Mammillary body abnormalities and cognitive outcomes in children cooled for neonatal encephalopathy

• Published in: Developmental medicine and child neurology Vol. 65; no. 6; pp. 792 - 802
• Main Authors: Spencer, Arthur P. C., Lequin, Maarten H., Vries, Linda S., Brooks, Jonathan C. W., Jary, Sally, Tonks, James, Cowan, Frances M., Thoresen, Marianne, Chakkarapani, Ela
• Format: Journal Article
• Language: English; Norwegian
• Published: England John Wiley and Sons Inc 01.06.2023
• Subjects: Brain Diseases; Child; Cognition; Diffusion Magnetic Resonance Imaging; Fornix, Brain - pathology; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Magnetic Resonance Imaging; Mammillary Bodies - diagnostic imaging; Mammillary Bodies - pathology; Original
• ISSN: 0012-1622; 1469-8749
• DOI: 10.1111/dmcn.15453

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. 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. We investigated mammillary body abnormalities in early school‐age children without cerebral palsy cooled for neonatal hypoxic‐ischaemic encephalopathy, and controls matched for age, sex, and socioeconomic status. A third of cooled children had abnormal mammillary bodies, compared to none of the control group. Cooled children with abnormal mammillary bodies had reduced cognitive outcome scores, smaller hippocampi, and altered diffusion properties in the mammillothalamic tract compared to cooled children without mammillary body abnormalities, and controls.