Effect of Active Motor Learning Interventions on Gross Motor Function and Mobility in Children Aged 2 to 6 Years With Bilateral Cerebral Palsy: A Systematic Review and Meta-analysis.

PURPOSE: The purpose of this systematic review is to identify evidence-based interventions to promote active motor learning in children aged 2 to 6 years with bilateral cerebral palsy. SUMMARY OF KEY POINTS: Seven randomized clinical trials of active motor learning interventions targeting gross motor function and mobility were included. Two studies compared context-focused therapy to child-focused therapy. Five studies compared active motor therapy to usual care. Context-focused therapy, child-focused therapy, and active motor therapy were comparable to usual care to improve functional mobility and gross motor function. CONCLUSIONS AND RECOMMENDATIONS FOR CLINICAL PRACTICE: There are limited active intervention studies targeting gross motor function for young children with bilateral cerebral palsy. The authors recommend consideration of the clinical good practice guidelines, dosage parameters, and improved reporting methods when implementing active motor learning interventions targeting gross motor function and mobility for children with cerebral palsy.

Interventions to improve physical function for children and young people with cerebral palsy: international clinical practice guideline.

AIM: To provide recommendations for interventions to improve physical function for children and young people with cerebral palsy. METHOD: An expert panel prioritized questions and patient-important outcomes. Using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods, the panel assessed the certainty of evidence and made recommendations, with international expert and consumer consultation. RESULTS: The guideline comprises 13 recommendations (informed by three systematic reviews, 30 randomized trials, and five before-after studies). To achieve functional goals, it is recommended that intervention includes client-chosen goals, whole-task practice within real-life settings, support to empower families, and a team approach. Age, ability, and child/family preferences need to be considered. To improve walking ability, overground walking is recommended and can be supplemented with treadmill training. Various approaches can facilitate hand use goals: bimanual therapy, constraint-induced movement therapy, goal-directed training, and cognitive approaches. For self-care, whole-task practice combined with assistive devices can increase independence and reduce caregiver burden. Participation in leisure goals can combine whole-task practice with strategies to address environmental, personal, and social barriers. INTERPRETATION: Intervention to improve function for children and young people with cerebral palsy needs to include client-chosen goals and whole-task practice of goals. Clinicians should consider child/family preferences, age, and ability when selecting specific interventions.

A pilot feasibility study of gabapentin for managing pain in children with dystonic cerebral palsy.

BACKGROUND: Gabapentin is often used to manage pain in children with dystonic cerebral palsy, however the evidence for its effectiveness in this population is limited. The primary objective of this feasibility pilot study was to assess the factors which might impact on a future randomised controlled trial including the ability to recruit and retain participants, assess adherence/compliance to the prescribed intervention, and ability to complete all outcome assessments. The secondary objective was to gather preliminary evidence for the effectiveness of gabapentin at reducing pain, improving comfort and reducing dystonia in children with dystonic cerebral palsy. METHODS: This open label pilot study recruited children aged 5-18 years with dystonic cerebral palsy and accompanying pain affecting daily activities from four centres around Australia. Children were prescribed gabapentin for 12 weeks and were assessed at baseline, 6 weeks and 12 weeks. The primary outcome was feasibility of the protocol. Secondary outcomes were pain behaviour, pain intensity, care and comfort, individualised goal setting and dystonia severity. RESULTS: Thirteen children (mean age 10.4 years (SD 2.4yrs), 9 females) were recruited from 71 screened over 15 months. Two children withdrew while eight children experienced side effects. There were issues with adherence to medication dosage regimens and data collection. Improvements were seen in pain behaviour, comfort and pain related goals at 12 weeks. Dystonia was not significantly changed. CONCLUSIONS: Whilst gabapentin has potential to improve pain and comfort in children with dystonic CP, the feasibility of implementing a definitive randomised controlled trial is low. Alternative trials designs are required to further examine the effectiveness of gabapentin in this heterogeneous population. TRIAL REGISTRATION: The trial was registered with the Australian Clinical Trial Registry ( ACTRN12616000366459 ) on 22/03/2016 and the Therapeutic Goods Administration (CT-2016-CTN-00500-1) on 22/06/2016.

Brain magnetic resonance imaging is a predictor of bimanual performance and executive function in children with unilateral cerebral palsy.

AIM: To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP). METHOD: Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent). RESULTS: From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p<0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings. INTERPRETATION: Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than information processing.

La resonancia magnética cerebral es un predictor del rendimiento bimanual y la función ejecutiva en niños con parálisis cerebral unilateral OBJETIVO: Examinar la asociación entre las características de la resonancia magnética cerebral (RMN) y la función ejecutiva y el rendimiento bimanual en niños con parálisis cerebral unilateral (PC). MÉTODO: Los escáneres cerebrales de resonancia magnética clínica se clasificaron como: (1) patrón patológico predominante (normal, lesión de la sustancia blanca [WMI]; lesión de la materia gris; lesiones vasculares focales [FVI]; malformaciones; o varios); y (2) lesiones focales (ganglios frontales, basales y / o tálamo). Las evaluaciones incluyeron: (1) desempeño bimanual; (2) destreza unimanual; y (3) tareas de funciones ejecutivas (procesamiento de información, control de atención, flexibilidad cognitiva y fijación de objetivos) y calificaciones de comportamiento (padres). RESULTADOS: De 131 niños reclutados, 60 no fueron elegibles para el análisis, dejando 71 niños (47 varones, 24 mujeres) en la muestra final (edad media 9 años [DE 2 años], 6 años - 12 años 8 meses). Las RMN cerebrales fueron WMI (69%) y FVI (31%); y frontal (59%), talámico (45%), ganglios basales (37%) y ganglios basales más talámico (21%). El rendimiento bimanual fue menor en FVI versus WMI (p <0,003), y con lesiones frontales (p = 0,36), ganglios basales (p = 0,032) y talámicas / ganglios basales (p = 0,013). Aparte del procesamiento de la información, las tareas de la función ejecutiva no se asociaron con el patrón predominante. Las lesiones frontales predijeron el control de la atención (p = 0,049) y la flexibilidad cognitiva (p = 0,009) pero no el establecimiento de objetivos, el procesamiento de la información o las clasificaciones de comportamiento. INTERPRETACIÓN: La resonancia magnética cerebral clínica predice los resultados cognitivos y motores cuando se consideran las lesiones focales y los patrones de lesiones predominantes.

Imagem por ressonância magnética do cérebro como preditora do desempenho bimanual e função executiva de crianças com paralisia cerebral unilateral OBJETIVO: Examinar a associação entre as características do exame de imagem por ressonância magnética (IRM) e a função executiva e desempenho bimanual em crianças com paralisia cerebral (PC) unilateral. MÉTODO: Escaneamentos clínicos de IRM cerebrais foram classificados como: 1) padrão patológico predominante (normal, lesão da substância branca [LSB]; lesão da substância cinzenta; insultos vasculares focais [IVF]; malformações; ou outro); e (2) lesões focais (frontal, gânglios basais, e/ou tálamo). As avaliações incluíram: (1) desempenho bimanual; (2) destreza unimanual; e (3) tarefas de função executiva (processamento de informações, controle da atenção, flexibilidade cognitiva, e estabelecimento de metas) e pontuações comportamentais (pais). RESULTADOS: De 131 crianças recrutadas, 60 eram inelegíveis para análise, restando 71 crianças (47 do sexo masculino, 24 do sexo feminino) na amostra final (média de idade 9a [DP 2a], 6a-12a 8m). IRMs cerebrais eram do tipo LSB (69%) e IVFs (31%); e frontais (59%), talâmicas (45%), de gânglios da base (37%), e de gânglios da base mais talâmicas (21%). O desempenho bimanual foi menor em IVF versus LSB (p<0,003), e com lesões frontais (p=0,36), gânglios da base (p=0,032), e talâmicas/gânglios da base (p=0,013). Com exceção do processamento de informações, as tarefas da função executiva não foram associadas com o padrão predominante. Lesões frontais foram preditivas do controle da atenção (p=0,049) e flexibilidade cognitiva (p=,.009) mas não do estabelecimento de metas, processamento de informações, e pontuações comportamentais. INTERPRETAÇÃO: A IRM cerebral clínica prediz resultados cognitivos e motores quando lesões focais e padrões predominantes de lesão são considerados.

Constraint-induced movement therapy in children with unilateral cerebral palsy.

BACKGROUND: Unilateral cerebral palsy (CP) is a condition that affects muscle control and function on one side of the body. Children with unilateral CP experience difficulties using their hands together secondary to disturbances that occur in the developing fetal or infant brain. Often, the more affected limb is disregarded. Constraint-induced movement therapy (CIMT) aims to increase use of the more affected upper limb and improve bimanual performance. CIMT is based on two principles: restraining the use of the less affected limb (for example, using a splint, mitt or sling) and intensive therapeutic practice of the more affected limb. OBJECTIVES: To evaluate the effect of constraint-induced movement therapy (CIMT) in the treatment of the more affected upper limb in children with unilateral CP. SEARCH METHODS: In March 2018 we searched CENTRAL, MEDLINE, Embase, CINAHL, PEDro, OTseeker, five other databases and three trials registers. We also ran citation searches, checked reference lists, contacted experts, handsearched key journals and searched using Google Scholar. SELECTION CRITERIA: Randomised controlled trials (RCTs), cluster-RCTs or clinically controlled trials implemented with children with unilateral CP, aged between 0 and 19 years, where CIMT was compared with a different form of CIMT, or a low dose, high-dose or dose-matched alternative form of upper-limb intervention such as bimanual intervention. Primarily, outcomes were bimanual performance, unimanual capacity and manual ability. Secondary outcomes included measures of self-care, body function, participation and quality of life. DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts to eliminate ineligible studies. Five review authors were paired to extract data and assess risk of bias in each included study. GRADE assessments were undertaken by two review authors. MAIN RESULTS: We included 36 trials (1264 participants), published between 2004 and 2018. Sample sizes ranged from 11 to 105 (mean 35). Mean age was 5.96 years (standard deviation (SD) 1.82), range three months to 19.8 years; 53% male and 47% participants had left hemiplegia. Fifty-seven outcome measures were used across studies. Average length of CIMT programs was four weeks (range one to 10 weeks). Frequency of sessions ranged from twice weekly to seven days per week. Duration of intervention sessions ranged from 0.5 to eight hours per day. The mean total number of hours of CIMT provided was 137 hours (range 20 to 504 hours). The most common constraint devices were a mitt/glove or a sling (11 studies each).We judged the risk of bias as moderate to high across the studies. KEY RESULTS: Primary outcomes at primary endpoint (immediately after intervention)CIMT versus low-dose comparison (e.g. occupational therapy)We found low-quality evidence that CIMT was more effective than a low-dose comparison for improving bimanual performance (mean difference (MD) 5.44 Assisting Hand Assessment (AHA) units, 95% confidence interval (CI) 2.37 to 8.51).CIMT was more effective than a low-dose comparison for improving unimanual capacity (Quality of upper extremity skills test (QUEST) - Dissociated movement MD 5.95, 95% CI 2.02 to 9.87; Grasps; MD 7.57, 95% CI 2.10 to 13.05; Weight bearing MD 5.92, 95% CI 2.21 to 9.6; Protective extension MD 12.54, 95% CI 8.60 to 16.47). Three studies reported adverse events, including frustration, constraint refusal and reversible skin irritations from casting.CIMT versus high-dose comparison (e.g. individualised occupational therapy, bimanual therapy)When compared with a high-dose comparison, CIMT was not more effective for improving bimanual performance (MD -0.39 AHA Units, 95% CI -3.14 to 2.36). There was no evidence that CIMT was more effective than a high-dose comparison for improving unimanual capacity in a single study using QUEST (Dissociated movement MD 0.49, 95% CI -10.71 to 11.69; Grasp MD -0.20, 95% CI -11.84 to 11.44). Two studies reported that some children experienced frustration participating in CIMT.CIMT versus dose-matched comparison (e.g. Hand Arm Bimanual Intensive Therapy, bimanual therapy, occupational therapy)There was no evidence of differences in bimanual performance between groups receiving CIMT or a dose-matched comparison (MD 0.80 AHA units, 95% CI -0.78 to 2.38).There was no evidence that CIMT was more effective than a dose-matched comparison for improving unimanual capacity (Box and Blocks Test MD 1.11, 95% CI -0.06 to 2.28; Melbourne Assessment MD 1.48, 95% CI -0.49 to 3.44; QUEST Dissociated movement MD 6.51, 95% CI -0.74 to 13.76; Grasp, MD 6.63, 95% CI -2.38 to 15.65; Weightbearing MD -2.31, 95% CI -8.02 to 3.40) except for the Protective extension domain (MD 6.86, 95% CI 0.14 to 13.58).There was no evidence of differences in manual ability between groups receiving CIMT or a dose-matched comparison (ABILHAND-Kids MD 0.74, 95% CI 0.31 to 1.18). From 15 studies, two children did not tolerate CIMT and three experienced difficulty. AUTHORS' CONCLUSIONS: The quality of evidence for all conclusions was low to very low. For children with unilateral CP, there was some evidence that CIMT resulted in improved bimanual performance and unimanual capacity when compared to a low-dose comparison, but not when compared to a high-dose or dose-matched comparison. Based on the evidence available, CIMT appears to be safe for children with CP.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

BACKGROUND: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. METHODS/DESIGN: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. DISCUSSION: This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. TRIAL REGISTRATION: ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

Intervenções para promover função física de crianças e jovens com paralisia cerebral: diretriz internacional de prática clínica.

OBJETIVO: Fornecer recomendações de intervenções para promoção da função física de crianças e jovens com paralisia cerebral. MÉTODO: Um painel de especialistas priorizou perguntas e desfechos importantes para o paciente. Usando o Grading of Recommendations Assessment, Development and Evaluation (GRADE), o painel avaliou a certeza das evidências e fez recomendações, com consultoria de especialistas internacionais e consumidores. RESULTADOS: A diretriz compreende 13 recomendações (informadas por três revisões sistemáticas, 30 estudos randomizados e cinco estudos pré-pós). Para alcance de objetivos funcionais, recomenda-se que a intervenção inclua objetivos escolhidos pelo cliente, prática completa da tarefa em ambientes da vida real, suporte para empoderar as famílias e uma abordagem em equipe. Idade, habilidade e preferências da criança/família precisam ser consideradas. Para melhora da habilidade da marcha, recomenda-se marcha no solo, que pode ser complementada com treinamento em esteira. Várias abordagens podem facilitar os objetivos relacionados ao uso das mãos: terapia bimanual, terapia de contensão induzida, treino direcionado a objetivos e abordagens cognitivas. Para auto-cuidado, prática da tarefa completa, combinada com recursos assistivos podem aumentar a independência e reduzir a sobrecarga do cuidador. A participação em objetivos de lazer pode combinar prática da tarefa completa com estratégias direcionadas para barreiras ambientais, pessoais e sociais. INTERPRETAÇÃO: Intervenção para promoção da função de crianças e jovens com paralisia cerebral precisa incluir objetivos escolhidos pelo cliente e a prática da tarefa completa dos objetivos. Os clínicos devem considerar as preferências da criança/família, idade e habilidade ao selecionarem intervenções específicas.

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.

Construct validity of the Quality of Upper Extremity Skills Test for children with cerebral palsy.

AIM: The aim of the study was to investigate the construct validity of the Quality of Upper Extremity Skills Test (QUEST) in children with cerebral palsy (CP). METHOD: A total of 170 QUEST assessments from a convenience sample of 94 children with CP involved in clinical and research treatment programmes (54 males, 40 females; mean age 6y 10mo, SD 2y 11mo, range 2-16y; Gross Motor Function Classification System levels I-V) were reviewed. RESULTS: The QUEST was not unidimensional; many items demonstrated poor fit when total scores were analysed; goodness of fit improved when domains were considered independently and limbs separately examined. QUEST items involving elbow flexion and/or forearm in pronation were easily achieved, thus reducing test sensitivity. Postures items in the grasp domain behaved erratically, with little total score relationship. INTERPRETATION: Calculating total scores is discouraged. Reporting QUEST results separately for domains and each limb is recommended. Posture items in the grasp domain had little relationship with total scores and it is recommended that they be removed from the test.

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.

Reliability of the quality of upper extremity skills test for children with cerebral palsy aged 2 to 12 years.

AIM: To investigate reliability of the Quality of Upper Extremity Skills Test (QUEST) scores for children with cerebral palsy (CP) aged 2-12 years. METHOD: Thirty-one QUESTs from 24 children with CP were rated once by two raters and twice by one rater. Internal consistency of total scores, inter- and intra-rater reliability findings for total, domain, and item scores were calculated. RESULTS: Total scores inter-rater reliability, Intra-class Correlation Coefficient (ICC) was 0.86, and for intra-rater reliability, ICC was 0.96. Domains had high reliability (ICC > 0.80) within raters and between raters except for grasp (moderate at ICC = 0.67). Item inter-rater reliability was moderate or better for 80% of items; item intra-rater reliability was moderate or better for 87% of items. Total score internal consistency was high (α = 0.97). IMPLICATIONS: The QUEST has proven reliability for children with CP aged 18 months to 8 years. This study demonstrates strong reliability for children aged 2-12 years.

Preschool HABIT-ILE: study protocol for a randomised controlled trial to determine efficacy of intensive rehabilitation compared with usual care to improve motor skills of children, aged 2-5 years, with bilateral cerebral palsy.

INTRODUCTION: Young children with bilateral cerebral palsy (BCP) often experience difficulties with gross motor function, manual ability and posture, impacting developing independence in daily life activities, participation and quality of life. Hand Arm Bimanual Intensive Training Including Lower Extremity (HABIT-ILE) is a novel intensive motor intervention integrating upper and lower extremity training that has been developed and tested in older school-aged children with unilateral and BCP. This study aims to compare an adapted preschool version of HABIT-ILE to usual care in a randomised controlled trial. METHODS AND ANALYSIS: 60 children with BCP aged 2-5 years, Gross Motor Function Classification System (GMFCS) II-IV will be recruited. Children will be stratified by GMFCS and randomised using concealed allocation to either receive Preschool HABIT-ILE or usual care. Preschool HABIT-ILE will be delivered in groups of four to six children, for 3 hours/day for 10 days (total 30 hours). Children receiving Preschool HABIT-ILE be provided a written home programme with the aim of achieving an additional 10 hours of home practice (total dose 40 hours). Outcomes will be assessed at baseline, immediately following intervention and then retention of effects will be tested at 26 weeks. The primary outcome will be the Peabody Developmental Motors Scales-Second Edition to evaluate gross and fine motor skills. Secondary outcomes will be gross motor function (Gross Motor Function Measure-66), bimanual hand performance (Both Hands Assessment), self-care and mobility (Pediatric Evaluation of Disability Inventory-Computer Adapted Test), goal attainment (Canadian Occupational Performance Measure), global performance of daily activities (ACTIVLIM-CP), cognition and adaptive function (Behavior Rating Inventory of Executive Function-Preschool Version), habitual physical activity (ActiGraph GT3X+) and quality of life (Infant Toddler Quality of Life Questionnaire and Child Health Utility Index-9). Analyses will follow standard principles for RCTs using two-group comparisons on all participants on an intention-to-treat basis. Comparisons between groups for primary and secondary outcomes will be conducted using regression models. ETHICS AND DISSEMINATION: Ethics approval has been granted by the Medical Research Ethics Committee Children's Health Queensland Hospital and Health Service Human Research Ethics Committee (HREC/19/QCHQ/59444) and The University of Queensland (2020000336/HREC/19/QCHQ/59444). TRIAL REGISTRATION NUMBER: ACTRN126200000719.

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.