The Journal of the Lebanese Dental Association Official organ of the Lebanese Dental Association

Trigeminal autonomic cephalalgias are a group of disabling and excruciating primary headache disorders, consisting of cluster headaches, paroxysmal hemicrania, and short-lasting unilateral neuralgiform headaches with conjunctival injection and tearing (SUNCT). The attacks are strictly unilateral, presenting predominantly in the orbital, peri-orbital, and temporal regions, although pain may radiate to teeth and jaws. Pain is typically accompanied by prominent ipsilateral cranial autonomic symptoms. Ppathophysiology of these disorders is unknown and has therefore driven a number of studies using a variety of neuroimaging modalities in an attempt to unravel this. In this paper, we review the literature for neuroimaging studies that have been performed in these headache disorders and present their findings. 1 Ph.D student, Department of Oral Surgery, Dental Institute, King’s College, London-KCL, England, UK 2 Consultant Oral Surgeon, Professor and Head, Department of Oral Surgery, Dental Institute, King’s College, LondonKCL, England, UK * Fellow of the Higher Education Academy 14 Journal of the Lebanese Dental Association Volume 48 No 2 December 2013 SUNCT, cranial autonomic features (especially conjunctival injection and tearing) are prominent features and pain is often predominantly in the ophthalmic distribution of trigeminal nerve (V1). Moreover, patients with SUNCT are usually able to trigger an attack immediately following the previous one, thus do not have a refractory period.1,5 Hemicrania Continua (HC), described and coined in 1984 by Sjaastad and Spierings, features continuous head pain (continua) and unilaterality of head pain (hemicrania). Pain is moderate, rarely approaching a high intensity level, with nocturnal awakenings, but most patients are able to work. Several theories have been put forward in an attempt to explain the pathophysiology behind this group of headaches. Cluster headache was initially thought to be a vascular headache originating from an inflammation within cavernous sinus. Resulting venous stasis causes pressure on trigeminal nerve and simultaneously activates intersecting parasympathetic and sympathetic nerves, eliciting pain and autonomic symptoms respectively.2-5 Moreover, vasoconstrictive effect of sumatriptan, a 5-hydroxytryptamine (5-HT)* agonist, in aborting these attacks, further supported this hypothesis.6,7 However, this theory could not explain circadian rhythmicity of attacks. Hence, it was superseded by the hypothalamic theory. Circadian and seasonal periodicity of cluster headaches indicate a possible central involvement, with the human biological clock implicated as a potential site. This is situated in the suprachiasmatic nucleus within the hypothalamus, which is also responsible for regulating hormonal activities. This correlated with the findings of a significant decrease in plasma testosterone levels in male cluster headache patients. A reduced response to thyrotropin-releasing hormone further supported this hypothesis. Furthermore, a blunted nocturnal peak in melatonin**, a circadian system biomarker, has been found in patients with cluster headache.4,6 This concept of a possible central involvement has led to much of the neuroimaging studies in this group of headaches, in an attempt to unravel the pathophysiological basis of these rare disorders. Much of the work done in this field has concentrated on cluster headaches, with few studies on paroxysmal hemicrania and SUNCT. However, due to their distinctive clinical phenotype, this group of disorders are assumed to have the same pathophysiological basis. This review aims to highlight the various methods used and the main findings of these studies. NITROGLYCERIN: A RELIABLE TRIGGER? The episodic nature of cluster headache makes it difficult to capture data on patients during spontaneous attacks, thus most neuroimaging studies to date have been performed on evoked attacks. The use of nitroglycerin (a potent vasodilator prescribed in angina pectoris and chronic heart failure) as a triggering agent has been studied by Ekbom8 who deduced that attacks are inducible whilst patients are in their cluster period, with sensitivity being highest in the middle of a bout and gradually reducing towards the end. The onset of the attack ranges from 30-50 minutes following administration of nitroglycerin, and it is preceded by a fairly transient pulsation and pressure in temples and forehead. There is a refractory period of 6-8 hours following an attack and patients outside their cluster bout remain insensitive to provocation. The first positron emission tomography (PET) study on cluster headache was performed by Hsieh and associates9 in 1996, using butanol as the tracer for regional cerebral blood flow (rCBF). They studied four right-handed patients during their active cluster period, two with right-sided and two with left-sided attacks. The headaches were elicited within 18-35 minutes of administration of 1 mg sublingual nitroglycerin and successfully terminated following subcutaneous administration of sumatriptan (a synthetic drug of the triptan class, prescribed in migraine headaches). A 100 mm visual analogue scale (VAS) was used to enable patients to rate their headache intensity. Each patient underwent six scans: two at baseline (10 minutes apart), one following nitroglycerin administration, two following onset of cluster headaches (10 minutes apart) 15 Journal of the Lebanese Dental Association * 5-hydroxytryptamine or serotonin is a monoamine neurotransmitter primarily found in GI tract, patelet, and CNS. It is popularly thought to be a contributor to feelings of well-being and happiness. **Melatonin (N-acetyl-5-methoxytryptamine) is a hormone that entertains circadin rhythms of several biological functions. It also protects nuclear and mitochondrial DNA and has a pervasive and antioxidant roles. Abu Bakar N, Renton T