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. 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. Several studies using neuroimaging techniques or measuring hormone levels supported the hypothesis of a hypothalamic involvement. Animal studies added further evidence regarding this hypothesis. 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 futur