Abstract
Background
Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or stabbing headache, and associated trigeminal autonomic symptoms, such as paroxysmal hemicrania or cluster headache. Recognizing and adequately treating SUNHA is essential but current treatment methods are ineffective in treating SUNHA.
Methods
We reviewed the changes in the concept of short-lasting unilateral neuralgiform headache attacks and provide a narrative review of the current medical and surgical treatment options, from the first choice of treatment for patients to treatments for selective intractable cases.
Results
Unlike the initial impression of an intractable primary headache disorder affecting older men, SUNHA affects both sexes throughout their lifespan. One striking feature of SUNHA is that the attacks are triggered by cutaneous or intraoral stimulation. The efficacy of conventional treatments is disappointing and challenging, and preventive therapy is the mainstay of treatment because of highly frequent attacks of a very brief duration. Amongst them, lamotrigine is effective in approximately two-third of the patients with SUNHA, and intravenous lidocaine is essential for the management of acute exacerbation of intractable pain. Topiramate, oxcarbazepine and gabapentin are considered good secondary options for SUNHA, and botulinum toxin can be used in selective cases. Neurovascular compression is commonly observed in SUNHA, and surgical approaches, such as neurovascular compression, have been reported to be effective for intractable cases.
Conclusions
Recent advances in the understanding of SUNHA have improved the recognition and treatment approaches for this unique condition.
Keywords
Introduction
Short-lasting unilateral neuralgiform headache attacks (SUNHA) have the shortest duration of strictly unilateral pain attacks among trigeminal autonomic cephalalgia (1,2). Two subtypes are recognized according to the associated autonomic symptoms: short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) and short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA). SUNHA has episodic and chronic subtypes. SUNCT is a rare intractable primary headache disorder (3,4). Patients with SUNHA show features of both short-lasting unilateral neuralgiform pain, such as trigeminal neuralgia or stabbing headache, and associated trigeminal autonomic symptoms, such as paroxysmal hemicrania or cluster headache (5). However, carbamazepine, which is effective in treating trigeminal neuralgia, and medications such as indomethacin or oxygen, which are used to treat paroxysmal hemicrania or cluster headaches, are ineffective in treating SUNHA. Therefore, recognizing and adequately treating SUNHA is essential for managing relatively rare primary headache disorders, such as trigeminal autonomic cephalalgia, other primary headache disorders and cranial neuralgia (4,6).
Epidemiology
The epidemiology of SUNHA is uncertain; no SUNHA cases have been identified in a prospective population-based study to estimate the prevalence of SUNHA (Table 1). Among 9605 participants assessed for suspected trigeminal neuralgia in a population-based study in Turkey, one patient was diagnosed with SUNCT, resulting in an estimated prevalence of 10.4 per 100,000 (4). Another population-based study identified only two patients with SUNCT-like traits from 1838 participants (7), but the diagnosis of SUNCT was denied in a later study (8).
Epidemiology studies of SUNCT and SUNA. a
SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms.
Diagnosis based on ICHD-2 (18).
The frequency of SUNHA has been estimated to range between 0.06 and 0.2%, based on several single-or multicenter studies conducted in headache or orofacial pain clinics (9,10). These studies supported the notion that SUNHA is a rare headache disorder (Table 1). According to a prospective multicenter study in Korea, only one patient was diagnosed with SUNCT from among 1627 participants on their first visit for headache evaluation (9). A nationwide retrospective registry identified 24 patients with SUNCT from 20,083 patients in Italy (6). Another study analyzed 17 patients with SUNCT and seven patients with SUNA and/or SUNCT by examining their headache registry and directly questioning all other neurological referral centers in a specific region of Australia (11). The estimated prevalence and annual incidence was 6.6 per 100,000 and 1.2 per 100,000, respectively, based on an estimated background population of 500,000 (11).
The age of onset of SUNHA ranges between 37.2 and 51.4 years according to several previous studies (Table 2). SUNHA was previously known to have a male predominance; however, recent articles have reported no predominance of SUNCT and a female predominance of SUNA (5,11–13).
Clinical features of SUNCT and SUNA in the previous studies. a
NA, not available; SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms
Studies were selected based on the recent publication date among multiple publication from the same institute, countries, and the number of enrolled patients.
Diagnosis was rechecked by ICHD-3.
Exclude 2 cases with secondary causes.
50% or more improvement.
Debates and evolution of terminology of SUNCT, SUNA and SUNHA
The histories of SUNCT, SUNA, and SUNHA are long, dynamic and similar. Sjaastad et al. (14) published an article describing a new headache disorder in three men aged 51–72 years in 1989. The original report of a single case is in the Proceedings of the Scandinavian Migraine Society in 1978 (15). This disorder is characterized by severe unilateral pain lasting only a few seconds accompanied by profound tearing, conjunctival injections, sweating and rhinorrhea. It is a refractory primary headache disorder that is resistant to most drug therapies, including indomethacin, and was later referred to as SUNCT in 1991. Initially, SUNCT was considered to be associated with a disorder in older males. However, subsequent case reports in females and children as young as six years have expanded the recognized range of SUNCT, indicating that it can affect both sexes throughout their lifespan (16,17).
SUNCT was first included in the second version of the International Classification of Headache Disorders (ICHD-2) as a subtype of trigeminal autonomic cephalalgia in 2004 (18). However, differentiation from trigeminal neuralgia is clinically challenging, and the coexistent diagnosis of trigeminal neuralgia is allowed with SUNCT in ICHD-2 (18). Probable SUNCT is possible in patients with attacks that fulfil all but one of the criteria for SUNCT. However, the actual application of probable diagnosis in cases without autonomic symptoms is not persuasive. In addition, all patients with SUNCT must have both conjunctival injection and tearing; however, experts suggest that the presentation of SUNCT can vary. Based on these problems, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA) are included in the appendix of the ICHD-2 as a broader term, including SUNCT (18). In the SUNA criteria, no refractory period following triggered attacks was included to differentiate it from trigeminal neuralgia. The first case of SUNA in an 11-year-old girl who had intractable headaches for seven months with minimal gabapentin control was reported in 2005 (19). Consequent nine cases of SUNA met the diagnostic criteria, but pure SUNA was rarer than SUNCT (20).
Short-lasting unilateral neuralgiform headache attacks (SUNHA) were included as a subtype of trigeminal autonomic cephalalgia in the beta version of the third edition of the International Classification of Headache Disorders in 2013 (21) and were finalized in the third edition of the International Classification of Headache Disorders (ICHD-3) in 2018 (22). The diagnostic criteria for SUNHA include at least 20 attacks of moderate or severe unilateral head pain lasting from one second to ten minutes, occurring as single stabs, series of stabs or in a sawtooth pattern, along with the presence of at least one cranial autonomic symptom. The requirement of a lack of a refractory period in the appendix criteria of SUNA has been moved from the criteria to the comments section in ICHD-3. Therefore, the diagnosis of both SUNHA and trigeminal neuralgia is now possible in complex cases.
Although Sjaastad and Fredriksen (7) emphasized the rarity and profound autonomic symptoms of SUNCT and argued against any link with trigeminal neuralgia, neurovascular compression, such as trigeminal neuralgia, has been reported in 17–88% of SUNCT/SUNA (11,23). Unlike the early concerns regarding the ominous therapeutic prognosis of SUNHA, medical and interventional treatments, including microvascular decompression, have been reported to be effective and promising (3,24).
The subclassification of SUNCT and SUNA is not as clear as simply applying diagnostic criteria. There is controversy regarding whether the diagnoses of SUNA and SUNCT are mutually exclusive or whether there is a continuum between them (12,25,26). SUNCT is characterized by prominent cranial autonomic features, most likely single tabs, and better response to lamotrigine and topiramate. By contrast, SUNA showed a female predominance, more spontaneous attacks, prone to grouped stabbing and poor response in general, favoring gabapentin or lamotrigine. Although there are some differences in clinical features and functional imaging findings between SUNCT and SUNA, the similar prevalence of neurovascular compression between SUNCT and SUNA supports that subclassification into the two conditions may not be necessary for managing SUNHA (27).
Clinical manifestations
SUNHA presents with moderate-to-severe pain, characterized by brief, stabbing, burning sensations, or sensations akin to electrical shocks in the unilateral orbital, periorbital or temporal area, accompanied by ipsilateral cranial autonomic symptoms. Occasionally, pain may also be experienced in other areas, such as the top, side or back of the head, as well as in the trigeminal second and third distributions (22,28).
The attacks can last up to 600 seconds and may overlap with the duration of paroxysmal hemicrania, which typically lasts 2–30 minutes. The frequency of these episodes varies widely, ranging from one to 600 times per day, with an average of fewer than 100 daily occurrences. A distinct “saw-tooth” pattern is noted when paroxysms of pain occur without intervals of relief (29). To diagnose SUNCT, ipsilateral conjunctival injection and tearing must occur simultaneously, whereas only one of these two symptoms may occur in SUNA. Other cranial autonomic symptoms, such as nasal blockage, rhinorrhea, eyelid edema and ptosis, are also present on SUNCT/SUNA. Restlessness and agitation may present in 62% of SUNCT patients and 56% of SUNA patients (1,26).
Up to 80% of patients with SUNHA experience attacks triggered by cutaneous or intraoral stimulation, which is a striking feature of headache. Several case reports of cluster-tic syndrome or paroxysmal hemicrania-tic syndrome have highlighted the co-occurrence of two or more headache disorders in the same patient (30,31). Although triggers are often considered as essential features of SUNHA, they are not included in the diagnostic criteria. Common triggers include any form of trigeminal nerve irritation such as chewing, facial contact, tooth brushing, exposure to temperature changes and exposure to loud noises (29,32). Previous studies have shown that most SUNHA patients experience both spontaneous and triggered attacks, whereas 12–14% of SUNCT and 27% of SUNA patients experience only spontaneous attacks. Rarely, cases with only triggered attacks have been reported, comprising 2% of SUNCT cases (1,23).
Previously, consecutive, briefly provoked attacks without pauses indicated the absence of a refractory period in SUNHA (33). However, video monitoring during attacks has revealed that there can be a variable duration of the refractory period (ranging from one to 10 minutes) or even failed triggered attacks in some patients with SUNCT. Although patients with SUNHA do not have a refractory period to trigger, a refractory period may be present in some instances (2–4% for SUNCT and 3–18% for SUNA) (22,25). This variability makes differentiating SUNHA from trigeminal difficult.
Pathophysiology
The pathophysiology of SUNHA involves a complex interplay between the central and peripheral mechanisms involving the posterior hypothalamus and potential trigeminal sensory root demyelination. Several imaging studies in patients with SUNCT support activation of the hypothalamus and pain-sensitive structures (Table 3).
Neuroimaging findings in SUNCT
CI, confidence interval; DTI; diffusion tensor imaging; MR, magnetic resonance; MRI, magnetic resonance imaging; NVC; neurovascular contact; OR, odds ratio; SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms
*Six consecutive spontaneous attacks lasting from 36 to 96 seconds, with interattack intervals of 2 to 3.5 minutes.
Twenty-one provoked attacks by touching the upper with lower lip lasting about 25 seconds.
Reference numbers indicated in parenthesis.
Central role of the posterior hypothalamus
The intense cranial autonomic symptoms associated with pain are thought to originate centrally. This condition shares the central disinhibition of the trigeminal autonomic reflex with other trigeminal autonomic cephalalgias (34,35). The posterior hypothalamus, which regulates pain and autonomic pathways, specifically the trigeminovascular nociceptive pathway, is implicated in this mechanism (36). Dysfunction of this pathway may catalyze the excessive production of the nociceptive orexin B, thus activating the trigeminohypothalamic tract and subsequently initiating the pain pathway. Previous functional magnetic resonance imaging (MRI) studies demonstrated thalamic activation during attacks (20,37,38). Secondary activation of the cortical regions after engagement of the trigeminocervical complex intensifies the pronounced pain characteristic of this disorder (39).
Peripheral mechanisms and parallels with trigeminal neuralgia
The clinical similarities between SUNCT and trigeminal neuralgia, coupled with the observation that many patients with SUNCT have ipsilateral trigeminal neurovascular compression corresponding to the pain side, suggest the involvement of peripheral mechanisms in the complex pathophysiology (28). In some patients with SUNCT and SUNA, vascular compression with irritation of the trigeminal sensory root may explain short and intense episodes of pain and triggerability. In support of this, a previous study analyzing MR tractography in two SUNCT cases observed delineated structural changes in the trigeminal nerve secondary to vascular compression (40). A recent high-resolution MRI study of both SUNCT and SUNA found more vascular contact with the symptomatic trigeminal nerve than with the non-symptomatic side. The contact with the artery, particularly at the proximal and superior segments, was greater on the symptomatic side. Vascular contact with morphological changes was a predictor of the symptomatic side (odds ratio = 2.80, 95% confidence interval = 1.44–5.44, p = 0.002) (Table 3) (27,40).
The autonomic features of SUNHA arise from activation of the trigeminal nucleus caudalis by the contacted trigeminal nerve, followed by stimulation of the superior salivatory nucleus and sphenopalatine ganglion, ultimately triggering the trigemino-parasympathetic reflex.
Differential diagnosis
SUNCT and SUNA can be differentiated from other trigeminal autonomic cephalalgias, including paroxysmal hemicrania, cluster headache, trigeminal neuralgia and primary stabbing headache. The key features of differentiation between other trigeminal autonomic cephalalgias are the duration and frequency of pain and treatment response to indomethacin, and between trigeminal neuralgias are their associated autonomic features and response to carbamazepine (Table 4).
SUNHA, short-lasting unilateral neuralgiform headache attacks.
Paroxysmal hemicrania
Paroxysmal hemicrania is a rare type of trigeminal autonomic cephalalgia characterized by brief and extremely severe unilateral pain episodes, often accompanied by cranial autonomic symptoms. The most distinct difference between the SUNCT/SUNA is the absolute response to indomethacin for pain relief. In paroxysmal hemicrania, the majority of attacks are spontaneous, but they can also be triggered by mechanical actions such as head movements and alcohol ingestion (41,42). By contrast, SUNCT/SUNA do not respond to indomethacin and can be triggered by cutaneous factors such as touch, chewing or talking.
Cluster headache
Cluster headache and SUNCT share several similarities, such as side-lock unilateral orbital, supraorbital and temporal pain of severe intensity, clustering of attacks, and profound ipsilateral cranial autonomic symptoms (43,44). SUNCT can be referred to as cluster headache by a primary physician who is unfamiliar with the subtypes of trigeminal autonomic cephalalgia.
Unlike cluster headaches, SUNCT attacks last for less than 10 minutes, and usually do not respond to oxygen or triptan. These features help differentiate between the two painful disorders, but atypical long-lasting attacks of probable SUNCT can mimic cluster headache. In a case with both SUNCT and cluster headache, separate treatment for each disease is required (45).
Trigeminal neuralgia
Distinguishing SUNCT from trigeminal neuralgia poses a clinical challenge because of overlapping symptomatology and neuroimaging. Both conditions manifest as brief, high-frequency, unilateral headaches triggered by similar factors, and typically occur on one side of the head. Traditionally, trigeminal neuralgia lacks autonomic symptoms, exhibits a refractory period to triggers and primarily affects the second or third divisions of the trigeminal distribution, characterized by intense, shock-like, nocturnal pain compared to SUNCT. However, approximately 70% of patients with trigeminal neuralgia who undergo neurovascular decompression have at least one autonomic symptom that correlates with worse surgical outcomes, and the first division of trigeminal neuralgia is distinguished from SUNCT (46,47). By contrast, SUNCT is characterized by autonomic symptoms during attacks and usually does not have a refractory period for triggering. Medical treatment responses also differ; trigeminal neuralgia often responds to carbamazepine, oxcarbazepine or pregabalin, whereas SUNCT may respond to lamotrigine or intravenous lidocaine (13,48).
Primary stabbing headache
Primary stabbing headaches typically lack a specific localization pattern, resulting in pain attacks that radiate in multiple directions from onset. The attacks usually do not encompass the area innervated by the trigeminal nerve and are very short, lasting one second or less (49,50). They occur spontaneously and are the sole symptoms of primary stabbing headaches, often without any accompanying autonomic symptoms. By contrast, the pain associated with SUNCT/SUNA follows a unilateral trigeminal distribution. The duration of the attacks is known to range from one to 600 seconds, with the majority lasting longer than ten seconds. The most distinctive features of SUNCT and SUNA compared to primary stabbing headache are the presence of accompanying autonomic symptoms, and attacks can be triggered by cutaneous stimuli on the trigeminal innervated areas (51–53).
Secondary short‑lasting unilateral neuralgiform headache attacks
Secondary causes of SUNCT have also been reported. The most commonly affected secondary cause of SUNCT was the pons, involving the trigeminal nerve root entry zone (53,54). The second most common location was the cavernous sinus, which includes the pituitary gland (55). Additionally, there have been cases of lesions in the medulla and ocular lesions (56,57). Figure 1 provides information on the locations of secondary causes associated with SUNCT and compares them with cluster headache and trigeminal neuralgia.
Location of secondary causes associated with SUNCT, cluster headache and trigeminal neuralgia. SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing.
Secondary causes of trigeminal neuralgia are frequently found in the root entry zone, pons and medullary lesions. In the case of cluster headache, secondary causes are most commonly found in the cavernous sinus, followed by the paranasal sinus and carotid artery lesions (58–60).
Treatment
As a result of the very brief duration of attacks in SUNHA, preventive treatment has become the primary approach rather than acute attack therapy strategies. Figure 2 illustrates the recommended treatment option for SUNCT/SUNA.
Treatment option for SUNHA, SUNCT and SUNA. SUNHA, short-lasting unilateral neuralgiform headache attacks: SUNCT, short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing; SUNA, short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms.
Preventive medical treatment
Lamotrigine is the most effective preventive treatment and is considered the drug of choice for the preventive treatment of SUNHA (61). When using lamotrigine, it is important to titrate the dose slowly because of potential drug-related side effects. An excellent response to lamotrigine was reported in five patients with SUNCT, and a dose-response relationship was found, with the maximum effect observed at a higher dose of 200 mg/day (62). A higher dose of up to 600 mg/day was associated with a moderate-to-good response in 62% of the cases, and tolerability of doses up to 700 mg/day was reported (20). Lamotrigine is known for its efficacy in episodic SUNCT. However, chronic SUNCT and SUNA can be challenging to treat, and high doses of medication may be necessary before considering them ineffective (23).
Other suggested preventive treatment options included oxcarbazepine (46% response rate), duloxetine (30% response rate), carbamazepine (26% response rate), topiramate (25% response rate), pregabalin (10% response rate) and gabapentin (10% response rate). A recent audit demonstrated that topiramate was more effective in patients with SUNCT compared to SUNA patients (25). Gabapentin, used with responder rates ranging from 27% to 48%, tended to benefit SUNA patients more than SUNCT (63,64).
Transitional treatment and the next options for treatments
There can be a lag of several days to a few weeks before the efficacy of preventive treatments becomes apparent (22). Transitional treatments that rapidly suppress attacks for a limited period can be used while waiting for the beneficial effects of preventive treatments to become evident.
Occipital nerve blocks can be used as transitional treatments. Occipital nerve block utilized 80 mg of methylprednisolone and 2 ml of 2% lidocaine, with a reported improvement rate of 27% (13). In cases of severe exacerbation of SUNCT and SUNA, intravenous lidocaine can be considered, which shows a 97% response rate (48,65). Intravenous lidocaine was started at 1 mg/min, dosed up to 2 mg/min after four hours, until a significant decrease in pain level or pain freedom was achieved for 12–24 hours, in less than seven days. The detailed protocols are presented in supplementary Table 1. The efficacy of oral or intravenous corticosteroid is controversial, but it can be considered as the next option (13,25,34).
Botulinum toxin therapy has shown promise for treating refractory SUNCT/SUNA, similar to its efficacy in trigeminal neuralgia (32). Similar to trigeminal neuralgia, 2.5–5 units of botulinum toxin are injected just below the epidermis at pain sites, spaced 1.5 cm apart in a grid pattern, for a total of 75–100 units (66). Additionally, the effects of anti-calcitonin-gene-related peptide monoclonal antibodies, erenumab and galcanezumab, have been reported in SUNCT, making them potential considerations for refractory patients (67,68).
Surgical treatment
Several surgical approaches have been used to treat SUNHA. Several surgical treatments, including microvascular decompression (MVD), occipital nerve stimulation (ONS) and deep brain stimulation (DBS), have demonstrated effectiveness in the management of medically intractable SUNHA.
Williams and Broadley (11) reported that a significant proportion (88%) of patients with SUNCT and SUNA exhibited vascular loops in contact with the trigeminal nerve, suggesting that MVD is a potential treatment option. Previous case reports and a small case series suggested a beneficial effect of trigeminal MVD in SUNHA, with 63% of patients achieving pain-free outcomes (69,70). In a recent largest prospective study on trigeminal MVD, 79% of patients (37 of 47 patients) obtained an excellent or good response and 66% of patients (31 of 47 patients) remained excellent/good responders at final follow-up with the mean ± SD of 57.4 ± 24.3 months (range 11–96 months) (24).
Miller et al. (71) presented findings from 31 patients with SUNHA treated with ONS, showing a 69% improvement in attack frequency, a 77% response rate, reduced attack severity by 4.7 points and shorter attack durations. Recurrence often occurs after battery failure or stimulator deactivation, with a low rate of adverse events (3% superficial wound infection).
In an open-label study, 11 patients underwent ipsilateral ventral tegmental area DBS, resulting in a median improvement of 78% in daily attack frequency, an 82% response rate and some patients experiencing extended pain-free periods. The headache load improved by 99%, with mild adverse events, including incision site pain, minor implant-related issues, oscillopsia and one patient requiring system removal as a result of a wound infection (72).
However, when considering surgical options, it is essential to weigh factors such as invasiveness, associated risks, need for implanted hardware and treatment costs.
Clinical implications
SUNHA is characterized by prominent, strict, unilateral cranial autonomic symptoms and short-lasting neuralgiform headaches easily triggered by various cutaneous or intraoral stimuli. Lamotrigine is the first choice of treatment for SUNHA, and topiramate, oxcarbazepine and gabapentin can be a second option. Intravenous lidocaine may be considered for the management of acute exacerbation of intractable pain. Neurovascular compression is often observed in SUNHA. If there is evidence of vascular contact on the symptomatic side of the trigeminal nerve, especially at the proximal segment and superior point, considering neurovascular decompression may be warranted.
Supplemental Material
sj-pdf-1-cep-10.1177_03331024241232256 - Supplemental material for SUNCT, SUNA and short-lasting unilateral neuralgiform headache attacks: Debates and an update
Supplemental material, sj-pdf-1-cep-10.1177_03331024241232256 for SUNCT, SUNA and short-lasting unilateral neuralgiform headache attacks: Debates and an update by Mi-Kyoung Kang and Soo-Jin Cho in Cephalalgia
Footnotes
Author contributions
Soo-Jin Cho. Mi-Kyoung Kang were responsible for the conceptualization, analysis, writing the draft manuscript, reviewing and editing, and giving final approval to the final version of the manuscript submitted for publication.
Declaration of conflicting interests
The authors declare that there are no potential conflicts of interest with respect to the research, authorship and/or publication of this article.
Funding
No funding was received.
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References
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