Hemicrania Continua

Hemicrania continua is a continuous strictly unilateral headache of moderate intensity with superimposed severe exacerbations, ipsilateral cranial autonomic features or restlessness, and an absolute response to indomethacin. It is a trigeminal autonomic cephalalgia.

It is rare, with a prevalence of about 1 in 1,000 or fewer. It is more common in women (about 2:1) and begins in early to mid adult life, often after 30 years.

Forms. Remitting (continuous periods with remission lasting 24 hours or more) and unremitting (continuous without remission for at least 1 year).

Secondary causes. Rarely, mass lesions of the pituitary, sphenoid or posterior fossa, and previous head injury.

Pathophysiology.

Activation of trigeminal autonomic reflex circuits and posterior hypothalamic regions causes continuous pain with cranial autonomic features.

Indomethacin acts through mechanisms that remain unclear, including cyclo oxygenase inhibition and effects on nitric oxide signalling.

• Continuous strictly unilateral pain that does not shift sides, moderate in intensity, with severe exacerbations lasting minutes to days.
• Ipsilateral conjunctival injection, tearing, nasal congestion, rhinorrhoea, ptosis, miosis or eyelid oedema during exacerbations, or restlessness.
• Migrainous features (nausea, photophobia) in some.
• Foreign body sensation in the eye and ipsilateral scalp tenderness.

Red flags.

• Headache with neurological deficit, papilloedema, or visual loss.
• Onset over age 50, or poor indomethacin response.
• Progressive course or abnormal MRI.

• ICHD-3 criteria: unilateral headache for over 3 months with exacerbations, at least one autonomic feature or restlessness, and an absolute response to indomethacin.
• Indomethacin test: 25 mg orally three times daily for 3 days, then 50 mg three times daily for 3 days, then 75 mg three times daily for 3 days; response usually appears within 1 to 3 days at an effective dose. Intramuscular indomethacin 50 mg can be used under supervision.
• MRI of the brain and pituitary with contrast to exclude secondary causes.
• Baseline blood pressure, renal function and review of gastrointestinal risk.

Differential diagnosis. Chronic migraine, new daily persistent headache, cluster headache, paroxysmal hemicrania, cervicogenic headache, trigeminal neuralgia, temporomandibular disorder, giant cell arteritis and secondary headache.

• Indomethacin 25 mg orally three times daily with food, increased every 3 days to 50 mg three times daily then 75 mg three times daily until pain resolves, then reduced to the lowest effective dose. Usual maintenance 25 to 150 mg daily. Maximum 225 mg daily. Continue for 6 to 12 months, then try a slow reduction. Monitor blood pressure, renal function, blood count and gastrointestinal bleeding. Avoid in peptic ulcer, heart failure, asthma sensitive to NSAIDs, renal impairment (eGFR under 30), the third trimester of pregnancy and with anticoagulants or lithium; reduce dose in hepatic impairment.
• Gastroprotection: omeprazole 20 mg orally once daily while taking indomethacin. Maximum 40 mg daily. Monitor magnesium and B12 with long term use. Reduce dose to 10 to 20 mg in severe hepatic impairment; no renal adjustment; avoid with clopidogrel and use caution with long term use because of fracture risk.
• When indomethacin is not tolerated or contraindicated: celecoxib 100 mg orally twice daily, increased to 200 mg twice daily if needed. Maximum 400 mg daily. Monitor blood pressure, renal function and cardiovascular risk. Contraindicated in ischaemic heart disease, stroke, heart failure and sulphonamide allergy; reduce dose in moderate hepatic impairment and avoid in eGFR under 30 and in pregnancy.
• Greater occipital nerve block with local anaesthetic and corticosteroid by a specialist, as a bridge.
• Topiramate, melatonin or neuromodulation by a headache specialist if non-steroidal drugs fail.
• Gradual dose reduction every 3 to 6 months to avoid unnecessary long term exposure.

Monitoring. Review at 4 weeks, then every 3 months while taking indomethacin, with blood pressure, renal function and symptoms of gastrointestinal bleeding.

Referral and escalation. Headache specialist for diagnosis and long term treatment; gastroenterology review for bleeding.

Special groups. Older adults: higher risk of renal and gastrointestinal harm, so use the lowest dose. Pregnancy: avoid indomethacin in the third trimester.