title: Clinical application of viral cerebrospinal fluid PCR testing for diagnosis of central nervous system disorders: a retrospective 11-year experience.
abstract: The cerebrospinal fluid (CSF) polymerase chain reaction (PCR) is the gold standard to detect cerebral viral activity. As positive findings do not prove an impact on the neurological disorder, data interpretation is difficult. To better assess the impact of positive CSF PCR findings in different neurological diseases and to identify coherences facilitating CSF PCR data interpretation, we performed this retrospective analysis of CSF PCR data of 481 pediatric and 2604 adult patients, including herpes simplex virus (HSV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), human herpesvirus 6 (HHV-6), and enteroviruses (EV). Nucleic acid of EBV was detected in 1.6% (39/2449), of VZV in 1.3% (34/2624), of HSV in 1.24% (37/2994), of EV in 0.4% (10/2364), of HHV-6 in 0.17% (4/2417), and of CMV in 0.2% (5/2514) of the patients. Newborns and elderly people showed highest infection rates. HSV, VZV, and EV prevailed in typical infectious central nervous system (CNS) diseases; EBV, in further inflammatory neurological diseases; HSV and EBV, in immunocompromised patients; and EBV, HSV, and HHV-6, in further non-inflammatory neurological diseases. Analysis of successive PCR studies revealed delayed viral detection for EBV (6/147) and HSV (1/217), respectively. Rapid viral clearance was typical for HSV, VZV, CMV, and EV infections, although the maximum duration of viral detection was 15days for HSV and 12days for VZV, respectively. This suggests that the detection of HSV, VZV, CMV, and EV strongly indicates symptomatic viral CNS disease. Secondary viral reactivation mostly underlies positive EBV and HHV-6 findings. Their detection does not rule out clinical impact but recommends searching for additional underlying conditions.
authors.affiliation: Division of Virology, Medical University of Innsbruck, Innsbruck, Austria. Electronic address: mkleines@ukaachen.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Kleines
authors.affiliation: Department of Infection Control and Infectious Diseases, RWTH Aachen University Hospital, Aachen, Germany. Electronic address: sscheithauer@ukaachen.de.
authors.forename: Simone
authors.initials: S
authors.lastname: Scheithauer
authors.affiliation: Department of Neurology, RWTH Aachen University Hospital, Aachen, Germany. Electronic address: jschiefer@ukaachen.de.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schiefer
authors.affiliation: Department of Pediatrics, Division of Pediatric Neurology and Social Pediatrics, RWTH Aachen University Hospital, Aachen, Germany. Electronic address: haeusler@rwth-aachen.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Häusler
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002493:Central Nervous System Diseases / Q000175:diagnosis*; D002555:Cerebrospinal Fluid / Q000821:virology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D025202:Molecular Diagnostic Techniques / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods*; D012189:Retrospective Studies; D014777:Virus Diseases / Q000175:diagnosis*; D014780:Viruses / Q000145:classification / Q000302:isolation & purification*; D055815:Young Adult
keywords: Cerebrospinal fluid analysis; Cytomegalovirus; Enteroviruses; Epstein–Barr virus; Herpes simplex virus; Human herpesvirus type 6; Human immunodeficiency virus infection; PCR; Stroke; Virobiome