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Migraine and Chronic Daily Headache Laurence J. Kinsella, M.D., F.A.A.N. You Make the Call: Case 1 37-year-old man with lifelong migraine and develops 6 weeks of unremitting headache (HA) Bitemporal, throbbing, 3-7/10, morning HA Relieved with acetaminophen/aspirin/caffeine (Excedrin Migraine®) No visual disturbances, scotomata, nausea, photophobia 3 months of cyclosporin (Neoral®) for alopecia universalis Audience Question What is the diagnosis? 1. 2. 3. 4. Transformed migraine Medication overuse headache Cyclosporin induced headache Chronic tension type headache You Make the Call: Case 2 55-year-old woman 10/10 throbbing right periorbital HA awakens her every night at 3 a.m. Gets relief after 45 minutes with combination of icepack, T#3 x2, acetaminophen/aspirin/caffeine x2, acetaminophen/pseudoephedrine (Tylenol Sinus®) x2 Audience Question Diagnosis? 1. 2. 3. 4. 5. Cluster headache Thunderclap migraine Raeder’s Paratrigeminal headache Aneurysmal headache Temporal arteritis You Make the Call: Case 3 75-year-old woman with right occipital/ burning 8/10 HA, radiating to vertex No nausea/photophobia/visual disturbances Present for 2 months, constant No relief with over-the-counter medications Exam is normal Audience Question Diagnosis? 1. 2. 3. 4. Occipital Neuralgia Cervicocephalgia Temporal arteritis Post herpetic neuralgia History, History, History P - Precipitating/palliative factors - diet, exercise, caffeine, OTC drugs Q - Quality of the pain - burning, aching, stabbing, squeezing, pressure, throbbing R - Radiation/location of pain S - Severity - range of pain (least to the most) on analog scale 1-10 T - Temporal factors - what time of day International Headache Classification Primary headaches - “benign” disorders Migraine (with and without aura) Tension type (episodic or chronic) Cluster, chronic paroxysmal hemicrania Other benign HA (cough, coital, cold, icepick, exertional HAs) Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 International Headache Classification (Cont.) Secondary headaches - symptomatic of organic disease or medication overuse Posttraumatic Medication overuse HA Subarachnoid hemorrhage Temporal arteritis Meningitis High pressure/low pressure Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 International Headache Classification (Cont.) Cranial neuralgias, nerve trunk pain Headache or facial pain associated with disorders of the cranium, neck, eyes, nose, sinuses, teeth, mouth or other facial or cranial structures Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 Chronic Daily Headache Not a diagnosis but a category of primary and secondary headache types > 15 days/month for > 3 months > 4 hours/day 4% prevalence; 5% of all women 40-80% of patients referred to HA centers Matthew NT et al. (1987), Headache 27:102-106; Colas R et al. (2004), Neurology 62:338-342 Chronic Daily Headache Subtypes include: Transformed migraine/chronic migraine Chronic tension-type headache New daily persistent headache Hemicrania continua All may be complicated by: Medication overuse headache Silberstein SD et al. (1996), Neurology 47:871-875 Transformed Migraine (TM) > 15 days/month head pain Headache > 4 hours/day At least 1 of: Previous HA fulfills IHS criteria for migraine Increasing frequency > 3 months Medication overuse in 80% with TM Silberstein SD et al. (1996), Neurology 47:871-875; Bigal ME et al. (2002), Cephalalgia 22:432-438 Migraine Without Aura Common Migraine Mnemonic: SULTANS Headache has at least 2 of the following characteristics: S = severe UL = unilateral T = throbbing A = activity worsens HA And at least 1 of the following during headache: N = nausea or vomiting S = sensitivity to light/sound Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 Diagnostic Criteria for Migraine With Aura (Classic Migraine) At least 2 attacks Aura must exhibit at least 3 of the following characteristics: Fully reversible Gradual onset Lasts less than 60 minutes Followed by headache within 60 minutes HA may begin before or simultaneously with the aura Normal neurologic exam and no evidence of organic disease that could cause headaches Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 Migraine: Abortive Therapy Individual Attacks at Home Aspirin/APAP/caffeine (Excedrin®) Sumatriptan (Imitrex), zolmitriptan (Zomig®), rizatriptan (Maxalt®) Isometheptene/dichlo/apap (Midrin®) Ergot tart/caffeine (Cafergot®) Butalbital NSAID Do not exceed 2-3 days treatment in 1 week rebound Silberstein SD (2000), Neurology 55(6):754-762 ED management of migraine is ineffective 57 patients in ED 95% met migraine criteria (SULTANS) by questionnaire Only 32% given a dx of migraine 59% “cephalgia”, “HA NOS” 65% txed with “migraine cocktail”benadryl, reglan, toradol 24% opioids Only 7% given specific Tx- triptan, DHE 60% had HA 24 hrs later Headache 2003;43:1026-31. Migraine: Abortive Therapy Emergency Room Dihydroergotamine mesylate (DHE 45) .5-1 mg q 8 hrs Metoclopramide (reglan) 10 mg IV Dexamethasone (Decadron) 16-24mg IV x1 Reduces recurrent HA at 72 hours Sumatriptan (SC Imitrex®) 4-6 mg SQ, 5 mg Nasal Ketorolac injection (Toradol®) 15mg IV/IM Cochrane Review: Steroids and Migraine. BMJ 2008 Jun 14; 336:1359 Silberstein SD (2000), Neurology 55(6):754-762 ED Management of Migraine Prochlorperazine (Compazine®) 10 mg IV vs. metoclopramide* (Reglan®) 20 mg IV Both given with 25mg IV diphenhydramine (Benadryl®) Randomized, controlled trial; 77 patients Mean VAS change of 5.5 vs 5.2 Similar at 2 and 24 hours later Compazine assoc with non-statistical increase in side effects A randomized controlled trial of prochlorperazine versus metoclopramide for treatment of acute migraine. Ann Emerg Med. 2008; 52(4):399-406 Triptans Major advance in migraine therapy 5-HT1B/1D agonists Vasoconstriction All act by suppressing nausea, confusion, autonomic dysfunction and pain associated with migraine attack Differ only in pharmacokinetics Johnston MM, Rapoport AM. Triptans for the management of migraine. Drugs. 2010 Aug 20;70(12):1505-18 Triptans List Sumatriptan 25-100 mg po/6 mg sq/5 mg nasal at HA onset, rpt 1 hr sq, 2 hr po/nasal Zolmitriptan 2.5-5 mg Rizatriptan 10 mg SL Eletriptan (Relpax®), frovatriptan (Frova®), almotriptan (Axert®), others Johnston MM, Rapoport AM. Triptans for the management of migraine. Drugs. 2010 Aug 20;70(12):1505-18 Migraine Prophylaxis First Line (Pregnancy Class) -blockers (C): propranolol LA (Inderal-LA) FDA 60 mg qd, timolol 20 mg qd FDA Anticonvulsants: topiramate FDA (Topamax®) (was C, now D- 3/28/11 due to cleft palate) 25-100 mg bid Lower toxicity than divalproex (Depakote®), no weight gain Tricyclics antidepressants (D): nortriptyline (Pamelor®) 10-60 mg NSAID: naproxen sodium (Anaprox DS®) (C) (menstrual migraine - 550 mg bid x 10 days) Silberstein SD (2000), Neurology 55(6):754-762 Migraine Prophylaxis Other Options Divalproex (Depakote®) (D) FDA Gabapentin (Neurontin®) (C) Baclofen (Lioresal®) (C) “MigreLief”1,2 $20 /60 pills Riboflavin (Vitamin B2) 400 mg/day (A) Magnesium oxide 360 mg/day (B) Feverfew 100 mg/day Petadolex 1 tid (Butterbur extract) (A) 1Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the Prophylaxis of Migraine A Double-Blind, Placebo-Controlled Study. Cephalalgia 1996;16:436-40. 2Schoenen J, Lenaerts M, Bastings E. High-dose Riboflavin as a Prophylactic Treatment of Migraine: Results of an Open Pilot Study. Cephalalgia 1994;l14:328-9 Transformed Migraine/Status Migrainosus Unremitting headache > 72 hours fulfilling criteria for migraine 80% associated with medication overuse Transformed Migraine/Status Migrainosus Treatment Withdraw all medication Raskin protocol: DHE IV 0.5 mg/metoclopramide (Reglan®) 10 mg IV q 8 hours for 3 days1 Dexamethasone (Decadron-LA®) 10-24 mg IV x1 Dexamethasone (Decadron®) 2 mg bid for 3-5 days Prednisone (Deltasone®) 60 mg daily for 3-5 days BMJ 2008 Jun 14; 336:1359 Am Fam Physician. 2011;83(3):271-280. 1Raskin NH (1986), Neurology 36(7):995-997 *FDA boxed warning 2/26/09 – Long-term or high-dose use of metoclopramide has been linked to tardive dyskinesia. Complicated Migraine Persistent neurologic residue of a migraine attack Migraine with dramatic focal neurologic features (include ophthalmoplegic, hemiplegic, basilar migraine) Chronic Daily Headache Subtypes include: Transformed migraine/chronic migraine Chronic tension-type headache New daily persistent headache Hemicrania continua All may be complicated by: Medication overuse headache Silberstein SD et al. (1996), Neurology 47:871-875 Chronic Tension Type HA Head pain > 15 d/mo for at least 6 months Last hours, or may be continuous Pressing, tightening quality Mild-to-moderate intensity Bilateral, often occipital/posterior May have mild nausea, photophobia Do not fulfill migraine criteria Consider other causes: ICP (Intracranial Pressure), SDH (Subdural Hematoma), CO poisoning Tension-Type Headache (TTH) Considered the most common HA type (ICHD) 30-78% prevalence Squeezing, band-like or global headache Environmental stressors May or may not limit function Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 TTH Frequent overlap with other HA subtypes Migraine Medication overuse Ask about over-the-counter medication especially those with caffeine (Excedrin/Anacin/APC) How many cups/pots of coffee/tea daily? How many 2-liter bottles of soda? Chronic Daily Headache Subtypes include Transformed Migraine/Chronic Migraine Chronic Tension Type Headache New Daily Persistent Headache Hemicrania continua All may be complicated by: Medication Overuse Headache Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headaches: field trial of revised HIS criteria. Neurology 1996;47:871-875 New Daily Persistent HA > 3 mo, daily within 3 days of onset 82% recall exact day of HA onset Bilateral, pressing quality Mild-moderate Nausea, photophobia MRI, MRV to exclude venous thrombosis LP with opening pressure to exclude intracranial hypotension Li, D & Rozen, TD (2002). "The clinical characteristics of new daily persistent headache." Cephalalgia 22 (1), 66-69. Cerebral Venous Thrombosis 54 yo M with new onset headaches, syncope with exertion Sudden onset bi-occipital HA 8/10 aching without relief, worsened supine Exam normal, except loss of venous pulsations. MRI normal, MRV abnl. IV Venogram shows stenotic left lateral sinus. Chronic Daily Headache Subtypes include Transformed Migraine/Chronic Migraine Chronic Tension Type Headache New Daily Persistent Headache Hemicrania continua All may be complicated by Medication Overuse Headache Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headaches: field trial of revised HIS criteria. Neurology 1996;47:871-875 Hemicrania Continua Cluster variant Unilateral pain without side-shift Daily and continuous Moderate to severe At least 1 of: Conjunctival injection or lacrimation Nasal congestion or rhinorrhea Ptosis or miosis Complete response to indomethacin Cluster Headache Uncommon (69/100,000) Men:women 6:1 Headaches begin 20-50 years of age (mean 30) High incidence of smoking, Peptic Ulcer Disease (PUD) Familial cases unusual Cluster Headache (Cont.) Abrupt onset of pain, builds in 2-15 minutes Pain is excruciating, severe (deep, constant, stabbing, explosive or pulsatile) Location: in and around 1 eye Unilateral, usually same side Patient up and pacing due to pain Cluster Headache (Cont.) Duration: 30 minutes - 2 hours 75% of attacks between 9 p.m.-10 a.m.1 Awakens from sleep 1-2 clusters per year, 4-8 weeks or longer 1Russell D (1981), Cephalalgia 1:209-216 Cluster Headache Associated Symptoms and Signs Lacrimation Blocked nostril Rhinorrhea Conjunctival injection Temporary ipsilateral Horner’s (2/3) Sweating of forehead Pallor or flushing Nausea Bradycardia Other Cluster Variants Chronic paroxysmal hemicrania Multiple short, severe HA occurring daily Short episodes of cluster 1-2 minutes Average 14 daily SUNCT (Short-Lasting, Unilateral, Neuralgiform headaches with Conjunctival injection and Tearing) 30-100 attacks daily Usually < 30 seconds Responds to indomethacin Cluster Headache: Treatment Stop smoking Prophylactic treatment of chronic cluster Indomethacin (Indocin®) 75 mg SR, 25-100 mg tid Avoid over age 60 Lithium carbonate 300-900 mg daily Methysergide (Sansert®) 2-8 mg daily Propranolol, Nifedipine (Procardia®), verapamil (Calan®) Silberstein SD (2000), Neurology 55(6):754-762 Cluster Headache: Treatment (Cont.) Abortive therapy Rectal ergot for nocturnal attacks 100% oxygen Sumatriptan injection Prednisone or dexamethasone: burst and taper Silberstein SD (2000), Neurology 55(6):754-762 Chronic Daily Headache Subtypes include Transformed Migraine/Chronic Migraine Chronic Tension Type Headache New Daily Persistent Headache Hemicrania continua All may be complicated by: Medication Overuse Headache Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and near-daily headaches: field trial of revised HIS criteria. Neurology 1996;47:871-875. Medication Overuse Headache Prevalence 1-2% Morning headaches Chronic daily headache > 15 days/month Simple analgesics > 15 days/month Ergots, triptans, opioids, combo NSAIDS > 10 days per month Most have baseline migraine HA Dodick DW (2006), N Engl J Med 354(2):158-165; Zwart JA (2003), Neurology 61:160-164 Medication Overuse Headache Treatment Stop all OTC analgesics, caffeine consumption Wean butalbital, opioids, benzodiazepines Ketorolac PO 60 mg x1, 10 mg q 6 hours x 3 days Tizanidine (Zanaflex®) 2-8 mg tid1 May require hospitalization Raskin protocol: DHE 0.5-1 mg IV q 8 hours/ metoclopramide 10 mg for 3 days 1Saper JR et al. (2002), Headache 42(6):470-482 Steroids ineffective for MOH Neurology 2007 Randomized controlled trial of 100 patients 51 rcvd prednisone 60 mg taper, 49 placebo No change in mean HA (MH) severity or frequency © Boe, M. G. et al. Neurology 2007;69:26-31 “Sinus Headaches”? Over-diagnosed and over-treated Not a recognized form of HA by the IHS except in setting of acute bacterial sinusitis 74% fulfill IHS migraine criteria 45-50% of asymptomatic adults have evidence of sinus mucosal thickening or edema Utility of routine CT sinuses not established Gupta M, Silberstein SD. Expert Opin Pharmacotherapy 2005;6:715-722. Mehle ME, Kremer PS. Sinus CT scan findings in “sinus headache “ migraneurs. Headache 2008;48:67. How often is “Sinus” Headache Really Migraine? Migraine with or w/o Aura (IHS 1.1, 1.2) 80 Migrainous (IHS 1.7) 8 Recurrent episodes (at least 6 in the past 6 months) 8 No fever or purulent discharge No history of abnormal sinus radiographs Episodic Tensiontype (IHS 2.1) Other 4 0 20 40 60 Subject (%) Schreiber CP, et al. Arch Intern Med. 2004;164:1769-1772 80 100 Treatment of Transformed Migraine and Medication Overuse Headache Education, close followup for 8-12 weeks Lifestyle changes: caffeine, smoking, sleep Behavioral therapy Abrupt withdrawal of analgesics except: Barbiturates: wean over 1 month Opioids: clonidine withdrawal Dodick DW (2006), N Engl J Med 354(2):158-165 Bridging Medications for Outpatient Treatment Tizanidine 2-6 mg po TID Baclofen 10-20mg TID Hydroxyzine 25-50mg PO, IM NSAIDS (Naproxen 500 mg, Ketorolac 10-30 po) Dihydroergotamine 0.5-1 mg nasal, IM, subq Antiemetics: metoclopramide 10-20 mg Intravenous Therapies for Intractable Headaches IV DHE 1 mg (FDA)/ Reglan 10 mg q8 x 3 days IV DHE 3mg/L NS over 24 hrsx3 IV decadron 12-24 mg IV x1 IV Magnesium 1 gm x 1 IV depacon 250 mg q 12 hr IV Keppra 500 mg q 12 hr Propafol, others Saper J. Intravenous management of intractable headache. American Academy of Neurology Course. 2010 Emerging Therapies • Calcitonin gene-related peptide (CGRP) antagonists Olcegepant (Phase II) Telcagepant (withdrawn due to increased LFTs) • Combinations • Sumatriptan and naproxen (Treximet®) - (FDA) • Anticonvulsants Pregabalin Zonisamide Levetiracetam Lacosamide Carabersat lamotrigine Arulmozhi DK et al. (2009), Vascul Pharmacol 43(3):176-187; Rapoport AM, Bigal ME (2005), Neurol Sci 26(suppl 2):S111-S120; Available at: www.clinicaltrials.gov Physical Examination Blood pressure Funduscopy: papilledema in idiopathic Intracranial hypertension, tumor; subhyaloid hemorrhage in SAH Temporal artery tenderness: temporal arteritis Neck stiffness, Kernig’s/Brudzinski’s, orbital tenderness: meningitis SAH = subarachnoid hemorrhage Worrisome HA Red Flags “SNOOPS” Systemic symptoms: fever, weight loss Neurologic symptoms or signs: confusion, depressed alertness or consciousness Onset: sudden, abrupt, split-second Older: new HA > 50 years old - temporal arteritis Previous HA history: change in usual HA pattern - change in frequency, character, severity Secondary risk factors: HIV, cancer Headaches to be Considered for Emergency Referral Abrupt onset of “the worst HA of my life” Change in an established HA pattern Headache plus: Stiff neck Fever Confusion, alteration of consciousness Focal neurologic signs Inability to walk Headaches to be Considered for Emergency Referral (Cont.) Any patient over 50 years old with new onset of headaches Get a sedimentation rate (ESR) Headaches that last more than 72 hours Summary Chronic daily headache is common Transformed migraine, tension type and cluster variants Medication overuse HA is seen in all subtypes History is critical SULTANS and SNOOPS Questions from the Audience? References 1. Dodick DW. Chronic Daily headache. NEJM 2006;354:158-165. 2. Headache Classification Subcommittee of the International Headache Society (2004), Cephalalgia 24:1-150 3. Edlow JA. Diagnosis of subarachnoid hemorrhage in the emergency department. Emerg Med Clin North Am 2003;21:73-87. 4. Silberstein SD. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2000 Sep 26;55(6):754-62. 5. Freitag FG. Acute treatment of migraine and the role of triptans. Curr Neurol Neursci Rep 2001;1:125-132. 6. Silberstein SD, Liu D. Drug overuse and rebound headache. Curr Pain Headache Rep 2002;6:240-247. 7. Snow V, et al. pharmacologic management of acute attacks of migraine and prevention of migraine headache.Ann Intern Med 2002;137:840-849. 8. Silberstein SD, Lipton RB, Sliwinski M. Classification of daily and neardaily headaches: field trial of revised HIS criteria. Neurology 1996;47:871-875