Association of nonpolio enteroviral infection in the central nervous system of children with febrile seizures

Objective. To clarify the relationship between enteroviral infection and febrile seizures. Study Design. Cerebrospinal fluid (CSF), serum, throat swab, and rectal swab samples were collected for virologic examination from 67 children with febrile seizures from April 1997 to March 1999. Those samples were examined for the presence of enterovirus using cell culture and 2 polymerase chain reaction (PCR) methods. Results. No enterovirus was isolated from cell culture of CSF, throat swab, or rectal swab samples. All samples were screened for the presence of enteroviral sequences using a sensitive PCR method (PCR-Fukushima). We obtained positive results from 14 of 67 CSF samples, 10 of 62 serum samples, 12 of 64 throat swab samples, and 13 of 64 rectal swab samples. Of 21 patients in whom febrile seizures had developed during the summer months (June through August), 13 (61.9%) had positive PCR results in the CSF. Forty-seven of the 49 samples with a positive result using PCR-Fukushima were reexamined independently for the presence of the enteroviral genome using another PCR method (PCR-Mitsubishi). PCR-Mitsubishi had slightly lower sensitivity than PCR-Fukushima but identified genotypes of enterovirus by subsequent sequence analysis of the PCR products. The presence of the enteroviral genome was confirmed in 39 of the samples (83.0%). In 8 of the 9 enteroviruses detected in the CSF and/or serum samples using PCR-Mitsubishi, the genotypes were identified as coxsackieviruses group A, which are usually difficult to isolate using cell culture methods. Conclusions. These findings proved that the causative agents of febrile illness associated with seizures in summer were primarily enteroviruses, especially coxsackieviruses group A, and that febrile seizures might be caused by enteroviral infection in the central nervous system.