Pathology of multiple sclerosis

Question 1

What type of disorder of the central nervous system is multiple sclerosis and how to describe it?

Answer 1

MS is a demyelinating disorder of the CNS:

• an autoimmune neuroinflammation and neurodegeneration
• immune-mediated destruction of myelin and neuronal death

Question 2

What are the 3 ways tissue damage occurs in multiple sclerosis histopathology?

Answer 2

1. T-cell mediated
2. Complement mediated
3. Caused by macrophages and microglia

Question 3

What happens to astrocytes due to the loss of neurons in multiple sclerosis histopathology?

Answer 3

Astrogliosis: abnormal increase in the number of astrocytes due to the destruction of nearby neurons from central nervous system

Question 4

What happens to microglia during multiple sclerosis histopathology?

Answer 4

Become “activated” microglia: phenotype change to act more like a macrophage => increases tissue damage

Question 5

What are the initial inflammatory steps in multiple sclerosis histopathology?

Answer 5

• Elevated cytokines and up-regulation of leukocyte adhesion molecules on the BBB => BBB-breakdown
• Infiltration of CD4+ and CD8+ T-cells and blood-borne macrophages

Question 6

What are the later steps (no direct inflammatory component) in multiple sclerosis histopathology?

Answer 6

• Glia scar formation/astrogliosis
• Demyelination and axonal loss
• Oxidative stress

Question 7

What causes the relapsing/remitting of multiple sclerosis (RRMS) neuropathology and what are the 4 different patterns causing it?

Answer 7

RRMS is mostly caused by active focal lesions
T-cell and macrophage infiltration cause myelin loss and axonal loss in 4 patterns:
1. CD8+ and macrophage mediated demyelination
2. antibody mediated demyelination (mainly IgG)
3. hypoxia-like tissue injury
4. increased susceptibility of the target tissue

Question 8

What can be said on the neuropathology of primary progressive and secondary progressive multiple sclerosis?

Answer 8

• Cortical demyelination
• Rare active focal lesions
• Diffuse T-cell infiltrates
• Persistent microglia activation

Question 9

What can be said on the re-myelination phenomenon in the histopathology of multiple sclerosis?

Answer 9

• Migration of the oligodendrocyte progenitor cells into damaged sites
• Not only found in inactive lesions, but also in lesions with ongoing demyelinating activity
• Repair processes occur mostly in the early disease phase
• Re-myelination in late stage MS appears sparse and restricted to borders of inactive lesions
  => Re-myelination often fails, newly produced myelin sheets are aberrant and trigger secondary demyelination

Question 10

What are the mutual hallmarks of the MS and EAE histopathology?

Answer 10

• Signs of the vascular permeability (disrupted BBB)
• Infiltration of immune cells into CNS parenchyma
• Activation of the brain resident microglia (activated microglia)
• Glia scar formation by astrocytes (astrogliosis)
• Glutamate neurotoxicity
• Complement activation
• Antibody dependent cytotoxicity