Strictly unilateral headaches: considerations of a clinician

The aim of the lecture is to draw attention to the role that clinical practice and clinical observation have had in stimulating research on the pathophysiology of cluster headache (CH) and other trigeminal autonomic cephalalgias (TACs). The symptoms of cluster headache-in particular the typical circadian periodicity of the headaches and the seasonal recurrence of cluster periods-were fundamental in shifting attention away from peripheral pathogenetic hypotheses to the idea that cluster headache could have a central origin. Initially, solid neuroendocrinological data pointed to hypothalamic involvement. For example, CH patients were shown to have alterations in biorhythms. Subsequently, modern functional neuroimaging techniques were able to demonstrate that the homolateral posterior hypothalamus is activated during TAC headaches, so implicating this region in TAC pathogenesis. It is known that the hypothalamus has a modulatory effect on nociceptive and autonomic pathways, particularly on the nociceptive trigeminovascular system. Future research should clarify whether the hypothalamus is the generator of TAC headaches, or whether it is activated in response to an alteration of the homeostatic equilibrium between limbic emotional-affective components and autonomic-nociceptive components modulated by the hypothalamus.