Time and headache: Insights into timing processes in primary headache disorders for diagnosis, underlying pathophysiology and treatment implications

Background: Time in headache disorders is crucial for diagnosis and gives insight into headache pathophysiology. Objective: To summarize published studies which describe timing processes in both attack presentation (onset, duration) and disease characterization (age of onset, evolution over time) in primary headache disorders and link to pathophysiology. Methods: A comprehensive search was conducted through Ovid MEDLINE(R) and PubMed, focusing on English-language articles from 1946 to 2023 to write the review. The International Classification of Headache Disorders, 3rd edition provided the framework for the review of primary headache disorders (migraine, tension-type headache and cluster headache). Results: Attack presentation: Migraine attacks exhibit significant circadian and infradian rhythms, influenced by hormonal levels, light sensitivity, and hypothalamic activation. Tension-type headache lacks clear chronobiological patterns, with limited understanding of its underlying mechanisms. Cluster headache displays a distinct circannual pattern, with attacks often occurring at night and relevant involvement of the hypothalamus. Disease characterization: Age of onset exhibits the earliest peak in migraine; frequency and typical features of primary headache disorders decrease over time. Conclusion: This comprehensive analysis of time patterns in primary headache disorders underscores their role in phenotyping, understanding and treating primary headache disorders, offering promising avenues for advancing and tailoring headache management.