Migraine

Definition

Epidemiology

• Affects 15-20% of women and 4-7% of men; estimated 1 billion people worldwide
• In children, prevalence is up to 17%, equal in boys and girls; rises sharply in girls at puberty
• Peak prevalence: ages 25-55 years
• Migraine with aura affects ~5% of adults; 90% of auras are visual
• More prevalent in White individuals and those with lower socioeconomic status
• Women are affected 3 times more often than men; 90% have a positive family history
• Comorbidities include epilepsy, stroke, depression, anxiety, asthma, irritable bowel syndrome, fibromyalgia, and patent foramen ovale
• Goldman-Cecil Medicine, p. 725; Textbook of Family Medicine 9e, p. 1217

Pathophysiology

Cortical Spreading Depression (CSD)

• The aura of migraine is thought to result from cortical spreading depression (CSD) - a slow wave of neuronal depolarization that spreads at ~3 mm/min across the cortex
• CSD is associated with a brief reduction in blood flow followed by hyperemia
• This slow spread explains why migraine aura typically lasts 5-60 minutes (vs. epileptic auras, which last <30 seconds due to faster propagation)

Trigeminovascular Pathway

• Pain occurs when trigeminal afferents of the dura are stimulated
• Activation of the trigeminovascular system releases neuropeptides, including calcitonin gene-related peptide (CGRP), causing neurogenic inflammation

Serotonin (5-HT) Hypothesis

• Plasma and platelet 5-HT concentrations vary with different phases of the attack
• Urinary 5-HT and its metabolites are elevated during most attacks
• Agents that release 5-HT (e.g., reserpine, fenfluramine) can precipitate migraine
• 5-HT1B/1D receptor agonists (triptans) are the most effective acute treatments
• The mechanism involves constriction of intracranially dilated blood vessels and inhibition of trigeminovascular neuropeptide release
• Goodman & Gilman's Pharmacological Basis of Therapeutics, p. 3042-3056; Goldman-Cecil Medicine, p. 732-733

Classification and Clinical Features

Phases of a Migraine Attack

Types

Aura Characteristics

• Visual aura (most common - 90%): positive (photopsias, scintillating scotoma - zigzag lines) and negative (scotomas) features
• Sensory aura: spreading paresthesias/numbness with a "marching" quality, often ipsilateral arm or periorbital
• Motor aura: spreading deficits
• Speech aura: mild dysphasia
• Textbook of Family Medicine 9e, p. 1217; Goldman-Cecil Medicine, p. 724-741

Diagnosis

IHS/ICHD Criteria for Migraine Without Aura

1. Duration 4-72 hours
2. At least 2 of: (a) unilateral location, (b) pulsating quality, (c) moderate-severe intensity, (d) aggravated by routine activity
3. During headache, at least 1 of: (a) nausea/vomiting, (b) photophobia AND phonophobia

POUND Mnemonic (ED use)

When to Image

• If history suggests secondary headache (red flags: thunderclap onset, focal neurological deficits, papilledema, age >50, systemic illness, immunocompromise), order MRI
• If headache is typical of migraine with normal neurological exam, no further studies are needed
• Tintinalli's Emergency Medicine, p. 1326; Goldman-Cecil Medicine, p. 744-747

Triggers

Treatment

Acute (Abortive) Treatment

Mild-Moderate Attacks

• NSAIDs (ibuprofen, naproxen, aspirin) - first line for mild attacks
• Acetaminophen (alone or combined with caffeine/aspirin)
• Combination analgesics (e.g., acetaminophen + aspirin + caffeine)

Moderate-Severe Attacks - Migraine-Specific

• Triptans (5-HT1B/1D agonists) - first-line home therapy for moderate-to-severe migraine
  • Sumatriptan (first triptan; intranasal, subcutaneous, oral), zolmitriptan, rizatriptan, eletriptan, almotriptan, naratriptan, frovatriptan
  • Contraindicated in coronary artery disease, uncontrolled hypertension, hemiplegic/basilar migraine
• Ergotamines (ergotamine, dihydroergotamine) - older agents; significant contraindications
• CGRP receptor antagonists (gepants): ubrogepant, rimegepant - newer; useful when triptans are contraindicated
• Lasmiditan (5-HT1F agonist) - no vasoconstrictive activity

Emergency Department Treatment

• IV dopamine receptor antagonists: prochlorperazine, metoclopramide, droperidol (first-line in ED)
• IV NSAIDs (ketorolac)
• Antihistamines (diphenhydramine 25-50 mg IV) combined to prevent akathisia from antiemetics
• IV steroids (dexamethasone) to reduce headache recurrence after discharge
• Opiates and barbiturate-containing agents should NOT be used routinely

Preventive (Prophylactic) Treatment

Non-Pharmacologic Management

• Identify and avoid triggers
• Regular sleep schedule and exercise
• Stress management
• Biofeedback and cognitive-behavioral therapy
• Goldman-Cecil Medicine, p. 750; Textbook of Family Medicine 9e, p. 1217; Tintinalli's Emergency Medicine, p. 1330-1340; Goodman & Gilman's, p. 3050-3056

Special Populations

Pregnancy

• Over 80% of women with migraine improve during pregnancy, especially in 2nd and 3rd trimesters
• 5% worsen; those with migraine with aura and menstrual migraine are less likely to improve
• Contraindicated in pregnancy: triptans, ergotamines, valproate (teratogenic), topiramate (teratogenic), CGRP monoclonal antibodies (theoretical risk to uteroplacental blood flow)
• Safe options: acetaminophen (first-line), metoclopramide (FDA category B), opioids or corticosteroids (cautiously); NSAIDs until third trimester
• Migraine in pregnancy increases risk for preeclampsia, peripartum stroke, gestational hypertension
• Bradley and Daroff's Neurology, p. 2860-2871; Tintinalli's Emergency Medicine, p. 1338

Differential Diagnosis

• Tension-type headache: bilateral, pressing/tightening quality, mild-moderate, no nausea/photophobia, not worsened by activity
• Cluster headache: unilateral orbital/periorbital, severe, autonomic features (lacrimation, rhinorrhea), short duration (15 min-3 hrs), cyclical
• Subarachnoid hemorrhage: thunderclap "worst headache of life," requires urgent CT/LP
• Temporal arteritis: age >50, jaw claudication, elevated ESR, risk of visual loss
• Occipital lobe seizures: shorter aura (<30 sec), followed by migraine-like headache (can be difficult to distinguish)

Key Points Summary

• Migraine is a common, disabling neurological disorder affecting ~1 billion people globally
• Pathophysiology involves cortical spreading depression (aura) and trigeminovascular activation (pain), with serotonin and CGRP as key mediators
• Diagnosis is clinical (ICHD criteria); imaging only if red flags are present
• Triptans are first-line for moderate-to-severe acute attacks at home; dopamine antagonists (metoclopramide, prochlorperazine) are first-line in the ED
• CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab) represent a major advance in preventive treatment
• Valproate and topiramate are contraindicated or restricted in women of childbearing age due to teratogenicity