Reviewing the complex relationship between circadian rhythms and cluster headache.

Cluster headache attacks display uniquely rhythmic patterns in their manifestations. Multiple international studies have shown circadian and even circannual timing of attacks, although we do not yet fully understand the effects of culture, sleep, chronotype, seasonal changes, temperature or inter-individual changes over time. Multiple cluster headache treatments alter the core circadian oscillator, although they affect the oscillator differently and are not well understood. Multiple small genetic studies have shown core circadian gene variants to be cluster headache susceptibility genes, whereas larger genetic studies have not shown core circadian gene variants but have also not documented the presence or absence of circadian rhythmicity. In this narrative review, we describe the multi-level circadian features of cluster headache and propose future circadian directions, including a clinical definition of circadian attacks, a potential animal model of circadian headache and study design changes to incorporate circadian features into larger genetic studies.