Interleukin-8 predicts fatigue at 12 months post-injury in children with traumatic brain injury

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 reliably predicted persisting fatigue (up to 3 years post‐injury). This study aimed to establish if persisting fatigue is predicted by serum biomarker concentrations in child TBI. We examined if 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 (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 hours of injury [interleukin‐6 (IL‐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 interleukin‐8 (IL‐8) was the best serum biomarker for estimating the probability of children experiencing fatigue at 12 months post‐injury. IL‐8 also significantly improved predictive models of fatigue based on severity

Social Functioning in Children with Brain Insult

Social dysfunction is commonly reported by survivors of brain insult, and is often rated as the most debilitating of all sequelae, impacting on many areas of daily life, as well as overall quality of life. Within the early brain insult (EBI) literature, physical and cognitive domains have been of primary interest and social skills have received scant attention. As a result it remains unclear how common these problems are, and whether factors predictive of recovery (insult severity, lesion location, age at insult, environment) in other functional domains (motor, speech, cognition) also contribute to social outcome. This study compared social outcomes for children sustaining EBI at different times from gestation to late childhood to determine whether EBI was associated with an increased risk of problems. Children with focal brain insults were categorized according to timing of brain insult: (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. Children's teachers completed questionnaires measuring social function (Strengths and Difficulties Questionnaire, Walker–McConnell Scale of Social Competence and School Adjustment). Results showed that children with EBI were at increased risk for social impairment compared to normative expectations. EBI before age 2 years was associated with most significant social impairment, while children with EBI in the preschool years and in late childhood recorded scores closer to normal. Lesion location and laterality were not predictive of social outcome, and nor was social risk. In contrast, presence of disability (seizures) and family function were shown to contribute to aspects of social function

Psychosocial outcomes following paediatric arterial ischaemic stroke

© 2017 Dr. Mardee Lee GreenhamPaediatric arterial ischaemic stroke (PAIS) affects 1.3 to 1.6 per 100,000 children and is one of the top 10 cause of death in children. PAIS can occur at any stage during childhood, a time of rapid brain development, with the potential to cause impairment in already developed skills and disrupt the development of emerging skills and the neural networks underpinning them. A high proportion of children experience long-term residual neurological impairment, including motor, cognitive and language deficits. Despite this, relatively little is known about psychosocial outcomes following PAIS. The overall aim of this thesis was to examine psychosocial function in children following PAIS and to investigate factors that might impact outcome, including neurobiological (lesion characteristics, neurological impairment, age at stroke), child (pre-stroke functioning, post-stroke functional impairment) and environmental factors (parent mental health, family functioning, socio-economic status). This thesis addressed these aims across four studies. Study 1 examined the environmental contributions to psychosocial outcomes following PAIS. Children with PAIS were compared to typically developing controls and a control group of children with chronic illness not involving the CNS (asthma). Chronic illness (PAIS and asthma) was found to predict psychosocial impairment, with the addition of brain insult (PAIS) placing further burden on social participation. Parent mental health, family function and parent education were associated with child outcomes. Study 2 explored psychosocial function in the first year following PAIS and factors that may be associated with outcome. Compared to pre-PAIS, social function was poorer 6 and 12-months post-PAIS. Psychological function at 12-months was also significantly impaired. Older age at stroke, acute neurological impairment and poorer pre-stroke social function predicted poorer social function at 12-months post-stroke. Poorer parent mental health was associated with poorer child psychological and social function. Lesion location, cognitive function and socioeconomic status (SES) were not associated with outcome. Study 3 examined psychosocial function five years post-PAIS and early predictors of outcome. Psychosocial function was impaired, with older age at PAIS, larger lesion size, as well as poorer cognitive function and psychological problems at 12-months post-PAIS predictive of poorer outcome. Neurological impairment, child social function, parent mental health (all 12-months post-PAIS) and SES were not associated with outcome. Study 4 explored social function, including social competence, social cognition and social participation, five years post-PAIS and the impact of function impairment on social outcome. To explore the impact of age at PAIS, the sample was divided into neonatal vs older age at onset. The older age at onset group had poorer social adjustment compared to the neonatal onset group. The contribution of functional impairment on social function was explored across both age at stroke groups. Fatigue contributed to poorer social adjustment and social participation. Intellectual function was also associated with social cognition. Neurological impairment, attention, pragmatic language, behaviour and motor function were not associated with outcome. Together results from the studies presented in this thesis indicate that children are at risk of psychosocial impairment following PAIS. Older age at PAIS onset was found to be predictive of poorer psychological and social outcome, while lesion location was not. Rather, findings suggest family environment and having a chronic illness play a key role. Factors within the child, such as pre-stroke functioning, as well as impairment resulting from the stroke, were also found to be important predictors of outcome. Findings indicate the need for a focus on psychosocial function in rehabilitation services and routine screening

Children's executive functions: Are they poorer after very early brain insult

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