Cluster Headache: Epidemiology, Pathophysiology, Clinical Features, and Diagnosis

Abstract

Cluster headache is a primary headache disorder affecting up to 0.1% of the population. Patients suffer from cluster headache attacks lasting from 15 to 180 min up to 8 times a day. The attacks are characterized by the severe unilateral pain mainly in the first division of the trigeminal nerve, with associated prominent unilateral cranial autonomic symptoms and a sense of agitation and restlessness during the attacks. The male-to-female ratio is approximately 2.5:1. Experimental, clinical, and neuroimaging studies have advanced our understanding of the pathogenesis of cluster headache. The pathophysiology involves activation of the trigeminovascular complex and the trigeminal-autonomic reflex and accounts for the unilateral severe headache, the prominent ipsilateral cranial autonomic symptoms. In addition, the circadian and circannual rhythmicity unique to this condition is postulated to involve the hypothalamus and suprachiasmatic nucleus. Although the clinical features are distinct, it may be misdiagnosed, with patients often presenting to the otolaryngologist or dentist with symptoms. The prognosis of cluster headache remains difficult to predict. Patients with episodic cluster headache can shift to chronic cluster headache and vice versa. Longitudinally, cluster headache tends to remit with age with less frequent bouts and more prolonged periods of remission in between bouts.

Keywords: Cluster headache; diagnosis; epidemiology; pathophysiology; trigeminal autonomic cephalalgias.

Figure 1

Cluster headache pathophysiology. Pain afferents from the trigeminovascular system traverse the ophthalmic division of the trigeminal nerve, taking signals from the cranial vessels and dura mater (shown by purple fibers). These inputs synapse in the TCC and project to higher brain structures such as the thalamus (T) and cortex resulting in pain perception (shown in blue fibers). Activation of the trigeminovascular system by stimulation of dural structures also causes neuronal activation in the SSN within the pons, which is the origin of cells for the cranial parasympathetic autonomic vasodilator pathway. There is subsequent activation of this parasympathetic reflex through the outflow from the SSN and is relayed through the SPG (shown by pink fibres), but also through the facial (VII^th cranial) nerve (not shown). Activation of both trigeminal and autonomic nerves defines the trigeminal autonomic reflex arc, which is integral to the pathophysiology of cluster headache and the other TACs. The HT is functionally connected to the ipsilateral trigeminal system and other brain areas of the pain matrix. Red dashed lines indicate the pathways by which the HT controls or triggers pain. A third-order sympathetic nerve lesion thought to be caused by vascular changes to the ICA in the cavernous sinus with subsequent irritation of the local plexus of nerve fibers, can give rise to sympathetic symptoms (incomplete Horner syndrome) (shown by yellow fibers). IML = Intermediolateral tract of spinal cord, SCG = Superior cervical ganglion, SN = Suprachiasmatic nucleus, TCC = Trigeminocervical complex, SSN = Superior salivatory nucleus, SPG = Sphenopalatine ganglion, HT = Hypothalamus, ICA = Internal carotid artery