More Than Microcephaly: Congenital Zika Syndrome

Laura A. Stokowski, RN, MS; William B. Dobyns, MD


September 21, 2016

In This Article

Postnatal Microcephaly in Congenital Zika Syndrome

Medscape: What can you tell us about infants now being identified with probable congenital Zika infection who do not exhibit microcephaly at birth? In June, a study in the Lancet[10] reported that one-fifth of babies with Zika-related brain disorders had normal-sized heads. Is this the phenomenon now being called late-onset microcephaly?

Dr Dobyns: Doctors in Brazil started to see a smaller group of children who looked, clinically, like they had congenital Zika syndrome, but their head sizes were normal. I prefer the term postnatal microcephaly to describe infants born with normal head sizes who have slow head growth and fall below the curve at 6 to 12 months of age.

Zika testing has only recently become available in Brazil, so we don't have documentation of infection for all of these children or their mothers. Dr André Pessoa, a colleague of mine in northeastern Brazil who examined all of these children, was able to pull together the records of nine children for us to review. It turns out that their head sizes do not encompass the entire normal range. All of these children had head sizes below the 50th percentile, and most were below the 25th percentile—so in the lower-normal ranges.

What do these children have? They have evidence of brain injury on CT and MRI scans, such as enlarged ventricles, suggesting a loss in brain volume, but less severe. The features of their brains and neurologic exams are similar to those of severely affected children. On exam, the infants were spastic, irritable, and tremulous. In children with a low-normal head size at birth, evidence of injury on brain scan, and abnormal neurologic exams, brain growth is not going to be normal. Head growth will decline, and by the age of 12 months (or perhaps earlier), I would not be surprised if these children meet the criteria for microcephaly.

Data being gathered by the CDC (not yet published) show that some of these babies develop microcephaly later, a condition they have been calling secondary microcephaly. But the more scientifically on-point term is postnatal microcephaly. These babies are primarily infected in the second trimester, but we don't have enough data to say that this is associated with second-trimester Zika infection. Furthermore, there is a range in the severity of infection.

If you change the label of the disorder that these babies have from generic microcephaly to congenital Zika syndrome, then we can ask, "Do all children with congenital Zika syndrome have microcephaly at birth?" The answer is probably not. To prove that, we need a prospective study in which babies undergo Zika testing before they are born.

Medscape: Can Zika affect older infants, children, and adults in the same way? Is there a connection between the Zika virus and reports of Guillain-Barré syndrome in adults?

Laboratory studies have shown that the Zika virus infects (or is trophic for) certain nerve cell types in particular. The Zika virus is mildly trophic for all neurons and glia, and probably the supporting cells, called radial glia. However, Zika has a stunning tropism for the neural stem cells, the progenitor cells of the developing brain.

By the time the fetus reaches the third trimester, and after birth, there are still neural stem cells in the brain, primarily in the hippocampus and in the cortex of the brain proper. The function of these cells is less clear, but we still have them.

Then the question is, "Are those cell types at risk in older infants, children, and adults?" Nobody has done any testing, for example, in adults after Zika infection to see whether they have memory problems. For the moment, the main concern is the third trimester and perhaps newborn infants who become infected with Zika.

Adults are supposed to recover fully. Children have a mature immune system within the first months of life and may then be able to fight off the Zika virus fast enough that it doesn't cause severe neurologic problems. So, the largest cohort of affected infants may be infants with early prenatal exposure and infants with severe microcephaly, but we don't know that.

This is unrelated to Guillain-Barré syndrome, which probably has a completely different mechanism of occurrence.


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