From the Journals

Congenital Zika syndrome includes range of neurologic abnormalities

Publish date: October 3, 2016

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Much to be learned about Zika virus and pregnancy

Many unanswered questions remain about Zika virus: How frequently does asymptomatic infection or second- and third-trimester infection lead to CNS disease? What are the long-term sequelae of intrauterine Zika virus infection? What is the reason for the substantial size, severity, and unexpected complications of the recent Zika virus outbreak in the Americas, compared with what has been seen with this virus in the past? And a broader question: How many CNS birth defects presently of unclear cause will be found to be virus induced?

It would be valuable to have adult and pediatric neurologists network with the U.S. Centers for Disease Control and Prevention to establish a surveillance system that could track Zika virus–induced Guillain-Barré syndrome and CNS disease. This would facilitate the identification and characterization of disorders, the formation of a registry, and the mounting of comprehensive epidemiological studies.

Dr. Raymond P. Roos is with the Department of Neurology at the University of Chicago. These comments are adapted from an accompanying editorial (JAMA Neurol. 2016 Oct 3. doi: 10.1001/jamaneurol.2016.3677). No conflicts of interest were declared.

Researchers have proposed the term “congenital Zika syndrome” to cover the range of severe damage and developmental abnormalities – including microcephaly – caused by Zika virus infection.

In the Oct. 3 online edition of JAMA Neurology, Adriana Suely de Oliveira Melo, MD, PhD, of the Instituto de Pesquisa Professor Amorim Neto in Campina Grande, Brazil, and her coauthors report on 11 babies with congenital Zika virus infection who were followed from gestation to 6 months of age.

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Nine of the infants had a head circumference two standard deviations below the gestational age in most infants, with severe cerebral atrophy on abdominal and transvaginal ultrasonography. However, two of the infants had a normal or enlarged head circumference with severe ventriculomegaly.

Researchers observed hypoplasia of the cerebellar vermis and cerebellum in nine patients, while MRI and CT imaging also found that all patients showed callosal hypoplasia, reduced cerebral volume, abnormal cortical development, and subcortical calcifications.

Four of the infants showed gyral disorganization, five showed evidence of pachygyria, and two had lissencephaly (JAMA Neurol. 2016 Oct 3. doi: 10.1001/jamaneurol.2016.3720).

“Although there was variable damage resulting from brain lesions associated with [Zika virus] congenital infection, a common pattern of brain atrophy and changes associated with disturbances in neuronal migration were observed,” the authors wrote. “Some patients presented with mild brain atrophy and calcifications, and others presented with more severe malformations, such as the absence of the thalamus and lissencephaly.”

Three of the infants died after delivery, representing a fatality rate of 27.3%. All three were found to have akinesia deformation sequence or arthrogryposis. One of the three pregnancies also involved polyhydramnios, and the infant was delivered at 36 weeks because of severe maternal respiratory distress.

All but one of the pregnant women had reported a skin rash at a median of 9.5 weeks in the pregnancy, suggesting Zika virus infection was acquired early.

Postmortem tissue analysis of two of the infants who died found Zika virus genome in the brain, cerebellum, spinal cord, and lung; a higher viral load in the tissue of one of the infants was associated with more severe brain damage.

Overall, nine patients tested positive for Zika virus using real-time reverse-transcription polymerase chain

reactions during gestation and/or after birth, while two patients only had serologic evidence of infection.

“It was interesting to note that the viral sequences amplified from patients 1 and 7 after birth gained a new substitution, V23I, which is located in the envelope domain I and may be implicated in viral tropism to different tissues.”

The study was supported by Consellho Nacional de Desenvolvimento e Pesquisa, Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, and Prefeitura Municipal de Campina Grande. No conflicts of interest were declared.