Radiologic-pathologic evidence of brain injury: hypoperfusion in the Papez circuit results in poor neurodevelopmental outcomes in neonatal hypoxic ischemic encephalopathy.

Abstract

To provide radiologic-pathologic correlation of brain injury in the Papez circuit in hypoxic-ischemic encephalopathy (HIE) neonates and correlate radiologic findings with long-term neurodevelopmental outcomes. Twenty full-term HIE neonates were evaluated. Cerebral blood flow (CBF) values, obtained through pulsed arterial spin labeling (ASL) perfusion-weighted MRI, were compared by permutation test to identify brain regions with statistically significant perfusion changes between 14 HIE neonates without evidence of developmental delay by Bayley-III (mean age 8.2 ± 7.2days) and 6 HIE neonates with evidence of developmental delay (mean age 13.1 ± 8.0days). Four histopathologic studies on specimens were taken from post-mortem brains of another group of infants (mean age 10 ± 6.8days) with HIE. The infants were not the same ones who had MRIs. Significantly decreased perfusion in Papez circuit was found in HIE neonates with developmental delay compared with HIE neonates without delay. Decreased ASL perfusion values were seen in Papez circuit structures of the fornix (p = 0.002), entorhinal cortex (p = 0.048), amygdala (p = 0.036), hippocampus (p = 0.033), and thalamus (p = 0.036). In autopsy specimens of neonates with HIE, anoxic (eosinophilic) neurons, reactive astrocytes, and white matter rarefaction were observed in these regions, providing pathology correlation to the imaging findings of HIE. The Papez circuit is susceptible to hypoxic-ischemic injury in neonates as demonstrated by perfusion-weighted imaging and histopathology. This sheds new light onto a possible non-familial mechanism of neuropsychiatric disease evolution initiated in the infant period and raises the potential for early identification of at-risk children.