A poliolike condition that left more than 100 children in the U.S. at least partially paralyzed in 2014 is back, and not much more is known this time around, officials with the U.S. Centers for Disease Control and Prevention say. The CDC is not ruling out any possible triggers—from infections to toxins, autoimmune reactions to bug bites.

“We have not been able to find a cause for the majority of these” cases, Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Diseases, said Wednesday at a news conference. “And I’m frustrated that despite all of our efforts, we have not been able to identify the cause of this mystery illness.”

But researchers who have studied the muscle-weakening disease—called acute flaccid myelitis (AFM)—most closely say they now have a good understanding of its primary cause, although they still do not know how to treat the condition or halt its progression.

Scientists at the University of Colorado School of Medicine infected mice with a virus that was circulating during the 2014 AFM outbreak as well as during similar spikes of the disease in 2016 and this year. The virus triggered a paralyzing illness in the mice that “looked an awful lot like what we saw in children,” says Kenneth Tyler, chairman of the school’s Department of Neurology. Tyler thinks the virus, called enterovirus D68, has changed since it was first identified in 1962, becoming more dangerous. He has bred mice that develop paralysis after an infection with the current version of enterovirus D68 but not from earlier strains. He has tested a number of possible treatments on his mice but has not yet found any that make a significant difference in the course of their AFM-like illness.

Enterovirus D68 has been linked to some of the human cases of the disease, and although it is not the only cause, it has likely been a driving force behind the three recent outbreaks, says Kevin Messacar, an infectious disease physician and researcher at Children’s Hospital Colorado. He and Tyler say the CDC has been cautious about acknowledging enterovirus D68’s role in the outbreaks.

The virus’s symptoms are similar to those of the common cold and can include coughing, shortness of breath and other asthmalike breathing problems. “Many people will get the infection and very few will get the neurologic disease” that leads to paralysis, Messacar says. In rare cases, about a week after the infection, the child will develop weakness in his or her arms, legs or muscles of the face or throat, he says. Although there is no definitive diagnosis, doctors can identify AFM from a combination of symptoms and an MRI scan, which can reveal spine inflammation.

The CDC’s Messonnier describes AFM as “pretty dramatic” and says the federal agency is escalating its response compared with that in previous years. She also emphasizes it is extremely rare, striking about one in a million children, so parents should not panic—but they should seek medical attention if their child shows signs of sudden weakness or loss of muscle tone in their arms or legs. Since July the CDC has confirmed 62 cases of AFM in 22 states, and is investigating 65 more possible cases. One child with AFM died last year. Ninety percent of the cases have been in children, she says.

Messonnier did not address enterovirus D68 directly during the news conference and said the CDC has not yet had time to fully analyze the cases from this summer and fall. She said the cases were definitely not caused by the polio virus, which has not been found in any of the stool samples from affected children. There is no evidence of infection with the mosquito-borne West Nile virus either, she says, although she still encourages parents to send their children out with bug repellent. Some children with AFM recover full motion and strength—usually within a few months—whereas in others the nerve damage seems permanent, she says.

Mitchel Seruya, a surgeon at Children’s Hospital Los Angeles, says when he has operated on children with AFM, he has been amazed by how unresponsive their affected nerves are. He can hit them with an electric shock akin to touching a car battery, he says, but they do not move. That suggests to him the disease can completely wipe out the nerves. Seruya has operated on 15 children whose AFM-induced paralysis lasted at least three months. He redirects redundant nerves from other parts of the arm or abdomen to replace those lost to the disease. He says he has had very good outcomes in 14 of the 15 patients; the one girl who did not regain full function had “a suboptimal result, but [her parents are] happy she got something back.” But treatments for the infection itself remain elusive.

Mark Hicar, a pediatric infectious disease specialist and assistant professor at the University at Buffalo, S.U.N.Y., has treated two children with AFM, one in 2014 and one this year. Both were boys—one age six, one three; each had a common cold–like illness and spiked a fever about a day before they stopped using one leg. Neither boy tested positive for enterovirus D68—or A71, a similar virus also linked to AFM—but the tests are not definitive, he says. The three-year-old improved significantly within the first two days but then plateaued and is now back in the hospital being treated with anti-inflammatory medications, says Hicar, who is hoping the drugs will prevent the boy’s immune response from exacerbating the damage. But data on the efficacy of treatments is so thin that he says he is not sure whether the therapy is helping the boy or not.

A vaccine against enterovirus D68 would be scientifically possible, although may not be currently economically feasible, Messacar says. Polio is a very similar virus—and there’s a vaccine to protect against it. The Chinese have developed a vaccine against enterovirus A71, but it is not available in the U.S., he adds. Because AFM is so rare and has several potential causes, it would be hard for a company to make money on a vaccine, Messacar says.

The illness pattern is very similar to the polio outbreak of the 1940s and 1950s, says Andrew Pavia, chief of the Division of Pediatric Infectious Diseases at The University of Utah, except for its scale. Whereas polio infected tens of thousands of children, AFM has struck just over 100 every other year. Many people who had polio as children and recovered suffered muscle weakness again decades later. It’s unclear from mouse studies whether AFM symptoms will return in afflicted individuals, Tyler says.

According to the CDC, there were 120 confirmed cases of AFM in the second half of 2014, 22 in 2015, 149 in 2016 and 33 in 2017. “There’s been an increase in AFM in even-numbered years since 2014 that doesn’t appear to be random,” Messacar says, noting that enterovirus infections are most common from July through October in northern states, although they are less seasonal in the South. Research suggests dew point temperature—a combination of humidity and temperature—seem to affect the seasonality and geographic distribution of enteroviruses, he says.

Pavia agrees enterovirus D68 is the most likely cause for the majority of AFM cases, but “we have to wait and see” whether this year’s outbreak will follow the same pattern as 2014 and 2016. The primary methods for preventing infection with the virus are the same as for any cold: wash hands frequently, sneeze into your arm or elbow and try to avoid close contact with people who are ill, Pavia says.

Enterovirus D68 is probably contagious for about as long as the common cold, Messacar says. Whereas the viruses associated with AFM are contagious, AFM does not spread from person to person because it is a rare neurologic complication.

That was certainly true in Sarah Pilarowski’s family. Her eight-year-old son Liam got a horrible cold in 2014 but then recovered, but her six-year-old daughter, Lydia, developed a cold and fever that seemed to linger forever, says Pilarowski, a Denver pediatrician. When Lydia was not strong enough to hold an ear of corn in her left hand, Pilarowski got worried. Lydia was diagnosed with AFM and endured months of occupational and physical therapy, followed by psychotherapy to resolve her nightmares and lingering anxieties. She did not test positive for enterovirus D68, but Pilarowski is convinced both her children had the virus, which was making the rounds in the Denver area the summer her kids got sick.

Although there is not currently a vaccine or specific treatments with proved efficacy, there are still things researchers can do to combat AFM, Messacar says, such as keeping better track of enterovirus D68 and A71 infections, learning more about the link between the viruses and AFM, and systematically studying the efficacy of treatment and rehabilitation therapies being used. “Let’s start doing something about it. Let’s get funding,” he says. “Let’s not act like this is a surprise if this comes back in 2020, but let’s be more prepared.”

Editor’s Note: (10/18/18): For purposes of clarification, this story was edited and updated after its original posting.