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Mesial Temporal Sclerosis Is Linked with Human Herpes Virus 6


NEW ORLEANS—Patients with drug-resistant epilepsy and mesial temporal sclerosis (MTS) were more likely to be positive for human herpes virus 6 (HHV6) than those with other disorders, according to new findings from the National Institute of Neurological Disorders and Stroke (NINDS) presented here at the American Epilepsy Society annual meeting.

The findings add to the body of evidence that MTS and HHV6 infection are linked and bolster the case for investigating potential clinical treatments in certain patients with HHV6 infection, the researchers said. They noted, though, that more progress needs to be made before that line of inquiry can occur.

"For many years, there has been interest in a possible association between infection with human herpes virus 6 and epilepsy, and that has mainly come up in the context of children with febrile seizures," said presenting author and NINDS senior investigator William H. Theodore, MD, FAAN.

A small percentage of these children went on to develop epilepsy — mainly those with febrile status epilepticus or prolonged or complicated febrile seizures associated with other neurological deficits, he said.

The current study included 66 patients who had focal resection for drug-resistant epilepsy, with a mean onset age of 12 and a mean age at surgery of 29. Forty-two of the patients had MST, 16 had focal cortical dysplasia, four had venous malformations, three had tumors, and one had chronic encephalitis.

"We were interested to see whether patients who had surgery for drug-resistant epilepsy had increased viral loads of HHV6 in the resected specimens," Dr. Theodore said.

The research team found that patients with MTS were more likely to be positive for HHV6 than those with other pathologies (p<0.01). The MTS cohort was the only group in which more patients were positive for HHV6 (approximately 60 percent) than were negative. By comparison, for example, fewer than one-third of the patients in the focal cortical dysplasia group were positive for the virus.

Dr. Theodore pointed to the FEBSTAT study as pivotal for the field in moving forward with efforts to target HHV6 therapeutically. In that study, children with febrile status epilepticus have been evaluated with sequential magnetic resonance imaging, and fluids were collected to see whether there is any relationship between HHV6 infection and development of MTS and epilepsy.

Dr. Theodore said those results will be crucial in knowing which steps to take toward clinical application.

"We really need to wait on the results of the FEBSTAT study," Dr. Theodore said. "Because if we can show that children with febrile status epilepticus who have HHV6 infection are more likely to develop epilepsy later on, then we could potentially design a clinical trial to see whether an antiviral intervention would be helpful. But we don't yet know that."

Shlomo Shinnar, MD, PhD, FAAN, professor of neurology at Albert Einstein College of Medicine and immediate past president of the American Epilepsy Society, said the findings build on prior work. He is the lead investigator on the FEBSTAT study.

"FEBSTAT data suggest that HHV6 is a common cause of febrile illness associated with status (epilepticus)" but without any difference in outcomes, he said. 

He said the question of cause is still unanswered.

"Herpes viruses have a predilection for the hippocampus and all of us likely carry them in our brain," he said. "So the question remains whether findings in this study simply reflect the distribution of herpes virus in our brain, or a causal relationship."

Dr. Theodore disclosed that he is the treasurer of the American Epilepsy Society. The Society receives funding from Eisai, Lundbeck, Upsher-Smith, Greenwich Biosciences, Supernus, Zogenix, and Sun Neuroscience. Dr. Theodore does not receive funding from any commercial  source and has no personal conflicts to report.


AES Abstract 1.081: Theodore W, Leibovitch E, Billioux B, et al. Human herpes virus 6 in patients with drug-resistant epilepsy.