Hydranencephaly and porencephaly predominated among neuropathologic findings in stillborn and neonatal piglets during the first major outbreak of Japanese encephalitis in Australia

In 2022, piggeries in southeastern Australia experienced an increase in reproductive losses and occasional neurologic disease in neonates with up to 100% mortality in some litters. Molecular testing identified a genotype IV Japanese encephalitis virus (JEV) as the etiological agent, detected for the first time in Australia. Necropsy of 235 JEV-positive domestic piglets, mostly stillbirths with 30% mummified, revealed hydranencephaly-porencephaly impacting the dorsal cerebrum as the most common lesion. Microscopically, this was characterized by varying degrees of parenchymal collapse as a result of liquefactive necrosis, hypoplasia, and dysplasia, with nonsuppurative inflammation and mineralization. In the most severe cases, hydranencephaly reduced the cerebral parenchyma to a thin membrane enclosing dilated lateral ventricles. Histologically, the affected neuroparenchyma was largely devoid of mature neurons, axons, myelin, and oligodendrocytes. What remained was mostly a dense population of IBA-1-positive histiocytes and few CD3-positive T-lymphocytes, interspersed within a dense network of GFAP-positive astrocytic processes. Immunohistochemistry for flaviviral antigen showed colocalization of viral antigen-positive neurons and necrotic foci. In less severe cases, cerebral necrosis occurred in well-demarcated, locally extensive regions or isolated gyri, sometimes with a vascular distribution, resulting in porencephaly. In addition, vascular calcification was noted, although with unknown significance and pathogenesis. Arthrogryposis, scoliosis, and kyphosis were observed in a small subset of the cases, which had myelodysplasia. Myelodysplastic changes varied and included central canal duplication, dysplastic gray matter, and bifurcation of the ventral medial sulcus. Multifocal necrosis and inflammation were also observed in the spinal cord, although the extent was typically limited.