The new test detected antibodies for two types of enteroviruses in the spinal fluid of dozens of patients diagnosed with acute flaccid myelitis (AFM), a disease that causes potentially permanent and sometimes life-threatening paralysis in young children.
The two viruses, EV-D68 and EV-A71, previously had been found in cases of AFM, but this study provides the clearest evidence to date that the disease is caused by an enterovirus, researchers said.
"It certainly lays the groundwork for further testing so we can be confident that most, if not all, of AFM cases are caused by enteroviruses," said lead researcher Dr. Ryan Schubert, a clinical fellow with the University of California, San Francisco's (UCSF) department of neurology.
This explanation would make sense, since polio itself belongs to the family of enteroviruses.
AFM usually causes weakness in the arms and legs, but in rare cases can cause life-threatening respiratory failure, according to the U.S. Centers for Disease Control and Prevention.
AFM has tended to strike in the United States every other year, with 236 cases reported in 41 states in 2018, the CDC said.
The first wave of AFM hit in 2014, when 120 children across 34 states were stricken with mysterious muscle weakness. Another wave hit in 2016, with 149 patients affected in 39 states.
Until now, researchers looking into the causes of AFM have searched for the presence of enteroviruses by looking for direct genetic evidence of the viruses in people's spinal fluid, Schubert said.
Enterovirus outbreaks are common and usually cause nothing more severe than common cold-like symptoms, but experts realized that these outbreaks tended to coincide with spikes in AFM, the study authors explained in background notes.
Unfortunately, tests looking for the RNA of enteroviruses in AFM patients tended to be less-than-adequate, Schubert said.
The virus could not be found in 98% of AFM patients who had their spinal fluid tested, and even when found the viruses are "detected at very low levels," Schubert said.
"The amount of virus is just very, very low," Schubert continued. "We don't know for sure why that is, but it was also the case with polio virus that it was difficult to detect that virus in the spinal fluid."
That led some skeptics to question whether AFM is actually an autoimmune disorder or is caused by some other as-yet-undiscovered virus, the researchers said.
"People were hung up on the fact that enteroviruses were rarely detected in the cerebrospinal fluid of AFM patients," senior researcher Dr. Michael Wilson, an associate professor of neurology and member of the UCSF Weill Institute for Neurosciences, said in a statement. "They wanted to know how someone could get neurologic symptoms with no virus detectable in their central nervous system."
Wilson, Schubert and their colleagues suspected that they might be better able to detect the presence of enteroviruses if they instead searched for antibodies created by the immune system to fight off the viruses.
The investigators turned to a Harvard-developed virus-hunting tool called VirScan, which allowed the researchers to look for signs of immune response in the spinal fluid of AFM patients.
The team found enterovirus antibodies in the spinal fluid of nearly 70% of the 42 AFM patients they tested.
The researchers also tested 58 patients who had been diagnosed with other neurological disorders, and fewer than 7% tested positive for the same antibodies.
According to Dr. Amesh Adalja, a senior scholar at the Johns Hopkins Center for Health Security, "This new study adds critical information about the presence of enteroviruses in AFM cases. Understanding the role of enteroviruses will help propel further research to determine the specific risk factors that transform a relatively innocuous upper respiratory infection into a life-altering paralytic illness and spur vaccine development."
Schubert agreed, suggesting that future AFM research should run along two parallel tracks.
On one track, researchers should use the new antibody test to completely nail down the link between enteroviruses and AFM, Schubert said.
On the other track, scientists should continue working on vaccines that will prevent infection by EV-D68 and EV-A71, as well as therapies that could neutralize the viruses before they cause AFM.
"This really suggests they're on the right track and should keep going," Schubert said of research teams already focused on enteroviruses and AFM.
The new study was published Oct. 21 in the journal Nature Medicine.