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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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

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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