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Key Features

  • A rare demyelinating CNS disorder

  • Caused by the reactivation of the JC virus (John Cunningham virus or JCV)

    • Virus remains latent in the kidneys, lymphoid tissues, epithelial cells, peripheral blood leukocytes, bone marrow, and possibly brain until reactivation occurs and symptoms become evident

    • Reactivation is usually seen in adults with

      • Impaired cell-mediated immunity, especially AIDS patients

      • Idiopathic CD4 lymphopenia syndrome

    • Virus reactivation is also reported among patients who have

      • Lymphoproliferative and myeloproliferative disorders

      • Granulomatous, inflammatory, and rheumatic diseases (systemic lupus erythematosus and rheumatoid arthritis in particular)

      • Undergone solid and hematopoietic cell transplantation

      • Other medical states, including cirrhosis and kidney disease (occasionally)

  • Medication-associated PML is described with the use of

    • Natalizumab

    • Rituximab

    • Infliximab

    • Efalizumab (withdrawn from the US market in April 2009)

    • Azathioprine with corticosteroids

    • Mycophenolate mofetil

  • Smoking is reportedly associated with an increased risk of PML

Clinical Findings

  • Altered mental status

  • Aphasia

  • Ataxia

  • Hemiparesis

  • Hemiplegia and visual field disturbances

  • Seizures

  • Involvement of cranial nerves and cervical spine (rare)

Diagnosis

  • Polymerase chain reaction (PCR) for JCV in cerebrospinal fluid; a quantitative PCR is more sensitive

  • Persistent JC viremia and increasing urinary JCV DNA may be predictive of PML

  • An anti-JCV immunoglobuin G (IgG) was higher 6 months before diagnosis but was not predictive of PML in a cohort of HIV-infected patients

  • MRIs of the brain show multifocal areas of white matter demyelination without mass effect or contrast enhancement; these findings may not be distinguishable from immune reconstitution inflammatory syndrome (IRIS)

  • Increased uptake of methionine with concomitant decreased uptake of fluorodeoxyglucose in positron emission tomography may be helpful for diagnosis

  • In the HIV-infected a syndrome of cerebellar degeneration is described

Treatment

  • Limiting the immunosuppression state without inducing IRIS represents the mainstay of therapy

    • In HIV-infected patients, antiretroviral therapy

    • Reduces the incidence of PML

      • Improves the clinical symptoms

      • Reverses some of the radiographic abnormalities

      • Improves the 1-year mortality rate, regardless of baseline CD4 count

    • In non-AIDS patients (eg, multiple sclerosis or transplant patients)

      • Cidofovir may be beneficial

      • Corticosteroids may be useful with immune reconstitution

      • Because the JCV infects cells through serotonin receptors, risperidone and mirtazapine are recommended by some clinicians

  • In natalizumab-associated PML, plasma exchange is used by some experts

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