International Headache Society (IHS) code and diagnosis: 3.3 Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT)

World Health Organization (WHO) code and diagnosis: This syndrome is not recognized in the current edition of the International Classification of Disease (ICD).

Short description: This syndrome is characterized by strictly unilateral, severe, neuralgic attacks centred on the ophthalmic trigeminal distribution that are brief in duration and very often occur in association with prominent lacrimation and redness of the ipsilateral eye.

Previously used terms: None.

Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome was first described relatively recently in 1978 (64). Since then 82 cases (64 primary or idiopathic, 18 secondary or symptomatic cases) have been reported in the English language literature. The prevalence and incidence of SUNCT are not known, though the extremely low number of reported cases suggests that it is a very rare syndrome. Primary SUNCT has a slight male predominance (35 males, 29 females) with a sex ratio of 1.2:1. In an earlier review of SUNCT syndrome the male predominance among primary cases was greater than that reported here, with a sex ratio of 3.75 (15 males, 4 females) (52). The trend toward decreasing male:female ratios over time probably reflects an ascertainment issue. The typical age of onset is between 35 and 65 years (69% of primary SUNCT cases), though it ranges from 10 to 77 years (mean 50 ± 15 years) (36).

The trigeminal autonomic cephalgias (TACs) are a group of primary headache disorders characterized by unilateral trigeminal distribution pain that occurs in association with ipsilateral cranial autonomic features (17). The group comprises SUNCT, paroxysmal hemicrania (PH), and cluster headache (CH). Any pathophysiologic construct for TACs must account for the two major clinical features characteristic of the various conditions that comprise this group: trigeminal distribution pain and ipsilateral autonomic features. The pain-producing innervation of the cranium projects through branches of the trigeminal and upper cervical nerves to the trigeminocervical complex, from which nociceptive pathways project to higher centers. This implies an integral role for the ipsilateral trigeminal nociceptive pathways in TACs. The ipsilateral autonomic features suggest cranial parasympathetic activation and sympathetic hypofunction. Goadsby and Lipton have suggested that the pathophysiology of the TACs revolves around the disinhibition of the trigeminal-autonomic reflex (17). There is considerable experimental animal literature to document that stimulation of trigeminal afferents can result in cranial autonomic outflow, the trigeminal-autonomic reflex (44). In fact, some degree of cranial autonomic symptomatology is a normal physiologic response to cranial nociceptive input (16,43) and patients with other headache syndromes may report these symptoms (1,3,6). The distinction between the TACs and other headache syndromes is the degree of cranial autonomic activation (18).

Cranial autonomic symptoms are likely to be prominent in the TACs due to a central disinhibition of the
trigeminal-autonomic reflex (18). Supporting evidence is emerging from functional imaging studies: a functional magnetic resonance imaging (fMRI) study in SUNCT (42) (see Fig. 98-1) and a positron emission tomography (PET) study in CH (41) have both demonstrated ipsilateral hypothalamic activation. Hypothalamic activation is specific to these syndromes and is not seen in migraine (2,71) or experimental ophthalmic trigeminal distribution head pain (45). There are direct hypothalamic-trigeminal connections (34) and the hypothalamus is known to have a modulatory role on the nociceptive (10,70) and autonomic pathways (33). Hence, SUNCT is possibly due to an abnormality in the hypothalamus, with subsequent trigeminovascular and cranial autonomic activation.

Several studies have demonstrated the diverse parasympathetic manifestations of SUNCT. Forehead sweating is usually increased during bouts (28), unlike PH, in which it is normal. Pupillary studies using pupillometry and pharmacologic approaches have revealed no abnormalities (73). Since conjunctival injection occurs during SUNCT, it is not surprising that intraocular pressure and corneal temperatures are elevated during attacks (67), most likely reflecting local vasodilation consequent to the marked parasympathetic activation. Similarly, a report of bradycardia in association with attacks of SUNCT indicates increased parasympathetic outflow (27). Systolic blood pressure is sometimes elevated, although ventilatory function is normal (26).

Orbital phlebography is reported to be abnormal in SUNCT syndrome, with a narrowed superior ophthalmic vein and the cavernous sinus homolateral to the pain (29). This finding leads to the suggestion that SUNCT syndrome may be a form of orbital venous vasculitis (20), although there are similar reports in CH, Tolosa-Hunt syndrome, and PH (17). However, transcranial Doppler and SPECT (single photon emission computed tomography) studies have not demonstrated convincing change in the vasomotor activity (63) or cerebral blood flow during attacks of pain (55). Similarly, no intracranial vessel activation was apparent in an fMRI study (42). The hypothalamic activation and the diverse parasympathetic manifestations taken together with the paucity of evidence for vascular changes favor a central pathogenesis for SUNCT rather than a peripheral vasculitic cause.