The Enigma of Childhood Predisposition in Enteroviral Infections

We read with great interest the article by Hedrera-Fernandez et al describing the spectrum of neurological presentations of enteroviral infections in a cohort of Spanish children over 1 year (2016).[1] Authors vividly describe the neurological manifestations, their management, and the outcome of the cohort. Enterovirus A71 (EV-A71) and EV-D68 were the common enteroviral infections and neurological manifestations ranged from aseptic meningitis, brainstem encephalitis, and acute flaccid myelitis (AFM). Similar to previous reports, authors highlight the poor diagnostic yield of cerebrospinal for enteroviral reverse transcription polymerase chain reaction and poor clinico-radiological correlation in AFM.[2] [3]

We concur with the authors' thoughts on the age predisposition (infancy and school-age group) for neurological presentations with the immaturity of the blood-brain barrier and immune system being the possible reasons. But perhaps these are not the only reasons. We would like to emphasize the possible role of seroprevalence due to subclinical and mild childhood infections in determining this age predominance. Enteroviruses are ubiquitous childhood pathogens. The seroprevalence of neutralizing antibodies (against EV-D68 and EV-A71) follows a parabolic curve with age with a high seroprevalence in newborns (due to placental transfer) and those aged 6 to 15years and nadir in late infancy when maternal antibodies decline.[4] [5] The spurt in antibody titer beyond 6 years represents the occurrence of natural infection (with few of them being neurological presentations while most being nonneurological manifestations). These neutralizing antibodies confer protection against reinfections and therefore the enteroviral infections in general and their neurological manifestations are rare in adolescents and adults.

Authors' Contributions

P.M. prepared the initial draft of the manuscript and reviewed the literature.

L.S. critical review of the manuscript and reviewed the literature, edited the final version of the manuscript.

Declarations of Interest

None.

Publication History

Received: 19 April 2021

Accepted: 11 December 2021

Article published online:
28 January 2022

• References

• 1 Hedrera-Fernandez A, Cancho-Candela R, Arribas-Arceredillo M. et al. Outbreak of enterovirus infection with neurological presentations in a pediatric population in Northern Spain: a clinical observational study. Neuropediatrics 2021; 52 (03) 192-200
• 2 Madaan P, Saini L. Nerve transfers in acute flaccid myelitis: a beacon of hope. Pediatr Neurol 2019; 93: 68
• 3 Madaan P, Keshavan S, Saini L. Poor clinico-radiological correlation: a hallmark of acute flaccid myelitis. Brain Dev 2019; 41 (05) 480-481
• 4 Vogt MR, Crowe Jr JE. Current understanding of humoral immunity to enterovirus D68. J Pediatric Infect Dis Soc 2018; 7 (suppl_2): S49-S53
• 5 Wei X, Yang J, Gao L. et al. The transfer and decay of maternal antibodies against enterovirus A71, and dynamics of antibodies due to later natural infections in Chinese infants: a longitudinal, paired mother-neonate cohort study. Lancet Infect Dis 2021; 21 (03) 418-426