Headache, Cluster
BASICS
DESCRIPTION
- A primary headache disorder characterized by circadian and circannual episodes consisting of multiple attacks of severe, unilateral sharp, searing, or piercing pain typically localized to the periorbital and/or temporal areas
- It is the most common headache among trigeminal autonomic cephalgias (TACs)
- Accompanied by signs of ipsilateral parasympathetic autonomic activation as well as restlessness or agitation
- Autonomic symptoms: signs of parasympathetic hyperactivity (ipsilateral lacrimation, eye redness, nasal congestion) and sympathetic hypoactivity (ipsilateral ptosis and miosis)
- Individual attacks occur from once every other day up to 8 times per day and can last 15 to 180 minutes per day if untreated.
- Attacks usually occur in series (cluster periods) that are often seasonal, lasting for weeks or months, and are separated by remission periods usually lasting months to years.
- About 10–15% of patients have chronic symptoms without remission periods (i.e., chronic cluster headache [cCH]).
EPIDEMIOLOGY
Prevalence
1 year prevalence: 53/100,000
- Gender: male > female; 4.3:1 overall
- Mean age of onset: 30 years; women often develop cluster headache (CH) earlier in life (20s).
ETIOLOGY AND PATHOPHYSIOLOGY
Complex and incompletely understood, possible mechanisms include the following:
- Activation of the trigeminovascular system which leads to the release of vasodilatory peptides including substance P, neurokinin, and calcitonin gene-related peptide (CGRP)
- Posterior hypothalamus activation and the hypothalamic-brainstem-cerebellar interconnections may trigger an attack by activating trigeminal nociceptive pathways through increased parasympathetic outflow.
- Alterations in the descending pain modulation network and disordered pain modulation during cluster periods
Genetics
- Autosomal dominant in 5% of cases; otherwise recessive or multifactorial
- First-degree relatives are 18 times more likely, and second-degree relatives are 1 to 3 times more likely to be affected by cluster headaches.
- >50% with migraine and 18% with CH in family history
- Association of core circadian genes and other clock-controlled genes (CCGs), which have a circadian pattern of expression
RISK FACTORS
- Age: 70% onset before age 30 years
- Cigarette smoking or childhood exposure to cigarette smoke
- History of head trauma
COMMONLY ASSOCIATED CONDITIONS
- Depression (24%) with increased risk of suicide
- History of migraine, frequently in female patients; medication-overuse headache
- Asthma (9%)
- Sleep apnea (30–80%)
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Citation
Domino, Frank J., et al., editors. "Headache, Cluster." 5-Minute Clinical Consult, 34th ed., Wolters Kluwer, 2026. Medicine Central, im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116254/all/Headache__Cluster.
Headache, Cluster. In: Domino FJF, Baldor RAR, Golding JJ, et al, eds. 5-Minute Clinical Consult. Wolters Kluwer; 2026. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116254/all/Headache__Cluster. Accessed July 29, 2025.
Headache, Cluster. (2026). In Domino, F. J., Baldor, R. A., Golding, J., & Stephens, M. B. (Eds.), 5-Minute Clinical Consult (34th ed.). Wolters Kluwer. https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116254/all/Headache__Cluster
Headache, Cluster [Internet]. In: Domino FJF, Baldor RAR, Golding JJ, Stephens MBM, editors. 5-Minute Clinical Consult. Wolters Kluwer; 2026. [cited 2025 July 29]. Available from: https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116254/all/Headache__Cluster.
* Article titles in AMA citation format should be in sentence-case
TY - ELEC
T1 - Headache, Cluster
ID - 116254
ED - Domino,Frank J,
ED - Baldor,Robert A,
ED - Golding,Jeremy,
ED - Stephens,Mark B,
BT - 5-Minute Clinical Consult, Updating
UR - https://im.unboundmedicine.com/medicine/view/5-Minute-Clinical-Consult/116254/all/Headache__Cluster
PB - Wolters Kluwer
ET - 34
DB - Medicine Central
DP - Unbound Medicine
ER -