Migraine Headache

Quick Reference

Critical Alerts

• Rule out secondary causes first: Thunderclap headache, worst headache of life, fever, focal deficits, new headache > 50 years
• Triptans are first-line abortive therapy: 5-HT1B/1D agonists effective within 2 hours if no contraindications
• IV fluids + IV antiemetic + IV NSAID = Effective ED cocktail: Metoclopramide 10-20 mg IV + ketorolac 15-30 mg IV + NS 500-1000 mL
• Status migrainosus needs aggressive treatment: Migraine lasting > 72 hours requires IV therapy, magnesium, steroids
• Avoid opioids: Not first-line; risk of medication overuse headache and dependence
• Triptans contraindicated in CAD, uncontrolled HTN, prior stroke: Vasoconstrictive mechanism
• CGRP monoclonal antibodies revolutionize prophylaxis: Erenumab, fremanezumab, galcanezumab for chronic/episodic migraine
• Medication overuse headache is common: ≥15 headache days/month with regular analgesic use ≥3 months

Red Flags (SNOOP4)

Emergency Treatments

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Definition

Overview

Migraine is a primary headache disorder characterized by recurrent, episodic, moderate-to-severe headaches often associated with nausea, vomiting, photophobia, and phonophobia. [1,2] Approximately 30% of patients experience migraine with aura, featuring transient focal neurological symptoms preceding the headache. [3] Migraine is a chronic neurological condition with episodic manifestations, not merely a severe headache.

Emergency department management focuses on:

1. Exclusion of secondary causes (SAH, meningitis, stroke, mass lesion)
2. Abortive therapy to terminate the acute attack
3. Prevention of recurrence within 24-72 hours
4. Identification of medication overuse headache (MOH)
5. Referral for prophylaxis if frequent attacks (≥4/month)

Classification

International Classification of Headache Disorders, 3rd Edition (ICHD-3) [1]

Migraine Without Aura

Most common (70-80% of migraine patients)

Diagnostic criteria (all required):

• A. At least 5 attacks fulfilling criteria B-D
• B. Headache lasting 4-72 hours (untreated or unsuccessfully treated)
• C. At least 2 of the following:
  • Unilateral location
  • Pulsating quality
  • Moderate-to-severe intensity
  • Aggravation by routine physical activity
• D. At least 1 of the following during headache:
  • Nausea and/or vomiting
  • Photophobia and phonophobia
• E. Not better accounted for by another ICHD-3 diagnosis

Migraine With Aura

30% of migraine patients; some have both aura and non-aura attacks

Diagnostic criteria:

• A. At least 2 attacks fulfilling criteria B-C
• B. One or more fully reversible aura symptoms:
  • "Visual (most common: scintillating scotoma, fortification spectra)"
  • Sensory (paresthesias, numbness)
  • Speech/language (dysphasia)
  • Motor (weakness) - hemiplegic migraine subtype
  • Brainstem (diplopia, ataxia, vertigo, tinnitus)
  • Retinal (monocular visual loss)
• C. At least 3 of the following:
  • At least 1 aura symptom spreads gradually over ≥5 minutes
  • Two or more aura symptoms occur in succession
  • Each aura symptom lasts 5-60 minutes
  • At least 1 aura symptom is unilateral
  • At least 1 aura symptom is positive (scintillations, tingling)
  • Aura accompanied or followed within 60 minutes by headache
• D. Not better accounted for by another diagnosis; TIA excluded

Chronic Migraine

≥15 headache days per month for > 3 months, with migraine features on ≥8 days/month. [4] Often associated with medication overuse headache. Significant disability; requires neurological referral for prophylaxis.

Status Migrainosus

Migraine attack lasting > 72 hours despite treatment. [1] Debilitating headache with persistent nausea/vomiting leading to dehydration. Requires aggressive ED or inpatient treatment. May require IV therapy and admission.

Hemiplegic Migraine

Migraine with aura including motor weakness (hemiparesis). [5] Familial hemiplegic migraine (FHM) is autosomal dominant with mutations in CACNA1A, ATP1A2, or SCN1A genes. Sporadic hemiplegic migraine has same phenotype without family history. Triptans and ergots contraindicated due to risk of prolonged aura.

Menstrual Migraine

• Pure menstrual migraine: Attacks occur exclusively on days -2 to +3 of menstruation (day 1 = first day of bleeding) in ≥2/3 cycles
• Menstrually-related migraine: Attacks occur both with menstruation and at other times
• Related to estrogen withdrawal; typically migraine without aura
• May benefit from perimenstrual prophylaxis or hormonal manipulation [6]

Epidemiology

Migraine is one of the most prevalent and disabling neurological conditions worldwide. [7,8]

Prevalence

• Global prevalence: 14.4% (1 in 7 people) [7]
• United States: 15.3% (38 million Americans) [8]
• Female prevalence: 18-20% (reproductive years)
• Male prevalence: 6-8%
• Female-to-male ratio: 3:1 after puberty (equal before puberty)
• Peak age: 25-55 years (most productive years)
• Chronic migraine: 1-2% of general population [4]

Burden and Disability

• Global Burden of Disease Study 2019: Migraine is the 2nd leading cause of years lived with disability (YLD) worldwide [7]
• Leading cause of disability in women aged 15-49 years [7]
• Annual economic burden in US: $36 billion (direct and indirect costs) [8]
• Workdays lost per year: Average 4.4 days for episodic migraine, 7.2 days for chronic migraine
• Emergency department visits: Approximately 1.2 million ED visits/year in US for headache (migraine most common primary headache)

Comorbidities

Patients with migraine have increased prevalence of:

• Psychiatric: Depression (2.5× risk), anxiety (2.4× risk), bipolar disorder
• Cardiovascular: Stroke (2× risk, especially migraine with aura), patent foramen ovale
• Neurological: Epilepsy (2× risk), essential tremor
• Pain conditions: Fibromyalgia, chronic pain syndromes
• Gastrointestinal: Irritable bowel syndrome

Etiology and Triggers

Migraine is a neurovascular disorder with genetic predisposition and environmental triggers. [2,9]

Genetic Factors

• Heritability: 40-60% for migraine without aura, up to 90% for hemiplegic migraine
• Polygenic inheritance: Most common migraine (multifactorial)
• Monogenic inheritance: Familial hemiplegic migraine (FHM1, FHM2, FHM3)
• First-degree relatives: 50% risk if one parent has migraine; 75% if both parents affected

Common Triggers

Trigger Management: Diary to identify triggers; lifestyle modification to avoid triggers; however, rigorous trigger avoidance may increase sensitivity and should be balanced.

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Pathophysiology

The pathophysiology of migraine involves cortical spreading depression, trigeminovascular activation, neurogenic inflammation, and central sensitization. [2,9,10]

Cortical Spreading Depression (CSD)

Cortical spreading depression is the likely mechanism of migraine aura. [10,11]

• Definition: Self-propagating wave of neuronal and glial depolarization spreading across the cortex at 2-6 mm/min
• Characteristics:
  • Initial neuronal excitation → Brief firing
  • Followed by prolonged neuronal suppression (30-60 minutes)
  • Spreading wave of depolarization across cortex
  • Associated with changes in cerebral blood flow (initial hyperperfusion → prolonged oligemia)
• Clinical correlation:
  • Speed of CSD (2-6 mm/min) matches speed of spread of visual aura symptoms
  • Duration of CSD (30-60 minutes) matches duration of aura
• Activation of trigeminovascular system: CSD activates trigeminal afferents → Headache phase
• Recent evidence: CSD may originate from influx of CSF solutes into trigeminal ganglion neurons [12]

Trigeminovascular System Activation

The trigeminal nerve innervates intracranial blood vessels (meningeal arteries, large cerebral arteries, venous sinuses). [9,10]

Mechanism:

1. CSD or other triggers activate trigeminal afferents
2. Peripheral nociceptor activation: Trigeminal nerve endings release vasoactive neuropeptides:
   • Calcitonin gene-related peptide (CGRP): Primary mediator
   • Substance P
   • Neurokinin A
3. Neurogenic inflammation: CGRP and substance P cause:
   • Vasodilation of meningeal vessels
   • Plasma protein extravasation
   • Mast cell degranulation
   • Sensitization of peripheral nociceptors
4. Peripheral sensitization: Increased sensitivity to normally non-painful stimuli (allodynia)
5. Central transmission: Pain signals transmitted to trigeminal nucleus caudalis (TNC) in brainstem
6. Central sensitization: Amplification of pain signals in TNC and thalamus
7. Cortical perception: Pain perceived in cortex with associated symptoms (nausea, photophobia, phonophobia)

Role of CGRP

Calcitonin gene-related peptide (CGRP) is the key mediator of migraine. [9,13]

• Evidence for CGRP in migraine:
  • CGRP levels elevated in jugular vein blood during migraine attacks
  • IV infusion of CGRP provokes migraine in susceptible individuals
  • CGRP receptor antagonists (gepants) abort migraine attacks
  • CGRP monoclonal antibodies prevent migraine attacks
• CGRP receptors: Located on meningeal vessels, trigeminal neurons, brainstem
• CGRP actions:
  • Vasodilation of intracranial vessels (especially meningeal arteries)
  • Sensitization of trigeminal nociceptors
  • Transmission of nociceptive signals in TNC
  • Modulation of pain pathways in brainstem and thalamus

CGRP-targeted therapies:

• Gepants (small molecule CGRP receptor antagonists): Ubrogepant, rimegepant (acute treatment); rimegepant, atogepant (prophylaxis)
• CGRP monoclonal antibodies: Erenumab (CGRP receptor mAb), fremanezumab, galcanezumab, eptinezumab (CGRP ligand mAbs) - prophylaxis

Central Sensitization

Central sensitization amplifies pain signals in the central nervous system. [9]

• Trigeminal nucleus caudalis (TNC): Second-order neurons become hyperexcitable
• Thalamus: Relay to cortex with amplification
• Clinical manifestations:
  • "Cutaneous allodynia: Scalp tenderness, pain from brushing hair, wearing glasses"
  • Occurs in 60-80% of migraine patients during attacks
  • Indicates central sensitization; suggests delayed triptan administration may be less effective
• Chronification: Repeated central sensitization may lead to chronic migraine

Brainstem and Hypothalamic Dysfunction

Premonitory symptoms (hours to days before headache): Yawning, food cravings, mood changes, neck stiffness, polyuria, fatigue. [2]

• Hypothalamus: Involved in premonitory phase (PET studies show hypothalamic activation 24 hours before headache)
• Dopaminergic dysfunction: Nausea, vomiting, yawning may be dopaminergic
• Brainstem nuclei: Periaqueductal gray, locus coeruleus involved in pain modulation

Aura Mechanisms

Visual aura (most common):

• Positive phenomena: Scintillations, fortification spectra (zigzag lines), flashing lights
• Negative phenomena: Scotoma (blind spot), hemianopia
• Pathophysiology: CSD in occipital cortex
• Retinotopic progression: Aura spreads across visual field matching CSD spread across occipital cortex

Sensory aura: Paresthesias spreading from hand → arm → face (cheiro-oral distribution). CSD in somatosensory cortex.

Speech/language aura: Dysphasia, paraphasia. CSD in language areas (dominant hemisphere).

Motor aura (hemiplegic migraine): Hemiparesis, hemiplegia. CSD in motor cortex. Aura may last hours to days.

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Clinical Presentation

Migraine Phases

Migraine attack consists of up to 4 phases: [2]

1. Premonitory phase (prodrome): Hours to 2 days before headache

   • Yawning, food cravings (especially carbohydrates), mood changes (depression, irritability, euphoria), fatigue, neck stiffness, polyuria, fluid retention
   • Occurs in 60-80% of patients
   • May help predict attack and allow early treatment

2. Aura phase: 5-60 minutes (typically 20-30 minutes)

   • Visual, sensory, speech, or motor symptoms
   • Fully reversible
   • Typically precedes headache but may overlap or occur without headache ("migraine aura without headache")

3. Headache phase: 4-72 hours (untreated)

   • Moderate-to-severe intensity
   • Unilateral (60%), bilateral (40%)
   • Pulsating/throbbing quality
   • Aggravated by physical activity
   • Nausea (90%), vomiting (30%), photophobia (80%), phonophobia (76%)
   • Osmophobia (smell sensitivity)
   • Cutaneous allodynia (60-80%)

4. Postdromal phase ("migraine hangover"): Up to 48 hours after headache resolves

   • Fatigue, weakness, difficulty concentrating, mood changes, muscle aches
   • Occurs in 80% of patients

Headache Features (POUND Mnemonic)

POUND criteria for migraine (sensitivity 77%, specificity 75% if ≥4 features present): [14]

Aura Symptoms

Visual aura (90% of aura cases): [3]

• Positive phenomena:
  • Scintillations (bright, shimmering lights)
  • Fortification spectra (zigzag lines, geometric patterns)
  • Flashing lights (photopsia)
• Negative phenomena:
  • Scotoma (blind spot, typically expanding)
  • Hemianopia (loss of half visual field)
  • Blurred vision
• Characteristics:
  • Typically starts in central vision
  • Expands over 5-30 minutes
  • Migrates peripherally
  • Lasts 5-60 minutes
  • Homonymous (both eyes, same visual field) - indicates occipital cortex origin

Sensory aura (30-40% of aura cases):

• Paresthesias (tingling, "pins and needles")
• Numbness
• Cheiro-oral distribution: Hand → arm → face/tongue (typical pattern)
• Unilateral
• Spreads over 5-20 minutes
• Lasts 5-60 minutes

Speech/language aura (10-20% of aura cases):

• Dysphasia (difficulty speaking)
• Paraphasia (word substitution errors)
• Difficulty understanding speech
• Lasts 5-60 minutes

Motor aura (rare, less than 5% - hemiplegic migraine):

• Hemiparesis or hemiplegia (weakness one side of body)
• May last hours to days (unlike other aura symptoms)
• Triptans and ergots contraindicated
• Consider imaging to exclude stroke on first presentation

Brainstem aura (rare - migraine with brainstem aura, formerly "basilar migraine"):

• Dysarthria, vertigo, tinnitus, diplopia, ataxia, decreased level of consciousness
• Bilateral visual symptoms
• Bilateral sensory symptoms
• Diagnosis of exclusion: Must rule out posterior circulation stroke

Associated Symptoms

• Photophobia (light sensitivity): 80% of patients; prefer dark room
• Phonophobia (sound sensitivity): 76% of patients; prefer quiet environment
• Osmophobia (smell sensitivity): Intolerance to odors (perfume, food)
• Nausea: 90% of patients
• Vomiting: 30% of patients; may lead to dehydration
• Cutaneous allodynia: Scalp tenderness, pain from brushing hair, wearing glasses (60-80%)
• Nasal congestion, lacrimation: May mimic cluster headache or sinusitis

History Taking

Headache Characterization:

• Onset: Gradual (migraine) vs. thunderclap (SAH)
• Duration: 4-72 hours for migraine
• Location: Unilateral or bilateral; frontal, temporal, periorbital
• Quality: Pulsating, throbbing, pressure
• Intensity: 0-10 scale; moderate-to-severe (≥5/10) for migraine
• Aggravating factors: Physical activity, head movement
• Relieving factors: Rest in dark, quiet room; sleep

Associated Symptoms:

• Nausea, vomiting
• Photophobia, phonophobia
• Aura symptoms (visual, sensory, speech, motor)
• Premonitory symptoms (yawning, food cravings, mood changes)
• Postdromal symptoms (fatigue, difficulty concentrating)

Migraine History:

• Prior similar headaches? Age of onset?
• Migraine diagnosis by physician?
• Frequency of attacks (days/month)?
• Typical duration of attacks?
• Triggers identified? (menstruation, sleep, stress, food, alcohol)
• Abortive medications used? Effectiveness?
• Prophylactic medications? Compliance?

Red Flag Assessment (SNOOP4):

• Systemic symptoms: Fever, weight loss, night sweats
• Systemic illness: Cancer, HIV, immunosuppression
• Neurological signs: Focal weakness, numbness, vision loss, ataxia, altered consciousness
• Onset sudden: Thunderclap ("worst headache of life" in less than 1 minute)
• Older age: New headache > 50 years (consider GCA, malignancy)
• Pattern change: Change in headache character, frequency, severity
• Precipitated by: Valsalva, exertion, position change, sexual activity
• Papilledema: Vision changes, transient visual obscurations
• Pregnancy/postpartum: Consider pre-eclampsia, CVT, PRES

Medication History:

• Current analgesics: Type, frequency, doses
• Medication overuse headache: Analgesic use ≥10-15 days/month for ≥3 months
  • "Simple analgesics (NSAIDs, acetaminophen): ≥15 days/month"
  • "Combination analgesics, triptans, opioids: ≥10 days/month"
• Prior prophylactic trials: Beta-blockers, anticonvulsants, antidepressants, CGRP mAbs
• Contraindications to triptans: CAD, stroke, uncontrolled HTN

Social and Family History:

• Family history of migraine (50% risk if one parent)
• Occupation, disability from headaches
• Tobacco use (may worsen migraine)

Physical Examination

Vital Signs:

• Blood pressure (uncontrolled HTN is triptan contraindication; hypertensive emergency)
• Heart rate (tachycardia may suggest dehydration)
• Temperature (fever suggests meningitis, encephalitis, sinusitis)

General Appearance:

• Level of distress
• Preference for dark, quiet room (photophobia, phonophobia)
• Hydration status (dry mucous membranes, poor skin turgor)

Neurological Examination:

Head/Scalp Examination:

• Temporal artery palpation (tenderness, decreased pulsation in GCA if > 50 years)
• Scalp tenderness (may indicate allodynia in migraine)
• Trauma (subdural, epidural hematoma)

Expected Findings in Typical Migraine:

• Normal neurological examination (key feature)
• Patient prefers dark, quiet room
• May have scalp tenderness (allodynia)
• May appear distressed, nauseated
• Vital signs typically normal (BP may be elevated from pain)

Red Flags on Examination:

• Focal neurological deficits: Weakness, sensory loss, ataxia, visual field defects → Imaging
• Papilledema: Increased ICP, mass, IIH → Imaging (CT/MRI), then LP if imaging normal
• Meningismus: Meningitis, SAH → LP
• Altered consciousness: Mass, encephalitis, severe SAH → Imaging
• Fever: Meningitis, encephalitis → LP, empiric antibiotics

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Red Flags and Secondary Headaches

SNOOP4 Mnemonic for Red Flags [15]

Specific Red Flag Scenarios

Thunderclap Headache (Sudden Onset less than 1 Minute)

"Worst headache of my life"

Differential Diagnosis:

Management: CT head without contrast → Lumbar puncture if CT negative (SAH may be CT-negative if > 6 hours from onset or small bleed)

Fever + Headache

Concern: Meningitis, encephalitis, brain abscess

Red flags: Meningismus, altered consciousness, seizures, rash (petechiae/purpura in meningococcemia)

Management:

• Lumbar puncture: Opening pressure, cell count, protein, glucose, Gram stain, culture
• Blood cultures before antibiotics
• Empiric antibiotics immediately if meningitis suspected (do NOT delay for LP or imaging if high suspicion)
  • Ceftriaxone 2 g IV + vancomycin 15-20 mg/kg IV
  • Add acyclovir 10 mg/kg IV if encephalitis suspected
  • Add dexamethasone 10 mg IV before antibiotics (reduces mortality in bacterial meningitis)
• CT head before LP if: Altered consciousness, focal deficits, seizures, immunocompromised, papilledema (risk of herniation with LP)

New Headache > 50 Years

Concern: Giant cell arteritis (GCA), malignancy

Giant Cell Arteritis (Temporal Arteritis):

• Features: New headache > 50 years, scalp tenderness, jaw claudication, vision changes (amaurosis fugax, sudden vision loss), temporal artery abnormalities (tenderness, decreased pulsation), polymyalgia rheumatica (shoulder/hip pain)
• Labs: ESR > 50 mm/hr (often > 100), CRP elevated
• Diagnosis: Temporal artery biopsy (may be negative due to skip lesions; 3-5 cm specimen needed)
• Management: Immediate high-dose corticosteroids (methylprednisolone 1 g IV or prednisone 60-80 mg PO) to prevent irreversible vision loss; do NOT delay for biopsy (can biopsy within 1-2 weeks of steroid initiation)

Malignancy:

• Primary brain tumor, metastases
• Features: Progressive headache, worse in morning, Valsalva, vomiting, focal deficits, seizures
• Imaging: MRI brain with contrast

Focal Neurological Deficits

Concern: Stroke, mass lesion, hemiplegic migraine, complicated migraine

Hemiplegic migraine vs. stroke:

• Hemiplegic migraine: Prior similar episodes, family history (FHM), gradual spread of symptoms (5-20 min), associated with typical aura and headache, younger age
• Stroke: Abrupt onset, maximal deficits at onset, vascular risk factors, older age
• Management: If first episode or atypical, treat as stroke until proven otherwise (CT/MRI, neurology consult)

Papilledema

Concern: Increased intracranial pressure (mass, hydrocephalus, IIH, CVT)

Features: Bilateral optic disc swelling, vision changes (transient visual obscurations, visual field defects), CN VI palsy (false localizing sign)

Management:

1. CT or MRI brain (mass, hydrocephalus, CVT)
2. If imaging shows mass or mass effect: Neurosurgery consult; LP contraindicated (risk of herniation)
3. If imaging normal: Lumbar puncture with opening pressure
   • Elevated opening pressure (> 25 cm H₂O): Idiopathic intracranial hypertension (IIH) - obesity, young women, vitamin A, tetracyclines
   • Normal opening pressure: Optic neuritis, other causes

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Differential Diagnosis

Primary Headache Disorders

Secondary Headache Disorders (Red Flags)

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Diagnostic Approach

Clinical Diagnosis

Migraine is a clinical diagnosis based on history and normal neurological examination. [1,2]

Key Principles:

1. Detailed history to meet ICHD-3 diagnostic criteria
2. Rule out red flags (SNOOP4)
3. Normal neurological examination (in typical migraine)
4. Imaging NOT routinely indicated for typical migraine with normal exam

Imaging Indications

American Academy of Neurology (AAN) Guidelines: Neuroimaging not usually warranted for patients with migraine and normal neurological examination. [16]

Indications for CT/MRI Brain:

Imaging NOT indicated:

• Typical migraine with normal neurological exam
• Stable headache pattern with prior migraine diagnosis
• No red flags

Laboratory Studies

Not routinely indicated for typical migraine

Lumbar Puncture Indications and Interpretation

Indications:

• Thunderclap headache with negative CT (SAH)
• Fever + headache + meningismus (meningitis)
• Altered consciousness + fever (encephalitis)
• Papilledema with normal imaging (IIH - measure opening pressure)

Contraindications:

• Mass lesion or mass effect on imaging (risk of herniation)
• Coagulopathy (correct before LP)
• Thrombocytopenia less than 50,000 (relative)
• Infection at LP site

Interpretation:

SAH and Xanthochromia:

• Xanthochromia: Yellow CSF from bilirubin (breakdown of RBCs)
• Peak at 12 hours to 2 weeks after SAH
• Spectrophotometry more sensitive than visual inspection
• If LP less than 12 hours after thunderclap: May not have xanthochromia yet; RBC count > 100,000 cells/μL suggests SAH (vs. traumatic tap)
• Traumatic tap: RBCs clear from tube 1 → tube 4; no xanthochromia

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Treatment

Principles of Acute Migraine Management

1. Exclude secondary causes: Red flags → Imaging/LP as indicated
2. Rehydration: IV fluids (NS 500-1000 mL) - dehydration common with vomiting
3. Antiemetics: Relieve nausea; dopamine antagonists (metoclopramide, prochlorperazine) have intrinsic analgesic properties
4. Abortive therapy: NSAIDs, triptans, or CGRP antagonists (gepants) to terminate attack
5. Adjunctive therapy: Steroids (dexamethasone) to reduce 24-72 hour recurrence
6. Rescue therapy: Magnesium, valproate, DHE for refractory cases
7. Avoid opioids: Not first-line; risk of medication overuse headache, dependence, ED recidivism
8. Early treatment: Treat within 1-2 hours of onset; central sensitization/allodynia indicates delayed treatment may be less effective

Evidence-Based ED "Migraine Cocktail"

Standard Regimen (Level A evidence): [17,18,19]

Alternative Antiemetic:

• Prochlorperazine 10 mg IV: Similar efficacy to metoclopramide; also causes akathisia (give with diphenhydramine)

Metoclopramide Evidence [17]:

• Friedman et al., Neurology 2017: RCT of IV metoclopramide 20 mg + diphenhydramine 25 mg vs. placebo
  • 76% sustained headache freedom at 48 hours (vs. 47% placebo)
  • NNT 3.4 for sustained headache freedom
  • "Combination with diphenhydramine: Akathisia 4% (vs. 28% without diphenhydramine)"

Dexamethasone Evidence [20]:

• Colman et al., BMJ 2008: Meta-analysis of dexamethasone for acute migraine
  • "Reduces headache recurrence at 24-72 hours: RR 0.74 (95% CI 0.60-0.90), NNT 9"
  • "Dose: 10 mg IV or IM most common"

Triptans (5-HT1B/1D Receptor Agonists)

Mechanism: [21]

• 5-HT1B receptor agonism: Vasoconstriction of dilated intracranial vessels (especially meningeal arteries)
• 5-HT1D receptor agonism: Inhibits CGRP release from trigeminal nerve terminals; blocks nociceptive transmission in TNC

Efficacy: [21,22]

• Pain-free at 2 hours: 30-45% (vs. 10% placebo)
• Headache relief at 2 hours: 60-70%
• NNT: 6-8 for pain-free at 2 hours
• Most effective if taken early (less than 1-2 hours from onset, before central sensitization/allodynia)
• Subcutaneous sumatriptan most effective route (6 mg SC: pain-free 2h ~50%)

Available Triptans:

Contraindications (Vasoconstrictive effects):

• Coronary artery disease: Myocardial infarction, angina, vasospastic angina
• Cerebrovascular disease: Prior stroke, TIA
• Peripheral vascular disease: Claudication, Raynaud's
• Uncontrolled hypertension: SBP > 140 or DBP > 90 mmHg
• Hemiplegic or basilar migraine: Risk of prolonged vasoconstriction in affected territory
• Recent use of ergots (less than 24 hours): Additive vasoconstriction
• Recent use of MAO inhibitors (less than 2 weeks)
• Age less than 18 years (not FDA-approved; some evidence for adolescents)

Adverse Effects:

• Triptan sensations (10-20%): Chest tightness/pressure (usually benign, not cardiac), neck tightness, tingling, warmth, flushing
  • "Chest pain/tightness: Usually not cardiac (esophageal spasm, chest wall); if persistent or concerning → ECG, troponin"
• Nausea, dizziness, drowsiness (10%)
• Recurrence (20-40%): Headache returns within 24 hours; may re-dose after 2 hours if initial response
• Serotonin syndrome (rare): With SSRIs/SNRIs (theoretical risk; actual risk very low)

2025 American College of Physicians (ACP) Guideline [22]:

• Triptans recommended for acute episodic migraine in outpatients
• Oral triptans equally effective (choice based on cost, availability, patient preference)
• Consider subcutaneous sumatriptan if rapid onset needed or vomiting

NSAIDs and Acetaminophen

NSAIDs (COX inhibitors): [18,19,22]

• Mechanism: Inhibit prostaglandin synthesis; anti-inflammatory; reduce peripheral and central sensitization
• Efficacy: NNT 6-7 for pain-free at 2 hours (comparable to triptans for mild-moderate migraine)
• First-line for mild-moderate migraine; triptans for moderate-severe

Common NSAIDs for Migraine:

Combination Analgesics:

• Aspirin 250 mg + acetaminophen 250 mg + caffeine 65 mg (Excedrin Migraine): Effective for mild-moderate migraine; NNT 5.6
• Caffeine enhances analgesic effect (vasoconstriction, adenosine antagonism)

Acetaminophen:

• Dose: 1000 mg PO
• Efficacy: Less effective than NSAIDs or triptans (NNT ~12); safe in pregnancy
• Combination with caffeine: Improves efficacy

Contraindications to NSAIDs:

• Renal impairment (Cr > 1.5 mg/dL, CKD)
• GI bleeding, active peptic ulcer disease
• Aspirin allergy
• Anticoagulation (relative contraindication)

CGRP Antagonists (Gepants)

Mechanism: Small molecule CGRP receptor antagonists; block CGRP binding to receptors on meningeal vessels and trigeminal neurons. [13,23]

Advantages over triptans:

• No vasoconstriction: Safe in cardiovascular disease, stroke, uncontrolled HTN
• No medication overuse headache (emerging evidence)
• Can be used in hemiplegic and basilar migraine

Available Gepants for Acute Treatment:

Gepants for Prophylaxis:

• Rimegepant 75 mg every other day: Reduces monthly migraine days by 4.3 days (vs. 3.5 placebo)
• Atogepant 60 mg daily: Reduces monthly migraine days by 4 days; effective in chronic migraine with medication overuse [24]

Adverse Effects: Nausea (6-11%), somnolence (3-6%); generally well-tolerated

Limitations: Cost (not yet generic); limited long-term data

Antiemetics

Dopamine Antagonists (D2 receptor antagonists): Antiemetic AND analgesic properties. [17,18,19]

Mechanism of analgesia: D2 antagonism in chemoreceptor trigger zone; may also modulate pain pathways in brainstem.

Akathisia:

• Incidence: 10-30% with metoclopramide or prochlorperazine
• Presentation: Restlessness, inability to sit still, anxiety (occurs 15-30 min after IV dose)
• Prevention: Diphenhydramine 25-50 mg IV given BEFORE or WITH dopamine antagonist
• Treatment: Diphenhydramine 25-50 mg IV; benzodiazepines (lorazepam 1-2 mg IV) if severe

5-HT3 Antagonists (No analgesic effect; antiemetic only):

• Ondansetron 4-8 mg IV: Effective antiemetic; NO analgesic properties in migraine (no better than placebo for pain)
• Use if nausea prominent and dopamine antagonists contraindicated or not tolerated

Corticosteroids

Dexamethasone reduces 24-72 hour headache recurrence after ED discharge. [20]

Evidence:

• Colman et al., BMJ 2008: Meta-analysis of 7 RCTs (N=1,425)
  • "Dexamethasone reduces recurrence at 24-72 hours: RR 0.74 (95% CI 0.60-0.90), NNT 9"
  • "Dose: 10-24 mg IV or IM"

Recommended Regimen:

• Dexamethasone 10 mg IV or IM as single dose in ED

Mechanism: Anti-inflammatory; reduces neurogenic inflammation and meningeal vessel inflammation

Adverse Effects: Minimal with single dose; hyperglycemia in diabetics, insomnia

Discharge Steroid Taper (Optional):

• Some providers prescribe short taper (e.g., dexamethasone 4 mg PO daily × 2 days) to further reduce recurrence; limited evidence

Magnesium Sulfate

Mechanism: NMDA receptor antagonist; blocks cortical spreading depression; vasodilator. [18,19]

Evidence:

• Effective for migraine with aura
• Meta-analyses show modest benefit (NNT ~10-15)
• Safe, well-tolerated

Dose:

• 1-2 g IV over 15-30 minutes

Indications:

• Migraine with aura (especially visual aura)
• Refractory migraine not responding to other therapies
• Pregnancy (safe)

Adverse Effects: Flushing, warmth, hypotension (rare); reduce infusion rate if occurs

Valproate Sodium

Mechanism: Unknown for migraine; may inhibit CGRP release, modulate ion channels. [18]

Dose:

• 500-1000 mg IV over 15-30 minutes (loading dose)

Efficacy:

• Effective for refractory migraine, status migrainosus
• NNT ~10 for pain-free at 2 hours

Indications:

• Status migrainosus (migraine > 72 hours)
• Refractory migraine not responding to standard therapies

Contraindications:

• Pregnancy (teratogenic: neural tube defects, fetal valproate syndrome)
• Liver disease
• Pancreatitis

Adverse Effects: Sedation, dizziness, nausea; rare hepatotoxicity, pancreatitis

Dihydroergotamine (DHE)

Mechanism: Ergot alkaloid; 5-HT1B/1D agonist (like triptans); also alpha-adrenergic agonist. [18,19]

Dose:

• 0.5-1 mg IV over 2-3 minutes (may repeat every 8 hours; max 3 mg/24h)
• 1 mg IM or SC (may repeat)

Efficacy:

• Effective for refractory migraine, status migrainosus
• Lower recurrence rate than triptans (long half-life)

Indications:

• Status migrainosus
• Refractory migraine
• Patients with high recurrence rate with triptans

Contraindications (Same as triptans + additional):

• Coronary artery disease, peripheral vascular disease, uncontrolled HTN
• Sepsis (risk of vasoconstriction in hypoperfusion)
• Renal or hepatic impairment
• Pregnancy (uterine contraction)
• Recent triptan use (less than 24 hours): Additive vasoconstriction; MUST WAIT 24 hours after triptan before DHE

Adverse Effects:

• Nausea (very common; give with antiemetic)
• Cramping, diarrhea
• Chest tightness
• Ergotism (with prolonged use): Peripheral vasoconstriction, ischemia

Pretreatment:

• Metoclopramide 10 mg IV or ondansetron 4 mg IV 30 minutes before DHE to prevent nausea

Opioids (NOT Recommended)

Current Recommendations: Avoid opioids for acute migraine. [18,19,22]

Reasons to Avoid:

1. Less effective than triptans, NSAIDs, or migraine cocktail
2. Medication overuse headache: Opioid use ≥10 days/month → Chronic daily headache
3. Dependence and addiction risk
4. ED recidivism: Higher return rates with opioid use
5. Adverse effects: Nausea (worsens migraine nausea), sedation, respiratory depression

Quality Metrics: Many EDs track "opioid avoidance for migraine" as quality indicator (target > 80% avoidance)

When Opioids May Be Considered (Last Resort):

• All other therapies failed or contraindicated
• Status migrainosus refractory to IV cocktail, magnesium, valproate, DHE
• Document rationale

If Used:

• Morphine 0.1 mg/kg IV or hydromorphone 0.5-1 mg IV
• Single dose only; avoid prescribing opioids at discharge
• Counsel on risks of medication overuse headache

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Status Migrainosus

Definition: Migraine attack lasting > 72 hours despite treatment, with debilitating intensity. [25]

Clinical Features

• Continuous severe headache > 72 hours
• Refractory to usual abortive medications
• Nausea, vomiting → Dehydration
• Inability to function or tolerate oral intake
• May require hospitalization

ED Management [25,26]

Aggressive IV Therapy:

DHE Protocol (If no contraindications):

1. Pretreatment: Metoclopramide 10 mg IV or ondansetron 4 mg IV (30 min before DHE)
2. DHE: 0.5-1 mg IV over 2-3 minutes
3. Repeat: q8h up to 3 mg/24 hours (total max 6 mg/week)
4. Continue until headache-free for 24 hours

Continuous DHE Infusion (Inpatient, Specialized Headache Centers):

• DHE 0.5-1 mg IV q8h for 2-5 days
• Highly effective for status migrainosus, refractory chronic migraine
• Requires headache specialist supervision

Admission Criteria

• Refractory to ED therapies after 6-12 hours
• Intractable vomiting, unable to tolerate oral intake, severe dehydration
• Requires continuous IV therapy (DHE protocol)
• Social factors (unable to care for self at home)

Disposition

• Admit for IV DHE protocol, continuous IV therapy if refractory
• Neurology or headache specialist consult for inpatient management
• Transition to prophylaxis after acute treatment (topiramate, propranolol, CGRP mAb)

---

Chronic Migraine and Medication Overuse Headache

Chronic Migraine

Definition (ICHD-3): [1,4]

• ≥15 headache days per month for > 3 months
• With features of migraine on ≥8 days per month

Epidemiology:

• Prevalence: 1-2% of general population
• Progression from episodic migraine: 2.5-3% per year
• Risk factors: Medication overuse, obesity, depression, traumatic life events, frequent episodic migraine

Disability:

• Severe impact on quality of life, work productivity
• Higher healthcare utilization, costs

Management:

1. Rule out medication overuse headache (MOH)
2. Prophylactic therapy: Topiramate, propranolol, amitriptyline, CGRP mAbs (erenumab, fremanezumab, galcanezumab), onabotulinumtoxinA (Botox)
3. Neurology referral: Chronic migraine requires specialist management
4. Lifestyle modifications: Sleep hygiene, stress management, regular exercise, trigger avoidance
5. Behavioral therapy: Cognitive-behavioral therapy (CBT), biofeedback

Medication Overuse Headache (MOH)

Definition (ICHD-3): [27,28]

• Headache ≥15 days/month in patient with pre-existing headache disorder (usually migraine)
• Regular overuse of acute headache medication for > 3 months:
  • "Simple analgesics (NSAIDs, acetaminophen): ≥15 days/month"
  • "Triptans, combination analgesics, opioids, ergots: ≥10 days/month"
• Headache worsens with medication use
• Headache improves within 2 months of cessation

Epidemiology:

• Affects 1-2% of general population, 30-50% of chronic migraine patients
• Female predominance (3-4:1)
• Major cause of chronic daily headache

Pathophysiology: [27,28]

• Central sensitization: Frequent analgesic use → Increased pain sensitivity
• Downregulation of endogenous pain modulation
• Dopaminergic and serotonergic dysfunction

Clinical Features:

• Daily or near-daily headache (bilateral, dull, pressing)
• Superimposed episodic migraine attacks
• Early morning headache
• Headache improves temporarily with medication → Rebound → Need for more medication (vicious cycle)
• Associated anxiety, depression, sleep disturbance

Culprit Medications:

• Triptans (most common in migraine patients)
• Combination analgesics (aspirin + acetaminophen + caffeine; butalbital combinations)
• Opioids
• NSAIDs (ibuprofen, naproxen)
• Acetaminophen

Diagnosis:

• Detailed medication history: Type, frequency, doses
• Headache diary: Track headache days and medication use
• ≥10-15 days/month medication use for ≥3 months

Management: [27,28]

1. Education and Counseling:

   • Explain MOH mechanism (medication causing headache)
   • Set expectation: Headache will worsen for 2-4 weeks after cessation before improvement
   • Importance of compliance with withdrawal

2. Medication Withdrawal:

   • Abrupt cessation (preferred for most medications)
     • NSAIDs, acetaminophen, triptans: Abrupt stop
     • Opioids, butalbital: May require taper (withdrawal symptoms, seizure risk with butalbital)
   • Withdrawal symptoms: Headache worsening (peak 2-10 days), nausea, vomiting, anxiety, sleep disturbance
   • Duration: Symptoms improve after 2-4 weeks; headache pattern normalizes within 2 months in 50-70%

3. Bridge Therapy (During Withdrawal):

   • Naproxen 500 mg PO BID for 2 weeks (if not overusing NSAIDs)
   • Prednisone 60-100 mg daily for 5 days (then taper or stop) - reduces withdrawal headache
   • Antiemetics: Ondansetron, metoclopramide PRN for nausea

4. Initiate Prophylaxis (Start immediately):

   • Topiramate 50-100 mg daily (titrate slowly)
   • Propranolol 80-160 mg daily
   • Amitriptyline 25-75 mg at bedtime
   • CGRP monoclonal antibodies: Erenumab, fremanezumab, galcanezumab (highly effective; atogepant shown effective in chronic migraine with MOH) [24]

5. Acute Medication Limits (After Withdrawal):

   • Limit to less than 10 days/month for triptans, combination analgesics
   • Limit to less than 15 days/month for simple analgesics
   • Use prophylaxis to reduce attack frequency

6. Neurology Referral:

   • MOH requires specialist management
   • Consider inpatient withdrawal if severe, multiple prior failed outpatient attempts

Prognosis:

• 50-70% improve within 2 months of cessation
• Relapse common (30-50% within 1 year) → Need for ongoing prophylaxis, education

---

Prophylactic Therapy

Indications for Prophylaxis: [29,30]

• ≥4 migraine days per month (or ≥2 disabling attacks/month)
• Frequent attacks interfering with daily life despite acute treatment
• Contraindication or failure of acute therapies
• Medication overuse headache
• Patient preference
• Specific subtypes: Hemiplegic migraine, migraine with prolonged aura, migrainous infarction

Goals:

• Reduce attack frequency by ≥50%
• Reduce attack severity and duration
• Improve response to acute treatment
• Reduce disability
• Prevent progression to chronic migraine

First-Line Prophylactic Medications [29,30]

2025 ACP Guideline [30]: Propranolol, topiramate, amitriptyline, or CGRP mAbs recommended for episodic migraine prophylaxis.

CGRP Monoclonal Antibodies (First-Line for Chronic Migraine) [13,23]

Mechanism: Monoclonal antibodies targeting CGRP ligand or CGRP receptor.

Advantages:

• Highly effective: 50-60% responders (≥50% reduction in migraine days)
• Excellent tolerability: Minimal adverse effects (injection site reactions, constipation)
• No drug interactions: Monoclonal antibodies not metabolized by liver
• Safe in cardiovascular disease: No vasoconstriction (unlike triptans)
• Pregnancy: Unknown safety; avoid (limited data)

European Headache Federation 2022 Guideline [23]:

• CGRP mAbs are first-line for chronic migraine and episodic migraine with ≥4 attacks/month
• Especially recommended if prior failure of ≥2 oral prophylactics

Cost: Expensive (~$6,000-8,000/year); insurance coverage variable; patient assistance programs available.

Second-Line and Alternative Prophylactics

OnabotulinumtoxinA (Botox) for Chronic Migraine

Indication: Chronic migraine (≥15 headache days/month with ≥8 migraine days/month)

Dose: 155 units IM every 12 weeks

• 31 injection sites across 7 head/neck muscle areas (frontalis, corrugator, procerus, temporalis, occipitalis, cervical paraspinal, trapezius)

Efficacy:

• Reduces migraine days by 8-9 days/month (vs. 6-7 days with placebo)
• 50% responder rate: 47% (vs. 35% placebo)

Mechanism: Inhibits neurotransmitter release (CGRP, glutamate, substance P) from peripheral nerve endings; blocks peripheral sensitization.

Adverse Effects: Neck pain, muscle weakness, ptosis, injection site pain (mild, transient)

Administration: Requires neurologist or headache specialist; injections every 12 weeks

Prophylaxis Selection

Considerations:

• Comorbidities:
  • Hypertension → Propranolol, candesartan
  • Depression → Amitriptyline, venlafaxine
  • Epilepsy → Topiramate, valproate
  • Obesity → Topiramate (weight loss)
  • Insomnia → Amitriptyline
• Contraindications:
  • Asthma → Avoid beta-blockers
  • Pregnancy → Avoid valproate, topiramate; consider propranolol (Category C), CGRP mAbs (unknown)
  • Kidney stones → Avoid topiramate
  • CAD, heart block → Avoid beta-blockers
• Prior failures: If failed ≥2 oral prophylactics → CGRP mAbs
• Cost: Generic oral medications cheapest; CGRP mAbs expensive but highly effective

Trial Duration: ≥2-3 months at therapeutic dose before assessing efficacy (allow time for onset)

Titration: Start low, titrate slowly (especially topiramate, amitriptyline) to improve tolerability

Combination Therapy: May combine prophylactics if monotherapy insufficient (e.g., propranolol + topiramate; CGRP mAb + oral prophylactic)

---

Menstrual Migraine

Definition: [6,31]

• Pure menstrual migraine: Attacks occur exclusively on days -2 to +3 of menstruation (day 1 = first day of bleeding) in ≥2/3 cycles
• Menstrually-related migraine: Attacks occur both with menstruation and at other times (most common)

Epidemiology:

• 60% of women with migraine report perimenstrual worsening
• 7-14% have pure menstrual migraine

Pathophysiology:

• Estrogen withdrawal at end of luteal phase (just before menstruation) triggers migraine
• Rapid drop in estrogen → Increased prostaglandins, decreased endorphins

Clinical Features:

• Typically migraine without aura
• More severe, longer duration, more refractory to treatment than non-menstrual attacks
• Predictable timing (days -2 to +3 of menstruation)

Management [6,31]

Acute Treatment (Same as non-menstrual migraine):

• Triptans (sumatriptan, rizatriptan, eletriptan)
• NSAIDs (naproxen, ibuprofen)
• Combination therapy (triptan + NSAID)

Short-Term Prophylaxis (Perimenstrual Prophylaxis):

Hormonal Management:

• Extended-cycle oral contraceptives: Continuous OCP (skip placebo pills) → Fewer menstrual periods → Fewer menstrual migraines
• Estrogen supplementation: Estradiol patch 100 mcg applied 2 days before expected estrogen drop → Continue through menstruation (prevents estrogen withdrawal)
• Menstrual suppression: GnRH agonists, progestin-only contraceptives (limited evidence; consider if refractory)

Continuous Prophylaxis (If frequent non-menstrual migraines also):

• Standard prophylactics (propranolol, topiramate, CGRP mAbs)

---

Special Populations

Pregnancy [32]

Epidemiology:

• Migraine improves in pregnancy: 50-80% of women experience improvement (especially 2nd and 3rd trimesters)
• Improvement due to stable high estrogen levels
• Migraine with aura less likely to improve than migraine without aura

Acute Treatment:

Prophylaxis:

• Avoid most prophylactics in pregnancy (teratogenicity)
• Propranolol: Relatively safe (Category C); IUGR risk
• Magnesium: 400 mg daily (safe)
• Non-pharmacologic: Biofeedback, relaxation, trigger avoidance

Red Flags in Pregnancy:

• New headache in 2nd half of pregnancy: Consider pre-eclampsia (BP > 140/90, proteinuria, edema), PRES, CVT
• Severe headache with neurological signs: Eclampsia (seizures), stroke, CVT
• Postpartum headache: CVT (peak 1-2 weeks postpartum), PRES, posterior circulation stroke

Elderly (> 65 Years) [33]

New Headache > 50 Years → Red Flag:

• Giant cell arteritis (GCA): ESR, CRP, temporal artery biopsy
• Malignancy: Brain tumor, metastases
• Secondary causes more common

Triptans in Elderly:

• Use with caution: Higher prevalence of cardiovascular disease, hypertension, stroke
• Screen for CAD, PAD before prescribing
• Consider alternatives: NSAIDs, antiemetics, gepants (no cardiovascular contraindications)

"Late-Life Migraine Accompaniments" [33]:

• Migraine aura without headache in older patients
• Visual aura (scintillating scotoma) without subsequent headache
• Differential: TIA, stroke, retinal detachment (rule out with imaging if first episode or atypical)

Medication Overuse Headache (Discussed Above)

See "Chronic Migraine and Medication Overuse Headache" section.

---

Disposition and Follow-Up

Discharge Criteria

• Pain adequately controlled (headache reduced to mild or resolved)
• Able to tolerate oral intake (no vomiting)
• No red flag symptoms
• Normal neurological examination (or back to baseline if hemiplegic migraine)
• Follow-up arranged with PCP or neurology

Admission Criteria

• Status migrainosus (> 72 hours) not responding to ED treatment
• Intractable vomiting, dehydration requiring IV hydration
• Serious secondary cause identified (SAH, meningitis, stroke, mass)
• Need for continuous IV medications (DHE protocol)
• Hemiplegic migraine with prolonged aura (rule out stroke)
• Social factors: Unable to care for self at home, lack of support

Referral to Neurology or Headache Specialist

Indications:

• Frequent migraines (≥4/month) requiring prophylaxis
• Chronic migraine (≥15 headache days/month)
• Medication overuse headache
• Refractory migraine (failed multiple abortive or prophylactic medications)
• Atypical features (prolonged aura, motor aura, brainstem aura, first episode > 40 years)
• Hemiplegic migraine
• Need for specialized therapies: Botox, CGRP mAbs, DHE infusion

Discharge Prescriptions

Abortive Medications:

• Triptan: Sumatriptan 100 mg PO (#9, take 1 at onset, may repeat × 1 after 2 hours if needed; max 2 doses/24h; limit to 9 doses/month)
  • "Alternative: Rizatriptan 10 mg, eletriptan 40 mg, zolmitriptan 5 mg"
• NSAID: Naproxen sodium 500 mg PO (#20, take 1-2 at onset, may repeat BID PRN; limit to less than 15 days/month)
  • "Alternative: Ibuprofen 600-800 mg"
• Antiemetic: Ondansetron 4-8 mg PO ODT (#6, take 1 PRN nausea) OR metoclopramide 10 mg PO (#12, take 1 PRN nausea; max TID)

Steroid Taper (Optional, to reduce recurrence):

• Dexamethasone 4 mg PO daily × 2 days (#2 tablets)

Instructions:

• Limit acute medication use to less than 10 days/month (triptans) or less than 15 days/month (NSAIDs) to prevent medication overuse headache
• Take medications early in migraine attack (within 1-2 hours of onset)
• Avoid opioids

Patient Education

Condition Explanation:

• "Migraine is a neurological condition that causes severe headaches with nausea, light sensitivity, and sometimes visual disturbances (aura)."
• "It's caused by changes in brain activity and blood vessel inflammation, not a dangerous condition in most cases."
• "We can treat acute attacks and help prevent future ones with prophylactic medications."

Trigger Identification and Avoidance:

• Keep headache diary: Track headache days, triggers (food, sleep, stress, menstruation), medication use
• Common triggers: Menstruation, sleep changes, stress, alcohol, certain foods (aged cheese, chocolate, MSG), bright lights, strong odors
• Avoid rigorous trigger avoidance (may increase sensitivity); balanced approach

Lifestyle Modifications:

• Regular sleep schedule: 7-8 hours/night; avoid oversleeping on weekends
• Regular meals: Avoid skipping meals, fasting
• Hydration: 8 glasses water/day
• Regular exercise: Aerobic exercise 30 min 3-5×/week (may reduce migraine frequency)
• Stress management: Relaxation techniques, meditation, biofeedback, CBT

Medication Use:

• Take abortive medications early (within 1-2 hours of onset) for best efficacy
• Limit acute medication use to prevent medication overuse headache:
  • "Triptans, combination analgesics: less than 10 days/month"
  • "Simple analgesics (NSAIDs, acetaminophen): less than 15 days/month"
• If using acute medications ≥10-15 days/month, discuss prophylaxis with PCP or neurologist

Warning Signs to Return to ED:

• Thunderclap headache: Sudden severe headache reaching maximum intensity in less than 1 minute ("worst headache of my life")
• Fever with headache: Especially with neck stiffness, rash, confusion
• Focal neurological deficits: Weakness, numbness, vision loss, difficulty speaking (not typical aura)
• Headache with altered consciousness: Confusion, difficulty waking up
• Prolonged aura: Aura lasting > 1 hour (consider stroke)
• Headache not responding to usual treatment
• New type of headache (different from usual migraine)

Follow-Up:

• PCP within 1-2 weeks for:
  • Prophylaxis discussion if ≥4 migraines/month
  • Medication review
  • Headache diary review
• Neurology referral if frequent, refractory, or atypical features

---

Quality Metrics and Performance Indicators

ED Performance Indicators

Documentation Requirements

Essential Documentation:

1. Headache characterization (POUND):
   • Pulsating quality
   • One-day duration (4-72 hours)
   • Unilateral location
   • Nausea/vomiting
   • Disabling intensity
2. Red flag assessment (SNOOP4):
   • Systemic symptoms/illness
   • Neurological signs
   • Onset sudden
   • Older age
   • Pattern change, Precipitated by, Papilledema, Pregnancy
3. Neurological examination findings:
   • Mental status, cranial nerves, motor, sensory, reflexes, coordination, gait, neck
   • Normal exam expected in typical migraine
4. Prior migraine history: Frequency, prior diagnosis, triggers, medications
5. Medication overuse assessment: Current analgesic use (days/month)
6. Medications given and response: Pain scale before/after treatment
7. Imaging rationale (if obtained): Which red flag prompted imaging
8. Discharge instructions: Abortive medications, warning signs, follow-up
9. Referral (if indicated): Neurology for frequent migraines, prophylaxis

---

Key Clinical Pearls

Diagnostic Pearls

• Migraine is a clinical diagnosis: Based on ICHD-3 criteria (POUND mnemonic) and normal neurological exam
• SNOOP4 for red flags: Rule out SAH, meningitis, GCA, mass, stroke before diagnosing migraine
• Thunderclap headache = SAH until proven otherwise: CT → LP if CT negative
• New headache > 50 years = GCA or malignancy until proven otherwise: ESR, imaging
• Normal neurological exam expected in migraine: Focal deficits → Imaging (rule out stroke, mass, hemiplegic migraine)
• Imaging NOT routinely indicated for typical migraine: Only for red flags
• Medication overuse is common: Ask about analgesic use frequency (≥10-15 days/month → MOH)
• Aura timing: Aura precedes headache by 5-60 minutes, fully reversible; prolonged aura (> 1 hour) → Consider stroke

Treatment Pearls

• ED migraine cocktail: IV fluids + metoclopramide 10-20 mg + diphenhydramine 25-50 mg + ketorolac 15-30 mg + dexamethasone 10 mg
• Antiemetics have analgesic properties: Metoclopramide, prochlorperazine (D2 antagonists) - not just for nausea!
• Diphenhydramine prevents akathisia: Give prophylactically with metoclopramide/prochlorperazine (not as treatment)
• Triptans are first-line abortive: If no contraindications (CAD, stroke, uncontrolled HTN)
• Subcutaneous sumatriptan fastest: 6 mg SC, onset 10-15 min, pain-free 2h ~50%
• Take triptans early (less than 1-2 hours from onset): More effective before central sensitization/allodynia
• Dexamethasone reduces recurrence: 10 mg IV reduces 24-72h recurrence by 26% (NNT 9)
• Avoid opioids: Less effective, medication overuse headache risk, ED recidivism
• Magnesium for aura or refractory cases: 1-2 g IV over 15 min (NMDA antagonist, blocks cortical spreading depression)
• Status migrainosus (> 72h) → DHE protocol: 0.5-1 mg IV q8h (pretreat with antiemetic); highly effective

Prophylaxis Pearls

• ≥4 migraine days/month → Prophylaxis: Reduces frequency, severity, disability
• First-line prophylactics: Propranolol, topiramate, amitriptyline, CGRP mAbs
• CGRP mAbs are game-changers: Erenumab, fremanezumab, galcanezumab - highly effective, minimal side effects, no drug interactions, safe in CVD
• Trial ≥2-3 months at therapeutic dose: Allow time for prophylaxis to work before deeming ineffective
• Topiramate and valproate are teratogenic: Avoid in women of childbearing age unless contraception reliable
• Botox for chronic migraine: 155 units IM q12 weeks (requires specialist)
• Medication overuse headache → Withdrawal + prophylaxis: Stop overused medication (headache worsens 2-4 weeks, then improves); start prophylaxis immediately

Disposition Pearls

• Most patients can be discharged: With adequate pain control, abortive prescriptions, follow-up
• Admit for status migrainosus refractory to ED treatment: May need IV DHE protocol, continuous therapy
• Neurology referral for frequent migraines: ≥4 attacks/month for prophylaxis discussion
• Educate on medication limits: less than 10 days/month triptans, less than 15 days/month NSAIDs (prevent MOH)
• Red flag → Imaging: Do not discharge without imaging if red flags present

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