jason chiang, md, phd & clayton wiley, md, phd university of pittsburgh medical center

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

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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? - PowerPoint PPT Presentation

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Page 1: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Jason Chiang, MD, PhD & Clayton Wiley, MD, PhDUniversity of Pittsburgh Medical CenterDepartment of Pathology Division of Neuropathology

Page 2: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

• 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?

Case History

2

Page 3: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

• New onset of arm dysmetria, slurred speech and choking• Describe MRI findings

Case History

3

Page 4: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Radiologic Findings - MRI T1 + Contrast

R R

4

Page 5: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Radiologic Findings - MRI FLAIR/T2

R R

5

Page 6: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

• 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

Further Studies and Clinical Course

6

Page 7: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Gross Neuropathology Findings

RR

7

Page 8: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

8

Peri-ventricular Area Cerebellum

2x

20x

Microscopic Findings

H&E

Page 9: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Microscopic Findings

LFB/CV

Peri-ventricular Area Cerebellum

2x

20x

9

Page 10: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Neurofilament stain

10

Peri-ventricular Area Cerebellum

20x

Page 11: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Further StudiesPeri-ventricular Area

CD68

CD3

Cerebellum

10x

11

CD8

CD4CD68

CD3

Page 12: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

JC Virus in situ Hybridization

12

4x 40x

Cerebellum

Page 13: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

Timeline

13

Death10/5/2012

MRI6/5/2012

MRI9/10/2012

PML

Symptoms

TysabriTysabriTysabriTysabriTysabri PlasmapheresesSteroid

IRIS

MS

MS39 years

Page 14: Jason Chiang, MD, PhD & Clayton Wiley, MD, PhD University of Pittsburgh Medical Center

• 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

Final Diagnosis

14

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