4.6 Multiple Sclerosis

Question 1

Typical age of onset of MS is…

Answer 1

20-40 years old

Question 2

What are the four disease courses of MS (names)?

Answer 2

• Primary progressive
• Secondary progressive
• Relapsing remitting
• Progressive relapsing

Question 3

What is the most common MS disease course?

Answer 3

Relapsing remitting

Question 4

Describe the progression of relapsing remitting MS

Answer 4

• Sudden increase in disability
• This gets better with time, leading to a period of remission, with disability still worse than pre-spike
• Repeats

Question 5

Describe the course of primary progressive MS

Answer 5

Linear increase in disease; no relapses

Question 6

Describe secondary progressive MS

Answer 6

After a period of relapsing remitting MS, moves to linear progression

Question 7

Describe progressive relapsing MS

Answer 7

Relapse spikes, separated by linear increases in disability.

Question 8

Specifically, which parts of the peripheral nervous system are affected by MS?

Answer 8

• None
• CNS only

Question 9

Describe the pathophysiology of MS, and link this to disease process. What causes worsening/remission of the disease?

Answer 9

• Inflammation of CNS leads to release of inflammatory mediators, infiltration of CD8 T cells that kill oligodendrocytes, and B cells whose antibodies bind to myelin
• Leads to demyelination and oligodendrocyte death
• Remyelination (this is our “remission”, so in RR MS it goes back and forth here)
• Eventually, the mechanisms of remyelination may become exhausted (nutrients, growth factors, progenitors etc.), leading to dysfunction, and neuronal death (permanent disability)

Question 10

List some different symptoms of MS

Answer 10

• Motor: spasms, weakness, balance/coordination issues
• Fatigue
• Vertigo, pins and needles, neuralgia
• Bladder incontinence/constipation
• Memory loss, depression, cognitive difficulties

Question 11

If someone has an identical twin who has MS, their chance of developing the disease is…

Answer 11

50%

Question 12

True or false: presence of another autoimmune disease increases MS risk

Answer 12

True :(

Question 13

What are some environmental factors that can drive MS?

Answer 13

• Smoking
• Sunlight (more sun -> less MS)
• Viral infection
• Diet

Question 14

What is the role of CD4 T Cells in the pathogenesis of MS?

Answer 14

• Release inflammatory cytokines
• Damaging the blood brain barrier and recruiting neutrophils, monocytes, and macrophages

Question 15

Which cytokines to CD4 T cells release that are involved in the pathogenesis of MS?

Answer 15

• IL-17 (neutrophil recruitment)
• Interferon Gamma (activates CD8 cells and macrophages)
• Granulocyte-macrophage colony stimulating factor (GM CSF)

Question 16

What are the subsets of CD4 T cells important for the pathogenesis of MS?

Answer 16

Th1 and Th17

Question 17

What is the role of CD8 T cells in the pathogenesis of MS?

Answer 17

Cytotoxic to oligodendrocytes

Question 18

What is the role of B cells in the pathogenesis of MS?

Answer 18

• Produce antibodies that bind to and destroy myelin
• Present antigen to CD4 T Cells

Question 19

Where is it thought that autoreactive lymphocytes first gain access to the CNS?

Answer 19

Through the choroid plexus

Question 20

How does closeness to the equator link to risk of MS (this is very cool)?

Answer 20

• Closer to the equator = more sunlight
• More sunlight = lower risk of MS
• Therefore, the closer we get to the equator, the lower the risk of MS

Question 21

What are some potential reasons why vitamin D might decrease the risk of MS?

Answer 21

• Strengthens immune system
• Influences cytokine expression
• Increase production of immunosuppressive factors in CNS

Question 22

Which two viruses are most associated with the development of MS?

Answer 22

• Epstein Barr virus
• Herpes Human Virus 6

Question 23

Name 3 pharamacological treatments for MS prevention, and give a very brief outline of their mechanisms where applicable.

Answer 23

• Beta interferon (alters T cell activity)
• Glatiramer acetate (unknown)
• Dimethyl fumarate (anti inflammatory)

Question 24

In terms of monoclonal antibodies for MS therapy: as we progress through first/second/third line therapy, what happens to safety and efficacy?

Answer 24

• Safety decreases
• Efficacy increases

Question 25

What factors allow the CNS to be an "immune privileged" site?

Answer 25

- Blood brain barrier - Lack of lymphatic drainage - Limited expression of MHC molecules

Question 26

What is the role of T regulatory cells in MS?

Answer 26

Loss of regulation of autoreactive B cells and CD8 T cells -> CNS inflammation

Question 27

In terms of B cells, how might EBV worsen MS?

Answer 27

- Latent memory of infection resides in memory B cells - Leads to larger autoimmune response within CNS