1. Migraine Headaches Jim Ducharme MD CM FRCP Professor, Emergency Medicine Dalhousie University

2. A 34 year-old woman arrives with 24 hours of pulsating frontal headache. She has vomited twice, and wants the lights off. What questions do you want answered?

3. n Previous headache history n Onset of headache n Analgesic use n Any identified trigger n Allergies/Medication intolerance

4. Risk factors suggesting a serious underlying cause of headache n First or worst headache, especially if abrupt onset n Change in pattern of normal headaches n New progressive persistent headache CMAJ 1997

5. Risk factors suggesting a serious underlying cause of headache n Headache brought on by Valsalva n Accompanying systemic symptoms: – myalgia, fever, malaise, weight loss, jaw claudication, tender scalp n Focal neurological signs or symptoms n Altered mental status CMAJ 1997

6. How do you decide this is a migraine and does it matter?

7. I.H.S. Diagnostic Criteria n Migraine without aura – > 5 episodes – Duration 4-72 hours – 2/4 of: increase with activity, moderate to severe intensity, pulsatile at some point, visual complaints – 1 of 2 of: photo/phonophobia, nausea/vomiting – Normal exam

8. Her physical exam is normal other than her obvious pain. You would like to treat her headache. What 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?

9. Pathophysiology n Aura – Spreading cortical depression, not ischemia n Brainstem – Migraine “generator” in dorsal raphe, locus ceruleus and periaqueductal gray matter – PET scans show increased blood flow, even after cessation of headache

10. Pathophysiology n Genetic predisposition – Deficient habituation during repetitive stimulation – Allows for surpassing or modification of threshold for migraine n External: prophylaxis, psychosocial n Internal: estrogen, stress response, foods

11. Pathophysiology n Threshold surpassed: – Brainstem “generator” liberates CGRP – Activation of trigeminovascular system n CGRP also elevated with pulsating chronic tension-type headaches

12. Pathophysiology n Nitric oxide – Vasodilator – Promotes central sensitization of trigeminal nociceptors – Sumatriptan decreases NO release in addition to inhibiting CGRP release

13. Pathophysiology n Trigeminal Stimulation – Ca channel activation: substance P release – Feedback to DRG: NMDA & AMPA release, leading to wind up – Release of prostaglandins, kinins that induce perivascular inflammation – NO and CGRP further capillary leakage

14. Pathophysiology n Potentials for future abortive treatment: – Antagonists of: CGRP, NO, Glutamate – Agonists of adenosine A1 receptors

15. Yeah, yeah and the moon is actually made of Gruyère not Emmental….. My patient still has her headache, so what do I give her?

16. Effective Abortive Agents n Triptans n Dihydroergotamine n NSAIDs n Anti-emetics n Lidocaine? n Opioids?

17. Triptans n 5-HT 1B action: vasoconstriction by acting against NO n 5-HT 1D action: inhibit CGRP release n Should be very effective, yet only 70-80% effective, with 50% headache recurrence. – Cardiac risk, side effects further limit use

18. Triptans n PO versions require 60-90 minutes to effect n 50% success rate PO vs. 75-80% s/c n Newer triptans offer no real advantage over original n Subset of patients do respond well to this abortive agent in home setting

19. Dihydroergotamine n Same 5-HT action, but slower binding – Impact of IM may require 2 hours – Nasal version requires up to 4 hours n If given IV may initially increase CGRP release, producing dramatic headache increase n Does not increase N&V n Most initial research success probably due to adjunctive anti-emetics

20. NSAIDs n Excellent for mild to moderate migraines n No effect on neurotransmitters n Direct inhibition of most perivascular inflammation n Ketorolac at best 50-60% success as abortive for severe migraines

21. Dopamine Antagonists n Phenothiazines n Butyrophenones n Metoclopramide

22. Dopamine Antagonists n High adverse event rate – Need to treat prophylactically: benztropine, lorazepam, diphenhydramine n Low headache recurrence rate n Only droperidol as effective IM as IV n Dysphoria cannot be treated, found to be horrible by some patients

23. Lidocaine n Intranasal lidocaine found effective in two studies, but of very short duration, 70% headache recurrence n Mechanism of action uncertain as blocks Na+ channels not Ca++ ones

24. Opioids n At best 50% effective, high recurrence rate n Often required in combination for complex cases n Biggest effect: allows patient to enter REM sleep, which shuts down dorsal raphe activity

25. So back to that lady: what are you going to give her? What should be your first choice?

26. 1)Prochlorperazine 5 mg IV plus 1 mg benztropine 2)Droperidol 2.5 mg IM or IV plus benztropine 3)Sumatriptan 6 mg s/c

27. Analgesia-induced rebound headaches n Obtain good headache medication history n May occur with simple analgesics or with opioids n If cessation of medication may take 3 months to return to baseline headache frequency n DHE IV q8h x 2-3 days resolves problem

28. Migraine: headache recurrence n First identified 1989 n As high as 50-60% at 24 hours in some trials n Often as debilitating as original headache n Need to distinguish from analgesia rebound headache

29. Preventing recurrence n Innes et al: dexamethasone IV n Ducharme et al: complete elimination of pain before discharge n Choice of abortive agent – serotonin agonists have highest recurrence rate

30. Preventing Future Headaches n Headache diary: identifying triggers n Prophylaxis – Diet – Exercise – Sleep – Stress modification

31. Preventing Future Headaches n Medications: – Valproate: 45% patients more than placebo with 50% decrease in headache rate – Beta Blockers: 40% – Flunarazine: 42% – Pizotifen: 20% – Riboflavin: 37%

32. Your patient is pain free, leaves your ED with a smile, and you finish your shift …….….. With a throbbing headache of your own!