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 (CNS) which almost always occurs in an immunocompromised patient.
Indications for Testing
Demyelinating central nervous system (CNS) lesions in an immunocompromised patient
- Polymerase chain reaction (PCR) – cerebrospinal fluid (CSF)
- Positive CSF test with appropriate clinical symptoms strongly supports diagnosis (high sensitivity)
- May obviate need for brain biopsy (Berger, 2013)
- Negative test does not rule out progressive multifocal leukoencephalopathy (PML)
- Blood and urine tests available but do not correlate with active CNS infection
- Other CSF testing
- Use to exclude other, more common diagnoses (eg, bacterial or viral meningitis, encephalitis)
- Should include cell count with differential, protein, glucose, and bacterial culture
- Culture for JC virus (JCV) should not be performed outside of a research setting (growth is too slow)
- JCV antibodies
- Use to stratify risk for PML prior to high-risk treatments (eg, natalizumab)
- Not useful for diagnosis – >50-86% of people have been exposed to JCV and have positivity
- Brain biopsy – gold standard and usually diagnostic
- Most useful if JCV is not detected in CSF
- May not be feasible to perform 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 oligodendroglial cells and astrocytes
- Computed tomography (CT) – patchy or confluent hypodense white matter lesions
- Magnetic resonance imaging (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 or conform to cerebrovascular territories
- Cerebral infarction
- Other neurologic diseases
- CNS lymphoma
- Metastatic cancer
- >50-86% of population is JC virus (JCV) infected, typically by late childhood
- Progressive multifocal leukoencephalopathy (PML) presentation of the infection is rare
- Age – all ages
- Sex – M>F
- JCV is a nonenveloped double-stranded DNA virus of the Polyomaviridae (formerly Papovaviridae) family, which also includes BK virus (BKV) and simian virus 40 (SV40)
- JCV infects only humans
- JCV and BKV – names were derived from initials of first patients identified with these diseases
- HIV infection
- Malignancy (eg, leukemia, lymphoma)
- Medications – benefits of treatment must be weighed against known risk of PML
- Dimethyl fumarate (Tecfidera) – multiple sclerosis (MS)
- Natalizumab (Tysabri) – MS, Crohn disease
- Rituximab – psoriasis, systemic lupus erythematosus (SLE)
- Efalizumab – psoriasis treatment (withdrawn from market due to PML risk)
- Ocrelizumab – multiple sclerosis (suspected risk due to medication class)
- Alemtuzumab – select lymphomas, relapsing MS
- Brentuximab – select lymphomas
- Mycophenolate mofetil – immunosuppression following organ transplantation
- 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 is diverse
- Characterized by multiple focal lesions that gradually increase in size
- Typical presentation involves distinct focal symptoms, followed by progression (vs. global presentation of more diffuse encephalopathy)
- Presentation reflects location of lesion(s) – demyelinating regions can occur anywhere in the brain
- Found almost exclusively in severely immunocompromised patients
- Considered an AIDS-defining illness – 85% of cases occur in this group
- Usually occurs when CD4 count <200 cells/mm3
- Characterized by multiple focal lesions that gradually increase in size
- Inflammatory PML
- Usually occurs during immune reconstitution in HIV patients
- More favorable outcome than PML
- JCV cerebellar granule cell neuronopathy
- Ataxia, cerebellar atrophy
- JCV encephalopathy
- Aphasia, cognitive decline
- Rapidly fatal in case reports
- JCV meningitis
- Presents with signs and symptoms of chronic meningitis
ARUP Laboratory Tests
Semi-Quantitative Enzyme-Linked Immunosorbent Assay (ELISA)/Semi-Quantitative Chemiluminescent Immunoassay (CLIA)
Panel includes measles (rubeola) antibody, IgG, CSF; measles (rubeola) antibody, IgM, CSF; mumps virus antibody, IgG, CSF; mumps virus antibody, IgM, CSF; varicella-zoster virus antibody, IgG, CSF; varicella-zoster virus antibody, IgM by ELISA (CSF); herpes simplex virus type 1 and/or 2 antibodies, IgM by ELISA, CSF; herpes simplex virus type 1 and/or 2 antibodies, IgG, CSF; herpes simplex virus type 1 glycoprotein G-specific antibody, IgG by ELISA, CSF; herpes simplex virus type 2 glycoprotein G-specific antibody, IgG by ELISA, CSF; West Nile virus antibody, IgG by ELISA, CSF; West Nile virus antibody, IgM by ELISA, CSF
Reflex: if HSV 1 and/or 2 IgG, CSF is 1.10 IV or greater, then HSV 1 G-specific IgG, CSF and HSV 2 G-specific IgG, CSF will be added
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