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.

Risk Factors for the Development of Bilateral Ménière's Disease.

OBJECTIVE: To identify key risk factors for the development of bilateral Ménière's disease. STUDY DESIGNS: Observational study. SETTING: Four NHS Trusts and four independent hospitals or clinics, within three distinct urban and rural regions within the United Kingdom (Norfolk, Leicestershire, and London). METHODS: Patients with Ménière's disease were identified at ENT or audiovestibular medicine secondary/tertiary care and specialist private clinics. A range of patient-reported data, questionnaire data, and clinical data (audiometric, radiological, and specialist balance testing data) was inputted into a bespoke database. A logistic regression model was used to identify potential risk factors for bilateral Ménière's disease compared with unilateral Ménière's disease. RESULTS: A total of 411 participants were recruited into this study, 263 from NHS Trusts and 148 from independent hospitals or clinics. In our cohort of patients, 22% of individuals were identified as having bilateral Ménière's disease. Two statistically significant independent variables were identified as risk factors for the development of bilateral Ménière's disease: the presence of psoriasis and a history of ear infections. CONCLUSIONS: Psoriasis and a history of ear infection have been identified as key risk factors for the development of bilateral Ménière's disease. It is anticipated that further work based on this finding will allow a better understanding of the underlying pathophysiological mechanisms that predispose to the development of Ménière's disease symptoms.

Betahistine Prescribing Practices in England: An Analysis of Prescribing and National Spending Pre- and Post-BEMED Trial.

OBJECTIVE: Betahistine has not been proven to be superior to placebo in the BEMED study, a multicenter, double-blind, randomized, placebo controlled trial. Our study aimed to establish the prescribing practices of clinicians in England in relation to betahistine and to assess if there has been any change in prescribing practices since the publication of the BEMED trial. STUDY DESIGN: Retrospective study and clinician survey. PATIENTS: All patients who were prescribed betahistine from primary care. MAIN OUTCOME MEASURE: Total quantity of betahistine prescribed and total actual cost. RESULTS: The average total monthly quantity prescribed was 11,143,253 tablets (range, 10,056,516-12,276,423). Prescribing did not decrease from the period before (January 2014-February 2016) to after (February 2016-February 2021) the publication of the BEMED trial, with the average monthly prescribing before publication being 11,294,848 tablets (range, 10,280,942- 12,276,423) and the average monthly prescribing after publication being 11,081,123 tablets (range, 10,056,516-11,915,707). The average actual monthly cost increased from the period before publication to after publication from a sum of £279,264.82 to a sum of £428,846.22. Most (90.5%) of the survey respondents prescribed betahistine for Menière's disease. Less than half (38.09%) prescribed betahistine for indications other than Menière's disease. Only 45.24% of the clinicians were aware of the results of the BEMED trial. CONCLUSIONS: Knowledge of the BEMED trial among otology and neurotology subspecialists is lacking. The results of the BEMED have made no difference to prescribing practice, and in fact, the cost of the medication to the health bill has increased.

Tablet and web-based audiometry to screen for hearing loss in adults with cystic fibrosis.

INTRODUCTION: Individuals with chronic lung disease (eg, cystic fibrosis (CF)) often receive antimicrobial therapy including aminoglycosides resulting in ototoxicity. Extended high-frequency audiometry has increased sensitivity for ototoxicity detection, but diagnostic audiometry in a sound-booth is costly, time-consuming and requires a trained audiologist. This cross-sectional study analysed tablet-based audiometry (Shoebox MD) performed by non-audiologists in an outpatient setting, alongside home web-based audiometry (3D Tune-In) to screen for hearing loss in adults with CF. METHODS: Hearing was analysed in 126 CF adults using validated questionnaires, a web self-hearing test (0.5 to 4 kHz), tablet (0.25 to 12 kHz) and sound-booth audiometry (0.25 to 12 kHz). A threshold of ≥25 dB hearing loss at ≥1 audiometric frequency was considered abnormal. Demographics and mitochondrial DNA sequencing were used to analyse risk factors, and accuracy and usability of hearing tests determined. RESULTS: Prevalence of hearing loss within any frequency band tested was 48%. Multivariate analysis showed age (OR 1.127; (95% CI: 1.07 to 1.18; p value<0.0001) per year older) and total intravenous antibiotic days over 10 years (OR 1.006; (95% CI: 1.002 to 1.010; p value=0.004) per further intravenous day) were significantly associated with increased risk of hearing loss. Tablet audiometry had good usability, was 93% sensitive, 88% specific with 94% negative predictive value to screen for hearing loss compared with web self-test audiometry and questionnaires which had poor sensitivity (17% and 13%, respectively). Intraclass correlation (ICC) of tablet versus sound-booth audiometry showed high correlation (ICC >0.9) at all frequencies ≥4 kHz. CONCLUSIONS: Adults with CF have a high prevalence of drug-related hearing loss and tablet-based audiometry can be a practical, accurate screening tool within integrated ototoxicity monitoring programmes for early detection.

Long-Term Follow-Up of Intratympanic Methylprednisolone Versus Gentamicin in Patients With Unilateral Menière's Disease.

OBJECTIVES: To determine whether long term (>48 months) symptomatic vertigo control is sustained in patients with Menière's disease from a previous comparative trial of intratympanic methylprednisolone versus gentamicin, and if the two treatments remain nonsignificantly different at long-term follow-up. STUDY DESIGN: Mail survey recording vertigo frequency in the previous one and six months, further intratympanic treatment received, and validated symptom questionnaires. SETTING: Outpatient hospital clinic setting. PATIENTS: Adult patients with definite unilateral refractory Menière's disease, who previously received intratympanic treatment in a comparative trial. INTERVENTION: A survey of trial participants who received intratympanic gentamicin (40 mg/mL) or methylprednisolone (62.5 mg/mL). OUTCOME MEASURES: Primary: number of vertigo attacks in the 6 months prior to receiving this survey compared with the 6 months before the first trial injection. Secondary number of vertigo attacks over the previous 1 month; validated symptom questionnaire scores of tinnitus, dizziness, vertigo, aural fullness, and functional disability. RESULTS: Forty six of the 60 original trial patients (77%) completed the survey, 24 from the gentamicin and 22 from the methylprednisolone group. Average follow-up was 70.8 months (standard deviation 17.0) from the first treatment injection. Vertigo attacks in the 6 months prior to receiving the current survey reduced by 95% compared to baseline in both drug groups (intention-to-treat analysis, both p < 0.001). No significant difference between drugs was found for the primary and secondary outcomes. Eight participants (methylprednisolone = 5 and gentamicin = 3) required further injections for relapse after completing the original trial. CONCLUSION: Intratympanic methylprednisolone treatment provides effective long-lasting relief of vertigo, without the known inner-ear toxicity associated with gentamicin. There are no significant differences between the two treatments at long term follow-up.

No evidence of cholesteatoma in untreated otitis media with effusion in children with primary ciliary dyskinesia.

INTRODUCTION: Primary Ciliary Dyskinesia (PCD) describes a group of inherited disorders that result in abnormal ciliary motion leading to mucous stasis. Clinical features include almost universally otitis media with effusion (OME), particularly in infants. PCD patients provide us with a cohort of patients with OME that is not treated with ventilatory tube (VT) insertion as these have been shown to result in frequent complications including chronic otorrhoea, early extrusion and persistent perforation without significant improvement to hearing in the long term. This cohort was used to investigate whether children with PCD and OME not treated with VT were predisposed to cholesteatoma formation in the setting of a paediatric quaternary referral centre. METHODS: A retrospective chart review was performed of all the children attending a multi-disciplinary PCD clinic at a national quaternary referral centre with a diagnosis of OME. We reviewed otoscopic findings, and audiometry and tympanometry results. We assessed the children in four groups: Watchful waiting, hearing aids, VT, and VT and hearing aids. RESULTS: One-hundred-and-one of 107 patients included in the study had a diagnosis of otitis media with effusion. No child with OME and PCD was diagnosed with a cholesteatoma during the follow up period. The only children who had insertion of a ventilatory tube were those who had the procedure prior to the formal diagnosis of PCD. We found a significant complication rate in the children with VT insertion. Hearing improved over time. The prevalence of retraction pockets in untreated OME was 1.72% (3 out of 174 ears). CONCLUSIONS: In children with PCD, OME is an almost universal finding in younger children, but not in adolescents. The study supports the current preference to avoid VT insertion in children with PCD as it confers a significantly higher rate of complications. No cases of cholesteatoma were found in this cohort of PCD children with OME managed without VTs.

Intratympanic methylprednisolone versus gentamicin in patients with unilateral Ménière's disease: a randomised, double-blind, comparative effectiveness trial.

BACKGROUND: Ménière's disease is characterised by severe vertigo attacks and hearing loss. Intratympanic gentamicin, the standard treatment for refractory Ménière's disease, reduces vertigo, but damages vestibular function and can worsen hearing. We aimed to assess whether intratympanic administration of the corticosteroid methylprednisolone reduces vertigo compared with gentamicin. METHODS: In this double-blind comparative effectiveness trial, patients aged 18-70 years with refractory unilateral Ménière's disease were enrolled at Charing Cross Hospital (London, UK) and Leicester Royal Infirmary (Leicester, UK). Patients were randomly assigned (1:1) by a block design to two intratympanic methylprednisolone (62·5 mg/mL) or gentamicin (40 mg/mL) injections given 2 weeks apart, and were followed up for 2 years. All investigators and patients were masked to treatment allocation. The primary outcome was vertigo frequency over the final 6 months (18-24 months after injection) compared with the 6 months before the first injection. Analyses were done in the intention-to-treat population, and then per protocol. This trial is registered with ClinicalTrials.gov, number NCT00802529. FINDINGS: Between June 19, 2009, and April 15, 2013, 256 patients with Ménière's disease were screened, 60 of whom were enrolled and randomly assigned: 30 to gentamicin and 30 to methylprednisolone. In the intention-to-treat analysis (ie, all 60 patients), the mean number of vertigo attacks in the final 6 months compared with the 6 months before the first injection (primary outcome) decreased from 19·9 (SD 16·7) to 2·5 (5·8) in the gentamicin group (87% reduction) and from 16·4 (12·5) to 1·6 (3·4) in the methylprednisolone group (90% reduction; mean difference -0·9, 95% CI -3·4 to 1·6). Patients whose vertigo did not improve after injection (ie, non-responders) after being assessed by an unmasked clinician were eligible for additional injections given by a masked clinician (eight patients in the gentamicin group vs 15 in the methylprednisolone group). Two non-responders switched from methylprednisolone to gentamicin. Both drugs were well tolerated with no safety concerns. Six patients reported one adverse event each: three in the gentamicin group and three in the methylprednisolone group. The most common adverse event was minor ear infections, which was experienced by one patient in the gentamicin group and two in the methylprednisolone group. INTERPRETATION: Methylprednisolone injections are a non-ablative, effective treatment for refractory Ménière's disease. The choice between methylprednisolone and gentamicin should be made based on clinical knowledge and patient circumstances. FUNDING: Ménière's Society and National Institute for Health Research Imperial Biomedical Research Centre.

Peripheral vestibular dysfunction in patients with primary ciliary dyskinesia: abnormal otoconial development?

HYPOTHESIS: Patients with primary ciliary dyskinesia (PCD) have absent or reduced otoconial function compared to the normal population. BACKGROUND: Investigations in zebrafish show that ciliation is important for the development of the otolith organs, but this has never been evaluated in humans. PCD is a congenital defect of ciliary structure. We undertook a pilot study to determine whether patients with PCD have absent or reduced otoconial function compared to the normal population. METHODS: Vestibular function testing, including utricular centrifugation (UCF) testing, vestibular evoked myogenic potentials (VEMPs), and electronystagmography, was undertaken in five patients with known PCD. Patients also completed validated questionnaires regarding subjective balance function and symptoms. RESULTS: There were markedly reduced or unobtainable VEMPs bilaterally in three of the five subjects and unilaterally in the remaining two subjects. No subject had a pathological UCF asymmetry, but three subjects showed utricular abnormalities. The vestibulo-ocular reflex (VOR) at 0.25 Hz sinusoidal rotation was normal in all subjects. There were no subjective dizzy symptoms or balance issues. CONCLUSION: We speculate that the reduced saccular and utricular function in PCD patients observed in this pilot study suggests a relationship between cilia structure and/or motility, and otoconia seeding and/or positioning. Further investigation is warranted.

Aggressive papillary tumor of the middle ear: a true entity or an endolymphatic sac neoplasm?

Aggressive papillary tumors of the middle ear are rare, and their true origin is not clear. We describe the clinical, radiologic, genetic, and histopathologic features of a papillary epithelial tumor filling the middle ear of a 68-year-old woman. Imaging revealed no evidence of petrous temporal bone apex involvement, nor did genetic studies demonstrate the von Hippel-Lindau mutation. A literature search revealed 24 previously reported cases of such a papillary epithelial tumor of the middle ear. All except 2 cases demonstrated apical petrous temporal bone invasion on imaging, and it has been suggested that they arose from a primary endolymphatic sac tumor, which has a similar papillary epithelial histology. Substantial numbers of cases of papillary epithelial tumors involving the middle ear are reported to be associated with von Hippel-Lindau disease, as are known cases of endolymphatic sac tumor. This is the third reported case of papillary epithelial tumor of the middle ear that does not show apical petrous temporal bone invasion on imaging, suggesting that such neoplasms do not always arise from a primary in the endolymphatic sac.

Primary ciliary dyskinesia: current state of the art.

Primary ciliary dyskinesia (PCD) is usually inherited as an autosomal recessive disorder and presents with upper and lower respiratory tract infection, and mirror image arrangement in around 50% of cases. Cilia dysfunction is also implicated in a wider spectrum of disease, including polycystic liver and kidney disease, central nervous system problems including retinopathy and hydrocephalus, and biliary atresia. Cilia are complex structures, containing more than 250 proteins; recent studies have begun to locate PCD genes scattered throughout the genome. Screening tests for PCD include nasal nitric oxide and in vivo tests of ciliary motility such as the saccharin test. Specific diagnosis requires examination of cilia by light and electron microscopy, with epithelial culture in doubtful cases. This is only available in supra-regional centres, recently centrally funded by the National Commissioning Group. Treatment is not evidence based and recommendations are largely extrapolated from cystic fibrosis and other suppurative lung diseases.