Cluster headache

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Cluster headache
Classification and external resources
ICD-10 G44.0
ICD-9 339.00,339.01,339.02,
DiseasesDB 2850
MedlinePlus 000786
eMedicine EMERG/229 article/1142459
Patient UK Cluster headache
MeSH D003027

Cluster headache (CH) is a neurological disorder characterized by recurrent, severe headaches on one side of the head, typically around the eye.[1] There are often accompanying autonomic symptoms during the headache such as eye watering, nasal congestion and swelling around the eye, typically confined to the side of the head with the pain.[1]

Cluster headache belongs to a group of primary headache disorders, classified as the trigeminal autonomic cephalalgias or (TACs). Cluster Headache is named after the demonstrated grouping of headache attacks occurring together (cluster).[1] Individuals typically experience repeated attacks of excruciatingly severe unilateral headache pain.[2] Cluster Headache attacks often occur periodically; spontaneous remissions may interrupt active periods of pain, though about 10–15% of chronic CH never remit.[2] The cause of Cluster Headache has not been identified.

While there is no known cure, cluster headaches can sometimes be prevented and acute attacks treated. Recommended treatments for acute attacks include oxygen or a fast acting triptan.[3] Primary recommended prevention is verapamil. Steroids may be used as a transitional treatment and may prevent attack recurrence until preventative treatments take effect. The condition affects approximately 0.2% of the general population,[4] and men are more commonly affected than women, by a ratio of about 2.5:1 to 3.5:1.[1]

Signs and symptoms[edit]

Cluster headaches are recurring bouts of excruciating unilateral headache attacks[5] of extreme intensity.[6] The duration of a typical CH attack ranges from about 15 to 180 minutes.[3] Most untreated attacks (about 75%) last less than 60 minutes.[7]

The onset of an attack is rapid and most often without preliminary signs that are characteristic in migraine. Preliminary sensations of pain in the general area of attack, referred to as "shadows", may signal an imminent CH, or these symptoms may linger after an attack has passed, or even between attacks.[8] Though a CH is strictly unilateral, there are some documented cases of "side-shift" between cluster periods, extremely rare, simultaneously (within the same cluster period) bilateral headache.[9]


The pain occurs only on one side of the head (unilateral), around the eye (orbital), particularly above the eye (supraorbital), in the temple (temporal), or in any combination. The pain of CH is remarkably greater than in other headache conditions, including severe migraine. The term "headache" does not adequately convey the severity of the condition; the disease may be the most painful condition known to medical science.[10] The pain is described as burning, stabbing, boring or squeezing and may be located near or behind the eye.[11] Those with cluster headaches may experience suicidal thoughts during an attack as a result of the pain.[12][13]

Other symptoms[edit]

The typical symptoms of cluster headache are grouping (cluster) of recurring headache attacks of severe or very severe unilateral orbital, supraorbital and/or temporal pain. If left untreated, attack frequency will range from one attack every two days to eight attacks a day.[2][3] The 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, commonly but not always appearing on the same side of the head as the pain.[2]

Restlessness (for example, pacing or rocking back and forth), photosensitivity, aversion to light (photophobia) or sensitivity to noise (phonophobia) may occur during a CH. Nausea is a rare symptom, although it has been reported.[5] Secondary effects may include inability to organize thoughts and plans, physical exhaustion, confusion, agitation, aggressiveness, depression and anxiety.[14]



Cluster headaches are occasionally referred to as "alarm clock headaches" because of the regularity of their timing, CH attacks may awaken individuals from sleep. Both individual attacks and the cluster grouping can have a metronomic regularity; attacks striking at a precise time of day each morning or night is typical. The grouping of headache clusters can occur more often around solstices, or spring and autumn equinoxes, sometimes showing circannual periodicity. This has prompted researchers to speculate involvement, or dysfunction of the hypothalamus. The Hypothalamus controls the body's "biological clock" and circadian rhythm.[18][19] Conversely, attack frequency may be highly unpredictable, showing no periodicity at all.

In episodic cluster headaches, 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 chronic, with multiple headaches occurring every day for years, sometimes without any remission.[medical citation needed]

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 clusters may be classified as episodic. If attacks occur for more than a year without pain-free remission of at least one month, the condition is classified chronic.[2] Chronic CH occurs continuously without any remission periods between cycles; there may be high and low variation in cycles, meaning the frequency and severity of attacks may change without predictability, for a period of time. The amount of change 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.[20]


Voxel-based morphometry (VBM) shows brain area structural differences

The cause of cluster headache is unknown.[21]


Cluster headache may, but rarely, run in some families in an autosomal dominant inheritance pattern.[21] People with a first degree relative with the condition are about 14-48 times more likely to develop it themselves,[1] and between 1.9 and 20% of persons with CH have a positive family history.[21] This suggests that genetic factors are important, but the type and number of genes involved is unclear.[21]




One theory is that the cause is dysfunction of the hypothalamus, which may explain why cluster headaches frequently strike around the same time each day, and during a particular season.[medical citation needed] One of the functions of the hypothalamus is regulation of the biological clock. Metabolic abnormalities have also been reported.[medical citation needed] The positron emission tomography (PET) scans indicate the brain areas which are activated during pain of attack only, compared to pain free periods. These pictures show brain areas which are active during pain in yellow/orange color (called "pain matrix"). The area in the center (in all three views) is specifically activated during CH only. The bottom row voxel-based morphometry (VBM) shows structural brain differences between individuals with and without CH; only a portion of the hypothalamus is different.[23]


Cluster headache has been historically classified as vascular headaches; for decades, it has been proposed that intense pain was caused by dilation of blood vessels which was thought to create pressure on the trigeminal nerve. While this theory was thought to be the immediate cause of the pain, the etiology (underlying cause or causes) is not fully understood and CH pathogenesis is the subject of ongoing debate.[24] Investigations into the vascular theory of headache disorders are helping to identify the role of other possible causative mechanisms in CH.[25]


Cluster headaches are often misdiagnosed, mismanaged, or undiagnosed for many years; they may be confused with migraine, "cluster-like" headache (or mimics), CH subtypes, other TACs, or other types of primary or secondary headache syndrome.[26] Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache.[2]

A detailed oral history aids correct differential diagnosis, as there are no confirmatory tests for CH. 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 is a necessary tool for initial and correct differential diagnosis in headache conditions.[27]

Correct diagnosis of CH is a challenge for practitioners, and is especially problematic in hospital emergency departments, where staff are not trained in the diagnosis of rare or complex chronic disease.[28] Although experienced ER staff are sometimes trained to detect headache types,[29] CH attacks themselves are not life-threatening.[30]

Individuals with CH typically experience a lengthy delay before correct diagnosis.[26][31] People are often misdiagnosed due to reported neck, tooth, jaw, and sinus symptoms and may unnecessarily endure many years of referral to ear, nose and throat (ENT) specialists for investigation of sinuses; dentists for tooth assessment; chiropractors and manipulative therapists for treatment; or psychiatrists, psychologists and other medical disciplines before their headaches are correctly diagnosed.[32] Often there is a delay of several years before the correct diagnosis is reached.[33] Medical students receive little training in differential diagnoses and management of headaches.[34]


Cluster headache may be misdiagnosed as migraine or sinusitis.[33] Other types of headache are sometimes mistaken for, or may mimic closely, CH. Incorrect terms like "cluster migraine" confuse headache types for both practitioner and patient, confound differential diagnosis and are often the cause of unnecessary diagnostic delay,[35] ultimately delaying appropriate specialist treatment.

Headaches that may be confused with CH include:




The recommended first-line preventative therapy is verapamil, a calcium channel blocker.[3][38] Verapamil was previously underused in people with cluster headache.[5]


There is little evidence to support a long-term benefit from steroids,[3] but they may be used until other medications take effect as they appear to be effective at three days.[3] They are generally discontinued after 8–10 days of treatment.[5]


Nerve simulators may be an option in the small number of people who do not improve with medications.[39][40] Two procedures, deep brain stimulation or occipital nerve stimulation, may be useful;[3] early experience shows a benefit in about 60% of cases.[41] It typically takes weeks or months for this benefit to appear.[40] A non-invasive method using transcutaneous electrical nerve stimulation (TENS) is being studied.[40]

A number of surgical procedures, such as a rhizotomy or microvascular decompression, may also be considered,[40] but evidence to support them is limited and there are cases of people ending up worse off.[40]


Lithium, methysergide, and topiramate are recommended alternative treatments,[38][42] although there is little evidence supporting the use of topiramate or methysergide.[3][43] This is also true for melatonin and ergotamine.[3] Valproate, sumatriptan and oxygen are not recommended as preventative measures.[3] Botox injection have shown mixed success.[44]


Treatment for cluster headache is divided into three primary categories: abortive, transitional, and preventative.[45] There are two primary treatments for acute CH: oxygen and triptans,[3] but they are underused due to misdiagnosis of the syndrome.[5] During bouts of headaches, triggers such as alcohol, nitroglycerine and naps during the day should be avoided.[7]


Oxygen therapy may help people with CH, but it does not help prevent future episodes.[3] Typically it is given via a non-rebreather mask at 12-15 liters per minute for 15–20 minutes.[3] Around 70% improve within 15 minutes.[7]


The other primarily recommended treatment of acute attacks is subcutaneous or intranasal sumatriptan.[38] Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack with sumatriptan being superior.[46] Because of the vasoconstrictive action of triptans, they are contraindicated in people with ischemic heart disease.[3]


The use of opioid medication in management of CH is not recommended;[47] they may make headache syndromes worse[48][49] and their long-term use is associated with dependency, addiction and withdrawal syndromes.[50] Prescription of opioid medication may additionally lead to a delay in diagnosis, undertreatment, and mismanagement. [47]


The vasoconstricting ergot compounds may be useful,[7] but have not been well studied in acute attacks.[46]


Cluster headache effects about 0.2% of the general population,[4] or 56 to 326 people per 100,000.[51] Males are affected more commonly than females, in a ratio of about 2.5:1 to 3.5:1.[1] The condition usually starts between the ages of 20 and 50 years, although it can occur at any age.[1]


The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia.[52][53][54] Descriptions of CH date to 1745 and probably earlier.[55]

The condition was originally named Horton's cephalalgia after B.T. Horton, a US neurologist who postulated the first theory as to their pathogenesis. His original paper describes the severity of the headaches as being able to take normal men and force them to attempt or complete suicide; his 1939 paper said:


CH has alternately been called erythroprosopalgia of Bing, ciliary neuralgia, erythromelalgia of the head, Horton's headache, histaminic cephalalgia, petrosal neuralgia, sphenopalatine neuralgia, vidian neuralgia, Sluder's neuralgia, and hemicrania angioparalyticia.[57]

Society and culture[edit]

Robert Shapiro, a professor of neurology, says that while cluster headaches are about as common as multiple sclerosis with a similar disability level, as of 2013, the US National Institutes of Health had spent $1.872 billion on research into multiple sclerosis in one decade, but less than $2 million on CH research in 25 years.[58] Due to an occasional association with suicidal thoughts, cluster headaches have been colloquially named "suicide headaches."[12]

Research directions[edit]

Some controversial case reports suggest that ingesting tryptamines such as LSD, psilocybin or DMT can reduce pain and interrupt cluster headache cycles.[59][60] A 2006 interview/survey of 53 individuals with CH said that psilocybin extended remission periods in 10% cases.[60] The survey was not a blinded or controlled study, and was "limited by recall and selection bias".[59]


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