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Cluster headache is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s).<ref name="Nesbitt2012" /> There is often accompanying eye watering, nasal congestion, or swelling around the eye on the affected side.<ref name="Nesbitt2012">Template:Cite journal</ref> These symptoms typically last 15 minutes to 3 hours.<ref name="AFP2013" /> Attacks often occur in clusters which typically last for weeks or months and occasionally more than a year.<ref name="AFP2013" /> The disease is considered among the most painful conditions known to medical science.<ref name="birth">Template:Cite journal</ref><ref>Template:Cite journal</ref>
The cause is unknown,<ref name="AFP2013" /> but is most likely related to dysfunction of the posterior hypothalamus.<ref name=":2">Template:Cite book</ref> Risk factors include a history of exposure to tobacco smoke and a family history of the condition.<ref name=AFP2013/> Exposures which may trigger attacks include alcohol, nitroglycerin, and histamine.<ref name=AFP2013/> They are a primary headache disorder of the trigeminal autonomic cephalalgias (TAC) type.<ref name=AFP2013/> Diagnosis is based on symptoms.<ref name=AFP2013/>
Recommended management includes lifestyle adaptations such as avoiding potential triggers.<ref name=AFP2013/> Treatments for acute attacks include oxygen or a fast-acting triptan.<ref name=AFP2013>Template:Cite journal</ref><ref name=Rob2016>Template:Cite journal</ref> Measures recommended to decrease the frequency of attacks include steroid injections, galcanezumab, civamide, verapamil, or oral glucocorticoids such as prednisone.<ref name=":2" /><ref name=Rob2016/><ref name=Gaul11>Template:Cite journal</ref> Nerve stimulation or surgery may occasionally be used if other measures are not effective.<ref name=AFP2013/><ref name=":2" />
The condition affects about 0.1% of the general population at some point in their life and 0.05% in any given year.<ref name=Fis2008/> The condition usually first occurs between 20 and 40 years of age.<ref name=AFP2013/> Men are affected about four times more often than women.<ref name=Fis2008>Template:Cite journal</ref> Cluster headaches are named for the occurrence of groups of headache attacks (clusters).<ref name=Nesbitt2012/> They have also been referred to as "suicide headaches".<ref name=AFP2013/>
Signs and symptomsEdit
Cluster headaches are recurring bouts of severe unilateral headache attacks.<ref name=Beck>Template:Cite journal</ref><ref name="pmid16628535">Template:Cite journal</ref> The duration of a typical cluster headache ranges from about 15 to 180 minutes.<ref name=AFP2013/> About 75% of untreated attacks last less than 60 minutes.<ref name=EM2009>Template:Cite journal</ref> However, women may have longer and more severe cluster headaches.<ref name=CHandM2019>Template:Cite journal</ref>
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.<ref>Template:Cite journal</ref> Though cluster headaches are strictly unilateral, there are some documented cases of "side-shift" between cluster periods,<ref>Template:Cite journal</ref> or, rarely, simultaneous (within the same cluster period) bilateral cluster headaches.<ref>Template:Cite journal</ref>
PainEdit
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.<ref name="MehtaMaloney2011">Template:Cite book</ref> While suicide is rare, those with cluster headaches may experience suicidal thoughts (giving the alternative name "suicide headache" or "suicidal headache").<ref name=Rob2013/><ref>Template:Cite book</ref>
Dr. Peter Goadsby, Professor of Clinical Neurology at University College London, a leading researcher on the condition has commented: <templatestyles src="Template:Blockquote/styles.css" />
"Cluster headache is probably the worst pain that humans experience. I know that's quite a strong remark to make, but if you ask a cluster headache patient if they've had a worse experience, they'll universally say they haven't. Women with cluster headache will tell you that an attack is worse than giving birth. So you can imagine that these people give birth without anesthetic once or twice a day, for six, eight, or ten weeks at a time, and then have a break. It's just awful."<ref>{{#invoke:citation/CS1|citation
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Other symptomsEdit
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.<ref name=AFP2013/><ref name=IHS/> 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.<ref name=IHS/> 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.<ref name=Beck/>
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.<ref name="Rob2013"/>
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,<ref name="Rob2013"/> serious depressive disorders,<ref>Template:Cite journal</ref> social withdrawal and isolation.<ref>Template:Cite journal</ref>
Cluster headaches have been recently associated with obstructive sleep apnea comorbidity.<ref>Template:Cite journal</ref>
RecurrenceEdit
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.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> 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.<ref name="NHS">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
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.<ref name=IHS>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> 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.<ref>Template:Cite journal</ref>
CausesEdit
| 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.<ref name=":2" /> The Third Edition of the International Classification of Headache disorders classifies cluster headaches as belonging to the trigeminal autonomic cephalalgias.<ref>Template:Cite journal</ref>
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.<ref name=":2" />
NervesEdit
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.<ref name=":2" /> Two nerves thought to play an important role in cluster headaches include the trigeminal nerve and the facial nerve.<ref name="image">Template:Cite journal</ref>
GeneticsEdit
Cluster headache may run in some families in an autosomal dominant inheritance pattern.<ref name="updateongenetics">Template:Cite journal</ref><ref name="Pinessi2005">Template:Cite journal</ref> People with a first degree relative with the condition are about 14–48 times more likely to develop it themselves,<ref name=Nesbitt2012 /> and around 8 to 10% of persons with cluster headaches have a family history.<ref name="updateongenetics" /><ref name=":0">Template:Cite journal</ref> Several studies have found a higher number of relatives affected among females.<ref name=":0" /> Others have suggested these observations may be due to lower numbers of females in these studies.<ref name=":0" /> Possible genetic factors warrant further research, current evidence for genetic inheritance is limited.<ref name=Pinessi2005 />
Genes that are thought to play a role in the disease are the hypocretin/orexin receptor type 2 (HCRTR2), alcohol dehydrogenase 4(ADH4), G protein beta 3 (GNB3), pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1), and membrane metalloendopeptidase (MME) genes.<ref name="updateongenetics" />
Tobacco smokingEdit
About 65% of persons with cluster headache are, or have been, tobacco smokers.<ref name=Nesbitt2012 /> Stopping smoking does not lead to improvement of the condition, and cluster headaches also occur in those who have never smoked (e.g., children);<ref name=Nesbitt2012 /> it is thought unlikely that smoking is a cause.<ref name=Nesbitt2012 /> People with cluster headaches may be predisposed to certain traits, including smoking or other lifestyle habits.<ref name="pmid18474191">Template:Cite journal</ref>
HypothalamusEdit
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.<ref>Template:Cite journal</ref>
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.<ref>Template:Cite journal</ref>
DiagnosisEdit
Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache.<ref name=IHS/>
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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Correct diagnosis presents a challenge as the first cluster headache attack may present where staff are not trained in the diagnosis of rare or complex chronic disease.<ref name="EM2009"/> Experienced ER staff are sometimes trained to detect headache types.<ref>Template:Cite journal</ref> While cluster headache attacks themselves are not directly life-threatening, suicide ideation has been observed.<ref name=Rob2013>Template:Cite journal</ref>
Individuals with cluster headaches typically experience diagnostic delay before correct diagnosis.<ref>Template:Cite journal</ref> 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.<ref name=Flanders>Template:Cite journal</ref> Under-recognition of cluster headaches by health care professionals is reflected in consistent findings in Europe and the United States that the average time to diagnosis is around seven years.<ref name=Tfelt-Hansen2012 />
DifferentialEdit
Cluster headache may be misdiagnosed as migraine or sinusitis.<ref name=Tfelt-Hansen2012>Template:Cite journal</ref> Other types of headache are sometimes mistaken for, or may mimic closely, cluster headaches. Incorrect terms like "cluster migraine" confuse headache types, confound differential diagnosis and are often the cause of unnecessary diagnostic delay,<ref>Template:Cite journal</ref> ultimately delaying appropriate specialist treatment.
Other types of headaches that may be confused with cluster headache include:
- Chronic paroxysmal hemicrania is a unilateral headache condition, without the male predominance usually seen in cluster headaches. Paroxysmal hemicrania may also be episodic but the episodes of pain seen in chronic paroxysmal hemicrania are usually shorter than those seen with cluster headaches. Chronic paroxysmal hemicrania typically responds "absolutely" to treatment with the anti-inflammatory drug indomethacin<ref name=IHS/> where in most cases cluster headaches typically show no indomethacin response, making "indomethacin response" an important diagnostic tool for specialist practitioners seeking correct differential diagnosis between the conditions.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
- Hemicrania continua<ref name="newdifferital">Template:Cite journal</ref>
- Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a headache syndrome belonging to the group of TACs.<ref name=IHS/><ref name="Rizzoli2017">Template:Cite journal</ref>
- Trigeminal neuralgia is a unilateral headache syndrome,<ref name=Flanders/> or "cluster-like" headache.<ref>Template:Cite journal</ref>
PreventionEdit
Management for cluster headache is divided into three primary categories: abortive, transitional, and preventive.<ref name=Nal2012>Template:Cite book</ref> Preventive treatments are used to reduce or eliminate cluster headache attacks; they are generally used in combination with abortive and transitional techniques.<ref name=Beck />
VerapamilEdit
The recommended first-line preventive therapy is verapamil, a calcium channel blocker.<ref name=AFP2013/><ref name=EFNS>Template:Cite journal</ref> Verapamil was previously underused in people with cluster headache.<ref name=Beck/> Improvement can be seen in an average of 1.7 weeks for episodic cluster headache and 5 weeks for chronic cluster headache when using a dosage of ranged between 160 and 720 mg (mean 240 mg/day).<ref name="vera">Template:Cite journal</ref> Preventive therapy with verapamil is believed to work because it has an effect on the circadian rhythm and on CGRPs as CGRP-release is controlled by voltage-gated calcium channels.<ref name="vera"/>
GlucocorticoidsEdit
Since these compounds are steroids, there is little evidence to support long-term benefits from glucocorticoids,<ref name=AFP2013/> but they may be used until other medications take effect as they appear to be effective at three days.<ref name=AFP2013/> They are generally discontinued after 8–10 days of treatment.<ref name=Beck/> Prednisone is given at a starting dose of 60–80 milligrams daily; then it is reduced by 5 milligrams every day. Corticosteroids are also used to break cycles, especially in chronic patients.<ref name=":1">Template:Cite book</ref>
SurgeryEdit
Nerve stimulators may be an option in the small number of people who do not improve with medications.<ref>Template:Cite book</ref><ref name=EU2013>Template:Cite journal</ref> Two procedures, deep brain stimulation or occipital nerve stimulation, may be useful;<ref name=AFP2013/> early experience shows a benefit in about 60% of cases.<ref>Template:Cite journal</ref> It typically takes weeks or months for this benefit to appear.<ref name=EU2013/> A non-invasive method using transcutaneous electrical nerve stimulation (TENS) is being studied.<ref name=EU2013/>
A number of surgical procedures, such as a rhizotomy or microvascular decompression, may also be considered,<ref name=EU2013/> but evidence to support them is limited and there are cases of people whose symptoms worsen after these procedures.<ref name=EU2013/>
OtherEdit
Lithium, methysergide, and topiramate are recommended alternative treatments,<ref name=EFNS/><ref>Template:Cite journal</ref> although there is little evidence supporting the use of topiramate or methysergide.<ref name=AFP2013/><ref name=CE2010>Template:Cite journal</ref> This is also true for tianeptine, melatonin, and ergotamine.<ref name=AFP2013/> Valproate, sumatriptan, and oxygen are not recommended as preventive measures.<ref name=AFP2013/> Botulinum toxin injections have shown limited success.<ref>Template:Cite journal</ref> Evidence for baclofen, botulinum toxin, and capsaicin is unclear.<ref name=CE2010/>
ManagementEdit
There are two primary treatments for acute CH: oxygen and triptans,<ref name=AFP2013/> but they are underused due to misdiagnosis of the syndrome.<ref name=Beck/> During bouts of headaches, triggers such as alcohol, nitroglycerine, and naps during the day should be avoided.<ref name=EM2009/>
OxygenEdit
Oxygen therapy may help to abort attacks, though it does not prevent future episodes.<ref name=AFP2013 /> Typically it is given via a non-rebreather mask at 12–15 liters per minute for 15–20 minutes.<ref name=AFP2013 /> One review found about 70% of patients improve within 15 minutes.<ref name=EM2009 /> The evidence for effectiveness of 100% oxygen, however, is weak.<ref name="EM2009"/><ref name=pmid26709672>Template:Cite book</ref> Hyperbaric oxygen at pressures of ~2 times greater than atmospheric pressure may relieve cluster headaches.<ref name=pmid26709672/>
TriptansEdit
The other primarily recommended treatment of acute attacks is subcutaneous or intranasal sumatriptan.<ref name=EFNS/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack with sumatriptan being superior.<ref name=Law2013>Template:Cite book</ref> Because of the vasoconstrictive side-effect of triptans, they may be contraindicated in people with ischemic heart disease.<ref name=AFP2013/> The vasoconstrictor ergot compounds may be useful,<ref name=EM2009/> but have not been well studied in acute attacks.<ref name=Law2013/>
OpioidsEdit
The use of opioid medication in management of cluster headache is not recommended<ref name=Pae2008/> and may make headache syndromes worse.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Long-term opioid use is associated with well known dependency, addiction, and withdrawal syndromes.<ref>Template:Cite journal</ref> Prescription of opioid medication may additionally lead to further delay in differential diagnosis, undertreatment, and mismanagement.<ref name=Pae2008>Template:Cite journal</ref>
OtherEdit
Intranasal lidocaine (sprayed in the ipsilateral nostril) may be an effective treatment with patient resistant to more conventional treatment.<ref name=CHandM2019/>
Octreotide administered subcutaneously has been demonstrated to be more effective than placebo for the treatment of acute attacks.<ref>Template:Cite journal</ref>
Sub-occipital steroid injections have shown benefit and are recommended for use as a transitional therapy to provide temporary headache relief as more long term prophylactic therapies are instituted.<ref>Template:Cite journal</ref>
EpidemiologyEdit
Cluster headache affects about 0.1% of the general population at some point in their life.<ref name=Fis2008/> Males are affected about four times more often than females.<ref name=Fis2008/> The condition usually starts between the ages of 20 and 50 years, although it can occur at any age.<ref name=Nesbitt2012 /> About one in five affected adults report the onset of cluster headache between 10 and 19 years of age.<ref name="Abu-Arafeh2016">Template:Cite book</ref>
HistoryEdit
The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia.<ref>Harris W.: Neuritis and Neuralgia. p. 307-12. Oxford: Oxford University Press 1926.</ref><ref>Template:Cite journal</ref><ref>Template:Cite journal</ref> Descriptions of cluster headache date to 1745 and probably earlier.<ref>Template:Cite journal</ref>
The condition was originally named Horton's cephalalgia after Bayard Taylor 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 die by suicide; his 1939 paper said:<templatestyles src="Template:Blockquote/styles.css" />
"Our patients were disabled by the disorder and suffered from bouts of pain from two to twenty times a week. They had found no relief from the usual methods of treatment. Their pain was so severe that several of them had to be constantly watched for fear of suicide. Most of them were willing to submit to any operation which might bring relief."<ref>Template:Cite journal</ref>{{#if:|{{#if:|}}
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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, Sluder's syndrome, and hemicrania angioparalyticia.<ref>Template:Cite bookTemplate:Page needed</ref>
Society and cultureEdit
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 cluster headache research in 25 years.<ref name=Unlocking>Template:Cite news</ref>
Research directionsEdit
Some case reports suggest that ingesting lysergamides such as LSD, tryptamines such as psilocybin (as found in hallucinogenic mushrooms), or DMT can abort attacks and interrupt cluster headache cycles.<ref name=Sun2011>Template:Cite journal</ref><ref name=Vollenweider2010>Template:Cite journal</ref> The hallucinogen DMT has a chemical structure that is similar to the triptan sumatriptan, indicating a possible shared mechanism in preventing or stopping migraine and TACs.<ref name=":1" /> In a 2006 survey of 53 individuals, 18 of 19 psilocybin users reported extended remission periods. The survey was not a blinded or a controlled study, and was "limited by recall and selection bias".<ref name=Sun2011/> The safety and efficacy of psilocybin is currently being studied in cluster headache, with the extension phase of one randomized controlled trial demonstrating reduced cluster attack burden after a 3-dose pulse of psilocybin.<ref>Template:Cite journal</ref><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite journal</ref> In Canada, a first cluster headache patient gained access to psychedelic-assisted therapy via Canada’s special access scheme for psilocybin.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>
Fremanezumab, a humanized monoclonal antibody directed against calcitonin gene-related peptides alpha and beta, was in phase 3 clinical trials for cluster headaches, but the studies were stopped early due to a futility analysis demonstrating that a successful outcome was unlikely.<ref>Template:Cite journal</ref><ref>Template:Cite journal</ref>
ReferencesEdit
External linksEdit
- Clusterbusters patient support and advocacy
- Organisation for the Prevention of Intense Suffering (OPIS) resource page on cluster headachesTemplate:Medical resources