MINI REVIEW article

Front. Neurol.

Sec. Neuroinfectious Diseases

Volume 16 - 2025 | doi: 10.3389/fneur.2025.1575653

This article is part of the Research TopicProgressive Multifocal Leukoencephalopathy: From Risk Stratification to TreatmentView all articles

Natalizumab-Associated Progressive Multifocal Leukoencephalopathy

Provisionally accepted
  • 1Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, United States
  • 2Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States

The final, formatted version of the article will be published soon.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease of the brain resulting from infection of oligodendrocytes by JC virus (JCV) typically occurring in association with defects of cell-mediated immunity. The clinical presentation of PML depends on its area of effect in the central nervous system and can include a broad spectrum of deficits such as focal weakness, speech difficulties, visual changes, cognitive disruptions, or ataxia. While the disease was first described in patients with B cell malignancies (Hodgkins's lymphoma and chronic lymphocytic leukemia), a large array of immunosuppressive conditions, most notably human immunodeficiency virus, may predispose to the disorder. From 2005 on, PML was observed in patients with multiple sclerosis (MS) and Crohn's disease being treated with natalizumab, a monoclonal antibody inhibiting α4β1 and α4β7 integrins. This observation was quite surprising as PML had never been seen with either MS or inflammatory bowel diseases previously despite the widespread use of immunosuppressive agents in their treatment. In this context, rRisk factors for PML development were identified, and an effective risk mitigation strategy chiefly predicated on the JCV antibody index was established (an antibody index less than 0.4 is considered negative, 0.4 to 0.9 low risk, 0.9 to 1.5 medium risk, and greater than 1.5 high risk). Here we review risk stratification, diagnosis, and treatment of PML in patients receiving natalizumab.

Keywords: progressive multifocal leukoencephalopathy, natalizumab, JC Virus, Relapsing Remitting Multiple Sclerosis, Demyelimating diseases

Received: 12 Feb 2025; Accepted: 05 Jun 2025.

Copyright: © 2025 Glenn, Berger and McEntire. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Trevor Glenn, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, Massachusetts, United States

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