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Research probes cause of acute flaccid myelitis in children

Jun. 8, 2022, 10:00 AM

by Bill Snyder

Research that began at Vanderbilt University Medical Center has found evidence that a viral infection followed by a “robust” immune response is the cause of a polio-like paralyzing illness in children called acute flaccid myelitis (AFM).

Matthew Vogt, MD, PhD, a former research fellow at VUMC who is now on the faculty at the University of North Carolina School of Medicine at Chapel Hill, is lead author of the study’s findings, published on May 26 as a case report in The New England Journal of Medicine.

AFM is a serious neurologic condition that causes muscle weakness, sometimes leading to permanent paralysis. Of the 682 AFM cases confirmed in the United States since 2014, only two deaths have been reported, but patients rarely recover full strength.

The suspect virus, enterovirus D68 (EV-D68), can cause mild to severe symptoms including runny nose, wheezing, cough, body aches, and muscle aches. EV-D68 has been detected in respiratory specimens from AFM patients, but firm evidence of direct causation was lacking — until now.

The study began at VUMC in 2019, when Vogt was a fellow in pediatric infectious diseases in the laboratory of James Crowe, Jr., MD. Crowe’s lab has developed ultra-fast methods for discovering highly potent human monoclonal antibodies against a wide range of viral diseases including COVID-19.

By examining autopsy specimens from a 5-year-old boy who died from AFM in 2008, the researchers discovered the virus, EV-D68, had directly infected neurons in the spinal cord. They also noted the presence of cytolytic CD8+ T cells, immune cells that normally kill infected cells during a viral infection.

“Sometimes when there’s an immune response to an infection, it can cause lasting damage to the infected tissues, even affecting surrounding cells that are not infected,” Vogt said in a news release.

Vogt, assistant professor of pediatrics and microbiology & immunology at UNC, said he and his colleagues have used monoclonal antibodies to neutralize EV-D68 in animal studies. While further research is needed, the study could point the way to improvements in the treatment of AFM.

The research highlights the importance of autopsies and biobanking tissues for future study. The decision by the family of the 5-year-old boy to have an autopsy performed “could in turn be lifesaving for future children diagnosed with AFM,” Vogt said.

Crowe is the Ann Scott Professor, professor of Pediatrics and of Pathology, Microbiology & Immunology, and director of the Vanderbilt Vaccine Center. VUMC co-author Kelli Boyd, DVM, PhD, and colleagues in the Department of Pathology, Microbiology & Immunology performed the pathological studies of the spinal cord tissues.

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