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Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases

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ABSTRACT

The implementation of a variety of immunosuppressive therapies has made drug-associated progressive multifocal leukoencephalopathy (PML) an increasingly prevalent clinical entity. The purpose of this study was to investigate its diagnostic characteristics and to determine whether differences herein exist between the multiple sclerosis (MS), neoplasm, post-transplantation, and autoimmune disease subgroups. Reports of possible, probable, and definite PML according to the current diagnostic criteria were obtained by a systematic search of PubMed and the Dutch pharmacovigilance database. Demographic, epidemiologic, clinical, radiological, cerebrospinal fluid (CSF), and histopathological features were extracted from each report and differences were compared between the disease categories. In the 326 identified reports, PML onset occurred on average 29.5 months after drug introduction, varying from 14.2 to 37.8 months in the neoplasm and MS subgroups, respectively. The most common overall symptoms were motor weakness (48.6 %), cognitive deficits (43.2 %), dysarthria (26.3 %), and ataxia (24.1 %). The former two also constituted the most prevalent manifestations in each subgroup. Lesions were more often localized supratentorially (87.7 %) than infratentorially (27.4 %), especially in the frontal (64.1 %) and parietal lobes (46.6 %), and revealed enhancement in 27.6 % of cases, particularly in the MS (42.9 %) subgroup. Positive JC virus results in the first CSF sample were obtained in 63.5 %, while conversion after one or more negative outcomes occurred in 13.7 % of cases. 52.2 % of patients died, ranging from 12.0 to 83.3 % in the MS and neoplasm subgroups, respectively. In conclusion, despite the heterogeneous nature of the underlying diseases, motor weakness and cognitive changes were the two most common manifestations of drug-associated PML in all subgroups. The frontal and parietal lobes invariably constituted the predilection sites of drug-related PML lesions.

Electronic supplementary material: The online version of this article (doi:10.1007/s00415-016-8217-x) contains supplementary material, which is available to authorized users.

No MeSH data available.


Number of published reports on drug-associated PML throughout the years, as included in this paper
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Fig1: Number of published reports on drug-associated PML throughout the years, as included in this paper

Mentions: PML has traditionally been associated with an intrinsically compromised immune system. In the past few years, a considerable number of immunosuppressive drugs has been approved by the authorities and implemented into clinical practice to broaden the therapeutic spectrum of a variety of medical conditions [4–6]. Consequently, medication-associated PML has become an increasingly prevalent clinical entity, as reflected by an exponential increase in the number of published cases (Fig. 1). Because of the frequently poor prognosis of PML, it is of paramount importance to establish this diagnosis at an early stage. However, a comprehensive, quantitative analysis of the clinical, radiological, and CSF features of drug-associated PML and its subgroups, based on the underlying disease categories, has never been conducted thus far. Nevertheless, for an early diagnosis it is crucial for clinicians across various specialties to be aware of the preferential clinical and radiological presentation and the potential differences herein between the subgroups. In this study, we aimed to address this urgent medical need for advances in knowledge on drug-associated PML by outlining its specific clinical, radiological, and CSF characteristics. A quantitative assessment of the degree of association between any particular drug and PML has been reported previously, and therefore fell beyond the scope of this paper [7].Fig. 1


Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases
Number of published reports on drug-associated PML throughout the years, as included in this paper
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5037162&req=5

Fig1: Number of published reports on drug-associated PML throughout the years, as included in this paper
Mentions: PML has traditionally been associated with an intrinsically compromised immune system. In the past few years, a considerable number of immunosuppressive drugs has been approved by the authorities and implemented into clinical practice to broaden the therapeutic spectrum of a variety of medical conditions [4–6]. Consequently, medication-associated PML has become an increasingly prevalent clinical entity, as reflected by an exponential increase in the number of published cases (Fig. 1). Because of the frequently poor prognosis of PML, it is of paramount importance to establish this diagnosis at an early stage. However, a comprehensive, quantitative analysis of the clinical, radiological, and CSF features of drug-associated PML and its subgroups, based on the underlying disease categories, has never been conducted thus far. Nevertheless, for an early diagnosis it is crucial for clinicians across various specialties to be aware of the preferential clinical and radiological presentation and the potential differences herein between the subgroups. In this study, we aimed to address this urgent medical need for advances in knowledge on drug-associated PML by outlining its specific clinical, radiological, and CSF characteristics. A quantitative assessment of the degree of association between any particular drug and PML has been reported previously, and therefore fell beyond the scope of this paper [7].Fig. 1

View Article: PubMed Central - PubMed

ABSTRACT

The implementation of a variety of immunosuppressive therapies has made drug-associated progressive multifocal leukoencephalopathy (PML) an increasingly prevalent clinical entity. The purpose of this study was to investigate its diagnostic characteristics and to determine whether differences herein exist between the multiple sclerosis (MS), neoplasm, post-transplantation, and autoimmune disease subgroups. Reports of possible, probable, and definite PML according to the current diagnostic criteria were obtained by a systematic search of PubMed and the Dutch pharmacovigilance database. Demographic, epidemiologic, clinical, radiological, cerebrospinal fluid (CSF), and histopathological features were extracted from each report and differences were compared between the disease categories. In the 326 identified reports, PML onset occurred on average 29.5 months after drug introduction, varying from 14.2 to 37.8 months in the neoplasm and MS subgroups, respectively. The most common overall symptoms were motor weakness (48.6 %), cognitive deficits (43.2 %), dysarthria (26.3 %), and ataxia (24.1 %). The former two also constituted the most prevalent manifestations in each subgroup. Lesions were more often localized supratentorially (87.7 %) than infratentorially (27.4 %), especially in the frontal (64.1 %) and parietal lobes (46.6 %), and revealed enhancement in 27.6 % of cases, particularly in the MS (42.9 %) subgroup. Positive JC virus results in the first CSF sample were obtained in 63.5 %, while conversion after one or more negative outcomes occurred in 13.7 % of cases. 52.2 % of patients died, ranging from 12.0 to 83.3 % in the MS and neoplasm subgroups, respectively. In conclusion, despite the heterogeneous nature of the underlying diseases, motor weakness and cognitive changes were the two most common manifestations of drug-associated PML in all subgroups. The frontal and parietal lobes invariably constituted the predilection sites of drug-related PML lesions.

Electronic supplementary material: The online version of this article (doi:10.1007/s00415-016-8217-x) contains supplementary material, which is available to authorized users.

No MeSH data available.