UCSF finds major clue to the cause of sudden-onset paralysis in children
UCSF scientists have found striking new evidence that a specific virus is causing an epidemic of sudden-onset paralysis that has rolled across the country in recent years, baffling doctors even as it disabled hundreds of children.
Scientists have been trying for eight years to figure out what's behind the polio-like illness that's struck nearly 600 people, mostly children, across the United States, including dozens in the Bay Area. Early signs pointed to an enterovirus - a family of viruses that generally cause mild illnesses but includes a strain that causes polio - but it was all circumstantial. The specific virus that causes polio was ruled out early on.
The new UCSF study, published Monday in the journal Nature Medicine, used advanced screening tools to hunt for antibodies that would prove certain viruses had infiltrated a patient's spinal fluid. Scientists found antibodies pointing to an enterovirus in nearly 70% of the samples they tested.
That's the strongest evidence so far that an enterovirus is to blame, said scientists and doctors who have been studying the illness, which is formally known as acute flaccid myelitis. Indeed, it's powerful enough proof that scientists may start using the screening tool to help diagnose new cases, which could be critical as a new wave of illness is expected next year
"Our study points at the virus and says, this is the way we should be testing for it, with antibodies," said Dr. Ryan Schubert, a UCSF neurologist and author of the study. "If acute flaccid myelitis comes back next year, which we're all worried about, then more antibody testing and prospectively confirming all of this would be the next step."
Acute flaccid myelitis is an illness of the central nervous system that causes weakness or full paralysis in one or more limbs. Many cases start with cold symptoms before progressing a week or more later to more serious problems. The paralysis is often permanent.
Cases began to pop up as early as 2011, with a small cluster of about a dozen patients in California. But the numbers didn't creep high enough to gain national attention until 2014, when 120 cases were confirmed.
Since then, the illness has struck the country in every-other-year waves. There were fewer than 100 cases total in 2015, 2017 and this year - but 153 cases in 2016 and 236 in 2018. With that in mind, doctors are bracing for another rise in cases in 2020.
Tracking down the cause of the illness is key to addressing the epidemic, because scientists need a specific target to develop vaccines or drug therapies. Enterovirus 68, a relatively common pathogen that usually causes mild cold symptoms, was identified early on as a possible culprit.
Many of the children tested positive for the virus in samples taken from their nose, mouth or stools, and upswings in the cases of paralysis often coincided with increases in enterovirus infections overall. Other signs pointed to the virus: In studies of mice, Enterovrius 68 was shown to cause limb paralysis in some cases; and scientists found that the virus had mutated in recent years, which could mean that it had changed in such a way to suddenly make it more dangerous.
But doctors were still missing an important piece of the puzzle: proof that an enterovirus had invaded patients' spinal fluid. If the virus was causing paralysis, it would have to make its way into the spinal cord, which is a protected space that's not common for pathogens to access. When scientists looked for the virus in paralysis patients' spinal fluid, they rarely found it, even using the world's most advanced tools to search traces of viral genetic material.
The fact that scientists couldn't find the virus didn't mean it wasn't to blame - it was likely, in fact, that the body had cleared out the virus by the time patients were tested for it. Still, doctors wanted positive proof that the virus had been in or near the spinal cord.
The UCSF team decided to look not for Enterovirus 68, but for antibodies created by the immune system in response to the virus. To do that, the scientists put together a library of half a million genetic fragments from 3,000 viruses, then exposed samples of patients' spinal fluid with the library. Antibodies in the spinal fluid attached themselves to the genetic fragments that they were made to fight.
Scientists then tested those antibody-binded fragments to determine what virus they came from. In 29 of 42 samples, enterovirus antibodies were found. When scientists did the same testing on samples taken from people who had not been diagnosed with acute flaccid myelitis, they found enterovirus in only four of 58 cases.
"We had this really comprehensive library to test against, and we said, let's see where the chips fall. And they fell right where we were expecting," said Dr. Michael Wilson, a UCSF neurologist and senior author of the paper.
About a third of the samples from paralysis patients did not test positive for the antibodies, which was not surprising, Wilson said. It takes the immune system several days to create antibodies, and the samples may have been taken from those patients before that happened.
It's still not clear whether the virus itself is causing the paralysis or if patients' immune reactions are to blame - but the virus almost certainly plays a central role, said scientists involved with the new research and others who have been studying acute flaccid myelitis.
Dr. Keith Van Haren, a Stanford neurologist who treated some of the first Bay Area paralysis patients and was not involved in the new research, said he was excited by the antibody testing results, and he believes it's time to focus resources on how to fight the virus, whether that's through a vaccine or new therapies.
"This paper further demonstrates that enteroviruses are so tightly interwoven with this syndrome that we've really moved beyond simple correlation. There's no getting around the association anymore of the virus and the syndrome," Van Haren said. "The complex part is what is the best response. That's next."
Erin Allday is a San Francisco Chronicle staff writer. Email: [email protected] Twitter: @erinallday
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