Cluster Headache
Severe unilateral periorbital headache with ipsilateral autonomic features; 'suicide headache.'
Also known as: cluster headache, trigeminal autonomic cephalalgia, TAC, Horton headache
Overview
Primary headache disorder belonging to the trigeminal autonomic cephalalgias, characterized by attacks of severe strictly unilateral pain in orbital, supraorbital, and/or temporal locations lasting 15-180 minutes, accompanied by ipsilateral autonomic features and/or restlessness/agitation. Attacks occur from once every other day up to 8 times per day, often clustering over weeks-months ('cluster periods'), with remissions of months-years.
Epidemiology
Prevalence ~1 in 1000. Male-to-female ratio ~3:1 (narrowing in newer studies). Onset typically 20-40 years.
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Risk factors
- Male sex
- Family history (uncommon but recognized)
- Tobacco use (very strong association)
- Alcohol — triggers attacks during a cluster period (not between periods)
- Nitroglycerin and other vasodilators provoke attacks (clinical/research test)
- Sleep — REM sleep particularly; many attacks occur at the same time each night
- Histamine, strong odors
Pathophysiology
Activation of the trigeminal-autonomic reflex with central drive from the posterior hypothalamus (demonstrated on functional imaging) — explaining the circadian/circannual periodicity. Trigeminal activation produces severe periorbital pain; parasympathetic outflow via the facial nerve produces ipsilateral autonomic features (lacrimation, rhinorrhea, conjunctival injection). Sympathetic dysfunction may cause partial Horner syndrome (ptosis, miosis).
Clinical presentation
Symptoms
- Excruciating ('worst pain imaginable,' 'ice pick in the eye') unilateral periorbital/temporal pain
- Duration 15-180 minutes per attack
- Frequency: 1 every other day to 8 per day, often at the same time(s) daily
- Cluster period: weeks to months of frequent attacks, then remission for months to years (episodic, ~80%); chronic (~20%) has no remission >3 months
- Patient is restless, pacing, agitated (NOT lying still like migraine)
- Often nocturnal — wakes patient 1-2 hours after sleep onset
Signs / physical exam
- Ipsilateral autonomic features during attack: conjunctival injection, lacrimation, nasal congestion, rhinorrhea, eyelid edema, forehead/facial sweating, miosis, ptosis (partial Horner — may persist between attacks)
- Restlessness/agitation during attack
- Normal exam between attacks
Classic findings
Severe unilateral periorbital pain + ipsilateral autonomic features + restlessness, attacks clustered in time.
Differential diagnosis
- Migraine — Patient prefers to lie still in dark room; cluster patient is restless and pacing. Migraine more often bilateral, longer duration, with nausea
- Other trigeminal autonomic cephalalgias — Paroxysmal hemicrania (shorter attacks 2-30 min, absolute response to indomethacin), SUNCT/SUNA (1-600 sec attacks, very frequent), hemicrania continua (continuous unilateral pain, also indomethacin-responsive)
- Trigeminal neuralgia — Brief electric-shock-like pains seconds long, triggered by light touch in V2/V3 distribution; no autonomic features
- Acute angle-closure glaucoma — Severe eye pain, halos around lights, fixed mid-dilated pupil, cloudy cornea, elevated IOP — ophthalmologic emergency
- Carotid artery dissection — Unilateral head/neck pain, partial Horner syndrome, possibly ischemic symptoms; CTA neck diagnostic
- Sinusitis — Bilateral or maxillary pressure, nasal discharge, fever, recent URI; not as severe or paroxysmal
- Pituitary tumor — Can mimic cluster; MRI brain with pituitary protocol if atypical or refractory
Diagnostic workup
Diagnostic criteria
ICHD-3: ≥5 attacks, severe unilateral orbital/supraorbital/temporal pain lasting 15-180 min (untreated), with ≥1 ipsilateral autonomic feature OR sense of restlessness, occurring once every other day to 8 per day.
Labs
- Not typically helpful for diagnosis
Imaging
- MRI brain with pituitary protocol recommended at least once for all patients with cluster headache to exclude structural lesion (pituitary tumor, carotid lesion, AVM)
- Consider MRA if dissection suspected
Diagnostic algorithm
| Feature | Cluster | Migraine |
|---|---|---|
| Location | Strictly unilateral periorbital | Unilateral or bilateral |
| Duration | 15-180 min | 4-72 hours |
| Frequency | 1 every other day to 8/day | Variable, usually <15/month |
| Behavior | Restless, agitated, pacing | Lying still in dark, quiet room |
| Autonomic features | Prominent ipsilateral (tearing, rhinorrhea, miosis, ptosis) | Uncommon |
| Sex predominance | Male | Female |
| First-line acute | 100% O2 12-15 L/min; SC sumatriptan | Triptan PO, NSAID, gepant |
| First-line prevention | Verapamil | Propranolol, topiramate, CGRP mAb |
Treatment
First-line
- Acute (abortive): high-flow 100% oxygen 12-15 L/min via non-rebreather mask for 15-20 min (works in ~70%, no contraindications)
- Triptan — sumatriptan 6 mg SC (most effective formulation) or 20 mg intranasal, zolmitriptan 5-10 mg nasal — faster routes preferred because attacks are short
- Avoid oral triptans (too slow)
- Intranasal lidocaine 4% — adjunct
- Transitional bridge therapy at start of cluster period: prednisone 60 mg taper over 2-3 weeks or suboccipital steroid injection — rapidly suppresses attacks until preventive takes effect
Second-line / adjunct
- Preventive (start at the beginning of each cluster period): verapamil 240-960 mg/day (first-line; ECG monitoring for AV block as dose escalates)
- Lithium 600-1200 mg/day (especially chronic cluster) — monitor levels, renal/thyroid function
- Topiramate 50-200 mg/day, valproate, melatonin 10 mg at bedtime
- Galcanezumab (CGRP monoclonal antibody) — FDA-approved for episodic cluster
- Greater occipital nerve block
- Sphenopalatine ganglion stimulation, occipital nerve stimulation, deep brain stimulation of posterior hypothalamus — for refractory chronic cluster
- Avoid triggers during cluster period: alcohol, nitroglycerin, naps; smoking cessation
Complications
- Severe pain leading to suicidal ideation ('suicide headache')
- Depression, anxiety
- Permanent partial Horner syndrome on the affected side
- Medication overuse headache (less common than in migraine)
- Verapamil-induced bradycardia or AV block
- Disability and lost productivity during cluster periods
PANCE pearls
- Cluster headache + restlessness; migraine + lying still — this behavioral feature is one of the best discriminators.
- High-flow oxygen is uniquely effective and SHOULD be prescribed for home use — DME companies provide tanks for this indication.
- Always image the brain (MRI with pituitary protocol) at least once — pituitary tumors can mimic cluster.
- Verapamil is the preventive of choice; doses often exceed cardiology norms (up to 720-960 mg/day) — ECG before escalation and at each step.
- Indomethacin-responsive headaches (paroxysmal hemicrania, hemicrania continua) must be excluded — they look like cluster but absolutely respond to indomethacin.
References
- AAN 2010 — Practice Parameter: Treatment of Cluster Headache (Francis et al., Neurology 2010)
- AHS 2016 — Treatment of Cluster Headache: AHS Evidence-Based Guidelines (Robbins et al., Headache 2016)
- ICHD-3 — International Classification of Headache Disorders, 3rd edition (Cephalalgia 2018)
- Galcanezumab — Galcanezumab in Episodic Cluster Headache (Goadsby et al., NEJM 2019)
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