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Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center Department of Pathology Division of Neuropathology. Case History. 67 years old male with multiple sclerosis (MS) for 39 years Treated with Tysabri (Natalizumab) during the past 5 years What is MS?

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Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center


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    1. Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center Department of Pathology Division of Neuropathology

    2. Case History • 67 years old male with multiple sclerosis (MS) for 39 years • Treated with Tysabri (Natalizumab) during the past 5 years • What is MS? • What is Tysabri?

    3. Case History • New onset of arm dysmetria, slurred speech and choking • Describe MRI findings

    4. Radiologic Findings - MRI T1 + Contrast R R

    5. Radiologic Findings - MRI FLAIR/T2 R R

    6. Further Studies and Clinical Course • CSF analysis: • Normal differential count and glucose level • Elevated protein level, elevated IgG index and oligoclonal bands • Tysabri discontinued, plasmapheresis, IV dexamethasone • Why are they stopping the Tysabri? • Died 25 days after MRI

    7. Gross Neuropathology Findings R R

    8. Microscopic Findings Peri-ventricular Area Cerebellum 2x 20x H&E

    9. Microscopic Findings Peri-ventricular Area Cerebellum 2x 20x LFB/CV

    10. Neurofilament stain Peri-ventricular Area Cerebellum 20x

    11. Further Studies Peri-ventricular Area Cerebellum CD68 CD68 CD4 10x CD3 CD3 CD8

    12. JC Virus in situ Hybridization Cerebellum 4x 40x

    13. Timeline MRI 6/5/2012 MRI 9/10/2012 Death 10/5/2012 MS 39 years Plasmaphereses Tysabri Tysabri Tysabri Tysabri Tysabri Steroid MS PML Symptoms IRIS

    14. Final Diagnosis • Progressive multifocal leukoencephalopathy (PML) • Bilateral cerebellar white matter • Dentate nuclei • Middle cerebellar peduncles • Superimposed immune reconstitution inflammatory syndrome (IRIS) • Quiescent multiple sclerosis (MS) plaques • Multiple areas of cerebral peri-ventricular white matter • Gray and white matter of spinal cord