Table 1.

Main radiological abnormalities of the CNS described in fetuses and neonates with presumed congenital ZIKV infection

References	Country, region/states	Subjects	Other infectious agents evaluated	ZIKV identification method	Clinical features	Radiological findings
Aragao et al52	Brazil, Pernambucoa	23 children with microcephaly	Paired serology (IgM and IgG) of infants and mothers for CMV, toxoplasmosis, rubella, HIV syphilis	IgM antibody-capture ELISA performed in six CSF samples: all positive. Others not tested	Birth weight categorized as small for gestational age (39%). Premature closure of anterior fontanel (87%). Microcephaly	CT (22 infants): decreased brain volume (95%), ventriculomegaly (86%), calcifications in cortical and subcortical junctions (100%), basal ganglia (59%), periventricular (45%), hypoplasia of cerebellum (27%), and brainstem (45%). MRI (eight infants): decreased brain volume and ventriculomegaly (100%), simplified gyral pattern (75%), hypogenesis/hypoplasia of corpus callosum (75%), and delayed myelination (88%)
Brasil et al50	Brazil, Rio de Janeiro	72 pregnant women with positive ZIKV infection and 16 noninfected, followed prospectively	Immunes to rubella and CMV; negative for syphilis; positive dengue-IgG antibodies in 88%	Real-time RT-PCR assays for ZIKV on blood and urine samples of pregnant womenb	Two fetal deaths at 36 and 38 weeks of gestation in ZIKV-positive women. Six newborns: macular lesions (33%), small for age (33%), EEG abnormalities	Fetal US (12 ZIKV-positive women): abnormal amniotic fluid volume (25%), growth restriction (42%), microcephaly (33%), and brain calcifications (33%). Newborn CT (one case): cerebral calcifications and global cerebral atrophy
Cavalheiro et al53	Brazil, Pernambuco/Maranhão/Rio Grande do Norte	13 infants with congenital microcephaly; radiologic examinations retrospectively reviewed	Negative serological tests for toxoplasmosis, rubella, CMV, herpes virus, and syphilis	Mothers presented with rash during pregnancy (100%). ZIKV infection was not laboratory confirmed in infants or mothers	Infants were born after the 37th gestational week by cesarean section; no other clinical features were described	CT/MRI: decreased cortical and white matter (100%), hypoplastic corpus callosum (100%), secondary ventriculomegaly (100%), lissencephaly (100%), calcifications in subcortical/cortical transition regions and basal ganglia (92%)
Calvet et al41	Brazil, Paraíba	Two pregnant women with symptoms whose fetuses had microcephaly	Toxoplasmosis, HIV, syphilis, measles, rubella, CMV, herpes simplex, parvovirus B19 screens were negative. RT-qPCR for dengue and chikungunya virus were negative in urine and serum	Amniocentesis at gestational week 28: RT-qPCRs for ZIKV were positive in the amniotic fluids and negative in urine and serum samples in both patients	Symptoms (rash, arthralgia, fever) at 10 and 18 weeks of gestation. Neonate 1: head circumference of 30 cm at 40 weeks. Neonate 2: microphthalmia, cataract, arthrogryposis in legs and arms	Patient 1: fetal US at 16 weeks: normal; at 21 weeks: microcephaly, moderate ventriculomegaly, partial agenesis of the cerebellar vermis; at 27 weeks: relevant dilation of ventricles, asymmetry of hemispheres, hypoplastic cerebellum with complete absence of the cerebellar vermis; at 40 weeks: microcephaly, calcification areas. Patient 2: fetal US at 22 weeks: mild cerebellar vermis hypoplasia; at 25 weeks: hypoplasia of the cerebellar vermis, enlargement of the posterior fossa, microcephaly
Driggers et al48	Washington, DC, USA (travels to Mexico, Guatemala, and Belize)	Case report: 33 year-old pregnant woman	Dengue virus: positive IgG antibodies and negative IgM. Serologic test for chikungunya virus was negative	Positive IgG and IgM antibodies. Positive RT-PCR against ZIKV in maternal serum, fetal brain, placenta, and other fetal tissues	At eleventh gestational week: ocular pain, myalgia, mild fever, and skin rash. Pregnancy was terminated at 21st week	Fetal US 13, 16, and 17 weeks of gestation: no evidence of microcephaly or intracranial calcifications. At 19 weeks: reduced cerebral mantle, enlarged frontal horns (intraventricular hemorrhage questioned), dilation of the third ventricle, dilation of the frontal horns of the lateral ventricles Fetal MRI at 20 weeks: diffuse atrophy of the cerebral mantle (frontal and parietal lobes) with the absence of normal lamination pattern, hypoplastic corpus callosum
Guillemette-Artur et al59	French Polynesia	Retrospectively analyzed MRI findings of three fetuses	PCR for CMV and lymphocytic choriomeningitis virus was negative	PCR for ZIKV was positive	Two mothers had ZIKV-like symptoms during the first trimester of pregnancy. In all cases, pregnancies were electively terminated	Fetal US: calcifications and ventriculomegaly (100%). Fetal MRI: micrencephaly (100%), polymicrogyria with laminar necrosis and opercular dysplasia (100%), absent/or hypoplastic corpus callosum (67%), low cerebellar biometry (67%)
Hazin et al51	Brazil, Pernambucoc	23 infants with congenital microcephaly	Toxoplasmosis, syphilis, varicella, parvovirus, HIV, rubella, CMV, and herpes simplex were excluded by serological tests	ZIKV IgM antibodies were detected in the cerebrospinal fluid in seven of 23 infants	No clinical description	CT: ventriculomegaly and global hypogyration (100%). Calcifications (100%): frontal and parietal lobes, basal ganglia and thalamus; cerebellar hypoplasia (74%), white matter hypodensity (100%)
Meaney-Delman et al49	The USA (travels to American Samoa, Brazil, El Salvador, Guatemala, Haiti, Honduras, Mexico, Puerto Rico, and Samoa)	Nine pregnant women with positive ZIKV		RT-PCR, IHC, and serologic testing	All women had rash. Four cases were described: one had radiological examinations	Patient 1: Fetal US at 20 weeks of gestation: absence of the corpus callosum, ventriculomegaly, and brain atrophy. Fetal MRI: severe brain atrophy
Mlakar et al45	Ljubljana, Slovenia (lived in northeast of Brazil)	Case report: 25-year-old pregnant woman	PCR assays were negative for other flaviviruses, CMV, rubella virus, varicella-zoster virus, herpes simplex virus, parvovirus B19, enteroviruses, and Toxoplasma gondii	Positive results for ZIKV were obtained by RT-PCR in fetal brain	At 13th week of gestation, there were symptoms of generalized rash, fever, musculoskeletal, and retroocular pain. Pregnancy was terminated at 32 weeks. Fetal autopsy: micrencephaly, agyria, hydrocephalus, and multifocal dystrophic calcifications in the cortex and in the subcortical white matter	Fetal US at 14 and 20 weeks: normal fetal growth and anatomy. At 29 weeks of gestation: intrauterine growth retardation, microcephaly, moderate ventriculomegaly; placenta calcifications
Schuler-Faccini et al44	Brazil, eight states, not specified	35 infants with congenital microcephaly	Negative serological tests for syphilis, toxoplasmosis, rubella, CMV, and herpes simplex virus	Reported maternal rash during pregnancy (71%). ZIKV infection was not laboratory confirmed in infants or mothers	Low birth weight (26%), arthrogryposis (11%), hypertonia/spasticity (37%), hyperreflexia (20%), irritability (20%), tremors (11%), and seizure	CT and TUS: lissencephaly, pachygyria (33%), cortical/subcortical atrophy, nonhypertensive ventricular enlargement (44%), periventricular, parenchymal, thalamic, basal ganglia brain calcifications (74%)
Werner et al54	Rio de Janeiro, Brazil	Case report: 27-year-old pregnant woman	Serology testing for toxoplasmosis, rubella, CMV, and herpes simplex, dengue and chikungunya virus was negative		Symptoms 12th week of gestation. Male infant born at 38 weeks, with microcephaly. Cephalic circumference of 32 cm at 1-month-old. No other clinical features were described	Fetal US: microcephaly and diffuse brain calcifications were identified at 37 weeks. Fetal MRI: reduced gyration and asymmetric colpocephaly. Transfontanellar US: subcortical and periventricular calcifications, ventricular dilatation. Postnatal CT: brain calcifications, cortical atrophy, small anterior fontanel and premature closure of coronal and metopic sutures. Postnatal MRI: pachygyria, corpus callosum dysgenesis, brain calcifications

Notes:

^aAssociation for AACD.

^bQuantiTect Probe RT-PCR Kit (Qiagen NV, Venlo, the Netherlands): blood and urine samples.

^cProfessor Fernando Figueira Integral Medicine Institute (IMIP).

Abbreviations: AACD, Assistance of Disabled Children; CMV, cytomegalovirus; CNS, central nervous system; CSF, cerebrospinal fluid; CT, computed tomography; EEG, electroencephalogram; ELISA, enzyme-linked immunosorbent assay; HIV, human immunodeficiency virus; IHC, immunohistochemical; IgM, Immunoglobulin M; Igg Immunoglobulin G; MRI, magnetic resonance imaging; PCR, polymerase chain reaction; qPCR, quantitative PCR; RT, reverse transcriptase; TUS, transfontanellar ultrasound; US, ultrasound; ZIKV, Zika virus.