Abstract
Cluster headache is characterized by unilateral attacks of severe pain accompanied by cranial autonomic features. Apart from these there are also sleep-related complaints and strong chronobiological features. The interaction between sleep and headache is complex at any level and evidence suggests that it may be of critical importance in our understanding of primary headache disorders. In cluster headache several interactions between sleep and the severe pain attacks have already been proposed. Supported by endocrinological and radiological findings as well as the chronobiological features, predominant theories revolve around central pathology of the hypothalamus. We aimed to investigate the clinical presentation of chronobiological features, the presence of concurrent sleep disorders and the relationship with particular sleep phases or phenomena, the possible role of hypocretin as well as the possible involvement of cardiac autonomic control. We conducted a questionnaire survey on 275 cluster headache patients and 145 controls as well an in-patient sleep study including 40 CH-patients and 25 healthy controls. The findings include: A distinct circannual connection between cluster occurrence and the amount of daylight, substantially poorer sleep quality in patients compared to controls which was present not only inside the clusters but also outside, affected REM-sleep in patients without a particular temporal connection to nocturnal attacks, equal prevalence of sleep apnea in both patient and control groups, reduced levels of hypocretin-1 in the cerebrospinal fluid of patients and finally a blunted response to the change from supine to tilted position in the head-up tilt table test indicating a weakened sympathoexcitatory or stronger parasympathetic drive. Overall, these findings support a theory of involvement of dysregulation in hypothalamic and brainstem nuclei in cluster headache pathology. Further, it is made plausible that the headache attacks are but one aspect of a more complex syndrome of central dysregulation manifesting as sleep-related complaints, sub-clinical autonomic dysregulation and of course the severe attacks of unilateral headache. Future endeavors should focus on pathological changes which persist in the attack-free periods but also heed the possibility of long-lived, cluster-induced pathology.
Highlights
One of the earliest descriptions of cluster headache (CH) in medical literature is provided by 17th century Dutch surgeon and mayor of Amsterdam Nicolaes Tulp (Famously depicted in Rembrandt’s The Anatomy Lesson of Dr Nicolaes Tulp.) [1]:“. . . in the beginning of the summer season, [Isaak van Halmaal] was afflicted with a very severe headache, occurring and disappearing daily on fixed hours, with such an intensity that he often assured me that he could not bear the pain anymore or he would succumb shortly.For rarely it lasted longer than two hours
Part one: Cross-sectional questionnaire and interview Patients Patients diagnosed with Episodic cluster headache (ECH) or Chronic cluster headache (CCH) were recruited from a register of present and former contacts at the Danish Headache Center
Few other disorders show this kind of strong chronobiological features, and those that do have some interesting similarities with CH, such as the rare lithium responsive [69], recurrent hypersomnia Kleine-Levin syndrome [70]
Summary
. in the beginning of the summer season, [Isaak van Halmaal] was afflicted with a very severe headache, occurring and disappearing daily on fixed hours, with such an intensity that he often assured me that he could not bear the pain anymore or he would succumb shortly. For rarely it lasted longer than two hours. Accounts of the predictable attack patterns and how oxygen, almost by miracle, alleviates the headache have fascinated many, but true progress in our understanding of the disorder is lacking
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