Botulinum Toxin Intervention in Cerebral Palsy-Induced Spasticity Management: Projected and Contradictory Effects on Skeletal Muscles

Abstract

Spasticity, following the neurological disorder of cerebral palsy (CP), describes a pathological condition, the central feature of which is involuntary and prolonged muscle contraction. The persistent resistance of spastic muscles to stretching is often followed by structural and mechanical changes in musculature. This leads to functional limitations at the respective joint. Focal injection of botulinum toxin type-A (BTX-A) is effectively used to manage spasticity and improve the quality of life of the patients. By blocking acetylcholine release at the neuromuscular junction and causing temporary muscle paralysis, BTX-A aims to reduce spasticity and hereby improve joint function. However, recent studies have indicated some contradictory effects such as increased muscle stiffness or a narrower range of active force production. The potential of these toxin- and atrophy-related alterations in worsening the condition of spastic muscles that are already subjected to changes should be further investigated and quantified. By focusing on the effects of BTX-A on muscle biomechanics and overall function in children with CP, this review deals with which of these goals have been achieved and to what extent, and what can await us in the future.

Keywords: active muscle; botulinum toxin; cerebral palsy; muscle biochemistry; muscle morphology; muscle structure; passive muscle; spastic muscle; spasticity management.

Figure 1

Passive muscle properties of rat hindlimb muscles are illustrated based on [159,160,161,190,192,193]. (a) Increases in passive (i.e., resting) state muscle forces in BTX-A exposed muscles compared with those of the control group The bars indicate that passive state forces increase in different percentages at different muscle lengths, and maximal increments are presented. EDL: extensor digitorum longus; NS indicates changes are non-significant. (b) Intramuscular collagen amounts of both BTX-A exposed and control group muscles. Data for both the injected and non-injected but diffused muscles due to the spread of the toxin are illustrated. The dotted shaded graph areas represent the studies in which the amount of collagen was quantitatively measured, whereas, in other areas, the percentages of ECM presented relative to fiber content.

Figure 2

Active muscle properties of rat hindlimb muscles are illustrated based on [159,160,161,190,192,193]. (a) Decreases in active state muscle forces in BTX-A exposed muscles compared with those of the control group. The bars indicate that active state forces decrease in different percentages at different muscle lengths. EDL: extensor digitorum longus. (b) The muscle length range of force exertion of both BTX-A exposed and control group muscles. Data for both the injected and non-injected but diffused muscles due to the spread of the toxin are illustrated. NS indicates that changes are non-significant.