title: Diagnostic significance of intrathecally produced herpes simplex and varizella-zoster virus-specific antibodies in central nervous system infections.
abstract: OBJECTIVE
  The optimal strategy for the diagnosis of herpes simplex virus (HSV) and varizella-zoster virus (VZV) disease of the central nervous system is the detection of viral DNA by polymerase chain reaction assay (PCR) in cerebrospinal fluid (CSF) and the examination of intrathecal production of specific antibodies. However, in acute neurological disease caused by either HSV or VZV, dual intrathecal synthesis of HSV-1, 2- as well as VZV-specific antibodies may be detectable and thus can hamper accurate aetiological diagnosis. This paper illustrates such equivocal findings in two case reports, investigates their frequency and discusses the possible reasons.
  
  
  METHODS
  Consecutive CSF/serum pairs of two patients with central nervous system (CNS) disease were tested by HSV-1-, HSV-2-, and VZV-specific PCR and by different serological assays for detection of neurotropic viruses and bacteria. Additionally, the results of microbiological investigations of 1'155 CSF/serum samples were retrospectively analyzed for coincident intrathecal antibody synthesis against HSV-1, 2 and VZV.
  
  
  RESULTS
  Although only HSV-1 and VZV-specific DNA was detectable in the CSF of two patients with encephalitis and chronic meningitis, respectively, increasing intrathecal antibody production against both virus species could be demonstrated. Retrospective analysis of 1155 CSF/serum pairs revealed 55 (4.8%) pairs with evidence for intrathecally produced antibodies against either HSV-1, 2 (30/55) or VZV (14/55). Eleven of these 55 (20%) pairs showed intrathecal antibody-production against both virus species.
  
  
  CONCLUSIONS
  Patients with CNS infection with HSV and VZV can be diagnosed by detecting intrathecally produced virus-specific antibodies, in addition to virus-specific PCR. However, in an appreciable proportion of patients a correct diagnosis is hampered by coincidentally detected antibodies in CSF against both virus species. Possible reasons for these equivocal findings are given.
authors.affiliation: Institute for Clinical Microbiology and Immunology, St. Gallen, Switzerland. detlev.schultze@ikmi.ch
authors.forename: Detlev
authors.initials: D
authors.lastname: Schultze
authors.forename: Bruno
authors.initials: B
authors.lastname: Weder
authors.forename: Pascal
authors.initials: P
authors.lastname: Cassinotti
authors.forename: Lucie
authors.initials: L
authors.lastname: Vitek
authors.forename: Konrad
authors.initials: K
authors.lastname: Krausse
authors.forename: Walter
authors.initials: W
authors.lastname: Fierz
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000914:Antibodies, Viral / Q000097:blood / Q000134:cerebrospinal fluid*; D000918:Antibody Specificity; D020805:Central Nervous System Viral Diseases / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D002555:Cerebrospinal Fluid / Q000166:cytology; D004279:DNA, Viral / Q000134:cerebrospinal fluid; D018792:Encephalitis, Viral / Q000134:cerebrospinal fluid / Q000175:diagnosis; D005260:Female; D006561:Herpes Simplex / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D006562:Herpes Zoster / Q000134:cerebrospinal fluid / Q000175:diagnosis*; D014645:Herpesvirus 3, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000134:cerebrospinal fluid; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D018139:Simplexvirus / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D004279:DNA, Viral; D007074:Immunoglobulin G