Association of Nonpolio Enteroviral Infection in the Central Nervous System of Children With Febrile Seizures

Abstract

ABSTRACT. 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. Pediatrics 2001;107(1). URL: http://www. pediatrics.org/cgi/content/full/107/1/e12; enterovirus, coxsackievirus group A, febrile seizures, polymerase chain reaction.ABBREVIATIONS. CNS, central nervous system; CSF, cerebrospinal fluid; PCR, polymerase chain reaction; bp, base pair. E nteroviruses-polioviruses, echoviruses, coxsackieviruses group A and group B, and enteroviruses-are responsible for significant and frequent human illness, including various neurologic manifestations. The most common neurologic illness is aseptic meningitis. Encephalitis and other manifestations, such as paralysis, Guillain-Barré syndrome, transverse myelitis, cerebellar ataxia, and peripheral neuritis, also occur. 1 The association of enteroviral infection in the central nervous system (CNS) with febrile seizures, however, has not been demonstrated. In general, the causative agent of the infection is not detected in the CNS of patients with febrile seizures using standard techniques.We previously reported that the enteroviral genome was detected in cerebrospinal fluid (CSF) samples collected from some children with transient neurologic complications, such as seizures and altered states of consciousness associated ...

Direct Serotyping of Enteroviruses in Cerebrospinal Fluid of Children With Aseptic Meningitis

“…There are also other reports from Ahvaz about the frequency of enteroviruses in one of the hospitals in Ahvaz and the frequency of Echo 30 in enteroviral meningitis patients (17,18). Another study showed that the frequency of enteroviruses in viral meningitis in Tehran is similar to other countries (1,2,(4)(5)(6)(7).…”

“…Traditional methods of detecting enteroviruses such as viral culture are time-consuming, labor-intensive procedures especially for CSF samples (1,2,4,5,(7)(8)(9). Enterovirus molecular assays are the most sensitive and specific ones and the results will be available within several hours of specimen collection (10)(11)(12).…”

“…Detection of the 5` non-coding region of the Enterovirus genome in CSF is the golden standard for the diagnosis of Enterovirus infection. Serotype identification should be conducted by sequence analysis of the amplified VP1 region as the major surfaceneutralization epitopes in the Picornaviridae that correlates with the serotype classification (1,2,10). This study has been conducted to identify the prevalent serotypes of enteroviruses in young children with aseptic meningitis during 2009 -2010 in Iran.…”

“…Aseptic meningitis is a common syndrome with acute onset of meningeal inflammation symptoms, fever, and pleocytosis of the cerebrospinal fluid (1,2). Viral and bacterial meningitis cannot be differentiated properly.…”

“…Viral and bacterial meningitis cannot be differentiated properly. However examination of cerebrospinal fluid could result in excluding bacterial meningitis, and identification of the specific viral causes (1,3,4). Enteroviruses belong to the family of Picornaviridae, non-enveloped, single-stranded positive sense RNA viruses, which represent the major causes of aseptic meningitis worldwide (4,5); although, most enteroviral infections are subclinical and self-limited severe illnesses such as meningitis, encephalitis, and paralysis, are resulted from the infection of central nervous system (CNS) (5-8).…”