The Extracellular Vesicle Citrullinome and Signature in a Piglet Model of Neonatal Seizures.

Neonatal seizures are commonly associated with acute perinatal brain injury, while understanding regarding the downstream molecular pathways related to seizures remains unclear. Furthermore, effective treatment and reliable biomarkers are still lacking. Post-translational modifications can contribute to changes in protein function, and post-translational citrullination, which is caused by modification of arginine to citrulline via the calcium-mediated activation of the peptidylarginine deiminase (PAD) enzyme family, is being increasingly linked to neurological injury.

Early assessment of injury with optical markers in a piglet model of neonatal encephalopathy.

Background: Opportunities for adjunct therapies with cooling in neonatal encephalopathy are imminent; however, robust biomarkers of early assessment are lacking. Using an optical platform of broadband near-infrared spectroscopy and diffuse correlation spectroscopy to directly measure mitochondrial metabolism (oxCCO), oxygenation (HbD), cerebral blood flow (CBF), we hypothesised optical indices early (1-h post insult) after hypoxia-ischaemia (HI) predicts insult severity and outcome.

Methods: Nineteen newborn large white piglets underwent continuous neuromonitoring as controls or following moderate or severe HI.

Heart rate variability analysis for the prediction of EEG grade in infants with hypoxic ischaemic encephalopathy within the first 12 h of birth.

Background And Aims: Heart rate variability (HRV) has previously been assessed as a biomarker for brain injury and prognosis in neonates. The aim of this cohort study was to use HRV to predict the electroencephalography (EEG) grade in neonatal hypoxic-ischaemic encephalopathy (HIE) within the first 12 h.

Methods: We included 120 infants with HIE recruited as part of two European multi-centre studies, with electrocardiography (ECG) and EEG monitoring performed before 12 h of age.

Machine learning for the early prediction of infants with electrographic seizures in neonatal hypoxic-ischemic encephalopathy.

Objective: To assess if early clinical and electroencephalography (EEG) features predict later seizure development in infants with hypoxic-ischemic encephalopathy (HIE).

Methods: Clinical and EEG parameters <12 h of birth from infants with HIE across eight European Neonatal Units were used to develop seizure-prediction models. Clinical parameters included intrapartum complications, fetal distress, gestational age, delivery mode, gender, birth weight, Apgar scores, assisted ventilation, cord pH, and blood gases.

Brain temperature monitoring in newborn infants: Current methodologies and prospects.

Brain tissue temperature is a dynamic balance between heat generation from metabolism, passive loss of energy to the environment, and thermoregulatory processes such as perfusion. Perinatal brain injuries, particularly neonatal encephalopathy, and seizures, have a significant impact on the metabolic and haemodynamic state of the developing brain, and thereby likely induce changes in brain temperature. In healthy newborn brains, brain temperature is higher than the core temperature.

Effectiveness of early spectacle intervention on visual outcomes in babies at risk of cerebral visual impairment: a parallel group, open-label, randomised clinical feasibility trial protocol.

Introduction: Hypoaccommodation is common in children born prematurely and those with hypoxic ischaemic encephalopathy (HIE), with the potential to affect wider learning. These children are also at risk of longer-term cerebral visual impairment. It is also well recognised that early intervention for childhood visual pathology is essential, because neuroplasticity progressively diminishes during early life.

Optical Monitoring in Neonatal Seizures.

Background: Neonatal seizures remain a significant cause of morbidity and mortality worldwide. The past decade has resulted in substantial progress in seizure detection and understanding the impact seizures have on the developing brain. Optical monitoring such as cerebral near-infrared spectroscopy (NIRS) and broadband NIRS can provide non-invasive continuous real-time monitoring of the changes in brain metabolism and haemodynamics.

The Role of Music Therapy with Infants with Perinatal Brain Injury.

Perinatal brain injury occurs in 5.14/1000 live births in England. A significant proportion of these injuries result from hypoxic ischaemic encephalopathy (HIE) in term infants and intracranial haemorrhage (IVH) or periventricular leukomalacia (PVL) in preterm infants.

Broadband-NIRS System Identifies Epileptic Focus in a Child with Focal Cortical Dysplasia-A Case Study.

Epileptic seizures are transiently occurring symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Previous functional near-infrared spectroscopy (fNIRS) studies during seizures have focused in only monitoring the brain oxygenation and haemodynamic changes. However, few tools are available to measure actual cellular metabolism during seizures, especially at the bedside.

Prognostic value of neonatal EEG following therapeutic hypothermia in survivors of hypoxic-ischemic encephalopathy.

Objective: Early prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes.

Role of Optical Neuromonitoring in Neonatal Encephalopathy-Current State and Recent Advances.

Neonatal encephalopathy (NE) in term and near-term infants is a significant global health problem; the worldwide burden of disease remains high despite the introduction of therapeutic hypothermia. Assessment of injury severity and effective management in the neonatal intensive care unit (NICU) relies on multiple monitoring modalities from systemic to brain-specific. Current neuromonitoring tools provide information utilized for seizure management, injury stratification, and prognostication, whilst systemic monitoring ensures multi-organ dysfunction is recognized early and supported wherever needed.

Absolute quantification of cerebral tissue oxygen saturation with multidistance broadband NIRS in newborn brain.

Tissue oximetry with near-infrared spectroscopy (NIRS) is a technique for the measurement of absolute tissue oxygen saturation (StO). Offering a real-time and non-invasive assessment of brain oxygenation and haemodynamics, StO has potential to be used for the assessment of newborn brain injury. Multiple algorithms have been developed to measure StO, however, issues with low measurement accuracy or extracranial tissue signal contamination remain.

Optimizing hemodynamic care in neonatal encephalopathy.

Hemodynamic impairment occurs in up to 80% of infants with neonatal encephalopathy (NE). Not all infants benefit from therapeutic hypothermia (HT); there are some indications that the trajectory of brain injury might be modified by neurologic monitoring and early management over the first 72-h period. It is also possible that optimizing hemodynamic management may further improve outomes.

Metabolic brain measurements in the newborn: Advances in optical technologies.

Neonatal monitoring in neonatal intensive care is pushing the technological boundaries of newborn brain monitoring in order to improve patient outcome. There is an urgent need of a cot side, real time monitoring for assessment of brain injury severity and neurodevelopmental outcome, in particular for term newborn infants with hypoxic-ischemic brain injury. This topical review discusses why brain tissue metabolic monitoring is important in this group of infants and introduces the currently used neuromonitoring techniques for metabolic monitoring in the neonatal intensive care unit (NICU).

Cerebral Near Infrared Spectroscopy Monitoring in Term Infants With Hypoxic Ischemic Encephalopathy-A Systematic Review.

Neonatal hypoxic ischemic encephalopathy (HIE) remains a significant cause of mortality and morbidity worldwide. Cerebral near infrared spectroscopy (NIRS) can provide cot side continuous information about changes in brain hemodynamics, oxygenation and metabolism in real time. To perform a systematic review of cerebral NIRS monitoring in term and near-term infants with HIE.

Changes in Brain Tissue Oxygenation and Metabolism During Rewarming After Neonatal Encephalopathy are Related to Electrical Abnormality.

Hypoxic ischemic encephalopathy (HIE) leads to significant mortality and morbidity, and therapeutic hypothermia (TH) has become a standard of care following HIE. After TH, the body temperature is brought back to 37 °C. Early electroencephalography (EEG) is a reliable outcome biomarker following HIE.

Near-Infrared Spectroscopy Measured Cerebral Blood Flow from Spontaneous Oxygenation Changes in Neonatal Brain Injury.

Neonates with hypoxic-ischaemic (HI) brain injury were monitored using a broadband near-infrared spectroscopy (NIRS) system in the neonatal intensive care unit. The aim of this work is to use the NIRS cerebral oxygenation data (HbD = oxygenated-haemoglobin - deoxygenated-haemoglobin) combined with arterial saturation (SaO) from pulse oximetry to calculate cerebral blood flow (CBF) based on the oxygen swing method, during spontaneous desaturation episodes. The method is based on Fick's principle and uses HbD as a tracer; when a sudden change in SaO occurs, the change in HbD represents a change in tracer concentration, and thus it is possible to estimate CBF.

Quantification of the severity of hypoxic-ischemic brain injury in a neonatal preclinical model using measurements of cytochrome-c-oxidase from a miniature broadband-near-infrared spectroscopy system.

We describe the development of a miniaturized broadband near-infrared spectroscopy system (bNIRS), which measures changes in cerebral tissue oxyhemoglobin ( ) and deoxyhemoglobin ([HHb]) plus tissue metabolism via changes in the oxidation state of cytochrome-c-oxidase ([oxCCO]). The system is based on a small light source and a customized mini-spectrometer. We assessed the instrument in a preclinical study in 27 newborn piglets undergoing transient cerebral hypoxia-ischemia (HI).

Investigation of the Pattern of the Hemodynamic Response as Measured by Functional Near-Infrared Spectroscopy (fNIRS) Studies in Newborns, Less Than a Month Old: A Systematic Review.

It has been 20 years since functional near-infrared spectroscopy (fNIRS) was first used to investigate the evoked hemodynamic response to a stimulus in newborns. The hemodynamic response to functional activation is well-established in adults, with an observed increase in concentration change of oxygenated hemoglobin (Δ[HbO]) and decrease in deoxygenated hemoglobin (Δ[HHb]). However, functional studies in newborns have revealed a mixed response, particularly with Δ[HHb] where an inconsistent change in direction is observed.

Proton magnetic resonance spectroscopy lactate/N-acetylaspartate within 2 weeks of birth accurately predicts 2-year motor, cognitive and language outcomes in neonatal encephalopathy after therapeutic hypothermia.

Objective: Brain proton (H) magnetic resonance spectroscopy (MRS) lactate/N-acetylaspartate (Lac/NAA) peak area ratio is used for prognostication in neonatal encephalopathy (NE). At 3 Tesla in NE babies, the objectives were to assess: (1) sensitivity and specificity of basal ganglia and thalamus (BGT) H MRS Lac/NAA for the prediction of Bayley III outcomes at 2 years using optimised metabolite fitting (Tarquin) with threonine and total NAA; (2) prediction of motor outcome with diffusion-weighted MRI; (3) BGT Lac/NAA correlation with the National Institute of Child Health and Human Development (NICHD) MRI score.

Subjects And Methods: 55 (16 inborn, 39 outborn) infants at 39w+5 d (35w+5d-42w+0d) with NE admitted between February 2012 and August 2014 to University College London Hospitals for therapeutic hypothermia underwent MRI and H MRS at 3T on day 2-14 (median day 5).