Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content + Download Section PDF Listen ++ For further information, see CMDT Part 32-03: Other Neurotropic Viruses + Key Features Download Section PDF Listen +++ ++ A rare demyelinating CNS disorder Caused by the reactivation of two polyoma viruses, the JC virus (John Cunningham virus or JCV) and, less commonly, the BK virus (associated with nephropathy) JCV 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(occasionally) Medication-associated PML is described with the use of Natalizumab Rituximab Infliximab Efalizumab (withdrawn from the US market in April 2009) Azathioprine with corticosteroids Mycophenolate mofetil Smoking is reportedly associated with an increased risk of PML +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 Download Section PDF Listen +++ ++ Altered mental status Aphasia Ataxia Hemiparesis Hemiplegia and visual field disturbances Seizures Involvement of cranial nerves and cervical spine (rare) + Diagnosis Download Section PDF Listen +++ ++ 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 patients living with HIV 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 patients living with HIV, a syndrome of cerebellar degeneration is described + Treatment Download Section PDF Listen +++ ++ Limiting the immunosuppression state without inducing IRIS represents the mainstay of therapy In patients living with HIV, 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 Pembrolizumab, a down-regulator of PD-1 Entails inhibition of the programmed cell death protein (PD-1), a negative regulator of immune clearance Reduces JC viral load Increases CD4+ and CD8+ activity against the virus in a preliminary set of eight patients with PML with different predisposing conditions In addition, allogeneic BK virus–specific T cells are useful in lowering JC viral load