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

Kim V Annink,Niek E Van Der Aa,Floris Groenendaal,Maarten Lequin,Linda S De Vries,Monique M J Van Schooneveld,Rian M J C Eijsermans,Jeroen Dudink,Manouk Mocking,Manon J N L Benders,Henrica L M Van Straaten

doi:10.1038/s41598-021-83982-8

Abstract

The 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.

Highlights

The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE)
In this study we examined the association between MB atrophy, brain volumes and white matter microstructure at 10 years of age and neurodevelopmental outcome in children with a history of HIE with and without therapeutic hypothermia
This study shows that children at 10 years of age with a history of HIE due to presumed perinatal asphyxia have long-term neurodevelopmental problems

Summary

Introduction

The mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at schoolage. MB Mammillary bodies PIQ Performance intelligence quotient TBSS Tract-based spatial statistics TBV Total brain volume TIQ Total intelligence quotient VIQ Verbal intelligence quotient WISC Wechsler intelligence scale for children. Infants with moderate to severe HIE are treated with whole body hypothermia This has shown to improve 18–24 month survival without neurological disabilities and to reduce cerebral palsy (CP) and epilepsy at school-age[1,3,4,5,6]. To understand and adequately predict neurodevelopmental problems at school-age in children with HIE treated with hypothermia, it is important to elucidate which brain areas are injured and contribute to long-term problems. MB are known to be important for memory function[11]

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Conclusion