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Outcome Predictors in Progressive Multifocal Leukoencephalopathy Associated With Multiple Sclerosis Treatments: A
Julie Céline Blant1, Nicola De Rossi2, Ralf Gold3
1Service of Neurology, Department of Clinical Neurosciences, Lausanne University Hospital (Centre Hospitalier Universitaire Vaudois) and University of Lausanne, Switzerland.
Neurology(R) Neuroimmunology & Neuroinflammation
|February 20, 2026
Summary
Higher pre-PML disability, elevated CSF JCV viral load, and symptomatic onset predict worse outcomes in multiple sclerosis patients with progressive multifocal leukoencephalopathy (PML). PML-immune reconstitution inflammatory syndrome (PML-IRIS) is linked to better outcomes.
Area of Science:
- Neurology
- Infectious Diseases
- Immunology
Background:
- Progressive multifocal leukoencephalopathy (PML) is a rare but serious complication of disease-modifying therapies (DMTs) for multiple sclerosis (MS).
- JC virus (JCV) reactivation triggers PML, with natalizumab (NTZ) being the most common associated DMT, but other DMTs like sphingosine-1-phosphate receptor modulators (S1P-RM), dimethyl fumarate (DMF), and ocrelizumab are also implicated.
- Identifying factors influencing PML outcomes is crucial for managing MS patients undergoing DMT.
Purpose of the Study:
- To identify predictors of worse outcomes in patients with MS-associated PML.
- To investigate the impact of PML-immune reconstitution inflammatory syndrome (PML-IRIS), plasma exchange (PlEx), corticosteroids, and DMT reintroduction on PML prognosis.
- To analyze factors associated with PML-IRIS development and recurrent MS activity.
Main Methods:
- A retrospective multicenter cohort study included 94 MS patients with JCV-associated PML or granule cell neuronopathy from 42 centers (2009-2022).
- The primary outcome was disability at 12 months, assessed using the modified Rankin Scale (mRS).
- Multivariable analyses were performed to identify predictors of poor outcomes, PML-IRIS, and recurrent MS activity.
Main Results:
- Higher pre-PML disability, elevated cerebrospinal fluid (CSF) JCV viral load, and symptomatic presentation at onset were significantly associated with worse 12-month outcomes.
- PML-IRIS was associated with significantly better outcomes.
- Plasma exchange (PlEx) and corticosteroid use did not demonstrate a negative impact on outcomes.
Conclusions:
- This study identifies key factors influencing PML prognosis in MS patients, including baseline disability, JCV viral load, and symptomatic onset.
- PML-IRIS appears to be a positive prognostic indicator.
- Findings can inform clinical decision-making regarding treatments like PlEx, corticosteroids, and management of PML-IRIS in iatrogenic PML.
