HHV-6 and hippocampal volume in patients with mesial temporal sclerosis
Elizabeth O Akinsoji1, Emily Leibovitch2, B Jeanne Billioux2
1Clinical Epilepsy Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland.
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.
Insights
Human herpes virus 6 (HHV-6) infection may play a role in mesial temporal sclerosis (MTS). HHV-6 positive patients showed less hippocampal volume loss compared to HHV-6 negative patients with MTS.
Area of Science:
- Neurology
- Virology
- Neuroimaging
Background:
- Mesial temporal sclerosis (MTS) is a common cause of intractable epilepsy.
- Human herpes virus 6 (HHV-6) is a potential, yet understudied, etiological factor in MTS.
- Previous research suggests a higher prevalence of HHV-6 in MTS resections.
Purpose of the Study:
- To investigate the impact of HHV-6 infection on hippocampal volume in patients diagnosed with MTS.
- To compare hippocampal asymmetry and volume differences between HHV-6 positive and negative MTS patients.
Main Methods:
- Utilized FreeSurfer for automated cortical segmentation and hippocampal volume analysis in 41 epilepsy patients.
- Performed manual hippocampal tracing by a blinded investigator for cross-validation.
- Quantified HHV-6 DNA in temporal lobe resections using real-time PCR and digital droplet PCR.
Main Results:
- HHV-6 DNA was detected in 22 out of 41 patients.
- Patients negative for HHV-6 exhibited significantly greater hippocampal asymmetry and reduced ipsilateral hippocampal volume compared to HHV-6 positive patients.
- Epilepsy duration and age of onset did not influence the observed results.
Conclusions:
- The findings suggest that HHV-6 may represent one of several potential etiologies for MTS.
- HHV-6 infection appears to be associated with less severe hippocampal damage in MTS compared to other causative factors.
