Current Australian clinical practice in use of botulinum toxin-A to manage paediatric hypertonicity.

AIM: To describe current rehabilitation paediatricians' use of intramuscular botulinum toxin-A (BoNT-A) to manage hypertonicity. METHODS: Cross-sectional survey. RESULTS: In late 2019, 32 of the 35 identified Australian rehabilitation paediatricians who use BoNT-A to manage paediatric hypertonicity completed the survey. Annually, they administer just over 3750 courses of BoNT-A to manage hypertonicity with a mean of 11 years of clinical experience. Sedation was used by all but 1 clinician who used a number of other strategies during the procedure. Mean (and median) maximum dose of OnabotulinumtoxinA (Botox) was 400 Units (range 300-450 Units). Only three clinicians indicated that they used AbobotulinumtoxinA (Dysport) - the other BoNT-A preparation approved for children available in Australia; analysis of its use was not performed. Dose modifications were made by clinicians according to a patient's response to a previous course of BoNT-A (88% of respondents); patient experience of a previous adverse event (78%); history of aspiration or dysphagia (65 and 63%, respectively); and the presence of dystonia; and where the patient was GMFCS level V (53% each). Intervals between courses ranged from 3 to 24 months with the variation due to clinical circumstances. CONCLUSION: Clinical practice in BoNT-A management of paediatric hypertonicity was largely consistent in regard to maximum doses of OnabotulinumtoxinA (Botox) used. Dose modification and time between injection courses varied according to individual clinical presentation. Procedural sedation was used extensively.

Systemic adverse events after botulinum neurotoxin A injections in children with cerebral palsy.

AIM: To identify factors that increase the likelihood of systemic adverse events after botulinum neurotoxin A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A prospective observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Occurrences of systemic adverse events, defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death were determined at follow-up. The relationship between systemic adverse events and eight preinjection variables (age, Gross Motor Function Classification System [GMFCS] level, history of dysphagia, gastrostomy, aspiration pneumonia, recent history of illness, BoNT-A dose, and type of sedation) were examined using univariable and multivariable logistic regression with generalized estimating equations methods. RESULTS: In total 591 children underwent 2219 injection episodes with follow-up in 2158 (97%) cases. Systemic adverse events were reported in 77 (3.6%) injection episodes. Univariable analysis suggested that GMFCS levels IV and V, a history of dysphagia, gastrostomy, aspiration pneumonia, and increasing BoNT-A dose increase the likelihood of systemic adverse events. In multivariable analysis, a history of dysphagia (odds ratio [OR] 3.42) and/or aspiration pneumonia (OR 2.31) remained associated with increased likelihood of systemic adverse events. INTERPRETATION: A history of dysphagia and/or aspiration pneumonia are the factors that most increase the likelihood of systemic adverse events after BoNT-A. WHAT THIS PAPER ADDS: Systemic adverse events occur in 3.6% of botulinum neurotoxin A (BoNT-A) injection episodes. Dysphagia and/or aspiration pneumonia are associated with increased likelihood of systemic adverse events. Multivariable models showed no evidence of association between Gross Motor Function Classification System and systemic adverse events. Multivariable models showed no evidence of association between BoNT-A dose and systemic adverse events.

Severity of cerebral palsy and likelihood of adverse events after botulinum toxin A injections.

AIM: To determine the incidence of common adverse events after botulinum toxin A (BoNT-A) injections in children with cerebral palsy (CP) and to identify whether the severity of CP influences the incidence of adverse events. METHOD: This was an observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Data examined included procedural adverse events at the time of injection and at follow-up. Systemic adverse events were defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death. Severity of CP was categorized by the Gross Motor Function Classification System (GMFCS). The relationships between GMFCS and adverse events were analysed using negative binomial regression models. RESULTS: In total, 591 children underwent 2219 injection episodes. Adverse events were reported during the procedure (130 [6%] injection episodes) and at follow-up (492 [22%] injection episodes). There were significantly increased rates of systemic adverse events in injection episodes involving children in GMFCS level IV (incidence rate ratio [IRR] 3.92 [95% confidence interval] 1.45-10.57]) and GMFCS level V (IRR 7.37 [95% confidence interval 2.90-18.73]; p<0.001). INTERPRETATION: Adverse events after BoNT-A injections are common but mostly mild and self-limiting. Children in GMFCS levels IV and V are at increased risk of systemic adverse events. The relationship between CP severity and BoNT-A adverse events is complex and further research is required to better understand this relationship. WHAT THIS PAPER ADDS: Adverse events reported at the time of botulinum toxin A injection occurred in 6% of injection episodes. Adverse events were reported at follow-up in 22% of injection episodes. Children in Gross Motor Function Classification System (GMFCS) levels IV and V have increased rates of systemic adverse events. Children in GMFCS levels IV and V report less local weakness and pain.

Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy.

AIM: The aim of this study was to assess changes in health status before and after, as well as adverse events after, botulinum toxin type A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A total of 334 children (190 male; 144 female) aged 1y 6mo to 19y 4mo (mean 9y 2mo, SD 4y) with CP who were undergoing BoNT-A injections (596 injection courses in total) were clinically audited over a 16-month period. Of the 334 children, 62 were classified at Gross Motor Function Classification System (GMFCS) level I, 52 of whom had unilateral CP and 10 of whom had bilateral CP. Eighty-six children were classified at GMFCS level II, 39 of whom had unilateral CP and 47 of whom had bilateral CP. Forty-four children were classified at GMFCS level III, two of whom had unilateral CP and 42 of whom had bilateral CP. Sixty-six of the 334 children were classified at GMFCS level IV and 76 as level V. All the children classified as level IV or V had bilateral involvement. The health status of the children in the month before and a prospective audit of health status and adverse events in the month after BoNT-A injections were examined in order to assess the effects of the toxin. RESULTS: The data gathered for the month before administration of BoNT-A indicated that children with CP had significant background morbidities. After injection of BoNT-A, adverse events occurred in 23.2% of children. All adverse events were temporary and there were no deaths. INTERPRETATION: The results of this audit indicate that there is insufficient evidence to warrant restriction of the administration of BoNT-A in children with CP at any GMFCS level in our service.

Functional outcomes of intramuscular botulinum toxin type a and occupational therapy in the upper limbs of children with cerebral palsy: a randomized controlled trial.

OBJECTIVE: To investigate the functional outcomes of botulinum toxin type A (BTX-A) injections to the upper limb in combination with occupational therapy (OT) in children with cerebral palsy (CP). DESIGN: Randomized controlled trial with follow-up at 2 weeks, 3 months, and 6 months. SETTING: Specialist outpatient physical disabilities clinic within a public pediatric teaching hospital. PARTICIPANTS: Eighty children with spastic quadriplegic, triplegic, or hemiplegic CP from these clinics were randomly assigned to BTX-A plus OT, BTX-A alone, OT alone, or a no-treatment control group. INTERVENTIONS: Single set of BTX-A (Botox) injections and 12 weeks of OT. MAIN OUTCOME MEASURES: Canadian Occupational Performance Measure (COPM) and Goal Attainment Scale (GAS). RESULTS: The combination of BTX-A and OT resulted in accelerated attainment of functional goals measured by the COPM and GAS. There were no differences between groups on the Melbourne Assessment of Unilateral Upper Limb Function, Quality of Upper Extremity Skills Test, Pediatric Evaluation of Disability Inventory, Child Health Questionnaire, or active and passive range of motion. As expected, there was a significant reduction in muscle tone at follow-up 2 weeks after injection, which returned to baseline level by 6 months. CONCLUSIONS: OT enhanced individualized functional outcomes following BTX-A injections in the upper limbs of children with CP.

Functional outcomes of intramuscular botulinum toxin type A in the upper limbs of children with cerebral palsy: a phase II trial.

OBJECTIVE: To describe the functional and family-centered assessment protocol and outcomes of a phase II trial evaluating upper-limb function after botulinum toxin injections in children with cerebral palsy (CP). DESIGN: Intervention study, case series, phase II trial, follow-up at 2 weeks and 3 and 6 months. SETTING: Specialist outpatient physical disabilities clinic within a public pediatric teaching hospital. PARTICIPANTS: Convenience sample of 16 children with CP (age range, 2-12y). INTERVENTIONS: Botulinum toxin type A (Botox) injections after electrical stimulation localization of appropriate muscle. MAIN OUTCOME MEASURES: The Canadian Occupational Performance Measure (COPM), Goal Attainment Scale (GAS), Melbourne Assessment of Unilateral Upper Limb Function, Child Health Questionnaire (CHQ), parent questionnaire, Modified Ashworth Scale (MAS), Tardieu scale, and active (AROM) and passive (PROM) range of motion. RESULTS: On the COPM, there was significant improvement at 3 months and 6 months. On the GAS, the T-scores were 42 and 47 at 3 and 6 months, respectively. On the Melbourne Assessment and CHQ, there was no significant change. The parent questionnaire indicated acceptability of injections and positive outcomes. On the MAS, there was a significant reduction in tone at 2 weeks, with a return to baseline by 6 months. On the Tardieu scale, there was a significant increase in angle of first catch at 2 weeks, but only the elbow maintained a significant difference at 3 and 6 months. No significant change was found for AROM or PROM. CONCLUSIONS: Sustained functional outcomes occurred after botulinum toxin injections despite increasing muscle tone after an initial reduction in tone. Randomized controlled trials are required.