Intrauterine Zika virus infection associated with significant fetal brain abnormalities

1. In a case series of 23 infants with Zika virus infection, computed tomography (CT) of the head demonstrated a high prevalence of punctate intracranial calcifications, primarily within the frontal and parietal lobes with associated severe lateral ventriculomegaly.

2. Other common, non-specific brain findings include global hypogyration, cerebellar hypoplasia, and diffuse white matter hypodensity likely representative of global hypomyelination, together suggesting a disruption in brain development rather than brain destruction.

Evidence Rating Level: 4 (Below Average)

Study Rundown: Zika virus is a member of the Flaviviridae family of viruses that are commonly transmitted by Aedes mosquitoes. Although the clinical manifestations of Zika virus infections are relatively benign in adults, there is significant concern that Zika virus may cause significant congenital birth defects marked by severe microcephaly for children born to women who contract Zika virus during gestation. There have been limited data describing the anatomical fetal brain changes associated with an intrauterine Zika virus infection, and such data continue to remain elusive. This case-series reviewed the CT scans of 23 infants with congenital microcephaly and clinical and biochemical evidence consistent with Zika virus infection in Brazil with the intention to provide early descriptions of the patterns of brain abnormalities among this population. Patients were between the ages of 3 days to 5 months at the time the CT scans were obtained. Within this case-series, there was a high prevalence of intracranial punctate calcifications in band-like distributions, located predominantly within the frontal and parietal lobes, and at the corticomedullary junction, basal ganglia, and thalamus. Additionally, there was a high prevalence of severe ventriculomegaly of the lateral ventricles, global hypogyration of the cerebral cortex, cerebellar hypoplasia, and diffuse white matter hypodensities of the cerebral lobes, suggestive of global hypomyelination or dysmyelination. The pattern of injury is commonly seen in other congenital infections, however, the global nature of these findings suggests that Zika virus may cause disruptions in brain development rather than neuronal destruction as a mechanism of injury. This was one of the first reports to describe the neonatal brain abnormalities associated with an intrauterine Zika virus infection. As an early report, it is limited by a small sample size and the lack of definitive confirmation of Zika virus infection in the mother in most patients. Additional large prospective trials are needed to confirm these associations.

Click to read the study in NEJM

Relevant Reading: Zika virus intrauterine infection causes fetal brain abnormality and microcephaly: tip of the iceberg?

In-Depth [retrospective cohort]: This was a case study of 23 infants (10 male) with clinical or biochemical data consistent with intrauterine Zika virus infection in Brazil. Cerebrospinal fluid samples were collected from 7 (30%) of 23 infants which all demonstrated positive Zika virus IgM antibodies. None of the 23 infants demonstrated serological evidence of any TORCH infections. Head CTs were obtained at a mean age of 36 days. At the conclusion of the trial, all infants demonstrated intracranial calcifications, most commonly in the frontal lobes (69% to 78%), parietal lobes (83% to 87%), corticomedullary junction (53% to 86%), basal ganglia (57% to 65%), and hypothalamus (39% to 43%). Severe ventriculomegaly was noted in 53% of infants, affecting predominantly the lateral ventricles. Additional abnormalities included cerebellar hypoplasia (74%) and diffuse abnormal white matter hypodensities (87%).

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