Migraine
Recurrent primary headache disorder with unilateral throbbing pain, photophobia, nausea.
Also known as: migraine, migraine with aura, migraine without aura, common migraine, classic migraine
Overview
Primary headache disorder characterized by recurrent attacks of moderate-to-severe headache (usually unilateral and pulsating) lasting 4-72 hours, accompanied by nausea, vomiting, photophobia, and/or phonophobia. May be preceded by aura (visual, sensory, language, or motor symptoms) in ~25% of patients.
Epidemiology
Affects ~12% of adults (18% women, 6% men). Peak prevalence age 25-55. Third most common disease worldwide; second leading cause of disability under age 50.
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Risk factors
- Female sex (estrogen fluctuation), family history (~60% heritability)
- Triggers: stress, menstruation (perimenstrual estrogen drop), sleep deprivation or oversleep, fasting/skipped meals, certain foods (aged cheese, processed meats with nitrates, MSG, alcohol especially red wine), weather changes, bright lights, strong odors
- Hormonal contraceptives (especially combined OCPs in migraine with aura — increased stroke risk)
- Comorbidities: depression, anxiety, fibromyalgia, IBS, epilepsy, patent foramen ovale
Pathophysiology
Trigeminovascular activation with release of CGRP (calcitonin gene-related peptide), substance P, and neurokinin A causes neurogenic inflammation and meningeal vasodilation. Cortical spreading depression — a wave of depolarization followed by suppression across the cortex — is thought to underlie aura. Central sensitization in the trigeminal nucleus caudalis produces allodynia and prolonged pain.
Clinical presentation
Symptoms
- Prodrome (hours-days before): mood changes, food cravings, neck stiffness, yawning, urinary frequency
- Aura (~25%): visual (scintillating scotoma, fortification spectra, hemianopia), sensory (paresthesias marching up arm to face), language (aphasia) — typically lasts 5-60 min and precedes headache
- Headache: unilateral (60%) or bilateral, pulsating/throbbing, moderate-severe, lasting 4-72 hours
- Photophobia, phonophobia, osmophobia, nausea, vomiting
- Worsens with routine physical activity; patient prefers dark quiet room
- Postdrome: fatigue, cognitive slowing, mood changes for 24 hours
Signs / physical exam
- Usually normal neurologic exam
- Allodynia (light touch becomes painful) during attack
- Pallor, photophobia evident on exam
- Cranial nerve deficits should prompt imaging (red flag)
Classic findings
POUND mnemonic: Pulsatile, One-day duration (4-72 h), Unilateral, Nausea, Disabling — 4 of 5 features highly suggest migraine.
Differential diagnosis
- Tension-type headache — Bilateral, band-like pressure, no nausea or photophobia, mild-moderate intensity, not aggravated by routine activity
- Cluster headache — Severe unilateral periorbital pain, autonomic features (lacrimation, conjunctival injection, rhinorrhea), restlessness, 15-180 min, cluster periods
- Subarachnoid hemorrhage — Thunderclap onset (worst headache of life), neck stiffness — first or worst headache must be evaluated emergently
- Meningitis — Fever, photophobia, neck stiffness, gradual onset, altered mental status
- Temporal arteritis (GCA) — Age >50, new headache, jaw claudication, scalp tenderness, vision changes, elevated ESR/CRP
- Idiopathic intracranial hypertension — Obese young woman, daily headache, transient visual obscurations, papilledema, elevated opening pressure on LP
- Medication overuse headache — Daily/near-daily headache in patient using analgesics, triptans, or opioids >10-15 days/month
- Cervicogenic headache — Neck pain and limited ROM, unilateral, mechanically reproducible
Diagnostic workup
Diagnostic criteria
ICHD-3 criteria: ≥5 attacks lasting 4-72 hours, with ≥2 of [unilateral, pulsating, moderate-severe, aggravated by activity] AND ≥1 of [nausea/vomiting, photophobia + phonophobia].
Labs
- Generally not indicated for typical migraine
- ESR/CRP if temporal arteritis suspected (age >50)
- CBC, BMP if atypical features
Imaging
- Neuroimaging NOT routinely indicated for typical migraine with normal exam
- MRI brain indicated for: red flags (SNOOP: Systemic symptoms/Secondary risk factors, Neurologic signs, Onset sudden/thunderclap, Older age >50 with new headache, Pattern change/Progressive/Positional/Precipitated by Valsalva)
- Lumbar puncture if SAH or meningitis suspected after negative CT
Diagnostic algorithm
| Phase | Timing | Features |
|---|---|---|
| Prodrome | Hours to days before | Mood changes, food cravings, yawning, neck stiffness, fatigue |
| Aura | 5-60 min before/with HA | Visual scotoma, paresthesias, aphasia — fully reversible |
| Headache | 4-72 hours | Unilateral pulsating moderate-severe pain, nausea, photo/phonophobia |
| Postdrome | Up to 24 hours after | Fatigue, cognitive fog, mood changes, mild residual head discomfort |
Treatment
First-line
- Abortive: NSAIDs (ibuprofen 400-800 mg, naproxen 500 mg) for mild-moderate attacks
- Triptan — sumatriptan 50-100 mg PO (also 6 mg SC, 20 mg nasal), rizatriptan 10 mg, eletriptan 40 mg — best taken at headache onset; contraindicated with CAD, uncontrolled HTN, prior stroke, hemiplegic/basilar migraine, ergot use within 24 h
- Combination (sumatriptan-naproxen) more effective than either alone
- Antiemetic — metoclopramide 10 mg, prochlorperazine 10 mg, ondansetron 4-8 mg — adjunct, also has independent abortive effect
- Gepant (CGRP receptor antagonist) — ubrogepant 50-100 mg, rimegepant 75 mg — no vasoconstriction, safe in CAD
- Ditans — lasmiditan 50-200 mg — 5-HT1F agonist, no vasoconstriction; sedating, driving restriction
Second-line / adjunct
- Prophylaxis indicated for ≥4 migraine days/month, attacks interfering with QOL, or contraindication to abortives
- Beta-blocker — propranolol 80-240 mg/day, metoprolol, timolol (level A evidence)
- Antiepileptic — topiramate 50-100 mg, valproate 500-1500 mg (avoid in pregnancy — teratogen)
- Tricyclic antidepressant — amitriptyline 25-100 mg at bedtime, nortriptyline
- CGRP monoclonal antibody — erenumab 70-140 mg SC monthly, fremanezumab, galcanezumab, eptinezumab IV q3 months
- OnabotulinumtoxinA (Botox) for chronic migraine (≥15 headache days/month)
- Magnesium 400-600 mg/day, riboflavin 400 mg/day, CoQ10 100 mg TID (evidence-based supplements)
- Lifestyle: regular sleep, exercise, hydration, trigger avoidance, stress management
Complications
- Status migrainosus (continuous migraine >72 h) — may require IV therapy and brief steroid taper
- Medication overuse headache (rebound)
- Migrainous infarction (rare — aura symptoms persist >60 min with imaging evidence of stroke)
- Increased risk of ischemic stroke in migraine with aura (especially with smoking, OCPs)
- Chronic migraine (≥15 days/month for >3 months)
- Depression, anxiety, reduced QOL and work productivity
PANCE pearls
- Triptans are most effective when taken at the very start of the headache, before central sensitization develops.
- Migraine with aura + combined hormonal contraceptive significantly increases ischemic stroke risk — use progestin-only or non-hormonal methods.
- Hemiplegic migraine and basilar-type migraine are contraindications to triptans (theoretical risk of vasoconstriction in already-affected vessels).
- First or worst-of-life headache, focal deficits outlasting aura duration, or any 'thunderclap' onset = imaging mandatory.
- Medication overuse headache: taper offending agent; can transition acute therapy to gepants (no rebound risk).
References
- AAN/AHS 2021 — Acute Treatment of Migraine in Adults: AHS Consensus Statement (Ailani et al., Headache 2021)
- AHS 2024 — Pharmacologic Treatment for Migraine Prevention in Adults: AHS Position Statement (Charles et al., Headache 2024)
- ICHD-3 — International Classification of Headache Disorders, 3rd edition (Headache Classification Committee of the International Headache Society, Cephalalgia 2018)
- AAN Imaging — Choosing Wisely: Don't perform neuroimaging studies in patients with stable headaches that meet criteria for migraine (American Academy of Neurology)
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