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

Lisa M Graf,Angelique Hölzemer,Julian Schulze Zur Wiesch,Marylyn M Addo,Claudia Beisel,Sabine Jordan,Christian Hagel,Manuel A Friese,Sina C Rosenkranz,Einar Goebell

doi:10.3389/fneur.2021.632535

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.

Highlights

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system that is caused by reactivation of the JC virus (JCV) in immunocompromised individuals [1]
Patients were referred from specialized neurologists to the multiple sclerosis outpatient and inpatient clinic and from infectious diseases specialists to the HIV medical department and its outpatient center
Between January 2013 and August 2019, a total of 37 patients with the diagnosis of PML were consecutively identified at the University Medical Center Hamburg-Eppendorf and included in this retrospective monocenter study

Summary

Introduction

Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system that is caused by reactivation of the JC virus (JCV) in immunocompromised individuals [1]. JCV infection is diagnosed in patients with no apparent immune defect or immunosuppression. Primary infection with JCV occurs early on in childhood and stays asymptomatic. In immunocompetent individuals JCV remains latent in kidneys and lymphoid organs. JCV can invade the brain and induce a lytic infection of oligodendrocytes [3]. PML is the result from of a primary infection with JCV and not always means a reactivation of a latent JCV infection. 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

Results

Conclusion