Progressive multifocal leukoencephalopathy: A 25-year retrospective cohort study

Abstract

Objective: To characterize the risk factors, clinical course, and treatment of patients with progressive multifocal leukoencephalopathy (PML) diagnosed and followed over a 25-year epoch at 2 academic hospitals.

Methods: Patients with a definite diagnosis of PML were identified by positive CSF PCR for JC virus or histopathology between January 1, 1994, and January 1, 2019. Demographic and PML-specific variables were recorded on symptomatic presentation and at follow-up, including risk factors, clinical outcome, neuroimaging findings, and modified Rankin Scale (mRS) score at last follow-up.

Results: There were 91 patients with confirmed PML. HIV infection was the most common risk factor, identified in 49% (n = 45). Other frequent risk factors included lymphoma, leukemia, or myelodysplasia, identified in 31% of patients (n = 28); exposure to chemotherapeutic medications (30%, n = 27); and exposure to monoclonal antibody therapies (19%, n = 17). Thirty percent of the cohort was alive at the time of censoring, with a median mRS of 2 points, indicating slight disability at last follow-up. Median survival following PML diagnosis in HIV-infected patients was longer than in HIV-uninfected patients (1,992 vs 101 days, p = 0.024). Forty patients survived more than 1 year after PML symptom onset, of whom 24 were HIV infected (60%). Thirteen patients survived more than 10 years after PML symptom onset, all HIV infected, of the 59 patients diagnosed before June 1, 2009, and eligible for 10-year survivor status (22%).

Conclusions: We add to the limited literature on PML by reporting its epidemiology in a large observational cohort. These parameters may be useful for future clinical trials that measure survival and clinical outcomes.

Figure 1. Flowchart describing the selection of this cohort

Figure 2. The Kaplan-Meier estimator demonstrating survival following progressive multifocal leukoencephalopathy diagnosis in HIV-infected and HIV-uninfected patients^a,b

^aVital status could not be obtained for 1 patient, who was excluded from analysis. ^bA second patient was deceased on day 0 of diagnosis.

Figure 3. MRI in 4 of 13 patients who survived 10 or more years after the onset of PML symptoms

Case 1: A 37-year-old HIV-infected woman was nonadherent with her combined antiretroviral therapy for 2 years and presented with dysarthria and left hand clumsiness. (A) T2-weighted fluid attenuation inversion recovery (FLAIR) sequences revealed a large zone of hyperintensity involving the right frontal lobe, extending into the deep white matter and sparing the cortical ribbon. (B) Follow-up MRI 12 years later demonstrated tissue loss involving the right frontal lobe with associated ex vacuo dilatation of the frontal horn of the right lateral ventricle. Case 2: a 39-year-old HIV-infected man presented with gait ataxia and falls. (C) MRI revealed T2-FLAIR hyperintensity predominantly involving the left cerebellar hemisphere. (D) Follow-up MRI 12 years later demonstrated severe cerebellar and brainstem volume loss. Case 3: a 48-year-old injection drug user presented with behavioral changes, seizures, and aphasia and was found to be HIV infected. (E) MRI revealed multifocal areas of subcortical T2/FLAIR hyperintensity. (F) Follow-up MRI 10 years later revealed asymmetric volume loss. PML = progressive multifocal leukoencephalopathy.