Fatigue Following Pediatric Arterial Ischemic Stroke: Prevalence and Associated Factors.

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.

Social Cognitive Dysfunction Following Pediatric Arterial Ischemic Stroke: Evidence From a Prospective Cohort Study.

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.

Neonatal jaundice and developmental impairment among infants in Kilifi, Kenya.

BACKGROUND: Neonatal jaundice (NNJ) is common in sub-Saharan Africa (SSA), and it is associated with sepsis. Despite the high incidence, little has been documented about developmental impairments associated with NNJ in SSA. In particular, it is not clear if sepsis is associated with greater impairment following NNJ. METHODS: We followed up 169 participants aged 12 months (57 cases and 112 controls) within the Kilifi Health Demographic Surveillance System. The diagnosis of NNJ was based on clinical laboratory measurement of total serum bilirubin on admission, whereas the developmental outcomes were assessed using the Developmental Milestones Checklist and Kilifi Development Inventory. RESULTS: There were significant differences between the cases and controls in all developmental domains. Cases scored lower in language functioning (mean [M] = 6.5, standard deviation [SD] = 4.3 vs. M = 8.9, SD = 4.6; p < .001); psychomotor functioning (Mdn = 23, interquartile range [IQR] = 17-34 vs. Mdn = 31.0, IQR = 22.0-44.0; Mann-Whitney U = 4,122, p = .002); and socio-emotional functioning ([Mdn = 30.0, IQR = 27.0-33.0 vs. Mdn = 34.0, IQR = 30.0-37.0], Mann-Whitney U = 4,289, p < .001). There was no evidence of association between sepsis and psychomotor (rpb = -.2, p = .214), language (rpb = -.1, p = .510), and socio-emotional functioning (rpb = .0, p = .916). Significant and medium to large portions of the variance (34-64%) in the developmental outcomes among children who survived NNJ were associated with home birth, low maternal education, and feeding problems during the first days of life. CONCLUSIONS: NNJ is associated with developmental impairments in the early childhood years; however, NNJ associated with sepsis does not lead to more severe impairment. Prenatal and postnatal care services are needed to reduce the negative impact of NNJ for children from low resourced settings.

Cognitive resilience following paediatric stroke: Biological and environmental predictors.

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.

A randomized control trial of phototherapy and 20% albumin versus phototherapy and saline in Kilifi, Kenya.

OBJECTIVE: The study evaluated the efficacy of phototherapy and 20% albumin infusion to reduce total serum bilirubin (TSB) in neonates with severe hyperbilirubinemia. The primary outcome was a reduction of TSB at the end of treatment. The secondary outcomes were the need for exchange transfusion, inpatient mortality, neurological outcomes at discharge, and development outcomes at 12-months follow-up. RESULTS: One hundred and eighteen neonates were randomly assigned to phototherapy and 20% albumin (n = 59) and phototherapy and saline (n = 69). The median age at admission was 5 (interquartile range (IQR) 3-6) days, and the median gestation was 36 (IQR 36-38) weeks. No significant differences were found in the change in TSB (Mann-Whitney U =609, p = 0.98) and rate of change in TSB per hour after treatment (Mann-Whitney U = 540, p = 0.39) between the two groups. There were no significant differences between the two groups in the proportion of participants who required exchange transfusion (χ2 (2) = 0.36, p = 0.546); repeat phototherapy (χ2 (2) = 2.37, p = 0.123); and those who died (χ2 (2) = 0.92, p = 0.337). Trial registration The trial was registered in the International Standardized Randomized Controlled Trial Number (ISRCTN); trial registration number ISRCTN89732754.

Motor function daily living skills 5 years after paediatric arterial ischaemic stroke: a prospective longitudinal study.

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.

Self-reported needs after pediatric stroke.

BACKGROUND: Pediatric stroke has the potential for long term impact on the lives of children and their families. Child-centred intervention depends on understanding of needs from diagnosis onwards. However, little is known about the health and care support self-reported needs of this population. AIMS: This study aimed to describe the nature and extent of needs (met and unmet) of pediatric stroke patients and their families and compare these with previously reported adult stroke needs. METHODS: The questionnaire, adapted from a previously published adult stroke study, was conducted with parents of children who had an ischemic or haemorrhagic stroke between birth - 18 years, and young people with stroke now aged between 12 and 18 years. Participants were recruited from three tertiary pediatric stroke clinics in England. Levels and type of needs, and self-reported neurological impairment were captured. Comparisons of needs was reported descriptively and explored using Chi-square test. RESULTS: Of 44 participants (39 parents, 5 young people), over two thirds reported at least one unmet need. Over half had difficulties in school-related activities, and over one-third in leisure activities and social relationships. Participants reported similar nature and extent of need when compared to previously reported adult stroke needs. Higher severity of neurological impairment was associated with higher number of needs. CONCLUSIONS: Children and young people and their parents have high levels of unmet need across a range of health domains in the months and years after pediatric stroke. This information supports the importance of a needs-based approach to maximising health and well-being.

Social functioning following pediatric stroke: contribution of neurobehavioral impairment.

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.

The Pediatric Stroke Outcome Measure: A predictor of outcome following arterial ischemic stroke.

OBJECTIVE: To evaluate the relationship between neurologic outcome at 1 month following diagnosis of pediatric arterial ischemic stroke (AIS) and motor and adaptive behavior outcomes at 12 months. METHODS: This prospective longitudinal observational cohort study recruited children from a single tertiary children's hospital diagnosed with first AIS between December 2007 and November 2013. Neurologic impairment was evaluated at 4 time points using the Pediatric Stroke Outcome Measure (PSOM) or Recovery and Recurrence Questionnaire following diagnosis of AIS (acute, 1, 6, and 12 months). Motor function and adaptive behavior were assessed at 12 months using standardized measures. Children were grouped for analysis, according to age at diagnosis (neonates vs preschool vs school-aged). The relationship between neurologic impairment and 12-month functional outcomes were examined. RESULTS: Sixty-four children were recruited (27 neonates, 19 preschool-aged, and 18 school-aged). Presence of impairment on the PSOM at 1 month was associated with lower 12-month fine motor z scores (p = 0.004), gross motor z scores (p = 0.001), and adaptive behavior standard scores (p = 0.004). One-month PSOM impairment score was more predictive than age group or lesion size of 12-month motor and adaptive behavior outcome. CONCLUSIONS: The PSOM has value as a predictive tool when used at 1 month after first AIS diagnosed acutely in relation to motor and adaptive behavior, with variation according to age group.

Early predictors of psychosocial functioning 5 years after paediatric stroke.

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, 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.

Trajectories of Motor Recovery in the First Year After Pediatric Arterial Ischemic Stroke.

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.

Psychosocial function in the first year after childhood stroke.

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.

Factors associated with six-month outcome of pediatric stroke.

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.

Technology-aided assessment of sensorimotor function in early infancy.

There is a pressing need for new techniques capable of providing accurate information about sensorimotor function during the first 2 years of childhood. Here, we review current clinical methods and challenges for assessing motor function in early infancy, and discuss the potential benefits of applying technology-assisted methods. We also describe how the use of these tools with neuroimaging, and in particular functional magnetic resonance imaging (fMRI), can shed new light on the intra-cerebral processes underlying neurodevelopmental impairment. This knowledge is of particular relevance in the early infant brain, which has an increased capacity for compensatory neural plasticity. Such tools could bring a wealth of knowledge about the underlying pathophysiological processes of diseases such as cerebral palsy; act as biomarkers to monitor the effects of possible therapeutic interventions; and provide clinicians with much needed early diagnostic information.

Functioning and disability after stroke in children: using the ICF-CY to classify health outcome and inform future clinical research priorities.

AIM: The International Classification of Functioning Disability and Health, Child-Youth version (ICF-CY) provides a framework for describing and evaluating health, intervention outcomes, and needs assessment. It can, however, also serve as a system for classifying the focus of outcome studies and identification of gaps in current knowledge. METHOD: The paediatric arterial ischaemic stroke (AIS) population was targeted. Multiple databases were systematically searched for AIS outcome studies focussing on functioning or disability. Findings were rated using the ICF-CY framework. RESULTS: Twenty-eight studies were identified. Most were cross-sectional and age range at assessment varied widely. Sixty-seven different standardized measures were used, predominantly evaluating body functions. The most common domains of activity and participation reported were learning and applying knowledge, general tasks and demands, and self-care skills. Health-related quality of life was measured in nine papers. Environmental factors were rarely evaluated. INTERPRETATION: AIS outcome studies addressing the relationship between body structures and functions (e.g. brain lesion characteristics, neurological examination findings) and activities, participation, and quality of life have emerged in recent years. Comparison of findings across studies is complicated by design and tool selection. The relationship between components of activity limitation and participation restriction is rarely explored.

Pediatric stroke outcome measure: predictor of multiple impairments in childhood stroke.

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.

Hypertension at time of diagnosis and long-term outcome after childhood ischemic stroke.

OBJECTIVE: To determine the prevalence of hypertension (HPT) in the acute phase after ischemic stroke (IS) and explore its relationship to outcome. METHODS: We performed a retrospective review of children aged 1 month to 18 years with first IS admitted to a tertiary hospital between 2003 and 2008. Blood pressure readings recorded over the first 72 hours after diagnosis and morbidity or mortality at 12 months were documented. HPT was defined as 2 consecutive readings of systolic blood pressure ≥95th percentile for age. RESULTS: Ninety children were identified (median age 3.8 years). Fifty-three of 84 patients (63%) who had blood pressure readings available had at least 1 episode of HPT and 19 (22%) had HPT on 3 consecutive days. HPT was more prevalent at both ends of the age spectrum. The relative risk of 12-month mortality was 4.5 times higher (95% confidence interval = 0.6-34.5, p = 0.096) and relative risk of death in the hospital was 1.7 times higher (95% confidence interval = 1.4-2.0, p = 0.05) if the patient experienced HPT. There was no association between HPT and vascular territory, etiology, or neurologic disability. CONCLUSIONS: HPT is prevalent in children with IS in the first 3 days after diagnosis and is associated with increased risk of death. Larger prospective studies involving systematic recording of blood pressure are required to delineate the impact of HPT on risk of death or disability.

Corticospinal tract integrity and motor function following neonatal stroke: a case study.

BACKGROUND: New MRI techniques enable visualisation of corticospinal tracts and cortical motor activity. The objective of this case study was to describe the magnetic resonance evidence of corticospinal pathway reorganisation following neonatal stroke. CASE PRESENTATION: An 11 year old boy with a neonatal right middle cerebral artery territory ischaemic stroke was studied. Functional MRI was undertaken with a whole hand squeezing task, comparing areas of cortical activation between hands. White matter tracts, seeded from the area of peak activation in the cortex, were visualised using a diffusion weighted imaging probabilistic tractography method. Standardised evaluations of unilateral and bilateral motor function were undertaken. Clinically, the child presented with a left hemiparesis. Functional MRI demonstrated that movement of the hemiparetic hand resulted in activation in the ipsi-lesional (right) hemisphere only. Diffusion tractography revealed pathways in the right (lesioned) hemisphere tracked perilesionally to the cortical area identified by functional MRI. CONCLUSION: Our case demonstrates that neonatal stroke is associated with maintenance of organization of corticospinal pathways sufficient to maintain some degree of hand function in the affected hemisphere. Functional MRI and diffusion weighted imaging tractography may inform our understanding of recovery, organisation and reorganisation and have the potential to monitor responses to intervention following neonatal stroke.

Rehabilitation for children after acquired brain injury: current and emerging approaches.

Evidence is emerging of diverse, chronic, cumulative disabilities experienced by children in the months and years after acquired brain injury. The long-held assumption that younger children recover better from brain injury than older children or adults has been challenged by recent studies. Populations with acquired brain injury include children with traumatic brain injury and stroke, and a proportion of children with cerebral palsy. Although characteristics of brain injury in children vary, subgroups of this population offer the potential to inform our understanding of developing brain structure-function relationships in response to intervention. Limited evidence and few controlled rehabilitation trials exist regarding children with neurologic conditions. A number of rehabilitation approaches produced benefits in adult stroke, and cerebral palsy populations may be applied to children with other acquired brain injuries. Rehabilitation approaches that have been applied to children with acquired brain injuries, or hold promise for future applications, are reviewed.