The Efficacy of Repeat Botulinum Toxin Injections in the Management of Spasticity in Children and Young Adults with Cerebral Palsy: A Systematic Review
Background: Botulinum toxin (BT) is a common treatment intervention for the management of spasticity in children with Cerebral Palsy (CP). There are no national or internationally recognised clinical guidelines that provide clear information about the recommended frequency of repeat doses of BT and there are inconsistencies in clinical practice. The primary aim of this review was to determine the efficacy of repeat BT injections in the management of clinical outcomes in children with CP. The secondary aim was to compare the efficacy findings with the current National Institute for Health and Care Excellence (NICE) clinical guidelines to determine if the guidelines incorporate evidence-based recommendations concerning the timing and frequency of botulinum toxin injections.
Method: A systematic literature search was conducted across five databases to identify relevant articles. Eligibility criteria included participants aged between birth to 21 years old at time of enrolment, clinical diagnosis of CP, presence of spasticity, treatment intervention of two or more BT treatments, and a comparison intervention of either a different frequency of BT, other interventions, or no BT treatment. Three independent reviewers identified eligible studies. Nineteen randomised controlled trials (RCTs) and 17 observational studies met the inclusion criteria, and the 19 RCTs were analysed in this project. Study characteristics and findings were extracted, and methodological quality was assessed using Version 2 of the Cochrane risk-of-bias tool for randomised controlled trials (RoB 2). A descriptive analysis was performed to assess outcomes and determine the efficacy of i) different frequencies of repeat BT injections, ii) repeated BT versus no BT, and iii) repeated BT versus other interventions.
Results: A higher frequency of BT (4-monthly versus 12-monthly) resulted in significant short-term improvements in gait and adverse events were found to be twice as frequent. Reduced frequency of BT was found to improve outcomes in occupational performance when compared to OT only. Repeated BT compared with placebo injection resulted in improvements in gait and active ROM. Repeated BT compared with other interventions such as BT only, OT only or surgical intervention resulted in significant improvements in ROM and spasticity.
Implications: The findings of this review provide evidence to support repeated BT improves spasticity, ROM and gait in the short-term only when compared to physiotherapy (PT) only, OT only or placebo injection. The recommended treatment frequency of BT is 12-monthly when the goal is to improve ROM and spasticity and 4-monthly when goal is to improve gait in the short-term only. Seven future recommendations suggest additional guidelines and changes to current NICE guidelines for translation to clinical practice. Future studies to investigate the long-term effectiveness of repeated BT in children with CP is required ensuring findings capture health related quality of life (HRQL) as a measure of participation.