Introduction: Non-traumatic headache is a common emergency department (ED) presentation, yet identifying intracranial causes remains challenging in the absence of neurological deficits. In this study we aimed to evaluate the incidence and predictive ability of clinical red flag signs and symptoms for intracranial pathology.
\nMethods: We conducted a prospective, multicenter, cross-sectional study across six academic EDs with residency programs in Türkiye. We enrolled consecutive adult patients with non-traumatic headache and no neurological deficits who had cranial computed tomography (CT) at the discretion of the treating attending physician. Exclusion criteria were recent trauma, pregnancy, fever, hematologic conditions, and known intracranial pathology. We recorded clinical features using standardized forms. The primary outcome was the presence of intracranial pathology confirmed by CT or subsequent diagnosis within a one-month follow-up.
\nResults: Of 1,522 patients, 57 (3.7%, 95% CI, 2.8-4.8) had intracranial pathology; 104 (6.8%) patients could not be reached during the one-month follow-up. The most common diagnoses were subarachnoid hemorrhage (SAH) (n = 20, 35.1%); ischemic stroke (n = 16, 28.1%); subdural hemorrhage (n = 6, 10.5%); and sinus vein thrombosis (n = 6, 10.5%). Both univariate and multivariate analyses identified that headache aggravated by physical activity (OR 5.98; 95% CI, 2.3-15.2) and age > 50 years (OR 3; 95% CI, 1.65-5.5) independently predicted the cause of the headache. For SAH, headache exacerbated by physical activity (OR 18.6; 95% CI, 5.6-62.3), and syncope (OR 5.7; 95% CI, 1.4-24.3) were independent risk factors. Notably, “sudden onset” and “worst headache ever” were not significant predictors of intracranial pathology in this cohort. The prevalence of sudden-onset headache (45%, n = 9, vs 50.3%, n = 753; P = .64) and “worst headache ever” (55%, n = 11, vs 59.4%, n = 890; P = .69) did not differ significantly between patients with and those without SAH. The odds ratios from the multivariable analyses for sudden onset (OR 1.13, 95% CI, 0.4-3.0) and “worst headache ever” (OR 1.38, 95% CI, 0.47-4.0) were not statistically significant for SAH.
\nConclusion: In ED patients presenting with non-traumatic headache and no focal neurological deficits, headache aggravated by physical activity is a significant indicator for any intracranial pathology causing headache and, specifically, for subarachnoid hemorrhage. While age > 50 years was associated with intracranial pathology causing headache, syncope was specifically linked to subarachnoid hemorrhage. These findings may help refine clinical decision-making for neuroimaging in this patient population.
","language":"eng","license":{"name":"Creative Commons Attribution 4.0","short_name":"CC BY 4.0","text":"Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made. You may do so in any reasonable manner, but not in any way that suggests the licensor endorses you or your use.\r\n\r\nNo additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.","url":"https://creativecommons.org/licenses/by/4.0"},"keywords":[{"word":"non-traumatic headache"},{"word":"subarachnoid hemorrhage"},{"word":"red flags"},{"word":"emergency department"},{"word":"computed tomography"},{"word":"secondary headache"}],"section":"Neurology","is_remote":true,"remote_url":"https://escholarship.org/uc/item/3z80f7ws","frozenauthors":[{"first_name":"Mustafa","middle_name":"","last_name":"serinken","name_suffix":"","institution":"Denipollife Hospital, Department of Emergency Medicine, Denizli, Türkiye","department":""},{"first_name":"Cenker","middle_name":"","last_name":"Eken","name_suffix":"","institution":"Denipollife Hospital, Department of Emergency Medicine, Denizli, Türkiye","department":""},{"first_name":"faruk","middle_name":"","last_name":"güngör","name_suffix":"","institution":"ASV Yaşam Hospital, Department of Emergency Medicine, Antalya, Türkiye","department":""},{"first_name":"ömer","middle_name":"","last_name":"akdağ","name_suffix":"","institution":"Isparta State Hospital, Department of Emergency Medicine, Isparta, Türkiye","department":""},{"first_name":"Veli","middle_name":"","last_name":"Citisli","name_suffix":"","institution":"Pamukkale University, Department of Neurosurgery, Denizli, Türkiye","department":""}],"date_submitted":"2025-06-18T14:21:48.197000+06:00","date_accepted":"2025-10-30T14:08:20.415000+06:00","date_published":"2026-01-27T21:35:00+06:00","render_galley":null,"galleys":[{"label":"PDF","type":"pdf","path":"https://journalpub.escholarship.org/westjem/article/48670/galley/49053/download/"}]}