A Case of Congenital Human Parechovirus Type 3 Meningoencephalitis.

Abstract

To the Editors Human parechovirus type 3 (HPeV3) is associated with severe acute disease in infants under 3 months and may have long-term neurologic sequelae.1 The second-born infant is at a 9-fold increased risk of infection.2 We report a case of congenitally acquired HPeV3 neonatal encephalitis, likely acquired from an older sibling. A 31-year-old woman underwent a non-elective cesarean section, at 36 weeks and 4 days gestational age, for fetal tachycardia and decreased movements. A 2-year-old sibling had a febrile illness and rash 10 days prior. A female neonate was delivered in good condition, birth weight 3.01 kg but was described as “irritable” and “difficult to settle.” At 9 hours of age, she was noted to be febrile and had repeated episodes of desaturation and bradycardia associated with abnormal limb movements. Cefotaxime, acyclovir and a dose of phenobarbitone (20 mg/kg) were administered. An amplitude-integrated electroencephalography monitor confirmed bihemispheric seizure activity. At 28 hours of age, the infant had further apneic episodes corresponding with electrographic seizures on amplitude-integrated electroencephalography. She received further anticonvulsants, was intubated, ventilated and received inotropic support for cardiorespiratory instability. Electrocardiogram and echocardiogram demonstrated normal biventricular function and no dysrhythmia or features suggestive of myocarditis. Over the next 24 hours, she stabilized, allowing tapering of inotropes and seizure medications. An magnetic resonance imaging performed on day 2 of life (Fig. 1) demonstrated white matter inflammatory changes. Additional investigations including broad viral and bacterial testing and a basic metabolic screen were undertaken. As part of these investigations, a lumbar puncture was performed on day 3 of life demonstrating <1 white cell ×106/L and 1 red blood cell ×106/L, protein of 1.21 (0.3–1 g/L) and glucose of 3 mmol/L (2.4–4.9 mmol/L). Paired capillary glucose was 4.9 mmol/L. Nucleic acid amplification testing detected HPeV on throat and rectal swabs collected day 1 of life and on cerebrospinal fluid. Testing for other causes of congenital infection was reported as negative.FIGURE 1.: A–F, Magnetic resonance imaging brain on day 2 of life (A–D) diffusion-weighted imaging, trace map on the left, and ADC map on the right, demonstrating restricted diffusion along the deep medullary veins in the white matter with additional areas of less pronounced restricted diffusion in the corpus callosum, internal capsules and ventrolateral thalami. E, Axial T2 weighted imaging on the left at the supraganglionic level showing linear areas of T2 hypointensity along the deep medullary veins with corresponding areas of hyperintensity on the T1 weighted imaging (F). G, A neighbor-joining phylogenetic tree was constructed from a 566-nucleotide region within the VP3/VP1 genes of circulating HPeV strains between January and April 2020 and aligned to Parechovirus reference strains [Genbank ID MF797929.1 (HPeV3) and EU556224 (HPeV7)].The virus was subtyped as HPeV3. A phylogenetic tree was constructed, utilizing Australian isolates (Fig. 1) and was highly similar to other contemporary circulating strains. The infant was extubated on day 7 of life and after a brief hospital stay, discharged home. Hearing screen was within normal ranges. No retinal changes were noted on examination. Convergent strabismus was noted at a subsequent review. At 4 months, there was evidence of dystonia in the upper and lower limbs, with spasticity of lower limbs. She was subsequently formally diagnosed with cerebral palsy. The combination of the antenatal presentation of fetal tachycardia and decreased movements, coupled with the onset of symptoms on the first day of life are consistent with intrauterine acquisition of HPeV3 infection. This is further supported by detection of HPeV on clinical samples on the first day of life. Although HPeV is widely recognized as causing sepsis-like illness in young infants, this is the first reported confirmed congenital HPeV3 infection. A previous case of presumed intrauterine HPeV has been reported.3 However, the interval between delivery and HPeV testing may have permitted postnatal acquisition.3 The assertion of causality could have been strengthened by performing testing on sibling and mother. The utility of this step was balanced against the potential of distressing the family and, consequently, not pursued. The neurologic sequelae, in this case, have been significant, with signs consistent with cerebral palsy at 4 months. The absence of protective maternal antibodies may have permitted both congenital infection and more severe disease.4 Congenital infection with HPeV3 can occur and can cause significant long-term neurodevelopmental sequelae. This report supports the consideration of HPeV3 in the differential diagnosis of a newborn presenting with seizures.