Infectious/Autoimmune Disorders

Role of HHV6B Infection in Mesial Temporal Lobe Epilepsy

Authors: {'first_name': 'John', 'last_name': 'Millichap', 'middle_name': 'J'},{'first_name': 'J', 'last_name': 'Millichap', 'middle_name': 'Gordon'}

Abstract

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.
Keywords: Human Herpesvirus 6Temporal LobeMesial Temporal Sclerosis 
DOI: http://doi.org/10.15844/pedneurbriefs-29-5-7
 Accepted on 27 May 2015            Submitted on 20 May 2015

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. [1]

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 [2]. 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 [5]. In the recent FEBSTAT study, HHV-6B viremia is reported in 54 of 169 subjects (32%) at the time of FSE [2].

A relationship between MTS and a history of febrile seizures and HHV-6B positivity is demonstrated in the current study [1]. Further, the viral load of HHV-6B correlates with markers that reflect inflammatory injury. Neuroinflammation is recognized as a key component of epilepsy pathogenesis [6]. 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 [6].

Disclosures

The author(s) have declared that no competing interests exist.

References

  1. Kawamura, Y Nakayama, A Kato, T Miura, H Ishihara, N Ihira, M et al. (2015). Pathogenic Role of Human Herpesvirus 6B Infection in Mesial Temporal Lobe Epilepsy. J Infect Dis, Epub 2015 Apr 3.DOI: https://doi.org/10.1093/infdis/jiv160 [PubMed]  

  2. Epstein, LG Shinnar, S Hesdorffer, DC Nordli, DR Hamidullah, A Benn, EK et al. (2012). Human herpesvirus 6 and 7 in febrile status epilepticus: the FEBSTAT study. Epilepsia 53(9): 1481–8, DOI: https://doi.org/10.1111/j.1528-1167.2012.03542.x [PubMed]  

  3. Falconer, MA, Serafetinides, EA and Corsellis, JA (1964). Etiology and Pathogenesis of Temporal Lobe Epilepsy. Arch Neurol 10: 233–48, DOI: https://doi.org/10.1001/archneur.1964.00460150003001 [PubMed]  

  4. Falconer, MA and Taylor, DC (1968). Surgical treatment of drug-resistant epilepsy due to mesial temporal sclerosis. Etiology and significance. Arch Neurol 19(4): 353–61, DOI: https://doi.org/10.1001/archneur.1968.00480040019001 [PubMed]  

  5. Cavanagh, JB and Meyer, A (1956). Aetiological aspects of Ammon's horn sclerosis associated with temporal lobe epilepsy. Br Med J 2(5006): 1403–7, DOI: https://doi.org/10.1136/bmj.2.5006.1403 [PubMed]  

  6. Leibovitch, EC and Jacobson, S (2015). Human Herpesvirus 6 as a Viral Trigger in Mesial Temporal Lobe Epilepsy. J Infect Dis, Epub 2015 Apr 3.DOI: https://doi.org/10.1093/infdis/jiv162 [PubMed]