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

Aura Subtypes

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

Hemiplegic Migraine

• Motor aura (hemiparesis) + ≥1 other aura type; weakness may last hours to days
• Triptans traditionally avoided (though evidence for harm is limited)

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%

Triptans (5-HT_1B/1D Agonists)

• Vasoconstriction (5-HT_1B) + inhibit trigeminovascular neuropeptide release (5-HT_1D)
• Most effective within 2 h of onset; avoid in CAD, uncontrolled HTN, stroke/TIA, PVD

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 → 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

Ditans & Other Acute Therapies

• Lasmiditan (5-HT_1F): 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

Indications

• ≥4 migraine days/month, significant disability, failed/contraindicated acute treatments, or medication overuse

First-Line Oral Preventives

CGRP Monoclonal Antibodies

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

Overuse Thresholds

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

Pregnancy

• Acute: acetaminophen first-line; metoclopramide for nausea; NSAIDs acceptable in 1st and early 2nd trimester; avoid after 20 weeks (oligohydramnios) and especially after 30 weeks (premature ductus arteriosus closure)
• 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

Diagnostic Criteria (Lempert 2012 / Bárány Society 2022)

• A. ≥5 episodes of vestibular symptoms of moderate or severe intensity, lasting 5 minutes to 72 hours
• B. Current or previous history of migraine with or without aura (ICHD-3 criteria)
• C. ≥50% of vestibular episodes accompanied by ≥1 migrainous feature: headache (with ≥2 of unilateral, pulsating, moderate/severe, aggravated by activity), photophobia and phonophobia, or visual aura
• D. Not better accounted for by another vestibular or ICHD-3 diagnosis

Clinical Notes

• Most common cause of episodic spontaneous vertigo in adults; lifetime prevalence ~1%
• Vertigo and headache often dissociate — headache may be absent during vertigo episode
• Treatment mirrors migraine prophylaxis (propranolol, topiramate, amitriptyline, venlafaxine, CGRP mAbs); vestibular rehabilitation adjunct

Diagnostic Criteria

• A. A migraine with aura attack typical of previous attacks, except that one or more aura symptoms persist for >60 minutes
• B. Neuroimaging demonstrates ischemic infarction in a relevant territory
• C. Aura symptoms occur during a typical migraine-with-aura attack
• D. Not better accounted for by another diagnosis

Clinical Notes

• Most often in posterior circulation (PCA territory); young women with migraine with aura are highest-risk group
• Must exclude other stroke etiologies (cardioembolic, dissection, hypercoagulable, vasculopathy) — migrainous infarction is a diagnosis of exclusion
• Distinguish from persistent aura without infarction (1.4.2): aura >1 week, no infarct on imaging

Definition

• Debilitating migraine attack lasting >72 hours despite treatment (ICHD-3 1.4.1)
• Pain-free intervals <12 hours not counted as interruption (excludes sleep)

IV / ED Management

• IV fluids: normal saline bolus for volume/rehydration
• IV ketorolac 30 mg (NSAID; avoid if renal disease, GI bleed, recent surgery)
• IV metoclopramide 10 mg or prochlorperazine 10 mg + diphenhydramine 25–50 mg (prevents akathisia/dystonia)
• IV magnesium sulfate 1–2 g — particularly effective for migraine with aura
• IV dexamethasone 10–20 mg single dose — reduces 24–72 h headache recurrence
• DHE Raskin protocol: 0.5–1 mg IV every 8 h × 9 doses with antiemetic pre-treatment; avoid within 24 h of triptans, in CAD, uncontrolled HTN, pregnancy, peripheral vascular disease
• Avoid opioids (ineffective, high MOH risk, central sensitization)

Acute & Preventive Devices

Nutraceuticals (AAN/AHS Level B, prevention)

• Magnesium 400–600 mg/day — especially migraine with aura, menstrual migraine, pregnancy.
• Riboflavin (vitamin B2) 400 mg/day — classic mitochondrial-targeted preventive; few side effects (orange urine).
• CoQ10 100 mg TID — mitochondrial cofactor; pediatric option.
• Feverfew (Tanacetum parthenium) — Level B; rebound headache and oral ulcers possible.
• Butterbur (Petasites) — Level A by efficacy but AHS/AAN no longer recommends due to hepatotoxicity from unregulated pyrrolizidine alkaloid content. Avoid unless PA-free preparation confirmed.
• Melatonin 3 mg qhs — emerging evidence for prevention; particularly useful in cluster headache prophylaxis (9 mg qhs).

Clinical Overlap

• TGA: abrupt, isolated anterograde amnesia with repetitive questioning, lasting <24 h (typically 4–8 h), no other neurological deficits, no LOC, no seizure features.
• Patients with a personal history of migraine have higher TGA incidence; the migraine-TGA association is a long-recognized board-level link.
• Common triggers: emotional stress, Valsalva (cold water immersion, sexual activity), pain — reflect proposed mechanism of venous congestion of medial temporal lobes.
• DWI signature: punctate dot-like hyperintensities in the lateral hippocampus (CA1 Sommer sector), best seen at 48–72 h.
• Distinguish from transient epileptic amnesia (recurrent, brief, often on waking, EEG abnormal) and from posterior circulation TIA (other deficits, vascular risk factors).

Evidence Summary

• PFO closure is NOT routinely recommended for migraine prevention — not a standard migraine therapy
• MIST (2008): first randomized sham-controlled trial; negative for primary endpoint (migraine cessation)
• PRIMA (2016): negative for primary endpoint (reduction in monthly migraine days in migraine with aura)
• PREMIUM (NEJM/JACC 2017): negative for primary endpoint; secondary analysis suggested benefit in migraine-with-aura subgroup

When Closure May Be Considered

• Patient has refractory migraine with aura AND a clinically appropriate indication for PFO closure (e.g., cryptogenic stroke meeting RoPE/PASCAL criteria with high-risk PFO features)
• Migraine improvement, if it occurs, is considered a possible secondary benefit — not the indication

Five Evidence-Based Lifestyle Pillars