Migraine (ไมเกรน)

• ICD-10:
  • G43.0 – Migraine without aura (common migraine)
  • G43.1 – Migraine with aura (classical migraine)
  • G43.2 – Status migrainosus
  • G43.3 – Complicated migraine
  • G43.9 – Migraine, unspecified
• ICD-11:
  • 8A80 – Migraine
  • 8A80.0 – Migraine without aura
  • 8A80.1 – Migraine with aura
  • 8A80.2 – Chronic migraine
  • 8A80.3 – Hemiplegic migraine
  • 8A80.4 – Retinal migraine
  • 8A80.Y – Other specified migraine
  • 8A80.Z – Migraine, unspecified

Overview

Migraine is a chronic, recurrent neurological disorder characterised by episodic attacks of moderate to severe headache, often pulsating and unilateral, associated with nausea, vomiting, photophobia, and phonophobia. It is a disabling condition and one of the leading causes of years lived with disability (YLDs) globally.

The World Health Organization classifies migraine under ICD-11 code 8A80 as a primary headache disorder. The disease spectrum ranges from episodic migraine (fewer than 15 days/month) to chronic migraine (≥15 days/month for more than 3 months, with at least 8 migraine days). Migraine affects quality of life and productivity, often triggered by stress, hormonal fluctuations, lack of sleep, dehydration, or certain foods (e.g. chocolate, cheese, caffeine withdrawal).

Epidemiology

Migraine is a common neurological disorder affecting approximately 15–20% of the global population. Prevalence is higher in women (3:1 female-to-male ratio) due to hormonal influences, particularly oestrogen fluctuations during menstruation and perimenopause. The typical onset is in adolescence or early adulthood, peaking between 25 and 45 years of age.

Lifetime prevalence:

• Women: ~18–25%
• Men: ~6–10%

Genetic predisposition plays a major role; about 60–70% of patients report a positive family history.

The Global Burden of Disease (GBD 2020) ranks migraine as the second leading cause of disability worldwide among neurological disorders. It is estimated to contribute to significant socioeconomic costs due to absenteeism, reduced work productivity, and healthcare utilisation.

Pathophysiology

These mechanisms interact in a cycle of neuronal hyperexcitability, neuroinflammation, and vascular changes that produce migraine’s distinctive episodic nature.

Clinical Presentation

Migraine typically progresses through four phases: prodrome, aura, headache, and postdrome. Not all patients experience every phase.

Phase	Symptoms	Pathophysiology	Frequency
Prodrome	Fatigue, mood change, food craving, neck stiffness	Hypothalamic dysfunction; dopamine fluctuation	30–60%
Aura	Visual: scintillating scotoma, zigzag lines Sensory: paresthesia Speech: dysphasia	Cortical spreading depression	25–30%
Headache	Unilateral, pulsatile pain (4–72 h) with nausea, photophobia, phonophobia	Trigeminovascular activation, CGRP release	Nearly all patients
Postdrome	Tiredness, cognitive slowing, mild residual headache	Neuronal recovery phase	50–70%

Common triggers include hormonal changes (menstruation), emotional stress, lack of sleep, fasting, alcohol (especially red wine), caffeine withdrawal, strong odours, and bright light.

Investigation

Diagnosis of migraine is clinical; investigations are used primarily to exclude secondary causes of headache.

• Neuroimaging: MRI brain is recommended if there are atypical features, aura with motor symptoms, new-onset headache after age 50, or focal neurological signs.
• CT brain: Used in emergency settings to rule out haemorrhage or mass lesion.
• EEG: Indicated only if seizure is suspected.
• Laboratory tests: CBC, ESR, TSH if systemic or endocrine cause is suspected.

Most migraine patients with a normal neurological examination and typical features do not require neuroimaging.

Diagnosis Criteria (Dx)

Diagnosis is based on the International Classification of Headache Disorders (ICHD-3) criteria for migraine without aura:

• At least 5 attacks fulfilling the following:
• Headache lasting 4–72 hours (untreated or unsuccessfully treated)
• Headache has ≥2 of the following:
  • Unilateral location
  • Pulsating quality
  • Moderate or severe pain intensity
  • Aggravation by or causing avoidance of routine physical activity
• During headache, at least one of the following:
  • Nausea and/or vomiting
  • Photophobia and phonophobia
• Not better accounted for by another ICHD-3 diagnosis.

Differential Diagnosis (DDx)

Disease	Distinguishing Features	Investigations	Comments
Tension-type headache	Bilateral, pressure-like, mild–moderate intensity, no nausea or photophobia	Normal exam	Most common primary headache; stress-related
Cluster headache	Severe unilateral orbital pain, lacrimation, nasal congestion, short duration (15–180 min)	Normal MRI	Predominantly affects middle-aged men; circadian pattern
Trigeminal neuralgia	Brief, electric-shock-like pain in facial region triggered by touch	MRI brain with contrast	Distinguished by paroxysmal nature and trigger points
Subarachnoid haemorrhage	“Thunderclap” headache, sudden onset, may have neck stiffness	CT brain ± LP	Medical emergency; rule out urgently
Idiopathic intracranial hypertension	Diffuse daily headache with papilloedema, visual blurring	Ophthalmoscopy, MRI + MRV, LP opening pressure	Common in obese young women
Brain tumour / mass lesion	Progressive headache, worse in morning, focal neurological deficits	MRI brain with contrast	Consider if new onset >50 years or personality change

Treatment Overview

The management of migraine is guided by frequency, severity, associated disability, and response to prior therapy. Treatment encompasses both acute (abortive) therapy aimed at relieving symptoms during an attack and preventive (prophylactic) therapy designed to reduce attack frequency and severity. The cornerstone of management includes identification and avoidance of triggers, optimisation of lifestyle, pharmacologic therapy, and patient education.

Non-pharmacological strategies play an equally important role and include maintaining regular sleep, adequate hydration, balanced diet, stress management, and consistent caffeine intake. Behavioural interventions such as biofeedback, relaxation training, and cognitive behavioural therapy (CBT) have demonstrated long-term benefit.

Goals of Treatment

• Terminate acute migraine attacks rapidly and consistently.
• Restore the patient’s functional capacity.
• Reduce the frequency, duration, and severity of attacks.
• Improve quality of life and reduce disability.
• Minimise medication overuse and adverse effects.

Therapeutic Approach

1. Acute (Abortive) therapy: Administered at the onset of migraine to relieve pain and associated symptoms.
2. Preventive (Prophylactic) therapy: Used in patients with frequent or disabling attacks (≥4 per month or ≥8 headache days per month).
3. Adjunctive and non-pharmacological measures: Education, lifestyle modification, trigger management, and stress reduction.

Pharmacology

Migraine pharmacotherapy involves multiple classes of medications targeting distinct pathophysiological mechanisms—serotonergic modulation, inhibition of neurogenic inflammation, and attenuation of central sensitisation. Selection of drug class depends on the phase of treatment (acute or preventive), comorbidities, and risk of overuse.

1. Acute (Abortive) Medications

These are used to stop or reduce the severity of attacks once they begin. Efficacy is greatest when taken early in the headache phase.

Drug Class	Example	Mechanism	Typical Dose	Comments
NSAIDs	Ibuprofen, Naproxen, Diclofenac	COX inhibition reduces prostaglandin-mediated inflammation and pain	Ibuprofen 400–800 mg; Naproxen 500–550 mg	First-line for mild–moderate migraine; caution in GI or renal disease
Triptans	Sumatriptan, Rizatriptan, Zolmitriptan	5-HT1B/1D receptor agonist; vasoconstriction and inhibition of CGRP release	Sumatriptan 50–100 mg PO or 6 mg SC	Most effective abortive class; avoid in vascular disease or uncontrolled HTN
Dopamine antagonists	Metoclopramide, Domperidone	Blocks dopamine receptors, reduces nausea and enhances gastric motility	Metoclopramide 10 mg PO/IV	Often combined with analgesics; helps nausea and vomiting
Ergot derivatives	Ergotamine, Dihydroergotamine	Nonselective serotonin receptor agonist; vasoconstriction	Ergotamine 1–2 mg PO; DHE 1 mg IM/IV	Less used; contraindicated in pregnancy and vascular disease
Gepants	Ubrogepant, Rimegepant	CGRP receptor antagonist; blocks neurogenic inflammation	Ubrogepant 50–100 mg PO	Well tolerated, useful in triptan non-responders
Lasmiditan	Lasmiditan (Reyvow)	Selective 5-HT1F agonist; inhibits trigeminal pain without vasoconstriction	50–200 mg PO once	Alternative for patients with cardiovascular risk

2. Preventive (Prophylactic) Medications

Preventive therapy is indicated in patients with ≥4 attacks per month, prolonged attacks, medication overuse, or poor response to acute therapy. The goal is to reduce migraine days by ≥50% within 2–3 months.

Drug Class	Example	Mechanism	Starting Dose	Notes
Beta-blockers	Propranolol, Metoprolol	Modulates adrenergic tone, reduces cortical excitability	Propranolol 20–40 mg BID	First-line; avoid in asthma, bradycardia
Anticonvulsants	Topiramate, Valproate	Stabilises neuronal membranes, inhibits excitatory neurotransmission	Topiramate 25–100 mg/day	Topiramate preferred; avoid Valproate in pregnancy
Calcium channel blockers	Flunarizine, Verapamil	Inhibits Ca2+ influx, stabilises vascular tone	Flunarizine 5–10 mg HS	Useful in migraine with aura
Tricyclic antidepressants	Amitriptyline, Nortriptyline	Inhibits reuptake of serotonin and norepinephrine	Amitriptyline 10–50 mg HS	Helpful if comorbid insomnia or depression
Angiotensin blockers	Candesartan, Lisinopril	Modulates vascular reactivity	Candesartan 8–16 mg/day	Alternative if beta-blockers contraindicated
CGRP monoclonal antibodies	Erenumab, Fremanezumab, Galcanezumab	Inhibit CGRP ligand or receptor to prevent trigeminovascular activation	Erenumab 70–140 mg SC monthly	Effective for refractory or chronic migraine
OnabotulinumtoxinA	Botox injections (PREEMPT protocol)	Inhibits release of pain mediators at neuromuscular junction	155–195 units IM every 12 weeks	Approved for chronic migraine (≥15 days/month)

Preventive therapy should be started at low dose and titrated upward gradually. Evaluate efficacy after 8–12 weeks. Continue for at least 6 months before considering tapering.

Treatment Guideline (Evidence-based Summary)

Treatment recommendations are based on international consensus from the American Academy of Neurology (AAN), European Federation of Neurological Societies (EFNS), and NICE guidelines.

1. Step 1: Assessment and Education Identify migraine type, frequency, and triggers. Explain disease mechanism and importance of early treatment.
2. Step 2: Acute Treatment Strategy
   • Mild to moderate attacks – NSAIDs or Paracetamol ± antiemetic.
   • Moderate to severe attacks – Triptans as first-line; repeat dose after 2 hours if partial response.
   • Non-responders – Consider gepants or lasmiditan.
   • Avoid ergotamine within 24 hours of triptan use.
3. Step 3: Preventive Therapy Initiate if:
   • ≥4 migraine days/month or ≥8 headache days/month
   • Attacks prolonged or refractory
   • Medication overuse or contraindications to abortive drugs
4. Step 4: Lifestyle and Non-pharmacological Therapy Maintain headache diary, avoid triggers, regular sleep, hydration, exercise, mindfulness, and cognitive-behavioural therapy (CBT).
5. Step 5: Monitoring and Follow-up Review treatment efficacy every 2–3 months. Educate about medication overuse headache (MOH): avoid analgesics >10 days/month.

For chronic migraine (≥15 headache days/month for >3 months): combination therapy may include onabotulinumtoxinA and CGRP monoclonal antibody with gradual withdrawal of overused medications.

Example Doctor’s Orders

Prognosis

Migraine is a chronic but manageable disorder. Most patients respond well to lifestyle adjustment and pharmacologic therapy. Spontaneous remission occurs in approximately 30% over time, whereas a subset progresses to chronic migraine, often due to medication overuse or persistent triggers.

With effective preventive therapy, attack frequency can be reduced by 50–70%. Adherence to treatment and trigger control are key to long-term stability. Chronic migraine is associated with greater disability and comorbid depression, anxiety, and sleep disorders, but outcomes improve significantly with multidisciplinary care.

Prevention

• Maintain a regular sleep schedule (7–8 hours per night).
• Eat balanced meals; avoid skipping meals or fasting.
• Identify and avoid known triggers (e.g., alcohol, stress, dehydration).
• Limit caffeine to a consistent, moderate intake.
• Stay hydrated (≥2 L water per day).
• Engage in aerobic exercise 3–4 times per week.
• Manage stress via yoga, mindfulness, or relaxation therapy.
• Avoid analgesic overuse (>10 days/month).

Conclusion

Quiz (USMLE OSCE)

Frequently Asked Questions (FAQ)

Are migraines hereditary?

Yes. Approximately 70% of patients report a positive family history. Genetic variants in ion-channel genes contribute to susceptibility.

Can caffeine help migraine?

Caffeine may provide short-term relief by vasoconstriction but excessive use or withdrawal can trigger migraine.

What is medication overuse headache?

Headache occurring on >15 days/month in a patient using acute headache medication on >10–15 days/month for ≥3 months.

When should MRI be performed in migraine?

If new neurological deficit, change in headache pattern, new-onset after age 50, or red-flag symptoms (seizure, fever, papilloedema).

Can hormonal changes cause migraine?

Yes. Fluctuations in oestrogen levels during menstruation or perimenopause are strong triggers for menstrual migraine.

Why is Ergotamine no longer recommended for migraine treatment?

Ergotamine was once used as an abortive therapy for migraine, but it is now largely avoided due to its strong vasoconstrictive effects, which can lead to severe adverse events such as coronary ischemia, peripheral vascular spasm, and hypertension. Additionally, combining Ergotamine with Triptans within 24 hours significantly increases the risk of vasospasm and myocardial infarction. Modern guidelines recommend using Triptans or CGRP antagonists instead, as they are safer, more selective, and better tolerated in both acute and chronic migraine management.