Multiple Sclerosis

Question 1

What is MS?

Answer 1

Autoimmune inflammatory disease which attacks myelinated axons in the CNS

Question 2

How is MS diagnosed?

Answer 2

Neurological symptoms/previous neurologic episode lasting 24 hours
- no evidence of infection/fever/encephalopathy

Question 3

What are the most common symptoms of MS?

Answer 3

• sensory/motor (tingling/numbness of arms and legs, electric current sensation down back/legs)
• vision problems (blurriness/loss/diplopia)
• slow progressive/subacute motor deficits

Question 4

What are more rarer symptoms? (less than 5% patients experience)

Answer 4

• bladder dysfunction (frequency, incomplete emptying)
• heat intolerance (heat causes nerves to conduct less efficiently)
• paroxysmal symptoms
• pain movement disorders
• dementia

Question 5

What are the 3 main characteristics of an MRI on MS?

Answer 5

• Flair lesion spread out in space (in more than 2 CNS areas, lesion in corpus callosum/periventricular/spinal cord)
• Flair lesion occurring at different points in time (development of new lesion after seeing old one)
• Brain atrophy

Question 6

What is the significance of a lumbar puncture for MS?

Answer 6

• safe if sterile
• atraumatic needle (no damage to dura)
• compares components of CSF to plasma (blood cells, lymphocytes)
• measures neurofilaments

Question 7

What is the significance of neurofilament amount?

Answer 7

• high = indicates ongoing nerve loss

- protein component of axons

Question 8

What are the diagnostic criteria of MS?

Answer 8

• dissemination in space (symptoms in more than 1 place in CNS)
• dissemination in time (chronic condition)
• rule out all other diagnoses

Question 9

What are the types of MS?

Answer 9

• relapsing-remitting (attack occurs then goes back to baselines)
• secondary-progressive (relapse-remitting is not treated so condition becomes progressive)
• primary progressive (patient never relapses and progressively gets worse)
• progressive-relapsing (between relapses disease will get worse)

Question 10

What are relapses?

Answer 10

Attacks of symptoms

Question 11

What is the genetic component of MS?

Answer 11

• associated with HLA-DRB1*1501

- not very relevant as offspring chances are relatively low

Question 12

What are the causes of MS?

Answer 12

relatively unknown:

• viral infection of neurons
• mitochondrial dysfunction
• release of heat shock

Question 13

What is the pathology of MS?

Answer 13

• axons still present but no myelin around them

Question 14

Which cells are involved in MS?

Answer 14

• neurons
• astrocytes
• oligodendrocytes
• microglia

Question 15

What are the 4 types of lesions?

Answer 15

• pre-active lesion (activated microglia and myelin loss)
• active lesion (lymphocyte infiltration around vessels)
• chronic active lesion (lymphocyte spread out around lesion, macrophages engulf myelin and sit on lesion edge)
• chronic inactive lesion (remyelination attempt however already significant enough demyelination and axon loss = astrocytic scar)

Question 16

How does an astrocytic scar present?

Answer 16

Black hole on MRI/shadow plaque

Question 17

What is the cycle of neuron MS damage?

Answer 17

Immune response -> CNS inflammation -> neurodegeneration

CNS inflammation = immune response so cycle, positive feedback

Question 18

What treatment should be given during an attack?

Answer 18

• prednisolone

- high dose, earlier treatment the better

Question 19

What are the 2 strategies of treatment?

Answer 19

• maintenance escalation (not super aggressive drugs, not many side effects)
• induction (very aggressive anti-inflammatory drugs with serious side effects)

Question 20

What are some first line disease modifying drugs?

Answer 20

• escalation (injectables - IFNb, natalizumab)

- induction (alemtuzumab, mitoxantro, HSCT)

Question 21

What are some second line disease modifying drugs?

Answer 21

Natalizumab
HSCT - haematopoietic stem cell transplantation
Fingolimod