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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
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
Smoking is reportedly associated with an increased risk of PML
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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
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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