18.1.1 Introduction

When SUNCT was first described in the 1980s, the cranial autonomic symptoms including conjunctival injection and tearing (‘C’ and ‘T’ in the nomenclature) were noted to be prominent [2]. However subsequent patients were identified with an almost identical syndrome, with cranial autonomic symptoms, but lacking either conjunctival injection or tearing or both. This syndrome was labelled SUNA (cranial ‘a’utonomic symptoms) [3]. Although the SUNCT syndrome has been validated, very limited data are available for SUNA, despite the diagnostic criteria were set to suggest that SUNCT forms a subset of a the broader SUNA entity [4]. For this reason the two conditions are currently classified as a separate subtype, although studies on this are ongoing.

18.1.2 Epidemiology

SUNCT is relatively rare, with a recent study showing a prevalence of 6.6/100,000 and an incidence of 1.2/100,000 [5]. The disorder seems to have a male preponderance, with a gender ratio of 2:1. In a small case series of nine SUNA patients, the disorder seemed to display a female preponderance with a gender ratio of 2:1. The typical age of onset is between 40 and 70 years, with a mean age of onset at 48 years [6].

18.1.3 Clinical Phenotype

Headache attacks in SUN are strictly unilateral with a slight preponderance of right-sided attacks. However patients with unilateral, side-alternating attacks and seldom patients with bilateral attacks have been reported [6]. The pain in SUN is predominantly centred over the periorbital, retro-orbital and temporal regions, though 1/3 of patients experience pain radiation in the second branch of the trigeminal territory and 1/3 of SUNA patients can experience pain in the third branch of the trigeminal territory.

Classically the attacks last a few seconds or minutes at a time, in a ‘stab’-like pattern. However these stabs can group together to give the impression of a longer-lasting attack, or if multiple stabs occur without resolution of the pain to baseline between the stabs, then a ‘sawtooth’ pattern is experienced, and this may last up to an hour [6]. This may lead to diagnostic confusion, and the syndrome may be mistaken for cluster headache or paroxysmal hemicrania. Figure 18.1 depicts the three types of attacks in SUN.

By definition, all of the SUNCT patients have both ipsilateral conjunctival injection and lacrimation accompanying the attacks. Almost half of the patients also report ipsilateral eyelid oedema, ptosis, nasal blockage and rhinorrhoea associated with their attacks. A small percent of the SUNCT patients reports facial flushing and facial sweating.

The other TACs also have agitation in their list of features; typically during an attack, patients cannot sit still and feel the need to rock or pace the floor. This is thought to be due to activation in the region of the posterior hypothalamus, which has been reported in all the TACs [7–10]. Agitation is thought to be also a feature of SUN [6], though this is not included in the current diagnostic criteria.

The vast majority of SUNCT patients could trigger their attacks by various cutaneous stimulations. Touching the face ipsilaterally to the side of the pain, chewing, eating, wind blowing on the face, washing the face and brushing teeth were the most prevalent types of triggers. Alcohol seems not to be a trigger unlike cluster headache. The majority of SUN patients denies the presence of a refractory period, which is the ability of triggering an attack immediately after the cessation of the previous one. This seems to constitute a meaningful distinguishing clinical feature to trigeminal neuralgia, which traditionally manifests refractory periods after triggered attacks [6].

The SUN headache syndromes can be episodic or chronic, just as in cluster headache or paroxysmal hemicrania. Unlike cluster headache, SUN presents more frequently with the chronic form ab initio or evolved from an episodic form. In the episodic form, bouts of SUNCT last between 7 days and 1 year and can remit for usually a year, up to 7 years [6]. In the chronic form, as in the other TACs, attacks are present for at least a year with no more than 7 days’ break [1].

18.1.4 Differential Diagnosis of SUN

The differential diagnosis of the SUN headaches includes any short-lasting unilateral headache attack with ipsilateral autonomic features, that is, cluster headache and paroxysmal hemicrania. However the attacks in PH are longer lasting and less frequent than in SUN (2–30 min, several or many attacks per day), and those in CH are longer and less frequent still (up to 180 min, from one every other day up to eight attacks per day) [1, 4]. Another clinical feature that may help differentiating SUN from the other TACs is the presence of attacks triggered by cutaneous/intraoral stimulation. These triggers do not occur in the other TACs. In complex cases or poor patient history, diagnostic trials of certain medications such as sumatriptan 6 mg subcutaneous injection, high flow oxygen (100%, 12–15 litres/minute) and indometacin can help in ruling out cluster headache and the indometacin-sensitive headaches.

SUN may also be confused with trigeminal neuralgia (TN), in view of the multiple neuralgiform short-lasting attacks of unilateral facial pain. However, although autonomic symptoms may be present in TN due to the trigeminal autonomic reflex, the autonomic symptoms are generally much more prominent in SUN [11]. Also the agitation seen in SUN is presumed to be of hypothalamic origin [12] and is a defining feature of the TACs. Furthermore the lack of refractory period between attacks of SUN [6], such that an attack of SUN can be triggered immediately on top of a previous attack, can generally distinguish SUN in its purest form from TN. SUN can coexist with TN as two separate entities [13].

18.1.5 Secondary/Symptomatic SUN

Pituitary lesions are well recognised to cause any type of headache syndrome, most commonly migraine. However studies have shown that SUNCT and SUNA are present in higher proportions in cohorts of patients with pituitary adenomata (5% in one series of 88 patients) [14] than in the general population (usually quoted as 6.6 per 100,000 population) [5]. Both micro- and macro-adenomata are able to cause a secondary SUN syndrome; therefore it is not purely due to the size of the lesion and its local mass effect; rather it is thought to be due to neurohormonal mechanisms. Table 18.2 lists some of the recognised causes of secondary SUN.

18.1.6 Diagnostic Workup

It is recommended that patients with SUNCT or SUNA, especially those with atypical features or with abnormal findings on neurological examination, should have MRI imaging of the brain, particularly to rule out any pituitary or posterior fossa lesions. Dedicated fine cut or high-resolution scanning through the trigeminal nerves should also be performed to look for neurovascular conflict to the ipsilateral trigeminal nerve [15].

18.1.7 Medical and Surgical Treatments

The management of SUN have historically been considered challenging. Due to the rarity of these disorders, no randomised placebo-controlled trials have ever been conducted. The series published so far have included very small numbers of patients and have produced data on a very limited number of medications. As far as SUNA is concerned, it is still unclear whether medications effective in SUNCT are also effective in SUNA.

18.1.8 Abortive Treatments

Since the attacks are very short lasting, abortive therapy strategies are not a useful concept in SUNCT/SUNA.

18.1.9 Preventive Treatments

Several case reports and small case series have shown the efficacy of lamotrigine in SUNCT, with a response rate of almost 70% [8]. The dose reported to be effective in SUN ranges between 50 and 600 mg/day. On the basis of the current evidence and although no randomised-controlled trials have been published, lamotrigine is at present considered the drug of choice for the preventive treatment of SUNCT [16].

Other anticonvulsants have been reported to have some effect in SUN.

Topiramate was reported to be effective in five SUNCT patients at doses up to 300 mg daily [17, 18]. Subsequently, 11 of 21 SUNCT patients (52%) benefited from topiramate given up to a dose of 400 mg/day in an open-label study, whereas the only SUNA patient treated with topiramate did not notice any benefit [8]. A placebo-controlled trial of Topiramate in SUNCT showed that three out of five patients received some benefit in reduction of attack frequency or attack load [19].

Zonisamide, which has got similar mechanisms of action to topiramate, has been tried in a SUNCT patient who did not tolerate carbamazepine with excellent results on long-term follow-up [20].

SUNCT has been shown to respond to gabapentin, with complete suppression of attacks in three of nine patients treated with 800 to 2700 mg daily [21–23]. When tried in an open-label fashion in 22 SUNCT and 5 SUNA patients at up to 3600 mg daily, it was reported to be effective in 60% of SUNA but only 45% of SUNCT patients [8].

Carbamazepine was beneficial in 11 of 33 (33%) of SUNCT patients. Among these, 8 of the 33 patients had a partial response, and 3 had a complete or almost complete response [24]. In a recent open-label series of 36 SUNCT and 5 SUNA patients treated with carbamazepine, 40% of SUNCT and 20% of SUNA patients reported a favourable response [8]. Two case reports only support the effectiveness of oxcarbazepine in the prevention of SUNCT [25, 26].

OnabotulinumtoxinA infiltrated at four points around the orbit, 10 U at each site, was reported to be consistently effective in a SUNCT patient refractory to oral treatments after 2.5 years of follow-up [27].

18.1.10 Transitional Treatments

There can be a lag of several days to a few weeks before the efficacy of preventive treatments becomes apparent. Transitional treatments, which produce a rapid suppression of the attacks for a limited period of time, can be used when waiting for the beneficial effect of a preventive treatment to become evident.

The administration of intravenous (IV) lidocaine at a rate of 1.3 to 3.3 mg/kg/h suppressed the headaches in four patients with SUNCT syndrome [28]. Subsequently 11 SUNCT and 4 SUNA patients reported a favourable outcome during administration of IV lidocaine at the dose of 1.5–3.5 mg/kg/h. Seven SUNCT patients were pain free for times varying between the duration of the infusion to 6 months. Three SUNCT patients had reduced attack frequency or severity, and one was lost to follow-up. All SUNA patients were pain free for 2 days to 12 weeks [8]. It is advisable to use IV lidocaine as a short-term treatment in patients who present in a so-called SUNCT status [29] and also in order to avoid breakthrough attacks while switching from one preventive drug to another in patients with high load of attacks. Twenty-four-hour ECG monitoring is mandatory during the infusion.

A suboccipital injection of a combination of lidocaine and a steroid was beneficial in five out of eight SUNCT patients [8]. Greater occipital nerve injections may render the patient pain free for weeks or months, allowing the introduction and dose escalation of preventive medications. Oral or intravenous corticosteroids have been reported to be effective in some cases of SUNCT. Partial or complete responses have been described. However in most of the initial cases, corticosteroids were used in combination with other oral medicines, which may have potentially biased their overall effect. Similarly to cluster headache, there can be a recrudescence of pain on either lowering the dose or discontinuing the corticosteroids. Intravenous methylprednisolone was reported to suppress SUNCT attacks completely [30, 31]. More evidence is needed before recommending oral or intravenous corticosteroids for the management of SUN.

18.1.11 Surgical Management

Some patients with the chronic form of SUNCT and SUNA are refractory to the available medical treatments. The extent of this problem is unknown. This group of patients are left with severe disability. For these patients surgical approaches may be justified. The approaches can be subdivided into three main groups: ablative procedures of the trigeminal nerve, microvascular decompression of the trigeminal nerve and neurostimulation techniques.

18.1.12 Ablative Procedures of the Trigeminal Nerve

Data on ablative procedures on the trigeminal nerve are limited to isolated cases reports, and there is considerable potential for bias due to under-reporting of unsuccessful cases or those with adverse outcomes. Additionally, these procedures may have irreversible complications, such as residual hypoesthesia, anaesthesia dolorosa and keratitis. Procedures that have been tried in SUNCT syndrome include retrogasserian glycerol rhizolysis, percutaneous trigeminal ganglion compression, trigeminal ganglion thermocoagulation and gamma knife surgery. In view of the poor quality of data and the destructive nature, these procedures are not indicated in SUN.

18.1.13 Microvascular Decompression of the Trigeminal Nerve

Trigeminal microvascular decompression is considered the surgical treatment of choice for refractory trigeminal neuralgia with evidence of trigeminal neurovascular conflict [32]. In view of the clinical overlap between TN, SUNCT and SUNA, Williams and Broadley systematically looked for trigeminal neurovascular conflict with dedicated trigeminal MRI scans and found a high proportion of ipsilateral vascular loops in contact with the trigeminal nerve in SUNCT and SUNA (88%, n = 15/17) [5]. Ninety percent of the aberrant vessels were pressing on the symptomatic trigeminal nerve, compared to only 7% abutting on the asymptomatic nerve. This supported the notion of microvascular decompression (MVD) being a potential treatment for these conditions. To date, ten case reports and a case series of nine SUNCT and SUNA patients, who underwent MVD of the trigeminal nerve, have been reported [33–39]. After a median follow-up of 14 months (range: 0.5–32 months), 12 of 19 (63%) of cases were pain free, whereas in the remaining patients, the procedure had little or no effect. Two patients suffered from persistent complications, such as ataxia and hearing loss, whereas in five cases transient complications were only reported. Although series with longer follow-ups would be ideal to assess the long-term efficacy of MVD for chronic medically intractable SUNCT/SUNA, at present this approach may be considered a valuable option in refractory patients with ipsilateral trigeminal nerve compression due to a vascular loop, though possible benefit should be weighed against operation-related risks of permanent neurological deficits.

18.1.14 Peripheral and Central Neurostimulation