Mild Hypoxic-ischemic Encephalopathy Research Articles

Therapeutic hypothermia for encephalopathic newborns with congenital heart defect: A cross-sectional survey on current practices and opinions in Germany.

BackgroundTherapeutic hypothermia (TH) reduces neonatal mortality and long-term neurodevelopmental impairment in infants with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) caused by perinatal asphyxia. There is an increasing trend to apply TH in other indications and populations, such as infants with mild HIE or neonates with congenital heart defects (CHD), even though there is little evidence to support or refute this.ObjectiveThe aim of this survey was to analyze practice variations with respect to TH use in neonates with CHD and to assess expert opinions on this topic across tertiary neonatal departments in Germany.Methods/DesignA web-based survey was sent to all tertiary neonatal departments in Germany. The questionnaire contained 32 multiple-choice questions. The survey inquired current practices on TH in newborns with CHD and expert opinions on various clinical scenarios.Main resultsA total 80 (51.3%) neonatal departments partially completed the survey, and 69 (44.2%) respondents filled out the whole questionnaire. All 80 (100.0%) departments perform TH. TH is offered by 76 (95.0%) respondents to encephalopathic newborns with simple CHD. In infants with critical/complex CHD, TH is offered after perinatal asphyxial HIE and in newborns with encephalopathy after severe acidosis associated with cardiac complications by 25 (31.3%), or 17 (22.1%) respondents, respectively, whereas a clear majority of centers reject TH in these infants. Unclear effects of TH on any ongoing prostaglandin therapy (57.6 and 52.3%, respectively), an increased risk for adverse reactions during TH (51.6 and 52.3%, respectively) and lack of evidence (33.3 and 53.8%, respectively) are the most frequently cited reasons for not performing TH in these infants. The majority of experts from neonatal departments providing comprehensive care for neonates with severe CHD support the initiation of TH in encephalopathic neonates.DiscussionThe considerable heterogeneity in the use of TH in neonates with CHD emphasizes the need for further research to optimize treatment strategies for these patients.

Brain injury patterns in hypoxic ischemic encephalopathy of term neonates.

Topographic patterns of brain injury in neonates can help with differentiation and prognostic categorization of hypoxic ischemic encephalopathy (HIE). In this study, we quantitatively and objectively characterized the location of hypoxic ischemic lesions in term neonates with varying severity of HIE. We analyzed term neonates (born ≥37 postmenstrual gestational weeks) with MRI diffusion-weighted imaging (DWI) and diagnoses of HIE. Neonates' HIE was categorized into mild, moderate, and severe. The hypoxic ischemic lesions were segmented on DWI series with attention to T1- and T2-weighted images and then co-registered onto standard brain space to generate summation maps for each severity category. Applying voxel-wise general linear models, we also identified cerebral regions more likely to infarct with increasing severity of HIE, after correction for lesion volume and time-to-scan as covariates. We included 33 neonates: 20 with mild, eight with moderate, and five with severe HIE. Infarct volumes (p=.00052) and Appearance, Pulse, Grimace, Activity, and Respiration scores at 1minute (p=.032) differed between HIE severity categories. Hypoxic ischemic lesions in neonates with mild and moderate HIE were predominant in subcortical and deep white matter along the border zones of arterial supply territories, while severe HIE also involved basal ganglia, hippocampus, and thalamus. In voxel-wise analysis, higher severity of HIE was associated with the presence of lesions in hippocampus, thalamus, and lentiform nucleus. In term neonates, mild/moderate HIE is associated with infarctions of arterial territory watershed zones, whereas severe HIE distinctively involves basal ganglia, thalami, and hippocampi.

ROLE OF SERUM S-100B PROTEIN AND MRI IN PREDICTING THE NEUROLOGICAL OUTCOME AND SEQUELAE IN NEONATES ≥ 36 WEEKS WITH BIRTH ASPHYXIA.

A prompt diagnosis of neonatal hypoxic-ischemic encephalopathy (HIE) remains a clinical challenge. This study aimed at exploring the potential of Serum protein S100B as a biomarker for evaluating neonatal HIE in newborns with moderateto-severe hypoxic-ischemic encephalopathy. Blood samples were collected from neonates with mild, moderate, or severe HIE who were admitted to the Department of Neonatology, Madras Medical College (MMC), Chennai between September 2016 to March 2017. The plasma levels of S100 B protein were measured at different time points. Additionally, Neurodevelopmental outcomes were also studied using MRI in surviving infants (> 2 weeks). Eighty-four neonates enrolled in the study had moderate (n = 37), severe (n = 13) and mild HIE (n= 36). At birth, serum protein S100 B increased with the severity of HIE (P < .001), and remained elevated in neonates with moderate to severe HIE. Serum protein S100 B was greater up to 72 hours in moderate to severe vs mild HIE. The Elevated levels of S100B were associated with increased brain injury as studied by MRI. The study suggests S S100 B may serve as a potential biomarker for neonatal mild HIE (n=36), moderate (n=37) and severe (n=13) could be used for stratication at birth as elevated levels are correlated with the severity of HIE.

Semi-mechanistic Modeling of Hypoxanthine, Xanthine, and Uric Acid Metabolism in Asphyxiated Neonates.

Previously, we developed a pharmacokinetic-pharmacodynamic model of allopurinol, oxypurinol, and biomarkers, hypoxanthine, xanthine, and uric acid, in neonates with hypoxic-ischemic encephalopathy, in which high initial biomarker levels were observed suggesting an impact of hypoxia. However, the full pharmacodynamics could not be elucidated in our previous study. The current study included additional data from the ALBINO study (NCT03162653) placebo group, aiming to characterize the dynamics of hypoxanthine, xanthine, and uric acid in neonates with hypoxic-ischemic encephalopathy. Neonates from the ALBINO study who received allopurinol or placebo mannitol were included. An extended population pharmacokinetic-pharmacodynamic model was developed based on the mechanism of purine metabolism, where synthesis, salvage, and degradation via xanthine oxidoreductase pathways were described. The initial level of the biomarkers was a combination of endogenous turnover and high disease-related amounts. Model development was accomplished by nonlinear mixed-effects modeling (NONMEM®, version 7.5). In total, 20 neonates treated with allopurinol and 17 neonates treated with mannitol were included in this analysis. Endogenous synthesis of the biomarkers reduced with 0.43% per hour because of precursor exhaustion. Hypoxanthine was readily salvaged or degraded to xanthine with rate constants of 0.5 1/h (95% confidence interval 0.33-0.77) and 0.2 1/h (95% confidence interval 0.09-0.31), respectively. A greater salvage was found in the allopurinol treatment group consistent with its mechanism of action. High hypoxia-induced initial levels of biomarkers were quantified, and were 1.2-fold to 2.9-fold higher in neonates with moderate-to-severe hypoxic-ischemic encephalopathy compared with those with mild hypoxic-ischemic encephalopathy. Half-maximal xanthine oxidoreductase inhibition was achieved with a combined allopurinol and oxypurinol concentration of 0.68 mg/L (95% confidence interval 0.48-0.92), suggesting full xanthine oxidoreductase inhibition during the period studied. This extended pharmacokinetic-pharmacodynamic model provided an adequate description of the complex hypoxanthine, xanthine, and uric acid metabolism in neonates with hypoxic-ischemic encephalopathy, suggesting a positive allopurinol effect on these biomarkers. The impact of hypoxia on their dynamics was characterized, underlining higher hypoxia-related initial exposure with a more severe hypoxic-ischemic encephalopathy status.

Brain injury following mild hypoxic-ischemic encephalopathy in neonates-Ten-year experience in a tertiary perinatal center.

We aimed to evaluate abnormal magnetic resonance imaging (MRI) findings in neonates with mild hypoxic-ischemic encephalopathy (HIE). This was a single-center, retrospective study of mild HIE conducted from 2011 to 2020. Almost all neonates with mild HIE received management targeted to a temperature of 36 ± 0.5°C for 72 h and underwent MRI (135 of 145). We evaluated medical records and assessed amplitude-integrated electroencephalography (aEEG). All participants survived until discharge. Abnormal MRI findings were present in 23/135 (17%) neonates. The normal versus abnormal MRI-finding groups had similar characteristics, except discontinuous aEEG patterns (p = 0.002) and inotropic drugs (p = 0.035). Regression analyses showed discontinuous aEEG patterns (odds ratio = 19.3, 95% confidence interval=1.88-197, p = 0.013) being associated with higher odds of abnormal MRI findings. Our study suggests that a discontinuous aEEG pattern is associated with abnormal MRI findings and can be used to discuss the definition of mild HIE.

Evolution of early cerebral NIRS in hypoxic ischaemic encephalopathy.

AimTo describe early cerebral oxygenation (cSO2) and fractional tissue oxygen extraction (FTOE) values and their evolution over the first days of life in infants with all grades of hypoxic‐ischaemic encephalopathy (HIE) and to determine whether cSO2 and FTOE measured early (6 and 12 h) can predict short‐term outcome.MethodsProspective, observational study of cerebral near‐infrared spectroscopy (NIRS) in infants >36 weeks' gestation with HIE. Ten one‐hour epochs of cSO2 and FTOE were extracted for each infant over the first 84 h. Infants with moderate and severe HIE received therapeutic hypothermia (TH). Abnormal outcome was defined as abnormal magnetic resonance imaging (MRI) and/or death.ResultsFifty‐eight infants were included (28 mild, 24 moderate, 6 severe). Median gestational age was 39.9 weeks (IQR 38.1–40.7) and birthweight was 3.35 kgs (IQR 2.97–3.71). cSO2 increased and FTOE decreased over the first 24 h in all grades of HIE. Compared to the moderate group, infants with mild HIE had significantly higher cSO2 at 6 h (p = 0.003), 9 h (p = 0.009) and 12 h (p = 0.032) and lower FTOE at 6 h (p = 0.016) and 9 h (0.029). cSO2 and FTOE at 6 and 12 h did not predict abnormal outcome.ConclusionInfants with mild HIE have higher cSO2 and lower FTOE than those with moderate or severe HIE in the first 12 h of life. cSO2 increased in all grades of HIE over the first 24 h regardless of TH status.

Impact of Hypoxia-Ischemia on Neurogenesis and Structural and Functional Outcomes in a Mild-Moderate Neonatal Hypoxia-Ischemia Brain Injury Model.

Hypoxic-ischemic encephalopathy (HIE) is a common type of brain injury caused by a lack of oxygen and blood flow to the brain during the perinatal period. The incidence of HIE is approximately 2–3 cases per 1000 live births in high-income settings; while in low- and middle-income countries, the incidence is 3–10-fold higher. Therapeutic hypothermia (TH) is the current standard treatment for neonates affected by moderate–severe HIE. However, more than 50% of all infants with suspected HIE have mild encephalopathy, and these infants are not treated with TH because of their lower risk of adverse outcomes. Despite this, several analyses of pooled data provide increasing evidence that infants who initially have mild encephalopathy may present signs of more significant brain injury later in life. The purpose of this study was to expand our knowledge about the effect of mild–moderate hypoxia-ischemia (HI) at the cellular, structural, and functional levels. An established rat model of mild–moderate HI was used, where postnatal day (P) 7 rats were exposed to unilateral permanent occlusion of the left carotid artery and 90 min of 8% hypoxia, followed by TH or normothermia (NT) treatment. The extent of injury was assessed using histology (P14 and P42) and MRI (P11 and P32), as well as with short-term and long-term behavioral tests. Neurogenesis was assessed by BrdU staining. We showed that mild–moderate HI leads to a progressive loss of brain tissue, pathological changes in MRI scans, as well as an impairment of long-term motor function. At P14, the median area loss assessed by histology for HI animals was 20% (p < 0.05), corresponding to mild–moderate brain injury, increasing to 55% (p < 0.05) at P42. The data assessed by MRI corroborated our results. HI led to a decrease in neurogenesis, especially in the hippocampus and the lateral ventricle at early time points, with a delayed partial recovery. TH was not neuroprotective at early time points following mild–moderate HI, but prevented the increase in brain damage over time. Additionally, rats treated with TH showed better long-term motor function. Altogether, our results bring more light to the understanding of pathophysiology following mild-moderate HI. We showed that, in the context of mild-moderate HI, TH failed to be significantly neuroprotective. However, animals treated with TH showed a significant improvement in motor, but not cognitive long-term function. These results are in line with what is observed in some cases where neonates with mild HIE are at risk of neurodevelopmental deficits in infancy or childhood. Whether TH should be used as a preventive treatment to reduce adverse outcomes in mild-HIE remains of active interest, and more research has to be carried out in order to address this question.

Microstructural Alterations in Projection and Association Fibers in Neonatal Hypoxia-Ischemia.

Diffusion MRI (dMRI) is known to be sensitive to hypoxic-ischemic encephalopathy (HIE). However, existing dMRI studies used simple diffusion tensor metrics and focused only on a few selected cerebral regions, which cannot provide a comprehensive picture of microstructural injury. To systematically characterize the microstructural alterations in mild, moderate, and severe HIE neonates compared to healthy neonates with advanced dMRI using region of interest (ROI), tract, and fixel-based analyses. Prospective. A total of 42 neonates (24 males and 18 females). 3-T, diffusion-weighted echo-planar imaging. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD), axial diffusivity (AD), fiber density (FD), fiber cross-section (FC), and fiber density and cross-section (FDC) were calculated in 40 ROIs and 6 tracts. Fixel-based analysis was performed to assess group differences in individual fiber components within a voxel (fixel). One-way analysis of covariance (ANCOVA) to compare dMRI metrics among severe/moderate/mild HIE and control groups and general linear model for fixel-wise group differences (age, sex, and body weight as covariates). Adjusted P value < 0.05 was considered statistically significant. For severe HIE, ROI-based analysis revealed widespread regions, including the deep nuclei and white matter with reduced FA, while in moderate injury, only FC was decreased around the posterior watershed zones. Tract-based analysis demonstrated significantly reduced FA, FD, and FC in the right inferior fronto-occipital fasciculus (IFOF), right inferior longitudinal fasciculus (ILF), and splenium of corpus callosum (SCC) in moderate HIE, and in right IFOF and left anterior thalamic radiation (ATR) in mild HIE. Correspondingly, we found altered fixels in the right middle-posterior IFOF and ILF, and in the central-to-right part of SCC in moderate HIE. For severe HIE, extensive microstructural injury was identified. For moderate-mild HIE, association fiber injury in posterior watershed area with a rightward lateralization was found. 1 TECHNICAL EFFICACY: Stage 3.

Concentration of Serum Biomarkers of Brain Injury in Neonates With a Low Cord pH With or Without Mild Hypoxic-Ischemic Encephalopathy.

ObjectiveTo determine the concentrations of four neuroprotein biomarkers and 68 miRNAs in neonates with low cord pH and/or mild hypoxic-ischemic encephalopathy (HIE).Study DesignA prospective cohort study enrolled neonates with low cord pH (n = 18), moderate-severe HIE (n = 40), and healthy controls (n = 38). Groups provided serum samples at 0–6 h of life. The concentrations of biomarkers and miRNAs were compared between cohorts.ResultThe low cord pH and moderate-severe HIE groups had increased concentrations of GFAP, NFL and Tau compared to controls (P < 0.05, P < 0.001, respectively). NFL concentrations in mild HIE was higher than controls (P < 0.05) but less than moderate-severe HIE (P < 0.001). Of 68 miRNAs, 36 in low cord pH group and 40 in moderate-severe HIE were upregulated compared to controls (P < 0.05). Five miRNAs in low cord pH group (P < 0.05) and 3 in moderate-severe HIE were downregulated compared to controls (P < 0.05).ConclusionA biomarker panel in neonates with low cord pH may help clinicians make real-time decisions.

Prognostic value of colour Doppler brain sonography for the neurodevelopmental outcome in term neonates with hypoxic ischaemic encephalopathy.

Aim To determine a prognostic value of cerebral blood flow parameters for the development of neurological sequelae in term neonates with hypoxic ischaemic encephalopathy (HIE). Methods We reviewed medical records of 47 term neonates with HIE who survived until the age of 12 months of life. According to the Sarnat and Sarnat clinical score, neonates were divided into 3 groups: mild HIE, moderate HIE and severe HIE. All included neonates had the colour Doppler brain sonography performed in the first 24 hours of life. The neurological assessment was done at the age of 12 months of life by using the Denver Developmental Screening Test (DDST). Logic regression analysis was performed using the colour doppler brain sonography parameters with the development of neurological impairment as the primary outcome. Results Out of 47 neonates, 19 (40.4%) were with mild, 17 (36.2%) with moderate and 11 (23.4%) with severe HIE. The values of cerebral blood flow parameters and resistance index (RI) significantly correlated with the neurological impairment at the age of 12 months of life (p<0.001). The limit value of RI indicating the poor neurodevelopmental outcome was 0.81, sensitivity 80%, specificity 85.3%, positive predictive value 52.2% and negative predictive value 95.2%. Conclusion The cerebral blood flow parameters measured with colour doppler brain sonography are good indicators of the severity of HIE and later neurodevelopmetal outcome.

EE245 Cost-Effectiveness of Therapeutic Hypothermia for Neonates with Mild Hypoxic-Ischemic Encephalopathy

Infants with mild hypoxic-ischemic encephalopathy (HIE) are at risk for neurodevelopmental impairment. Despite insufficient evidence, therapeutic hypothermia (TH) has become more prevalent over time in the management of infants with mild HIE, but treatment remains controversial and inconsistent. This research aims to determine the cost-effectiveness of TH for neonates with mild HIE compared to standard care (normothermia).

An Observational Study of Therapeutic Hypothermia and Factors Associated With Mortality in Late-Preterm and Term Neonates With Hypoxic-Ischemic Encephalopathy in a Middle-Income Country.

ObjectivesTo investigate the types of therapeutic hypothermia (TH) used and risk factors associated with mortality in late-preterm and term neonates (LPTN, gestation of ≥35 weeks) with hypoxic-ischemic encephalopathy (HIE) in a middle-income country.DesignThis was an observational retrospective cohort study.SettingA total of 44 neonatal intensive care units (NICUs) in the Malaysian National Neonatal Registry participated in the study.PatientsAll LPTN without major malformations and diagnosed to have HIE were included.Main Outcome MeasuresNumber of in-hospital mortality, and types of TH used [no TH, TH using commercially available servo-controlled devices (SCDs), passive TH by exposing neonates to NICU’s air-conditioned ambient temperature with/without the use of cooled gel packs (P±CGPs)].ResultsOf a total of 2,761 HIE neonates, 66.3% received TH. All NICUs provided TH; 55.4% NICUs had SCDs, which was administered to 43.6% (248/569) of severe, 51.6% (636/1,232) of moderate, and 18.6% (179/960) of mild HIE neonates. P±CGPs was used on 26.9% of severe, 33.4% of moderate, and 21.1% of mild HIE neonates. There were 338 deaths. Multiple logistic regression analysis showed that 5-min Apgar scores <5 (aOR: 1.436; 95% CI: 1.019, 2.023), Cesarean section (aOR: 2.335; 95% CI: 1.700, 3.207), receiving no TH (aOR: 4.749; 95% CI: 3.201, 7.045), TH using P±CGPs (aOR: 1.553; 95% CI: 1.031, 2.338), NICUs admitted <50 HIE cases (aOR: 1.898; 95% CI: 1.225, 2.940), NICUs admitted 50-<100 HIE cases (aOR: 1.552; 95% CI: 1.065, 2.260), moderate HIE (aOR: 2.823; 95% CI: 1.495, 5.333), severe HIE (aOR: 34.925, 95% CI: 18.478, 66.012), Thompson scores of 7–13 (aOR: 1.776; 95% CI: 1.023,3.082), Thompson scores of ≥14 (aOR: 3.641; 95% CI: 2.000, 6.629), pneumothorax (aOR: 3.435; 95% CI: 1.996, 5.914), and foreigners (aOR: 1.646; 95% CI: 1.006, 2.692) were significant risk factors associated with mortality.ConclusionBoth SCD and P±CGP were used for TH. Moderate/severe HIE and receiving passive/no TH were among the risk factors associated with mortality.

Defining Longer-Term Outcomes in an Ovine Model of Moderate Perinatal Hypoxia-Ischemia

Hypoxic-ischemic encephalopathy (HIE) is the leading cause of neonatal morbidity and mortality worldwide. Approximately 1 million infants born with HIE each year survive with cerebral palsy and/or serious cognitive disabilities. While infants born with mild and severe HIE frequently result in predictable outcomes, infants born with moderate HIE exhibit variable outcomes that are highly unpredictable. Here, we describe an umbilical cord occlusion (UCO) model of moderate HIE with a 6-day follow-up. Near-term lambs (n = 27) were resuscitated after the induction of 5 min of asystole. Following recovery, lambs were assessed to define neurodevelopmental outcomes. At the end of this period, lambs were euthanized, and brains were harvested for histological analysis. Compared with prior models that typically follow lambs for 3 days, the observation of neurobehavioral outcomes for 6 days enabled identification of animals that recover significant neurological function. Approximately 35% of lambs exhibited severe motor deficits throughout the entirety of the 6-day course and, in the most severely affected lambs, developed spastic diparesis similar to that observed in infants who survive severe neonatal HIE (severe, UCOs). Importantly, and similar to outcomes in human neonates, while initially developing significant acidosis and encephalopathy, the remainder of the lambs in this model recovered normal motor activity and exhibited normal neurodevelopmental outcomes by 6 days of life (improved, UCOi). The UCOs group exhibited gliosis and inflammation in both white and gray matters, oligodendrocyte loss, neuronal loss, and cellular death in the hippocampus and cingulate cortex. While the UCOi group exhibited more cellular death and gliosis in the parasagittal cortex, they demonstrated more preserved white matter markers, along with reduced markers of inflammation and lower cellular death and neuronal loss in Ca3 of the hippocampus compared with UCOs lambs. Our large animal model of moderate HIE with prolonged follow-up will help further define pathophysiologic drivers of brain injury while enabling identification of predictive biomarkers that correlate with disease outcomes and ultimately help support development of therapeutic approaches to this challenging clinical scenario.

Increase of Parkin and ATG5 plasmatic levels following perinatal hypoxic-ischemic encephalopathy

Brain injury at birth is an important cause of neurological and behavioral disorders. Hypoxic-ischemic encephalopathy (HIE) is a critical cerebral event occurring acutely or chronically at birth with high mortality and morbidity in newborns. Therapeutic strategies for the prevention of brain damage are still unknown, and the only medical intervention for newborns with moderate-to-severe HIE is therapeutic hypothermia (TH). Although the neurological outcome depends on the severity of the initial insult, emerging evidence suggests that infants with mild HIE who are not treated with TH have an increased risk for neurodevelopmental impairment; in the current clinical setting, there are no specific or validated biomarkers that can be used to both correlate the severity of the hypoxic insult at birth and monitor the trend in the insult over time. The aim of this work was to examine the presence of autophagic and mitophagic proteins in bodily fluids, to increase knowledge of what, early at birth, can inform therapeutic strategies in the first hours of life. This is a prospective multicentric study carried out from April 2019 to April 2020 in eight third-level neonatal intensive care units. All participants have been subjected to the plasma levels quantification of both Parkin (a protein involved in mitophagy) and ATG5 (involved in autophagy). These findings show that Parkin and ATG5 levels are related to hypoxic-ischemic insult and are reliable also at birth. These observations suggest a great potential diagnostic value for Parkin evaluation in the first 6 h of life.

Predictive Value of Heat-Shock Protein Gene Expression on Severe Neonatal Hypoxic-Ischemic Encephalopathy

This study aims to evaluate significant gene expression in severe hypoxic ischemic encephalopathy (HIE) in newborns, which can be used as a predictable measure for high-risk HIE infants. The study prospectively recruited 77 inborn near-term or term HIE newborns between January 2018 and December 2020. We measured six different genes within 6 h of life among the HIE infants and compared the gene levels between the mild- and severe-HIE groups. Among these, 64 HIE infants (83.1%) did not receive therapeutic hypothermia (TH) because they were categorized as mild HIE, and the 13 remaining (16.9%) infants were categorized as ≥ moderate-HIE group and received TH. More abnormal MRI findings, seizure, and use of anti-convulsant were more found in the ≥ moderate = HIE group along with longer mechanical ventilation days and hospitalization. Heat-shock protein 70 family 1 A (HSPA1A) and serpin family H member 1 (SERPINH1) genes, which encode heat-shock protein (HSP) 70 and 47, respectively, were significantly elevated in the ≥ moderate-HIE, seizure, and abnormal MRI groups. HSP 70 and 47 were significantly elevated in the severe-HIE group, possibly playing protective roles in inhibiting exacerbated neuroinflammation and maintaining a cellular homeostasis. At 18–24 months, ≥ moderate-HIE group manifested a significant language delay.

Mild hypoxic-ischemic encephalopathy (HIE): timing and pattern of MRI brain injury

BackgroundMild hypoxic-ischemic encephalopathy (HIE) is increasingly recognized as a risk factor for neonatal brain injury. We examined the timing and pattern of brain injury in mild HIE.MethodsThis retrospective cohort study includes infants with mild HIE treated at 9 hospitals. Neonatal brain MRIs were scored by 2 reviewers using a validated classification system, with discrepancies resolved by consensus. Severity and timing of MRI brain injury (i.e., acute, subacute, chronic) was scored on the subset of MRIs that were performed at or before 8 days of age.ResultsOf 142 infants with mild HIE, 87 (61%) had injury on MRI at median age 5 (IQR 4–6) days. Watershed (23%), deep gray (20%) and punctate white matter (18%) injury were most common. Among the 125 (88%) infants who received a brain MRI at ≤8 days, mild (44%) injury was more common than moderate (11%) or severe (4%) injury. Subacute (37%) lesions were more commonly observed than acute (32%) or chronic lesions (1%).ConclusionSubacute brain injury is common in newborn infants with mild HIE. Novel neuroprotective treatments for mild HIE will ideally target both subacute and acute injury mechanisms.ImpactAlmost two-thirds of infants with mild HIE have evidence of brain injury on MRI obtained in the early neonatal period.Subacute brain injury was seen in 37% of infants with mild HIE.Neuroprotective treatments for mild HIE will ideally target both acute and subacute injury mechanisms.

Characteristics of Hypoxic Ischemic Encephalopathy among Neonates in Sanglah General Hospital

Hypoxic ischemic encephalopathy (HIE) is a worldwide problem. It is a type of brain injury that occurs when the brain doesn’t receive enough oxygen or blood flow occurring during pregnancy, labor and delivery or in the postnatal period. We aimed to investigate the characteristics of HIE among neonates admitted to Sanglah General Hospital. This observational retrospective study was conducted from January 2018 to December 2020 in Neonatology Ward of Sanglah General Hospital. This study was dominated by male subject, mild HIE (65.4%) with caesarian section (65.4%) and referred from other hospital (60.6%). Moreover the cases of seizure, neonatal sepsis and neonatal pneumonia accounted for 20.2%, 73.1%, and 34.6%, respectively. Mortality occurred in 28.8% neonates, but only 17.6% moderate HIE and 47.4% severe HIE got cooling therapy. Maternal characteristics were severe preeclampsia, placenta previa, previous abortion, hypertension, asthma and diabetes mellitus. This study demonstrated that HIE characteristics in neonates of Sanglah General Hospital mostly were mild stages, male gender, caesarean section as mode of delivery and majority was referred from other hospital.

The role of MRI-based texture analysis to predict the severity of brain injury in neonates with perinatal asphyxia.

To evaluate the efficacy of the MRI-based texture analysis (TA) of the basal ganglia and thalami to distinguish moderate-to-severe hypoxic-ischemic encephalopathy (HIE) from mild HIE in neonates. This study included 68 neonates (15 with mild, 20 with moderate-to-severe HIE, and 33 control) were born at 37 gestational weeks or later and underwent MRI in first 10 days after birth. The basal ganglia and thalami were delineated for TA on the apparent diffusion coefficient (ADC) maps, T1-, and T2 weighted images. The basal ganglia, thalami, and the posterior limb of the internal capsule (PLIC) were also evaluated visually on diffusion-weighted imaging and T1 weighted sequence. Receiver operating characteristic curve and logistic regression analyses were used. Totally, 56 texture features for the basal ganglia and 46 features for the thalami were significantly different between the HIE groups on the ADC maps, T2-, and T2 weighted sequences. Using a Histogram_entropy log-10 value as >1.8 from the basal ganglia on the ADC maps (p < 0.001; OR, 266) and the absence of hyperintensity of the PLIC on T1 weighted images (p = 0.012; OR, 17.11) were found as independent predictors for moderate-to-severe HIE. Using only a Histogram_entropy log-10 value had an equal diagnostic yield when compared to its combination with other texture features and imaging findings. The Histogram_entropy log-10 value can be used as an indicator to differentiate from moderate-to-severe to mild HIE. MRI-based TA may provide quantitative findings to indicate different stages in neonates with perinatal asphyxia.

Long-term neuropsychological and behavioral outcome of mild and moderate hypoxic ischemic encephalopathy

BackgroundOutcomes for infants who survive mild-moderate hypoxic ischemic encephalopathy (HIE) into adolescence is relatively uncharted. AimsWe examined neuropsychological and behavioral outcomes in adolescents with mild and moderate HIE, using both parent and self - informants, and including healthy peers and nearest age siblings as controls. Participants23 adolescents with a history of mild-moderate HIE (M age = 14.45 years, SD = 1.03; 14 boys and 9 girls) were recruited from an original cohort of 53. A group of their nearest – age siblings (n = 13), and healthy peers (n = 14) were recruited as controls. Outcome measuresA number of neuropsychological sub-tests, taken from the WISC-V.UK, Children's Memory Scale, NEPSY, WIAT-III.UK, Rey Complex Figure Copy Test and British Picture Vocabulary Scale were administered. Behavioral adjustment was assessed using the Strengths and Difficulties Questionnaire and the competence subscales of the Child Behavior Checklist. ResultsNo differences in neuropsychological and behavioral outcomes were observed between mild and moderate HIE cohorts. Together they had significantly lower scores on tests of attention/executive functioning, verbal reasoning and sensory-motor ability compared to healthy peers, with moderate to large effect sizes. Remedial provision at school was greater in the HIE group. Parents reported elevated levels of peer problems in the HIE group compared to both siblings and healthy peers. Reduced competencies were also observed. ConclusionsWe found evidence that both mild and moderate survivors of HIE experience neuropsychological, school and peer relationship problems in adolescence.

Magnetic Resonance Spectroscopy of Hypoxic-Ischemic Encephalopathy After Cardiac Arrest.

To correlate brain metabolites with clinical outcome using magnetic resonance spectroscopy (MRS) in patients undergoing targeted temperature management (TTM) after cardiac arrest and assess their relationships to MRI and EEG variables. A prospective cohort of 50 patients was studied. The primary outcome was coma recovery to follow commands. Comparison of MRS measures in the posterior cingulate gyrus, parietal white matter, basal ganglia, and brainstem were also made to 25 normative controls. Fourteen of 50 patients achieved coma recovery before hospital discharge. There was a significant decrease in total N-acetylaspartate (NAA/Cr) and an increase in lactate/creatine (Lac/Cr) in patients who did not recover, with changes most prominent in the posterior cingulate gyrus. Patients who recovered had decrease in NAA/Cr as compared to controls. NAA/Cr had a strong monotonic relationship with MRI cortical apparent diffusion coefficient (ADC); Lac level exponentially increased with decreasing ADC. EEG suppression/burst suppression was strongly associated with Lac elevation. NAA and Lac changes are associated with clinical/MRI/EEG changes consistent with hypoxic-ischemic encephalopathy (HIE) and are most prominent in the posterior cingulate gyrus. NAA/Cr decrease observed in patients with good outcomes suggests mild HIE in patients asymptomatic at hospital discharge. The appearance of cortical Lac represents a deterioration of aerobic energy metabolism and is associated with EEG background suppression, synaptic transmission failure, and severe, potentially irreversible HIE. This study provides Class IV evidence that in patients undergoing TTM after cardiac arrest, brain MRS-determined decrease in total NAA/Cr and an increase in Lac/Cr are associated with an increased risk of not recovering.