Brain imaging of infants with confirmed or presumed congenital Zika virus infection showed both a reduction in brain volume, as well as abnormal development in certain areas of the brain, a small retrospective analysis of Brazilian infants found.

In addition to more publicized abnormalities, such as microcephaly and intracranial calcifications, most infants had prenatal or postnatal evidence of ventriculomegaly (expansion of the lateral ventricles of the brain) and abnormal cortical development, reported Patricia Soares de Oliveira-Szejnfeld, MD, of Federal University of São Paulo in Brazil, and colleagues.

The authors published their findings in a special report in Radiology.
Congenital abnormalities, including neurological abnormalities, have been linked with classic TORCH infections, but anomalies associated with congenital Zika virus infection in this small sample appeared to be much more severe. Not surprisingly, all but one of these infants had evidence of microcephaly -- with head circumferences below the fifth percentile at least once during the second trimester. However, normal head circumference was misleading in several cases, as ventriculomegaly may have given the appearance of a normal head size.

But the researchers argued that "microcephaly" is a non-specific term that merely refers to head circumference smaller than normal for gestational age. They sought to identify more specific neurologic abnormalities linked with congenital Zika virus infection, which would be visible via diagnostic imaging.



Four radiologists examined images from two small cohorts: one with 17 infants whose mothers had confirmed Zika virus infection via RT-PCR or serologic testing, and a second cohort comprised of 28 infants with intracranial calcifications consistent with Zika virus infection. Overall, there were 42 postnatal CT scans, 12 fetal MRI examinations and 11 postnatal MRI examinations from the Instituto de Pesquisa in Campina Grande State Paraiba in northeastern Brazil.

"Microcephaly is only one of the severe radiologic features," said co-author Fernanda Tovar-Moll, MD, of Federal University of Rio de Janeiro, in a statement. "Imaging is essential for identifying the presence and the severity of the structural changes induced by the infection, especially in the central nervous system."

All examined neonatal images noted a reduction in brain volume, and ventriculomegaly was observed in 94%-96% of infants with confirmed or probable Zika virus infection. There were also cortical migration abnormalities in nearly all of these infants, potentially indicating structurally abnormal or missing areas of the cerebral cortex.

In addition, abnormalities of the corpus callosum (the band of nerve fibers joining both hemispheres of the brain) were seen in more than three-quarters of infants with confirmed or presumed Zika virus infection.

"The severity of the cortical malformation and associated tissue changes, and the localization of the calcifications at the grey-white matter junction were the most surprising findings in our research," said Tovar-Moll.

Nearly all (88%-100%) of both cohorts had intracranial calcifications at the gray matter-white matter junction of the brain. Notably, calcifications on the basal ganglia (which helps control motor function) and/or in the thalamus (which helps regulate sensory and motor signals) were seen in two-thirds of infants. The authors noted that the gray matter-white matter junction is "an area not classically or commonly targeted in other congenital infections," and may suggest a vascular component to congenital Zika infection.

Although up to 80% of Zika infections can be asymptomatic, around three-fourths of women in both cohorts presented with a rash during their first trimester of pregnancy.

"This correlates well with the finding of severe cerebral dysmorphisms associated with infection during a time of rapid brain development," they wrote, adding that the CDC estimates the risk of microcephaly at 1%-13% after maternal infection with Zika virus in the first trimester.

Limitations to this research include that it was a convenience sample of imaging findings, which was taken from a referral center for high-risk pregnancy and may not be generalizable. The authors also acknowledge that microcephaly may be due to infections other than Zika virus, which had yet to be diagnosed.