Restlessness in cluster headache: unveiling the role of its key associations and clinical implications from a cohort study

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.