Neurology · PANCE / PANRE

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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Question 1NeurologyEasy
A 25-year-old woman has a unilateral throbbing headache with nausea and photophobia, preceded by 20 minutes of visual zigzag lines. She has had several similar episodes, and her neurologic examination between attacks is normal. Which of the following is the most appropriate acute abortive therapy?
  • ATopiramate
  • BVerapamil
  • CPropranolol
  • DSumatriptan
Reveal answer & full explanation
Correct answer: D — Sumatriptan
  • ATopiramate
  • BVerapamil
  • CPropranolol
  • DSumatriptan

Why Sumatriptan is correct

  • The unilateral throbbing headache with nausea and photophobia preceded by a visual aura is migraine with aura; acute abortive therapy is a triptan (5-HT1B/1D agonist), often combined with an NSAID.
  • Triptans abort the attack by causing cranial vasoconstriction and inhibiting trigeminal nociceptive transmission.
  • They are avoided in hemiplegic migraine, migraine with brainstem aura (formerly basilar migraine), and in coronary artery disease or uncontrolled hypertension.

Why the others are wrong

  • Topiramate — used for migraine prophylaxis when attacks are frequent, not to abort an acute attack (right-diagnosis-wrong-step).
  • Verapamil — first-line prophylaxis for cluster headache, not an abortive migraine therapy (buzzword-matching headache to the wrong syndrome).
  • Propranolol — a migraine prophylactic agent, not an abortive therapy (right-diagnosis-wrong-step).
Question 2NeurologyEasy
A 32-year-old woman presents to the office during an acute, severe migraine headache with throbbing unilateral pain, photophobia, and nausea. Her past medical history is unremarkable, she has no cardiovascular disease, and she is not pregnant. Which of the following is the most appropriate agent to abort the current attack?
  • ATopiramate
  • BSumatriptan
  • CAmitriptyline
  • DPropranolol
Reveal answer & full explanation
Correct answer: B — Sumatriptan
  • ATopiramate
  • BSumatriptan
  • CAmitriptyline
  • DPropranolol

Why Sumatriptan is correct

  • Sumatriptan is a 5-HT1B/1D receptor agonist used to abort an acute migraine attack
  • It is the most appropriate agent to treat the active headache described, in a patient with no cardiovascular contraindication
  • Abortive therapy targets the ongoing attack, distinct from preventive therapy taken daily to reduce attack frequency

Why the others are wrong

  • Topiramate — an antiepileptic used for migraine PREVENTION, not to abort an acute attack (right-disease-wrong-indication)
  • Amitriptyline — a tricyclic used for migraine PREVENTION, especially with comorbid tension headache or insomnia; it does not abort an attack (right-disease-wrong-indication)
  • Propranolol — a beta-blocker used for migraine PREVENTION with strong evidence, but it has no role in aborting an active migraine (right-disease-wrong-indication)
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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

PhaseTimingFeatures
ProdromeHours to days beforeMood changes, food cravings, yawning, neck stiffness, fatigue
Aura5-60 min before/with HAVisual scotoma, paresthesias, aphasia — fully reversible
Headache4-72 hoursUnilateral pulsating moderate-severe pain, nausea, photo/phonophobia
PostdromeUp to 24 hours afterFatigue, cognitive fog, mood changes, mild residual head discomfort
Phases of a migraine attack — not all patients experience all phases.

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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