Multiple sclerosis

Question 1

What is optic neuritis and what does it cause?

Answer 1

Inflammation of the optic nerve - causes pain and loss of vision

Question 2

What is the prognosis of optic neuritis (how many go on to return to visual acuity)?

Answer 2

95% return to visual acuity of 6/12 or greater within 12 months

Question 3

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

Answer 3

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

Question 4

What is the association between optic neuritis and MS?

Answer 4

50% of people who have suffered from optic neuritis go on to develop MS within 10 years

Question 5

What is transverse myelitis, what is the prognosis and symptoms?

Answer 5

Inflammation inside the spinal cord - often pure sensory, may affect the bladder, experience Lhermittes phenomenon. It is often mild with a good prognosis

Question 6

What is Lhermittes phenomenon?

Answer 6

Sudden, uncomfortable sensation which travels from your neck down your spine - like electric shocks going through your body

Question 7

What is the association between transverse myelitis and MS?

Answer 7

50% of sufferers go on to develop MS

Question 8

What kind of diagnosis is MS?

Answer 8

A clinical diagnosis

Question 9

What criteria aid in the diagnosis of MS?

Answer 9

Macdonald criteria

Question 10

How would optic neuritis and transverse myelitis occur in clinically definite MS?

Answer 10

Optic neuritis and transverse myelitis at different times

Question 11

What 3 situations involving optic neuritis and transverse myelitis would not be clinically definite MS?

Answer 11

1) Myelitis and optic neuritis at the same time
2) Recurrent myelitis
3) Recurrent or sequential optic neuritis

Question 12

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

Answer 12

MS

Question 13

Which sex is more susceptible to MS?

Answer 13

Females

Question 14

What is the most common age of onset of MS?

Answer 14

30-40 years

Question 15

What are the highest risk ethnicities and lowest risk ethnicities for MS?

Answer 15

Highest risk: Northern European, US Caucasians, Canadians

Lowest risk: African blacks, orientals

Question 16

What is thought to be the reason behind the association between prevelance of MS and latitude?

Answer 16

Prevalence is strongly dependent on latitude - due to environmental factors such as habitat, diet, infections

Question 17

What is MS?

Answer 17

A disease of the CNS - an inflammatory reaction in the CNS causes loss of myelin and slowing of nerve conduction, get areas of demyelination and loss of axons

Question 18

What are thought to be the 2 main possible mechanisms behind demyelination in MS?

Answer 18

1) Immune cell mediated injury - auto Ab activate lymphocytes which activate macrophages and CD8+ cells to attack the axon myelin
2) Antibody mediated injury - Ab to myelin cause complement to attack the myelin of axons

Question 19

What are disease modifying drugs?

Answer 19

Group of drugs used in the treatment of relapsing multiple sclerosis

Question 20

What are the 4 types of disease progression in MS?

Answer 20

1) Relapsing-remitting MS - get flare ups and periods of improvement but generally relapses get worse over time
2) Primary progressive MS (10% of cases) - MS gets gradually worse over time with no periods of remitting
3) Secondary progressive MS - initially relapsing and remitting then becomes progressive and no longer get any periods of improvement
4) Progressive relapsing MS (

Question 21

How effective is the DMD Interferon Beta - at which point is it most effective?

Answer 21

Reduces the number of relapses by 1/3
Effective early in the disease course
No evidence of long term effect on disability

Question 22

What is the sight of injection, frequency and side effects of the DMD Betaferon 1b?

Answer 22

Subcut injection
Alternate days
Side effects = flu like symptoms, ISR

Question 23

What is the sight of injection, frequency and side effects of the DMD Avonex 1a?

Answer 23

IM injection
Once weekly
Side effects = flu like symptoms

Question 24

What is the sight of injection, frequency and side effects of the DMD Refib 1a?

Answer 24

Subcut injection
3 times a week
Side effects = flu like symptoms, ISR

Question 25

What is the sight of injection, frequency and side effects of the DMD glatiramer acetate?

Answer 25

Subcut injection
Daily
Side effects = acute reaction

Question 26

TYSABRI is the first humanised monoclonal Ab approved for the treatment of MS, how does it work?

Answer 26

Inhibits adhesion molecules on the surface of immune cells this is through to prevent immune cells from migrating from the blood stream into the brain where they can can cause inflammation and potentially damage nerve fibres and there insulation

Question 27

How are humanized monoclonal Abs produced?

Answer 27

Using genetic engineering in mice

Question 28

Which adhesion molecule on the activated leukocyte interacts with VCAM-1 on the blood brain barrier to enable immune cell adhesion and migration?

Answer 28

Alpha 4 integrin

Question 29

Natalizumab prevents migration of immune cells across the blood brain barrier by selectively attaching to which molecule?

Answer 29

The adhesion molecule alpha 4 integrin found on activated leucocytes

Question 30

Give the 3 new oral treatments for MS?

Answer 30

1) Fingolimod
2) Teriflunomide
3) Dimethyl Fumarate

Question 31

What is the overall mechanism of action of fingolimod?

Answer 31

Sphingosine 1-phosphate (S1P) receptor modulator
Prevents T cell invasion of CNS
Traps circulating lymphocytes in peripheral lymph nodes

Question 32

How does Fingolimod trap circulating lymphocytes in peripheral lymph nodes?

Answer 32

Fingolimod results in the internalisation of the receptor S1P1
This blocks lymphocyte movement movement out of the lymph nodes whilst sparing immune surveillance by circulating memory cells

Question 33

How does the reduction in relapse rate compare between Fingolimod and interferon 1a?

Answer 33

52% reduction in relapse rate with fingolimod compared to Interferon 1a

Question 34

Which virus has Fingolimod been associated with and which 1 side effect?

Answer 34

Associated with 2 incidences of fatal herpes zoster virus infection
Troublesome bradychardia after first dose

Question 35

How can brain imaging help to diagnose MS?

Answer 35

see brain atrophy

Question 36

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

Answer 36

15%

Question 37

What are the 2 different types of treatment in MS?

Answer 37

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

Question 38

What 7 problems can symptomatic treatments treat in MS?

Answer 38

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

Question 39

What are the 7 targets for neuroprotective therapy?

Answer 39

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

Question 40

What are the 3 main current problems in MS management?

Answer 40

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

Question 41

Is MS an autoimmune disease?

Answer 41

Yes

Question 42

What is the most common course of the disease?

Answer 42

Relapsing phase followed by a progressive phase in most cases