Tuesday, September 27, 2016

Zika virus and microcephaly 3

Antonio Augusto Moura da SilvaComments to Author , Jucelia Sousa Santos Ganz, Patricia da Silva Sousa, Maria Juliana Carvalho Doriqui, Marizelia Rodrigues Costa Ribeiro, Maria dos Remédios Freitas Carvalho Branco, Rejane Christine de Sousa Queiroz, Maria de Jesus Torres Pacheco, Flavia Regina Vieira da Costa, Francelena de Sousa Silva, Vanda Maria Ferreira Simões, Marcos Antonio Barbosa Pacheco, Fernando Lamy-Filho, Zeni Carvalho Lamy, and Maria Teresa Seabra Soares de Britto e Alves.   Early growth and neurologic outcomes of infants with probable congenital Zika virus syndrome.  Emerging infectious diseases.  Volume 22, Number 11—November 2016.

We report the early growth and neurologic findings of 48 infants in Brazil diagnosed with probable congenital Zika virus syndrome and followed to age 1–8 months. Most of these infants had microcephaly (86.7%) and craniofacial disproportion (95.8%). The clinical pattern included poor head growth with increasingly negative z-scores, pyramidal/extrapyramidal symptoms, and epilepsy.


"These babies do not catch up as they grow," says Dr. Antonio Augusto Moura da Silva of the Federal University of Maranhao, Sao Luis, Brazil.

He's describing the findings from a study of 48 babies whose mothers were believed to have been infected with the Zika virus. Forty-two of the children were diagnosed with microcephaly. The study, on the early neurological growth pattern of the infants, will be published in the journal Emerging Infectious Diseases in November but was released early online.

The infants were studied for about four months and up to 8 months of age. Born below average on measures of weight, length and head circumference, they fell even further below average as time passed.

"As they grow, they get worse, and we would expect that they will continue to fall further behind," says da Silva, who was part of the research team. "We were expecting some degree of falling behind average, but we were astonished by the degree to which they were lagging behind."

Even when babies exposed to the Zika virus in the uterus are born with normal-size heads, they might suffer other forms of brain damage. In fact, da Silva says, six of the Zika-infected babies in the study did not have microcephaly. And yet, when examined with electroencephalographs to measure brain activity, they showed evidence of brain damage that caused problems including seizures and involuntary muscle movements.

Most of the mothers of the 48 babies were thought to be infected with Zika during the first trimester of their pregnancy. And because the babies were enrolled at a regional center that assists children with neurological disorders, their symptoms may be among the most severe. Some questions are still unanswered, da Silva says: If an infant is infected after birth, is the virus still able to damage the baby's brain? And what will be the long-term consequences for infants born with less severe cases of microcephaly? "So far, we've studied only the tip of the iceberg," da Silva says.

Courtesy of Doximity


  1. Recently, reports of newborns without microcephaly at birth but with abnormal results on neurologic exams have surfaced. Ventura and colleagues concluded that "microcephaly should not be a required criterion for congenital Zika virus infection diagnosis." The prognosis for infants without microcephaly at birth and the correlation between this condition and the timing of maternal Zika infection are areas of great interest, although few data are available. In a media briefing, the CDC reported that babies with so-called late-onset microcephaly have been born to mothers infected during the third trimester of their pregnancies.

    Medscape: What do we know about neonatal neurodevelopmental effects when the mother is infected with Zika during pregnancy?

    William B. Dobyns, MD: We know a lot about the children who have clear-cut microcephaly at birth, but less about children who have a normal head size at birth and then develop microcephaly. I'll start with the former.

    Late last year, reports started appearing from Brazil about an increase in the frequency of babies with microcephaly at birth, particularly in northeastern Brazil, where the Zika virus was spreading in an epidemic fashion. The Brazilian Ministry of Health clearly demonstrated that there was an increased rate of microcephaly. After that, we got a few scattered reports of what the babies looked like through photographs and some prenatal studies. The reports, which continued well into 2016, persistently talked about microcephaly as if that was the diagnosis.

    But that was just scratching the surface. The physicians who were initially writing about the affected Brazilian infants had no background in pediatric developmental disorders. Reports gradually appeared over the next couple of months from expert Brazilian specialists, and they started to describe the problem more accurately. With a group of doctors, including some from Brazil, I have submitted a paper on 57 children with very detailed evaluations of what the kids look like clinically and radiologically, on brain scans.(continued)

  2. (continued)In infants with a small head size at birth, we are now able to recognize a congenital Zika syndrome, the preferred diagnostic label that is now being substituted for the very inadequate designation of microcephaly. Babies with congenital Zika syndrome have multiple other features.

    When you examine the babies, their head sizes vary, but they are often very small. In our 57 children with microcephaly, head circumferences ranged from 2 standard deviations below the mean to 7 standard deviations below the mean(and 85%–90% were more than 3 SDs below the mean). This means that the head sizes of a large majority of these children are not even borderline; they are very small. There is a spectrum. Although we do see children whose head sizes are only slightly small, most are very small.

    Small head size is the first of multiple features. Clinically, these babies all have marked developmental delays and very abnormal neurologic exams. Very early on, they are spastic and stiff—that's cerebral palsy—and they tend to be very irritable and tremulous. Most have significant feeding problems.

    These abnormalities don't take months to show up, as in some other neurodevelopmental disorders. The neurologist was able to describe abnormalities on his first examination of these babies.

    Medscape: What is happening in babies with so-called shrinking brains and collapsing skulls?

    Dr Dobyns: About half of these babies have a condition called fetal brain disruption sequence. Their heads have a very striking appearance; the skull appears to have collapsed over the (shrinking) brain…

    The frontal and parietal bones collapse over each other, and the occipital bone (which doesn't have a suture line down the middle) no longer articulates with the other skull bones. We call this occipital bone, which is left sticking out, an occipital shelf…

    Medscape: What are the radiologic features of congenital Zika syndrome?

    Dr Dobyns: On imaging, there is a significant loss of brain volume. No matter how small their heads are, their brains are usually even smaller. We typically see excess cerebrospinal fluid surrounding the brain and enlarged ventricles. This is what happens when there is not enough brain tissue during critical developmental periods.

    All affected infants have cortical malformations, and these are not just the effect of disruption. For a cortical malformation to develop, there must be damage to certain types of critical developmental cells, called radial glial cells, in the late first or early second trimesters of pregnancy. A radial glial cell is an early cell type in the brain that sends a fiber from the ventricular zone (the base—the deepest layer of the brain) up to the surface. Developing nerve cells essentially climb up these radial glial cells to get to the cortex. Radial glial cells have two functions. They are the progenitor cells that give rise to the neurons and other proliferating brain cells and are the scaffolding of the developing embryonic brain, enabling the migration of neurons to other parts of the brain. If you infect and lose radial glial cells, not only is the number of neurons reduced, the ladder is also lost.