{"title":"Restlessness in cluster headache: unveiling the role of its key associations and clinical implications from a cohort study.","authors":"Edis Hacılar, Pınar Yalınay Dikmen, Esme Ekizoğlu, Elif Ilgaz Aydınlar, Elif Kocasoy Orhan, Ferda Selçuk, Aynur Özge, Ayşenur Şahin, Tuba Erdogan Soyukibar, Bahar Taşdelen, Mustafa Ertaş, Betül Baykan","doi":"10.3389/fneur.2026.1946721","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>ICHD-3 recognizes restlessness/agitation as an accompanying feature of cluster headache (CH). However, its phenotypic significance within CH remains uncertain. We compared patients with CH with (CHwR) and without restlessness (CHwoR) to characterize the clinical features and symptom burden associated with restlessness.</p><p><strong>Methods: </strong>We conducted a cross-sectional cohort study of Turkish patients with CH (<i>n</i> = 318) across tertiary neurology clinics, using a standardized clinician-administered questionnaire. We compared patients with CHwR versus CHwoR across clinical domains, applied multivariable logistic regression to identify independent correlates, and used Partitioning Around Medoids clustering (six pre-specified variables) to explore data-driven profiles.</p><p><strong>Results: </strong>There were no patients diagnosed with restlessness alone, without any autonomic symptoms. Restlessness co-occurred with cranial autonomic symptoms-particularly eyelid ptosis and sweating-and also with photophobia, nausea and vomiting. Independent correlates were photophobia (OR 2.91; 95% CI 1.65-5.14), sweating (1.96; 1.04-3.71), and eyelid ptosis (1.75, 1.01-3.03). Workplace burden tended to be greater in CHwR (work-day loss median 10 vs. 5 days; work-life impact 84.1% vs. 73.4%), with higher work-life impact and a borderline difference in work-day loss. Exploratory clustering showed a graded pattern of restlessness, highest in the earlier-onset/high-burden profile.</p><p><strong>Conclusion: </strong>In this tertiary-care cohort, restlessness was associated with a broader, symptom-rich CH phenotype characterized by both cranial autonomic and migrainous features and greater clinical burden. As no migraine comparison group was included, its diagnostic discriminatory value cannot be directly assessed. These findings suggest that restlessness may be better interpreted in the context of the overall CH phenotype rather than as an isolated diagnostic feature.</p>","PeriodicalId":12575,"journal":{"name":"Frontiers in Neurology","volume":"17 ","pages":"1946721"},"PeriodicalIF":3.3000,"publicationDate":"2026-10-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13677482/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fneur.2026.1946721","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2026/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: ICHD-3 recognizes restlessness/agitation as an accompanying feature of cluster headache (CH). However, its phenotypic significance within CH remains uncertain. We compared patients with CH with (CHwR) and without restlessness (CHwoR) to characterize the clinical features and symptom burden associated with restlessness.
Methods: We conducted a cross-sectional cohort study of Turkish patients with CH (n = 318) across tertiary neurology clinics, using a standardized clinician-administered questionnaire. We compared patients with CHwR versus CHwoR across clinical domains, applied multivariable logistic regression to identify independent correlates, and used Partitioning Around Medoids clustering (six pre-specified variables) to explore data-driven profiles.
Results: There were no patients diagnosed with restlessness alone, without any autonomic symptoms. Restlessness co-occurred with cranial autonomic symptoms-particularly eyelid ptosis and sweating-and also with photophobia, nausea and vomiting. Independent correlates were photophobia (OR 2.91; 95% CI 1.65-5.14), sweating (1.96; 1.04-3.71), and eyelid ptosis (1.75, 1.01-3.03). Workplace burden tended to be greater in CHwR (work-day loss median 10 vs. 5 days; work-life impact 84.1% vs. 73.4%), with higher work-life impact and a borderline difference in work-day loss. Exploratory clustering showed a graded pattern of restlessness, highest in the earlier-onset/high-burden profile.
Conclusion: In this tertiary-care cohort, restlessness was associated with a broader, symptom-rich CH phenotype characterized by both cranial autonomic and migrainous features and greater clinical burden. As no migraine comparison group was included, its diagnostic discriminatory value cannot be directly assessed. These findings suggest that restlessness may be better interpreted in the context of the overall CH phenotype rather than as an isolated diagnostic feature.
背景：ICHD-3识别躁动/不安是丛集性头痛（CH）的伴随特征。然而，其在CH中的表型意义仍不确定。我们比较了伴有（CHwR）和不伴有躁动（CHwoR）的CH患者，以表征与躁动相关的临床特征和症状负担。方法：我们对三级神经病学诊所的土耳其CH患者（n = 318）进行了一项横断面队列研究，采用标准化的临床管理问卷。我们比较了不同临床领域的CHwR和CHwoR患者，应用多变量逻辑回归来识别独立相关性，并使用Partitioning Around medioids聚类（六个预先指定的变量）来探索数据驱动的概况。结果：所有患者均无躁动症状，无自主神经症状。烦躁不安与颅自主神经症状（尤其是眼睑下垂和出汗）以及畏光、恶心和呕吐同时发生。独立相关因素为畏光（OR 2.91; 95% CI 1.65-5.14）、出汗（1.96;1.04-3.71）和眼睑下垂（1.75,1.01-3.03）。在CHwR中，工作场所负担往往更大（工作日损失中位数为10 vs. 5 天；工作-生活影响中位数为84.1% vs. 73.4%），工作-生活影响较高，工作日损失差异处于边缘。探索性聚类显示了不安的分级模式，在发病早/负担高的情况下最高。结论：在这个三级医疗队列中，躁动与更广泛、症状丰富的CH表型相关，其特征是颅自主神经和偏头痛特征以及更大的临床负担。由于没有纳入偏头痛对照组，其诊断鉴别价值不能直接评估。这些发现表明，在整体CH表型的背景下，烦躁可能更好地解释，而不是作为一个孤立的诊断特征。
期刊介绍：
The section Stroke aims to quickly and accurately publish important experimental, translational and clinical studies, and reviews that contribute to the knowledge of stroke, its causes, manifestations, diagnosis, and management.
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