HHV-6 and hippocampal volume in patients with mesial temporal sclerosis

Objective: To study the effects of human herpes virus 6 (HHV-6) on the hippocampal volume in patients with mesial temporal sclerosis (MTS). Background: HHV-6 may play an etiologic role in MTS. Previous studies found a possible association with febrile status epilepticus. Several investigators have reported a higher prevalence of HHV-6 in MTS resections compared to other epilepsy etiologies. Design/Methods: We used FreeSurfer to segment cortical structures and obtain whole hippocampal and subfield volumes in 41 patients with intractable epilepsy. In addition, an investigator blinded to other data traced hippocampi manually on each slice. The main study outcome measure was the asymmetry index (AI) between hippocampal volumes ipsilateral and contralateral to seizure foci compared between HHV-6 positive and negative patients. Viral DNA was isolated from fresh brain tissue obtained at temporal lobectomy. For 25 patients, viral detection was performed using quantitative real-time PCR specific for HHV-6A and HHV-6B. For 16 patients, viral DNA detection was performed using digital droplet PCR specific for HHV-6A and HHV-6B. Results: Twenty-two patients were positive (14 of 25 tested with real-time PCR, and 8 of 16 with digital droplet PCR), and 19 negatives for HHV-6. HHV-6 negative patients had significantly greater AI and lower total hippocampal volume ipsilateral to seizure foci than HHV-6 positive patients. Epilepsy duration and age of onset did not affect results. Interpretation: Our data suggest multiple potential etiologies for MTS. HHV-6 may have a less severe effect on the hippocampus than other etiologies.