Reduced Cross-Sectional Muscle Growth Six Months after Botulinum Toxin Type-A Injection in Children with Spastic Cerebral Palsy

Abstract

Botulinum Neurotoxin type-A (BoNT-A) injections are widely used as first-line spasticity treatment in spastic cerebral palsy (SCP). Despite improved clinical outcomes, concerns regarding harmful effects on muscle morphology have been raised. Yet, the risk of initiating BoNT-A to reduce muscle growth remains unclear. This study investigated medial gastrocnemius (MG) morphological muscle growth in children with SCP (n = 26, median age of 5.2 years (3.5)), assessed by 3D-freehand ultrasound prior to and six months post-BoNT-A injections. Post-BoNT-A MG muscle growth of BoNT-A naive children (n = 11) was compared to (a) muscle growth of children who remained BoNT-A naive after six months (n = 11) and (b) post-BoNT-A follow-up data of children with a history of BoNT-A treatment (n = 15). Six months after initiating BoNT-A injection, 17% decrease in mid-belly cross-sectional area normalized to skeletal growth and 5% increase in echo-intensity were illustrated. These muscle outcomes were only significantly altered when compared with children who remained BoNT-A naive (+4% and -3%, respectively, p < 0.01). Muscle length growth persevered over time. This study showed reduced cross-sectional growth post-BoNT-A treatment suggesting that re-injections should be postponed at least beyond six months. Future research should extend follow-up periods investigating muscle recovery in the long-term and should include microscopic analysis.

Keywords: 3D freehand ultrasound; botulinum neurotoxin type-A; muscle growth rate; spastic cerebral palsy.

Figure 1

Schematic overview of the research aims. BoNT-A, botulinum neurotoxin type-A.

Figure 2

Scatter dot plot with median, interquartile range and individual values of (A) the change in muscle volume and (B) change in the normalized muscle volume (normalized to product for body mass and length) for the botulinum neurotoxin type-A (BoNT-A) naive treatment (triangls) and BoNT-A naive untreated group (squares). mL, milliliter; kg, kilogram; cm, centimeter.

Figure 3

Scatter dot plot with median, interquartile range and individual values of the muscle volume growth rate during follow-up for the botulinum neurotoxin type-A (BoNT-A) naive treatment (triangles) and BoNT-A untreated group (squares). Muscle growth rate was calculated as ratio of change in muscle volume (milliliter) per time of follow-up (months). mL, milliliter; mo, months.

Figure 4

Scatter dot plot with median, interquartile range and individual values of (A) the change in normalized muscle volume (normalized to product of body mass and length), (B) change in the normalized anatomical cross-sectional area (normalized to body mass) and (C) growth rate during follow-up for the botulinum neurotoxin type-A (BoNT-A) naive treatment (triangles) and BoNT-A not-naive treatment group (dots). mL, milliliter; kg, kilogram; cm, centimeter; mm, millimeter; mo, months.

Figure 5

Schematic representation of the main findings in the current stud. On top (A), the medial gastrocnemius muscle of typically developing (TD) children is represented including the key morphological outcomes: muscle–tendon unit complex length (MTUL), tendon length (TL), muscle belly length (ML) and anatomical cross-sectional area (aCSA). The latter is represented separately using circle areas for clarity. The echo-intensity is represented with a pattern fill of the aCSA. Below (B), the comparison in outcomes prior to and six months after BoNT-A injection is shown for the botulinum neurotoxin type-A (BoNT-A) naive treatment group indicating the reduced aCSA and increased muscle lengths. At the bottom, the comparison in outcomes over six months follow-up for the BoNT-A naive children who remained treatment naive is shown, indicating increased cross-sectional and longitudinal muscle growth.