Investigators from Fujita Health University, Toyoake, and National Epilepsy Center, Shizuoka, Japan, studied the pathogenic role of HHV-6B in patients with mesial temporal lobe epilepsy (MTLE). Of 75 intractable MTLE patients, 52 had mesial temporal sclerosis (MTS) and 23 were non-MTS patients. Resected samples of hippocampus, amygdala, and mixed samples of amygdala and uncus were examined by real-time polymerase chain reaction (PCR) and reverse-transcriptase PCR to detect viral DNA and messenger RNA (mRNA), respectively. Detection of HHV-6 DNA was higher in MTS patients than non-MTS patients. Of 9 herpes viruses analyzed, HHV-6 was the most frequently detected. DNA was determined in 12/27 HHV-6 DNA-positive samples and no HHV-6B mRNA were detected in all samples. In MTS patients, expression of monocyte chemotactic protein-1 and glial fibrillary acidic protein were significantly higher in the amygdala samples with HHV-6 DNA than those without viral DNA. The number of prolonged febrile seizures early in life was higher in the MTS patients than the non-MTS patients. HHV-6B may play an important role in the pathogenesis of MTS via modification of host gene expression. Latent infection rather than reactivation of HHV-6 probably contributes to the development of MTS. 
COMMENTARY. Prolonged febrile seizures or febrile status epilepticus (FSE) are associated with an increased risk of MTS and TLE, the subject of an ongoing, prospective multicenter study, the FEBSTAT study . In 1964 and 1968, Falconer MA, Neurosurgeon at the Maudsley Hospital, London, UK, investigating the etiology of TLE, reported 13 (28%) of 47 cases with a history of infantile convulsions ascribed to fever [3, 4]. In comparison, 7 (15%) had a history of difficult birth. As early as 1956, Cavanagh and Meyer noted the high incidence of febrile convulsions preceding onset of TLE . In the recent FEBSTAT study, HHV-6B viremia is reported in 54 of 169 subjects (32%) at the time of FSE .
A relationship between MTS and a history of febrile seizures and HHV-6B positivity is demonstrated in the current study . Further, the viral load of HHV-6B correlates with markers that reflect inflammatory injury. Neuroinflammation is recognized as a key component of epilepsy pathogenesis . If HHV-6-related febrile seizures are involved in the etiology of temporal sclerosis and TLE, antivirals that penetrate the blood-brain barrier administered at a young age for treatment of prolonged febrile seizures could prevent the development of MTLE .