title: Treatment-Related Progressive Multifocal Leukoencephalopathy in Multiple Sclerosis: A Comprehensive Review of Current Evidence and Future Needs.
abstract: Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection of the central nervous system caused by the John Cunningham virus (JCV) that has been associated with therapeutic immunosuppression in patients with multiple sclerosis (MS). So far, more than 600 cases of PML have been reported in association with natalizumab administration. There have also been confirmed cases of PML in individuals who received fingolimod and dimethyl fumarate without previous natalizumab treatment. The new licensed disease-modifying therapies for MS carry the risk of immunosuppressant and so of JCV reactivation. Various factors have been identified with increased risk of developing PML, including a positive JCV serology, natalizumab administration for >2 years, and prior use of immunosuppressive agents. Clinicians can employ such tools for patients' risk stratification, but the incidence of PML among patients receiving natalizumab therapy has not changed. In this review we outline the current state of understanding of PML pathogenesis and patients' risk stratification. The landscape of MS is dramatically changing and knowledge of the side effects of the licensed therapies is imperative to enable optimal decision making.
authors.affiliation: Multiple Sclerosis Center, Policlinico G. Rodolico, Via Santa Sofia, 78, Catania, 95123, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: D'Amico
authors.affiliation: Multiple Sclerosis Center, Policlinico G. Rodolico, Via Santa Sofia, 78, Catania, 95123, Italy.
authors.forename: Aurora
authors.initials: A
authors.lastname: Zanghì
authors.affiliation: Multiple Sclerosis Center, Policlinico G. Rodolico, Via Santa Sofia, 78, Catania, 95123, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Leone
authors.affiliation: Klinik und Poliklinik für Neurologie der Universität Ulm, Oberer Eselsberg 45, 89081, Ulm, Germany.
authors.forename: Hayrettin
authors.initials: H
authors.lastname: Tumani
authors.affiliation: Multiple Sclerosis Center, Policlinico G. Rodolico, Via Santa Sofia, 78, Catania, 95123, Italy. patti@unict.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Patti
mesh_terms: D019317:Evidence-Based Medicine; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015994:Incidence; D007968:Leukoencephalopathy, Progressive Multifocal / Q000139:chemically induced*; D009103:Multiple Sclerosis / Q000188:drug therapy*; D000069442:Natalizumab / Q000009:adverse effects / Q000627:therapeutic use*; D012307:Risk Factors
chemical_list: D007166:Immunosuppressive Agents; D000069442:Natalizumab