Multiple Sclerosis

Question 1

TRUE or FALSE: MS affects an older population

Answer 1

FALSE: younger population

Question 2

What percentage of MS is pediatric? What percentage of MS patients have an onset or less than or equal to age 18?

Answer 2

• 6% total
• 3-10% under 18

Question 3

Does MS affect males or females more?

Answer 3

females

Question 4

TRUE or FALSE: there is decreased axonal density in MS plaques

Answer 4

TRUE

Question 5

What are the causes of MS?

Answer 5

• genes
• infections (mono)
• sun
• smoking
• salt???

Question 6

Which gene is associated with MS?

Answer 6

HLA

Question 7

How is EAE produced and transmitted in animals?

Answer 7

1. mice injected with myelin basic protein (MBP) and complete Freund’s adjuvant develop demyelinating disease (EAE)
2. disease is mediated by myelin basic protein-specific TH1 cells
3. disease can be transmitted by transfer of T cells from affected animal

Question 8

Explain the model of molecular mimicry

Answer 8

1. inject virus with MBP
2. antigen presentation of virus to naive T cells
3. expansion of virus-specific T cells + expansion of cross-reactive MBP-specific T cells
4. enter CNS, recognize MBP, initiate inflammatory damage

Question 9

What cells do CD4 T cell differentiate into in the CNS. What are the associated cytokines?

Answer 9

• TH1–> IL-2, IK-12, IFN-gamma, TNF-alpha
• TH17 –> IL-17, IL-23

Question 10

What cells do CD4 T cells differentiate into in the respiratory system? What are the associated cytokines?

Answer 10

• TH2 –> IL-4, IL-5, IL-10, IL-13, IL-25, TGF-beta
• Treg –> TGF-beta, IL-10, IL-35

Question 11

There is _____________ inflammation in MS plaques

Answer 11

peri-vascular

Question 12

What pathogenetic events occur in MS?

Answer 12

• inflammation
• ionic imbalance and increased sodium levels
• microglia activation
• energy failure
• glutamate excitotoxicity
• astrocyte activation
• neuro-axonal degeneration

Question 13

TRUE or FALSE: axonal transection in acute MS lesions can be remyelinated

Answer 13

FALSE

Question 14

What is MS triggered by?

Answer 14

inflammation

Question 15

Describe neurodegeneration in MS pathogenesis.

Answer 15

1. mitochondrial injury leads to energy deficiencies
2. oxidative stress leads to demyelination
3. ionic imbalance due to glutamate excitotoxicity
4. atrophy and degeneration

Question 16

TRUE or FALSE: myelin loss and axon loss increase with the clinical course of MS

Answer 16

TRUE (see slide 27 chart?)

Question 17

How do ocular lesions in MS manifest?

Answer 17

• blurred vision
• diplopia

Question 18

How do cerebellar lesions in MS manifest?

Answer 18

• ataxic walk
• vertigo
• nystagmus

Question 19

How do autonomic lesions in MS manifest?

Answer 19

• urinary incontinence
• sexual disorders

Question 20

How do motor lesions manifest in MS?

Answer 20

• reduced strength and activity
• muscle spasms
• muscle weakness and loss of strength

Question 21

How do sensory lesions manifest in MS?

Answer 21

• sensory loss
• hypesthesia

Question 22

Why is it important to localize the lesion in MS before prognosis?

Answer 22

neurological symptoms depend on where the lesion is

Question 23

Which reflex is primarily affected in MS?

Answer 23

motor reflex arc –> leads to spasticity

Question 24

What is the definition of fatigue?

Answer 24

a feeling of physical tiredness and lack of energy distinct from sadness or weakness

Question 25

Fatigue is severe in up to ____% of patients.

Answer 25

74

Question 26

What is the worst symptom of MS in 50-60% of patients?

Answer 26

fatigue

Question 27

What percentage of MS patients are affected by bladder dysfunction? What are some forms of bladder dysfunction?

Answer 27

- 75% of patients - bladder overactivity: urgency, frequency, urge incontinence - bladder inefficiency: incomplete emptying, residual urine - detrusor-sphincter dyssynergia: co-contraction of bladder and urethral sphincter

Question 28

Which fibers innervate the bladder?

Answer 28

- sympathetic - parasympathetic - somatic

Question 29

What percentage of MS patients are affected by pain? In what ways can it present in MS?

Answer 29

- 40-50% - PERSISTENT NEUROGENIC PAIN: burning dysesthesia of the limbs and/or trunk attributed to disruption of the SPINOTHALAMIC pathway - PAROXYSMAL NEUROGENIC PAIN (trigeminal neuralgia): excruciating facial pain

Question 30

Which cranial nerve is compressed in trigeminal neuralgia?

Answer 30

cranial nerve V (all 3 regions)

Question 31

What do existing treatments for MS primarily target?

Answer 31

inflammation

Question 32

What are the 3 main aspects of MS that should be targeted?

Answer 32

inflammation, neurodegeneration/demyelination, failure of repair/gliosis

Question 33

There is a need for novel agents that directly target ___________.

Answer 33

PROTECTION and REPAIR of the CNS as well as targeting INFLAMMATION

Question 34

What are traditional injectables for MS?

Answer 34

- beta-interferons (IFN-beta) - glatiramer acetate

Question 35

What are some oral therapies for MS?

Answer 35

- dimethylfumarate (DMF) - fingolimod - teriflunomide - cladribine

Question 36

What are some monoclonal antibodies for treating MS?

Answer 36

- natalizumab - alemtuzumab - ocrelizumab - ofatumumab

Question 37

What are some chemotherapies for MS?

Answer 37

- mitoxantrone - cyclophosphamide

Question 38

What is an experimental MS therapy option as of 2023?

Answer 38

autologous stem cell transplant

Question 39

What is the mechanism of action for IFN-beta in treating MS? How effective is it?

Answer 39

- IFN-beta inhibits antigen presentation and T cell activation via IFN-beta receptor - decrease pro-inflammatory TH1 cytokines - nonspecific but effective, also side effects