Botulinum toxin A for nonambulatory children with cerebral palsy: a double blind randomized controlled trial.

OBJECTIVES: To examine the efficacy and safety of intramuscular botulinum toxin A (BoNT-A) to reduce spasticity and improve comfort and ease of care in nonambulant children with cerebral palsy (CP). STUDY DESIGN: Nonambulant children with CP (n = 41; Gross Motor Function Classification System level IV = 3, level V = 38; mean age 7.1 years, range 2.3-16 years, 66% male) were randomly allocated to receive either intramuscular BoNT-A injections (n = 23) or sham procedure (n = 18) combined with therapy. The analysis used generalized estimating equations with primary outcome the Canadian Occupational Performance Measure (COPM) at 4 weeks postintervention and retention of effects at 16 weeks. Adverse events (AE) were collected at 2, 4, and 16 weeks by a physician masked to group allocation. RESULTS: There were significant between group differences favoring the BoNT-A-treated group on COPM performance at 4 weeks (estimated mean difference 2.2, 95% CI 0.8, 3.5; P = .002) and for COPM satisfaction (estimated mean difference 2.2, 95% CI 0.5, 3.9; P = .01). These effects were retained at 16 weeks for COPM satisfaction (estimated mean difference 1.8, 95% CI 0.1, 3.5; P = .04). There were more mild AE at 4 weeks for the BoNT-A group (P = .002), however, there were no significant between-group differences in the reporting of moderate and serious AE. CONCLUSIONS: In a double-blind randomized sham-controlled trial, intramuscular BoNT-A and therapy were effective for improving ease of care and comfort for nonambulant children with CP. There was no increase in moderate and severe AE in the children who had BoNT-A injections compared with the sham group.

Evaluation of the effects of botulinum toxin A injections when used to improve ease of care and comfort in children with cerebral palsy whom are non-ambulant: a double blind randomized controlled trial.

BACKGROUND: Children with cerebral palsy (CP) whom are non-ambulant are at risk of reduced quality of life and poor health status. Severe spasticity leads to discomfort and pain. Carer burden for families is significant. This study aims to determine whether intramuscular injections of botulinum toxin A (BoNT-A) combined with a regime of standard therapy has a positive effect on care and comfort for children with CP whom are non-ambulant (GMFCS IV/V), compared with standard therapy alone (cycle I), and whether repeated injections with the same regime of adjunctive therapy results in greater benefits compared with a single injecting episode (cycle II). The regime of therapy will include serial casting, splinting and/or provision of orthoses, as indicated, combined with four sessions of goal directed occupational therapy or physiotherapy. METHOD/DESIGN: This study is a double blind randomized controlled trial. Forty participants will be recruited. In cycle I, participants will be randomized to either a treatment group who will receive BoNT-A injections into selected upper and/or lower limb muscles, or a control group who will undergo sham injections. Both groups will receive occupational therapy and /or physiotherapy following injections. Groups will be assessed at baseline then compared at 4 and 16 weeks following injections or sham control. Parents, treating clinicians and assessors will be masked to group allocation. In cycle II, all participants will undergo intramuscular BoNT-A injections to selected upper and/or lower limb muscles, followed by therapy.The primary outcome measure will be change in parent ratings in identified areas of concern for their child's care and comfort, using the Canadian Occupational Performance Measure (COPM). Secondary measures will include the Care and Comfort Hypertonicity Scale (ease of care), the Cerebral Palsy Quality of Life Questionnaire (CP QoL-Child) (quality of life), the Caregiver Priorities and Child Health Index of Life with Disabilities Questionnaire (CPCHILD©) (health status) and the Paediatric Pain Profile (PPP) (pain). Adverse events will be carefully monitored by a clinician masked to group allocation. DISCUSSION: This paper outlines the theoretical basis, study hypotheses and outcome measures for a trial of BoNT-A injections and therapy for children with non-ambulant CP. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry:N12609000360213.

Exploring functional outcomes and allied health staffing levels in an inpatient paediatric rehabilitation unit.

PURPOSE: This study provides data from a paediatric tertiary hospital on the length of stay, functional improvement and allied health workload for children and adolescents on active inpatient rehabilitation programs. METHODS: An audit was conducted of records of patients managed through an inpatient rehabilitation program at a 359 bed tertiary children's hospital in Brisbane, Australia between December 2014 and December 2015. Data relating to diagnosis, length of stay, functional change, occasions of allied health service and hours of patient attributable allied health professional time were collected. RESULTS: Data on 94 children and adolescents with a total of 102 rehabilitation episodes of care were sourced. The greatest average length of stay was for the "Stroke" group. The highest average allied health professional contact hours were for the "Brain Dysfunction - Traumatic" group. The greatest average functional change was observed in the "Brain Dysfunction- Traumatic group." Physiotherapy accounted for the largest proportion of allied health professional service time, with an average of 32% of total time. CONCLUSIONS: This review from a tertiary hospital-based inpatient paediatric rehabilitation service provides information regarding the length of stay, functional change and allied health workload for children and adolescents on active inpatient rehabilitation programs. As expected, total and rehabilitation episode length of stay, functional improvement and allied health contact and input varied according to diagnostic groups. This information is likely to be of value to other Paediatric Rehabilitation Medicine inpatient units when developing staffing for services and benchmarking service delivery. Implications for Rehabilitation Paediatric Rehabilitation Medicine supports children and adolescents to achieve the highest level possible of physical, cognitive, psychological and social functioning following accident or injury. There are little data in the literature to inform the optimal allied health staffing levels required for intensive inpatient multidisciplinary for children and adolescents suffering acquired neurological impairments. Data from this tertiary hospital-based paediatric inpatient rehabilitation program provide information on the length of stay, functional improvement and allied health professional contact for patients across broad diagnostic groupings. This information is useful for other paediatric rehabilitation services when planning for allied health staffing in service development.

Australian children undergoing selective dorsal rhizotomy: protocol for a national registry of multidimensional outcomes.

INTRODUCTION: Selective dorsal rhizotomy (SDR) is a neurosurgical intervention intended to permanently reduce spasticity in the lower limbs and improve mobility in selected children with cerebral palsy (CP). Despite SDR having been performed worldwide for the past 30 years, there is moderate quality of evidence that SDR is effective in reducing spasticity with low to very low evidence of its effectiveness in improving gait, function and participation, using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system. Published studies have described outcomes for groups that differ in selection, surgical technique and postoperative rehabilitation making it difficult for clinicians to use this information to advise families on best management. There is substantial community interest in SDR. A small number of children with CP undergo SDR in Australia each year and some families seek the intervention at international sites. Capturing clinical outcomes and adverse event (AE) data for Australian children undergoing SDR will provide clinicians with information to help guide families considering SDR. METHODS AND ANALYSIS: The Australian SDR Research Registry is a national registry of multidimensional outcomes for Australian children undergoing SDR in an Australian or overseas centre. Data will be collected for up to 10 years following the surgery, to include surgery and admission details, surgical and long-term AEs, and outcome measures across the body structure and functions, activity and participation domains of the International Classification of Functioning, Disability and Health. Data will be collected at baseline, during inpatient admission and at 1, 2, 5 and 10 years post. The aim of collecting these data is to improve understanding of short-, medium- and long-term outcomes and adverse effects of the intervention. ETHICS AND DISSEMINATION: This study was approved by the individual Human Research and Ethics committees at the five Australian tertiary hospitals involved. Results will be disseminated via peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: ACTRN12618000985280; Pre-results.

Safety of Botulinum Toxin Type A for Children With Nonambulatory Cerebral Palsy.

OBJECTIVE: To determine safety of intramuscular botulinum toxin A (BoNT-A) injections to reduce spasticity and improve care and comfort of nonambulatory children with cerebral palsy (CP). METHODS: Nonambulatory children with CP were randomly allocated to receive either BoNT-A (n = 23) or sham procedure (n = 18) in Cycle 1. In Cycle 2, the BoNT-A group received a second episode of BoNT-A (n = 20) and sham group received their first episode of BoNT-A (n = 17). A pediatric rehabilitation specialist masked to group allocation graded each adverse event (AE) according to system, severity (mild, moderate, serious, sentinel) and causality (unlikely/unrelated; possible; probable/definite). RESULTS: There was no difference for all moderate/serious AEs between the BoNT-A and sham/control groups in either Cycle 1 (incident rate ratio = 1.30, 95% confidence interval = 0.43-4.00; P = .64) or Cycle 2 (incident rate ratio = 0.72, 95% confidence interval = 0.30-1.75; P = .47). In Cycle 2, 1 serious, 3 moderate (single-episode group), and 24 mild (single-episode group n = 10; 2 episode group n = 14) AEs were probably/definitely related to BoNT-A. CONCLUSIONS: Children receiving BoNT-A were at no greater risk of moderate/serious AEs compared with a sham control procedure. There was no increased risk of moderate/serious AEs between one and two episodes of BoNT-A.

Combined pituitary hormone deficiency in Australian children: clinical and genetic correlates.

OBJECTIVE: Mutations in the gene for the POU domain transcription factor POU1F1 (human Pit-1) have been reported in patients with GH, TSH and PRL deficiencies. PROP1 (Prophet of Pit-1) gene mutations also cause gonadotrophin deficiencies and in some cases partial ACTH deficiency. This study analyses the POU1F1 and PROP1 genes in a cohort of Australian children with combined pituitary hormone deficiency (CPHD) and correlates results with patient phenotype. PATIENTS AND DESIGN: Genomic analysis was carried out on 33 patients with CPHD referred from centres around Australia. Clinical data were collected from medical records and referring physicans. RESULTS: POU1F1 mutations were identified in two of four patients with a suggestive phenotype. In a female patient, novel compound heterozygous POU1F1 mutations were identified: Arg143Leu in exon 3 and Leu194Gln in exon 4. This patient presented with failure to thrive at 6 weeks of age and has deficiencies of TSH and GH. A previously described heterozygous Arg271Trp mutation in exon 6 of the POU1F1 gene was identified in a female infant who presented with growth failure and was diagnosed with TSH then GH deficiencies. No PROP1 mutations were identified; however, we describe a number of previously unreported PROP1 polymorphisms. No patients presenting with deficiencies of all anterior pituitary hormones early in life had POU1F1 or PROP1 gene mutations. CONCLUSIONS: In 33 Australian children with CPHD we have identified POU1F1 mutations in two patients and no PROP1 mutations. We speculate that in the majority of children other genes must be responsible for the CPHD phenotype.