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

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.


Flowchart of the search strategy, selection, and inclusion of articles and reports from the Dutch pharmacovigilance database
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC5037162&req=5

Fig2: Flowchart of the search strategy, selection, and inclusion of articles and reports from the Dutch pharmacovigilance database

Mentions: References were identified by means of a three-step PubMed search conducted on August 30, 2015 (Fig. 2). To obtain a first inventory of the drugs that might trigger PML occurrence, the search terms ‘progressive multifocal leukoencephalopathy’, ‘drug induced’, ‘chemically induced’, ‘medication induced’, ‘adverse event’, ‘adverse effect’, and ‘side effect’ were used in the ‘all fields’ menu without limits of time. Second, combinations of ‘progressive multifocal leukoencephalopathy’ and the names of each of the individual drugs that had been identified in the first step were applied to collect all reports of potentially drug-associated PML. Finally, reference lists of all included articles were screened for any additional relevant reports.Fig. 2


Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases
Flowchart of the search strategy, selection, and inclusion of articles and reports from the Dutch pharmacovigilance database
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig2: Flowchart of the search strategy, selection, and inclusion of articles and reports from the Dutch pharmacovigilance database
Mentions: References were identified by means of a three-step PubMed search conducted on August 30, 2015 (Fig. 2). To obtain a first inventory of the drugs that might trigger PML occurrence, the search terms ‘progressive multifocal leukoencephalopathy’, ‘drug induced’, ‘chemically induced’, ‘medication induced’, ‘adverse event’, ‘adverse effect’, and ‘side effect’ were used in the ‘all fields’ menu without limits of time. Second, combinations of ‘progressive multifocal leukoencephalopathy’ and the names of each of the individual drugs that had been identified in the first step were applied to collect all reports of potentially drug-associated PML. Finally, reference lists of all included articles were screened for any additional relevant reports.Fig. 2

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.