Multiple Sclerosis

Question 1

What is MS?

Answer 1

Idiopathic inflammatory demyelinating disease of the CNS
Acute episodes of inflammation are associated with focal neurological deficits
If left untreated, patients become progressively more disabled

Question 2

Name the five subtypes of MS.

Answer 2

Relapsing remitting MS 
Primary progressive MS 
Secondary progressive MS 
Progressive-relapsing MS
Benign MS

Question 3

What is meant by relapsing remitting MS?

Answer 3

Unpredictable attacks which may or may not leave permanent deficits, followed by periods of remission

Question 4

What is meant by progressive relapsing MS?

Answer 4

Steady decline since the onset, with super-imposed attacks

Question 5

What is meant by primary progressive MS?

Answer 5

Steady increase in disability from onset, without any attacks

Question 6

What is meant by secondary progressive MS?

Answer 6

Initial relapsing remitting MS that suddenly begins to decline without periods of remission

Question 7

Which symptoms commonly develop into MS?

Answer 7

Optic neuritis
Clinically isolated syndromes
Transverse myelitis
Radiologically isolated syndromes

Question 8

What is optic neuritis and what is the risk of developing MS after an attack?

Answer 8

Painful vision loss that comes on over a few days
- demyelination of the optic nerve
- may resolve after a few weeks
30% develop MS after 5 years
50% develop MS after 15 years
Risk depends on MRI scan and oligoclonal bands in the CSF

Question 9

What are the symptoms of optic neuritis?

Answer 9

Blurry vision
Loss of colour vision
Pain
Vision loss

Question 10

What is transverse myelitis?

Answer 10

Inflammation of the spinal cord

Causes weakness, sensory loss and incontinence

Question 11

What is a clinically isolated syndrome?

Answer 11

Single episode of neurological disability due to focal CNS inflammation
- e.g. optic neuritis or transverse myelitis

Question 12

When is MS diagnosed?

Answer 12

When on MRI, there is evidence of 2 OR MORE EPISODES of DEMYELINATION, DISSEMINATION in SPACE AND TIME.

• inflammation of two different parts of the CNS - disseminated in space
• evidence of active and past inflammation - disseminated in time

Question 13

What causes MS?

Answer 13

Genetic factors - low in China
Sunlight/Vit D
Viral triger (EBV)
Smoking (increases rate of disability progression)

Question 14

When should you suspect MS in a patient?

Answer 14

Neurological symptoms that develop over a few days
A history of transient neurological symptoms that lasted 24 hours and spontaneously resolved
Hidden relapses
- optic neuritis
- Bell’s palsy
- labyrinthitis
- sensory symptoms
- bladder symptoms in young men and women without children

Question 15

List some of the main symptoms of MS.

Answer 15

Depends on the area of demyelination

• fatigue
• depression
• optic neuritis
• dysarthria
• dysphagia
• weakness of limbs
• pain
• incontinence
• diarrhoea

Question 16

What signs and symptoms indicate MS might not be the cause?

Answer 16

Sudden onset
Peripheral signs - areflexia, glove and stocking distribution, muscle wasting and fascicualtions
Major cognitive involvement 
Prominent seizures 
Pyrexia
Normal MRI

Question 17

What is radiologically isolated syndrome?

Answer 17

MRI scan performed on patient who doesnt have signs or symptoms of MS
- incidental finding that looks like MS
May develop into MS, but might not
Unnecessary distress for patient (VOMIT)

Question 18

How do you investigate suspected MS with an MRI?

Answer 18

MRI of the brain and cervical spine with gadolinium contrast

• evidence of demyelination in 2 regions to indicate dissemination in space
• enhancing and non-enhancing areas of demyelination indicate dissemination in time

Question 19

Name a T2 hyperintensity.

Answer 19

Dawson’s fingers

• demyelinating plaques through the corpus collosum
• specific for MS

Question 20

What investigations can you do to test someone for MS?

Answer 20

Lumbar puncture
MRI
Blood - exclude other conditions 
Visual evoked potentials
Chest X-Ray - exclude sarcoidosis

Question 21

What are you looking for in the CSF after a lumbar puncture?

Answer 21

Oligoclonal bands - bands of immunoglobulin
Cell count - to exclude mimics
Glucose - matches blood sample
Protein

Question 22

What are oligoclonal bands?

Answer 22

Immunoglobulin bands seen in blood and spinal fluid after protein electrophoresis
(suggests inflammation)
- suggestive of MS when bands aren’t also present in the blood (means inflammation is in the CNS)
- can be seen in other conditions or after brain surgery

Question 23

What blood tests do you do if you suspect MS?

Answer 23

Mainly to exclude other possible causes

• B12/folate
• serum ACE
• lyme serology
• ESR/CRP (should be normal)
• ANA/ANCA/RA
• aquaporin-4 antibodies (show up in transverse myelitis and optic neuritis)

Question 24

What are visual evoked potentials?

Answer 24

Measure of conduction of nerve signals in optic nerves to look for subclinical neuritis

• conduction is slower if patient has had optic neuritis in the past
• conduction should be the same on both sides

Question 25

What is the difference between a relapse or a pseudo-relapse in MS?

Answer 25

Relapse - new neurological symptoms they have never had before - lasts more than 24 hours in the absence of temperature or infection Pseudo-relapse - flaring of an old area of demyelination causing re-emergance of pervious neurological symptoms (usually caused by heat or infection)

Question 26

How are MS relapses managed?

Answer 26

Treatment isn't always needed High dose steroids can be used to suppress the inflammation - not given if any evidence of inflammation Physiotherapy Occupational therapy RRMS - MRI to check for active disease and see if they need new treatment

Question 27

Describe the steroid regime for relapse?

Answer 27

``` 1g of IV methylprednisolone for 3 days OR 500mg oral methylprednisolone for 5 days AND PPI for gastroprotection ```

Question 28

What are the two different methods of giving disease modifying therapies in RRMS.

Answer 28

Induction therapy - therapy started with more effective drugs, but they are hard on the body Escalation therapy - start with less effective, but more safe drugs

Question 29

Name some disease modifying drugs for RRMS.

Answer 29

``` Powerful drugs - Alemtuzumab - Natalizumab Oral treatments - Fingolimod - Dimethyl Fumerate ```

Question 30

What are the pros and cons of Alemtuzumab?

Answer 30

``` Pros - two short courses over a year - stops relapse in 40% of patients - may improve disability Cons - high risk of secondary autoimmune problems (thyroid, ITP) ```

Question 31

What are the pros and cons of Natalizumab?

Answer 31

``` Pros - monthly infusions - very effective Cons - serious risk of fatal PML is infected with JC virus ```

Question 32

What are the pros and cons of Fingolimod?

Answer 32

Pros - less side effects compared to the more powerful drugs Cons - daily tablet - less effective than natalizumab or alemtuzumab - risk of infection - slows heart rate

Question 33

What are the pros and cons of dimethyl fumerate?

Answer 33

``` Pros - less side effects compared to the more powerful drugs Cons - twice daily tablet - less effective than Fingolimod - low WCCs - risk of infections ```

Question 34

Name some of the older treatments for MS.

Answer 34

Beta interferon and Copaxone | - less effective than Fingolimod or monoclonal antibodies

Question 35

What is the cause of primary progressive MS?

Answer 35

JC virus - can lead to PML in the immunocompromised - progressive destruction of white matter in the brain

Question 36

How is primary progressive MS diagnosed?

Answer 36

At least one year of disease progression MRI scan supports diagnosis of MS Oligoclonal bands support diagnosis of MS

Question 37

How is secondary progressive MS diagnosed?

Answer 37

When they have had RRMS in the past, but have no started exhibiting signs of progressive disease without relapses on scan

Question 38

What is the treatment for progressive MS?

Answer 38

Treating symptoms Effective treatment for RRMS reduces progression to secondary progressive MS. Potential treatment for PPMS - ocrelizumab Potential treatment for SPMS - siponimod

Question 39

Describe the symptom management for secondary progressive MS

Answer 39

Rehabilitation | Control symptoms of the bladder, fatigue, mood, spacicity and mobility