title: Large-scale analysis of viral nucleic acid spectrum in temporal lobe epilepsy biopsies.
abstract: OBJECTIVE
  Chronic inflammatory processes are important promotors of temporal lobe epilepsy (TLE) development. Based on human herpesvirus 6 (HHV-6) DNA detection in brain tissue from patients with TLE, an association of persistent viral infection with TLE has been discussed. Individual studies reported increased HHV-6 DNA in patients with clinical signs of previous inflammatory brain reaction, that is, febrile seizures or meningoencephalitis. However, detection rates vary considerably between different studies. Here we performed a large-scale analysis of viral DNA/RNA spectrum in high-quality TLE biopsies. In addition to all Herpesviridae, we addressed potentially relevant neurotropic RNA viruses.
  
  
  METHODS
  DNA and RNA were extracted from 346 fresh-frozen tissue samples removed by epilepsy surgery. Real-time polymerase chain reaction (PCR) and nested PCR were performed for Herpesviridae and RNA viruses, respectively. Clinical data were analyzed for earlier signs of inflammatory brain reactions. Fresh-frozen hippocampal tissue samples from patients without chronic central nervous system (CNS) disease served as controls (n = 62). Seven previous PCR studies with overall 178 TLE patients were additionally analyzed regarding a correlation of clinical parameters and HHV-6 detection.
  
  
  RESULTS
  PCR revealed HHV-6B DNA in 34 specimens (9.8%) from TLE patients. HHV-6B DNA was also present in eight control samples (12.9%; p > 0.05), but showed a lower virus concentration (p < 0.001). Other herpesviruses and RNA viruses were virtually absent. In patients with clinical signs of previous brain inflammation, HHV-6B DNA was observed in 15.0%, whereas only 6.3% of the samples from patients without febrile seizures or meningoencephalitis were positive for HHV-6B DNA (p < 0.05). A meta-analysis of the eight HHV-6 PCR studies revealed similar results.
  
  
  CONCLUSIONS
  This biopsy-based study shows no differences in frequency of HHV-6B DNA detection between TLE patients and controls. These results do not support the hypothesis of a persistent HHV-6B infection as a major pathogenetic factor in TLE. However, the higher virus load in TLE patients and the increased detection rate of HHV-6B DNA in patients with previous inflammatory brain reactions require further investigations.
authors.affiliation: Department of Neuropathology, University of Bonn Medical Center, Bonn, Germany.
authors.forename: Laura
authors.initials: L
authors.lastname: Esposito
authors.forename: Jan F
authors.initials: JF
authors.lastname: Drexler
authors.forename: Oliver
authors.initials: O
authors.lastname: Braganza
authors.forename: Elke
authors.initials: E
authors.lastname: Doberentz
authors.forename: Alexander
authors.initials: A
authors.lastname: Grote
authors.forename: Guido
authors.initials: G
authors.lastname: Widman
authors.forename: Christian
authors.initials: C
authors.lastname: Drosten
authors.forename: Anna M
authors.initials: AM
authors.lastname: Eis-Hübinger
authors.forename: Susanne
authors.initials: S
authors.lastname: Schoch
authors.forename: Christian E
authors.initials: CE
authors.lastname: Elger
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Becker
authors.forename: Pitt
authors.initials: P
authors.lastname: Niehusmann
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D004279:DNA, Viral / Q000032:analysis*; D004833:Epilepsy, Temporal Lobe / Q000473:pathology* / Q000821:virology; D005260:Female; D015654:Herpesvirus 6, Human / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: Encephalitis; Epileptogenesis; Febrile seizures; HHV-6; Inflammation