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Natalizumab-associated progressive multifocal leukoencephalopathy
Trevor Glenn1, Joseph R Berger2, Caleb R S McEntire1
1Department of Neurology, Mass General Brigham, Boston, MA, United States.
Abstract:
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. Risk 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.
Insights
Progressive multifocal leukoencephalopathy (PML) is a brain disease caused by JC virus (JCV) in immunocompromised individuals. A JCV antibody index helps manage PML risk in patients treated with natalizumab.
Area of Science:
- Neuroimmunology
- Infectious Diseases
- Neurology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare, fatal demyelinating disease of the central nervous system.
- PML is caused by the JC virus (JCV) and typically occurs in patients with compromised cell-mediated immunity.
- The incidence of PML increased with the use of natalizumab, a monoclonal antibody for multiple sclerosis and Crohn's disease.
Purpose of the Study:
- To review risk stratification, diagnosis, and treatment of PML in patients receiving natalizumab.
- To discuss the role of the JCV antibody index in managing PML risk.
- To provide an overview of PML in the context of natalizumab therapy.
Main Methods:
- Review of existing literature on PML, JCV, and natalizumab.
- Analysis of risk factors and mitigation strategies for PML development.
- Discussion of diagnostic approaches and treatment options for PML.
Main Results:
- The JCV antibody index is a key tool for stratifying PML risk in natalizumab-treated patients.
- Risk levels are categorized based on the JCV antibody index: negative (<0.4), low (0.4-0.9), medium (0.9-1.5), and high (>1.5).
- Understanding risk factors and implementing mitigation strategies are crucial for managing PML.
Conclusions:
- Effective risk stratification using the JCV antibody index is essential for PML prevention in natalizumab users.
- Early diagnosis and appropriate management are critical for improving outcomes in PML patients.
- Continued research and vigilance are necessary to combat PML in immunosuppressed populations.
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