Migraine
Migraine
What Do You Need to Know?
- 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 symptom 5–60 min, 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 = ATP1A3, 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) — safe in vascular disease unlike triptans
- MOH threshold: triptans/ergots/opioids/combination ≥10 d/month; simple analgesics ≥15 d/month
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. ≥1 of: nausea/vomiting OR photophobia AND phonophobia (both required together)
- 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 lasts 5–60 min, ≥1 unilateral, ≥1 positive symptom, accompanied/followed within 60 min by headache
Key Diagnostic Thresholds
| Feature | Without Aura (1.1) | With Aura (1.2) |
|---|---|---|
| Minimum attacks | 5 | 2 |
| Duration | 4–72 h | Aura 5–60 min each |
| Headache features required | ≥2 of 4 | Not required |
| Associated symptoms | ≥1 of 2 | Not required |
| Aura characteristics | N/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
| Type | Frequency | Features |
|---|---|---|
| Visual | ~90% | Scintillating scotoma (fortification spectra), photopsia; binocular |
| Sensory | ~30% | Paresthesias spreading hand → arm → face; cheiro-oral distribution |
| Speech/language | ~10% | Dysphasia (expressive > receptive) |
| Motor | Rare | Hemiparesis; only in hemiplegic migraine |
| Brainstem | Rare | Dysarthria, vertigo, tinnitus, diplopia, ataxia, ↓ consciousness |
| Retinal | Very rare | Monocular 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
Migraine Subtypes
Hemiplegic Migraine
- Motor aura (hemiparesis) + ≥1 other aura type; weakness may last hours to days
- Triptans traditionally avoided (though evidence for harm is limited)
| Type | Gene | Protein | Key Association |
|---|---|---|---|
| FHM1 | CACNA1A | P/Q-type Ca2+ channel | Most common; also EA-2, SCA6 |
| FHM2 | ATP1A2 | Na+/K+-ATPase α2 | Childhood seizures, intellectual disability |
| FHM3 | SCN1A | NaV1.1 | Also Dravet syndrome, GEFS+ |
Vestibular Migraine
- ≥5 episodes of vestibular symptoms (moderate/severe, 5 min–72 h)
- Current or past migraine history (with or without aura)
- ≥50% of vestibular episodes with ≥1 migraine feature (headache, photo/phonophobia, visual aura)
- Most common cause of episodic vertigo in young adults
Migraine With Brainstem Aura
- ≥2 brainstem symptoms: dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia, ↓ consciousness
- NO motor weakness (would be hemiplegic migraine); triptans traditionally avoided
Chronic Migraine
- ≥15 headache days/month for >3 months; ≥8 days with migraine features
- Must exclude MOH; prevalence ~2%
💎 Board Pearl
- CACNA1A: FHM1, EA-2, SCA6 — all from the same P/Q-type calcium channel gene
- SCN1A causes both FHM3 AND Dravet syndrome — board favorite genotype-phenotype link
Acute Treatment
Triptans (5-HT1B/1D Agonists)
- Vasoconstriction (5-HT1B) + inhibit trigeminovascular neuropeptide release (5-HT1D)
- Most effective within 2 h of onset; avoid in CAD, uncontrolled HTN, stroke/TIA, PVD
| Triptan | Route | Onset | Half-Life | Key Feature |
|---|---|---|---|---|
| Sumatriptan | SC, PO, nasal | SC: 10 min | ~2 h | SC = fastest onset of all triptans |
| Rizatriptan | PO, ODT | 30 min | 2–3 h | Reduce dose with propranolol |
| Zolmitriptan | PO, nasal, ODT | 45 min | ~3 h | Nasal spray good for nausea |
| Eletriptan | PO | 30 min | ~4 h | Highest efficacy (NNT ~3) |
| Almotriptan | PO | 30–60 min | 3–4 h | Best tolerability; approved ≥12 yr |
| Naratriptan | PO | 60 min | 5–6 h | Lower recurrence; menstrual migraine |
| Frovatriptan | PO | 2–4 h | 26 h | Longest half-life; menstrual prophylaxis |
Gepants (CGRP Receptor Antagonists)
- Ubrogepant: 50–100 mg PO; acute only
- Rimegepant: 75 mg PO/ODT; dual acute + preventive (every other day)
- Zavegepant: 10 mg nasal spray; rapid onset acute use
- No vasoconstriction → safe in cardiovascular disease
Ditans & Other Acute Therapies
- Lasmiditan (5-HT1F): 50–200 mg PO; no vasoconstriction; CNS effects — no driving for 8 h; Schedule V
- NSAIDs: ibuprofen, naproxen, diclofenac; ketorolac IM/IV for ED
- Anti-emetics: metoclopramide (also analgesic), prochlorperazine — effective as monotherapy in ED
- DHE: IV protocol for refractory/status migrainosus; avoid within 24 h of triptans
💎 Board Pearl
- Gepants safe in cardiovascular disease unlike triptans — key board differentiator
- Sumatriptan SC = fastest; frovatriptan = longest half-life (26 h); eletriptan = highest efficacy
- Reduce rizatriptan dose with propranolol (MAO-A inhibition raises rizatriptan levels)
Preventive Treatment
Indications
- ≥4 migraine days/month, significant disability, failed/contraindicated acute treatments, or medication overuse
First-Line Oral Preventives
| Drug | Dose Range | Key Side Effects | Notes |
|---|---|---|---|
| Propranolol | 40–240 mg/d | Fatigue, bradycardia, depression | Level A; avoid in asthma |
| Topiramate | 50–200 mg/d | Cognitive dulling, weight loss, stones | Level A; teratogenic (cleft lip/palate) |
| Valproate | 500–1500 mg/d | Weight gain, tremor, hepatotoxicity | Level A; contraindicated in pregnancy |
| Amitriptyline | 10–150 mg/d | Sedation, weight gain, dry mouth | Level B; best with comorbid insomnia |
CGRP Monoclonal Antibodies
| Drug | Target | Route | Dosing | Key Feature |
|---|---|---|---|---|
| Erenumab | CGRP receptor | SC | 70–140 mg monthly | Only receptor-targeted mAb |
| Fremanezumab | CGRP ligand | SC | 225 mg monthly / 675 mg quarterly | Quarterly option |
| Galcanezumab | CGRP ligand | SC | 240 mg load → 120 mg monthly | Also for cluster headache |
| Eptinezumab | CGRP ligand | IV | 100–300 mg quarterly | Only IV mAb; fastest onset |
OnabotulinumtoxinA (Botox)
- Chronic migraine only (≥15 days/month); NOT effective for episodic migraine
- PREEMPT protocol: 155 units, 31 injection sites, every 12 weeks
- Mechanism: inhibits CGRP and substance P release from trigeminal sensory neurons
💎 Board Pearl
- Topiramate = cleft lip/palate; valproate = NTDs + reduced IQ — must counsel on contraception
- Erenumab targets the CGRP receptor; the other 3 mAbs target the ligand
- Botox for chronic migraine ONLY (PREEMPT); no benefit in episodic migraine
Medication Overuse Headache (MOH)
Overuse Thresholds
| Medication Class | Threshold | MOH Risk |
|---|---|---|
| Opioids | ≥10 days/month | Highest risk; fastest onset |
| Triptans | ≥10 days/month | Moderate |
| Ergotamines | ≥10 days/month | Moderate |
| Combination analgesics | ≥10 days/month | Higher than simple analgesics |
| Simple analgesics | ≥15 days/month | Lowest risk |
Management
- Withdrawal: abrupt preferred (except opioids/barbiturates — taper); rebound worsening 2–10 days
- Bridge: short course NSAIDs, corticosteroids, or nerve blocks
- Preventive: start simultaneously; topiramate and CGRP mAbs have best MOH evidence
- Patient education: limit acute medications to ≤2–3 days/week
💎 Board Pearl
- Opioids = highest MOH risk + least effective for migraine — avoid in migraine management
- Simple analgesics = 15 days/month; everything else = 10 days/month
Special Populations
Pregnancy
- Acute: acetaminophen first-line; metoclopramide for nausea; NSAIDs 2nd trimester only
- Avoid: triptans, ergotamines (uterotonic), valproate, topiramate
- Preventive: propranolol (taper before delivery), magnesium; GON blocks (lidocaine) safe
- Migraine often improves 2nd–3rd trimester (estrogen stabilization)
Menstrual Migraine
- Occurs −2 to +3 days of menses (estrogen withdrawal); frovatriptan 2.5 mg BID or naproxen 500 mg BID starting 2 days before menses
Pediatric Migraine
- Shorter duration (2–72 h adolescents; 1–2 h in children); often bilateral; prominent GI symptoms
- Acute: ibuprofen first-line; sumatriptan nasal spray approved ≥12 yr
- CHAMP trial: amitriptyline and topiramate NOT superior to placebo in children
Migraine & Stroke Risk
- Migraine with aura → ~2× ischemic stroke risk (especially young women)
- Multiplicative: migraine with aura + OCP + smoking = dramatically elevated risk
- Estrogen-containing contraceptives contraindicated in migraine with aura; progestin-only acceptable
Clinical Pearl
Migraine with aura + estrogen-containing OCP + smoking creates multiplicative stroke risk. Combined hormonal contraceptives are contraindicated in migraine with aura regardless of smoking status.
💎 Board Pearl
- CHAMP trial: amitriptyline and topiramate no better than placebo in pediatric migraine
- Frovatriptan (longest half-life) is preferred for perimenstrual prophylaxis
References
- Headache Classification Committee of the IHS. The International Classification of Headache Disorders, 3rd edition (ICHD-3). Cephalalgia. 2018;38(1):1-211.
- Silberstein SD, Holland S, Freitag F, et al. Evidence-based guideline update: pharmacologic treatment for episodic migraine prevention. Neurology. 2012;78(17):1337-1345.
- American Headache Society. Consensus statement: update on integrating new migraine treatments into clinical practice. Headache. 2021;61(7):1021-1039.
- Dodick DW. A phase-by-phase review of migraine pathophysiology. Headache. 2018;58(Suppl 1):4-16.
- Powers SW, Coffey CS, Chamberlin LA, et al. Trial of amitriptyline, topiramate, and placebo for pediatric migraine (CHAMP). N Engl J Med. 2017;376(2):115-124.
- Lipton RB, Tepper SJ, Reuter U, et al. Erenumab in chronic migraine (STRIVE, ARISE, LIBERTY trials). N Engl J Med. 2017;377(22):2123-2132.