Cluster headache
Cluster headache | |
---|---|
civamide,[4] | |
Treatment | Oxygen therapy, triptans[2][4] |
Frequency | ~0.1% at some point in time[5] |
Cluster headache (CH) is a neurological disorder characterized by recurrent severe headaches on one side of the head, typically around the eye(s).[1] There is often accompanying eye watering, nasal congestion, or swelling around the eye on the affected side.[1] These symptoms typically last 15 minutes to 3 hours.[2] Attacks often occur in clusters which typically last for weeks or months and occasionally more than a year.[2]
The cause is unknown,
Recommended management includes
The condition affects about 0.1% of the general population at some point in their life and 0.05% in any given year.[5] The condition usually first occurs between 20 and 40 years of age.[2] Men are affected about four times more often than women.[5] Cluster headaches are named for the occurrence of groups of headache attacks (clusters).[1] They have also been referred to as "suicide headaches".[2]
Signs and symptoms
Cluster headaches are recurring bouts of severe unilateral headache attacks.[8][9] The duration of a typical CH attack ranges from about 15 to 180 minutes.[2] About 75% of untreated attacks last less than 60 minutes.[10] However, women may have longer and more severe CH.[11]
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 CH, or these symptoms may linger after an attack has passed, or between attacks.[12] Though CH is strictly unilateral, there are some documented cases of "side-shift" between cluster periods,[13] or, rarely, simultaneous (within the same cluster period) bilateral cluster headaches.[14]
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.[15] While suicide is rare, those with cluster headaches may experience suicidal thoughts (giving the alternative name "suicide headache" or "suicidal headache").[16][17] The term "headache" does not adequately convey the severity of the condition; the disease may be the most painful condition known to medical science.[18][19]
Dr. Peter Goadsby, Professor of Clinical Neurology at University College London, a leading researcher on the condition has commented:
"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."[20]
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.
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.[16]
People with CH 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
Cluster headaches have been recently associated with obstructive sleep apnea comorbidity.[24]
Recurrence
Cluster headaches may occasionally be referred to as "alarm clock headache" because of the regularity of their recurrence. CH attacks often awaken individuals from sleep. Both individual attacks and the cluster grouping can have a metronomic regularity; attacks typically striking at a precise time of day each morning or night. The recurrence of headache cluster grouping may occur more often around
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.[21] Chronic CH both occurs and recurs 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.[28]
Causes
Positron emission tomography (PET) shows brain areas being activated during pain. | ||
Voxel-based morphometry (VBM) shows brain area structural differences. |
The specific causes and pathogenesis of cluster headaches are not fully understood.[6] The Third Edition of the International Classification of Headache disorders classifies CH as belonging to the trigeminal autonomic cephalalgias.[29]
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.[6]
Nerves
Therapies acting on the vagus nerve (CN 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.[6] Two nerves thought to play an important role in CH include the trigeminal nerve and the facial nerve.[30]
Genetics
Cluster headache may run in some families in an
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.[31]
Tobacco smoking
About 65% of persons with CH are, or have been, tobacco smokers.[1] Stopping smoking does not lead to improvement of the condition and CH also occurs in those who have never smoked (e.g. children);[1] it is thought unlikely that smoking is a cause.[1] People with CH may be predisposed to certain traits, including smoking or other lifestyle habits.[34]
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 CH occurs with diurnal and seasonal rhythmicity.[35]
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 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.[36]
Diagnosis
Cluster-like head pain may be diagnosed as secondary headache rather than cluster headache.[21]
A detailed oral history aids practitioners in 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 are a necessary tool for initial and correct differential diagnosis in headache conditions.[37]
Correct diagnosis presents a challenge as the first CH attack may present where staff are not trained in the diagnosis of rare or complex chronic disease.
Individuals with CH typically experience
Differential
Cluster headache may be misdiagnosed as migraine or sinusitis.[41] Other types of headache are sometimes mistaken for, or may mimic closely, CH. Incorrect terms like "cluster migraine" confuse headache types, confound differential diagnosis and are often the cause of unnecessary diagnostic delay,[42] ultimately delaying appropriate specialist treatment.
Headaches that may be confused with CH include:
- Hemicrania continua[45]
- Trigeminal neuralgia is a unilateral headache syndrome,[40] or "cluster-like" headache.[47]
Prevention
Management for cluster headache is divided into three primary categories: abortive, transitional, and preventive.[48] Preventive treatments are used to reduce or eliminate cluster headache attacks; they are generally used in combination with abortive and transitional techniques.[8]
Verapamil
The recommended first-line preventive therapy is verapamil, a calcium channel blocker.[2][49] Verapamil was previously underused in people with cluster headache.[8] Improvement can be seen in an average of 1.7 weeks for episodic CH and 5 weeks for chronic CH when using a dosage of ranged between 160 and 720 mg (mean 240 mg/day).[50] 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.[50]
Glucocorticoids
Since these compounds are steroids, there is little evidence to support long-term benefits from glucocorticoids,[2] but they may be used until other medications take effect as they appear to be effective at three days.[2] They are generally discontinued after 8–10 days of treatment.[8] 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.[51]
Surgery
Nerve stimulators may be an option in the small number of people who do not improve with medications.[52][53] Two procedures, deep brain stimulation or occipital nerve stimulation, may be useful;[2] early experience shows a benefit in about 60% of cases.[54] It typically takes weeks or months for this benefit to appear.[53] A non-invasive method using transcutaneous electrical nerve stimulation (TENS) is being studied.[53]
A number of surgical procedures, such as a rhizotomy or microvascular decompression, may also be considered,[53] but evidence to support them is limited and there are cases of people whose symptoms worsen after these procedures.[53]
Other
Lithium, methysergide, and topiramate are recommended alternative treatments,[49][55] although there is little evidence supporting the use of topiramate or methysergide.[2][56] This is also true for tianeptine, melatonin, and ergotamine.[2] Valproate, sumatriptan, and oxygen are not recommended as preventive measures.[2] Botulinum toxin injections have shown limited success.[57] Evidence for baclofen, botulinum toxin, and capsaicin is unclear.[56]
Management
There are two primary treatments for acute CH:
Oxygen
Oxygen therapy may help to abort attacks, though it does not prevent future episodes.[2] Typically it is given via a non-rebreather mask at 12–15 liters per minute for 15–20 minutes.[2] One review found about 70% of patients improve within 15 minutes.[10] The evidence for effectiveness of 100% oxygen, however, is weak.[10][58] Hyperbaric oxygen at pressures of ~2 times greater than atmospheric pressure may relieve cluster headaches.[58]
Triptans
The other primarily recommended treatment of acute attacks is subcutaneous or intranasal
Opioids
The use of opioid medication in management of CH is not recommended[61] and may make headache syndromes worse.[62][63] Long-term opioid use is associated with well known dependency, addiction, and withdrawal syndromes.[64] Prescription of opioid medication may additionally lead to further delay in differential diagnosis, undertreatment, and mismanagement.[61]
Other
Intranasal lidocaine (sprayed in the ipsilateral nostril) may be an effective treatment with patient resistant to more conventional treatment.[11]
Octreotide administered subcutaneously has been demonstrated to be more effective than placebo for the treatment of acute attacks.[65]
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.[66]
Epidemiology
Cluster headache affects about 0.1% of the general population at some point in their life.[5] Males are affected about four times more often than females.[5] The condition usually starts between the ages of 20 and 50 years, although it can occur at any age.[1] About one in five of adults reports the onset of cluster headache between 10 and 19 years.[67]
History
The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia.[68][69][70] Descriptions of CH date to 1745 and probably earlier.[71]
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:
"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."[72]
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.[73]
Society and culture
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.[74]
Research directions
Some case reports suggest that ingesting tryptamines such as LSD, psilocybin (as found in hallucinogenic mushrooms), or DMT can abort attacks and interrupt cluster headache cycles.[75][76] 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.[51] 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".[75] The safety and efficacy of psilocybin is currently being studied in cluster headache.[77][78]
Fremanezumab, a humanized monoclonal antibody directed against calcitonin gene-related peptides alpha and beta, was in phase 3 clinical trials for CH, but stopped early due to a futility analysis demonstrating that a successful outcome was unlikely.[79][80]
References
- ^ S2CID 5479248.
- ^ from the original on 30 December 2019. Retrieved 24 July 2017.
- PMID 28939471.
- ^ PMID 27432623.
- ^ S2CID 2471915.
- ^ ISBN 978-1264268504.
- PMID 21912573.
- ^ from the original on 13 November 2015.
- S2CID 260319925.
- ^ PMID 19218020.
- ^ PMID 30242519.
- S2CID 153838.
- PMID 19495933.
- S2CID 46463344.
- ISBN 978-1-118-20995-0. Archivedfrom the original on 14 February 2017.
- ^ S2CID 35296409.
- ISBN 9781451148121. Archivedfrom the original on 10 September 2017.
- S2CID 19601387.
- S2CID 43918900.
- ^ Goadsby P, Mitchell N (1999). "Cluster Headaches". Australian Broadcasting Corporation. Archived from the original on 22 September 2011.
- ^ a b c d e f "IHS Classification ICHD-3 3.1.2 Cluster headache". The International Headache Society. Archived from the original on 8 February 2024. Retrieved 8 February 2024.
- S2CID 23184973.
- S2CID 38485245.
- ^ Tabaee D., Payam; Rizzoli, P; Pecis, M (2020). "Right-to-left shunt and obstructive sleep apnea in cluster headache". Neurology & Neurosc. 1 (1): 1–3. Archived from the original on 24 October 2020. Retrieved 22 January 2021.
- PMID 11858532.
- S2CID 6029272.
- ^ "Cluster headaches:Pattern of attacks". NHS. Gov.UK. 22 May 2017. Archived from the original on 20 June 2019. Retrieved 13 December 2018.
- S2CID 37173661.
- (PDF) from the original on 9 February 2020. Retrieved 16 August 2019.
- S2CID 91190597.
- ^ PMID 32310255.
- ^ PMID 16362673.
- ^ PMID 32334514.
- S2CID 29434840.
- PMID 11858532.
- S2CID 35178080.
- ^ "Headache diary: helping you manage your headache" (PDF). NPS.org.au. Archived from the original (PDF) on 21 September 2013. Retrieved 2 January 2014.
- PMID 16024902.
- S2CID 22500766.
- ^ PMID 19402567.
- ^ S2CID 22522914.
- S2CID 40116437.
- S2CID 5938778.
- PMID 20626997.
- S2CID 5938778.
- PMID 28939471.
- PMID 26516482.
- ISBN 9781461451648. Archivedfrom the original on 10 September 2017.
- ^ PMID 16987158.
- ^ S2CID 198193843.
- ^ OCLC 1259297708. Archivedfrom the original on 28 November 2022. Retrieved 19 September 2022.
- PMID 21422783.
- ^ PMID 24144382.
- S2CID 2063863.
- S2CID 40081324.
- ^ PMID 21718584.
- S2CID 10284630.
- ^ PMID 26709672.
- ^ "Cluster headache". MedlinePlus Medical Encyclopedia. 2 November 2012. Archived from the original on 5 April 2014. Retrieved 5 April 2014.
- ^ PMID 20393964.
- ^ S2CID 28752169.
- S2CID 5697283.
- PMID 19762094.
- S2CID 39617729.
- PMID 21718584.
- from the original on 30 October 2022. Retrieved 30 October 2022.
- ISBN 978-3-319-28628-0. Archivedfrom the original on 10 September 2017.
- ^ Harris W.: Neuritis and Neuralgia. p. 307-12. Oxford: Oxford University Press 1926.
- PMID 13655672.
- S2CID 25747361.
- PMID 17940171.
- ^ Horton BT, MacLean AR, Craig WM (1939). "A new syndrome of vascular headache: results of treatment with histamine: preliminary report". Mayo Clinic Proceedings. 14: 257.
- ^ Silberstein SD, Lipton RB, Goadsby PJ (2002). Headache in Clinical Practice (Second ed.). Taylor & Francis.[page needed]
- ^ Johnson, Tim (16 May 2013). "Researcher works to unlock mysteries of migraines". USA Today. Archived from the original on 17 May 2013. Retrieved 4 January 2013.
- ^ PMID 21352222.
- S2CID 16588263.
- PMID 31997136.
- ^ "Psilocybin for the Treatment of Cluster Headache - Full Text View - ClinicalTrials.gov". clinicaltrials.gov. Archived from the original on 27 May 2020. Retrieved 15 February 2020.
- ^ "A Study Comparing the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Chronic Cluster Headache (CCH)". ClinicalTrials.gov. 28 January 2021. Archived from the original on 3 May 2020. Retrieved 30 November 2017.
- ^ "A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH)". ClinicalTrials.gov. 2 July 2020. Archived from the original on 1 May 2020. Retrieved 30 November 2017.