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Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy
Arthur P C Spencer1,2, Maarten H Lequin3,4, Linda S de Vries5,6
1Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK.
Insights
Therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy increases mammillary body abnormalities in children. These abnormalities correlate with lower cognitive scores, smaller hippocampi, and altered brain tract diffusivity.
Area of Science:
- Neuroscience
- Pediatric Neurology
- Radiology
Background:
- Neonatal hypoxic-ischaemic encephalopathy (HIE) is a significant cause of brain injury in newborns.
- Therapeutic hypothermia is a standard treatment for HIE, but long-term neurodevelopmental outcomes require further investigation.
- Mammillary body abnormalities have been observed in various neurological conditions, but their specific impact following neonatal HIE is less understood.
Purpose of the Study:
- To investigate the prevalence of mammillary body abnormalities in school-age children treated with therapeutic hypothermia for neonatal HIE.
- To assess the association between mammillary body abnormalities and cognitive outcomes, hippocampal volume, and white matter tract diffusivity (mammillothalamic tract and fornix).
Main Methods:
- Retrospective analysis of T1-weighted and diffusion-weighted MRI scans in 32 children treated with therapeutic hypothermia (cases) and 35 matched controls without cerebral palsy.
- Mammillary body abnormalities were scored visually from MRI.
- Cognitive function was assessed using the Wechsler Intelligence Scale for Children (WISC-IV).
- Hippocampal volume and white matter microstructure (radial diffusivity, fractional anisotropy) in the mammillothalamic tract (MTT) and fornix were quantified.
Main Results:
- Mammillary body abnormalities were significantly more frequent in the HIE cases (34%) compared to controls (0%; p < 0.001).
- Children with mammillary body abnormalities exhibited lower scores in all cognitive domains, including processing speed and full-scale IQ, compared to both HIE children without abnormalities and controls.
- Cases with abnormal mammillary bodies had smaller hippocampal volumes and increased radial diffusivity in the right mammillothalamic tract.
Conclusions:
- Children treated with therapeutic hypothermia for neonatal HIE are at an increased risk for developing mammillary body abnormalities.
- These abnormalities are associated with significant long-term neurocognitive deficits and structural brain changes, including reduced hippocampal volume and altered white matter integrity in the mammillothalamic tract.
- The findings highlight the mammillary bodies as a potential indicator of long-term neurological sequelae following neonatal HIE and therapeutic hypothermia.
Aim:
To evaluate mammillary body abnormalities in school-age children without cerebral palsy treated with therapeutic hypothermia for neonatal hypoxic-ischaemic encephalopathy (cases) and matched controls, and associations with cognitive outcome, hippocampal volume, and diffusivity in the mammillothalamic tract (MTT) and fornix.
Method:
Mammillary body abnormalities were scored from T1-weighted magnetic resonance imaging (MRI) in 32 cases and 35 controls (median age [interquartile range] 7 years [6 years 7 months-7 years 7 months] and 7 years 4 months [6 years 7 months-7 years 7 months] respectively). Cognition was assessed using the Wechsler Intelligence Scale for Children, Fourth Edition. Hippocampal volume (normalized by total brain volume) was measured from T1-weighted MRI. Radial diffusivity and fractional anisotropy were measured in the MTT and fornix, from diffusion-weighted MRI using deterministic tractography.
Results:
More cases than controls had mammillary body abnormalities (34% vs 0%; p < 0.001). Cases with abnormal mammillary bodies had lower processing speed (p = 0.016) and full-scale IQ (p = 0.028) than cases without abnormal mammillary bodies, and lower scores than controls in all cognitive domains (p < 0.05). Cases with abnormal mammillary bodies had smaller hippocampi (left p = 0.016; right p = 0.004) and increased radial diffusivity in the right MTT (p = 0.004) compared with cases without mammillary body abnormalities.
Interpretation:
Cooled children with mammillary body abnormalities at school-age have reduced cognitive scores, smaller hippocampi, and altered MTT microstructure compared with those without mammillary body abnormalities, and matched controls.
What This Paper Adds:
Cooled children are at higher risk of mammillary body abnormalities than controls. Abnormal mammillary bodies are associated with reduced cognitive scores and smaller hippocampi. Abnormal mammillary bodies are associated with altered mammillothalamic tract diffusivity.
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