JC Virus - PML

  • Diagnosis
  • Background
  • Lab Tests
  • References
  • Related Content

Indications for Testing

  • Demyelinating lesions in an immunocompromised patient

Laboratory Testing

  • Cerebrospinal fluid (CSF) testing – useful to exclude other more common diagnoses (eg, meningitis, encephalitis)
    • Should include cell count with differential, protein, glucose, and culture
    • PCR testing – positive test with appropriate clinical symptoms strongly supports diagnosis
      • May obviate need for brain biopsy
      • Negative test does not rule out PML

Histology

  • Brain biopsy – usually diagnostic; most useful if JC virus (JCV) not detected in CSF
    • May not be able to perform biopsy on debilitated patients
    • Key histologic features
      • Multifocal demyelination
      • Enlarged oligodendrocytes with nuclear inclusions
      • Large, bizarre astrocytes, reactive gliosis
        • Unusual astrocytes may cause confusion with glioma on biopsy
      • Minimal inflammation
  • Immunohistochemistry – JCV staining in oligodendrial cells and astrocytes

Imaging Studies

  • CT – patchy or confluent hypodense lesions in CNS white matter
  • MRI – more sensitive than CT
    • Recommended initial scan if suspicion for PML 
    • Hyperintense subcortical white matter lesions on T2-weighted images
  • Lesions do not have an anatomic predisposition

Differential Diagnosis

JC virus (JCV) is a human neurotropic polyomavirus that is the etiologic agent of progressive multifocal leukoencephalopathy (PML). PML is a rare, fatal, demyelinating disease of the central nervous system which almost always occurs in an immune-compromised setting.

Epidemiology

  • Incidence 
    • ≥50% of population is JC virus infected 
    • PML presentation of the infection is rare
  • Age – all ages
  • Sex – M>F

Organism

  • JCV is a nonenveloped double-stranded DNA virus of the Polyomaviridae (formerly Papovaviridae) family, which also includes BK virus (BKV) and SV40
    • JCV infects only humans
    • JCV and BKV – named using the initials of the first patients identified with these diseases

Risk Factors

  • HIV infection
  • Use of immunomodulation therapy
    • Monoclonal antibodies
      • Natalizumab
      • Efalizumab
      • Alemtuzumab
      • Rituximab
      • Brentuximab
    • Mycophenolate mofetil
    • Malignancy (eg, leukemia, lymphoma)

Pathophysiology

  • Multifocal demyelination caused by lytic infection of the oligodendrocytes
    • Lesions range in size from 1 mm to several centimeters
    • Lesions may coalesce
    • Myelin loss may be extensive
    • Atrophy may occur

Clinical Presentation

  • Clinical presentation is diverse
  • Hemiplegia, visual disturbances, and subcortical dementia
    • Progressive – fatal within 3-6 months
  • Other symptoms – motor weakness, incoordination, gait abnormalities
  • May also have JC granule cell neuropathy, JC encephalopathy, JC meningitis
  • Found almost exclusively in patients with severe immune compromise
    • Considered an AIDS-defining illness – 85% of cases occur in this group
      • Usually occurs when CD4 count <200 cells/mm3
    • Also associated with lymphoproliferative disease, natalizumab therapy (Tysabri), rituximab

Indications for Laboratory Testing

Tests generally appear in the order most useful for common clinical situations.
Click on number for test-specific information in the ARUP Laboratory Test Directory

JC Virus by PCR 0099169
Method: Qualitative Polymerase Chain Reaction

Limitations

Negative test does not rule out PML

Additional Tests Available

Cell Count, CSF 0095018
Method: Cell Count/Differential

Comments

Evaluate for bacterial versus viral etiology for CNS disorder

Findings not specific for JCV infections

Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

Comments

Evaluate protein level in suspected infectious meningitis/encephalitis

Findings not specific for JCV infections

Cerebrospinal Fluid (CSF) Culture and Gram Stain 0060106
Method: Stain/Culture/Identification

Comments

Confirm organism involved in CNS infection

Encephalitis Panel with Reflex to Herpes Simplex Virus Types 1 and 2 Glycoprotein G-Specific Antibodies, IgG, CSF 2008916
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Chemiluminescent Immunoassay

Comments

Rule out other forms of encephalitis

Glucose, CSF 0020515
Method: Enzymatic

Comments

May be helpful in differentiating bacterial from viral etiology

Usually low (<10 mg/dL) in bacterial meningitis and tuberculous disease

Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Comments

Quantifies glucose to match CSF glucose values

Guidelines

Berger J, Aksamit A, Clifford D, Davis L, Koralnik I, Sejvar J, Bartt R, Major E, Nath A. PML diagnostic criteria: consensus statement from the AAN Neuroinfectious Disease Section. Neurology. 2013; 80(15): 1430-8. PubMed

General References

Berger J. Progressive multifocal leukoencephalopathy. Handb Clin Neurol. 2014; 123: 357-76. PubMed

Jiang M, Abend J, Johnson S, Imperiale M. The role of polyomaviruses in human disease. Virology. 2009; 384(2): 266-73. PubMed

Pinto M, Dobson S. BK and JC virus: a review. J Infect. 2014; 68 Suppl 1: S2-8. PubMed

Tan C, Koralnik I. Progressive multifocal leukoencephalopathy and other disorders caused by JC virus: clinical features and pathogenesis. Lancet Neurol. 2010; 9(4): 425-37. PubMed

Tyler K. Emerging viral infections of the central nervous system: part 2. Arch Neurol. 2009; 66(9): 1065-74. PubMed

Wang Y, Kirby J, Qian Q. Effective use of JC virus PCR for diagnosis of progressive multifocal leukoencephalopathy. J Med Microbiol. 2009; 58(Pt 2): 253-5. PubMed

Medical Reviewers

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Last Update: December 2015