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Updated: Dec 6 2018

JC Virus

  • Snapshot
    • A 47-year-old man is brought to the emergency room by his wife for right leg weakness. He first had some right lower leg weakness a week ago which progressed to almost full paralysis of the entire right leg. He has a past medical history of HIV infection, though he has not been on any antiretroviral medications and does not follow up at his HIV clinic regularly. His last CD4 cell count was 2 years ago and was > 500/μL. On physical exam, he is unable to move his right leg. A brain MRI shows non-enhancing white matter lesions. A lumbar puncture is done and the cerebral spinal fluid is sent for polymerase chain reaction testing. He is started on antiretroviral medications.
  • Introduction
    • Classification
      • John Cunningham virus (JC virus)
        • a non-enveloped, circular, double-stranded DNA virus
          • a polyomavirus
        • causes progressive multifocal leukoencephalopathy (PML)
        • transmission via respiratory or oral
    • Epidemiology
      • incidence
        • 4-5% of patients with acquired immune deficiency syndrome (AIDS)
      • demographics
        • occurs in immunosuppressed patients
      • location
        • central nervous system (CNS)
          • parietal and occipital
      • risk factors
        • transplant patients
        • HIV/AIDS patients
          • in those with low CD4 cell counts (< 200/μL)
        • hematologic malignancy
        • immunotherapy
          • natalizumab
          • rituximab
    • Pathogenesis
      • PML results from reactivation of latent JC virus infection
        • the virus is latent in the kidneys, brain, and lymphoreticular tissues
        • when a patient is immunosuppressed, the virus replicates and disseminates to the brain
        • infection of the oligodendrocytes leads to demyelination of the CNS
    • Prognosis
      • fatal within weeks to months
  • Presentation
    • Symptoms
      • symptoms occur over days to weeks
      • headache
      • behavioral changes
    • Physical exam
      • focal neurologic deficits
        • aphasia
        • ataxia
        • gait abnormalities
        • visual impairment
        • limb weakness
      • seizures
  • Imaging
    • Brain magnetic resonance imaging (MRI)
      • indication
        • all patients
      • findings
        • non-enhancing white matter lesions
  • Studies
    • Labs
      • cerebrospinal fluid (CSF) studies
        • can have elevated protein
        • detection of DNA with polymerase chain reaction (PCR)
    • Brain biopsy
      • indication
        • CSF fluid did not yield any diagnosis
      • findings
        • demyelination
        • astrocytes with atypical nuclei
        • ballooned oligodendroglial nuclei
    • Making the diagnosis
      • based on clinical presentation and either histopathologic features on biopsy, PCR, or radiologic evidence
  • Differential
    • Cerebral toxoplasmosis
      • distinguishing factor
        • typically has a more acute onset of hours to days rather than PML’s subacute onset of days to weeks
  • Treatment
    • Management approach
      • mainstay of treatment is antiretroviral therapy and supportive care
      • if on immunotherapy, patients should discontinue immediately
    • Conservative
      • supportive care
        • indication
          • all patients
    • Medical
      • antiretroviral therapy
        • indication
          • patients with HIV
  • Complications
    • Permanent neurologic sequelae
    • PML-immune reconstitution inflammatory syndrome
      • may occur about 1 month after reversing immunosuppression, such as through starting antiviral therapy or discontinuing immunotherapy (up to 17%)
      • presentation
        • presents with increased neurologic deficits and brain edema
      • treatment
        • corticosteroids
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