessment of muscle volume. 11 Freehand 3D ultrasound involves combining two-dimensional ultrasound images of the transverse plane of the muscle with 3D motion data to reconstruct the muscle volume in 3D. 11 Freehand 3D ultrasound involves combining two-dimensional ultrasound images of the transverse plane of the muscle with 3D motion data to reconstruct the muscle volume in 3D.…”

“…9 From early childhood to adulthood the increase in muscle size is primarily caused by hypertrophy which, to a large extent, is predetermined genetically but may, in part, be associated with the function or intensity of workload that the muscle is exposed to during growth. 11 Although other studies have not examined muscle growth in children with CP directly, in a cross-sectional study medial gastrocnemius muscle volume has been shown to increase by 17% one year after gastrocnemius recession surgery in children with bilateral CP (BCP) (n=7). With limited information about muscle growth mechanisms from human studies and fewer from studies of children with CP, much of the available information was drawn from animal studies.…”