• Clinical science
  • Clinician

Migraine

Summary

Migraine is a primary headache characterized by recurrent episodes of unilateral, localized pain that are frequently accompanied by nausea, vomiting, and sensitivity to light and sound. In approximately 25% of cases, patients experience an aura preceding the headache, which involves reversible focal neurologic abnormalities, e.g., visual field defects (scotomas) or paresis lasting less than an hour. Migraine is a clinical diagnosis and imaging is generally not indicated. Treatment of attacks consists of general measures (e.g., minimizing light and sound) together with administration of nonsteroidal anti-inflammatory drugs (e.g., aspirin) and antiemetics (e.g., prochlorperazine) if nausea is present. In severe cases, triptans may be added. Prophylactic treatment (e.g., beta blockers) may be indicated if migraines are especially frequent or long-lasting, or if abortive therapy fails or is contraindicated.

Epidemiology

  • Prevalence: ∼ 17% of females and ∼ 6% of males [1]
  • Peak incidence: 30–39 years [2][3]
  • Migraine is the second most common type of headache.

Epidemiological data refers to the US, unless otherwise specified.

Etiology

  • The exact pathophysiology is unclear. [4]
  • Genetic predisposition
  • Potential triggers
    • Certain food and beverages: alcohol, nicotine, citrus fruits, dairy products, food containing tyramine (e.g., chocolate, red wine)
    • Poor sleeping habits
    • Emotional stress
    • Weather changes
    • Hormonal changes in women: menstruation, hormone intake (oral contraceptive pills)

Pathophysiology

The pathophysiology of migraine is not fully understood. Different aspects contribute to the development and severity of migraine, e.g.: [5]

  • Vascular dysregulation: Vasodilation appears to play a role and there is an association between migraine and disorders with generalized vasospasms.
  • Meningeal irritation
  • Dysregulation of pain sensitization in the trigeminal system (CN V)
  • Release of vasoactive neuropeptides such as substance P or calcitonin gene-related peptide (CGRP)
  • Cortical spreading depression: continuously spreading depolarization of neuronal cells in the cortex

Clinical features

Migraine is characterized by recurrent attacks and may occur with aura (∼ 25% of cases) or without aura (∼ 75% of cases). A typical migraine attack passes through four stages, and the aura (if present) typically occurs before the headache. However, migraine patterns may differ and not follow the characteristic stages.

1. Prodrome (facultative)

  • 24–48 hours before the headache starts
  • Excessive yawning
  • Difficulties with writing or reading
  • Sudden hunger or lack of appetite
  • Mood changes

2. Aura

Paroxysmal, focal, neurologic symptoms that precede (or, in some cases, occurring during) the headache.

  • Typical aura [6][7]
    • Visual disturbances, sensory and/or speech symptoms (positive and/or negative ;)
    • No motor symptoms
    • Develops gradually
    • Completely reversible
    • Symptoms last ≤ 60 minutes each
  • Atypical aura
    • Paresis
    • Dizziness
    • Persistent or long-lasting symptoms

3. Headache

  • Localization
    • Typically unilateral, but bilateral headache is possible
    • Especially frontal, frontotemporal, retro-orbital
  • Duration: usually 4–24 hours (rarely over 72 hours)
  • Course: progression of pulsating, throbbing, or pounding pain
  • Exacerbated by physical activity
  • Accompanying symptoms: photophobia, phonophobia, and nausea/vomiting

4. Postdrome (facultative)

  • Feeling of exhaustion or euphoria
  • Muscle weakness
  • Anorexia or food cravings

The typical migraine headache is “POUND”: Pulsatile, One-day duration, Unilateral, Nausea, Disabling intensity.

Subtypes and variants

All variants of acute migraine should raise suspicion for other diagnoses (e.g., transient ischemic attack), especially if the first aura occurs after 40 years of age, auras last an atypical amount of time, or symptoms are predominantly negative.

Migraine with brainstem aura [6]

Vestibular migraine [6][8]

  • Most common cause of spontaneous episodic vertigo
  • Diagnosed migraine plus ≥ 5 episodes of vestibular symptoms (e.g., vertigo) lasting ≤ 72 hours
  • Treatment may be complemented with antivertigo agents (e.g., dimenhydrinate ).

Hemiplegic migraine [6]

  • May be familial or sporadic
  • Main differential diagnosis: epilepsy
  • Fully reversible aura (lasts ∼ 72 hours) consisting of both motor weakness and visual, sensory, or speech impairment

Retinal migraine [6]

  • Aura consists of monocular visual phenomena (e.g., scintillation, scotoma, blindness).
  • All symptoms are fully reversible.
  • Aura fulfills ≥ 2 of the following criteria:
    • Spread: gradually over ≥ 5 minutes
    • Duration: 5–60 minutes
    • Onset of headache: within 60 minutes

Typical aura without headache (silent migraine) [6]

  • Aura symptoms are present.
  • Aura lasts for ≥ 60 minutes before the onset of the headache, which might not develop at all.
  • Episodes may coexist with typical migraine symptoms.

Chronic migraine [6]

  • Patients with migraine diagnosis (with or without aura) presenting with a ≥ 3-month history of the following:
    • Headaches (variable in intensity and type ) ≥ 15 days/month
    • ≥ 8 days/month headache has migraine characteristics or is relieved by migraine-specific medication (triptans, ergotamine).
  • A headache diary is recommended for patients to help optimize treatment.
  • Main differential diagnosis: medication overuse headache

Diagnostics

Migraine is a clinical diagnosis based on history and physical examination. The most important step is to exclude red flags for headache that suggest a secondary headache (e.g., infection, hemorrhage, intracranial mass) and require more exhaustive investigation (e.g., imaging). Suspect a primary headache when no red flags are identified, and confirm the diagnosis using the diagnostic criteria for migraine. [6][9]

Migraine is a clinical diagnosis that is based on patient history and physical examination.

Diagnostic criteria

Diagnostic criteria for migraine [6]
Migraine without aura Migraine with aura
Number of attacks (total lifetime)
  • ≥ 5
  • ≥ 2
Duration
  • 4–72 hours
  • N/a
Characteristics
  • ≥ 2 of the following:
    • Unilateral
    • Pulsating
    • Moderate or severe pain
    • Worsened by routine physical activity
  • Concomitant symptoms (≥ 1 of the following):
    • Nausea/vomiting
    • Photophobia/phonophobia
  • ≥ 3 of the following aura characteristics:
    • ≥ 1 spreads gradually over ≥ 5 minutes.
    • ≥ 2 occur in succession.
    • Each one lasts 5–60 minutes.
    • ≥ 1 is unilateral.
    • ≥ 1 involves a positive symptom.
    • Accompanied or followed by headache (within 60 minutes)

Imaging [9][10][11]

Neurological imaging is not routinely indicated for uncomplicated migraine.

Differential diagnoses

The differential diagnoses listed here are not exhaustive.

Treatment

Abortive therapy

All patients

Mild to moderate headache [12][6]

Moderate to severe headache [12][6]

  • Start a migraine-specific agent: triptans (e.g., sumatriptan) or ergotamine (do not combine these agents!)
    • First-line: oral or parenteral triptans
      • If tolerating PO, consider one of the following:
      • If nausea/vomiting are present or there is a higher analgesic requirement, consider one of the following:
    • Second-line: consider one of the following
      • A parenteral ergotamine (e.g., dihydroergotamine )
      • Butorphanol
        • Consider in patients who cannot receive triptans or ergotamines.
        • Use with caution due to frequent side effects , risk of rebound, and medication dependency.
  • Consider recurrence prevention with dexamethasone . [16]

Do not combine triptans and ergotamines (within a 24-hour period) because of potentially dangerous drug interactions (e.g., coronary vasospasm and serotonin syndrome). [17]

Overview of migraine-specific agents

Migraine-specific agents
Triptans

Ergotamine

Agents
Mechanism of action
Indications
Side effects
Contraindications

Triptans and ergotamine have severe pharmacological interactions (e.g., coronary spasm, serotonin syndrome) with one another and with other drugs (e.g., SSRI, macrolides). ALWAYS take a detailed history of the patient's usual and recent medications before selecting a drug.

Triptans and ergotamines are contraindicated in pregnancy.

A SUMo wrestler TRIPs ANd falls on his head: SUMaTRIPtANs are used for headaches (cluster and migraine).

Prophylactic therapy

Nonpharmacological [19]

  • Lifestyle modifications
    • Exercise in moderation
    • Maintain a healthy diet
    • Identify and try to avoid potential triggers
    • Follow a regular sleeping schedule
  • Other: There is some evidence that the following nonpharmacological interventions have some benefits for patients with migraine

Pharmacological [20]

  • Indications [21][22]
    • ≥ 2 attacks/month that produce disability that lasts ≥ 3 days
    • Severe disability regardless of frequency (e.g., hemiplegic migraine)
    • ≥ 2 attacks/week regardless of severity
    • Failure/contraindications/major side effects from acute medications
  • General considerations [20]
    • Consider comorbidities when selecting a drug.
    • Encourage headache diary to assess response to treatment.
    • Start with a low dose and increase until reaching the therapeutic goal.
    • Goals of prophylaxis
      • Reduce frequency, severity, and duration of attacks.
      • Improve response to acute treatment.
  • General prophylaxis
  • Menstrual-related migraine [20]
    • First-line: frovatriptan [20]
    • Second-line
      • Naratriptan [20]
      • Zolmitriptan [20]
  • Chronic migraine

Complications

Status migrainosus [6]

  • Description: Debilitating migraine attack in a patient with a known migraine diagnosis (with or without aura)
    • Exceptional in duration (≥ 72 hours) and severity
    • Often related to medication overuse
  • Treatment: stepwise therapy with reassessment between drug administration [24]

We list the most important complications. The selection is not exhaustive.

Acute management checklist

  • Migraine of any severity [12][26][27][28]
    • Consider CT/MRI of the brain with or without contrast if the presentation is atypical or red flags for headache are present. [29][30]
    • Reduce light/noise in the patient's environment.
    • Fluid hydration
    • Begin pharmacologic treatment within 1 hour of symptom onset, if possible.
    • Treat nausea/vomiting, if present.
  • Mild to moderate headache
  • Moderate to severe headache, or if the above treatments fail
    • Start a migraine-specific agent.
    • Consider recurrence prevention with dexamethasone.
  • Status migrainosus refractory to above [24]
  • 1. Lipton RB, Bigal ME, Diamond M, et al. Migraine prevalence, disease burden, and the need for preventive therapy. Neurology. 2007; 68(5): pp. 343–9. doi: 10.1212/01.wnl.0000252808.97649.21.
  • 2. Lipton RB, Stewart WF, Diamond S, Diamond ML, Reed M. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001; 41(7): pp. 646–57. doi: 10.1046/j.1526-4610.2001.041007646.x.
  • 3. Straube A, Andreou A. Primary headaches during lifespan. The journal of headache and pain. 2019; 20(1): p. 35. doi: 10.1186/s10194-019-0985-0.
  • 4. Sathasivam S, Sathasivam S. Patent foramen ovale and migraine: what is the relationship between the two?. J Cardiol. 2013; 61(4): pp. 256–259. doi: 10.1016/j.jjcc.2012.12.005.
  • 5. Burstein R, Noseda R, Borsook D. Migraine: multiple processes, complex pathophysiology. J Neurosci. 2015; 35(17): pp. 6619–6629. doi: 10.1523/jneurosci.0373-15.2015.
  • 6. Headache Classification Committee of the International Headache Society (IHS). The International Classification of Headache Disorders, 3rd edition. Cephalalgia. 2018; 38(1): pp. 1–211. doi: 10.1177/0333102417738202.
  • 7. Dodick DW. Migraine. The Lancet. 2018; 391(10127): pp. 1315–1330. doi: 10.1016/s0140-6736(18)30478-1.
  • 8. Bisdorff AR. Management of vestibular migraine. Therapeutic Advances in Neurological Disorders. 2011; 4(3): pp. 183–191. doi: 10.1177/1756285611401647.
  • 9. Micieli A, Kingston W. An Approach to Identifying Headache Patients That Require Neuroimaging. Frontiers in Public Health. 2019; 7. doi: 10.3389/fpubh.2019.00052.
  • 10. Weatherall MW. The diagnosis and treatment of chronic migraine. Therapeutic Advances in Chronic Disease. 2015; 6(3): pp. 115–123. doi: 10.1177/2040622315579627.
  • 11. Evans RW, Burch RC, Frishberg BM, et al. Neuroimaging for Migraine: The American Headache Society Systematic Review and Evidence‐Based Guideline. Headache: The Journal of Head and Face Pain. 2019; 60(2): pp. 318–336. doi: 10.1111/head.13720.
  • 12. Orr SL, Friedman BW, Christie S, et al. Management of Adults With Acute Migraine in the Emergency Department: The American Headache Society Evidence Assessment of Parenteral Pharmacotherapies. Headache: The Journal of Head and Face Pain. 2016; 56(6): pp. 911–940. doi: 10.1111/head.12835.
  • 13. D’Souza RS, Mercogliano C, Ojukwu E, et al. Effects of prophylactic anticholinergic medications to decrease extrapyramidal side effects in patients taking acute antiemetic drugs: a systematic review and meta-analysis. Emergency Medicine Journal. 2018; 35(5): pp. 325–331. doi: 10.1136/emermed-2017-206944.
  • 14. Al‐Saffar A, Lennernäs H, Hellström PM. Gastroparesis, metoclopramide, and tardive dyskinesia: Risk revisited. Neurogastroenterology & Motility. 2019: p. e13617. doi: 10.1111/nmo.13617.
  • 15. Wijemanne S, Jankovic J, Evans RW. Movement Disorders From the Use of Metoclopramide and Other Antiemetics in the Treatment of Migraine. Headache: The Journal of Head and Face Pain. 2015; 56(1): pp. 153–161. doi: 10.1111/head.12712.
  • 16. Colman I, Friedman BW, Brown MD, et al. Parenteral dexamethasone for acute severe migraine headache: meta-analysis of randomised controlled trials for preventing recurrence. BMJ. 2008; 336(7657): pp. 1359–1361. doi: 10.1136/bmj.39566.806725.be.
  • 17. Volpi-Abadie J, Kaye AM, Kaye AD. Serotonin syndrome. Ochsner J. 2013; 13(4): pp. 533–540. pmid: 24358002.
  • 18. Brunton L. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 13th Edition. New York: McGraw-Hill Education / Medical; 2017.
  • 19. Puledda F, Shields K. Non-Pharmacological Approaches for Migraine. Neurotherapeutics. 2018; 15(2): pp. 336–345. doi: 10.1007/s13311-018-0623-6.
  • 20. Loder E, Burch R, Rizzoli P. The 2012 AHS/AAN Guidelines for Prevention of Episodic Migraine: A Summary and Comparison With Other Recent Clinical Practice Guidelines. Headache: The Journal of Head and Face Pain. 2012; 52(6): pp. 930–945. doi: 10.1111/j.1526-4610.2012.02185.x.
  • 21. Estemalik E, Tepper. Preventive treatment in migraine and the new US guidelines. Neuropsychiatric Disease and Treatment. 2013: p. 709. doi: 10.2147/ndt.s33769.
  • 22. Silberstein S, Goadsby P. Migraine: Preventive Treatment. Cephalalgia. 2002; 22(7): pp. 491–512. doi: 10.1046/j.1468-2982.2002.00386.x.
  • 23. Frampton JE, Silberstein S. OnabotulinumtoxinA: A Review in the Prevention of Chronic Migraine. Drugs. 2018; 78(5): pp. 589–600. doi: 10.1007/s40265-018-0894-6.
  • 24. Marshall RS, Mayer SA. On Call Neurology. Elsevier; 2020.
  • 25. Shahien R, Saleh SA, Bowirrat A. Intravenous sodium valproate aborts migraine headaches rapidly. Acta Neurol Scand. 2011; 123(4): pp. 257–265. doi: 10.1111/j.1600-0404.2010.01394.x.
  • 26. Oskoui M, Pringsheim T, Holler-Managan Y, et al. Practice guideline update summary: Acute treatment of migraine in children and adolescents. Neurology. 2019; 93(11): pp. 487–499. doi: 10.1212/wnl.0000000000008095.
  • 27. American Headache Society. The American Headache Society Position Statement On Integrating New Migraine Treatments Into Clinical Practice. Headache: The Journal of Head and Face Pain. 2018; 59(1): pp. 1–18. doi: 10.1111/head.13456.
  • 28. Marmura MJ, Silberstein SD, Schwedt TJ. The Acute Treatment of Migraine in Adults: The American Headache Society Evidence Assessment of Migraine Pharmacotherapies. Headache: The Journal of Head and Face Pain. 2015; 55(1): pp. 3–20. doi: 10.1111/head.12499.
  • 29. 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; 55(6): pp. 754–762. doi: 10.1212/wnl.55.6.754.
  • 30. Holle D, Obermann M. The role of neuroimaging in the diagnosis of headache disorders. Therapeutic Advances in Neurological Disorders. 2013; 6(6): pp. 369–374. doi: 10.1177/1756285613489765.
  • Rizzato B, Leone G, Misaggi G, Zivi I, Diomedi M. Efficacy and Tolerability of Pregabalin Versus Topiramate in the Prophylaxis of Chronic Daily Headache With Analgesic Overuse. Clin Neuropharmacol. 2011: pp. 74–78. doi: 10.1097/wnf.0b013e318210ecc9.
  • Diener H-C, Bussone G, Oene JV, Lahaye M, Schwalen S, Goadsby P. Topiramate Reduces Headache Days in Chronic Migraine: A Randomized, Double-Blind, Placebo-Controlled Study. Cephalalgia. 2007; 27(7): pp. 814–823. doi: 10.1111/j.1468-2982.2007.01326.x.
  • Pageler L, Katsarava Z, Diener H, Limmroth V. Prednisone vs. Placebo in Withdrawal Therapy Following Medication Overuse Headache. Cephalalgia. 2007; 28(2): pp. 152–156. doi: 10.1111/j.1468-2982.2007.01488.x.
  • Krymchantowski AV, Moreira PF. Out-patient detoxification in chronic migraine: comparison of strategies. Cephalalgia. 2003; 23(10): pp. 982–93. doi: 10.1046/j.1468-2982.2003.00648.x.
  • Drucker P, Tepper S. Daily sumatriptan for detoxification from rebound. Headache. 1998; 38(9): pp. 687–90. doi: 10.1046/j.1526-4610.1998.3809687.x.
  • Tepper SJ. Medication-Overuse Headache. CONTINUUM: Lifelong Learning in Neurology. 2012; 18: pp. 807–822. doi: 10.1212/01.con.0000418644.32032.7b.
  • Tassorelli C, Jensen R, Allena M, et al. A consensus protocol for the management of medication-overuse headache: Evaluation in a multicentric, multinational study. Cephalalgia. 2014; 34(9): pp. 645–655. doi: 10.1177/0333102414521508.
  • Créac’h C, Frappe P, Cancade M, et al. In-patient versus out-patient withdrawal programmes for medication overuse headache: A 2-year randomized trial. Cephalalgia. 2011; 31(11): pp. 1189–1198. doi: 10.1177/0333102411412088.
  • Katsarava Z, Obermann M. Medication-overuse headache. Curr Opin Neurol. 2013; 26(3): pp. 276–281. doi: 10.1097/wco.0b013e328360d596.
  • Da Silva AN, Lake AE. Clinical Aspects of Medication Overuse Headaches. Headache: The Journal of Head and Face Pain. 2013; 54(1): pp. 211–217. doi: 10.1111/head.12223.
  • Diener HC, Limmroth V. Medication-overuse headache: a worldwide problem. The Lancet. Neurology. 2004; 3(8): pp. 475–83. doi: 10.1016/S1474-4422(04)00824-5.
  • Pascual J, Colás R, Castillo J, et al. Epidemiology of chronic daily headache. Curr Pain Headache Rep. 2001; 5(6): pp. 529–36. doi: 10.1007/s11916-001-0070-6.
  • Kristoffersen ES, Lundqvist C. Medication-overuse headache: epidemiology, diagnosis and treatment. Therapeutic advances in drug safety. 2014; 5(2): pp. 87–99. doi: 10.1177/2042098614522683.
  • Wakerley BR et al. Medication-overuse headache. Pract Neurol. 2019; 19(5): pp. 399–403. doi: 10.1136/practneurol-2018-002048.
  • Bendtsen L, et al. EFNS guideline on the treatment of tension-type headache - Report of an EFNS task force. European Journal of Neurology. 2010; 17(11): pp. 1318–1325. doi: 10.1111/j.1468-1331.2010.03070.x.
  • Krymchantowski A, Barbosa J. Prednisone as Initial Treatment of Analgesic-Induced Daily Headache. Cephalalgia. 2000; 20(2): pp. 107–113. doi: 10.1046/j.1468-2982.2000.00028.x.
  • Altieri M, Di Giambattista R, Di Clemente L, et al. Combined Pharmacological and Short-Term Psychodynamic Psychotherapy for Probable Medication Overuse Headache: A Pilot Study. Cephalalgia. 2009; 29(3): pp. 293–299. doi: 10.1111/j.1468-2982.2008.01717.x.
  • Evers S, Jensen R. Treatment of medication overuse headache - guideline of the EFNS headache panel. Eur J Neurol. 2011; 18(9): pp. 1115–1121. doi: 10.1111/j.1468-1331.2011.03497.x.
  • Rossi P, Lorenzo CD, Faroni J, Cesarino F, Nappi G. Advice Alone Vs. Structured Detoxification Programmes for Medication Overuse Headache: A Prospective, Randomized, Open-Label Trial in Transformed Migraine Patients With Low Medical Needs. Cephalalgia. 2006; 26(9): pp. 1097–1105. doi: 10.1111/j.1468-2982.2006.01175.x.
  • Shevel E. The extracranial vascular theory of migraine: an artificial controversy. J Neural Transm (Vienna). 2011; 118(4): pp. 525–530. doi: 10.1007/s00702-010-0517-1.
  • Modi S, Lowder DM. Medications for migraine prophylaxis. Am Fam Physician. 2006; 73(1): pp. 72–78. pmid: 16417067.
  • Bajwa Zh, Smith JH. Preventive treatment of migraine in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/preventive-treatment-of-migraine-in-adults?source=search_result&search=migraine&selectedTitle=3~150#H23. Last updated February 27, 2017. Accessed April 2, 2017.
  • Bajwa Zh, Smith JH. Acute treatment of migraine in adults. In: Post TW, ed. UpToDate. Waltham, MA: UpToDate. https://www.uptodate.com/contents/acute-treatment-of-migraine-in-adults?source=search_result&search=triptans&selectedTitle=1~115#H6. Last updated February 27, 2017. Accessed April 2, 2017.
  • Silberstein SD, Blumenfeld AM, Cady RK, et al. OnabotulinumtoxinA for treatment of chronic migraine: PREEMPT 24-week pooled subgroup analysis of patients who had acute headache medication overuse at baseline. J Neurol Sci. 2013; 331(1-2): pp. 48–56. doi: 10.1016/j.jns.2013.05.003.
last updated 11/20/2020
{{uncollapseSections(['_Da5S5', 'ZwaZh5', '0waeh5', 'Ywanh5', 'bwaHh5', 'Xwa9h5', '1wa235', 'dwao35', 'VwaG35', 'ewax35', 'yh1dgg0'])}}