Multiple Sclerosis 1

Question 1

What is optic neuritis?

Answer 1

Inflammation of the optic nerve

Question 2

What are the main symptoms of optic neuritis? 2

Answer 2

Pain and loss of vision

Question 3

Can optic neuritis be visualised using fundoscopy?

Answer 3

No, it is frequently not visible as it is retro bulbar

Question 4

What is the prognosis of optic neuritis, what percentage return to visual acuity within 6/12?

Answer 4

95%

Question 5

What is the treatment for optic neuritis, does this effect final acuity?

Answer 5

High dose steroids - these speed up recovery but have no effect on final acuity

Question 6

What percentage of people who have suffered from optic neuritis go on to develop MS within 10 years?

Answer 6

50%

Question 7

What is transverse myelitis?

Answer 7

Inflammation inside the spinal cord

Question 8

What is Lhermitte’s sign/phenomenon?

Answer 8

Sudden sensation resembling an electric shock which passes down the back of the neck and onto the spine and may radiate into the arms and legs, usually triggered by bending your head forward towards your chest

Question 9

Is transverse myelitis normally severe? What is the prognosis?

Answer 9

Normally mild, with a good prognosis

Question 10

What are the 3 main symptoms of transverse myelitis?

Answer 10

1) Often purely sensory symptoms
2) Lhermitte’s sign
3) May affect the bladder

Question 11

What percentage of people with transverse myelitis go on to develop MS?

Answer 11

50%

Question 12

Is MS mainly a clinical or imaging diagnosis?

Answer 12

Mainly a clinical diagnosis

Question 13

What criteria can be used for diagnosing MS?

Answer 13

Macdonald criteria 2010 (2nd revision)

Question 14

In what situation could you diagnose clinically definite MS?

Answer 14

Optic neuritis and transverse myelitis at different times

Question 15

In which 4 situations is a clinical diagnosis of MS not definite?

Answer 15

1) Clinically isolated syndrome (CIS)
2) Myelitis and optic neuritis at the same time
3) Recurrent myelitis
4) Recurrent or sequential optic neuritis

Question 16

What is the most common cause of neurological disability in young people?

Answer 16

MS

Question 17

Is MS more common in females or males?

Answer 17

Females (2:1)

Question 18

What is the most common age of onset of MS?

Answer 18

30-40 years

Question 19

In which ethnicity is susceptibility to MS highest?

Answer 19

Northern Europeans, US Caucasians, Canadians

Question 20

Prevelance of MS is strongly dependent on latitude, which factors can this be attributed to?

Answer 20

Environmental factors such as habitat, diet and infections

Question 21

MS is a disease of which body system?

Answer 21

CNS

Question 22

What is MS?

Answer 22

Autoimmune disease - inflammatory reaction in the CNS which causes loss of myelin and slowing of nerve conduction. Get areas of demyelination and loss of axons

Question 23

Give 2 possible mechanisms of demyelination in MS?

Answer 23

1) immune mediated - macrophages destroy myelin

2) Antibody mediated destruction of myelin

Question 24

Give 9 disease modifying treatments used in MS?

Answer 24

1) Interferon beta 1-b
2) Interferon beta 1-a
3) Glatiramer acetate
4) Teriflunamide
5) Dimethyl fumarate
6) Fingolimod
7) Natalizumab
8) Alemtuzumab
9) Mitoxantrone

Question 25

How does interferon beta treatment reduce the number of relapses in MS and when is it most effective?

Answer 25

1) Reduces the number of relapses by 1/3

2) Effective early in the disease course - no evidence on long term effect on disability

Question 26

TYSABRI (Natalizumab) is the first humanized mAb approved for the treatment of MS, how is it thought to work?

Answer 26

It inhibits adhesion molecules on the surface of immune cells, its is thought to work by preventing immune cells from migrating into the bloodstream and into the brain where they can cause inflammation and potentially damage nerve fibres and their insulation

Question 27

Which molecules on the activated leucocyte and the BBB are the key components involved in immune cell adhesion and migration?

Answer 27

1) Activated leucocyte - a4-integrin

2) BBB - VCAM-1

Question 28

Which molecule on the activated leucocyte is blocked by Natalizumab?

Answer 28

a4-integrin - prevent it interacting with VCAM-1 on the BBB

Question 29

Name 3 new oral treatments for MS?

Answer 29

1) Fingolimod
2) Teriflunomide
3) Dimethyl fumarate

Question 30

Fingolimod (a new oral therapy to treat MS) is what kind of drug?

Answer 30

Sphingosine 1-phosphate (S1P) receptor modulator

Question 31

How simply does Fingolimod work to treat MS?

Answer 31

It prevents T cell invasion of the CNS by trapping encirculating lymphocytes in peripheral lymph nodes

Question 32

How does Fingolimod trap circulating lymphocytes in peripheral lymph nodes?

Answer 32

Fingolimod causes the internalisation of the receptor S1P1 (on the T cell)
This blocks the T cell from moving out of lymph nodes while sparing immune surveillance by circulating memory T cells

Question 33

What are the 2 main side effects identified for Fingolimod?

Answer 33

1) 2 incidences of fatal herpes virus infection (type 1 encephalitis and disseminated zoster)
2) Bradychardia after 1st dose

Question 34

What is the difference in relapse rate between Fingolimod and IM interferon 1a?

Answer 34

Fingolimod caused a 52% relapse reduction rate compared to IM interferon 1a

Question 35

What are the 4 types of MS?

Answer 35

1) Relapsing -remitting MS - periods where symptoms flare up aggressively followed by periods of good or complete recovery
2) Secondary progressive MS - initially diagnosis of relapsing-remitting and over time frequency of relapses decreases but disability increases
3) Primary progressive MS - form in which disability increases from outset
4) Progressive relapsing MS - Disability increases from the outset but along the way have periods of relapse where symptoms flare up aggressively with remission but never full recovery

Question 36

Although symptoms and inflammation can relapse and remit, what is the course of axonal loss in MS?

Answer 36

Gradual increase in axonal loss - straight line graph

Question 37

What would brain imaging of someone with MS show over time?

Answer 37

Brain atrophy

Question 38

What percentage of MS patients are confined to a wheelchair within 10 years of diagnosis?

Answer 38

15%

Question 39

What are the 2 main categories of treatment in MS?

Answer 39

1) Symptomatic treatments - management of the acute relapse (corticotherapy)
2) Modifying course treatments

Question 40

What 7 things do symptomatic treatments for MS relapses aim to treat?

Answer 40

1) Fatigue
2) Mood problems
3) Pain
4) Pain
5) Sensory problems
6) Genitosphincteral problems
7) Tremor
8) Spasticity

Question 41

What is benign MS?

Answer 41

A version of relapsing-remitting MS with very mild attacks separated by long periods with no symptoms

Question 42

What are the 7 potential targets for neuroprotective therapy in MS?

Answer 42

1) Inflammatory mechanisms
2) Excitotoxic mechanisms
3) Energy depletion
4) Genetic determination
5) Apoptotic mechanisms
6) Depletion of growth factors
7) Demyelination induced damage

Question 43

Is MS treatable?

Answer 43

yes, but not curable

Question 44

What are the 3 main current problems in MS management?

Answer 44

1) We don’t know if treating the relapsing phase aggressively helps delay or prevent the progressive process
2) Still no effective treatment for progressive MS
3) There is no way of telling benign patients at the start of the disease

Question 45

What is the most common type of MS?

Answer 45

Secondary progressive MS - relapsing phase followed by progressive phase