Migraine

Migraine

Reading Document

Medical Text Search

migraine pathophysiology classification diagnosis clinical features

Medical Text Search

migraine treatment acute abortive therapy preventive management

Medical Image Search

migraine aura visual symptoms diagram

GradeResponse

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.

This is a shared conversation. Sign in to Orris to start your own chat.