cluster headache

Cluster headaches are recurring bouts of severe unilateral headache attacks.{{cite journal |vauthors=Beck E, Sieber WJ, Trejo R |title=Management of cluster headache |journal= American Family Physician|volume=71 |issue=4 |pages=717–24 |date=February 2005 |pmid=15742909 |url=http://www.aafp.org/afp/2005/0215/p717.html |type=Review |url-status=live |archive-url=https://web.archive.org/web/20151113055721/http://www.aafp.org/afp/2005/0215/p717.html |archive-date=13 November 2015 }}{{cite journal |doi=10.1055/s-2006-939925 |pmid=16628535 |title=Diagnosis and Treatment of Cluster Headache |journal=Seminars in Neurology |volume=26 |issue=2 |pages=242–59 |year=2006 |last1=Capobianco |first1=David |last2=Dodick |first2=David |s2cid=260319925 }} The duration of a typical cluster headache ranges from about 15 to 180 minutes. About 75% of untreated attacks last less than 60 minutes.{{cite journal |doi=10.1016/j.emc.2008.09.005 |pmid=19218020 |pmc=2676687 |title=Diagnosis and Management of the Primary Headache Disorders in the Emergency Department Setting |journal=Emergency Medicine Clinics of North America |volume=27 |issue=1 |pages=71–87, viii |year=2009 |last1=Friedman |first1=Benjamin Wolkin |last2=Grosberg |first2=Brian Mitchell }} However, women may have longer and more severe cluster headaches.{{cite journal |vauthors=Vollesen AL, Benemei S, Cortese F, Labastida-Ramírez A, Marchese F, Pellesi L, Romoli M, Ashina M, Lampl C, ((School of Advanced Studies of the European Headache Federation (EHF-SAS)))|title=Migraine and cluster headache - the common link. |date=2018 |journal= The Journal of Headache and Pain|volume=19 |issue=1 |page=89 |doi=10.1186/s10194-018-0909-4|pmid=30242519 |pmc=6755613 |doi-access=free }}

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.{{cite journal |doi=10.1177/0333102410372423 |pmid=20974600 |title=Interictal pain in cluster headache |journal=Cephalalgia |volume=30 |issue=12 |pages=1531–4 |year=2010 |last1=Marmura |first1=Michael J |last2=Pello |first2=Scott J |last3=Young |first3=William B |s2cid=153838 }} Though cluster headaches are strictly unilateral, there are some documented cases of "side-shift" between cluster periods,{{cite journal |doi=10.1007/s10194-009-0129-z |pmid=19495933 |pmc=3451747 |title=Lateralization in cluster headache: A Nordic multicenter study |journal=The Journal of Headache and Pain |volume=10 |issue=4 |pages=259–63 |year=2009 |last1=Meyer |first1=Eva Laudon |last2=Laurell |first2=Katarina |last3=Artto |first3=Ville |last4=Bendtsen |first4=Lars |last5=Linde |first5=Mattias |last6=Kallela |first6=Mikko |last7=Tronvik |first7=Erling |last8=Zwart |first8=John-Anker |last9=Jensen |first9=Rikke M. |last10=Hagen |first10=Knut }} or, rarely, simultaneous (within the same cluster period) bilateral cluster headaches.{{cite journal |pmid=11839832 |title=Cluster headache: A prospective clinical study with diagnostic implications |journal=Neurology |volume=58 |issue=3 |pages=354–61 |year=2002 |last1=Bahra |first1=A |last2=May |first2=A |last3=Goadsby |first3=PJ |doi=10.1212/wnl.58.3.354|s2cid=46463344 }}

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.{{cite book|author1=Noshir Mehta|author2=George E. Maloney|author3=Dhirendra S. Bana|author4=Steven J. Scrivani|title=Head, Face, and Neck Pain Science, Evaluation, and Management: An Interdisciplinary Approach|url=https://books.google.com/books?id=hgzeUKoeaTcC&pg=PT199|date=20 September 2011|publisher=John Wiley & Sons|isbn=978-1-118-20995-0|page=199|url-status=live|archive-url=https://web.archive.org/web/20170214214959/https://books.google.com/books?id=hgzeUKoeaTcC&pg=PT199|archive-date=14 February 2017}} While suicide is rare, those with cluster headaches may experience suicidal thoughts (giving the alternative name "suicide headache" or "suicidal headache").{{cite book|title=The 5-Minute Sports Medicine Consult|date=2012|publisher=Lippincott Williams & Wilkins|isbn=9781451148121|page=87|edition=2|url=https://books.google.com/books?id=-LOm9enAxQ8C&pg=PA87|url-status=live|archive-url=https://web.archive.org/web/20170910172156/https://books.google.com/books?id=-LOm9enAxQ8C&pg=PA87|archive-date=10 September 2017}}

Dr. Peter Goadsby, Professor of Clinical Neurology at University College London, a leading researcher on the condition has commented: {{blockquote|"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."{{cite web|author=Goadsby P, Mitchell N|year=1999|title=Cluster Headaches|publisher=Australian Broadcasting Corporation |url=https://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s42434.htm |url-status= dead|archive-url=https://web.archive.org/web/20110922070249/https://www.abc.net.au/rn/talks/8.30/helthrpt/stories/s42434.htm|archive-date=22 September 2011}}}}

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,{{cite journal |doi=10.1177/0333102412469738 |pmid=23212294 |title=Cluster headache is associated with an increased risk of depression: A nationwide population-based cohort study |journal=Cephalalgia |volume=33 |issue=3 |pages=182–9 |year=2012 |last1=Liang |first1=Jen-Feng |last2=Chen |first2=Yung-Tai |last3=Fuh |first3=Jong-Ling |last4=Li |first4=Szu-Yuan |last5=Liu |first5=Chia-Jen |last6=Chen |first6=Tzeng-Ji |last7=Tang |first7=Chao-Hsiun |last8=Wang |first8=Shuu-Jiun |s2cid=23184973 |doi-access=free }} social withdrawal and isolation.{{cite journal |doi=10.1111/j.1468-2982.2007.01330.x |pmid=17459083 |title=Burden of Cluster Headache |journal=Cephalalgia |volume=27 |issue=6 |pages=535–41 |year=2016 |last1=Jensen |first1=RM |last2=Lyngberg |first2=A |last3=Jensen |first3=RH |s2cid=38485245 }}

Cluster headaches have been recently associated with obstructive sleep apnea comorbidity.{{cite journal |title=Right-to-left shunt and obstructive sleep apnea in cluster headache |journal=Neurology & Neurosc. |volume=1 |issue=1 |pages=1–3 |year=2020 |last1=Tabaee D. |first1=Payam |last2=Rizzoli |first2=P |last3=Pecis |first3=M |url=https://www.sciencexcel.com/articles/Right-to-left%20shunt%20and%20obstructive%20sleep%20apnea%20in%20cluster%20headache |access-date=22 January 2021 |archive-date=24 October 2020 |archive-url=https://web.archive.org/web/20201024174835/https://www.sciencexcel.com/articles/Right-to-left%20shunt%20and%20obstructive%20sleep%20apnea%20in%20cluster%20headache |url-status=live }}

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.{{cite journal |doi=10.1017/S0317167100001694 |pmid=11858532 |title=Cluster Headache: Evidence for a Disorder of Circadian Rhythm and Hypothalamic Function |journal=The Canadian Journal of Neurological Sciences |volume=29 |issue=1 |pages=33–40 |year=2014 |last1=Pringsheim |first1=Tamara |doi-access=free }}{{cite journal |doi=10.1046/j.1526-4610.2003.03055.x |pmid=12603650 |title=Clinical, Anatomical, and Physiologic Relationship Between Sleep and Headache |journal=Headache: The Journal of Head and Face Pain |volume=43 |issue=3 |pages=282–92 |year=2003 |last1=Dodick |first1=David W. |last2=Eross |first2=Eric J. |last3=Parish |first3=James M. |s2cid=6029272 }} 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.{{cite web |url=https://www.nhs.uk/conditions/cluster-headaches/ |title=Cluster headaches:Pattern of attacks |author= |date=22 May 2017 |website=NHS |publisher=Gov.UK |access-date=13 December 2018 |archive-date=20 June 2019 |archive-url=https://web.archive.org/web/20190620122856/https://www.nhs.uk/conditions/cluster-headaches/ |url-status=live }}

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.{{cite web |url= https://ichd-3.org/3-trigeminal-autonomic-cephalalgias/3-1-cluster-headache/3-1-2-chronic-cluster-headache/ |title= IHS Classification ICHD-3 3.1.2 Cluster headache |publisher= The International Headache Society |access-date= 2024-02-08 |archive-date= 8 February 2024 |archive-url= https://web.archive.org/web/20240208085008/https://ichd-3.org/3-trigeminal-autonomic-cephalalgias/3-1-cluster-headache/3-1-2-chronic-cluster-headache/ |url-status= live }}

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.{{cite journal |doi=10.1007/s11916-002-0026-5 |pmid=11749880 |title=What predicts evolution from episodic to chronic cluster headache? |journal=Current Pain and Headache Reports |volume=6 |issue=1 |pages=65–70 |year=2002 |last1=Torelli |first1=Paola |last2=Manzoni |first2=Gian Camillo |s2cid=37173661 }}

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.{{cite journal |author=Headache Classification Committee of the International Headache Society (IHS) |s2cid=78846027 |date=2013 |title=The International Classification of Headache Disorders, 3rd edition (beta version) |journal=Cephalalgia |volume=33 |issue=9 |pages=629–808 |doi=10.1177/0333102413485658 |pmid=23771276 |url=https://www.zora.uzh.ch/id/eprint/89115/1/89115.pdf |access-date=16 August 2019 |archive-date=9 February 2020 |archive-url=https://web.archive.org/web/20200209062132/https://www.zora.uzh.ch/id/eprint/89115/1/89115.pdf |url-status=live }}

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.

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.{{cite journal |vauthors =Ferraro S, Nigri A, Bruzzone MG, Demichelis G, Pinardi C, Brivio L, Giani L, Proietti A, Leone M, Chiapparini L| s2cid =91190597 | title =Cluster headache: insights from resting-state functional magnetic resonance imaging | journal = Neurological Sciences| date = 2019 | volume =40| issue =Suppl 1| pages =45–47| doi =10.1007/s10072-019-03874-8| pmid = 30941629}}

Cluster headache may run in some families in an autosomal dominant inheritance pattern.{{cite journal |vauthors=Waung MW, Taylor A, Qualmann KJ, Burish MJ| title = Family History of Cluster HeadacheA Systematic Review | journal = JAMA Neurology| date = 2020 | volume = 77 | issue = 7 | pages = 887–896 | doi = 10.1001/jamaneurol.2020.0682 | pmid = 32310255 | pmc = 7644512 }}{{cite journal |last1=Pinessi |first1=L. |last2=Rainero |first2=I. |last3=Rivoiro |first3=C. |last4=Rubino |first4=E. |last5=Gallone |first5=S. |year=2005 |title=Genetics of cluster headache: An update |journal=The Journal of Headache and Pain |volume=6 |issue=4 |pages=234–6 |doi=10.1007/s10194-005-0194-x |pmc=3452030 |pmid=16362673}} 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.{{Cite journal|last1=O'Connor|first1=Emer|last2=Simpson|first2=Benjamin S.|last3=Houlden|first3=Henry|last4=Vandrovcova|first4=Jana|last5=Matharu|first5=Manjit|date=2020-04-25|title=Prevalence of familial cluster headache: a systematic review and meta-analysis|journal=The Journal of Headache and Pain|volume=21|issue=1|pages=37|doi=10.1186/s10194-020-01101-w|issn=1129-2377|pmc=7183702|pmid=32334514 |doi-access=free }} 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), G protein beta 3 (GNB3), pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1), and membrane metalloendopeptidase (MME) genes.

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.{{cite journal |doi=10.1007/s11916-008-0022-5 |pmid=18474191 |title=Cluster headache and lifestyle habits |journal=Current Pain and Headache Reports |volume=12 |issue=2 |pages=115–21 |year=2008 |last1=Schürks |first1=Markus |last2=Diener |first2=Hans-Christoph |s2cid=29434840 }}

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.{{cite journal |last=Pringsheim |first=Tamara |title=Cluster headache: evidence for a disorder of circadian rhythm and hypothalamic function |journal=Canadian Journal of Neurological Sciences |date=February 2002 |volume=29 |issue=1 |pages=33–40 |doi=10.1017/S0317167100001694 |pmid=11858532|doi-access=free }}

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.{{cite journal |doi=10.1007/s11916-007-0010-1 |pmid=17367592 |title=Cluster headache: A review of neuroimaging findings |journal=Current Pain and Headache Reports |volume=11 |issue=2 |pages=131–6 |year=2007 |last1=Dasilva |first1=Alexandre F. M. |last2=Goadsby |first2=Peter J. |last3=Borsook |first3=David |s2cid=35178080 }}

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.{{cite web |url= http://www.nps.org.au/__data/assets/pdf_file/0010/160003/NPS_Headache_Diary_0612.pdf |title= Headache diary: helping you manage your headache |publisher= NPS.org.au |access-date= 2014-01-02 |url-status= dead |archive-url= https://web.archive.org/web/20130921054005/http://www.nps.org.au/__data/assets/pdf_file/0010/160003/NPS_Headache_Diary_0612.pdf |archive-date= 21 September 2013 }}

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. Experienced ER staff are sometimes trained to detect headache types.{{cite journal |doi=10.1136/jnnp.2004.057968 |pmid=16024902 |pmc=1739753 |title=Ability of a nurse specialist to diagnose simple headache disorders compared with consultant neurologists |journal=Journal of Neurology, Neurosurgery & Psychiatry |volume=76 |issue=8 |pages=1170–2 |year=2005 |last1=Clarke |first1=C E }} While cluster headache attacks themselves are not directly life-threatening, suicide ideation has been observed.{{cite journal |doi=10.1007/s11916-012-0313-8 |title=The Psychiatric Comorbidities of Cluster Headache |journal=Current Pain and Headache Reports |volume=17 |issue=2 |year=2013 |last1=Robbins |first1=Matthew S.|s2cid=35296409 |pmid=23296640 |page=313}}

Individuals with cluster headaches typically experience diagnostic delay before correct diagnosis.{{cite journal |doi=10.1046/j.1600-0404.2003.00237.x |pmid=14763953 |title=Diagnostic delays and mis-management in cluster headache |journal=Acta Neurologica Scandinavica |volume=109 |issue=3 |pages=175–9 |year=2004 |last1=Bahra |first1=A. |last2=Goadsby |first2=P. J. |s2cid=22500766 |doi-access=free }} 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.{{cite journal |pmid=19402567 |year=2009 |last1=Van Alboom |first1=E |title=Diagnostic and therapeutic trajectory of cluster headache patients in Flanders |journal=Acta Neurologica Belgica |volume=109 |issue=1 |pages=10–7 |last2=Louis |first2=P |last3=Van Zandijcke |first3=M |last4=Crevits |first4=L |last5=Vakaet |first5=A |last6=Paemeleire |first6=K }} 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.

Cluster headache may be misdiagnosed as migraine or sinusitis.{{cite journal |doi=10.2165/11632850-000000000-00000 |pmid=22650381 |title=Management of Cluster Headache |journal=CNS Drugs |volume=26 |issue=7 |pages=571–80 |year=2012 |last1=Tfelt-Hansen |first1=Peer C. |last2=Jensen |first2=Rigmor H. |s2cid=22522914 }} 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,{{cite journal |doi=10.1046/j.1526-4610.2000.00127.x |pmid=11091291 |title=The Misdiagnosis of Cluster Headache: A Nonclinic, Population-Based, Internet Survey |journal=Headache |volume=40 |issue=9 |pages=730–5 |year=2000 |last1=Klapper |first1=Jack A. |last2=Klapper |first2=Amy |last3=Voss |first3=Tracy |s2cid=40116437 }} 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 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.{{cite journal |doi=10.1177/0333102409357642 |pmid=20656709 |title=Cluster headache responsive to indomethacin: Case reports and a critical review of the literature |journal=Cephalalgia |volume=30 |issue=8 |pages=975–82 |year=2010 |last1=Prakash |first1=Sanjay |last2=Shah |first2=Nilima D |last3=Chavda |first3=Bhavna V |s2cid=5938778 }}{{cite journal |pmid=20626997 |year=2010 |last1=Sjaastad |first1=O |title=Indomethacin responsive headache syndromes: Chronic paroxysmal hemicrania and Hemicrania continua. How they were discovered and what we have learned since |journal=Functional Neurology |volume=25 |issue=1 |pages=49–55 |last2=Vincent |first2=M }}
• Hemicrania continua{{cite journal |author=Sanjay Prakash |author2=Nilima D Shah |author3=Bhavna V Chavda | s2cid =5938778 | title =Cluster headache responsive to indomethacin: Case reports and a critical review of the literature | journal =Cephalalgia | date = 2010 | volume =30 | issue =8 | pages =975–982 | doi= 10.1177/0333102409357642| pmid =20656709 }}
• Short-lasting unilateral neuralgiform headache with conjunctival injection and tearing (SUNCT) is a headache syndrome belonging to the group of TACs.{{cite journal|last1=Rizzoli|first1=P|last2=Mullally|first2=WJ|title=Headache|journal=American Journal of Medicine|date=September 2017|volume=S0002-9343|issue=17|pages=30932–4|doi=10.1016/j.amjmed.2017.09.005|pmid=28939471|type=Review|doi-access=free}}
• Trigeminal neuralgia is a unilateral headache syndrome, or "cluster-like" headache.{{cite journal |doi=10.1177/2049463712456355 |pmid=26516482 |pmc=4590147 |title=Trigeminal autonomic cephalgias |journal=British Journal of Pain |volume=6 |issue=3 |pages=106–23 |year=2012 |last1=Benoliel |first1=Rafael }}

Management for cluster headache is divided into three primary categories: abortive, transitional, and preventive.{{cite book|author1=Nalini Vadivelu|author2=Alan David Kaye|author3=Jack M. Berger|title=Essentials of palliative care|publisher=Springer|location=New York, NY|isbn=9781461451648|page=335|url=https://books.google.com/books?id=hGBSe3r_VDUC&pg=PA335|date=2012-11-28|url-status=live|archive-url=https://web.archive.org/web/20170910172156/https://books.google.com/books?id=hGBSe3r_VDUC&pg=PA335|archive-date=10 September 2017}} Preventive treatments are used to reduce or eliminate cluster headache attacks; they are generally used in combination with abortive and transitional techniques.

The recommended first-line preventive therapy is verapamil, a calcium channel blocker.{{cite journal |doi=10.1111/j.1468-1331.2006.01566.x |pmid=16987158 |title=EFNS guidelines on the treatment of cluster headache and other trigeminal-autonomic cephalalgias |journal=European Journal of Neurology |volume=13 |issue=10 |pages=1066–77 |year=2006 |last1=May |first1=A. |last2=Leone |first2=M. |last3=Áfra |first3=J. |last4=Linde |first4=M. |last5=Sándor |first5=P. S. |last6=Evers |first6=S. |last7=Goadsby |first7=P. J. |doi-access=free }} Verapamil was previously underused in people with cluster headache.

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).{{cite journal |vauthors=Petersen AS, Barloese MC, Snoer A, Soerensen AM, Jensen RH | title =Verapamil and Cluster Headache: Still a Mystery. A Narrative Review of Efficacy, Mechanisms and Perspectives | journal =Headache| date = 2019 | volume =59| issue =8| pages =1198–1211| pmid = 31339562| doi = 10.1111/head.13603| s2cid =198193843 }} 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.

Since these compounds are steroids, there is little evidence to support long-term benefits from glucocorticoids, but they may be used until other medications take effect as they appear to be effective at three days. They are generally discontinued after 8–10 days of treatment. 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.{{Cite book |last=Butticè |first=Claudio |url=https://www.abc-clio.com/products/a6280c/ |title=What you need to know about headaches |publisher=Greenwood |year=2022 |isbn=978-1-4408-7531-1 |location=Santa Barbara, California |oclc=1259297708 |access-date=19 September 2022 |archive-date=28 November 2022 |archive-url=https://web.archive.org/web/20221128083152/https://www.abc-clio.com/products/a6280c/ |url-status=live }}

Nerve stimulators may be an option in the small number of people who do not improve with medications.{{cite book |doi=10.1159/000323045 |pmid=21422783 |chapter=Peripheral Nerve Stimulation in Chronic Cluster Headache |title=Peripheral Nerve Stimulation |volume=24 |pages=126–32 |series=Progress in Neurological Surgery |year=2011 |last1=Magis |first1=Delphine |last2=Schoenen |first2=Jean |isbn=978-3-8055-9489-9 }}{{cite journal |doi=10.1186/1129-2377-14-86 |title=Neuromodulation of chronic headaches: Position statement from the European Headache Federation |journal=The Journal of Headache and Pain |volume=14 |year=2013 |last1=Martelletti |first1=Paolo |last2=Jensen |first2=Rigmor H |last3=Antal |first3=Andrea |last4=Arcioni |first4=Roberto |last5=Brighina |first5=Filippo |last6=De Tommaso |first6=Marina |last7=Franzini |first7=Angelo |last8=Fontaine |first8=Denys |last9=Heiland |first9=Max |last10=Jürgens |first10=Tim P |last11=Leone |first11=Massimo |last12=Magis |first12=Delphine |last13=Paemeleire |first13=Koen |last14=Palmisani |first14=Stefano |last15=Paulus |first15=Walter |last16=May |first16=Arne |issue=1 |page=86 |pmc=4231359 |pmid=24144382 |doi-access=free }} Two procedures, deep brain stimulation or occipital nerve stimulation, may be useful; early experience shows a benefit in about 60% of cases.{{cite journal |doi=10.1097/wco.0b013e32832ae61e |pmid=19434793 |title=Neurostimulation approaches to primary headache disorders |journal=Current Opinion in Neurology |volume=22 |issue=3 |pages=262–8 |year=2009 |last1=Bartsch |first1=Thorsten |last2=Paemeleire |first2=Koen |last3=Goadsby |first3=Peter J |s2cid=2063863 }} It typically takes weeks or months for this benefit to appear. A non-invasive method using transcutaneous electrical nerve stimulation (TENS) is being studied.

A number of surgical procedures, such as a rhizotomy or microvascular decompression, may also be considered, but evidence to support them is limited and there are cases of people whose symptoms worsen after these procedures.

Lithium, methysergide, and topiramate are recommended alternative treatments,{{cite journal |doi=10.1517/14656566.2010.496454 |pmid=20569084 |title=Pharmacotherapy of cluster headache |journal=Expert Opinion on Pharmacotherapy |volume=11 |issue=13 |pages=2121–7 |year=2010 |last1=Evers |first1=Stefan |s2cid=40081324 }} although there is little evidence supporting the use of topiramate or methysergide.{{cite journal|author=Matharu M|title=Cluster headache|journal=Clinical Evidence|date=9 February 2010|volume=2010|pmid=21718584|type= Review|pmc=2907610}} This is also true for tianeptine, melatonin, and ergotamine. Valproate, sumatriptan, and oxygen are not recommended as preventive measures. Botulinum toxin injections have shown limited success.{{cite journal |doi=10.1007/s11916-009-0028-7 |pmid=19272284 |title=The role of nerve blocks and botulinum toxin injections in the management of cluster headaches |journal=Current Pain and Headache Reports |volume=13 |issue=2 |pages=164–7 |year=2009 |last1=Ailani |first1=Jessica |last2=Young |first2=William B. |s2cid=10284630 }} Evidence for baclofen, botulinum toxin, and capsaicin is unclear.

There are two primary treatments for acute CH: oxygen and triptans, but they are underused due to misdiagnosis of the syndrome. During bouts of headaches, triggers such as alcohol, nitroglycerine, and naps during the day should be avoided.

Oxygen therapy may help to abort attacks, though it does not prevent future episodes. Typically it is given via a non-rebreather mask at 12–15 liters per minute for 15–20 minutes. One review found about 70% of patients improve within 15 minutes. The evidence for effectiveness of 100% oxygen, however, is weak.{{cite book |doi=10.1002/14651858.CD005219.pub3 |pmid=26709672 |chapter=Normobaric and hyperbaric oxygen therapy for the treatment and prevention of migraine and cluster headache |title=Cochrane Database of Systematic Reviews |issue=12 |pages=CD005219 |year=2015 |last1=Bennett |first1=Michael H |last2=French |first2=Christopher |last3=Schnabel |first3=Alexander |last4=Wasiak |first4=Jason |last5=Kranke |first5=Peter |last6=Weibel |first6=Stephanie |volume=2016 |pmc=8720466 }} Hyperbaric oxygen at pressures of ~2 times greater than atmospheric pressure may relieve cluster headaches.

The other primarily recommended treatment of acute attacks is subcutaneous or intranasal sumatriptan.{{cite web |url=https://www.nlm.nih.gov/medlineplus/ency/article/000786.htm |title=Cluster headache |publisher=MedlinePlus Medical Encyclopedia |date=2012-11-02 |access-date=2014-04-05 |url-status=live |archive-url=https://web.archive.org/web/20140405112718/http://www.nlm.nih.gov/medlineplus/ency/article/000786.htm |archive-date=5 April 2014 }} Sumatriptan and zolmitriptan have both been shown to improve symptoms during an attack with sumatriptan being superior.{{cite book |doi=10.1002/14651858.cd008042.pub3 |chapter=Triptans for acute cluster headache |title=Cochrane Database of Systematic Reviews |issue=4 |pages=CD008042 |year=2013 |last1=Law |first1=Simon |last2=Derry |first2=Sheena |last3=Moore |first3=R Andrew |volume=2018 |pmc=4170909 |pmid=20393964}} Because of the vasoconstrictive side-effect of triptans, they may be contraindicated in people with ischemic heart disease. The vasoconstrictor ergot compounds may be useful, but have not been well studied in acute attacks.

The use of opioid medication in management of cluster headache is not recommended and may make headache syndromes worse.{{cite journal |doi=10.1177/0333102412467512 |pmid=23144180 |title=Medication-overuse headache and opioid-induced hyperalgesia: A review of mechanisms, a neuroimmune hypothesis and a novel approach to treatment |journal=Cephalalgia |volume=33 |issue=1 |pages=52–64 |year=2012 |last1=Johnson |first1=Jacinta L |last2=Hutchinson |first2=Mark R |last3=Williams |first3=Desmond B |last4=Rolan |first4=Paul |s2cid=5697283 |hdl=2440/78280 |hdl-access=free }}{{cite journal |doi=10.1016/j.tips.2009.08.002 |pmid=19762094 |pmc=2783351 |title=The "Toll" of Opioid-Induced Glial Activation: Improving the Clinical Efficacy of Opioids by Targeting Glia |journal=Trends in Pharmacological Sciences |volume=30 |issue=11 |pages=581–91 |year=2009 |last1=Watkins |first1=Linda R. |last2=Hutchinson |first2=Mark R. |last3=Rice |first3=Kenner C. |last4=Maier |first4=Steven F. }} Long-term opioid use is associated with well known dependency, addiction, and withdrawal syndromes.{{cite journal |doi=10.1007/s40263-013-0081-y |pmid=23925669 |title=Medication Overuse Headache: History, Features, Prevention and Management Strategies |journal=CNS Drugs |volume=27 |issue=11 |pages=867–77 |year=2013 |last1=Saper |first1=Joel R. |last2=Da Silva |first2=Arnaldo Neves |s2cid=39617729 }} Prescription of opioid medication may additionally lead to further delay in differential diagnosis, undertreatment, and mismanagement.{{cite journal |doi=10.1007/s11916-008-0023-4 |pmid=18474192 |title=Medication-overuse headache in patients with cluster headache |journal=Current Pain and Headache Reports |volume=12 |issue=2 |pages=122–7 |year=2008 |last1=Paemeleire |first1=Koen |last2=Evers |first2=Stefan |last3=Goadsby |first3=Peter J. |s2cid=28752169 }}

Intranasal lidocaine (sprayed in the ipsilateral nostril) may be an effective treatment with patient resistant to more conventional treatment.

Octreotide administered subcutaneously has been demonstrated to be more effective than placebo for the treatment of acute attacks.{{cite journal |pmid=21718584 |pmc=2907610 |year=2010 |last1=Matharu |first1=M |title=Cluster headache |journal=BMJ Clinical Evidence |volume=2010 }}

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.{{cite journal |last1=Malu |first1=Omojo Odihi |last2=Bailey |first2=Jonathan |last3=Hawks |first3=Matthew Kendall |title=Cluster Headache: Rapid Evidence Review |journal=American Family Physician |date=January 2022 |volume=105 |issue=1 |pages=24–32 |pmid=35029932 |url=https://www.aafp.org/pubs/afp/issues/2022/0100/p24.html#afp20220100p24-b45 |issn=1532-0650 |access-date=30 October 2022 |archive-date=30 October 2022 |archive-url=https://web.archive.org/web/20221030054813/https://www.aafp.org/pubs/afp/issues/2022/0100/p24.html#afp20220100p24-b45 |url-status=live }}

Cluster headache affects about 0.1% of the general population at some point in their life. Males are affected about four times more often than females. The condition usually starts between the ages of 20 and 50 years, although it can occur at any age. About one in five affected adults report the onset of cluster headache between 10 and 19 years of age.{{cite book|author1=Ishaq Abu-Arafeh|author2=Aynur Özge|title=Headache in Children and Adolescents: A Case-Based Approach|url=https://books.google.com/books?id=sf3cDAAAQBAJ&pg=PA62|date=2016|publisher=Springer International Publishing Switzerland|isbn=978-3-319-28628-0|page=62|url-status=live|archive-url=https://web.archive.org/web/20170910172156/https://books.google.com/books?id=sf3cDAAAQBAJ&pg=PA62|archive-date=10 September 2017}}

The first complete description of cluster headache was given by the London neurologist Wilfred Harris in 1926, who named the disease migrainous neuralgia.Harris W.: Neuritis and Neuralgia. p. 307-12. Oxford: Oxford University Press 1926.{{cite journal |doi=10.1016/S0140-6736(59)90651-8 |title=The periodic migrainous neuralgia of Wilfred Harris |year=1959 |author=Bickerstaff E |journal=The Lancet |volume=273 |issue=7082 |pages=1069–71 |pmid=13655672 }}{{cite journal |doi=10.1046/j.1468-2982.2002.00360.x |pmid=12100097 |title=Wilfred Harris' Early Description of Cluster Headache |journal=Cephalalgia |volume=22 |issue=4 |pages=320–6 |year=2016 |last1=Boes |first1=CJ |last2=Capobianco |first2=DJ |last3=Matharu |first3=MS |last4=Goadsby |first4=PJ |s2cid=25747361 }} Descriptions of cluster headache date to 1745 and probably earlier.{{cite journal |doi=10.1136/jnnp.2007.123091 |pmid=17940171 |pmc=2117620 |title=Gerardi van Swieten: Descriptions of episodic cluster headache |journal=Journal of Neurology, Neurosurgery & Psychiatry |volume=78 |issue=11 |pages=1248–9 |year=2007 |last1=Pearce |first1=J M S }}

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:{{blockquote|"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."{{cite journal |vauthors=Horton BT, MacLean AR, Craig WM |journal= Mayo Clinic Proceedings |year= 1939 |volume= 14 |page= 257 |title= A new syndrome of vascular headache: results of treatment with histamine: preliminary report}}}}

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.{{cite book |vauthors=Silberstein SD, Lipton RB, Goadsby PJ |title= Headache in Clinical Practice |edition= Second |publisher= Taylor & Francis |year= 2002 }}{{page needed|date=July 2017}}

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.{{cite news |url= https://www.usatoday.com/story/news/nation/2013/05/16/researcher-unlocking-mysteries-migraines/2165363/ |title= Researcher works to unlock mysteries of migraines |author= Johnson, Tim |work= USA Today |date= 16 May 2013 |access-date= 4 January 2013 |url-status= live |archive-url= https://web.archive.org/web/20130517025701/http://www.usatoday.com/story/news/nation/2013/05/16/researcher-unlocking-mysteries-migraines/2165363/ |archive-date= 17 May 2013 }}

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.{{cite journal |doi=10.1111/j.1526-4610.2011.01846.x |pmid=21352222 |title=Alternative Headache Treatments: Nutraceuticals, Behavioral and Physical Treatments |journal=Headache |volume=51 |issue=3 |pages=469–83 |year=2011 |last1=Sun-Edelstein |first1=Christina |last2=Mauskop |first2=Alexander |doi-access=free }}{{cite journal |doi=10.1038/nrn2884 |pmid=20717121 |title=The neurobiology of psychedelic drugs: Implications for the treatment of mood disorders |journal=Nature Reviews Neuroscience |volume=11 |issue=9 |pages=642–51 |year=2010 |last1=Vollenweider |first1=Franz X. |last2=Kometer |first2=Michael |s2cid=16588263 }} 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. 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". 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.{{Cite journal|last1=Brandt|first1=Roemer B.|last2=Doesborg|first2=Patty G. G.|last3=Haan|first3=Joost|last4=Ferrari|first4=Michel D.|last5=Fronczek|first5=Rolf|date=2020-02-01|title=Pharmacotherapy for Cluster Headache|journal=CNS Drugs|language=en|volume=34|issue=2|pages=171–184|doi=10.1007/s40263-019-00696-2|pmid=31997136|pmc=7018790|issn=1179-1934|doi-access=free}}{{Cite web|url=https://clinicaltrials.gov/ct2/show/NCT02981173|title=Psilocybin for the Treatment of Cluster Headache - Full Text View - ClinicalTrials.gov|website=clinicaltrials.gov|language=en|access-date=2020-02-15|archive-date=27 May 2020|archive-url=https://web.archive.org/web/20200527221712/https://clinicaltrials.gov/ct2/show/NCT02981173|url-status=live}}{{Cite journal |last1=Schindler |first1=Emmanuelle A.D. |last2=Sewell |first2=R. Andrew |last3=Gottschalk |first3=Christopher H. |last4=Flynn |first4=L. Taylor |last5=Zhu |first5=Yutong |last6=Pittman |first6=Brian P. |last7=Cozzi |first7=Nicholas V. |last8=D'Souza |first8=Deepak C. |date=May 2024 |title=Psilocybin pulse regimen reduces cluster headache attack frequency in the blinded extension phase of a randomized controlled trial |url=https://doi.org/10.1016/j.jns.2024.122993 |journal=Journal of the Neurological Sciences |volume=460 |pages=122993 |doi=10.1016/j.jns.2024.122993 |pmid=38581739 |issn=0022-510X|url-access=subscription }} In Canada, a first cluster headache patient gained access to psychedelic-assisted therapy via Canada’s special access scheme for psilocybin.{{Cite web |last=Busby |first=Mattha |date=2024-06-27 |title=Cluster Headache Patient Wins Federal Court Case to Access Mushrooms |url=https://doubleblindmag.com/cluster-headaches-mushrooms/ |access-date=2025-03-12 |website=DoubleBlind Mag |language=en-US}}

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.{{cite journal |url=https://clinicaltrials.gov/ct2/show/NCT02964338 |title=A Study Comparing the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Chronic Cluster Headache (CCH) |website=ClinicalTrials.gov |date=28 January 2021 |access-date=30 November 2017 |archive-date=3 May 2020 |archive-url=https://web.archive.org/web/20200503040323/https://clinicaltrials.gov/ct2/show/NCT02964338 |url-status=live }}{{cite journal |url=https://clinicaltrials.gov/ct2/show/NCT02945046 |title=A Study to Evaluate the Efficacy and Safety of TEV-48125 (Fremanezumab) for the Prevention of Episodic Cluster Headache (ECH) |website=ClinicalTrials.gov |date=2 July 2020 |access-date=30 November 2017 |archive-date=1 May 2020 |archive-url=https://web.archive.org/web/20200501103107/https://clinicaltrials.gov/ct2/show/NCT02945046 |url-status=live }}

{{Reflist}}

• [https://clusterbusters.org/ Clusterbusters] patient support and advocacy
• [https://www.preventsuffering.org/cluster-headaches/ Organisation for the Prevention of Intense Suffering (OPIS)] resource page on cluster headaches{{Medical resources

| DiseasesDB = 2850

| ICD10 = {{ICD10|G|44|0|g|40}}

| ICD9 = {{ICD9|339.00}},{{ICD9|339.01}},{{ICD9|339.02}},

| ICDO =

| OMIM =

| MedlinePlus = 000786

| eMedicineSubj = EMERG

| eMedicineTopic = 229

| eMedicine_mult = {{eMedicine2|article|1142459}}

| MeshID = D003027

}}

{{Diseases of the nervous system}}

{{Headache}}

{{DEFAULTSORT:Cluster Headache}}

Category:Ailments of unknown cause

Category:Headaches

Category:Neurological disorders

Category:Pain management

Category:Wikipedia emergency medicine articles ready to translate

Category:Wikipedia medicine articles ready to translate