aEEG Use in Pediatric Critical Care—An Online Survey

Background: Evidence supporting continuous EEG monitoring in pediatric intensive care is increasing, but continuous full-channel EEG is a scarce resource. Amplitude-integrated EEG (aEEG) monitors are broadly available in children's hospitals due to their use in neonatology and can easily be applied to older patients. Objective: The aim of this survey was to evaluate the use of amplitude-integrated EEG in German and Swiss pediatric intensive care units (PICUs). Design: An online survey was sent to German and Swiss PICUs that were identified via databases provided by the German Pediatric Association (DGKJ) and the Swiss Society of Intensive Care (SGI). The questionnaire contained 18 multiple choice questions including the PICU size and specialization, indications for aEEG use, perceived benefits from aEEG, and data storage. Main results: Forty-three (26%) PICUs filled out the questionnaire. Two thirds of all interviewed PICUs use aEEG in non-neonates. Main indications were neurological complications or disease and altered mental state. Features assessed were mostly seizures and side differences, less frequently height of amplitude and background pattern. Interpretation of raw EEG also played an important role. All interviewees would appreciate the establishment of reference values for toddlers and children. Conclusions: aEEG is used in a large proportion of the interviewed PICUs. The wide-spread use without validation of data generates the need for further evaluation of this technique and the establishment of reference values for non-neonates

Incidence of brain injuries in a large cohort of very preterm and extremely preterm infants at term-equivalent age: results of a single tertiary neonatal care center over 10 years

OBJECTIVES Cerebral magnetic resonance imaging (cMRI) at term-equivalent age (TEA) can detect brain injury (BI) associated with adverse neurological outcomes in preterm infants. This study aimed to assess BI incidences in a large, consecutive cohort of preterm infants born < 32 weeks of gestation, the comparison between very (VPT, ≥ 28 + 0 to < 32 + 0 weeks of gestation) and extremely preterm infants (EPT, < 28 + 0 weeks of gestation) and across weeks of gestation. METHODS We retrospectively analyzed cMRIs at TEA of VPT and EPT infants born at a large tertiary center (2009-2018). We recorded and compared the incidences of BI, severe BI, intraventricular hemorrhage (IVH), periventricular hemorrhagic infarction (PVHI), cerebellar hemorrhage (CBH), cystic periventricular leukomalacia (cPVL), and punctate white matter lesions (PWML) between VPTs, EPTs, and across weeks of gestation. RESULTS We included 507 preterm infants (VPT, 335/507 (66.1%); EPT, 172/507 (33.9%); mean gestational age (GA), 28 + 2 weeks (SD 2 + 2 weeks); male, 52.1%). BIs were found in 48.3% of the preterm infants (severe BI, 12.0%) and increased with decreasing GA. IVH, PVHI, CBH, cPVL, and PWML were seen in 16.8%, 0.8%, 10.5%, 3.4%, and 18.1%, respectively. EPT vs. VPT infants suffered more frequently from BI (59.3% vs. 42.7%, p < 0.001), severe BI (18.6% vs. 8.7%, p = 0.001), IVH (31.9% vs. 9.0%, p < 0.001), and CBH (18.0% vs. 6.6%, p < 0.001). CONCLUSION Brain injuries are common cMRI findings among preterm infants with a higher incidence of EPT compared to VPT infants. These results may serve as reference values for clinical management and research. CLINICAL RELEVANCE STATEMENT Our results with regard to gestational age might provide valuable clinical insights, serving as a key reference for parental advice, structured follow-up planning, and enhancing research and management within the Neonatal Intensive Care Unit. KEY POINTS Brain injury is a common cMRI finding in preterm infants seen in 48.3% individuals. • Extremely preterm compared to very preterm infants have higher brain injury incidences driven by brain injuries such as intraventricular and cerebellar hemorrhage. • Reference incidence values are crucial for parental advice and structured follow-up planning

Neonatal high pressure hydrocephalus is associated with elevation of pro-inflammatory cytokines IL-18 and IFNgamma in cerebrospinal fluid

BACKGROUND: In human neonatal high pressure hydrocephalus (HPHC), diffuse white matter injury and gliosis predispose to poor neuro-developmental outcome. The underlying mechanism for diffuse white matter damage in neonatal HPHC is still unclear. Analogous to inflammatory white matter damage after neonatal hypoxemia/ischemia, we hypothesized that pro-inflammatory cytokines could be involved in neonatal HPHC. If so, early anti-inflammatory therapy could ameliorate white matter damage in HPHC, before irreversible apoptosis has occurred. In HPHC and control neonates, we therefore aimed to compare cerebrospinal fluid (CSF) concentrations of IL18, IFNγ and sFasL (interleukin 18, interferon gamma and apoptosis marker soluble-Fas ligand, respectively). METHODS: In neonatal HPHC (n = 30) and controls (n = 15), we compared CSF concentrations of IL18, IFNγ and sFasL using sandwich ELISA. HPHC was grouped according to etiology: spina bifida aperta (n = 20), aqueduct stenosis (n = 4), and fetal intra-cerebral haemorrhage (n = 6). Neonatal control CSF was derived from otherwise healthy neonates (n = 15), who underwent lumbar puncture for exclusion of meningitis. RESULTS: In all three HPHC groups, CSF IL18 concentrations were significantly higher than control values, and the fetal intracranial haemorrhage group was significantly higher than SBA group. Similarly, in all HPHC groups CSF-IFNγ concentrations significantly exceeded the control group. In both HPHC and control neonates, CSF FasL concentrations remained within the range of reference values. CONCLUSION: Independent of the pathogenesis, neonatal HPHC is associated with the activation of the pro-inflammatory cytokines (IL-18 and IFNγ) in the CSF, whereas CSF apoptosis biomarkers (sFasL) were unchanged. This suggests that anti-inflammatory treatment (in addition to shunting) could be helpful to preserve cerebral white matter

Early Pro-inflammatory Microglia Activation After Inflammation-Sensitized Hypoxic-Ischemic Brain Injury in Neonatal Rats

Background: Perinatal asphyxia, leading to neonatal encephalopathy, is one of the leading causes for child mortality and long-term morbidities. Neonatal encephalopathy rates are significantly increased in newborns with perinatal infection. Therapeutic hypothermia is only neuroprotective in 50% of cooled asphyxiated newborns. As shown experimentally, cooling has failed to be neuroprotective after inflammation-sensitized hypoxic ischemic (HI) brain injury. Microglia are thought to be key players after inflammation-sensitized HI brain injury. We performed this study investigating early microglia phenotype polarization in our newborn animal model of inflammation-sensitized HI brain injury, better understanding the underlying pathophysiological processes.Methods: Seven days old Wistar rat pups were injected with either vehicle (NaCl 0.9%) or E. coli lipopolysaccharide (LPS), followed by left carotid ligation combined with global hypoxia inducing a mild unilateral hypoxic-ischemic injury. Pups were randomized to (1) Sham group (n = 41), (2) LPS only group (n = 37), (3) Veh/HI group (n = 56), and (4) LPS/HI group (n = 79). On postnatal days 8 and 14 gene-expression analysis or immunohistochemistry was performed describing early microglia polarization in our model.Results: We confirmed that LPS pre-sensitization significantly increases brain area loss and induced microglia activation and neuronal injury after mild hypoxia-ischemia. Additionally, we show that microglia upregulate pro-inflammatory genes involving NLRP-3 inflammasome gene expression 24 h after inflammation-sensitized hypoxic-ischemic brain injury.Conclusion: These results demonstrate that microglia are early key mediators of the inflammatory response following inflammation-sensitized HI brain injury and that they polarize into a predominant pro-inflammatory phenotype 24 h post HI. This may lead to new treatment options altering microglia phenotype polarization early after HI brain injury

Modeling Cerebral Blood Flow Dependence on Carbon Dioxide and Mean Arterial Blood Pressure in the Immature Brain With Accounting for the Germinal Matrix

Intraventricular hemorrhage (IVH) is one of the most critical complications in the development of preterm infants. The likelihood of IVH is strongly associated with disturbances in cerebral blood flow (CBF) and with microvascular fragility in the germinal matrix (GM). The CBF value and its reactivity to changes in arterial carbon dioxide pressure (pCO2) and mean arterial blood pressure (MABP) are relevant indicators in the clinical assessment of preterm infants. The objective of the present study is mathematical modeling of the influence of pCO2 and MABP on CBF in immature brain, based on clinical data collected from 265 preterm infants with 23–30 gestational weeks. The model was adapted to the peculiarities of immature brain by taking into account the morphological characteristics of the GM capillary network and vascular reactivity, according to gestational and postnatal age. An analysis of model based values of CBF and its reactivity to changes in MABP and pCO2 was performed separately for each gestational week and for the first two days of life both for preterm infants with and without IVH. The developed model for the estimation of CBF was validated against equivalent experimental measurements taken from the literature. A good agreement between the estimated values of CBF, as well as its reaction on changes in MABP and pCO2 and the equivalent values obtained in experimental studies was shown

Elevated nerve growth factor and neurotrophin-3 levels in cerebrospinal fluid of children with hydrocephalus

BACKGROUND: Elevated intracranial pressure (ICP) resulting from impaired drainage of cerebrospinal fluid (CSF) causes hydrocephalus with damage to the central nervous system. Clinical symptoms of elevated intracranial pressure (ICP) in infants may be difficult to diagnose, leading to delayed treatment by shunt placement. Until now, no biochemical marker of elevated ICP has been available for clinical diagnosis and monitoring. In experimental animal models, nerve growth factor (NGF) and neurotrophin-3 (NT-3) have been shown to be produced by glial cells as an adaptive response to hypoxia. We investigated whether concentrations of NGF and NT-3 are increased in the CSF of children with hydrocephalus. METHODS: NGF was determined in CSF samples collected from 42 hydrocephalic children on 65 occasions (taps or shunt placement surgery). CSF samples obtained by lumbar puncture from 22 children with suspected, but unconfirmed bacterial infection served as controls. Analysis was performed using ELISA techniques. RESULTS: NGF concentrations in hydrocephalic children were over 50-fold increased compared to controls (median 225 vs 4 pg/mL, p < 0.0001). NT-3 was detectable (> 1 pg/mL) in 14/31 hydrocephalus samples at 2–51 pg/mL but in none of 11 control samples (p = 0.007). CONCLUSION: NGF and NT-3 concentrations are increased in children with hydrocephalus. This may represent an adaptive response of the brain to elevated ICP

Impact of the first COVID lockdown on accident- and injury-related pediatric intensive care admissions in Germany - a multicenter study

Children’s and adolescents’ lives drastically changed during COVID lockdowns worldwide. To compare accident- and injury-related admissions to pediatric intensive care units (PICU) during the first German COVID lockdown with previous years, we conducted a retrospective multicenter study among 37 PICUs (21.5% of German PICU capacities). A total of 1444 admissions after accidents or injuries during the first lockdown period and matched periods of 2017–2019 were reported and standardized morbidity ratios (SMR) were calculated. Total PICU admissions due to accidents/injuries declined from an average of 366 to 346 (SMR 0.95 (CI 0.85–1.05)). Admissions with trauma increased from 196 to 212 (1.07 (0.93–1.23). Traffic accidents and school/kindergarten accidents decreased (0.77 (0.57–1.02 and 0.26 (0.05–0.75)), whereas household and leisure accidents increased (1.33 (1.06–1.66) and 1.34 (1.06–1.67)). Less neurosurgeries and more visceral surgeries were performed (0.69 (0.38–1.16) and 2.09 (1.19–3.39)). Non-accidental non-suicidal injuries declined (0.73 (0.42–1.17)). Suicide attempts increased in adolescent boys (1.38 (0.51–3.02)), but decreased in adolescent girls (0.56 (0.32–0.79)). In summary, changed trauma mechanisms entailed different surgeries compared to previous years. We found no evidence for an increase in child abuse cases requiring intensive care. The increase in suicide attempts among boys demands investigation