Key Facts

Migraine is a highly prevalent neurological condition causing substantial disability. Accurate diagnosis, avoidance of medication overuse, and appropriate use of both acute and preventive therapies are key to management.

Epidemiology

Prevalence ~15% in UK (~10 million people). F:M 3:1 (hormonal influence — prevalence equalises before puberty and after menopause). Peak age 25-55 years. Migraine is the 6th most disabling condition worldwide (Global Burden of Disease). Economic impact: ~25 million workdays lost per year in UK.

Aetiology

• Genetic predisposition: polygenic; first-degree relatives have 2-3× increased risk; familial hemiplegic migraine (FHM) — rare monogenic forms (CACNA1A, ATP1A2, SCN1A)
• Triggers: stress, sleep disruption, menstruation, alcohol (red wine), certain foods (cheese, chocolate, caffeine withdrawal), bright lights, weather changes, skipping meals
• Hormonal: menarche, menstruation (menstrual migraine), OCP, pregnancy (often improves), menopause

Pathophysiology

Migraine is a neurovascular disorder, NOT simply a vascular headache:

• Cortical spreading depression (CSD): wave of neuronal depolarisation across cortex → aura symptoms; triggers trigeminal activation
• Trigeminovascular activation: release of CGRP (calcitonin gene-related peptide), substance P, neurokinin A from trigeminal afferents → neurogenic inflammation, vasodilation of meningeal vessels → pain
• Central sensitisation: repeated trigeminal activation → allodynia, photophobia, phonophobia
• Brainstem activation: PAG (periaqueductal grey), locus coeruleus, raphe nuclei — "migraine generator"
• CGRP is the key mediator (basis for CGRP-targeted therapies)

Migraine Without Aura (ICHD-3 Criteria)

• ≥5 attacks fulfilling criteria
• Headache lasting 4-72 hours (untreated)
• ≥2 of: unilateral, pulsating, moderate-severe, aggravated by routine physical activity
• ≥1 of: nausea/vomiting, photophobia AND phonophobia

Migraine With Aura (ICHD-3 Criteria)

• ≥2 attacks with aura fulfilling criteria
• Aura: fully reversible visual (zigzag lines/fortification spectra, scotoma — most common), sensory (tingling, numbness), or speech/language symptoms
• ≥3 of: aura develops gradually over ≥5 min, 2+ symptoms occur in succession, each symptom lasts 5-60 min, ≥1 symptom is unilateral, aura accompanied/followed by headache within 60 min

Other Subtypes

• Chronic migraine: ≥15 headache days/month for ≥3 months (≥8 meeting migraine criteria)
• Menstrual migraine: occurs within 2 days of onset of menstruation; purely menstrual vs menstrually-related
• Hemiplegic migraine: motor weakness as part of aura (may mimic stroke)
• Migraine with brainstem aura: vertigo, dysarthria, tinnitus, diplopia, decreased consciousness

Red Flags (SNOOP)

• Systemic symptoms (fever, weight loss, cancer, HIV)
• Neurological signs (focal deficit persisting after headache)
• Onset sudden (thunderclap — SAH until proven otherwise)
• Older (new onset >50 years — GCA, space-occupying lesion)
• Pattern change (progressive worsening, change in character)

Clinical Diagnosis

• Migraine is a clinical diagnosis based on ICHD-3 criteria; no investigation required for typical presentation
• Headache diary: essential for tracking frequency, triggers, medication use

When to Investigate (Red Flags)

• CT head (urgent): thunderclap headache (exclude SAH)
• MRI brain: atypical features, new onset >50, focal neurological signs, progressive headache, seizures
• LP: after CT if SAH suspected (xanthochromia at 12 hours); raised CSF pressure (IIH)
• ESR/CRP: if >50 years → exclude GCA

Bloods (Rarely Needed)

• Only if secondary cause suspected: ESR, CRP, TFTs, FBC

Acute Treatment (NICE CG150)

• Mild-moderate: aspirin 900 mg or ibuprofen 400 mg + antiemetic if needed
• Moderate-severe: oral triptan (sumatriptan 50-100 mg, zolmitriptan 2.5-5 mg, rizatriptan 10 mg) + NSAID (ibuprofen 400 mg) or paracetamol 1g
• Antiemetics: metoclopramide 10 mg, prochlorperazine 10 mg (also enhances analgesic absorption)
• SC sumatriptan 6 mg: for rapid onset/vomiting; nasal sumatriptan/zolmitriptan alternatives
• Triptans contraindicated in: uncontrolled HTN, IHD, cerebrovascular disease, peripheral vascular disease, hemiplegic migraine, migraine with brainstem aura
• Avoid opioids: risk of MOH, poor efficacy
• Medication overuse: limit acute treatments to ≤10 days/month (triptans/opioids) or ≤15 days/month (simple analgesics)

Preventive Treatment (≥2 Attacks/Month or Significant Disability)

• First-line (NICE CG150): propranolol 40-240 mg/day (contraindicated in asthma) or topiramate 25-100 mg/day (teratogenic — PPP; side effects: weight loss, cognitive impairment, paraesthesiae, renal stones)
• Amitriptyline 10-50 mg ON (off-label; good if coexistent tension-type headache or insomnia)
• Candesartan 8-16 mg OD (off-label; good evidence)
• Menstrual migraine: frovatriptan 2.5 mg BD (perimenstrual — 2 days before onset for 5-7 days); consider continuous OCP or desogestrel for hormonal manipulation

CGRP-Targeted Therapies (NICE TA)

• Erenumab 70-140 mg SC monthly (anti-CGRP receptor; NICE TA764)
• Fremanezumab 225 mg SC monthly or 675 mg quarterly (anti-CGRP; NICE TA764)
• Galcanezumab 120 mg SC monthly (anti-CGRP; NICE TA919)
• Indicated for chronic migraine (≥15 days/month) with ≥3 prior preventive treatment failures; or episodic migraine with ≥4 days/month and ≥3 prior failures

Other

• Botulinum toxin A (onabotulinumtoxinA): PREEMPT protocol for chronic migraine; NICE TA260; 155 units across 31 injection sites; every 12 weeks
• Greater occipital nerve block: local anaesthetic ± steroid; evidence for refractory migraine

Non-Pharmacological

• Identify and avoid triggers (diary)
• Regular sleep, meals, hydration, exercise
• CBT, mindfulness, biofeedback
• Acupuncture: NICE recommends as an option for prophylaxis

Referral Criteria

• Headache clinic/neurology: diagnostic uncertainty, chronic migraine, medication overuse headache, failure of ≥2 preventives
• Emergency: thunderclap headache, new neurological deficit, papilloedema

Migraine is a lifelong condition for most; ~50% of patients have significant improvement by their 50s. Chronic migraine develops in ~3% of episodic migraine patients per year (risk factors: medication overuse, obesity, depression, high attack frequency). CGRP antibodies and botulinum toxin have transformed outcomes for chronic migraine. Migraine with aura carries a modestly increased risk of ischaemic stroke (especially in women who smoke and take the combined OCP — avoid COCP in migraine with aura).

Migraine Preventive Medications Comparison

Combined OCP and Migraine