Abstracts

Rationale: Recent reports have shown that certain viral infections, such as rotavirus, human parechovirus and enterovirus, can cause or are associated with seizures accompanied by diffuse cerebral white matter lesions in newborn infants. Typically, when viruses infect mammalian or human cells, host cell pattern recognition receptors, such as Toll-like receptor 3, 7 or 8 recognize specific viral molecular motifs and induce production of type I interferons (INF-α and INF-β) and proinflammatory cytokines. Type I interferons play critical roles in human innate immunity, particularly against viral infections. This study aimed to test for increased level of type I interferons and proinflammatory cytokines in the CSF of newborn infants with diffuse cerebral white matter lesions on brain diffusion-weighted imaging (DWI) and evidence of rotavirus infection in conjunction with seizures. Methods: We examined levels of type I interferons (INF-α and INF-β) and proinflammatory cytokines (interleukin 6 [IL-6] and interferon gamma [INF-γ]) by enzyme-linked immunosorbent assay (ELISA) using the CSF samples from 23 newborn infants admitted to the neonatal intensive care unit at Ulsan University Hospital between 2011 and 2013 who fulfilled the following criteria: (1) seizures, (2) diffusion-restricted lesions in diffuse symmetric cerebral white matter on diffusion-weighted MRI, and (3) evidence of rotavirus infection. Real-time reverse transcription-polymerase chain reaction (RT-PCR) was also performed to detect rotavirus, human parechovirus and enterovirus. Results: Twenty-two patients were full-term newborns and one was a preterm infants. One-minute and 5-minute Apgar scores ranged between 7 and 10. The patients' age at seizure onset was 4.5±0.9 days (range, 3-7 days). One patient (4.3%) had fever. Stool specimens from all 23 patients were positive for rotavirus. Enterovirus was also detected in 3 patient stool samples. However, we did not isolate rotavirus, human parechvirus and enterovirus from CSF specimens obtained from all patients. No CSF pleocytosis was detected. IL-6 and INF-γ were detected in CSF samples of 17 (73.9%) and 8 patients (34.8%), respectively, whereas INF-α was not detected in any patients, and INF-β in only 2 patients (8.7%). The mean CSF IL-6 and INF-γ levels were 9.00 pg/mL (range, 3.13-23.11 pg/mL) and 63.12 pg/mL (range, 18.24-158.75 pg/mL), respectively. We detected INF-β levels of 50.69 pg/mL and 258.85 pg/mL in 2 patients. Conclusions: Compared to CSF levels of IL-6 and INF-γ, CSF type I interferons were detected in few patients. This result suggests that the occurrence of extensive white matter injury in the newborn infants with rotavirus infection and seizures may result from immaturity of the innate immune system that produce type I interferons against viral infection during the newborn period.