Migraine Migraine Age Specific Prevalence in the United States. Headache International Headache Society Classification

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1 28 Primary Care Medicine Principles and Practice 29 October 28 Professor Peter J. Goadsby Department of Neurology Headache International Headache Society Classification Primary Tension-type headache 3. Trigeminal autonomic cephalalgias 3.1 Cluster headache 3.2 Paroxsymal hemicrania 3.3 SUNCT 4. Other Headaches 4.1 Primary Stabbing 4.2 Cough Headache 4.3 Exertional headache 4.4 Sex headache 4.5 Hypnic headache 4.6 Primary Thunderclap Headache 4.7 Hemicrania continua Secondary infection hemorrhage trauma tumour CSF pressure change (Cephalalgia 24;24:1-16) % patients Age Specific Prevalence in the United States >6 (Lipton et al., Headache 21; 41: ) 7 female male Landmark Study How often are physicians wrong when they diagnose non-migraine in a patient complaining of primary headache? Prospective, open-label study Patients tracked for three months or six attacks Assigned IHS diagnoses by experts % Patients with non-migraine, (Tepper et al., Headache 24;44: ) 18 Migrainous 1

2 Update in Classification & Diagnosis Pathophysiology Treatment Classification Is there Medication Overuse? Analgesics ten days or more per month Feature full headache Throbbing, unilateral, photophobia, phonophobia, movement effect Is there headache on 15 days or more per month? Episodic Chronic (15+ days/month) with aura without aura International Headache Society Migrene Vanligvis episodisk hodepine (4-72 timer) med visse kjennetegn (& ingen annen årsak): Minst 2 av- ensidig pulserende Moderat til alvorlig Forverrelse ved aktivitet Minst en av- kvalme/brekninger foto/fonofobia (after International Headache Society, 1988) Attacks The Attacks & the Disorder Premonitory symptoms Pain unilateral throbbing movement worse Nausea Sensory sensitivity photophobia phonophobia osmophobia Aura Disorder Repeated attacks < 15 days/month: Episodic 15 days/month: Chronic Family history Triggers (biology) Sleep: missing/excess Food: skipping meals Chemical: alcohol or nitroglycerin Weather Sensory: light, smells Hormonal Stress- relaxation The simple headaches have the same characters, and occur under the same causal conditions of heredity &c, as those in which there are additional other sensory symptoms Gowers

3 Medication Overuse and the evolution of chronic migraine AMPP Sample- 16,339 Progression to Chronic migraine in 2.5% over one year Acetaminophen use does not predict risk Predictors Barbiturates at 5 day/month Opioids at 1 days/month Triptans at 13 days/month NSAIDs are protective if used more than five days a month Update in Classification & Diagnosis Pathophysiology Genetics Aura Pain Treatment Bigal et al., Headache 28;48: in press Genetics of Familial Hemiplegic - an ionopathy aura FHM-I CACNA1A: P/Q voltage-gated Ca 2+ channel chr 19 Ophoff et al. Cell 1996; 87:543 FHM-II ATP1A2: Na + /K + ATPase chr 1q23 De Fusco et al. Nat Gen 23;33:192 FHM-III SCN1A: Voltage-gated Na + channel chr 2 Dichgans et al., Lancet 25;366:371 FHM-IV?:? Silberstein et al., Headache in Clinical Practice 2nd Ed 22 3

4 Infarctions in the Migrainous Brain? a systems disorder 18Jan6 3Feb6 Kruit et al., Brain 25;128:268 Rozen Cephalalgia 27;27: (after Goadsby et al., NEJM 22; 346:257-27) The tentorial nerve is a branch of V 1 and the Neck Referred Pain in the Trigeminocervical Complex (TCC) dura mater V ganglion trigeminal nucleus (Feindel et al., Neurology 196;1:555) Cervical input C 1 C 2 }TCC 4

5 Neck and Headache Cranial Autonomic Features and Experimental Head Pain 8 patients lacrimation conjunctival injection nasal congestion ptosis miosis Bartsch & Goadsby Current Pain and Headache Reports 23;7: (Frese et al., Cephalalgia 23;23:67-68) Trigeminal Autonomic Cephalalgias trigeminal-autonomic activation When does migraine start? 1 (Giffin et al., Neurology 23; 6:935-94) dura mater V ganglion pterygopalatine ganglion C1 C2 SSN trigeminal nucleus VAS rating of state of health premonitory headache Time (hours) 5

6 %patients tiredness A11 and the Premonitory Phase stiff neck premonitory headache postdrome yawn polyuria hunger thirst A11 neurons contain tyrosine hydroxylase (green) but not dopamine β-hydroxylase (red) emotional Charbit, Akerman Update in Classification & Diagnosis Pathophysiology Treatment - Current - Recent - Future (Giffin et al., Neurology 23;6:935-94) Therapy in migraine Non-drug Choice of treatment in acute migraine Acute attack treatments Behavioural modification relaxation therapy meditation biofeedback Acupuncture Natural remedies feverfew Non-proven options homeopathy Proven not to work chiropractic osteopathy Non-specific aspirin or acetaminophen NSAIDS ibuprofen naproxen tolfenamic acid opioids Specific ergotamine derivatives ergotamine dihydroergotamine Triptans sumatriptan almotriptan eletriptan frovatriptan naratriptan rizatriptan zolmitriptan 6

7 Preventives By mechanism Amine modulation 5-HT 2 : cyproheptadine, methysergide β- blockers: propranolol Tricylics: amitriptyline MAOI s: Phenelzine Channel modulation Gabapentin Topiramate Valproate Other - Neurtriceuticals: riboflavin - Botulinum toxin Trigeminovascular System & (Goadsby et al., NEJM 22; 346:257-27) %patients Acute Treatment of with Sumatriptan and Naproxen Double-blind randomized parallel group single attack adult migraineurs Placebo Naproxen 5 mg SumaRT 85 mg SUMA+Npx Study I Study II Meta-analysis n = pain free 2hr pain free 2hr Sumatriptan 1 mg Brandes et al., JAMA 27;297:1443 SumaRT/Nap Ferrari et al., Lancet 21;358:1668 sumatriptan %patients Acute Treatment of with Sumatriptan and Naproxen Double-blind randomized parallel group single attack adult migraineurs Placebo Naproxen 5 mg SumaRT 85 mg SUMA+Npx n = Sustain pain free Sustained pain free Sumatriptan 1 mg Brandes et al., JAMA 27;297:1443 SumaRT/Nap Ferrari et al., Lancet 21;358:1668 sumatriptan AEs Nausea Somnolence Dizziness Paresthesia Dyspepsia 7

8 Trigeminovascular System & 5-HT 1D CGRP Trigeminal ganglion stimulation increases CGRP in the cranial circulation Hou et al., Brain Res 21;99: (pmol/l) control VG stimulation 4 2 (Goadsby et al., NEJM 22; 346:257-27) CGRP Substance P CGRP Substance P Cat Human (Goadsby, Edvinsson & Ekman Ann Neurol 1988;23:193) Superior sagittal sinus (SSS) stimulation in cat Neuropeptide changes Calcitonin Gene-Related Peptide (CGRP) and 2 CGRP is released in the cranial circulation in migraine 1 BIBN496BS (olcegepant), a CGRP receptor antagonist, is effective in migraine 2 (pmol/l) control SSS (pmol/l) placebo BIBN496BS 2.5mg CGRP Substance P VIP Neuropeptide Y (Zagami, Goadsby & Edvinsson, Neuropeptides 199;16:69-74) HA response Aes CGRP Sub P control MWA MWOA 1 Goadsby et al., Ann Neurol 199;28:183 2 Olesen et al NEJM 24;35:114 8

9 CGRP receptor antagonists are effective in acute migraine Double-blind randomized parallel group single attack adult migraineurs Pain Free at 2 hours 5 45 Placebo %patients n = R1 S1 Ho et al., Neurology 28;7:14 telcagepant 9 Ferrari et al., Lancet 21;358:1668 sumatriptan CGRP receptor antagonist telcagepant is effective in the treatment of acute migraine (% patients) Double-blind parallel group randomised controlled trial 2 Hour pain free Placebo T-15 T-3 Z5 Z Ho et al., Ferrari et al., Headache 28;48:S7-S8 Lancet 21;358; N = CGRP receptor antagonist telcagepant is effective in the treatment of acute migraine CGRP receptor antagonist telcagepant is effective in the treatment of acute migraine Sustained pain free (SPF) at 24 and 48 hr 3 SPF 2-24 SPF Placebo T-15 T-3 Z5 5.7 (% patients) Placebo T-15 T-3 Zolmitriptan-5 (Headache 28;48:S7-S8) (% patients) Aes Triptan-like Aes?Cagepant-class AEs- dry mouth, fatigue (Headache 28;48:S7-S8) 9

10 and the pons Brainstem activations in right and left-sided headache with PET Left-sided headache Right-sided headache Nitroglycerin-triggered Spontaneous Bahra et al Lancet 21;357: Afridi et al. Arch Neurol 25;62, Afridi et al., Brain 25; 128: dura mater Vg pterygopalatine ganglion trigeminal nucleus C 2 nausea 1