{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T09:32:08Z","timestamp":1786440728127,"version":"build-2736575974"},"reference-count":77,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Young-onset ischemic stroke shows substantial etiologic heterogeneity. However, the value and diagnostic yield of advanced cardiac and autoimmune evaluations in young adults remain uncertain. Methods: Patients aged 25\u201355 years admitted with acute ischemic stroke to King Fahd University Hospital in Saudi Arabia between January 2020 and December 2025 were included. Evaluation followed a multidisciplinary young-stroke pathway, incorporating neurovascular imaging, cardiac assessment, and targeted autoimmune and rheumatologic investigations. A Clinically Meaningful Diagnostic Yield (CMDY) was defined as a diagnostic finding that resulted in etiologic reclassification, management modification, or changes to secondary prevention strategy. Results: A total of 480 patients were included (median age, 40 years; 67.7% men). CMDY was observed in 200 (41.7%) patients. Among 79 patients initially classified as having embolic stroke of an undetermined source, 35 (44.3%) were assigned a determined etiologic mechanism following evaluation and follow-up. Patients with undetermined stroke etiology decreased from 16.5% after first-pass evaluation to 9.2% after diagnostic completion. Patent foramen ovale\/atrial septal defect-associated stroke mechanisms were identified in 61 patients (12.7%), autoimmune\/inflammatory stroke mechanisms in 26 patients (5.4%), and atrial fibrillation-related cardioembolic stroke in 18 patients (3.8%). Clinically relevant mechanisms were identified in 169 patients (35.2%) whose primary etiologic classification remained unchanged. Independent predictors of CMDY were hypertension, prior stroke or transient ischemic attack, multi-territory infarction, and cortical infarction. Conclusions: Etiologic evaluation yielded clinically meaningful findings in over two-fifths of young adults with ischemic stroke and influenced etiologic assessment, treatment, and secondary prevention. Diagnostic yield was greatest among patients with prior cerebrovascular events and cortical or multi-territory infarctions, supporting a selective, phenotype-driven approach that warrants prospective multicenter validation.<\/jats:p>","DOI":"10.3390\/jcm15166205","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T08:09:36Z","timestamp":1786435776000},"page":"6205","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diagnostic Yield of Comprehensive Etiologic Evaluation in Young Adults with Ischemic Stroke: Toward a Phenotype-Driven Approach"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1297-3515","authenticated-orcid":false,"given":"Aishah Ibrahim","family":"Albakr","sequence":"first","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alia","family":"Alokley","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Department, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5164-7096","authenticated-orcid":false,"given":"Feras","family":"AlSulaiman","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa Ahmed","family":"Alqarni","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saud A.","family":"Alnaaim","sequence":"additional","affiliation":[{"name":"Clinical Neurosciences Department, College of Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali Hafiz","family":"Alhashim","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1861-8218","authenticated-orcid":false,"given":"Mohammed","family":"Alshurem","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7740-4730","authenticated-orcid":false,"given":"Abrar J.","family":"Alwaheed","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3994-8216","authenticated-orcid":false,"given":"Safi G.","family":"Alqatari","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2608-1107","authenticated-orcid":false,"given":"Erum","family":"Sharif","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azra","family":"Zafar","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9053-0301","authenticated-orcid":false,"given":"Kawther Mohammed","family":"Hadhiah","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Foziah Jabbar","family":"Alshamrani","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rizwana","family":"Shahid","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1274-2626","authenticated-orcid":false,"given":"Ammar S.","family":"Bukhamsin","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahad Hammad F.","family":"Alrayes","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahaf Marhoom","family":"Alsaadi","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-2154-8508","authenticated-orcid":false,"given":"Farah Abdullah","family":"Alsaqr","sequence":"additional","affiliation":[{"name":"Department of Neurology, College of Medicine, Imam Abdulrahman Bin Faisal University, Dammam 34212, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1161\/STROKEAHA.122.040524","article-title":"Risk Factors and Causes of Ischemic Stroke in 1322 Young Adults","volume":"54","author":"Ekker","year":"2023","journal-title":"Stroke"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1016\/S1474-4422(21)00252-0","article-title":"Global, Regional, and National Burden of Stroke and Its Risk Factors, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 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