Migraine and its Treatment

Question 1

Migraine attack profile

Answer 1

headache lasts 4-6hrs for diagnosis
premonitary symptoms - 2/3 days prior, tiredness, fatigue,photophobic (bright lights misprocessed)
aura (visual flashing lights/tunnel vision)
building headache phase
postdrome syndrome (3/4 days after attack-washed out)

Question 2

evolving theories of migraine

Answer 2

previously thought to be vascular (due to vasodilation) now expected to be a neurovascular disorder (because dilation in MCA/ICAcerebral/ICAcavernous, not in the ECA/STA/MMA/ICAcervical and no association between throbbing pain and arterial output)

Question 3

Areas affected

Answer 3

abnormally activated prior to pain (headache) hypothalamus (balances homeostasis) and BS-PAG involved in pain processing
during premonitary phase - linked to symptoms

Question 4

disorder of sensory processing

Answer 4

meninges synapse in spinal cord
cranial parasympathetic outflow (common in cluster headaches) causes rebound activation and cranial autonomic features (teething/lacrimation/blocked nose)
processed in hypothalamus - thalamus - cortex

Question 5

gain of sensory function

Answer 5

photophobia
phonophobia (noise)
nausea
osmophobia (smell)
pain and allodynia

(nerves sit below threshold for activation, smaller stimuli activate nerves to reach threshold, sensitised nerves respond to smaller stimuli)

Question 6

pharmacological migraine therapy

Answer 6

preventative - prophylatic (3-4 attacks/month) >3 months to see results - use beta blockers
single attack - acute (treatment of individual attack)

Question 7

neuromodulation

Answer 7

transcranial magnetic stimulation - device for aura (not effective)
greater occipital nerve stimulation (blocks nerve) - TENS
vagus nerve stimulation (reduces sensory input/input sagging) - works in cluster headache

Question 8

acute (non-specific) migraine therapy

Answer 8

aspirin/paracetamol - mild
opioids - crisis
combinations
NSAIDS: naproxen (long half life)/ibuprofen/tolfenamic acid

Question 9

specific acute migraine therapy

Answer 9

dihydroergotamine (strong vasoconstrictor-stops blow flow to fingers (necrotic))
triptans: sumatriptan/almotriptan/eletriptan

Question 10

preventative amine modulation

Answer 10

5HT2 (pizotifen)
beta blockers: propranolol, atenolol, metoprolol
tricyclics: amitriptyline

Question 11

preventative channel modulation

Answer 11

topiramate:Na/K channels, GABAa/AMPA/Kainate receptors - 2-3x risk of birth defects (used in birth control/epilepsy)
valproate: Na channels

Question 12

preventative monoclonal antibodies

Answer 12

targets CGRP or its receptor

Question 13

other preventatives

Answer 13

flunarizine: CaV/H1R
botulinum toxin (available on the NHS-8/10 attacks are chronic migraines) - cleaves SNAP/SNARE, prevents NT release-relaxes muscle
melatonin (sleep stabilisation)

Question 14

triptans

Answer 14

5HT R agonists
5HT1D/1B sometimes 5HTIF subunit
increased 5-hydroxyindoleacetic acid/decreased 5-ht platelet levels/IV 5-HT could abort migraine
effective when pain is mild - works in thalamus/periphery/trigeminal cervical complex (20-40% patients report 2hr pain free)

Question 15

5HT expression

Answer 15

1B = vasoconstrictive (located on blood vessels)
1D = on peripheral neurons
central neurons (C1) contains: 5HT1B/1D/1F
triptans prevents CGRP release at 1B/1D not vasoconstrictive variable BBB penetrations- act centrally and periphery
7 claases (5HT1-7)

Question 16

limitations of triptans

Answer 16

contraindicated in ischaemic heart disease/stroke - vasoconstrictive
30% effect
variable CNS permeability
expensive
less effective when pain>mild
less effective in females (phase I mostly in males with lower BMI/no pregnant women - more rebound headache/more dosing)

Question 17

medication overuse headache

Answer 17

> 15 days a month of headache (8 migraines) and overuse of acute medication for >3 months
triptans - 10days/month
NSAIDS - 15days/month
resolved once medication is withdrawn/ increased risk of relapse

Question 18

Rat sensory testing in paws

(De Felice et al., 2009)

Answer 18

excess sumotriptan = hypersensitive to stimuli

Question 19

What is the effect of Triptan overuse?

Answer 19

increases CGRP in nerves (constantly blocking release despite CGRP production)

Question 20

botox for chronic headaches

Answer 20

injection sites: forehead/trapezoid (no NMJ activation)
SNAP/SNARE bind to vesicles

Question 21

Greater occipital nerve (GON)

Answer 21

give steroid/anaesthesia injection = dampens pain
give stimulation = no effect