Cluster Analysis to Identify Clinical Subtypes of Ménière's Disease.

OBJECTIVE: To identify distinct clinical subtypes of Ménière's disease by analyzing data acquired from a UK registry of patients who have been diagnosed with Ménière's disease. STUDY DESIGN: Observational study. METHODS: Patients with Ménière's disease were identified at secondary/tertiary care clinics. Cluster analysis was performed by grouping participants sharing similar characteristics and risk factors into groups based on a defined measure of similarity. RESULTS: A total of 411 participants were recruited into this study. Two main clusters were identified: participants diagnosed with ear infections (OR = 0.30, p < 0.014, 95% CI: 0.11-0.78) were more likely to be allocated in Cluster 1 (C1). Participants reporting tinnitus in both ears (OR = 11.89, p < 0.001, 95% CI: 4.08-34.64), low pitched tinnitus (OR = 21.09, p < 0.001, 95% CI: 7.47-59.54), and those reporting stress as a trigger for vertigo attacks (OR = 14.94, p < 0.001, 95% CI: 4.54-49.10) were significantly more likely to be in Cluster 2 (C2). Also, participants diagnosed with Benign Paroxysmal Positional Vertigo (OR = 13.14, <0.001, 95% CI: 4.35-39.74), autoimmune disease (OR = 5.97, p < 0.007, 95% CI: 1.62-22.03), depression (OR = 4.72, p < 0.056, 95% CI: 0.96-23.24), migraines (OR = 3.13, p < 0.008, 95% CI: 1.34-7.26), drug allergy (OR = 3.25, p < 0.029, 95% CI: 1.13-9.34), and hay fever (OR = 3.12, p < 0.009, 95% CI: 1.33-7.34) were significantly more likely to be clustered in C2. CONCLUSIONS: This study supports the hypothesis that Ménière's disease is a heterogeneous condition with subgroups that may be identifiable by clinical features. Two main clusters were identified with differing putative etiological factors. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:3286-3292, 2024.

Diagnostic and therapeutic strategies for Meniere's disease of the Japan Society for Equilibrium Research.

OBJECTIVE: We provided diagnostic and therapeutic strategies for Meniere's disease in accordance with Japanese Clinical Practice Guideline of Meniere's disease and delayed endolymphatic hydrops 2nd ed. Tokyo: Kanehara Shuppan; 2020 edited by the Japan Society for Equilibrium Research. METHODS: The Committee for Clinical Practice Guidelines was entrusted with a review of the scientific literature on the above topic. Clinical Questions (CQs) concerning the treatment for Meniere's disease were produced, and the literature according to each of them including CQ was searched. The recommendations are based on the literature review and the expert opinion of a subcommittee. RESULTS: Diagnosis criteria of Meniere's disease are classified into Meniere's disease with typical cochlear and vestibular symptoms, and atypical Meniere's disease with either cochlear symptoms or vestibular symptoms. Treatment of Meniere's disease was composed of lifestyle changes, medications such as anti-vertigo drugs and diuretics, middle ear positive pressure treatment, and selective destruction of the vestibule. CONCLUSION: Meniere's disease is diagnosed based on clinical histories and examination findings after processes of differential diagnosis. Treatment option of the disease should be selected in order of invasiveness, according to the severity of the disease and the response to each treatment.

Magnetic resonance imaging of Ménière's disease: early clinical experience in a UK centre.

BACKGROUND: Recent developments in magnetic resonance imaging have enabled demonstration of endolymphatic hydrops, and the clinical application of these imaging studies in Ménière's disease is being explored. OBJECTIVE: To evaluate our centre's experience to date of hydrops magnetic resonance imaging in patients with episodic vertigo. METHODS: Magnetic resonance imaging was performed using a high-resolution three-dimensional fluid-attenuated inversion recovery sequence on a 3 Tesla scanner at 4 hours following double-dose gadolinium administration. RESULTS: The study included 31 patients, 28 of whom had a clinical diagnosis of Ménière's disease. In unilateral Ménière's disease, magnetic resonance imaging was able to lateralise endolymphatic hydrops to the clinically symptomatic ear in all cases. Mild hydrops was often seen in clinically asymptomatic ears. CONCLUSION: There is a good correlation between the clinical symptoms and lateralisation of hydropic changes on magnetic resonance imaging. Further refinements of imaging techniques and grading system will likely improve the diagnostic accuracy and clinical utilisation of hydrops magnetic resonance imaging.

Could there be any merit in lumping primary open-angle glaucoma, idiopathic intracranial hypertension and Meniere's disease into a novel and discrete category of fluid tension disorders?

Open-angle glaucoma, idiopathic intracranial hypertension, and Meniere's disease are disorders managed by different specialties in medicine viz. ophthalmology, neurology, and otorhinolaryngology respectively. By working in silos, the similarity of these disorders is overlooked. Close inspection of these disorders reveals the presence of signs and symptoms triggered by fluid under high pressure within relatively closed chambers. There is a similarity in the capillary production of fluid, which then circulates and drains into the venous system. Management practices that reduce fluid production, decrease fluid pressure or enhance fluid drainage are employed for the treatment of all three disorders. A search for a unifying mechanism explaining the pathophysiology of all three disorders may unlock effective and perhaps curative measures for these disorders.

The value of four stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI.

PURPOSE: There is still a clinical-radiologic discrepancy in patients with Menière's disease (MD). Therefore, the purpose of this study was to investigate the reliability of current MRI endolymphatic hydrops (EH) criteria according to Baráth in a larger study population and the clinical utility of new imaging signs such as a supplementary fourth low-grade vestibular EH and the degree of perilymphatic enhancement (PE) in patients with Menière's disease (MD). METHODS: This retrospective study included 148 patients with probable or definite MD according to the 2015 American Academy of Otolaryngology, Head and Neck Surgery criteria who underwent a 4-h delayed intravenous Gd-enhanced 3D-FLAIR MRI between January 2015 and December 2016. Vestibular EH, vestibular PE, cochlear EH, and cochlear PE were reviewed twice by three experienced readers. Cohen's Kappa and multivariate logistic regression were used for analysis. RESULTS: The intra- and inter-reader reliability for the grading of vestibular-cochlear EH and PE was excellent (0.7 < kappa < 0.9). The two most distinctive characteristics to identify MD are cochlear PE and vestibular EH which combined gave a sensitivity and specificity of 79.5 and 93.6%. By addition of a lower grade vestibular EH, the sensitivity improved to 84.6% without losing specificity (92.3%). Cochlear EH nor vestibular PE showed added-value. CONCLUSIONS: MRI using vestibular-cochlear EH and PE grading system is a reliable technique. A four-stage vestibular EH grading system in combination with cochlear PE assessment gives the best diagnostic accuracy to detect MD.

Clinical Subtyping of Ménière's Disease.

Fundamentally, Ménière's disease is a constellation of symptoms and, as such, may represent the final common pathway for a number of disease processes, as opposed to being the consequence of a single isolated pathology. Within this type of consideration, much can be learned regarding the etiology, presentation, prognosis, and treatment of these individual conditions by applying subtyping techniques currently employed to better understand similar disease processes that are encountered in other allied fields of medicine. This commentary proposes the principles, required processes, and benefits of subtyping for Ménière's disease.

On the classification of hydropic ear disease (Menière's disease).

More than 150 years after its initial description by Prosper Menière, the disease named after him is still at the center of scientific debates. Two recent developments have specifically created a breeding ground for controversy: (1) Since its first description 10 years ago, magnetic resonance imaging diagnosis of endolymphatic hydrops in living patients has seen an increasing and worldwide application. (2) The Bárány Society Classification Committee published diagnostic criteria for Menière's disease in 2015 and proposed a concept of the disease that has elicited widespread criticism. In order to promote the understanding of the underlying controversies and arguments, this article gives an overview of and discusses relevant classification proposals for Menière's disease, including the new classification system of hydropic ear disease.

Video-head impulse test results in patients with Menière's disease related to duration and stage of disease.

BACKGROUND: The video-head impulse test employs the vestibulo-ocular reflex (VOR) to assess vestibular function. To this day, no consensus has been reached among scientists in terms of whether or not vHIT results change in MD patients as the disease progresses. OBJECTIVE: To assess whether the vHIT is more often abnormal in later stages of MD compared to earlier stages. METHODS: We retrospectively analyzed patients with 'definite' MD who had undergone a vHIT and caloric test between 2012 and 2015. Patients were evaluated based on duration of disease in years (≤1, >1≤5, >5≤10, >10) and stage of disease (stage I and II versus III and IV). For the vHIT, an abnormal vestibulo-ocular reflex was defined as a gain cut-off value of≤0.8 and presence of correction saccades including subanalyses using a cut-off value of≤0.9. RESULTS: In 89 definite MD patients (42 (47%) male, mean age 55±5 (SD)), data on both the caloric test and the vHIT were available. The risk of an abnormal vHIT was 25% in patients with a duration of disease over 10 years compared to 22% in the patients with a disease duration of 10 years or less (risk difference 3%, 95% CI:- 28% to 35%), p = 0.82). The risk for an abnormal vHIT in the Stage I and Stage II was 17% compared to 26% in Stage III and IV (risk difference 9%, 95% CI:- 30% to 11%). When using a cut-off value of 0.9 we also did not demonstrate a relationship between the duration of disease and the proportion of abnormal vHIT test results. CONCLUSIONS: There is no relationship between the proportion of abnormal vHIT test results in patients with MD in either duration or stage of disease.

Menière and Friends: Imaging and Classification of Hydropic Ear Disease.

BACKGROUND: Over 75 years ago, endolymphatic hydrops was discovered as the pathologic correlate of Menière's disease. However, this pathologic finding could be ascertained only in postmortem histologic studies. Due to this diagnostic dilemma and the variable manifestation of the various audiovestibular symptoms, diagnostic classification systems based on clinical findings have been used hitherto. METHODS: A review of the literature of magnetic resonance (MR) imaging of hydropic ear disease. RESULTS: Recent developments of high resolution MR imaging of the inner ear have now enabled us to visualize in vivo endolymphatic hydrops in patients with suspected Menière's disease. The existing knowledge from temporal bone histologic studies and from the emerging evidence on imaging based evaluation of patients with suspected Menière's disease indicate that endolymphatic hydrops not only is responsible for the full-blown clinical triad of simultaneous attacks of auditory and vestibular dysfunction, but also for other clinical presentations such as "vestibular" and "cochlear Menière's disease." CONCLUSION: As a consequence, we propose the term "Hydropic Ear Disease" as a new terminology which is based on symptomatic and imaging characteristics of these clinical entities to clarify and simplify their diagnostic classification.

Die Behandlung des M. Menière mit Betahistin: Kritische Anmerkungen zur BEMED-Studie.

The BEMED study (BMJ 2016; 352: DOI 10.1136) was designed as multi-centric, double-blind, plaebo-controlled study in patients with Menière's disease. It should compare a low-level (2 × 24 mg/d) vs. high-level (3 × 48 mg/d) betahstine intake vs. placebo. The primary endpoint was the "number of vertigo attacks lasting longer than 20 min as documented in a patient's diary". The main finding of the study was that betahistine did not significantly better reduced the number of vertigo attacks than placebo. Therefore, the BEMED study should be critically discussed in the present paper.

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

OBJECTIVES: 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. DESIGN: A cross-sectional study with a two-step cluster analysis. SETTINGS: A tertiary referral multicenter study. PARTICIPANTS: Nine hundred and eighty-eight adult patients with unilateral MD. MAIN OUTCOME MEASURES: best predictors to define clinical subgroups with potential different aetiologies. RESULTS: 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. CONCLUSIONS: 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.

Diagnostic criteria for Menière's disease.

This paper presents diagnostic criteria for Menière's disease jointly formulated by the Classification Committee of the Bárány Society, The Japan Society for Equilibrium Research, the European Academy of Otology and Neurotology (EAONO), the Equilibrium Committee of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) and the Korean Balance Society. The classification includes two categories: definite Menière's disease and probable Menière's disease. The diagnosis of definite Menière's disease is based on clinical criteria and requires the observation of an episodic vertigo syndrome associated with low- to medium-frequency sensorineural hearing loss and fluctuating aural symptoms (hearing, tinnitus and/or fullness) in the affected ear. Duration of vertigo episodes is limited to a period between 20 minutes and 12 hours. Probable Menière's disease is a broader concept defined by episodic vestibular symptoms (vertigo or dizziness) associated with fluctuating aural symptoms occurring in a period from 20 minutes to 24 hours.

Analysis of auditory and vestibular function in patients with unilateral Meniere's disease.

CONCLUSION: The percentage of the unilateral weakness of the caloric response also reflects the clinical progress of Meniere's disease (MD), including clinical hearing loss. OBJECTIVE: To evaluate the relationship between hearing status and vestibular function in patients with MD. METHODS: Seventy-nine patients with unilateral definite MD underwent bithermal air caloric testing, vestibular evoked myogenic potential (VEMP) testing, and pure tone audiometry (PTA). The stages of the disease, clinical hearing level of the diseased ears, and dPTA (the difference in hearing level between ears in each patient) were compared with the percentage of the unilateral weakness of the caloric response and the interaural amplitude difference (IAD) ratio of the VEMP response. RESULTS: Twenty ears (25.3%) revealed normal caloric responses and 59 ears (74.7%) showed reduced caloric responses. Testing revealed that the VEMPs were normal in 49 ears (62%), while 30 ears (38%) had abnormal VEMPs. The percentage of the unilateral weakness of the caloric response was positively correlated with the clinical hearing level of the diseased ears (p = 0.006) and the dPTA (p = 0.013).

Cluster analysis of auditory and vestibular test results in definite Menière's disease.

OBJECTIVES/HYPOTHESIS: To determine whether patients with Menière's disease can be grouped into distinct subtypes based on a cluster analysis of distinct disease parameters. STUDY DESIGN: Prospective study at a tertiary center associated with a university hospital. METHODS: The study included 153 patients diagnosed with unilateral definite Menière's disease. The main variables employed were taken from auditory, vestibular, posturographic, and disability assessments. RESULTS: A four-cluster solution best fitted the data. Each cluster represented a distinct patient profile. Cluster 1 patients (13.1%) were the eldest, with the worst hearing bilaterally and good vestibular function but with a significant postural impact and a low level of disability. Cluster 2 patients (41.2%) were the least affected in all the parameters that were close to normal. Cluster 3 patients (34.6%) were the most affected, experiencing frequent and intense vertigo attacks, and they were visually dependent. Cluster 4 patients (11.1%) had strong asymmetric hearing between both ears and the most uncompensated vestibular deficit; they were moderately disabled. CONCLUSIONS: We have identified four distinct profiles of patients with definite Menière's disease that we consider as "mildly active elderly," "mildly active young," "active compensated," and "active uncompensated." We have demonstrated that only in a restricted population of patients can the American Academy of Otolaryngology-Head and Neck Surgery staging system provide analysis of subtypes of the disease.

Use of ICF in assessing the effects of Meniere's disorder on life.

OBJECTIVES: We sought to determine the value of the World Health Organization's International Classification of Functioning, Disability and Health (ICF) in subjects with Meniere's disorder in relation to their quality of life. METHODS: We asked 228 members of the Finnish Meniere Federation to report the effects that Meniere's disorder had on their lives. The replies were classified on the basis of the ICF classification and related to the EuroQol 5D score and disease-specific impact. Logistic regression and decision tree analyses were used to determine the relationships. RESULTS: Seventy percent of the patients listed impairments, 39% activity limitations, 47% participation restrictions, 16% effects on environmental contextual factors, and 28% effects on personal contextual factors. The EuroQol 5D score was explained by reported vertigo, anxiety, fatigue, restriction of life, and communication problems. The disease-specific impact was explained by episodes of vertigo, fatigue, communication problems, inability to work, restriction of life, and uncertainty of life. Both analysis models provided the same outcome variables, although the decision tree separated the results better (80%) into correct classes than did logistic regression analysis (60%). CONCLUSIONS: Self-reported participation restriction, activity limitation, and personal contextual factors describe the limitations of general life in subjects with Meniere's disorder. The use of the ICF classification provides an instrument that can be used in enablement of subjects with Meniere's disorder.

Magnetic resonance imaging of the inner ear in Meniere's disease.

Recent magnetic resonance imaging (MRI) techniques have made it possible to examine the compartments of the cochlea using gadolidium-chelate (GdC) as a contrast agent. As GdC loads into the perilymph space without entering the endolymph in healthy inner ears, the technique provides possibilities to visualize the different cochlear compartments and evaluate the integrity of the inner ear barriers. This critical review presents the recent advancements in the inner ear MRI technology, contrast agent application and the correlated ototoxicity study, and the uptake dynamics of GdC in the inner ear. GdC causes inflammation of the mucosa of the middle ear, but there are no reports or evidence of toxicity-related changes in vivo either in animals or in humans. Intravenously administered GdC reached the guinea pig cochlea about 10 minutes after administration and loaded the scala tympani and scala vestibuli with the peak at 60 minutes. However, the perilymphatic loading peak was 80 to 100 minutes in mice after intravenous administration of GdC. In healthy animals the scala media did not load GdC. In mice in which GdC was administered topically onto the round window, loading of the cochlea peaked at 4 hours, at which time it reached the apex. The initial portions of the organ to be filled were the basal turn of the cochlea and vestibule. In animal models with endolymphatic hydrops (EH), bulging of the Reissner's membrane was observed as deficit of GdC in the scala vestibuli. Histologically the degree of bulging correlated with the MR images. In animals with immune reaction-induced EH, MRI showed that EH could be limited to restricted regions of the inner ear, and in the same inner ear both EH and leakage of GdC into the scala media were visualized. More than 100 inner ear MRI scans have been performed to date in humans. Loading of GdC followed the pattern seen in animals, but the time frame was different. In intravenous delivery of double-dose GdC, the inner ear compartments were visualized after 4 hours. The uptake pattern of GdC in the perilymph of humans between 2 hours and 7 hours after local delivery needs to be clarified. In almost all patients with probable or suspected Ménière's disease, EH was verified. Specific algorithms with a 12-pole coil using fluid attenuation inversion recovery sequences are recommended for initial imaging in humans.

[The 'dizziness handicap inventory': initial psychometric evaluation of the German version]. / Das "Dizziness Handicap Inventory": Erste psychometrische Kennwerte einer Deutschen Version.

BACKGROUND: Dizziness has a clear impact on quality of life of patients. Standardized instruments such as the "Dizziness Handicap Inventory" (DHI) help clinicians assess this impact systematically. The purpose of this study was to analyse the psychometric quality of a German version of the DHI. METHODS: One hundred and five patients with dizziness as their primary complaint have completed the DHI and undergone vestibular examination. The structure of the DHI was determined with a factor analysis, a principal component analysis with a Varimax rotation. To evaluate the reliability, internal consistency (Cronbach's alpha) was estimated. RESULTS: A three-factor solution was extracted. The factors obtained from the German version of the DHI related to (1) activity and participation limitations (2) emotional problems and (3) motion sensitivity in everyday life of patients. Overall, there was a close correspondence of the factors of the German and the original version. The correlation analysis indicated a close relationship between the DHI-scores and the frequency of dizziness attacks. CONCLUSION: The German version of the DHI exhibited a multidimensional structure and good psychometric quality to assess the impact of dizziness in every day life.