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Cluster Headaches

What Are They, Causes, Treatment, and More

Author:Anna Hernández, MD

Editors:Alyssa Haag,Emily Miao, PharmD

Illustrator:Jillian Dunbar

Copyeditor:Sadia Zaman, MBBS, BSc


What is a cluster headache?

Cluster headaches are a primary headache disorder characterized by attacks of intense headaches on one side of the head. These attacks are associated with agitation or restlessness, as well as accompanying ipsilateral autonomic symptoms, such as lacrimation, nasal congestion, and swelling around the eye. Cluster headache is a rare disorder,  but it is the most common amongst a group of primary headaches called trigeminal autonomic cephalgias. Although anyone can experience cluster headaches, it is most common in those assigned male at birth.

What causes cluster headaches?

The exact cause of cluster headaches is not completely understood. However, there are three key components involved in the pathology of cluster attacks: the trigeminovascular system, the trigeminal-autonomic reflex, and the hypothalamus. First, the trigeminovascular system consists of neurons that innervate the cerebral blood vessels and dura mater, as well as cortical structures involved in pain processing, such as the frontal cortex, insulae, and cingulate cortex. When these neurons are activated, they release neuropeptides, like the calcitonin gene‑related peptide (CGRP), which trigger the perception of pain. Second, the trigeminal-autonomic reflex is activated upon irritation of the trigeminal nerve fibers and produces parasympathetic symptoms, like lacrimation, conjunctival injection (i.e., dilation of conjunctival blood vessels), and nasal congestion. Finally, the hypothalamus is a part of the brain that helps maintain the body’s internal functions and is responsible for regulating the biological clock. Research shows that posterior hypothalamus activation plays an important role in the episodic occurrence of cluster headaches and probably contributes to the initiation of cluster attacks. 

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What does a cluster headache feel like?

Cluster headaches start suddenly and are characterized by attacks of extremely intense pain on one side of the head, typically periorbitally (i.e., around the eye). The cluster attacks are often accompanied by ipsilateral autonomic symptoms, including conjunctival hyperemia, increased lacrimation, rhinorrhea and nasal congestion, swelling around the eye, and ptosis (i.e., a drooping eyelid). Commonly, once the pain starts, individuals may pace around or appear agitated and restless due to poor pain-relief options.

How long do cluster headaches last?

Individuals with cluster headaches experience cluster attacks that last anywhere between 15 minutes to 3 hours; these attacks can occur from 1 to 8 times a day. Episodic cluster headaches, which are the most common form, are characterized by attacks that occur daily during a cluster period. Most individuals experience cluster periods that last a few weeks or months, followed by months or even years of remission before recurring. When chronic, cluster attacks occur for more than one year without remission, or with remissions lasting less than 3 months. 

How is a cluster headache diagnosed?

Diagnosis of cluster headache begins with a thorough clinical history and physical exam. The diagnostic criteria includes experiencing a minimum of 5 cluster attacks characterized by severe unilateral orbital or periorbital pain, with a duration of 15 to 180 minutes; experiencing 1 to 8 episodes daily; presenting with one or more autonomic symptoms on the same side as the headache; or a sense of agitation or restlessness. Although the diagnosis is largely clinical, diagnostic imaging techniques, like a CT scan or MRI, are generally performed to rule out cranial lesions that could be causing the headaches

How is a cluster headache treated?

Treatment of cluster headaches includes abortive treatment to relieve the pain, as well as preventive medications aimed at reducing the number of attacks during cluster periods. Abortive treatment typically consists of 100% oxygen and triptan medications, which act as agonists for serotonin receptors located in cerebral blood vessels and nerve endings of the brain. Triptan medications, like sumatriptan and zolmitriptan, can be administered orally, subcutaneously, or via a nasal spray. These medications have largely replaced ergotamines, an older class of medications used to treat migraines and cluster headaches, due to their lower side effect profile. 

Prevention of cluster headaches involves maintenance medications, like verapamil or topiramate, as well as short-term medications, like corticosteroids. These usually suppress the attacks during the time it takes for maintenance medications to become effective. More recently newer agents, such as galcanezumab, a selective CGRP antagonist, are being studied as preventive treatment for migraines and cluster headaches. If these conservative measures alone are not sufficient to prevent cluster headaches, other procedures, like blockade of the greater occipital nerve, may be performed. As cluster attacks have also been linked with cigarettes and alcohol, individuals may be advised to avoid smoking and reduce their alcohol intake. 

What are the most important facts to know about cluster headaches?

Cluster headaches are the rarest form of primary headache and usually occur in males. They present as excruciating, stabbing pain on one side of the head, typically around the eye. Cluster attacks are associated with a sense of agitation or restlessness alongside autonomic symptoms on the affected side, such as lacrimation, nasal congestion, and a drooping eyelid. Cluster headaches tend to occur every day during cluster periods that can last for weeks to months. Cluster headache periods may have intervals of attack-free remissions of varying duration, depending on whether the individual has episodic cluster headache or chronic cluster headache. Acute pain relief options include 100% oxygen and sumatriptan, a selective serotonin receptor agonist. To prevent cluster headaches, medications like verapamil and other newer agents may be used.

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Related links

Cluster headaches
Headaches: Clinical practice
Headaches: Pathology review
Migraine
Migraine medications

Resources for research and reference

Hoffmann, J., & May, A. (2018). Diagnosis, pathophysiology, and management of cluster headache. The Lancet Neurology, 17(1), 75–83. DOI: 10.1016/s1474-4422(17)30405-2 

Wei, D. Y., & Goadsby, P. J. (2021). Cluster headache pathophysiology — insights from current and emerging treatments. Nature Reviews Neurology, 17(5), 308–324. DOI: 10.1038/s41582-021-00477-w 

Wei, D. Y., Yuan Ong, J. J., & Goadsby, P. J. (2018). Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis. Annals of Indian Academy of Neurology, 21(Suppl 1), S3–S8. DOI: 10.4103/aian.AIAN_349_17

Whyte, C. A., & Tepper, S. J. (2010). Pearls & Oy-sters: Trigeminal autonomic cephalalgias. Neurology, 74(11), e40–e42. DOI: 10.1212/wnl.0b013e3181d55f12