oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Synonyms: migrainous neuralgia; histamine headache; 'alarm clock headache'; ciliary neuralgia; hemicrania neuralgiformis chronica; Horton's headache; petrosal neuralgia; Bing's erythroprosopalgia; suicide headache
Recognised over 100 years ago, this condition is different from migraine - clinically, aetiologically and genetically. It is a disorder producing extreme, strictly unilateral pain, localised in or around the eye and accompanied by ipsilateral autonomic features.
More awareness of the condition has reduced the time to diagnosis and better understanding of the pathophysiology along with improvements in treatment should improve help for sufferers of this excruciating pain syndrome. It is quite rare, often misdiagnosed and frequently poorly managed.
Cluster headache (CH) sufferers deserve more attention, as the pain is often described as one of the most painful conditions known to mankind, with female patients describing the pain of attacks as worse than childbirth.
- The prevalence has been variously estimated to be from 56-69 per 100,000 up to 279 per 100,000.
- The incidence quoted in a study from the Mayo Clinic, suggested a figure of 2.07/100,000 person-years in 1989-1990, curiously less than earlier age- and sex-adjusted data from ten years previously.
- This suggests between 1 and 5 sufferers per GP and between 34,000 and 150,000 sufferers in the UK.
- Prevalence in men is 3 to 4 times higher.
- It usually begins between the ages of 20 and 40 years but can start at any age.
It is still not known why some individuals suffer from CH or why they exhibit the characteristic periodicity. However, progress is being made and a number of theories are plausible and may help progress with new treatments. Briefly:
- A small number of family and twin studies have shown that genetic factors are important, although such studies are difficult because of the low prevalence and complexity of the disorder. First-degree relatives of CH patients are more likely to have CH than the general population. About 1 in 20 sufferers has another family member who also has CH (with an autosomal dominant inheritance pattern). A significant association between the HCRTR2 gene and the disease has been reported.
- Positron emission tomography during cluster attacks has revealed that the ipsilateral hypothalamic grey matter is the area most activated. Goadsby has proposed that CH be regarded as a neurovascular headache to emphasise the hypothalamic dysfunction associated with vascular changes. It is thought that hypothalamic dysfunction causes dilatation of cranial vessels mediated by trigeminoparasympathetic reflexes. Neuroimaging may shed further light on the dysfunction within the posterior hypothalamus.
- Altered melatonin levels in CH have been found. This finding suggests a mechanism for CH periodicity and some useful therapeutic interventions. A double-blind placebo-controlled trial shows melatonin is effective in CH prevention and case reports indicate this may be helpful in chronic and episodic CH.
- It is possible that biological oscillators or synchronisers, postulated to lie within the hypothalamus, mediate seasonal changes seen in animals, which are linked to photoperiodic changes. Although speculative, these theories offer interesting explanations of the periodicity of CH and suggest further novel therapeutic options. It has been suggested that the relationship of melatonin to the light/dark cycle makes light therapy a possible therapeutic option.
An accurate description of the clinical features is essential to diagnosis.
It is important to distinguish between cluster attacks (individual episodes of pain) and cluster bouts (the time over which recurrent attacks occur). It is also important to distinguish between episodic CH and chronic CH. CHs have the following features:
- The pain comes on rapidly (without aura) over about 10 minutes. The pain maintains an intensity, is excruciating, sharp and penetrating (not pulsatile as with migraine). It typically lasts from 45 to 90 minutes (range 15 minutes to 3 hours). Attacks of pain occur once- or twice-daily (occasionally more often, even up to 8 times daily), typically at night 1 to 2 hours after falling asleep ('alarm clock headache').
- The pain is centred around or behind the eye, temple or forehead, although the neck and other parts of the head can be involved.
- Pain is unilateral and mostly stays on the affected side with each attack.
- The circadian pattern is accompanied in 85% of patients (episodic CH) with remissions of 1 to 4 years. About 10-15% of patients suffer chronically with no remission (chronic CH). Often the interval between bouts is the same and there is a tendency for the interval to lengthen with age. Unfortunately, in 10% of episodic sufferers, chronic CH develops (about a third of chronic sufferers become episodic).
- Pain is accompanied by ipsilateral lacrimation, rhinorrhoea, nasal congestion, eyelid swelling, facial sweating or flushing and conjunctival injection. A partial Horner's syndrome with miosis and ptosis may occasionally occur ipsilaterally.
- Nausea may accompany the pain, but is much less of a feature than with migraine.
- Sufferers, unlike with migraine, cannot keep still and are described typically as restless. Patients pace around, occasionally banging their heads on walls and furniture.
- Alcohol is a potent precipitant of attacks (It has been found that CH sufferers are protected from hazardous drinking) although, in episodic CH, normal alcohol consumption can be resumed once the cluster period is over. Histamine and nitroglycerine are also provokers of attacks in chronic CH and during cluster periods in episodic CH. For some patients, heat, exercise and solvents can precipitate attacks. Disruption to sleep patterns (for example, by shift work, jet lag, etc) can also exacerbate or trigger CHs.
- The autonomic features are usually transient, lasting only during the attack and there are usually no clinical signs.
The diagnosis is made from the history. The International Headache Society (IHS) guidelines have suggested the following diagnostic criteria:
- At least five attacks fulfilling the criteria below.
- Severe, or very severe, unilateral orbital, supraorbital and/or temporal pain lasting 15 to 180 minutes if untreated.
- Headache accompanied by at least one of: ipsilateral conjunctival injection and/or lacrimation; ipsilateral nasal congestion and/or rhinorrhoea; ipsilateral eyelid oedema; ipsilateral forehead and facial sweating; ipsilateral miosis and/or ptosis; a sense of restlessness or agitation.
- Attacks occur from one every other day to eight times daily.
- Not attributable to another disorder.
Episodic cluster headache
These are CHs occurring in periods lasting from seven days to one year, separated by pain-free periods lasting a month or longer. Cluster periods usually last between two weeks and three months.
Chronic cluster headache
These are defined as CHs occurring for one year without remissions or with short-lived remissions of less than a month. Chronic CH may arise de novo or develop from episodic CH.
This could include a longer list of causes of headache but those most similar to CH in the IHS guidelines are:
- Paroxysmal hemicrania.
- Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT).
- Probable diagnoses (of CH, SUNCT and paroxysmal hemicrania) where insufficient attacks have occurred or diagnostic criteria are not fulfilled.
Usually, only history and neurological examination are required to make the diagnosis. As with any primary headache, some patients may need imaging, and the red flags of headache indicating the need to search for a secondary cause are:
- Change in pattern of headache.
- New headache at age over 50.
- Onset of seizures.
- Headache with systemic illness.
- Personality change.
- Symptoms suggestive of raised intracranial pressure (morning headache, headache with coughing, sneezing, straining).
- Acute onset of the worst headache ever (possible intracranial aneurysm).
It should be remembered that:
- Some patients are likely to have found medical interventions unhelpful or difficult to tolerate.
- They may not have had the benefit of up-to-date review of treatment.
- They may be depressed or despondent about the condition.
- Whether episodic or chronic, it is generally a lifelong condition.
It is therefore important to:
- Establish rapport with the patient, based on knowledge and understanding of the condition generally and the patient's particular experience.
- Anticipate that polypharmacy is likely to be required.
- Be prepared to follow up closely to monitor efficacy of treatments, side-effects, etc.
- Consider drawing up a programme of measures, perhaps with a patient-held record book or diary.
- Be prepared for attacks. Patients should be encouraged to have both acute and preventative treatments available. This may involve completion of Home Oxygen Order Forms (HOOFs) if oxygen is to be used.
- Stop smoking, as this can increase the risk of chronic CH developing.
- Abstain from alcohol during periods of CH and in chronic CH.
- Maintain a regular sleep routine and good sleep hygiene (avoiding tea, coffee, etc).
Sumatriptan - by subcutaneous injection - and oxygen are likely to be the mainstay of treatment for most patients:
- Sumatriptan 6 mg subcutaneously is effective. The best evidence for benefit is from sumatriptan subcutaneously. However, for regular attacks over several weeks, there is a danger of overdosage. Other acute therapies like oxygen should be used in addition to preventative measures.
- Sumatriptan nasal spray works less well for most patients (use when the subcutaneous route is unacceptable). It is not licensed for use in CH.
- Oxygen - 100% oxygen, given for 15 minutes up to five times per day, is safe and effective in 80% of cases. It is given by a tight-fitting mask (not a standard mask or nasal cannulae) at 12 L/minute. It is particularly useful for night attacks. The most convenient form is the 460 L CD oxygen cylinder (lasts about 40 minutes at high flow rates) with concentration venturis. HOOF forms will need to be completed for oxygen supply. Useful guidance for patients is available on the OUCH (UK) website.
Other possible treatments for acute attacks include:
- Ergotamine which is of limited use in view of its poor oral absorption and side-effect profile. Before the advent of sumatriptan it was used more often.
- Anti-inflammatories such as indomethacin which can be used.
- Metoclopramide, which may be useful as an adjunct to acute treatments.
- Lidocaine 1 ml of 4% lidocaine, which can be given intranasally to the affected side.
Verapamil should be considered for prophylaxis of cluster headache. It is started at doses of 40 mg twice-daily, building up to as much as 960 mg daily. Side-effects may limit use in some. ECG monitoring is required at doses over 120 mg daily and fortnightly ECG monitoring is required with successive dose increases (because of the risk of dysrhythmias). If unfamiliar with this use, or the patient does not respond to treatment, seek specialist advice.
Other possible prophylactic treatments include:
- Melatonin - this is a safe and promising addition to the list of prophylactic agents for nocturnal attacks. It is taken at night at doses of 7.5-10 mg but, with currently available formulations, administration has to be timed to half an hour before the anticipated attack (difficult). Slow-release preparations may be more effective, but this is speculative until more evidence is forthcoming.
- Topiramate - this may be useful but only under specialist supervision and only in chronic CH.
- Sodium valproate - has also been used for prophylaxis, usually in chronic CH.
- Ergotamine - can be used two hours prior to a predicted attack. 2 mg orally or 1 mg rectally. Addiction is rare.
- Methysergide - up to 6 mg in divided doses can be used (more if under specialist care) and is most useful in the episodic form (used for less than six months at a time). There is a risk of retroperitoneal fibrosis if used for several weeks.
- Lithium - this is useful in the chronic form of CHs.
- Calcium-channel blockers verapamil and nifedipine, which can also be useful in the chronic form.
- Deep brain stimulation for intractable chronic CH, which seems to be effective in limited reports with complete relief and apparently few side-effects. The ipsilateral posterior hypothalamus is targeted for electrical stimulation.
- Surgery - occipital nerve blockade gives temporary relief if medical therapy is not helping.
More invasive procedures are used as a last resort. These involve chemical or physical ablation to parts of the trigeminal nerve. These can be effective and are likely to be reserved for chronic cluster headache. Refractory cases require referral for consideration of neuromodulation and more invasive treatments.
Alternative therapies, such as acupuncture, have anecdotally been very helpful to some patients. Unfortunately, the evidence of benefit is poor and better trials are needed.
Urgent referral is recommended for all people with suspected CH, for confirmation of the diagnosis, investigation of secondary causes of CH, and initiation of preventative treatment.Referral should be to a neurologist interested and expert in this condition. Other indications include:
- Diagnostic uncertainty.
- Imaging or further investigation.
- Failure of treatment.
- For new or invasive treatments.
- Identify and review CH patients. There will not be many.
- How well managed are their CHs? Identify ways in which management might be improved with new or different treatments - by referral, by changes in lifestyle.
- Take an interest and encourage regular review.
- Encourage patients to be better informed by, for example, joining OUCH (UK).
Further reading & references
- May A; Cluster headache: pathogenesis, diagnosis, and management.; Lancet. 2005 Sep 3-9;366(9488):843-55.
- OUCH (UK) - Organisation for the Understanding of Cluster Headache
- Matharu MS, Goadsby PJ; Cluster headache: focus on emerging therapies.; Expert Rev Neurother. 2004 Sep;4(5):895-907.
- Torelli P, Beghi E, Manzoni GC; Cluster headache prevalence in the Italian general population.; Neurology. 2005 Feb 8;64(3):469-74.
- Black DF, Swanson JW, Stang PE; Decreasing incidence of cluster headache: a population-based study in Olmsted County, Minnesota.; Headache. 2005 Mar;45(3):220-3.
- Schurks M; Genetics of cluster headache. Curr Pain Headache Rep. 2010 Apr;14(2):132-9.
- Goadsby PJ; Cluster headache: new perspectives.; Cephalalgia. 1999 Dec;19 Suppl 25:39-41.
- May A, Bahra A, Buchel C, et al; Hypothalamic activation in cluster headache attacks.; Lancet. 1998 Jul 25;352(9124):275-8.
- May A, Bahra A, Buchel C, et al; PET and MRA findings in cluster headache and MRA in experimental pain.; Neurology. 2000 Nov 14;55(9):1328-35.
- Iacovelli E, Coppola G, Tinelli E, et al; Neuroimaging in cluster headache and other trigeminal autonomic cephalalgias. J Headache Pain. 2011 Nov 25.
- Peres MF; Melatonin, the pineal gland and their implications for headache disorders.; Cephalalgia. 2005 Jun;25(6):403-11.
- Pringsheim T; Cluster headache: evidence for a disorder of circadian rhythm and hypothalamic function.; Can J Neurol Sci. 2002 Feb;29(1):33-40.
- Peres MF, Rozen TD; Melatonin in the preventive treatment of chronic cluster headache.; Cephalalgia. 2001 Dec;21(10):993-5.
- Costa A, Leston JA, Cavallini A, et al; Cluster headache and periodic affective illness: common chronobiological features.; Funct Neurol. 1998 Jul-Sep;13(3):263-72.
- Headaches: diagnosis and management of headaches in young people and adults; NICE Clinical Guideline (September 2012)
- Schurks M, Kurth T, Knorn P, et al; Predictors of hazardous alcohol consumption among patients with cluster headache.; Cephalalgia. 2006 May;26(5):623-7.
- Diagnosis and Management of Migraine, Tension-Type, Cluster and Medication-Overuse Headache; British Association for the Study of Headache (BASH) Guidelines, (2010)
- Goadsby PJ; To scan or not to scan in headache.; BMJ. 2004 Aug 28;329(7464):469-70.
- Ekbom K, Hardebo JE; Cluster headache: aetiology, diagnosis and management.; Drugs. 2002;62(1):61-9.
- More evidence on chronic headache, Bandolier, Nov 2001
- Headache - cluster; NICE CKS, August 2009
- Pearce JMS in Oxford Textbook of Medicine, 3rd Edition. Eds; Weatherall DA et al. OUP 1996.
- Capobianco DJ, Dodick DW; Diagnosis and treatment of cluster headache; Semin Neurol. 2006 Apr;26(2):242-59.
- Leone M, May A, Franzini A, et al; Deep brain stimulation for intractable chronic cluster headache: proposals for patient selection.; Cephalalgia. 2004 Nov;24(11):934-7.
- Leone M, Franzini A, Felisati G, et al; Deep brain stimulation and cluster headache.; Neurol Sci. 2005 May;26 Suppl 2:s138-9.
- Lovely TJ, Kotsiakis X, Jannetta PJ; The surgical management of chronic cluster headache.; Headache. 1998 Sep;38(8):590-4.
- Gaul C, Diener HC, Muller OM; Cluster headache: clinical features and therapeutic options. Dtsch Arztebl Int. 2011 Aug;108(33):543-9. Epub 2011 Aug 19.
- Acupuncture for Recurrent Headache, Bandolier, 1998
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Dr Richard Draper
Dr Richard Draper
Dr Adrian Bonsall