Clinical Headache

Migraine

Migraine

What You'll Learn

  • ICHD-3 without aura: ≥5 attacks, 4–72 h, 2 of 4 headache features + 1 of 2 associated symptoms
  • Aura timing: gradual spread ≥5 min; each non-motor aura symptom usually lasts 5–60 min; motor aura in hemiplegic migraine may last up to 72 h; followed by headache within 60 min
  • CSD: cortical spreading depression (3–5 mm/min) — aura is cortical, NOT vascular
  • Hemiplegic migraine genetics: FHM1 = CACNA1A (most common), FHM2 = ATP1A2 (Na+/K+-ATPase α2 subunit), FHM3 = SCN1A
  • Triptan window: 5-HT1B/1D agonists most effective within 2 h of onset; contraindicated in cardiovascular disease
  • CGRP pathway: gepants (acute) + mAbs (preventive) — non-vasoconstrictive option when triptans are contraindicated by CAD, stroke, PVD, or hemiplegic/brainstem aura migraine; monitor for new/worsening HTN and Raynaud phenomenon per labeling (not risk-free in uncontrolled HTN)
  • MOH threshold: triptans/ergots/opioids/combination ≥10 d/month; simple analgesics ≥15 d/month
HighYield Pearls
  • ICHD-3 without aura: ≥5 attacks, 4–72 h untreated, ≥2 of (unilateral, pulsating, moderate/severe, aggravated by routine activity) + ≥1 of (N/V, photo/phonophobia)
  • ICHD-3 with aura: ≥2 attacks with ≥1 reversible aura (visual, sensory, language, motor, brainstem, retinal); each non-motor aura symptom usually lasts 5–60 min (motor aura in hemiplegic migraine may last up to 72 h); headache within 60 min
  • Chronic migraine: ≥15 headache days/mo × ≥3 mo with ≥8 days meeting migraine criteria
  • Hemiplegic migraine genetics: FHM1 = CACNA1A, FHM2 = ATP1A2, FHM3 = SCN1A — AVOID triptans (use gepants/ditans/NSAIDs)
  • Status migrainosus: >72 h disabling migraine → IV fluids, antiemetic, ketorolac, magnesium, valproate, DHE, occipital nerve block; AVOID opioids
  • MOH: ≥10 d/mo triptans/ergots/opioids OR ≥15 d/mo simple analgesics → withdraw + bridge
  • Triptan contraindications: CAD, uncontrolled HTN, stroke, hemiplegic migraine / migraine with brainstem aura
  • Gepants vs ditans: gepants (rimegepant, ubrogepant, atogepant, zavegepant) = CGRP receptor antagonists, non-vasoconstrictive when triptans are contraindicated (monitor for new/worsening HTN + Raynaud per labeling); ditan (lasmiditan) = 5-HT1F agonist with CNS impairment, Schedule V, mandatory 8 h driving restriction
  • CGRP mAbs (prevention): erenumab, fremanezumab, galcanezumab, eptinezumab
  • Botox (onabotulinumtoxinA): CHRONIC migraine only (PREEMPT protocol 155–195 U, 31–39 sites, q12wk) — NOT episodic
  • Prevention thresholds: ≥4 migraine days/mo or significant disability → propranolol/metoprolol/timolol, topiramate, valproate, amitriptyline, venlafaxine, atogepant/rimegepant
  • Pregnancy: acetaminophen +/- metoclopramide is the usual first-line acute approach; AVOID topiramate (cleft lip) + valproate (teratogen); AVOID NSAIDs at ≥20 weeks gestation unless specifically indicated and supervised (FDA 2020), especially at ≥30 weeks (ductus arteriosus closure risk)
  • SNOOP red flags: Systemic, Neurologic deficit, Onset thunderclap, Older >50, Positional/Progressive/Pattern change → image (MRI ± MRA/MRV)
🔍 Quick ReferenceClinical · Imaging / red flags · Treatment / pharmacology
Clinical phenotype
  • Throbbing/pulsating unilateral pain + N/V + photo/phonophobiaMigraine
  • Scintillating scotoma, fortification spectra, zigzag expanding from centerVisual aura
  • Cheiro-oral sensory marchSensory aura
  • Prodrome: yawning, cravings, mood changesMigraine prodrome
  • Alice in Wonderland syndrome (size/shape distortion)Rare migraine aura
  • Allodynia / cutaneous sensitizationCentral sensitization in migraine
  • Dizziness + migraine featuresVestibular migraine
  • Monocular visual loss with migraineRetinal migraine
  • Motor auraHemiplegic migraine
  • Vertigo, dysarthria, diplopia, tinnitus, ataxia, ↓ consciousnessMigraine with brainstem aura (formerly "basilar migraine")
  • Cyclic vomiting, abdominal migraine, benign paroxysmal vertigoChildhood migraine variants
  • >72 h disabling migraineStatus migrainosus
Imaging / red flags
  • SNOOP red flagsMRI ± MRA/MRV workup
  • Nonspecific white matter hyperintensities (more with aura)Migraine brain MRI
  • Anterior temporal pole WM + lacunes, AD inheritanceCADASIL
  • Stroke-like episodes + lactic acidosisMELAS
  • Focal pulsatile headacheAVM
  • Thunderclap + segmental vasoconstrictionRCVS
  • Vasogenic edema parieto-occipitalPRES
  • Prolonged aura >60 min, motor/brainstem aura, age >50 onsetImage to exclude mimics
Treatment / pharmacology pearls
  • Sumatriptan SC 6 mgFastest acute migraine + cluster onset
  • Rimegepant / ubrogepant (gepants)CGRP receptor antagonists; non-vasoconstrictive when triptans contraindicated (CAD/stroke/PVD/hemiplegic/brainstem aura) — monitor for new/worsening HTN and Raynaud per labeling
  • Rimegepant every other dayAlso approved for prevention
  • Lasmiditan (ditan)5HT1F agonist, no vasoconstriction, 8 h driving restriction
  • Erenumab / fremanezumab / galcanezumab / eptinezumabCGRP mAbs for prevention
  • OnabotulinumtoxinA (PREEMPT 155–195 U, 31–39 sites, q12wk)Chronic migraine only
  • TopiramatePrevention; cleft lip in pregnancy, kidney stones, cognitive slowing
  • Propranolol / metoprolol / timololβ-blocker prevention
  • Amitriptyline / venlafaxineAdjunct prevention
  • Atogepant / rimegepantOral gepants for prevention
  • Riboflavin 400 mg, magnesium 400–600 mg, CoQ10Nutraceutical prevention
  • IV DHE, magnesium, valproate, ketorolac, antiemeticStatus migrainosus bundle
  • AVOID triptansCAD, uncontrolled HTN, stroke, hemiplegic migraine / migraine with brainstem aura
  • AVOID opioids / butalbitalMOH and bounce-back headache
  • Acetaminophen first-linePregnancy migraine
ICHD-3 Diagnostic Criteria

Migraine Without Aura (1.1)

  • A. ≥5 attacks fulfilling B–D
  • B. Duration 4–72 h (untreated or unsuccessfully treated)
  • C. ≥2 of 4: unilateral, pulsating, moderate-severe, aggravated by routine physical activity
  • D. During headache, ≥1 of: (a) nausea and/or vomiting, OR (b) photophobia AND phonophobia (both required together as a single criterion — not all of D required)
  • E. Not better accounted for by another diagnosis

Migraine With Aura (1.2)

  • A. ≥2 attacks fulfilling B–C
  • B. ≥1 fully reversible aura symptom (visual, sensory, speech/language, motor, brainstem, retinal)
  • C. ≥3 of 6: gradual spread ≥5 min, 2+ symptoms in succession, each non-motor symptom lasts 5–60 min (motor aura in hemiplegic migraine may last up to 72 h), ≥1 unilateral, ≥1 positive symptom, accompanied/followed within 60 min by headache

Key Diagnostic Thresholds

FeatureWithout Aura (1.1)With Aura (1.2)
Minimum attacks52
Duration4–72 hEach non-motor aura symptom 5–60 min (motor aura in hemiplegic migraine up to 72 h)
Headache features required≥2 of 4Not required
Associated symptoms≥1 of 2Not required
Aura characteristicsN/A≥3 of 6
💎 Board Pearl
  • Without aura requires 5 attacks; with aura requires only 2 — classic board trap
  • Photophobia and phonophobia count as a single criterion — both must be present together
Aura Types & Pathophysiology

Aura Subtypes

TypeFrequencyFeatures
Visual~90%Scintillating scotoma (fortification spectra), photopsia; binocular
Sensory~30%Paresthesias spreading hand → arm → face; cheiro-oral distribution
Speech/language~10%Dysphasia (expressive > receptive)
MotorRareHemiparesis; only in hemiplegic migraine
BrainstemRareDysarthria, vertigo, tinnitus, diplopia, ataxia, ↓ consciousness
RetinalVery rareMonocular visual symptoms

Cortical Spreading Depression (CSD)

  • Wave of neuronal/glial depolarization propagating at 3–5 mm/min across cortex
  • Brief excitation → prolonged cortical suppression → transient oligemia
  • Follows gray matter, respects sulcal boundaries; explains gradual aura march
  • CSD activates trigeminovascular afferents → CGRP release → neurogenic inflammation

Trigeminovascular System

  • Trigeminal ganglion → perivascular C-fibers → CGRP/substance P release → neurogenic inflammation
  • Relay: trigeminal nucleus caudalis → thalamus (VPM) → cortex
  • Peripheral sensitization → central sensitization (cutaneous allodynia) → reduced treatment efficacy
💎 Board Pearl
  • Aura is a cortical phenomenon (CSD), NOT vascular — favorite board question
  • CSD velocity (3–5 mm/min) matches gradual aura spread; seizure propagation is much faster
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