Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 May 20:13:898022.
doi: 10.3389/fneur.2022.898022. eCollection 2022.

Cluster Analysis Revealed Two Hidden Phenotypes of Cluster Headache

Pinar Yalinay Dikmen  1 , Cagla Ari  2 , Erdi Sahin  3 , Mustafa Ertas  3 , Fusun Mayda Domac  4 , Elif Ilgaz Aydinlar  1 , Aysenur Sahin  1 , Aynur Ozge  5 , Hilal Ozguner  5 , Omer Karadas  6 , Javid Shafiyev  6 , Doga Vuralli  7   8   9 , Cile Aktan  7 , Emel Oguz-Akarsu  10 , Necdet Karli  10 , Mehmet Zarifoglu  10 , Hayrunisa Bolay  7   8   9 , Esme Ekizoglu  3 , Elif Kocasoy Orhan  3 , Bahar Tasdelen  11 , Betul Baykan  3
Affiliations

Cluster Analysis Revealed Two Hidden Phenotypes of Cluster Headache

Pinar Yalinay Dikmen et al. Front Neurol. .

Abstract

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 (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).

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.

Keywords: Cluster Headache; autonomic features; cigarette smoking; cluster analysis; tobacco exposure; trigeminal autonomic cephalagia.

PubMed Disclaimer

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
A flow chart of the study design.
Figure 2
Figure 2
The cluster 1 and 2 patients with Cluster Headache.
See this image and copyright information in PMC

References

    1. Headache Classification Committee of the International Headache Society (IHS) . The International Classification of Headache Disorders, 3rd edition. Cephalalgia. (2018) 38:1–211. 10.1177/0333102417738202 - DOI - PubMed
    1. Marziniak M, Gralow I, Evers S. The incidence and prevalence of cluster headache: a meta-analysis of population-based studies. Cephalalgia. (2008) 28:614–8. 10.1111/j.1468-2982.2008.01592.x - DOI - PubMed
    1. Russell MB. Epidemiology and genetics of cluster headache. Lancet Neurol. (2004) 3:279–83. 10.1016/S1474-4422(04)00735-5 - DOI - PubMed
    1. Malick A, Strassman RM, Burstein R. Trigeminohypothalamic and reticulohypothalamic tract neurons in the upper cervical spinal cord and caudal medulla of the rat. J Neurophysiol. (2000) 84:2078–112. 10.1152/jn.2000.84.4.2078 - DOI - PubMed
    1. May A, Bahra A, Büchel C, Frackowiak RS, Goadsby PJ. Hypothalamic activation in cluster headache attacks. Lancet. (1998) 352:275–8. 10.1016/S0140-6736(98)02470-2 - DOI - PubMed

LinkOut - more resources