In Babies With Microcephaly, Unique Damage Wreaked By Zika
Dr. Adriana Scavuzzi, the women’s health coordinator at IMIP hospital in Recife, Brazil, points to calcium deposits in the brain scan of a microcephaly patient. (Michelle Mizner/FRONTLINE)
From the outside, babies born with microcephaly all have the telltale features: Doll-sized heads on human-sized bodies, their foreheads sloped precipitously away from their faces.
But on the inside, the babies’ brains can differ dramatically depending on what specifically has caused their damage. And the injury caused by Zika is unique enough that doctors believe they may soon be able to identify it as the likely culprit in a case by looking at brain scans alone.
There are a handful of classic causes of microcephaly: Rubella, cytomegalovirus, genetics, exposure to certain toxins, and maternal drug use, among others. When Brazilian doctors first noticed an unusual number of babies born with microcephaly last year, they initially wondered if it was due to an uptick in one of those causes.
But that theory was quickly rejected, in part because their tiny patients’ brain damage was notably different than what they were accustomed to seeing in microcephaly patients. In case after case, they were observing a new, specific pattern of damage.
There is now widespread scientific consensus that the source of these new microcephaly cases is the Zika virus, a recent arrival in the Americas that rarely causes problems for adults, but can tear asunder the developing nervous system of a fetus. On Wednesday, the director of the Centers for Disease Control and Prevention said there was no longer ambiguity on this point: “There is no longer any doubt that Zika causes microcephaly,” said Dr. Thomas R. Frieden, the agency’s director.
Neuroscientists believe the virus has a taste for neural stem cells, the cells from which a fetus’s brain grows in utero. In one study, researchers put neural stem cells and Zika virus in a petri dish together. In three days, 90 percent of the stem cells were infected by the Zika virus.
“Not only that, once they got infected they turned into a so-called viral factory, meaning they actually produced more virus,” said Dr. Guo-li Ming, a neuroscientist at Johns Hopkins’ Institute for Cell Engineering.
Zika’s damage is likely worst when it hits a fetus in the first trimester of pregnancy, the crucial time in brain development. By the time the baby’s immune system begins to combat the virus, much of the damage has been done.
Doctors cannot tell if a baby has microcephaly until much later in the pregnancy — the signs only begin appearing near the third trimester. At that point the Zika virus has long since come and gone; no trace of it remains in the baby’s blood stream. Like archaeologists investigating a ruined village, doctors must piece together what may have happened from the wreckage left behind.
The first clue that Zika may have ransacked a baby’s brain is the ventricular system, said Dr. Ana Van der Linden, one of the Brazilian pediatric neurologists who first took note of the epidemic. The ventricles are a system of canals in the brain filled with cerebrospinal fluid. In a typical infant, the largest of the ventricles is under a centimeter in diameter. In the microcephaly cases Van der Linden has seen in recent months — which now count in the hundreds — they are immensely swollen; brains scans show them taking up a third or more of the width of the brain.
Van der Linden paired with Johns Hopkins researcher Andrea Poretti for a study that examined 23 babies, all of whom had microcephaly linked to Zika. In all 23 cases, the babies had inflated ventricles.
As these cavities bloat like balloons, they squeeze the developing cerebral cortex — the part of the brain responsible for intellectual development, said Dr. Adriana Scavuzzi, the women’s health coordinator at IMIP hospital in Recife, Brazil, the epicenter of the microcephaly outbreak.
The second clue to Zika-instigated damage is that the brain tissue is riddled with calcium deposits. These deposits are “a kind of scar that damages the brain” that don’t appear in normal brains, Scavuzzi said.
Calcium deposits can also appear in babies whose microcephaly was caused by other viruses. But the precise pattern of deposits in the brain is different, said Van der Linden. For instance, in cytomegalovirus, calcium deposits typically clump tightly around the ventricles, whereas the Zika-caused cases often develop right at the juncture of the baby’s white and grey matter — the two types of tissue in the brain.
In her office in Recife, Scavuzzi pulled up a brain scan on her computer of a microcephalic baby. Her finger traced a loose halo of bright white stains — the calcium deposits — and then pointed to a pair of large black spheres in the center of the scan — the enlarged ventricles. The slender ring of grey in between, she said, were the neurons that had managed to develop around the destruction wreaked by the infection.
“Radiologists say that it’s the same pattern” in all the Zika-infected babies they see, Scavuzzi said. “According to this scan we assume the baby won’t have a normal development at all. They will be deeply injured by this virus.”
Poretti said his team is now taking MRI images of 100 microcephalic babies’ brains, which will give far more detailed insight into these patterns than the CT scans that have been done so far.
Zika’s devastation does not stop at the brain. Ophthamologist Camila Ventura has been studying the eyes of babies born with microcephaly in Recife. “The last time I counted I had seen 149 babies with microcephaly,” she said. She and other researchers have found that these babies are frequently vision-impaired. This is not surprising: Other causes of microcephaly can also harm developing eyes.
But the sight of Zika-infected babies is being affected in special ways. The specific damage to their retinas and optic nerves is distinctive, and unlike the damage seen in their counterparts. “The differences are subtle but clear,” Ventura said.
These subtle, clear differences in the brain and optic system are already proving useful to doctors as they try to parse out which babies’ microcephaly was triggered by the classic causes, and which can be attributed to Zika.
As doctors zero in on the specific patterns of damage done by various causes, they are beginning to identify Zika-caused microcephaly simply by looking at those patterns. This is useful because to date, there is no easy way to tell if a baby was infected with the Zika virus in the womb.
“In the future we want to make a spectrum” of specific damage caused by each culprit of microcephaly, Ventura said. For instance, one kind of lesions on the optic nerve would indicate that rubella caused the disease; another would imply Zika, she said. “You would look at it and you would know straight away what caused this damage.”