Episodic and Chronic Cluster Headache: Differences in Family History, Traumatic Head Injury, and Chronorisk

Mads C. J. Barloese, PhD; Rasmus P. Beske, MD; Anja S. Petersen, MD; Bryan Haddock, MS; Nunu Lund, PhD; Rigmor H. Jensen, DMSc


Headache. 2020;60(3):515-525. 

In This Article

Abstract and Introduction


Objective and Background: The diagnostic criteria of episodic and chronic cluster headache (cCH) were recently modified, yet pathophysiological differences between the two are still unclear. The aim of this cross-sectional study is to identify and characterize other differences between episodic and cCH.

Methods: Data from a retrospective, questionnaire- and interview-based study were analyzed with a focus on associated factors including traumatic head injury (THI), familial history, and change of phenotype. Attack patterns were analyzed using Gaussian and spectral modeling.

Results: 400 patients and 200 controls participated. A positive family history was more prevalent in chronic than episodic cluster headache (eCH) (34/146 (23%) vs 33/253 (13%), respectively, P = .008). A history of THI was more common in patients than controls (173/400 (43%) vs 51/200 (26%), respectively, P < .0001) and in chronic compared to eCH (77/146 (53%) vs 96/253 (37%), respectively, P = .004). Patients with a positive family history had a unique diurnal attack pattern with twice the risk of nocturnal attacks as patients who did not report family history. Patients reporting phenotype change had a chronobiological fingerprint similar to the phenotype they had experienced a transition into. A higher attack frequency in chronic patients was the only difference in symptom manifestation across all analyzed subgroups of patients.

Conclusions: cCH is associated with a positive family history and THI. In familial CH, a peak in nocturnal chronorisk may implicate genes involved in diurnal-, sleep- and homeostatic regulation. The stereotypical nature of the CH attacks themselves is confirmed and differences between subgroups should be sought in other characteristics.


Cluster headache (CH) is a particularly enigmatic chronobiological disorder. Especially in its chronic form it is severely disabling and represents a considerable clinical challenge. Despite advancements in diagnostic technology and increased focus, there have not been breakthroughs in our understanding of the stereotypical, unilateral, severe headache attacks. With a recent elongation of the remission period duration criterion in the classification, the dichotomization between the episodic (eCH) and chronic (cCH) has gained interest.[1,2] The change accommodated the argument that some episodic patients have a disease burden similar to, or exceeding, chronic patients but the dichotomization still only reflects disease burden[3] with no pathophysiological correlate.

Identified differences between eCH and cCH are minimal and the significance of these is difficult to establish. Investigating specific factors that have been linked to an increased manifestation of CH, but not studied for the individual subdiagnoses may aid our understanding. Existing studies have shown that first-degree relatives are more likely to have CH than the general population[4] and CH may be associated with traumatic head injury (THI) but neither is known to be specifically associated with cCH or eCH.[5] Lastly, the background behind the seemingly spontaneous conversion from episodic to chronic CH and back again is unresolved. Using data from the Danish Cluster Headache Survey, we characterized differences between eCH and cCH with a focus on family history, traumatic history, and change in phenotype to test the hypothesis that these specific acquired and inherited factors differ between the subtypes.