Multiple Sclerosis

Question 1

What is multiple sclerosis?

Answer 1

Autoimmune disease - idiopathic

CNS demyelination causing plaque formation in the brain and spinal cord

Question 2

How do plaques in multiple sclerosis look?

Answer 2

Areas of myelin loss in the CNS with infiltration of lymphocytes and mø

Question 3

Epidemiology of multiple sclerosis

Answer 3

100-150 per 100,000

7 incidences per 100,000 in the UK each year

20-40 year olds

M:F 2:1

Rare near equator - role of vitamin D is the hypothesis

Question 4

Aetiology of multiple sclerosis

Answer 4

T-cell mediated immune response

Trigger: multifactorial, genes, environment

Question 5

MS pathophysiology

Answer 5

Unknown tirgger allows T-cells through blood brain barrier

T-cells primed against myelin attack the myelin and oligodendrocytes

3 processes:

1. Demyelination: destruction of sheath and oligodendrocytes (the cells that produce myelin sheath in the CNS)
2. Acute inflammation and demyelination
3. Incomplete healing and plaque formation

Question 6

What are oligodendrocytes?

Answer 6

Large glial cells in the CNS that make myelin sheath

Question 7

Discuss the healing and progressive stages of MS

Answer 7

Healing: demyelination occurs and neurones try to repair but this is an incomplete process and plaques form

Progressive: eventually poor healing leads to progressive neurological dysfunction without remission

Question 8

Clinical features of MS

Answer 8

Visual, motor, sensory and autonomic signs dominate

45%: motor symptoms + sensory symptoms

20%: spasticity (increased muscle tone)

10%: brain stem dysfunction e.g. double vision

25% have a combination of the above

Memory loss

Depends on site of lesion e.g. if optic nerve affected: visual loss, frontal lobes affected: disinhibition

Question 9

Eponymous signs in MS

Answer 9

Lhermitte’s sign: neck flexion = tingling down spine

Uhthoff’s phenomenon: symptoms get worse when body temp changes e.g. loss of vision when exercising

Question 10

Discuss MS relapses

Answer 10

• Occur without warning but stress and infection increase likelihood

Question 11

What is a state that decreases MS relapses?

Answer 11

Pregnancy - although relapse risk increases following

Question 12

What are the 4 clinical patterns of MS

Answer 12

1. Relapsing remitting
2. Primary progressive
3. Secondary progressive
4. Progressive relapsing

Question 13

Relapsing remitting MS

Answer 13

Most common type: 85%

As disease progressive there is less recovery

Question 14

Primary progressive MS

Answer 14

10-15%

Average onset = 40yrs

More common in men

SDisability progressive from onset with no remission

Question 15

Secondary progressive MS

Answer 15

Starts off as relapsing-remitting but then becomes progressive with no remission

Occurs in 50-60% after around 10-15yrs

Question 16

Progressive relapsing MS

Answer 16

Most rare form, pattern is no remission - instead of remission patients have period where the condition gets rapidly worse

Question 17

What is clinically isolated syndrome?

Answer 17

CIS = first incidence of neurological symptoms that last for >24hrs and isnt causes by anything that can be explained e.g. fever/ infection

CIS can be the first sign of MS - although at this time it is not diagnosed

MRI scan may show lesions in brain/ spinal cord similar to those in MS and this makes changes of further episodes and a diagnosis of MS more likely

Not diagnosed as MS at that stage because MS requires 2 isolated incidents showing demyelination (unless evidence of a previous attack on MRI)

• At this stage patients may be given disease modifying drugs

Question 18

Which imaging modality is used to support a diagnosis of MS?

Answer 18

MRI - lesions look like smudges

Shows contrast-enhancing lesions in the white matter especially around the ventricles, brainstem and cerebellar peduncles

Question 19

How is MS diagnosed?

Answer 19

Usually a clinical diagnosis

Supported by neuro imaging and CSF analysis

Conduction velocity studies can support the diagnosis

Question 20

Discuss CSF analysis in MS

Answer 20

Presence of oligoclonal bands of IgG in the CSF because B cells in the CNS make more IgG

If a patient has unpaired oligoclonal bands in the CSF (and not in the blood) think MS

Question 21

Is there a cure for MS?

Answer 21

No - treatment aims to limit relapses and improve function while controlling symptoms

Question 22

How are acute relapses of MS managed?

Answer 22

3 day course of oral/ IV methylprednisolone

Reduces symptoms + speeds recovery

Doesn’t impact relapse rate or long-term disability

Question 23

Disease modifying drugs in MS

Answer 23

Used to reduce rate of relapse

- All apart from beta interferon are only used for relapsing-remitting MS

Natalizumab = most widely used

Question 24

Natalizumab

Answer 24

Used to reduce relapse rate in relapsing-remitting MS

Blocks migration of WBCs through BBB

Given IV every month

Question 25

Beta-interferon

Answer 25

*Not available as a new prescription in the UK as of 2018 as too expensive*

Reduces WBCs crossig BBB, enhances T-cell apoptosis

Question 26

Symptom control in MS

Answer 26

Spasticity: baclofen, gabapentin, botox injections

Fatigue: modafanil

Bladder dysfunction: anticholinergics e.g. oxybutynin, botox injections in bladder, self-catheterisation

Depression: SSRIs, sounselling

Question 27

Average life expectancy in MS

Answer 27

5-10 years less than normal population

Worse prognosis for those with progressive types, males and those of older age

The condition itself is not a cause of death but its complications can be e.g. dysphagia - aspiration pneumonia