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Updated: May 6, 2026
Comprehensive Autopsy Program for Individuals with Multiple Sclerosis
Published on: July 19, 2019
Natalizumab-associated progressive multifocal leukoencephalopathy in a patient with multiple sclerosis: a postmortem
Christian Wüthrich1, Bogdan F Gh Popescu, Sarah Gheuens
1From the Division of Neurovirology, Department of Neurology (CW, SG, EN, XD, IJK), and Center for Virology and Vaccine Research, Department of Medicine (CW, SG, EN, XD, IJK), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts; Department of Anatomy and Cell Biology (BFGhP, MT), and Cameco MS Neuroscience Research Center (BFGh.P, MT), University of Saskatchewan, Saskatoon, Saskatchewan, Canada; Providence Saint Joseph Medical Center, The Hycy and Howard Hill Neuroscience Institute, Movement Disorder Center, Burbank (MM); David Geffen School of Medicine, University of California, Los Angeles, Los Angeles (RZ); Department of Medicine, Northridge Hospital Medical Center, Northridge (RZ); and Buddhist Tzu Chi Medical Center, Alhambra, California (SPD); and Department of Laboratory Medicine and Pathology (JEP), and Department of Neurology (CFL), Mayo Clinic, Rochester, Minnesota.
This study examined a multiple sclerosis (MS) patient who developed progressive multifocal leukoencephalopathy (PML) while on natalizumab. Findings show distinct MS and PML lesions, with PML inflammation not affecting MS plaques.
Area of Science:
- Neuroimmunology
- Neuropathology
Background:
- Natalizumab, a treatment for multiple sclerosis (MS), is linked to progressive multifocal leukoencephalopathy (PML).
- Histologic studies on the interplay between MS and PML lesions are limited.
Observation:
- A case study of an MS patient who developed PML after 32 months of natalizumab monotherapy.
- The patient received plasma exchange, mefloquine, and mirtazapine after natalizumab withdrawal, but died.
- Postmortem brain and spinal cord examination revealed extensive PML lesions with JC virus DNA.
Findings:
- Active PML lesions showed prominent inflammatory infiltrates (CD4+/CD8+ T cells), indicative of immune reconstitution inflammatory syndrome (IRIS).
- Identified MS lesions were chronic, inactive plaques, devoid of JC virus DNA and active inflammation.
- Chronic inactive MS lesions were histologically distinct and separate from adjacent PML lesions.
Implications:
- This case demonstrates the coexistence of MS and PML lesions without apparent interplay.
- Immune reconstitution inflammatory syndrome appears to influence PML lesion appearance but not MS lesions.
- Further research is needed to understand the complex interactions between MS, natalizumab, and PML.
