JC Virus - PML

Diagnosis

Indications for Testing

  • Demyelinating lesions in an immunocompromised patient

Laboratory Testing

  • Cerebrospinal fluid (CSF) testing – rule out other etiologies (eg, meningitis, encephalitis)
    • Should include cell count with differential, protein, glucose, and culture
  • JCV PCR testing in CSF – positive test with appropriate clinical symptoms strongly supports diagnosis

Histology

  • Brain biopsy – usually diagnostic; useful if 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
      • Minimal inflammation
      • Unusual astrocytes may cause confusion with glioma on biopsy
  • Immunohistochemistry – JCV staining

Imaging Studies

  • CT – patchy or confluent hypodense lesions in CNS white matter
  • MRI – more sensitive than CT
    • Hyperintense subcortical white matter lesions – T2-weighted images
  • Lesions do not have an anatomic predisposition

Differential Diagnosis

Clinical Background

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.

Epidemiology

  • Incidence – 4/100,000
    • PML presentation 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

Pathophysiology

  • Multiple foci of demyelination caused by lytic infection of the oligodendrocytes
  • Seroconversion – 90% by age 20
  • Establishes lifelong subclinical infection in immunocompetent patients

Clinical Presentation

  • Hemiplegia, visual disturbances, and subcortical dementia
    • Progressive – fatal within 3-6 months
  • Other symptoms – muscle weakness, cognitive dysfunction, gait disturbances
  • Found almost exclusively in patients with severely impaired immunity
    • Considered an AIDS-defining illness – 85% of cases occur in this group
  • May also have JC granule cell neuropathy, JC encephalopathy, JC meningitis

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
Test Name and Number Recommended Use Limitations Follow Up
Cell Count, CSF 0095018
Method: Cell Count/Differential

Evaluate for bacterial versus viral etiology for CNS disorder

Findings not specific for JCV infections

  
Protein, Total, CSF 0020514
Method: Reflectance Spectrophotometry

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

Confirm alternative etiology of infection

    
Meningoencephalitis Panel, CSF with Reflex to HSV Type 1 and Type 2 Glycoprotein G-Specific Ab, IgG 2001765
Method: Semi-Quantitative Enzyme-Linked Immunosorbent Assay/Semi-Quantitative Indirect Fluorescent Antibody/Semi-Quantitative Chemiluminescent Immunoassay

Rule out other forms of encephalitis

Panel includes California encephalitis, Eastern equine encephalitis, St. Louis equine encephalitis, Western equine encephalitis, West Nile virus, measles, mumps, varicella-zoster virus, HSV type 1 and 2, and lymphocytic choriomeningitis antibodies

    
Glucose, CSF 0020515
Method: Enzymatic

May be helpful in differentiating bacterial from viral etiology

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

    
Glucose, Plasma or Serum 0020024
Method: Quantitative Enzymatic

Quantifies glucose to match CSF glucose values

    
JC Virus by PCR 0099169
Method: Qualitative Polymerase Chain Reaction

Diagnose JCV when appropriate clinical symptoms are present