BALTIMORE — For most of the children who fell ill last year during an outbreak of enterovirus, the symptoms were relatively mild — fever, runny nose, coughing and sneezing.
But then there was this mystery: More than 100 kids suffered an unexplained, polio-like paralysis that struck quickly but even now continues to stump researchers and upend the lives of the families across the country.
For Priya Duggal and her colleagues at Johns Hopkins University, the biggest puzzle is why those children became paralyzed while their brothers and sisters, who also were exposed to the virus, escaped largely unscathed.
“Is there something in these [paralyzed] kids that is different than the kids that are fine?” said Duggal, a genetic epidemiologist. “Maybe it’s the host, and the virus is a trigger that sets off the paralysis. . . . Maybe it’s something in their genetic makeup.”
Duggal and fellow researchers Aaron Milstone and David Thomas, who are gathering DNA from patients around country, are among the experts trying to find answers for families affected by the paralysis.
Doctors believe the condition, known as “acute flaccid myelitis,” is linked to last year’s nationwide outbreak of enterovirus D68, or EV-D68 — part of a family of viruses that appears in summer and fall — but they haven’t proved a connection. The outbreak probably sickened millions of children and sent thousands to doctors’ offices and emergency rooms with severe respiratory problems.
Many of the children with paralysis also got the virus, but initially they weren’t any sicker than their siblings or peers — until they experienced sudden muscle weakness days later.
Some of the children, whose average age is a little younger than 8, have lost the use of an arm or a leg. Some have ended up in wheelchairs or on breathing machines. Although some have improved, according to the Centers for Disease Control and Prevention, almost none have fully recovered.
Recently, as part of the Hopkins genetic study, Duggal sent DNA kits to some of the families wrestling with their new reality. One of the kits arrived at the Sheehan residence in Welches, Ore., a hamlet near Mount Hood.
Bailey Sheehan, then 7, had woken up Oct. 21 with a headache and pain in her neck and back. She soon developed a respiratory infection. The rest of the family — her parents; brother Caleb, 5; and sister Andi, 4 months — also came down with flu-like symptoms.
Everyone but Bailey recovered. Her respiratory problems cleared up, but the nerve pain got worse. One morning she had trouble lifting her arms. She later collapsed while trying to get up from the couch. “Mom,” she shouted, “my leg’s not working!”
Mikell Sheehan rushed her daughter to Randall Children’s Hospital in Portland, an hour’s drive away. Bailey’s right arm had grown weak from shoulder to elbow; her right leg was numb from ankle to knee. She underwent tests, including for West Nile virus and Guillain-Barré syndrome. Physicians determined that Bailey had been infected by enterovirus D68, but they couldn’t say for sure whether that caused the paralysis.
“The doctors just tell us they don’t know [the cause],” Sheehan said. “It’s the most terrible feeling to have to tell your little girl, who’s in so much pain and whose leg won’t work, ‘I don’t know how to fix it and neither do the doctors.’ ”
In her hunt for answers, Sheehan has scoured medical literature, called experts at the CDC and traded information online with other parents whose children have been affected. She has written to President Obama and other elected officials, talked to reporters, and enrolled her daughter in studies like the one at Johns Hopkins.
Nearly four months after her ordeal began, Bailey, now 8, still undergoes intense physical therapy six days a week. She’s learning to ride a bike again; her paralyzed foot must be strapped to the pedals. She recently returned to second grade but still uses a leg brace and a walker.
Other children are having similar struggles.
A 13-year-old boy from Joplin, Mo., spent months in a wheelchair after he became paralyzed in September; he still uses a cane to walk. A first-grade boy in Tennessee lost the use of his right arm. Another girl in Oregon was almost completely paralyzed from the neck down.
In Seabrook, N.H., Dan Dugan, 13, spent nearly 50 days in Boston hospitals last fall after he had paralysis in his left arm and leg. Friends and businesses organized fundraisers. A store posted a sign saying, “Pray for Danny.” After months of rehabilitation, Dan, the youngest of six children, was able to move from a wheelchair to a walker and he recently began using special crutches.
“He’s got a good attitude,” said his father, Patrick Dugan, a mechanic who owns Pat’s Towing in Seabrook. “He’s not down about what happened. He has kind of accepted everything.”
Mary Anne Jackson, chief of infectious diseases at Children’s Mercy Hospital in Kansas City, Mo., is one of the researchers trying to explain the inexplicable condition.
When several cases surfaced at her hospital last year in children between the ages of 4 and 13, she and other doctors suspected that enterovirus was the culprit.
“We looked at blood, spinal fluid, stool — thinking we’d find [the EV-D68] virus,” Jackson said. “It just wasn’t there.”
They also saw on MRIs what other doctors nationwide were noticing: distinctive damage to a specific part of the spinal cord. “That’s the classic feature of polio,” Jackson said. “On the scan, it looks like polio.”
Doctors in Kansas City and at other children’s hospitals are examining hundreds of old MRIs of children who had suffered from limb weakness to see if the same pattern on the images may have been overlooked in the past.
Researchers at the CDC are equally perplexed.
In any given year, it’s not uncommon for several cases of acute flaccid paralysis to occur, said Jim Sejvar, a CDC neuroepidemiologist. But when the agency queried doctors around the country, he said, “almost unanimously, you get a response that they’ve really never seen anything like this.”
Like other specialists, Sejvar thinks there’s a striking association between EV-D68 and the sudden onset of paralysis. “If you overlay the epidemiological curves,” he said, “they are almost identical.”
CDC scientists haven’t had any more luck than other researchers in finding a direct link. They recently developed a test for antibodies in the blood that was designed to show whether children who became paralyzed were more likely to have had EV-D68 than other children.
But when officials tested the blood of children who had experienced severe respiratory problems and other flu-like symptoms from last fall and from previous years, nearly all of them possessed antibodies to the virus, offering no new evidence that EV-D68 was the cause of the paralysis cases. It was another dead end.
“We were really hoping that would pan out,” Sejvar said. “Everybody wants an answer.”
The CDC is putting together a long-term study to track the 112 children it has identified so far with the condition — how their paralysis progresses, whether they improve over time, which treatments work.
Kevin Messacar, an infectious-diseases physician at Children’s Hospital Colorado in Aurora, will be part of that effort. He and several colleagues recently published a study in the Lancet describing a dozen children with the disease who were treated at the hospital. Their findings suggested “the possibility of an association” between EV-D68 and the neurological problems that followed, saying it could represent a newly emerged strain or a viral mutation. “We don’t have an answer, but I think science progresses by generating hypotheses and theories that get further tested,” Messacar said.
He and others have been helping set up a multidisciplinary clinic where paralyzed children and their families can receive medical care but also can come together for emotional support while they wait for answers.
“It’s got to be very frustrating as a parent to not know,” Messacar said. “Our obligation is to be honest with them. At this time, there’s so much that’s unknown about a new condition like this. Our job is to provide physical and psychological support to help them deal with this.”
Hopkins researchers are eager to compare the DNA of children who experienced paralysis with that of their siblings who didn’t. “It’s highly likely that children in the same family got the same virus. . . . But one got this severe outcome, and one only got a viral infection,” Duggal said. “It raised flags to us that it potentially could be something genetic.”
Sheehan thinks that theory makes sense. On Feb. 17, in between Bailey’s doctors’ visits and physical therapy sessions, she collected saliva samples from Bailey and Caleb in two plastic tubes from Hopkins. She slipped them into a pre-addressed envelope and dropped it off at a post office.
She knows it could take a year or longer for the study to produce results, and even then the answers might remain elusive. But knowing that experts are working on the mystery helps soothe what has become her biggest fear.
“I’m scared,” she said, “that Bailey and these other kids are going to be forgotten.”