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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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
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)
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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