Implications of providing wrist-hand orthoses for children with cerebral palsy: evidence from a randomised controlled trial.

PURPOSE: To investigate the effects of providing rigid wrist-hand orthoses plus usual multidisciplinary care, on reducing hand impairments in children with cerebral palsy. METHODS: A pragmatic, multicentre, assessor-blinded randomised controlled trial aimed to enrol 194 children aged 5-15 years, with wrist flexor Modified Ashworth Scale score ≥1. Randomisation with concealed allocation was stratified by study site and passive wrist range. The treatment group received a rigid wrist-hand orthosis, to wear ≥6 h per night for 3 years. Analysis included repeated measures mixed-effects linear regression models, using intention-to-treat principles. RESULTS: The trial stopped early due to insufficient recruitment: 74 children, across all Manual Ability Classification System levels, were randomised (n = 38 orthosis group; n = 36 control). Mean age was 10.2 (SD 3.1) years (orthosis group) and 9.1 (SD 2.8) years (control). Data showed some evidence that rigid wrist-hand orthosis impacted passive wrist extension with fingers extended in the first year [mean difference between-groups at 6 months: 13.15° (95%CI: 0.81-25.48°, p = 0.04); 12 months: 20.94° (95%CI: 8.20-33.69°, p = 0.001)]. Beyond 18 months, participant numbers were insufficient for conclusive findings. CONCLUSION: The study provided detailed data about short- and long-term effects of the wrist-hand orthosis and highlighted challenges in conducting large randomised controlled trials with this population. Trial Registration: Australia and New Zealand Clinical Trials Registry: U1111-1164-0572 IMPLICATIONS FOR REHABILITATIONThere may be incremental benefit, for children with cerebral palsy, at 6 and 12 months on passive wrist range from wearing a rigid wrist-hand orthosis designed according to this protocol.The rigid-wrist-hand orthosis evaluated in this study, which allowed for some tailoring for individual children's presentations, differed in design from past recommendations for "resting hand" positioning.Longitudinal follow up of children with cerebral palsy prescribed a rigid wrist-hand orthosis is essential to monitor any benefit.Minor adverse events were commonly experienced when wearing the orthosis and should be discussed prior to prescription of a rigid wrist-hand orthosis.

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.

Efficacy and safety of onabotulinumtoxinA with standardized occupational therapy for treatment of pediatric upper limb spasticity: Phase III placebo-controlled randomized trial.

BACKGROUND: This is the first large study of onabotulinumtoxinA as treatment for pediatric upper limb spasticity. OBJECTIVE: Evaluate efficacy and safety of a single treatment with onabotulinumtoxinA plus occupational therapy (OT). METHODS: In this registrational phase III, multinational study (NCT01603602), participants were randomized 1:1:1 to onabotulinumtoxinA 3 U/kg/OT, 6 U/kg/OT, or placebo/OT. Primary endpoint was average change from baseline at weeks 4 and 6 in Modified Ashworth Scale-Bohannon (MAS) score. Secondary endpoints included Modified Tardieu Scale (MTS), Clinical Global Impression of Change (CGI) and functional Goal Attainment Scale (GAS). RESULTS: 235 participants were randomized. At weeks 4 and 6, onabotulinumtoxinA groups had greater mean reductions in MAS (both -1.9; p < 0.001) versus placebo (-1.2). OnabotulinumtoxinA doses improved dynamic tone per MTS. Mean CGI at weeks 4 and 6 was unchanged in the overall population, but improved in a post hoc analysis of patients with a single affected upper limb (UL) muscle group (elbow or wrist). GAS score for passive goals was significantly higher for 6 U/kg versus placebo at week 12. Most AEs were mild/moderate in severity; overall incidence was similar between groups. CONCLUSIONS: OnabotulinumtoxinA (3 and 6 U/kg) was safe and effective in reducing upper limb spasticity in pediatric participants.

Early Intervention for Children Aged 0 to 2 Years With or at High Risk of Cerebral Palsy: International Clinical Practice Guideline Based on Systematic Reviews.

Importance: Cerebral palsy (CP) is the most common childhood physical disability. Early intervention for children younger than 2 years with or at risk of CP is critical. Now that an evidence-based guideline for early accurate diagnosis of CP exists, there is a need to summarize effective, CP-specific early intervention and conduct new trials that harness plasticity to improve function and increase participation. Our recommendations apply primarily to children at high risk of CP or with a diagnosis of CP, aged 0 to 2 years. Objective: To systematically review the best available evidence about CP-specific early interventions across 9 domains promoting motor function, cognitive skills, communication, eating and drinking, vision, sleep, managing muscle tone, musculoskeletal health, and parental support. Evidence Review: The literature was systematically searched for the best available evidence for intervention for children aged 0 to 2 years at high risk of or with CP. Databases included CINAHL, Cochrane, Embase, MEDLINE, PsycInfo, and Scopus. Systematic reviews and randomized clinical trials (RCTs) were appraised by A Measurement Tool to Assess Systematic Reviews (AMSTAR) or Cochrane Risk of Bias tools. Recommendations were formed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework and reported according to the Appraisal of Guidelines, Research, and Evaluation (AGREE) II instrument. Findings: Sixteen systematic reviews and 27 RCTs met inclusion criteria. Quality varied. Three best-practice principles were supported for the 9 domains: (1) immediate referral for intervention after a diagnosis of high risk of CP, (2) building parental capacity for attachment, and (3) parental goal-setting at the commencement of intervention. Twenty-eight recommendations (24 for and 4 against) specific to the 9 domains are supported with key evidence: motor function (4 recommendations), cognitive skills (2), communication (7), eating and drinking (2), vision (4), sleep (7), tone (1), musculoskeletal health (2), and parent support (5). Conclusions and Relevance: When a child meets the criteria of high risk of CP, intervention should start as soon as possible. Parents want an early diagnosis and treatment and support implementation as soon as possible. Early intervention builds on a critical developmental time for plasticity of developing systems. Referrals for intervention across the 9 domains should be specific as per recommendations in this guideline.

Associations of Neonatal Noncardiac Surgery with Brain Structure and Neurodevelopment: A Prospective Case-Control Study.

OBJECTIVE: To examine the associations of neonatal noncardiac surgery with newborn brain structure and neurodevelopment at 2 years of age. STUDY DESIGN: Infants requiring neonatal noncardiac surgery for congenital diaphragmatic hernia, esophageal atresia, or anterior abdominal wall defect were compared with infants who did not require surgery, matched for sex, gestation at birth, and postmenstrual age at magnetic resonance imaging. Cerebral magnetic resonance imaging was performed at a mean (SD) postmenstrual age of 41.6 (1.7) weeks. Images were assessed qualitatively for brain maturation and injury and quantitatively for measures of brain size, cerebrospinal fluid spaces, and global abnormality. Neurodevelopment was then assessed at 2 years using the Bayley Scales of Infant and Toddler Development, 3rd edition. RESULTS: Infants requiring surgery (n = 39) were 5.9 times (95% CI, 1.9-19.5; P < .01) more likely to have delayed gyral maturation and 9.8 times (95% CI, 1.2-446; P = .01) more likely to have white matter signal abnormalities compared with controls (n = 39). Cases were more likely to have higher global abnormality scores, smaller biparietal diameters, and larger ventricular sizes than controls. Infants who had surgery had lower mean composite scores in the language (mean difference, -12.5; 95% CI, -22.4 to -2.7) and motor domains (mean difference, -13.4; 95% CI, -21.1 to -5.6) compared with controls. CONCLUSIONS: Infants requiring neonatal noncardiac surgery have smaller brains with more abnormalities compared with matched controls and have associated neurodevelopmental impairment at 2 years of age. Prospective studies with preoperative and postoperative imaging would assist in determining the timing of brain injury.

REACH: study protocol of a randomised trial of rehabilitation very early in congenital hemiplegia.

OBJECTIVES: Congenital hemiplegia is the most common form of cerebral palsy (CP). Children with unilateral CP show signs of upper limb asymmetry by 8 months corrected age (ca) but are frequently not referred to therapy until after 12 months ca. This study compares the efficacy of infant-friendly modified constraint-induced movement therapy (Baby mCIMT) to infant friendly bimanual therapy (Baby BIM) on upper limb, cognitive and neuroplasticity outcomes in a multisite randomised comparison trial. METHODS AND ANALYSIS: 150 infants (75 in each group), aged between 3 and 6 months ca, with asymmetric brain injury and clinical signs of upper extremity asymmetry will be recruited. Children will be randomised centrally to receive equal doses of either Baby mCIMT or Baby BIM. Baby mCIMT comprises restraint of the unimpaired hand using a simple restraint (eg, glove, sock), combined with intensive parent implemented practice focusing on active use of the impaired hand in a play-based context. In contrast, Baby BIM promotes active play requiring both hands in a play-based context. Both interventions will be delivered by parents at home with monthly home visits and interim telecommunication support by study therapists. Assessments will be conducted at study entry; at 6, 12 months ca immediately postintervention (primary outcome) and 24 months ca (retention). The primary outcome will be the Mini-Assisting Hand Assessment. Secondary outcomes include the Bayley Scale for Infant and Toddler Development (cognitive and motor domains) and the Hand Assessment of Infants. A subset of children will undertake MRI scans at 24 months ca to evaluate brain lesion severity and brain (re)organisation after intervention. ETHICS AND DISSEMINATION: Full ethical approvals for this study have been obtained from the relevant sites. The findings will be disseminated in peer-reviewed publications. TRIAL REGISTRATION NUMBER: Australian and New Zealand Clinical Trials Registry: ACTRN12615000180516, Pre results.

Early, Accurate Diagnosis and Early Intervention in Cerebral Palsy: Advances in Diagnosis and Treatment.

Importance: Cerebral palsy describes the most common physical disability in childhood and occurs in 1 in 500 live births. Historically, the diagnosis has been made between age 12 and 24 months but now can be made before 6 months' corrected age. Objectives: To systematically review best available evidence for early, accurate diagnosis of cerebral palsy and to summarize best available evidence about cerebral palsy-specific early intervention that should follow early diagnosis to optimize neuroplasticity and function. Evidence Review: This study systematically searched the literature about early diagnosis of cerebral palsy in MEDLINE (1956-2016), EMBASE (1980-2016), CINAHL (1983-2016), and the Cochrane Library (1988-2016) and by hand searching. Search terms included cerebral palsy, diagnosis, detection, prediction, identification, predictive validity, accuracy, sensitivity, and specificity. The study included systematic reviews with or without meta-analyses, criteria of diagnostic accuracy, and evidence-based clinical guidelines. Findings are reported according to the PRISMA statement, and recommendations are reported according to the Appraisal of Guidelines, Research and Evaluation (AGREE) II instrument. Findings: Six systematic reviews and 2 evidence-based clinical guidelines met inclusion criteria. All included articles had high methodological Quality Assessment of Diagnostic Accuracy Studies (QUADAS) ratings. In infants, clinical signs and symptoms of cerebral palsy emerge and evolve before age 2 years; therefore, a combination of standardized tools should be used to predict risk in conjunction with clinical history. Before 5 months' corrected age, the most predictive tools for detecting risk are term-age magnetic resonance imaging (86%-89% sensitivity), the Prechtl Qualitative Assessment of General Movements (98% sensitivity), and the Hammersmith Infant Neurological Examination (90% sensitivity). After 5 months' corrected age, the most predictive tools for detecting risk are magnetic resonance imaging (86%-89% sensitivity) (where safe and feasible), the Hammersmith Infant Neurological Examination (90% sensitivity), and the Developmental Assessment of Young Children (83% C index). Topography and severity of cerebral palsy are more difficult to ascertain in infancy, and magnetic resonance imaging and the Hammersmith Infant Neurological Examination may be helpful in assisting clinical decisions. In high-income countries, 2 in 3 individuals with cerebral palsy will walk, 3 in 4 will talk, and 1 in 2 will have normal intelligence. Conclusions and Relevance: Early diagnosis begins with a medical history and involves using neuroimaging, standardized neurological, and standardized motor assessments that indicate congruent abnormal findings indicative of cerebral palsy. Clinicians should understand the importance of prompt referral to diagnostic-specific early intervention to optimize infant motor and cognitive plasticity, prevent secondary complications, and enhance caregiver well-being.

Unimanual versus bimanual therapy in children with unilateral cerebral palsy: Same, same, but different.

BACKGROUND: There is high-level evidence supporting constraint-induced movement therapy (CIMT) and bimanual therapy for children with unilateral cerebral palsy. Evidence-based intervention includes time-limited, goal-directed, skills-based, intensive blocks of practice based on motor learning theory. AIM AND METHODS: Using supporting literature and clinical insight, we provide a theoretical rationale to highlight previously unreported differences between CIMT and bimanual therapy. DISCUSSION: The current emphasis on total dosage of practice for achieving positive outcomes fails to recognise the influence of other critical concepts within motor learning. Limitations exist in the application of motor learning principles using CIMT due to its unimanual nature. CIMT is effective for development of unimanual actions brought about by implicit learning, however it is difficult to target explicit learning that is required for learning how to use two hands together. Using bimanual therapy, object properties can be adapted to trigger goal-related perceptual and cognitive processes required for children to learn to recognise when two hands are required for task completion. CONCLUSION: CIMT and bimanual should be viewed as complementary. CIMT could be used to target unimanual actions. Once these actions are established, bimanual therapy could be used for children to learn how to use these actions for bimanual skill development.

Minimising impairment: Protocol for a multicentre randomised controlled trial of upper limb orthoses for children with cerebral palsy.

BACKGROUND: Upper limb orthoses are frequently prescribed for children with cerebral palsy (CP) who have muscle overactivity predominantly due to spasticity, with little evidence of long-term effectiveness. Clinical consensus is that orthoses help to preserve range of movement: nevertheless, they can be complex to construct, expensive, uncomfortable and require commitment from parents and children to wear. This protocol paper describes a randomised controlled trial to evaluate whether long-term use of rigid wrist/hand orthoses (WHO) in children with CP, combined with usual multidisciplinary care, can prevent or reduce musculoskeletal impairments, including muscle stiffness/tone and loss of movement range, compared to usual multidisciplinary care alone. METHODS/DESIGN: This pragmatic, multicentre, assessor-blinded randomised controlled trial with economic analysis will recruit 194 children with CP, aged 5-15 years, who present with flexor muscle stiffness of the wrist and/or fingers/thumb (Modified Ashworth Scale score ≥1). Children, recruited from treatment centres in Victoria, New South Wales and Western Australia, will be randomised to groups (1:1 allocation) using concealed procedures. All children will receive care typically provided by their treating organisation. The treatment group will receive a custom-made serially adjustable rigid WHO, prescribed for 6 h nightly (or daily) to wear for 3 years. An application developed for mobile devices will monitor WHO wearing time and adverse events. The control group will not receive a WHO, and will cease wearing one if previously prescribed. Outcomes will be measured 6 monthly over a period of 3 years. The primary outcome is passive range of wrist extension, measured with fingers extended using a goniometer at 3 years. Secondary outcomes include muscle stiffness, spasticity, pain, grip strength and hand deformity. Activity, participation, quality of life, cost and cost-effectiveness will also be assessed. DISCUSSION: This study will provide evidence to inform clinicians, services, funding agencies and parents/carers of children with CP whether the provision of a rigid WHO to reduce upper limb impairment, in combination with usual multidisciplinary care, is worth the effort and costs. TRIAL REGISTRATION: ANZ Clinical Trials Registry: U1111-1164-0572 .

Development of the Mini-Assisting Hand Assessment: evidence for content and internal scale validity.

AIM: To describe the development of the Mini-Assisting Hand Assessment (Mini-AHA) for children with signs of unilateral cerebral palsy (CP) aged 8 to 18 months, and evaluate aspects of content and internal scale validity. METHOD: The ability of the video-recorded Mini-AHA play session to provoke bimanual performance in children with unilateral CP and typical development was evaluated. Original AHA test items were examined for their suitability for younger children and possible new items were generated. Data from 108 assessments of children with unilateral CP (86 children, 53 males, 33 females; mean age 13 mo, SD 3 mo, range 8-18 mo) were entered into a Rasch measurement model analysis to evaluate internal scale validity. A Spearman's correlation analysis explored the relationship between age and ability measures for children with unilateral CP. The frequency of maximum scores in 40 children with typical development (22 males, 18 females; mean age 12 mo, SD 3 mo) was examined. RESULTS: The Mini-AHA play session provoked bimanual responses in typically developing children 99% of the time. Person and item fit criteria established 20 items for the scale. The resultant unidimensional scale also demonstrated excellent discriminative features through high separation reliability. The item calibration values covered the range of person ability measures well. Age was not related to the ability measures for children with unilateral CP (rs =0.178). All children with typical development achieved maximum scores. INTERPRETATION: Accumulated evidence shows that the Mini-AHA validly measures use of the affected hand during bimanual performance for children with unilateral CP aged 8 to 18 months. The Mini-AHA has the potential to be a useful assessment to evaluate functional hand use and the effects of intervention in an age group when potential for change is high.

Bimanual behaviours in children aged 8-18 months: a literature review to select toys that elicit the use of two hands.

Toys that provoke the use of both hands are required to develop a test of bimanual performance in children 8-18 months with unilateral cerebral palsy (Mini-AHA). To choose the toys, a conceptual model based on perception-action theory and object use was used to guide a literature review. Evidence was sought for three critical relationships identified in the model which help determine bimanual performance: (1) the child-toy relationship, (2) the child-task relationship, and (3) the toy-task relationship. Evidence for both typically developing children and children with unilateral CP in this age range was sought. Thirty-five papers provided information about one or more of the relationships in typically developing children. No evidence was found for children with unilateral CP. Synthesis of the evidence from these three relationships informed toy selection for this new assessment.

The new staging system for lung cancer: imaging and clinical implications.

Accurate staging of lung cancer is necessary to describe and communicate disease extent, predict prognosis, determine therapy, and evaluate the results of clinical trials. The Union Internationale Contre le Cancer and the American Joint Committee on Cancer published the seventh edition of tumor, node, and metastasis in lung cancer in 2009. Changes to the sixth edition have been based on the analysis of a large database of patients with lung cancer by the International Staging Committee of the International Association for the Study of Lung Cancer. This study reviews the new seventh edition of the tumor, node, and metastasis lung cancer staging system and discusses the radiologic and therapeutic implications.

Assessing bimanual performance in young children with hemiplegic cerebral palsy: a systematic review.

AIM: This systematic review investigated the availability of assessment tools to evaluate bimanual skills in young children (< or = 3y) with hemiplegic cerebral palsy. Evidence for validity, reliability, and clinical utility of the identified instruments was sought. METHOD: Ten electronic databases and grey literature were searched (earliest 1806) to February 2009 to identify articles that met criteria related to the child's age and diagnosis, and included a discrete bimanual assessment. Further searches for evidence of psychometric properties of each identified assessment were undertaken. For quality criteria, we evaluated the internal validity of each study and appraised the validity and reliability of identified assessments. RESULTS: From 1435 papers retrieved, 15 were eligible for inclusion, and 11 assessments of bimanual performance were identified. Ten assessments had inadequate evidence for reliability and validity. Only the Assisting Hand Assessment had evidence for reliability and validity for its intended purposes. INTERPRETATION: Reliability and validity are fundamental considerations when developing or selecting assessments. Additional considerations for assessing young children include the following: (1) standardized administration and scoring; (2) items that capture the complexity of bimanual behaviour; and (3) protocols and items targeted within a small age range to meet specific developmental needs. A validated assessment of younger infants is needed to support early intervention during this period of rapid brain development.

Repeat botulinum toxin-A injections in the upper limb of children with hemiplegia: a randomized controlled trial.

AIM: To test the effectiveness of repeat botulinum toxin A (BoNT-A) injections in the affected arm of 22 children with hemiplegic cerebral palsy (19 males, three females), aged 1 year 10 months to 4 years 10 months (mean 3y 8mo, SD 9mo) in a randomized controlled trial. METHOD: Children received either three series of BoNT-A injections plus twice-weekly occupational therapy (OT) or OT alone in 16-week cycles. Muscles targeted at each injection cycle in the 11 children receiving BoNT-A+OT were the adductor pollicis (n=9), flexor pollicis longus (n=5), flexor digitorum superficialis (n=8), flexor digitorum profundus (n=8), flexor carpi radialis (n=2), flexor carpi ulnaris (n=6), pronator teres (n=10), and biceps brachii (n=11). Parental perception of treatment efficacy was assessed using the Canadian Occupational Performance Measure (COPM) and the Goal Attainment Scale (GAS), quality of movement using the Quality of Upper Extremity Skills Test (QUEST), fine motor skills using the Peabody Developmental Motor Scale - Fine Motor (PDMS-FM), and spasticity using the Modified Tardieu Scale (MTS). Between-group differences at 12 months were analysed using independent-sample t-tests. RESULTS: All children were at Gross Motor Function Classification System levels I (BoNT-A+OT n=6; OT n=8) or II (n=5 and n=3 respectively) and were too young to be classified using the Manual Ability Classification System. The BoNT-A+OT group had higher COPM performance scores (mean difference -0.8, 95% confidence interval [CI] -1.5-0.0) and higher GAS T scores (mean difference -6.9, 95% CI -13.8 to -0.1]). No significant difference was found for the COPM satisfaction, PDMS-FM, or QUEST scores. The BoNT-A+OT group showed progressive reduction in spasticity compared with the OT group. At study completion MTS mean difference was 50.0 degrees (95% CI 22.4-77.6) for pronators and 20.9 degrees (95% CI 2.4-39.4) for wrist flexors. INTERPRETATION: Repeat BoNT-A injections in the upper limb combined with OT resulted in progressively reduced spasticity and improved parental perception of performance.