Dallas News
written by Anna Kuchment and Seema Yasmin and AP
Thursday October 16, 2014
Last year, Dr. Benjamin Greenberg noticed some unusual symptoms in the patients he was seeing. A neurologist at UT Southwestern Medical Center, Greenberg treats children with rare forms of paralysis.
He noticed that a handful of his patients, who fly to see him from different parts of the country, had floppy limbs. But they had none of the other signs that typically accompany sudden paralysis, like muscle stiffness and a certain pattern on MRI scans. Many had recently had colds. Few improved with treatment.
Colleagues in other states were seeing a similar pattern.
As anxiety rages over the Ebola case in North Texas, pediatricians and infectious disease experts are trying to solve a medical mystery that has sickened far more Americans — most of them children, including an 11-year-old boy in Allen.
A once-rare virus, enterovirus D68, or EV-D68, has spread across 46 states and the District of Columbia and infected nearly 700 individuals. Most have typical cold symptoms, but some have ended up in hospitals on ventilators.
On Friday, a 21-month-old girl died from EV-D68, according to Children’s Hospital of Michigan in Detroit. In late September, a New Jersey state medical examiner said that a 4-year-old boy died of the virus. The Centers for Disease Control and Prevention confirmed that the New Jersey boy and four other people infected with the virus have died, but it’s not clear what role the virus played.
Greenberg believes the virus may also be behind 17 cases of an unexplained neurologic illness that the CDC is investigating. In those cases, children suffered damage to their spinal cords and brainstems that caused double vision, facial drooping and weakness in the arms and legs.
No direct evidence
So far, there is no direct evidence of a link. Last spring, doctors at Lucile Packard Children’s Hospital at Stanford University reported five cases of a “polio-like syndrome” in children. Two of the patients had evidence of EV-D68 in their nasal passages.
On Oct. 3, the CDC reported a cluster of nine patients in Colorado with similar symptoms; four tested positive for EV-D68.
To prove that EV-D68 causes paralysis, researchers would have to find the virus in a patient’s spinal fluid. No one has done that yet.
But Greenberg believes the possibility remains alive. Viruses like EV-D68 — which contains DNA’s more fragile cousin RNA — degrade very rapidly once sampled in a spinal tap.
“Literally from the time it hits the tube to walking to the lab, the RNA could be all gone,” said Greenberg. The fact that the CDC has not found EV-D68 in spinal fluid does not mean it wasn’t once there, he said.
There are other theories as to what may be causing the paralysis. Greenberg believes it is either EV-D68 or another enterovirus. Others believe it may be a new pathogen that researchers have not yet identified. A third idea is that the damage results from a mistaken immune response that the body mounts after an infection.
Dr. Avindra Nath, an expert on infections of the nervous system at the National Institutes of Health, believes the virus theory makes more sense given the three-day to one-week time period between the start of cold symptoms and the first signs of muscle weakness in some patients.
“It’s a very short interval,” he said. “There’s not that much time to have a massive immune response.”
Starts with a cold
The children who have developed paralysis first came down with a cold. Bryan Sotelo of Allen developed a cough and fever in late July. One week later, his mother, Yadira Garcilazo, noticed he’d stopped moving his right arm.
She took him to the emergency room at Children’s Health Children’s Medical Center, where his illness progressed rapidly.
“In three days, he could not move at all,” she said.
He spent a month in intensive care. Today, Bryan — for whom CDC lab tests for EV-D68 are still pending — is recovering at an inpatient rehabilitation center. While Bryan still cannot walk and needs a tracheostomy to help his breathing, Garcilazo says her son has managed to reverse around 75 percent of his paralysis and is continuing to get better.
Few of the other patients have recovered.
Dr. Samuel Dominguez, a pediatric infectious disease expert at Children’s Hospital Colorado near Denver, said that of the 10 cases his hospital has seen (the nine it originally reported to the CDC plus one new one) since Aug. 8, only one has resolved.
That patient had the mildest symptom: double vision. “The other patients really have had very minimal improvement, if any,” he said. Three remain hospitalized and in rehabilitation. One has needed a tracheostomy and feeding tube.
“It will take months before we know what will happen with these children,” he said.
MRI scans of the neurology cases have shown damage to patients’ lower motor neurons, cells that extend from the spinal cord to the muscles. In some cases, there have been abnormalities in the brain stem as well.
Dr. Daniel Pastula, a CDC neurologist in Fort Collins, Colo., reviewed MRI scans for the nine children in Colorado. “My first impression was that this was something very rare,” he said.
The spinal cord is a long rope-like structure that connects the brain to the muscles and nerves of the rest of the body. The inner core, made up of gray matter, is enveloped in white matter. Most of the cases in Colorado had abnormalities in the gray matter part of the spinal cord. “It was the spinal cord changes that were most odd,” said Pastula.
Largest U.S. outbreak
The clusters of paralysis have occurred against a backdrop of the largest outbreak of EV-D68 that the United States has seen.
First isolated in California in 1962, the virus caused only 26 reported infections between 1970 and 2005. Since then, cases have climbed slowly, until this year.
In 2012, researchers from Columbia University’s Mailman School of Public Health noted a surge of cases in Japan, the Philippines, the Netherlands and pockets of the U.S. The report also identified new genetic variations of the virus, which may help explain the wide range of symptoms associated with it.
Among the many unanswered questions: Has this been part of a one-time outbreak, or will the disease return season after season? Some viruses, like Spanish influenza, have seemingly come out of nowhere and then vanished. Polio would wax and wane, causing large and small outbreaks in unpredictable patterns.
Dominguez said the CDC is “working frantically” to get answers.
Mark Pallansch, director of the CDC’s Division of Viral Diseases, has sent questionnaires to doctors in search of new cases. The surveys will help determine which neurologic cases are linked and what is causing them. The agency is also asking doctors to send throat swabs, spinal fluid, blood and other samples to the CDC for testing.
The number of cases will rise next week, said Pallansch, as doctors send back the questionnaires. While EV-D68 is one possible cause of the neurologic illness, “at this point the data is inconclusive,” he said.
Pallansch said the agency has developed a new test for EV-D68 that specifically detects the virus and is much quicker, providing results in two days instead of one week.
“The current test detects most enteroviruses and rhinoviruses but can’t identify them specifically,” said Pallansch. The CDC is currently testing around 100 specimens a day for EV-D68 but they will be able to do “many times that amount with less than half the people” using the new test, he said.
The new test will be used to get rid of the backlog of specimens that are waiting to be tested and could be sent to state health departments so that they can test specimens themselves.
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