Cluster headache is a neurological disorder characterized by episodes of severe headaches on one side of the head, typically around the eye and temple, lasting between 15 minutes to three hours. Episodes are often accompanied by eye watering, nasal congestion, drooping eyelids, or swelling around the eye on the affected side. Cluster headaches are unique in their periodicity and regularity: the headaches occur at around the same hour every day during a cluster period, which typically lasts 8–10 weeks a year. Between cluster periods are pain-free intervals without headaches, which last a little less than one year, but some patients can have chronic cluster headaches without remission periods. The disease is considered among the most painful conditions known to medical science.
Cluster headache shows strong circadian and seasonal periodicity, with attacks often recurring at similar times of day, sometimes during sleep, and seasonal peaks in spring and autumn. This has prompted research into the role of the hypothalamus and the body's biological clock.
Triggers of cluster headaches may include alcohol, weather changes, smells, bright/flashing lights, television viewing, and nitroglycerin, among others. Histamine can also precipitate attacks, while a history of exposure to tobacco smoke, whether personal or secondhand, is a risk factor. The underlying cause is unknown, but may include a genetic component, as a family history of migraines increases risk. Structurally, the disease is likely related to dysfunction of the posterior hypothalamus.
The diagnosis is based on the unique pattern of headaches and associated symptoms. There are no specific laboratory tests, physical exam maneuvers, or neuroimaging findings associated with the disease. However, neuroimaging may be required in the case of patients with red flag symptoms, such as a sudden change in the characteristics of the headache.
Recommended management includes lifestyle adaptations, including smoking cessation and avoiding potential triggers. Medical treatments for acute attacks include oxygen or a fast-acting triptan. Preventative medications recommended to decrease the frequency of attacks include steroid injections, galcanezumab, civamide, verapamil, or oral glucocorticoids such as prednisone. Nerve stimulation or surgery may occasionally be used if other measures are not effective.
The condition affects about 0.1% of the general population at some point in their life and 0.05% in any given year. The condition usually first occurs between 20 and 40 years of age. Men are affected about four times more often than women. These debilitating headaches significantly impact daily activities, and due to the severity of the pain, they have also been referred to as "suicide headaches".
Signs and symptoms Cluster headaches are recurring bouts of severe unilateral headache attacks. The duration of a typical cluster headache ranges from about 15 to 180 minutes. About 75% of untreated attacks last less than 60 minutes. However, women may have longer and more severe cluster headaches.
The onset of an attack is rapid and typically without an aura. Preliminary sensations of pain in the general area of attack, referred to as "shadows", may signal an imminent cluster headache, or these symptoms may linger after an attack has passed, or between attacks. Though cluster headaches are strictly unilateral, there are some documented cases of "side-shift" between cluster periods, or, rarely, simultaneous (within the same cluster period) bilateral cluster headaches.
Pain The pain occurs only on one side of the head, around the eye, particularly behind or above the eye, in the temple. The pain is typically greater than in other headache conditions, including migraines, and is usually described as burning, stabbing, drilling or squeezing. While suicide is rare, those with cluster headaches may experience suicidal thoughts (giving the alternative name "suicide headache" or "suicidal headache").
Dr. Peter Goadsby, Professor of Clinical Neurology at University College London, and Chair and Patron of OUCH(UK), a leading researcher on the condition has commented:
Other symptoms The typical symptoms of cluster headache include grouped occurrence and recurrence (cluster) of headache attack, severe unilateral orbital, supraorbital and/or temporal pain. If left untreated, attack frequency may range from one attack every two days to eight attacks per day. Cluster headache attack is accompanied by at least one of the following autonomic symptoms: drooping eyelid, pupil constriction, redness of the conjunctiva, tearing, runny nose and less commonly, facial blushing, swelling, or sweating, typically appearing on the same side of the head as the pain. Similar to a migraine, sensitivity to light (photophobia) or noise (hyperacusis) may occur during a cluster headache. Nausea is a rare symptom although it has been reported.
Restlessness (for example, pacing or rocking back and forth) may occur. Secondary effects may include the inability to organize thoughts and plans, physical exhaustion, confusion, agitation, aggressiveness, depression, and anxiety.
People with cluster headaches may dread facing another headache and adjust their physical or social activities around a possible future occurrence. Likewise they may seek assistance to accomplish what would otherwise be normal tasks. They may hesitate to make plans because of the regularity, or conversely, the unpredictability of the pain schedule. These factors can lead to generalized anxiety disorders, panic disorder, serious depressive disorders, social withdrawal and isolation.
Cluster headaches have been recently associated with obstructive sleep apnea comorbidity.
Recurrence Cluster headaches may occasionally be referred to as "alarm clock headache" because of the regularity of their recurrence. Cluster headaches often awaken individuals from sleep. Both individual attacks and the cluster grouping can have a metronomic regularity; attacks typically strike at a precise time of day each morning or night. The recurrence of headache cluster grouping may occur more often around solstices, or seasonal changes, sometimes showing circannual periodicity. Conversely, attack frequency may be highly unpredictable, showing no periodicity at all. These observations have prompted researchers to speculate an involvement or dysfunction of the hypothalamus. The hypothalamus controls the body's "biological clock" and circadian rhythm. In episodic cluster headache, attacks occur once or more daily, often at the same time each day for a period of several weeks, followed by a headache-free period lasting weeks, months, or years. Approximately 10–15% of cluster headaches are chronic, with multiple headaches occurring every day for years, sometimes without any remission.
In accordance with the International Headache Society (IHS) diagnostic criteria, cluster headaches occurring in two or more cluster periods, lasting from 7 to 365 days with a pain-free remission of one month or longer between the headache attacks may be classified as episodic. If headache attacks occur for more than a year without pain-free remission of at least three months, the condition is classified as chronic. Chronic cluster headaches both occur and recur without any remission periods between cycles; there may be variation in cycles, meaning the frequency and severity of attacks may change without predictability for a period of time. The frequency, severity, and duration of headache attacks experienced by people during these cycles varies between individuals and does not demonstrate complete remission of the episodic form. The condition may change unpredictably from chronic to episodic and from episodic to chronic.
Causes Positron emission tomography (PET) shows brain areas being activated during pain. Voxel-based morphometry shows brain area structural differences. The specific causes and pathogenesis of cluster headaches are not fully understood. The Third Edition of the International Classification of Headache disorders classifies cluster headaches as belonging to the trigeminal autonomic cephalalgias.
Some experts consider the posterior hypothalamus to be important in the pathogenesis of cluster headaches. This is supported by a relatively high success ratio of deep-brain stimulation therapy on the posterior hypothalamic grey matter.
In a 2012 U.S. survey of 1,134 people with cluster headache, reported attack triggers included beer (57%), red wine (50%), hard liquor (49%), weather changes (36%), smells (28%), bright lights (23%), flashing lights (17%), television viewing (12%), hot wraps or hot showers (8%), and nitroglycerin (3%).
Nerves Therapies acting on the vagus nerve (cranial nerve X) and the greater occipital nerve have both shown efficacy in managing cluster headache, but the specific roles of these nerves are not well-understood. Two nerves thought to play an important role in cluster headaches include the trigeminal nerve and the facial nerve.
Genetics Cluster headache may run in some families in an autosomal dominant inheritance pattern. People with a first degree relative with the condition are about 14–48 times more likely to develop it themselves, and around 8 to 10% of persons with cluster headaches have a family history. Several studies have found a higher number of relatives affected among females. Others have suggested these observations may be due to lower numbers of females in these studies. Possible genetic factors warrant further research, current evidence for genetic inheritance is limited.
Genes that are thought to play a role in the disease are the hypocretin/orexin receptor type 2 (HCRTR2), alcohol dehydrogenase 4 (ADH4), β3 subunit of G proteins (GNB3), pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1), and membrane metallo-endopeptidase (MME) genes.
Tobacco smoking About 65% of persons with cluster headache are, or have been, tobacco smokers. Stopping smoking does not lead to improvement of the condition, and cluster headaches also occur in those who have never smoked (e.g., children); it is thought unlikely that smoking is a cause. People with cluster headaches may be predisposed to certain traits, including smoking or other lifestyle habits.
Hypothalamus A review suggests that the suprachiasmatic nucleus of the hypothalamus, which is the major biological clock in the human body, may be involved in cluster headaches, because cluster headaches occur with diurnal and seasonal rhythmicity.
Positron emission tomography (PET) scans indicate the brain areas which are activated during attack only, compared to pain free periods. These pictures show brain areas that are active during pain in yellow/orange color (called "pain matrix"). The area in the center (in all three views) is activated only during cluster headaches. The bottom row voxel-based morphometry shows structural brain differences between individuals with and without CH; only a portion of the hypothalamus is different.
Diagnosis Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache.
A detailed oral history aids practitioners in correct differential diagnosis, as there are no confirmatory tests for cluster headache. A headache diary can be useful in tracking when and where pain occurs, how severe it is, and how long the pain lasts. A record of coping strategies used may help distinguish between headache type; data on frequency, severity and duration of headache attacks are a necessary tool for initial and correct differential diagnosis in headache conditions.
The Erwin test is a 3-item screening questionnaire assessing pain intensity, attack duration and the presence of autonomic symptoms. It has been described as an easy-to-use tool that could facilitate earlier diagnosis. An interactive version of the Erwin test is available online.