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.

The NICE CKS guide of headache assessment outlines a number of circumstances when you need to consider alternative causes of a headache.

Atypical aura

The neurological symptoms brought on by migraine with aura can be challenging to distinguish from a TIA/Stroke. The NICE CKS on Migraine specifically highlights features that should raise suspicion of a secondary cause. Auras that feature motor, brainstem or retinal symptoms are not typical. In particular NICE highlight 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.

Headache characteristics

• Severe sudden onset: consider causes like SAH, venous sinus thrombosis, vertebral artery dissection
• Progressive or persistent, acute change: consider space occupying lesions, subdural haematoma
• Worse on standing: consider CSF leak
• Worse on lying: consider causes of raised ICP; space occupying lesions, venous sinus thrombosis

Precipitating factors

• Recent trauma: consider subdural haematoma (subacute/chronic)
• Triggered by Valsalva manoeuvre: consider posterior fossa lesion or Chiari 1 malformation

Associated features

• 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

Patient factors and comorbidities

• Age > 50: consider sinister causes such as giant cell arteritis and space occupying lesions
• Age < 10: consider evalutaion for secondary causes
• Immunodeficiency: in particular increased risk of malignancy and infection
• Active or previous cancer: consider metastatic spread, cancer therapy may increase risk of infection
• Pregnancy: consider causes like pre-eclampsia and venous sinus thrombosis

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.

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

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.

Galcenezumab is a novel therapy recently made available on the NHS (NICE TA 659) for patients who:

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

It 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%

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

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.

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.

If this is ineffective NICE CKS advise the consideration of the following medications (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 efficacy of treatment.

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 stoke. 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: July 2021