In animal models, neonatal seizures (NS) alter hippocampal development and lead to long-term deficits. Whether NS similarly affect humans is not known. The goal of this study was to assess whether NS are associated with altered hippocampal microstructure in neonates with hypoxic ischemic encephalopathy.

We included 6 neonates with and 27 without seizures. All were treated with therapeutic hypothermia after birth. Neonatal (median 5 days) and 6-month diffusion tensor imaging was used to measure apparent diffusion coefficient (ADC) from regions of interest (ROIs) in the hippocampus, basal ganglia, thalamus and frontal white matter.

ADC was significantly lower on the 6-month scan as compared to the neonatal scan for all ROIs. There were no significant differences in ADC on the early scan when comparing neonates with and without seizures. At 6 months, infants with seizures as neonates had a 6% higher hippocampal ADC (95% confidence interval: 0–11%, p<0.05). There was no significant difference in ADC for the other ROIs.

These preliminary results suggest that NS are associated with altered hippocampal structural development. Because the difference was seen only in the hippocampus, and on follow-up imaging but not the neonatal scan, we speculate that NS may have a negative effect on hippocampal development. However, these results could also be explained by unmeasured neoantal hypoxic-ischemic injury. The findings are in keeping with studies that suggest NS are an independent risk factor for adverse neurodevelopmental outcome. Further studies are needed to confirm whether seizures harm newborns.

Acknowledgements NIH/NCRR (UL1 RR024131); NIH/NINDS P50NS035902.