MRI reveals segmental distribution of enterovirus lesions in the central nervous system: a probable clinical evidence of retrograde axonal transport of EV-A71

J Neurovirol. 2019 Jun;25(3):354-362. doi: 10.1007/s13365-019-00724-3. Epub 2019 Feb 7.

Abstract

Enterovirus 71 (EV-A71) is a major causative agent for hand, foot, and mouth disease (HFMD), especially severe HFMD characterized by neurologic involvement. The objective of this study is to investigate the relationship between the distribution of neurologic infection and the outcomes of severe HFMD. A total of 139 suspected severe HFMD cases (92 were confirmed as EV-A71 infection) underwent clinical and laboratory diagnosis as well as magnetic resonance imaging (MRI) scans of the nervous system. Only those who were confirmed with EV-A71 infection were included in our study. The image data of severe EV-A71-related HFMD cases were retrospectively analyzed, and they were grouped according to lesion site location indicated by MRI. The distribution of lesions in the central nervous system shown by MRI indicated that there were 47 (51%) in brainstem, 33 (36%) in spinal nerve roots lower than T1 thoracic spine, four (5%) in brainstem plus cervical spinal cord involvement, three (3%) in cervical spinal cord, three (3%) in brainstem plus spinal nerve root lower than T1, and two (2%) in cervical and thoracic spinal cord lower than T1. Our analysis strongly substantiates the hypothesis of retrograde axonal transport (RAT) of EV-A71 pathogenesis, suggesting that the pharyngeal branch of the vagus nerve is a major route to the brainstem, and that ascending transportation via the spinal cord does not occur when spinal nerve roots are infected by EV-A71 via RAT. Graphical abstract ᅟ.

Keywords: Enterovirus 71 (EV-A71); Hand, foot and mouth disease (HFMD); Infection; Magnetic resonance imaging (MRI); Retrograde axonal transport (RAT).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Axonal Transport / physiology*
  • Brain / virology*
  • Child
  • Child, Preschool
  • Enterovirus A, Human / pathogenicity*
  • Female
  • Hand, Foot and Mouth Disease / virology*
  • Humans
  • Infant
  • Magnetic Resonance Imaging
  • Male
  • Retrospective Studies
  • Spinal Cord / virology*