Showing papers in "Developmental Medicine & Child Neurology in 2013"

A systematic review of interventions for children with cerebral palsy: state of the evidence.

Abstract: Aim The aim of this study was to describe systematically the best available intervention evidence for children with cerebral palsy (CP). Method This study was a systematic review of systematic reviews. The following databases were searched: CINAHL, Cochrane Library, DARE, EMBASE, Google Scholar MEDLINE, OTSeeker, PEDro, PsycBITE, PsycINFO, and speechBITE. Two independent reviewers determined whether studies met the inclusion criteria. These were that (1) the study was a systematic review or the next best available; (2) it was a medical/allied health intervention; and (3) that more than 25% of participants were children with CP. Interventions were coded using the Oxford Levels of Evidence; GRADE; Evidence Alert Traffic Light; and the International Classification of Function, Disability and Health. Results Overall, 166 articles met the inclusion criteria (74% systematic reviews) across 64 discrete interventions seeking 131 outcomes. Of the outcomes assessed, 16% (21 out of 131) were graded ‘do it’ (green go); 58% (76 out of 131) ‘probably do it’ (yellow measure); 20% (26 out of 131) ‘probably do not do it’ (yellow measure); and 6% (8 out of 131) ‘do not do it’ (red stop). Green interventions included anticonvulsants, bimanual training, botulinum toxin, bisphosphonates, casting, constraint-induced movement therapy, context-focused therapy, diazepam, fitness training, goal-directed training, hip surveillance, home programmes, occupational therapy after botulinum toxin, pressure care, and selective dorsal rhizotomy. Most (70%) evidence for intervention was lower level (yellow) while 6% was ineffective (red). Interpretation Evidence supports 15 green light interventions. All yellow light interventions should be accompanied by a sensitive outcome measure to monitor progress and red light interventions should be discontinued since alternatives exist.

An update on the prevalence of cerebral palsy: a systematic review and meta-analysis.

Abstract: Aims The aim of this study was to provide a comprehensive update on (1) the overall prevalence of cerebral palsy (CP); (2) the prevalence of CP in relation to birthweight; and (3) the prevalence of CP in relation to gestational age. Method A systematic review and meta-analysis was conducted and reported, based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) statement. Population-based studies on the prevalence of CP in children born in 1985 or after were selected. Statistical analysis was carried out using computer package R, version 2.14. Results A total of 49 studies were selected for this review. The pooled overall prevalence of CP was 2.11 per 1000 live births (95% confidence interval [CI] 1.98–2.25). The prevalence of CP stratified by gestational age group showed the highest pooled prevalence to be in children weighing 1000 to 1499g at birth (59.18 per 1000 live births; 95% CI 53.06–66.01), although there was no significant difference on pairwise meta-regression with children weighing less than 1000g. The prevalence of CP expressed by gestational age was highest in children born before 28 weeks' gestation (111.80 per 1000 live births; 95% CI 69.53–179.78; p<0.0327). Interpretation The overall prevalence of CP has remained constant in recent years despite increased survival of at-risk preterm infants.

Understanding performance deficits in developmental coordination disorder: a meta-analysis of recent research

Abstract: Aim Developmental coordination disorder (DCD) is a significant disorder of childhood, characterized by core difficulties in learning fine and/or gross motor skills, and the attendant psychosocial problems. The aim of the meta-analysis presented here (the first on DCD since 1998) was to summarize trends in the literature over the past 14 years and to identify and describe the main motor control and cognitive deficits that best discriminate children with DCD from those without. Method A systematic review of the literature published between January 1997 and August 2011 was conducted. All available journal papers reporting a comparison between a group of children with DCD and a group of typically developing children on behavioural measures were included. Results One hundred and twenty-nine studies yielded 1785 effect sizes based on a total of 2797 children with DCD and 3407 typically developing children. Across all outcome measures, a moderate to large effect size was found, suggesting a generalized performance deficit in children with DCD. The pattern of deficits suggested several areas of pronounced difficulty, including internal (forward) modelling, rhythmic coordination, executive function, gait and postural control, catching and interceptive action, and aspects of sensoriperceptual function. Interpretation The results suggest that the predictive control of action may be a fundamental disruption in DCD, along with the ability to develop stable coordination patterns. Implications for theory development and intervention are discussed.

A systematic review of tests to predict cerebral palsy in young children.

Abstract: Aim This systematic review evaluates the accuracy of predictive assessments and investigations used to assist in the diagnosis of cerebral palsy (CP) in preschool-age children (<5y). Method Six databases were searched for studies that included a diagnosis of CP validated after 2 years of age. The validity of the studies meeting the criteria was evaluated using the Standards for Reporting Diagnostic Accuracy criteria. Where possible, results were pooled and a meta-analysis was undertaken. Results Nineteen out of 351 studies met the full inclusion criteria, including studies of general movements assessment (GMA), cranial ultrasound, brain magnetic resonance imaging (MRI), and neurological examination. All studies assessed high-risk populations including preterm (gestational range 23–41wks) and low-birthweight infants (range 500–4350g). Summary estimates of sensitivity and specificity of GMA were 98% (95% confidence interval [CI] 74–100%) and 91% (95% CI 83–93%) respectively; of cranial ultrasound 74% (95% CI 63–83%) and 92% (95% CI 81–96%) respectively; and of neurological examination 88% (95% CI 55–97%) and 87% (95% CI 57–97%) respectively. MRI performed at term corrected age (in preterm infants) appeared to be a strong predictor of CP, with sensitivity ranging in individual studies from 86 to 100% and specificity ranging from 89 to 97% There was inadequate evidence for the use of other predictive tools. Summary This review found that the assessment with the best evidence and strength for predictive accuracy is the GMA. MRI has a good predictive value when performed at term-corrected age. Cranial ultrasound is as specific as MRI and has the advantage of being readily available at the bedside. Studies to date have focused on high-risk infants. The accuracy of these tests in low-risk infants remains unclear and requires further research.

A systematic review of risk factors for cerebral palsy in children born at term in developed countries.

Abstract: Aim The aim of this study was to conduct a systematic review in order to identify the risk factors for cerebral palsy (CP) in children born at term. The secondary aim was to ascertain if the potential for prevention of these risk factors has been adequately explored. Method A MEDLINE search up to 31 July 2011 was completed, following the Meta-Analysis of Observational Studies in Epidemiology guidelines. Publications were reviewed to identify those with both a primary aim of identifying risk factors for all children or term-born children with CP and a cohort or case–control study design. Studies were examined for potential chance or systematic bias. The range of point estimates of relative risk is reported. Results From 21 articles meeting inclusion/exclusion criteria and at low risk of bias, data from 6297 children with CP and 3 804 791 children without CP were extracted. Ten risk factors for term-born infants were statistically significant in each study: placental abnormalities, major and minor birth defects, low birthweight, meconium aspiration, instrumental/emergency Caesarean delivery, birth asphyxia, neonatal seizures, respiratory distress syndrome, hypoglycaemia, and neonatal infections. Strategies for possible prevention currently exist for three of these. Interpretation Ten consistent risk factors have been identified, some with potential for prevention. Efforts to prevent these risk factors to interrupt the pathway to CP should be extended.

Efficacy of interventions to improve motor performance in children with developmental coordination disorder: a combined systematic review and meta-analysis.

Abstract: Aim The aim of this study was to review systematically evidence about the efficacy of motor interventions for children with developmental coordination disorder (DCD), and to quantify treatment effects using meta-analysis. Method Included were all studies published between 1995 and 2011 that described a systematic review, (randomized) clinical trial, or crossover design about the effect of motor intervention in children with DCD. Studies were compared on four components: design, methodological quality, intervention components, and efficacy. Twenty-six studies met the inclusion criteria for the review. Interventions were coded under four types: (1) task-oriented intervention, (2) traditional physical therapy and occupational therapy, (3) process-oriented therapies, and (4) chemical supplements. For the meta-analysis, effect sizes were available for 20 studies and their magnitude (weighted Cohen’s d [dw]) was compared across training types. Results The overall effect size across all intervention studies was dw=0.56. A comparison between classes of intervention showed strong effects for task-oriented intervention (dw=0.89) and physical and occupational therapies (dw=0.83), whereas that for process-oriented intervention was weak (dw=0.12). Of the chemical supplements, treatment with methylphenidate was researched in three studies (dw=0.79) and supplementation of fatty acids plus vitamin E in one study (no effect). The post hoc comparison between treatment types showed that the effect size of the task-oriented approach was significantly higher than the process-oriented intervention (p=0.01) and comparison (p=0.006). No significant difference in the magnitude of effect size between traditional physical and occupational therapy approaches and any of the other interventions emerged. Interpretation In general, intervention is shown to produce benefit for the motor performance of children with DCD, over and above no intervention. However, approaches from a task-oriented perspective yield stronger effects. Process-oriented approaches are not recommended for improving motor performance in DCD, whereas the evidence for chemical supplements for children with DCD is currently insufficient for a recommendation.

The effect of pediatric traumatic brain injury on behavioral outcomes: a systematic review

Abstract: An average of 634,000 incidents of traumatic brain injury (TBI) occurs among children each year in the United States, with the highest TBI-related emergency room visits occurring in children under the age of 4 years and adolescents 15 years or older.1 Pediatric TBI in young children (<4y) is commonly caused by falls, which may account for approximately 40% of head injuries requiring hospitalization for children less than 4 years old.1 Inflicted injuries acquired secondary to child abuse (e.g. shaken baby syndrome) may account for 20 to 70% of hospitalizations in young children.2–4 In older children, motor-vehicle accidents are the more prevalent causes.1 Although focal brain lesions sustained during childhood generally show favorable recovery,5 the diffuse brain insult that frequently occurs in some combination with focal insults in TBI appears more threatening to the developing brain.6,7 Despite the prevalence and threat of childhood TBI, however, the impact of such damage on the brain remains poorly understood, especially within pediatric populations. Assessing sequelae from brain injury of varying etiologies on the developing brain remains a challenge for researchers. Even within the literature, the physical and cognitive consequences of pediatric TBI have historically received greater attention than behavioral and psychosocial problems. This is surprising as behavioral and psychosocial problems are often more concerning for parents and teachers, and may also more negatively influence patients’ lives than intellectual or physical problems.8,9 Early work by Rutter et al. showed that among children with severe head injury, rates of new psychiatric disorders were three times more common than in orthopedic injury comparisons.10,11 Left untreated, these adverse outcomes of childhood brain injury may persist into adulthood, predisposing individuals to violent crime12 or mental health disorders.13 It is commonly believed that children with behavioral problems are at greater risk for experiencing a TBI event, owing to their inability to predict the consequences of their actions and resulting tendency to be more accident prone.14 However, this belief is largely based on research using post-injury recall of pre-injury behavior.15 Prospective studies using pre-injury data collected before the TBI event, therefore avoiding potential recall bias, have demonstrated that pre-injury behavior does not actually serve as a significant predictor for a TBI event.14,16,17 It is thus critical that patients, families, and healthcare workers do not assume that post-injury behavioral deficits simply reflect an individual’s pre-injury characteristics or developmental trajectory.18 Rather, behavioral problems are a real and potential consequence of TBI that have detrimental effects on children’s long-term functioning and quality of life. In light of the growing recognition that childhood brain injury may contribute to the development of adverse, lifelong behavioral outcomes, it is critical to review systematically the recent empirical evidence and provide a comprehensive overview of the ongoing progress in this area. Despite the emerging research over the past two decades on the presentation, risk factors for and correlates of behavioral outcomes after pediatric brain injury, few have taken a systematic approach to evaluate the effects of TBI on behavioral outcomes. In the present review, therefore, we therefore examine the relationship between childhood TBI and behavioral problems, as well as possible contributing factors, to help inform healthcare professionals, patients, families, and future research efforts.

Preterm birth and behaviour problems in infants and preschool-age children: a review of the recent literature.

Abstract: The behaviour problems of children born preterm at school age are well known, but there have been few studies on the behaviour problems of preterm-born infants during infancy and at preschool age. Fourteen cohort studies published in PubMed and PsycINFO between 2000 and 2012 were reviewed with a focus on the type, occurrence, comorbidity, stability, prediction, perinatal, social, and relational risk factors for behaviour problems of preterm-born children in infancy (0-2y) and at preschool age (3-5y). The relational risk factor was considered in an additional four papers. Very-preterm, very-low-birthweight, and moderately-preterm children, in both age groups, show more behaviour problems than term-born comparison children even after perinatal and social risk factors and cognitive performance have been controlled for. Poor social/interactive skills, poor behavioural and emotional self-regulation, emotional difficulties, and reduced attention are the most common behaviour problems. Behaviour problems in infancy are predictive of later behaviour problems and they should be included in follow-up programmes.

Peer support for parents of children with chronic disabling conditions: a systematic review of quantitative and qualitative studies

Abstract: AIM: To review the qualitative and quantitative evidence of the benefits of peer support for parents of children with disabling conditions in the context of health, well-being, impact on family, and economic and service implications. Method: We comprehensively searched multiple databases. Eligible studies evaluated parent-to-parent support and reported on the psychological health and experience of giving or receiving support. There were no limits on the child's condition, study design, language, date, or setting. We sought to aggregate quantitative data; findings of qualitative studies were combined using thematic analysis. Qualitative and quantitative data were brought together in a narrative synthesis. Results: Seventeen papers were included: nine qualitative studies, seven quantitative studies, and one mixed-methods evaluation. Four themes were identified from qualitative studies: (1) shared social identity, (2) learning from the experiences of others, (3) personal growth, and (4) supporting others. Some quantitative studies reported a positive effect of peer support on psychological health and other outcomes; however, this was not consistently confirmed. It was not possible to aggregate data across studies. No costing data were identified. Conclusion: Qualitative studies strongly suggest that parents perceive benefit from peer support programmes, an effect seen across different types of support and conditions. However, quantitative studies provide inconsistent evidence of positive effects. Further research should explore whether this dissonance is substantive or an artefact of how outcomes have been measured. © The Authors © 2013 Mac Keith Press.

Development of the Performance of the Upper Limb module for Duchenne muscular dystrophy.

Abstract: Aim: An international Clinical Outcomes Group consisting of clinicians, scientists, patient advocacy groups, and industries identified a need for a scale to measure motor performance of the upper limb. We report the steps leading to the development of the Performance of the Upper Limb (PUL), a tool specifically designed for assessing upper limb function in ambulant and non-ambulant patients with Duchenne muscular dystrophy (DMD). Method: The development of the PUL followed a number of steps, from the systematic review and a preliminary study exploring the suitability of the existing measures, to the application of a pilot version in a multicentric setting, with Rasch analysis of the preliminary results, leading to a revised pro forma. Results: The PUL was specifically designed for DMD, with a conceptual framework reflecting the progression of weakness and natural history of functional decline in DMD. Modern psychometric methods were used to create a scale with robust internal reliability, validity, and hierarchical scalability; males with DMD and their families were involved iteratively throughout the process of the clinician-reported outcome assessment tool development to establish clinical meaningfulness and relevance of individual PUL items to activities of daily living. Interpretation: The module was developed using innovative approaches and will be useful for designing clinical trials. © 2013 Mac Keith Press.

Behaviour in children with neurofibromatosis type 1: cognition, executive function, attention, emotion, and social competence

Abstract: Aim This systematic review aimed to pull together the findings from research into behavioural systems and attention in children with neurofibromatosis type 1 (NF1) and to identify areas that need further study. Method Relevant papers were identified through searches of electronic databases (MEDLINE, PsycINFO, EMBASE) and manual searches through reference lists. In total, 5746 articles were identified and 57 met the inclusion criteria. The data were synthesized using the narrative approach, as the studies varied considerably in terms of participants and measures. Results The results of the review showed that intelligence, academic skills, visuospatial skills, social competence, and attention are impaired in children with NF1. Evidence of deficits in memory, motor functioning, language, and executive functions was less clear. Interpretation Research has made marked progress in outlining the behavioural phenotype of NF1. However, although the general areas of impairment are becoming better known, the exact nature of the impairment is still not understood in many areas of behaviour. Care needs to be taken with the way in which behavioural constructs are defined and measured, and the variability of problems in NF1 is a particular challenge. Nevertheless, research is steadily moving towards comprehensive understanding of behaviour in children with NF1.

Characteristics of post‐traumatic headaches in children following mild traumatic brain injury and their response to treatment: a prospective cohort

Abstract: AIM: Post-traumatic headaches (PTHs) following mild traumatic brain injury (mTBI) are common; however, few studies have examined the characteristics of PTHs or their response to treatment. The aims of this study were (1) to describe the clinical characteristics of PTH in a prospective cohort of children presenting to a paediatric emergency department with mTBI, and (2) to evaluate the response of PTH to treatment. METHOD: The emergency department cohort was obtained from a prospective longitudinal cohort study of symptoms following mTBI (n=670; 385 males, 285 females) and a comparison group of children with extracranial injury (n=120; 61 males, 59 females). A retrospective chart review of a separate cohort of children from a brain injury clinic (the treatment cohort) treated for PTH was performed (n=44; 29 females, 15 males; mean age 14y 1mo, SD 3y 1mo). The median time since injury was 6.9 months (range 1-29mo). The mean follow-up interval after treatment started was 5.5 weeks (SD 4.3wks). RESULTS: Among the emergency department cohort (n=39; 20 males, 19 females; mean age 11y 1mo, SD 4y 3mo) 11% of children were symptomatic with PTHs at a mean of 15.8 days (SD 11.6d) post injury. Three months post injury, 7.8% of children complained of headaches; of those, 56% had pre-existing headaches and 18% had experienced migraine before the injury. Although headache type varied, 55% met the criteria for migraine. A family or past medical history of migraine was present in 82% of cases. Among the treatment cohort, medications included amitriptyline, flunarizine, topiramate, and melatonin, with an overall response rate of 64%. CONCLUSION: This is the first prospective cohort study to describe the clinical characteristics of PTHs following mTBI in children. Migraine was the most common headache type seen; other headaches included tension-type, cervicogenic, and occipital neuralgias, and 64% responded to treatment. Referral to a headache specialist should be considered, especially when the features are not typical of one of the primary headache disorders. Language: en

Autism and other psychiatric comorbidity in neurofibromatosis type 1: evidence from a population-based study.

Abstract: AIM: To investigate psychopathology in children with neurofibromatosis type 1 (NF1), particularly the prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD) symptomatology, using a population-based sampling approach. METHOD: Standard questionnaire screen reports were analysed for ASD (Social Responsiveness Scale, SRS), ADHD (Conners' Parent Rating Scale- Revised, CPRS-R), and other psychiatric morbidity (Strengths and Difficulties Questionnaire, SDQ) from parents and teachers of children aged from 4 to 16 years (112 females, 95 males) on the UK North West Regional Genetic Service register for NF1. RESULTS: Parental response rate was 52.7% (109/207 children; 59 females, 50 males, mean age 9 y 11 mo, SD 3 y 3 mo). The SRS showed that in 29.4% (32/109) of children, autism was in the severe, clinical range (T-score>75) and in 26.6% (29/109) in the mild to moderate range (T-score 60-75). CPRS-R scores showed that in 53.8% (57/106) of children autism was in the clinical ADHD range (ADHD index T-score>65). Based on their scores on the SDQ total difficulties scale, 41.5% (44/106) of children were in the abnormal range and 14.2% (15/106) were in the borderline range. Twenty-five per cent (26/104) of children met criteria for both clinical autism and ADHD. INTERPRETATION: This representative population-based sample of children with NF1 indicates a high prevalence of ASD symptoms associated with NF1 as well as substantial co-occurrence with ADHD symptoms. The findings clarify the psychopathology of NF1 and show the disorder as a potentially important single-gene cause for autism symptoms.

Neurocognitive consequences of a paediatric brain tumour and its treatment: a meta-analysis.

Abstract: Aim This meta-analysis provides a systematic review of studies into intellectual and attentional functioning of paediatric brain tumour survivors (PBTS) as assessed by two widely used measures: the Wechsler Intelligence Scale for Children (3rd edition; WISC-III) and the Conners’ Continuous Performance Test (CPT). Method Studies were located that reported on performance of PBTS (age range 6–16y). Meta-analytic effect sizes were calculated for Full-scale IQ, Performance IQ, and Verbal IQ as measured by the WISC-III, and mean hit reaction time, errors of omission, and errors of commission as measured by the CPT. Exploratory analyses investigated the possible impacts of treatment mode, tumour location, age at diagnosis, and time since diagnosis on intelligence. Results Twenty-nine studies were included: 22 reported on the WISC-III in 710 PBTS and seven on CPT results in 372 PBTS. PBTS performed below average (ps<0.001) on Full-scale IQ (Cohen’s d=−0.79), Performance IQ (d=−0.90), and Verbal IQ (d=−0.54). PBTS committed more errors of omission than the norm (d=0.82, p<0.001); no differences were found for mean hit reaction time and errors of commission. Cranial radiotherapy, chemotherapy, and longer time since diagnosis were associated with lower WISC-III scores (ps<0.05). Interpretation PBTS have seriously impaired intellectual functioning and attentiveness. Being treated with cranial radiotherapy and/or chemotherapy as well as longer time since diagnosis leads to worse intellectual functioning.

Neurodevelopmental outcome, psychological adjustment, and quality of life in adolescents with congenital heart disease.

Abstract: Aim The aim of this study was to examine neurodevelopment, psychological adjustment, and health-related quality of life (HRQoL) in adolescents after bypass surgery for congenital heart disease (CHD) during early childhood. Method Fifty-nine adolescents (34 females, 25 males) with CHD were examined at a median age of 13 years 8 months (range 11y 5mo–16y 11mo). Outcome was assessed with the Wechsler Intelligence Scale for Children, (fourth edition); the Beery Test of Visual-Motor Integration; the Rey–Osterrieth Complex Figure Test; the Zurich Neuromotor Assessment; the Strengths and Difficulties Questionnaire; and the KIDSCREEN questionnaires. Results were compared with those of 40 age- and sex-matched healthy comparison individuals. Results Outcome with regard to full-scale IQ, perceptual reasoning, and the working memory scale was poorer in patients with CHD than in the comparison group (all p≤0.001). Visual perception, visuomotor integration (p≤0.001), and executive functions (Rey figure copy: p=0.05) were also affected. Patients with CHD also had lower scores on all motor domains (p<0.02) except static balance. Psychological adjustment was affected only in the ‘peer relationship’ domain (p=0.05). Quality of life was similar to that of typically developing peers. Interpretation Adolescents with CHD may manifest persistent cognitive and motor impairments, while psychological adjustment and self-reported HRQoL are mostly typical. Thus, long-term neurodevelopmental evaluations are necessary to provide early educational and therapeutic support.

Proportion of life lived with dystonia inversely correlates with response to pallidal deep brain stimulation in both primary and secondary childhood dystonia

Abstract: Aim The aim of this study was to examine the impact of dystonia aetiology and duration, contracture, and age at deep brain stimulation (DBS) surgery on outcome in a cohort of children with medically refractory, disabling primary, secondary-static, or secondary-progressive dystonias, including neurodegeneration with brain iron accumulation (NBIA). Method Dystonia severity was assessed using the Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) motor score at baseline and 6 and 12 months postoperatively in a cohort of 70 consecutive children undergoing DBS between June 2005 and July 2011. Results Two children (3%) received unilateral DBS for hemidystonia and were excluded and five (7%) developed infections requiring part-DBS removal within 6 months, leaving 63 children (90%) undergoing bilateral DBS for follow-up (34 males, 29 females; mean age at surgery for the whole group 10y 4mo, SD 4y 2mo, range 1–14y). Seventeen children were classified with primary dystonia: mean age 12 years 11 months, SD 4 years 6 months range 4 years 6 months to 17 years 3 months; 28 as having secondary-static dystonia: mean age 10 years 2 months, SD 4 years 9 months (range 3y 3mo–20y); five as having secondary-progressive dystonia: mean age 8 years 11 months, SD 3 years 9 months (range 5y 5mo–13y 1mo); and 13 as having NBIA dystonia: mean age 10 years 2 months, SD 3 years 11 months (range 1–14y). Children with primary dystonias demonstrated greater improvements in BFMDRS motor score than those in the other aetiological categories (Kruskal–Wallis test, p<0.001), which correlated negatively with dystonia duration and more strongly still against the ratio of dystonia duration normalized to age at surgery (DD/AS ratio) at 1 year (Spearman's rank correlation coefficient 0.4752 and −0.599 respectively). A similar significant negative correlation was found in the secondary-static dystonia group between outcome at 1 year and DD/AS ratio (−0.461). Poorer outcome in secondary dystonia coincided with the absence of a period of normal motor development in comparison with the primary dystonia group. A significant improvement in BFMDRS motor score was seen in the NBIA group at 6, but not 12 months (Wilcoxon signed rank test p=0.028, p=0.85 respectively). No reduction in efficacy was seen in children with a musculoskeletal deformity at the time of surgery. Conclusion Response to pallidal DBS in the treatment of dystonia declines with the proportion of life lived with dystonia in primary and secondary dystonia. Other intrinsic factors reduce the median magnitude of reduction in secondary dystonia after DBS. DBS should be offered early, preferably within 5 years of onset, to maximize benefits and reduce the childhood experience of dystonia, including musculoskeletal deformity. Other multidimensional assessments are required to understand how DBS improves the lives of children with dystonia.

Symptomatology of autism spectrum disorder in a population with neurofibromatosis type 1.

Abstract: Aim Difficulties in neurocognition and social interaction are the most prominent causes of morbidity and long-term disability in children with neurofibromatosis type 1 (NF1). Symptoms of attention-deficit–hyperactivity disorder (ADHD) have also been extensively recognized in NF1. However, systematic evaluation of symptoms of autism spectrum disorder (ASD) in children with NF1 has been limited. Method We present a retrospective, cross-sectional study of the prevalence of symptoms of ASD and ADHD and their relationship in a consecutive series of 66 patients from our NF1 clinic. The Social Responsiveness Scale and the Vanderbilt ADHD Diagnostic Parent Rating Scale were used to assess symptoms of ASD and ADHD. Results Sixty-six participants (42 males, 24 females) were included in this study. Mean age at assessment was 10 years 11 months (SD 5y 4mo). Forty percent of our NF1 sample had raised symptom levels reaching clinical significance on the Social Responsiveness Scale (T ≥ 60), and 14% reached levels consistent with those seen in children with ASDs (T ≥ 75). These raised levels were not explained by NF1 disease severity or externalizing/internalizing behavioral disorders. There was a statistically significant relationship between symptoms of ADHD and ASD (χ2=9.11, df=1, p=0.003, φ=0.56). Particularly salient were the relationships between attention and hyperactivity deficits, with impairments in social awareness and social motivation. Interpretation We found that symptoms of ASD in our NF1 population were raised, consistent with previous reports. Further characterization of the specific ASD symptoms and their impact on daily function is fundamental to the development and implementation of effective interventions in this population, which will probably include a combination of medical and behavioral approaches.

Clinical tools to assess balance in children and adults with cerebral palsy: a systematic review

Abstract: We aimed to review tools used to assess balance in clinical practice in children and adults with cerebral palsy (CP), to describe their content and measurement properties and to evaluate the quality of the studies that have examined these properties. CINAHL, Embase, and PubMed/MEDLINE were searched. The COnsensus-based Standards for selection of health Measurement INstruments (COSMIN) was used to assess the ‘quality of studies’ and the Terwee criteria were used to assess the ‘result of studies’. Twenty-two clinical balance tools were identified from 35 papers. The content and focus of the tools varied significantly. There was moderate or limited levels of evidence for most of the measurement properties of the tools; the strongest level of evidence was found for the Trunk Control Measurement Scale and the Level of Sitting Scale, in the category ‘maintain balance’, the Timed Up and Go and the Segmental Assessment of Trunk Control in the categories ‘achieve balance’ and ‘restore balance’ respectively. Information on responsiveness was scarce. Further studies providing better evidence for reliability and responsiveness for clinical balance tools are needed. In the meantime, results of studies evaluating effects of treatment of balance in individuals with CP should be interpreted with caution.

Does the Bayley‐III Motor Scale at 2 years predict motor outcome at 4 years in very preterm children?

Abstract: Aim To assess the predictive validity of the Bayley Scales of Infant and Toddler Development – Third Edition (Bayley-III) for later motor outcome. Method Ninety-six infants (49 males, 47 females) born at less than 30 weeks' gestation admitted to two tertiary hospitals in Melbourne, Australia, were assessed with the Bayley-III Motor Scale at 2 years' corrected age and were classified as suspect or definite motor impairment if they scored less than −1 or −2 standard deviations respectively, relative to the test mean. At 4 years' corrected age, children completed Movement Assessment Battery for Children – Second Edition (MABC-2); for the total motor score, cut-offs of not more than the 15th were used to classify motor development and cut-offs of not more than the 15th centile were classified as having a significant movement difficulty. Results Of the 96 children assessed at both ages, at 2 years 9% had suspect and 4% had definite motor impairment; however, by 4 years, rates had increased to 22% and 19% respectively. The specificity of the Bayley-III for motor impairments for later motor outcome was excellent (ranging from 94 to 100% for cerebral palsy [CP] and 97 to 100% for motor impairment), although the sensitivity was low (ranging from 67 to 83% for CP and 18 to 37% for motor impairment); many children with later impairment were not identified by the Bayley-III. Interpretation The Bayley-III Motor Scale at 2 years underestimates later rates of motor impairment, particularly in the absence of CP at 4 years on the MABC-2 total motor score in children born at less than 30 weeks' gestational age.

Iron‐deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years

Abstract: Aim The aim of this study was to assess the effects of iron-deficiency anemia (IDA) in infancy on executive functioning at age 10 years, specifically inhibitory control on the Go/No-Go task. We predicted that children who had IDA in infancy would show poorer inhibitory control. Method We assessed cognitive inhibitory control in 132 Chilean children (mean [SD] age 10y [1mo]): 69 children had IDA in infancy (45 males, 24 females) and 63 comparison children who did not have IDA (26 males, 37 females). Participants performed the Go/No-Go task with event-related potentials. Group differences in behavioral (accuracy, reaction time) and electrophysiological outcomes (N2 and P300 components) were analyzed using repeated-measures analyses of variance. N2 and P300 are interpreted to reflect attention and resource allocation respectively. Results Relative to comparison participants, children who had IDA in infancy showed slower reaction time (mean [SE], 528.7ms [14.2] vs 485.0ms [15.0], 95% confidence interval [CI] for difference between groups 0.9–86.5); lower accuracy (95.4% [0.5] vs 96.9% [0.6], 95% CI −3.0 to −0.1); longer latency to N2 peak (378.9ms [4.9] vs 356.9ms [5.0], 95% CI 7.5–36.6); and smaller P300 amplitude (4.5μV [0.8] vs 7.6μV [0.9], 95% CI−5.5 to −0.5). Interpretation IDA in infancy was associated with slower reaction times and poorer inhibitory control 8 to 9 years after iron therapy. These findings are consistent with the long-lasting effects of early IDA on myelination and/or prefrontal–striatal circuits where dopamine is the major neurotransmitter.

Towards a definition of neurodisability: a Delphi survey

Abstract: Aim The aim of this study was to develop, systematically, a consensus-based definition for ‘neurodisability’ that is meaningful to health professionals and parents of children with neurological conditions. Method A multidisciplinary group of health professionals was recruited through child development teams and professional societies in the UK; several parents of children with neurological conditions worked with the research team. Professionals participated in three rounds of a Delphi survey. Participants rated their agreement with a proposed definition in each round, and feedback was used to refine the definition. Finally, a perspective was sought from international experts. Results Responses to the three rounds were as follows: round 1, 245 out of 290 (84.4%); round 2, 242 out of 300 (80.6%); and round 3, 237 out of 297 (79.7%). Agreement with the proposed definition was extremely high in every round (89.0%, 90.1%, and 93.6% respectively). The final version of the definition was widely endorsed among professionals, parents, and a small number of international colleagues. The final definition is as follows: ‘Neurodisability describes a group of congenital or acquired long-term conditions that are attributed to impairment of the brain and/or neuromuscular system and create functional limitations. A specific diagnosis may not be identified. Conditions may vary over time, occur alone or in combination, and include a broad range of severity and complexity. The impact may include difficulties with movement, cognition, hearing and vision, communication, emotion, and behaviour'. Interpretation An agreed definition of neurodisability will be useful for conducting research or clinical evaluations with people affected by neurological problems.

Two types of exercise-induced neuroplasticity in congenital hemiparesis: a transcranial magnetic stimulation, functional MRI, and magnetoencephalography study.

Abstract: Aim Early unilateral brain lesions can lead to a persistence of ipsilateral corticospinal projections from the contralesional hemisphere, which can enable the contralesional hemisphere to exert motor control over the paretic hand. In contrast to the primary motor representation (M1), the primary somatosensory representation (S1) of the paretic hand always remains in the lesioned hemisphere. Here, we report on differences in exercise-induced neuroplasticity between individuals with such ipsilateral motor projections (ipsi) and individuals with early unilateral lesions but ‘healthy’ contralateral motor projections (contra). Method Sixteen children and young adults with congenital hemiparesis participated in the study (contralateral [Contra] group: n=7, four females, three males; age range 10–30y, median age 16y; ipsilateral [Ipsi] group: n=9, four females, five males; age range 11–31y, median age 12y; Manual Ability Classification System levels I to II in all individuals in both groups). The participants underwent a 12-day intervention of constraint-induced movement therapy (CIMT), consisting of individual training (2h/d) and group training (8h/d). Before and after CIMT, hand function was tested using the Wolf Motor Function Test (WMFT) and diverging neuroplastic effects were observed by transcranial magnetic stimulation (TMS), functional magnetic resonance imaging (fMRI), and magnetoencephalography (MEG). Statistical analysis of TMS data was performed using the non-parametric Wilcoxon signed-rank test for pair-wise comparison; for fMRI standard statistical parametric and non-parametric mapping (SPM5, SnPM3) procedures (first level/second level) were carried out. Statistical analyses of MEG data involved analyses of variance (ANOVA) and t-tests. Results While MEG demonstrated a significant increase in S1 activation in both groups (p=0.012), TMS showed a decrease in M1 excitability in the Ipsi group (p=0.036), but an increase in M1 excitability in the Contra group (p=0.043). Similarly, fMRI showed a decrease in M1 activation in the Ipsi group, but an increase in activation in the M1–S1 region in the Contra group (for both groups p<0.001 [SnPM3] within the search volume). Interpretation Different patterns of sensorimotor (re)organization in individuals with early unilateral lesions show, on a cortical level, different patterns of exercise-induced neuroplasticity. The findings help to improve the understanding of the general principles of sensorimotor learning and will help to develop more specific therapies for different pathologies in congenital hemiparesis.

Progressive resistance training and mobility-related function in young people with cerebral palsy: a randomized controlled trial.

Abstract: Aim The aim of this study was to investigate whether individualized resistance training improves the physical mobility of young people with cerebral palsy (CP). Method Forty-eight participants with spastic diplegic CP (26 males, 22 females; mean age 18y 1mo, SD 1y 11mo) classified as level II or III on the Gross Motor Function Classification System were allocated randomly to progressive resistance training or usual-care control. Resistance training was completed twice weekly for 12 weeks at a community gymnasium under the supervision of a physiotherapist. Exercises were based on instrumented gait analysis and targeted muscles contributing to walking difficulties. Outcomes at 12 weeks and 24 weeks included objective measures of mobility (6-min walk test, instrumented gait analysis, and Gross Motor Function Measure dimensions D and E), participant-rated measures of mobility (Functional Mobility Scale and Functional Assessment Questionnaire), and muscle performance. Results The strength of targeted muscles increased by 27% (95% CI 8–46%) compared with control group. There were no between-group differences in any objective measure of mobility at 12 weeks (6-min walk test: mean difference 0.1m; 95% CI −21 to 21m) or at 24 weeks. Participant-rated mobility improved (Functional Mobility Scale at 5m: mean 0.6 units; 95% CI 0.1–1.1 units; Functional Assessment Questionnaire: 0.8 units; 95% CI 0.1–1.6 units) compared with control group at 12 weeks. Interpretation Individualized progressive resistance training increased strength in adolescents and young adults with spastic diplegic CP. Despite participant-rated benefits, the increased strength did not result in objective improvements in mobility.

Passive muscle properties are altered in children with cerebral palsy before the age of 3 years and are difficult to distinguish clinically from spasticity

Abstract: Aim Clinical determination of spasticity is confounded by the difficulty in distinguishing reflex from passive contributions to muscle stiffness. There is, therefore, a risk that children with cerebral palsy (CP) receive antispasticity treatment unnecessarily. To investigate this, we aimed to determine the contribution of reflex mechanisms to changes in the passive elastic properties of muscles and tendons in children with CP. Method Biomechanical and electrophysiological measures were used to determine the relative contribution of reflex and passive mechanisms to ankle muscle stiffness in 35 children with spastic CP (21 males, 14 females; mean age 9y, SD 3y 4mo; range 3–15y) and 28 control children without CP (19 males, nine females; mean age 8y 11mo, SD 2y 10mo; range 3–15y). Twenty-seven children were diagnosed as having spastic hemiplegia, six with spastic diplegia, and two with spastic tetraplegia. According to the Gross Motor Function Classification System, 31 children were classified in level I, two in level II, and two in level III. Results Only seven children with spastic CP showed reflex stiffness outside the range of the control children. In contrast, 20 children with spastic CP showed abnormal passive muscle stiffness (p<0.001). No correlation between increased reflex or increased passive muscle stiffness and age was observed within the age range studied. Interpretation These data suggest that increased reflex-mediated muscle stiffness is difficult to distinguish clinically from changes in passive muscle stiffness and that signs of changes in muscle properties are already present from the age of 3 years in children with CP. This emphasizes the importance of accurately distinguishing different contributions to muscle stiffness to avoid unnecessary antispasticity treatment.

The mirror mechanism and its potential role in autism spectrum disorder

Abstract: The mirror mechanism allows the direct translation of a perceived (seen, felt, heard) action into the same motor representation of its related goal. This mechanism allows a direct comprehension of others' goals and motor intentions, enabling an embodied link between individuals. Because the mirror mechanism is a functional expression of the motor system, these findings suggest the relevance of the motor system to social cognition. It has been hypothesized that the impaired understanding of others' intentions, sensations, and emotions reported in autism spectrum disorder (ASD) could be linked to an alteration of the mirror mechanism in all of these domains. In this review, we address the theoretical issues underlying the social impairments in ASD and discuss them in relation to the cognitive role of the mirror mechanism.

The association of cerebral palsy with birth asphyxia: a definitional quagmire.

Abstract: Aim The aim of this study was to investigate whether current literature provides a useful body of evidence reflecting the proportion of cerebral palsy (CP) that is attributable to birth asphyxia. Method We identified 23 studies conducted between 1986 and 2010 that provided data on intrapartum risks of CP. Results The proportion of CP with birth asphyxia as a precursor (case exposure rate) varied from less than 3% to over 50% in the 23 studies reviewed. The studies were heterogeneous in many regards, including the definitions for birth asphyxia and the outcome of CP. Interpretations Current data do not support the belief, widely held in the medical and legal communities, that birth asphyxia can be recognized reliably and specifically, or that much of CP is due to birth asphyxia. The very high case exposure rates linking birth asphyxia to CP can probably be attributed to several factors: the fact that the clinical picture at birth cannot specifically identify birth asphyxia; the definition of CP employed; and confusion of proximal effects – results – with causes. Further research is needed.

Evidence for outcomes of motivational rehabilitation interventions for children and adolescents with cerebral palsy: an American Academy for Cerebral Palsy and Developmental Medicine systematic review.

Abstract: This study reviewed evidence regarding the effect of motivational rehabilitation interventions on outcomes in children with cerebral palsy. Six databases were searched for literature published up to May 2012. Included studies measured the purported motivating effects of motor-based rehabilitation interventions and the measured impact on outcomes. The American Academy for Cerebral Palsy and Developmental Medicine (AACPDM) systematic review methodology was used as a framework. Eight studies evaluated outcomes of studies using virtual reality interventions and one in a functional therapy context. Conflicting evidence from three (level II and level III) studies exists about the impact of these motivating interventions on motor outcomes measured in body functions. No statistical evidence regarding activity and participation outcomes exists. A single level II study found no significant difference in participants' motivation between motivational and conventional interventions. This review revealed a paucity of research on the effects of motivational interventions. Weaknesses include a lack of consistency in the examination of motivational interventions, limited use of definitions or theories to ground the concept of motivation, and reliance on non-validated methodological tools. This body of evidence would be strengthened by the use and development of robust outcome measures of motivation.

Understanding relationships between autism, intelligence, and epilepsy: a cross-disorder approach

Abstract: AIM As relationships between autistic traits, epilepsy, and cognitive functioning remain poorly understood, these associations were explored in the biologically related disorders tuberous sclerosis complex (TSC), neurofibromatosis type 1 (NF1), and epilepsy. METHOD The Social Responsiveness Scale (SRS), a quantitative measure of autistic traits, was distributed to caregivers or companions of patients with TSC, NF1, and childhood-onset epilepsy of unknown cause (EUC), and these results were compared with SRS data from individuals with idiopathic autism spectrum disorders (ASDs) and their unaffected siblings. Scores and trait profiles of autistic features were compared with cognitive outcomes, epilepsy variables, and genotype.

Intensive therapy following upper limb botulinum toxin A injection in young children with unilateral cerebral palsy: a randomized trial

Abstract: Aim Botulinum toxin A (BoNT-A) combined with occupational therapy is effective in improving upper limb outcomes in children with unilateral cerebral palsy (CP). It is now essential to identify the most effective therapies following BoNT-A. Given the added burden for children and families, the aim of this study was to explore whether modified constraint-induced movement therapy (mCIMT) leads to sufficiently superior gains compared with bimanual occupational therapy (BOT) in young children with unilateral CP following BoNT-A injections. Method In this randomized, controlled, evaluator-blinded trial, 34 children (20 males, 14 females; mean age 3y, SD 1y 4mo, range 18mo–6y) with unilateral CP were randomized using concealed allocation to one of two 8-week interventions. The experimental group (n=17) received BoNT-A and mCIMT. The comparison group (n=17) received BoNT-A and BOT. Participants were recruited from a physical rehabilitation clinic and randomized between August 2003 and May 2009. Primary outcome was measured using the Assisting Hand Assessment at 3 months. Secondary outcomes were measured at 3 months and 6 months using the Quality of Upper Extremity Skills Test, the Pediatric Evaluation of Disability Inventory, Canadian Occupational Performance Measure, and the Goal Attainment Scale. Results There were no clinically important differences between groups at baseline. Immediately following intervention, there was no evidence of a superior effect for BoNT-A + mCIMT as determined by the Assisting Hand Assessment (estimated mean difference [EMD] 0.81, upper 95% confidence limit 3.6; p=0.32) or secondary outcomes. However, both groups showed improvement over time (BoNT-A + mCIMT: EMD 2.7, 95% confidence interval [CI] 0.7–5.2; BONT-A + BOT: EMD 4.7, 95% CI 2.1–8.6). Follow-up at 6 months also demonstrated no superior effect for BoNT-A + mCIMT. Interpretation Following upper limb injection of BoNT-A, there was no evidence that mCIMT, despite the significantly increased intensity of the home programme, produced a superior effect across a range of outcomes compared with a structured programme of BOT in young children with unilateral CP.

Reduced satellite cell population may lead to contractures in children with cerebral palsy.

Abstract: Aim Satellite cells are the stem cells residing in muscle responsible for skeletal muscle growth and repair. Skeletal muscle in cerebral palsy (CP) has impaired longitudinal growth that results in muscle contractures. We hypothesized that the satellite cell population would be reduced in contractured muscle. Method We compared the satellite cell populations in hamstring muscles from participants with CP contracture (n=8; six males, two females; age range 6–15y; Gross Motor Function Classification System [GMFCS] levels II–V; 4 with hemiplegia, 4 with diplegia) and from typically developing participants (n=8; six males, two females, age range 15–18y). Muscle biopsies were extracted from the gracilis and semitendinosus muscles and mononuclear cells were isolated. Cell surface markers were stained with fluorescently conjugated antibodies to label satellite cells (neural cell adhesion molecule) and inflammatory and endothelial cells (CD34 and CD4 respectively). Cells were analyzed using flow cytometry to determine cell populations. Results After gating for intact cells a mean of 12.8% (SD 2.8%) were determined to be satellite cells in typically developing children, but only 5.3% (SD 2.3%; p 0.05) suggesting the isolation procedure was valid. Interpretation A reduced satellite cell population may account for the decreased longitudinal growth of muscles in CP that develop into fixed contractures or the decreased ability to strengthen muscle in CP. This suggests a unique musculoskeletal disease mechanism and provides a potential therapeutic target for debilitating muscle contractures.