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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. 42 children were examined with structural magnetic-resonance imaging (sMRI), including a SWI sequence, within 8-weeks post-injury. The PedsQL Multi-Dimensional Fatigue Scale (MFS) was administered 24-months post-injury. Compared to population expectations, the TBI group displayed significantly higher levels of general fatigue (Cohen's d = 0.44), cognitive fatigue (Cohen's d = 0.59), sleep/rest fatigue (Cohen's d = 0.37), and total fatigue (Cohen's d = 0.63). In multi-variate models adjusted for TBI severity, child demographic factors and depression, sub-acute 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 volume of SWI lesions explained up to 24% additional variance in multi-dimensional fatigue, over-and-above known risk factors. 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 scores, which could help to identify high-risk children who are likely to benefit from targeted psychoeducation and/or preventive strategies to minimize risk of persisting fatigue.

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.

Non-accidental injuries remain a leading cause of preventable morbidity and mortality in young children. The accurate identification of the full spectrum of injuries in children presenting with suspected abuse is essential to ensure the appropriate protective intervention is taken. The identification of occult bone fractures in this cohort is important as it raises the level of concern about the mechanism of injury and maintaining the child's safety. Radiographic imaging remains the modality of choice for skeletal assessment; however, current studies report concerns regarding the ability of radiographs to detect certain fractures in the acute stage. As such, alternative modalities for the detection of fractures have been proposed. This article reviews the current literature regarding fracture detectability and radiation dose burden of imaging modalities currently used for the assessment of occult bony injury in young children in whom non-accidental injury is suspected.Copyright © 2021 The Royal Australian and New Zealand College of Radiologists

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(s): 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. Result(s): 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(s): 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.Copyright © 2018 Mac Keith Press

BACKGROUND: Our aims were to evaluate the ultrasound scan (USS) criteria in diagnosing hypertrophic pyloric stenosis (HPS), determine the best diagnostic threshold values for pyloric muscle thickness (PMT) and pyloric canal length (PCL), and assess the accuracy of flow through the pylorus. METHOD(S): All patients who underwent pyloromyotomy at our tertiary paediatric surgery centre between July 2013 and June 2019 were identified (Group 1). All patients undergoing an USS to investigate for a possible HPS and did not undergo pyloromyotomy were also identified (Group 2). Accuracy was determined by Youden's Index (J) with the highest J determining the ideal cut-off value. RESULT(S): Two hundred and eighty-four patients (142 patients in each group) were included in the analysis. Using only the last USS before surgery, PMT provided an area under the curve (AUC) of 0.987 (n =275), and PCL an AUC of 0.977 (n =267). Ideal threshold values were 3.0mm for PMT (J =0.92), and 14.5mm for PCL (J =0.87). Combining PMT >=3.0mm with a PCL >=14.5mm resulted in a sensitivity of 95% and specificity of 99% (J = 0.94). The absence of flow through the pylorus on dynamic USS provided a sensitivity of 99% and specificity of 91% (J =0.91; n =277). CONCLUSION(S): Combining threshold values of 3.0mm for PMT and 14.5mm PCL provides the highest accuracy for diagnosing pyloric stenosis on an ultrasound scan. These combined values were more accurate than observing for the absence of flow through the pylorus.Copyright © 2021 Royal Australasian College of Surgeons.

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. Method(s): 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. Result(s): 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. Conclusion(s): 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.Copyright © 2021 Lippincott Williams and Wilkins. All rights reserved.

Therapeutic hypothermia (TH) is standard care in high-resource birth settings for infants with neonatal encephalopathy. TH is partially effective and adjuvant therapies are needed. Here, we examined whether the antioxidant melatonin (MLT) provides additive benefit with TH, compared to TH alone or MLT alone, to improve recovery from acute encephalopathy in newborn lambs. Immediately before cesarean section delivery, we induced asphyxia in fetal sheep via umbilical cord occlusion until mean arterial blood pressure fell from 55 +/- 3 mm Hg in sham controls to 18-20 mm Hg (10.1 +/- 1.5 minutes). Lambs were delivered and randomized to control, control + MLT (60 mg iv, from 30 minutes to 24 hours), asphyxia, asphyxia + TH (whole-body cooling to 35.1 +/- 0.8degreeC vs. 38.3 +/- 0.17degreeC in sham controls, from 4-28 hours), asphyxia + MLT, and asphyxia + TH + MLT. At 72 hours, magnetic resonance spectroscopy (MRS) was undertaken, and then brains were collected for neuropathology assessment. Asphyxia induced abnormal brain metabolism on MRS with increased Lactate:NAA (P =.003) and reduced NAA:Choline (P =.005), induced apoptotic and necrotic cell death across gray and white matter brain regions (P <.05), and increased neuroinflammation and oxidative stress (P <.05). TH and MLT were independently associated with region-specific reductions in oxidative stress, inflammation, and cell death, compared to asphyxia alone. There was an interaction between TH and MLT such that the NAA:Choline ratio was not significantly different after asphyxia + TH + MLT compared to sham controls but had a greater overall reduction in neuropathology than either treatment alone. This study demonstrates that, in newborn lambs, combined TH + MLT for neonatal encephalopathy provides significantly greater neuroprotection than either alone. These results will guide the development of further trials for neonatal encephalopathy.Copyright © 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd

Introduction: This case series summarises our institution's preliminary experience of using computed tomography skeletal surveys (CT-SS) for the assessment of infants with suspected non-accidental injury (NAI) who were unable to undergo radiographic skeletal surveys (SS). This paper describes our experience using CT-SS in terms of radiation doses achieved, occult bony injury detection and forensic utility. Method(s): Ten infants aged between two weeks and ten months underwent a CT-SS. The results of the CT-SS were compared with concurrent imaging results where available. Radiation doses from imaging procedures were calculated for each patient. Result(s): Six infants had abnormalities identified on CT-SS. Two patients had both an ante-mortem CT-SS and post-mortem imaging. All fractures identified on alternate imaging modalities were visible on at least one CT-SS reconstruction. The radiation dose associated with CT-SS imaging ranged from 0.73 to 1.46mSv. Conclusion(s): The radiation dose received by the ten infants in this study was greater than the two skeletal survey approach but was less than the dose received during a bone scintigraphy examination, sometimes used to assess for occult bony injury in this setting. While CT-SS imaging results could not be compared with those obtained with current contemporaneous gold standard imaging techniques, CT-SS identified all fractures observed on the radiographic images where performed. CT-SS also identified additional rib fractures in two patients. Our preliminary findings indicate the need for future prospective studies to clarify the ability of CT-SS to detect metaphyseal fractures reliably.Copyright © 2021 The Royal Australian and New Zealand College of Radiologists

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. Method(s): 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. Result(s): 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. Conclusion(s): 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

Background: Organ size is influenced by a number of factors. Age, height, weight, and ethnicity are known influencing factors. Pediatric populations have changed over time, puberty beginning earlier resulting in a changing growth pattern of their organs. Hence, contemporary charts using local data are considered the most appropriate for a given population. Sonographic charts for liver size for a predominantly Caucasian population are limited, which has implications for clinical practice. The aim of this study was to define a contemporary normative range of liver and spleen sizes for a healthy, predominantly Caucasian population and for all pediatric age groups (0-18 years) and to investigate whether there is a size difference between genders and ethnicities. Method(s): Retrospective study including children with normal sonographic findings and no evidence of liver or splenic disease clinically. Craniocaudal and anteroposterior dimensions are measured for the right and left lobe of the liver, and craniocaudal dimension for the spleen. Relationship of the liver and spleen dimensions with age, body length, body surface area, weight, and gender were investigated. Charts of normal values were established. Values were compared to studies involving other ethnicities and to one study carried out in 1983 involving the same ethnicity. Result(s): Seven hundred thirty-six children (371 boys, 365 girls) aged 1 day - 18.4 years were included. From the second year of life, the craniocaudal dimension of the right lobe of the liver is 1-2 cm larger in the Central European population compared with non-Caucasian populations at a given age. Liver size of Central European children in 2020 is greater compared to a similar population almost 40 years ago. The craniocaudal dimension of the spleen of Central European, US-American and Turkish children is similar. The difference between genders is statistically significant for both the liver and the spleen, being larger in boys. Conclusion(s)

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 th

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 outcom

Therapeutic hypothermia (TH) is standard care in high-resource birth settings for infants with neonatal encephalopathy. TH is partially effective and adjuvant therapies are needed. Here, we examined whether the antioxidant melatonin (MLT) provides additive benefit with TH, compared to TH alone or MLT alone, to improve recovery from acute encephalopathy in newborn lambs. Immediately before cesarean section delivery, we induced asphyxia in fetal sheep via umbilical cord occlusion until mean arterial blood pressure fell from 55 ± 3 mm Hg in sham controls to 18-20 mm Hg (10.1 ± 1.5 minutes). Lambs were delivered and randomized to control, control + MLT (60 mg iv, from 30 minutes to 24 hours), asphyxia, asphyxia + TH (whole-body cooling to 35.1 ± 0.8°C vs. 38.3 ± 0.17°C in sham controls, from 4-28 hours), asphyxia + MLT, and asphyxia + TH + MLT. At 72 hours, magnetic resonance spectroscopy (MRS) was undertaken, and then brains were collected for neuropathology assessment. Asphyxia induced abnormal brain metabolism on MRS with increased Lactate:NAA (P = .003) and reduced NAA:Choline (P = .005), induced apoptotic and necrotic cell death across gray and white matter brain regions (P < .05), and increased neuroinflammation and oxidative stress (P < .05). TH and MLT were independently associated with region-specific reductions in oxidative stress, inflammation, and cell death, compared to asphyxia alone. There was an interaction between TH and MLT such that the NAA:Choline ratio was not significantly different after asphyxia + TH + MLT compared to sham controls but had a greater overall reduction in neuropathology than either treatment alone. This study demonstrates that, in newborn lambs, combined TH + MLT for neonatal encephalopathy provides significantly greater neuroprotection than either alone. These results will guide the development of further trials for neonatal encephalopathy.

Aim: To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP). Method(s): Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent). Result(s): From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p<0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings. Interpretation(s): Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than info

There are no publications reporting on scan duration and Doppler use during neonatal cranial ultrasound scans. We investigated current practice of neonatal cranial ultrasound at four large tertiary neonatal intensive care units in Australia. Cranial scans were prospectively recorded between March 2015 and November 2016. Variables, including total number of scans, scan duration and frequency and duration of colour and spectral Doppler mode, were extracted. A total of 196 scans formed the final cohort. The median (range) number of scans for each neonate was 1 (1-12). The median (range) overall total scan duration was 309 (119-801) s. Colour mode with or without spectral Doppler mode was used in approximately half of the cohort (106/196, 54%). Our findings comport with our hypotheses. Operators performing neonatal cranial scans in Australia have low overall scan durations. Although the use of Doppler mode during neonatal cranial scans is not standard practice in all neonatal intensive care units, it is used widely irrespective of the degree of prematurity or the presence of brain pathology. Further efforts are required to incorporate recommendations on scan duration and the routine use of Doppler mode during neonatal cranial scans. This is especially imperative given that the most vulnerable neonates with the greater neural tissue sensitivity are likely to be scanned more often.Copyright © 2020

BACKGROUND: Intussusception is a common, potentially life-threatening paediatric condition. Non-operative treatment with an air enema has been established as the clinical gold standard. There is no validated model for the training of this procedure. Our aim was to produce a novel air enema reduction simulator and validate its use as a training tool. METHOD(S): A low-cost paediatric intussusception air enema simulator was created. It was designed to include essential key clinical procedural steps. Participants included both procedural experts and novices from the Departments of Paediatric Radiology and Surgery. The simulator was assessed for face and content validity and its physical, conceptual and experiential fidelity by a structured questionnaire using a 5-point Likert's scale. Statistical analysis included a t-test, and a P-value of <0.05 was considered significant. RESULT(S): Twenty-four clinicians completed the simulation activity (expert: 13 and novices: 11). All experts had performed a minimum of 40 clinical procedures, and 46% had performed >50 procedures. All scores were favourable in all domains for face and content validity: 3.5 (physical appearance), 3.3 (insertion of the tube and taping), 3.1 (holding of the buttocks) and 3.5 (performing the air enema). The simulator also scored highly with fidelity assessment; visual 3.5, conceptual 3.4. There was no difference in procedural confidence with experts (3.8 versus 3.6, P=0.28), but there was for novices (1.0 versus 2.9, P=0.0002). CONCLUSION(S): This low-cost air enema reduction simulator for intussusception has an excellent educational potential for use in a training program in a tertiary centre, as well as, resource-constrained environments.Copyright © 2018 Royal Australasian College of Surgeons.

AIM: To examine the association between brain magnetic resonance imaging (MRI) characteristics and executive function and bimanual performance in children with unilateral cerebral palsy (CP). METHOD: Clinical MRI brain scans were classified as: (1) predominant pathological pattern (normal, white matter injury [WMI]; grey matter injury; focal vascular insults [FVI]; malformations; or miscellaneous); and (2) focal lesions (frontal, basal ganglia, and/or thalamus). Assessments included: (1) bimanual performance; (2) unimanual dexterity; and (3) executive function tasks (information processing, attention control, cognitive flexibility, and goal setting) and behavioural ratings (parent). RESULTS: From 131 recruited children, 60 were ineligible for analysis, leaving 71 children (47 males, 24 females) in the final sample (mean age 9y [SD 2y], 6y-12y 8mo). Brain MRIs were WMI (69%) and FVI (31%); and frontal (59%), thalamic (45%), basal ganglia (37%), and basal ganglia plus thalamic (21%). Bimanual performance was lower in FVI versus WMI (p<0.003), and with frontal (p=0.36), basal ganglia (p=0.032), and thalamic/basal ganglia lesions (p=0.013). Other than information processing, executive function tasks were not associated with predominant pattern. Frontal lesions predicted attention control (p=0.049) and cognitive flexibility (p=0.009) but not goal setting, information processing, or behavioural ratings. INTERPRETATION: Clinical brain MRI predicts cognitive and motor outcomes when focal lesions and predominate lesion patterns are considered. What this paper adds Early brain magnetic resonance imaging (MRI) predicts bimanual performance and cognitive outcomes. Brain MRI may identify children requiring targeted interventions. Basal ganglia with/without thalamic lesions predicted bimanual performance. Frontal lesions were associated with attention control and cognitive flexibility. Brain MRI predominant patterns predicted motor, not cognitive outcomes, other than information

Background: Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not sensitive enough to detect subtle structural abnormalities in the FGR brain. We examined whether advanced MRI analysis techniques have the capacity to detect brain injury (particularly white matter injury) caused by chronic hypoxia-induced fetal growth restriction in newborn preterm lambs. Method(s): Surgery was undertaken in twin bearing pregnant ewes at 88-90 days gestation (term = 150 days) to induce FGR in one fetus. At 127 days gestation (~32 weeks human brain development), FGR and control (appropriate for gestational age, AGA) lambs were delivered by caesarean section, intubated and ventilated. Conventional and advanced brain imaging was conducted within the first two hours of life using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) structural imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis of dMRI data included the following regions of interest (ROIs): subcortical white matter, periventricular white matter, cerebellum, hippocampus, corpus callosum and thalamus. Fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of the dMRI data was performed and compared between FGR and AGA lambs. Lambs were euthanised immediately after the scans and brain histology performed in the regions of interest to correlate with imaging. Result(s): FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p = .002) MRI brain scans were analysed. There were no statistically significant differences observed between the groups in conventional T1w, T2w or MRS brain data. Mean, axial and radial diffusivity, and fractional anisotropy indices obtained from DTI modelling also did not show any statistical

Introduction: Motor outcomes of children with unilateral cerebral palsy (CP) are clearly documented, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Patients and Methods: This was a prospective, cross-sectional multi-centre observational study. A convenience sample of 78 children (46 males, 37 left hemiplegia, mean age 9.0y, SD 1.9y; MACS I [n=24], MACS II [n=54]) with unilateral CP and without intellectual impairment were recruited. We examined associations between cognition, namely executive functions (EF), and bimanual performance. Primary outcomes included: Bimanual performance - the Assisting Hand Assessment (AHA) and Cognition (EF) - information processing (NEPSY - semantics total score); attention control (Test of Everyday Attention for Children (TEA-Ch) - time/target scores); cognitive flexibility (Neuropsychology Assessment for Children-II (NEPSY) - inhibition combined scores); and goal setting (Tower of London - total z-scores). Data were analysed using linear regression models. The model was adjusted for unimanual capacity and general cognitive ability. Result(s): Prior to adjusting for covariates, all 4 domains of EF including information processing (p=0.006), attention control (p=0.015), cognitive flexibility (p=<0.001), and goal setting (p=0.015) significantly impacted bimanual performance (AHA). After adjusting for general cognitive ability and unimanual capacity, only a significant effect for cognitive flexibility on bimanual performance remained (p=0.04). Conclusion(s): This data partially supports our hypothesis that high-level cognitive function (particularly cognitive flexibility) may impact how children with unilateral CP, without intellectual impairment, perform bimanual tasks.

Background: Reference charts depicting normal growth are important for the sonographic assessment of the pediatric kidney. Limited charts are available for clinical use in an Australian population. Objective(s): To retrospectively collate sonographic renal length measurements in a cohort of low-risk Australian children aged newborn to 16 years to produce a reference table and comparison with other published charts. Material(s) and Method(s): We identified consecutive pediatric patients who were at low risk for renal disease and had renal lengths measured. After exclusions, we included 941 renal lengths (male 490, female 451). We used linear regression to estimate the relationship of renal length with age, gender and side. We calculated percentile values of renal length according to age categories. Result(s): No statistically significant differences in mean renal length were observed between males and females, or for left and right kidneys. We tabulated reference data and provide them in a reference chart (1-, 2.5-, 5-, 10-, 50-, 90-, 97.5- and 99-percentiles). Conclusion(s): We calculated new reference ranges for pediatric renal length using a larger cohort than previously published, from a population with diverse ethnicity.Copyright © 2019, Springer-Verlag GmbH Germany, part of Springer Nature.

Background and Objective(s): Research suggests that specific cognitive functions may be associated with bimanual task performance in children with unilateral cerebral palsy (CP), yet it is unclear whether this is influenced by the neuropathological heterogeneity of this clinical population. We examined whether neuropathology (magnetic resonance imaging (MRI) abnormality classification), and other clinical characteristics mediate the relationship between executive function (EF) and bimanual performance in children with unilateral CP. Study Design: Prospective, cross-sectional multi-centre observational study. Study Participants & Setting: The sample comprised 64 children, including 39 males (61%), aged 6-12 years at recruitment (mean age 9.0y; SD 1.9y), recruited from five Australian paediatric treatment centres between July 2012 and August 2015, with unilateral CP (53% right hemiparesis; CS I (n=16), CS II (n=47), CS III (n=1)). Materials/Methods: The Assisting Hand Assessment (AHA), a standardized, criterion-referenced test of bimanual performance was the primary outcome. MRI were coded using an established protocol and data extracted retrospectively from clinical MRI scans, coded as normal or any of the five predominant pathological patterns: White Matter Injury (WMI), Grey Matter Injury (GMI), Focal Vascular Injury (FVI), malformations and miscellaneous pathologies. Parents completed a global EF questionnaire, and children completed standardised tests of EF (information processing, attention control, cognitive flexibility and goal setting) and intellectual function. The relationship between bimanual performance and the four EF domains, general executive functioning and MRI pathology type were examined using linear regression models Results: Comparisons were between WMI and FVI pathologies. No children had GMI. There were few children with mixed pathologies on MRI (n=3), normal MRI scans (n=2), malformations (n=4) and miscellaneous lesions (n=1); these were exclud

BACKGROUND: Fetal growth restriction (FGR) is a serious pregnancy complication associated with increased risk of adverse neurodevelopment and neuromorbidity. Current imaging techniques, including conventional magnetic resonance imaging (MRI), are not sensitive enough to detect subtle structural abnormalities in the FGR brain. We examined whether advanced MRI analysis techniques have the capacity to detect brain injury (particularly white matter injury) caused by chronic hypoxia-induced fetal growth restriction in newborn preterm lambs. METHODS: Surgery was undertaken in twin bearing pregnant ewes at 88-90 days gestation (term = 150 days) to induce FGR in one fetus. At 127 days gestation (~32 weeks human brain development), FGR and control (appropriate for gestational age, AGA) lambs were delivered by caesarean section, intubated and ventilated. Conventional and advanced brain imaging was conducted within the first two hours of life using a 3T MRI scanner. T1-weighted (T1w) and T2-weighted (T2w) structural imaging, magnetic resonance spectroscopy (MRS), and diffusion MRI (dMRI) data were acquired. Diffusion tensor imaging (DTI) modelling and analysis of dMRI data included the following regions of interest (ROIs): subcortical white matter, periventricular white matter, cerebellum, hippocampus, corpus callosum and thalamus. Fixel-based analysis of 3-tissue constrained spherical deconvolution (CSD) of the dMRI data was performed and compared between FGR and AGA lambs. Lambs were euthanised immediately after the scans and brain histology performed in the regions of interest to correlate with imaging. RESULTS: FGR and AGA lamb (body weight, mean (SD): 2.2(0.5) vs. 3.3(0.3) kg, p = .002) MRI brain scans were analysed. There were no statistically significant differences observed between the groups in conventional T1w, T2w or MRS brain data. Mean, axial and radial diffusivity, and fractional anisotropy indices obtained from DTI modelling also did not show any statistically s

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.

Background: Motor outcomes of children with unilateral cerebral palsy are clearly documented and well understood, yet few studies describe the cognitive functioning in this population, and the associations between the two is poorly understood. Using two hands together in daily life involves complex motor and cognitive processes. Impairment in either domain may contribute to difficulties with bimanual performance. Research is yet to derive whether, and how, cognition affects a child's ability to use their two hands to perform bimanual tasks. Methods/Design: This study will use a prospective, cross-sectional multi-centre observational design. Children (aged 6-12 years) with unilateral cerebral palsy will be recruited from one of five Australian treatment centres. We will examine associations between cognition, bimanual performance and brain neuropathology (lesion type and severity) in a sample of 131 children. The primary outcomes are: Motor - the Assisting Hand Assessment; Cognitive - Executive Function; and Brain - lesion location on structural MRI. Secondary data collected will include: Motor - Box and Blocks, ABILHAND- Kids, Sword Test; Cognitive - standard neuropsychological measures of intelligence. We will use generalized linear modelling and structural equation modelling techniques to investigate relationships between bimanual performance, executive function and brain lesion location. Discussion(s): This large multi-centre study will examine how cognition affects bimanual performance in children with unilateral cerebral palsy. First, it is anticipated that distinct relationships between bimanual performance and cognition (executive function) will be identified. Second, it is anticipated that interrelationships between bimanual performance and cognition will be associated with common underlying neuropathology. Findings have the potential to improve the specificity of existing upper limb interventions by providing more targeted treatments and influence the devel

Purpose: A longitudinal study spanning 10 years to investigate impact of radiation dose to Paediatric CT patients when Filtered Back Projection (FBP) and multigenerational Iterative Reconstruction (IR) techniques were utilised. Methods and Materials: Retrospective analysis of 243 paediatric patients for routine CT Chest imaging (age ranging from 23 days to 16 years, median of 5 years) and 216 paediatric patients for routine CT Abdomen imaging (age ranging from 47 days to 16 years, median of 9 years) spanning 2007-2017 were included in this study. Groupings used were 0-1 Years; 2-5 Years; 6-11 Years and 12-16 Years. Period of 2007-2011, CT systems used FBP. Between 2011-2013, Statistical IR (SIR) was routinely utilised. Post 2013, involved routine use of Model-Based IR (MBIR). Average CT Dose Index (CTDIvol) was recorded to best demonstrate differences in actual radiation dose administration. Result(s): Of the 243 CT Chest paediatric patients, 61 (25%) were scanned using FBP, 69 (28%) were scanned using SIR and 113 (47%) were scanned using MBIR. Of the 213 CT Abdomen paediatric patients, 50 (23%) scanned with FBP, 52 (24%) scanned with SIR and 114 (53%) scanned with MBIR. Post SIR introduction, dose administration reduced by an average of 65.32% and an average of 54.73% respectively for paediatric CT Chest and CT abdomen studies across. Post MBIR, dose further reduced by an average of 11.42% and an average of 4.81% for the same studies respectively. Total dose reduction for the same studies was an average of 69.30% and an average of 56.91% respectively. Conclusion(s): In this longitudinal study the use of multigenerational IR techniques for routine Paediatric CT Chest and CT Abdomen studies have significantly impacted administered radiation, achieving an average of 69.30% and 56.91% in overall reduction respectively. Paediatric radio-sensitivity is higher compared to adults thereby requiring the minimum prescribed diagnostic dose achievable. Use of IR should be consi

Perinatal asphyxia remains a principal cause of infant mortality and long-term neurological morbidity, particularly in low-resource countries. No neuroprotective interventions are currently available. Melatonin (MLT), a potent antioxidant, anti-inflammatory and antiapoptotic agent, offers promise as an intravenous (IV) or transdermal therapy to protect the brain. We aimed to determine the effect of melatonin (IV or transdermal patch) on neuropathology in a lamb model of perinatal asphyxia. Asphyxia was induced in newborn lambs via umbilical cord occlusion at birth. Animals were randomly allocated to melatonin commencing 30 minutes after birth (60 mg in 24 hours; IV or transdermal patch). Brain magnetic resonance spectroscopy (MRS) was undertaken at 12 and 72 hours. Animals (control n = 9; control+MLT n = 6; asphyxia n = 16; asphyxia+MLT [IV n = 14; patch n = 4]) were euthanised at 72 hours, and cerebrospinal fluid (CSF) and brains were collected for analysis. Asphyxia resulted in severe acidosis (pH 6.9 +/- 0.0; lactate 9 +/- 2 mmol/L) and altered determinants of encephalopathy. MRS lactate:N-acetyl aspartate ratio was 2.5-fold higher in asphyxia lambs compared with controls at 12 hours and 3-fold higher at 72 hours (P <.05). Melatonin prevented this rise (3.5-fold reduced vs asphyxia; P =.02). Asphyxia significantly increased brain white and grey matter apoptotic cell death (activated caspase-3), lipid peroxidation (4HNE) and neuroinflammation (IBA-1). These changes were significantly mitigated by both IV and patch melatonin. Systemic or transdermal neonatal melatonin administration significantly reduces the neuropathology and encephalopathy signs associated with perinatal asphyxia. A simple melatonin patch, administered soon after birth, may improve outcome in infants affected by asphyxia, especially in low-resource settings.Copyright © 2018 The Authors. Journal of Pineal Research Published by John Wiley & Sons Ltd