The patient’s unmet needs (PUNs)
Your next patient is a 35-year-old man who last attended over five years ago. He explains that he has been woken at night for the past few weeks with an excruciating, boring pain in one eye, accompanied by a runny nose and eye watering on the same side. Each episode lasts about an hour. ‘Something’s obviously not right’, he says. ‘I think I need a scan.’ Examination reveals no obvious abnormality and you explain that he probably has cluster headache. ‘What’s brought it on?’ he asks. ‘Am I stuck with this forever? And can you give me something so I can get through the night?’
The doctor’s educational needs (DENs)
What are the diagnostic criteria for cluster headache?
Cluster headache1 is among the most painful disorders known. Sufferers endure recurrent daily attacks, lasting up to three hours, up to several times a day for several weeks or months at a time. The attacks ‘cluster’ into bouts before disappearing, only to return months or years later. 10% of sufferers have no remission periods, and are deemed to have the chronic form of the disorder. Misdiagnosis is common, as are damaging and unhelpful procedures such as sinus or root canal surgery, so careful attention must be paid to the exact features of the attacks. Diagnosis is made by history taking alone, as a sufferer is unlikely to present to primary care in the midst of an attack.
The pain of an attack is strictly unilateral and usually, but not always, confined to the first division of the trigeminal nerve. Sufferers describe it as the worst pain they have ever experienced and describe it as though an invisible force is trying to squeeze their eye out of its orbit, or drill into their temple.
Attacks arise centrally from midbrain and brainstem structures. They are classically associated with a set of ipsilateral cranial autonomic symptoms and signs, which, although may be present to a lesser extent in migraine, are usually much more exaggerated in cluster headache attacks. These include redness of the cornea, watering of the eye, partial ptosis, miosis, periorbital oedema, nostril congestion and profuse watery rhinorrhoea.
What is thought to cause the problem? Are there any triggers that patients can avoid?
The causes and triggers of cluster headache are unknown but the trigemino-thalamic pathway (similar to migraine) is involved. Unlike migraine, exogenous triggers such as sleep deprivation and particular foods are not associated with this condition. Cluster headaches are more common in men than women, whereas in migraine, women outnumber men by more than 2:1.
What is the differential diagnosis?
A key differentiator between cluster headache and migraine is the profound sense of restlessness and agitation a cluster headache sufferer feels with an attack. They will pace up and down, rock, cradle or hit their heads, and cannot keep still. This is in stark contrast to a migraine attack, during which a sufferer will seek to lie very still.
Cluster headache attacks may be associated with photophobia, but this is usually unilateral only, and ipsilateral to the side of the pain.
Untreated attacks last between 15 minutes and three hours. They occur between once every 48 hours and up to eight times in a 24-hour period. Attacks are most likely to arise at almost exact times of the day and night and will classically wake a sufferer 60-90 minutes after falling asleep.
Patients with shorter, more frequent attacks, which otherwise resemble cluster headache, raise the possibility of rarer associated disorders such as paroxysmal hemicrania (which responds to prophylactic indomethacin) or short-lasting unilateral neuralgiform (SUNCT/SUNA) headache attacks, with conjunctival injection and tearing or autonomic features. In these paroxysmal hemicranias, the attacks are much shorter (usually lasting seconds, and certainly under a minute), whereas they typically last for several minutes in cluster headache syndromes. The attacks may rarely be mimicked by other disorders, particularly pituitary tumours, so magnetic resonance imaging is appropriate at least once to exclude a hypothalamic or pituitary lesion.
Should all new cases be scanned or referred? Which patients do require referral?
A specialist referral for all new onset cluster headache patients should be considered so that a definitive diagnosis and exclusion of “secondary” headache syndrome can be established. All new- onset headaches should be considered for referral unless you are confident in your diagnosis.
What are the most effective acute treatments?
Treatment of the disorder consists of a combined acute (to terminate the attack) and preventive (to prevent attacks from occurring) approach. The only acute treatments supported by randomised controlled evidence are high-flow oxygen2 (15 litres per minute using a non-rebreathing mask) and parenteral triptans3 (subcutaneous sumatriptan, nasal sumatriptan or zolmitriptan). No other analgesic works acutely, and a combination of these must be made available to all patients. Cluster headache is a licenced indication for home oxygen listed on the NHS Home Oxygen Order Form.
Bridging treatments, which offer short-term preventive relief, can be offered while a preventive treatment is initiated. These therapies include a greater occipital nerve block on the side of pain (if available locally) and a short course of oral prednisolone (1mg/kg for five days with rapid taper). A preventive medication can then be initiated concurrently. The drug of choice is standard release verapamil, given three times daily, and increased by 80mg a fortnight until attacks are controlled. High doses (up to 960mg daily) are often needed to achieve this.
It is of crucial importance that a baseline ECG, and serial ECGs each time a dose adjustment is made, are carried out, as cardiac arrhythmias (particularly PR interval prolongation) are common. If a sufficient dose of verapamil is achieved during an attack, without undue side effects, then this can be tapered and stopped at the end of the attack and reinstated at the maximum dose achieved at the onset of subsequent bouts.
Which prophylactic treatments should the GP consider?
Other preventive agents used by physicians include lithium, topiramate, gabapentin and melatonin. Lithium is quite a tricky substance to use, requiring monitoring of levels and managing the extensive side effect profile. Anticonvulsants such as gabapentin and topiramate can certainly be trialled in primary care.
Chronic patients who are refractory to drug treatments may be offered neurostimulation procedures such as sphenopalatine ganglion stimulation or occipital nerve stimulation. These extracranial procedures should be trialled before deep brain stimulation is considered. New developments in treatment include a non-invasive vagus nerve stimulation device, which is currently undergoing a series of randomised controlled trials.
Dr Omar Malik is a consultant neurologist at The London Clinic and Imperial College Healthcare NHS Trust