MRI reveals segmental distribution of enterovirus lesions in the central nervous system: a probable clinical evidence of retrograde axonal transport of EV-A71
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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.
KeywordsEnterovirus 71 (EV-A71) Hand, foot and mouth disease (HFMD) Infection Magnetic resonance imaging (MRI) Retrograde axonal transport (RAT)
We thank Ann Turnley, PhD, from Liwen Bianji, Edanz Group China (www.liwenbianji.cn/ac), for editing the English text draft of this manuscript.
HL designed and supervised the study. LS collected and analyzed data. TZ and FH collected and collated data. YY designed study and write the manuscript.
This work was supported by the Science and Technology Planning Project of Guangdong Province, China (2017A020215071).
- Guerra AM, Waseem M (2017)[Updated 2018 Oct 27]. Hand foot and mouth disease. In: Treasure Island. StatPearls Publishing(Internet), FL. 2018 JanGoogle Scholar
- Ooi MH, Solomon T, Podin Y, Mohan A, Akin W, Yusuf MA, del Sel S, Kontol KM, Lai BF, Clear D, Chieng CH, Blake E, Perera D, Wong SC, Cardosa J (2007) Evaluation of different clinical sample types in diagnosis of human enterovirus 71-associated hand-foot-and-mouth disease. J Clin Microbiol 45:1858–1866CrossRefPubMedCentralGoogle Scholar
- Shen WC, Chiu HH, Chow KC, Tsai CH (1999) MR imaging findings of enteroviral encephaloymelitis: an outbreak in Taiwan. AJNR Am J Neuroradiol 20:1889–1895Google Scholar
- Skorzewska A, Bruska M, Wozniak W (1994) The development of the spinal accessory nerve in human embryos during 5th week (stages 14 and 15). Folia Morphol (Warsz) 53:177–184Google Scholar
- Teoh HL, Mohammad SS, Britton PN, Kandula T, Lorentzos MS, Booy R, Jones CA, Rawlinson W, Ramachandran V, Rodriguez ML, Andrews PI, Dale RC, Farrar MA, Sampaio H (2016) Clinical characteristics and functional motor outcomes of enterovirus 71 neurological disease in children. JAMA Neurol 73:300–307CrossRefGoogle Scholar
- Wong KT, Ng KY, Ong KC, Ng WF, Shankar SK, Mahadevan A, Radotra B, Su IJ, Lau G, Ling AE, Chan KP, Macorelles P, Vallet S, Cardosa MJ, Desai A, Ravi V, Nagata N, Shimizu H, Takasaki T (2012) Enterovirus 71 encephalomyelitis and Japanese encephalitis can be distinguished by topographic distribution of inflammation and specific intraneuronal detection of viral antigen and RNA. Neuropathol Appl Neurobiol 38:443–453CrossRefGoogle Scholar