Bilateral Meniere's Disease Research Articles

The relationship between endolymphatic hydrops features and hearing loss in Bilateral Meniere's disease

BackgroundThis study aimed to investigate the relationship between the features of endolymphatic hydrops and hearing loss in patients with Bilateral Meniere's Disease.MethodsA retrospective analysis was conducted on 77 patients diagnosed with Bilateral Meniere's Disease. The features of endolymphatic hydrops in the affected ear were evaluated through gadolinium-enhanced inner ear Magnetic resonance imaging. The Spearman correlation coefficient, paired t-tests, and Wilcoxon signed-rank tests were employed for data analysis.ResultsThe analysis revealed a significant correlation between the degree of endolymphatic hydrops and hearing loss across all frequencies(0.125–8 kHz), including the cochlear, vestibular, and overall degree of endolymphatic hydrops. The strongest correlation between the overall degree of endolymphatic hydrops and hearing loss was observed at low frequencies (r = 0.571, p < 0.05), followed by mid-frequencies (r = 0.508, p < 0.05), and high-frequencies (r = 0.351, p < 0.05), with a correlation of r = 0.463, p < 0.05 for the staging of Meniere's disease. Affected Ears with endolymphatic hydrops both in the cochlea and vestibule exhibited more severe hearing loss and Meniere's disease staging compared to those with isolated endolymphatic hydrops within the same patient.ConclusionsThe features of endolymphatic hydrops in patients with Bilateral Meniere's Disease were found to correlate with the severity of hearing loss and the staging of Meniere's disease.

Visualization and clinical relevance of the endolymphatic duct and sac in Ménière's disease.

Ménière's disease (MD) is a chronic inner ear disorder with a multifactorial etiology. Decreased visualization of the endolymphatic duct (ED) and sac (ES) is thought to be associated with MD, although controversy exists about whether this finding is specific to MD. Recent literature has revealed that two distinct ES pathologies, developmental hypoplasia and epithelial degeneration, can be distinguished in MD using the angular trajectory of the vestibular aqueduct (ATVA) or ED-ES system as a radiographic surrogate marker. It has been suggested that these two subtypes are associated with distinct phenotypical features. However, the clinical differences between the ATVA subtypes require further validation. The objective of this study is to investigate whether (1) non-visualization of the ED-ES system is a discriminative radiological feature for MD in a cohort of vertigo-associated pathologies (VAPs) and whether (2) different angular trajectories of the ED-ES system in MD are associated with distinguishable clinical features. The study was conducted in the Vertigo Referral Center (Haga Teaching Hospital, The Hague, the Netherlands). We retrospectively assessed 301 patients (187 definite MD and 114 other VAPs) that underwent 4h-delayed 3D FLAIR MRI. We evaluated (1) the visibility of the ED-ES system between MD and other VAP patients and (2) measured the angular trajectory of the ED-ES system. MD patients were stratified based on the angular measurements into αexit ≤ 120° (MD-120), αexit 120°-140° (MD-intermediate), or αexit ≥ 140° (MD-140). Correlations between ATVA subgroups and clinical parameters were evaluated. Non-visualization of the ED-ES system was more common in definite MD patients compared with other VAPs (P < 0.001). Among definite MD patients, the MD-140 subtype demonstrated a longer history of vertigo (P = 0.006), a higher prevalence of bilateral clinical disease (P = 0.005), and a trend toward a male preponderance (p = 0.053). No significant differences were found between ATVA subgroups regarding the presence or severity of auditory symptoms, or the frequency of vertigo attacks. Non-visualization of the ED-ES system is significantly associated with MD. Among MD patients with a visible ED-ES system, we demonstrated that the MD-140 subtype is associated with a longer disease duration, a higher prevalence of bilateral MD, and a trend toward a male preponderance.

The role of cochlear implantation in alleviating Tumarkin drop attacks of Meniere's disease; a case report

Ménière's disease (MD) patients may suffer episodes of sudden falls, named Tumarkin drop attacks (DAs). This fall occurs abruptly and without warning or loss of consciousness. DAs usually aggravate the clinical picture of MD and are challenging to manage. The present report describes a case treated by cochlear implantation (CI) due to concomitant deafness and offers some clinical considerations for this condition. A male patient aged 48 years with a 10-year history of definite bilateral MD had profound SNHL on the right and severe SNHL on the left side. He suffered from intermittent attacks of vertigo, ear fullness, and tinnitus and, in the last year, had developed DAs and experienced 14 episodes in the previous six months. The preoperative category of acoustic performance was 3. The Dizziness Handicap Inventory (DHI) questionnaire showed a total score of 46, which indicated a moderate degree of disability. A CI was planned for the right side. The patient did not report any further DAs episode for two years since then. The postoperative category of acoustic performance became 11, and the postoperative DHI questionnaire showed a decrease in the total score (from 46 to 19), which indicated a mild disability. Unilateral CI effectively alleviated the DAs associated with bilateral MD. Our report proposes a new modality for managing vertiginous symptoms in cases of MD with hearing loss without the need for more aggressive surgical interventions with the need for clinical trials to confirm our results.

Endolymphatic Hydrops Magnet Resonance Imaging in Ménière's Disease Patients after Cochlea Implantation.

Cochlear implantation in patients with Ménière's disease (MD) is the treatment of choice in cases of functional deafness. Additional vertigo control is of central importance in this group of patients. Endolymphatic hydrops (ELH) is the pathophysiological correlate of MD and can be evaluated by magnet resonance imaging (MRI). Bilateral MD occurs in 10-33% and can be the reason for a postoperative persisting or newly occurring vertigo in this group. Recent developments in the field of implant magnets and experience in MRI sequences allow the diagnostic performance of MRI in cochlear implantees to be evaluated. The aim of the present study was to evaluate the possibility of MRI as a visual diagnostic tool for endolymphatic hydrops in cochlear implantees. This was a retrospective study including three cochlear implantees (age: 61-76 years, one female, two male) suffering from MD who, postoperatively, had a recurrence of vertigo with Ménière's-like symptoms. An MRI was performed for the evaluation of ELH (ELH-MRI). MRI observation was performed by a 4 h iv. delayed Gad 3 D Flair sequence. In all cases, the ipsilateral implant magnet artifact covered the vestibulum, the semicircular canals and the cochlea. The contralateral vestibulum, the semicircular canal and the cochlea were fully observable, and a classification of the ELH-MRI could be performed. ELH-MRI scanning allows for the detection of contralateral labyrinthine endolymphatic hydrops and is a tool for the postoperative evaluation of vertigo in cochlear implantees.

Confrontation of endolymphatic hydrops diagnosis on 3-Tesla MRI to clinical and audiovestibular findings in Meniere's disease.

The aim of this study was to compare different MRI diagnostic criteria for endolymphatic hydrops (EH) and to investigate the relation between audiovestibular and MRI findings in Meniere's disease (MD). Prospective cross-sectional cohort study in 2 referral centers included 76 patients with unilateral (n = 62) or bilateral (n = 14) MD. All patients underwent inner ear 3T-MRI 4 h (n = 52) or >24H (n = 24) following audiovestibular tests. T2-CISS and 3D-FLAIR images 4H after gadolinium were obtained. EH diagnosis was based on saccular morphology on coronal views (T2 and 3D-FLAIR), semi quantitative estimation of endolymphatic space enlargement, and saccule utricle ratio inversion (SURI) on 3D-FLAIR axial views. SURI was the best criterion related to the disease side (43 SURI+ on symptomatic ears, n = 77, vs. 6 SURI+ on asymptomatic ears, n = 53, p < 0.0001, Chi-2). Same-day MRI revealed relation between EH, hearing loss and caloric weakness which could not be detected on delayed MRI: SURI was associated with a higher pure-tone average (43 ± 4.1 dB in SURI+ ears, n = 42 vs. 23 ± 2.6 SURI-, n = 62, p < 0.0001, unpaired t-test,), and a higher proportion of vestibular caloric weakness (23/46 SURI+ ears vs. 4/62 SURI-, p < 0.001, Chi-2). Among all criteria, SURI combined to caloric weakness was the best predictor of the affected side in a logistic regression model. SURI had the strongest relation to the side the disease and audio vestibular findings for unilateral, probable and definite meniere disease. A short delay between MRI and audio vestibular tests improved the coherence between the findings.

2D Measurements of the Angle of the Vestibular Aqueduct Using CT Imaging.

Recently, Bächinger et al. developed a software that measures the angle between the vestibular aqueduct proximal to the vestibule and the distal vestibular aqueduct on computed tomography (CT) scans and found differences in the vestibular aqueduct angle between the hypoplastic and degenerative categories of Meniere's disease (MD). Hypoplastic radiological findings were associated with the development of bilateral MD and hypoplastic changes were not found outside of fetal temporal bones and individuals with MD. The purpose of this study is to examine how the software developed by Bächinger et al. performs when applied to a large dataset of adult patients with varied otologic diagnoses. Adult patients who underwent high resolution flat panel CT scans without intravenous contrast (n = 301) were retrospectively reviewed. Measurements of the angle of the vestibular aqueduct were made using the previously developed software tool. The tool could be applied to measure the vestibular aqueduct angle in most CT scans of the temporal bones (n = 572 ears, 95%). While the majority of ears fell within the normal range of &lt;120 degrees (n = 462, 80%), fourteen ears (2.3%) in 13 patients were found to have vestibular aqueduct angles that meet criteria for hypoplastic MD (&gt;140 degrees). Only one of the 13 patients had a diagnosis of MD and not in the ear in the hypoplastic category. An inconsistent pattern of other otologic diagnoses were found among the 13 individuals meeting criteria for hypoplastic MD. Although prior reports indicate the software has prognostic value in individuals with MD, these results suggest that the software may have lower positive predictive value when applied to a large population of individuals with varied otologic diagnoses.

Characteristics of clinical details and endolymphatic hydrops in unilateral and bilateral Ménière's disease in a single Asian group.

ObjectivesTo elucidate the characteristics of the clinical details and endolymphatic hydrops (EH) in bilateral Ménière's disease (BMD).MethodsA total of 545 patients with definite MD were enrolled. Demographic variables; the age of onset; disease course; inner ear function; the coexistence of related disorders such as migraine, delayed MD, drop attacks, and autoimmune diseases; familial history; and characteristics of EH were analyzed.ResultsIn the study population, the prevalence of BMD was 15.4%. The disease duration of BMD (84.0 ± 89.6 months) was significantly longer than that of unilateral MD (UMD, 60.1 ± 94.0 months) (P = 0.001). As evaluated by hearing thresholds and cervical and ocular vestibular evoked myogenic potentials, inner ear functions were more deteriorated in BMD (P < 0.05) than in UMD. The proportions of delayed MD and a family history of vertigo were significantly larger in BMD (P < 0.05). EH was observed in 100% of cases on the clinically affected side and 6.1% of cases on the unaffected side.ConclusionA low prevalence of BMD, longer disease duration, higher frequencies of delayed MD, and family history of vertigo in patients with BMD were significant findings observed in the present study. All affected ears presented with EH, and a low percentage of unaffected sides presented with EH.

Cytokines and Inflammation in Meniere Disease.

Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evidence to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.

A Predictive Model of Bilateral Sensorineural Hearing Loss in Meniere Disease Using Clinical Data.

Meniere disease (MD) is defined by a clinical syndrome of recurrent attacks of spontaneous vertigo associated with tinnitus, aural fullness, and sensorineural hearing loss (SNHL). Most patients have unilateral SNHL, but some of them will develop contralateral SNHL during the course of the disease. Several studies have reported a frequency of 2 to 73% SNHL in the second ear, according to the duration of disease and the period of follow-up. We hypothesize that unilateral and bilateral MD are different conditions, the first would initially involve the apical turn of the cochlea, while bilateral MD would affect the entire length of the cochlea. The aim of the study is to search for clinical predictors of bilateral SNHL in MD to build a predictive model of bilateral involvement. A retrospective, longitudinal study including two cohorts with a total of 400 patients with definite MD was carried out. The inception cohort consisted of 150 patients with MD and the validation cohort included 250 cases. All of the cases were diagnosed of unilateral MD according to their hearing loss thresholds. The following variables were assessed as predictors of bilateral SNHL for the two cohorts: sex, age of onset, familiar history of MD, migraine and high-frequency hearing loss (HFHL, defined if hearing threshold >20 dB in two or more consecutive frequencies from 2 to 8 KHz). A descriptive analysis was carried out according to the presence of HFHL in the first audiogram for the main variables. By using multiple logistic regression, we built-up several predictive models for the inception cohort and validated it with the replication cohort and merged dataset. Twenty-three (19.3%) and 78 (41%) of patients with HFHL developed contralateral SNHL during the follow-up, in the inception and validation cohorts, respectively. In the inception cohort, the best predictive model included HFHL in the first audiogram (OR = 6.985, p = 0.063) and the absence of migraine (OR = 0.215, p = 0.144) as clinical predictors for bilateral SNHL [area under the curve (AUC) = 0.641, p = 0.002]. The model was validated in the second cohort (AUC = 0.621, p < 0.001). Finally, we merged both datasets to improve the precision of the model including HFHL in the first audiogram (OR = 3.168, p = 0.001), migraine (OR = 0.482, p = 0.036) and age of onset >35 years old (OR = 2.422, p = 0.006) as clinical predictors (AUC = 0.639, p < 0.001). A predictive model including the age of onset, HFHL in the first audiogram and migraine can help to assess the risk of bilateral SNHL in MD. This model may have significant implications for clinical management of patients with MD.

Personality and psychopathology in Ménière's disease

Introduction and ObjectivesPsychological factors in vertigo patients have been extensively studied but the role of anxiety and personality traits in the clinical course of Ménière's disease (MD) is unknown. The objectives of this study are to identify and characterize psychopathology in MD and to find risk factors for an increased rate and intensity of crisis and chronic symptoms. Materials and MethodsWe performed a transversal study in all patients diagnosed with definite MD in our department during a 5-year period. Sample subjects were interviewed in 3 steps: first, an otorhinolaryngologist collected information about clinical and pharmacological background of MD; second, a psychiatrist screened for mood, anxiety and personality disorders; in a third stage, the patient completed the DHI (Dizziness Handicap Inventory), STAI-Y (State Trait Anxiety Inventory), NEO-PI-R (Neo Personality Inventory Reviewed) and VAS (Visual Analogue Scale) for vertigo and dizziness. Statistical analysis was performed to search for risk factors for multiple and intense crisis and chronic symptoms. ResultsThirty-four patients completed all 3 phases of the study. A predominant dysfunctional personality trait was identified in 80% of patients (predominantly cluster C type), 35% were being treated with psychiatric medication and 34.4% had a considerable mood or anxiety disorder. All patients scored high (>7) in VAS during crisis. There was a statistically significant positive correlation between crisis rate and STAI, anxiety-subscale (N1) in NEO-PI-R, VAS and DHI scores (p<.044). Crises were more common in bilateral MD (p=.041). DHI scores were higher with higher STAI and N1 (p=.001). Disease duration and pure tone average were found to have a positive moderate correlation (p=.017). ConclusionsThe positive correlations between crisis rate, chronic dizziness and anxiety-related personality traits reveal a bidirectional and intimate relationship between personality, anxiety and MD, affecting these patients’ quality of life. These results support the relevance of prospecting adjuvant psychological and psychiatric approaches to these patients.

Radiological Configuration of the Vestibular Aqueduct Predicts Bilateral Progression in Meniere's Disease.

Objective: 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.Methods: Patients with unilateral MD and radiological evidence for ES hypoplasia in either the clinically affected inner ear (cohort MDuni-hpuni) or both inner ears (cohort MDuni-hpbi) were included. Given our hypothesis that ES hypoplasia critically predisposes the inner ear to MD, we expected progression to bilateral MD only in the MDuni-hpbi 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.Results: A total of 44 patients were included in the MD-hpuni (n = 15) and MDuni-hpbi (n = 29) cohorts. In line with our radiology-based predictions, none (0/15) of the MD-hpuni patients exhibited progression to bilateral MD, whereas 20/29 (69%) MD-hpbi patients have already progressed to bilateral MD. Using the Kaplan–Meier estimator, bilateral disease progression would be observed in 100% of MD-hpbi patients 31 years after the initial diagnosis with an estimated median time to bilateral progression of 12 years. The nine MD-hpbi 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.Conclusion: 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.

Personality and psychopathology in Ménière's disease

Introduction and ObjectivesPsychological factors in vertigo patients have been extensively studied but the role of anxiety and personality traits in the clinical course of Ménière's disease (MD) is unknown. The objectives of this study are to identify and characterize psychopathology in MD and to find risk factors for an increased rate and intensity of crisis and chronic symptoms. Materials and MethodsWe performed a transversal study in all patients diagnosed with definite MD in our department during a 5-year period. Sample subjects were interviewed in 3 steps: first, an otorhinolaryngologist collected information about clinical and pharmacological background of MD; second, a psychiatrist screened for mood, anxiety and personality disorders; in a third stage, the patient completed the DHI (Dizziness Handicap Inventory), STAI-Y (State Trait Anxiety Inventory), NEO-PI-R (Neo Personality Inventory Reviewed) and VAS (Visual Analogue Scale) for vertigo and dizziness. Statistical analysis was performed to search for risk factors for multiple and intense crisis and chronic symptoms. ResultsThirty-four patients completed all 3 phases of the study. A predominant dysfunctional personality trait was identified in 80% of patients (predominantly cluster C type), 35% were being treated with psychiatric medication and 34.4% had a considerable mood or anxiety disorder. All patients scored high (>7) in VAS during crisis. There was a statistically significant positive correlation between crisis rate and STAI, anxiety-subscale (N1) in NEO-PI-R, VAS and DHI scores (p<.044). Crises were more common in bilateral MD (p=.041). DHI scores were higher with higher STAI and N1 (p=.001). Disease duration and pure tone average were found to have a positive moderate correlation (p=.017). ConclusionsThe positive correlations between crisis rate, chronic dizziness and anxiety-related personality traits reveal a bidirectional and intimate relationship between personality, anxiety and MD, affecting these patients’ quality of life. These results support the relevance of prospecting adjuvant psychological and psychiatric approaches to these patients.

Understanding Fluctuating Hearing Loss

Understanding Fluctuating Hearing Loss

Etiology and clinical symptoms of bilateral vestibulopathy

To identify etiology, clinical symptoms of bilateral vestibulopathy (BV) depending on etiology. Idiopathic BV was identifies in one third of patients. The most common identified reasons are Meniere's disease, meningitis and ototoxicity. BV develops more often without incidental hearing loss in case of idiopathic, autoimmune etiology, ototoxicity and bilateral vestibular neuronitis. BV after neuroinfection is characterized by prompt symptoms development, bilateral severe hearing loss, Gain reduction in vHIT lower 0.4 and loss of more than 8 lines in DVA test. BV after bilateral Meniere's disease is characterized by Gain higher than 0.4 and typical clinical picture of the primary disease.

Endolymphatic volume in patients with meniere's disease and healthy controls: Three-dimensional analysis with magnetic resonance imaging.

ObjectiveRecently, 3‐Tesla magnetic resonance imaging (MRI) with intravenous gadolinium injection has been used to reveal endolymphatic hydrops (EH). In the present study, we aimed to evaluate EH in patients with Meniere's disease (MD) objectively and quantitatively, and compared the endolymphatic space (ELS) in individuals with MD and healthy controls, to gain understanding of the characteristics of MD.MethodsEighty‐two patients with unilateral MD (uMD), 16 patients with bilateral MD (bMD), and 47 healthy volunteers were enrolled. All participants underwent 3‐T MRI at 4 hours after intravenous gadolinium injection. The volumes of the total fluid space (TFS) and ELS were measured semiautomatically using our workstation, and the percentage of ELS to TFS (ELS percentage) was calculated.ResultsThe ELS percentage was 13.9 in the ears of controls, 18.2 in the contralateral ear of individuals with uMD, 26.1 in the affected ears of these individuals, and 23.0 in both ears of individuals with bMD. The ELS percentages in the affected ear of uMD and the ears of bMD individuals were significantly higher than that in the ears of control individuals (P < .01, one‐way analysis of variance (ANOVA), Tukey's test).ConclusionThe ELS is significantly larger in the affected ears of uMD and in both ears of bMD individuals. Accurate diagnosis of MD can be facilitated by using 3‐T MRI 4 hours after intravenous gadolinium injection and performing volumetric measurements of the ELS.Level of Evidence2b

Perioperative vestibular assessment and testing

Vestibular disorders can be difficult to accurately diagnose and manage. A careful history and focused physical examination are typically adequate to establish a diagnosis and initiate medical treatment. Vestibular testing is an important component of the work-up, but it is particularly essential for patients being considered for surgical intervention for a vestibular disorder, where the testing can be used to more definitively confirm a suspected diagnosis and to determine baseline vestibular organ function. In this article, we will first briefly review key components of the history and physical examination of patients with vestibular complaints. We will then discuss the most commonly used vestibular tests and their role in the preoperative assessment of patients undergoing vestibular surgery, including nystagmography, caloric testing, rotary chair testing, video head impulse testing, and vestibular evoked myogenic potential testing.

Management of Ménière's Disease: How Does the Coexistence of Vestibular Migraine Affect Outcomes?

To report the incidence of vestibular migraine (VM) in patients with Ménière's disease (MD) and investigate whether management outcomes of MD differ by the association of VM. Retrospective cohort study. Tertiary care academic center. MD patients (n = 251) with/without VM who were managed for 5 years in a dizziness clinic. Influence of VM on management outcomes and hearing at the latest follow-up in stepwise management options. Incidence of VM was 35% in MD patients. VM was more common in women than men (40 vs. 22%) and in probable MD than definite MD (43 vs. 29%). Bilateral MD was more frequent with coexistence of VM than without VM in definite MD (14 vs. 0%) as well as probable MD (24 vs. 7%). At the latest follow-up, preventive medications were effective in controlling vertigo in most (80%) patients (74%/90% in definite/probable MD). Additional intratympanic steroids were required in 16% (20%/10% in definite/probable MD) and intratympanic gentamicin or surgeries in 9 (6%) patients with intractable MD. The percentage of intractable MD did not differ with coexistence of VM, though definite MD showed a significantly higher percentage of intractable MD than probable MD (6 vs. 0%, respectively, p = 0.002). Worsening hearing was more frequent in definite MD than probable MD (19 vs. 4%), and association of VM did not influence the incidence of worsening hearing. Coexistence of VM was about 30 to 40% in definite and probable MD, especially frequent in bilateral MD (77%) and women with probable MD (50%), requiring identification of coexisting VM while managing MD patients. Management outcomes and worsening hearing in MD patients are not dependent on the coexistence of VM, when both are managed.

Regulation of Fn14 Receptor and NF-κB Underlies Inflammation in Meniere's Disease.

Meniere’s disease (MD) is a rare disorder characterized by episodic vertigo, sensorineural hearing loss, tinnitus, and aural fullness. It is associated with a fluid imbalance between the secretion of endolymph in the cochlear duct and its reabsorption into the subarachnoid space, leading to an accumulation of endolymph in the inner ear. Epidemiological evidence, including familial aggregation, indicates a genetic contribution and a consistent association with autoimmune diseases (AD). We conducted a case–control study in two phases using an immune genotyping array in a total of 420 patients with bilateral MD and 1,630 controls. We have identified the first locus, at 6p21.33, suggesting an association with bilateral MD [meta-analysis leading signal rs4947296, OR = 2.089 (1.661–2.627); p = 1.39 × 10−09]. Gene expression profiles of homozygous genotype-selected peripheral blood mononuclear cells (PBMCs) demonstrated that this region is a trans-expression quantitative trait locus (eQTL) in PBMCs. Signaling analysis predicted several tumor necrosis factor-related pathways, the TWEAK/Fn14 pathway being the top candidate (p = 2.42 × 10−11). This pathway is involved in the modulation of inflammation in several human AD, including multiple sclerosis, systemic lupus erythematosus, or rheumatoid arthritis. In vitro studies with genotype-selected lymphoblastoid cells from patients with MD suggest that this trans-eQTL may regulate cellular proliferation in lymphoid cells through the TWEAK/Fn14 pathway by increasing the translation of NF-κB. Taken together; these findings suggest that the carriers of the risk genotype may develop an NF-κB-mediated inflammatory response in MD.

Extended phenotype and clinical subgroups in unilateral Meniere disease: A cross-sectional study with cluster analysis.

To define clinical subgroups by cluster analysis in patients with unilateral Meniere disease (MD) and to compare them with the clinical subgroups found in bilateral MD. A cross-sectional study with a two-step cluster analysis. A tertiary referral multicenter study. Nine hundred and eighty-eight adult patients with unilateral MD. best predictors to define clinical subgroups with potential different aetiologies. We established five clusters in unilateral MD. Group 1 is the most frequently found, includes 53% of patients, and it is defined as the sporadic, classic MD without migraine and without autoimmune disorder (AD). Group 2 is found in 8% of patients, and it is defined by hearing loss, which antedates the vertigo episodes by months or years (delayed MD), without migraine or AD in most of cases. Group 3 involves 13% of patients, and it is considered familial MD, while group 4, which includes 15% of patients, is linked to the presence of migraine in all cases. Group 5 is found in 11% of patients and is defined by a comorbid AD. We found significant differences in the distribution of AD in clusters 3, 4 and 5 between patients with uni- and bilateral MD. Cluster analysis defines clinical subgroups in MD, and it extends the phenotype beyond audiovestibular symptoms. This classification will help to improve the phenotyping in MD and facilitate the selection of patients for randomised clinical trials.

Cochlear Implantation in Ménière's Disease With and Without Labyrinthectomy.

To investigate outcomes of cochlear implantation (CI) in patients with Ménière's disease (MD) with and without surgical labyrinthectomy. Retrospective study. Multiple tertiary referral centers. Thirty one ears from 27 patients (17 men, 10 women, aged 42-84) with CI in ipsilateral MD ear. CI in ears with intact labyrinths (Group 1), CI with simultaneous surgical labyrinthectomy (Group 2), and CI sequential to surgical labyrinthectomy (Group 3). Within-subject improvement on Bamford Kowal Bench test or City University of New York open set sentence tests. Majority of ears achieved excellent open-set speech recognition by 12 months post-CI, irrespective of intervention group. Preoperative details including patient age and sex, implant, MD and previous intervention, and audiological test results did not significantly affect outcomes. Patients with MD undergoing CI only may experience vestibular dysfunction which may cause long-term concerns. Incidental finding was noted of eight ears with fluctuating symptoms in ipsilateral ear during 12-month period post-CI, with five of eight ears showing objective fluctuating impedances and mapping. CI in MD can yield good hearing outcomes in all three groups and this is possible even after a long delay after labyrinthectomy. Bilateral MD patients are complex and prospective quality of life (QoL) measures would be beneficial in being better able to manage the vestibular outcomes as well as the audiological ones.