September 3, 2019Gastroenterology
Acute flaccid myelitis (AFM) is a polio-like illness that affects the nerve cells (motor neurons) in the gray matter of the spinal cord. It is thought to be due to a viral infection. Children with AFM have acute (rapid) onset of flaccid (floppy) paralysis, usually in an arm or leg. They may also have trouble moving their face or trouble swallowing. This weakness may progress to weakness of the muscles that control breathing, so seeking care for a child who is developing weakness is important. AFM is rare, but an increasingly recognized cause of paralysis, occurring primarily in children. In recent history, AFM has been observed in clusters that seem to occur every two years. The first notable increase occurred in 2014, with additional spikes in 2016 and 2018.
There have been 570 confirmed cases since CDC began tracking AFM in August 2014. AFM outbreaks were reported to the CDC in 2014, 2016 and 2018. Spikes in AFM cases, primarily in children, have coincided in time and location with outbreaks of EV-D68 and a related enterovirus, EV-A71. Both of these viruses typically cause mild respiratory illness from which most people recover fully. Despite the epidemiological link between enterovirus circulation and AFM cases, evidence of direct causality has not been found.
According to a study published in mBIO (13 August 2019), direct evidence of enterovirus infection was examined in the cerebrospinal fluid (CSF) of 13 children and one adult diagnosed with AFM in 2018. The authors also examined five CSF samples taken from people with other central nervous system diseases. The team used a new tool they developed called VirCapSeq-VERT, which can detect any viral genetic material that is at least 60% like that of any known vertebrate virus. Results found enteroviral genetic material (EV-A71) in only the one adult AFM case and genetic material from another enterovirus (echovirus 25) in one of the non-AFM cases. The authors then sought indirect evidence of enterovirus infection by looking for antibodies to enteroviruses made by the immune system in response to an infection. The team developed a microchip assay, AFM-SeroChip-1, that detects the presence of antibodies generated in response to any human enterovirus (EV-A, EV-B, EV-C or EV-D) infection. Using this assay, the team tested the same 14 CSF samples from the AFM patients. They also tested CSF samples taken from 11 adults with central nervous system conditions, such as multiple sclerosis, and from 10 children with Kawasaki disease, none of whom had AFM.
Results showed that EV-specific antibodies were detected in the CSF of 79% (11 of 14) of the AFM cases. Of those, six samples were positive for EV-D68, strongly indicating that enterovirus had been in the central nervous system, even though it had not been detected by VirCapSeq-VERT. None of the CSF samples from children with Kawasaki disease had antibodies that reacted with any enterovirus. While other etiologies of AFM continue to be investigated, this study provides further evidence that enterovirus infection may be a factor in AFM. According to the authors, in the absence of direct detection of a pathogen, antibody evidence of pathogen exposure within the central nervous system can be an important indicator of the underlying cause of disease.