Early automated classification of neonatal hypoxic-ischemic encephalopathy - An aid to the decision to use therapeutic hypothermia.

OBJECTIVE: The study aimed to address the challenge of early assessment of neonatal hypoxic-ischemic encephalopathy (HIE) severity to identify candidates for therapeutic hypothermia (TH). The objective was to develop an automated classification model for neonatal EEGs, enabling accurate HIE severity assessment 24/7. METHODS: EEGs recorded within 6 h of life after perinatal anoxia were visually graded into 3 severity groups (HIE French Classification) and quantified using 6 qEEG markers measuring amplitude, continuity and frequency content. Machine learning models were developed on a dataset of 90 EEGs and validated on an independent dataset of 60 EEGs. RESULTS: The selected model achieved an overall accuracy of 80.6% in the development phase and 80% in the validation phase. Notably, the model accurately identified 28 out of 30 children for whom TH was indicated after visual EEG analysis, with only 2 cases (moderate EEG abnormalities) not recommended for cooling. CONCLUSIONS: The combination of clinically relevant qEEG markers led to the development of an effective automated EEG classification model, particularly suited for the post-anoxic latency phase. This model successfully discriminated neonates requiring TH. SIGNIFICANCE: The proposed model has potential as a bedside clinical decision support tool for TH.

Advances in Electroencephalographic Biomarkers of Neonatal Hypoxic Ischemic Encephalopathy.

Electroencephalography (EEG) is a key objective biomarker of newborn brain function, delivering critical, cotside insights to aid the management of encephalopathy. Access to continuous EEG is limited, forcing reliance on subjective clinical assessments. In hypoxia ischaemia, the primary cause of encephalopathy, alterations in EEG patterns correlate with. injury severity and evolution. As HIE evolves, causing secondary neuronal death, EEG can track injury progression, informing neuroprotective strategies, seizure management and prognosis. Despite its value, challenges with interpretation and lack of on site expertise has limited its broader adoption. Technological advances, particularly in digital EEG and machine learning, are enhancing real-time analysis. This will allow EEG to expand its role in HIE diagnosis, management and outcome prediction.

Oxidative and Antioxidative Biomarker Profiles in Neonatal Hypoxic-Ischemic Encephalopathy: Insights for Pathophysiology and Treatment Strategies.

BACKGROUND Neonatal hypoxic-ischemic encephalopathy (HIE) is a significant cause of perinatal and postnatal morbidity and mortality worldwide. Catalase (CAT) activity detection is used to determine levels of inflammation and oxidative stress. Glutathione (GSH) is the most critical non-enzymatic endogenous antioxidant. Lipid peroxidation levels marked after hypoxia can be detected based on the level of malondialdehyde (MDA). Ischemia-modified albumin (IMA) is considered a biomarker for cardiac ischemia and is known to increase in the liver, brain, and kidney in states of insufficient oxygenation. We aimed to explain the results and relations between the oxidant and antioxidants to detail oxidant-antioxidant balance and cellular mechanisms. MATERIAL AND METHODS Serum levels of IMA and MDA, as an oxidative stress marker, and CAT and GSH, as antioxidant enzymes, were measured in first blood samples of 59 neonates diagnosed with HIE, with pH <7, base excess >12, and APGAR scores. RESULTS Neonates who were ≥37 weeks of gestation and had hypoxia were included. Compared with healthy newborns (n=32), CAT was statistically significantly lower in the hypoxia group (P=0.0001), while MDA serum levels were significantly higher in neonates with hypoxia (P=0.01). There was no difference between hypoxic and healthy neonates in GSH and IMA measurements (P=0.054, P=0.19 respectively). CONCLUSIONS HIE pathophysiology involves oxidative stress and mitochondrial energy production failure. Explaining the pathways between oxidant-antioxidant balance and cell death, which explains the pathophysiology of HIE, is essential to develop treatment strategies that will minimize the effects of oxygen deprivation on other body organs, especially the brain.

Persistent pulmonary hypertension and short-term neurological outcomes in infants with moderate to severe hypoxic ischemic encephalopathy.

BACKGROUND: Our aim was to investigate the relationship between persistent pulmonary hypertension of the newborn (PPHN), short-term brain injury or death, and clinical parameters in infants with moderate to severe hypoxic ischemic encephalopathy (HIE). METHODS: Retrospective single-center cohort study of 274 HIE infants, 230 underwent Therapeutic Hypothermia (TH). Primary outcome was severe HIE brain injury on MRI and/or death within the first month of life in relation to presence and severity of PPHN (clinical or echocardiographic). Secondary outcomes were HIE brain injury pattern, abnormal electroencephalogram (EEG), seizures, clinical, and laboratory differences. A logistic regression model was performed to evaluate PPHN presence and severity as risk factor for brain injury or death. RESULTS: The combined outcome of severe brain injury or death was higher in the clinical PPHN group vs non-PPHN (32.6 vs 22.8%, p = 0.014). There was no difference in brain injury, seizure burden or EEG abnormalities associated with PPHN, despite those with PPHN being sicker with higher ventilation needs and worse laboratory values than those without. Mortality had a strong correlation with echocardiographic PPHN with the highest incidence in severe (36%) vs moderate (7.7%) vs mild PPHN (10%, p = 0.002). Highest mortality had those with 'early exit' who did not complete 72 hours of TH (71.4%). CONCLUSIONS: In infants with HIE, PPHN was not associated with increased risk of brain injury as evident on MRI, nor seizure burden, despite being sicker with worse laboratory values. However, mortality rates were higher the worse the PPHN, especially with early exit from TH.

Burst-Suppression EEG Reactivity to Photic Stimulation-A Translational Biomarker in Hypoxic-Ischemic Brain Injury.

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic-ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.

Modulation of brain activity in brain-injured patients with a disorder of consciousness in intensive care with repeated 10-Hz transcranial alternating current stimulation (tACS): a randomised controlled trial protocol.

INTRODUCTION: Therapeutic interventions for disorders of consciousness lack consistency; evidence supports non-invasive brain stimulation, but few studies assess neuromodulation in acute-to-subacute brain-injured patients. This study aims to validate the feasibility and assess the effect of a multi-session transcranial alternating current stimulation (tACS) intervention in subacute brain-injured patients on recovery of consciousness, related brain oscillations and brain network dynamics. METHODS AND ANALYSES: The study is comprised of two phases: a validation phase (n=12) and a randomised controlled trial (n=138). Both phases will be conducted in medically stable brain-injured adult patients (traumatic brain injury and hypoxic-ischaemic encephalopathy), with a Glasgow Coma Scale score ≤12 after continuous sedation withdrawal. Recruitment will occur at the intensive care unit of a Level 1 Trauma Centre in Montreal, Quebec, Canada. The intervention includes a 20 min 10 Hz tACS at 1 mA intensity or a sham session over parieto-occipital cortical sites, repeated over five consecutive days. The current's frequency targets alpha brain oscillations (8-13 Hz), known to be associated with consciousness. Resting-state electroencephalogram (EEG) will be recorded four times daily for five consecutive days: pre and post-intervention, at 60 and 120 min post-tACS. Two additional recordings will be included: 24 hours and 1-week post-protocol. Multimodal measures (blood samples, pupillometry, behavioural consciousness assessments (Coma Recovery Scale-revised), actigraphy measures) will be acquired from baseline up to 1 week after the stimulation. EEG signal analysis will focus on the alpha bandwidth (8-13 Hz) using spectral and functional network analyses. Phone assessments at 3, 6 and 12 months post-tACS, will measure long-term functional recovery, quality of life and caregivers' burden. ETHICS AND DISSEMINATION: Ethical approval for this study has been granted by the Research Ethics Board of the CIUSSS du Nord-de-l'Île-de-Montréal (Project ID 2021-2279). The findings of this two-phase study will be submitted for publication in a peer-reviewed academic journal and submitted for presentation at conferences. The trial's results will be published on a public trial registry database (ClinicalTrials.gov). TRIAL REGISTRATION NUMBER: NCT05833568.

Heart rate variability for neuro-prognostication after CA: Insight from the Parisian registry.

BACKGROUND: Hypoxic ischemic brain injury (HIBI) induced by cardiac arrest (CA) seems to predominate in cortical areas and to a lesser extent in the brainstem. These regions play key roles in modulating the activity of the autonomic nervous system (ANS), that can be assessed through analyses of heart rate variability (HRV). The objective was to evaluate the prognostic value of various HRV parameters to predict neurological outcome after CA. METHODS: Retrospective monocentric study assessing the prognostic value of HRV markers and their association with HIBI severity. Patients admitted for CA who underwent EEG for persistent coma after CA were included. HRV markers were computed from 5 min signal of the ECG lead of the EEG recording. HRV indices were calculated in the time-, frequency-, and non-linear domains. Frequency-domain analyses differentiated very low frequency (VLF 0.003-0.04 Hz), low frequency (LF 0.04-0.15 Hz), high frequency (HF 0.15-0.4 Hz), and LF/HF ratio. HRV indices were compared to other prognostic markers: pupillary light reflex, EEG, N20 on somatosensory evoked potentials (SSEP) and biomarkers (neuron specific enolase-NSE). Neurological outcome at 3 months was defined as unfavorable in case of best CPC 3-4-5. RESULTS: Between 2007 and 2021, 199 patients were included. Patients were predominantly male (64%), with a median age of 60 [48.9-71.7] years. 76% were out-of-hospital CA, and 30% had an initial shockable rhythm. Neurological outcome was unfavorable in 73%. Compared to poor outcome, patients with a good outcome had higher VLF (0.21 vs 0.09 ms2/Hz, p < 0.01), LF (0.07 vs 0.04 ms2/Hz, p = 0.003), and higher LF/HF ratio (2.01 vs 1.01, p = 0.008). Several non-linear domain indices were also higher in the good outcome group, such as SD2 (15.1 vs 10.2, p = 0.016) and DFA α1 (1.03 vs 0.78, p = 0.002). These indices also differed depending on the severity of EEG pattern and abolition of pupillary light reflex. These time-frequency and non-linear domains HRV parameters were predictive of poor neurological outcome, with high specificity despite a low sensitivity. CONCLUSION: In comatose patients after CA, some HRV markers appear to be associated with unfavorable outcome, EEG severity and PLR abolition, although the sensitivity of these HRV markers remains limited.

Grey-to-White Matter Ratio Values in Early Head Computed Tomography (CT) as a Predictor of Neurologic Outcomes in Survivors of Out-of-Hospital Cardiac Arrest Based on Severity of Hypoxic-Ischemic Brain Injury.

BACKGROUND: Hypoxic-ischemic brain injury (HIBI) is a common complication of out-of-hospital cardiac arrest (OHCA). OBJECTIVES: We investigated whether grey-to-white matter ratio (GWR) values, measured using early head computed tomography (HCT), were associated with neurologic outcomes based on the severity of HIBI in survivors of OHCA. METHODS: This retrospective multicenter study included adult comatose OHCA survivors who underwent an HCT scan within 2 h after the return of spontaneous circulation. HIBI severity was assessed using the revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST) scale (low, moderate, and severe). Poor neurologic outcomes were defined as Cerebral Performance Categories 3 to 5 at 6 months after OHCA. RESULTS: Among 354 patients, 27% were women and 224 (63.3%) had poor neurologic outcomes. The distribution of severity was 19.5% low, 47.5% moderate, and 33.1% severe. The area under the receiver operating curves of the GWR values for predicting rCAST severity (low, moderate, and severe) were 0.52, 0.62, and 0.79, respectively. The severe group had significantly higher predictive performance than the moderate group (p = 0.02). Multivariate logistic regression analysis revealed a significant association between GWR values and poor neurologic outcomes in the moderate group (adjusted odds ratio = 0.012, 95% CI 0.0-0.54, p = 0.02). CONCLUSIONS: In this cohort study, GWR values measured using early HCT demonstrated variations in predicting neurologic outcomes based on HIBI severity. Furthermore, GWR in the moderate group was associated with poor neurologic outcomes.

Ultrasonic vocalization emission is altered following neonatal hypoxic-ischemic brain injury in mice.

Neonatal hypoxic-ischemic (HI) brain injury leads to cognitive impairments including social communication disabilities. Current treatments do not sufficiently target these impairments, therefore new tools are needed to examine social communication in models for neonatal brain injury. Ultrasonic vocalizations (USVs) during early life show potential as a measurement for social development and reflect landmark developmental stages in neonatal mice. However, changes in USV emission early after HI injury have not been found yet. Our current study examines USV patterns and classes in the first 3 days after HI injury. C57Bl/6 mice were subjected to HI on postnatal day (P)9 and USVs were recorded between P10 and P12. Audio files were analyzed using the VocalMat automated tool. HI-injured mice emitted less USVs, for shorter durations, and at a higher frequency compared to control (sham-operated) littermates. The HI-induced alterations in USVs were most distinct at P10 and in the frequency range of 50-75 kHz. At P10 HI-injured mouse pups also produced different ratios of USV class types compared to control littermates. Moreover, alterations in the duration and frequency were specific to certain USV classes in HI animals compared to controls. Injury in the striatum and hippocampus contributed most to alterations in USV communication after HI. Overall, neonatal HI injury leads to USV alterations in newborn mice which could be used as a tool to study early HI-related social communication deficits.

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

CT brain perfusion patterns and clinical outcome after successful cardiopulmonary resuscitation: A pilot study.

AIM: CT perfusion is a valuable tool for evaluating cerebrovascular diseases, but its role in patients with hypoxic ischaemic encephalopathy is unclear. This study aimed to investigate 1) the patterns of cerebral perfusion changes that may occur early on after successful resuscitation, and 2) their correlation with clinical outcome to explore their value for predicting outcome. METHODS: We conducted a retrospective analysis of perfusion maps from patients who underwent CT brain perfusion within 12 h following successful resuscitation. We classified the perfusion changes into distinct patterns. According to the cerebral performance category (CPC) score clinical outcome was categorised as favourable (CPC 1-2), or unfavourable (CPC 3-5). RESULTS: A total of 87 patients were included of whom 33 had a favourable outcome (60.6% male, mean age 60 ± 16 years), whereas 54 exhibited an unfavourable outcome (59.3% male, mean age 60 ± 19 years). Of the patients in the favourable outcome group, 30.3% showed no characteristic perfusion changes, in contrast to the unfavourable outcome group where all patients exhibit changes in perfusion. Eighteen perfusion patterns were identified. The most significant patterns for prediction of unfavourable outcome in terms of their high specificity and frequency were hypoperfusion of the brainstem as well as coexisting hypoperfusion of the brainstem and thalamus. CONCLUSION: This pilot study identified various perfusion patterns in patients after resuscitation, indicative of circulatory changes associated with post-cardiac-arrest brain injury. After validation, certain patterns could potentially be used in conjunction with other prognostic markers for stratifying patients and adjusting personalized treatment following cardiopulmonary resuscitation. Normal brain perfusion within 12 h after resuscitation is predictive of favourable outcome with high specificity.

Shining a light on cerebral autoregulation: Are we anywhere near the truth?

The near-infrared spectroscopy (NIRS)-derived cerebral oximetry index (COx) has become popularized for non-invasive neuromonitoring of cerebrovascular function in post-cardiac arrest patients with hypoxic-ischemic brain injury (HIBI). We provide commentary on the physiologic underpinnings and assumptions of NIRS and the COx, potential confounds in the context of HIBI, and the implications for the assessment of cerebral autoregulation.

The role of the sensory input intervention in recovery of the motor function in hypoxic ischemic encephalopathy rat model.

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.NEW & NOTEWORTHY Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs.

Clinical outcome prediction with an automated EEG trend, Brain State of the Newborn, after perinatal asphyxia.

OBJECTIVE: To evaluate the utility of a fully automated deep learning -based quantitative measure of EEG background, Brain State of the Newborn (BSN), for early prediction of clinical outcome at four years of age. METHODS: The EEG monitoring data from eighty consecutive newborns was analyzed using the automatically computed BSN trend. BSN levels during the first days of life (a of total 5427 hours) were compared to four clinical outcome categories: favorable, cerebral palsy (CP), CP with epilepsy, and death. The time dependent changes in BSN-based prediction for different outcomes were assessed by positive/negative predictive value (PPV/NPV) and by estimating the area under the receiver operating characteristic curve (AUC). RESULTS: The BSN values were closely aligned with four visually determined EEG categories (p < 0·001), as well as with respect to clinical milestones of EEG recovery in perinatal Hypoxic Ischemic Encephalopathy (HIE; p < 0·003). Favorable outcome was related to a rapid recovery of the BSN trend, while worse outcomes related to a slow BSN recovery. Outcome predictions with BSN were accurate from 6 to 48 hours of age: For the favorable outcome, the AUC ranged from 95 to 99% (peak at 12 hours), and for the poor outcome the AUC ranged from 96 to 99% (peak at 12 hours). The optimal BSN levels for each PPV/NPV estimate changed substantially during the first 48 hours, ranging from 20 to 80. CONCLUSIONS: We show that the BSN provides an automated, objective, and continuous measure of brain activity in newborns. SIGNIFICANCE: The BSN trend discloses the dynamic nature that exists in both cerebral recovery and outcome prediction, supports individualized patient care, rapid stratification and early prognosis.

Perinatal compromise affects development, form, and function of the hippocampus part two; preclinical studies.

The hippocampus is a vital brain structure deep in the medial temporal lobe that mediates a range of functions encompassing emotional regulation, learning, memory, and cognition. Hippocampal development is exquisitely sensitive to perturbations and adverse conditions during pregnancy and at birth, including preterm birth, fetal growth restriction (FGR), acute hypoxic-ischaemic encephalopathy (HIE), and intrauterine inflammation. Disruptions to hippocampal development due to these conditions can have long-lasting functional impacts. Here, we discuss a range of preclinical models of prematurity and FGR and conditions that induce hypoxia and inflammation, which have been critical in elucidating the underlying mechanisms and cellular and subcellular structures implicated in hippocampal dysfunction. Finally, we discuss potential therapeutic targets to reduce the burden of these perinatal insults on the developing hippocampus. IMPACT: The review explores the preclinical literature examining the association between pregnancy and birth complications, and hippocampal form and function. The developmental processes and cellular mechanisms that are disrupted within the hippocampus following perinatal compromise are described, and potential therapeutic targets are discussed.

Perinatal compromise affects development, form, and function of the hippocampus part one; clinical studies.

The hippocampus is a neuron-rich specialised brain structure that plays a central role in the regulation of emotions, learning and memory, cognition, spatial navigation, and motivational processes. In human fetal development, hippocampal neurogenesis is principally complete by mid-gestation, with subsequent maturation comprising dendritogenesis and synaptogenesis in the third trimester of pregnancy and infancy. Dendritogenesis and synaptogenesis underpin connectivity. Hippocampal development is exquisitely sensitive to perturbations during pregnancy and at birth. Clinical investigations demonstrate that preterm birth, fetal growth restriction (FGR), and acute hypoxic-ischaemic encephalopathy (HIE) are common perinatal complications that alter hippocampal development. In turn, deficits in hippocampal development and structure mediate a range of neurodevelopmental disorders, including cognitive and learning problems, autism, and Attention-Deficit/Hyperactivity Disorder (ADHD). In this review, we summarise the developmental profile of the hippocampus during fetal and neonatal life and examine the hippocampal deficits observed following common human pregnancy complications. IMPACT: The review provides a comprehensive summary of the developmental profile of the hippocampus in normal fetal and neonatal life. We address a significant knowledge gap in paediatric research by providing a comprehensive summary of the relationship between pregnancy complications and subsequent hippocampal damage, shedding new light on this critical aspect of early neurodevelopment.

Dysmaturation of sleep state and electroencephalographic activity after hypoxia-ischaemia in preterm fetal sheep.

Antenatal hypoxia-ischaemia (HI) in preterm fetal sheep can trigger delayed evolution of severe, cystic white matter injury (WMI), in a similar timecourse to WMI in preterm infants. We therefore examined how severe hypoxia-ischaemia affects recovery of electroencephalographic (EEG) activity. Chronically instrumented preterm fetal sheep (0.7 gestation) received 25 min of complete umbilical cord occlusion (UCO, n = 9) or sham occlusion (controls, n = 9), and recovered for 21 days. HI was associated with a shift to lower frequency EEG activity for the first 5 days with persisting loss of EEG power in the delta and theta bands, and initial loss of power in the alpha and beta bands in the first 14 days of recovery. In the final 3 days of recovery, there was a marked rhythmic shift towards higher frequency EEG activity after UCO. The UCO group spent less time in high-voltage sleep, and in the early evening (7:02 pm ± 47 min) abruptly stopped cycling between sleep states, with a shift to a high frequency state for 2 h 48 min ± 40 min, with tonic electromyographic activity. These findings demonstrate persisting EEG and sleep state dysmaturation after severe hypoxia-ischaemia. Loss of fetal or neonatal sleep state cycling in the early evening may be a useful biomarker for evolving cystic WMI.

Blood-brain barrier permeability for the first 24 hours in hypoxic-ischemic brain injury following cardiac arrest.

BACKGROUND: This study aimed to explore the changes in blood-brain barrier (BBB) permeability and intracranial pressure (ICP) for the first 24 h after the return of spontaneous circulation (ROSC) and their association with injury severity of cardiac arrest. METHODS: This prospective study analysed the BBB permeability assessed using the albumin quotient (Qa) and ICP every 2 h for the first 24 h after ROSC. The injury severity of cardiac arrest was assessed using Pittsburgh Cardiac Arrest Category (PCAC) scores. The primary outcome was the time course of changes in the BBB permeability and ICP for the first 24 h after ROSC and their association with injury severity (PCAC scores of 1-4). RESULTS: Qa and ICP were measured 274 and 197 times, respectively, in 32 enrolled patients. Overall, the BBB permeability increased progressively over time after ROSC, and then it increased significantly at 18 h after ROSC compared with the baseline. In contrast, the ICP revealed non-significant changes for the first 24 h after ROSC. The Qa in the PCAC 2 group was < 0.01, indicating normal or mild BBB disruption at all time points, whereas the PCAC 3 and 4 groups showed a significant increase in BBB permeability at 14 and 22 h, and 12 and 14 h after ROSC, respectively. CONCLUSION: BBB permeability increased progressively over time for the first 24 h after ROSC despite post-resuscitation care, whereas ICP did not change over time. BBB permeability has an individual pattern when stratified by injury severity.

Hydrogen gas can ameliorate seizure burden during therapeutic hypothermia in asphyxiated newborn piglets.

BACKGROUND: We previously reported that hydrogen (H2) gas combined with therapeutic hypothermia (TH) improved short-term neurological outcomes in asphyxiated piglets. However, the effect on seizure burden was unclear. Using amplitude-integrated electroencephalography (aEEG), we compared TH + H2 with TH alone in piglets 24 h after hypoxic-ischemic (HI) insult. METHODS: After a 40-min insult and resuscitation, 36 piglets ≤24 h old were divided into three groups: normothermia (NT, n = 14), TH alone (33.5 ± 0.5 °C, 24 h, n = 13), and TH + H2 (2.1-2.7% H2 gas, 24 h, n = 9). aEEG was recorded for 24 h post-insult and its background pattern, status epilepticus (SE; recurrent seizures lasting >5 min), and seizure occurrence (Sz; occurring at least once but not fitting the definition of SE) were evaluated. Background findings with a continuous low voltage and burst suppression were considered abnormal. RESULTS: The percentage of piglets with an abnormal aEEG background (aEEG-BG), abnormal aEEG-BG+Sz and SE was lower with TH + H2 than with TH at 24 h after HI insult. The duration of SE was shorter with TH + H2 and significantly shorter than with NT. CONCLUSIONS: H2 gas combined with TH ameliorated seizure burden 24 h after HI insult. IMPACT: In this asphyxiated piglet model, there was a high percentage of animals with an abnormal amplitude-integrated electroencephalography background (aEEG-BG) after hypoxic-ischemic (HI) insult, which may correspond to moderate and severe hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) was associated with a low percentage of piglets with EEG abnormalities up to 6 h after HI insult but this percentage increased greatly after 12 h, and TH was not effective in attenuating seizure development. H2 gas combined with TH was associated with a low percentage of piglets with an abnormal aEEG-BG and with a shorter duration of status epilepticus at 24 h after HI insult.