title: Drug-associated progressive multifocal leukoencephalopathy: a clinical, radiological, and cerebrospinal fluid analysis of 326 cases.
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.
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Route 935, PO Box 9101, 6500 HB, Nijmegen, The Netherlands. roderick.maas@radboudumc.nl.
authors.forename: Roderick P P W M
authors.initials: RP
authors.lastname: Maas
authors.affiliation: Netherlands Pharmacovigilance Center Lareb, 's-Hertogenbosch, The Netherlands.
authors.forename: Annemarie H G
authors.initials: AH
authors.lastname: Muller-Hansma
authors.affiliation: Department of Neurology, Donders Institute for Brain, Cognition, and Behaviour, Radboud University Medical Center, Route 935, PO Box 9101, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Rianne A J
authors.initials: RA
authors.lastname: Esselink
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Murk
authors.affiliation: Department of Neurology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Clemens
authors.initials: C
authors.lastname: Warnke
authors.affiliation: Department of Neurology, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Joep
authors.initials: J
authors.lastname: Killestein
authors.affiliation: Department of Radiology and Nuclear Medicine, VU Medical Center, Amsterdam, The Netherlands.
authors.forename: Mike P
authors.initials: MP
authors.lastname: Wattjes
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use; D002540:Cerebral Cortex / Q000000981:diagnostic imaging; D004247:DNA / Q000134:cerebrospinal fluid*; D016208:Databases, Factual / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007577:JC Virus / Q000235:genetics; D007968:Leukoencephalopathy, Progressive Multifocal / Q000134:cerebrospinal fluid* / Q000145:classification / Q000175:diagnosis* / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D000069442:Natalizumab / Q000627:therapeutic use; D009426:Netherlands; D059906:Neuroimaging; D060735:Pharmacovigilance
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007155:Immunologic Factors; D000069442:Natalizumab; D004247:DNA
keywords: Adverse event; Drugs; Medication; Progressive multifocal leukoencephalopathy; Side effect