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Cited by 274Infectious Encephalopathies and EncephalitisViral Infections and Immunology ResearchVirology and Viral Diseases

Molecular Methods for Diagnosis of Viral Encephalitis

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DeBiasi, Roberta L., Tyler, Kenneth L.·2004·Clinical Microbiology Reviews
DOI 10.1128/cmr.17.4.903-925.2004PMC PMC523566
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Abstract

SUMMARY: Hundreds of viruses cause central nervous system (CNS) disease, including meningoencephalitis and postinfectious encephalomyelitis, in humans. The cerebrospinal fluid (CSF) is abnormal in >90% of cases; however, routine CSF studies only rarely lead to identification of a specific etiologic agent. Diagnosis of viral infections of the CNS has been revolutionized by the advent of new molecular diagnostic technologies to amplify viral nucleic acid from CSF, including PCR, nucleic acid sequence-based amplification, and branched-DNA assay. PCR is ideally suited for identifying fastidious organisms that may be difficult or impossible to culture and has been widely applied for detection of both DNA and RNA viruses in CSF. The technique can be performed rapidly and inexpensively and has become an integral component of diagnostic medical practice in the United States and other developed countries. In addition to its use for identification of etiologic agents of CNS disease in the clinical setting, PCR has also been used to quantitate viral load and monitor duration and adequacy of antiviral drug therapy. PCR has also been applied in the research setting to help discriminate active versus postinfectious immune-mediate disease, identify determinants of drug resistance, and investigate the etiology of neurologic disease of uncertain cause. This review discusses general principles of PCR and reverse transcription-PCR, including qualitative, quantitative, and multiplex techniques, with comment on issues of sensitivity, specificity, and positive and negative predictive values. The application of molecular diagnostic methods for diagnosis of specific infectious entities is reviewed in detail, including viruses for which PCR is of proven efficacy and is widely available, viruses for which PCR is less widely available or for which PCR has unproven sensitivity and specificity, and nonviral entities which can mimic viral CNS disease.

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  • Molecular testing has improved sensitivity and is faster than culture, becoming the standard of care for many viral CNS infections, such as for the herpesviruses, EV, and HPeV.

    “As for the detection of viruses, molecular testing has improved sensitivity and is faster than culture, becoming the standard of care for many viral CNS infections, such as for the herpesviruses, EV, and HPeV (23).”

    From Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens (2016) · cites this paper as [23]

    The CSF PCR section says PCR is faster than culture, and the section on viruses for which PCR is of proven efficacy reports greater sensitivity than culture for enteroviruses. The Multiplex and Consensus Primer PCRs section calls PCR the diagnostic gold standard for HSV and enterovirus infections. Our copy does not address HPeV; searches for “HPeV” and “parechovirus” found no supporting passage, so that example is unsupported. (LLM, conf=0.88)

    Experimental — accuracy not yet measured

  • The other herpesviruses (CMV, VZV, and HHV-6) are critical pathogens in certain populations, including immunosuppressed patients, and are best detected in the CNS by molecular methods.

    “They are critical pathogens in certain populations, including immunosuppressed patients (34), and are best detected in the CNS by molecular methods (23).”

    From Multicenter Evaluation of BioFire FilmArray Meningitis/Encephalitis Panel for Detection of Bacteria, Viruses, and Yeast in Cerebrospinal Fluid Specimens (2016) · cites this paper as [23]

    The CSF PCR section describes molecular testing as a useful way to diagnose viral CNS infections, and the CMV section reports high sensitivity and specificity for CSF PCR in HIV-infected patients. But the VZV section says intrathecal antibody testing may be more reliable than PCR in subacute or chronic CNS infection, while the HHV-6 section cautions that detecting viral DNA does not necessarily establish disease. The unqualified claim that all three are best detected by molecular methods therefore overstates the source. Page numbers were not available in our copy. (LLM, conf=0.88)

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Research works printed but not linked: 4

  1. [60]60. Coyle, P. 2000. Postinfectious encephalomyelitis, p. 83-108. In K. P. Davis (ed.), Infectious diseases of the nervous system. Butterworth-Heinemann, Oxford, United Kingdom.
  2. [104]104. Hamilton, R. L., C. Achim, M. R. Grafe, J. C. Fremont, D. Miners, and C. A. Wiley. 1995. Herpes simplex virus brainstem encephalitis in an AIDS patient. Clin. Neuropathol. 14: 45-50.
  3. [115]115. Johnson, R. T. 1998. Viral infections of the nervous system, 2nd ed. Lippincott-Raven Press, Philadelphia, Pa.
  4. [237]237. van der Meer, J. T., W. L. Drew, R. A. Bowden, G. J. Galasso, P. D. Griffiths, D. A. Jabs, C. Katlama, S. A. Spector, and R. J. Whitley. 1996. Summary of the International Consensus Symposium on Advances in the Diagnosis, Treatment and Prophylaxis and Cytomegalovirus Infection. Antiviral Res. 32: 119-140.

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Authors
DeBiasi, R. L., & Tyler, K. L.
Affiliations
  • Denver VA Medical Center (US)
  • University of Colorado Health (US)
ORCID
Venue
Clinical Microbiology Reviews
Publisher
American Society for Microbiology
Published
2004-10
Volume
17
Issue
4
Pages
903-925
ISSN
  • 0893-8512 (ISSN-L)
  • 1098-6618
DOI
10.1128/cmr.17.4.903-925.2004
PMC
PMC523566
OpenAlex
W2136484280
Cited by
274
References
139
Citations by year
2026: 9 · 2025: 12 · 2024: 15 · 2023: 13 · 2022: 14 · 2021: 10 · 2020: 11 · 2019: 19 · 2018: 21 · 2017: 16 · 2016: 13 · 2015: 19 · 2014: 10 · 2013: 10 · 2012: 7
FWCI
1.07
Type
journal article
Language
en
Open access
Licence
journals.asm.org/non-commercial-tdm-license (tdm)
Locations
  • Clinical Microbiology Reviews (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Viral Infections and Immunology Research
  • Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords
viral encephalitis, meningoencephalitis, post-infectious encephalomyelitis, cerebrospinal fluid, PCR, reverse transcription PCR, NASBA, branched DNA assay, viral load quantification, antiviral therapy monitoring, sensitivity and specificity, viral infections of the central nervous system
MeSH terms
Cytomegalovirus Infections, Cytomegalovirus, Humans, Polymerase Chain Reaction, Encephalitis, Viral

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