By Dorothy Brooks
Researchers have finally confirmed that enterovirus (EV) D68 does cause acute flaccid myelitis (AFM), the polio-like illness that has affected mostly young children in recent years. The virus was considered one of the chief causes of AFM, but the suspicion was not confirmed until researchers, led by Matthew Vogt, MD, PhD, re-examined the autopsy specimens of a child who died from AFM in 2008.1
“There was definitely virus infecting the motor neurons in the spinal cord of this patient,” explains Vogt, an assistant professor of pediatrics and microbiology and immunology at the University of North Carolina. “No doubt, there are also other viruses that can cause AFM, but EV-D68 has been the main driver of the surges we have seen ... which we used to see every other year until 2020.”
Researchers believe all the behavior changes that resulted from the early days of the COVID-19 pandemic disrupted the usual every-other-year pattern of EV-D68 outbreaks that preceded surges in AFM cases. Now that people are returning to society, modeling studies suggest frontline providers could see a significant uptick in cases this year.2
“There is definitely [evidence suggesting] EV-D68 is starting to circulate again. Usually, the peak is in September and October, so it is good time to put the potential for AFM cases in the minds of emergency providers,” Vogt says. “We are all a bit apprehensive about what the next couple of months may hold.”
Still, Vogt’s research sheds important light on the disease process that takes place in children who develop AFM. This is progress that can help lead to new treatment possibilities. Investigators uncovered evidence that EV-D68 directly infects neurons in the spinal cord, prompting an immune response that leads to the limb weakness that is characteristic of AFM. Vogt observes the whole purpose of disease-fighting CD8-T cells in the body is to find and kill virus-infected cells so those cells stop supporting the virus. “That is all well and good in [a person’s] airways or GI tract where there are lots of stem cells proliferating and creating more cells,” Vogt says.
However, this action is not so good in the central nervous system. “Essentially, once those neurons die, there is limited if any capacity to replace their function. The CD8-T cells are doing what they are supposed to do; unfortunately, they may be doing more harm than good in the long term,” Vogt explains.
As for providing treatment, an approach that includes antiviral and anti-inflammatory medication would be beneficial for patients with AFM. There are no antiviral drugs for EV-D68, but such medicines are in development. “People often use IVIG, steroids, and plasma pheresis,” Vogt shares.
If a child presents with suspected AFM, emergency providers should order a spinal cord MRI and quickly collect specimens that can be tested for virus. “Those are going to be respiratory specimens, blood, stool, and spinal fluid,” Vogt notes. “A lot of times, the virus has actually already left the respiratory tract, even as it is causing all the damage in the spinal cord ... the earlier we test for viruses, the more likely we are to find them.”
Further, while these data are collected, frontline providers must immediately think ahead to the possibility the patient might need advanced care. “As soon as possible, talk to a pediatric neurologist and/or a pediatric infectious disease doctor,” Vogt says. “Start making arrangements for the child to go to a center that has pediatric intensive care capabilities if [he or she] is not already at a center that has these capabilities. This disease can progress pretty rapidly. Symptoms that start as limb weakness can progress all the way to full paralysis in as little as 24 hours.”
Although this rapid progression is a major hallmark of AFM, it is often not apparent to frontline providers because AFM is a tough diagnosis. “AFM is usually on the differential diagnosis with things like Guillain-Barré syndrome, for example, and there is a lot of work that goes into diagnostics to try and figure this out,” Vogt shares. “It may take a few days for people to be comfortable with the diagnosis, and by then you may lose the idea that the disease progresses so rapidly.”
REFERENCES
1. Vogt MR, Wright PF, Hickey WF, et al. Enterovirus D68 in the anterior horn cells of a child with acute flaccid myelitis. N Engl J Med 2022;386:2059-2060.
2. Park WP, Pons-Salort M, Messacar K, et al. Epidemiological dynamics of enterovirus D68 in the United States and implications for acute flaccid myelitis. Sci Transl Med 2021;13:eabd2400.
RESOURCES
• American Academy of Pediatrics. Acute Flaccid Myelitis - What Pediatricians Should Know About Diagnosis, Treatment, and Care of Pediatric Patients.
• Centers for Disease Control and Prevention. Acute flaccid myelitis.
Researchers uncovered evidence indicating enterovirus D68 directly infects neurons in the spinal cord, prompting an immune response that leads to the limb weakness that is characteristic of acute flaccid myelitis. Investigators shed important light on the disease process that takes place in children who develop this polio-like illness. This is progress that can help lead to better treatments.
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