Nejm 2002;346:257

Cause:Genetic?

Pathophys:(Nejm 1994;331:1713) Angiographically documented cerebrovascular constriction, shunting; perhaps from 5-HT–induced vascular and neurogenic (Nejm 1991;325:353) changes; perhaps sludging leads to brain ischemia, which causes vasodilatation and pain, esp in external carotid distribution. Or all neurologic deficits due to "the spreading depression of Leao"

Perhaps autosomal dominant with incomplete penetrance; 80% have pos family hx. Higher incidence in obsessive/compulsives, patients with family hx of epilepsy, after psychologic trauma, and patients who had motion sickness as children

Common and classic: female/male ratio = 3-4:1; in women on bc pills, incidence increased × 9, 10% have each year, 15% have in lifetime; estrogen likely causative agent (Jama 2006;295:1824). Cluster: male/female ratio = 10:1

Sx:

(Nejm 1982;307:1029)

Common (80%): slow onset over 4 h, no scotomata or other aura; prodrome of yawning, euphoria, depression; usually bilateral; lasts 4-72 h

Classic (10%): precipitated by bright light, sound, or idiopathic; usually unilateral headache follows 20-30 min scotomata, which spread then recede, or other sensory, speech, or motor aura. Headache lasts 4-72 h; associated with NV+D, polyuria, and hemiplegias, all on opposite side of headache and scotomata. Consistently on one side 90% of time

Cluster (10%): "a migraine packed into 1 h." Clusters of several/week for ~1 mo; precipitated by vasodilators like alcohol, nitroglycerin during cluster period only; sweating, tearing, flush, salivation, runny nose; nocturnal; severe, may precipitate suicide

Si:

Ergotamine trials help most but not all

Common: eye tearing, face and neck muscle stiffness

Classic: on affected side, small pupil, external carotid pain; carotid sinus pressure temporarily relieves headache

Cluster: Horner's syndrome

Classic: relief with illness, steroids; after attack, ~1-week immunity from recurrence

CVA

r/o chronic daily headache, esp from HA medication overuse transformed to migraine (Nejm 2006;354:202), which rx w d/c of chr HA meds, caffeine, alcohol, plus amitriptyline hs and regular sleep plus exercise

Also glaucoma (distinguished by cupped discs), epilepsy (scotomata last longer with migraine), trauma/tpmor (in migraine no permanent scotomata except in very old, varies to opposite side 10% of time, headache not worse with Valsalva)

Lab:Noninv:EEG shows spike patterns (46%—Nejm 1967;276:23)

Xray: CT/MRI unnecessary if classic sx (Neurol 1994;44:1191, 1353)

Rx:

(Med Let 1995;37:17; Nejm 1993;329:1476)

Prevention

• Cluster: avoid vasodilators; lithium 300+ mg qd (Med Let 1979;21:78); verapamil 120 mg po tid (Neurol 2000;54:1382); High flow 02 @12 L/min for 15 min @ onset (Jama 2009; 302:2451)
• Common and classic: stop birth control pills; i ASA po qod (Jama 1990;264:1711); then,
• 1st:
• ß-blockers like propranolol, works in 70+%, 80-240 mg in bid doses or long-acting forms qd, or timolol (Blocadren) 10 mg po bid or 20 mg po qd, or metoprolol 100-200 mg qd
• TCAs like amitriptyline 10-50 mg po hs, or nortriptyline 25-75 mg po hs
• Valproate (Arch Neurol 1995;52:281) 250 mg po bid, or as Depakote ER 500-1000 mg po qd
• 2nd:
• Calcium channel blockers like verapamil 40-240 mg po qd, or nimodipine (Ann IM 1985;102:395)
• ACE inhibitors like lisinopril, or ARBs (Jama 2003;289:65)
• Topiramate (Topamax) gradually incr up to 50-100 mg po bid, reduces HA days by >1/3 (DBRCT—Jama 2004;291:965)
• Cyproheptadine (Periactin) 2 mg qd to 4 mg tid po
• 3rd:
• Botulinum toxin q3 mos marginally helpful (Med Let 2011;53;5)

Rx of acute attack

• Cluster: prednisone 40-60 mg po qd × 7 d (Nejm 1980;302:449); chlorpromazine 100-700 mg qd (Med Let 2005;47:9); sumatriptan (see below)
• Common or classic (Ann IM 2002;137:840); stepped care (Jama 2000;284:2599) based on severity or during attack w reevaluation q 2 h
• 1st
• Single-agent NSAIDs: ASA, ibuprofen, naprosyn
• ASA/acetaminophen/caffeine (Excedrin) i-ii tab po × 1; much better than placebo by RCT, NNT = 4 (Arch Neurol 1998;55:210), or
• ASA 900 mg + metoclopramide 10-20 mg po, as effective as po sumatriptan (Lancet 1995;346:923)
• 2nd
• Triptans (Nejm 2010;363:63); not more than 2 doses/wk; adverse reactions: drug interactions w MAO inhibitors, ergots, bcp's, cimetidine, and SSRIs, which could produce an excessive serotonergic response but rarely does; chest pain, angina, MI, HT, CVA; all po's about $25/dose, higher sl/intranasal if available
• Rizatriptan (Maxalt) 5-10 mg po/sl q 2 h up to 30 mg/24 h
• Sumatriptan (Imitrex) (serotonin [5-HT] analog) 6 mg sc × 1 helps 90% within 2 h ($58/dose), follow w 50 mg po; or 25-100 mg po once helps 50+% within 2 h; or as nasal spray 20 mg/dose helps w/i 15 min (generic $3)
• Zolmitriptan (Zomig) (Med Let 1998;40:27) 2.5-5 mg po, can repeat in 1-2 h, $13/dose; or as nasal form 5 mg, may repeat × 1 in 2 h (Med Let 2004;46:7), $25/dose
• Almotriptan (Axert) (Med Let 2002;44:19) 6.25-12.5 mg po
• Eletriptan (Relpax) (Med Let 2003;45:33) 20-40 mg po prn, may repeat in 2 h
• Frovatriptan (Frova) (Med Let 2002;44:19) 2.5 mg po; long half-life, less effective
• Naratriptan (Amerge) 1-2.5 mg, may repeat × 1, 4 h later; takes 4 h to work
• Other options:
• Combined sumatriptan 85 mg w naproxen 500 mg po × 1 helps 2/3 by DBCT (Jama 2007;297:1443)
• Dihydroergotamine 0.5-1 mg iv/im/sc repeat q1h; nasal spray (Migranal) (Med Let 1998;40:27; Neurol 1986;36:995) i inh each nostril repeat in 15 min; max on all = 3 mg/24 h; fewer side effects than ergotamine; $15/dose
• Caffeine/ergotamine 1 mg po or 1-2 mg pr, <6 mg/24 h, <10 mg/wk, used w Compazine 10 mg im + O₂ often; overdose can cause vascular occlusion
• Telcagepant (investigational CGRP receptor antagonist) 150-300 mg effective acutely and for up to 24 hours of sustained pain freedom (Neurol 2009;73:970)
• Butorphanol (Stadol) i nasal spray, may repeat × 1 in 1-2 h
• Lidocaine 4% intranasally, decr headache by 50% in 50% w/i 15 min (Jama 1996;276:319)
• Valproate 300-500 mg iv over 15-30 min
• Acupuncture no help by DBCT (Jama 2005;293:2118)