Pathophysiology of cluster headache: a trigeminal autonomic cephalgia

Summary Cluster headache is a form of primary neurovascular headache with the following features: severe unilateral, commonly retro-orbital, pain accompanied by restlessness or agitation, and cranial (parasympathetic) autonomic symptoms, such as lacrimation or conjunctival injection. It occurs in attacks typically of less than 3 h in length and in bouts (clusters) of a few months during which the patient has one or two attacks per day. The individual attack involves activation of the trigeminal-autonomic reflex; thus, such headaches can be broadly classified with the other trigeminal-autonomic cephalgias, such as paroxysmal hemicrania and the syndrome of short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing. Observations of circadian biological changes and neuroendocrine disturbances have suggested a pivotal role for the hypothalamus in cluster headache. Functional neuroimaging with PET and anatomical imaging with voxelbased morphometry have identified the posterior hypothalamic grey matter as the key area for the basic defect in cluster headache.