Lecture 18: Multiple Sclerosis

Question 1

What is Multiple Sclerosis (MS)?

Answer 1

• Chronic autoimmune disease of the central nervous system (CNS)
• Immune system attacks the myelin sheath around neurons
• Leads to lesions visible on MRI
• Results in scar tissue (sclerosis) that disrupts nerve signal transmission

Question 2

What are common symptoms of Multiple Sclerosis (MS)?

Answer 2

Pain
Fatigue
Tingling
Impaired gait (walking)
Vision problems
Bladder problems
Dizziness
Cognitive and mood issues
Paralysis

Question 3

What happens when inflammation occurs in Multiple Sclerosis (MS)?

Answer 3

• Inflammation recruits more immune cells
• Leads to lymphocytes crossing the blood-brain barrier
• Autoreactive CD4+ T cells re-encounter autoantigens on MHC II presented by macrophages

Question 4

Which immune cells contribute to demyelination in MS?

Answer 4

• Autoreactive T cells
• B cells
• Innate immune cells (like macrophages & microglia)

Question 5

How do Treg cells influence inflammation in MS?

Answer 5

1) Treg cells can temporarily regulate inflammation

2) However, in MS their regulatory function is often impaired

Question 6

What is the most common type of MS, and how does it progress?

Answer 6

(1) Relapsing-Remitting MS (RRMS) – 85% of cases

• Episodes of relapses (attacks), which may or may not leave permanent disability
• Followed by periods of remission where symptoms improve

Question 7

What is Primary Progressive MS (PPMS)?

Answer 7

• Steady increase in disability
• No relapses or remissions

Question 8

What is Progressive-Relapsing MS (PRMS)?

Answer 8

• Steady increase in disability
• With relapses (attacks)
• No remissions

Question 9

What is Secondary Progressive MS (SPMS) and how does it develop?

Answer 9

• Starts as Relapsing-Remitting MS (RRMS)
• Transitions into a steady increase in disability
• No more periods of remission

Question 10

What are the primary diagnostic tools used to diagnose MS?

Answer 10

1) MRI (to detect lesions in the CNS)
2) Evaluation of vision, coordination, and sense of balance
3) Spinal tap/Lumbar puncture (to assess CNS inflammation)
4) Blood tests (to rule out similar diseases)
5) Evoked potential tests (to measure the speed/accuracy of nervous system responses)

Question 11

How does an MRI assist in diagnosing MS?

Answer 11

An MRI detects lesions (areas of damage) in the brain and spinal cord that are characteristic of MS.

Question 12

Why are tests of vision, coordination, and balance important in diagnosing MS?

Answer 12

MS can impair these functions, so evaluating them helps determine the extent of neurological involvement.

Question 13

What is the purpose of a spinal tap (lumbar puncture) in the context of MS?

Answer 13

A spinal tap collects cerebrospinal fluid to measure the level of inflammation in the CNS.

Question 14

What role do blood tests play in the diagnosis of MS?

Answer 14

Blood tests help rule out other diseases that might present with similar symptoms.

Question 15

What do evoked potential tests measure in patients suspected of having MS?

Answer 15

They assess how quickly and accurately the nervous system responds to stimuli by recording electrical signals.

Question 16

What are the key features and mechanisms of IFNβ therapy in treating MS?

Answer 16

• Relapse Reduction: Lowers relapses by ~30%
• Administration: Weekly injection

Mechanisms:
- Controls secretion of pro- and anti-inflammatory cytokines
- Reduces lymphocyte migration across the blood-brain barrier
- Affects antigen-presenting cell (APC) function
- Inhibits some T cell differentiation & increases T cell apoptosis

Question 17

How do corticosteroids help manage MS symptoms?

Answer 17

• Immunosuppression: Reduces inflammation caused by pro-inflammatory cytokines
• Mechanisms:
• Increases apoptosis in lymphocytes
• Decreases migration of leukocytes to the brain

Question 18

What distinguishes dimethyl fumarate therapy from other MS treatments, and what are its mechanisms?

Answer 18

• Efficacy: Reduces relapses by ~50%
• Administration: Oral pills
• Approval & Side Effects: Approved in 2013 with fewer side effects
• Mechanisms:
• Exerts anti-inflammatory effects by suppressing pro-inflammatory cytokines
• Stimulates Tregs (regulatory T cells)
• Alters APCs by changing their maturation, availability, and antigen-presenting capacity

Question 19

What additional factors can contribute to MS progression?

Answer 19

(1) Lifestyle & Environmental:
Smoking
Diet
Physical inactivity
Body Mass Index (BMI)

(2) Biological & Genetic
Pathogens
Gut microbiome
Lipids and lipoproteins
Hypertension
Genetics
Diabetes