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

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.

scholarly journals New possibilities for neuroprotection in neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Author(s):  
Suresh Victor ◽  
Eridan Rocha-Ferreira ◽  
Ahad Rahim ◽  
Henrik Hagberg ◽  
David Edwards
Keyword(s):  
Clinical Trials ◽  
Animal Models ◽  
Therapeutic Hypothermia ◽  
Treatment Options ◽  
Standard Of Care ◽  
High Income ◽  
Hypoxic Ischemic Encephalopathy ◽  
Pharmacodynamic Modelling ◽  
Dose Ranging ◽  
Ischemic Encephalopathy

AbstractAround 0.75 million babies worldwide suffer from moderate or severe hypoxic-ischemic encephalopathy (HIE) each year resulting in around 400,000 babies with neurodevelopmental impairment. In 2010, neonatal HIE was associated with 2.4% of the total Global Burden of Disease. Therapeutic hypothermia (TH), a treatment that is now standard of care in high-income countries, provides proof of concept that strategies that aim to improve neurodevelopment are not only possible but can also be implemented to clinical practice. While TH is beneficial, neonates with moderate or severe HIE treated with TH still experience devastating complications: 48% (range: 44–53) combined death or moderate/severe disability. There is a concern that TH may not be effective in low- and middle-income countries. Therapies that further improve outcomes are desperately needed, and in high-income countries, they must be tested in conjunction with TH. We have in this review focussed on pharmacological treatment options (e.g. erythropoietin, allopurinol, melatonin, cannabidiol, exendin-4/exenatide). Erythropoietin and allopurinol show promise and are progressing towards the clinic with ongoing definitive phase 3 randomised placebo-controlled trials. However, there remain global challenges for the next decade. Conclusion: There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials to avoid exposure to harmful medications or abandoning putative treatments. What is Known:• Therapeutic hypothermia is beneficial in neonatal hypoxic-ischemic encephalopathy.• Neonates with moderate or severe hypoxic-ischemic encephalopathy treated with therapeutic hypothermia still experience severe sequelae. What is New:• Erythropoietin, allopurinol, melatonin, cannabidiol, and exendin-4/exenatide show promise in conjunction with therapeutic hypothermia.• There is a need for more optimal animal models, greater industry support/sponsorship, increased use of juvenile toxicology, dose-ranging studies with pharmacokinetic-pharmacodynamic modelling, and well-designed clinical trials.

Predictors of Long-Term Neurodevelopmental Outcome of Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia

2020 ◽  
Vol 40 (03) ◽  
pp. 322-334
Author(s):  
Ipsita Goswami ◽  
Mireille Guillot ◽  
Emily W. Y. Tam
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Prognostic Markers ◽  
Neurodevelopmental Outcome ◽  
Hypoxic Ischemic Encephalopathy ◽  
Secondary Brain Injury ◽  
Prognostic Utility ◽  
Initial Injury ◽  
Ischemic Encephalopathy

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.

scholarly journals Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis

Neonatology ◽  
2020 ◽  
Vol 117 (4) ◽  
pp. 411-427 ◽  
Author(s):  
Sabine Ouwehand ◽  
Lisanne C.A. Smidt ◽  
Jeroen Dudink ◽  
Manon J.N.L. Benders ◽  
Linda S. de Vries ◽  
...  
Keyword(s):  
Magnetic Resonance ◽  
Therapeutic Hypothermia ◽  
Meta Analysis ◽  
Neurodevelopmental Outcome ◽  
Hypoxic Ischemic Encephalopathy ◽  
Resonance Spectroscopy ◽  
Test Accuracy ◽  
Neurodevelopmental Outcomes ◽  
Posterior Limb ◽  
Ischemic Encephalopathy

<b><i>Introduction:</i></b> Prediction of neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy remains an important challenge. Various studies have shown that the predictive ability of different modalities changed after the introduction of therapeutic hypothermia. This paper reviews the diagnostic test accuracy of the different modalities that are being used to predict neurodevelopmental outcomes following therapeutic hypothermia. <b><i>Methods:</i></b> A systematic literature search was performed using Embase and PubMed. Two reviewers independently included eligible studies and extracted data. The quality of the studies was assessed using the Quality in Prognosis Studies Tool. Meta-analyses were performed where possible. <b><i>Results:</i></b> Forty-seven articles and 3 conference abstracts were included, reporting on 3,072<i></i>infants of whom 39% died or had an adverse neurodevelopmental outcome. A meta-analysis could be performed using 37 articles on (amplitude-integrated) electroencephalography (EEG), conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS). Amplitude-integrated EEG (aEEG) at 24 and 72 h showed similar high diagnostic OR, while aEEG at 6 h and EEG performed less, both due to a low specificity. For MRI, most studies reported scoring systems in which early (&#x3c;8 days) MRI performed better than late (≥8 days) MRI. Injury to the posterior limb of the internal capsule on MRI or to the thalami on DWI were strong individual predictors, as was an increased lactate/N-acetylaspartate peak on <sup>1</sup>H-MRS. <b><i>Conclusions:</i></b> In the era of therapeutic hypothermia, the different modalities remain good predictors of neurodevelopmental outcome. However, timing should be taken into account. aEEG may initially be false positive and gets more reliable after 24 h. In contrast, MRI should be used during the first week, as its predictive value decreases afterwards.

Case series of therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy during extracorporeal life support

Perfusion ◽  
2020 ◽  
Vol 35 (7) ◽  
pp. 700-706
Author(s):  
Prasad Bhandary ◽  
John M Daniel ◽  
Sean C Skinner ◽  
Matthew K Bacon ◽  
Mina Hanna ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Life Support ◽  
Extracorporeal Life Support ◽  
Case Series ◽  
Standard Of Care ◽  
Hypoxic Ischemic Encephalopathy ◽  
Short Term ◽  
Ischemic Encephalopathy

Therapeutic hypothermia initiated within 6 hours of birth is currently the standard of care for the management of neonates with hypoxic-ischemic encephalopathy. Neonates undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy are also at risk for severe respiratory failure and need for extracorporeal life support. The risks and benefits of therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support are still not well defined. We report our experience of a case series of six neonates who underwent therapeutic hypothermia for hypoxic-ischemic encephalopathy during extracorporeal life support. We also report long-term neurodevelopmental follow-up from 6 to 24 months and add to the current body of evidence regarding feasibility, clinical experience, and short-term complications.

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

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

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

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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