Therapeutic hypothermia for hypoxic-ischemic encephalopathy after perinatal sentinel events: less brain injury on MRI and improved neurodevelopmental outcome at 18–36 months

AbstractHypoxic-ischemic encephalopathy (HIE) is a manifestation of perinatal asphyxial insult that continues to evolve over days to weeks following the initial injury. Therapeutic hypothermia has demonstrated that a proportion of this secondary brain injury may indeed be preventable. However, therapeutic hypothermia has also altered the prognostic utility of many bedside tools that are commonly used as predictors of long-term neurodevelopmental outcome in HIE. Clinicians are often confronted with uncertainty when assessing the prognosis of infants with HIE. Improved understanding of the implications and limitations of individual investigations may inform clinical decisions and allow for timely intervention. This review summarizes the predictive value of currently available prognostic markers in HIE infants in the therapeutic hypothermia era, including clinical, biochemical, neurophysiological, physiological, and neuroimaging predictors.

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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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Acute Perinatal Sentinel Events, Neonatal Brain Injury Pattern, and Outcome of Infants Undergoing a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy

The Journal of Pediatrics ◽

10.1016/j.jpeds.2016.09.026 ◽

2017 ◽

Vol 180 ◽

pp. 275-278.e2 ◽

Cited By ~ 14

Author(s):

Seetha Shankaran ◽

Abbot R. Laptook ◽

Scott A. McDonald ◽

Susan R. Hintz ◽

Patrick D. Barnes ◽

...

Keyword(s):

Brain Injury ◽

Injury Pattern ◽

Hypoxic Ischemic Encephalopathy ◽

Neonatal Brain ◽

Neonatal Brain Injury ◽

Sentinel Events ◽

Ischemic Encephalopathy

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Wavelet Autoregulation Monitoring Identifies Blood Pressures Associated With Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy

Frontiers in Neurology ◽

10.3389/fneur.2021.662839 ◽

2021 ◽

Vol 12 ◽

Author(s):

Xiuyun Liu ◽

Aylin Tekes ◽

Jamie Perin ◽

May W. Chen ◽

Bruno P. Soares ◽

...

Keyword(s):

Blood Pressure ◽

Brain Injury ◽

Therapeutic Hypothermia ◽

Near Infrared ◽

Brain Regions ◽

Hypoxic Ischemic Encephalopathy ◽

Volume Index ◽

Arterial Blood ◽

Blood Pressures ◽

Ischemic Encephalopathy

Dysfunctional cerebrovascular autoregulation may contribute to neurologic injury in neonatal hypoxic-ischemic encephalopathy (HIE). Identifying the optimal mean arterial blood pressure (MAPopt) that best supports autoregulation could help identify hemodynamic goals that support neurologic recovery. In neonates who received therapeutic hypothermia for HIE, we hypothesized that the wavelet hemoglobin volume index (wHVx) would identify MAPopt and that blood pressures closer to MAPopt would be associated with less brain injury on MRI. We also tested a correlation-derived hemoglobin volume index (HVx) and single- and multi-window data processing methodology. Autoregulation was monitored in consecutive 3-h periods using near infrared spectroscopy in an observational study. The neonates had a mean MAP of 54 mmHg (standard deviation: 9) during hypothermia. Greater blood pressure above the MAPopt from single-window wHVx was associated with less injury in the paracentral gyri (p = 0.044; n = 63), basal ganglia (p = 0.015), thalamus (p = 0.013), and brainstem (p = 0.041) after adjustments for sex, vasopressor use, seizures, arterial carbon dioxide level, and a perinatal insult score. Blood pressure exceeding MAPopt from the multi-window, correlation HVx was associated with less injury in the brainstem (p = 0.021) but not in other brain regions. We conclude that applying wavelet methodology to short autoregulation monitoring periods may improve the identification of MAPopt values that are associated with brain injury. Having blood pressure above MAPopt with an upper MAP of ~50–60 mmHg may reduce the risk of brain injury during therapeutic hypothermia. Though a cause-and-effect relationship cannot be inferred, the data support the need for randomized studies of autoregulation and brain injury in neonates with HIE.

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Is Erythropoietin Combining with Therapeutic Hypothermia an Efficient and Safe Therapy in Neonatal Hypoxic Ischemic Encephalopathy: A Prospective and Randomized Clinical Trial

10.21203/rs.3.rs-26962/v1 ◽

2020 ◽

Author(s):

Liang-yan Zou ◽

Bing-xue Huang ◽

Peng Zhang ◽

Guo-qiang Cheng ◽

Chun-mei Lu ◽

...

Keyword(s):

Brain Injury ◽

Adverse Events ◽

Therapeutic Hypothermia ◽

Brain Mri ◽

Adverse Outcomes ◽

Hypoxic Ischemic Encephalopathy ◽

Control Group ◽

Term Infants ◽

Basal Nuclei ◽

Ischemic Encephalopathy

Abstract BackgroundTo evaluate the efficacy and safety of erythropoietin (Epo) combined with therapeutic hypothermia (TH) in neonatal hypoxic-ischemic encephalopathy (HIE).MethodsA total of 78 term infants with HIE were assigned randomly to receive Epo (n = 40) or placebo (n = 38). All infants received TH. Blood samples before TH, after TH and after Epo/placebo were collected for measuring TH associated adverse events, Epo associated factors and potential neural biomarkers. Basal ganglia/ watershed (BG/W) scoring system was used to assess brain injury in MRI. Neurodevelopmental evaluations were performed at 18 months by using BayleyScales of Infant Development II (Bayley II).ResultsEpo-treated group tend to have lower serum creatine kinase (CK) concentration (114 vs 202, P = .04) and higher serum K+, Mg2+ concentration (5.0 vs 4.5, P = .03; 1.0 vs 0.9, P = .02) than control group after intervention. Brain MRI was performed in 65 (83%) neonatal. Totally brain injury score was in even distribution between two groups (median, 0 vs 0, P = .61), but injury region in cortex plus basal nuclei comparing with in basal nuclei solely was less common in the Epo than in the control group (21% vs 31%, P = .046). Only forty patients (40/78, 51%) succeeded in achieving 18-month follow up data. The totally adverse outcomes were trend to decline in the Epo group (35% vs 60%, P = .21). No adverse events were ascribed to Epo treatment.ConclusionsThe combination of Epo and TH is proved to be feasible, safe and potential effective.Trial registration: ChiCTR-TRC-14004532, date of registration: April 18th, 2014.

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