{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:24:41Z","timestamp":1790295881572,"version":"4.1.0"},"reference-count":44,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"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:sec><jats:title>Introduction<\/jats:title><jats:p>M\u00e9ni\u00e8re\u2019s disease (MD) is characterized by fluctuating sensorineural hearing loss, tinnitus, aural fullness, and episodic vertigo. Although endolymphatic hydrops (EH) is recognized as a pathognomonic finding, the relationship between clinical presentation, disease duration, and EH severity remains controversial, especially in early-stage MD. This study aimed to determine the impact of disease onset, temporal variables, and clinical phenotypes on EH severity and audiovestibular performance in a cohort with very early MD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We evaluated 80 patients diagnosed with certain MD, with symptom duration of less than 3 years. All underwent 3T MRI with 3D-real-IR sequences for EH evaluation, graded using cochlear (HCAFF), vestibular (HVAFF), and volumetric vestibular ratio (RELAFF). Multiple regression and correlation analyses were used to examine relationships between EH and clinical time markers (TD1, TS1, TR1, TR2), phenotypes, onset patterns, and audiovestibular outcomes (PTA, cVEMP, oVEMP, vHIT). Statistical significance was set at <jats:italic>p<\/jats:italic> &amp;lt; 0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients exhibited some degree of EH, with 92.5% showing both cochlear and vestibular involvement. No significant correlations were found between time variables and EH severity. However, TS1 and TD1 were significantly associated with PTA in the affected ear (<jats:italic>r<\/jats:italic> = 0.277, <jats:italic>p<\/jats:italic> = 0.017 and <jats:italic>r<\/jats:italic> = 0.318, <jats:italic>p<\/jats:italic> = 0.006, respectively). Multinomial regression revealed that vestibular and complete onset patterns predicted more severe vestibular hydrops (HVAFF II and III: <jats:italic>p<\/jats:italic> = 0.019 and <jats:italic>p<\/jats:italic> = 0.020, respectively). The delayed phenotype was significantly associated with higher RELAFF values (<jats:italic>p<\/jats:italic> = 0.032), worse PTA in the affected ear (<jats:italic>p<\/jats:italic> = 0.005), and abnormal cVEMP responses (<jats:italic>p<\/jats:italic> = 0.002). No associations were found between phenotype or onset form and hydrops in general.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In very early MD, clinical time variables do not predict EH severity but correlate with hearing loss severity. The pattern of disease onset significantly impacts vestibular hydrops, whereas age correlates with cochlear EH, likely reflecting age-related hearing vulnerability. Phenotypic differences influence audiovestibular outcomes but not EH presentation. These findings highlight the diagnostic and prognostic utility of early symptom characterization and the need for standardization in defining disease duration in MD research.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2025.1566438","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:11:25Z","timestamp":1745813485000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Early and certain M\u00e9ni\u00e8re\u2019s disease characterization of predictors of endolymphatic hydrops"],"prefix":"10.3389","volume":"16","author":[{"given":"Joan","family":"Lorente-Piera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V\u00edctor","family":"Su\u00e1rez-Vega","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Blanco-Pareja","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Lia\u00f1o","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Octavio","family":"Garaycochea","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Dominguez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raquel","family":"Manrique-Huarte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"P\u00e9rez-Fern\u00e1ndez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"360","DOI":"10.1001\/jamaoto.2021.4282","article-title":"Pathogenesis and etiology of M\u00e9ni\u00e8re disease: a scoping review of a century of evidence","volume":"148","author":"Rizk","year":"2022","journal-title":"JAMA Otolaryngol Head Neck Surg"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1810","DOI":"10.1002\/lary.21844","article-title":"Cluster analysis of auditory and vestibular test results in definite Meni\u00e8re's disease","volume":"121","author":"Montes-Jovellar","year":"2011","journal-title":"Laryngoscope"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"1149","DOI":"10.1001\/archotol.134.11.1149","article-title":"Time course of episodes of definitive vertigo in Meniere's disease","volume":"134","author":"Perez-Garrigues","year":"2008","journal-title":"Arch Otolaryngol Head Neck Surg"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"e460","DOI":"10.1097\/MAO.0000000000001568","article-title":"Inpatient treatment of patients admitted for dizziness: a population-based healthcare research study on epidemiology, diagnosis, treatment, and outcome","volume":"38","author":"Renner","year":"2017","journal-title":"Otol Neurotol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1097\/MAO.0000000000002044","article-title":"A systematic review of the reported proportions of diagnoses for dizziness and Vertigo","volume":"40","author":"Parker","year":"2019","journal-title":"Otol Neurotol"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"601","DOI":"10.1016\/S0001-6519(03)78456-8","article-title":"Epidemiolog\u00eda de la enfermedad de meniere en cantabria","volume":"54","author":"Morales Angulo","year":"2003","journal-title":"Acta Otorrinolaringol Esp"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1016\/j.otc.2010.05.001","article-title":"Current epidemiology of Meniere\u2019s syndrome","volume":"43","author":"Alexander","year":"2010","journal-title":"Otolaryngol Clin N Am"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1111\/cge.12150","article-title":"Familial clustering and genetic heterogeneity in Meniere's disease","volume":"85","author":"Requena","year":"2014","journal-title":"Clin Genet"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/WCO.0000000000001227","article-title":"Epidemiology and genetics of Meniere\u2019s disease","volume":"37","author":"Lopez-Escamez","year":"2024","journal-title":"Curr Opin Neurol"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1159658","DOI":"10.3389\/fneur.2023.1159658","article-title":"Multiple genetic variants involved in both autoimmunity and autoinflammation detected in Chinese patients with sporadic Meniere's disease: a preliminary study","volume":"14","author":"Zou","year":"2023","journal-title":"Front Neurol"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"5974","DOI":"10.1038\/s41598-018-23911-4","article-title":"Proinflammatory cytokines and response to molds in mononuclear cells of patients with Meniere disease","volume":"8","author":"Frejo","year":"2018","journal-title":"Sci Rep"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"126","DOI":"10.1159\/000331945","article-title":"Evolution of symptoms in M\u00e9ni\u00e8re\u2019s disease","volume":"17","author":"Belinchon","year":"2012","journal-title":"Audiol Neurootol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1017\/S0022215122001773","article-title":"A longitudinal study of unilateral M\u00e9ni\u00e8re's disease and clinical evolutionary models","volume":"137","author":"P\u00e9rez-Carbonell","year":"2023","journal-title":"J Laryngol Otol"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1097\/MAO.0000000000001674","article-title":"The progressive nature of Meni\u00e8re's disease: stress projections and lesion analysis","volume":"39","author":"Pender","year":"2018","journal-title":"Otol Neurotol"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1585","DOI":"10.1097\/MAO.0000000000003352","article-title":"Ductus Reuniens and its possible role in Meni\u00e8re\u2019s disease","volume":"42","author":"Hornibrook","year":"2021","journal-title":"Otol Neurotol"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"662530","DOI":"10.3389\/fsurg.2021.662530","article-title":"A synchrotron and Micro-CT study of the human endolymphatic duct system: is Meniere's disease caused by an acute endolymph backflow?","volume":"8","author":"Li","year":"2021","journal-title":"Front Surg"},{"key":"ref17","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":"ref18","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1097\/MAO.0b013e31829e83df","article-title":"Endolymphatic hydrops in M\u00e9ni\u00e8re\u2019s disease: cause, consequence, or epiphenomenon?","volume":"34","author":"Foster","year":"2013","journal-title":"Otol Neurotol"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1097\/MLG.0b013e31802c300c","article-title":"Visualization of endolymphatic Hydrops in patients with Meniere\u2019s disease","volume":"117","author":"Nakashima","year":"2007","journal-title":"Laryngoscope"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1159\/000084024","article-title":"Communication between the perilymphatic scalae and spiral ligament visualized by in vivo MRI","volume":"10","author":"Zou","year":"2005","journal-title":"Audiol Neurootol"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1080\/00016489.2020.1792550","article-title":"Comparison between high-resolution 3D-IR with real reconstruction and 3D-flair sequences in the assessment of endolymphatic hydrops in 3 tesla","volume":"140","author":"Su\u00e1rez Vega","year":"2020","journal-title":"Acta Otolaryngol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"474","DOI":"10.3109\/00016489.2010.534114","article-title":"Endolymphatic hydrops and blood-labyrinth barrier in M\u00e9ni\u00e8re\u2019s disease","volume":"131","author":"Tagaya","year":"2011","journal-title":"Acta Otolaryngol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"438","DOI":"10.1177\/000348948709600418","article-title":"Localization, frequency, and severity of endolymphatic hydrops and the pathology of the labyrinthine membrane in Meni\u00e8re\u2019s disease","volume":"96","author":"Okuno","year":"1987","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.anl.2020.10.009","article-title":"Committee for Clinical Practice Guidelines of Japan Society for Equilibrium Research. Diagnostic and therapeutic strategies for Meniere's disease of the Japan Society for Equilibrium Research","volume":"48","author":"Iwasaki","year":"2021","journal-title":"Auris Nasus Larynx"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"876","DOI":"10.1097\/MAO.0000000000003051","article-title":"Isolated saccular Hydrops on high-resolution MRI is associated with full Spectrum Meni\u00e8re\u2019s disease","volume":"42","author":"Maxwell","year":"2021","journal-title":"Otol Neurotol"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"5116","DOI":"10.1002\/lary.31655","article-title":"Comparing the saccule-to-utricle ratio in early- versus late-stage Meniere's disease patients","volume":"134","author":"Deng","year":"2024","journal-title":"Laryngoscope"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1111\/coa.12844","article-title":"Meniere's disease consortium (MeDiC). Extended phenotype and clinical subgroups in unilateral Meniere disease: a cross-sectional study with cluster analysis","volume":"42","author":"Frejo","year":"2017","journal-title":"Clin Otolaryngol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"205","DOI":"10.3389\/fneur.2015.00205","article-title":"The effects of aging on clinical vestibular evaluations","volume":"6","author":"Maheu","year":"2015","journal-title":"Front Neurol"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1097\/MAO.0000000000000947","article-title":"Age-related Refixating saccades in the three-dimensional video-head-impulse test: source and dissociation from unilateral vestibular failure","volume":"37","author":"Rambold","year":"2016","journal-title":"Otol Neurotol"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1080\/21695717.2019.1591009","article-title":"Air and bone stimulation in vestibular evoked myogenic potentials in patients with unilateral M\u00e9ni\u00e8re\u2019s disease and in controls","volume":"17","author":"Guajardo-Vergara","year":"2019","journal-title":"Hear Balance Commun"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1387","DOI":"10.3174\/ajnr.A3856","article-title":"Detection and grading of endolymphatic hydrops in Meni\u00e8re disease using MR imaging","volume":"35","author":"Bar\u00e1th","year":"2014","journal-title":"Am J Neuroradiol"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1007\/s00234-019-02155-7","article-title":"The value of four stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Meni\u00e8re\u2019s disease on MRI","volume":"61","author":"Bernaerts","year":"2019","journal-title":"Neuroradiology"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1016\/j.anl.2018.08.014","article-title":"Endolymphatic hydrops severity in magnetic resonance imaging evidences disparate vestibular test results","volume":"46","author":"P\u00e9rez-Fern\u00e1ndez","year":"2019","journal-title":"Auris Nasus Larynx"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"5965","DOI":"10.3390\/jcm12185965","article-title":"Magnetic resonance volumetric quantification of vestibular endolymphatic Hydrops in patients with unilateral definite Meniere's disease using 3D inversion recovery with real reconstruction (3D-REAL-IR) sequence","volume":"12","author":"Su\u00e1rez-Vega","year":"2023","journal-title":"J Clin Med"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.3233\/VES-150549","article-title":"Classification Committee of the Barany Society; Japan Society for Equilibrium Research; European academy of otology and Neurotology (EAONO); equilibrium Committee of the American Academy of otolaryngology-head and neck surgery (AAO-HNS); Korean balance society. Diagnostic criteria for Meni\u00e8re's disease","volume":"25","author":"Lopez-Escamez","year":"2015","journal-title":"J Vestib Res"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"E144","DOI":"10.1002\/lary.28576","article-title":"The correlation between endolymphatic Hydrops and clinical features of Meniere disease","volume":"131","author":"Zhang","year":"2021","journal-title":"Laryngoscope"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"937703","DOI":"10.3389\/fneur.2022.937703","article-title":"Correlation of clinical parameters with endolymphatic hydrops on MRI in Meniere's disease","volume":"13","author":"Han","year":"2022","journal-title":"Front Neurol"},{"key":"ref38","doi-asserted-by":"publisher","first-page":"7212","DOI":"10.1038\/s41598-021-86589-1","article-title":"The relationship between clinical characteristics and magnetic resonance imaging results of M\u00e9ni\u00e8re disease: a prospective study","volume":"11","author":"Xie","year":"2021","journal-title":"Sci Rep"},{"key":"ref39","doi-asserted-by":"publisher","first-page":"1040","DOI":"10.1097\/MAO.0b013e31825d9a95","article-title":"In vivo visualized endolymphatic hydrops and inner ear functions in patients with electrocochleographically confirmed M\u00e9ni\u00e8re's disease","volume":"33","author":"G\u00fcrkov","year":"2012","journal-title":"Otol Neurotol"},{"key":"ref40","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1002\/lary.25576","article-title":"The correlation between symptoms of definite Meniere's disease and endolymphatic hydrops visualized by magnetic resonance imaging","volume":"126","author":"Wu","year":"2016","journal-title":"Laryngoscope"},{"key":"ref41","doi-asserted-by":"publisher","first-page":"6036","DOI":"10.1007\/s00330-024-10620-y","article-title":"Correlation of endolymphatic hydrops and perilymphatic enhancement with the clinical features of M\u00e9ni\u00e8re's disease","volume":"34","author":"Li","year":"2024","journal-title":"Eur Radiol"},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s11135-022-01563-x","article-title":"Quality principles of retrospective data collected through a life history calendar","volume":"57","author":"Chevallereau","year":"2022","journal-title":"Qual Quant"},{"key":"ref43","doi-asserted-by":"publisher","first-page":"23","DOI":"10.5604\/01.3001.0016.2701","article-title":"Detailed clinical characteristics and its correlation with the diagnostic test results in patients with defined M\u00e9ni\u00e8re\u2019s disease","volume":"77","author":"Jasi\u0144ska-Nowacka","year":"2023","journal-title":"Otolaryngol Pol"},{"key":"ref44","doi-asserted-by":"publisher","first-page":"622","DOI":"10.1002\/lary.21335","article-title":"Hearing assessment in Meni\u00e8re's disease","volume":"121","author":"Belinchon","year":"2011","journal-title":"Laryngoscope"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1566438\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T04:11:26Z","timestamp":1745813486000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fneur.2025.1566438\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":44,"alternative-id":["10.3389\/fneur.2025.1566438"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2025.1566438","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"article-number":"1566438"}}