Kim Annink

114 Chapter 6 ABSTRACT Background: The Papez circuit is important for memory function, which is often affected following neonatal hypoxic ischemic encephalopathy (HIE). The primary aim of this study was to investigate the association between injury to the Papez circuit, brain volumes, structural connectivity and neurodevelopmental outcome in 10-year-old children with a history of HIE. The secondary aim was to assess school- age outcome and brain development in children with a history of HIE, treated with or without hypothermia. Methods: Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (HT group, 22 children) or would have qualified but were born before therapeutic hypothermia became standard of care (non-HT group, 28 children). Children completed neuropsychological and motor assessments and MRI. Grey and white matter volumes were automatically segmented. Mammillary bodies (MB) were scored as normal or atrophic. Tract-based spatial statistics was used to investigate the association between fractional anisotropy (FA) and MB, hippocampal volumes and neuropsychological assessments . Results: Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both HT and non-HT groups. Normal MB and a larger hippocampus were positively associated with FA values. Performance IQ and visual-spatial long-term memory (delayed recall) were significantly associated with higher FA values. Atrophy of the MB at school-age could be predicted using neonatal MRI. Conclusion: Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia treatment. Injury to the Papez circuit (hippocampus, fornix and MB) was associated with neurocognition and memory.