Multiple Sclerosis

Question 0

MRI contrast agent to detect DIT?

Answer 0

Gadolinium

Question 1

First line treatments?

Answer 1

Interferon beta

Glatiramer acetate

Question 2

Acute relapse management?

Answer 2

3-5 day course of high-rose intravenous corticosteroids (e.g. Prednisolone)

Immunosuppressive effect that shortens relapses and provides symptomatic relief.

Does not improve long-term outcome.

Question 3

Interferon Beta

Answer 3

Cytokines that influence immune response.

Mechanism of action not certain, but interferons are known to have immune modulating and anti-inflammatory properties.

Neuroimaging studies show that they reduce inflammatory CNS lesions by more than 50%.

Flu-like symptoms for 24-48 hours after injection.
Long-term risk of liver function abnormalities and immunosuppression.

Not recommended for pregnancy.

2 forms: 1a (Intramuscular and subcutaneous, x3 week, weekly, fortnightly); 1b (subcutaneous, alt days)

Question 4

Glatiramer acetate

Answer 4

Synthetic mixture of polypeptides contains four amino acids that are present in myelin basic protein (glutamic acid, alanine, tyrosine, lysine).

Daily subcutaneous injection.

Intended to mimic mbp but actual mechanism of action is it certain. Promotes secretion of anti-inflammatory cytokines.

Usually no side effects. Not recommended for children or pregnancy.

Question 5

Natalizumab

Answer 5

Monoclonal antibody (IgG).

Recognises an adhesion molecule called a4 integrin which binds to vascular cell adhesion molecule (VCAM-1) on endothelial cells. Designed to prevent leukocyte from binding to blood vessels, reducing number entering the CNS from the bloodstream.

Intravenous injection every 28 days.

Trials show two-thirds reduction in relapses.

Side effects: headache, nausea, vomiting. Rare association with Progressive Multifocal Leukoencephalopathy.

Question 6

Progressive Multifocal Leukoencephalopathy

Answer 6

White matter disease.

Opportunistic infection caused by deactivation of a papovavirus that infects oligodendrocytes. Infectious agent is called JV virus.

High mortality rate. Survivors generally left with severe neurological disabilities.

Question 7

Fingolimod

Answer 7

First oral agent licensed.

Trials show reduction of relapses by ~50%.

Inhibition of sphingosine 1-phosphate receptors which blocks lymphocyte migration from lymph nodes.

Potential serious side effects: bradycardia, immunosuppression, liver toxicity and allergic reactions.

Only used in RRMS, particularly those not responding to first-line.

Question 8

Unlicensed drugs

Answer 8

Mitoxantrone