{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T22:13:00Z","timestamp":1793657580798,"version":"4.5.1"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T00:00:00Z","timestamp":1623110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> Meniere's disease (MD) progresses from unilateral to bilateral disease in up to 50% of patients, often chronically and severely impairing balance and hearing functions. According to previous studies, 91% of bilateral MD patients demonstrate bilateral hypoplasia of the endolymphatic sac (ES) upon histological and radiological examination of their inner ears. Here, we seek to validate a radiological marker for ES hypoplasia that predicts the risk for future progression to bilateral MD in individual patients.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Patients with unilateral MD and radiological evidence for ES hypoplasia in either the clinically affected inner ear (cohort MD<jats:sub>uni<\/jats:sub>-hp<jats:sub>uni<\/jats:sub>) or both inner ears (cohort MD<jats:sub>uni<\/jats:sub>-hp<jats:sub>bi<\/jats:sub>) were included. Given our hypothesis that ES hypoplasia critically predisposes the inner ear to MD, we expected progression to bilateral MD only in the MD<jats:sub>uni<\/jats:sub>-hp<jats:sub>bi<\/jats:sub> cohort. To investigate eventual progression to bilateral MD, clinical, audiometric, and imaging data were retrospectively collected over follow-up periods of up to 31 years.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 44 patients were included in the MD-hp<jats:sub>uni<\/jats:sub> (<jats:italic>n<\/jats:italic> = 15) and MD<jats:sub>uni<\/jats:sub>-hp<jats:sub>bi<\/jats:sub> (<jats:italic>n<\/jats:italic> = 29) cohorts. In line with our radiology-based predictions, none (0\/15) of the MD-hp<jats:sub>uni<\/jats:sub> patients exhibited progression to bilateral MD, whereas 20\/29 (69%) MD-hp<jats:sub>bi<\/jats:sub> patients have already progressed to bilateral MD. Using the Kaplan\u2013Meier estimator, bilateral disease progression would be observed in 100% of MD-hp<jats:sub>bi<\/jats:sub> patients 31 years after the initial diagnosis with an estimated median time to bilateral progression of 12 years. The nine MD-hp<jats:sub>bi<\/jats:sub> patients who, so far, remained with unilateral disease demonstrated a median time since initial (unilateral) MD diagnosis of only 6 years and are thus still expected to progress to bilateral disease.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> Progression to bilateral MD adheres to predictions based on the radiological presence or absence of ES hypoplasia. This prognostic tool, if validated by prospective long-term studies, will provide clinically relevant information about a patient's future disease burden and will help to select more personalized treatment regimens.<\/jats:p>","DOI":"10.3389\/fneur.2021.674170","type":"journal-article","created":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T06:07:50Z","timestamp":1623132470000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":38,"title":["Radiological Configuration of the Vestibular Aqueduct Predicts Bilateral Progression in Meniere's Disease"],"prefix":"10.3389","volume":"12","author":[{"given":"David","family":"B\u00e4chinger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Schuknecht","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Dlugaiczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andreas H.","family":"Eckhard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,6,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1016\/S0194-5998(95)70102-8","article-title":"Committee on hearing and equilibrium guidelines for the diagnosis and evaluation of therapy in Meni\u00e8re's disease. American Academy of otolaryngology-head and neck foundation, Inc","volume":"113","author":"Monsell","year":"1995","journal-title":"Otolaryngol Head Neck Surg."},{"key":"B2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1097\/00129492-200501000-00013","article-title":"Pathophysiology of Meniere's syndrome: are symptoms caused by endolymphatic hydrops?","volume":"26","author":"Merchant","year":"2005","journal-title":"Otol Neurotol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"543","DOI":"10.3109\/00016486709139139","article-title":"Hearing in meni\u00e8re's disease: a study of pure-tone audiograms in 334 patients","volume":"64","author":"Enander","year":"1967","journal-title":"Acta Otolaryngol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1177\/003591577106400823","article-title":"Long-term follow up of 610 cases of M\u00e9ni\u00e8re's disease","volume":"64","author":"Thomas","year":"1971","journal-title":"J R Soc Med."},{"key":"B5","doi-asserted-by":"publisher","first-page":"72","DOI":"10.3109\/00016488309123007","article-title":"The natural course of Meniere's disease","volume":"406","author":"Friberg","year":"1984","journal-title":"Acta Otolaryngol Suppl."},{"key":"B6","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1007\/s00415-020-10243-5","article-title":"Bilateral vestibulopathy: beyond imbalance and oscillopsia","volume":"267","author":"Lucieer","year":"2020","journal-title":"J Neurol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3109\/00016487609107484","article-title":"Advanced meniere's disease: a study of 356 severely disabled patients","volume":"81","author":"Stahle","year":"1976","journal-title":"Acta Otolaryngol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"415","DOI":"10.3109\/00016489509125286","article-title":"Epidemiological study of severe cases of meniere's disease in Japan","volume":"115","author":"Shojaku","year":"1995","journal-title":"Acta Otolaryngol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1007\/s00401-018-1927-7","article-title":"Inner ear pathologies impair sodium-regulated ion transport in Meniere's disease","volume":"137","author":"Eckhard","year":"2019","journal-title":"Acta Neuropathol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e548","DOI":"10.1097\/MAO.0000000000002198","article-title":"Vestibular aqueduct morphology correlates with endolymphatic sac pathologies in Meni\u00e8re's disease-a correlative histology and computed tomography study","volume":"40","author":"B\u00e4chinger","year":"2019","journal-title":"Otol Neurotol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"303","DOI":"10.3389\/fneur.2019.00303","article-title":"Endotype-phenotype patterns in meniere's disease based on gadolinium-enhanced mri of the vestibular aqueduct","volume":"10","author":"B\u00e4chinger","year":"2019","journal-title":"Front Neurol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/BF00168023","article-title":"Meniere's disease","volume":"252","author":"Merchant","year":"1995","journal-title":"Eur Arch Oto-Rhino-Laryngol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/VES-150549","article-title":"Diagnostic criteria for Meni\u00e8re's disease","volume":"25","author":"Lopez-Escamez","year":"2015","journal-title":"J Vestib Res Equilib Orientat."},{"key":"B14","volume-title":"Schuknecht's Pathology of the Ear, 3rd ed","author":"Merchant","year":"2010"},{"key":"B15","doi-asserted-by":"publisher","first-page":"431","DOI":"10.3389\/fneur.2019.00431","article-title":"Clinical imaging findings of vestibular aqueduct trauma in a patient with posttraumatic Meniere's syndrome","volume":"10","author":"B\u00e4chinger","year":"2019","journal-title":"Front Neurol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1097\/MOO.0b013e3283304cb3","article-title":"Bilateral M\u00e9ni\u00e8re's disease","volume":"17","author":"Nabi","year":"2009","journal-title":"Curr Opin Otolaryngol Head Neck Surg."},{"key":"B17","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1097\/MLG.0b013e31802c300c","article-title":"Visualization of endolymphatic hydrops in patients with Meniere's disease","volume":"117","author":"Nakashima","year":"2007","journal-title":"Laryngoscope."},{"key":"B18","doi-asserted-by":"publisher","first-page":"62","DOI":"10.3174\/ajnr.A3856","article-title":"Detection and grading of endolymphatic hydrops in Meniere disease using MR imaging","volume":"59","author":"Bar\u00e1th","year":"2014","journal-title":"Am J Neuroradiol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1177\/000348946907800512","article-title":"Bilateral multiple otosclerotic foci and endolymphatic hydrops: Histopathological case report","volume":"78","author":"Black","year":"1969","journal-title":"Ann Otol Rhinol Laryngol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1177\/000348947208100209","article-title":"Abnormalities of the endolymphatic sac system","volume":"81","author":"Gussen","year":"1972","journal-title":"Ann Otol Rhinol Laryngol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1177\/000348947608500307","article-title":"Unilateral endolymphatic hydrops and associated abnormalities","volume":"85","author":"Sando","year":"1976","journal-title":"Ann Otol Rhinol Laryngol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"226","DOI":"10.1177\/019459987808600226","article-title":"Hypoplasia of the vestibular aqueduct and endolymphatic sac in endolymphatic hydrops","volume":"86","author":"Egami","year":"1978","journal-title":"Otolaryngology."},{"key":"B23","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1007\/s00441-019-03062-2","article-title":"Immunolocalization of calcium sensing and transport proteins in the murine endolymphatic sac indicates calciostatic functions within the inner ear","volume":"378","author":"B\u00e4chinger","year":"2019","journal-title":"Cell Tissue Res"},{"key":"B24","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.anl.2016.02.017","article-title":"Identification of operculum and surgical results in endolymphatic sac drainage surgery","volume":"44","author":"Kitahara","year":"2017","journal-title":"Auris Nasus Larynx."},{"key":"B25","doi-asserted-by":"publisher","first-page":"CD005395","DOI":"10.1002\/14651858.CD005395.pub3","article-title":"Surgery for M\u00e9ni\u00e8re's disease","volume":"2","author":"Pullens","year":"2013","journal-title":"Cochrane Database Syst Rev."},{"key":"B26","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1097\/01.mlg.0000216815.75512.03","article-title":"Vestibular evoked myogenic potentials (VEMP) can detect asymptomatic saccular hydrops","volume":"116","author":"Lin","year":"2006","journal-title":"Laryngoscope."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1097\/MAO.0000000000002375","article-title":"Predicting development of bilateral Meni\u00e8re's disease based on cVEMP threshold and tuning","volume":"40","author":"Noij","year":"2019","journal-title":"Otol Neurotol."},{"key":"B28","first-page":"336","article-title":"Bilateral Meni\u00e8re's disease in surgical versus nonsurgical patients","volume":"12","author":"Rosenberg","year":"1991","journal-title":"Am J Otol."},{"key":"B29","first-page":"170","article-title":"Long-term progression of Meni\u00e8re's disease","volume":"10","author":"Stahle","year":"1989","journal-title":"Am J Otol."}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.674170\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,6,8]],"date-time":"2021-06-08T06:07:55Z","timestamp":1623132475000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2021.674170\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,6,8]]},"references-count":29,"alternative-id":["10.3389\/fneur.2021.674170"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2021.674170","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,6,8]]},"article-number":"674170"}}