Changing clinical and laboratory characteristics of Progressive Multifocal Leukoencephalopathy: a retrospective national cohort study

Abstract

Background: Progressive Multifocal Leukoencephalopathy (PML) is a severe demyelinating disease caused by JC polyomavirus (JCV), affecting immunocompromised individuals. We describe PML demographic, clinical, radiological and laboratory characteristics and survival over time and according to underlying condition in a large retrospective patient cohort.

Methods: This is a retrospective cohort including Italian PML patients observed between 1987 and 2024, with known year of diagnosis and underlying disease.

Results: We included 456 cases with either a definite (n=376, 82.4%) or clinico-radiological (n=80, 17.6%) PML diagnosis. The relative frequency of HIV-associated cases decreased through four time periods (1987-1996; 1997-2004; 2005-2012; 2013-2024) from 99% to 43%, in parallel with increasing age (p<0.0001), proportion of women (p<0.001) and CD4+ counts (p<0.001), but not cerebrospinal fluid (CSF) or plasma JCV-DNA levels at diagnosis. One-year survival probability increased from 23.8% in 1987-1996 to 59.2% in 2013-2024, with highest values in natalizumab-treated multiple sclerosis (93.8%), followed by combination antiretroviral treatment (cART)-treated HIV infection (55%), hematological malignancies (50.8%), primary immunodeficiencies (41.3%) and cART-untreated HIV infection (11.9%). At multivariate analysis excluding cART-untreated people with HIV, JCV-DNA levels in both CSF and plasma were independently associated with an increased mortality risk of 2.9% and 7.2%, respectively, for each Log increase in JCV-DNA.

Conclusions: This observational study showed a changing epidemiological context over 37 years. Although survival improved over time, it remained poor even in the last decade, with a one-year survival probability of 59.2%.

Keywords: JC virus; JCV; PML; Progressive Multifocal Leukoencephalopathy.