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%

Your patient is pain free, leaves yourYour patient is pain free, leaves yourED with a smile, and you finish your shiftED with a smile, and you finish your shift…………..……....

With a throbbing headache of your own!With a throbbing headache of your own!