Human Herpes Virus 6 In Human Epilepsy: Data From Surgical Resections

Human Herpes Virus 6 is a ubiquitous virus, with a seroprevalence approaching 100% in the general population. There are two variants of HHV-6, A and B, which have been determined to be separate species. HHV-6B is the etiologic agent of roseola, while HHV-6A is associated with central nervous system disorders and may be more neurotropic than HHV-6B. HHV-6 has been associated with epilepsy, particularly with prolonged febrile seizures in children and mesial temporal lobe epilepsy (MTLE). Prolonged febrile seizures have been linked to the later development of MTLE. Previous studies have suggested a possible role for HHV-6, in particular HHV-6B, in MTLE, with the detection of viral DNA in epilepsy tissue using real time and nested polymerase chain reaction (PCR). These older forms of PCR are limited in their the detection of HHV-6; nested PCR is not quantitative, while real time PCR depends on a standard curve for quantitation. In this study, we used digital droplet PCR, a third generation PCR technique, for the precise quantification of HHV-6A and B viral DNA in epilepsy brain samples. Using this technique, target DNA sequences can be quantified without the need of a standard curve. We used digital droplet PCR (ddPCR) to examine HHV-6A and HHV-6B viral DNA in brain samples taken during epilepsy surgery from 24 patients. Our cohort included 13 MTLE patients, 9 focal cortical dysplasia (FCD) patients, and 2 patients with other epilepsy subtypes. Viral DNA was detected in 62.5% of MTLE patients. The frequency of positivity is consistent with previous findings. In addition, we detected HHV-6A as well as HHV-6B. HHV-6A and HHV-6B DNA also were detected in a subset of FCD patients. The detected viral copy numbers varied across a wide range between patients and even within a given patient, depending on regional sampling. This data suggest viral presence in patients with FCD and extend previous findings in patients with MTLE, with the detection of HHV-6A not previously reported.