FRCA Notes

Migraine

There are no specific curriculum items covering migraine, nor has it formed the subject of a past exam question.

Resources

  • A primary headache disorder, diagnosed based on clinical findings, history and a normal neurological examination

Classification

  • Classified using the 3rd International Classification of Headache Disorders (ICHD-3)
  • Can be:
    • Episodic: <15 headache days per month
    • Chronic: ≥15 headache days per month
  • Can occur with or without aura

Epidemiology

  • Affects 15% of the population
  • Three times more common in women (22% vs 7%)
  • Second highest worldwide cause of disability, and the highest in young women
  • Accounts for around a fifth of acute hospital admissions for neurological conditions

Risk factors and triggers

  • Family history (heritability 34–64%)
  • Polygenic gene involvement

  • Triggers:
    • Emotional stress
    • Sleep disturbance
    • Dietary factors e.g. caffeine, alcohol
    • Hormonal e.g. menstrual
  • Classic 'triggers' such as chocolate and red wine may actually reflect food cravings during the prodrome
  • Comorbidities include anxiety, depression, cognitive disturbance and fatigue

ICHD-3 diagnostic criteria

Migraine without aura Migraine with aura
≥5 attacks lasting 4–72 h ≥2 attacks with ≥1 fully reversible aura symptom: visual, sensory, speech, motor, brainstem or retinal
≥2 of: unilateral; pulsating; moderate–severe intensity; worse with routine activity ≥3 of: gradual spread over ≥5 min; symptoms occur in succession; each lasts 5–60 min; ≥1 unilateral; ≥1 positive; headache within 60 min
≥1 of: nausea and/or vomiting; photophobia and phonophobia


  • A migraine attack has four phases, although these are increasingly thought of as a continuum rather than distinct stages

1. Prodrome

  • Occurs 24–48 h before headache or aura; around two thirds of patients
  • Fatigue, neck stiffness, mood change, poor concentration, yawning, food cravings
  • Triptans given during the prodrome may reduce progression to headache

2. Aura

  • Fully reversible neurological symptoms in around a third of patients with most resolving within 60min
  • Visual aura is the most common (90%) and motor aura is rare
  • Symptoms may be:
    • Positive: flashing lights, zig-zag lines, tinnitus, paraesthesia
    • Negative: scotoma, tunnel vision, hearing loss, limb weakness
  • Aura evolves gradually and spreads sequentially; TIA symptoms are sudden and simultaneous
  • Rarer forms: migraine with brainstem aura (previously basilar migraine), hemiplegic migraine, retinal migraine (monocular symptoms)

3. Headache (ictal phase)

  • Unilateral (60%), throbbing, lasting 4–72hrs, worse with activity and often relieved by sleep
  • Associated photophobia (90%), phonophobia (80%), osmophobia, nausea and vomiting
  • Around half have a cranial autonomic symptom e.g. lacrimation, nasal congestion

4. Postdrome

  • A migraine 'hangover' affects around 80%
  • Neck stiffness, tiredness, cognitive impairment, mood change

Complications

  • Status migrainosus: severe migraine lasting >72hrs (see below)
  • Ischaemic stroke: migraine with aura increases risk, particularly in women who smoke and take the combined oral contraceptive pill
  • Migralepsy: seizures associated with migraine with aura

  • Migraine is now considered a disorder of brain sensory processing rather than a primarily vascular disorder

Hypothalamus

  • Activated early in the attack (prodrome) on functional imaging
  • Its role in sleep, appetite and fluid balance explains many premonitory symptoms

Cortical spreading depression

  • Slow wave of neuronal depolarisation starting in the occipital cortex (2–6mm/min), followed by suppression of cortical activity
  • Thought to underlie aura, and may activate the trigeminovascular system

Trigeminovascular system

  • Bipolar neurones with cell bodies in the trigeminal ganglion, innervating cranial vessels, dura and venous sinuses
  • Trigeminal afferents and C1–3 nerve roots converge on the trigeminal nucleus caudalis (trigeminocervical complex)
    • This explains occipital and neck pain and is the rationale for occipital nerve interventions

  • Ophthalmic (V1) division activation explains the common periorbital pain
  • Activation releases neuropeptides: CGRP, substance P, PACAP
  • Projections to the thalamus explain sensitivity to light, sound and smell
  • Parasympathetic connections via the sphenopalatine ganglion explain cranial autonomic features

Calcitonin gene-related peptide (CGRP)

  • Potent vasodilator and pain-signalling neuropeptide
  • Levels rise during attacks and fall with sumatriptan treatment
  • CGRP infusion can trigger migraine
  • Target of the monoclonal antibodies and gepants

Hormonal influences

  • The fall in oestrogen at menstruation triggers menstrual migraine
  • Most women improve during pregnancy due to stable, high oestrogen levels

Diagnosis

  • Clinical: thorough history and normal neurological examination
  • Routine imaging is not required unless red flags are present
  • Headache diary helps diagnosis and monitoring of response to treatment

Red flags

  • Associated systemic features
  • Focal neurological deficit or papilloedema
  • Age >50 yr
  • Thunderclap headache
  • Headache worse with Valsalva e.g. coughing, bending

General principles

  • Rest in a dark, quiet room
  • Most attacks resolve within 4 h; no response at 2 h means a drug is unlikely to work
  • Treatment can be stepwise (escalate from simple analgesia) or stratified by attack severity; stratified care has better outcomes
  • Opioids should not be used

Treatment options

Drug class Key points
Simple analgesics
(NSAID, aspirin, paracetamol)		 First-line for mild to moderate attacks
Add an antiemetic (e.g. metoclopramide, domperidone, prochlorperazine) even without nausea
Triptans
(e.g. sumatriptan)		 5-HT1B/1D agonists: cranial vasoconstriction and ↓ neuropeptide release
First-line for moderate to severe attacks, alone or with an NSAID
Take early in the headache phase; ineffective during aura
Try another triptan if one fails; s.c. or nasal routes if vomiting
Gepants
(e.g. rimegepant)		 Oral CGRP receptor antagonists; no vasoconstriction
Reserved for failure of two triptans or contraindication to triptans
Ditans
(e.g. lasmiditan)		 5-HT1F agonists; no coronary vasoconstriction
Not available in the UK

Triptan contraindications

  • Ischaemic heart disease
  • Cerebrovascular disease
  • Uncontrolled severe hypertension

Medication overuse headache

  • Can occur with all acute treatments except CGRP antagonists
  • Highest risk: opioids and combination analgesics; intermediate: triptans; lowest: NSAIDs
  • Patients should limit acute treatment to no more than 2 days per week

Definition

  • Severe, unremitting migraine lasting ≥72hrs
  • Up to 10% of acute hospital admissions for headache
  • Secondary causes of headache must be excluded
  • Risk of severe dehydration from vomiting

Management

  • A stepwise approach is used although there are no guidelines:
  1. IV fluids
  2. IV antiemetic e.g. prochlorperazine or metoclopramide
  3. IV analgesia e.g. paracetamol plus NSAID
  4. Rimegepant 75 mg or sumatriptan 6 mg

  5. In refractory cases, consider:
    • Magnesium sulphate 0.5–1 g IV
    • Sodium valproate 500 mg IV
    • Chlorpromazine 10 mg IV
    • Dihydroergotamine 0.5–1 mg IV
    • Greater occipital nerve block or dexamethasone 4–24 mg IV

Indications

  • ≥4 migraine days per month
  • Inadequate response, intolerance or contraindication to acute treatment
  • Lower threshold in hemiplegic migraine, migraine with brainstem aura or migrainous infarction

Principles

  • Choice guided by comorbidities, pregnancy plans and side-effect profile
  • Start low and titrate; continue for at least 6–8 weeks before judging effect
  • Meaningful response: 50% reduction in headache days in episodic, 30% in chronic migraine
  • Continue for 6–12 months, then consider gradual withdrawal

First-line oral treatments

Drug Notes
Amitriptyline Start 10 mg nocte
Drowsiness, dry mouth, fatigue
Propranolol Start 10–20 mg BD
Avoid in asthma, COPD, peripheral vascular disease
Fatigue, vivid dreams, depression
Candesartan 16 mg comparable to propranolol 160 mg
Well tolerated; dizziness
Topiramate Only if no alternative in women of childbearing potential (MHRA)
Paraesthesia, weight loss, cognitive effects
Sodium valproate Use limited by teratogenicity

Second-line treatments

  • Expensive so are recommended by NICE only after failure of at least three preventive treatments
  • OnabotulinumtoxinA (Botox):
    • Chronic migraine only
    • 155 units injected into 31 sites across the head and neck muscles every 3 months
    • Thought to inhibit sensory nerve endings and reduce CGRP release
    • Stopped if <30% response after two cycles
    • Avoid in neuromuscular disorders

  • CGRP monoclonal antibodies:
    • Erenumab targets the receptor; fremanezumab, galcanezumab and eptinezumab target the ligand
    • Monthly s.c. injection (eptinezumab is a 3-monthly i.v. infusion)
    • Side-effect profile similar to placebo

  • Gepants: atogepant (daily) and rimegepant (alternate days) orally

Peripheral nerve blocks

  • Used as acute or 'transitional' treatment, in the emergency or outpatient setting

  • Greater occipital nerve block is the most common:
    • Rationale: convergence of occipital and trigeminal afferents in the trigeminocervical complex
    • Local anaesthetic with or without steroid; can be repeated every 3 months

  • Other targets: lesser occipital, supraorbital, supratrochlear and auriculotemporal nerves

  • Sphenopalatine ganglion block:
    • Parasympathetic ganglion responsible for cranial autonomic symptoms
    • Performed transnasally with lidocaine 2% or bupivacaine 0.5%
  • Safe and well tolerated, including in pregnancy

Neuromodulation

  • Modifies neural circuits using electrical or magnetic stimulation; peripherally slows conduction and inhibits small fibre nociceptive input, with additional central effects
  • Non-invasive, portable devices for acute and preventive use:
    • Single-pulse transcranial magnetic stimulation
    • Non-invasive vagal nerve stimulation
    • External trigeminal (supraorbital) nerve stimulation
    • Remote electrical neuromodulation via an armband
  • Most are not funded on the NHS as they are appraised via interventional procedure guidance
  • Occipital nerve stimulation: invasive, reserved for intractable chronic migraine in specialist centres
Advantages Disadvantages
Non-invasive devices: minimal side-effects e.g. mild tingling Non-invasive devices: limited NHS availability
No risk of medication overuse headache Variable quality of evidence
Option in pregnancy or where drugs are contraindicated Occipital nerve stimulation: infection, bleeding, lead migration requiring revision


Acute treatment

  • Two thirds of women improve during pregnancy
  • Paracetamol and sumatriptan are considered safe
  • NSAIDs can be used until 32 weeks' gestation
  • Metoclopramide and domperidone as antiemetics
  • Avoid opioids; codeine only if other drugs are ineffective

Prevention

  • Ideally avoided
  • If required, low-dose amitriptyline or propranolol
  • Greater occipital nerve block and non-invasive neuromodulation are considered safe

Avoid

  • CGRP monoclonal antibodies and gepants due to lack of safety data
  • Sodium valproate and topiramate are teratogenic