This article is from the source 'nytimes' and was first published or seen on . It last changed over 40 days ago and won't be checked again for changes.

You can find the current article at its original source at http://www.nytimes.com/2016/08/24/health/zika-a-formidable-enemy-attacks-and-destroys-parts-of-babies-brains.html

The article has changed 3 times. There is an RSS feed of changes available.

Version 0 Version 1
Zika, a Formidable Enemy, Attacks and Destroys Parts of Babies’ Brains Brain Scans of Brazilian Babies Show Array of Zika Effects
(about 11 hours later)
The images tell a heartbreaking story: Zika’s calamitous attack on the brains of babies — as seen from the inside.The images tell a heartbreaking story: Zika’s calamitous attack on the brains of babies — as seen from the inside.
With a macabre catalog of brain scans and ultrasound pictures, a new study details the devastation done to 45 Brazilian babies whose mothers were infected with Zika during pregnancy. The study, published Tuesday in the journal Radiology, is the most comprehensive collection of such images so far, and it reveals a virus that can launch assaults beyond microcephaly, the condition of unusually small heads that has become the sinister signature of Zika. A study of brain scans and ultrasound pictures of 45 Brazilian babies whose mothers were infected with Zika in pregnancy shows that the virus can inflict serious damage to many different parts of the fetal brain beyond microcephaly, the condition of unusually small heads that has become the sinister signature of Zika.
Most of the babies in the study were born with microcephaly, but many of them also suffered other impairments, including damage to important parts of the brain: the corpus callosum, which connects the two hemispheres of the brain; the cerebellum, which plays a significant role in movement, balance and speech; the basal ganglia, which are involved in thinking and emotion. The images, published Tuesday in the journal Radiology, also suggest a grim possibility: Because some of the damage was seen in brain areas that continue to develop after birth, it may be that babies born without obvious impairment will experience problems as they grow.
“It’s not just the small brain, it’s that there’s a lot more damage,” said Dr. Deborah Levine, an author of the study and a professor of radiology at Harvard Medical School in Boston. “The abnormalities that we see in the brain suggest a very early disruption of the brain development process.” “It really brings to the forefront the importance of truly understanding the impact of Zika virus and the fact that we need to follow children who not only are exposed to Zika in pregnancy, but even those who don’t appear to have any complications at birth,” said Dr. Catherine Y. Spong, chief of the pregnancy and perinatology branch of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, who was not involved in the study.
The findings also raised worrisome concerns about whether babies born without such obvious impairments could develop brain damage as they grow. For example, almost all the babies in the study had problems in the cortex, including clumps of calcium and neurons that did not reach the right location in the brain. Because the cortex keeps developing after birth, Dr. Levine said, “we’re concerned that there might be mild cases that we haven’t seen yet, and we should keep monitoring the babies after birth to see if they have cortical abnormalities.” Most of the babies in the study were born with microcephaly, although three were not. Each also suffered other impairments, almost all of which emerge earlier than microcephaly because a smaller head is really a consequence of a brain that has failed to develop fully or has been damaged along the way, experts said.
The images studied came from 17 babies whose mothers had a confirmed Zika infection during pregnancy and from 28 without laboratory proof but with all indications of Zika. Dr. Levine worked with colleagues in Brazil, which has had more than 1,800 cases of Zika-related microcephaly, to analyze images from the Instituto de Pesquisa in Paraiba in the northeastern part of the country. Three of the babies died in the first three days of life, and researchers studied their autopsy reports. “The brain that should be there is not there,” said Dr. Deborah Levine, an author of the study and a professor of radiology at Harvard Medical School. “The abnormalities that we see in the brain suggest a very early disruption of the brain development process.”
The scans show the range of Zika’s brain targets, some of which experts knew about, including the corpus callosum, which facilitates communication between the two hemispheres; the cerebellum, which plays a significant role in movement, balance and speech; and the basal ganglia, which are involved in thinking and emotion.
“I think we were all aware that Zika causes brain abnormalities, but it’s been more generic,” said Dr. Rita Driggers, an associate professor of gynecology and obstetrics at Johns Hopkins University School of Medicine, who was not involved in the study. “Now we know more specifically what we’re looking for in terms of brain abnormalities before the microcephaly occurs.”
Together, the images provide a more detailed guide that might help doctors diagnose Zika-related fetal damage earlier — possibly in the second trimester at a point early enough to help women decide whether to terminate a pregnancy, said Dr. Adre du Plessis, director of the Fetal Medicine Institute of Children’s National Health System, who was not involved in the study.
At the same time, the study may eventually help doctors rule out damage caused by Zika infection. “If there’s any uncertainty on ultrasound, we’re concerned that couples that are not risk-takers and don’t want to gamble might be terminating perfectly normal babies, which is of course a concern to us,” he said. “So there is a lot riding on being able to image accurately.”
One finding that surprised several experts could become an especially meaningful diagnostic clue. Many infections that target the brain produce clumps of calcium, called calcification. But in Zika-infected babies, calcification often occurred in an unusual place: at the intersection of the gray matter of the outer layer of the brain, the cortex, and the white matter of the layer just below that.
That pattern could emerge as a particular stamp of Zika infection, experts said. Dr. Spong said that because the area involves two different types of blood vessels, it might suggest that Zika targets vascular areas.
And it could signal why the virus wreaks such ruthless effects on brain development.
“That is a critical area for brain formation,” Dr. du Plessis said. At the gray-white matter intersection, healthy cells “release certain chemicals that allow the neurons to find their precise destination.”
“When that gets scrambled they end up in the wrong place, they don’t function the way they should, and messaging and connectivity is severely deranged.”
Most of the babies in the study had such damage in the cortex, which plays a crucial role in learning, memory and coordination, and also continues to develop at least through infancy, suggesting that Zika-infected babies who seemed to emerge unscathed might be vulnerable to difficulties as they grow.
Another abnormality seen in most of the babies’ brains involved the ventricles or cavities of the brain becoming so full of cerebrospinal fluid that they “blow up like a balloon,” Dr. Levine said. The ventricles may be filling with fluid because Zika is obstructing their ability to drain normally, or because damage to other brain areas leaves a kind of vacuum that the enlarged ventricles fill.
The fluid-filled ventricles can make the head size seem normal earlier in pregnancy, Dr. Levine said. But as scans of one pregnancy taken at 36 weeks gestation show, the fluid can be so prominent that the scan shows what “looks like the skull and very little brain tissue inside it,” she said.
At some point, these ventricles, “like a balloon, can pop,” she said. And if they do, “the brain will collapse on itself.”
The images come from 17 babies whose mothers had confirmed Zika infection during pregnancy and 28 without laboratory confirmation but with all indications of Zika infection. Dr. Levine worked with colleagues in Brazil, which has more than 1,800 cases of microcephaly, to analyze images from the Instituto de Pesquisa in Paraiba in the northeastern part of the country. Three of the babies died in the first three days of life, and researchers studied autopsy reports in those cases.
The images include scans of twin girls, who both developed microcephaly. The pictures show folds of overlapping skin and a sloping forehead, indications not only that the brain is smaller, but also that the forebrain has not developed normally, Dr. Levine said.The images include scans of twin girls, who both developed microcephaly. The pictures show folds of overlapping skin and a sloping forehead, indications not only that the brain is smaller, but also that the forebrain has not developed normally, Dr. Levine said.
The researchers said they are making many of the images public so doctors around the world will have a better idea of what to look for in the brains of fetuses and newborns afflicted with the virus. Images of another baby girl show contracted hands and arms, the result of another common symptom. Zika seems to damage the nerves in a developing fetus so that sometimes “muscles aren’t developing normally because they don’t have the nerve impulses to move normally,” she said. “And then when they’re born, they’re stuck in this contracted position.”
The study suggests that Zika is a formidable enemy, able to strike in many ways. Dr. Levine, who is also director of obstetric and gynecologic ultrasound at Beth Israel Deaconess Medical Center, described its three-pronged attack. Dr. Levine said the images suggest that Zika is like a formidable enemy able to do damage in three ways: keeping parts of the brain from forming normally, obstructing areas of the brain, and destroying parts of the brain after they form.
The virus causes dysgenesis, in which parts of the brain do not form normally. It causes obstruction, primarily because it keeps the ventricles or cavities of the brain so full of fluid that they “blow up like a balloon,” she said. And it destroys parts of the brain after they form. With such a vicious and unpredictable virus, “it’s key to realize that Zika is more than microcephaly, that there’s a number of other abnormalities as they’ve shown in this paper, and its effects are going to be even more broad,” said Dr. Spong, whose agency has begun a study of what will ultimately be 10,000 babies born in Zika epidemic areas including Brazil and Puerto Rico.
“The brain that should be there,” Dr. Levine said, “is not there.” “It’s going to be essential to follow them to look at their development, to look at their ability to learn, to look at hearing problems, balance problems, behavior problems, all those issues, to make sure that we don’t miss anyone.”
The baby below was one of three in the study whose head size was not small enough to meet the medical definition of microcephaly. But that, said Dr. Levine, is likely because his ventricles are filled with cerebrospinal fluid that has been unable to drain.
“The ventricles have blown up, and they’ve kept the skull even bigger,” she said.
In the brain scans, taken at 36 weeks into pregnancy and one day after birth, fluid is so prominent, “it looks like the skull, and very little brain tissue inside it,” she said. On the top of the baby’s head are folds indicating that the head was once bigger or that the skin continued to grow as the head stopped.
“There’s too much skin for the size of the head,” Dr. Levine said.
What will happen as this baby develops is unclear. Ventricles, she said, “like a balloon, can pop.” And if they do, “the brain will collapse on itself.”
An accompanying video shows a series of scans of the brain of the same baby taken one day after birth. It essentially provides a tour of the brain from bottom to top, Dr. Levine said. At about 3 seconds into the video, the images reveal a head so filled with fluid-enlarged ventricles that it is difficult to see signs of other brain matter.
The baby girl below was born with microcephaly. In the brain scan, the arrows point to calcium deposits in the basal ganglia, a very deep part of the brain, Dr. Levine said. The L-shaped white area above and to the left of the arrows shows calcification at the intersection of the brain’s gray matter and white matter, a juncture that the study found was commonly damaged, for reasons unclear.
The baby’s contracted hands and arms show another common symptom, Dr. Levine said. Zika seems to damage the nerves in a developing fetus so that sometimes “muscles aren’t developing normally because they don’t have the nerve impulses to move normally,” she said. “And then when they’re born, they’re stuck in this contracted position.” This baby, she said, “probably can’t move her hands.”
The twins included in the study both developed microcephaly. While in some cases, one twin will develop microcephaly and the other will not, in this case, the twins sustained a similar degree of brain damage, suggesting that in their mother’s womb, “they both got infected at the same time,” Dr. Levine said.
The brain scans of the twin girls show that the babies have little or no corpus callosum to help one side of the brain communicate with the other.
“The corpus callosum is very important,” Dr. Levine said. “It is the largest structure that connects the two sides of the brain.”
Abnormalities in the corpus callosum were found in 38 babies. “In some of them I’m sure it wasn’t there,” she said. “That either means it never formed or it was destroyed.”