Human Paraechovirus Encephalitis in Children
Children 14 years of age and younger hospitalized with suspected encephalitis in five Australian pediatric tertiary care hospitals were prospectively enrolled in the Australian Childhood Encephalitis (ACE) study between May 2013 and November 2014. Molecular testing for various pathogens was performed on clinical samples including cerebrospinal fluid (CSF).
Thirteen infants with suspected encephalitis and confirmed HPeV infection were identified out of a total of 133 encephalitis cases of all causes. After expert panel review, nine of the 13 infants were determined to have encephalitis. Seven of the nine infants were female, five were born prematurely, all cases occurred in infants younger than 2 months of age (median age 13 days). All presented as outpatients with fever, lethargy, or irritability. Seizure occurred in eight of nine patients. Rash was present in five patients; four had multi-organ dysfunction. HPeV RNA was detected in CSF in all nine patients. Subtyping was performed in four, and all of these were genotype 3. Cranial ultrasound was abnormal in only two children. MRI was performed in seven children, and all of these studies were abnormal with T2 hyperintensity with corresponding diffusion restriction involving periventricular and subcortical white matter and thalamus. Electroencephalogram (EEG) was performed on seven children and was abnormal in six. CSF pleocytosis was absent in all. Eight children required intensive care unit admission, and five patients required mechanical ventilation. All patients received empirical antibiotics for variable periods of time, and seven of nine children received acyclovir. Neurologic outcome at hospital discharge was consistent with none or minor neurologic damage in six children, but longer-term follow-up of eight children at about 12 months after discharge demonstrated that five of eight had significant developmental problems, including cerebral palsy in two and central visual impairment in one. Seven of the eight children had gross motor subscale abnormalities, and this appeared to correlate with the degree of MRI abnormalities.
COMMENTARY
This prospective study demonstrates that approximately 10% of childhood encephalitis cases during the study period were caused by HPeV. Young age and prematurity were risk factors for development of HPeV encephalitis. All presumably acquired infection in the home during their first weeks of life. While short-term outcomes seemed reassuring, longer-term follow-up demonstrated significant neurodevelopmental sequelae, and these effects were correlated with severity of white matter changes seen on MRI during the acute illness. These MRI findings are not specific for HPeV infection and can be seen in other neonatal encephalitides1,2 and from other causes.3,4 Unfortunately, no specific therapy exists for HPeV infection or most of the other viral infections, which can contribute to devastating CNS damage in neonates.
REFERENCES
- Wu T, et al. Enterovirus infections are associated with white matter damage in neonates. J Paediatr Child Health 2014;50:817-822.
- Verboon-Maciolek MA, et al. White matter damage in neonatal enterovirus meningoencephalitis. Neurology 2006;68:1267-1269.
- Back SA. Perinatal white matter injury: The changing spectrum and emerging insights into pathogenic mechanisms. Ment Retard Dev Disabil Res Rev 2006;12:129-140.
- Khwaja O, et al. Pathogenesis of cerebral white matter injury of prematurity. Arch Dis Child Fetal Neonatal Ed 2008;93:F153-F161.
Human paraechovirus (HPeV) causes encephalitis and is more common in very young or premature female infants. Affected children commonly present with seizures. Diffusion restriction on MRI in the absence of CSF pleocytosis is seen. Neurodevelopmental sequelae are common after long-term follow up.
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