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Progressive multifocal leucoencephalopathy (PML) is an opportunistic infection caused by JC virus (JCV) in immunodeficient individuals. The pathological hallmark is irreversible white matter demyelination. The diagnosis is supported by the clinical presentation (subacute motor deficits, ataxia and cortical visual symptoms), characteristic findings on magnetic resonance imaging (MRI) of the brain (bilateral, asymmetric, well-demarcated, T2 hyperintense white matter lesions with no oedema) and JCV detection by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF).

We obtained retrospective data for all JCV PCR test results performed on CSF samples between March 2002 and November 2011 from HIV-seropositive patients at Chelsea & Westminster Hospital NHS Trust. In total, 564 CSF samples from HIV-positive patients were tested for JCV during 117 months, of which seven (1.24%) were positive. Contemporaneous MRI imaging of the brain was performed in 360 of 564 patients (63.8%) (Table 1).

Table 1. Correlation of MRI brain findings with JCV positivity in the CSF
Contemporaneous MRI of the brain reportNumber of CSF samples tested for JCVNumber of positive JCV testsPercentage of positive samples
  1. CSF, cerebrospinal fluid; JCV, JC virus; MRI, magnetic resonance imaging; PML, progressive multifocal leucoencephalopathy.

Suggestive of PML6434.69
Suggestive of an infectious, but non-PML, pathology7722.60
Normal or suggestive of a noninfectious pathology21910.46
MRI not performed20410.49

The gold standard for diagnosis of PML is brain biopsy. However, this is often unsafe, unethical or unnecessary. The combination of an appropriate clinical presentation and typical findings on brain MRI is often sufficient to make the diagnosis, for which highly active antiretroviral therapy (HAART) is the evidence-based treatment[1]. The utility of JCV PCR testing in the CSF of HIV-seropositive individuals is under question (sensitivity for MRI-proven PML = 24–89.5% [2, 3]). Unsurprisingly, the use of HAART has been shown to reduce the sensitivity of this test (57.5% vs. 89.5% in patients not on HAART [3]).

JCV was infrequently detected in the CSF of HIV-positive individuals over a 9-year period. Although JCV was more frequently found in the CSF of patients with MRI findings suggestive of PML, the detection rate was still <5%, suggesting a very high false negative rate for this test. CSF JCV testing should not be performed routinely when MRI of the brain is normal or suggestive of a noninfectious pathology. Even when PML is suspected on MRI of the brain, JCV CSF is unlikely to be positive. We conclude that many of these tests are unnecessary, offering a potential to significantly reduce costs without compromising patient care.

References

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  2. References
  • 1
    Nelson M, Dockrell DH, Edwards S. British HIV Association and British Infection Association guidelines for the treatment of opportunistic infection in HIV-seropositive individuals 2011. HIV Medicine 2011; 12: 15.
  • 2
    Wang Y, Kirby JE, Qian Q. Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy. Journal of Medical Microbiology 2009; 58: 253255.
  • 3
    Marzocchetti A, Di Giambenedetto S, Cingolani A et al. Reduced Rate of Diagnostic Positive Detection of JC Virus DNA in Cerebrospinal Fluid in Cases of Suspected Progressive Multifocal Leukoencephalopathy in the Era of Potent Antiretroviral Therapy. Journal of Clinical Microbiology 2005; 43: 41754177.