Cluster headaches

Synonyms: migrainous neuralgia; histamine headache; 'alarm clock headache'; ciliary neuralgia; hemicrania neuralgiformis chronica; Horton's headache; petrosal neuralgia; Bing's erythroprosopalgia; suicide headache

What is a cluster headache?

Recognised over 100 years ago, this condition is different from migraine - clinically, aetiologically and genetically. This is reflected in the fact that the latest version of the International Classification of Headache Disorders third edition (ICHD-3) moves cluster headache from Migraine to Trigeminal Autonomic Cephalgias.¹

It is a disorder producing severe unilateral pain, localised in or around the eye and accompanied by ipsilateral autonomic features. It is quite rare, often misdiagnosed and frequently poorly managed.²

Although short-lasting, the extremely painful nature of the headache causes patients very great distress and has earned the name 'suicide headache'. It is described as one of the most painful conditions known to man.³ The clustering of attacks means that there is significant interruption to life and work. The underlying mechanism of headache is not fully understood and prophylactic treatments are therefore empirical.

Episodic cluster headaches (CHs)

These are CHs occurring in periods lasting from seven days to one year. The National Institute for Health and Care Excellence (NICE) specifies a pain-free period lasting a month or longer; the International Headache Society (IHS) specifies at least three months. ¹⁴

Chronic CHs

These are defined as CHs occurring for one year without remissions or with short-lived remissions. The NICE definition specifies a remission period of less than one month, whilst the IHS classification specifies less than three months. ¹Chronic CH may arise de novo or develop from episodic CH.⁴

How common are cluster headaches? (Epidemiology)⁵

• CH has an estimated one-year prevalence of 53 per 100,000 adults. The lifetime prevalence is 124 per 100,000.

• The typical age of onset of CH is 20 to 40 years. About 7 out of 10 patients report onset before the age of 30.

• About 4 times more males are affected than females. The male-to-female ratio is significantly higher for chronic CH (15:1) than for episodic CH (3.8:1).

• About 80-90% of people with episodic cluster headache have recurrent bouts separated by remission periods of more than a month.

• Cigarette smoking, a history of head injury, having an affected 1st degree relative and alcohol use are also associated risk factors for the development of cluster headache.⁶

Pathophysiology⁶

A complete picture of the pathophysiological processes which cause a CH has been difficult to elucidate, particularly because the condition is rare and sample sizes are small. Vasodilation is known to occur during an attack. This is associated with activation of the trigeminovascular system causing perivascular afferent nerves to activate. The activation of the trigeminal nerve is believed to be unilateral, although this has not been confirmed by imaging. Complete trigeminal nerve root section does not affect the number or frequency of attacks, so clearly this is not the whole story.

An association with the hypothalamus has been confirmed. Attacks have a circadian periodicity, and occur most often at night. PET scans demonstrate activation of the inferior hypothalamic grey matter while the patient is having an attack. Anatomical abnormalities have been detected within this same region of the hypothalamus. Stimulation of the hypothalamus does not, however, trigger attacks. In fact, some research suggests that stimulation of the hypothalamus may abort an attack.

Parasympathetic nerve fibres are involved, and cause the autonomic symptoms, including conjunctival injection or lacrimation, rhinorrhoea, and facial vasodilation. How these are activated as part of the trigeminal reflex is activated is uncertain.

Clinical features of cluster headaches ^{14 5 6}

Nature of symptoms

• The pain comes on rapidly (without aura) over about 10 minutes.

• The pain maintains an intensity, is excruciating, sharp and penetrating.

• For most sufferers the headache comes on at the same time of night or day, usually at night, demonstrating a circadian pattern.

• 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 same affected side with each attack.

• It can last from 15 minutes to three hours (if untreated).

• Attacks of pain occur from once to up to eight times daily.

• Associated ipsilateral autonomic features of lacrimation, rhinorrhoea, nasal congestion, eyelid swelling, facial sweating or flushing and conjunctival injection and a partial Horner's syndrome with miosis and ptosis may be present: two or more in the presence of the extremely severe periocular headache will secure the diagnosis.

• 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 and agitated.

Diagnosis of cluster headaches ¹

The diagnosis is made from the history and examination. Once cluster headache is suspected, guidelines differ regarding the need for specialist referral and neuro-imaging. The 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 15-180 minutes (if untreated).

• Headache accompanied by at least one or both of the following:

  • Agitation or restlessness

  • At least one of the following, ipsilateral to the headache:

    • Conjunctival injection and/or lacrimation.

    • Nasal congestion and/or rhinorrhoea.

    • Eyelid oedema.

    • Forehead and facial sweating.

    • Miosis and/or ptosis.

• Attacks occur from one every other day to eight times daily.

• Not attributable to another disorder.

Urgent referral is recommended for all patients in whom CH is suspected. For more information see "Referral Guidance" below.

Episodic or chronic cluster headache?

Diagnostic criteria for episodic or chronic CH vary between guidelines.

NICE guideline defines the type of CH as:⁴

• Episodic CHs fulfil the criteria above and occur from once every other day to eight times a day with a pain-free period of greater than one month.

• Chronic CHs occur from once every other day to eight times a day with a continuous pain-free period of less than one month in a 12-month period.

The International Headache Society defines the type of CH as:¹

• Episodic CHs fulfil the criteria above and occur in bouts (cluster periods). At least two cluster periods last from 7 days to 1 year (untreated), separated by pain-free remission intervals of at least 3 months.

• Chronic CHs fulfil the criteria above and attacks occur without a remission period, or with remissions lasting less than 3 months, for a minimum of 1 year.

Most episodic CHs demonstrate remission periods of months or years. Often the interval between bouts is the similar, with a tendency for the interval to lengthen with age.

Triggers for attacks

• Alcohol is the most common trigger. However, 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, exertion, stress, nitrate-containing foods, solvents and disruption to sleep patterns can precipitate attacks.

Differential diagnosis

This could include a much longer list of causes of headache (particularly considering the red flags listed below) but those most similar to CH in the IHS guidelines are: ⁷

• 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.

Red flags in assessment^{4 56789}

The red flags of headache indicating the need to urgently refer for same-day assessment to investigate for a secondary cause are:

• Worsening headache with fever, neck pain or stiffness, seizure or reduced consciousness or any features suggestive of infection.

• Sudden‑onset headache reaching maximum intensity within five minutes.

• New‑onset cognitive impairment or neurological deficit.

• Papilloedema.

• Vestibular dysfunction or visual disturbance.

• Change in personality.

• Headache triggered by a Valsalva manoeuvre (such as a cough or sneeze).

• Orthostatic headache (headache that changes with posture).

• Symptoms suggestive of giant cell arteritis.

• Symptoms and signs of acute narrow-angle glaucoma.

• A progressive, persistent headache or substantial change in the characteristics of their usual headache including atypical migrainous aura.

• Vomiting. This is unlikely in cluster headache.

• Contacts with similar symptoms.

• Patients on immunosuppression.

• Patients with cancer or a history of cancer.

• Patients who are pregnant.

• Recent, (typically within the last 3 months) head trauma.

Treatment for cluster headaches

It should be remembered that:

• Specialist advice is recommended regarding treatment.

• Some patients will have found medical interventions unhelpful or hard to tolerate.

• Patients may be depressed or despondent about the condition.

• Patients experiencing their first attacks will be greatly distressed and will need reassurance.

• Drug treatment is always necessary for effective control.

• The realistic aim of treatment is suppression of the attack and reduction in frequency and severity of attacks. There is no likely prospect, at present, of curative medical treatment.

• Prophylaxis should begin as soon as possible after the start of a new cluster period, as there is evidence that it is most effective at this point.⁷

• Failure of one drug does not predict failure of another.

• All treatments are potentially toxic and shared risk/benefit evaluation is an essential part of management.

• When benefit is not seen within one week of reaching the maximum dose of a drug then it should be changed or supplemented.

• Acute therapy may be used in addition to prophylactic therapy if breakthrough attacks continue.

It is therefore important to:

• Establish rapport, 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.

General advice

• Be prepared for attacks. Patients should be encouraged to have both acute and preventative treatments available.

• Patients should be advised to try and identify if they have particular triggers for their CH.

• Stop smoking, as this can increase the risk of chronic CH developing.

• Abstain completely from alcohol during periods of CH and in chronic CH.

• There is no evidence that abstinence from smoking during attacks affects CH. ⁷

• Maintain a regular sleep routine and good sleep hygiene.

Acute attack

A triptan and oxygen are likely to be the mainstay of treatment for most patients:^{4 10}

• Offer oxygen and/or a subcutaneous or nasal triptan (eg, sumatriptan) for the acute treatment of a cluster attack. Arrange provision of both home and ambulatory oxygen therapy.

• Subcutaneous triptans are not recommended for patients under the age of 18 years.

• A sumatriptan or zolmitriptan nasal spray should be offered if the subcutaneous route is unacceptable (both are unlicensed for this use).

• Oxygen - use 100% oxygen at a flow rate of at least 12 litres per minute with a non‑rebreathing mask and a reservoir bag. It is particularly useful for night attacks. Standard high flow oxygen and demand valve oxygen types are available. Useful guidance for patients is available on the OUCH (UK) website.²

• Do not offer other painkillers such as paracetamol, opioids or NSAIDS.

• NHS England has recently agreed to fund the provision of a device called gammaCore® which delivers a low-level electric current to the vagus nerve via the neck.¹¹

Prophylaxis

Verapamil

• This should be considered for prophylaxis of CH (unlicensed use).⁴ It is the first-line choice for both episodic and chronic CH.

• The BNF recommends a dosage range for adults of 240-480 mg daily in 2-3 divided doses.¹⁰

• Side-effects of constipation and flushing may limit use in some.

• Multiple cardiac contraindications and medication interactions exist.

• ECG monitoring (for AV block) is required at doses over 120 mg daily and fortnightly ECG monitoring is required before treatment each time it is used, and with successive dose increases (because of the risk of dysrhythmias).

• Some experts believe that standard-release verapamil formulations are more effective in CH than the modified-release versions.

• If unfamiliar with this use of verapamil, or if the patient does not respond to treatment, the GP should seek specialist advice.

NICE only recommends verapamil for the prophylaxis of CHs. Other medications have been tried, with varying degrees of success.⁶ These include lithium, oral steroids, valproic acid, melatonin, topiramate, ergotamine, methysergide and nifedipine.

Deep brain stimulation⁶

• This may have a place in intractable chronic CH. It has been quite useful in drug-resistant patients.

• The ipsilateral posterior hypothalamus is targeted for electrical stimulation.

Surgery

Trigeminal nerve resection has not been shown to be helpful but decompression of the nerve has been shown to be temporarily effective in a small series of patients.¹²

More invasive procedures

These are used as a last resort. They involve chemical or physical ablation to parts of the trigeminal nerve. These can be effective but are likely to be reserved for refractory chronic CH. ¹³

Alternative therapies

Therapies such as acupuncture have anecdotally been very helpful to some patients. One study found that it was more beneficial when the acupuncture points stimulated were those used for trigeminal neuralgia, rather than migraine.¹⁴

Referral guidance

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.^{4 5}

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.¹³

Treatment review

• It is good practice to review CH patients at least annually, both to discuss their medication and to enable planning for attack management: the average GP will have fewer than 1 in 1,000 affected patients.

• Reviewing patients when they are well and discussing how they might manage possible attacks, offering them easy routes to contact you in the case of a new cluster of headaches, is likely to increase patient confidence and compliance.

• Encourage patients to be better informed by, for example, joining OUCH (UK).

Prognosis^{5 6}

There is an absence of good-quality evidence regarding prognosis. Available data suggest that about 25% of patients experience a CH as an isolated incident. Another 15-20% of patients will have chronic CHs, Of those, 10-20% develop resistance to medication. The condition was once thought to be lifelong but it is now known that it often resolves in approximately 15 years.

Periods of remission tend to increase as people get older.

Dr Mary Lowth is an author or the original author of this leaflet.