Mirgraine

Question 1

Explain the features of a primary headache, and 3 examples.

Answer 1

Something has gone wrong in the brain circulatory.
Migraine
Tension type
Cluster

Question 2

Give 3 examples of secondary headaches.

Answer 2

Tumour
Meningitis - build up of fluid on the brain
Giant cell artheritis

Question 3

Describe a migraine.

Answer 3

Common and debilitating neurovascular disease.

Attacks of severe headaches and autonomic dysfunction.

Question 4

What is a common migraine?

Answer 4

Migraine without aura.

Question 5

What is a classic migraine?

Answer 5

Migraine with aura.

Question 6

What criteria classify a migraine?

Answer 6

5 or more attacks lasting 4-72 hours.
>2 of the following - unilateral, pulsating, moderate/severe intensity, aggregated by routine physical activity.
1 or more of…nausea/vomiting, photophobia/phonophobia.

Question 7

Give some epidemiological facts about migraine.

Answer 7

11% of USA and Europe suffer an attack in a year.
More men than women.
Peaks in early-mid adolescence.

Question 8

Is the brain completely insensitive?

Answer 8

Yes - except for the meninges…
Dura mater, arachnoid mater and pia mater which are densely innervated and receive blood from the middle cerebral and middle meningial arteries.

Question 9

What 4 areas are involved in migraine?

Answer 9

Blood vessels, trigeminal nerve, dorsal raphe nucleus and locus coeruleus.

Question 10

Describe the aura experienced before a migraine.

Answer 10

A wave of oligema (poor blood supply), a response to depressed neuronal function, passes over the cortex (2-6mm/minute).
Stays until the migraine starts.

Question 11

What is CSD?

Answer 11

Cortical spreading depression - increase K+ and NTs…transient increase in cortical blood flow followed by sustained decrease.

Question 12

Explain the pain associated with a migraine.

Answer 12

Not completely understood.
Migraine involves the dysfunction of the brain stem that normally modulates sensory inputs from the trigeminal ganglion.

3 key factors:
Cranial BVs in dura
Trigeminal sensory nerve innervation of those BVs
Trigeminal links with brainstem, transmits and modulates info to the cortex and via autonomic reflex back to dura!

Question 13

What roles do the sensory nerves play?

Answer 13

C (unmyelinated) and Adelta (myelinated)

• transmit sensory information to the CNS - initiate reflex
• release neuropeptide…Calcitonin gene related peptide. (CGRP)

Question 14

What effects does release CGRP have on arterioles?

Answer 14

Vasodilation.

Question 15

What effect does substance P have on venules?

Answer 15

Causes plama extravastion - oedema.

BUT NK1 receptor antagonists are not useful in the treatment of migraine.

Question 16

What role does 5HT play in migraine?

Answer 16

Increase 5HT metabolite excreted in urine in migraine.
Platelet 5HT rapidly drops at migraine onset.
i.v. 5HT can abort migraine.

Question 17

What non-pharmacological treatments are there for migraine?

Answer 17

Avoid triggers - mutation in VOCC?
Avoid light noise trigger.]
Avoid dietary triggers…
-tyramine in cheese (vasoconstrictor effect…if MAO inhibited)
-Chocolate (phenyltheylamine - amine metabolised by MAO) (theobromine and caffiene - may alter cerebral blood flow and release of NA).

Caffeine - the abrupt withdrawal of caffeine leads to headaches and may exacerbate the migraine.

Question 18

Name 5 preventative medicines for migraine.

Answer 18

Anticonvulsants; gabapentin
Antidepressants; TCAs, SSRIs, MAOIs
Calcium channel antagonists; verapamil
Seretonin antagonists; methysergide
Beta blockers; propanolol.

Question 19

How would you treat an acute migraine attack?

Answer 19

As soon as migraine is indicated (by aura)…
-NSAIDs/COX inhibitors…aspirin, ibuprofen etc
- and an anti-emetic for absorption.
Ergot derivative - dihyroergotamine (vasoconstrictor).

Question 20

Explain the rationale behind triptan use.

Answer 20

‘atypical’ 5HT receptor - 5HT1B/D…found in cerebral circulation and coronary BVs. AGONST.
Moderate side effects - dont use in CV disease.

COSTLY.

Question 21

Name 3 potential antimigraine mechanisms.

Answer 21

Cranial vasoconstriction.
Peripheral neuronal inhibition
Inhibition of nerve transmission in trigeminal cervial complex

Question 22

Sumatriptan?

Answer 22

Effective, short acting, expensive

Associated with recurrence.

Question 23

Naratriptan?

Answer 23

Longer half life than sumatriptan…better oral availability.

Question 24

CGRP antagonists?

Answer 24

effective in advanced clinical trials. NOT USED - liver adverse effects

Act postsynaptically - CGRP effect (vasodilation) is blocked on BV.

Question 25

Botox for migraine?

Answer 25

Reduce pain.
Smooth muscle relaxant.
Approved for chronic migraine.