Evaluation of a Clustering Approach to Define Distinct Subgroups of Patients With Migraine to Select Electroacupuncture Treatments
Jixin Liu, Shilan Quan, Ling Zhao, Kai Yuan, Yanan Wang, Yutong Zhang, Ziwen Wang, Mingsheng Sun, Li Hu
Abstract
<h3>Background and Objectives:</h3> To propose a clustering approach to identifying migraine subgroups and test the clinical usefulness of the approach by providing prognostic information for electroacupuncture treatment selection. <h3>Methods:</h3> Participants with migraine without aura (MWoA) were asked to complete a daily headache diary, self-rating depression and anxiety, and quality-of-life questionnaires. Whole-brain functional connectivities (FCs) were assessed on resting-state fMRI. By integrating clinical measurements and fMRI data, partial least squares correlation and hierarchical clustering analysis were used to cluster participants with MWoA. Multivariate pattern analysis was applied to validate the proposed subgrouping strategy. Some participants had an 8-week electroacupuncture treatment, and the response rate was compared between different MWoA subgroups. <h3>Results:</h3> In study 1, 97 participants (age of 28.2 ± 1.0 years, 70 females) with MWoA and 77 healthy controls (HCs) (age of 26.8 ± 0.1 years, 61 females) were enrolled (dataset 1), and two MWoA subgroups were defined. The participants in subgroup 1 had a significantly lower headache frequency (times/month of 4.4 ± 1.1) and significantly higher self-ratings of depression (depression score of 49.5 ± 2.3) as compared with the participants in subgroup 2 (times/month of 7.0 ± 0.6 and depression score of 43.4 ± 1.2). The between-group differences of FCs were predominantly related to the amygdala, thalamus, hippocampus, and parahippocampal area. In study 2, 33 participants with MWoA (age of 30.9 ± 2.0 years, 28 females) and 23 HCs (age of 29.8 ± 1.1 years, 13 females) were enrolled as an independent dataset (dataset 2). The classification analysis validated the effectiveness of the two-cluster solution of participants with MWoA in datasets 1 and 2. In study 3, 58 participants with MWoA were willing to receive electroacupuncture treatment and were assigned to different subgroups. Participants in different subgroups exhibited different response rates (p = 0.03, OR CI = 0.086-0.93) to electroacupuncture treatment (18% and 44% for subgroups 1 and 2, respectively). <h3>Discussion:</h3> Our study proposed a novel clustering approach to define distinct MWoA subgroups, which could be useful for refining the diagnosis of participants with MWoA and guiding individualized strategies for pain prophylaxis and analgesia.