Paroxysmal Hemicrania

Paroxysmal hemicrania is a trigeminal autonomic cephalalgia with frequent, severe, short lasting unilateral orbital, supraorbital or temporal pain, with ipsilateral cranial autonomic features and an absolute response to indomethacin. Attacks last 2 to 30 minutes and occur more than 5 times daily.

It is rare, with a prevalence of about 1 in 50,000 to 1 in 100,000. It occurs with equal frequency in both sexes, at a mean age of about 35 years.

Forms. Episodic (remissions of 1 month or more) and chronic (no remission, or remission under 1 month).

Secondary causes. Pituitary tumours, vascular lesions and posterior fossa lesions are reported, so imaging is required.

Pathophysiology.

Activation of the trigeminal autonomic reflex with posterior hypothalamic involvement causes parasympathetic outflow and cranial autonomic features.

Indomethacin responsiveness is a defining feature, but the mechanism is not known.

• Severe, strictly unilateral stabbing or throbbing pain around the eye, temple or forehead, lasting 2 to 30 minutes, 5 or more times a day (often 10 to 40).
• Ipsilateral conjunctival injection, tearing, nasal congestion, rhinorrhoea, eyelid oedema, ptosis or miosis.
• Restlessness or agitation during attacks, and some triggered by neck movement or pressure.
• Normal examination between attacks.

Red flags.

• Neurological deficit, papilloedema or visual loss.
• Progressive worsening, or lack of response to indomethacin.
• Attack duration or pattern that changes.

• ICHD-3 criteria: at least 20 attacks of severe unilateral pain lasting 2 to 30 minutes, with at least one autonomic feature, frequency over 5 a day for more than half the time, 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; improvement usually occurs within 1 to 2 days.
• MRI of the brain and pituitary with contrast; baseline blood pressure and renal function.
• Headache diary of attack frequency and duration.

Differential diagnosis. Cluster headache, SUNCT and SUNA, trigeminal neuralgia, hemicrania continua, migraine, secondary headache and dental pain.

• 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 attacks stop, then reduced to the lowest effective dose. Usual maintenance 25 to 150 mg daily. Maximum 225 mg daily. Review remission at 6 to 12 months with a gradual 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.
• When indomethacin is not tolerated: verapamil 40 mg orally three times daily, increased every 1 to 2 weeks to a usual 120 to 240 mg three times daily as tolerated. Maximum 480 mg daily. Monitor ECG (PR interval) before and after each dose increase, blood pressure, heart rate and constipation. Avoid in heart block, severe left ventricular dysfunction and sinus node disease; reduce dose in hepatic impairment; use caution with statins and beta blockers.
• Topiramate 25 mg orally at night, increased by 25 mg weekly to 100 to 200 mg daily in 2 divided doses. Maximum 200 mg daily. Monitor bicarbonate, mood, weight and kidney stones. Halve the dose when creatinine clearance is under 70 mL/min; contraindicated in pregnancy and effective contraception is needed. Evidence is limited.
• Greater occipital nerve block as a bridge, by a specialist.
• Slow dose reduction every 3 to 6 months in episodic disease.

Monitoring. Review at 4 weeks, then every 3 months; track attack frequency, blood pressure, renal function and gastrointestinal symptoms.

Referral and escalation. Headache specialist for diagnosis; gastroenterology review for suspected bleeding.

Special groups. Pregnancy: avoid indomethacin in the third trimester; choose specialist led management.