聚类分析揭示了丛集性头痛的两种隐藏表型。
Cluster Analysis Revealed Two Hidden Phenotypes of Cluster Headache.
作者信息
Yalinay Dikmen Pinar, Ari Cagla, Sahin Erdi, Ertas Mustafa, Mayda Domac Fusun, Ilgaz Aydinlar Elif, Sahin Aysenur, Ozge Aynur, Ozguner Hilal, Karadas Omer, Shafiyev Javid, Vuralli Doga, Aktan Cile, Oguz-Akarsu Emel, Karli Necdet, Zarifoglu Mehmet, Bolay Hayrunisa, Ekizoglu Esme, Kocasoy Orhan Elif, Tasdelen Bahar, Baykan Betul
机构信息
Department of Neurology, Acibadem University School of Medicine, Istanbul, Turkey.
Department of Neurology, Siirt State Hospital, Siirt, Turkey.
出版信息
Front Neurol. 2022 May 20;13:898022. doi: 10.3389/fneur.2022.898022. eCollection 2022.
OBJECTIVE
To investigate the possible subgroups of patients with Cluster Headache (CH) by using K-means cluster analysis.
METHODS
A 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.
RESULTS
Cluster analysis revealed two subgroups. Cluster one patients ( = 81) had younger age at diagnosis (31.04 (9.68) vs. 35.05 (11.02) years; = 0.009), a higher number of autonomic symptoms (3.28 (1.16) vs. 1.99(0.95); < 0.001), and showed a better response to triptans (50.00% vs. 28.00; < 0.001) during attacks, compared with the cluster two subgroup ( = 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%; = 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; = 0.035) treatment and higher rates of emergency department visits in the last year (81.0 vs. 26.0%; < 0.001).
CONCLUSIONS
Cluster 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.
目的
采用K均值聚类分析研究丛集性头痛（CH）患者可能存在的亚组。
方法
共有209名个体（平均（标准差）年龄：39.8（11.3）岁）参与了这项横断面多中心研究，这些个体由头痛专家诊断为CH。所有患者均完成了一份半结构化调查问卷，最好是面对面完成，或者通过与医生进行电话访谈来完成。该调查问卷包含了关于社会人口学特征以及详细临床特征和治疗经历的问题。
结果
聚类分析揭示了两个亚组。与第二亚组（n = 122）相比，第一亚组患者（n = 81）诊断时年龄更小（31.04（9.68）岁 vs. 35.05（11.02）岁；p = 0.009），自主神经症状数量更多（3.28（1.16）个 vs. 1.99（0.95）个；p < 0.001），并且在发作期间对曲坦类药物的反应更好（50.00% vs. 28.00%；p < 0.001）。第二亚组患者当前吸烟率更高（76.0% vs. 33.0%；p = 0.002），诊断时吸烟率更高（78.0% vs. 32.0%；p = 0.006），童年时期父母吸烟/接触烟草的比例更高（72.0% vs. 33.0%；p = 0.010），发作持续时间更长（有治疗时为44.21（34.44）分钟 vs. 34.51（24.97）分钟；p = 0.005，无治疗时为97.50（63.58）分钟 vs. 83.95（49.07）分钟；p = 0.035），并且去年急诊科就诊率更高（81.0% vs. 26.0%；p < 0.001）。
结论
第一亚组和第二亚组患者具有不同的表型特征，可能表明存在不同的潜在遗传机制。第一亚组表型可能提示基于遗传或生物学的病因，而第二亚组表型可能与表观遗传机制有关。个人或间接接触香烟毒性似乎是第二亚组中的一个重要因素，可导致耐药性和更长时间的发作。我们需要更多研究来阐明吸烟与已识别的CH患者不同表型类别之间神经生物学途径的因果关系和缺失环节。
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