ObjectiveTo investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis.MethodsA total of 209 individuals (mean (SD) age: 39.8 (11.3) years), diagnosed with CH by headache experts, participated in this cross-sectional multi-center study. All patients completed a semi-structured survey either face to face, preferably, or through phone interviews with a physician. The survey was composed of questions that addressed sociodemographic characteristics as well as detailed clinical features and treatment experiences.ResultsCluster analysis revealed two subgroups. Cluster one patients (n = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; p = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); p < 0.001), and showed a better response to triptans (50.00% vs. 28.00; p < 0.001) during attacks, compared with the cluster two subgroup (n = 122). Cluster two patients had higher rates of current smoking (76.0 vs. 33.0%; p=0.002), higher rates of smoking at diagnosis (78.0 vs. 32.0%; p=0.006), higher rates of parental smoking/tobacco exposure during childhood (72.0 vs. 33.0%; p = 0.010), longer duration of attacks with (44.21 (34.44) min. vs. 34.51 (24.97) min; p=0.005) and without (97.50 (63.58) min. vs. (83.95 (49.07) min; p = 0.035) treatment and higher rates of emergency department visits in the last year (81.0 vs. 26.0%; p< 0.001).ConclusionsCluster one and cluster two patients had different phenotypic features, possibly indicating different underlying genetic mechanisms. The cluster 1 phenotype may suggest a genetic or biology-based etiology, whereas the cluster two phenotype may be related to epigenetic mechanisms. Toxic exposure to cigarettes, either personally or secondarily, seems to be an important factor in the cluster two subgroup, inducing drug resistance and longer attacks. We need more studies to elaborate the causal relationship and the missing links of neurobiological pathways of cigarette smoking regarding the identified distinct phenotypic classes of patients with CH.

Background: Our purpose was to investigate the demographics, diagnosis patterns, clinical characteristics, triggers, treatment experiences, and personal burden of patients with Cluster headache (CH) in Turkey, a country located between Europe and Asia.Methods: The study is a cross-sectional investigation based on data from eight headache centers in Turkey. All patients completed the semi-structured survey either face to face or by phone interview with a neurologist.Results: A total of 209 individuals with a mean age of 39.8 (11.3) completed the survey (176 males; 188 episodic, 21 chronic). The mean age at disease onset was 28.6 (10.2) years. The diagnostic delay was 4.9 years and misdiagnosis before CH was 57.9%. Of participants, 9.1% reported a positive family history for CH. Male patients with CH showed higher rates for being current smokers in comparison to females (59.7% vs. 24.2%; p<0.0001) and they also had significantly more past history of smoking at the time of first diagnosis (60.8% vs. 21.2%; p<0.0001). Females with CH had a previous diagnosis of migraine more frequently (57.6% vs. 27.3; p=0.001). Attack duration without treatment was significantly longer in female patients with CH compared to males (112 min vs. 87 min; p=0.029). Female participants had more migrainous features (57.6 % vs. 36.9%; p=0.033) and nausea/vomiting (48.5% vs. 30.1%; p=0.045) during their attacks. Only 42.1% of all participants reported satisfying treatment experiences. Of the participants, 85.9 % reported that oxygen was efficient for abortive treatment of CH; however, only 22 % of them had an oxygen tube at home. Female participants, as well as chronic CH patients, reported a higher likelihood of preventive treatment experiences. In this study, 49.3% of all participants appeared to be disabled by their headaches. Over one-quarter percent of our cohort reported that CH caused job-related burden.Conclusion: Remarkable diagnostic delay is an ongoing problem for CH and migraine was the most common misdiagnosis. Nearly half of the patients suffered from a burden of CH regardless of chronicity. Both past abortive and preventive treatment experiences of the participants highlight the insufficient efficacy of available choices and the necessity of more specific treatments for CH.