Pathology of Demyelinating Disease

1. Pathology of Demyelinating disease Thomas Shoemaker, MD PGY-4 Department of Neurology December 21st, 2015 School of Arts of and Sciences Department (Click here to edit)

2. CASE A 38 year old woman presented to the UPMC PUH ED with acute urinary retention and progressive paraplegia over 48 hours. She has a history of bilateral vision loss one year ago. MRI is on the next slide:

3. The antibody test you send is located where? A.) Neuronal Dendrites B.) Astrocytes C.) Ventricular lining D.) Microglia E.) Myelin basic protein

4. The antibody test you send is directed against what? A.) Neuronal Dendrites B.) Astrocytes C.) Ventricular lining D.) Microglia E.) Myelin basic protein

5. NeuromyelitisOptica Spectrum Disorder • Antibodies against aquaporin-4 are present in 80% of cases • IgG1 • Aquaporin-4 is a transmembrane protein located on astrocyte foot processes in contact with brain capillaries. • It is the predominant water channel in the CNS

7. NeuromyelitisOptica Spectrum Disorder (NMOSD)

8. NeuromyelitisOptica Spectrum Disorder (NMOSD) • NMOSD: unified term • Stratified by serostatusNMOSD with AQP4-IgG • NMOSD without AQP4-IgG (or testing unavailable) • Allows for future revisions e.g. discovery and validation of other antibodies associated with NMOSD clinical phenotype

11. NeuromyelitisOptica Spectrum Disorder (NMOSD) • Gross findings: • Swollen cord in acute phase • Tissue damage over multiple cord segments • Cord and optic nerve atrophy in later stages of the disease

12. NeuromyelitisOptica Spectrum Disorder (NMOSD) Devic disease (neuromyelitisoptica) at autopsy classically manifests severe necrotic lesions involving several levels of spinal cord.

13. NeuromyelitisOptica Spectrum Disorder (NMOSD) - ON

14. NeuromyelitisOptica Spectrum Disorder (NMOSD) • Microscopic features • Cavitary lesions may contain sheets of macrophages • Some cases show greater B cell, eosinophil, and neurophil inflammatory components than typical MS • Blood vessles in lesions are thickened and hyalinized

15. NeuromyelitisOptica Spectrum Disorder (NMOSD) • Immunohistochemical features • Desposits of IgG and IgM with complement activation in vasocentric pattern • Loss of immuno-staining for Aquaporin-4

16. NeuromyelitisOptica Spectrum Disorder (NMOSD) Eosinophils may also be seen in lesions of neuromyelitisopticabut are rare in MS.

17. NeuromyelitisOptica Spectrum Disorder (NMOSD) optic chiasm on a whole-mount section (A), with significant axonal loss (B) with significant axonal loss

18. NeuromyelitisOptica Spectrum Disorder (NMOSD) cavitary lesions containing macrophages

20. CASE • A 14 year old girl comes into the CHP ED after developing confusion and fevers which after several hours is complicaated by seizues and ataxia. MRI is shown on the next slide. She received a vaccination last week.

22. Microscopic features of this condition include: • A.) Eosinophil infiltration • B.) Loss of aquaporin-4 • C.) Narrow cuffs of myelin loss around venules • D.) Confluent areas of myelin loss around arterioles

23. Microscopic features of this condition include: • A.) Eosinophil infiltration • B.) Loss of aquaporin-4 • C.) Narrow cuffs of myelin loss around venules • D.) Confluent areas of myelin loss around arterioles

24. Acute Disseminated Encephalomyelitis (ADEM) • A/w infection or immunization • Lag of 2-10 days, may be 4 weeks • Signs: • Pyramidal signs (60- 90%) • Acute hemiplegia (76%) • Seizures (35%) • Fevers, headaches, AMS

25. Acute Disseminated Encephalomyelitis (ADEM) • Typically a monohpasic source • Recovery is typically rapid, within a week after onset

26. Acute Disseminated Encephalomyelitis (ADEM) • Gross • Patients dying in acute phases have diffuse cerebral edema and herniations • Demyelination is not obvious grossly

27. Acute Disseminated Encephalomyelitis (ADEM) • Microscopic features • Characteristic narrow cuffs or sleeves of myelin loss around small veins/venules • Lesions involve white matter, cortical gray matter and deep gray matters • Lesions are all the same age • Immunohistochemistry: no specific features

28. Acute Disseminated Encephalomyelitis (ADEM) Acute disseminated encephalomyelitis shows hypercellularperivenular lesions

29. Acute Disseminated Encephalomyelitis (ADEM) demyelination best appreciated on LFB-PAS staining

30. Acute Disseminated Encephalomyelitis (ADEM) perivascular lymphocytes and macrophages (LFB-PAS stain).

31. CASE: GG • 23M presented with progressively worsening headache x 5 days, aphasia, and cognitive decline. MRI shows prominent atypical signal change in a floral-like pattern. He died 3 ½ months after initial presentation.

33. What’s the diagnosis? • A. Schilder’s disease • B. Balo’s Concentric Sclerosis • C. Marburg Demyelination • D.Gliblastoma

34. What’s the diagnosis? • A. Schilder’s disease • B. Balo’s Concentric Sclerosis • C. Marburg Demyelination • D. Gliblastoma

35. Balo’s Concentric Sclerosis (BCS) • Clinical Presentation • Patients may present with severe monophasic illness • A fulminant course and rapid demise • Focal symptoms , behavioral changes, aphasia include initial symptoms • Symptoms in some cases are suggestive of increased ICP

36. Balo’s Concentric Sclerosis (BCS) • Radiographic features • Lamellar lesions in isolation (classic) or rarely accompanying typical MS-like lesions • Alternating zones of intensity on T1- and T2-weighted images • n The alternating zones may include contrast enhancement

37. Balo’s Concentric Sclerosis (BCS) • Gross • Multiple areas of gray discoloration throughout the white matter, • Localized to the cerebral hemispheres

38. Balo’s Concentric Sclerosis (BCS) Microscopic features • Concentric rings of alternating intact and absent myelin • Revealed w/myelin stains • The banding pattern is strikingly repetitive from case to case, with bands arranged in parallel waves and bands with intact myelin almost always narrower than in those with myelin loss • Fewer macrophages and more astrocytosis in the center of the rings • he edges of lesions show bands of demyelination with numerous LFB–containing macrophages, perivascular lymphocytes, and enlarged astrocytes (see Figure 5-50C); some residual axons within the demyelinated bands (see Figure 5-50D) • n Peculiar feature is the presence of cells containing clusters of dark nuclei, which represents endocytosis of oligodendrocytes by astrocytes

39. Balo’s Concentric Sclerosis (BCS) Microscopic features • Fewer macrophages and more astrocytosis in the center of the rings • Lesion edges show bands of demyelination with numerous LFB–containing macrophages • perivascular lymphocytes • Enlarged astrocytes

40. Balo’s Concentric Sclerosis (BCS) Microscopic features • Peculiar feature is the presence of cells containing clusters of dark nuclei, which represents endocytosis of oligodendrocytes by astrocytes

41. Balo’s Concentric Sclerosis (BCS) Whole mount section stained with LFB-PAS shows alternating ring-like bands of myelin loss and preservation

42. Balo’s Concentric Sclerosis (BCS) Baló variant of MS demonstrates bands arranged in parallel waves, with bands containing intact myelin almost always narrower than in those with myelin loss (LFB-H&E).

43. Balo’s Concentric Sclerosis (BCS) Acute myelin breakdown at the edges of lesions is evidenced by many macrophages containing LFB-positive materi

44. Balo’s Concentric Sclerosis (BCS) Axons are better preserved in the demyelinated bands, compared to the severity of myelin loss (Bielschowsky stain).