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Background and Purpose: The aims of this study were to assess the prevalence of multidimensional fatigue symptoms 5 years after pediatric arterial ischemic stroke and identify factors associated with fatigue. Methods: Thirty-one children (19 males) with pediatric arterial ischemic stroke, participating in a larger prospective, longitudinal study, were recruited to this study at 5 years poststroke. Parent- and self-rated PedsQL Multidimensional Fatigue Scale scores were compared with published normative data. Associations between parent-rated PedsQL Multidimensional Fatigue Scale, demographics, stroke characteristics, and concurrent outcomes were examined. Results: Parent-rated total, general and cognitive fatigue were significantly poorer than population norms, with more than half of all parents reporting fatigue symptoms in their children. One-third of children also reported experiencing fatigue symptoms, but their ratings did not differ significantly from normative expectations, as such, all further analyses were on parent ratings of fatigue. Older age at stroke and larger lesion size predicted greater general fatigue; older age, female sex, and higher social risk predicted more sleep/rest fatigue. No significant predictors of cognitive fatigue were identified and only older age at stroke predicted total fatigue. Greater fatigue was associated with poorer adaptive functioning, motor skills, participation, quality of life, and behavior problems but not attention. Conclusions: Fatigue is a common problem following pediatric arterial ischemic stroke and is associated with the functional difficulties often seen in this population. This study highlights the importance of long-term monitoring following pediatric arterial ischemic stroke and the need for effective interventions to treat fatigue in children.

To understand the systems underlying current rehabilitation models of care used with children and youth (0-21years) who sustain traumatic brain and/or spinal cord injuries. This study gathered qualitative data on service structures, service organization, and the barriers and facilitators of service provision in selected medical rehabilitation service(s) (MRS) and community-based rehabilitation service(s) (CBRS). Informants from 11 rehabilitation services were interviewed using a semi-structured interview guide. Interviews were analysed in NVivo using content analysis method. Experiences shared by the service representatives indicated that most services supported children and youth with brain injury, with a limited number also specializing in spinal cord injuries. MRS often delivered care in inpatient or outpatient settings, while CBRS offered home/community-based services. Care planning often started either prior to or shortly after admission from acute care settings, using either multidisciplinary or interdisciplinary teamwork models. Strengths of the services included innovation and provision of family-centred care; while challenges experienced included difficulty translating evidence into practice and poor team communication. Models of care were similar across services, with a focus on providing family-centred care. Several shared challenges were described, and service representatives expressed interest in forming partnerships and collaborations to address these challenges through innovative initiatives.

Background and Purpose: Childhood and adolescence coincide with rapid maturation of distributed brain networks supporting social cognition; however, little is known about the impact of early ischemic brain insult on the acquisition of these skills. This study aimed to examine the influence of arterial ischemic stroke (AIS) on facial emotion recognition and theory of mind (ToM) abilities of children and adolescents initially recruited to a single-center, prospective longitudinal study of recovery following AIS. Methods: The study involved 67 participants, including 30 children with AIS (mean time since stroke=5 years) and 37 age-matched typically developing controls who were assessed on measures of cognitive ToM, facial emotion recognition, and affective ToM. Acute clinical magnetic resonance imaging, including diffusion-weighted imaging sequences, were used to evaluate prospective structure-function relationships between acute lesion characteristics (size, location, and arterial territories affected) and long-term social cognitive abilities. Results: Relative to age-matched typically developing controls, children with AIS showed significantly worse performance on measures of basic facial emotion processing, cognitive ToM, and affective ToM. In univariate models, poorer ToM was associated with larger infarcts, combined cortical-subcortical pathology, and involvement of multiple arterial territories. In multivariate analyses, larger lesions and multiterritory infants were predictive of ToM processing but not facial emotion recognition. Poorer cognitive ToM predicted less frequent prosocial behavior and increased peer problems. Conclusions: Social cognitive skills appear vulnerable to disruption from early ischemic brain insult. In the first study to examine social cognition in a prospective cohort of children with AIS, our findings suggest that acute magnetic resonance imaging-based lesion characteristics may have predictive value for long-term social cognitive outcomes and may assist to identify children at elevated risk for social cognitive dysfunction.

Review the literature on predictors of participation and quality of life in children and young people who sustained a traumatic brain injury (TBI), spinal cord injury (SCI), and/or multi-trauma in a motor vehicle or other accident or trauma.This systematic review was conducted and reported in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol was registered on PROSPERO (registration number CRD42020131698). Electronic databases were searched for studies published between January 2000 and August 2020. Prospective and retrospective cohort studies were considered and risk of bias was assessed using the Quality In Prognosis Studies (QUIPS) tool.The search yielded 5771 articles of which 30 studies met the inclusion criteria. Nineteen studies included patients with TBI and 11 with SCI. No studies of patients with multi-trauma met criteria. Evidence was found for associations with various factors (e.g., injury severity, level of education, mental health problems), although these findings are limited due to the quality of the studies (5 studies moderate and 25 high risk of bias).Research on predictors of participation and quality of life following major traumatic injuries in childhood is lacking. More methodologically sound prospective, longitudinal studies are needed across different injury groups to further elucidate predictors of outcome.IMPLICATIONS FOR REHABILITATIONWhile long-term participation and quality of life is influenced by injury characteristics (i.e., injury severity), a number of potential modifiable factors can be targeted to improve outcomes following traumatic injuries in childhood.Young people should be provided with support to stay in school and pursue further education.Early intervention and prevention of mental health problems may improve long-term outcomes.Better management of ongoing medical problems and greater support for functional independence may improve participation.

To describe current rehabilitation models of care and programmes, in Australia and internationally, related to family-centred care, psychosocial support, and transitions used for children and youth who have sustained major traumatic brain and/or spinal cord injuries. Fourteen services were interviewed, including eight medical rehabilitation services, three community-based rehabilitation services, two insurance services, and one state-wide education service provider. Semi-structured interviews were transcribed and analysed using qualitative content analysis in NVivo. Compared to the number of services supporting children and youth with traumatic brain injury, a very limited number supported those with spinal cord injury. Although valued and often included in the model of care, family-centred care was rarely systematically evaluated by the services. Most services provided psychosocial and transition support to children and youth, and their families in the short-term post-injury, but not in the long-term. Several challenges also hindered the smooth delivery of these support services, including poor communication between service providers. These findings show that services aimed to provide the best possible care to these children and youth, and their families; guided by rehabilitation models of care. However, challenges persist with regards to delivering family-centred care, coordinating return to school, and providing long-term support for psychosocial problems and transition.

Childhood stroke results in long-term, multifaceted difficulties, affecting motor, cognitive, communication, and behavioral domains of function which impact on participation and quality of life. The Childhood Stroke Consensus Rehabilitation Guideline was developed to improve the care of children with stroke by providing health professionals with recommendations to assist in their rehabilitative treatment. Clinical questions were formulated to inform systematic database searches from 2001 to 2016, limited to English and pediatric studies. SIGN methodology and the National Health and Medical Research Council system were used to screen and classify the evidence. The Grade of Recommendation, Assessment, Development and Evaluation system was used to grade evidence as strong or weak. Where evidence was inadequate or absent, a modified Delphi consensus process was used to develop consensus-based recommendations. The guideline provides 56 recommendations (1 evidence-based recommendation and 55 consensus recommendations). These relate to the framework of rehabilitation service delivery as well as domain-specific rehabilitation treatment strategies for each domain of function. It is anticipated that this guideline will provide health professions with recommendations to improve the subacute care of children with stroke both in Australia and internationally.

Despite many children experiencing fatigue after childhood brain injury, little is known about the predictors of this complaint. To date, traditional indices of traumatic brain injury (TBI) severity have not predicted reliably persisting fatigue (up to three years post-injury). This study aimed to establish whether persisting fatigue is predicted by serum biomarker concentrations in child TBI. We examined whether acute serum biomarker expression would improve prediction models of 12-month fatigue based on injury severity. Blood samples were collected from 87 children (1-17 years at injury) sustaining mild to severe TBI (Glasgow Coma Scale [GCS] range 3-15; mean 12.43; classified as mild TBI [n = 50, 57%] vs. moderate/severe TBI [n = 37, 43%]), and presenting to the emergency departments (ED) and pediatric intensive care units (PICU) at one of three tertiary pediatric hospitals (Royal Children's Hospital (RCH); Hospital for Sick Children (HSC), Toronto; St Justine Children's Hospital (SJH), Montreal). Six serum biomarker concentrations were measured within 24 h of injury (interleukin-6, interleukin-8 [IL-8], soluble vascular cell adhesion molecule [SVCAM], S100 calcium binding protein B [S100B], neuron specific enolase [NSE], and soluble neural cell adhesion molecule [sNCAM]). Fatigue at 12 months post-injury was measured using the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (parent report), classified as present/absent using previously derived cut-points. At 12 months post-injury, 22% of participants experienced fatigue. A model including IL-8 was the best serum biomarker for estimating the probability of children experiencing fatigue at 12 months post-injury. The IL-8 also significantly improved predictive models of fatigue based on severity.

Pediatric stroke can result in long-term neurobehavioral impairments including cognitive, language, and motor deficits, all of which may disrupt the normal development of social skills. This study aimed to examine specific components of social function at 5-year poststroke at a group and individual level and explore the contribution of neurobehavioral impairment. Thirty-one children with arterial ischemic stroke participated in the study. Assessment included parent-rated questionnaires measuring social adjustment and social participation as well as behavior and fatigue. Children underwent testing of social cognition and neurobehavioral abilities (intellectual function, attention, pragmatic language, motor function, and neurological impairment). Group means for social function were generally within the normal range, with social adjustment poorer than normative expectations. Examination of impairment rates showed a significant proportion of children had impaired function across social domains. Childhood stroke was associated with poorer social adjustment and a range of neurobehavioral outcomes, compared to neonatal stroke. Social function was found to be impacted by fatigue and intellectual function, but not by attention, pragmatic language, behavior, motor function, or neurological impairment.

Objectives:Fatigue is a common and persisting symptom after childhood brain injury. This study examined whether child characteristics and symptomatology preinjury or 6 months postinjury (pain, sleep, and mood, inattention) predicted fatigue at 12months postinjury.Methods:Parents of 79 children (0–18 years) rated fatigue at 12 months after injury on a multidimensional scale (general, sleep/rest, and cognitive). Demographic and clinical data were collected at injury. Parents rated child sleep, pain, physical/motor function, mood, and inattention at injury (preinjury description), and 6 months postinjury. Children were divided into two traumatic brain injury severity groups:mild TBI(n=57) andmoderate/severe TBI(n=27). Hierarchical regression models were used to examine (i) preinjury factors and (ii) symptoms 6 months postinjury predictive of fatigue (general, sleep/rest, and cognitive) at 12 months postinjury.Results:Sleep/rest fatigue was predicted by preinjury fatigue (7% of variance) and psychological symptoms preinjury (10% of variance). General fatigue was predicted by physical/motor symptoms (27%), sleep (10%) and mood symptoms (9%) 6 months postinjury. Sleep/rest fatigue was predicted by physical/motor symptoms (10%), sleep symptoms (13%) and mood symptoms (9%) 6 months postinjury. Cognitive fatigue was predicted by physical/motor symptoms (17%) 6 months postinjury.Conclusions:Preinjury fatigue and psychological functioning identified those at greatest risk of fatigue 12 months post-TBI. Predictors of specific fatigue domains at 12 months differed across each of the domains, although consistently included physical/motor function as well as sleep and mood symptoms postinjury. (JINS, 2018,24, 224–236)

Aim Little is known about psychological and social outcomes after paediatric stroke. This study aimed to evaluate psychosocial outcomes in children 5 years after paediatric stroke and explore the contribution of early presenting factors. Method Thirty-one children (19 males and 12 females) with arterial ischemic stroke were involved in this prospective, longitudinal study. Children underwent intellectual assessment at 12 months poststroke and parents completed questionnaires rating their own mental health and their child's functioning at 12 months and 5 years poststroke. Results At 5-year follow-up, psychological and social function were significantly poorer than normative expectations. Exploration of early predictive factors showed poorer cognitive and psychological function at 12 months poststroke and older age at stroke onset was associated with poorer psychosocial function at 5 years. Larger lesion size was also associated with poorer psychological function at 5 years poststroke. Interpretation These early predictors of poorer psychosocial outcome suggest that screening children within the first year after stroke may identify children most at risk of later problems and facilitate early intervention.

Objectives:This study examined whether children with distinct brain disorders show different profiles of strengths and weaknesses in executive functions, and differ from children without brain disorder.Methods:Participants were children with traumatic brain injury (N=82; 8–13 years of age), arterial ischemic stroke (N=36; 6–16 years of age), and brain tumor (N=74; 9–18 years of age), each with a corresponding matched comparison group consisting of children with orthopedic injury (N=61), asthma (N=15), and classmates without medical illness (N=68), respectively. Shifting, inhibition, and working memory were assessed, respectively, using three Test of Everyday Attention: Children’s Version (TEA-Ch) subtests: Creature Counting, Walk-Don’t-Walk, and Code Transmission. Comparison groups did not differ in TEA-Ch performance and were merged into a single control group. Profile analysis was used to examine group differences in TEA-Ch subtest scaled scores after controlling for maternal education and age.Results:As a whole, children with brain disorder performed more poorly than controls on measures of executive function. Relative to controls, the three brain injury groups showed significantly different profiles of executive functions. Importantly, post hoc tests revealed that performance on TEA-Ch subtests differed among the brain disorder groups.Conclusions:Results suggest that different childhood brain disorders result in distinct patterns of executive function deficits that differ from children without brain disorder. Implications for clinical practice and future research are discussed. (JINS, 2017,23, 529–538)

Purpose of review The past 20 years have seen a 35% increase in prevalence of pediatric stroke. Contrary to widely held views, children do not recover better than adults. This review explores the impact of pediatric stroke on cognitive domains, including intellectual and executive functions, memory and behavior, and the influence of age, lesion characteristics, and comorbidities on outcome. Recent findings Cognitive problems occur in up to half of ischemic and hemorrhagic stroke survivors. Single-center studies have shown intelligence quotient scores skewed to the lower end of the average range, with greater impairment in performance than verbal domains. Executive function, such as attention and processing speed are particularly vulnerable to the effects of pediatric stroke. Age at stroke, larger infarct size, cortical/subcortical lesion location, epilepsy, and comorbid physical deficits are associated with poorer cognitive outcomes. Summary Cognitive impairment occurs relatively frequently following pediatric stroke but the nature, severity, and predictors of specific deficits are not well defined. Improving understanding of outcomes following pediatric stroke is a key priority for families but a paucity of data limits the ability to develop targeted disease, and age-specific pediatric rehabilitation strategies to optimize cognitive outcomes following pediatric stroke.

OBJECTIVES: To determine (1) the presence of fatigue symptoms and predictors of fatigue after childhood brain injury and examine (2) the feasibility, reliability, and validity of a multidimensional fatigue measure (PedsQL Multidimensional Fatigue Scale [MFS]) obtained from parent and child perspectives. SETTING: Emergency and intensive care units of a hospital in Melbourne, Australia. PARTICIPANTS: Thirty-five families (34 parent-proxies and 32 children) aged 8 to 18 years (mean child age = 13.29 years) with traumatic brain injury (TBI) of all severities (27 mild, 5 moderate, and 3 severe) admitted to the Royal Children's Hospital. DESIGN: Longitudinal prospective study. Fatigue data collected at 6-week follow-up (mean = 6.9 weeks). MAIN OUTCOME MEASURES: Postinjury child- and parent-rated fatigue (PedsQL MFS), mood, sleep, and pain based on questionnaire report: TBI severity (mild vs moderate/severe TBI). RESULTS: A score greater than 2 standard deviations below healthy control data indicated the presence of abnormal fatigue, rates of which were higher compared with normative data for both parent and child reports (47% and 29%). Fatigue was predicted by postinjury depression and sleep disturbance for parent, but not child ratings. Fatigue, as rated by children, was not significantly predicted by TBI severity or other symptoms. The PedsQL MFS demonstrated acceptable measurement properties in child TBI participants, evidenced by good feasibility and reliability (Cronbach α values >0.90). Interrater reliability between parent and child reports was poor to moderate. CONCLUSIONS: Results underscore the need to assess fatigue and associated sleep-wake disturbance and depression after child TBI from both parent and child perspectives.

Little is known about resilience after paediatric stroke (PS), or the factors that contribute to better outcomes. Rather, research emphasis has been on impairment, measured through cross-sectional or retrospective designs, often heavily weighted to children presenting for clinical or rehabilitation follow-up. Implementing a resilience framework, this study aimed to investigate cognitive recovery post-stroke and factors that contribute to cognitive resilience at 12 months following PS. In a single site, prospective, longitudinal study (baseline, 1, 6, 12 months post-stroke), 61 children (55.7% male) aged 0-18 years, with a diagnosis of acute arterial ischemic stroke were recruited. Neurological status, lesion and child characteristics were collected at diagnosis. Cognitive, language and motor skills were assessed directly using age-appropriate, standardised tools. Parents rated their mental health, and child social and adaptive abilities. Participants were classified as 'resilient' (74%) or 'vulnerable' based on 12-month cognitive scores. The resilient group demonstrated more intact acute neurological status and higher language and adaptive abilities 1-month post-stroke; 88% of the vulnerable group had strokes involving both cortical and subcortical regions. Neonatal stroke, large lesions, cortical-only lesions, and middle cerebral artery involvement were associated with poorer cognition over the 12 months post-stroke. Absence of seizures and older age at stroke predicted better cognitive outcomes. In summary, most children surviving PS are cognitively resilient at 12 months post-insult. Risk and protective factors identified may guide targeted clinical intervention for more vulnerable children. Future research is needed to explore cognitive resilience trajectories beyond 12 months post-stroke.

Summary Background Traumatic brain injury (TBI) is a major health problem in children. Blood-based biomarkers interpreted by use of normative values might improve the accuracy of diagnosis. Ultrasensitive assays can quantify serum concentrations of the neuronal microtubule-associated protein tau, which is increased in adult brains following TBI. We aimed to determine if serum total tau correlates with TBI diagnosis, severity, and radiological findings on CT scans in children younger than 18 years. Methods In this case-control study, we included venous blood samples from healthy control children in the Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) biobank. For TBI cases, we recruited children (aged 0–17 years) who presented to the emergency department within 24 h of a TBI in three tertiary-care paediatric hospitals (Toronto, Vancouver, and Melbourne). Children were eligible if they required hospital observation for a minimum of 4 h or admission to the intensive care unit, and were excluded if they had had hospital treatment for a previous TBI, had birth trauma, or their parents could not speak English or French and therefore could not readily give consent. All available control samples were used and a case-control match was therefore not done. Venous and arterial blood samples were collected from patients with TBI within 28 h of injury (day 1). We used an ultrasensitive single-molecule immunoassay to measure serum total tau in blood samples. We first generated reference intervals of serum total tau from the control group, and used these normative data to interpret injury-associated changes in serum total tau in children with TBI. Concentrations of serum tau were measured in all CALIPER participants and patients with TBI, and no participants were excluded before analysis. Findings We included samples from 416 control participants from the CALIPER cohort. Median total tau concentrations did not differ between sexes (p=0·12), but three significant reference intervals based on age groups were identified (1–3 years [0·88–19·2 pg/mL], 4–15 years [0·93–5·31 pg/mL], and 16–19 years [0·79–4·20 pg/mL]). Blood samples were obtained from 158 patients with TBI recruited between April 30, 2011, and June 28, 2013. Serum total tau on day 1 of TBI was negatively associated with Glasgow Coma Scale (GCS) score (rs=–0·42, 95% CI −0·55 to −0·28, p Interpretation Serum total tau might help to differentiate between patients with mild TBI (GCS 13–14 vs GCS 15), but larger studies are needed to validate these results before this biomarker can be used for diagnosis and prognosis. Funding Canadian Institutes of Health Research, Ontario Neurotrauma Foundation, and Victoria Neurotrauma Foundation

Previous studies investigating long-term outcomes in children following vitamin B12 deficiency during infancy have been limited to IQ or clinical observation. This paper seeks to describe comprehensive neuropsychological profiles in a case series of school-aged children who were treated for infantile vitamin B12 deficiency. This was a retrospective case series of seven children who were treated for vitamin B12 deficiency during infancy and aged 5 to 16 years at the time of testing. While most children had age-expected intellectual performance, the distribution of the sample was skewed to the lower end of the normal range. Furthermore, children were found to have impairments in a number of neuropsychological domains, most common were attention and memory, followed by executive function. These results suggest that while neurological symptoms quickly resolve following treatment, these effects on early brain development may disrupt brain maturation and have the potential to impact on later development.

Contrary to commonly held views, children do not recover better than adults after a stroke.1 The lifelong individual, family, and societal burden of stroke is likely to be greater than in adults because infants and children surviving stroke face many more years living with disability. The key difference between children and adults is that childhood stroke (occurring during the perinatal period and beyond) results primarily in a changed ability to achieve, rather than lose, functional independence. The extent and severity of deficits across motor, sensory, cognitive, social, and behavioral domains may not be apparent in the short-term after stroke, particularly in newborns and preschool children, who typically grow into their deficits.2,3 The World Health Organization’s International Classification of Functioning (ICF), Disability, and Health can be applied to childhood stroke to describe its impact across health domains, including impairment in body structures and functions, activity limitations and participation restrictions at individual, institutional and social levels. This review will focus on childhood stroke, defined as stroke from 1 month to 18 years of age, and where possible use the ICF framework to describe outcome after arterial ischemic stroke (AIS) and hemorrhagic stroke (HS). ### Mortality After Childhood Stroke Stroke is among the top 10 causes of death in the pediatric population. The reported mortality for AIS ranges from 7% to 28%1,4 and from 6% to 54% for HS.5 In the US study reporting stroke mortality during a 10-year period from 1979 to 1998, 4881 deaths could be attributed to childhood stroke, giving average annual mortality rates of 0.09 per 100 000 person-years for AIS 0.14 for intracerebral hemorrhage and 0.11 for subarachnoid hemorrhage.6 Risk of death was higher in infants, males, blacks, and children living in the South-Eastern Stroke belt States.6,7 Declining mortality rates have …

Aim To describe 5-year motor and functional outcomes after paediatric arterial ischaemic stroke (AIS) and to explore factors associated with poorer long-term outcome. Method Thirty-three children (21 males, 12 females) with AIS were recruited to a single-site, cross-sectional study, from a previously reported prospective longitudinal stroke outcome study. Children were stratified according to age at diagnosis: neonates (≤30d), preschool (>30d-5y), and school age (≥5y). Motor and functional outcomes were measured at 5 years after stroke. Neurological outcomes were evaluated using the Pediatric Stroke Outcome Measure (PSOM) at 1 month and more than 4 years after stroke. Results At 5 years after stroke, motor function, quality of life, fatigue, adaptive behaviour, activities of daily living, and handwriting speed were significantly poorer than age expectations. The preschool group had the highest percentage of fine and gross motor impairment. Poorer fine motor skills were associated with subcortical-only lesions and large lesion size. Poorer gross motor outcomes correlated with preschool age, bilateral lesions, and PSOM impairment at 1 month. Interpretation Children are at elevated risk for motor and functional impairments after AIS, with the preschool age group most vulnerable. Identifying early predictors of poorer outcomes facilitates targeted early intervention and long-term rehabilitation. What this paper adds Following paediatric stroke, children are at elevated risk of motor and functional difficulties. Stroke occurring between 30 days and 5 years of age may result in poorer motor and functional outcomes.

Exploration of the consequences of brain insult sustained early in life has a long history, dating back to the 1920s and the seminal works of Lashley (1929), Kennard (1938, 1942), and Hebb (1949), and later comprehensive reviews (e.g., Finger & Stein, 1982; Isaacson, 1975; St James-Roberts, 1975). In this literature, while insults in infancy and early childhood were regarded as qualitatively and quantitatively distinct from those occurring in adulthood, there was little agreement regarding the potential benefits and vulnerabilities of early brain insult.

Background Pediatric stroke outcome studies are often cross sectional in design. Prospective information regarding the clinical course following diagnosis is lacking, but may inform clinical management beyond the acute period. Aims To describe the outcome of arterial ischemic stroke in infants, children and adolescents at one-month and six-months post-stroke across health domains, and explore the relationship between lesion characteristics and early outcome with six-month adaptive behavior. Methods A single center prospective longitudinal study at a tertiary level children's hospital. Recruitment was undertaken from December 2007 to January 2012. Participants were children aged birth to 18 years presenting acutely with first diagnosed arterial ischemic stroke. Lesion characteristics on brain imaging were classified. Children were grouped according to age at diagnosis for analysis (neonates vs. those aged >30 days). Results In 50 children with a median age of 47 months at diagnosis, sensorimotor impairments were most evident upon neurological examination acutely, especially in the older children. At both one-month and six-months motor functioning was significantly impaired in the older age group but no significant cognitive or language sequelae were identified. Lesion characteristics alone were not associated with six-month adaptive behavior outcomes. Conclusions For patients surviving arterial ischemic stroke, the most significant clinical consequences both acutely and at six-months, are sensorimotor impairments, particularly evident in the older children. In contrast cognitive or language sequelae were not identified. Long-term surveillance is required to describe clinical course and rehabilitation needs, particularly for neonates and infants.

BACKGROUND: Longitudinal fatigue data in children suffering from traumatic brain injury (TBI) are lacking. OBJECTIVES: To examine the effects of time postinjury (6-12 months) and injury severity on fatigue after childhood TBI. Secondarily, we compared fatigue 12 months postinjury against published control data. SETTING: Three tertiary children's hospitals across Australia (n = 1) and Canada (n = 2). PARTICIPANTS: Parents (n = 109) of children (mean [M] = 9.9 years at injury; range, 1.0-16.9 years) admitted to one of 3 participating hospitals with mild (n = 69) or moderate/severe (n = 37) TBI. DESIGN: Longitudinal prospective study. MEASURES: Primary: Pediatric Quality of Life Multidimensional Fatigue Scale (total, general, sleep/rest, and cognitive), rated by parents 6 and 12 months postinjury. Secondary: Pediatric Injury Functional Outcome Scale (fatigue and sleep items, rated on recruitment and 6 and 12 months postinjury). Demographic and children data were collected at recruitment. RESULTS: Mixed-models analysis demonstrated nonsignificant effects of time (6 vs 12 months postinjury) on multidimensional fatigue scores. Cognitive fatigue worsened over time. Moderate/severe TBI was associated with worse fatigue 12 months postinjury (general, P = .03; cognitive, P = .02). Across all severities, fatigue 12 months postinjury was significantly worse compared with control data (total fatigue, P < .001; all domains, all Ps < .025). CONCLUSION: Fatigue remains significant at 12 months since injury, particularly for those with moderate/severe TBI.

BACKGROUND: Neuromotor impairments are common after pediatric stroke, but little is known about functional motor outcomes. We evaluated motor function and how it changed over the first 12 months after diagnosis. We also examined differences in outcome according to age at diagnosis and whether fine motor (FM) or gross motor (GM) function at 12 months was associated with adaptive behavior. METHODS: This prospective, longitudinal study recruited children (N = 64) from The Royal Children’s Hospital, Melbourne who were diagnosed with acute arterial ischemic stroke (AIS) between December 2007 and November 2013. Motor assessments were completed at 3 time points after the diagnosis of AIS (1, 6, and 12 months). Children were grouped as follows: neonates (n = 27), preschool-aged (n = 19), and school-aged (n = 18). RESULTS: A larger lesion size was associated with poorer GM outcomes at 12 months (P = .016). Neonatal AIS was associated with better FM and GM function initially but with a reduction in z scores over time. For the preschool- and school-aged groups, FM remained relatively stable over time. For GM outcomes, the preschool- and the school-aged age groups displayed similar profiles, with gradual recovery over time. Overall, poor FM and GM outcomes at 12 months were associated with poorer adaptive behavior scores. CONCLUSIONS: Motor outcomes and the trajectory of recovery post-AIS differed according to a child’s age at stroke onset. These findings indicate that an individualized approach to surveillance and intervention may be needed that is informed in part by age at diagnosis.

Aims The aims of the study were to investigate (1) the impact of age at brain insult on functional outcome and (2) the influence of insult and environmental factors on cognitive and behavioural outcomes. Method The study was a cross-sectional, retrospective observational study, involving 138 children (76 males, 62 females; mean age 13y 1mo, SD 1y 11mo, range 10–16y) with magnetic resonance imaging (MRI) evidence of focal brain insult sustained from the first trimester of pregnancy to adolescence. Children underwent MRI and intellectual, executive, behavioural, and social evaluation. Outcome predictors were insult (lesion location, laterality, and extent, history of seizures, age at insult) and environmental (social risk and family function) factors. Results Focal insult before the age of 3 years was associated with poorer outcomes than insult after the age of 3 years across all domains. For IQ outcomes, insult characteristics and seizures were highly predictive. For executive and behavioural domains, family function and social risk had the greatest impact. Earlier age at insult predicted poorer social competence. Interpretation Focal brain insult before age 3 years has devastating consequences for children's development. Findings suggest that greater emphasis should be placed on providing early intervention for children who sustain early focal brain insults.

Childhood stroke (CS) is a neurological condition occurring in 7:100000 children ( Hartel, Schilling, Sperner, & Theyen, 2004 ). Consequences include physical, cognitive, and language deficits and psychosocial disturbance, with the latter least researched. We critically reviewed the literature over the last 18 years. We identified 16 papers addressing psychosocial outcomes, which highlighted that CS confers increased risk of psychosocial impairment. Little is known regarding the contribution of stroke-specific and environmental influences. Small samples, variable age at onset and time since onset, lack of controls, and a focus on parent ratings limit generalizability of findings. Further investigation is needed to provide information regarding rehabilitation within the psychosocial domain.

Aim Childhood stroke disrupts brain development and emerging neural networks. Motor, cognitive, and language deficits are well recognized, yet little is known about psychosocial function after childhood stroke. This study aims to describe psychosocial function within the first year after childhood stroke, and to identify factors associated with outcome. Method Thirty-seven children were involved in a prospective, longitudinal study investigating recovery over the first year after childhood stroke. Children's social functioning was assessed at 6-months and 12-months poststroke and psychological function at 12-months poststroke, using standardized measures. Results Mean social function was poorer at both 6-months and 12-months poststroke, compared to prestroke. Psychological problems were more common than expected, with emotional difficulties and hyperactivity–inattention most significantly affected. Poorer social function was associated with older age at onset, acute neurological impairment, and prestroke social impairment. Social and psychological problems were associated with parent mental health. Interpretation While not all children are affected, psychosocial impairment affects a significant minority after childhood stroke. Older age at onset, acute neurological impairment, prestroke social problems, and poorer parent mental health were associated with deficits. Identifying early predictors of poorer outcome will facilitate early intervention. Of particular importance is parent mental health, suggesting support for families may improve child outcome.

Background Social functioning encompasses a range of important skills that an individual uses to interact with the social world. Previous studies suggest that social functioning (outcomes) may be impaired after childhood stroke, but research is limited. Aims We examined the following: ( 1 ) the effect of ischemic stroke upon social outcomes in children; ( 2 ) the correlation of cognitive abilities and problem behaviors with social outcomes; and ( 3 ) the role of infarct characteristics as predictors of social outcomes. Methods We conducted an observational case-controlled study to compare children with neonatal or childhood onset stroke and controls with chronic asthma. Neurological deficits were measured with the Pediatric Stroke Outcome Measure. Cognitive abilities, problem behavior, adaptive behavior, and social outcomes were assessed with standardized measures. Results Overall stroke cases were impaired in several areas of adaptive behaviors but not in cognitive ability, problem behaviors, or social outcomes. Children with more severe neurological deficits had impairments in a range of adaptive behaviors, social adjustment, and social participation. Impaired cognitive ability and more problem behaviors correlated with impaired social adjustment, particularly in stroke cases. Larger infarcts correlated with greater neurological impairment, lower IQ, and poorer social participation. Conclusions Stroke can result in impaired adaptive and social functioning without apparent deficits in IQ or behavior. Infarct size, residual neurological deficits, impaired cognitive ability, and problem behaviors increase the risk for poor social adjustment and participation. These findings can help the clinician anticipate impaired social functioning after pediatric stroke, which is important because age-specific treatments are available.

BackgroundHumans are by nature a social species, with much of human experience spent in social interaction. Unsurprisingly, social functioning is crucial to well-being and quality of life across the lifespan. While early intervention for social problems appears promising, our ability to identify the specific impairments underlying their social problems (eg, social communication) is restricted by a dearth of accurate, ecologically valid and comprehensive child-direct assessment tools. Current tools are largely limited to parent and teacher ratings scales, which may identify social dysfunction, but not its underlying cause, or adult-based experimental tools, which lack age-appropriate norms. The present study describes the development and standardisation of Paediatric Evaluation of Emotions, Relationships, and Socialisation(PEERS®), an iPad-based social skills assessment tool.MethodsThe PEERS project is a cross-sectional study involving two groups: (1) a normative group, recruited from early childhood, primary and secondary schools across metropolitan and regional Victoria, Australia; and (2) a clinical group, ascertained from outpatient services at The Royal Children’s Hospital Melbourne (RCH). The project aims to establish normative data for PEERS®, a novel and comprehensive app-delivered child-direct measure of social skills for children and youth. The project involves recruiting and assessing 1000 children aged 4.0–17.11 years. Assessments consist of an intellectual screen, PEERS® subtests, and PEERS-Q, a self-report questionnaire of social skills. Parents and teachers also complete questionnaires relating to participants’ social skills. Main analyses will comprise regression-based continuous norming, factor analysis and psychometric analysis of PEERS® and PEERS-Q.Ethics and disseminationEthics approval has been obtained through the RCH Human Research Ethics Committee (34046), the Victorian Government Department of Education and Early Childhood Development (002318), and Catholic Education Melbourne (2166). Findings will be disseminated through international conferences and peer-reviewed journals. Following standardisation of PEERS®, the tool will be made commercially available.

Mental health and social outcomes following acquired brain injury (ABI) in children are often considered to be due to brain insult, but other factors, such as environment, may also play a role. We assessed mental health and social function in children with chronic illness, with and without stroke (a form of ABI), and typically developing (TD) controls to examine environmental influences on these outcomes. We recruited 36 children diagnosed with stroke, 15 with chronic asthma, and 43 TD controls. Children and parents completed questionnaires rating child mental health and social function and distal and proximal environment. TD children had significantly less internalizing and social problems than stroke and asthma groups, and engaged in more social activities than children with stroke. Poorer parent mental health predicted more internalizing and social problems and lower social participation. Family dysfunction was associated with internalizing problems. Lower parent education contributed to children's social function. Children with chronic illness are at elevated risk of poorer mental health and social function. Addition of brain insult leads to poorer social participation. Quality of home environment contributes to children's outcomes, suggesting that supporting parent and family function provides an opportunity to optimize child mental health and social outcomes.

Limited information is available regarding predictors of psychosocial difficulties in children following stroke. This study aimed to (i) compare social competence of children with arterial ischemic stroke (AIS) to those with chronic illness and healthy controls and (ii) investigate the contribution of stroke pathology, neurological outcome and environment. Thirty-six children with AIS > 12 months prior to recruitment were compared with children with chronic illness (asthma) (n = 15) and healthy controls (n = 43). Children underwent intellectual assessment, and children and parents completed questionnaires to assess social competence. Children with AIS underwent MRI scan and neurological evaluation. Child AIS was associated with poorer social adjustment and participation, and children with AIS were rated as having more social problems than controls. Lesion volume was not associated with social outcome, but subcortical stroke was linked to reduced social participation and younger stroke onset predicted better social interaction and higher self-esteem. Family function was the sole predictor of social adjustment. Findings highlight the risk of social impairment following pediatric stroke, with both stroke and environmental factors influencing children's social competence in the chronic stages of recovery. They indicate the potential for intervention targeting support at the family level.

The ability to anticipate deficits would help with implementation of interventions for children affected by stroke. The Pediatric Stroke Outcome Measure (Measure) measures neurological impairment after stroke, but there has been little research examining the relationship between the Measure and functional outcomes. We hypothesized the Measure correlates with cognitive and behavioral outcomes. Thirty-six children with stroke were assessed with the Measure, and tested for cognitive ability, problem behavior, adaptive behavior, and social participation. We examined the correlation between the total Measure and outcomes and determined how subscale scores associated with outcomes. Higher total Measure scores correlated with poorer outcomes in cognitive ability, problem behaviors, adaptive behaviors, and social participation. Specific subscale scores correlated with poorer outcomes in multiple domains. The total Measure can be used to anticipate poor outcomes in multiple domains after stroke and can help the clinician in the treatment of children as they recover.

Introduction: Current treatments for multiple sclerosis (MS) remain partially successful, with certain patients remaining treatment resistant. A recent treatment, known as ‘immunoablation’ has been used in severe cases of adult MS with promising results. However, due to its high risk and reservation for severe or refractory cases, its full potential remains unknown.Methods: We report the case of MM, a 14-year-old boy diagnosed with MS and a concurrent diagnosis of Hodgkin's lymphoma.Results: After receiving aggressive chemotherapy (immunoablation) for Hodgkin's lymphoma, MM's MS symptoms appear to have remitted, and he has remained progression- and disease activity-free for over six years.Discussion: This case study will focus on MM's cognitive and behavioural development over this time, but will also discuss treatment implications raised by this rare case.

This study sought to investigate cognitive outcomes following pediatric arterial ischemic stroke and explore predictors. Participants included 36 children with perinatal or childhood arterial ischemic stroke and a comparison group of 15 children with asthma. Outcomes included cognitive ability, executive functions, and neurological function (Pediatric Stroke Outcome Measure). Magnetic resonance imaging measured lesion location and volume. Mean cognitive scores were at the low end of the average range. Children with arterial ischemic stroke performed significantly below normative populations and significantly below the asthma group on inhibitory control (Cohen’s d = .68). Both the Pediatric Stroke Outcome Measure and lesion volume were negatively correlated with cognitive outcome (Spearman r = –.01 to –.42 Pediatric Stroke Outcome Measure; r =–.14 to –.32 Volume). Following arterial ischemic stroke, children performed at the low end of the average range on measures of cognitive functioning. Cognitive outcomes depend on a variety of factors.

BACKGROUND: Stroke can affect children with long-term impairment of intellectual ability and increased risk of attention deficits and psychiatric disorders. Although limited studies in the literature suggest that stroke can chronically impair functional behavior and social adaptation, these functional outcomes have received little attention. We performed a pilot case-control study to examine the hypothesis that pediatric stroke impairs adaptive behavior, and we addressed the secondary hypotheses that stroke volume and location predict impaired functional behavior. METHODS: Children ages 6-15 years who had neonatal or childhood onset arterial ischemic stroke were identified by chart review at the Nationwide Children’s (Columbus, OH, USA) and Royal Children’s Hospital (Melbourne, Australia). Subjects were included if they could complete the test battery. Age- and gender-matched children who had asthma were selected as controls. Stroke cases were assessed with the Pediatric Stroke Outcome Measure and had an MRI brain scan after the acute phase of stroke. Cases and controls underwent functional assessments at least one year after the incident stroke. The battery of tests and ratings included the Wechsler Abbreviated Scales of Intelligence, WISC-IV Processing Speed Index, Child Behavior Checklist, Adaptive Behavior Assessment System, and Child & Adolescent Scale of Participation. Infarct volumes were measured by manual segmentation. RESULTS: The sample included 10 children with perinatal stroke, 26 with acquired childhood stroke, and 15 controls. Median age at assessment was 8.7 yrs (IQR 6.9-11.9) and median time after presentation was 5.1 yrs (IQR 2.8-7.4). The median PSOM for stroke cases was 1 (range 0-8.0) and for controls was 0 (range 0-1). Stroke was significantly associated with lower levels of multiple daily living skills (p range 0.001-0.025), functional academics (p=0.048), and self-care (p=0.020), as well as a trend toward impaired school participation (p=0.064), but was not associated with impaired intellectual functioning or behavioral adjustment. Larger Infarcts showed a trend association with higher PSOM total scores (p=0.091). Infarcts that involved both cortex and subcortical parenchyma were associated with poorer daily living skills (p range 0.005-0.052) and a trend toward impaired home community participation (p=0.079). Age of stroke onset was not associated with impairments. Conclusions: Stroke causes deficits that may not be appreciated by standard IQ screening or report of overt behavior disorders. These deficits can affect daily living skills and result in impaired adaptive behavior. Strokes involving both cortex and subcortex, as a proxy for more extensive strokes, may be particularly associated with impaired adaptive behavior. These results are “best case” estimates because our study excluded mentally retarded or grossly impaired children.

BACKGROUND: The Pediatric Stroke Outcome Measure (PSOM), a 10 point scale based on 5 domains, is one of the few measures of outcome in pediatric stroke. The PSOM has been used to estimate global deficit for studies of stroke outcome and post-stroke quality of life, but its sensitivity to cognitive and functional impairments has received little attention. To address this question, we examined the ability of the PSOM to predict cognitive functioning and behavior after childhood stroke. METHODS: Children ages 6-15 years who had neonatal or childhood onset arterial ischemic stroke were identified by chart review at the Nationwide Children’s Hospital (Columbus, OH, USA) and Royal Children’s Hospital (Melbourne, Australia). Subjects were included if they could complete the test battery. Age- and gender-matched children who had asthma were selected as controls. Stroke cases were assessed with the PSOM and had an MRI brain scan after the acute phase of stroke. Cases and controls underwent functional assessments at least 1 year after the incident stroke. The battery of tests and ratings included the Child Behavior Checklist, Adaptive Behavior Assessment System, Child and Adolescent Scales of Participation, the Wechsler Abbreviated Scales of Intelligence (WASI), and the WISC-4 Processing Speed Index. Infarct volumes were measured by manual segmentation. RESULTS: The sample included 36 children with perinatal or childhood stroke, and 15 controls. Median age at assessment was 8.7 yrs (IQR 6.9-11.9) and median time after presentation was 5.1 yrs (IQR 2.8-7.4). The total PSOM was significantly and inversely related to all measures of cognitive functioning (p range for WISC and WASI 0.001-0.048), multiple measures of adaptive behavior (p range for ABAS scales 0.000-0.031), and all measures of social participation (p range for CASP scales 0.000-0.007). The cognitive/behavioral (C/B) scale of the PSOM was significantly and inversely related to all measures of social participation (p values for CASP 0.000) and multiple measures of adaptive behavior (p range for ABAS scales 0.001-0.057), and positively related to multiple measures of behavior problems (p range for CBCL scales 0.001-0.037). Conclusions: The total PSOM can predict multiple areas of intellectual impairment, and also predicts impairment in adaptive behavior and social participation. In addition the C/B scale can predict behavior problems. The C/B scale depends upon parental report and the clinician's impression, so it is noteworthy that abnormalities on this four-point scale can suggest impairments in a broad range of domains. In addition to a quantitative measure of stroke outcome, the PSOM can serve as a useful screening tool for the identification of intellectual or functional deficits that warrant further investigation for appropriate intervention.

Objective Traditionally early brain insult (EBI) has been argued to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. This view was investigated by comparing neurobehavioral outcomes of children sustaining EBI at different developmental stages (gestation to late childhood). Methods One hundred and sixty four children who had sustained focal brain insult (confirmed by MRI) formed six groups, based on age at EBI, (a) Congenital; (b) Peri-natal; (c) Infancy; (d) Preschool; (e) Middle Childhood; (f) Late Childhood, and were compared on a range of standardized neurobehavioral measures. Groups were matched for lesion characteristics and demographics. Results Children sustaining EBI before age 2 recorded global deficits, while children with later EBI performed closer to average. Conclusion These results question the advantages of early brain plasticity, demonstrating poorer outcome from very early insults, and increasingly better function with lesions later in childhood.

Traditionally early brain insult (EBI) has been considered to have better outcome than later injury, consistent with the notion that the young brain is flexible and able to reorganize. Recent research findings question this view, suggesting that EBI might lead to poorer outcome than brain insult at any other age. Exploring this early vulnerability perspective, we investigated whether skills developing later in childhood, for example, executive functions (EF), would be at greater risk of disruption from EBI. The aim of this study was to investigate EF in children sustaining EBI at different developmental stages. We expected that brain insult during gestation and infancy, before the emergence of EF, would lead to global EF deficits. In contrast, we predicted that brain injury in late childhood would have fewer consequences. Using a cross-sectional, retrospective, group design we compared six groups of children (Total N = 164), with a history of brain insult and documented focal brain pathology, aged 10–16 years on a range of measures of EF. Groups were based on age of EBI: (1) Congenital; (2) Peri-natal; (3) Infancy; (4) Preschool; (5) Middle Childhood; and (6) Late Childhood. Children with EBI were at increased risk for impairment across all aspects of EF. Presence of seizures and/or frontal pathology were not predictive of outcome, but age at insult was. Children sustaining EBI before age 3 recorded more global and severe EF deficits, while children with later EBI performed closer to normal expectations. With the exception of attentional control, skills emerging at time of insult were found to be more vulnerable to disruption than those previously established, supporting the ‘early vulnerability’ model for EBI.

Until recently, the impact of early brain insult (EBI) has been considered to be less significant than for later brain injuries, consistent with the notion that the young brain is more flexible and able to reorganize in the context of brain insult. This study aimed to evaluate this notion by comparing cognitive and behavioural outcomes for children sustaining EBI at different times from gestation to late childhood. Children with focal brain insults were categorized according to timing of brain insult, represented by six developmental periods: (i) Congenital (n = 38): EBI: first-second trimester; (ii) Perinatal (n = 33); EBI: third trimester to 1 month post-natal; (iii) Infancy (n = 23): EBI: 2 months-2 years post-birth; (iv) Preschool (n = 19): EBI: 3-6 years; (v) Middle Childhood (n = 31): EBI: 7-9 years; and (vi) Late Childhood (n = 19): EBI: after age 10. Groups were similar with respect to injury and demographic factors. Children were assessed for intelligence, academic ability, everyday executive function and behaviour. Results showed that children with EBI were at increased risk for impairment in all domains assessed. Furthermore, children sustaining EBI before age 2 years recorded global and significant cognitive deficits, while children with later EBI performed closer to normal expectations, suggesting a linear association between age at insult and outcome. In contrast, for behaviour, children with EBI from 7 to 9 years performed worse than those with EBI from 3 to 6 years, and more like those with younger insults, suggesting that not all functions share the same pattern of vulnerability with respect to age at insult.

Sir, Many thanks for providing the opportunity to respond to the letter from Dr Gordon concerning our recent paper: Childhood brain insult: can age at insult help us predict outcome? (Anderson et al. , 2009). We are grateful for the chance to clarify the issues raised. The first point raised by Gordon (2009) correctly identified an error in the data presented in Table 5 of our paper. This error has been acknowledged and addressed separately in a recent Corrigendum published in Brain . Importantly, this was a clerical error regarding labelling of variables within the table. Interpretation of the results and data were not impacted by this error. The second issue of the contention relates to our finding that verbal IQ (VIQ) was consistently less than performance IQ (PIQ) in all groups in our sample. Subsequent analyses confirm …

Corrigendum to: Anderson V, Spencer-Smith M, Leventer R, Coleman L, Anderson P, Williams J, Greenham M, Jacobs R. Childhood brain insult: can age at insult help us predict outcome? Brain 2009; 132: 45–56 doi:10.1093/Brain/awn293