Abstracts

Rationale: Human herpesvirus-6 (HHV-6) is a common and relatively benign infection usually acquired in childhood. However, a potential role of this viral infection in the pathogenesis of various CNS disorders such as febrile seizures and febrile status epilepticus as well as temporal lobe epilepsy has been hypothesized. This systematic review aims to describe the prevalence and relationship between HHV-6 infection and seizure disorders in children and adults. Methods: Search Strategy: MEDLINE database was searched using the following search strategy: ((("Virus Diseases"[Mesh] OR HHV6 OR HHV7 OR HHV-6 OR HHV-7 OR viral infection* OR virus infection* OR viral disease* OR virus disease*) AND ("Status Epilepticus"[Mesh] OR status epilepticus)) OR (("Epilepsy"[Mesh] OR epilepsy*) AND (HHV6 OR HHV-6 OR "Herpesvirus 6, Human"[Mesh]))). We also reviewed the reference lists of the recruited studies. Selection Criteria: Studies that were in English, published after 1993, and described children or adults with evidence of HHV-6 infection and concomitant seizure or status epilepticus were included, as well as studies that described patients with other viral etiologies of status epilepticus. Studies that included immunocompromised subjects like post-transplant patients or HIV positive cases were excluded, as HHV-6 infection tends to have different clinical features in immunocompromised population. Additionally, cases with Rasmussen encephalitis, brain tumor and other epilepsy syndromes were excluded, as the seizure etiology may be confounded by other causes in these groups. In another part, studies describing the epilepsy surgery patients being evaluated for evidence of HHV-6 infection were recruited. Data Collection: Two reviewers independently screened and assessed the quality of the articles based on the eligibility criteria above. Results: We identified 503 articles, and included 146 studies. For "HHV-6 infection and seizure" 22 articles and for "HHV-6 infection and status epilepticus" 20 articles were included. 18 articles about "epilepsy and HHV-6 detection" and 72 studies for "other viral etiologies of status epilepticus" were found. Available information about febrile seizure shows that from 110 cases, 76 patients had simple and 34 had complex febrile seizures. Meta-analysis results showed that approximately 19 percent of children with febrile seizures may be infected with HHV-6, despite variable study populations and detection methods. Patients with "HHV-6 infection and status epilepticus" had a mean age of 16.2 months and mean seizure duration of 75.5 minutes. Conclusions: In children with febrile illnesses, a higher index of clinical suspicion and a sensitive detection test for HHV-6 infection may be required, because this infection is relatively common and can predispose such patients to develop epilepsy or other adverse neurologic outcomes in the future. Further studies including CSF and brain tissue may be needed to validate relationships between HHV6 infection and epilepsy. Funding: HHV-6 Foundation