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Factors influencing PCR detection of viruses in cerebrospinal fluid of patients with suspected CNS infections
  1. N W S Davies1,
  2. L J Brown2,3,
  3. J Gonde4,
  4. D Irish2,*,
  5. R O Robinson4,
  6. A V Swan1,
  7. J Banatvala2,3,
  8. R S Howard5,
  9. M K Sharief1,
  10. P Muir3,**
  1. 1Department of Clinical Neurosciences, King’s College London, London, UK
  2. 2Department of Infection, Guy’s and St Thomas’ Hospitals NHS Trust, London, UK
  3. 3Department of Infectious Diseases, King’s College London, London, UK
  4. 4Department of Paediatric Neurology, Guy’s and St Thomas’ Hospitals NHS Trust, London, UK
  5. 5Department of Neurology, Guy’s and St Thomas’ Hospitals NHS Trust, London, UK
  1. Correspondence to:
 Dr Nicholas Davies
 Department of Clinical Neurosciences, Hodgkin Building, Guy’s Hospital, London SE1 1UL, UK;


Background: Polymerase chain reaction (PCR) is used to detect viruses in the cerebrospinal fluid (CSF) of patients with neurological disease. However, data to assist its use or interpretation are limited.

Objective: We investigated factors possibly influencing viral detection in CSF by PCR, which will also help clinicians interpret positive and negative results.

Methods: CSF from patients with was tested for human herpesviruses types 1–6, JC virus, enteroviruses, and Toxoplasma gondii. The likelihood of central nervous system (CNS) infection was classified as likely, possible, or unlikely. PCR findings in these categories were compared using single variable and logistic regression analysis.

Results: Of 787 samples tested, 97 (12%) were PCR positive for one or more viruses. Of episodes likely to be CNS viral infections, 30% were PCR positive compared to 5% categorised as unlikely. The most frequent positive findings were Epstein Barr virus (EBV), enteroviruses, and herpes simplex virus (HSV). Enteroviruses and HSV were found predominantly in the likely CNS viral infection group, whereas EBV was found mainly in the unlikely group. Positive PCR results were more likely when there were 3–14 days between symptom onset and lumbar puncture, and when CSF white cell count was abnormal, although a normal CSF did not exclude a viral infection.

Conclusions: The diagnostic yield of PCR can be maximised by using sensitive assays to detect a range of pathogens in appropriately timed CSF samples. PCR results, in particular EBV, should be interpreted cautiously when symptoms cannot readily be attributed to the virus detected.

  • CI, confidence interval
  • CMV, cytomegalovirus
  • CNS, central nervous system
  • CSF, cerebrospinal fluid
  • EBV, Epstein Barr virus
  • HHV-6, human herpes virus type 6
  • HSV-1 and 2, herpes simplex virus types 1 and 2
  • JCV, human polyomavirus JC
  • NPV, negative predictive value
  • PCR, polymerase chain reaction
  • PPV, positive predictive value
  • NS, not significant
  • VZV, varicella zoster virus
  • WCC, white cell count
  • central nervous system
  • cerebrospinal fluid
  • infection
  • polymerase chain reaction
  • viruses

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  • * Current address: Department of Microbiology, Frimley Park NHS Trust, Surrey, UK

  • ** Current address: Health Protection Agency South West, Bristol, UK

  • NWSD was supported through a Personal Training Award from the Charitable Foundation of Guy’s and St Thomas’ Hospitals. LJB was supported by a Research Contract with Innogenetics N.V., Gent, Belgium.

  • Competing interests: Peter Muir received funds from Immogenisation N.V., Gent, Belgium to develop CSF testing for the diagnosis of CNS infections. None of the other authors has competing interests to declare.

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