Cluster headache

Cluster headache is a severe primary headache disorder characterised by recurrent unilateral headaches centred on the eye or temporal region.

They occur in short attacks (15-180 minutes) and are associated with ipsilateral autonomic signs (e.g. conjunctival injection, nasal congestion). It may be episodic (80-90%) with periods of remission or chronic (no periods of remission > 3 months). The severity of the pain should not be underestimated. It is often described as one of the most painful conditions and it can be enormously disruptive to normal life.

Cluster headache is the most common trigeminal autonomic cephalalgia - a group of primary headache disorders characterised by unilateral pain within the trigeminal distribution and associated ipsilateral autonomic signs.

Acute episodes are treated with triptans (e.g. sumatriptan) and further attacks may be prevented with verapamil.

The lifetime prevalence of cluster headaches is estimated to be 124 per 100,000 people.

Onset tends to be between the ages of 20-40. Males are affected four times more commonly than females.

The trigeminal autonomic cephalalgias (TACs) are a collection of primary headache disorders characterised by unilateral headache and parasympathetic autonomic features.

TACs are a relatively rare cause of primary headache disorder. There are four distinct forms (cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache and hemicrania continua) but they share a number of characteristics:

• Unilateral pain within the trigeminal distribution
• Ipsilateral cranial autonomic features

Cluster headache

Cluster headache is the most common type of TAC. Please see the rest of this note for further details on its presentation and management.

Paroxysmal hemicrania

Patients with paroxysmal hemicrania (PH) suffer from short (2-30 minutes), severe episodes of unilateral orbital, supraorbital and/or temporal pain. Attacks tend to happen several times over the course of a day.

Ipsilateral autonomic features include conjunctival injection and/or lacrimation, nasal congestion, rhinorrhoea, sweating, miosis/ptosis or eyelid oedema. Alternatively, or in addition, a sense of restlessness or agitation may also be present.

PH resolves completely with the administration of indomethacin (an NSAID).

SUNCT

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) is characterised by short (seconds to minutes) attacks of moderate to severe unilateral head pain with (as the name suggests) prominent lacrimation and conjunctival injection. Attacks can occur frequently throughout the day and other autonomic signs may be present.

Hemicrania continua

In hemicrania continua patients suffer from a persistent unilateral headache that persists for 3 months or longer.

Ipsilateral autonomic features (conjunctival injection and/or lacrimation, nasal congestion, rhinorrhoea, sweating, miosis/ptosis or eyelid oedema) are also present. Alternatively or in addition a sense of restlessness or agitation may also be present.

Like PH, it should resolve completely with indomethacin.

The pathophysiology of cluster headaches remains incompletely understood.

It is thought to occur due to abnormal activation of the trigeminal-parasympathetic reflex. This may occur secondary to hypothalamic activation though this pathway is not fully understood.

There is ongoing research involving imaging and electrophysiology studies and with time our understanding should continue to develop.

Cluster headaches have been defined in the International Classification of Headache Disorders 3rd edition (ICHD-3).

Cluster headaches are described in the ICHD-3 as:

'Attacks of severe, strictly unilateral pain which is orbital, supraorbital, temporal or in any combination of these sites, lasting 15-180 minutes and occurring from once every other day to eight times a day. The pain is associated with ipsilateral conjunctival injection, lacrimation, nasal congestion, rhinorrhoea, forehead and facial sweating, miosis, ptosis and/or eyelid oedema, and/or with restlessness or agitation.'

The following diagnostic criteria are given:

1. At least five attacks fulfilling criteria B-D
2. Severe or very severe unilateral orbital, supraorbital and/or temporal pain lasting 15-180 minutes (when untreated)
3. Either or both of the following:
   1. at least one of the following symptoms or signs, ipsilateral to the headache:
      1. conjunctival injection and/or lacrimation
      2. nasal congestion and/or rhinorrhoea
      3. eyelid oedema
      4. forehead and facial sweating
      5. miosis and/or ptosis
   2. a sense of restlessness or agitation
4. Occurring with a frequency between one every other day and 8 per day
5. Not better accounted for by another ICHD-3 diagnosis.

Cluster headaches can be further classified into two subtypes:

• Episodic: refers to patients where multiple attacks occur within periods lasting 7 days to 1 year but with pain-free intervals of at least 3 months between bouts. This is the more common form accounting for 80-90% of cases.
• Chronic: attacks occurring over a period of 1 year or longer without a period of remission greater than 3 months. This accounts for around 10-20% of cases.

For the full diagnostic criteria see the ICHD-3 website.

Other causes of headache, both primary and secondary, should be considered.

Primary headaches

• Migraines
• Tension-type headache
• Other TACs
• Other primary headache disorders

Secondary headaches

• Trauma
• Idiopathic intracranial hypertension
• Subarachnoid haemorrhage
• Space occupying lesion
• Giant cell arteritis
• Infection
• Drugs and medications
• Venous sinus thrombosis
• Malignant hypertension
• Temporomandibular disorder

You must consider potentially serious secondary causes of headaches and/or auras.

Whenever a patient presents with a headache, it is crucial as part of the assessment to exclude a potentially serious secondary cause of headache. Some of the key red flag signs that may indicate an underlying sinister cause of headache can be remembered by the mnemonic ‘HEADACHE PAINS’:

• H - Head injury (any history of trauma?)
• E - Eye pain +/- autonomic features
• A - Abrupt onset (i.e. thunderclap headache)
• D - Drugs (analgesia overuse or since new drug started)
• A - Atypical presentation or progressive headache
• C - Change in the pattern or recent-onset new headache
• H - High fever and systemic symptoms
• E - Exacerbating factors (worse on lying/standing, sneezing, coughing, exercise)
• P - Pregnancy or puerperium
• A - Age (onset > 50 years)
• I - Immunosuppressed (e.g. systemic therapy, HIV)
• N - Neoplasia (current or past history of cancer)
• S - Swollen optic discs (papilloedema)

Urgent referral

The NICE clinical practice guideline CG150 recommends further investigations (e.g. cerebral imaging) and/or referral for patients with new-onset headache and any of the following:

• Immunosuppressed or compromised immunity
• < 20 years old and a history of malignancy
• History of malignancy known to metastasise to the brain
• Vomiting without other obvious cause.

Other key precipitating factors that may suggest a secondary cause of headache include trauma (e.g. subdural haematoma) and headache triggered by Valsalva manoeuvre (e.g. posterior fossa lesion).

Associated features

In the assessment of headache always remember to determine these features from the history or examination:

• Fever, photophobia, neck stiffness: consider meningitis, encephalitis
• Papilloedema: consider BIH, venous sinus thrombosis, space-occupying lesions
• Dizziness/vertigo: consider stroke
• Visual changes: consider giant cell arteritis, glaucoma
• Vomiting: consider space-occupying lesions, carbon monoxide poisoning

NOTE: If multiple close contacts present with headache consider carbon monoxide poisoning!

Patients presenting with their first bout of a cluster-like headache should be referred to neurology for further review.

TACs and cluster headaches are relatively uncommon and all patients should receive a specialist neurology review to confirm the diagnosis.

Investigations typically consist of neuroimaging to exclude sinister causes for symptoms. Options include:

• MRI brain
• CT head

Patients with existing cluster headaches who present with new concerning or atypical features should also have a neurology review. Finally, all pregnant/breastfeeding patients should be referred.

Sumatriptan is often used first-line to terminate acute attacks.

Management revolves around terminating acute attacks and preventing further ones from occurring. In addition, patients should be encouraged to avoid potential triggers of their disease.

The severity and disabling nature of the condition can have profound effects on mental health. People with cluster headaches are at increased risk of depression and suicide. Patients should be regularly screened for mental illnesses and have their suicide risk assessed. Where appropriate referral to specialist services should be arranged.

Trigger avoidance

Some patients have identifiable triggers and where possible patients should avoid these. Both alcohol and smoking can trigger attacks, where appropriate offer cessation support.

Acute management

• Triptans: these are 5HT1-receptor agonists that can be taken via the subcutaneous or intranasal route. Subcutaneous or intranasal sumatriptan or intranasal zolmitriptan may be used.
• Short burst oxygen therapy: in the absence of contraindications 100% oxygen (12-15L/min) can be administered via a non-rebreather face mask for 15-20 minutes. It is possible to set up oxygen at home.

Traditional analgesic medications like paracetamol, opiates and NSAIDs are not recommended.

Preventative management

Preventative medications can help prevent the number of attacks a patient experiences. The initial option is normally verapamil (a calcium channel blocker).

Other options that may be used under specialist guidance include glucocorticoids, lithium and the monoclonal antibody galcanezumab.

Refractory disease

In patients with disease refractory to medical options there are a number of therapies that may aid resolution:

• Greater occipital nerve blocks
• Deep brain stimulation
• Trigeminal nerve compression

Cluster headaches appear to be a lifelong disorder in the majority of cases.

Patients who have episodic disease may develop chronic disease and vice versa. There is some evidence that the frequency of attacks falls with advancing age but our understanding of the disease course remains incomplete.

Last updated: March 2022