Characterizing light-dark cycles in the Neonatal Intensive Care Unit: a retrospective observational study.

Objectives: To characterize bedside 24-h patterns in light exposure in the Neonatal Intensive Care Unit (NICU) and to explore the environmental and individual patient characteristics that influence these patterns in this clinical setting. Methods: We conducted a retrospective cohort study that included 79 very preterm infants who stayed in an incubator with a built-in light sensor. Bedside light exposure was measured continuously (one value per minute). Based on these data, various metrics (including relative amplitude, intradaily variability, and interdaily stability) were calculated to characterize the 24-h patterns of light exposure. Next, we determined the association between these metrics and various environmental and individual patient characteristics. Results: A 24-h light-dark cycle was apparent in the NICU with significant differences in light exposure between the three nurse shifts (p < 0.001), with the highest values in the morning and the lowest values at night. Light exposure was generally low, with illuminances rarely surpassing 75 lux, and highly variable between patients and across days within a single patient. Furthermore, the season of birth and phototherapy had a significant effect on 24-h light-dark cycles, whereas no effect of bed location and illness severity were observed. Conclusion: Even without an official lighting regime set, a 24-h light-dark cycle was observed in the NICU. Various rhythmicity metrics can be used to characterize 24-h light-dark cycles in a clinical setting and to study the relationship between light patterns and health outcomes.

Susceptibility weighted imaging can be a sensitive sequence to detect brain damage in neonates with kernicterus: a case report.

BACKGROUND: Kernicterus in the acute phase is difficult to diagnose. It depends on a high signal on T1 at the globus pallidum and subthalamic nucleus level. Unfortunately, these areas also show a relatively high signal on T1 in neonates as an expression of early myelination. Therefore, a less myelin-dependent sequence, like SWI, may be more sensitive to detecting damage in the globus pallidum area. CASE PRESENTATION: A term baby developed jaundice on day three following an uncomplicated pregnancy and delivery. Total bilirubin peaked at 542 µmol/L on day four. Phototherapy was started, and an exchange transfusion was performed. ABR showed absent responses on day 10. MRI on day eight demonstrated abnormal high signal globus pallidus on T1w, isointense on T2w, without diffusion restriction, and high signal on SWI at globus pallidal and subthalamus level and phase image at globus pallidal level. These findings were consistent with the challenging diagnosis of kernicterus. On follow-up, the infant presented with sensorineural hearing loss and had a work-up for cochlear implant surgery. At 3 months of age, the follow-up MR shows normalization of the T1 and SWI signals and a high signal on T2. CONCLUSIONS: SWI seems more sensitive to injury than the T1w and lacks the disadvantage of the T1w sequence, where early myelin confers a high signal.

The developing brain by trimester.

Transient anatomical entities play a role in the maturation of brain regions and early functional fetal networks. At the postmenstrual age of 7 weeks, major subdivisions of the brain are visible. At the end of the embryonic period, the cortical plate covers the neopallium. The choroid plexus develops in concert with it, and the dorsal thalamus covers about half the diencephalic third ventricle surface. In addition to the fourth ventricle neuroepithelium the rhombic lips are an active neuroepithelial production site. Early reciprocal connections between the thalamus and cortex are present. The corticospinal tract has reached the pyramidal decussation, and the arteries forming the mature circle of Willis are seen. Moreover, the superior sagittal sinus has formed, and at the rostral neuropore the massa commissuralis is growing. At the viable preterm age of around 24 weeks PMA, white matter tracts are in full development. Asymmetric progenitor division permits production of neurons, subventricular zone precursors, and glial cells. Myelin is present in the ventral spinal quadrant, cuneate fascicle, and spinal motor fibers. The neopallial mantle has been separated into transient layers (stratified transitional fields) between the neuroepithelium and the cortical plate. The subplate plays an important role in organizing the structuring of the cortical plate. Commissural tracts have shaped the corpus callosum, early primary gyri are present, and opercularization has started caudally, forming the lateral fissure. Thalamic and striatal nuclei have formed, although GABAergic neurons continue to migrate into the thalamus from the corpus gangliothalamicum. Near-term PMA cerebral sublobulation is active. Between 24 and 32 weeks, primary sulci develop. Myelin is present in the superior cerebellar peduncle, rubrospinal tract, and inferior olive. Germinal matrix disappears from the telencephalon, except for the GABAergic frontal cortical subventricular neuroepithelium.

Cerebello-cerebral connectivity in the developing brain.

Disrupted cerebellar development and injury is associated with impairments in both motor and non-motor domains. Methods to non-invasively characterize cerebellar afferent and efferent connections during early development are lacking. The aim of this study was to assess the feasibility of delineating cortico-ponto-cerebellar (CPC) and cerebello-thalamo-cortical (CTC) white matter tracts during brain development using high angular resolution diffusion imaging (HARDI). HARDI data were obtained in 24 infants born between 24+6 and 39 weeks gestational age (median 33+4 weeks) and scanned between 29+1 and 44 weeks postmenstrual age (PMA) (median 37+1 weeks). Probabilistic tractography of CPC and CTC fibers was performed using constrained spherical deconvolution. Connections between cerebellum and contralateral cerebral hemisphere were identified in all infants studied. Fractional anisotropy (FA) values of CTC and CPC pathways increased with increasing PMA at scan (p < 0.001). The supratentorial regions connecting to contralateral cerebellum in most subjects, irrespective of PMA at scan, included the precentral cortex, superior frontal cortex, supplementary motor area, insula, postcentral cortex, precuneus, and paracentral lobule. This study demonstrates the feasibility of assessing CTC and CPC white matter connectivity in vivo during the early stages of development. The ability to assess cerebellar connectivity during this critical developmental period may help improve our understanding of the role of the cerebellum in a wide range of neuromotor and neurocognitive disorders.

Periconception Maternal Folate Status and Human Embryonic Cerebellum Growth Trajectories: The Rotterdam Predict Study.

We aimed to investigate whether periconceptional maternal folate status affects human embryonic cerebellar size and growth trajectories. In a prospective periconceptional cohort participants filled out questionnaires and received weekly transvaginal 3D-ultrasounds between 7+0 and 12+6 weeks gestational age (GA). Viable non-malformed singleton pregnancies were selected for cerebellar measurements; transcerebellar diameter, (TCD), left and right cerebellar diameters (LCD, RCD). Linear mixed models were performed to estimate associations between questionnaire data on the timing of maternal folic acid supplement initiation and longitudinal cerebellar measurements as a function of crown-rump length (CRL) and GA. Maternal red blood cell folate concentrations were analysed before 8 weeks GA to validate the associations. A total of 263 serial high quality three-dimensional ultrasound scans of 135 pregnancies were studied. Preconceptional compared to postconceptional initiation of folic acid use was associated with slightly larger cerebellar diameters per millimetre increase of CRL (TCD: ß = 0.260mm, 95%CI = 0.023-0.491, p<0.05; LCD: ß = 0.171mm, 95%CI = 0.038-0.305, p<0.05; RCD: ß = 0.156mm, 95%CI = 0.032-0.280, p<0.05) and with proportional cerebellar growth (TCD/CRL:ß = 0.015mm/mm, 95%CI = 0.005-0.024, p<0.01; LCD/CRL:ß = 0.012mm/mm, 95%CI = 0.005-0.018, p<0.01; RCD/CRL:ß = 0.011mm/mm, 95%CI = 0.005-0.017, p<0.01). Cerebellar growth was significantly highest in the third quartile of maternal red blood cell folate levels (1538-1813 nmol/L). These first findings show that periconceptional maternal folate status is associated with human embryonic cerebellar development. Implications of these small but significant variations for fetal cerebellar growth trajectories and the child's neurodevelopmental outcome are yet unknown and warrant further investigation.

DTI reveals network injury in perinatal stroke.

BACKGROUND: Previous research showed acute diffusion-weighted imaging changes in pulvinar after extensive cortical injury from neonatal stroke. The authors used diffusion tensor imaging (DTI) to see how separate regions of ipsilateral thalamus are directly affected after a primary hit to their connected cortex in neonatal stroke. METHODS: The authors analysed DTI images of three term infants with acute unilateral cortical arterial ischaemic stroke. Probabilistic tractography was used to define separate thalamic regions of interests (ROIs). The authors evaluated the three eigenvalues (EV) and apparent diffusion coefficient (ADC) values in the ROIs. RESULTS: The ADC and EV in voxels of ROIs placed within the nuclei corresponding to ischaemic cortex were significantly lower than those in the unaffected contralesional thalamic nuclei. CONCLUSIONS: Our findings support the concept of acute network injury in neonatal stroke. ADC and EV were altered in specific thalamic regions that corresponded to the specific cortical areas affected by the primary ischaemic injury.

Network injury to pulvinar with neonatal arterial ischemic stroke.

The purpose of this study is to establish that newborn stroke involving extensive parts of cerebral cortex immediately leads to secondary network injury in pulvinar. Seven term infants with cortical stroke presented with hypersignal in pulvinar on DWI. Stroke types included: complete MCA stroke (n=4); PCA stroke, ICA stroke and multiple artery stroke (1 each). Age range at scanning was between day 2 and 6 after birth (except for 1 infant scanned within 7 days of acute presentation during ECMO). ADC values in secondarily injured pulvinar were significantly higher than in the area with primary (sub)cortical injury (all patients scanned with identical MR image acquisition). In the absence of asphyxia and because pulvinar is outside of the primary area of infarction, we conclude that there are suggestions from imaging for acute secondary injury to pulvinar following primary damage of their cortical targets and/or connecting axons. Acute secondary injury is probably due to excitotoxicity and deafferentiation. The relevance of network injury for prognosis and the impact of early treatment on it have yet to be studied, in stroke but also in other acute perinatal brain disorders.