#Review of #neuroimaging #findings in #congenital #Zika virus syndrome and its relation to the time of infection (Neuroradiol J., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Neuroradiol J. 2020 Jan 2:1971400919896264. doi: 10.1177/1971400919896264. [Epub ahead of print]

Review of neuroimaging findings in congenital Zika virus syndrome and its relation to the time of infection.

Radaelli G1, Lahorgue Nunes M1,2,3, Bernardi Soder R1,3, de Oliveira JM1, Thays Konat Bruzzo F1, Kalil Neto F1, Leal-Conceição E1, Wetters Portuguez M1,3, Costa da Costa J1,2,3.

Author information: 1 Brain Institute of Rio Grande do Sul (BraIns), Pontifical Catholic University of Rio Grande do Sul, Brazil. 2 CNPq, Brazil. 3 School of Medicine, Pontifical Catholic University of Rio Grande do Sul, Brazil.




Many original articles and case series have been published emphasizing the neuroimaging findings of congenital Zika virus (ZIKV) infection. The majority of these studies do not follow a neuroradiological methodology to describe malformations and brain abnormalities resulting from ZIKV infection. The cause-and-effect correlation between the gestational period of maternal infection and the severity of encephalic changes at birth has rarely been reported. A systematic literature review was conducted on the neuroimaging findings in children affected with microcephaly due to ZIKV.


PubMed, Cochrane Library and Web of Science were searched for full-text articles published up to July 2019. Duplicate entries were removed. Two independent reviewers performed a quality assessment of all the studies included.


A total of 2214 publications were identified. Of these 2170 were excluded by analysis of titles and abstracts, resulting in the inclusion of only eight articles. Chi-square and Fisher’s exact tests were performed with a 95% confidence interval to verify the statistically significant differences in the neuroradiological findings between the cases of ZIKV infection in the first or second trimester of gestation. The studies published so far have described image abnormalities at random, without utilizing any pre-established neuroradiological criteria, and imaging modalities with different sensitivity and accuracy have been used, which jeopardizes a reliable and adequate statistical analysis.


Neuroimaging abnormalities are much more prevalent and severe when the infection by ZIKV is contracted in the first or second trimester of pregnancy.

KEYWORDS: Zika virus; magnetic resonance; microcephaly; tomography

PMID: 31896285 DOI: 10.1177/1971400919896264

Keywords: Zika Virus; Zika Congenital Syndrome; Neurology; Pediatrics; Imaging; Radiology.


#Discordant #Zika virus findings in #twin #pregnancies complicated by antenatal Zika virus exposure: a prospective cohort (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Discordant Zika virus findings in twin pregnancies complicated by antenatal Zika virus exposure: a prospective cohort

Nasim C Sobhani, MD, Elyzabeth Avvad-Portari, MD PhD, Aline C M Nascimento, MD, Heloisa N Machado, PhD, Daniel S S Lobato, MD, Jose Paulo Pereira, Jr, MD PhD, Mikaela S Esquivel, Zilton C Vasconcelos, PhD, Andrea A Zin, MD PhD, Irena Tsui, MD, Kristina Adachi, MD, Elizabeth B Brickley, PhD, Susan J Fisher, PhD, Karin Nielsen-Saines, MD, Patricia Brasil, MD, PhD, Maria E Moreira, MD PhD, Stephanie L Gaw, MD PhD

The Journal of Infectious Diseases, jiz629, https://doi.org/10.1093/infdis/jiz629

Published: 27 November 2019




There is limited data on the natural history of antenatal Zika virus (ZIKV) exposure in twin pregnancies, especially regarding inter-twin concordance of prenatal, placental, and infant outcomes.


This prospective cohort study included twin pregnancies referred to a single institution from September 2015 to June 2016 with maternal ZIKV. PCR testing of maternal, placental, and neonatal samples was performed. Prenatal ultrasounds were completed for each twin, and histomorphologic analysis was performed for each placenta. Abnormal neonatal outcome was defined as abnormal exam and/or abnormal imaging. Two- to three-year follow-up of infants included physical exams, neuroimaging, and Bayley-III developmental assessment.


Among 244 pregnancies, four twin gestations without co-infection were identified. ZIKV infection occurred at 16-33 weeks gestation. ZIKV PCR testing revealed discordance between dichorionic twins, between placentas in a dichorionic pair, between portions of a monochorionic placenta, and between a neonate and its associated placenta. Of the eight infants, three (38%) had an abnormal neonatal outcome. Of six infants with long-term follow-up, three (50%) have demonstrated ZIKV-related abnormalities.


Neonatal PCR testing, placental findings, and infant outcomes can be discordant between co-twins with antenatal ZIKV exposure. These findings demonstrate that each twin should be evaluated independently for vertical transmission.

TORCH infection, twin, vertical transmission, congenital Zika syndrome, perinatal infection

Topic:  polymerase chain reaction – pregnancy – vertical disease transmission – infant – newborn – twins – placenta  – prenatal care – zika virus

Issue Section: Major Article

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© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Zika Virus; Zika Congenital Infection; Pregnancy; Zika Congenital Syndrome.


Association of Severe #Hydrocephalus With #Congenital #Zika Syndrome (JAMA Neurol., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

JAMA Neurol. 2019 Feb 1;76(2):203-210. doi: 10.1001/jamaneurol.2018.3553.

Association of Severe Hydrocephalus With Congenital Zika Syndrome.

van der Linden V1,2, de Lima Petribu NC2, Pessoa A3,4, Faquini I5, Paciorkowski AR6,7,8,9, van der Linden H Jr10, Silveira-Moriyama L11, Cordeiro MT12, Hazin AN5, Barkovich AJ13, Raybaud C14, de Brito Abath M2, Ribeiro E3, Barros Jucá CE15, Aragão MFVV16, Coelho Travassos PT17, Jungmann P17.

Author information: 1 Association for Assistance of Disabled Children, Recife, Pernambuco, Brazil. 2 Barão de Lucena Hospital, Recife, Pernambuco, Brazil. 3 Albert Sabin Children Hospital, Fortaleza, Ceará, Brazil. 4 Christus University, Fortaleza, Ceará, Brazil. 5 Professor Fernando Figueira Integral Medicine Institute, Recife, Pernambuco, Brazil. 6 Department of Neurology, University of Rochester Medical Center, Rochester, New York. 7 Department of Pediatrics, University of Rochester Medical Center, Rochester, New York. 8 Departement of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York. 9 Department of Neuroscience, University of Rochester Medical Center, Rochester, New York. 10 Dr Henrique Santillo Rehabilitation Center, Goiania, Goiás, Brazil. 11 Postgraduate Program in Medicine, Universidade Nove de Julho, Uninove, Sao Paulo, Brazil. 12 Centro de Pesquisas Aggeu Magalhães-Fiocruz, Recife, Pernambuco, Brazil. 13 University of California, San Francisco, San Francisco, California. 14 University of Toronto, Toronto, Alberta, Canada. 15 Fortaleza University, Fortaleza, Ceará, Brazil. 16 Multimagem Diagnostic Center, Recife, Pernambuco, Brazil. 17 University of Pernambuco, Recife, Pernambuco, Brazil.




Hydrocephalus is a treatable but potentially fatal complication that has not been previously described in congenital Zika syndrome (CZS).


To describe the clinical features and imaging findings in 24 patients with congenital Zika syndrome (CZS) who developed hydrocephalus.


This case series included patients with hydrocephalus who were born in October and November 2015 and followed up until mid-2017 in the 2 largest national referral centers for CZS in Brazil. The participants included consecutively enrolled children with a clinical and laboratorial diagnosis of CZS who developed clinical and/or image findings suggestive of hydrocephalus and who were confirmed to experience increased intracranial hypertension during ventriculoperitoneal shunt procedures.


To retrospectively describe clinical and image findings in these 24 patients.


This multicenter cohort included 308 patients with CZS; 24 consecutive children were enrolled in this study. These children were aged between 3 to 18 months, and 13 of 24 (54%) were female. All patients presented with at least 1 positive test result for anti-Zika antibodies in cerebrospinal fluid or serum and had classic signs of CZS. At the time of hydrocephalus diagnosis, only 14 of 24 patients (58%) had symptoms and signs suggestive of hydrocephalus (mainly worsening seizures, vomiting, irritability, and/or sudden increase of head circumference percentile). Two of 24 patients (8%) had no symptoms suggestive of hydrocephalus but were found to have reduced brain volume on repeated imaging. Cerebellar or brainstem hypoplasia on baseline imaging were found in 18 of 23 patients (78%). At the second computed tomographic scan, all patients showed a marked increase of ventricular volume, compatible with communicating hydrocephalus, and reduction of brain tissue that was visibly worse than on baseline imaging for the 23 patients with repeated scans.


We present evidence that hydrocephalus is a complication of CZS in at least a proportion of patients. The clinical spectrum of this condition continues to evolve, but given that presenting signs and symptoms of hydrocephalus can be challenging to recognize in CZS, we provisionally recommend that high suspicion and appropriate monitoring for hydrocephalus should be part of the standard care of patients with CZS.

PMID: 30452526 PMCID: PMC6439957 DOI: 10.1001/jamaneurol.2018.3553 [Indexed for MEDLINE] Free PMC Article

Keywords: Zika Virus; Zika Congenital Syndrome; Hydrocephalus; Pediatrics; Neurology.


#Congenital #Zika #syndrome in #Argentina: case series study (Arch Argent Pediatr., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Arch Argent Pediatr. 2019 Dec 1;117(6):e635-e639. doi: 10.5546/aap.2019.e635.

[Congenital Zika syndrome in Argentina: case series study].

[Article in Spanish]

Pastrana A1, Albarracín M2, Hoffmann M3, Delturco G3, López R3, Gil R3, Guzmán A3, Del Barco M2, Espeche A3.

Author information: 1 Servicio de Neurología, Hospital Público Materno Infantil de Salta, Argentina. analia.pastrana@gmail.com. 2 Servicio de Neonatología, Hospital Público Materno Infantil de Salta, Argentina. 3 Servicio de Neurología, Hospital Público Materno Infantil de Salta, Argentina.



In 2015, there was an increase in the incidence of congenital microcephaly in newborns in Brazil. Months later, the causal relationship between Zika virus and these findings was discovered. In Argentina, during the first outbreak there were 5 cases of congenital Zika syndrome reported. In 2017, there was a new outbreak which involved Salta province. We describe 2 patients with autochthonous congenital Zika syndrome: one of the babies with severe congenital microcephaly with lissencephaly, calcifications and ventriculomegaly; and another baby with postnatal microcephaly with asymmetric polymicrogyria, calcifications and delayed myelination. The real impact of this disease is still uncertain, so it is necessary an adequate multidisciplinary monitoring of patients exposed to Zika virus to better understand the infection and its natural history.

Sociedad Argentina de Pediatría.

KEYWORDS: Zika virus; congenital Zika syndrome; microcephaly

PMID: 31758900 DOI: 10.5546/aap.2019.e635

Keywords: Zika Virus; Zika Congenital Syndrome; Microcephaly; Pediatrics; Argentina.


#Dental Changes In #Children With #Congenital #Zika Syndrome (Oral Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Oral Dis. 2019 Nov 19. doi: 10.1111/odi.13238. [Epub ahead of print]

Dental Changes In Children With Congenital Zika Syndrome.

de Lima Gusmão TP1, Barkokebas Santos de Faria A1, Leão Filho JC1, de Albuquerque Tavares Carvalho A1, Monteiro Gueiros LA1, Leão JC1.

Author information: 1 Oral Medicine Unit, Departamento de Clinica e Odontologia Preventiva, Federal University of Pernambuco, Pernambuco, Brazil.




To describe oral alterations in children with Congenital ZikaSyndrome (CZS).


This was a case series, whose research instrument was a structured questionnaire, associated with the use of medical record data and extra and intraoral clinical examination.


32 children were evaluated, the majority male (18/32%-56.3%), mean age 22 months (SD = 2.71). It was also observed that the majority of the patients (19/32%-59.4%) presented a low family income. All the children had a mean head circumference of 29.43 cm (SD = 1.42). Regarding the alterations, an ogival-shaped palate was observed in 14 children (43.7%), delayed chronology of eruption was observed in 15 children (46.9%), of whom 7 children (21.9%) did not present eruption of the upper left lateral incisor (p = .0002) and upper right-lateral incisor (p = .002) until the moment of analysis. Additionally, 03 children with yellowish dental pigmentation were identified in erupted teeth after the onset of phenobarbital use. Enamel hypoplasia was identified in 9 children (28.1%) and only one child with ankyloglossia.


CZS may present delayed chronology of eruption, ankyloglossia, ogivalshaped palate, enamel hypoplasia, requiring dental follow-up aimed at prevention, promotion and rehabilitation of the health of these children.

© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

KEYWORDS: epidemiology; oral manifestations; zika virus

PMID: 31742839 DOI: 10.1111/odi.13238

Keywords: Zika Virus; Zika Congenital Syndrome; Pediatrics.


#Subclinical in #utero #Zika virus #infection is associated with #interferon alpha #sequelae and sex-specific molecular #brain #pathology in asymptomatic porcine offspring (PLoS Pathog., abstract)

[Source: PLoS Pathogens, full page: (LINK). Abstract, edited.]


Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring

Ivan Trus , Daniel Udenze, Brian Cox , Nathalie Berube, Rebecca E. Nordquist, Franz Josef van der Staay, Yanyun Huang, Gary Kobinger, David Safronetz, Volker Gerdts, Uladzimir Karniychuk


Published: November 14, 2019 / DOI: https://doi.org/10.1371/journal.ppat.1008038



Zika virus (ZIKV) infection during human pregnancy may lead to severe fetal pathology and debilitating impairments in offspring. However, the majority of infections are subclinical and not associated with evident birth defects. Potentially detrimental life-long health outcomes in asymptomatic offspring evoke high concerns. Thus, animal models addressing sequelae in offspring may provide valuable information. To induce subclinical infection, we inoculated selected porcine fetuses at the mid-stage of development. Inoculation resulted in trans-fetal virus spread and persistent infection in the placenta and fetal membranes for two months. Offspring did not show congenital Zika syndrome (e.g., microcephaly, brain calcifications, congenital clubfoot, arthrogryposis, seizures) or other visible birth defects. However, a month after birth, a portion of offspring exhibited excessive interferon alpha (IFN-α) levels in blood plasma in a regular environment. Most affected offspring also showed dramatic IFN-α shutdown during social stress providing the first evidence for the cumulative impact of prenatal ZIKV exposure and postnatal environmental insult. Other eleven cytokines tested before and after stress were not altered suggesting the specific IFN-α pathology. While brains from offspring did not have histopathology, lesions, and ZIKV, the whole genome expression analysis of the prefrontal cortex revealed profound sex-specific transcriptional changes that most probably was the result of subclinical in utero infection. RNA-seq analysis in the placenta persistently infected with ZIKV provided independent support for the sex-specific pattern of in utero-acquired transcriptional responses. Collectively, our results provide strong evidence that two hallmarks of fetal ZIKV infection, altered type I IFN response and molecular brain pathology can persist after birth in offspring in the absence of congenital Zika syndrome.


Author summary

A number of studies showed that Zika virus (ZIKV) can cause severe abnormalities in fetuses, e.g., brain lesions, and subsequently life-long developmental and cognitive impairment in children. However, the majority of infections in pregnant women are subclinical and are not associated with developmental abnormalities in fetuses and newborns. It is known that disruptions to the in utero environment during fetal development can program increased risks for disease in adulthood. For this reason, children affected in utero even by mild ZIKV infection can appear deceptively healthy at birth but develop immune dysfunction and brain abnormalities during postnatal development. Here, we used the porcine model of subclinical fetal ZIKV infection to determine health sequelae in offspring which did not show apparent signs of the disease. We demonstrated that subclinical fetal infection was associated with abnormal immunological responses in apparently healthy offspring under normal environmental conditions and during social stress. We also showed silent sex-specific brain pathology as represented by altered gene expression. Our study provides new insights into potential outcomes of subclinical in utero ZIKV infection. It also emphasizes that further attempts to better understand silent pathology and develop alleviative interventions in ZIKV-affected offspring should take into account interactions of host factors, like sex, and environmental insults, like social stress.


Citation: Trus I, Udenze D, Cox B, Berube N, Nordquist RE, van der Staay FJ, et al. (2019) Subclinical in utero Zika virus infection is associated with interferon alpha sequelae and sex-specific molecular brain pathology in asymptomatic porcine offspring. PLoS Pathog 15(11): e1008038. https://doi.org/10.1371/journal.ppat.1008038

Editor: Ted C. Pierson, NIH, UNITED STATES

Received: May 8, 2019; Accepted: August 21, 2019; Published: November 14, 2019

Copyright: © 2019 Trus et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Data Availability: All relevant data are within the manuscript and its Supporting Information files.

Funding: Financial support was provided by Genome Canada, Emerging Issue Program grant #418402, the Public Health Agency of Canada and the Government of Saskatchewan through Innovation Saskatchewan #418836. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. https://www.genomecanada.ca/ https://innovationsask.ca/research/saskatchewan-advantage-innovation-fund

Competing interests: The authors have declared that no competing interests exist.

Keywords: Zika Virus; Pregnancy; Zika Congenital Infection; Zika Congenital Syndrome; Animal models.


#Clinical #findings in #congenital #infection by #Zika virus: a retrospective study in a reference hospital in Central-West #Brazil (BMC Pediatr., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

BMC Pediatr. 2019 Oct 29;19(1):389. doi: 10.1186/s12887-019-1762-6.

Clinical findings in congenital infection by Zika virus: a retrospective study in a reference hospital in Central-West Brazil.

de Paula Guimarães C1, Macedo MS2, Barbosa MA3, Marques SM4, Costa PS4, de Oliveira ÊC4.

Author information: 1 Hospital das Clínicas da UFG/EBSERH, Goiânia, GO, Brazil. enfguimaraes@yahoo.com.br. 2 Secretaria Municipal de Saúde, Goiânia, GO, Brazil. 3 Faculdade de Enfermagem da UFG, Goiânia, GO, Brazil. 4 Faculdade de Medicina da UFG, Goiânia, GO, Brazil.




An increased number of congenital Zika virus infections with neurological and musculoskeletal malformations have been diagnosed worldwide, however, there are still several gaps in the knowledge about this infection, its associated mechanism, timing of transmission, and description of throughout findings of signs and symptoms, which is described in this paper. The purpose of this study is to describe aspects of congenital Zika syndrome (CZS) beyond the central nervous system comprising detailed delineation of all the other clinical findings.


A retrospective research developed using electronic medical records. We analyzed the files of 69 children with an initial diagnosis of microcephaly by Zika vírus who were born in 2015, 2016 and 2017, treated during the period from 2016 to 2017.


The newborns presented several neurological and musculoskeletal malformations, eye damage, hearing impairment and other malformations.


The present study has significant impact for health care teams following lactents with Congenital Zika Syndrome.

KEYWORDS: Malformations; Microcephaly; Zika virus

PMID: 31660908 DOI: 10.1186/s12887-019-1762-6

Keywords: Zika Virus; Zika Congenital Syndrome; Pediatrics; Brazil.