{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:34:11Z","timestamp":1787045651009,"version":"build-2736575974"},"reference-count":33,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T00:00:00Z","timestamp":1787011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brain Sci.","Brain Sciences"],"abstract":"<jats:p>Background: The diagonal earlobe crease (DELC), or Frank\u2019s sign, has been associated with systemic vascular degeneration. Whether this cutaneous marker correlates with intracranial aneurysm (IA) instability remains unclear. Methods: We conducted a hospital-based observational registry study including 186 consecutive patients with IA. DELC was dichotomized into absent\/low-grade versus high-grade creases. Associations between DELC and aneurysm rupture, rupture at small sizes (&lt;7 mm), and clinical outcome were analyzed using multivariate logistic regression models adjusted for demographic and vascular risk factors. Results: High-grade DELC was significantly associated with overall aneurysm rupture (adjusted OR 3.42, 95% CI 1.39\u20138.41, p = 0.007). Patients with high-grade DELC harbored ruptured aneurysms at significantly smaller mean sizes than those without the sign (6.11 mm vs. 7.94 mm, p = 0.015). High-grade DELC was also associated with a distinct anatomical shift toward the anterior communicating artery complex (p = 0.021) and was independently associated with rupture at &lt;7 mm (adjusted OR 2.08, 95% CI 1.03\u20134.21, p = 0.041), even after adjustment for aspect ratio and clinical covariates. DELC was not independently associated with post-hemorrhagic clinical outcome. Conclusions: Frank\u2019s sign may represent a readily observable clinical marker associated with IA instability and rupture at conventionally low-risk sizes (&lt;7 mm). These findings support further investigation into DELC as a potential adjunct for individualized risk stratification in patients with small incidental intracranial aneurysms to prevent catastrophic subarachnoid hemorrhage.<\/jats:p>","DOI":"10.3390\/brainsci16080875","type":"journal-article","created":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T09:06:41Z","timestamp":1787044001000},"page":"875","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of Diagonal Earlobe Crease (Frank\u2019s Sign) with Intracranial Aneurysm Rupture at Small Sizes"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0345-2605","authenticated-orcid":false,"given":"Joel Abraham","family":"Velazquez-Castillo","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-6916","authenticated-orcid":false,"given":"Victor Ramzes","family":"Chavez-Herrera","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7029-1865","authenticated-orcid":false,"given":"Martin","family":"Paredes-Cruz","sequence":"additional","affiliation":[{"name":"Epidemiology and Health Services Research Unit, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-0612","authenticated-orcid":false,"given":"Pedro Adrian","family":"Gonzalez-Zavala","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Adolfo","family":"Abdo-Toro","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabindranath","family":"Garcia-Lopez","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Tellez-Medina","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eduardo","family":"Ichikawa-Escamilla","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Blas Ezequiel","family":"Lopez-Felix","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Hospital de Especialidades, Centro M\u00e9dico Nacional Siglo XXI, Mexico City 06720, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,18]]},"reference":[{"key":"ref_1","first-page":"46","article-title":"Epidemiological trends of subarachnoid hemorrhage at global, regional, and national level: A trend analysis study from 1990 to 2021","volume":"11","author":"Lv","year":"2024","journal-title":"Mil. 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