In 2014, a rare polio-like illness that attacks the nervous system of its often young victims first emerged in the U.S.—an illness with no clear cause, according to health agencies like the Centers for Disease Control and Prevention. Now, scientists at the University of California San Francisco say they’ve unearthed the most conclusive evidence to date that two viruses closely related to polio are to blame.The illness is called acute flaccid myelitis, or AFM. As the name indicates, victims experience a sudden weakness of their muscles, which can then become full-on paralysis. This typically affects the arms and legs but sometimes facial muscles and the throat as well. In the most serious of cases, the paralysis can cause life-threatening respiratory failure. Other times, people are left with lifelong neurological symptoms. Since 2014, around 600 children in the U.S. are thought to have developed AFM, but cases have been traced back as far as 2012. These waves of AFM have followed a peculiar pattern, with cases spiking every two years like clockwork. In 2018, for instance, there were more than 200 reported cases of AFM, but only 22 this year so far.The symptoms of AFM bear an uncanny resemblance to those occasionally caused by the polio virus. But thanks to routine vaccination, polio has been almost completely wiped out from the globe. Suspicion soon turned to the viruses closely related to polio, a group of germs called enteroviruses that infect us through food, water, and the air. Two in particular have been singled out: Enterovirus D68, which typically causes common cold symptoms in children, and A71, which can cause the rashy illness hand-and-foot disease.Both D68 and A71 have been found in the spinal fluid and guts of people with AFM, and more than 90 percent of victims report getting a mild cold before their paralysis began. Research has also found the strains plucked from human AFM victims can cause an AFM-like illness in mice. But despite an ongoing investigation, the CDC so far has only stated that AFM is probably caused by viruses, and that these viruses could include D68 and A71—much to the disappointment of some public health experts and scientists.One sticking point for the CDC is that most victims don’t show any direct evidence of a virus in their nervous system, let alone an enterovirus, such as viral DNA or RNA. But UCSF scientists say they’ve found a way to detect the hidden traces of D68 and A71 left behind in AFM patients, using a relatively new technology developed by Harvard Medical School researchers and others called Virscan. Virscan relies on bacteriophages (the viruses that hunt bacteria) to look for the antibodies our bodies produce to fend off viruses. But unlike older tests, Virscan is able to identify thousands of viral signatures at once.In their new study, published Monday in Nature Medicine, the authors used Virscan on the spinal fluid samples of 42 children with AFM as well as control samples taken from 58 children who had other neurological conditions. They found that more than two-thirds of AFM patients had an increased level of antibodies against enteroviruses in their spinal fluid, but not against any other known virus. Conversely, only 7 percent of control patients had enterovirus antibodies. The results were then confirmed through standard antibody testing.“The strength of this study is not just what was found, but also what was not found,” co-author Joe DeRisi, professor of biochemistry and biophysics at UCSF, said in a release from the university.Even before this new research, scientists have pleaded with the CDC to officially blame non-polio enteroviruses as the primary cause of AFM, arguing that the weight of the circumstantial evidence was already enough to render a verdict. In 2014, for instance, the first documented wave of AFM cases was closely preceded by a more serious than usual outbreak of D68. And the authors say theirs is the latest to provide “further evidence for a causal role of non-polio EVs in AFM.”Assuming the CDC does eventually agree with DeRisi and other experts, though, there are still plenty of mysteries to solve about AFM. It seems likely that something changed along the way in these viruses to start causing AFM, but we don’t know exactly what. We also don’t know why only a few people ever get AFM, given that enteroviruses commonly sicken people.But by settling on a culprit now, DeRisi and others hope that it’ll be easier to begin answering these questions and developing a real solution to AFM, such as a preventive vaccine.