Literature Review

Follow-Up of Infants With Zika Virus Identifies Several Neurologic Impairments


A report on 11 infants in Brazil suggests the term “congenital Zika syndrome” be used to describe the abnormalities associated with Zika virus infection because microcephaly is only one clinical sign of this congenital malformation disorder. The report was published online ahead of print October 3 in JAMA Neurology.

“To our knowledge,” the researchers wrote, “most reports to date have focused on select aspects of the maternal or fetal infection and fetal effects.” To provide a fuller description, the researchers sought to characterize the prenatal evolution and perinatal outcomes of 11 neonates who had developmental abnormalities and neurologic damage associated with Zika infection.

Follow-Up of 11 Neonates

Amilcar Tanuri, MD, PhD, Professor of Genetics and Chief of the Laboratory of Molecular Virology at the Institute of Biology, Federal University of Rio de Janeiro, and coauthors observed 11 infants with congenital Zika infection from gestation to six months in the state of Paraíba, Brazil. Cases were referred between October 2015 and February 2016. Ten of 11 women included in the study presented with symptoms of Zika infection during the first half of pregnancy, and all 11 had laboratory evidence of infection in several tissues by serology or polymerase chain reaction. Brain damage was confirmed through intrauterine ultrasonography and was complemented by MRI. Histopathologic analysis was performed on the placenta and brain tissue from infants who died. The ZIKV genome was investigated in several tissues and sequenced for further phylogenetic analysis.

Of the 11 infants, seven (63.6%) were female, and the median maternal age at delivery was 25. Three of the neonates died, giving a perinatal mortality rate of 27.3%. Zika virus was identified in amniotic fluid, placenta, cord blood, and neonatal tissues collected post mortem in the three babies who died within 48 hours of delivery.

Brain damage and neurologic impairments were identified in all patients, including microcephaly, a reduction in cerebral volume, ventriculomegaly, cerebellar hypoplasia, lissencephaly with hydrocephalus, and fetal akinesia deformation sequence. Testing for other causes of microcephaly, such as genetic disorders and infections, was negative. The ZIKV virus genome was found in tissues of the mothers and their babies.

“Combined findings from clinical, laboratory, imaging, and pathologic examinations provided a more complete picture of the severe damage and developmental abnormalities caused by ZIKV infection than has been previously reported,” Dr. Tanuri and colleagues said.

Formulating a Plan of Action

“Although we have limited ways to stop emerging pathogens, we now have powerful techniques to quickly identify the culprit, such as polymerase chain reaction and whole genome sequencing,” said Raymond P. Roos, MD, Marjorie and Robert E. Straus Professor in Neurologic Science in the Department of Neurology at the University of Chicago, in an accompanying editorial. “We also have novel methods to control vectors and produce vaccines in an accelerated time frame.”

But many unanswered questions remain, said Dr. Roos. Among those questions is what neurologists can do about the Zika virus. “It would be valuable to have adult and pediatric neurologists network with the US Centers for Disease Control and Prevention to establish a surveillance system that could track Zika virus-induced Guillain-Barré syndrome (GBS) and CNS disease. This [cooperation] would facilitate the identification and characterization of disorders, the formation of a registry, and the mounting of comprehensive epidemiologic studies. This approach would also help to identify long-term sequelae of intrauterine infection and clarify effective treatments of the GBS syndrome.”

Glenn S. Williams

Suggested Reading

Melo AS, Aguiar RS, Amorim MM, et al. Congenital Zika virus infection: beyond neonatal microcephaly. JAMA Neurol. 2016 Oct 3 [Epub ahead of print].

Roos RP. Zika virus-a public health emergency of international concern. JAMA Neurol. 2016 Oct 3 [Epub ahead of print].

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