Cluster Headache

Cluster headache is a primary trigeminal autonomic cephalalgia characterised by attacks of severe unilateral orbital, supraorbital or temporal pain lasting 15 to 180 minutes, accompanied by ipsilateral cranial autonomic features and restlessness, occurring from once every other day to eight times a day in bouts.

• Episodic form: attacks in clusters (weeks to months) separated by remission of at least 3 months; chronic form: attacks for over a year without remission, or remission under 3 months.
• Prevalence about 1 per 1000; men are affected 3 to 4 times more often than women; onset usually 20 to 40 years; about 70 to 80 percent smoke.
• Attacks are circadian and circannual, often occurring at the same time at night and in the same season, with hypothalamic involvement.
• It is among the most painful conditions known and carries a high risk of depression and suicidal thoughts; ask about suicidality directly.
• Triggers during a bout: alcohol (within an hour), nitrates, histamine, high altitude and sleep changes.

• Excruciating, stabbing or boring pain around or behind one eye, radiating to the temple, jaw or neck; the same side in a bout.
• Ipsilateral autonomic signs: lacrimation, conjunctival injection, nasal congestion or rhinorrhoea, eyelid oedema, ptosis, miosis, forehead and facial sweating.
• Restlessness and agitation: patients pace, rock or press on the eye (unlike migraine, where patients lie still).
• Attacks wake the patient from sleep, typically 1 to 2 hours after falling asleep.
• Examination between attacks is normal; during an attack, partial Horner syndrome may be present and may persist.

• Clinical, using a diary of timing and frequency; at least 5 attacks fulfilling duration, frequency and autonomic criteria.
• MRI brain with contrast and attention to the pituitary and cavernous sinus is advised at first presentation to exclude a structural cause (pituitary tumour, carotid dissection, cavernous sinus lesion, vascular malformation).
• Before verapamil: baseline 12 lead ECG.
• Differentials: paroxysmal hemicrania (attacks 2 to 30 minutes, more than 5 daily, complete response to indometacin), SUNCT and SUNA (attacks 1 to 600 seconds, up to hundreds daily), hemicrania continua, trigeminal neuralgia (electric shocks of seconds, triggered by touch), migraine, acute angle closure glaucoma, carotid dissection, sinusitis, giant cell arteritis.

Acute treatment (choose one, effective within 15 to 20 minutes)

• Oxygen 100 percent at 12 to 15 L/min through a non-rebreathing mask with reservoir for 15 to 20 minutes, sitting forward; works in about 60 to 70 percent; safe at home with a regulator, and without risk in smokers when handled correctly (no smoking near oxygen).
• Sumatriptan 6 mg subcutaneously at onset (maximum 12 mg in 24 hours, at least 1 hour apart); or sumatriptan 20 mg intranasally (may repeat after 2 hours, maximum 40 mg daily); or zolmitriptan 5 mg or 10 mg intranasally or 5 mg orally (nasal route is faster).
• Contraindicated: ischaemic heart disease, previous stroke or TIA, uncontrolled hypertension, hemiplegic or brainstem migraine, peripheral vascular disease, use of ergotamine in the previous 24 hours; do not use more than 2 injections daily.
• Avoid oral analgesics and opioids; they act too slowly.

Transitional (bridge) treatment at the start of a bout

• Prednisolone 60 mg orally once each morning for 5 days, then reduce by 10 mg every 2 days until stopped (total about 3 weeks); check blood pressure, glucose, and avoid in peptic ulcer disease, infection, uncontrolled diabetes. Gastroprotection with omeprazole 20 mg daily.
• Or greater occipital nerve block on the painful side with methylprednisolone 80 mg and lidocaine 2 percent 2 mL (repeat once after 1 week if needed).

Preventive treatment (start with the bridge, continue through the bout)

• Verapamil modified release 80 mg orally three times daily, increasing by 80 mg every 2 weeks to a typical dose of 240 to 480 mg daily (some require up to 960 mg). ECG at baseline and 10 to 14 days after each dose increase above 240 mg, then every 6 months: stop or hold if PR interval is over 240 ms or second or third degree block occurs. Side effects: constipation, ankle oedema, bradycardia, hypotension, gingival hyperplasia. Interaction with beta blockers, digoxin, simvastatin (limit to 10 mg), and clarithromycin.
• Lithium carbonate 400 mg to 600 mg orally at night, increasing to 800 to 1200 mg daily to a serum level of 0.4 to 0.8 mmol/L (12 hours after last dose); measure at 5 to 7 days and then monthly; monitor renal and thyroid function; avoid with NSAIDs and ACE inhibitors.
• Topiramate 25 mg at night, increasing weekly to 100 to 200 mg daily in divided doses.
• Galcanezumab 300 mg subcutaneously at the start of the bout, then monthly while the bout lasts (episodic cluster only).
• Melatonin 10 mg at night, a mild option.
• Taper the preventive after 2 or more weeks free of attacks (episodic form).

Chronic or refractory cases (specialist)

• Combination preventives, occipital nerve stimulation, sphenopalatine ganglion stimulation, or hypothalamic deep brain stimulation.

Lifestyle and safety

• Avoid alcohol during a bout, keep a regular sleep pattern, stop smoking.
• Screen for depression and suicidal ideation at every visit; give a safety plan to patients with severe disease.

Special groups

• Pregnancy: oxygen is first line; sumatriptan may be used when needed; verapamil is used as prevention with fetal monitoring; avoid lithium, topiramate and valproate.