Migraine

Migraine is a form of primary headache disorder.

Migraine describes a recurrent moderate to severe headache commonly associated with nausea, vomiting, photophobia and phonophobia. The headache is typically unilateral and pulsating in nature lasting 4-72 hours.

There are two major types of migraine:

• Migraine without aura: characteristic migraine headache with associated symptoms.
• Migraine with aura: a migraine headache that is preceded (and sometimes accompanied) by focal neurological symptoms.

Migraines are one of the most common disabling conditions in the world. In the 2019 Global Burden of Disease study, headaches (primarily migraine and tension-type headache) were ranked the 14th most common cause of disability-adjusted life years.

Management involves avoidance of potential triggers and preventative medications to reduce the frequency of attacks. The migraines themselves may be treated with anti-emetics, simple analgesia and triptans. This note focuses on the diagnosis and management of migraines in adult patients.

Migraine is estimated to have a global prevalence of 1 in 7 people.

Migraines most commonly occur between the ages of 25 - 55. Females (lifetime prevalence approximately 33%) are affected more than men (lifetime prevalence approximately 13%) though frequency is equal before puberty.

The definition and classification of migraines can be taken from the International Classification of Headache Disorders 3rd edition (ICHD-3).

Migraine is typically a unilateral, pulsating headache that is accompanied by symptoms such as nausea and vomiting, photophobia and phonophobia. Attacks typically last 4-72 hours. In children and adolescents the headache is more likely to be bilateral and attacks may be shorter. Patients struggle to get comfort and will often prefer to rest or sleep in a darkened room. Migraines may be episodic or chronic:

• Chronic migraine: headache on more than 15 days of each month, 8 of which have features of migraine.
• Episodic migraine: less frequency than described in the above definition.

Migraines may be associated with a preceding aura - neurological changes that precede and at times accompany the headache. Auras are highly variable, atypical auras are discussed in the red flags chapter below.

The below definitions rely on secondary causes of both aura symptoms and headache being excluded either clinically or with further investigations.

Migraine without aura

The ICHD-3 describes migraine without aura as:

Recurrent headache disorder manifesting in attacks lasting 4-72 hours. Typical characteristics of the headache are unilateral location, pulsating quality, moderate or severe intensity, aggravation by routine physical activity and association with nausea and/or photophobia and phonophobia.

A headache meets the diagnostic criteria if:

1. At least five attacks fulfilling criteria 2-4
2. Headache attacks lasting 4-72 hr (untreated or unsuccessfully treated)
3. Headache has at least two of the following four characteristics:
   • unilateral location
   • pulsating quality
   • moderate or severe pain intensity
   • aggravation by or causing avoidance of routine physical activity (eg, walking or climbing stairs)
4. During headache at least one of the following:
   • nausea and/or vomiting
   • photophobia and phonophobia
5. Not better accounted for by another ICHD-3 diagnosis.

Migraine without aura is often associated with female patients menstrual cycles, the headache occurring near the onset of menstruation. A headache diary can be useful to help characterise this association.

Migraine with aura

The ICHD-3 describes migraine with aura as:

Recurrent attacks, lasting minutes, of unilateral fully-reversible visual, sensory or other central nervous system symptoms that usually develop gradually and are usually followed by headache and associated migraine symptoms.

Around a third of patients with migraine have an aura. It refers to neurological symptoms that occur hours or sometimes days prior to the migraine itself. Auras are highly variable but visual disturbances (e.g. scintillating scotoma) are most common. Others experience sensory symptoms (e.g. numbness, tingling) or dysphasia.

Though listed in the diagnostic criteria motor, brainstem and retinal are less typical and should raise suspicion for an underlying cause. See the red flags section below for more on atypical auras.

A headache meets the diagnostic criteria if:

1. At least two attacks fulfilling criteria 2 and 3
2. One or more of the following fully reversible aura symptoms:
   • visual
   • sensory
   • speech and/or language
   • motor
   • brainstem
   • retinal
3. At least three of the following six characteristics:
   • at least one aura symptom spreads gradually over ≥5 minutes
   • two or more aura symptoms occur in succession
   • each individual aura symptom lasts 5-60 minutes
   • at least one aura symptom is unilateral
   • at least one aura symptom is positive
   • the aura is accompanied, or followed within 60 minutes, by headache
4. Not better accounted for by another ICHD-3 diagnosis.

You must consider potentially serious secondary causes of headaches and/or auras.

Whenever a patient presents with a headache, it is crucial as part of the assessment to exclude a potentially serious secondary cause of headache. Some of the key red flag signs that may indicate an underlying sinister cause of headache can be remembered by the mnemonic ‘HEADACHE PAINS’:

• H - Head injury (any history of trauma?)
• E - Eye pain +/- autonomic features
• A - Abrupt onset (i.e. thunderclap headache)
• D - Drugs (analgesia overuse or since new drug started)
• A - Atypical presentation or progressive headache
• C - Change in the pattern or recent-onset new headache
• H - High fever and systemic symptoms
• E - Exacerbating factors (worse on lying/standing, sneezing, coughing, exercise)
• P - Pregnancy or puerperium
• A - Age (onset > 50 years)
• I - Immunosuppressed (e.g. systemic therapy, HIV)
• N - Neoplasia (current or past history of cancer)
• S - Swollen optic discs (papilloedema)

Atypical aura

The neurological symptoms brought on by migraine with aura can be challenging to distinguish from a TIA/Stroke. Auras that feature motor, brainstem or retinal symptoms are not typical. In particular NICE highlights the following symptoms that warrant consideration of urgent neurological review:

• Motor weakness
• Double vision
• Visual symptoms affecting only one eye
• Poor balance
• Decreased level of consciousness

Aura without migraine

At times a typical aura may occur without a following migraine. This can be extremely challenging to differentiate from an acute neurological event (TIA / stroke). Investigation depends in part on the ‘aura’ symptoms and patient age but in general cases should be discussed and referred urgently to neurology.

Urgent referral

The NICE clinical practice guideline CG150 recommends further investigations (e.g. cerebral imaging) and/or referral for patients with new-onset headache and any of the following:

• Immunosuppressed or compromised immunity
• < 20 years old and a history of malignancy
• History of malignancy known to metastasise to the brain
• Vomiting without other obvious cause.

Other key precipitating factors that may suggest a secondary cause of headache include trauma (e.g. subdural haematoma) and headache triggered by Valsalva manoeuvre (e.g. posterior fossa lesion).

Associated features

In the assessment of headache always remember to determine these features from the history or examination:

• Fever, photophobia, neck stiffness: consider meningitis, encephalitis
• Papilloedema: consider BIH, venous sinus thrombosis, space-occupying lesions
• Dizziness/vertigo: consider stroke
• Visual changes: consider giant cell arteritis, glaucoma
• Vomiting: consider space-occupying lesions, carbon monoxide poisoning

NOTE: If multiple close contacts present with headache consider carbon monoxide poisoning!

Treatment options include simple analgesia, triptans and anti-emetics.

Treatment is determined by the individual patients presentation, preferences and co-morbidities. Those with relatively mild symptoms may be well managed with simple analgesia +/- an anti-emetic, though if ineffective triptans can be used.

In those with more severe headaches triptans may be introduced early and often offer patients significant symptomatic relief.

• Simple analgesia: paracetamol or NSAIDS (typically ibuprofen or aspirin) can be offered in the absence of contra-indications to be taken at the onset of a migraine headache. Diclofenac can be given as a suppository which may be preferable, particularly in the setting of nausea, for some patients.
• Triptans: these are 5HT₁-receptor agonist that can be taken at the onset of a migraine headache. It may be used alone or in combination with simple analgesia. Oral sumatriptan is considered first-line though alternative triptans and routes (e.g. nasal, subcutaneous) may be used if this is ineffective.
• Anti-emetics: buccal prochlorperazine is often given and helps to relieve nausea. Suppositories (e.g. domperidone) can again be given depending on patient preference.

KEY POINT: Migraine with aura is a contra-indication to the combined oral contraceptive pill and should be used with caution in migraine without aura due to the risk of ischaemic stroke. Where necessary the combined pill should be stopped and alternative contraceptive methods discussed.

Advanced therapies

In the UK, new calcitonin gene-related peptide (CGRP) inhibitors may be used in acute migraine in patients who fail to respond to triptans or other standard treatments, or that these treatments are not tolerated or contraindicated. The main drug licensed for this indication is Rimegepant, which can be taken orally. These medications bind to the CGRP receptor and subsequently block attachment of CGRP which is a potent vasodilator that can amplify and perpetuate migraine headache pain.

Prevention of migraines can involve avoidance of triggers and preventative therapies.

Trigger avoidance

Some patients have identifiable triggers and where possible patients should avoid these. Lifestyle factors are commonly implicated and advise should be given to maintain adequate hydration, get sufficient sleep and to stay healthy and active.

Where possible sources of stress should be avoided as well as other triggers (e.g. certain foods, smells, lights). A headache diary (maintained for at least 8 weeks) can make identification of triggers far easier.

Preventative treatment (traditional agents)

Prophylactic medications may be given to suitable patients. It should be considered where the symptoms significantly impact quality of life and daily function, acute treatments are inappropriate or ineffective or if the patient is at risk of medication overuse headache (see below).

There are a number of medications that can be used and prior to initiation a full discussion of the possible benefits and side effects should be had. The options include:

• Propranolol
• Topiramate (contraindicated in pregnancy, the BNF states in women with childbearing potential ‘a highly effective’ contraception is required prior to commencement)
• Amitriptyline

The efficacy should be reviewed regularly. If treatment fails consider referral to neurology. After 6-12 months of effective treatment consider gradual withdrawal of preventative treatments.

Non-medical therapies are also available. This includes behavioural interventions (e.g. mindfulness, relaxation techniques) and acupuncture.

Preventative treatment (newer agents)

Calcitonin gene-related peptide (CGRP) inhibitors are a new class of drug that may be used in patients with Migraine. There are several different agents available including:

• Erenumab (Aimovig): monoclonal antibody that blocks the CGRP receptor.
• Fremanezumab (Ajovy): monoclonal antibody that binds to the CGRP ligand preventing receptor activation
• Galcanezumab (Emgality): onoclonal antibody that binds to the CGRP ligand preventing receptor activation

In general, these drugs have specific guidance around their prescribing as per NICE. They may be given to patients who:

• have 4 or more migraine days a month
• have tried at least 3 other medicines and they have not worked

In addition, they should only be continued if after 12 weeks:

• episodic migraine (less than 15 headache days a month) reduced by at least 50%
• chronic migraine (15 headache days a month or more) reduced by at least 30%

Medication overuse headache

Medication ‘overuse’ itself has been shown to result in chronic headaches. As the name suggests this occurs when regular analgesia taken for symptomatic relief of headache causes or perpetuates the condition.

The International Headache Society defines it as 'Headache occurring on 15 or more days/month in a patient with a pre-existing primary headache and developing as a consequence of regular overuse of acute or symptomatic headache medication (on 10 or more or 15 or more days/month, depending on the medication) for more than 3 months. It usually, but not invariably, resolves after the overuse is stopped'.

Patients with menstrual-related migraine may be commenced on specific therapies if standard measures fail.

A menstrual-related migraine is broadly defined using the same ICHD-3 criteria, but the attacks should only occur within a 5-day menstrual period (e.g. days -2 to +3 of menstruation). They should occur in at least 2 of every 3 menstrual cycles and at no other times. This would be classed as a 'pure menstrual' migraine. If they also occur at other times then it is known as a 'menstrual-related' migraine. Women who have pure menstrual or menstrual-related migraine can be initiated on the standard lifestyle and trigger avoidance advice as well as standard acute treatment.

In the NICE clinical practice guideline CG150, the following medications can be considered for treatment (off-label) in the absence of contraindications:

• Frovatriptan
• Zolmitriptan

These can be taken daily on days migraine is anticipated or from two days before until three days after bleeding starts. All patients should be followed up to review the efficacy of treatment.

A network meta-analysis that enables the comparison of many different treatments even if they were not directly compared within a clinical trial suggests that Frovatriptan and Sumatriptan are the most effective treatments.

As discussed elsewhere migraine with aura is a contraindication to the use of the combined oral contraceptive pill due to the increased risk of ischaemic stroke. The combined pill should be used with caution in those with migraine without aura, particularly if there are additional risk factors present for vascular events.

There are a number of complications that may affect those with migraines.

• Status migrainosus: a debilitating migraine that persists for longer than 72 hours.
• Persistent aura without infarction: refers to symptoms of aura for one week or longer with no evidence of infarction of imaging.
• Migrainous infarction: describes a cerebral infarction that occurs during an aura whose symptoms then persist, imaging demonstrates an ischaemic infarction.
• Migraine aura-triggered seizure: migraine with aura that leads to a seizure.
• Ischaemic stroke: migraines, in particular with aura, is a risk factor for ischaemic stroke. As such patients should be strongly advised to optimise other risk factors such as weight, diet, smoking and exercise. Use of the combined oral contraceptive is contraindicated in patients with migraine with aura and must be used in caution in those with migraine.

Last updated: October 2024