Multiple Sclerosis

Question 1

What is the epidemiology of MS?

Answer 1

More common the further from the equator you are

Rare in Africa, Asia

Twice as common in women

Mean age of onset 20-45

Question 2

What is the aetiology and pathophysiology of MS?

Answer 2

Discrete plaques of demyelination occurs at multiple CNS sites from a T cell mediated immune response

Triggers are unknown

Sunlight may have a preventative action - early exposure to sun/vit D is important; UV exposure in those with established disease relates to fewer new lesions on MRI

Normally macrophages cannot easily cross BBB but in Ms they exhibit glycoprotein α4ß1 allowing them to adhere to and cross the endothelium

Antibodies to myelin basic protein can be found early in the disease

Lesions most commonly occur at the optic nerves, periventricular, brainstem and cerebellar connections

Demyelination heals poorly:
Can cause relapsing and remitting symptoms
Conduction loss or blockage is probably to blame for most of the symptoms of MS
Over an extended period → axonal loss and clinically progressive symptoms

Question 3

What are the 4 types of progression in MS?

Answer 3

Relapsing remitting (most common) - unpredictable attacks whhick may or may not leave permanent deficits followed by periods of remission

Secondary progressive - initial relapsing-remitting then suddenly begins to decline without periods of remission

Primary progressive (10-20%) - steady increase in disability without attacks

Progressive relapsing (<10%) - steady decline since onset with superimposed attacks

Question 4

How might MS present?

Answer 4

Can be almost any neurological sign - dependent on areas of demyelination

Eye signs, UMN signs, sensory signs, autonomic defects, cerebellar signs, cognitive decline, systemic features

Question 5

What are some eye signs?

Answer 5

Optic neuropathy:
Usually unilateral
Pain on eye movement
Rapid loss of central vision

Optic disc swelling, pupillary defects, diplopia, hemianopia

Question 6

What are some UMN signs?

Answer 6

Spasticity
Hyperreflexia
Hypertonia 
Positive Babinski 
Weakness

Question 7

What are some autonomic signs?

Answer 7

Urinary incontinence
Constipation
Sexual dysfunction

Question 8

What are some cerebellar signs?

Answer 8

Truncal and limb ataxia 
Intention tremor 
Coordination problems 
Nystagmus 
Monotonous speech 
Falls

Question 9

What are some sensory signs?

Answer 9

Parasthesia - burning/tingling in limbs
Numbness
Reduced vibration sense
Trigeminal neuralgia

Question 10

What are some cognitive changes?

Answer 10

Amnesia
Aphasia
Altered mood 
Personality change 
Reduced functioning

Question 11

What are some systemic signs?

Answer 11

Pyrexia
N+V
Seizures

Question 12

What are some early indications for poor prognosis?

Answer 12

Older 
Male 
Motor signs on onset 
Many early relapses 
Many MRI lesions 
Axonal loss

Question 13

What is Uthoff’s phenomena?

Answer 13

Signs (i.e. vision) worse on hot days/post exercise as heat slows condition in nerve fibres

Question 14

What is Lhermitte’s sign?

Answer 14

Aka ‘barber chair phenomena’

On voluntary flexing of the head there is an electric shock sensation travelling down the spine to the limbs

Question 15

How do you diagnose MS?

Answer 15

McDonald criteria for diagnosing MS

Uses number of attacks and objective clinical lesions ± MRI evidence to identify MS and its type:

At least 1 ‘attack’ + multiple plaques on MRI OR
A single attack/progressive MS + multiple plaques on MRI + other evidence (oligoclonal bands, VEPs etc)

(‘Lesions disseminated in time and space’ and unattributable to other causes)

Question 16

What will MRI show in MS?

Answer 16

85% of cases will show plaques so is best test out there, even though diagnosis still should be combined with a clinical picture

Plaques will be 2-10mm and show up as white (most commonly in the areas mentioned - e.g. optic nerves)

Question 17

What will VEPs show?

Answer 17

Visual evoked potentials

Can detect lesions in visual pathways

Patient has EEG probes on the skull → measure brain response to visual stimuli by timing the duration between image shown and brain response measured → if delayed = some kind of optic nerve lesion

Question 18

What are oligocloncal bands?

Answer 18

Bands of IgG in CSF on electrophoresis

If not present in serum, suggest CNS inflammation

Question 19

What is the non-pharmacological management of MS?

Answer 19

Encourage stress free life if possible (as can reduce chance of new lesions)

Minimize disability – OT, PT, diet, increase vit D exposure/supplement

Question 20

How are MS relapses managed?

Answer 20

Methylprednisolone

500mg PO OD for 5 days OR
Up to 1 g IV OD for up to 3-5 days

Shortens acute relapses

Use sparingly i.e. <2x/yr

No change to prognosis

Manage any other symptoms as appropriate (e.g. constipation, breathing etc)

Question 21

What is typically used in the long term management of MS?

Answer 21

Beta interferons – INF-1ß and -1α (given IM or SC) FREQUENCY

Naturally produced by body to reduce inflammation after an immune response

Decreases relapse by 30% in active relapse-remitting MS; decreases lesion accumulation on MRI

Question 22

What other agents can be used in MS?

Answer 22

Monoclonal antibodies:
Alemtuzumab - acts on T cells in relapsing-remitting MS
Natalizumab – acts on VLA-4 receptors that allow immune cells to cross the BBB; decreases relapse and MRI lesions in relapse-remitting MS

Azathioprine - for relapse-remitting

Question 23

What else is important in the management of MS?

Answer 23

Treat all infections promptly as they are known to exacerbate

For spasticity – Baclofen, diazepam, dantrolene, tizanidine, Sativex (endocannibinoid modulator)

For tremor – Botulinum toxin type A

For urgency/frequency – teach intermittent self-catheterisation, tolterodine