Pathophysiology of Cluster Headache: Current Status and Future Directions

Typical clinical features of cluster headache (CH) include trigeminal distribution of pain, circadian and circannual rhythmicity, and ipsilateral cranial autonomic features [1]. The striking circadian and circannual periodicity led to the suggestion that the hypothalamus, which is the structure involved in the human biological clock system, plays a pivotal role in the pathophysiology of this disorder [2]. Several studies using neuroimaging techniques or measuring hormone levels supported the hypothesis of a hypothalamic involvement [2–7]. Animal studies added further evidence regarding this hypothesis [8]. Based on previous data, even invasive treatment methods such as hypothalamic deep brain stimulation (DBS) were justified. More recent studies point towards a complex neural network performance deficit in CH with complex interactions and multiple influences that will have to be unravelled in the future [9, 10].