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.

Neurological safety of fingolimod: An updated review

“…The more specifically the immune system is targeted (as in NTZ‐induced PML), the better the prognosis in general. In contrast, if the immune system is suppressed as an intrinsic consequence of the disease process, such as PML as a result of HIV infection or hematological malignancies, the prognosis is generally poor 64, 65…”

The spectrum of progressive multifocal leukoencephalopathy: a practical approach

“…Whilst patients with hematological malignancies therefore still have a 2‐month survival rate as low as 10% , the 1‐year survival rate of HIV‐positive patients increases from 9%–23% before HAART to 50%–63% after the introduction of HAART . Mortality rates in drug‐associated PML have been reported as high as 56.2% for autoimmune diseases, 68.4% for post‐transplantation and 83.3% for neoplasms . The survival rate of natalizumab‐treated MS patients is higher with an overall survival of 76%.…”

High-frequency MRI monitoring should be performed in natalizumab-treated MS patients with higher risk of PML – Commentary

“…Fortunately, PML, although increasingly reported and recognized in therapy-induced immunosuppression, still is a rare disease. 9 It is almost impossible to provide class I evidence for a rare disease in a heterogeneous group of patients. As such, in the absence of evidence, expert opinions that guide clinicians and help to standardize patient care can be a valuable alternative.…”