Migraine

Migraine

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migraine pathophysiology classification diagnosis clinical features

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migraine treatment acute abortive therapy preventive management

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migraine aura visual symptoms diagram

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Overview

Migraine is a primary headache disorder characterized by recurrent episodes of moderate-to-severe head pain, typically unilateral and pulsating, accompanied by autonomic symptoms. It is one of the most prevalent neurological disorders worldwide, affecting approximately 15% of the population, with a 3:1 female predominance.

Pathophysiology

The current understanding centers on cortical spreading depression (CSD) — a slowly propagating wave of neuronal and glial depolarization that underlies the migraine aura and triggers trigeminovascular activation. Key mechanisms include:

Trigeminovascular system activation: Trigeminal nerve fibers innervate meningeal and cerebral blood vessels; their activation releases neuropeptides including CGRP (calcitonin gene-related peptide), substance P, and neurokinin A, producing neurogenic inflammation.
CGRP: A potent vasodilator and pain modulator, CGRP is central to migraine pathophysiology and is now the primary therapeutic target.
Sensitization: Both peripheral (trigeminal) and central (trigeminal nucleus caudalis, thalamus) sensitization contribute to allodynia and the throbbing quality of pain.
Genetic factors: Familial hemiplegic migraine (FHM) involves mutations in ion channel and transporter genes (CACNA1A, ATP1A2, SCN1A), highlighting channelopathy mechanisms.

Classification (ICHD-3)

Type	Key Features
Migraine without aura	Most common (~75–80%); episodic, fulfills POUND criteria
Migraine with aura	Aura in 20–25%; may precede or accompany headache
Chronic migraine	≥15 headache days/month for >3 months, ≥8 of which are migrainous
Hemiplegic migraine	Motor aura; sporadic or familial
Vestibular migraine	Vestibular symptoms + migraine history
Retinal migraine	Monocular visual disturbance
Menstrual migraine	Linked to menstrual cycle, often more severe

Clinical Features (Harrison's, p. 12214)

Migraine typically evolves through up to four phases:

1. Premonitory (Prodrome) — hours to 1–2 days before:

Yawning, fatigue, mood changes (irritability or euphoria), food cravings, neck stiffness, photophobia
Represents hypothalamic activation

2. Aura — 20–60 minutes:

Present in only 20–25% of patients
Visual (most common): scintillating scotoma, fortification spectra (zigzag lines), photopsia, visual snow (distinguish from visual snow syndrome, a separate entity)
Sensory: unilateral paresthesias spreading from hand to face ("march")
Dysphasic: word-finding difficulty
Motor (hemiplegic migraine only)
Each aura symptom develops gradually over ≥5 minutes; must be distinguished from TIA

3. Headache — 4–72 hours:

Unilateral in ~60% (can be bilateral)
Pulsating/throbbing quality
Moderate to severe intensity
Aggravated by routine physical activity
Nausea ± vomiting
Photophobia and phonophobia (often phonophobia > photophobia)
Osmophobia common

4. Postdrome:

Fatigue, cognitive dulling ("migraine hangover"), mood changes lasting hours to a day

Diagnostic Criteria (ICHD-3 — Migraine Without Aura)

≥5 attacks fulfilling:

Duration 4–72 hours (untreated/unsuccessfully treated)
At least 2 of: unilateral location, pulsating quality, moderate/severe intensity, aggravated by activity
At least 1 of: nausea/vomiting, photophobia AND phonophobia
Not better accounted for by another ICHD-3 diagnosis

Mnemonic — POUND: Pulsating, duration 4–72 hOurs, Unilateral, Nausea/vomiting, Disabling severity (≥4 criteria: LR+ ~24 for migraine)

Red Flags (Requiring Urgent Investigation)

Use SNOOP4 criteria:

Flag	Concern
Systemic symptoms (fever, weight loss)	Meningitis, malignancy
Neurological deficits	Structural lesion, stroke
Onset sudden ("thunderclap")	Subarachnoid hemorrhage
Older age (>50, new headache)	Giant cell arteritis, malignancy
Progressive/changing pattern	SOL, hydrocephalus
Postural aggravation	IIH, low-pressure headache
Papilledema	Raised ICP
Precipitated by Valsalva	Chiari, SOL

Treatment

Acute / Abortive Therapy

Stratify by attack severity using the MIDAS or HIT-6 score:

Drug Class	Agents	Notes
NSAIDs	Ibuprofen, naproxen, aspirin, celecoxib oral solution	First-line for mild-moderate
Triptans (5-HT1B/1D agonists)	Sumatriptan, rizatriptan, eletriptan, zolmitriptan	First-line for moderate-severe; contraindicated in CAD, stroke, uncontrolled HTN
Gepants (CGRP receptor antagonists)	Ubrogepant, rimegepant	No vasoconstriction; safe in CVD; can also be used preventively (rimegepant)
Ditans (5-HT1F agonists)	Lasmiditan	No vasoconstriction; CNS side effects (dizziness, sedation); no driving for 8h
Antiemetics	Metoclopramide, prochlorperazine, domperidone	Adjunct; also treat nausea; IV/IM prochlorperazine effective in ED
Ergotamines	DHE (IV, nasal, SC)	Useful for prolonged attacks; not first-line
Opioids	Avoid	Risk of medication overuse headache (MOH)

Medication Overuse Headache (MOH): Using acute treatments ≥10 days/month (triptans, ergots) or ≥15 days/month (NSAIDs) for >3 months transforms episodic into chronic migraine.

Preventive Therapy

Indicated when: ≥4 migraine days/month, or attacks significantly impair quality of life, or acute therapy is contraindicated/fails.

Category	Agents	Evidence
Beta-blockers	Propranolol, metoprolol, timolol	Level A
Antiepileptics	Topiramate, valproate	Level A
TCAs	Amitriptyline, nortriptyline	Level B
SNRIs	Venlafaxine	Level B
Anti-CGRP mAbs	Erenumab, fremanezumab, galcanezumab (SC monthly); eptinezumab (IV quarterly)	High efficacy, excellent tolerability; approved for episodic and chronic migraine
OnabotulinumtoxinA (Botox)	155–195 U IM q12 weeks	Approved for chronic migraine only
Gepants	Rimegepant (75 mg EOD), atogepant (daily)	Preventive CGRP antagonists

Non-Pharmacological

Per Integrating New Migraine Treatments Into Clinical Practice (p. 1):

Neuromodulation: External trigeminal nerve stimulation (Cefaly), noninvasive vagus nerve stimulation (gammaCore), single-pulse TMS (SpringTMS), remote electrical neuromodulation (Nerivio — acute use)
Biobehavioral: CBT, biofeedback, relaxation therapy, mindfulness-based therapies, acceptance and commitment therapy (ACT)

Special Populations

Population	Considerations
Pregnancy	Avoid triptans (relative CI), valproate, topiramate; acetaminophen ± caffeine, magnesium, nerve blocks preferred
Menstrual migraine	NSAIDs or frovatriptan mini-prophylaxis perimenstrually
Elderly	Rule out secondary causes; avoid vasoconstrictors; prefer gepants
Children/adolescents	Ibuprofen and sumatriptan nasal spray; topiramate, propranolol for prevention
CAD/stroke history	Gepants or ditans (avoid triptans and ergots)

Complications

Status migrainosus: Attack lasting >72 hours; treat with IV DHE, corticosteroids, IV valproate, IV magnesium
Migrainous infarction: Aura symptoms lasting >60 min with confirmed ischemic infarct (rare)
Chronic migraine: Transformation from episodic; treat MOH by withdrawal of overused medication
Persistent aura without infarction: Aura >1 week without imaging changes

Key Takeaways

Migraine is a trigeminal-CGRP mediated neurovascular disorder; CGRP is the central therapeutic target.
Aura is present in only 20–25% — absence does not exclude migraine.
Triptans remain the gold standard for acute moderate-severe attacks; gepants and ditans are newer vasoconstrictor-free alternatives.
Anti-CGRP monoclonal antibodies have transformed preventive therapy with superior tolerability.
Identify and treat MOH — it is a common and underrecognized cause of chronic daily headache.
Always screen for red flags (SNOOP4) before attributing headache to primary migraine.

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