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Migraine HeadachesMigraine Headaches
Jim Ducharme MD CM FRCPJim Ducharme MD CM FRCP
Professor, Emergency MedicineProfessor, Emergency Medicine
Dalhousie UniversityDalhousie University
A 34 year-old woman arrives with 24 hours of A 34 year-old woman arrives with 24 hours of pulsating frontal headache. She has vomited twice, pulsating frontal headache. She has vomited twice, and wants the lights off.and wants the lights off.
What questions do you want answered?
Previous headache historyPrevious headache history Onset of headacheOnset of headache Analgesic useAnalgesic use Any identified triggerAny identified trigger Allergies/Medication intoleranceAllergies/Medication intolerance
Risk factors suggesting a serious Risk factors suggesting a serious underlying cause of headacheunderlying cause of headache
First or worst headache, especially if abrupt First or worst headache, especially if abrupt onsetonset
Change in pattern of normal headachesChange in pattern of normal headaches New progressive persistent headacheNew progressive persistent headache
CMAJ 1997CMAJ 1997
Risk factors suggesting a serious Risk factors suggesting a serious underlying cause of headacheunderlying cause of headache
Headache brought on by ValsalvaHeadache brought on by Valsalva Accompanying systemic symptoms:Accompanying systemic symptoms:
– myalgia, fever, malaise, weight loss, jaw myalgia, fever, malaise, weight loss, jaw claudication, tender scalpclaudication, tender scalp
Focal neurological signs or symptomsFocal neurological signs or symptoms Altered mental statusAltered mental status
CMAJ 1997CMAJ 1997
How do you decide this is a migraine andHow do you decide this is a migraine anddoes it matter?does it matter?
I.H.S. Diagnostic CriteriaI.H.S. Diagnostic Criteria
Migraine without auraMigraine without aura– > 5 episodes> 5 episodes– Duration 4-72 hoursDuration 4-72 hours– 2/4 of: increase with activity, moderate to 2/4 of: increase with activity, moderate to
severe intensity, pulsatile at some point, visual severe intensity, pulsatile at some point, visual complaintscomplaints
– 1 of 2 of: photo/phonophobia, nausea/vomiting1 of 2 of: photo/phonophobia, nausea/vomiting– Normal examNormal exam
Her physical exam is normal other than her obviousHer physical exam is normal other than her obviouspain. You would like to treat her headache. What pain. You would like to treat her headache. What therapeutic endpoints do you establish before starting:therapeutic endpoints do you establish before starting:
• complete headache abolition?complete headache abolition?• reduction of her headache to a mild level?reduction of her headache to a mild level?• avoidance of significant adverse effects?avoidance of significant adverse effects?• avoidance of headache recurrence?avoidance of headache recurrence?
PathophysiologyPathophysiology
AuraAura– Spreading cortical depression, not ischemiaSpreading cortical depression, not ischemia
BrainstemBrainstem– Migraine “generator” in dorsal raphe, locus Migraine “generator” in dorsal raphe, locus
ceruleus and periaqueductal gray matterceruleus and periaqueductal gray matter– PET scans show increased blood flow, even PET scans show increased blood flow, even
after cessation of headacheafter cessation of headache
PathophysiologyPathophysiology
Genetic predispositionGenetic predisposition– Deficient habituation during repetitive Deficient habituation during repetitive
stimulationstimulation– Allows for surpassing or modification of Allows for surpassing or modification of
threshold for migrainethreshold for migraine External: prophylaxis, psychosocialExternal: prophylaxis, psychosocial Internal: estrogen, stress response, foodsInternal: estrogen, stress response, foods
PathophysiologyPathophysiology
Threshold surpassed:Threshold surpassed:– Brainstem “generator” liberates CGRPBrainstem “generator” liberates CGRP– Activation of trigeminovascular systemActivation of trigeminovascular system
CGRP also elevated with pulsating chronic CGRP also elevated with pulsating chronic tension-type headachestension-type headaches
PathophysiologyPathophysiology
Nitric oxideNitric oxide– VasodilatorVasodilator– Promotes central sensitization of trigeminal Promotes central sensitization of trigeminal
nociceptorsnociceptors– Sumatriptan decreases NO release in addition Sumatriptan decreases NO release in addition
to inhibiting CGRP releaseto inhibiting CGRP release
PathophysiologyPathophysiology
Trigeminal StimulationTrigeminal Stimulation– Ca channel activation: substance P releaseCa channel activation: substance P release– Feedback to DRG: NMDA & AMPA release, Feedback to DRG: NMDA & AMPA release,
leading to wind upleading to wind up– Release of prostaglandins, kinins that induce Release of prostaglandins, kinins that induce
perivascular inflammationperivascular inflammation– NO and CGRP further capillary leakageNO and CGRP further capillary leakage
PathophysiologyPathophysiology
Potentials for future abortive treatment:Potentials for future abortive treatment:– Antagonists of: CGRP, NO, GlutamateAntagonists of: CGRP, NO, Glutamate– Agonists of adenosine A1 receptorsAgonists of adenosine A1 receptors
Yeah, yeah and the moon is actually made ofYeah, yeah and the moon is actually made ofGruyGruyère not Emmental….. My patient still hasère not Emmental….. My patient still hasher headache, so what do I give herher headache, so what do I give her??
Effective Abortive AgentsEffective Abortive Agents
TriptansTriptans DihydroergotamineDihydroergotamine NSAIDsNSAIDs Anti-emeticsAnti-emetics Lidocaine?Lidocaine? Opioids?Opioids?
TriptansTriptans
5-HT5-HT1B 1B action: vasoconstriction by acting action: vasoconstriction by acting
against NOagainst NO 5-HT5-HT1D1D action: inhibit CGRP release action: inhibit CGRP release
Should be very effective, yet only 70-80% Should be very effective, yet only 70-80% effective, with 50% headache recurrence.effective, with 50% headache recurrence.– Cardiac risk, side effects further limit useCardiac risk, side effects further limit use
TriptansTriptans
PO versions require 60-90 minutes to effectPO versions require 60-90 minutes to effect 50% success rate PO vs. 75-80% s/c50% success rate PO vs. 75-80% s/c Newer triptans offer no real advantage over Newer triptans offer no real advantage over
originaloriginal Subset of patients do respond well to this Subset of patients do respond well to this
abortive agent in home settingabortive agent in home setting
DihydroergotamineDihydroergotamine
Same 5-HT action, but slower bindingSame 5-HT action, but slower binding– Impact of IM may require 2 hoursImpact of IM may require 2 hours– Nasal version requires up to 4 hoursNasal version requires up to 4 hours
If given IV may initially increase CGRP release, If given IV may initially increase CGRP release, producing dramatic headache increaseproducing dramatic headache increase
Does not increase N&VDoes not increase N&V Most initial research success probably due to Most initial research success probably due to
adjunctive anti-emeticsadjunctive anti-emetics
NSAIDsNSAIDs
Excellent for mild to moderate migrainesExcellent for mild to moderate migraines No effect on neurotransmittersNo effect on neurotransmitters Direct inhibition of most perivascular Direct inhibition of most perivascular
inflammationinflammation Ketorolac at best 50-60% success as Ketorolac at best 50-60% success as
abortive for severe migrainesabortive for severe migraines
Dopamine AntagonistsDopamine Antagonists
PhenothiazinesPhenothiazines ButyrophenonesButyrophenones MetoclopramideMetoclopramide
Dopamine AntagonistsDopamine Antagonists
High adverse event rateHigh adverse event rate– Need to treat prophylactically: benztropine, Need to treat prophylactically: benztropine,
lorazepam, diphenhydraminelorazepam, diphenhydramine Low headache recurrence rateLow headache recurrence rate Only droperidol as effective IM as IVOnly droperidol as effective IM as IV Dysphoria cannot be treated, found to be Dysphoria cannot be treated, found to be
horrible by some patientshorrible by some patients
LidocaineLidocaine
Intranasal lidocaine found effective in two Intranasal lidocaine found effective in two studies, but of very short duration, 70% studies, but of very short duration, 70% headache recurrenceheadache recurrence
Mechanism of action uncertain as blocks Mechanism of action uncertain as blocks Na+ channels not Ca++ onesNa+ channels not Ca++ ones
OpioidsOpioids
At best 50% effective, high recurrence rateAt best 50% effective, high recurrence rate Often required in combination for complex Often required in combination for complex
casescases Biggest effect: allows patient to enter REM Biggest effect: allows patient to enter REM
sleep, which shuts down dorsal raphe sleep, which shuts down dorsal raphe activityactivity
So back to that lady: what are you going to give her?So back to that lady: what are you going to give her?What should be your first choice?What should be your first choice?
1)1) Prochlorperazine 5 mg IV plus 1 mg benztropineProchlorperazine 5 mg IV plus 1 mg benztropine
2)2) Droperidol 2.5 mg IM or IV plus benztropineDroperidol 2.5 mg IM or IV plus benztropine
3)3) Sumatriptan 6 mg s/cSumatriptan 6 mg s/c
Analgesia-induced rebound Analgesia-induced rebound headachesheadaches Obtain good headache medication historyObtain good headache medication history May occur with simple analgesics or with opioidsMay occur with simple analgesics or with opioids If cessation of medication may take 3 months to If cessation of medication may take 3 months to
return to baseline headache frequencyreturn to baseline headache frequency DHE IV q8h x 2-3 days resolves problemDHE IV q8h x 2-3 days resolves problem
Migraine: headache recurrenceMigraine: headache recurrence
First identified 1989First identified 1989 As high as 50-60% at 24 hours in some As high as 50-60% at 24 hours in some
trialstrials Often as debilitating as original headacheOften as debilitating as original headache Need to distinguish from analgesia rebound Need to distinguish from analgesia rebound
headacheheadache
Preventing recurrencePreventing recurrence
Innes et alInnes et al: dexamethasone IV: dexamethasone IV Ducharme et alDucharme et al: complete elimination of : complete elimination of
pain before dischargepain before discharge Choice of abortive agentChoice of abortive agent
– serotonin agonists have highest recurrence rateserotonin agonists have highest recurrence rate
Preventing Future HeadachesPreventing Future Headaches
Headache diary: identifying triggersHeadache diary: identifying triggers ProphylaxisProphylaxis
– DietDiet– ExerciseExercise– SleepSleep– Stress modificationStress modification
Preventing Future HeadachesPreventing Future Headaches
Medications:Medications:– Valproate: 45% patients more than placebo Valproate: 45% patients more than placebo
with 50% decrease in headache ratewith 50% decrease in headache rate– Beta Blockers: 40%Beta Blockers: 40%– Flunarazine: 42%Flunarazine: 42%– Pizotifen: 20%Pizotifen: 20%– Riboflavin: 37%Riboflavin: 37%