Enterovirus and parechovirus meningoencephalitis in infants: A ten-year prospective observational study in a neonatal intensive care unit

Carlo Pietrasanta; Andrea Ronchi; Laura Bassi; Agnese De Carli; Luca Caschera; Francesco Maria Lo Russo; Beatrice Letizia Crippa; Silvia Pisoni; Riccardo Crimi; Giacomo Artieri; Laura Pellegrinelli; Robertino Dilena; Giorgio Conte; Fabio Mosca; Monica Fumagalli; Lorenza Pugni

doi:10.1016/j.jcv.2024.105664

Enterovirus and parechovirus meningoencephalitis in infants: A ten-year prospective observational study in a neonatal intensive care unit

J Clin Virol. 2024 Mar 5:173:105664. doi: 10.1016/j.jcv.2024.105664. Online ahead of print.

Authors

Carlo Pietrasanta¹, Andrea Ronchi², Laura Bassi², Agnese De Carli², Luca Caschera³, Francesco Maria Lo Russo³, Beatrice Letizia Crippa², Silvia Pisoni², Riccardo Crimi², Giacomo Artieri², Laura Pellegrinelli⁴, Robertino Dilena⁵, Giorgio Conte⁶, Fabio Mosca⁷, Monica Fumagalli⁷, Lorenza Pugni²

Affiliations

¹ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, NICU, Milan, Italy; University of Milan. Department of Clinical Sciences and Community Health, Milan, Italy. Electronic address: carlo.pietrasanta@unimi.it.
² Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, NICU, Milan, Italy.
³ Neuroradiology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy.
⁴ University of Milan. Department of Biomedical Sciences of Health, Milan, Italy.
⁵ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Clinical Neurophysiology Unit, Milan, Italy.
⁶ Neuroradiology Unit, Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico, Milan, Italy; University of Milan. Department of Pathophysiology and Transplantation, Milan, Italy.
⁷ Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, NICU, Milan, Italy; University of Milan. Department of Clinical Sciences and Community Health, Milan, Italy.

PMID: 38493709
DOI: 10.1016/j.jcv.2024.105664

Abstract

Background: Non-polio enteroviruses (EV) and human parechoviruses (HPeV) are known etiological agents of meningoencephalitis in neonates. However, reports of neuroradiological findings and neurodevelopmental outcomes in this population are scarce.

Objectives: to describe clinical characteristics, neuroradiological findings and, in a subset of patients, neurodevelopmental outcomes in a cohort of infants with EV or HPeV meningoencephalitis within 60 days of life.

Study design: clinical/laboratory data, neuroradiological findings (cranial ultrasound, cUS, brain magnetic resonance imaging, MRI), and neurodevelopmental outcomes assessed by Ages and Stages Questionnaires - third edition were prospectively collected.

Results: overall, 32 infants with EV (21, 67.8 %) or HPeV (11, 28.2 %) meningoencephalitis were enrolled. Infants with HPeV (73 %: type 3 HPeV) presented more frequently with seizures (18.2 % vs. 0, p value=0.03), lymphopenia (1120 vs. 2170 cells/mm³, p = 0.02), focal anomalies at electroencephalography (EEG) (63.6 vs. 23.8 %, p = 0.03), and pathological findings at MRI (72.7 % vs. 15.8 %, p value=0.004) compared to those affected by EV. cUS was not significantly altered in any of the enrolled infants. All infants with EV meningoencephalitis evaluated at 12-24 months and at 30-48 months were normal. Two out of the 7 infants with HPeV meningoencephalitis showed some concerns in gross motor (1/7, 14.3 %) or in problem solving (1/7, 14.3 %) function at 30-48 months of age.

Conclusions: In our cohort, neonates infected by HPeV had more severe clinical manifestations, more alterations at brain MRI, and some signs of long-term neurodevelopmental delay. Our data highlight the heterogeneity of manifestations in infants with EV or HPeV meningoencephalitis, and the need for long-term follow-up of those infected by HPeV in the neonatal period.

Keywords: Brain mri; Enterovirus; Meningoencephalitis; Neonatal encephalitis; Neurodevelopment; Newborn; Parechovirus.