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Summary Table

Domain	Details
Risk Factors	Female sex (3:1 F:M ratio), family history (70% have first-degree relative with migraine), age 25 to 55, hormonal fluctuations (menstruation, oral contraceptive use), stress, sleep deprivation, certain foods (aged cheese, chocolate, alcohol, MSG), weather changes
Etiology	Primary neurovascular disorder involving cortical hyperexcitability, trigeminovascular system activation, and release of calcitonin gene-related peptide (CGRP); strong genetic predisposition
Patient Presentation	Recurrent episodes of moderate-to-severe, unilateral, pulsating/throbbing headache lasting 4 to 72 hours, worsened by routine physical activity, associated with nausea/vomiting, photophobia, and phonophobia
Classic Physical Exam	Neurological exam is normal between attacks; during attack: patient prefers dark, quiet room and avoids movement; may exhibit pallor, scalp tenderness (allodynia), photophobia on light exposure
Key Diagnostic Results	Clinical diagnosis (no confirmatory lab or imaging test); neuroimaging (CT/MRI) is used only to exclude secondary causes; diagnosis is based on ICHD-3 criteria
Management	Acute: NSAIDs (ibuprofen, naproxen) for mild-moderate; triptans (sumatriptan) for moderate-severe. Prophylaxis: propranolol, topiramate, amitriptyline, valproate, or CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab)
Keywords	"Throbbing/pulsating headache," "unilateral," "photophobia and phonophobia," "nausea/vomiting," "aura," "scintillating scotoma," "prefers dark quiet room," "worsened by physical activity," "4 to 72 hours"

1. Pathophysiology

Migraine is not simply a vascular headache. It is a primary neurological disorder rooted in cortical hyperexcitability and abnormal activation of the trigeminovascular system. Understanding this mechanism is essential because vignettes often test whether students can connect the symptom pattern to the underlying biology.

The process begins centrally. In genetically predisposed individuals, the cerebral cortex has a lower threshold for depolarization. Various triggers (stress, hormonal shifts, sleep changes, dietary factors) can initiate abnormal neuronal activity in the brainstem and hypothalamus. This explains the prodromal phase, which occurs hours to days before the headache and manifests as fatigue, mood changes, food cravings, yawning, and neck stiffness. When these symptoms appear in a vignette before the headache begins, the test-writer is pointing you toward migraine.

In patients who experience aura, a phenomenon called cortical spreading depression (CSD) occurs. CSD is a slowly propagating wave of neuronal and glial depolarization that travels across the cortex at approximately 2 to 5 mm per minute, followed by a period of sustained suppression of neural activity. When CSD passes through the visual cortex (the most common location), it produces the classic visual aura: scintillating scotoma (a shimmering, zigzag crescent of light), fortification spectra, or a region of visual loss that expands gradually over 5 to 60 minutes. If it spreads to the somatosensory cortex, the patient reports unilateral paresthesias. If it involves language areas, the patient develops transient dysphasia. The key testing point is that aura symptoms develop gradually over 5 or more minutes and resolve fully within 60 minutes, which distinguishes them sharply from stroke (sudden onset, persistent deficits).

CSD triggers the next critical step: activation of the trigeminovascular system. The wave of depolarization causes release of inflammatory mediators (potassium, hydrogen ions, nitric oxide, arachidonic acid) from neurons and glia into the perivascular space. These substances activate the meningeal nociceptors of the trigeminal nerve (cranial nerve V), particularly the ophthalmic division (V1). Once these nociceptors fire, signals travel along the trigeminal nerve to the trigeminal nucleus caudalis in the brainstem, and then relay through the thalamus to cortical pain-processing regions.

Activation of the trigeminal nerve also causes antidromic release of CGRP, substance P, and neurokinin A from perivascular nerve terminals. CGRP is the most important of these peptides for exam purposes. CGRP causes meningeal vasodilation, plasma protein extravasation, mast cell degranulation, and neurogenic inflammation around the dural blood vessels. This creates a positive feedback loop that sustains and intensifies the headache. The recognition that CGRP is the central mediator of the pain cascade explains why anti-CGRP therapies (monoclonal antibodies and gepants) are effective.

The throbbing quality of the pain directly results from sensitization of perivascular nociceptors to arterial pulsation. As the attack progresses, central sensitization develops in the trigeminal nucleus caudalis and thalamus. This is why patients develop cutaneous allodynia (pain from normally non-painful stimuli such as touching the scalp, wearing eyeglasses, or combing hair). Once central sensitization is established, triptans become less effective, which is clinically important and frequently tested.

Photophobia and phonophobia arise from convergence of trigeminal and visual/auditory pathways in the brainstem and thalamus. Nausea and vomiting result from activation of the nucleus tractus solitarius and area postrema in the brainstem, which are closely connected to the trigeminal nucleus caudalis.

2. Classification and Clinical Manifestation

Migraine Classification (ICHD-3)

Type	Key Features
Migraine without aura	Most common type (~75% of all migraines). At least 5 attacks, each lasting 4 to 72 hours, with at least 2 of 4 headache characteristics (unilateral, pulsating, moderate-severe intensity, aggravated by routine physical activity) AND at least 1 of: nausea/vomiting OR photophobia and phonophobia
Migraine with aura	At least 2 attacks with fully reversible visual, sensory, speech/language, motor, brainstem, or retinal symptoms. At least 3 of: one aura symptom spreads gradually over 5+ minutes; two or more symptoms occur in succession; each symptom lasts 5 to 60 minutes; at least one symptom is unilateral; aura is accompanied by or followed within 60 minutes by headache
Chronic migraine	Headache occurring on 15 or more days per month for more than 3 months, with at least 8 days per month fulfilling migraine criteria
Hemiplegic migraine	Migraine with aura that includes motor weakness (reversible). Familial form (FHM) linked to mutations in CACNA1A, ATP1A2, or SCN1A genes. Triptans are traditionally contraindicated due to theoretical vasospasm risk
Migraine with brainstem aura (formerly basilar migraine)	Aura symptoms originating from brainstem: dysarthria, vertigo, tinnitus, hypacusis, diplopia, ataxia, decreased level of consciousness. Triptans are traditionally avoided
Retinal migraine	Repeated attacks of monocular visual disturbance (scintillations, scotoma, or blindness) associated with migraine headache. Must be distinguished from amaurosis fugax
Status migrainosus	Debilitating migraine lasting more than 72 hours
Medication overuse headache (MOH)	Headache occurring 15+ days/month in a patient who regularly overuses acute headache medication (analgesics 15+ days/month or triptans/opioids/combination analgesics 10+ days/month) for more than 3 months

Phases of a Migraine Attack

Phase	Timing	Symptoms
Prodrome	Hours to 2 days before headache	Fatigue, mood changes (irritability or euphoria), food cravings, yawning, neck stiffness, difficulty concentrating
Aura (if present)	5 to 60 minutes before or during headache	Visual symptoms (scintillating scotoma, fortification spectra) most common; sensory (paresthesias), speech/language disturbances, or motor weakness
Headache	4 to 72 hours	Unilateral, pulsating, moderate-to-severe, worsened by physical activity; nausea/vomiting; photophobia and phonophobia
Postdrome	Up to 48 hours after headache resolution	Fatigue, difficulty concentrating, neck stiffness, mood disturbance, residual sensitivity to light/sound

3. Diagnostic Workup

Test	Role	Key Findings / Notes
Clinical history and physical exam	The diagnostic standard. This is the only test you need.	Diagnosis is based on ICHD-3 criteria. Normal neurological exam is expected.
Neuroimaging (CT head without contrast)	Best initial test if a secondary cause must be excluded	Used when red flags are present (thunderclap onset, new headache in patients >50, focal neurologic deficits, papilledema, seizure, immunocompromised state, progressive worsening)
MRI brain with and without contrast	Most accurate imaging test for ruling out structural pathology	Superior to CT for posterior fossa lesions, white matter disease, vascular malformations, and small tumors
Lumbar puncture	Only if meningitis, subarachnoid hemorrhage (SAH), or idiopathic intracranial hypertension (IIH) is suspected	Opening pressure measurement, CSF analysis. Perform after CT if SAH is suspected but CT is negative
ESR / CRP	If giant cell arteritis (temporal arteritis) is suspected	New headache in patient >50 with jaw claudication, visual symptoms, scalp tenderness, and elevated ESR
Laboratory testing	No routine lab is needed for migraine diagnosis	CBC, metabolic panel, thyroid function may be checked to evaluate comorbidities or secondary causes

Migraine is a clinical diagnosis. There is no lab test, imaging study, or biomarker that confirms it. The diagnosis rests entirely on pattern recognition from the history, and this is exactly what the exam tests. A vignette will describe a young woman with recurrent episodes of unilateral, pulsating headache lasting several hours, worsened by walking upstairs, associated with nausea and sensitivity to light and sound, with a normal neurological exam. The correct answer is migraine, and the correct next step is no further workup needed.

The moment the exam tests diagnostic workup, it is testing your ability to recognize red flag features (sometimes called "SNOOP" criteria) that should prompt neuroimaging:

Systemic symptoms (fever, weight loss, immunosuppression, cancer history)
Neurological signs (focal deficits, papilledema, altered consciousness)
Onset that is sudden or "thunderclap" (peak intensity within seconds)
Older age at onset (new headache after age 50)
Progressive pattern (increasing frequency/severity, change in character)

If the vignette includes any of these red flags, the answer shifts to CT head without contrast as the best initial test, followed by MRI brain for more detailed evaluation if CT is normal but clinical suspicion remains. If the presentation suggests subarachnoid hemorrhage (sudden "worst headache of my life"), a negative CT should be followed by lumbar puncture looking for xanthochromia.

For a new headache in a patient over age 50, always consider giant cell arteritis. The best initial test in that scenario is ESR (markedly elevated, often > 50 mm/hr), and the most accurate test is temporal artery biopsy.

4. Management and Treatment

Acute Treatment

Severity	First-Line Therapy	Dose	Notes
Mild to moderate	NSAIDs	Ibuprofen 400 to 600 mg PO, Naproxen sodium 500 to 825 mg PO, Aspirin 900 to 1000 mg PO	Take as early as possible in the attack. May combine with metoclopramide 10 mg for nausea and to improve gastric absorption
Moderate to severe	Triptans (5-HT1B/1D agonists)	Sumatriptan 50 to 100 mg PO, or 6 mg SC; Rizatriptan 10 mg PO; Eletriptan 40 mg PO	Most effective when taken early, before central sensitization develops. Contraindicated in uncontrolled hypertension, coronary artery disease, stroke, hemiplegic migraine, and migraine with brainstem aura
NSAID/Triptan failure	Gepants (CGRP receptor antagonists)	Ubrogepant 50 to 100 mg PO; Rimegepant 75 mg PO (ODT)	No vasoconstrictive effect, therefore safe in patients with cardiovascular contraindications to triptans
Severe / Emergency	IV antiemetics (dopamine antagonists)	Metoclopramide 10 to 20 mg IV; Prochlorperazine 10 mg IV	Recommended as first-line parenteral therapy in emergency settings; often combined with IV fluids and diphenhydramine (to prevent akathisia)
Rescue / Refractory	Dexamethasone	10 mg IV (single dose)	Reduces headache recurrence within 24 to 72 hours; does not treat the acute attack itself

Prophylactic Treatment

Drug Class	Agent	Dose	Notes
Beta-blockers	Propranolol	40 to 240 mg/day in divided doses	First-line prophylaxis with strong evidence. Avoid in asthma, decompensated heart failure, and bradycardia. Also useful if patient has comorbid hypertension or essential tremor
Antiepileptics	Topiramate	25 to 100 mg/day (titrate slowly)	First-line. Side effects: weight loss, cognitive slowing ("dopamax"), paresthesias, nephrolithiasis. Contraindicated in pregnancy (teratogenic, cleft lip/palate)
	Valproate / Divalproex	500 to 1500 mg/day	Effective but absolutely contraindicated in pregnancy (neural tube defects). Avoid in women of childbearing potential not using reliable contraception. Side effects: weight gain, tremor, alopecia, hepatotoxicity, thrombocytopenia
Tricyclic antidepressants	Amitriptyline	10 to 75 mg at bedtime	Useful when patient has comorbid insomnia, depression, or tension-type headache. Side effects: sedation, weight gain, anticholinergic effects, cardiac conduction abnormalities
SNRIs	Venlafaxine	75 to 150 mg/day	Second-line. Consider if comorbid depression/anxiety
Calcium channel blockers	Verapamil	120 to 480 mg/day	Less commonly tested; more commonly first-line for cluster headache prophylaxis
CGRP monoclonal antibodies	Erenumab (anti-CGRP receptor)	70 to 140 mg SC monthly	Disease-targeted therapy. Recommended as first-line or after failure of 1 to 2 traditional oral preventives. Minimal side effects (injection site reactions, constipation with erenumab). No drug interactions. No teratogenicity data yet, so generally avoided in pregnancy
	Fremanezumab (anti-CGRP ligand)	225 mg SC monthly or 675 mg SC quarterly
	Galcanezumab (anti-CGRP ligand)	240 mg SC loading, then 120 mg SC monthly	Also approved for episodic cluster headache
	Eptinezumab (anti-CGRP ligand)	100 to 300 mg IV every 3 months	Only IV formulation; fastest onset of action among mAbs
Gepants (for prevention)	Atogepant	10 to 60 mg PO daily	Oral CGRP receptor antagonist approved for prevention
Gepants (for prevention)	Rimegepant	75 mg PO every other day	Unique dual-use: approved for both acute treatment and prevention
OnabotulinumtoxinA	Botox	155 units IM across 31 sites, every 12 weeks	Approved only for chronic migraine (15+ headache days/month). Not indicated for episodic migraine

Acute treatment should be initiated as early as possible once the headache begins. The concept of "treat early" is high-yield because early intervention (within 1 hour of onset) produces significantly better outcomes. For mild to moderate attacks, an NSAID such as ibuprofen 400 mg or naproxen sodium 500 mg is first-line. Adding metoclopramide 10 mg PO improves gastric motility (which is slowed during a migraine attack) and provides antiemetic benefit.

For moderate to severe attacks or when NSAIDs fail, triptans are the standard of care. Sumatriptan is the most commonly tested. Oral sumatriptan 50 to 100 mg may be given; subcutaneous sumatriptan 6 mg has the fastest onset and highest efficacy. Triptans work by agonizing 5-HT1B receptors on meningeal blood vessels (causing vasoconstriction) and 5-HT1D receptors on trigeminal nerve terminals (inhibiting CGRP release). Because of their vasoconstrictive properties, triptans are contraindicated in patients with coronary artery disease, prior stroke or TIA, uncontrolled hypertension, Prinzmetal angina, and peripheral vascular disease. They are also traditionally avoided in hemiplegic migraine and migraine with brainstem aura. Another critical contraindication is concurrent use of ergotamine (risk of prolonged vasospasm) and use within 2 weeks of an MAO inhibitor.

If a patient has cardiovascular contraindications to triptans, the exam often tests gepants as the alternative. Ubrogepant and rimegepant are oral CGRP receptor antagonists that provide acute relief without vasoconstriction, making them safe in patients with vascular risk factors. Lasmiditan, a 5-HT1F agonist (a "ditan"), is another non-vasoconstrictive option, but it causes dizziness and sedation, so patients should not drive within 8 hours of taking it.

Prophylactic therapy is indicated when the patient has 4 or more migraine days per month, significant disability despite acute treatment, contraindication to or overuse of acute medications, or presence of uncommon migraine subtypes (hemiplegic, brainstem aura, migrainous infarction). The traditional first-line oral agents are propranolol, topiramate, valproate, and amitriptyline. All require 2 to 3 months of adequate-dose treatment before efficacy can be assessed. The CGRP monoclonal antibodies (erenumab, fremanezumab, galcanezumab, eptinezumab) are now recommended as first-line or early-line preventive therapy by the AHS (2024 consensus), particularly in patients who have failed or cannot tolerate oral preventives. They are given as monthly or quarterly injections and have a favorable side-effect profile compared to traditional oral medications.

For chronic migraine that has not responded to at least 2 preventive medications, onabotulinumtoxinA (Botox) is an established treatment, given every 12 weeks. It works by inhibiting the release of CGRP and other nociceptive neurotransmitters from trigeminal nerve endings.

A crucial management pearl: always assess for and address medication overuse headache (MOH). If a patient with chronic daily headache is using simple analgesics 15 or more days per month, or triptans/opioids/combination analgesics 10 or more days per month, the most important next step is withdrawal of the offending medication combined with a preventive agent and a bridging strategy (short course of naproxen or prednisone).

5. Differential Diagnosis and Distractors

Differential	Why It Is Similar	Key Discriminator
Tension-type headache (TTH)	Also recurrent; also has photophobia or phonophobia. Very common alternative answer.	TTH is bilateral, non-pulsating (pressing/tightening "band-like"), mild-to-moderate, NOT worsened by physical activity, and has NO nausea/vomiting. TTH has photophobia OR phonophobia (not both). Migraine has at least one of: nausea/vomiting OR both photophobia and phonophobia.
Cluster headache	Severe unilateral headache with autonomic features	Cluster is periorbital, lasts 15 to 180 minutes (much shorter), occurs in clusters of 1 to 8 attacks daily for weeks, and produces ipsilateral autonomic signs (lacrimation, conjunctival injection, nasal congestion, ptosis/miosis). Patient is restless and agitated (pacing), unlike the migraine patient who lies still in a dark room. Male predominance.
Subarachnoid hemorrhage (SAH)	Sudden severe headache, nausea/vomiting	SAH is "thunderclap" onset reaching peak intensity within seconds. Migraine builds gradually. SAH has meningismus (neck stiffness), altered consciousness, and may have focal deficits. CT head is the best initial test; LP if CT is negative.
Idiopathic intracranial hypertension (IIH, pseudotumor cerebri)	Headache with visual disturbances and nausea	IIH occurs in obese women of childbearing age (same demographic as migraine). Key discriminator: IIH has papilledema on fundoscopy, pulsatile tinnitus, and elevated opening pressure on LP (> 25 cm H2O). Visual symptoms are transient visual obscurations (brief dimming, not the gradual scintillating scotoma of migraine).
Temporal arteritis (giant cell arteritis)	Unilateral headache, visual disturbance	Age > 50 (migraine typically starts younger). Presents with jaw claudication, tender/non-pulsatile temporal artery, weight loss, polymyalgia rheumatica. ESR is markedly elevated. Temporal artery biopsy is confirmatory.
Brain tumor	Headache with nausea/vomiting	Headache is progressive, worse in the morning, and worsened by Valsalva maneuver. Focal neurological deficits and papilledema are present. MRI brain with contrast is the test of choice.
Meningitis	Headache, photophobia, nausea/vomiting	Fever, neck stiffness, altered mental status (Kernig and Brudzinski signs). Acute onset rather than recurrent episodic pattern. LP shows pleocytosis.
Transient ischemic attack (TIA)	Focal neurological symptoms (similar to aura)	TIA symptoms are sudden onset (not gradual over 5+ minutes) and are purely negative (loss of vision, weakness, numbness) rather than the positive-then-negative march of migraine aura (scintillating scotoma spreading across visual field). No headache typically follows.

6. Traps and High-Yield Pearls

The most common trap on this topic is confusing the aura of migraine with a transient ischemic attack or stroke. The exam will present a young patient with transient visual or sensory symptoms followed by a headache. Students panic and choose stroke workup. The critical discriminator is tempo: migraine aura develops gradually over 5 or more minutes (the "march"), whereas TIA and stroke symptoms appear suddenly, within seconds. Additionally, migraine aura characteristically produces positive phenomena first (flashing lights, scintillating scotoma, tingling) followed by negative phenomena (visual loss, numbness), while ischemic events produce purely negative symptoms from the start.

Another frequent trap involves the management sequence. The vignette describes a patient who has been using sumatriptan 10 or more days per month for chronic daily headache. Students choose to increase the triptan dose or add another acute agent. The correct answer is to recognize medication overuse headache and withdraw the offending medication while initiating prophylaxis. The test-writer is checking whether you understand that overuse of acute migraine medications paradoxically perpetuates the headache cycle.

A third high-yield trap involves triptan contraindications. When the vignette describes a migraine patient with a history of coronary artery disease, prior myocardial infarction, or uncontrolled hypertension, the answer is never sumatriptan. The correct choice is an NSAID, a gepant (ubrogepant, rimegepant), or lasmiditan.

Students also miss the prophylaxis indication question. When a patient has frequent migraines (4+ days per month) causing disability, the next best step is to start a preventive medication, not to continue treating each individual attack. The exam is testing whether you can shift from acute management to prevention.

Finally, remember the pregnancy trap. A woman of childbearing potential with migraine should not receive valproate (neural tube defects) or topiramate (cleft lip/palate). The preferred prophylactic agent in pregnancy is a beta-blocker (propranolol) or, in more recent guidelines, a CGRP monoclonal antibody may be considered, though data in pregnancy remain limited. For acute treatment during pregnancy, acetaminophen is first-line, while triptans (particularly sumatriptan, which has the most safety data) may be used when the benefit outweighs the risk.

The core competency being tested across all migraine questions is threefold: (1) pattern recognition of the classic clinical presentation (unilateral, pulsating, 4 to 72 hours, nausea, photo/phonophobia, worsened by activity), (2) knowing when imaging is and is not indicated (red flags versus classic presentation), and (3) correct sequencing of acute versus prophylactic therapy with awareness of contraindications.

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