Summary
Migraine is a primary headache characterized by recurrent episodes of unilateral, localized pain that are frequently accompanied by nausea, vomiting, and sensitivity to light and sound. In approximately 25% of cases, patients experience an aura preceding the headache, which involves reversible focal neurologic abnormalities, e.g., visual field defects (scotomas) or paresis lasting less than an hour. Migraine is a clinical diagnosis and imaging is generally not indicated. Treatment of attacks consists of general measures (e.g., minimizing light and sound) together with administration of nonsteroidal anti-inflammatory drugs (e.g., aspirin) and antiemetics (e.g., prochlorperazine) if nausea is present. In severe cases, triptans may be added. Prophylactic treatment (e.g., beta blockers) may be indicated if migraines are especially frequent or long-lasting, or if abortive therapy fails or is contraindicated.
Epidemiology
- Prevalence: ∼ 17% of females and ∼ 6% of males [1]
- Peak incidence: 30–39 years [2][3]
- Migraine is the second most common type of headache.
Epidemiological data refers to the US, unless otherwise specified.
Etiology
- The exact pathophysiology is unclear. [4]
- Genetic predisposition
- Potential triggers
- Certain food and beverages: alcohol, nicotine, citrus fruits, dairy products, food containing tyramine (e.g., chocolate, red wine)
- Poor sleeping habits
- Emotional stress
- Weather changes
- Hormonal changes in women: menstruation, hormone intake (oral contraceptive pills)
Pathophysiology
- The pathophysiology of migraine is not fully understood.
- Various factors are thought to contribute to the development and severity of migraines.
-
Activation of meningeal nociceptors
- Dilatation of intracranial blood vessels → activation of meningeal nociceptors
- Activation of the trigeminovascular pathway: activation of trigeminal neurons → release of vasoactive neuropeptides such as substance P or calcitonin gene-related peptide (CGRP) → vasodilatation and release of proinflammatory molecules (histamine, bradykinin, serotonin, prostaglandins) → neurogenic inflammation → activation of meningeal nociceptors [5]
- Cortical spreading depression: excitation and inhibition of the cerebral cortex → changes in cortical enzymatic activity (proinflammatory molecules) → neurogenic inflammation → activation of meningeal nociceptors [6]
- Dysregulation of pain sensitization in the trigeminal system (CN V): cortical spreading depression → dysregulation of trigeminovascular neurons → neurogenic inflammation → hypersensitization → nausea, loss of appetite, yawning, fatigue, anxiety, depression [7]
- Genetic predisposition: in individuals with migraine, the brain does not have the ability to habituate itself to external stimuli (e.g., stress, hormonal changes) → hyperexcitable brain [6]
- Activation of the autonomic nervous system; : external physiological and emotional stimulation (e.g., hormonal changes, stress) → hypothalamic response to the change in homeostasis → hypothalamic neurons influence the autonomic nervous system → shift toward a parasympathetic tone → constriction and dilatation of intracranial, especially the meningeal, blood vessels [6]
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Activation of meningeal nociceptors
Vasodilatation is now considered an epiphenomenon rather than the primary cause of migraine headache. [5]
Clinical features
Migraine is characterized by recurrent attacks and may occur with aura (∼ 25% of cases) or without aura (∼ 75% of cases). A typical migraine attack passes through four stages, and the aura (if present) typically occurs before the headache. However, migraine patterns may differ and not follow the characteristic stages.
1. Prodrome (facultative)
- 24–48 hours before the headache starts
- Excessive yawning
- Difficulties with writing or reading
- Sudden hunger or lack of appetite
- Mood changes
2. Aura
Paroxysmal, focal, neurologic symptoms that precede (or, in some cases, occurring during) the headache.
-
Typical aura [8][9]
-
Visual disturbances, sensory and/or speech symptoms (positive and/or negative ;)
- Scintillating scotoma: an arch-shaped scotoma that starts centrally and shifts peripherally (appears for ∼ 15–30 minutes)
- Central scotoma
- Flashing lights
- Distorted color perception
- Fortification spectra: star-like, zigzag figures
- Impaired sensibility, paresthesia
- Aphasia
- No motor symptoms
- Develops gradually
- Completely reversible
- Symptoms last ≤ 60 minutes each
-
Visual disturbances, sensory and/or speech symptoms (positive and/or negative ;)
-
Atypical aura
- Paresis
- Dizziness
- Persistent or long-lasting symptoms
3. Headache
-
Localization
- Typically unilateral, but bilateral headache is possible
- Especially frontal, frontotemporal, retro-orbital
- Duration: usually 4–24 hours (rarely over 72 hours)
- Course: progression of pulsating, throbbing, or pounding pain
- Exacerbated by physical activity
- Accompanying symptoms: photophobia, phonophobia, and nausea/vomiting
4. Postdrome (facultative)
- Feeling of exhaustion or euphoria
- Muscle weakness
- Anorexia or food cravings
The typical migraine headache is “POUND”: Pulsatile, One-day duration, Unilateral, Nausea, Disabling intensity.
Subtypes and variants
All variants of acute migraine should raise suspicion for other diagnoses (e.g., transient ischemic attack), especially if the first aura occurs after 40 years of age, auras last an atypical amount of time, or symptoms are predominantly negative.
Migraine with brainstem aura [8]
- Previously known as basilar migraine
- Patients have episodes of migraine preceded at least some of the time by brainstem aura (but can also be preceded by typical aura).
- Criteria for brainstem aura
- ≥ 2 fully reversible brainstem symptoms (e.g., dysarthria, vertigo, tinnitus, diplopia, ataxia, hearing loss, impaired consciousness)
- No motor or retinal symptoms
Vestibular migraine [8][10]
- Most common cause of spontaneous episodic vertigo
- Diagnosed migraine plus ≥ 5 episodes of vestibular symptoms (e.g., vertigo) lasting ≤ 72 hours
- Treatment may be complemented with antivertigo agents (e.g., dimenhydrinate ).
Hemiplegic migraine [8]
- May be familial or sporadic
- Main differential diagnosis: epilepsy
- Fully reversible aura (lasts ∼ 72 hours) consisting of both motor weakness and visual, sensory, or speech impairment
Retinal migraine [8]
- Aura consists of monocular visual phenomena (e.g., scintillation, scotoma, blindness).
- All symptoms are fully reversible.
-
Aura fulfills ≥ 2 of the following criteria:
- Spread: gradually over ≥ 5 minutes
- Duration: 5–60 minutes
- Onset of headache: within 60 minutes
Typical aura without headache (silent migraine) [8]
- Aura symptoms are present.
- Aura lasts for ≥ 60 minutes before the onset of the headache, which might not develop at all.
- Episodes may coexist with typical migraine symptoms.
Chronic migraine [8]
- Patients with migraine diagnosis (with or without aura) presenting with a ≥ 3-month history of the following:
- Headaches (variable in intensity and type ) ≥ 15 days/month
- ≥ 8 days/month headache has migraine characteristics or is relieved by migraine-specific medication (triptans, ergotamine).
- A headache diary is recommended for patients to help optimize treatment.
- Main differential diagnosis: medication overuse headache
Diagnostics
Migraine is a clinical diagnosis based on history and physical examination. The most important step is to exclude red flags for headache that suggest a secondary headache (e.g., infection, hemorrhage, intracranial mass) and require more exhaustive investigation (e.g., imaging). Suspect a primary headache when no red flags are identified, and confirm the diagnosis using the diagnostic criteria for migraine. [8][11]
Migraine is a clinical diagnosis that is based on patient history and physical examination.
Diagnostic criteria
| Diagnostic criteria for migraine [8] | ||
|---|---|---|
| Migraine without aura | Migraine with aura | |
| Number of attacks (total lifetime) |
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| Duration |
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| Characteristics |
| |
| ||
Imaging [11][12][13]
Neurological imaging is not routinely indicated for uncomplicated migraine.
-
Indications
- Clinical features suggest a secondary headache (see red flags for headache and high-risk headache).
- Migraine with the following characteristics: [13]
- Unusual, prolonged, or persisting aura
- First episode of brainstem aura, hemiplegic migraine, retinal migraine, aura without headache
- Change in baseline migraine clinical features (frequency, severity, aura)
- Consider in first migraine
-
Procedure
- MRI is preferred over CT (except in emergency settings if there is suspicion of a vascular hemorrhagic event).
- See “Imaging for headaches.”
-
Findings [13]
- Typically normal
- Nonspecific white-matter changes may be seen [13]
Differential diagnoses
The differential diagnoses listed here are not exhaustive.
Treatment
Abortive therapy
All patients
- Limit stimuli (i.e., light, loud noises) and activity.
- Start abortive treatment as soon as possible.
-
Treat nausea/vomiting, if present.
- IV fluids
- Parenteral antiemetics [14]
- Consider extrapyramidal syndrome (EPS) prophylaxis with diphenhydramine. [15][16][17]
Mild to moderate headache [8][14]
-
First-line treatment consists of NSAIDs, acetaminophen, acetylsalicylic acid, or combinations including caffeine.
- If tolerating PO, consider one of the following:
- If nausea/vomiting are present, consider one of the following:
- Second-line: proceed to “Moderate to severe headache” below
- Children: ibuprofen and family counseling
Moderate to severe headache [8][14]
- Start a migraine-specific agent: triptans (e.g., sumatriptan) or ergotamine (do not combine these agents!)
- First-line: oral or parenteral triptans
- If tolerating PO, consider one of the following:
- Sumatriptan-naproxen
- Zolmitriptan
- If nausea/vomiting are present or there is a higher analgesic requirement, consider one of the following:
- Sumatriptan
- Zolmitriptan
- If tolerating PO, consider one of the following:
- Second-line: consider one of the following
- A parenteral ergotamine (e.g., dihydroergotamine )
-
Butorphanol
- Consider in patients who cannot receive triptans or ergotamines.
- Use with caution due to frequent side effects , risk of rebound, and medication dependency.
- First-line: oral or parenteral triptans
- Consider recurrence prevention with dexamethasone . [18]
Do not combine triptans and ergotamines (within a 24-hour period) because of potentially dangerous drug interactions (e.g., coronary vasospasm and serotonin syndrome). [19]
Overview of migraine-specific agents
| Migraine-specific agents | ||
|---|---|---|
| Triptans | Ergotamine | |
| Agents |
| |
| Mechanism of action |
|
|
| Indications |
|
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| Side effects |
|
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| Contraindications |
| |
Triptans and ergotamine have severe pharmacological interactions (e.g., coronary spasm, serotonin syndrome) with one another and with other drugs (e.g., SSRI, macrolides). ALWAYS take a detailed history of the patient's usual and recent medications before selecting a drug.
Triptans and ergotamines are contraindicated in pregnancy.
A SUMo wrestler TRIPs ANd falls on his head: SUMaTRIPtANs are used for headaches (cluster and migraine).
Prophylactic therapy
Nonpharmacological [21]
-
Lifestyle modifications
- Exercise in moderation
- Maintain a healthy diet
- Identify and try to avoid potential triggers
- Follow a regular sleeping schedule
-
Other: There is some evidence that the following nonpharmacological interventions have some benefits for patients with migraine
- Noninvasive neuromodulation
- Behavioral therapy
- Relaxation techniques
- Biofeedback
Pharmacological [22]
-
Indications [23][24]
- ≥ 2 attacks/month that produce disability that lasts ≥ 3 days
- Severe disability regardless of frequency (e.g., hemiplegic migraine)
- ≥ 2 attacks/week regardless of severity
- Failure/contraindications/major side effects from acute medications
-
General considerations [22]
- Consider comorbidities when selecting a drug.
- Encourage headache diary to assess response to treatment.
- Start with a low dose and increase until reaching the therapeutic goal.
- Goals of prophylaxis
- Reduce frequency, severity, and duration of attacks.
- Improve response to acute treatment.
-
General prophylaxis
-
First-line [22]
- Anticonvulsants (e.g., topiramate; , valproate ) [22]
- Beta blockers (e.g., propranolol , metoprolol , timolol ) [22]
- Petasites (butterbur) [22]
-
Second-line [22]
- Tricyclic antidepressant: amitriptyline [22]
- NSAIDs: fenoprofen [22]
- Other: calcium channel blockers (e.g., flunarizine)
-
First-line [22]
-
Menstrual-related migraine [22]
- First-line: frovatriptan [22]
- Second-line
- Naratriptan [22]
- Zolmitriptan [22]
-
Chronic migraine
- Botulinum toxin (e.g., OnabotulinumtoxinA ) [9][25]
- Monoclonal antibodies: anti-CGRP or anti-CGRP receptor (e.g., erenumab, galcanezumab, fremanezumab) [9]
Complications
Status migrainosus [8]
-
Description: Debilitating migraine attack in a patient with a known migraine diagnosis (with or without aura)
- Exceptional in duration (≥ 72 hours) and severity
- Often related to medication overuse
-
Treatment: stepwise therapy with reassessment between drug administration [26]
- IV fluids
- Antiemetic (e.g., metoclopramide )
- NSAID (e.g., ketorolac )
- Dihydroergotamine [26]
- Dexamethasone [18]
- Valproate [27]
- Consider inpatient management by a specialist if there is no improvement.
We list the most important complications. The selection is not exhaustive.
Acute management checklist
-
Migraine of any severity [14][28][29][30]
- Consider CT/MRI of the brain with or without contrast if the presentation is atypical or red flags for headache are present. [31][32]
- Reduce light/noise in the patient's environment.
- Fluid hydration
- Begin pharmacologic treatment within 1 hour of symptom onset, if possible.
- Treat nausea/vomiting, if present.
-
Mild to moderate headache
- Start a nonspecific agent (e.g., NSAID, acetaminophen, or combinations including caffeine).
-
Moderate to severe headache, or if the above treatments fail
- Start a migraine-specific agent.
- First-line: oral or parenteral triptans
- Second-line: parenteral ergotamines
- Consider recurrence prevention with dexamethasone.
- Start a migraine-specific agent.
-
Status migrainosus refractory to above [26]
- Escalating therapy with antiemetic, NSAID, dihydroergotamine, dexamethasone, and valproic acid
- Consider inpatient treatment.
- Neurology consultation
- Consider alternative diagnoses.