Cluster Headaches · What Are They, Causes, Treatment, and More

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. Pain from cluster headaches is among the most severe kinds of pain described by humans, and is often equated to pain from gunshot wounds, giving birth, and kidney stones. 

While cluster headache is a rare disorder, it’s the most common amongst a group of primary headaches called trigeminal autonomic cephalgias. Although anyone can experience cluster headaches, it’s most common in those assigned male at birth. 

The exact cause of cluster headaches is not completely understood. However, it’s thought 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.  

Individuals with cluster headaches experience cluster attacks that can last anywhere between 15 minutes to 3 hour ranging 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, which is a period of time where cluster attacks repeat daily. Interestingly, most individuals have a circadian pattern to their headaches, with symptoms starting around the same time each day. 

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 1 year without remission, or with remissions lasting less than 3 months.  

Differential diagnoses involve considering various possible conditions that could be causing symptoms and then ruling out each one through use of history, clinical evaluation, diagnostic tests, and critical thinking. This process helps to narrow down the list of potential diagnoses to determine the most likely cause of the symptoms.  

Differential diagnoses can be broken down into four categories: most likely, less likely, least likely, and can’t miss. Most likely diagnoses are conditions most probable based on symptoms and clinical presentation. Less likely diagnoses are not as probable but should still be considered. On the other hand, least likely diagnoses can be considered if other, more probable conditions are excluded. Finally, can’t miss diagnoses are less common but critical to promptly identify and treat as they can lead to severe consequences.  

Diagnosis of cluster headache begins with a thorough history and physical exam. The diagnostic criteria includes experiencing a minimum of 5 cluster attacks characterized by severe unilateral orbital or periorbital pain lasting 15 to 180 minutes; experiencing 1 every other day to 8 episodes daily; and 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.  

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. Corticosteroids are usually given to suppress the attacks during the time it takes for maintenance medications to become effective. Recently, the Food and Drug Administration (FDA) has approved galcanezumab (Emgality®), a selective CGRP antagonist, as the first specific preventive treatment for episodic cluster headache. This medication is administered as a subcutaneous injection once a month until the cluster period ends, aiming to reduce attack frequency. 

 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 cigarette smoking and alcohol, individuals may be advised to avoid smoking and reduce their alcohol intake.