American Association of Neuropathologists, Inc. Abstracts of the 92nd Annual Meeting June 16–19, 2016 Baltimore, MD

Congenital Zika virus infection is a developing public health emergency, leading to microcephaly, intracerebral calcifications, and often fetal death. Here we present the neuropathological findings from an autopsy of a 20week fetus in which congenital Zika virus infection was diagnosed in utero. Though microcephaly or intracerebral calcification was not yet identified, fetal ultrasound and MRI findings revealed mild hydrocephalus with a markedly thinned cortical rim and partial corpus callosum agenesis. Following pregnancy termination, autopsy revealed a brain within the normal weight range for gestational age, however the thinned cortex was grossly notable. Histologic evaluation of the brain showed abundant apoptosis diffusely involving the “intermediately differentiated” neurons in neocortex. The subventricular zone and white matter demonstrated severe volume loss with axonal injuries and macrophage infiltrates. Additionally, an aggregate of intracellular particles identified on electron microscopy was consistent with viral infection. There was relative sparing of the developmentally mature deep grey matter nuclei and limbic regions, which showed only rare microglial aggregates. Similarly, the germinal matrix of the ganglionic eminence was morphologically intact and void of inflammation. Our imaging and pathologic findings suggest that the Zika virus-associated brain injury is likely a consequence of direct viral injury and post-infectious inflammatory damage to a subpopulation of central nervous sytemsystem cells. Whether the viral infection has an effect on the developmental sequence remains unclear. Future studies across multiple time points of pregnancy will offer better insight into the role of Zika virus infection in brain development.