Multiple Sclerosis

Question 1

what type of disease is MS and where does it cause effect?

Answer 1

chronic autoimmune disease of CNS

Question 2

what happens to neurons with MS?

Answer 2

myelin sheath is destroyed and leaves scar tissue (sclerosis) so nerves cannot pass along their signals

Question 3

what part of MS does MRI detect?

Answer 3

MRI detects lesions of destroyed myelin sheath

Question 4

describe the steps of MS and the immune system (5)

Answer 4

1. unknown trigger induces inflammation
2. inflammation causes BBB to become permeable to leukocytes and blood proteins
3. autoreactive CD4+ T cells encounter their specific CNS autoantigen presented by MHC II on macrophages
4. further inflammatory reaction occurs in the brain, producing auto-antibodies, mast cells, cytokines, etc.
5. autoreactive T cells, B cells, and innate cells lead to demyelination

Question 5

what can regulate inflammation for a little bit?

Answer 5

Treg cells

Question 6

do we normally have autoreactive cells?

Answer 6

no they are normally removed from circulation when detected to be autoreactive, but with MS they will stay in circulation

Question 7

what are the 2 types of MS? which is more common?

Answer 7

1. relapse-remitting MS (85% of patients)
2. primary progressive MS

Question 8

what happens during relapse-remitting MS?

Answer 8

periods of remission followed by relapse

baseline of remission gets worse with each relapse

Question 9

what happens during primary progressive MS?

Answer 9

continuously gets worse

Question 10

what are the 4 stages of MS?

Answer 10

1. Radiologically Isolated Syndrome (RIS)
2. Clinically Isolated Syndrome (CIS)
3. Relapsing-Remitting MS (RRMS)
4. Secondary Progressive MS (SPMS)

Question 11

What happens during stage 1, Radiologically Isolated Syndrome (RIS)

Answer 11

Don’t know for sure if it MS, but some MRI activity indicating MS with some MRI lesions

Potential treatment window

Question 12

What happens during stage 2, Clinically Isolated Syndrome (CIS)?

Answer 12

Confirm it is MS, more MRI activity and lesions

Ideal treatment window

Question 13

What happens during stage 3, Relapsing-Remitting MS (RRMS)?

Answer 13

unpredictable patterns of remission and relapsing, lots of MRI activity and lesions

Brain volume starting to decline

Ideal treatment window

Question 14

What happens during stage 4, Secondary Progressive MS (SPMS)?

Answer 14

Continuously getting worse, declining brain volume

Untreatable

Question 15

what are 8 symptoms of MS?

Answer 15

1. Pain
2. Fatigue
3. Tingling
4. Impaired gait (walking pattern)
5. Vision problems
6. Bladder problems
7. Dizziness
8. Cognitive and mood problems

Question 16

how is MS diagnosed? (3)

Answer 16

1. MRI
2. Observe vision, coordination, sense of balance
3. Spinal tap or Lumbar puncture (collecting CSF to determine inflammation based on # of auto-ab)

Question 17

what are 2 treatments for MS?

Answer 17

1. IFN beta and corticosteroid therapy
2. Dimethyl fumarate

Question 18

by what percent do IFN beta and corticosteroids reduce relapse?

Answer 18

30%

Question 19

how often is IFN beta and corticosteroid administered?

Answer 19

weekly

Question 20

describe potential mechanisms of IFN beta therapy (5)

Answer 20

1. prevent lymphocytes from exiting lymph node so they cannot enter the brain
2. reduce ability of lymphocytes to cross BBB
3. affecting APC function
4. inhibit some T cell differentiation and increase T cell apoptosis
5. flu symptoms (bc TFN beta is anti viral cytokine)

Question 21

what is the mechanism of corticosteroids?

Answer 21

IMMUNOSUPPRESSANT
1. reduce inflammation caused by pro-inflammatory cytokines
2. increased lymphocyte apoptosis
3. reduce migration of leukocytes to brain

Question 22

by what percent does dimethyl therapy reduce relapse?

Answer 22

50%

Question 23

how is dimethyl therapy administered?

Answer 23

oral pills

Question 24

why could dimethyl fumarate be a better treatment than IFN beta / corticosteroid?

Answer 24

newer treatment so there are fewer cytokines

Question 25

what are 2 mechanisms of dimethyl fumarate?

Answer 25

1. anti-inflammatory effects --> suppress production of pro-inflammatory cytokines 2. may alter DC activation