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