1. “ Demyelinating” diseases Mark L Cohen, M.D. Department of Pathology University Hospitals Case Medical Center January 6 th , 2009

9. Normal vs. Leukodystrophy (ALD)

10. Rosenthal fibers Cytoskeletal Alexander disease Perivascular inflammation Peroxisomal Adreno- leukodystrophy Globoid (multinucleated) microglia Lysosomal Krabbe Disease Metachromatic sulfatides within macrophages Lysosomal Metachromatic Leukodystrophy Pathologic features Cellular defect Disease

11. Subcortical U-fibers Krabbe Disease Alexander Disease Now you see ‘em Now you don’t

12. Globoid cell leukodystrophy (Krabbe) ‏

13. Adrenoleukodystrophy Alexander disease Pelizaeus-Merzbacher Disease

17. Central pontine myelinolysis Marchifava-Bignami disease

19. HIV encephalitis P24 immunostaining

20. Progressive multifocal leukoencephalopathy

21. Progressive multifocal leukoencephalopathy JC virus immunostaining

22. Carswell, 1838 Babinski, 1885

23. 1868 Nystagmus, intention tremor, scanning speech Barber Chair phenomenon Worsening of vision with exercise in optic neuritis 1890 1920

24. Site Symptoms Signs Cerebrum Cognitive impairment Attention deficit, dementia (late) Optic Nerve Unilateral painful visual loss Scotoma, afferent pupillary defect Cerebellum Tremor Clumsiness Intention tremor Ataxia, dysarthria Brainstem Diplopia, vertigo, emotional lability Nystagmus, INO, ophthalmoplegias Spinal cord Spasms; bowel, bladder, erectile dysfunction Spasticity

28. Glia limitans perivascularis

29. 2 steps to neuroinflammation 1 2 Glia limitans perivascularis Post-capillary venule

31. Active demyelinating plaque CD68 IHC

32. Gross pathology

33. Gross pathology

34. Inactive plaque

35. MS: Active & inactive plaques

36. Evolution of an MS plaque