Dataset Information

Progressive multifocal leukoencephalopathy in Finland: a cross-sectional registry study.

ABSTRACT:

Objective

To investigate if progressive multifocal leucoencephalopathy (PML) incidence has increased in Finland like in the neighbouring Sweden.

Methods

National administrative registries were searched for all PML admissions aged 16 years or more in 2004-2014 on all neurological and internal medicine wards in Finland. The mortality data of the patients was extracted from the national causes of death registry. National level data on annual predisposing drug use was obtained from the national pharmaceutical authority.

Results

We identified 35 PML cases (57% male) with a peak in 2010-2011 that amounted to 49% of all cases. The annual incidence for the entire study period was 0.072/100,000 person-years (95% CI 0.050-0.10) with no temporal trend (p?=?0.18). Mean age was 57 years (22-88 years) with no sex difference (p?=?0.42). Neoplasms (60%), HIV infection (17%) and systemic connective tissue disorders (CTD, 14%) were the most common predisposing conditions. MS was recorded in three cases (9%). The national level use of drugs that predispose to PML increased during the study period, with the exceptions of alemtuzumab and fludarabine. Overall survival was 85% at 90 days, 79% at 1 year, and 66% at 5 years. Survival was worst in patients with malignancy and best in patients with CTD.

Conclusions

PML most often occurs in patients with malignancies and patients with HIV or CTD cover a third. PML incidence in Finland is lower than in Sweden and shows no temporal trend despite increasing use of predisposing drugs. Mortality after PML varies according to the predisposing condition.

SUBMITTER: Sipila JOT

PROVIDER: S-EPMC6373365 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Publications

Progressive multifocal leukoencephalopathy in Finland: a cross-sectional registry study.

Sipilä Jussi O T JOT Soilu-Hänninen Merja M Rautava Päivi P Kytö Ville V

Journal of neurology 20190105 2

<h4>Objective</h4>To investigate if progressive multifocal leucoencephalopathy (PML) incidence has increased in Finland like in the neighbouring Sweden.<h4>Methods</h4>National administrative registries were searched for all PML admissions aged 16 years or more in 2004-2014 on all neurological and internal medicine wards in Finland. The mortality data of the patients was extracted from the national causes of death registry. National level data on annual predisposing drug use was obtained from th ...[more]

PMID: 30612143

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Project description:BackgroundThe monoclonal antibody natalizumab (NTZ) is a highly effective treatment for patients with multiple sclerosis (MS). However, this drug is associated with increased risk of developing Progressive Multifocal Leukoencephalopathy (PML), an opportunistic infection of central nervous system (CNS) caused by the John Cunningham polyomavirus (JCV).ObjectiveTo describe the 12-month clinical course of 39 patients with MS (28 women, 11 men) who developed NTZ-related PML after a mean exposure of 39 infusions.MethodsAn Italian independent collaborative repository initiative collected and analyzed socio-demographic, clinical, magnetic resonance imaging (MRI) data and number of JCV-DNA copies detected on cerebrospinal fluid (CSF) samples of patients diagnosed as affected by NTZ-related PML. The evolution of disability, measured by the Expanded Disability Status Scale, was assessed at NTZ start, at PML diagnosis and after 2, 6 and 12 months from PML diagnosis. The effect of clinical and paraclinical characteristics at PML diagnosis on the final outcome was also investigated.ResultsTen patients (25.6%) were diagnosed before 24 NTZ infusions. In six cases (15.4%) the PML suspect was made on the basis of highly suggestive MRI findings in absence of any detectable change of clinical conditions (asymptomatic PML). In patients with symptomatic PML, the diagnosis was quicker for those who presented with cognitive symptoms (n = 12) rather than for those with other neurological pictures (n = 21) (p = 0.003). Three patients (7.7%) died during the 12-month observation period, resulting in a survival rate of 92.3%. Asymptomatic PML, more localized brain involvement and gadolinium-enhancement detected at MRI, as well as lower viral load were associated with a better disability outcome (p-values<0.01).ConclusionOur findings support that early PML diagnosis, limited CNS involvement and initial signs of immune restoration are associated with a better outcome and higher survival rate, and confirm the utility of MRI as a surveillance tool for NTZ-treated patients.

Project description:Progressive multifocal leukoencephalopathy (PML) is a rare demyelinating disorder of the brain caused by reactivation of the JC virus (JCV), a polyomavirus that infects at least 60% of the population but is asymptomatic or results in benign symptoms in most people. PML occurs as a secondary disease in a variety of disorders or as a serious adverse event from immunosuppressant agents, but is mainly found in three groups: HIV-infected patients, patients with hematological malignancies, or multiple sclerosis (MS) patients on the immunosuppressant therapy natalizumab. It is severely debilitating and is deadly in ~50% HIV cases, ~90% of hematological malignancy cases, and ~24% of MS-natalizumab cases. A PML risk prediction test would have clinical utility in all at risk patient groups but would be particularly beneficial in patients considering therapy with immunosuppressant agents known to cause PML, such as natalizumab, rituximab, and others. While a JC antibody test is currently used in the clinical decision process for natalizumab, it is suboptimal because of its low specificity and requirement to periodically retest patients for seroconversion or to assess if a patient's JCV index has increased. Whereas a high specificity genetic risk prediction test comprising host genetic risk variants (i.e., germline variants occurring at higher frequency in PML patients compared to the general population) could be administered one time to provide clinicians with additional risk prediction information that is independent of JCV serostatus. Prior PML case reports support the hypothesis that PML risk is greater in patients with a genetically caused immunodeficiency disorder. To identify germline PML risk variants, we performed exome sequencing on 185 PML cases (70 in a discovery cohort and 115 in a replication cohort) and used the gnomAD variant database for interpretation. Our study yielded 19 rare variants (maximum allele frequency of 0.02 in gnomAD ethnically matched populations) that impact 17 immune function genes (10 are known to cause inborn errors of immunity). Modeling of these variants in a PML genetic risk test for MS patients considering natalizumab treatment indicates that at least a quarter of PML cases may be preventable.

Dataset Information

Progressive multifocal leukoencephalopathy in Finland: a cross-sectional registry study.

Objective

Methods

Results

Conclusions

Publications

Progressive multifocal leukoencephalopathy in Finland: a cross-sectional registry study.

Similar Datasets

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