MS

Question 1

What is MS?

Answer 1

acute localised, and chronic diffuse, inflammation of the CNS and subsequent demyelination of neurone, following the infiltration of immune cells across the BBB

Question 2

What is the pathophysiology of MS (as a generality)?

Answer 2

• clonal expansion of immune cells (T and B cells) in peripheral compartment
• ->Immune attack against oligodendrocytes leading to:
• loss of nerve fibres (myelin sheaths): saltatory conduction altered
• pockets of inflammation: local oedema
• glial scarring or sclerosis

Question 3

How can you tell between a new and old lesion in MS?

Answer 3

• white around lesion is oedema (fried egg appearance): new

- if no oedema: old lesion

Question 4

What is comprised of the BBB?

Answer 4

endothelial cell, basement membrane, pericytes, astrocyte, neuron

Question 5

What is the pathophysiology of MS?

Answer 5

1. infection by bacteria or virus
2. antigen gets into the blood stream, digested by APC
3. macrophage cell displays antigen with MHC molecule
4. MHC-ag can be recognised by T cells
5. activated T cell crosses BBB
6. in CNS, Th cells encounter microglia (which are local APCs)
7. APCs present a MHC-ag complex (containing myelin product) to T cells. Th cells are locally reactivated when they recognise ag on surface of local APCs (epitope-self protein of the MBP, MOG or MAG)
8. activated Th cells secrete cytokines that:
   - stimulate microglia and astrocytes
   - recruit additional inflammatory cells from peripheral blood (macrophages, B cells)
   - induce antibody production (B cells)
   - complement system production
9. demyelination, oligodendrocyte degeneration

Question 6

What is the incidence of MS in the UK?

Answer 6

1:500

Question 7

What is the female:male ratio for MS?

Answer 7

3:1

Question 8

What is the genetic component in MS?

Answer 8

chromosome 6
colocalisation of genres involved in MS and MHC class 1, 2 and 3

Question 9

What is
MBP
MOG
MAG?

Answer 9

myelin basic protein
myelin oligodendrocytes glycoprotein
Myelin associated glycoprotein

Question 10

What are the difference molecular homology?

Answer 10

• sequence homology: sequence of amino acids

- structural homology: protein shape

Question 11

What are the different symptoms in MS?

Answer 11

• optic neuritis (pain on eye movement, blurring of vision, red colour saturation) + Uhthoff’s phenomenon (if there has been optic neuritis in the past and you get fever, it can irritate the scar tissue and cause symptoms)
• brainstem: vertigo slur speech, ataxia, incoordination, double vision
• spinal cord:
• > sensory: Lhermitte’s phenomenon: shock pain running gown spinal cord, irritation lesion)
• ->motor: upper and lower limb weakness
• ->autonomic: bowels, bladder, sexual dysfunction

MORE depends where they are

Question 12

How can you tell the difference between an upper and lower motor neurone lesion?

Answer 12

upper: increased tone, exaggerated reflexes, present Babinaski’s sign

Question 13

What are the different types of MS and how are they characterised?

Answer 13

1. relapsing-remitting (85-90%)
   - attacks (relapses) with complete or partial recovery
   - no progression between attacks (remission)
2. secondary progressing
   - initial relapse-remitting course followed by progression (usually 10-15 years)
   - with or without attacks
3. Primary progressive (10-15%)
   - progressive from onset, no attacks
4. progressive-relapsing (<5%)
   - progression from onset with attacks

Question 14

How do you diagnose MS,

Answer 14

history
MRI
CSF (oligoclonal IgG)
evoked potentials

Question 15

What is the 2017 McDonald Criteria for diagnosis of MS?

Answer 15

2 different attacks and 2 different times:

• dissemination on space (dvlpt of lesions in distinct anatomical locations within the CNS: multifocal CNS process)
• dissemination in Time (dvlpt or appearance of new CNS lesions over times + pos oligoclonal bands: bands take a while to appear so if they are there, they have been for a while)

Question 16

What is the better prognosis for MS?

Answer 16

caucasian
monodical onset
females
onset with optic neuritis or isolated sensory symptoms
low relate rate first 2-5 years
long interval to second relapse
no or low disability at 5 years
abnormal MR with low lesion load
high vit D

Question 17

What is worse prognosis for MS?

Answer 17

afro-american or non white
multifocal onset
males
onset with motor cerebellar or bladder or bowel symptoms
high relapse rate 2-5 years
short inter attack latency
disability at 5 years
abnormal MR with 2 contrast lesions
habit: smoking, high salt intake

Question 18

How do you treat MS?

Answer 18

high dose corticosteroids (orally or IV) for relapse: reduce inflammatory activity/stabilises BBB
BUT
-no significant effect on MS disease progression

Question 19

What is a myelin sheath made out of?

Answer 19

-lipids: galactocerebroside
-glycoproteins:
MBP
MOG
MAG