Cluster headache, SUNCT and SUNA: causes, symptoms, diagnosis and treatment

Trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterised by very severe unilateral pain and cranial autonomic symptoms (tearing, eye redness, nasal congestion). The most common TAC is cluster headache; rarer forms include SUNCT (short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing) and SUNA (short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms). For many years these conditions were considered “rare curiosities”, but today it is clear that cluster headache is at least as common as multiple sclerosis, and is often underdiagnosed and undertreated.

What are cluster headache, SUNCT and SUNA?

Trigeminal autonomic cephalalgias are primary headache disorders that combine:

• Very intense unilateral head pain, usually around the eye, temple or forehead.
• Cranial autonomic symptoms on the same side as the pain: tearing, conjunctival injection, eyelid swelling, nasal congestion or rhinorrhea, facial sweating, miosis and ptosis.

According to the International Classification of Headache Disorders, 3rd edition (ICHD-3), this group includes cluster headache, paroxysmal hemicrania, hemicrania continua and short-lasting unilateral neuralgiform headache attacks, the latter further subdivided into SUNCT and SUNA.^1,4,5,25

From a practical point of view, these disorders must be distinguished from each other because hemicranias are completely indomethacin-responsive, while cluster headache, SUNCT and SUNA are not and require different treatment strategies. This page focuses on cluster headache and the short-lasting neuralgiform attacks (SUNCT/SUNA).

How common are these disorders and who is at risk?

Cluster headache

Cluster headache is much more common than previously believed. Population-based studies suggest a lifetime prevalence of about 0.1%, which is comparable to the prevalence of multiple sclerosis in some regions.^10,11 The typical age of onset is in the 20s, but attacks may start earlier or later in life.

There is a clear male predominance (approximately 2:1 to 4:1), although women are relatively more likely to have the chronic form.^10,18–21 Around 6–8% of patients report a positive family history, with both autosomal dominant and recessive patterns described, which supports a genetic contribution.^15,16

Cluster headache is subdivided into:

• Episodic cluster headache – attacks occur in clusters (“bouts”, “cycles”) with remission periods of at least 3 months per year.
• Chronic cluster headache – attacks recur without remission or with remissions shorter than 3 months for at least 1 year.

Episodic cluster headache is 6–25 times more frequent than the chronic subtype, while chronic cluster headache is more often seen in women and in European/North-American cohorts compared with Asian populations.^10,17–21 Transitions between episodic and chronic forms are possible in both directions in a significant proportion of patients.²²

Cluster headache is strongly associated with smoking, sleep apnoea, depression and anxiety, and unfortunately with an increased risk of suicidal ideation and planning, especially during active bouts.^{7,13,17,23,24} This is one of the reasons why timely diagnosis and treatment are so important.

SUNCT and SUNA

SUNCT and SUNA are much rarer than cluster headache. Their combined prevalence is estimated at about 6.6 per 100,000 persons, with a slight male predominance and a typical onset between 35 and 65 years, i.e. later than for cluster headache.^68–71

As with cluster headache, episodic and chronic forms are distinguished, but in SUNCT/SUNA the chronic subtype predominates in most series.^4,72 The natural history is not fully understood; patients may transition between subtypes over time.

Clinical presentation and main symptoms

Cluster headache

There is no specific blood test or imaging marker for cluster headache; the diagnosis is clinical and based on ICHD-3 criteria.^2,25 The key features are:

• Very severe unilateral pain (orbital, supraorbital and/or temporal), usually lasting 15–180 minutes without treatment.
• Cranial autonomic symptoms on the same side as the pain: conjunctival injection and lacrimation, nasal congestion or rhinorrhea, eyelid oedema, facial sweating, miosis and ptosis.
• Marked inner restlessness or agitation – patients often pace, rock, hit their head or cannot sit still during an attack, in contrast to patients with migraine who prefer to lie still.
• Attack frequency from one every other day up to eight per day during a bout.

Pain intensity is extreme: in large surveys cluster headache scored on average 9.7 out of 10 on the numerical pain rating scale and is often described by patients as one of the worst pains a human being can experience.²⁷

Many patients report typical triggers such as alcohol, nitroglycerin or exposure to heat and intense physical activity. These triggers are particularly characteristic in episodic cluster headache, where they are active only during bouts and have no effect during remission.²⁹

A very important characteristic of cluster headache is its circadian and circannual rhythmicity. Attacks often occur at approximately the same time every day (classically around 2 a.m.), and bouts tend to start in particular seasons (spring and/or autumn).⁶ These patterns are highly suggestive of hypothalamic involvement.

SUNCT and SUNA

SUNCT and SUNA are characterised by very short, frequent and strictly unilateral attacks of stabbing or electric facial pain in the distribution of the trigeminal nerve, accompanied by autonomic symptoms.^4,70,71

Typical features:

• Attack duration from 1 to 600 seconds, with an average of about one minute.
• Attack frequency often dozens of attacks per day (median around 20–30).
• Three main attack patterns: single stabs, groups of stabs or a “saw-tooth” series.
• Sharp, stabbing, electric shock-like, shooting pain.
• Frequent cutaneous triggers such as light touch to the face, chewing, brushing teeth, cold air or wind. In contrast to classical trigeminal neuralgia, a refractory period is often absent.

SUNCT and SUNA differ only in which cranial autonomic symptoms are present: by definition, SUNCT requires both conjunctival injection and lacrimation, whereas SUNA includes one or neither of these, but may have other autonomic signs.²⁵

Diagnosis and differential diagnosis

Misdiagnosis and diagnostic delay are unfortunately very common. Many patients initially receive diagnoses of migraine, trigeminal neuralgia, sinusitis, dental disease or “atypical facial pain”.^17,30

The differential diagnosis of TACs includes:

• Other trigeminal autonomic cephalalgias (paroxysmal hemicrania, hemicrania continua).
• Migraine with prominent autonomic symptoms.
• Trigeminal neuralgia and other cranial neuralgias.
• Hypnic headache.
• Secondary causes (glaucoma, sinusitis, Tolosa–Hunt syndrome, temporal arteritis, carotid dissection, pituitary adenoma, meningioma, vascular malformations, etc.).^20,33,34

Because of this broad differential, all patients with suspected cluster headache, SUNCT or SUNA should undergo brain MRI with dedicated views of the pituitary and cavernous sinus. In complex or refractory cases, vascular imaging (MRA/CTA), pituitary hormone testing and evaluation for sleep apnoea are recommended.^35,36

Current concepts of pathophysiology

Modern data suggest that three interconnected systems play a key role in TACs: the hypothalamus, the trigeminovascular system and the cranial autonomic system.^1,20,37–43

• Hypothalamus. Functional MRI demonstrates activation of the posterior hypothalamus at the onset of cluster attacks; the circadian/circannual pattern points to the suprachiasmatic nucleus as a central clock.³⁷
• Trigeminovascular system. Pain signals from dura, intracranial vessels and facial structures are transmitted via the trigeminal ganglion and upper cervical roots to the trigeminocervical complex and onward to brainstem, thalamus and cortex. Calcitonin gene-related peptide (CGRP) is a key neuropeptide in this system; it is elevated during cluster attacks and its infusion can trigger attacks in susceptible patients.^39,40
• Cranial autonomic system. Parasympathetic outflow from the superior salivatory nucleus through the sphenopalatine ganglion to lacrimal glands and nasal mucosa mediates autonomic symptoms. Vasoactive intestinal polypeptide (VIP) is increased during attacks and its infusion may provoke headache in patients with cluster headache.^41,42

Genetic studies have identified several susceptibility loci for cluster headache, and imaging work has begun to delineate a potential structural and functional “biosignature” that distinguishes cluster headache from migraine and healthy controls.^44–48 For SUNCT/SUNA, neurovascular contact with the trigeminal nerve appears to be relevant, linking these conditions to both TACs and trigeminal neuralgia.^68,77

Management: acute, bridge and preventive treatment

Management should be individualised and guided by a neurologist with experience in headache disorders. In general, treatment is divided into:

• Acute (abortive) therapy – to stop or shorten individual attacks.
• Bridge therapy – short-term measures to quickly suppress attacks while preventive treatment is being introduced.
• Preventive therapy – to reduce attack frequency and severity during bouts or in chronic forms.

Acute treatment for cluster headache

Evidence-based first-line treatments include subcutaneous sumatriptan and high-flow oxygen delivered by non-rebreather mask.^20,51,52 Many patients use both modalities:

• Subcutaneous sumatriptan provides fast and convenient relief, but is limited by cardiovascular contraindications and the maximum allowable number of daily injections.
• High-flow oxygen (usually 12–15 L/min via non-rebreather mask) is safe for repeated use and can be very effective when started early in an attack.

Other acute options include nasal or oral zolmitriptan, intranasal lidocaine and non-invasive vagus nerve stimulation (for episodic cluster headache).^20,38,51,52

Bridge therapy

Short courses of systemic corticosteroids (for example, a tapering course of oral prednisone) or greater occipital nerve steroid injections are widely used as bridge therapy to rapidly suppress attacks at the beginning of a bout.^14,20,54 Because of the risk of systemic side effects, these treatments are time-limited and should be used under medical supervision.

Preventive treatment of cluster headache

The traditional first-line preventive drug is verapamil (usually in immediate-release form), titrated to an effective dose with ECG monitoring because of the risk of heart block.^55–57 Depending on comorbidities, other options include lithium, topiramate, gabapentin, melatonin and others.^20,51

A major recent advance is the use of galcanezumab, a monoclonal antibody against CGRP, which has been approved for episodic cluster headache at a higher dose than for migraine.^58,59 For some patients with chronic cluster headache, non-invasive vagus nerve stimulation may act as both acute and preventive therapy.³⁸

Management of SUNCT and SUNA

Because attacks are extremely short, classical acute therapies are usually ineffective. Management is therefore based on bridge and preventive strategies.^68–72,79

• IV lidocaine infusion in a monitored inpatient setting is considered one of the most effective options for severe exacerbations, but is limited by the need for telemetry and cardiac safety issues.
• Lamotrigine is regarded as the first-line preventive drug in many centres, supported by cohort data.⁷²
• Other potentially useful medications include carbamazepine, oxcarbazepine, topiramate, gabapentin, pregabalin, duloxetine and verapamil.^68,72,74

Special groups and invasive neuromodulation

In carefully selected patients with medically refractory chronic cluster headache, invasive neuromodulation may be considered in specialised centres. Techniques include occipital nerve stimulation, sphenopalatine ganglion stimulation and, rarely, hypothalamic deep brain stimulation.^60–62

Cluster headache can begin in childhood or adolescence, and treatment in children requires adaptation of doses and careful consideration of the risk–benefit ratio. During pregnancy and lactation, oxygen and intranasal lidocaine are generally considered safe, whereas data on triptans and preventive agents are more limited and extrapolated mainly from migraine studies.^32,64

When should you urgently see a neurologist?

You should seek urgent neurological evaluation if you experience:

• Sudden, very severe unilateral headache around the eye or temple, especially with tearing, eye redness or nasal congestion.
• Attacks that recur at the same time every day or in clear “bouts”.
• Very frequent, short stabbing facial pains with redness and tearing of the eye.
• Any signs of “red flags”: fever, visual loss, double vision, new neurological deficits, jaw claudication, recent head trauma, known cancer, or sudden change in headache pattern.

Early recognition and appropriate treatment of cluster headache, SUNCT and SUNA can dramatically improve quality of life and reduce the risk of unnecessary procedures, chronic pain and psychological consequences. If you suspect that your symptoms fit the description above, do not postpone consultation with a neurologist who is familiar with primary headache disorders.

References (selected)

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8. Medrea I, Christie S, Tepper SJ, Thavorn K, Hutton B. Network meta-analysis of therapies for cluster headache: effects of acute therapies for episodic and chronic cluster. Headache. 2022;62(4):482–511. doi: 10.1111/head.14283
9. Lambru G, Stubberud A, Rantell K, et al. Medical treatment of SUNCT and SUNA: a prospective open-label study including single-arm meta-analysis. J Neurol Neurosurg Psychiatry. 2021;92(3):233–241. doi: 10.1136/jnnp-2020-323999
10. Favoni V, Grimaldi D, Pierangeli G, Cortelli P, Cevoli S. SUNCT/SUNA and neurovascular compression: new cases and critical literature review. Cephalalgia. 2013;33(16):1337–1348. doi: 10.1177/0333102413494273