MS

Question 1

What is MS? What is the pathology?

Answer 1

A chronic autoimmune T-cell mediated inflammatory disorder of the CNS

Leads to inflammatory processes within the white matter of brain and spinal cord

Leads to plaques of demyelination affecting white matter and tracts within CNS

Question 2

Where is MS common?

Answer 2

Europe and North America, more common away from the equator, even within the UK it is more common up north

Question 3

UK prevalence of MS

Answer 3

Approx 80,000 people have it which is 1.2 in 1000

Question 4

M:F for MS

Answer 4

F:M 2:1 and is becoming wider - females becoming more affected

Question 5

Age of onset of MS

Answer 5

20-40 years

Question 6

Environmental risk factors for MS x4

Answer 6

Migrating from low risk area to high risk area

Viral infections can precipitate MS relapses and development of MS in susceptible individuals

Evidence of MS and EBV relationship

Exposure to infectious agents in children may reduce risk of developing MS and other autoimmune disorders

Question 7

Genetic susceptibility for MS

Answer 7

MZ = 30% concordance, DZ = 5% concordance

Over 60 genes found to be involved - polygenic disorder

80% of these related to immune system function and regulation

Question 8

Pathology of MS - what part of CNS is affected?

Answer 8

Plaques of demyelination 2-10mm in size in white matter (sometimes grey matter)

Axons relatively intact

Question 9

Pathology of MS - What causes the damage?

Answer 9

Evidence suggests a role of cytokines and inflammatory infiltrate - lymphocytes etc

Can get interstitial oedema in acute lesions

Question 10

Pathology of MS - Where in CNS in most commonly affected? x6

Answer 10

Optic nerves, periventricular region, corpus callosum, brainstem, cerebellar connections and cervical cord

Question 11

What causes MS relapse?

Answer 11

Focal inflammation with loss of myelination and conduction block

Recovery when inflammation goes down and nerves can remyelinate

If no remyelination - progressive disease

Question 12

Which is most common form of MS?

Answer 12

Relapsing-remitting MS (RRMS)
85-90% of cases

Relapsing attacks and okay between times

Average 1 relapse per year

Onset over days and recovery over weeks

Question 13

What usually follows RRMS?

Answer 13

Secondary-progressive - typically after 35years of RRMS

Gradual worsening of the disease over the years

Can still sometimes get relapses = relapsing-progressive

Question 14

What is 3rd least common type of MS?

Answer 14

Primary-progressive - 10-15%

No relapses but progressively worse disease. Usually less plaques/inflammatory changes on MRI and develops later

Question 15

What is benign MS?

Answer 15

When years between relapses - but term used with caution

Question 16

What are the 3 main types of symptoms?

Answer 16

Optic neuritis, brainstem lesions and spinal cord lesions

Question 17

Details about optic neuritis?

Answer 17

1st symptom in 20% of MS patients
Inflammatory optic neuropathy associated with pain and vision problems - usually unilateral

Also get RAPD

Question 18

Details about brainstem demyelination?

Answer 18

Diplopia, vertigo, facial weakness/numbness, dysphagia or dysarthria

Pyramidal signs if corticospinal tracts involved

Question 19

Spinal cord lesions?!

Answer 19

Paraparesis, tetraparesis - due to plaque in thoracic or cervical cord.

Tight band around chest if thoracic

Lhermitte’s symptom on flexion of neck - electric shock type symptoms

Question 20

General symptoms which accumulate over years x11

Answer 20

1) Vision Loss
2) Sensory symptoms
3) Clumsy/useless hand or limb
4) Unsteadiness/ataxia
5) Neuropathic pain
6) Spasticity
7) Urinary incontinence
8) Sexual dysfunction
9) Fatigue
10) Depression
11) Uhthoff’s phenomenon - worse with heat, eg. exercise, bath

Question 21

Progression of MS generally

Answer 21

15 years walking aid and 25years wheelchair

Question 22

Diagnosis of MS

Answer 22

2 attacks separated in time and place needed (different CNS lesions at different times - an MRI at least 1 month after the first MRI which shows development of new plaques)

One MRI is not sufficient because can have lots of incidental findings of asymptomatic plaques

Question 23

Investigations in MS x5

Answer 23

MRI Brain and Spinal Cord shows hyperintense lesions - oval up to 2cm in diameter
- Has limited specificity in over 50 because ischeamic lesions can look like demyelination

CT not very useful

CSF will show oligoclonal IgG in around 95% but not specific for MS - will also get raised WCC and proteins in 25% of patients

Blood tests to exclude other inflammatory disorders (SLE or sarcoid)

Evoked potentials - visual, brainstem (auditory) and somatosensory

Question 24

Treatment of MS

Answer 24

There is no cure

Disease modifying drugs =
Beta-interferon and glatiramer acetate - very expensive but can reduce relapse rate by 1/3 and serious relapses by up to 1/2 in RRMS - short term reduction of disability

SE’s = flu like symptoms and irritation at injection site (SC or IM)

Advised following 2 serious relapses in 1 year or 1 seriously debilitating relapse

Not effective in PPMS or SPMS

Stopped before pregnancy and in breastfeeding

Question 25

MS generally in pregnancy

Answer 25

Relapses decreased in pregnancy, especially 3rd trimester but increases first 3 months after birth

Question 26

Symptomatic treatment for bladder dysfunction in MS

Answer 26

Anticholinergics - oxybutynin - used to treat bladder dysfunction and urinary symptoms

Question 27

Life expectancy of MS

Answer 27

Reduced by 7 years average

5% have aggressive disease and die within 5 years

Question 28

Symptomatic treatment for spasticity in MS

Answer 28

Baclofen - GABA agonist
Diazepam - Benzodiazepine
Dantrolene - Post-synaptic muscle relaxant - decreases calcium release from ER
Tizanidine - A2 adrenergic agonist

Question 29

Symptomatic treatment for cerebellar intention tremor

Answer 29

Treat with clonazepam - benzodiazepine

Question 30

Treatment of acute MS relapses

Answer 30

Short treatment of steroids - methylprednisolone for 3days

Question 31

Treatment of aggressive MS

Answer 31

Immunomodulatory treatments
Natalizumab (also used in crohns)
Alemtuzumab (also used in lymphoma and leukaemia), Fingolimod (sequesters lymphocytes in lymph nodes)

Question 32

What is Behcets disease?

Answer 32

Relapsing remitting CNS disease

Rare immune-mediated small-vessel systemic vasculitis - often presents with mucous membrane ulceration and ocular problems

Question 33

What is transverse myelitis? What could cause it other than MS?

Answer 33

Inflammation of the spinal cord with weakness and sensory symptoms below the lesion - also autonomic, reflex and sphincter function affected

Could be due to spinal cord compression eg. prolapsed disc or brainstem lesion (if CN involvement)

Question 34

What is syringomyelia?

Answer 34

Cyst (syrinx) formation in spinal cord which expands
Usually gradually progressive and presents with signs of a central lesion in the spinal cord

Causes wasting and weakness of the hands, loss of arm reflexes
And pain and temp sensory loss in cervical dermatomes but not light touch or position sense (due to temp and pain decussating and light touch and position sense being in posterior columns)

Question 35

DDX of MS x7

Answer 35

1) Behcets disease
2) CNS sarcoid
3) SLE (antinuclear factor will be present)
4) Transverse myelitis from compression
5) Brown Sequard syndrome - purely unilateral and not involving face (hemiplegia)
6) Vitamin B12 deficiency (can cause optic neuropathy and myelopathy but more slowly progressive, no remission)
7) Syringomyelia but preservation of light touch and joint position sense and gradually progressive