EEG sharp waves are a biomarker of striatal neuronal survival after hypoxia-ischemia in preterm fetal sheep

Abstract

The timing of hypoxia-ischemia (HI) in preterm infants is often uncertain and there are few biomarkers to determine whether infants are in a treatable stage of injury. We evaluated whether epileptiform sharp waves recorded from the parietal cortex could provide early prediction of neuronal loss after HI. Preterm fetal sheep (0.7 gestation) underwent acute HI induced by complete umbilical cord occlusion for 25 minutes (n = 6) or sham occlusion (control, n = 6). Neuronal survival was assessed 7 days after HI by immunohistochemistry. Sharp waves were quantified manually and using a wavelet-type-2-fuzzy-logic-system during the first 4 hours of recovery. HI resulted in significant subcortical neuronal loss. Sharp waves counted by the automated classifier in the first 30 minutes after HI were associated with greater neuronal survival in the caudate nucleus (r = 0.80), whereas sharp waves between 2-4 hours after HI were associated with reduced neuronal survival (r = -0.83). Manual and automated counts were closely correlated. This study suggests that automated quantification of sharp waves may be useful for early assessment of HI injury in preterm infants. However, the pattern of evolution of sharp waves after HI was markedly affected by the severity of neuronal loss, and therefore early, continuous monitoring is essential.