SUNCT syndrome
Key points at a glance
Section titled “Key points at a glance”1. What is SUNCT syndrome?
Section titled “1. What is SUNCT syndrome?”SUNCT syndrome (Short-lasting Unilateral Neuralgiform headache attacks with Conjunctival injection and Tearing) is a type of trigeminal autonomic cephalalgia (TACs). It is characterized by short-lasting unilateral neuralgiform headache attacks accompanied by conjunctival injection and tearing. It is considered one of the rarest diseases among TACs.
SUNCT and SUNA (Short-lasting Unilateral Neuralgiform headache attacks with cranial Autonomic symptoms) are considered to be on the same disease spectrum. The difference between the two lies in the type of autonomic symptoms. In SUNCT, both conjunctival injection and tearing are required, whereas in SUNA, either one is sufficient.
History
Section titled “History”First reported in 1978, its clinical features were fully described in 1989. It was added to the International Classification of Headache Disorders (ICHD) in 2004 and classified as a subtype of SUNHA (short-lasting unilateral neuralgiform headache attacks) in 2013.
Epidemiology
Section titled “Epidemiology”The estimated prevalence is 6.6 per 100,000 people, and the annual incidence is 1.2 per 100,000 people (both may be underestimated). Age of onset ranges from 10 to 77 years, with most cases occurring between 35 and 65 years and a mean age of onset of 48 years. In adults, there is a male predominance, with a reported male-to-female ratio of 17:2.
Only 19 pediatric cases have been reported in the literature, with ages of onset ranging from 2 to 18 years (mean 9.9 years, median 11 years)2).
SUNCT requires both conjunctival injection and lacrimation as mandatory diagnostic criteria, whereas SUNA requires only one of these (or other cranial autonomic symptoms). Both are considered to be on the spectrum of the same disease 1), and transition from SUNCT to SUNA after peripheral nerve block has been reported.
2. Main Symptoms and Clinical Findings
Section titled “2. Main Symptoms and Clinical Findings”Subjective Symptoms
Section titled “Subjective Symptoms”- Unilateral orbital/periorbital pain: burning, stabbing, or electric shock-like severe pain. Mainly localized in the first division of the trigeminal nerve (V1: ophthalmic nerve). May radiate to the temple, nose, cheek, or palate.
- Attack duration: 1 to 600 seconds (average 61 seconds).
- Attack frequency: 3 to 100 times per day (average 28 times). During cluster periods, attacks recur daily.
- Attack patterns: “Plateau type” (continuous severe pain) and “Sawtooth type” (continuous pain with fluctuating intensity).
- Cluster periods and remission periods: Alternating cluster periods lasting several weeks and remission periods lasting several weeks to several months.
- Daytime predominance: No tendency for nighttime predominance.
- Triggers: Triggered by tactile stimulation of the forehead or orbit, use of facial or masticatory muscles, washing the face, shaving, talking, coughing, etc. 2).
Clinical Findings (Findings Confirmed by Physician Examination)
Section titled “Clinical Findings (Findings Confirmed by Physician Examination)”During attacks, ipsilateral cranial autonomic symptoms appear.
- Conjunctival injection: The most common autonomic symptom. Appears and disappears simultaneously with pain.
- Lacrimation: A diagnostic requirement for SUNCT along with conjunctival injection. Appears and disappears simultaneously with pain2).
- Rhinorrhea/nasal congestion: Occurs in about two-thirds of cases.
- Forehead sweating: Observed on the ipsilateral forehead during attacks.
- Pseudoptosis: Due to vascular edema of the eyelid.
- Elevated intraocular pressure/increased corneal temperature: Reported in some cases.
- Ptosis, miosis, anhidrosis: Reported in 2 cases, indicating decreased sympathetic nervous system activity2).
- Photophobia: Reported in 18 of 52 SUNHA patients (35%), with light as a trigger in only 4 cases (8%)1).
They can be triggered by tactile stimulation of the forehead or orbit, use of facial or masticatory muscles (chewing, talking, etc.), washing the face, shaving, or coughing2). Often have trigger zones similar to trigeminal neuralgia.
3. Causes and Risk Factors
Section titled “3. Causes and Risk Factors”Most cases are idiopathic (primary). However, some cases are secondary SUNCT due to an underlying disease.
Causes of Secondary SUNCT
Section titled “Causes of Secondary SUNCT”- Pituitary lesions: Prolactinoma is the most common. In a UK case series, pituitary lesions were found in 8% of SUNCT phenotype cases 1). Prolactin- or growth hormone-secreting adenomas are frequent 1).
- Posterior fossa lesions: Pilocytic astrocytoma, cavernous hemangioma, arteriovenous malformation, brainstem ischemic lesions, etc. 2).
- Cavernous sinus and orbital lesions: Neurofibromatosis type 2, metastatic tumors, etc. 2).
- Trigeminal neurovascular compression: Compression of the trigeminal nerve root by a vascular loop 2).
Pathogenesis of Secondary SUNCT
Section titled “Pathogenesis of Secondary SUNCT”Dural stretching due to pituitary tumor, cavernous sinus invasion, increased intrasellar pressure, hormonal dysregulation, and changes in hypothalamic neurotransmitter activity (especially dopamine) are thought to activate the trigeminovascular system 1).
MRI is recommended in all cases because secondary SUNCT cannot be distinguished from primary SUNCT based on clinical features alone 2). MRI of the posterior cranial fossa and pituitary fossa is essential to rule out organic lesions.
4. Diagnosis and examination methods
Section titled “4. Diagnosis and examination methods”ICHD-3 Diagnostic Criteria
Section titled “ICHD-3 Diagnostic Criteria”The diagnostic criteria for SUNCT according to the International Classification of Headache Disorders, 3rd edition (ICHD-3) are as follows2).
- A. At least 20 attacks fulfilling criteria B–D
- B. Unilateral orbital, supraorbital, or temporal stabbing/pulsating pain lasting 1–600 seconds
- C. Accompanied by ipsilateral conjunctival injection and lacrimation
- D. Occurring with a frequency of at least once a day
- E. Not better accounted for by another ICHD-3 diagnosis
Distinction between episodic and chronic forms: The chronic form is defined as persistence for more than 1 year without remission (or with remission lasting less than 3 months)2).
Imaging studies
Section titled “Imaging studies”MRI of the posterior cranial fossa and pituitary fossa is essential to exclude secondary SUNCT1).
Differential diagnosis
Section titled “Differential diagnosis”The main diseases to differentiate from SUNCT are listed below.
| Disease name | Key differentiating features |
|---|---|
| Cluster headache | Longer duration (15–180 minutes). Responds to oxygen and sumatriptan. |
| Paroxysmal hemicrania | Highly responsive to indomethacin (SUNCT does not respond). |
| Trigeminal neuralgia | Very short duration with refractory period. Autonomic symptoms are mild |
| Primary stabbing headache | No autonomic symptoms. Pain location varies each time |
Additional explanation is needed for differentiation from trigeminal neuralgia. Trigeminal neuralgia presents as electric shock-like pain lasting seconds, occurs in 4-5 per 100,000 people, and is more common in elderly women. The main differentiating points from SUNCT are the absence of prominent autonomic symptoms and the presence of a refractory period.
5. Standard treatment
Section titled “5. Standard treatment”There is no established single effective treatment for SUNCT. Individual differences are large, and treatment response varies from case to case.
Pharmacotherapy
Section titled “Pharmacotherapy”- Lamotrigine: The drug with the strongest evidence. It exerts its effect by blocking Na⁺ channels and suppressing excessive glutamate release2). Start at a low dose and gradually increase. In children, use at 25–100 mg/day has been reported2). Caution is needed for severe skin adverse effects (Stevens-Johnson syndrome)2).
- Carbamazepine: Effective in some cases. It is also used for trigeminal neuralgia (Tegretol®) and has Na⁺ channel blocking action.
- Oxcarbazepine: A metabolite of carbamazepine. There are reports of effective cases.
- Topiramate, Gabapentin, Pregabalin: Each has reports of effectiveness1).
- Duloxetine: Reported effective in some cases1).
- Intravenous lidocaine: Used under inpatient management with cardiac monitoring for refractory cases1).
Peripheral Nerve Block
Section titled “Peripheral Nerve Block”GON block (greater occipital nerve block), SON/STN block (supraorbital/supratrochlear nerve block), and SPG block (sphenopalatine ganglion block) combined with steroids have been reported to reduce attack frequency and severity by 60%1). Combinations of multiple cranial nerve blocks may be more effective than single blocks1).
Surgical Treatment (Refractory Cases Only)
Section titled “Surgical Treatment (Refractory Cases Only)”- Percutaneous trigeminal ganglion compression: Considered for cases resistant to pharmacotherapy.
- Microvascular decompression of the trigeminal nerve root (Jannetta procedure): Performed when compression by a vascular loop is present. The same procedure is also used for trigeminal neuralgia, but recurrence occurs in about 20% of cases.
- Deep brain stimulation (DBS): Electrode placement in the ipsilateral hypothalamus. Has been performed for refractory TACs.
- Resection of causative lesion in secondary SUNCT: Complete remission after pituitary adenoma resection has been reported1).
There is no single established effective treatment. Lamotrigine is considered the drug with the strongest evidence2), but its effects vary greatly among individuals, and it is often necessary to try multiple medications. In refractory cases, peripheral nerve blocks or surgical treatments are selected.
6. Pathophysiology and Detailed Mechanisms
Section titled “6. Pathophysiology and Detailed Mechanisms”The basis of SUNCT attacks is pathological activation of the trigeminal autonomic reflex (TAR). This involves a physiological pathway in the brainstem connecting the trigeminal nerve and the facial nerve parasympathetic outflow (superior salivatory nucleus: SSN). The SSN innervates the nasal glands, lacrimal glands, submandibular glands, and palate, and activation of this pathway causes conjunctival injection, rhinorrhea, miosis, lacrimation, and facial sweating.
Hypothalamic involvement is also an important finding. fMRI has confirmed activation of the ipsilateral hypothalamic gray matter during attacks, and the hypothalamus may control both pain and autonomic symptoms through connections with pain modulation systems and the SSN2). There are also reports of marked improvement after DBS of the hypothalamus.
Vascular involvement has been reported, including increased intraocular pressure and corneal indentation pulse amplitude (suggesting increased intraocular blood flow) during attacks, as well as abnormal venography of the superior ophthalmic vein and cavernous sinus on the headache side.
Role of CGRP/PACAP: CGRP is an important vasodilatory neuropeptide in the trigeminovascular system, involved not only in pain but also in photophobia. PACAP is expressed in the trigeminal ganglion and pterygopalatine ganglion, and activates dural C-fibers via the PAC1 receptor1).
Effect of circadian rhythm: Attacks are more common during the day, but in cases with prolactin-secreting microadenomas, nocturnal clustering has been reported. A neuromodulatory effect of prolactin on trigeminal ganglion sensory neurons has been hypothesized 2).
Cesaroni et al. (2021) argued that dramatic improvement after tumor resection or microvascular decompression supports the involvement of peripheral mechanisms. Vascular or tumor compression of the trigeminal nerve and infectious destruction may contribute through ephaptic pain generation mechanisms 2).
7. Latest Research and Future Perspectives (Research-stage Reports)
Section titled “7. Latest Research and Future Perspectives (Research-stage Reports)”Deepening of the SUNCT/SUNA spectrum concept: Both share the same pathophysiology, and transitions from SUNCT to SUNA after peripheral nerve block have been reported. The possibility that they represent a spectrum of the same disease is increasing, and reconsideration of diagnostic categories is being discussed 1).
Complete remission after pituitary adenoma resection: A 47-year-old man (recurrent growth hormone adenoma, 2-year chronic SUNCT with photophobia) experienced complete resolution of pain and photophobia after endoscopic transnasal transsphenoidal surgery to remove a dural-invasive adenoma 1). This finding highlights the importance of treating the causative lesion in secondary SUNCT.
Research on the therapeutic mechanism of SPG block: Transnasal sphenopalatine ganglion block is attracting attention as a mechanism that blocks the parasympathetic outflow in the treatment of pituitary lesion-related SUNCT 1).
Application of botulinum toxin in children: A 12-year-old child with SUNCT received a total of 70 U of botulinum toxin injected into the periorbital, temporal, and upper gingival areas, resulting in a good response 2). The number of cases is small, and further study is needed.
Need for improved recognition of pediatric SUNCT: Diagnostic delays lead to unnecessary tests and ineffective treatments. No chronic forms have been reported in children, and the natural course may differ from that in adults 2).
8. References
Section titled “8. References”- Demirel-Ozbek E, Berker M, Unal-Cevik I. The Resolution of Photophobia and Short-Lasting Unilateral Neuralgiform Headache Attacks with Conjunctival Injection and Tearing (SUNCT) Subsequent to Growth Hormone Adenoma Resection: Elucidating the Proposed Pathophysiological Mechanisms. Neuro-Ophthalmology. 2025;49(5):408-414.
- Cesaroni CA, Pruccoli J, Bergonzini L, et al. SUNCT/SUNA in Pediatric Age: A Review of Pathophysiology and Therapeutic Options. Brain Sci. 2021;11(9):1252.
- Pareja JA, Cuadrado ML. SUNCT syndrome: an update. Expert Opin Pharmacother. 2005;6(4):591-9. PMID: 15934885.