Neurologic Outcomes in Human Parechovirus Meningoencephalitis

Source: Shah N, Katragkou A, Fortin O, et al. Predicting severe short-term neurologic outcomes in human parechovirus meningoencephalitis. Pediatrics. 2025;156(4):e2025071878; doi: 10.1542/peds.2025-071878.Investigators from multiple institutions conducted a retrospective study to describe the clinical characteristics and risk factors for complicated disease in infants with human parechovirus (PeV) meningoencephalitis (ME). For the study, they reviewed the medical records of patients with PeV ME treated at 7 institutions in the US during the 2022 PeV ME outbreak. A diagnosis of PeV ME was confirmed by detection of PeV in cerebrospinal fluid (CSF) and/or blood. Demographic information, medical history, clinical symptoms, laboratory, and imaging data were collected on study participants. Patients were classified as having complicated disease if they required ICU admission, had abnormal brain MRI findings, or had an abnormal electroencephalogram (EEG). Infants with PeV ME were otherwise categorized as having uncomplicated disease. Characteristics of those with uncomplicated or complicated disease were compared using chi-square, Fisher exact, t-tests, or Mann Whitney U tests. Risk factors for having an abnormal MRI also were assessed in a multivariate regression model.Data were analyzed on 139 infants with PeV ME. Cases were detected between March and October 2022, with 51% occurring in June or July. The median age of study patients was 19 days. PeV was identified in the CSF in 134 (96.4%) infants and in blood in 45 (32.3%). Laboratory values tended to be within the normal range. The median white blood cell (WBC) count was 5.6/nL, and median CSF WBC was 3/μL. A total of 124 (89.2%) patients presented with fever (≥38.0°C), while 20 (14.3%) were hypothermic (<36.0°C). There were 42 (30%) infants with complicated disease, including 31 requiring ICU care, 32 with an abnormal brain MRI, 25 with an abnormal EEG, and 27 meeting multiple criteria. Patients with complicated disease were less likely than those with uncomplicated PeV ME to have fever (66.6% vs 98.9%; P <0.001) and more likely to have hypothermia (36.5% vs 5.1%; P <0.001), seizures (57.1% vs 4.1%; P <0.001), hemodynamic instability (28.5% vs 3.0%; P <0.001), apnea/breath holding (40.4% vs 0; P <0.001), somnolence (38.1% vs 13.4%; P = 0.003), and poor feeding (76.1% vs 47.4%; P = 0.001). The median age of infants with complicated disease was 16 days compared to 20 days for those with uncomplicated disease (P = 0.003). Among 56 patients who had a brain MRI, findings were abnormal in 32 (57%). Independent risk factors for an abnormal brain MRI identified in the multivariate regression model included younger age (P = 0.045) and seizures (P = 0.03).The authors conclude that PeV ME in infants frequently is associated with complicated disease.Dr Brady has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The authors highlight an uncommon but serious neonatal infection. Parechoviruses, previously classified as enteroviruses, are transmitted via the fecal-oral and respiratory routes, from symptomatic or asymptomatic individuals.1 Older siblings with mild upper-respiratory infections and gastroenteritis may be the source of infection.2Clinical manifestations in neonatal PeV infections are variable.1 Often, those with the most complicated disease present with nonspecific findings (eg, hypothermia, apnea, somnolence, and poor feeding). Infants can have serious infections without fever, so the recommendations for the evaluation of the 'ill appearing' neonate are helpful despite the lack of fever.3,4 Peripheral WBC, C-reactive protein, procalcitonin, and CSF WBC and protein may be normal in infants with PeV ME.Specific nucleic acid amplification tests (NAATs) are the best diagnostic test for PeVs.1 Enterovirus NAATs will not detect PeVs (and vice versa). Some but not all multiplex NAATs designed to detect bacterial and viral agents of meningitis and encephalitis include PeV. The CDC’s Non-polio Enterovirus Laboratory offers PeV NAATs on blood, CSF, and other body fluids.5Infants with confirmed PeV infection are managed in contact precautions for the duration of their illness.1 No specific therapy is available. The current authors report that one-third of infants developed neurologic complications, including motor impairments. Close follow-up of hearing and developmental outcomes is recommended for infants with PeV ME.6Parechoviruses should be considered in the evaluation of the ill neonate. Laboratory values may be normal despite disease-associated ME.As long-term patient follow-up was not reported in this study, the actual number of children with neurodevelopmental sequelae as a consequence of PeV infection cannot be ascertained.