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Published on: October 28, 2022
Disrupted brain connectivity in children treated with therapeutic hypothermia for neonatal encephalopathy
Arthur P C Spencer1, Jonathan C W Brooks2, Naoki Masuda3
1Clinical Research and Imaging Centre, University of Bristol, Bristol, United Kingdom.
Insights
Therapeutic hypothermia improves outcomes for newborns with birth asphyxia but can lead to subtle neurodevelopmental deficits. This study reveals white matter abnormalities and altered brain network efficiency in school-aged children, impacting cognitive functions.
Area of Science:
- Neuroscience
- Developmental Pediatrics
- Medical Imaging
Background:
- Therapeutic hypothermia is standard care for neonatal encephalopathy due to birth asphyxia, reducing mortality and cerebral palsy.
- However, long-term neurodevelopmental deficits, including cognitive and motor impairments, persist in survivors without cerebral palsy.
Purpose of the Study:
- To investigate white matter integrity and structural brain network alterations in school-aged children treated with therapeutic hypothermia.
- To correlate brain network properties with cognitive outcomes like IQ in this cohort.
Main Methods:
- Acquired diffusion-weighted imaging data from children treated with therapeutic hypothermia and a matched control group.
- Utilized voxelwise analysis and probabilistic tractography to assess white matter microstructure and brain network topology.
- Employed graph-theoretic measures and network-based statistics to analyze structural connectivity and identify affected brain regions.
Main Results:
- Reduced fractional anisotropy (a measure of white matter integrity) was observed in widespread brain regions in the hypothermia group.
- Structural brain networks showed altered network efficiency measures that correlated with IQ in treated children.
- Network-based statistics highlighted the precuneus, thalamus, and parietal/temporal gyri as key regions implicated in visuo-spatial and attention deficits.
Conclusions:
- Therapeutic hypothermia, while life-saving, is associated with persistent white matter microstructural and network-level brain development impairments.
- These neurobiological findings align with observed subtle cognitive and attentional deficits in school-aged survivors.
- Further research is needed to understand and mitigate these long-term neurodevelopmental consequences.
Abstract:
Therapeutic hypothermia following neonatal encephalopathy due to birth asphyxia reduces death and cerebral palsy. However, school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy still have reduced performance on cognitive and motor tests, attention difficulties, slower reaction times and reduced visuo-spatial processing abilities compared to typically developing controls. We acquired diffusion-weighted imaging data from school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal encephalopathy at birth, and a matched control group. Voxelwise analysis (33 cases, 36 controls) confirmed reduced fractional anisotropy in widespread areas of white matter in cases, particularly in the fornix, corpus callosum, anterior and posterior limbs of the internal capsule bilaterally and cingulum bilaterally. In structural brain networks constructed using probabilistic tractography (22 cases, 32 controls), graph-theoretic measures of strength, local and global efficiency, clustering coefficient and characteristic path length were found to correlate with IQ in cases but not controls. Network-based statistic analysis implicated brain regions involved in visuo-spatial processing and attention, aligning with previous behavioural findings. These included the precuneus, thalamus, left superior parietal gyrus and left inferior temporal gyrus. Our findings demonstrate that, despite the manifest successes of therapeutic hypothermia, brain development is impaired in these children.
