JC Virus

Diagnostic Algorithm

Clinical Background

The human neurotropic polyomavirus (JCV) is the etiologic agent of progressive multifocal leukoencephalopathy (PML).

Epidemiology

• Prevalence
  • Seroconversion is 90% by age 20
    • Establishes lifelong sub-clinical infection in immunocompetent patients
  • Presentation of PML is rare
• Age – all ages
• Sex – M>F

Organism

• JCV is a nonenveloped DNA virus
• BK virus and SV-40 are also members of the polyomavirus family
• JC and BK viruses were named using the initials of the first patients discovered with these diseases

Pathophysiology

• Multiple foci of demyelination caused by lytic infection of the oligodendrocytes

Clinical Presentation

• Progressive multifocal leukoencephalopathy (PML)
  • Fatal demyelinating disease of the central nervous system (CNS)
    • Progressive, fatal within 3-6 months
  • Almost exclusively in patients with severely impaired immunity
    • Considered an AIDS-defining illness
  • Hemiplegia, visual disturbances and subcortical dementia

Treatment

• No known treatment for virus
• Treatment of underlying disease may help slow the progress
• Disease is routinely fatal in neurologically symptomatic patients

Diagnosis

• Indications for testing – demyelinating lesions in an immunocompromised patient
• Laboratory testing
  • JC virus DNA PCR testing in CSF – positive test with appropriate clinical syndrome strongly supports the diagnosis
• Histology
  • Brain biopsy – usually diagnostic
    • Key histologic features
      • Multifocal demyelination
      • Enlarged oligodendrocytes with nuclear inclusions
      • Large, bizarre astrocytes
      • Minimal inflammation
    • May not be able to perform biopsy on debilitated patients
• Imaging studies
  • CT – patchy or confluent hypodense lesions in the white matter
  • MRI – hyperintense subcortical white matter lesions (T₂-weighted images)
  • Lesions do not have an anatomic predisposition

Differential Diagnosis

• Multiple sclerosis
• Acute demyelinating encephalomyelitis
• Cerebral infarction
• Subacute sclerosing panencephalitis
• Parkinson disease
• Alzheimer disease
• Bovine spongiform encephalopathy (BSE) (mad cow disease)
• Unusual astrocytes may cause confusion with glioma on biopsy

Pharmacogenetics and Therapeutic Drug Monitoring

Screening

Monitoring

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

General References