Predictive value of early EEG for seizures in neonates with hypoxic–ischemic encephalopathy undergoing therapeutic hypothermia

Objective Elevation of serum troponin I has been reported in newborns with hypoxic ischemic encephalopathy (HIE), but it is diagnostic and prognostic utility for newborn under 6 hours is not clear. Study the predictive value of early serum troponin I levels in newborns with HIE undergoing therapeutic hypothermia (TH) for persistent residual encephalopathy (RE) at discharge. Study Design Retrospective chart review of newborns admitted with diagnosis of HIE to neonatal intensive care unit (NICU) for TH over a period of 3 years. Troponin levels were drawn with the initial set of admission laboratories while initiating TH. Newborns were followed up during hospital course and stratified into three groups based on predischarge examination and their electrical encephalography and cranial MRI findings: Group 1: no RE, Group 2: mild-to-moderate RE, and Group 3: severe RE or needing assisted medical technology or death. Demographic and clinical characteristics including troponin I levels were compared in each group. Results Out of 104 newborns who underwent TH, 65 infants were in Group 1, 26 infants in Group 2, and 13 newborns in Group 3. All groups were comparable in demographic characteristics. There was a significant elevation of serum troponin in group 2 (mild-to-moderate RE) and group 3 (severe RE) as compared with group 1 (no RE). Receiver operator curve analysis for any RE (groups 2 and 3) compared with group 1 (no RE as control) had 0.88 (0.81–0.95) area under curve, p < 0.001. A cut-off level of troponin I ≥0.12 µg/L had a sensitivity of 77% and specificity of 78% for diagnosis of any RE, positive predictive value of 68%, and a negative predictive value of 84%. Conclusion In newborns undergoing TH for HIE, the elevation of troponin within 6 hours of age predicts high risk of having RE at discharge. Key Points

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Visual outcomes in children with neonatal hypoxic ischemic encephalopathy treated with therapeutic hypothermia

Journal of Perinatology ◽

10.1038/s41372-021-01101-x ◽

2021 ◽

Author(s):

Jerry Hsu ◽

Noreen Shaikh ◽

Hantamalala Ralay Ranaivo ◽

Andrea C. Pardo ◽

Rebecca B. Mets-Halgrimson

Keyword(s):

Therapeutic Hypothermia ◽

Hypoxic Ischemic Encephalopathy ◽

Visual Outcomes ◽

Ischemic Encephalopathy

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Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy

Scientific Reports ◽

10.1038/s41598-021-83982-8 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Kim V. Annink ◽

Linda S. de Vries ◽

Floris Groenendaal ◽

Rian M. J. C. Eijsermans ◽

Manouk Mocking ◽

...

Keyword(s):

Therapeutic Hypothermia ◽

Memory Function ◽

Neurodevelopmental Outcome ◽

Standard Of Care ◽

Hypoxic Ischemic Encephalopathy ◽

School Age ◽

Brain Volumes ◽

Mammillary Bodies ◽

Memory Problems ◽

Ischemic Encephalopathy

AbstractThe mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.

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Inhaled H2 or CO2 Do Not Augment the Neuroprotective Effect of Therapeutic Hypothermia in a Severe Neonatal Hypoxic-Ischemic Encephalopathy Piglet Model

International Journal of Molecular Sciences ◽

10.3390/ijms21186801 ◽

2020 ◽

Vol 21 (18) ◽

pp. 6801

Author(s):

Viktória Kovács ◽

Gábor Remzső ◽

Valéria Tóth-Szűki ◽

Viktória Varga ◽

János Németh ◽

...

Keyword(s):

Caudate Nucleus ◽

Therapeutic Hypothermia ◽

Neuroprotective Effect ◽

Fold Increase ◽

Hypoxic Ischemic Encephalopathy ◽

Mrna Levels ◽

Treatment Groups ◽

Apoptosis Inducing Factor ◽

Co2 Treatment ◽

Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy (HIE) is still a major cause of neonatal death and disability as therapeutic hypothermia (TH) alone cannot afford sufficient neuroprotection. The present study investigated whether ventilation with molecular hydrogen (2.1% H2) or graded restoration of normocapnia with CO2 for 4 h after asphyxia would augment the neuroprotective effect of TH in a subacute (48 h) HIE piglet model. Piglets were randomized to untreated naïve, control-normothermia, asphyxia-normothermia (20-min 4%O2–20%CO2 ventilation; Tcore = 38.5 °C), asphyxia-hypothermia (A-HT, Tcore = 33.5 °C, 2–36 h post-asphyxia), A-HT + H2, or A-HT + CO2 treatment groups. Asphyxia elicited severe hypoxia (pO2 = 19 ± 5 mmHg) and mixed acidosis (pH = 6.79 ± 0.10). HIE development was confirmed by altered cerebral electrical activity and neuropathology. TH was significantly neuroprotective in the caudate nucleus but demonstrated virtually no such effect in the hippocampus. The mRNA levels of apoptosis-inducing factor and caspase-3 showed a ~10-fold increase in the A-HT group compared to naïve animals in the hippocampus but not in the caudate nucleus coinciding with the region-specific neuroprotective effect of TH. H2 or CO2 did not augment TH-induced neuroprotection in any brain areas; rather, CO2 even abolished the neuroprotective effect of TH in the caudate nucleus. In conclusion, the present findings do not support the use of these medical gases to supplement TH in HIE management.

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Development and Evaluation of Computable Phenotypes in Pediatric Epilepsy:3 Cases

Journal of Child Neurology ◽

10.1177/08830738211019578 ◽

2021 ◽

pp. 088307382110195

Author(s):

Sabrina Pan ◽

Alan Wu ◽

Mark Weiner ◽

Zachary M Grinspan

Keyword(s):

Positive Predictive Value ◽

Predictive Value ◽

Juvenile Myoclonic Epilepsy ◽

Myoclonic Epilepsy ◽

Hypoxic Ischemic Encephalopathy ◽

Pediatric Epilepsy ◽

Health Record ◽

Treatment Resistant ◽

Ischemic Encephalopathy ◽

F Measure

Introduction: Computable phenotypes allow identification of well-defined patient cohorts from electronic health record data. Little is known about the accuracy of diagnostic codes for important clinical concepts in pediatric epilepsy, such as (1) risk factors like neonatal hypoxic-ischemic encephalopathy; (2) clinical concepts like treatment resistance; (3) and syndromes like juvenile myoclonic epilepsy. We developed and evaluated the performance of computable phenotypes for these examples using electronic health record data at one center. Methods: We identified gold standard cohorts for neonatal hypoxic-ischemic encephalopathy, pediatric treatment-resistant epilepsy, and juvenile myoclonic epilepsy via existing registries and review of clinical notes. From the electronic health record, we extracted diagnostic and procedure codes for all children with a diagnosis of epilepsy and seizures. We used these codes to develop computable phenotypes and evaluated by sensitivity, positive predictive value, and the F-measure. Results: For neonatal hypoxic-ischemic encephalopathy, the best-performing computable phenotype (HIE ICD-9 /10 and [brain magnetic resonance imaging (MRI) or electroencephalography (EEG) within 120 days of life] and absence of commonly miscoded conditions) had high sensitivity (95.7%, 95% confidence interval [CI] 85-99), positive predictive value (100%, 95% CI 95-100), and F measure (0.98). For treatment-resistant epilepsy, the best-performing computable phenotype (3 or more antiseizure medicines in the last 2 years or treatment-resistant ICD-10) had a sensitivity of 86.9% (95% CI 79-93), positive predictive value of 69.6% (95% CI 60-79), and F-measure of 0.77. For juvenile myoclonic epilepsy, the best performing computable phenotype (JME ICD-10) had poor sensitivity (52%, 95% CI 43-60) but high positive predictive value (90.4%, 95% CI 81-96); the F measure was 0.66. Conclusion: The variable accuracy of our computable phenotypes (hypoxic-ischemic encephalopathy high, treatment resistance medium, and juvenile myoclonic epilepsy low) demonstrates the heterogeneity of success using administrative data to identify cohorts important for pediatric epilepsy research.

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