Early brain morphometrics from neonatal MRI predict motor and cognitive outcomes at 2-years corrected age in very preterm infants.

Infants born very preterm face a range of neurodevelopmental challenges in cognitive, language, behavioural and/or motor domains. Early accurate identification of those at risk of adverse neurodevelopmental outcomes, through clinical assessment and Magnetic Resonance Imaging (MRI), enables prognostication of outcomes and the initiation of targeted early interventions. This study utilises a prospective cohort of 181 infants born <31 weeks gestation, who had 3T MRIs acquired at 29-35 weeks postmenstrual age and a comprehensive neurodevelopmental evaluation at 2 years corrected age (CA). Cognitive, language and motor outcomes were assessed using the Bayley Scales of Infant and Toddler Development - Third Edition and functional motor outcomes using the Neuro-sensory Motor Developmental Assessment. By leveraging advanced structural MRI pre-processing steps to standardise the data, and the state-of-the-art developing Human Connectome Pipeline, early MRI biomarkers of neurodevelopmental outcomes were identified. Using Least Absolute Shrinkage and Selection Operator (LASSO) regression, significant associations between brain structure on early MRIs with 2-year outcomes were obtained (r = 0.51 and 0.48 for motor and cognitive outcomes respectively) on an independent 25% of the data. Additionally, important brain biomarkers from early MRIs were identified, including cortical grey matter volumes, as well as cortical thickness and sulcal depth across the entire cortex. Adverse outcome on the Bayley-III motor and cognitive composite scores were accurately predicted, with an Area Under the Curve of 0.86 for both scores. These associations between 2-year outcomes and patient prognosis and early neonatal MRI measures demonstrate the utility of imaging prior to term equivalent age for providing earlier commencement of targeted interventions for infants born preterm.

Cortical grey matter changes, behavior and cognition in children with sleep disordered breathing.

This paper investigated cortical thickness and volumetric changes in children to better understand the impact of obstructive sleep disordered breathing (SDB) on the neurodevelopment of specific regions of the brain. We also aimed to investigate how these changes were related to the behavioral and cognitive deficits observed in the condition. Neuroimaging, behavioral, and sleep data were obtained from 30 children (15 non-snoring controls, 15 referred for assessment of SDB) aged 7 to 17 years. Gyral-based regions of interest were identified using the Desikan-Killiany atlas. Student's t-tests were used to compare regions of interest between the controls and SDB groups. We found that the cortical thickness was significantly greater in the right caudal anterior cingulate and right cuneus regions and there were volumetric increases in the left caudal middle frontal, bilateral rostral anterior cingulate, left, right, and bilateral caudate brain regions in children with SDB compared with controls. Neither cortical thickness nor volumetric changes were associated with behavioral or cognitive measures. The findings of this study indicate disruptions to neural developmental processes occurring in structural regions of the brain; however, these changes appear unrelated to behavioural or cognitive outcomes.

Evaluation of a Cranial Ultrasound Screening Protocol for Very Preterm Infants.

OBJECTIVES: Cranial ultrasound (cUS) screening is recommended for preterm neonates born before 32 weeks' gestational age (GA). The primary aim of this study was to determine if both a day 3 and day 8 cUS screening examination is necessary for all neonates. METHODS: A retrospective observational study was performed at a tertiary-level Australian hospital. Frequencies of cranial ultrasound abnormality (CUA) were compared between routine screening performed at postnatal days 3, 8, and 42. Univariate and multivariate analyses of risk factors for intraventricular hemorrhage (IVH) was performed using logistic regression. RESULTS: cUS examinations on 712 neonates born before 32 weeks' GA were included. Neonates were divided into 2 groups: 99 neonates in the 23-25 weeks 6 days GA (group A) and 613 neonates in the 26-31 weeks 6 days GA (group B). All CUA occurred more frequently in group A neonates and in the subset of group B neonates who had defined risk factors. Low-risk group B neonates had lower incidence of CUAs demonstrated on day 8 cUS than high-risk group B neonates, with no significant differences between day 3 and day 8. Logistic regression analysis identified a number of risk factors (vaginal delivery, small for GA, Apgar score <7 at 5 minutes, intubation, patent ductus arteriosus and infection) that were associated with increased frequency of IVH on day 8. In neonates born between 30 and 31 weeks 6 days GA, 35% had a CUA identified. CONCLUSIONS: Low-risk preterm neonates born between 26 and 31 weeks 6 days GA, without complications, could be screened with a single early cUS examination around day 8 without missing substantial abnormality.

Pediatric reference values of anterior visual pathway structures measured with axis-correction on high-resolution 3D T2 fast spin echo sequences.

BACKGROUND: The size of the anterior visual pathway (AVP) structures is affected by patient age and pathology. Normative data is useful when determining whether pathology is present. AVP structures do not respect the standard planes of magnetic resonance (MR) imaging. The aim of this study was to produce normative age-related and axis-corrected data of the AVP structures using multiplanar reformation (MPR) of high-resolution 3D T2-weighted fast spin echo (3D T2w FSE) images. METHODS: For each patient 32 measurements of AVP structures were obtained in 145 children (2 months - 18 years) with normal brain MR studies on high-resolution 3D T2w FSE images adjusted to the axis of each AVP structure. Descriptive statistics were calculated for different age classes and growth models were fitted to the data and assessed for their performance to create a formal statistical model that allows inference beyond the sample. RESULTS: Descriptive statistics were compiled in a reference table and prediction plots in relation to age, height, and body surface area (BSA) were obtained from the best overall performing statistical model, also taking field strength (1.5 vs. 3 T) into account. Intraclass correlation coefficient values were calculated for all variables ranging from 0.474 to 0.967, the most reliable being the transverse diameter of the globe, the maximum diameter of the retrobulbar nerve sheath, the intracranial segment of the optic nerve and the transverse diameter of the chiasm. The maximum retrobulbar diameter of the optic nerve sheath and the lateral superoinferior diameter of the chiasm showed no statistically significant change with age. CONCLUSION: Detailed charts of reference values for AVP structures as well as prediction plots in relation to age, height and BSA were established using axis-corrected measurements from the MPR of high-resolution 3D T2w FSE images. Furthermore, an Excel spreadsheet that allows users to calculate normative values for the 9 AVP structures of key interest is provided as supplementary material.

Radiographic features of magnesium-based bioabsorbable screw resorption in paediatric fractures.

BACKGROUND: Resorption of magnesium-based alloy bioabsorbable screws produces hydrogen gas, which can be mistaken as a sign of infection and may affect the physis or fixed bone fragment. OBJECTIVE: We evaluated the temporal and spatial occurrence of gas and the occurrence of a breakage of the fixed bone fragment or screw following magnesium screw fixation. MATERIALS AND METHODS: Radiographs of paediatric patients treated with magnesium screws were retrospectively reviewed. Temporal occurrence and distribution of gas in the bone, the physis and soft tissues, breakage of the screw or fixed bone fragment and joint effusion were assessed. RESULTS: One hundred and three radiographs in 35 paediatric patients were reviewed (mean age: 10.6 years). Follow-up ranged from 1 to 730 days. Gas in the bone increases up to week 5, remains constant up to week 16 and then decreases. Gas in soft tissues, intra-articular gas and joint effusions gradually reduce over time. In 1/23 (4.3%) patients with an open physis, gas intrusion into the physis occurred. Breakage of the bone fragment fixated by the screw was observed in 4/35 (11.4%) patients within the first 6 weeks. Screw breakage was observed in 16/35 (45.7%) patients, with a median time to first detection of 300 days. CONCLUSION: Gas bubbles in bone and soft tissue are normal findings in the context of screw resorption and should not be confused with soft-tissue infection or osteomyelitis. Gas is rarely visible in the physis. Breakage of the fixed bone fragment and/or screw can occur.

Organ-based tube current modulation and bismuth eye shielding in pediatric head computed tomography.

BACKGROUND: Exposure of the eye lens to ionizing radiation results in cataract. Several dose optimization techniques to protect the lens are available for computed tomography (CT). OBJECTIVE: The radiation dose to the eye lens, volume CT dose index (CTDIvol) and image quality of various methods of dose optimization were evaluated for pediatric head CT: automated tube current modulation (ATCM), automated tube voltage selection (ATVS), organ-based tube current modulation (OBTCM) and bismuth shielding. MATERIALS AND METHODS: An anthropomorphic phantom of a 5-year-old child was scanned with nine protocols: no dose optimization technique and then adding different dose optimization techniques alone and in combination. Dose to the eye, thyroid and breast were estimated using metal oxide semiconductor field effect transistor (MOSFET) dosimetry. CTDIvol, influence of timing of shield placement, image noise and attenuation values in 13 regions of interest of the head and subjective image quality were compared. RESULTS: The eye shield significantly reduced the eye lens dose when used alone, to a similar degree as when using all software-based techniques together. When used in combination with software-based techniques, the shield reduced the eye lens dose by up to 45% compared to the no dose optimization technique. Noise was significantly increased by the shield, most pronounced in the anterior portion of the eye. CONCLUSION: The combination of ATCM, ATVS, OBTCM and a bismuth shield, with the shield placed after acquiring the localizer image, should be considered to reduce the radiation dose to the eye lens in pediatric head CT.

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.

Melatonin augments the neuroprotective effects of hypothermia in lambs following perinatal asphyxia.

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.

Normal sonographic liver and spleen dimensions in a central European pediatric population.

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. METHODS: 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. RESULTS: 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: Contemporary and ethnically appropriate reference charts for liver and spleen measurements should be used, especially for liver size. The effect of ethnicity is reduced if patient height rather than age is referenced.

Brain magnetic resonance imaging is a predictor of bimanual performance and executive function in children with unilateral cerebral palsy.

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 processing.

La resonancia magnética cerebral es un predictor del rendimiento bimanual y la función ejecutiva en niños con parálisis cerebral unilateral OBJETIVO: Examinar la asociación entre las características de la resonancia magnética cerebral (RMN) y la función ejecutiva y el rendimiento bimanual en niños con parálisis cerebral unilateral (PC). MÉTODO: Los escáneres cerebrales de resonancia magnética clínica se clasificaron como: (1) patrón patológico predominante (normal, lesión de la sustancia blanca [WMI]; lesión de la materia gris; lesiones vasculares focales [FVI]; malformaciones; o varios); y (2) lesiones focales (ganglios frontales, basales y / o tálamo). Las evaluaciones incluyeron: (1) desempeño bimanual; (2) destreza unimanual; y (3) tareas de funciones ejecutivas (procesamiento de información, control de atención, flexibilidad cognitiva y fijación de objetivos) y calificaciones de comportamiento (padres). RESULTADOS: De 131 niños reclutados, 60 no fueron elegibles para el análisis, dejando 71 niños (47 varones, 24 mujeres) en la muestra final (edad media 9 años [DE 2 años], 6 años - 12 años 8 meses). Las RMN cerebrales fueron WMI (69%) y FVI (31%); y frontal (59%), talámico (45%), ganglios basales (37%) y ganglios basales más talámico (21%). El rendimiento bimanual fue menor en FVI versus WMI (p <0,003), y con lesiones frontales (p = 0,36), ganglios basales (p = 0,032) y talámicas / ganglios basales (p = 0,013). Aparte del procesamiento de la información, las tareas de la función ejecutiva no se asociaron con el patrón predominante. Las lesiones frontales predijeron el control de la atención (p = 0,049) y la flexibilidad cognitiva (p = 0,009) pero no el establecimiento de objetivos, el procesamiento de la información o las clasificaciones de comportamiento. INTERPRETACIÓN: La resonancia magnética cerebral clínica predice los resultados cognitivos y motores cuando se consideran las lesiones focales y los patrones de lesiones predominantes.

Imagem por ressonância magnética do cérebro como preditora do desempenho bimanual e função executiva de crianças com paralisia cerebral unilateral OBJETIVO: Examinar a associação entre as características do exame de imagem por ressonância magnética (IRM) e a função executiva e desempenho bimanual em crianças com paralisia cerebral (PC) unilateral. MÉTODO: Escaneamentos clínicos de IRM cerebrais foram classificados como: 1) padrão patológico predominante (normal, lesão da substância branca [LSB]; lesão da substância cinzenta; insultos vasculares focais [IVF]; malformações; ou outro); e (2) lesões focais (frontal, gânglios basais, e/ou tálamo). As avaliações incluíram: (1) desempenho bimanual; (2) destreza unimanual; e (3) tarefas de função executiva (processamento de informações, controle da atenção, flexibilidade cognitiva, e estabelecimento de metas) e pontuações comportamentais (pais). RESULTADOS: De 131 crianças recrutadas, 60 eram inelegíveis para análise, restando 71 crianças (47 do sexo masculino, 24 do sexo feminino) na amostra final (média de idade 9a [DP 2a], 6a-12a 8m). IRMs cerebrais eram do tipo LSB (69%) e IVFs (31%); e frontais (59%), talâmicas (45%), de gânglios da base (37%), e de gânglios da base mais talâmicas (21%). O desempenho bimanual foi menor em IVF versus LSB (p<0,003), e com lesões frontais (p=0,36), gânglios da base (p=0,032), e talâmicas/gânglios da base (p=0,013). Com exceção do processamento de informações, as tarefas da função executiva não foram associadas com o padrão predominante. Lesões frontais foram preditivas do controle da atenção (p=0,049) e flexibilidade cognitiva (p=,.009) mas não do estabelecimento de metas, processamento de informações, e pontuações comportamentais. INTERPRETAÇÃO: A IRM cerebral clínica prediz resultados cognitivos e motores quando lesões focais e padrões predominantes de lesão são considerados.

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.

Normal sonographic renal length measurements in an Australian pediatric population.

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: 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. MATERIALS AND METHODS: 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. RESULTS: 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: We calculated new reference ranges for pediatric renal length using a larger cohort than previously published, from a population with diverse ethnicity.

Systemic and transdermal melatonin administration prevents neuropathology in response to perinatal asphyxia in newborn lambs.

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.

Cognition and bimanual performance in children with unilateral cerebral palsy: protocol for a multicentre, cross-sectional study.

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: 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 development of novel methods to improve both cognitive and motor outcomes in children with unilateral cerebral palsy. TRIAL REGISTRATION: ACTRN12614000631606 ; Date of retrospective registration 29/05/2014.

Three-dimensional ultrasound cranial imaging and early neurodevelopment in preterm growth-restricted infants.

AIM: Fetal growth restriction (FGR) is associated with increased perinatal morbidity, mortality and long-term neurodevelopmental sequelae. The objective of this study was to examine whether information about early neurodevelopmental deficits was evident using three-dimensional head ultrasound and developmental assessments in preterm infants with FGR, compared with appropriate for gestational age (AGA) infants in the early post-natal period. METHODS: Twenty preterm FGR infants weighing <10th centile and born between 28 and 32 weeks were compared with age-matched AGA infants. In the second post-natal week after birth, we used three-dimensional ultrasound to assess cerebral ventricular volumes. Prechtl General Movement Assessments were performed at 4-6 weeks after birth. Test of Infant Motor Performance (TIMP) to measure functional motor behaviour was performed at 4-6 and 12-14 weeks corrected age. RESULTS: There was no statistically significant difference in the combined cerebral ventricular volume between the two groups (FGR, 0.81 ± 0.42 vs. AGA 0.72 ± 0.38 cm3 , P = 0.4). The TIMP assessment at 12-14 week term corrected demonstrated lower scores (worse performance) in FGR infants compared with the AGA cohort (regression coefficient: -7.74 (95% CI -16.06, 0.57); P = 0.07). We observed a significant correlation between greater ventricular volume and lower TIMP scores in the cohorts separately and also overall (FGR, r = -0.5, P = 0.06 vs. AGA, r = -0.62, P = 0.007 and overall, r = -0.53, P = 0.001). CONCLUSION: Ultrasound in the early weeks may be useful to detect the neuropathology which could then mediate functional consequences.

Knowledge of Safety, Training, and Practice of Neonatal Cranial Ultrasound: A Survey of Operators.

OBJECTIVES: Ultrasound can lead to thermal and mechanical effects in interrogated tissues. This possibility suggests a potential risk during neonatal cranial ultrasound examinations. The aim of this study was to explore safety knowledge and training of neonatal cranial ultrasound among Australian operators who routinely perform these scans. METHODS: An online survey was administered on biosafety and training in neonatal cranial ultrasound, targeting all relevant professionals who can perform neonatal cranial ultrasound examinations in Australia: namely, radiologists, neonatologists, sonographers, and pediatricians. The survey was conducted between November 2013 and May 2014. RESULTS: A total of 282 responses were received. Twenty of 208 (10%) answered all ultrasound biosafety questions correctly, and 49 of 169 (29%) correctly defined the thermal index. Two-thirds (134 of 214 [63%]) of respondents failed to recognize that reducing the overall scanning time is the most effective method of reducing the total power exposure. Only 13% (31 of 237) indicated that a predetermined fixed period of training or that a specified minimum number of supervised scans was used during training. The reported number of supervised scans during training was highly variable. Almost half of the participants (82 of 181 [45%]) stated that they had received supervision for 10 to 50 scans (median, 20 scans). CONCLUSIONS: There is a need to educate operators on biosafety issues and approaches to minimize power outputs and reduce the overall duration of cranial ultrasound scans. Development of standardized training requirements may be warranted.

Retrospective review of screening for Sturge-Weber syndrome with brain magnetic resonance imaging and electroencephalography in infants with high-risk port-wine stains.

BACKGROUND: There is a lack of consensus regarding how best to screen children with facial port-wine stains for Sturge-Weber syndrome. Many favor brain magnetic resonance imaging, and adjunctive electroencephalography is increasingly used. However, the sensitivity, specificity, and negative and positive predictive value of magnetic resonance imaging and electroencephalography and whether screening improves seizure recognition is unclear. METHODS: A retrospective review of children with high-risk port-wine stains presenting consecutively to the outpatient laser clinic of a tertiary pediatric hospital between December 2015 and November 2016 was undertaken. Primary outcome measures were yield, accuracy, age of and protocols for screening magnetic resonance imaging and electroencephalography, type of and age at presenting seizure, and percentage referred to neurology. RESULTS: Of 126 patients with facial port-wine stains, 25.4% (32/126) were at high risk of Sturge-Weber syndrome (hemifacial, median, and forehead PWS phenotypes); 43.7% of these (14/32) underwent screening magnetic resonance imaging. Sturge-Weber syndrome was detected in 7.1% (1/14). Magnetic resonance imaging had false-negative results in 23.1% (3/13) of those screened. Screening magnetic resonance imaging had sensitivity of 25%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 76.9% for the detection of Sturge-Weber syndrome (hemifacial, median and forehead PWS phenotypes). Only one-third of those with false-negative magnetic resonance imaging were referred to neurology. Mean age of first seizure in those with false-negative screening magnetic resonance imaging was 28 months, vs 14 months in those not screened. Abnormal electroencephalographic signs were detected in the two infants who underwent presymptomatic electroencephalography. CONCLUSIONS: Findings from this small cohort of individuals with port-wine stains that put them at high risk of Sturge-Weber syndrome suggest that children with positive screening magnetic resonance imaging will almost certainly develop Sturge-Weber syndrome but that negative screening magnetic resonance imaging cannot exclude Sturge-Weber syndrome (in up to 23.1% of cases). False-negative magnetic resonance imaging may delay seizure recognition. Seizure education, monitoring, and consideration of adjunctive electroencephalography are important irrespective of magnetic resonance imaging findings.

Screening for Sturge-Weber syndrome: A state-of-the-art review.

Infants with a high-risk distribution of port-wine stains are commonly screened for Sturge-Weber syndrome using brain magnetic resonance imaging. There is no consensus about which port-wine stain phenotypes to screen, optimal timing, screening sensitivity, or whether presymptomatic diagnosis improves neurodevelopmental outcomes. This state-of-the-art review examines the evidence in favor of screening for Sturge-Weber syndrome, based on its effect on neurodevelopmental outcomes, against the risks and limitations of screening magnetic resonance imaging and electroencephalography. A literature search of PubMed/MEDLINE was conducted between January 2005 and May 2017 using key search terms. Relevant articles published in English were reviewed; 34 articles meeting the search criteria were analyzed according to the following outcome measures: neurodevelopmental outcome benefit of screening, diagnostic yield, financial costs, procedural risks, and limitations of screening magnetic resonance imaging and electroencephalography. There is no evidence that a presymptomatic Sturge-Weber syndrome diagnosis with magnetic resonance imaging results in better neurodevelopmental outcomes. The utility of electroencephalographic screening is also unestablished. In Sturge-Weber syndrome, neurodevelopmental outcomes depend on prompt recognition of neurologic red flags and early seizure control. Small numbers and a lack of prospective randomized controlled trials limit these findings. For infants with port-wine stain involving skin derived from the frontonasal placode (forehead and hemifacial phenotypes), we recommend early referral to a pediatric neurologist for parental education, counselling, and monitoring for neurologic red flags and seizures and consideration of electroencephalography regardless of whether magnetic resonance imaging is performed or its findings.