Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study

Abstract

Purpose: In a prospective study, Consequences of Prolonged Febrile Seizures in Childhood (FEBSTAT), we determined the frequency of human herpesvirus (HHV)-6 and HHV-7 infection as a cause of febrile status epilepticus (FSE).

Methods: Children ages 1 month to 5 years presenting with FSE were enrolled within 72 h and received a comprehensive assessment including specimens for HHV-6 and HHV-7. The presence of HHV-6A, HHV-6B, or HHV-7 DNA and RNA (amplified across a spliced junction) determined using quantitative polymerase chain reaction (qPCR) at baseline indicated viremia. Antibody titers to HHV-6 and HHV-7 were used in conjunction with the PCR results to distinguish primary infection from reactivated or prior infection.

Key findings: Of 199 children evaluated, HHV-6 or HHV-7 status could be determined in 169 (84.9%). HHV-6B viremia at baseline was found in 54 children (32.0%), including 38 with primary infection and 16 with reactivated infection. No HHV-6A infections were identified. HHV-7 viremia at baseline was observed in 12 children (7.1%), including eight with primary infection and four with reactivated infection. Two subjects had HHV-6/HHV-7 primary coinfection at baseline. There were no differences in age, characteristics of illness or fever, seizure phenomenology or the proportion of acute EEG or imaging abnormalities in children presenting with FSE with or without HHV infection.

Significance: HHV-6B infection is commonly associated with FSE. HHV-7 infection is less frequently associated with FSE. Together, they account for one third of FSE, a condition associated with an increased risk of both hippocampal injury and subsequent temporal lobe epilepsy.

Figure 1

PCR primer pairs and probes specific for HHV6A, HHV-6B and HHV-7

Figure 2

Components of primary infection or reactivation with HHV6 or HHV7 at baseline (N=58)