Short-lasting unilateral neuralgiform headache attacks: Clinical features and diagnosis

INTRODUCTION AND CLASSIFICATION — The trigeminal autonomic cephalalgias (TACs) are a group of primary headache disorders characterized by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features [1,2]. The TACs include cluster headache, paroxysmal hemicrania, short-lasting unilateral neuralgiform headache attacks, and hemicrania continua [3].

There are two subtypes of short-lasting unilateral neuralgiform headache attacks [3,4]:

●Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)

●Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)

The clinical features and diagnosis of SUNCT and SUNA will be reviewed here. The management of these syndromes are discussed separately. (See "Short-lasting unilateral neuralgiform headache attacks: Treatment and prognosis".)

Other TACs are discussed elsewhere.

●(See "Cluster headache: Epidemiology, clinical features, and diagnosis" and "Cluster headache: Treatment and prognosis".)

●(See "Paroxysmal hemicrania: Clinical features and diagnosis" and "Paroxysmal hemicrania: Treatment and prognosis".)

●(See "Hemicrania continua".)

HISTORICAL ASPECTS — SUNCT is a rare primary headache syndrome first reported in 1978 [5] and later described more fully [6,7]. In 2004, SUNCT syndrome was included in the International Classification of Headache Disorders, 2^nd edition [8], as was the related syndrome SUNA. In 2013, both SUNCT and SUNA were classified as subtypes of short-lasting unilateral neuralgiform headache attacks (table 1) by the International Classification of Headache Disorders, 3^rd edition beta [3].

EPIDEMIOLOGY — Both SUNCT and SUNA are rare headache syndromes, but the prevalence and incidence are uncertain. A study from Australia reported an estimated annual incidence of 1.2 per 100,000 and prevalence of 6.6 per 100,000 [9]. By contrast, an epidemiologic study from Norway found two subjects with SUNCT-like syndromes among a group of 1838 subjects, corresponding to a prevalence of 109 per 100,000 [10].

The typical age of onset is between 30 and 60 years but may range from 5 to 88 years [11-13]. The largest case series found the mean age of onset for SUNCT and SUNA was approximately 44 years [13].

SUNCT and SUNA have a female predominance [13]. The female-to-male ratio is 1.7:1, with the female preponderance being more pronounced in patients with SUNA (2.4:1) compared with those with SUNCT (1.2:1) [13].

There is one reported kindred of a family history of SUNCT [14]. However, SUNCT and SUNA are so rare that an accurate evaluation of their genetic status is difficult.

CLINICAL FEATURES — SUNCT and SUNA are characterized by sudden brief attacks of severe unilateral head pain in any of the three divisions of the trigeminal nerve accompanied by ipsilateral cranial autonomic symptoms [13,15].

For patients with SUNCT, the ipsilateral autonomic symptoms consist of both conjunctival injection and lacrimation. For those with SUNA, the autonomic symptoms may include either conjunctival injection or lacrimation but not both. Otherwise, the presence of cranial autonomic symptoms for SUNCT and SUNA is similar and may include nasal congestion, rhinorrhea, miosis, ptosis, eyelid edema, or forehead and facial sweating and/or flushing [16].

Site of pain — The pain in SUNCT and SUNA is unilateral and commonly located in ophthalmic (V1) and maxillary (V2) divisions of the trigeminal nerve; however, up to one-third of patients also have involvement in the mandibular (V3) division [13]. On rare occasions, the pain can radiate to the occiput, neck, or ear [13,15].

Temporal profile of individual attacks — The International Classification of Headache Disorders, 3^rd edition criteria for short-lasting unilateral neuralgiform headache attacks specify an attack length of 1 to 600 seconds, with an attack frequency of at least once a day for more than half the time when the disorder is active [3].

Patterns of attack recurrence — In a series of 43 patients with SUNCT and 9 with SUNA, attacks were categorized into one or more of four forms (figure 1) [15]:

●Single stabs of pain with a median duration of 58 seconds (interquartile range [IQR] 10 to 120 seconds)

●Repetitive stabs of pain with a median attack duration of 180 seconds (IQR 60 to 300 seconds)

●"Saw-tooth" attacks of continuous pain with multiple superimposed stabs (serrated attacks) with a median attack duration of 240 seconds (IQR 60 to 420 seconds)

●Plateau-type attacks with a median duration of 300 seconds (IQR 20 to 600 seconds)

Almost half of patients have more than one of these different forms of attacks [13], and there is wide interpatient variation in both the length of attacks and number of attacks per day [15]. SUNCT patients appear more likely to experience single stabs, and SUNA patients more likely to experience repetitive stabs. The saw-tooth and plateau patterns may occur with similar frequency in both SUNCT and SUNA [17].

Lack of refractory period between attacks — SUNCT and SUNA symptoms generally do not have a refractory period [6,13,15,18]. In a review with data available for 93 patients with SUNCT and SUNA, there was no refractory period in 90 percent [16]. In the largest series, spontaneous or triggered attacks could occur immediately after cessation of the previous attack in 84 percent of SUNCT and 79 percent of SUNA [13]. Only 7 percent of patients had a refractory period, typically lasting between 2 and 10 minutes.

Periodicity — In some cases, SUNCT or SUNA is an episodic disorder, with bouts of attacks alternating with remissions. In a report of 21 patients with SUNCT, symptomatic bouts typically occurred once or twice a year and lasted from days to months, with remissions lasting months at a time [6]. Results from another series of 24 patients with SUNCT or SUNA suggested that the episodic form (attacks lasting seven days to one year, separated by a pain-free period lasting one month or longer) was more common than the chronic form (14 versus 10 subjects) [9]. However, the time since diagnosis was relatively short for most of the patients in this series, and the natural progression of these syndromes points to a tendency to become chronic.

By contrast, a large series of 133 patients with longer follow-up reported chronic symptoms was noted in 62 of 70 patients (89 percent) with SUNCT and 58 of 63 patients (92 percent) patients with SUNA [13].

Interictal pain — Background pain between attacks is present in some patients with SUNCT and SUNA. In one series, persistent background pain was present in 53 percent of patients with SUNCT and 43 percent of those with SUNA [13]. While one series reported that a history of migraine was associated with an interictal headache [17], a larger prospective series did not confirm this finding [13].

Triggers — Multiple triggers have been associated with short-lasting unilateral neuralgiform headache attacks [6,13,19]:

●Touching the face or scalp

●Bathing or showering

●Washing or brushing hair

●Shaving

●Nose blowing

●Chewing or eating

●Brushing teeth

●Talking

●Valsalva maneuvers

●Exercise

●Bright light (including sunlight and fluorescent lights)

Neck movement may precipitate attacks in some patients or abort attacks in others [6,7,20]. Some triggers characteristically associated with cluster headache, such as alcohol, smoke, strong smells, or a warm environment, may also trigger SUNCT or SUNA [21].

Most patients have either a mixture of spontaneous and triggered attacks or purely spontaneous attacks, but purely triggered attacks are rare, occurring in only 4 percent [13]. A potential explanation is that some cases of purely triggered attacks may be incorrectly diagnosed with trigeminal neuralgia. Thus, it is useful to recognize that occasional patients with SUNCT may experience only triggered attacks.

Neurologic examination — The neurologic examination is usually normal in patients with short-lasting unilateral neuralgiform headache attacks, although ipsilateral trigeminal sensory findings are present in occasional patients. In our series, abnormal sensation to pinprick (mainly hypesthesia) in trigeminal V1 or V2 distribution was present in 6 of 43 patients (14 percent) with SUNCT and 2 of 9 with SUNA [15]. Others have reported allodynia or hyperesthesia in the face [6,22-24], a sensory deficit of the ophthalmic (V1) division of the trigeminal nerve [25], and a persistent ipsilateral Horner syndrome [26].

DIAGNOSIS — The diagnosis of SUNCT or SUNA is based upon a compatible clinical history, typically in the setting of a normal neurologic examination. The diagnosis is supported by a lack of response to indomethacin and oxygen.

Brain magnetic resonance imaging (MRI) is suggested for all patients being evaluated for SUNCT and SUNA. (See 'Neuroimaging' below.)

Diagnostic criteria — The diagnosis of short-lasting unilateral neuralgiform headache attacks, according to the International Classification of Headache Disorders 3rd edition (ICHD-3), requires fulfilling all of the following criteria (table 1) [3]:

●At least 20 attacks

●Attacks consist of moderate or severe unilateral head pain, with orbital, supra-orbital, temporal and/or other trigeminal distribution, lasting for 1 to 600 seconds and occurring as single stabs, a series of stabs, or in a saw-tooth pattern

●At least one of the following cranial autonomic symptoms or signs occurs ipsilateral to the pain:

•Conjunctival injection and/or lacrimation

•Nasal congestion and/or rhinorrhea

•Eyelid edema

•Forehead and facial sweating

•Miosis and/or ptosis

●Attacks have a frequency of at least one a day for more than half of the time when the disorder is active

●Not better accounted for by another ICHD-3 diagnosis

SUNCT is diagnosed if both conjunctival injection and lacrimation (tearing) occur ipsilateral to the pain [3]. SUNA is diagnosed if only one or neither of conjunctival injection and lacrimation occurs. SUNCT syndrome may be a subform of SUNA. A comparative study of SUNCT and SUNA found no major clinical differences between these subtypes [13].

Both SUNCT and SUNA can occur as episodic or chronic conditions [3]:

●Episodic forms are characterized by at least two bouts of attacks occurring in periods lasting from seven days to one year (when untreated), separated by pain-free periods lasting three months or more

●Chronic forms are characterized by attacks occurring for more than one year without remission, or with remission periods lasting less than three months

Distinguishing features — Ascertaining the length and type of attacks is necessary to distinguish SUNCT and SUNA from other trigeminal autonomic cephalalgias, and thus obtaining a good history is paramount. This point is particularly important when the episodes consist of a series of saw-tooth pattern attacks or groups of stabs that have a longer duration [3]. (See 'Temporal profile of individual attacks' above and 'Diagnostic criteria' above.)

The presence of a cutaneous trigger and the lack of a refractory period between attacks, as well as the prominence of cranial autonomic symptoms, distinguish SUNCT from trigeminal neuralgia. In addition, cutaneous (or other) triggering of attacks and the lack of a response to indomethacin distinguish SUNCT from paroxysmal hemicrania and from hemicrania continua, which are both indomethacin-responsive.

Neuroimaging — Neuroimaging is useful to exclude SUNCT or SUNA caused by pituitary, posterior fossa, or focal lesions.

For the initial evaluation of SUNCT/SUNA symptoms, we suggest brain MRI for patients with either a normal or abnormal neurologic exam because of the possibility of underlying or alternative diagnoses. Imaging should include sequences to assess the posterior fossa and pituitary structures. (See 'Secondary headache' below and "Causes, presentation, and evaluation of sellar masses".)

Response to treatment — The diagnosis of SUNCT and SUNA is supported by a lack of response to indomethacin or oxygen, and by a good response to intravenous lidocaine.

To exclude other trigeminal autonomic cephalalgia headache syndromes and aid in the diagnosis of SUNCT and SUNA, we suggest trials of indomethacin and oxygen [27]. In a cohort of 10 patients with SUNCT and four with SUNA, the response to intramuscular indomethacin was no different than the response to saline placebo in all patients (ie, the test was negative, ruling out paroxysmal hemicrania and hemicrania continua), and oxygen was ineffective in all (ie, suggesting that the diagnosis was not cluster headache) [27].

●Indomethacin – A blinded parenteral indomethacin test (the modified indotest) is useful to rule out paroxysmal hemicrania and hemicrania continua [28,29]. This test is performed in two consecutive sessions with patients at baseline pain. In one session, indomethacin 100 mg is given by intramuscular injection. In the other session, saline placebo is given by intramuscular injection. A positive test requires a significant reduction in attacks after indomethacin but not after placebo. However, intramuscular indomethacin is not available in some countries, including the United States.

A trial of oral indomethacin can be used to rule out paroxysmal hemicrania and hemicrania continua when parenteral indomethacin is not available. Although there are variations in recommended titration schedules and dosages, we suggest a nine-day trial of oral indomethacin. During the nine-day trial, patients increase the indomethacin dose every three days (up to a maximum total daily dose of 225 mg) unless they have resolution of headache, in which case they continue at the effective dose. The starting dose is indomethacin 75 mg to 100 mg daily (given in three divided doses) for three days; the dose can then be increased if necessary to a total daily dose of 150 mg for three days, followed if necessary by a total daily dose of 200 mg to 225 mg daily (given in at least three divided doses per day) for three days. Completion of the test without headache resolution is considered a failed trial. (See "Paroxysmal hemicrania: Clinical features and diagnosis", section on 'Indomethacin trial' and "Hemicrania continua", section on 'Diagnostic indomethacin trial'.)

●Oxygen – The response to inhaled oxygen is helpful to exclude the diagnosis of cluster headache [30]. Pure (100 percent) oxygen is applied via a nonrebreathing facemask with a flow rate of at least 7 L/min (sometimes more than 10 L/min) for 15 minutes at the start of an attack with the patient sitting in an upright position. Oxygen is generally safe and without side effects. However, patients with severe chronic obstructive pulmonary disease should not be treated with inhaled oxygen because of the risk for developing severe hypercapnia and carbon dioxide (CO₂) narcosis. Oxygen is effective for up to 78 percent of patients with cluster headache. (See "Cluster headache: Treatment and prognosis", section on 'Oxygen'.)

Patients with acute symptoms due to SUNCT or SUNA typically respond to intravenous lidocaine. Infusions of intravenous lidocaine are performed in the hospital with continuous electrocardiogram monitoring and may be contraindicated in some patients, including those with cardiac conduction system abnormalities. The use of lidocaine for acute treatment of SUNCT and SUNA is discussed in greater detail separately. (See "Short-lasting unilateral neuralgiform headache attacks: Treatment and prognosis", section on 'Lidocaine'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis for SUNCT and SUNA includes the following conditions:

●Other trigeminal autonomic cephalalgias (ie, cluster headache, paroxysmal hemicrania, and hemicrania continua)

●Trigeminal neuralgia

●Secondary causes of SUNCT and SUNA, particularly a posterior fossa lesion

For cases where attacks appear to be prolonged, the main alternative diagnostic considerations are paroxysmal hemicrania and cluster headache. In cases of constant interictal pain, the main alternative diagnostic consideration is hemicrania continua. (See "Paroxysmal hemicrania: Clinical features and diagnosis" and "Cluster headache: Epidemiology, clinical features, and diagnosis".)

Trigeminal neuralgia — The diagnosis of SUNCT can be confused with trigeminal neuralgia [3]. Similar to SUNCT and SUNA, trigeminal neuralgia can be precipitated by trivial stimuli such as washing, shaving, smoking, talking, and brushing the teeth, although attacks can sometimes occur spontaneously. Neurovascular contact occurs in more than half of patients with both conditions [31-33]. (See "Trigeminal neuralgia".)

Features that may be helpful to distinguish between trigeminal neuralgia and SUNCT or SUNA include:

●Pattern of cranial autonomic features – The degree of cranial autonomic features (eg, conjunctival injection and tearing) within the ophthalmic division of trigeminal nerve is generally greater in patients with SUNCT than those with trigeminal neuralgia [15,34,35].

●Interval between attacks – The bouts of pain in trigeminal neuralgia typically remit for variable intervals, whereas interictal intervals are likelier to be regular in SUNCT and SUNA.

●Refractory period – Patients with trigeminal neuralgia typically report a refractory period after cessation of a bout of pain. SUNCT and SUNA symptoms generally do not have a refractory period [13].

However, some authors have suggested they should be classified as a cranial neuralgia rather than a trigeminal autonomic cephalalgia due to similarities with trigeminal neuralgia [36]. SUNCT and SUNA are likely to form part of a continuum with trigeminal neuralgia [31,36,37], although these syndromes are still classified independently.

Secondary headache — SUNCT and SUNA are usually a primary headache disorder. However, there are a number of cases that are potentially secondary to intracranial lesions, typically located either in the posterior fossa or in the pituitary gland, as described below. In addition, there are case reports of SUNCT following viral meningitis or meningoencephalitis [38,39] and traumatic head injury [25,40].

There is also a report of SUNCT secondary to an infraorbital metastatic bronchial carcinoid [41]. Although not in the posterior fossa, this report would meet proposed criteria to identify causal links in secondary SUNCT [42]. These criteria are the following:

●A close temporal relationship between the associated disease and the onset of pain

●Side concordance between the unilateral pain and the lesion, if localized

●Prompt remission after etiologic medical therapy, or remission after surgery; sufficient post-treatment follow-up is needed to exclude recurrence of the headache attacks or improvement due to spontaneous remission

Posterior fossa lesions — Reports of SUNCT or SUNA associated with a posterior fossa abnormality include the following cases:

●Ipsilateral cerebellopontine arteriovenous malformation [43,44]

●Brainstem cavernous hemangioma [45]

●Posterior fossa lesion associated with HIV/AIDS [1]

●Severe basilar impression causing pontomedullary compression in a patient with osteogenesis imperfecta [46]

●Craniostosis resulting in a foreshortened posterior fossa [47]

●Brainstem infarction [48,49]

●Pilocytic astrocytoma expanding to the trigeminal root entry zone [50]

●Vascular loops compressing the trigeminal nerve [15,51]

●Parietal and parieto-occipital space occupying lesions [15]

●Pathologic white matter lesions associated with multiple sclerosis [52]

●Vertebral artery dissection [53]

●Neuromyelitis optica spectrum disorder with a lesion in dorsolateral medulla [54]

●Cerebellopontine angle meningioma [55]

Pituitary lesions — SUNCT has been described in patients both with microadenomas [15,56,57] and macroadenomas [15,57-59], with attacks occurring on the side ipsilateral to the side of the tumor. In most cases, the pituitary adenomas associated with SUNCT have been prolactin or growth hormone secreting tumors. In addition, another patient with a pituitary macroadenoma had symptoms of SUNCT that were labeled as trigeminal neuralgia [60]. Headache symptoms can precede pituitary symptoms by 3 to 10 years [58,60].

The ipsilateral localization of headache suggests a role for a direct mode of action in pituitary macroadenomas, but this mechanism would not account satisfactorily for microadenomas. An alternative hypothesis is that the attacks are mediated predominantly by a neurohormonal mechanism rather than by the size or invasiveness of the tumor [59,61].

Trigeminal neurovascular loop — Neurovascular contact with morphological changes may be an underlying cause of some cases of SUNCT and SUNA. In a cohort of 80 patients with SUNCT and 79 with SUNA, the rate of neurovascular contact with the trigeminal nerve was higher on the symptomatic side (80 versus 57 percent) [31]. Neurovascular contact with morphological changes were also more prevalent on the symptomatic side (61 versus 31 percent).

These findings raise the possibility that peripheral mechanisms play a key role in the pathophysiology of SUNCT [62]. Some patients with SUNCT or SUNA may benefit from trigeminal microvascular decompression, as discussed separately. (See "Short-lasting unilateral neuralgiform headache attacks: Treatment and prognosis", section on 'Trigeminal nerve decompression'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Migraine and other primary headache disorders".)

SUMMARY AND RECOMMENDATIONS

●Classification – The trigeminal autonomic cephalalgias are a group of primary headache disorders characterized by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features. The disorders included in this category are cluster headache, paroxysmal hemicrania, hemicrania continua, and short-lasting unilateral neuralgiform headache attacks. (See 'Introduction and classification' above.)

There are two subtypes of short-lasting unilateral neuralgiform headache attacks (see 'Introduction and classification' above and 'Historical aspects' above):

•Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)

•Short-lasting unilateral neuralgiform headache attacks with cranial autonomic symptoms (SUNA)

●Epidemiology – Both SUNCT and SUNA are rare headache syndromes, but the prevalence and incidence are uncertain. The typical age of onset is between 30 and 60 years but may range from 5 to 88 years. The female-to-male ratio in SUNCT and SUNA is 1.7:1. (See 'Epidemiology' above.)

●Clinical features – SUNCT and SUNA are characterized by sudden brief attacks of severe unilateral pain commonly located in ophthalmic (V1) and maxillary (V2) divisions of the trigeminal nerve and accompanied by ipsilateral cranial autonomic symptoms. In SUNCT, the ipsilateral autonomic symptoms consist of both conjunctival injection and lacrimation. In SUNA, the autonomic symptoms may include either conjunctival injection or lacrimation but not both, and there can be other cranial autonomic symptoms (eg, nasal congestion and/or rhinorrhea, eyelid edema). (See 'Clinical features' above.)

●Attack patterns – In patients with SUNCT or SUNA, attacks can take one or more of four forms (figure 1) (see 'Clinical features' above and 'Temporal profile of individual attacks' above):

•Single stabs of pain

•Repetitive stabs

•A saw-tooth pattern of continuous pain with multiple superimposed stabs (serrated attacks)

•Plateau-type attacks

●Diagnosis and evaluation – The diagnosis of SUNCT or SUNA is based upon a compatible clinical history, typically in the setting of a normal neurologic examination, and fulfillment of diagnostic criteria (table 1). (See 'Diagnosis' above and 'Diagnostic criteria' above.)

•For the initial evaluation of patients with SUNCT and SUNA symptoms, we suggest brain magnetic resonance imaging for patients with a normal or abnormal neurologic exam because of the possibility of underlying or alternative diagnoses. Imaging should include sequences to assess the posterior fossa and pituitary structures. (See 'Neuroimaging' above.)

•The diagnosis of SUNCT or SUNA is supported by lack of response to indomethacin and oxygen and a good response to lidocaine. (See 'Response to treatment' above.)

●Differential diagnosis – The differential diagnosis for SUNCT and SUNA includes cluster headache, paroxysmal hemicrania, hemicrania continua, trigeminal neuralgia, and secondary causes of headache. (See 'Differential diagnosis' above.)