Multiple sclerosis

Question 1

What is it

Answer 1

Progressive autoimmune demyelination of CNS neurons

Question 2

Classification of profression os MS

Answer 2

Relapsing remitting
Primary progressive
Secondary progressive
Benign

Question 3

*Causes

Answer 3

Factors thought to contribute:

• type IV T-cell mediated immune response
• viruses may play a role
• smoking is a risk factor

Question 4

Epidemiology

Answer 4

Those who live further down from the equator and Sardinians are at greater risk than other populations

Question 5

Give example of virus that could play a role

Answer 5

Epstein-Barr virus

Question 6

Pathophysiology

Answer 6

Plaques of demyelination, disseminated in time and space, interfere with neuronal transmission
Often patients enter remission but then relapse. This is because the demyelinated neurons do not heal fully

Question 7

Signs and symptoms

Answer 7

Usually monosymptomatic
Symptoms relate to the location where plaques of demyelination occur - remember these as DOTS:
Diplopia, Dysaesthesia
Optic neuritis
Trigeminal neuralgia, Trunk and limb ataxia (diplopia)
Sense of vibration decreased
Uhthoffs phenomenon

Question 8

What is Uhthoffs phenomenon

Answer 8

Symptoms worsen in hot conditions

Question 9

Investigations

Answer 9

LP - some proteins are altered in MS e.g. oligoclonal bands

MRI scan - shows regions affected byinflammation and scarring e.g. Dawson’s fingers

Question 10

Treatment - conservative

Answer 10

Patient education

Use diagnostic McDonald criteria and regulary assess ADLs as well as psychosocial impact of disease

Question 11

Treatment - medical

Answer 11

Interferon
Corticosteroid - Methylprednisolone
Immunomodulator - Glatiramer acetate
Natalizumab or Alemtuzumab - Monoclonal antibodies

Others:
Azathioprine - purine analogue (immunosuppressant)
Mitoxantrone - doxorubicin analogue

Question 12

Complications

Answer 12

Bowel incontinence
Urinary incontinence
Depression
Epilepsy
Paralysis

Question 13

More detailed pathophysiology

Answer 13

Autoimmune mediated demyelination at multiple CNS (oligodendrocytes targetted) sites, resulting in discrete plaques of demyelination
Affects white matter of brain.
T-cell mediated in that T-cells activate B-cells to produce autoantibodies against myelin.
T lymphocytes can cross BBB to cause a cascade of destruction to neuronal cells in brain.
Results in demyelination and destruction of conduction along axons
New myelin is less efficient and temperature dependent (high temp decreases conduction).

Question 14

Diagnosis

Answer 14

Requires at least 2 attacks affecting different parts of CNS

Question 15

What cells are targeted in MS

Answer 15

Oligodendrocytes

Question 16

Which distinct CNS sites have a predilection for demyelination by MS

Answer 16

Optic nerves
Around ventricles of brain
Corpus callosum
Brainstem and cerebellar connections
Cervical cord (corticospinal tract and dorsal column)

Question 17

Types of MS

Answer 17

Relapsing and remitting (80%)
Secondary progressive
Primary progressive

Question 18

Relapsing and remitting type of MS

Answer 18

Most common MS pattern
symptoms occur in attacks (relapses) with onset over days
recovery over weeks
patients can accumulate disability over time if they do not recover fully
periods of good health or remission are followed by sudden symptoms or relapses

Question 19

Secondary progressive type of MS

Answer 19

Follows on from relapsing and remitting MS

Late stage MS that consists of gradually worsening symptoms with fewer remissions

Question 20

Primary progressive type of MS

Answer 20

Gradually worsening disability WITHOUT relapses or remissions
Typically presents later and is associated with fewer inflammatory changes on MRI

Question 21

Describe the new myelin made

Answer 21

Temperature dependent (hotter temp decreases effectiveness) and less efficient