Multiple sclerosis

Question 1

What are the symptoms of multiple sclerosis?

Answer 1

tingling/numbness
problems with balance
poor muscle co-ordination and weakness
changes in vision
fatigue
slurred speech/stuttering
bladder/bowel problems

Question 2

MS has periods of symptoms followed by periods without. What are each of these periods known as?

Answer 2

relapse = symptoms
- new symptoms may appear
- can cause permanent damage

remission = symptoms subside

Question 3

There are 54 different categories of Ms what are they?

Answer 3

• Relapsing Remitting (RRMS) (or Benign MS)
  Where symptoms always resolve between attacks: 80% patients, common
  Unpredictable relapses (months to years)
• Primary Progressive (PPMS)
  No remission: 10% patients
• Secondary Progressive (galloping MS, SPMS)
  An initial relapsing‐remitting turns into continuous progression
  65% patients initially diagnosed with RRMS, transition to SPMS at some point
• Progressive Relapsing Remitting (PRMS)
• Consists of overall steady neurologic decline with periodic relapses: least common, 5%

Question 4

Why is myelin important in MS?

Answer 4

MS is where the immune system attacks and destroys myelin
- chronic autoimmune disorder which results in a demyelination disease

Question 5

What is the function of oligodendrocytes?

Answer 5

create and maintains myelin sheath

Question 6

What happens to oligodendrocytes during MS?

Answer 6

they are destroyed through apoptosis

however, oligodendrocytes are responsible for remission of symptoms as they can repair damaged myelin

Question 7

What is formed as a consequence of the immune system attacking myelin?

Answer 7

scleroses or plaques/lesions (scars)
- these affect the white matter of the central nervous system (CNS)

Question 8

The loss of myelin causes impaired nervous system transmission. Why does myelin loss change which affects transmission?

Answer 8

without myelin propagation of the axon potential is lost
- saltatory conduction cannot occur (jump)

Question 9

Impaired nervous transmission lead to neurological symptoms. What are these symptoms?

Answer 9

abnormal sensations
vision problems
weakness

Question 10

What is the role of T cells in MS?

Answer 10

trigger the immune response against myelin

Question 11

In MRI scans of patients with MS the affected spots are in white matter areas of the brain. What is the affected regions of the brain that can be seen in MRI images?

Answer 11

ventricles of cerebellum
brain stem
basal ganglia
spinal cord
optic nerve

Question 12

What is the blood brain barrier?

Answer 12

highly selective semipermeable border which separates the circulating blood from the brain
- highly selective due to tight junctions

usually prevents T cells from getting into the CNS

Question 13

Why do T cells attack myelin once they can enter the brain circulation?

Answer 13

T cells are not usually exposed to myelin due to the BBB
- once BBB is lost or altered T cells come in contact with myelin and detects it as ‘non-self’

Question 14

Which proteins form the tight junction between endothelial cells of the BBB?

Answer 14

occludin
claudin 3/5
JAM

these proteins are connected to the cytoskeleton

Question 15

What occurs after T cells come into contact with myelin to lead to myelin being phagocytosed?

Answer 15

T cells release cytokines

cytokines increase BBB permeability allowing the entry of B cells and macrophages

B cells create antibodies against myelin

macrophages then phagocytose myelin

Question 16

Q
Macrophages and microglia produce high amounts of ROS and nitric oxide (NO). What substances are susceptible to peroxidation by ROS?

Answer 16

lipids and lipoproteins

Question 17

In demyelination plaques in brain, plasma and CSF of MS patients an increase in lipid peroxidation products was found. What do oxides lipids cause?

Answer 17

further demyelination and damage to axonal membranes
- oxidised lipids mediate inflammatory processes

creates a positive feedback loop as further demyelination results in more peroxidation

Question 18

Macrophages and microglia cause the production of ROS and NO in MS. How does this affect mitochondria in the neurons?

Answer 18

ROS and NO causes swelling and damage to intra-axonal mitochondria
- neurons will then increase mitochondria content in the area of inflammatory damage
- even with an increase of mito damage is still occurring which leads to more damage occurring.
- this causes a lack of ATP for neuronal cells