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Original Investigation
November 19, 2018

Association of Severe Hydrocephalus With Congenital Zika Syndrome

Author Affiliations
  • 1Association for Assistance of Disabled Children, Recife, Pernambuco, Brazil
  • 2Barão de Lucena Hospital, Recife, Pernambuco, Brazil
  • 3Albert Sabin Children Hospital, Fortaleza, Ceará, Brazil
  • 4Christus University, Fortaleza, Ceará, Brazil
  • 5Professor Fernando Figueira Integral Medicine Institute, Recife, Pernambuco, Brazil
  • 6Department of Neurology, University of Rochester Medical Center, Rochester, New York
  • 7Department of Pediatrics, University of Rochester Medical Center, Rochester, New York
  • 8Departement of Biomedical Genetics, University of Rochester Medical Center, Rochester, New York
  • 9Department of Neuroscience, University of Rochester Medical Center, Rochester, New York
  • 10Dr Henrique Santillo Rehabilitation Center, Goiania, Goiás, Brazil
  • 11Postgraduate Program in Medicine, Universidade Nove de Julho, Uninove, Sao Paulo, Brazil
  • 12Centro de Pesquisas Aggeu Magalhães-Fiocruz, Recife, Pernambuco, Brazil
  • 13University of California, San Francisco, San Francisco, California
  • 14University of Toronto, Toronto, Alberta, Canada
  • 15Fortaleza University, Fortaleza, Ceará, Brazil
  • 16Multimagem Diagnostic Center, Recife, Pernambuco, Brazil
  • 17University of Pernambuco, Recife, Pernambuco, Brazil
JAMA Neurol. 2019;76(2):203-210. doi:10.1001/jamaneurol.2018.3553
Key Points

Question  Can hydrocephalus be part of the clinical spectrum of congenital Zika syndrome?

Findings  This case series describes 24 patients who developed hydrocephalus between 3 and 18 months of age and had at least 1 test positive for anti-Zika antibodies, including 14 who had symptoms and signs suggestive of hydrocephalus, 18 who had cerebellar or brainstem hypoplasia at baseline, and 2 who had no such symptoms but were found to have reduced brain volume on repeated imaging; at a second computed tomographic scan, all showed marked increases of ventricular volume and reduction of brain tissue.

Meaning  Hydrocephalus may be a complication of congenital Zika syndrome with presenting signs and symptoms that are challenging to recognize; monitoring for it, including assessing the potential harbinger of cerebellar or brainstem hypoplasia, should be part of the standard care of patients with this condition.


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

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

Design, Setting, and Participants  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.

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

Results  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.

Conclusions and Relevance  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.