Multiple Sclerosis Flashcards
what type of disease is MS and where does it cause effect?
chronic autoimmune disease of CNS
what happens to neurons with MS?
myelin sheath is destroyed and leaves scar tissue (sclerosis) so nerves cannot pass along their signals
what part of MS does MRI detect?
MRI detects lesions of destroyed myelin sheath
describe the steps of MS and the immune system (5)
- unknown trigger induces inflammation
- inflammation causes BBB to become permeable to leukocytes and blood proteins
- autoreactive CD4+ T cells encounter their specific CNS autoantigen presented by MHC II on macrophages
- further inflammatory reaction occurs in the brain, producing auto-antibodies, mast cells, cytokines, etc.
- autoreactive T cells, B cells, and innate cells lead to demyelination
what can regulate inflammation for a little bit?
Treg cells
do we normally have autoreactive cells?
no they are normally removed from circulation when detected to be autoreactive, but with MS they will stay in circulation
what are the 2 types of MS? which is more common?
- relapse-remitting MS (85% of patients)
- primary progressive MS
what happens during relapse-remitting MS?
periods of remission followed by relapse
baseline of remission gets worse with each relapse
what happens during primary progressive MS?
continuously gets worse
what are the 4 stages of MS?
- Radiologically Isolated Syndrome (RIS)
- Clinically Isolated Syndrome (CIS)
- Relapsing-Remitting MS (RRMS)
- Secondary Progressive MS (SPMS)
What happens during stage 1, Radiologically Isolated Syndrome (RIS)
Don’t know for sure if it MS, but some MRI activity indicating MS with some MRI lesions
Potential treatment window
What happens during stage 2, Clinically Isolated Syndrome (CIS)?
Confirm it is MS, more MRI activity and lesions
Ideal treatment window
What happens during stage 3, Relapsing-Remitting MS (RRMS)?
unpredictable patterns of remission and relapsing, lots of MRI activity and lesions
Brain volume starting to decline
Ideal treatment window
What happens during stage 4, Secondary Progressive MS (SPMS)?
Continuously getting worse, declining brain volume
Untreatable
what are 8 symptoms of MS?
- Pain
- Fatigue
- Tingling
- Impaired gait (walking pattern)
- Vision problems
- Bladder problems
- Dizziness
- Cognitive and mood problems
how is MS diagnosed? (3)
- MRI
- Observe vision, coordination, sense of balance
- Spinal tap or Lumbar puncture (collecting CSF to determine inflammation based on # of auto-ab)
what are 2 treatments for MS?
- IFN beta and corticosteroid therapy
- Dimethyl fumarate
by what percent do IFN beta and corticosteroids reduce relapse?
30%
how often is IFN beta and corticosteroid administered?
weekly
describe potential mechanisms of IFN beta therapy (5)
- prevent lymphocytes from exiting lymph node so they cannot enter the brain
- reduce ability of lymphocytes to cross BBB
- affecting APC function
- inhibit some T cell differentiation and increase T cell apoptosis
- flu symptoms (bc TFN beta is anti viral cytokine)
what is the mechanism of corticosteroids?
IMMUNOSUPPRESSANT
1. reduce inflammation caused by pro-inflammatory cytokines
2. increased lymphocyte apoptosis
3. reduce migration of leukocytes to brain
by what percent does dimethyl therapy reduce relapse?
50%
how is dimethyl therapy administered?
oral pills
why could dimethyl fumarate be a better treatment than IFN beta / corticosteroid?
newer treatment so there are fewer cytokines
what are 2 mechanisms of dimethyl fumarate?
- anti-inflammatory effects –> suppress production of pro-inflammatory cytokines
- may alter DC activation
