Multiple Sclerosis

Question 1

What would the presentation be with someone with optic neuritis?

Answer 1

history of pain in the eye and blurred vision

• reduced colour vision (Ishihara chart)
• reduced pupillary light responses (RAPD)
• hole in visual field (scotoma)

Question 2

What is the Ishihara chart?

Answer 2

it is a form of colour vision deficiency test that is used in diagnosing colour blindness

Question 3

What is RAPD?

Answer 3

relative afferent pupillary defect

the pupils respond differently to light stimuli shone in one eye at a time

this is due to unilateral or asymmetrical disease of the retina or optic nerve

Question 4

what is meant by scotoma?

Answer 4

an area of partial alteration in the field of vision consisting of a partially diminished or entirely degenerated visual acuity

this is surrounded by a field of normal vision

Question 5

What is optic neuritis?

Answer 5

inflammation of the optic nerve

this causes pain and loss of vision

Question 6

Why is optic neuritis frequently not visible?

Answer 6

it affects the retrobulbar space

this is the area located behind the globe of the eye

Question 7

What is the prognosis of optic neuritis like?

What can speed up rate of recovery?

Answer 7

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

high dose steroids speed up rate of recovery but have no effect on final acuity

Question 8

how is optic neuritis related to MS?

Answer 8

50% of cases go on to develop MS within 10 years

Question 9

What are some of the presenting signs and symptoms of transverse myelitis?

Answer 9

• tingly numbness starting in both feet and gradually ascending to level around the chest
• unsteady walking and fatigued easily
• electric shock sensation running down body whenever patient bends head

Question 10

What is transverse myelitis?

Answer 10

inflammation inside the spinal cord in one section

it damages the myelin covering nerve cell fibres and interrupts messages sent from spinal cord nerves throughout the body

Question 11

What type of sensation tends to be affected in transverse myelitis?

Answer 11

it is often purely sensory

it may affect the bladder

Question 12

What is Lhermittes phenomenon in transverse myelitis?

Answer 12

an electric shock-like sensation that occurs on flexion of the neck

the sensation radiates down the spine, often into the legs, arms and sometimes to the trunk

Question 13

How is transverse myelitis related to MS?

Answer 13

50% of patients go on to develop multiple sclerosis

Question 14

What is involved in diagnosing MS?

Answer 14

clinical diagnosis

relies on dissemination in time and place

the Macdonald criteria is used

Question 15

What is meant by clinically definite MS?

Answer 15

optic neuritis and transverse myelitis at different times

Question 16

What is involved in diagnosing not definite MS?

Answer 16

• clinically isolated syndrome (CIS)
• myelitis and optic neuritis at the same time
• recurrent myelitis
• recurrent or sequential optic neuritis

Question 17

How are cases with optic neuritis and transverse myelitis treated?

Answer 17

intravenous methylprednisolone 1 g daily for 3 days

Question 18

What is meant by ‘relapsing-remitting multiple sclerosis’?

Answer 18

the patient has attacks where their symptoms flare up

an attack is followed by a time of recovery where the patient has few or no symptoms (this is remission)

Question 19

What is a treatment for relapsing-remitting multiple sclerosis?

Answer 19

dimethyl fumarate

240mg twice daily

this condition usually starts in 20-30s

Question 20

Why is MS so prominent?

Answer 20

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

Question 21

What sex, ages and ethnicity are more susceptible to MS?

Answer 21

sex ratio is 2 female : 1 male

most common age of onset is 30-40 years

most prevalent in northern europeans, US caucasians and canadians

Question 22

What system is affected by MS?

What does this lead to?

Answer 22

it is a disease of the central nervous system (CNS)

an inflammatory reaction in the CNS causes loss of myelin and slowing of nerve conduction

there are areas of demyelination and loss of axons

Question 23

What are the 2 possible mechanisms of demyelination?

Answer 23

1. immune mediated injury
2. antibody mediated injury

Question 24

In immune mediated injury, how can T cells cause demyelination?

Answer 24

• T cells become activated and enter the CNS through blood vessels

once inside the CNS, T cells release chemicals that cause inflammation and damage and result in damage to myelin

• T regulatory cells do not function correctly and do not effectively turn off inflammation
• cytotoxic T cells directly attack and destroy cells bearing certain characteristics

Question 25

How are B cells involved in antibody mediated injury to myelin?

Answer 25

B cells produce antibodies and stimulate other proteins

In MS, B cells cause damage in the CNS

Question 26

What are the disease modifying treatments available for multiple sclerosis?

Answer 26

• interferon beta 1-b
• interferon beta 1-a
• glatiramer acetate
• teriflunamide
• dimethyl fumarate
• fingolimod
• natalizumab (tysabri)
• alemtuzumab (lemtrada)
• mitoxantrone
• ocrelizumab (ocrevus)

Question 27

What is dimethylfumarate?

What was it initially used to treat?

Answer 27

dimethylfumarate (DMF) is the methyl ester of fumaric acid

DMF combined with three other fumaric acid esters was licensed as oral therapy for psoriasis

Question 28

What is responsible for the immunomodulatory actions of dimethylfumarate?

Answer 28

glutathione depletion and subsequent induction of the anti-inflammatory stress protein HO-1 is thought to be one of the mechanisms responsible

Question 29

What is the first humanised monoclonal antibody approved for the treatment of MS?

Answer 29

TYSABRI

it prevents immune cells from migrating from the bloodstream into the brain where they can cause inflammation and potentially damage nerve fibres and their insulation

Question 31

How does Natalizumab work?

Answer 31

it is a human monoclonal antibody that interacts with adhesion molecule a4-integrin

this is on the activated leukocyte with VCAM-1 on the blood-brain barrier

these are key components involved in immune cell adhesion and migration

Question 32

How does Natalizumab prevent movement of immune cells?

Answer 32

it prevents the migration of immune cells across the blood-brain barrier by selectively attaching to a4-integrin

Question 33

What is the JC virus?

What happens if someone with multiple sclerosis contracts JC virus?

Answer 33

JC (John Cunningham) virus is very common and most adults have been exposed to it

if the immune system is weakened, JC virus can reactivate

it can then cause serious and potentially fatal inflammation and damage to the brain known as progressive multifocal leukoencephalopathy (PML)

Question 34

What is the treatment for someone with JC virus and MS?

Answer 34

Tysabri infusions for 24 months

this is then changed to oral fingolimod

Question 35

How does fingolimod work?

Answer 35

it prevents T cell invasion of the CNS

it traps circulating lymphocytes in peripheral lymph nodes

Question 36

What receptor is targeted by fingolimod?

Answer 36

fingolimod results in internalisation of the receptor S1P1

this blocks lymphocyte egress from lymph nodes while sparing immune surveillance by circulating memory T cells

Question 37

What is spastic paraparesis?

Answer 37

progressive weakness and spasticity (stiffness of the legs)

there is initially mild gait difficulties and stiffness

it suggests a spinal cord problem

Question 38

What are the 4 types of disease progression in MS?

Answer 38

• relapsing-remitting MS
• primary progressive MS
• secondary progressive MS
• progressive relapsing MS

Question 39

What is meant by axonal loss in MS?

Answer 39

loss of axons and neurones is the major cause of progressive neurological decline

primary inflammatory demyelination is the underlying cause of axonal loss

Question 40

What is shown in this image?

Answer 40

the natural history of brain atrophy in MS

Question 41

What % of MS patients are confined to a wheelchair?

Answer 41

15% of MS patients are confined to a wheelchair within 10 years of diagnosis

Question 42

What is meant by symptomatic treatments in MS?

Answer 42

they are involved in management of acute relapse and treatment of symptoms

e.g. fatigue, mood problems, pain, tremor, sensory problems