Nonmicrocephalic Infants with Congenital Zika Syndrome Suspected Only after Neuroimaging Evaluation Compared with Those with Microcephaly at Birth and Postnatally: How Large Is the Zika Virus "Iceberg"?

Abstract

Background and purpose: Although microcephaly is the most prominent feature of congenital Zika syndrome, a spectrum with less severe cases is starting to be recognized. Our aim was to review neuroimaging of infants to detect cases without microcephaly and compare them with those with microcephaly.

Materials and methods: We retrospectively evaluated all neuroimaging (MR imaging/CT) of infants 1 year of age or younger. Patients with congenital Zika syndrome were divided into those with microcephaly at birth, postnatal microcephaly, and without microcephaly. Neuroimaging was compared among groups.

Results: Among 77 infants, 24.6% had congenital Zika syndrome (11.7% microcephaly at birth, 9.1% postnatal microcephaly, 3.9% without microcephaly). The postnatal microcephaly and without microcephaly groups showed statistically similar imaging findings. The microcephaly at birth compared with the group without microcephaly showed statistically significant differences for the following: reduced brain volume, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, an enlarged extra-axial space, an enlarged cisterna magna (all absent in those without microcephaly), and polymicrogyria (the only malformation present without microcephaly). There was a trend toward pachygyria (absent in groups without microcephaly). The group with microcephaly at birth compared with the group with postnatal microcephaly showed significant differences for simplified gyral pattern, calcifications outside the cortico-subcortical junctions, corpus callosum abnormalities, moderate-to-severe ventriculomegaly, and an enlarged extra-axial space.

Conclusions: In microcephaly at birth, except for polymicrogyria, all patients showed abnormalities described in the literature. In postnatal microcephaly, the only abnormalities not seen were a simplified gyral pattern and calcifications outside the cortico-subcortical junction. Infants with normocephaly presented with asymmetric frontal polymicrogyria, calcifications in the cortico-subcortical junction, mild ventriculomegaly, and delayed myelination.

Fig 1.

MR imaging and CT of an 8-month-old girl without microcephaly with probable congenital Zika syndrome. Sagittal T1-weighted image shows a normal corpus callosum and cisterna magna (A) and a small hyperintense focus of dystrophic calcification in the junction between the cortical and subcortical white matter (long white arrow) and left frontal polymicrogyria (short white arrow) (B). Axial T2-weighted image (C) shows right polymicrogyria (white arrows) and mildly decreased right hemisphere volume. CT scans show asymmetric hemispheres, with an enlarged right lateral ventricle (white arrow) (D) and small punctate foci, representing calcifications, at the cortico-subcortical white matter junction bilaterally in the frontal lobes (white arrows) (E and F).

Fig 2.

MR imaging and CT of an 11-month-old girl without microcephaly with probable congenital Zika syndrome. Sagittal T1-weighted image shows a normal corpus callosum and cisterna magna (A) and left polymicrogyria (white arrows) (B). Axial T2-weighted image (C) shows left polymicrogyria (white arrow) and mild left ventriculomegaly. A gradient-echo image (D) shows very few small and subtle punctate foci, representing calcifications, at the cortico-subcortical white matter junction (white arrow). Axial CT scans (E and F) show right frontal and left parietal punctate foci (white arrows).

Fig 3.

MR imaging and CT of an 11-month-old girl without microcephaly with probable congenital Zika syndrome. Sagittal T1-weighted image shows a normal corpus callosum and cisterna magna (A). Axial T2-weighted image (B) shows a normal cortex. A gradient-echo image (C) shows small and subtle punctate foci, representing calcifications, at the cortico-subcortical white matter junction (white arrows). Axial CT scan (D) shows punctate foci in the right hemisphere (white arrows).

Fig 4.

MR imaging and CT of a 10-month-old girl with microcephaly developed postnatally with possible congenital Zika syndrome. Sagittal T1-weighted image shows frontal polymicrogyria (medium white arrows) and very subtle hyperintense punctate foci, representing calcifications at the cortico-subcortical white matter junction (small white arrows). Coronal and axial T2-weighted images (B and C, respectively) show the thick and irregular cortex at the superior frontal sulcus (white arrows). Axial SWI (D) shows a small punctate focus, representing calcification at the cortico-subcortical white matter junction (white arrow). Axial CT scan (E) shows punctate foci in both frontal lobes. An echo-spoiled gradient-echo volumetric (3D reconstruction) image (F) shows malformation and prominence of brain high frontoparietal convexity gyri and sulci, predominantly at the left hemisphere: The superior frontal sulcus (medium white arrows) is well-identified bilaterally, as well as precentral (short black arrows), central (short white arrows), and intraparietal (long white arrows) sulci. The left hemisphere is more reduced than the right hemisphere; the left precentral gyrus (large black arrows) seems to be the most reduced in volume. These findings are located probably where the polymicrogyria is most severe, according to the T2-weighted images (B and C). These findings are better seen in a 3D reconstruction (F) than in sectional images (A–C), despite the presence of movement artifacts in the former.

Fig 5.

MR imaging of a 4-month-old boy with microcephaly with confirmed congenital Zika syndrome. Sagittal T2-weighted image (A) shows a hypogenetic corpus callosum (short white arrow), pons hypoplasia (medium white arrow), and an enlarged cisterna magna (long white arrow). An axial T2-weighted image (B) shows a diffuse simplified gyral pattern (note the thin cortex) (short white arrows), an enlarged extra-axial CSF space (medium white arrows), and severe ventriculomegaly (long white arrows). An axial T1-weighted image (C) shows hyperintense punctate foci, representing calcifications, at the cortico-subcortical white matter junction (small white arrows). Axial SWI (D) shows several punctate foci at the cortico-subcortical white matter junction (short white arrows).