Clinical Presentation and Disease Course of 37 Consecutive Cases of Progressive Multifocal Leukoencephalopathy (PML) at a German Tertiary-Care Hospital: A Retrospective Observational Study

Abstract

Background: Progressive multifocal leukoencephalopathy (PML) caused by JCV is a rare but frequently fatal disease of the central nervous system, usually affecting immunocompromised individuals. Our study aims to expand the data on patient characteristics, diagnosis, clinical course, possible PML-directed treatment, and outcome of patients with PML at a German tertiary-care hospital. Methods:In this single-center observational cohort study, 37 consecutive patients with a confirmed diagnosis of PML seen at the University Medical Center Hamburg-Eppendorf from 2013 until 2019 were retrospectively analyzed by chart review with a special focus on demographics, risk factors, and clinical aspects as well as PML-directed treatment and survival. Results:We identified 37 patients with definite, probable, and possible PML diagnosis. 36 patients (97%) had underlying immunosuppressive disorders such as HIV/AIDS (n = 17; 46%), previous treatment with monoclonal antibodies (n = 6; 16%), hematological or oncological malignancies (n = 6; 16%), sarcoidosis (n = 5; 14%), solid organ transplantation (n = 1; 3%), and diagnosis of mixed connective tissue disease (n = 1; 3%). In only one patient no evident immunocompromised condition was detected (n = 1; 3%). Treatment attempts to improve the outcome of PML were reported in 13 patients (n = 13; 35%). Twenty seven percent of patients were lost to follow-up (n = 10). Twenty four-month survival rate after diagnosis of PML was 56% (n = 15). Conclusion: This interdisciplinary retrospective study describes epidemiology, risk factors, clinical course, and treatment trials in patients with PML at a German tertiary-care hospital. Acquired immunosuppression due to HIV-1 constituted the leading cause of PML in this monocenter cohort.

Keywords: HIV; JCV; PML-directed treatment; progressive multifocal leukoencephalopathy (PML); risk factors; survival rate.

Figure 1

Diagnostic flowchart of patients with diagnosed PML. As underlying immunosuppressive condition patients with possible PML (n = 4) all suffered from HIV.

Figure 2

MRI scan and hispathology after stereotactic brain biopsy in a representative patient with PML. (A) Superatentional cPML lesion in an immunosuppressed patient with typical moderate mass effect in relation to size of the lesion. T1 weighted imaging before (1) and after contrast administration (2) showing a centrally hypointense lesion with a slightly hyperintense rim that enhances gadolinium (arrow) (3). The lesion typically involves the subcortical U-fibers in T2 weighted images (4). The ADC map of diffusion weighted imaging showing a restricted diffusion in the region of the enhancing ring (dotted arrow) and facilitated diffusion in the rest of the lesion. (B) Left. Stereotactic biopsy revealed active inflammation with demyelination. T cell infiltrates, numerous foamy macrophages (asterisks) and reactive gliosis (arrows); middle, immunohistochemical labeling of large reactive astrocytes (arrow) with antibodies against glial fibrillary acidic protein; right, immunohistochemical demonstration of SV40 protein in scattered cell nuclei; scale = 50 μm.