Migraine Flashcards
What are primary headaches and give examples
- Headaches not caused by another medical condition
- Examples:
Migraine, Cluster Headache, Tension Type Headache, Other primary headaches
Who do migraines most commonly affect?
More common in women
Most productive years: 18 to 55 years
What do migraines with aura present with
Additional visual or sensory disturbances
What do migraines without aura present with
Most common
More debilitating
Higher attack frequency
What is the diagnostic criteria for a migraine
- At least FIVE headache attacks lasting between 4-72 hours (untreated or unsuccessfully treated)
2. Headache must have TWO of following: Unilateral Location: one position Pulsating quality Moderate or severe pain intensity Aggravation by or causing avoidance of routine physical activity
- During headache: one of the following:
Nausea and/or vomiting
Photophobia and phonophobia
What is diagnostic criteria: migraine with aura? (10)
- At least TWO headache attacks lasting between 4-72 hours
- Patients must have no motor weakness and have aura consisting of:
Fully reversible visual symptoms including positive features e.g. flickering lights, spots or lines
Fully reversible sensory symptoms including negative features e.g. loss of vision
Fully reversible sensory symptoms including positive features e.g. pins and needles
Fully reversible sensory symptoms including negative features e.g. numbness
Fully reversible dysphasic speech disturbance
Two of the following:
1. Visual symptoms and/or unilateral symptoms
- At least one aura symptom develops gradually over >5 minutes and/or different aura
- Each symptom lasting more than or equal to 5 and or less than or equal to 60
Migraine without aura can then follow
If a migraine starts, how can you rule out it is not a stroke
Status Migrainous: attack lasts more than 72 hours
Migrainous Infarction: aura lasts more than 1 hour
Persistant aura without infarction: aura lasts more than 1 week
Migraine aura triggers seizure
What is the migraine pathophysiology
Complex genetic disorder, likely a polygenic multifactorial inheritance
Present understanding from familial hemiplegic migraine (FHM): a rare monogenic, autosomal dominant form of migraine with aura
Three genes: ion channels, transporters
What is the current migraine theory
- Neurovascular disease
- Activation and sensitisation in the Trigeminovascular pain pathway: controls nerves in mouth and face
- Innervates cranial tissues: particularly meninges and large blood vessels
- Cortical spreading depression: neurophysical correlate of migraine aura: slowly propagating wave of strong neuronal and glial depolarisation
Describe the trigeminovascular pain pathway
An afferent pathway:
Dura and pia mater in cerebral cortex
Trigemina ganglion
Trigeminal nucleus caudal
Medulla
Hypothalamus, thalamus, hippocampus, corpus, cortex
What is familial hemiplegic migraine type 1
Mutation of neuronal Cav2.1 channels
Multiple mutations identified- gain a function increased open probability
Shifted activation to more negative voltages
What are the common prescriptions used for migraineurs
Hypertension
Beta blocker
Calcium Channel Blocker
Pain
Narcotic analgesics: codeine
Antidepressants TCA Monoamine oxidase inhibitor SSRIs SNRIs
Anti wrinkle
Botox
MIGRAINE
TRIPTANS
What is the main molecular mediator of a migraine and what did it lead to discover
- 5-HT: pathophysiology of migraine as levels decrease during attacks
- Slow IV of 5-HT can abort migraine
- Led to triptans discovered, 5-HT 1D/B/F receptor agonists like sumatriptan (1st gen), zolmitriptan, rizatriptan (2nd gen)
- Provides relief of migraines
What are the mechanism of actions of 5-HT 1B/D or F receptor agonists like triptans
Constriction of cranial arteries
Inhibitory actions on the CNS
Inhibition of presynaptic TG neurons (includes 5-HT1BDF)
What is contraindicated in triptans and what can overuse lead to
- Contraindicated: coronary or cardiovascular disease, hypertension, pregnant women
- Overuse: severe rebound attacks and headache
What are the acute treatments for a migraine
Simple analgesic: paracetamol and aspirin
Anti-emetics: metoclopramide
Ergots: partial agonists for 5-HT: Ergotamine and dihydroergotamine
Opioid: codeine: last resort if triptans inefficient
When are prophylactic treatments for a migraine used and give examples of some (9)
- Patients suffering 4+ actions a month
- beta blockers: metoprolol or propranolol
- TCA: Amitriptyline and Nortriptylline: prevents reuptake of 5-HT and antagonist of 5-HT2 receptors
- Anti-convulsant: Sodium valproate, gabapentin
- NSAIDS: Naproxen
- Calcium channel blockers: verapamil
- Anti-serotonergic drugs: Pizotifen: antagonist of 5-HT receptors
- Methysergide: semi synthetic ergot alkaloid, administed under hospital supervision due to side effects
- Botulinum toxin A: licensed for treatment of chronic migraine: relaxes muscles and inhibits release of peripheral nociceptive neurotransmitters: CGRP
What is the calcitonin gene related peptide and why is it important in migraine attacks
CGRP: alternative processing of calcitonin gene
Potent vasodilator: involved in neurogenic inflammation and nociception
Migraine attacks: Increased CGRP in serum and saliva
Injection of CGRP into migraineurs leads to delayed migraine like headaches
What makes up the CGRP receptor and what does it lead to
CLR (calcitonin receptor like receptor)
RAMP (Receptor activity modifying protein 1)
Angiogenesis, Proliferation, vasodilation
What are used to target CGRP receptors
Gepants: CGRP receptor antagonists
Example of first clinical trial: Oicegepant
Example of phase III clinical trial: Telcagepant
used to target episodic and chronic migraine through injection
What are additional migraine treatment targets
gap junction blockers: tonaberset
Angiotensin II receptor antagonists: candesartan
TRPV1: transient receptor potential channel vanillin 1 antagonists
