Migraine — Aura, CGRP Inhibitors, Triptans & Prevention Guide — Symptoms, Causes & Treatment | MyMedicPlus

Migraine is a chronic primary neurological disorder characterised by recurrent episodic attacks of moderate-to-severe headache lasting 4-72 hours, typically unilateral and pulsating, accompanied by nausea, vomiting, photophobia, and phonophobia, and aggravated by routine physical activity. Migraine affects approximately 1 billion people globally — a prevalence of 15% — making it the second leading cause of years lived with disability worldwide. It affects women three times more commonly than men, with peak prevalence between ages 25-55 (prime working years). Approximately 30% of migraineurs experience aura — transient reversible neurological symptoms (most commonly visual) preceding or accompanying the headache phase. Episodic migraine (under 15 headache days per month) progresses to chronic migraine (15+ headache days per month, including 8+ migraine days) in 2-3% of patients annually, often from medication overuse. The pathophysiological hallmark is cortical spreading depression (CSD) — a slowly propagating wave of neuronal depolarisation followed by sustained suppression, originating in the occipital cortex and activating the trigeminovascular system, leading to CGRP (calcitonin gene-related peptide) release and neurogenic inflammation.

Migraine is a polygenic disorder with strong heritability — first-degree relatives of migraineurs have a 3-6 times higher risk; familial hemiplegic migraine (FHM) is caused by mutations in CACNA1A, ATP1A2, or SCN1A genes encoding ion channels. The central mechanism involves dysregulation of the trigeminovascular system: cortical spreading depression activates the trigeminal nucleus caudalis, promoting release of CGRP, substance P, and other neuropeptides that cause meningeal vasodilation, neurogenic inflammation, and central sensitisation. CGRP is the primary mediator of migraine pain — serum CGRP rises during attacks and normalises with triptan therapy; anti-CGRP monoclonal antibodies exploit this mechanism. Common triggers: hormonal fluctuations — perimenstrual migraine (falling oestrogen levels); stress and stress letdown ('weekend migraine'); sleep disruption (too much or too little); fasting and dehydration; alcohol (particularly red wine — tyramine and histamine); caffeine withdrawal; bright lights, loud sounds, strong odours; weather changes; and specific foods (chocolate, aged cheese, processed meats — biogenic amines). Triggers are highly individual and should be identified through a headache diary.

Migraine attacks progress through four phases. Prodrome (24-48 hours before headache): mood changes (depression, euphoria, irritability), food cravings (particularly sweet foods), neck stiffness, yawning, fatigue, and urinary frequency — experienced by 60-80% of migraineurs; useful for early triptan dosing. Aura (20-60 minutes, resolves before or within 1 hour of headache onset): visual aura is most common — positive phenomena (scintillating scotoma — flickering arc of zigzag lights or fortification spectra — gradually enlarging over 20-30 minutes across the visual field) or negative (scotoma, homonymous hemianopia); sensory aura (unilateral tingling or numbness, characteristically spreading slowly across the face and hand — 'march of paraesthesiae'); motor aura (weakness — hemiplegic migraine); speech aura (dysphasia). Headache phase: moderate-to-severe unilateral (60%) or bilateral (40%) pulsating pain; aggravated by routine physical activity (walking upstairs); severe nausea and vomiting; photophobia and phonophobia; osmophobia; cutaneous allodynia (skin becomes exquisitely tender — even light touch is painful, suggesting central sensitisation). Postdrome (24-48 hours after headache): fatigue, cognitive impairment ('brain fog'), mood change, residual head tenderness.

Migraine is a clinical diagnosis based on the International Classification of Headache Disorders (ICHD-3) criteria. Migraine without aura: at least 5 attacks; duration 4-72 hours (untreated); at least 2 of — unilateral location, pulsating quality, moderate/severe intensity, aggravated by routine activity; and at least 1 of — nausea/vomiting or photophobia and phonophobia; and not better accounted for by another ICHD diagnosis. Migraine with aura: at least 2 attacks; at least 1 fully reversible aura symptom; gradual onset over 5+ minutes and lasting 5-60 minutes; headache during or within 60 minutes of aura. A headache diary (Migraine Buddy, N1-Headache app) documents attack frequency, duration, severity, triggers, and treatment response — essential for diagnosis, prevention threshold assessment, and treatment monitoring. Red flags (SNOOP4 mnemonic) requiring urgent neuroimaging to exclude secondary headache: Systemic disease/Symptoms, Neurological deficits, Onset sudden (thunderclap), Older age (new headache over 50), Positional component, Progressive worsening, Papilloedema, Precipitated by Valsalva.

Acute (abortive) treatment: Triptans (serotonin 5-HT1B/1D agonists): first-line for moderate-severe attacks — sumatriptan (50-100 mg oral, 6 mg subcutaneous, 20 mg intranasal), rizatriptan (10 mg oral), eletriptan (40-80 mg oral), zolmitriptan, almotriptan, naratriptan (slower but longer lasting). Take early in attack for best efficacy; avoid in cardiovascular disease. Analgesics: NSAIDs (ibuprofen 400-600 mg, naproxen 500-1000 mg, aspirin 900 mg — all effective for mild-moderate attacks) combined with an antiemetic (domperidone 10-20 mg or metoclopramide 10 mg — accelerates gastric absorption and reduces nausea). Gepants (CGRP receptor antagonists): rimegepant (75 mg oral) and ubrogepant (50-100 mg) — acute treatment without cardiovascular contraindications; no medication overuse risk; rimegepant also licensed for prevention (every other day). Ditans: lasmiditan — 5-HT1F agonist, for cardiovascular disease patients; causes sedation and dizziness. Preventive treatment (indicated for 4+ attacks/month, disabling attacks, or medication overuse headache): Anti-CGRP monoclonal antibodies: erenumab (Aimovig — targets CGRP receptor, monthly SC injection), fremanezumab (Ajovy — targets CGRP ligand, monthly or quarterly SC), galcanezumab (Emgality — monthly SC), eptinezumab (Vyepti — IV infusion quarterly) — all reduce migraine days by 50% in approximately 50% of patients; superior tolerability compared to oral preventives. Oral preventives: topiramate (25-100 mg nocte — weight loss side effect), propranolol (40-160 mg daily — first choice in hypertension), amitriptyline (10-75 mg nocte — useful with comorbid sleep disorder), candesartan, valproate (highly effective but teratogenic — avoid in women of childbearing potential). Botulinum toxin A (Botox, 155-195 units IM, 31 sites, every 12 weeks): NICE-approved for chronic migraine (15+ headache days/month for 3 months).

Chronic migraine (15+ headache days per month, including 8 migraine days) develops in 2-3% of episodic migraine patients annually — the most important chronic complication. Medication overuse headache (MOH — formerly 'rebound headache'): daily or near-daily headache from overuse of acute treatments — triptans (over 10 days/month for 3 months), analgesics (over 15 days/month); paradoxically, overuse worsens headache frequency; treatment requires gradual or abrupt withdrawal of the overused medication. Status migrainosus: a migraine attack lasting over 72 hours despite treatment — requires hospital management (IV fluids, IV antiemetics, IV dihydroergotamine or corticosteroids). Migraine with aura significantly increases stroke risk — particularly in women who smoke and use combined oral contraceptives (relative risk 4-9 times baseline); oestrogen-containing contraception is contraindicated in migraine with aura. Persistent aura without infarction and migrainous infarction are rare but serious neurological complications.

Identify and avoid personal triggers through a digital headache diary (Migraine Buddy app) — common triggers include irregular sleep, dehydration, skipped meals, alcohol (particularly red wine), stress, and hormonal fluctuations. Lifestyle regularity is the most consistently evidence-based preventive strategy: maintain fixed sleep and wake times (even at weekends), regular meals, and 1.5-2 litres daily hydration. Physical exercise: regular aerobic exercise (30 minutes, 3 times per week) reduces migraine frequency by 30-40% in RCTs — equivalent to topiramate for some patients. Limit caffeine to under 2 cups of coffee daily and avoid caffeine withdrawal (do not skip caffeine on weekends if you regularly consume it during the week). Stress management: CBT (cognitive behavioural therapy), mindfulness-based stress reduction, and biofeedback all have RCT evidence for migraine prevention. Hormonal triggers: perimenstrual migraine can be managed with frovatriptan mini-prophylaxis (2.5 mg BD on days prior to and during menstruation) or transdermal oestrogen. Pharmacological preventive treatment should be offered when attacks occur 4+ times per month, are severely disabling, or when medication overuse is developing.

Call 999 or attend A&E immediately for: the worst headache of your life, sudden thunderclap onset ('hitting like a thunderbolt') — possible subarachnoid haemorrhage; new severe headache with fever, neck stiffness, photophobia, and rash — possible meningitis; headache with focal neurological deficit (weakness, diplopia, speech disturbance) that does not resolve with aura duration — possible stroke or intracranial mass; and headache with papilloedema or reduced conscious level. See a GP for: new migraine symptoms requiring diagnosis and management; 4 or more migraine attacks per month (preventive treatment threshold); increasing headache frequency despite acute treatment (possible medication overuse headache); migraine aura with any neurological symptom lasting over 1 hour; and new headache after age 50. Request neurologist referral for: chronic migraine unresponsive to oral preventives; consideration of anti-CGRP monoclonal antibody therapy; or diagnostic uncertainty.