Migraine

What it is

Migraine is a primary headache disorder, meaning the headache is the condition itself rather than a sign of another illness. It is characterised by recurring attacks that are often lifelong, usually last 4 to 72 hours and are accompanied by nausea, vomiting, or sensitivity to light (photophobia) and sound (phonophobia)¹.

An estimated 1.04 billion people had migraine in 2016, and because of its high disability weight it caused far more years lived with disability than the more common tension-type headache². Migraine most often begins around puberty and is more common in women, possibly because of hormonal influences¹.

Doctors distinguish migraine without aura, the most common type, from migraine with aura, in which attacks are preceded or accompanied by temporary visual, sensory or speech disturbances⁷. When headache occurs on 15 or more days a month for more than three months, it is called chronic migraine⁷.

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Visual cortexMeninges

Brain imaging during visual aura has recorded a slow wave of changing activity spreading across the visual cortex at the back of the brain, consistent with cortical spreading depolarisation^3,14.

The coverings of the brain and their blood vessels are supplied by trigeminal nerve fibres, the trigeminovascular system, whose activation is central to migraine pain¹⁰.

Signs and symptoms

An attack can unfold in phases. Some people notice warning signs hours or days beforehand, such as yawning, food cravings, mood changes or a stiff neck, and tiredness or poor concentration may linger for a day or two afterwards^6,7.

• Headache of moderate or severe intensity, often on one side and pulsating or throbbing⁴.
• Pain made worse by routine physical activity such as walking or climbing stairs⁴.
• Nausea and/or vomiting⁴.
• Sensitivity to light and sound⁴.
• Aura in some people: zigzag lines, flashing lights or blind spots, pins and needles, or difficulty speaking, usually lasting less than an hour^6,7.
• In children, attacks are typically shorter and abdominal symptoms more prominent¹.

Causes and risk factors

The cause of migraine is not fully understood, but it is regarded as a disorder of brain sensitivity with a strong inherited component, in which both genes and environment play a part^3,6. Having a close family member with migraine makes it more likely⁶.

• Sex and hormones: migraine is more common in females, and attacks may be linked to the menstrual cycle, pregnancy or contraception; many women improve after menopause⁷.
• Common triggers reported by patients include alcohol, disrupted sleep and certain foods¹.
• Stress, tiredness, anxiety and periods are frequently reported triggers⁶.
• Frequent use of painkillers or triptans can cause medication-overuse headache, the most common secondary headache disorder^1,8.
• Migraine often coexists with depression, anxiety, sleep disorders and epilepsy^3,7.

Genetics

For most people, migraine is a complex genetic condition: many common gene variants each add a small amount of risk. A genome-wide association study (a scan of the genome across very large groups of people) of more than 100,000 people with migraine identified 123 risk regions, including genes for calcitonin gene-related peptide and the serotonin 1F receptor, both of which are targets of modern migraine medicines⁵.

Rare single-gene forms also exist. In familial hemiplegic migraine, a form of migraine with aura that includes temporary weakness of one side of the body, disease-causing variants have been identified in the CACNA1A, ATP1A2 and SCN1A genes, which encode ion channels and pumps that regulate nerve cell excitability⁴.

What happens in the brain

Migraine was once thought to be mainly a disorder of blood vessels, but widening of vessels is now regarded as a secondary phenomenon³. Current models focus on the brain and on the trigeminovascular system, the network of trigeminal nerve fibres that supply sensation to blood vessels and the coverings of the brain¹⁰.

Aura is thought to be caused by cortical spreading depolarisation, a slowly advancing wave of intense nerve cell activity followed by suppression that moves across the brain surface; this may also help to trigger activation of trigeminal pain pathways³.

When activated, trigeminal nerves release signalling molecules such as calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase-activating polypeptide (PACAP), small proteins that dilate blood vessels and promote pain signalling. Infusion of PACAP can provoke attacks in people with migraine, which supports a causal role for these molecules¹⁰.

How it is diagnosed

There is no blood test or scan that confirms migraine. Diagnosis is clinical, based on a careful history and examination using internationally agreed criteria⁴. Keeping a headache diary that records symptoms, timing, medicines and possible triggers can help a doctor identify patterns⁷.

• For migraine without aura: at least five attacks lasting 4 to 72 hours⁴.
• The headache has at least two of: one-sided location, pulsating quality, moderate or severe intensity, or worsening with routine activity⁴.
• During the headache, nausea and/or vomiting, or both light and sound sensitivity⁴.
• The symptoms are not better explained by another diagnosis⁴.
• Brain scans are not needed to confirm typical migraine and are used when features suggest another cause: in India, the ICMR Standard Treatment Workflow reserves imaging for atypical symptoms¹¹, and in the United Kingdom NICE advises against scanning solely for reassurance⁸.

How scientists study it

Current treatments

Research frontiers

Living with the condition and seeking help

Migraine is usually managed by a general practitioner, with referral to a specialist when attacks are frequent, difficult to treat or atypical. Taking acute treatment early in an attack, avoiding overuse of painkillers and keeping a diary can all help^6,8.

Urgent advice should be sought if an attack lasts longer than 72 hours, if aura lasts longer than an hour, or during pregnancy or soon after giving birth⁶. Emergency help is needed for a sudden, very severe headache, or for headache with symptoms such as weakness on one side, confusion, problems speaking, loss of vision, a seizure, or a very high temperature with signs of meningitis, as these can signal other serious conditions⁶. In India, the national emergency number is 112 and the ambulance number is 108^12,13.

Migraine can affect school, work and family life, and anxiety and depression are more common in people with migraine¹. Patient organisations and specialist headache services can provide information and support.