Prospective Associations of Susceptibility-Weighted Imaging Biomarkers with Fatigue Symptom Severity in Childhood Traumatic Brain Injury.

Fatigue may be among the most profound and debilitating consequences of pediatric traumatic brain injury (TBI); however, neurostructural risk factors associated with post-injury fatigue remain elusive. This prospective study aimed to evaluate the independent value of susceptibility-weighted imaging (SWI) biomarkers, over-and-above known risk factors, to predict fatigue symptom severity in children with TBI. Forty-two children were examined with structural magnetic resonance imaging (sMRI), including a SWI sequence, within eight weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24 months post-injury. Compared with population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen d = 0.44), cognitive fatigue (Cohen d = 0.59), sleep/rest fatigue (Cohen d = 0.37), and total fatigue (Cohen d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors, and depression, we found that subacute volume of SWI lesions was independently associated with all fatigue symptom domains. The magnitude of the brain-behavior relationship varied by fatigue symptom domain, such that the strongest relationships were observed for the cognitive fatigue and total fatigue symptom scales. Overall, we found that total subacute volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. The subacute SWI has potential to improve prediction of post-injury fatigue in children with TBI. Our preliminary findings suggest that volume of SWI lesions may represent a novel, independent biomarker of post-injury fatigue, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of long-term post-injury fatigue.

Infliximab for Paradoxical Reactions in Pediatric Central Nervous System Tuberculosis.

Paradoxical reactions in central nervous system tuberculosis (CNS-TB) are associated with significant morbidity and mortality. We describe 4 HIV-uninfected children treated for CNS-TB with severe paradoxical reactions unresponsive to corticosteroids. All made recovery after treatment with infliximab, highlighting the safety and effectiveness of infliximab for this complication, and need for prospective trials.

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.

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.

Use of bevacizumab as a single agent or in adjunct with traditional chemotherapy regimens in children with unresectable or progressive low-grade glioma.

In pediatric low-grade gliomas not amenable to complete resection, various chemotherapy regimens are the mainstream of treatment. An excellent overall survival of these patients makes justification of the intensification of chemotherapy difficult and calls for the development of new strategies. Bevacizumab, a humanized monoclonal antibody directed against Vascular endothelial growth factor (VEGF), has been successfully used in combination with irinotecan in a number of adult and pediatric studies and reports. Fifteen patients at median age of 7 years old (range 3 months to 15 years) were treated with bevacizumab in combination with conventional low-toxicity chemotherapy. The majority had chiasmatic/hypothalamic and midline tumors, seven had confirmed BRAF pathway alterations including neurofibromatosis type 1 (2). Fourteen patients had more than one progression and three had radiotherapy. No deaths were documented, PFS at 11 and 15 months was 71.5% ± 13.9% and 44.7% ± 17.6% respectively. At the end of follow-up 40% of patients has radiologically stable disease, three patients progressed shortly after completion of bevacizumab and two showed mixed response with progression of cystic component. Rapid visual improvement was seen in 6/8 patients, resolution of endocrine symptoms in 2/4 and motor function improvement in 4/6. No relation between histology or BRAF status and treatment response was observed. Treatment-limiting toxicities included grade 4 proteinuria (2) and hypertension (2) managed with cessation (1) and pausing of therapy plus antihypertensives (1). In conclusion, bevacizumab is well tolerated and appears most effective for rapid tumor control to preserve vision and improve morbidity.

Spinal Cord Hyperintensities in Neurofibromatosis Type 1: Are They the Cord Equivalent of Unidentified Bright Objects in the Brain?

BACKGROUND: Focal areas of T2 hyperintensity are seen on magnetic resonance imaging (MRI) in patients with neurofibromatosis type 1 (NF1). These lesions are commonly known as "unidentified bright objects" of the brain. We have seen similar lesions in the spinal cord of the same patient population. Our aim was to determine the prevalence and characterize the imaging features of these T2 hyperintense spinal cord lesions in children with NF1. METHODS: A search of our hospital's medical imaging database yielded all children with NF1 and MRI of the brain and/or spine between February 2014 and April 2017. Medical imaging was reviewed for T2 hyperintense signal changes and medical records were reviewed of those children with T2 hyperintense spinal cord lesions. RESULTS: During the study period 155 children underwent a brain MRI and 72 had a spine MRI. One hundred twenty-three (79%) showed multiple cerebral T2 hyperintense lesions and six (8%) had non-contrast enhancing spinal cord T2 hyperintensities with five children having had a follow-up scan. The one child without follow-up imaging was not further pursued. Interval scanning showed stable appearance of the spinal cord lesions in four children and signal reduction in one child. All five children with T2 hyperintense changes in the spinal cord had an MRI brain and all (100%) also exhibited cerebral T2 hyperintensities. CONCLUSIONS: Focal areas of signal hyperintensity in the spinal cord are the corollary of the better described cerebral T2 hyperintensities in individuals with NF1.

Genetic, Radiologic, and Clinical Variability in Brown-Vialetto-van Laere Syndrome.

Brown-Vialetto-van Laere syndrome is characterized by a progressive sensorimotor neuropathy, optic atrophy, hearing loss, bulbar dysfunction, and respiratory insufficiency. Mutations in SLC52A2 and SLC52A3, encoding riboflavin transporters RFVT2 and RFVT3, respectively, are the genetic basis of this disorder, often referred to as riboflavin transporter deficiency types 2 and 3, respectively. We present cases of both types of riboflavin transporter deficiency, highlighting the distinguishing clinical features of a rapidly progressive motor or sensorimotor axonal neuropathy, optic atrophy, sensorineural hearing loss, and bulbar dysfunction. One child presented with isolated central apnea and hypoventilation, not previously described in genetically confirmed Brown-Vialetto-van Laere, later complicated by diaphragmatic paralysis secondary to phrenic nerve palsy. Magnetic resonance imaging showed T2 hyperintensity in the dorsal spinal cord in 2 children, as well as previously unreported cervical nerve root enlargement and cauda equina ventral nerve root enhancement in 1 child. Novel homozygous mutations were identified in each gene-a NM_024531.4(SLC52A2):c.505C > T, NP_078807.1(SLC52A2):p.(Arg169Cys) variant in SLC52A2 and NM_033409.3(SLC52A3):c.1316G > A, NP_212134.3(SLC52A3):p.(Gly439Asp) variant in SLC52A3. Both treated children showed improvement on high-dose riboflavin supplementation, highlighting the importance of early recognition of this treatable clinical entity.

Histologic chorioamnionitis in preterm infants: correlation with brain magnetic resonance imaging at term equivalent age.

BACKGROUND: To explore the associations between histologic chorioamnionitis with brain injury, maturation and size on magnetic resonance imaging (MRI) of preterm infants at term equivalent age. METHODS: Preterm infants (23-36 weeks' gestational age) were recruited into two longitudinal cohort studies. Presence or absence of chorioamnionitis was obtained from placental histology and clinical data were recorded. MRI at term-equivalent age was assessed for brain injury (intraventricular haemorrhage, cysts, signal abnormalities), maturation (degree of myelination, gyral maturation) and size of cerebral structures (metrics and brain segmentation). Histologic chorioamnionitis was assessed as a predictor of MRI variables using linear and logistic regression, with adjustment for confounding perinatal variables. RESULTS: Two hundred and twelve infants were included in this study, 47 (22%) of whom had histologic chorioamnionitis. Histologic chorioamnionitis was associated with higher odds of intraventricular haemorrhage (odds ratio [OR] (95% confidence interval [CI]) = 7.4 (2.4, 23.1)), less mature gyral maturation (OR (95% CI) = 2.0 (1.0, 3.8)) and larger brain volume (mean difference in cubic centimeter (95% CI) of 14.1 (1.9, 26.2)); but all relationships disappeared following adjustment for perinatal variables. CONCLUSION: Histologic chorioamnionitis was not independently associated with IVH, less mature gyral maturation or brain volume at term-equivalent age in preterm infants.

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.

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.

Uncovering cortico-striatal correlates of cognitive fatigue in pediatric acquired brain disorder: Evidence from traumatic brain injury.

Cognitive fatigue is among the most profound and disabling sequelae of pediatric acquired brain disorders, however the neural correlates of these symptoms in children remains unexplored. One hypothesis suggests that cognitive fatigue may arise from dysfunction of cortico-striatal networks (CSNs) implicated in effort output and outcome valuation. Using pediatric traumatic brain injury (TBI) as a model, this study investigated (i) the sub-acute effect of brain injury on CSN volume; and (ii) potential relationships between cognitive fatigue and sub-acute volumetric abnormalities of the CSN. 3D T1 weighted magnetic resonance imaging sequences were acquired sub-acutely in 137 children (TBI: n = 103; typically developing - TD children: n = 34). 67 of the original 137 participants (49%) completed measures of cognitive fatigue and psychological functioning at 24-months post-injury. Results showed that compared to TD controls and children with milder injuries, children with severe TBI showed volumetric reductions in the overall CSN package, as well as regional gray matter volumetric change in cortical and subcortical regions of the CSN. Significantly greater cognitive fatigue in the TBI patients was associated with volumetric reductions in the CSN and its putative hub regions, even after adjusting for injury severity, socioeconomic status (SES) and depression. In the first study to evaluate prospective neuroanatomical correlates of cognitive fatigue in pediatric acquired brain disorder, these findings suggest that post-injury cognitive fatigue is related to structural abnormalities of cortico-striatal brain networks implicated in effort output and outcome valuation. Morphometric magnetic resonance imaging (MRI) may have potential to unlock early prognostic markers that may assist to identify children at elevated risk for cognitive fatigue post-TBI.

Autoimmune Pancreatitis and IgG4 Related Disease in Three Children.

We report 3 children who presented with fever and abdominal pain, deranged liver function tests, and on abdominal ultrasound were found to have an enlarged pancreas, substantial abdominal lymphadenopathy, and extrahepatic biliary duct dilatation. After ruling out malignancy, probable immunoglobulin G4-related disease (IgG4RD) associated with autoimmune pancreatitis was considered. This condition was first described in the adults and often mimics pancreatic cancer. It can involve multiple organs, either synchronously or metachronously, and is rarely reported in children. The disorder mostly responds to corticosteroid therapy and other immune suppression. We highlight the difficulty in diagnosing autoimmune pancreatitis/IgG4-related disease in children and illustrate the difference between pediatric and adult presentation.

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.

Predictors of longitudinal outcome and recovery of pragmatic language and its relation to externalizing behaviour after pediatric traumatic brain injury.

The purpose of the present investigation was to evaluate the contribution of age-at-insult and brain pathology on longitudinal outcome and recovery of pragmatic language in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with mild to severe TBI (n=112) were categorized according to timing of brain insult: (i) Middle Childhood (5-9 years; n=41); (ii) Late Childhood (10-11 years; n=39); and (iii) Adolescence (12-15 years; n=32) and group-matched for age, gender and socio-economic status (SES) to a typically developing (TD) control group (n=43). Participants underwent magnetic resonance imaging (MRI) including a susceptibility weighted imaging (SWI) sequence 2-8 weeks after injury and were assessed on measures of pragmatic language and behavioural functioning at 6- and 24-months after injury. Children and adolescents with TBI of all severity levels demonstrated impairments in these domains at 6-months injury before returning to age-expected levels at 2-years post-TBI. However, while adolescent TBI was associated with post-acute disruption to skills that preceded recovery to age-expected levels by 2-years post injury, the middle childhood TBI group demonstrated impairments at 6-months post-injury that were maintained at 2-year follow up. Reduced pragmatic communication was associated with frontal, temporal and corpus callosum lesions, as well as more frequent externalizing behaviour at 24-months post injury. Findings show that persisting pragmatic language impairment after pediatric TBI is related to younger age at brain insult, as well as microhemorrhagic pathology in brain regions that contribute to the anatomically distributed social brain network. Relationships between reduced pragmatic communication and more frequent externalizing behavior underscore the need for context-sensitive rehabilitation programs that aim to increase interpersonal effectiveness and reduce risk for maladaptive behavior trajectories into the long-term post injury.

Relationships between acute imaging biomarkers and theory of mind impairment in post-acute pediatric traumatic brain injury: A prospective analysis using susceptibility weighted imaging (SWI).

Theory of Mind (ToM) forms an integral component of socially skilled behavior, and is critical for attaining developmentally appropriate goals. The protracted development of ToM is mediated by increasing connectivity between regions of the anatomically distributed 'mentalizing network', and may be vulnerable to disruption from pediatric traumatic brain injury (TBI). The present study aimed to evaluate the post-acute effects of TBI on first-order ToM, and examine relations between ToM and both local and global indices of macrostructural damage detected using susceptibility-weighted imaging (SWI). 104 children and adolescents with TBI and 43 age-matched typically developing (TD) controls underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks post-injury and were assessed on cognitive ToM tasks at 6-months after injury. Compared to TD controls and children with mild-moderate injuries, children with severe TBI showed significantly poorer ToM. Moreover, impairments in ToM were related to diffuse neuropathology, and parietal lobe lesions. Our findings support the vulnerability of the immature social brain network to disruption from TBI, and suggest that global macrostructural damage commonly associated with traumatic axonal injury (TAI) may contribute to structural disconnection of anatomically distributed regions that underlie ToM. This study suggests that SWI may be a valuable imaging biomarker to predict outcome and recovery of social cognition after pediatric TBI.

The emergence of age-dependent social cognitive deficits after generalized insult to the developing brain: a longitudinal prospective analysis using susceptibility-weighted imaging.

Childhood and adolescence are critical periods for maturation of neurobiological processes that underlie complex social and emotional behavior including Theory of Mind (ToM). While structural correlates of ToM are well described in adults, less is known about the anatomical regions subsuming these skills in the developing brain or the impact of cerebral insult on the acquisition and establishment of high-level social cognitive skills. This study aimed to examine the differential influence of age-at-insult and brain pathology on ToM in a sample of children and adolescents with traumatic brain injury (TBI). Children and adolescents with TBI (n = 112) were categorized according to timing of brain insult: (i) middle childhood (5-9 years; n = 41); (ii) late childhood (10-11 years; n = 39); and (iii) adolescence (12-15 years; n = 32) and group-matched for age, gender, and socioeconomic status to a typically developing (TD) control group (n = 43). Participants underwent magnetic resonance imaging including a susceptibility-weighted imaging (SWI) sequence 2-8 weeks postinjury and were assessed on a battery of ToM tasks at 6- and 24-months after injury. Results showed that for adolescents with TBI, social cognitive dysfunction at 6- and 24-months postinjury was associated with diffuse neuropathology and a greater number of lesions detected using SWI. In the late childhood TBI group, we found a time-dependent emergence of social cognitive impairment, linked to diffuse neuropathology. The middle childhood TBI group demonstrated performance unrelated to SWI pathology and comparable to TD controls. Findings indicate that the full extent of social cognitive deficits may not be realized until the associated skills reach maturity. Evidence for brain structure-function relationships suggests that the integrity of an anatomically distributed network of brain regions and their connections is necessary for the acquisition and establishment of high-level social cognitive skills.

Subdural hemorrhage and hypoxia in infants with congenital heart disease.

BACKGROUND AND OBJECTIVES: It has been suggested that there is a causal relationship between hypoxia and subdural hemorrhage (SDH) in infancy. The purpose of this study was to review the incidence of SDH in infants with congenital heart disease and explore the relationship between SDH and hypoxia. METHODS: Review of data collected for a prospective longitudinal cohort study of infants undergoing surgery for congenital heart disease in New Zealand and Australia. Infants underwent serial MRI scans of the brain in the first 3 months of life. All oxygen saturation recordings and MRI results were extracted and infants assigned to categories by degree of hypoxia. The data were then examined for any statistically significant relationship between hypoxia and SDH. RESULTS: One hundred fifty-two infants underwent MRI scans, and 66 (43%) had 145 loci of SDH. New SDH was seen in 12 infants after cardiac surgery. Of the loci of SDH, 63 (43%) were supratentorial, and most of these were interhemispheric, parietal, or temporal. SDH present on the first MRI persisted beyond 28 days of life in 8 infants. There was no demonstrable relationship between SDH and hypoxia. CONCLUSIONS: Asymptomatic SDH is common in young infants with congenital heart disease, at a frequency similar to that of those without congenital heart disease. These SDHs may occur in locations where they occur in abusive head trauma, but they are typically small and resolve within 3 months of birth. We were unable to demonstrate any association between hypoxia and SDH in this cohort.