Viral Infections and the Neonatal Brain

This review includes the congenital infections best known by the acronym TORCH (Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes virus), as well as Zika virus infection and perinatally acquired infections (enterovirus, parechovirus, rotavirus, parvovirus). Congenital infections are due to pathogens that can cross the placenta and are more likely to injure the brain when the infection occurs early in pregnancy. There are many similarities, with regards to brain lesions, for congenital Zika syndrome and congenital cytomegalovirus infection. Perinatally acquired viral infections tend to injure the white matter, with cystic evolution being more likely in the (late) preterm infant compared to the full-term infant. Congenital and perinatally acquired viral infections can be associated with adverse neurological outcomes. Prevention is important, especially as therapeutic options are limited. In this review both congenital as well as perinatally acquired viral infections will be discussed with a focus on neuro-imaging findings

Automatic segmentation of MR brain images with a convolutional neural network

Automatic segmentation in MR brain images is important for quantitative analysis in large-scale studies with images acquired at all ages. This paper presents a method for the automatic segmentation of MR brain images into a number of tissue classes using a convolutional neural network. To ensure that the method obtains accurate segmentation details as well as spatial consistency, the network uses multiple patch sizes and multiple convolution kernel sizes to acquire multi-scale information about each voxel. The method is not dependent on explicit features, but learns to recognise the information that is important for the classification based on training data. The method requires a single anatomical MR image only. The segmentation method is applied to five different data sets: coronal T2-weighted images of preterm infants acquired at 30 weeks postmenstrual age (PMA) and 40 weeks PMA, axial T2- weighted images of preterm infants acquired at 40 weeks PMA, axial T1-weighted images of ageing adults acquired at an average age of 70 years, and T1-weighted images of young adults acquired at an average age of 23 years. The method obtained the following average Dice coefficients over all segmented tissue classes for each data set, respectively: 0.87, 0.82, 0.84, 0.86 and 0.91. The results demonstrate that the method obtains accurate segmentations in all five sets, and hence demonstrates its robustness to differences in age and acquisition protocol

Ultrasonographic Estimation of Ventricular Volume in Infants Born Preterm with Posthemorrhagic Ventricular Dilatation: A Nested Substudy of the Randomized Controlled Early Versus Late Ventricular Intervention Study (ELVIS) Trial

Objective: To study the potential role of ventricular volume (VV) estimation in the management of posthemorrhagic ventricular dilatation related to the need for ventriculoperitoneal (VP)-shunt insertion and 2-year neurodevelopmental outcome in infants born preterm. Study design: We included 59 patients from the Early vs Late Ventricular Intervention Study from 4 participating centers. VV was manually segmented in 209 3-dimensional ultrasound scans and estimated from 2-dimensional ultrasound linear measurements in a total of 1226 ultrasounds. We studied the association of both linear measurements and VV to the need for VP shunt and 2-year neurodevelopmental outcome in the overall cohort and in the 29 infants who needed insertion of a reservoir. We used general estimating equations to account for repeated measures per individual. Results: Maximum pre-reservoir VV (β coefficient = 0.185, P = .0001) and gestational age at birth (β = −0.338; P = .0001) were related to the need for VP shunt. The estimated optimal single VV measurement cut point of 17 cm3 correctly classified 79.31% with an area under the curve of 0.76 (CI 95% 0.74-0.79). Maximum VV (β = 0.027; P = .012) together with VP shunt insertion (β = 3.773; P = .007) and gestational age (β = −0.273; P = .0001) were related to cognitive outcome at 2 years. Maximum ventricular index and anterior horn width before reservoir insertion were independently associated with the need of VP shunt and the proposed threshold groups in the Early vs Late Ventricular Intervention Study trial were associated with long-term outcome. Conclusions: Pre-reservoir VV measurements were associated with the need for VP-shunt insertion and 2-year cognitive outcome among infants born preterm with posthemorrhagic ventricular dilatation. Trial registration: ISRCTN43171322

Physical activity in relation to motor performance, exercise capacity, sports participation, parental perceptions, and overprotection in school aged children with a critical congenital heart defect

OBJECTIVE: To depict objectively measured moderate-to-vigorous physical activity (MVPA), motor performance (MP), cardiorespiratory fitness (CRF), organized sports participation, parental perceptions of vulnerability and parenting style in children with a Critical Congenital Heart Disease (CCHD), and to explore whether these factors are associated with MVPA. STUDY DESIGN: A prospective observational cohort study in 62 7-10 years old children with a CCHD. RESULTS: On average, children with CCHD spent 64 min on MVPA per day (accelerometry), 61 % met the international WHO physical activity guideline. Only 12 % had >60 min of MVPA daily. Eighteen percent had a motor delay (movement-assessment-battery-for children-II) and 38 % showed a below average CRF (cardiopulmonary exercise test using the Godfrey ramp protocol). Seventy-seven percent participated in organized sports activities at least once a week. Twenty-one percent of the parents are classified as overprotective (parent protection scale) and 7.3 % consider their child as being vulnerable (child vulnerability scale). A significant positive association was found between MVPA and MP (rs = 0.359), CRF(V̇O 2peak/ml/kg: rs = 0.472 and W peak/kg: rs = 0.396) and sports participation (rs = 0.286). Children who were perceived as vulnerable by their parents showed a significantly lower MVPA (rs = -0.302). No significant associations were found between mean MVPA and parental overprotection. CONCLUSION: Even though the majority of school aged children with a CCHD is sufficiently active, counseling parents regarding the importance of sufficient MVPA and sports participation, especially in parents who consider their child being vulnerable, could be useful. Since motor delays can be detected at an early age, motor development could be an important target to improve exercise capacity and sports participation to prevent inactivity in children with a CCHD

The relationship between interhemispheric synchrony, morphine and microstructural development of the corpus callosum in extremely preterm infants

Publisher Copyright: © 2022 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.The primary aim of this study is to examine whether bursting interhemispheric synchrony (bIHS) in the first week of life of infants born extremely preterm, is associated with microstructural development of the corpus callosum (CC) on term equivalent age magnetic resonance imaging scans. The secondary aim is to address the effects of analgesics such as morphine, on bIHS in extremely preterm infants. A total of 25 extremely preterm infants (gestational age [GA] .5). ASI was positively associated with the administration of morphine (p <.05). Early cortical synchrony may be affected by morphine and is not associated with the microstructural development of the CC. More studies are needed to evaluate the long-term effects of neonatal morphine treatment to optimize sedation in this high-risk population.Peer reviewe

Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury.

Infants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs). OPCs, in turn, develop into premyelinating OLs and finally mature into myelinating OLs. Recent studies revealed that OPCs develop in multiple waves and form potentially heterogeneous populations. Furthermore, it has been shown that myelination is a dynamic and plastic process with an excess of OPCs being generated and then abolished if not integrated into neural circuits. Myelination patterns between rodents and humans show high spatial and temporal similarity. Therefore, experimental studies on OL biology may provide novel insights into the pathophysiology of WMI in the preterm infant and offers new perspectives on potential treatments for these patients.This work was funded by the Wilhelmina Children's Hospital Research Fund and the Brain Foundation Netherlands

Early human brain development:insights into macroscale connectome wiring

BACKGROUND: Early brain development is closely dictated by distinct neurobiological principles. Here, we aimed to map early trajectories of structural brain wiring in the neonatal brain. METHODS: We investigated structural connectome development in 44 newborns, including 23 preterm infants and 21 full-term neonates scanned between 29 and 45 postmenstrual weeks. Diffusion-weighted imaging data were combined with cortical segmentations derived from T2 data to construct neonatal connectome maps. RESULTS: Projection fibers interconnecting primary cortices and deep gray matter structures were noted to mature faster than connections between higher-order association cortices (fractional anisotropy (FA) F = 58.9, p < 0.001, radial diffusivity (RD) F = 28.8, p < 0.001). Neonatal FA-values resembled adult FA-values more than RD, while RD approximated the adult brain faster (F = 358.4, p < 0.001). Maturational trajectories of RD in neonatal white matter pathways revealed substantial overlap with what is known about the sequence of subcortical white matter myelination from histopathological mappings as recorded by early neuroanatomists (mean RD 68 regions r = 0.45, p = 0.008). CONCLUSION: Employing postnatal neuroimaging we reveal that early maturational trajectories of white matter pathways display discriminative developmental features of the neonatal brain network. These findings provide valuable insight into the early stages of structural connectome development

The mammillary bodies: a review of causes of injury in infants and children

SUMMARY: Despite their small size, the mammillary bodies play an important role in supporting recollective memory. However, they have typically been overlooked when assessing neurologic conditions that present with memory impairment. While there is increasing evidence of mammillary body involvement in a wide range of neurologic disorders in adults, very little attention has been given to infants and children. Literature searches of PubMed and EMBASE were performed to identify articles that describe mammillary body pathology on brain MR imaging in children. Mammillary body pathology is present in the pediatric population in several conditions, indicated by signal change and/or atrophy on MR imaging. The main causes of mammillary body pathology are thiamine deficiency, hypoxia-ischemia, direct damage due to masses or hydrocephalus, or deafferentation resulting from pathology within the wider Papez circuit. Optimizing scanning protocols and assessing mammillary body status as a standard procedure are critical, given their role in memory processes

The Association of Dexamethasone and Hydrocortisone with Cerebellar Growth in Premature Infants

Objectives: Corticosteroids are used to prevent or treat lung disease of prematurity. While neurological side effects have been reported, detailed effects on cerebellar growth are unknown. This study aimed to compare cerebellar growth in premature infants who received dexamethasone or hydrocortisone to premature infants who did not receive postnatal corticosteroids. Study Design: Retrospective case-control study in infants born at a gestational age of <29 weeks and admitted to two level 3 neonatal intensive care units. Exclusion criteria were severe congenital anomalies and cerebellar or severe supratentorial lesions. Infants were treated with dexamethasone (unit 1) or hydrocortisone (unit 2) for chronic lung disease. Controls (unit 1) did not receive postnatal corticosteroids. Sequential head circumference (HC) and ultrasound measurements of transcerebellar diameter (TCD), biparietal diameter (BPD), and corpus callosum-fastigium length (CCFL) were performed until 40 weeks' postmenstrual age (PMA). Growth was assessed using linear mixed models correcting for PMA at measurement, sex, HC z-score at birth, and a propensity score indicating illness severity. Group differences before treatment were assessed using linear regression. Results: 346 infants were included (68 dexamethasone, 37 hydrocortisone, 241 controls). Before starting corticosteroids, TCD, BPD, and HC measurements did not differ between patients and controls at a comparable PMA. After starting treatment, both types of corticosteroid had a negative association with TCD growth. BPD, CCFL, and HC growth were not negatively affected. Conclusion: Administration of dexamethasone and hydrocortisone are both associated with impaired cerebellar growth in premature infants without evident negative associations with cerebral growth