Phd in PHD PROGRAM IN BEHAVIORAL NEUROSCIENCE

Thesis title: Circadian Features and Sleep Parameters in an Italian Population of Patients with Cluster Headache

The hallmark of cluster headache, a rare form of trigeminal autonomic cephalalgia, is the circadian and circannual pattern of attacks. Headaches tend to occur with remarkable regularity during the day, often at fixed hours, with a peak incidence during the night and within specific periods of the year, known as cluster bouts. A dysfunction of the circadian system, involving the suprachiasmatic nucleus of the hypothalamus, the body’s master clock, is considered the pivotal pathogenic mechanism, with several repercussions on different biological rhythms. This study is divided into two main sections. In the first part, we examined factors that could influence the circadian pattern of attacks in a population of Italian patients with cluster headache. The enrollment of subjects from a single geographical and cultural background allowed us to minimize the influence of external environmental factors and to focus on endogenous variables, such as chronotype. In our sample, chronotype did not significantly influence the temporal distribution of attacks. However, patients with evening chronotype were younger and had shorter attacks, whereas those with morning chronotype were older and experienced longer attacks. These findings might suggest a possible progression of the disorder over time or a less favourable clinical course associated with the morning chronotype. When patients were compared based on the temporal distribution of attacks, those experiencing both diurnal and nocturnal episodes reported a higher number of previous therapeutic failures and more frequent use of combination therapy for managing the active cluster bout. In this light, a bimodal pattern of attacks might be a marker of a worse clinical profile. In the second part of the study, we assessed sleep parameters in a group of cluster headache patients using sleep diaries and actigraphic recordings, comparing them with healthy controls and with migraine patients experiencing predominantly nocturnal attacks. Cluster headache patients were poorer sleepers than controls, with increased wake time after sleep onset according to diary analyses. Diurnal and nocturnal attacks appeared equally to affect sleep architecture, leading to a longer total time spent in bed, greater wake time after sleep onset, and more frequent nocturnal awakenings. From this perspective, sleep impairment in cluster headache might represent a direct manifestation of the underlying circadian dysfunction, rather than the mere effect of nocturnal attacks. Therefore, interventions aimed at restoring normal sleep quality, too often neglected in clinical practice, should be considered a main therapeutic goal in cluster headache management.