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migraine headache

Classification: 1) International Headache Society a) 1.1 Migraine without aura b) 1.2 Migraine with aura c) 1.3 Ophthalmoplegic migraine d) 1.4 Retinal migraine e) 1.5 Childhood periodic syndromes f) 1.6 Complications of migraine g) 1.7 Other migraine disorders - hemiplegic migraine 2) chronic migraine a) headaches > 15 days/month b) at least 8 headaches must meet criteria for migraine or respond to migraine-specific medications Etiology: precipitating factors/agents, risk factors 1) nitrates/nitrites: reddened meats (hot dogs) 2) phenylethylamines: i.e. tyramine a) aged cheeses b) red wine c) champagne d) chocolate e) some nuts 3) monosodium glutamate (MSG) 4) caffeine withdrawal 5) fruits 6) dairy products 7) shellfish 8) hormonal factors a) menses, menstrual migraine b) ovulation c) pregnancy d) post partum 9) pharmaceutical agents a) contraceptives* b) niacin c) nitrates d) H2 receptor antagonists e) post menopausal estrogens 10) sinusitis, sinus headache - > 90% of patients with 'sinus headache' have migraine & respond to migraine treatment [24] 11) fatigue 12) altered sleep patterns - poor sleeo quality predicts recurrent migraine [79] 13) glaring lights 14) excessive noise 15) hydrocarbon fumes 16) cutaneous allodynia [21] 17) obesity [40] especially in white women < 50 years 18) not associated with patent foramen ovale [39] 19) functional GI disorders - 32% of children with migraine, vs 18% of controls [63] * avoid estrogen-containing oral contraception if migraine with aura due to increase risk of stroke [24] Epidemiology: - 90% of outpatients who present with recurrent primary headache have migraine Pathology: 1) alterations in blood flow may not be involved [38] a) oligemia spreading from occipital to frontal lobe b) extracranial blood flow increases 2) migraine is not a vascular disorder [38] 3) changes in serotoninergic transmission 4) role of cranial nerve 5 (trigeminal nerve) Genetics: - familial migraine syndrome linked to chromosome 19p13.1-2 Clinical manifestations: 1) aura or prodome* (30%) [24] a) generally visual 1] 'scintillating scotoma' 2] shimmering vision 3] flashing lights 4] visual changes lasting minutes (generally 5-60 minutes) - 'looking through frosted glass' [24] 5] aura lasting > 1 hour is a red flag [24] b) sensory, numbness, paresthesias c) motor d) affective, aphasia, confusion [24] e) each aura symptom develops gradually (> 4 minutes) & lasts < 60 minutes f) may be multiple aura symptoms, that occur sequentially g) migraine aura may occur without headache h) 50% of children & adolescents with migraine aura have patent foramen ovale (vs 25% of general population) [31] 2) migraine with brainstem aura [24] - vertigo, ataxia, dysarthria, diplopia, tinnitus, hyperacusis, alterations in consciousness 3) deep, throbbing (pulsatile) headache (may or may not be pulsatile) - unilateral or bilateral - unilateral, periorbital, severe, & nonpulsatile - begins within 1 hour of aura onset 4) nausea/vomiting common 5) diarrhea 6) photophobia, phonophobia 7) paresthesias 8) scalp tenderness 9) lightheadedness 10) vertigo 11) alterations in consciousness (uncommon with severe migraine) a) seizure b) syncope c) confusional state 12) activity worsens pain - bending or walking up stairs or down stairs [24] 13) usual migraine lasts 4-72 hours & is episodic - migraine lasting longer than 72 hours is status migrainosus 14) occipital/nuchal pain & sinus pain or pressure are common during migraine attacks 15) physical findings unremarkable other than patient often appears ill 16) sinus pressure &/or drainage common [24] 17) common triggers include stress, hormonal changes, weather patterns, exercise 18) postdrome (headache resolution to feeling normal) [62] a) fatigue (88%) b) difficulty concentrating (56%) c) stiff neck (42%) d) resolution of postdrome within 6 hours (54%), > 24 hours (7%) e) factors affecting postdrome unknown [62] * prodrome is the earliest phase of a migraine preceding headache onset, characterised by non-aura symptoms POUND mneumonic [24] - Pulsatile quality - One day's duration (4-72 hours) - Unilateral - Nausea & vomiting - Disabling intensity (patient goes to bed) * > 3 POUND features 90% predictive of migraine [53] Red Flags - abrupt onset (thunderclap headache reaches maximum intensity in < 1 minute) - new headache in a patient > 50 years of age - change in headache pattern - aura lasting > 1 hour is a red flag [24 Diagnosis: - see diagnostic criteria for migraine without aura Laboratory: - not helpful except for exclusion of other disease Radiology: 1) neuroimaging for stable headaches that meet criteria for migraine not indicated [24] 2) non-contrast head CT - thunderclap headache (subarachnoid hemorrhage) suspected 3) magnetic resonance imaging (MRI) a) atypical headache features - red flags (see Clinical manifestations:) - warning signs & symptoms of potentially serious cause of headache (see Complications:) b) unstable or progressive temporal pattern c) headaches that do not meet criteria for migraine d) white matter hyperintensities common, particularly in the posterior circulation [24] 1] small 1 mm focal areas of gliosis in the periphery of the periventricular white matter are common 2] increase in the number (but not size) of white matter hyperintensities with time in women (total lesion volume progression, 77% vs 60% over 9 years) 3] lesions not associated with cognitive decline or stroke [24,36,41] e) enlarged perivascular spaces in the centrum semiovale identified by ultra-high-field 7T MRI in patients with chronic or episodic migraine [88] Differential diagnosis: 1) cerebral hemorrhage 2) cerebral infarction 3) encephalitis 4) intracranial mass 5) meningitis 6) analgesic rebound headache a) daily use of analgesics b) often occur in the morning or upon awakening c) generally diffuse d) drug tolerance e) prophylactic medications are ineffective 7) tension headache - bilateral, not aggravated by activity, no nausea, non-pulsatile - no photophobia or phonophobia - lasts 30 minutes to 7 days 8) trigeminal neuralgia - brief paroxysms of unilateral lancinating pain in distribution of maxillary nerve (CN5-2) or mandibular nerve (CN5-3) [24] - may be triggered by light touch 9) cluster headache 10) thunderclap headache reaches maximum intensity in < 1 minute Complications: - increased risk of suicide (hazzard ratio = 1.5) [26] - migraine with aura may have increased risk of cardiovascular disease & stroke [19,25,27,44]; a) migraine without aura & tension headache do not [19,25] b) relative risk = 8 c) absolute risk low: 18-40 per 100,000/year - risk of perioperative stroke 0.9% vs 0.6% [65] - migraine without aura associated with increased risk of stroke due to cervical artery dissection (RR=1.74) [66] d) risk exacerbated by smoking, estrogen-containing oral contraceptives [24] e) all-cause mortality (21%) [27] f) increased risks for myocardial infarction (RR=1.4), stroke (RR=1.6), cardiovascular mortality (RR=1.4) [61] (information on aura not available in [61]) g) increased risk for ischemic stroke (RR=1.8) [73] h) increased risk for hemorrhagic stroke (RR=1.8) [73] i) increased risk for ischemic stroke with or without patent foramen ovale (PFO), although increased right-left shunt of PFO increases risk of migraine with aura [80] j) increased risk for atrial fibrillation or atrial flutter (RR=1.4) [73] - migraine with aura associated with increased risk for atrial fibrillation ((RR=1.3) [76] - increased risk for venous thromboembolism (RR=1.5) [73] - migraine with or without aura not associated with increased risk of cognitive decline [35,41] - midlife migraine (especially migraine with aura) may be associated with late life parkinsonism & resless legs syndrome [49] - increased risk (2-fold) for Bell's palsy [50] - increased risk for urinary calculus (RR=1.6) [51] - migraine patients who used cannabis were more likely to develop rebound headaches than those who did not [81] - increased risk of hypertension (RR=1.25-1.31) [89,91] - increased risk of vasomotor symptoms in menopausal women (RR=1.34) [91] - status migrainosus - prosopagnosia (facial blindness) Warning signs & symptoms of potentially serious cause of headache: 1) frequent headaches beginning after age 30 - new headache condition after age 50 [24] 2) frequent headaches localizing to one area 3) headaches associated with: a) altered mental status b) meningismus c) neurologic deficits - focal neurologic deficits - cerebellar signs: dysmetria d) seizures 4) headaches precipitated by: a) coughing b) bending over c) sneezing 5) headaches refractory to 1st line treatment 6) neurologic symptoms lasting > 1 hour [24] 7) recurrent headaches with pain during sleep or with morning emesis [77] 8) progressively worsening headaches [77] 9) recurrent headaches with focal neurologic findings [77] Management: === general === - lifestyle measures: regular meals, regular sleep, hydration, regular exercise [94] === pharmacologic therapy === - avoid estrogen-containing contraceptives in women with migraine with aura - increased risk for stroke [24] - see patient education (below under other therapy) ==== abortive therapy ==== 1) abortive therapy (at the onset) a) useful only during the aura or the start of a migraine b) acetaminophen for mild cases (1st line) - treatment of choice in pregnancy [24,43] c) non-steroidal anti-inflammatory agents (NSAIDs)* 1] first line therapy - agents of choice in treatment of migraine without aura [24] 2] work well in acute attacks for most people if other risk factors are under control 3] ibuprofen may work better than COX2 inhibitor [11] 4] Excedrin Migraine better than Imitrex 5] no good evidence supports superiority of one NSAID over another [24] d) acetaminophen/aspirin/caffeine [24] e) ergot alkaloids: 1] Cafergot 2] dihydroergotamine (contraindicated in pregnancy) [94] a] 1 mg intranasal [24,82] b] 1 mg IM at 1st sign of headache, then every hour as needed, NOT to exceed 3 mg in 24 hours c] IV dihydroergotamine for status migrainosus (migraine lasting longer than 72 hours) [24] f) triptans* 1] indicated for severe migraine or poor response to NSAIDs or acetaminophen - triptans indicated for patients with moderate to severe migraine who have not responded to NSAIDs for at least 3 migraine attacks [24] - 1st line for menstrual migraine not responsive to NSAIDs [94] - triptans more effective than CGRP inhibitors or lasmiditan [97] 2] contraindicated with cardiovascular disease, uncontrolled hypertension & migraines with brainstem or hemiplegic aura [24] - intermittent use of triptans ok in pregnancy [94] 3] sumatriptan (Imitrex) is drug of choice unless contraindicated: a] subcutaneous sumatriptan for migraine without aura not responding to NSAIDs or oral triptans [24] b] may be less effective for migraine with aura [54] c] treatment of choice for refractory migraine with aura [NEJM Knowledge+] d] naproxen/sumatriptan combination [24] e] sumatriptan 5-20 mg intranasal f) sumatriptan: 25, 50 & 100 mg PO (tablets) 4] almotriptan (Axert) 6.25-12.5 mg PO [4] 5] eletriptan (Relpax) 20-40 mg PO [4] 6] frovatriptan (Frova) 2.5 mg PO [6] 7] naratriptan (Amerge) 1.0-2.5 mg PO 8] rizatriptan (Maxalt) 5-10 mg PO 9] zolmitriptan (Zomig) 2.5-5 mg PO or 5 mg intranasal [4] 10] no good evidence supports superiority of one triptan over another [24] 11] combination of triptan & NSAID synergistic [17] - avoid frequent use of triptans &/or NSAIDs to prevent rebound headache [17,24] g) opiates 1] codeine, hydrocodone (Vicodin), oxycodone (Percocet) 2] if no relief 1 hour after triptan [24] 3] use in emergency departments common but inappropriate [68] 4] 1 mg hydromorphone IV less effective than 10 mg prochlorperazine IV + 25 mg diphenhydramine PO [71] h) avoid butalbital compounds [24] - Fiorinal, Fioricet i) isomethepene compounds - Midrin, Isocom j) intravenous therapy - metoclopramide 10 mg IV a] superior to valproate [48] b] superior to ketorolac on most outcomes [48] - ketorolac 30 mg IV superior to valproate [48] - valproate a] 300-500 mg IV over 15-30 minutes [4] b] 1 g IV [48] - dexamethasone 10-24 mg once [52] - NNT = 10 to prevent 1 recurrence [52] k) calcitonin gene-related peptide (CGRP) inhibitors [85] - rimegepant & ubrogepant approved for migraine treatment [85] - ubrogepant (Ubrelvy) taken during prodrome - zavegepant (Zavzpret) intranasal FDA-approved l) no data to support use of oxygen by face mask 10 L/min in treatment of migraine [24] 2) combination of NSAID plus triptan may be better than monotherapy [22] 3) interval therapy (during the headache) a) analgesics b) antiemetics (intramuscular) 1] metoclopramide (Reglan) [13,24] 2] promethazine (Phenergan) c) serotonin agonist (triptan), sumatriptan (Imitrex) - lasmiditan (Reyvow) 4) moderate to severe migraine a) ketorolac (Toradol) 60 mg IM (single dose) b) serotonin agonist (triptan), sumatriptan 6 mg SC c) dihydroergotamine (DHE) 1 mg IV/IM (max: 3 mg/day) - repetitive IV administration for status migrainosus [24] - migraine lasting > 72 hours [24] d) glucocorticoids - dexamethasone 20 mg IV - methylprednisolone 60 mg IV e) opioids - avoid when other options available [24] - butorphanol (Stadol) 2 mg IM or nasal spray - meperidine (Demerol) 75 mg IM + promethazine 75 mg IM - hydromorphone + prochlorperazine IV + diphenhydramine f) oxygen & cold compresses (1st step) g) intranasal ketamine for refractory chronic migraine [92] - relatively tolerable adverse events ==== prophylactic therapy ==== 1) exercise may be more effective migraine prophylaxis than pharmacologic therapy [87] a) strength training is the most effective form of exercise for reducing migraine b) high-intensity aerobics second most effective c) either beats topiramate or amitriptyline [87] 2) prophylactic pharmacologic therapy a) consider if patient has > 4 total days with headache/month [24] - indicated if patient has > 10 total days with headache/month [24] b) prophylaxis for periods of 3-6 months followed by a gradual taper to see if patient remains in remission c) most antiepileptic drugs are effective [33] evidence is weak [101] 1] valproic acid 500-1000 mg QD in divided doses 2] topiramate (Topamax) 50-200 mg QD [6,10,24]* a] useful for episodic & chronic migraine [24] b] not effective in pediatric migraine [64] d) certain beta-blockers are effective [24,33] 1] propranolol 40-240 mg QD - not useful for chronic migraine [24]* - evidence is weak for prevention of episodic or chronic migraine [101] 2] metoprolol effective [24]* 3] timolol 10-30 mg QD effective [24] 4] other beta-blockers are probably effective [33] a] atenolol 50-100 mg QD b] nadolol c] pindolol & other beta blockers with intrinsic sympathomimetic activity are NOT effective e) frovatriptan is effective [33] - other triptans (other than frovatriptan) are probably effective a] naratriptan b] zolmitriptan [33] f) calcitonin gene-related peptide (CGRP) inhibitors [69,72,75] - eptinezumab, erenumab, fremanezumab, galcanezumab after failure of 2-3 attempts of 1st line prophylaxis) [24] - erenumab 140 mg monthly may help achieve remission in patients with medication overuse migraines [98] (may be expensive) - gepants: rimegepant (Nurtec ODT), ubrogepant (Ubrelvy), atogepant (Qulipta) [95] - atogepant reduces mean monthly migraine days [96] g) angiotensin receptor antagonists [8] (30% fewer headaches) - candesartan 16 mg QD [99,101], telmisartan effective for episodic migraine [101] g) certain antidepressants are probably effective [33] 1] tricyclic antidepressants a] amitriptyline 25-150 mg QD; not effective in pediatric migraine [64] b] desipramine (Norpramin)' may be more effective with failure of beta-blocker prophylaxis c] tricyclic antidepressants more useful than SSRI [29] 2] venlafaxine 150 mg QD (effective) [24] 3] selective serotonin-reuptake inhibitors (SSRI) (may be least effective) h) NSAIDs are probably effective [33] 1] fenoprofen 600-1800 mg QD 2] ibuprofen 400 mg QD 3] ketoprofen 50 mg QD 4] naproxen 5] celecoxib [85] i) histamine SC is probably effective [33] j) herbal/natural medicine - Coenzyme Q10 (ubiquinone) 150 mg PO QD [7]; 100 mg TID [15] - riboflavin 400 mg PO QD probably effective [33] - Mg+2 300 mg QD probably effective [33] - dietary zinc may reduce risk [90] - butterbur, feverfew probably effective [15,33] k) Botox, benefit modest [34]* evidence weak [101] - may be useful for chronic migraine (> 15 headaches/month), - not useful for episodic migraine [24,34,60] - Botox injection FDA-approved 10/2010 [28] l) suggested, possibly effective 1] calcium channel blockers a] verapamil b] diltiazem 2] neurontin, titrate up to 2400 mg QD [9] 3] ACE inhibitors [4,5] - lisinopril (20% reduction in frequency & severity) 4] simvastatin + vitamin D [59] m) not effective 1] lamotrigine is not effective 2] topiramate not effective in pediatric migraine [64] 3] amitriptyline not effective in pediatric migraine [64] 4] montelukast is probably ineffective - may be used in combination with COX2 inhibitor [6] 5] acupuncture of no benefit [16] n) menstrual migraine prophylaxis 1] topiramate [24] 2] oral contraceptives may be helpful a] avoid in women with prolonged aura or other risk factors for stroke [24] b] see other considerations below 3] transdermal estradiol [24] 3) avoid estrogen-containing contraceptive in women with migraine with aura (further increases stroke risk) [24] === other therapy === 1) cognitive behavioral therapy - cognitive behavioral therapy plus amitriptyline for children & adolescents with migraine [47] 2) electrical nerve stimulation a) Cefaly TENS device FDA-approved for migraine prevention b) hand-held vagus nerve stimulator approved for treatment of migraine in adults c) remote electrical neuromodulation [85] 3) transcranial magnetic stimulation 4) acupuncture may lessen frequency & severity of migraines [67,78] 5) diet high in omega-3 fatty acids (eicosapentaenoic acid & docosahexaenoic acid) reduced headache frequency & intensity but did not affect scores on the HIT-6 quality of life [84] 6) patient education/lifestyle a) proper sleep habits b) regular exercise c) sexual activity d) avoidance of precipitating factors - intense exercise usually not a trigger, even when suspected - light alone even less likely to be a trigger - prospective confirmation of triggers necessary [37] e) daily headaches are due to analgesic abuse & withdrawal, NOT migraine f) oral contraceptives - women with migraine should not take oral contraceptives with > 20 ug of ethinyl estradiol - > 35 years of age with migraine should not take oral contraceptives 7) Follow-up: as needed. * only topiramate & Botox effective for chronic migraine [24]

Interactions

disease interactions

Related

analgesic rebound headache (transformed headache) diagnostic criteria for migraine with aura diagnostic criteria for migraine without aura

Specific

familial migraine syndrome hemiplegic migraine sinus headache status migrainosus

General

headache

Database Correlations

OMIM 157300

References

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