Clinical features and neuroimaging (CT and MRI) findings in presumed Zika virus related congenital infection and microcephaly: retrospective case series study

Abstract

Objective: To report radiological findings observed in computed tomography (CT) and magnetic resonance imaging (MRI) scans of the first cases of congenital infection and microcephaly presumably associated with the Zika virus in the current Brazilian epidemic.

Design: Retrospective study with a case series.

Setting: Association for Assistance of Disabled Children (AACD), Pernambuco state, Brazil.

Participants: 23 children with a diagnosis of congenital infection presumably associated with the Zika virus during the Brazilian microcephaly epidemic.

Main outcome measures: Types of abnormalities and the radiological pattern of lesions identified on CT and MRI brain scans.

Results: Six of the 23 children tested positive for IgM antibodies to Zika virus in cerebrospinal fluid. The other 17 children met the protocol criteria for congenital infection presumably associated with the Zika virus, even without being tested for IgM antibodies to the virus--the test was not yet available on a routine basis. Of the 23 children, 15 underwent CT, seven underwent both CT and MRI, and one underwent MRI. Of the 22 children who underwent CT, all had calcifications in the junction between cortical and subcortical white matter, 21 (95%) had malformations of cortical development, 20 (91%) had a decreased brain volume, 19 (86%) had ventriculomegaly, and 11 (50%) had hypoplasia of the cerebellum or brainstem. Of the eight children who underwent MRI, all had calcifications in the junction between cortical and subcortical white matter, malformations of cortical development occurring predominantly in the frontal lobes, and ventriculomegaly. Seven of the eight (88%) children had enlarged cisterna magna, seven (88%) delayed myelination, and six each (75%) a moderate to severe decrease in brain volume, simplified gyral pattern, and abnormalities of the corpus callosum (38% hypogenesis and 38% hypoplasia). Malformations were symmetrical in 75% of the cases.

Conclusion: Severe cerebral damage was found on imaging in most of the children in this case series with congenital infection presumably associated with the Zika virus. The features most commonly found were brain calcifications in the junction between cortical and subcortical white matter associated with malformations of cortical development, often with a simplified gyral pattern and predominance of pachygyria or polymicrogyria in the frontal lobes. Additional findings were enlarged cisterna magna, abnormalities of corpus callosum (hypoplasia or hypogenesis), ventriculomegaly, delayed myelination, and hypoplasia of the cerebellum and the brainstem.

Fig 1 Map of Brazil showing cities with notified cases of microcephaly in Brazil up to 13 February 2016. Adapted from Brazilian Ministry of Health

Fig 2 Microcephaly, cortical malformation, and brain calcification. Axial CT image (A) shows many small dystrophic calcifications in the junction between cortical and subcortical white matter (white arrows) and noticeable reduction of the brain parenchyma thickness. Sagittal T2 weighted image (B) shows hypogenesis of the corpus callosum (black arrow), enlarged cisterna magna (long white arrow), and pons hypoplasia (white arrow). Axial T2 weighted image (C) shows simplified gyral pattern (white arrows), ventriculomegaly (long black arrow) wildly open Sylvius fissure as well as enlargement of subarachnoid space (black arrow). Coronal T2 weighted image (D) shows pachygyria in the frontal lobes (black arrows). Note the bilateral cortical thickness in the pachygyric frontal lobe (black arrows), shown on axial and sagittal T2 weighted images (E and F)

Fig 3 Severe microcephaly. Sagittal T1 weighted image (A) shows a profound craniofacial disproportion, noticeably hypogenetic corpus callosum (short white arrow), and brainstem (long white arrow) and cerebellum hypoplasia (short black arrow). In addition, the cisterna magna is enlarged (long black arrow). Observe the small dystrophic calcifications hyperintense on T1 weighted image (B) in the frontal lobe (black arrows) and extremely simplified gyral pattern. Axial T2 weighted image (C) shows severe ventriculomegaly, mainly at the posterior horn and ventricular atrium (short white arrows). Note the bulging walls of the ventricle, the upward dilated third ventricle (black arrow), and enlargement of the subarachnoid space (long white arrows). Axial T1 weighted image fat suppression post-contrast (D) shows thickness and enhancement of frontal pachymeningis (black arrows). These last findings (C and D) may indicate a blockage in the cerebrospinal fluid pathways and/or reduced absorption of cerebrospinal fluid owing to impairment of the meninges or injury of arachnoid granulations

Fig 4 Microlissencephaly. Sagittal T2 weighted image (A) and axial T2 weighted image (B) show moderate microcephalic brain, almost completely smooth cerebral surface with a thick cortex (short white arrows), and hypoplasia of corpus callosum (black arrow). In addition, the cisterna magna (long white arrow) is enlarged. Axial T1 weighted image (C) shows multiple hyperintense subcortical punctate dystrophic calcifications (black arrows)

Fig 5 Mild microcephaly. Axial non-contrast CT image (A and B) shows multiple bilateral calcifications in the junction between cortical and subcortical white matter (white arrows). Axial susceptibility magnetic weighted image (C) shows multiple foci of T2-hypointensity in subcortical frontal white matter (black arrows), and axial T1 weighted image (D) shows linear or punctiform foci of T1-shortening (white arrows), which correspond to the calcifications on CT. Axial T2 weighted image (E) shows bilateral frontal and central sulcus polymicrogyria (black arrows). Note the thickened and irregular cortical-white matter junction. Sagittal T1 weighted image (F) shows enlarged cisterna magna (black arrow) and hypoplasic corpus callosum (white arrow)