Neurodevelopmental Outcomes of Infants Younger Than 90 Days Old Following Enterovirus and Parechovirus Infections of the Central Nervous System

Abstract

Enteroviruses (EVs) and human parechoviruses (HPeVs) are a major cause of central nervous system (CNS) infection in young infants. They have been implicated in neurodevelopmental delay, however limited data are available. The aim of this study is to describe the clinical outcome of young infants and to assess and compare the medium-term neurodevelopment following CNS infections caused by EV and HPeV. A multicentre observational ambispective study was conducted between May 2013 and March 2018. Children under 3 months of age with EV or HPeV CNS infection excluding encephalitis were included. Infants were contacted 1 year after the acute infection and their neurological development was evaluated using the Ages and Stages Questionnaire-3 (ASQ-3). If any area assessed was abnormal during the first round of tests, a second round was completed 6 to 12 months later. Forty-eight young infants with EV and HPeV CNS infection were identified: 33 (68.8%) were positive for EV and 15 (31.3%) for HPeV. At first assessment 14 out of 29 EV (48.3%) and 3 out of 15 HPeV (20%) positive cases presented some developmental concern in the ASQ-3 test. EV-positive infants showed mild and moderate alteration in all domains analyzed and HPeV-positive infants showed mild alterations only in gross and fine motor domains. Significant alterations in communication were observed in EV-positive but not in HPeV-positive infants (31 vs. 0%, p = 0.016). At second assessment 4 out of 13 EV-positive patients (30.8%) showed mild to moderate concerns in communication and gross motor function domains and 3 out of 13 (23.1%) showed significant concern in fine motor function. Although CNS infections without associated encephalitis are generally assumed to be benign our study shows that at a median age of 18 months almost half of the EV-infected infants (48.3%) and 20% of HPeV-positive infants presented some developmental concern in the ASQ-3 test. We recommend monitor the neurological development of infants during the first years of life after HPeV CNS infection and especially after EV CNS infection, even in mild cases, for an early intervention and stimulation of psychomotor development if necessary.

The role of latitude and infections in the month-of-birth effect linked to schizophrenia

“…Furthermore, the seasonality of non-polio enterovirus infections appears to be similar across different regions with a peak in the summer months ( van der Sanden et al, 2009 ; Bubba et al, 2020 ; Kadambari et al, 2014 ) and have consistently shown this seasonal variation over the last five decades ( van der Sanden et al, 2009 ). Central nervous system involvement in enterovirus infections during childhood is well established, with polio causing long-term neuropsychiatric complications ( Nielsen et al, 2007 ) and non-polio enteroviruses resulting in meningitis and subsequent neurodevelopmental complications ( Chang et al, 2007 ; de Ceano-Vivas et al, 2021 ). Our findings for the first time connect this neurotropic enterovirus infection to the window of vulnerability in the second trimester, bringing together two independent lines of research in schizophrenia pathogenesis.…”

Human parechovirus meningitis in children: state of the art

“…We identify 24 publications dealing with clinical outcome of HPeV meningitis, in term of hospital stay and long-term outcome [ 1 , 12 , 21 , 25 , 26 , 28 , 44 , 48 , 49 , 56 , 57 , 59 , 60 , 62 , 65 , 66 , 70 , 73 , 74 , 80 – 84 ].…”

“…Examining scientific reports from all over the world are increasing awareness of the risk connected to a severe parechovirus infection. In fact, out of the revised literature, cerebral palsy, vision and neuropsychomotor development impairment were reported in a high percentage of case series [ 65 , 80 , 83 ]. The appropriate duration of post hospitalisation follow-up is still being debated.…”

Update on nonpolio enterovirus and parechovirus infections in neonates and young infants

“…These findings highlight the importance of longitudinal neurodevelopmental assessments of infants with PeV-CNS infection [37]. In a multicenter follow-up study of Spanish infants less than 90 days of age who had mild CNS infection that did not include encephalitis, investigators found that at a median age of 18 months, almost half (48.3%) of the enterovirus-infected patients and 20% of PeV-positive patients had developmental concern in the Ages and Stages Questionnaire-3 test [38]. More long-term studies are needed, but the available studies suggest that close follow-up of neurodevelopment is needed.…”