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Introduction: Intratympanic corticosteroids are commonly used in the treatment of Menière's disease (MD). However, few and small randomised controlled trials (RCT) on the effectiveness of intratympanic corticosteroids have been performed. A recent Cochrane review suggested that a well-conducted placebo-controlled RCT with a large study population is required to evaluate the effectiveness of the use of intratympanic corticosteroids in MD. The following protocol describes a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial to compare the effectiveness of methylprednisolone (62.5 mg/mL) to a placebo (sodium chloride 0.9%)., Methods and Analysis: We aim to recruit 148 patients with unilateral MD from six hospitals in the Netherlands. Patients will be randomly assigned to either the methylprednisolone or the placebo group. Two injections will be given, one at baseline and one after 2 weeks. Follow-up assessments will be done at 3, 6, 9 and 12 months. The primary outcome will be the frequency of vertigo attacks. Attacks will be evaluated daily with the DizzyQuest app. Secondary outcomes include hearing loss, tinnitus, health-related quality of life, use of co-interventions and escape medication, (serious) adverse events and cost-effectiveness. These will be evaluated with audiometry and multiple commonly used, validated questionnaires. For the primary and secondary outcomes mixed model analysis, generalised estimating equation analysis and logistic regression analysis will be used., Ethics and Dissemination: This study was submitted via the Clinical Trials Information System, reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft and the local institutional review board of each participating centre. All data will be presented ensuring the integrity and anonymity of patients. Results will be published in scientific journals and presented on (inter)national conferences., Trial Registration Number: This study is registered at ClinicalTrials.gov Protocol Registration and Results System, with the registration ID: NCT05851508., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Objective: To investigate the safety and feasibility of precise delivery of a long-acting gel formulation containing 6% dexamethasone (SPT-2101) to the round window membrane for the treatment of Menière's disease., Study Design: Prospective, unblinded, cohort study., Setting: Tertiary care neurotology clinic., Patients: Adults 18 to 85 years with a diagnosis of unilateral definite Menière's disease per Barany society criteria., Interventions: A single injection of a long-acting gel formulation under direct visualization into the round window niche., Main Outcome Measures: Procedure success rate, adverse events, and vertigo control. Vertigo control was measured with definitive vertigo days (DVDs), defined as any day with a vertigo attack lasting 20 minutes or longer., Results: Ten subjects with unilateral Menière's disease were enrolled. Precise placement of SPT-2101 at the round window was achieved in all subjects with in-office microendoscopy. Adverse events included one tympanic membrane perforation, which healed spontaneously after the study, and two instances of otitis media, which resolved with antibiotics. The average number of DVDs was 7.6 during the baseline month, decreasing to 3.3 by month 1, 3.7 by month 2, and 1.9 by month 3. Seventy percent of subjects had zero DVDs during the third month after treatment., Conclusions: SPT-2101 delivery to the round window is safe and feasible, and controlled trials are warranted to formally assess efficacy., (Copyright © 2024, Otology & Neurotology, Inc.)

Purpose: Meniere's Disease is a condition known for its recurrent vertigo, fluctuating sensorineural hearing loss, aural fullness, and tinnitus. Previous studies have demonstrated significant influence of placebo treatments. Our objective was to quantify the magnitude of the placebo effect in randomized controlled trials for Meniere's Disease., Materials and Methods: A systematic review was performed by searching PubMed, SCOPUS, CINAHL, and Cochrane databases from inception through September 27, 2022. Data extraction, quality rating, and risk of bias assessment were performed by two independent reviewers. A meta-analysis of mean differences with 95 % confidence interval, weighted summary proportions, and proportion differences were calculated using random and fixed effects models., Results: A total of 15 studies (N = 892) were included in the review. Significant improvement was seen in the functional level scores of the pooled placebo groups, with a mean difference of -0.6 points, (95%CI: -1.2 to -0.1). There was no difference in pure tone audiometry, speech discrimination score, or vertigo frequency at 1 and 3 months for the placebo group. Patient-reported vertigo episodes were improved in 52.5 % (95%CI: 39.2 to 65.5) of the placebo group and was significantly less than the pooled experimental group (90.1 %, 95%CI: 39.2 to 65.5, p < 0.001)., Conclusions: The placebo effect in Meniere's Disease trials is associated with some symptomatic improvement in subjective outcomes, such as patient reported vertigo episodes. However, the clinical significance is questionable across other outcomes measures, especially when analyzing objective data. The extent and strength of the placebo effect continues to be a hurdle in the search for better treatment options., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Purpose: Meniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections., Materials and Methods: This study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed., Results: Before treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients., Conclusions: Low-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population., Competing Interests: Declaration of competing interest Authors declare no conflicts of interest related to this study., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Meniere's disease (MD) is an idiopatic condition characterized by recurrent attacks of vertigo, hearing loss, tinnitus, and aural fullness, affecting quality of life. Intravenous glycerol has shown potential as a therapeutic option. This study evaluates its efficacy in a larger patient cohort., Materials and Methods: Retrospective study with 168 patients having unilateral MD unresponsive to dietary restrictions. Intravenous 10 % glycerol with 0.9 % sodium chloride was administered for six months. Audio-vestibular assessments and questionnaires were used., Results: Significant improvements in vertigo control observed. 7.1 % achieved complete control, and 58.3 % had substantial control. Quality of life measures improved, and audiometry thresholds remained unchanged. No major adverse events reported., Discussion: Intravenous glycerol effectively controlled vertigo and improved MD patients' quality of life. Limitations include lack of a control group and a relatively short-term follow-up. Future prospects include randomized controlled trials and optimization of treatment protocols., Conclusion: Intravenous glycerol shows promise as a therapeutic option for MD, with notable improvements in vertigo control and quality of life. Further research is needed for validation and optimization., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To elucidate the relationship between vertigo and EH volume after medical treatment, we investigated changes in endolymphatic hydrops (EH) volume using inner ear magnetic resonance imaging (ieMRI) in relation to clinical results for vertigo and hearing after administration of the anti-vertiginous medications betahistine, adenosine triphosphate (ATP), isosorbide (ISO), and saireito (SAI) for Meniere's disease (MD)., Methods: We retrospectively enrolled 202 consecutive patients diagnosed with unilateral MD from 2015 to 2021 and assigned them to four groups: Group I (G-I), symptomatic oral medication with betahistine only (CONT); Group II (G-II), inner ear vasoactive oral medication (ATP); Group III (G-III), osmotic diuretic oral medication (ISO); and Group IV (G-IV), kampo oral medication (SAI). In total, 172 patients completed the planned one-year-follow-up, which included the assessment of vertigo frequency, hearing improvement, and changes in EH using ieMRI (G-I, n=40; G-II, n=42; G-III, n=44; G-IV, n=46). We constructed 3D MRI images semi-automatically and fused the 3D images of the total fluid space (TFS) of the inner ear and endolymphatic space (ELS). After fusing the images, we calculated the volume ratios of the TFS and ELS (ELS ratios)., Results: One year after treatment, vertigo was controlled with zero episodes per month in 57.5% (23/40) of patients in G-I, 78.6% (33/42) in G-II, 81.8% (36/44) in G-III, and 82.6% (38/46) in G-IV (statistical significance: G-I 10 dB in 5.0% (2/40) of patients in G-I, 16.7% (7/42) in G-II, 18.2% (8/44) in G-III, and 21.7% (10/46) in G-IV (statistical significance: G-I=G-II=G-III=G-IV). ELS ratios were significantly reduced after treatment only in the vestibule for G-II, G-III, and G-IV when compared with G-I. Especially among patients with complete control of vertigo after treatment, ELS ratios were significantly reduced after treatment in the vestibule and total inner ear for G-II; in the cochlea, vestibule, and total inner ear for G-III; and in the cochlea, vestibule, and total inner ear for G-IV compared with G-I. However, there were no significant findings in the relationship between hearing results and changes in ELS ratios., Conclusion: These results indicate that daily administration of anti-vertiginous medications including ATP, ISO, and SAI could be an effective treatment option for patients with MD at an early stage before it becomes intractable. Treatments to reduce EH might offer better control of vertigo rather than improve hearing., Competing Interests: Declaration of competing interest The authors have no conflicts of interest related to the present study to declare., (Copyright © 2023. Published by Elsevier B.V.)

Purpose of Review: Meniere's disease is caused by hydropic changes in the endolymphatic system, and manifests as a collection of vertigo, hearing loss, tinnitus, and aural fullness. Although high-quality clinical practice guidelines exist for the diagnosis and initial management of Meniere's disease, there is no strong consensus for treatment of medically refractory Meniere's disease. This review summarizes treatment options and highlights controversies surrounding surgical treatment of Meniere's disease., Recent Findings: Intratympanic steroid and intratympanic gentamicin injections continue to be widely used as in-office therapies in medically refractory Meniere's disease. Despite historical controversy surrounding the use of endolymphatic sac (ELS) surgery, the use of ELS decompression has been widely adopted by the international neurotologic community due to high vertigo control rate, coupled with low risk of audiovestibular loss. Wider decompression of the sac and surgical manipulation of the endolymphatic duct may impact outcome and are the subject of discussion. An emerging surgical technique called Triple Semicircular Canal Occlusion (TSCO) holds promise as a partially ablative procedure with high vertigo control rate in Meniere's disease. Cochlear implants may be placed in active Meniere's disease patients, or during an ablative surgery such as labyrinthectomy., Summary: For the medically refractory Meniere's disease patient, treatment options include intratympanic steroid injection, endolymphatic sac decompression, medical or surgical labyrinthectomy, and vestibular nerve section. TSCO holds promise as an emerging partially ablative procedure. Cochlear implants maintain an important role in the rehabilitation of hearing loss associated with Meniere's disease., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease., Study Designs: Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease., Setting: The United States and throughout Europe., Patients: Individuals with Ménière's disease aged 18 to 85 years., Interventions: All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in period, eligible patients received a single intratympanic injection of either 12 mg OTO-104 (otic formulation of dexamethasone in thermosensitive poloxamer) or placebo (1:1) and were observed for 3 months., Main Outcome Measures: The primary efficacy endpoint was measured by the number of definitive vertigo days (DVDs) at month 3. Secondary objective was OTO-104 safety and tolerability including adverse events, audiometry, tympanometry, and otoscopic examinations., Results: Although OTO-104 demonstrated numerically greater reductions in DVD compared with placebo across all three studies, statistical significance versus placebo (primary efficacy endpoint) was only achieved in one study, the AVERTS-2 study (n = 174, p = 0.029). Secondary vertigo efficacy endpoints were statistically significant at month 3 in that study including vertigo severity, the effect of vertigo on daily activity (days at home sick or bedridden), and vertigo frequency. In the AVERTS-1 study, which did not meet the primary endpoint, a subgroup analysis of the 115 patients (69.7% of study population) who did not previously receive intratympanic steroid injections demonstrated that OTO-104 patients had significantly lower mean DVD at month 3 than patients receiving placebo (1.9 for OTO-104 versus 3.0 for placebo; p = 0.045). Importantly, a significant placebo response was observed across studies in Ménière's disease patients. OTO-104 and the intratympanic injection procedure were well tolerated., Conclusions: In all three high-quality, randomized, double-blind, placebo-controlled, multicenter studies, a single intratympanic injection of 12 mg OTO-104 demonstrated numerically greater reductions in vertigo versus placebo in patients with Ménière's disease, but statistical separation from placebo was demonstrated in only one of the studies. OTO-104 was safe and well tolerated.(Otonomy, Inc. funded; NCT02717442, NCT02612337, NCT03664674)., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

Background: The aim of the current study was to explore the associations among different therapeutic procedures, self-administered exercise, and characteristics of Ménière's disease., Methods: The study used a retrospective design and included 539 people with Ménière's disease who were focusing on self-administered exercise. The mean age and history of Ménière's disease among these participants were 61.9 years and 15.6 years, respectively. Of the participants, 79.5% were female. The data were collected by an electronic questionnaire that focused on symptoms of Ménière's disease, exercise and training habits, balance problems, impacts of the complaints, quality of life, medical treatment, physiotherapy, and psychotherapy., Results: Of the participants, 79.3% used medical treatment. Betahistine (56.8%) was the most popular followed by periodical anti-emetic use (41.0%) and diuretics (22.4%). Of the participants 70% were doing some self-administered training. The frequency of training depended on age, severity of balance problems, vestibular drop attacks, and gait problems. The type of training depended on age, quality of life, vestibular drop attacks, and gait problems. No association was found between vertigo and frequency/type of balance training., Conclusion: The use or effect of therapeutic procedures for Ménière's disease patients was not related to symptoms experienced. Most participants with Ménière's disease used training programs that aimed to alleviate their condition, especially balance-, gait-, and vestibular drop attack-associated problems. Patient support organizations should be working to help characterize the types of balance disorders people are dealing with in order to individually tailor a rehabilitation program to the patient's needs.

Background: Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Corticosteroids are sometimes administered directly into the middle ear to treat this condition (through the tympanic membrane). The underlying cause of Ménière's disease is unknown, as is the way in which this treatment may work. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear., Objectives: To evaluate the benefits and harms of intratympanic corticosteroids versus placebo or no treatment in people with Ménière's disease., Search Methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with a diagnosis of Ménière's disease comparing intratympanic corticosteroids with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified).  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects (including tympanic membrane perforation). We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We included 10 studies with a total of 952 participants. All studies used the corticosteroid dexamethasone, with doses ranging from approximately 2 mg to 12 mg.  Improvement in vertigo Intratympanic corticosteroids may make little or no difference to the number of people who report an improvement in their vertigo at 6 to ≤ 12 months follow-up (intratympanic corticosteroids 96.8%, placebo 96.6%, risk ratio (RR) 1.00, 95% confidence interval (CI) 0.92 to 1.10; 2 studies; 60 participants; low-certainty evidence) or at more than 12 months follow-up (intratympanic corticosteroids 100%, placebo 96.3%; RR 1.03, 95% CI 0.87 to 1.23; 2 studies; 58 participants; low-certainty evidence). However, we note the large improvement in the placebo group for these trials, which causes challenges in interpreting these results.  Change in vertigo Assessed with a global score One study (44 participants) assessed the change in vertigo at 3 to < 6 months using a global score, which considered the frequency, duration and severity of vertigo. This is a single, small study and the certainty of the evidence was very low. We are unable to draw meaningful conclusions from the numerical results. Assessed by frequency of vertigo Three studies (304 participants) assessed the change in frequency of vertigo episodes at 3 to < 6 months. Intratympanic corticosteroids may slightly reduce the frequency of vertigo episodes. The proportion of days affected by vertigo was 0.05 lower (absolute difference -5%) in those receiving intratympanic corticosteroids (95% CI -0.07 to -0.02; 3 studies; 472 participants; low-certainty evidence). This is equivalent to a difference of approximately 1.5 days fewer per month affected by vertigo in the corticosteroid group (with the control group having vertigo on approximately 2.5 to 3.5 days per month at the end of follow-up, and those receiving corticosteroids having vertigo on approximately 1 to 2 days per month). However, this result should be interpreted with caution - we are aware of unpublished data at this time point in which corticosteroids failed to show a benefit over placebo. One study also assessed the change in frequency of vertigo at 6 to ≤ 12 months and > 12 months follow-up. However, this is a single, small study and the certainty of the evidence was very low. Therefore, we are unable to draw meaningful conclusions from the numerical results. Serious adverse events Four studies reported this outcome. There may be little or no effect on the occurrence of serious adverse events with intratympanic corticosteroids, but the evidence is very uncertain (intratympanic corticosteroids 3.0%, placebo 4.4%; RR 0.64, 95% CI 0.22 to 1.85; 4 studies; 500 participants; very low-certainty evidence)., Authors' Conclusions: The evidence for intratympanic corticosteroids in the treatment of Ménière's disease is uncertain. There are relatively few published RCTs, which all consider the same type of corticosteroid (dexamethasone). We also have concerns about publication bias in this area, with the identification of two large RCTs that remain unpublished. The evidence comparing intratympanic corticosteroids to placebo or no treatment is therefore all low- or very low-certainty. This means that we have very low confidence that the effects reported are accurate estimates of the true effect of these interventions. Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area, and enable meta-analysis of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits. Finally, we would also highlight the responsibility that trialists have to ensure results are available, regardless of the outcome of their study., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Background: Ménière's disease is a condition that causes recurrent episodes of vertigo, associated with hearing loss and tinnitus. Aminoglycosides are sometimes administered directly into the middle ear to treat this condition. The aim of this treatment is to partially or completely destroy the balance function of the affected ear. The efficacy of this intervention in preventing vertigo attacks, and their associated symptoms, is currently unclear., Objectives: To evaluate the benefits and harms of intratympanic aminoglycosides versus placebo or no treatment in people with Ménière's disease., Search Methods: The Cochrane ENT Information Specialist searched the Cochrane ENT Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 14 September 2022., Selection Criteria: We included randomised controlled trials (RCTs) and quasi-RCTs in adults with a diagnosis of Ménière's disease comparing intratympanic aminoglycosides with either placebo or no treatment. We excluded studies with follow-up of less than three months, or with a cross-over design (unless data from the first phase of the study could be identified).  DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were: 1) improvement in vertigo (assessed as a dichotomous outcome - improved or not improved), 2) change in vertigo (assessed as a continuous outcome, with a score on a numerical scale) and 3) serious adverse events. Our secondary outcomes were: 4) disease-specific health-related quality of life, 5) change in hearing, 6) change in tinnitus and 7) other adverse effects. We considered outcomes reported at three time points: 3 to < 6 months, 6 to ≤ 12 months and > 12 months. We used GRADE to assess the certainty of evidence for each outcome.  MAIN RESULTS: We included five RCTs with a total of 137 participants. All studies compared the use of gentamicin to either placebo or no treatment. Due to the very small numbers of participants in these trials, and concerns over the conduct and reporting of some studies, we considered all the evidence in this review to be very low-certainty.  Improvement in vertigo This outcome was assessed by only two studies, and they used different time periods for reporting. Improvement in vertigo was reported by more participants who received gentamicin at both 6 to ≤ 12 months (16/16 participants who received gentamicin, compared to 0/16 participants with no intervention; risk ratio (RR) 33.00, 95% confidence interval (CI) 2.15 to 507; 1 study; 32 participants; very low-certainty evidence) and at > 12 months follow-up (12/12 participants receiving gentamicin, compared to 6/10 participants receiving placebo; RR 1.63, 95% CI 0.98 to 2.69; 1 study; 22 participants; very low-certainty evidence). However, we were unable to conduct any meta-analysis for this outcome, the certainty of the evidence was very low and we cannot draw any meaningful conclusions from the results.  Change in vertigo Again, two studies assessed this outcome, but used different methods of measuring vertigo and assessed the outcome at different time points. We were therefore unable to carry out any meta-analysis or draw any meaningful conclusions from the results. Global scores of vertigo were lower for those who received gentamicin at both 6 to ≤ 12 months (mean difference (MD) -1 point, 95% CI -1.68 to -0.32; 1 study; 26 participants; very low-certainty evidence; four-point scale; minimally clinically important difference presumed to be one point) and at > 12 months (MD -1.8 points, 95% CI -2.49 to -1.11; 1 study; 26 participants; very low-certainty evidence). Vertigo frequency was also lower at > 12 months for those who received gentamicin (0 attacks per year in participants receiving gentamicin compared to 11 attacks per year for those receiving placebo; 1 study; 22 participants; very low-certainty evidence).  Serious adverse events None of the included studies provided information on the total number of participants who experienced a serious adverse event. It is unclear whether this is because no adverse events occurred, or because they were not assessed or reported.  AUTHORS' CONCLUSIONS: The evidence for the use of intratympanic gentamicin in the treatment of Ménière's disease is very uncertain. This is primarily due to the fact that there are few published RCTs in this area, and all the studies we identified enrolled a very small number of participants. As the studies assessed different outcomes, using different methods, and reported at different time points, we were not able to pool the results to obtain more reliable estimates of the efficacy of this treatment. More people may report an improvement in vertigo following gentamicin treatment, and scores of vertigo symptoms may also improve. However, the limitations of the evidence mean that we cannot be sure of these effects. Although there is the potential for intratympanic gentamicin to cause harm (for example, hearing loss) we did not find any information about the risks of treatment in this review.  Consensus on the appropriate outcomes to measure in studies of Ménière's disease is needed (i.e. a core outcome set) in order to guide future studies in this area and enable meta-analysis of the results. This must include appropriate consideration of the potential harms of treatment, as well as the benefits., (Copyright © 2023 The Authors. Cochrane Database of Systematic Reviews published by John Wiley & Sons, Ltd. on behalf of The Cochrane Collaboration.)

Purpose: To find out clinical features associated with poor response to treatment in vestibular migraine (VM)., Methods: VM patients treated with drugs recommended in migraine prophylaxis were included in this multicenter study. Migraine features including type, age of onset of headache and vertigo attacks, attack frequency, intensity, associated symptoms, triggering factors, presence of interictal dizziness/imbalance, anxiety, depression, history of motion sickness, and family history of migraine were noted. Amitriptyline, flunarizine, propranolol, topiramate and venlafaxine were chosen depending on patients' individual requirements. Maximum dose of each drug was tried for 2 months to decide its efficacy. In the case of inefficacy, it was changed with another preventive drug of different class. If there was still no improvement, two drugs of different classes were combined. ≥ 50% reduction in attack frequency and severity in patients using one drug and a combination of two drugs was compared, with patients showing <50% reduction despite combination therapy, regarding their clinical features., Results: The results of 430 VM patients, 65 men and 365 women with a mean age of 42.2 ± 12.2 years (range: 17-74 years), were analyzed., Conclusion: Cutaneous allodynia frequently associated with female sex, comorbid anxiety and depression and interictal dizziness/imbalance enhanced with comorbid anxiety were risk factors for reduced treatment response. Aural fullness might be the clue of impending concomitant Meniere's disease not responding to migraine preventives.

Purpose: Intratympanic (IT) drug delivery receives attention due to its effectivity in treatment for Menière's disease (MD). Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable., Methods: The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus (ICON) on treatment of Menière's disease (2018), Clinical Practice Guideline (2020) and European Position statement on Diagnosis and Treatment of Meniere's Disease (2018) are taken into account for reference, and follow advice from experts from Europe, USA and China., Results: Experts agree on the following: (1) The effectiveness of IT methylprednisolone (ITM) on vertigo control seems to be somewhat better than that of IT dexamethasone (ITD), and ITM can restore hearing in some cases. (2) Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin (ITG) in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. (3) Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear., Conclusion: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD., (© 2022. The Author(s).)

Background: Meniere's Disease (MD) is a complex and multifactorial inner ear problem characterized by episodic vertigo, unilateral sensori-neural hearing loss and tinnitus or fullness in the ear due to Endolymphatic hydrops. There are multiple treatment options available for this disease; from which cortisone therapy can be given in different routes and in different doses., Objectives: is to identify the successfulness of treatment of MD by multi-session intra-tympanic dexamethasone injection compared to the single-session method., Method: Interventional prospective study of study 70 cases of definite MD treated by 4 sessions of intra-tympanic injection weekly and compared to a control group of 66 cases of age matched patients with definite MD treated by the traditional single intra-tympanic injection. Patients In the study and the control group were observed for 6 months after the treatment for the development of any vertiginous attacks., Results: only 3 patients in the study group and 30 patients in the control group failed to respond to treatment and developed vertigo in the period of 6 months after treatment. The difference between the success rate in the two groups was statistically highly significant., Conclusion: multi-session Intra-tympanic dexamethasone injection is superior to the single injection in control of vertigo in patients with definite MD.

Background: Middle ear pressure therapy (MEPT) is effective for intractable vertigo in patients with definite Meniere's disease (MD) and treatment-refractory delayed endolymphatic hydrops (DEH). Four-month MEPT with the EFET01 ® , an MEPT device developed in Japan and covered by national health insurance since September 2018, has shown efficacy. However, efficacy and safety after 12 months of treatment, which is appropriate for determining the therapeutic effect of MEPT devices, is unclear., Objectives: Examine the therapeutic effect of 12-month MEPT using the ETET01 ® ., Material and Methods: Patients underwent MEPT using the EFET01 ® from September 2018 to July 2021. Thirty-three patients followed for >12 months were enrolled in this retrospective study. Clinical data were evaluated in the first and second 6-month treatment periods. Data from the second 6-month period were compared with data from an MEPT study using a different device., Results: MEPT with the EFET01 ® significantly improved vertigo in the first period, with further improvement in the second period. The efficacy and safety were comparable to MEPT with other devices., Conclusions: MEPT with the EFET01 ® is effective for intractable vertigo in patients with definite MD and DEH, and 12-month follow-up is recommended., Significance: The efficacy of 12-month MEPT with the EFET01 ® was demonstrated.

Background: Middle ear pressure therapy (MEPT) is effective in treating intractable vertigo in patients with definite Meniere's disease (MD) and delayed endolymphatic hydrops (DEH) refractory to conservative treatment. A novel middle ear pressure device, the EFET01 ® , which requires no transtympanic ventilation tubes, was developed in Japan, approved by the Japanese Ministry of Health, Labour and Welfare, and has been used under Japanese national health insurance since September 2018., Objectives: To examine short-term therapeutic effect of MEPT using the ETET01 ® compared with previous clinical trial results., Methods: Patients selected according to Japan Society for Equilibrium Research (JSER) guidelines underwent MEPT using the EFET01 from September 2018 to July 2021, and 44 patients were enrolled in this retrospective study. Clinical data analysed at 4 months after the start of MEPT were compared with those of the previous clinical trial for the EFET01., Results: MEPT using the EFET01 showed the same therapeutic efficacy as that of the previous clinical trial, i.e. improvement in the intensity and frequency of vertigo with no effect on hearing, even under JSER guidelines for proper use of MEPT., Conclusion: MEPT using the EFET01 provided an effective treatment option for intractable vertigo in patients with definite MD and DEH.

Introduction: Ménière's disease is a multifactorial disorder affecting the inner ear, characterized by episodes of spontaneous and recurrent vertigo, fluctuating hearing loss and tinnitus. Intratympanic gentamicin therapy has been used to reduce the intensity and frequency of attacks in intractable Ménière's disease, but it is associated with hearing loss. There is controversy regarding its efficacy and safety., Methods: We searched in Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified 13 systematic reviews that included 80 primary studies overall, of which three correspond to randomized trials. We concluded that intratympanic gentamicin may improve the control of vertigo, and result in little or no difference to tinnitus, but the certainty of the evidence is low. Furthermore, we are uncertain whether intratympanic gentamicin reduces hearing or the frequency of vertigo attacks as the certainty of the evidence has been assessed as very low.

Objectives: The efficacy of intratympanic steroid (ITS) injection for intractable Meniere's disease has been reported; however, its differences in responsiveness are not fully understood. This study investigated the clinical characteristics of patients who responded to ITS injection treatment., Methods: This retrospective study included 32 patients with Meniere's disease who were unable to control frequent vertigo attacks despite conservative treatment for at least 3 months. They received an intratympanic injection of dexamethasone (3.3 mg/mL) in the affected side at least three times. We measured hearing threshold, subjective symptom scores, cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP), and performed glycerol and bithermal caloric tests., Results: Satisfactory control of vertigo for 1 year after the first round of injection was found in 18 patients (56.3%; the response group). However, the injections failed to control vertigo in the other 14 patients (43.8%; the non-response group), and they were then treated with middle ear micropressure therapy. The response group showed improvement in low-frequency hearing, whereas hearing acuity did not change in the non-response group. Significantly reduced amplitude of cVEMP on the affected side was found in 62.5% of patients in the response group; however, no patients in the non-response group showed reduced amplitude of cVEMP., Conclusions: ITS injection significantly improved the subjective symptoms for intractable Meniere's disease; however, the long-term effects were heterogeneous. Our results suggest that reduced amplitude in cVEMP is associated with the effectiveness of ITS injection treatment., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To compare the efficacy of gentamicin and steroids in patients with Meniere's disease (MD)., Methods: The study protocol was structured in accordance with the Population, Intervention, Comparison and Outcome (PICO) framework. We used "Endnote" (Thomson ResearchSoft; Stanford, Connecticut, the United States) to retrieve database documents. A systematic literature search of Web of Science and PubMed Database through May 2020 was conducted using specific search terms. Inclusion criteria, exclusion criteria, vertigo improvement, and exact hearing changes were defined. Review Manager 5.3 (Cochrane) was used for data analysis., Results: A total of 80 articles were searched from Web of Science and 23 articles were searched from PubMed database. After further reviewing the specific points of the inclusion criteria and exclusion criteria, 9 papers were finally selected. Intratympanic gentamicin (ITG) was superior to intratympanic steroid (ITS) in reducing the number of vertigo attacks (odds ratio (OR) 3.08, 95% confidence intervals (CI) [2.05-3.65]), probability (P) < 0.01). As for hearing improvement, we did the analysis twice. With all the studies included, the odds of hearing improvement (by "x") was 0.31 among patients receiving gentamicin compared to those treated by steroids (OR 0.31, 95% CI [0.16-0.61]). But after removing one study with outlying results from the analysis, this effect disappeared. Hearing loss of ITG and ITS was not statistically significant (P = 0.29)., Conclusions: ITG is superior to ITS in reducing the number of vertigo attacks in the treatment of MD (P < 0.01); the impact on hearing is more heterogeneous in the studies. Overall, there was no clear difference between ITG and ITS on hearing improvement and on hearing loss., (© 2020. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: To assess the efficacy of a 4-week transtympanic dexamethasone perfusion using the Silverstein MicroWick TM in patients with Ménière's disease., Materials and Methods: A self-reported questionnaire was designed and sent to patients who underwent transtympanic dexamethasone perfusion using the Silverstein MicroWick TM from January 2017 to December 2020. A retrospective chart review was conducted to gather demographic and audiological data of those who responded., Results: Forty respondents were separated into Group 1 (n = 34), who required no further procedure, and Group 2 (n = 6), who required additional procedure for Ménière's disease. In Group 1, 50% reported subjective improvement in tinnitus, 59% in aural fullness, 79% in vertigo, and 21% in hearing loss after the MicroWick TM treatment. A statistical analysis of the scores revealed that the improvement in aural fullness and vertigo met significance (p = 0.03 and p = 0.002, respectively). In Group 2, no significant change was seen in their symptoms. Audiological data showed no significant change in the pure tone average or the word recognition score after the treatment., Conclusion: Transtympanic dexamethasone perfusion using the Silverstein MicroWick TM is a well-tolerated treatment option for patients with Ménière's disease. Our survey data suggest its significant efficacy in reducing aural fullness and vertigo attacks in these patients. Prospective studies will be conducted to further establish its potential role in successfully managing patients with Ménière's disease., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ménière disease is a disorder of the inner ear, characterized by rotational vertigo, hearing loss, tinnitus, and vegetative symptoms. The aim of the present research is to examine the effectiveness of betahistine and piracetam in the reduction of vertigo attacks in Ménière disease. To verify our hypothesis, 105 (31 male and 74 females, mean age [standard deviation], 57.4 [11.05]) adult patients with definite Ménière disease were enrolled in this investigation. Beside the analysis of the hospital records, the subjective complaints of the patients and the completed vertigo diaries were taken into consideration too. The statistical analysis was completed using the IBM SPSS version 24 software. Retrospective analysis, including a 12 years period was conducted. Based on our results, betahistine was successful in the reduction of attacks. Statistically significant decrease was achieved in frequency of dizziness ( P = .000331) and vertigo ( P < .00001) and in the duration of them ( P = .000098), although in the mean power of them was not ( P = .0887). The mean dose in the symptomatic treatment was determined as 87.5 ± 27.2 mg per day; however, there was no connection detected between the dose of the agent and the effectiveness of the symptomatic control. By using dual therapy (betahistine and piracetam), vertigo episodes appeared significantly less often ( P = .027, Odds ratio: 4.9, 95% confidence interval: 1.2-20.2). Finally, it can be concluded that betahistine is effective in Ménière disease, but the daily dose of it should be set up for every patient individually. The advantage of the dual therapy was also confirmed.

Background: Ménière's disease (MD), characterized by episodic vertigo attacks and fluctuating progressive hearing loss, is treated by low-dose intratympanic gentamicin (ITG) injections. Whether ITG causes hearing loss is controversial, and knowledge about its effects on the contralateral hearing and vestibular function is lacking., Aims/objectives: We aimed to evaluate the effect of ITG on bilateral auditory and otolith organ function in patients with unilateral refractory MD., Material and Methods: The data of 30 patients was collected, including history, and pure tone audiometry and vestibular-evoked myogenic potentials (VEMPs) results before and one month after ITG treatment. Changes in vertigo were assessed at a two-year follow-up., Results: One month after ITG injection, auditory thresholds between 125 Hz and 8 kHz on the injection side remained unchanged but have improved on the contralateral side at 125 Hz, 250 Hz, 1 kHz. The cervical and ocular VEMP solicitation rates on the injection side were lower than before the injection. Two years after treatment, vertigo was improved in 88.5% and complete controlled in 76.7% patients respectively., Conclusions and Significance: The intractable vertigo of MD can be effectively controlled by ITG injection. This can improve the low and medium frequency hearing level in the contralateral ear, suggesting that it might help prevent contralateral MD occurrence.

Background: Ménière's Disease (MD) is a chronic condition where patients suffer recurrent vertigo attacks. Evidence for treatment concepts are to this date low., Aims/objective: To evaluate the therapeutic effect of intratympanic lidocaine injections to reduce the number of attacks., Methods: Twenty patients diagnosed with definitive MD that were treated with 34 intratympanic lidocaine injections were included. Main outcome measures were the number of vertigo attacks in the previous four weeks, the attack free period and the subjective improvement of the condition., Results: Mean follow up after first lidocaine injection was 25.3 months (±22.2; range 1.9-79.7). Patients expressed subjective improvement in overall situation, vertigo, and aural fullness. The number of vertigo attacks before each assessment decreased from 7.1 (±5.9; range 2-20) per months at baseline to 1.9 (±3.8; range 0-15). 25% of the patients suffered no further attacks, the other patients had an average attack free period of 7.8 months (±15.4; range 0.2-58.4). Hearing thresholds remained unaffected. Repetitive injections proved effective., Conclusion and Significance: Intratympanic lidocaine is an effective nonsurgical and non-ablative therapy for MD. When patients experience an increase of attacks repetitive injections promise improvement.

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., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020. Published by Elsevier B.V.)

Introduction: The term Meniere disease (MD) gathers a set of rare diseases involving the inner ear characterized by episodic vertigo associated with fluctuating auditory symptoms. Five clinical subgroups of patients have been defined, including familial MD, autoimmune MD, and MD with migraine. The diagnosis is based on clinical criteria as no biomarker is available, but genetic factors have a significant contribution in familial and non-familial MD., Areas Covered: In this review, the authors summarize the pharmacological treatment for vertigo in MD, providing evidence from preclinical and clinical studies. However, evidence supporting the efficacy for betahistine, diuretics, and intratympanic administration of corticosteroids or gentamicin is limited., Expert Opinion: Randomized clinical trials should consider stratification by MD clinical subgroups. The treatment plan should be personalized according to the clinical subgroup, hearing stage, duration of the disease, vertigo attack profile, and comorbidities. The treatment should include therapeutic counseling, sodium-free diet, high-water intake, and a diary of vertigo attacks with symptoms during the episodes to improve phenotyping. Migraine or autoimmune comorbidities will also require pharmacotherapy. Genetic testing by exome/genome sequencing should be discussed with the patient for familial MD and individuals with an early onset for genetic counseling and future gene therapies.

Purpose: The aim of our study is to investigate the effectiveness and safety of the treatment, based on vertigo diaries and pure tone audiograms., Methods: The complete medical documentation of 105 definite patients suffering from Ménière's disease was analyzed. In the studied group, nine patients were treated with intratympanic gentamycine. Long-term follow-up of the patients was carried out, using vertigo diaries, medical letters, anamnestic data, and pure tone audiograms. Audiometric results and vertigo complaints before and after treatment were contrasted using IBM SPSS V24 software., Results: Based on our analysis, vertigo attacks appeared significantly less often after gentamycine treatment [p < 0.001; Odds ratio 0.003 (95% CI 0.001-0.012)], which confirms the efficacy of the therapy. Pure tone stages before and after the application of gentamycine were contrasted using the Mann-Whitney U test. When comparing the audiometric results of long-term follow-ups by using the logistic regression, a statistically significant difference was observed between the treated and not treated groups [p = 0.001; Odds ratio 0.141 (95% CI 0.064-0.313)], and based on the survivorship curve hearing impairment was more common in the not treated group which also supports our results. Based on the non-parametric test, there was no significant difference (p = 0.84) between the pure-tone stages of the control group and of those treated with gentamycine., Conclusion: Our results indicate that intratympanic gentamycine is effective in controlling vertigo attacks, and there is no higher risk for hearing loss than in case of spontaneous progression of the disorder.

Objective: To evaluate the efficacy of on demand and low dose intratympanic gentamicin (ITG) in patients with intractable Meniere's disease (MD)., Study Design: Clinical chart review., Setting: Secondary care center., Patients: Subjects with MD who failed conventional treatment and underwent on demand ITG infiltration from June 2013 to December 2018., Intervention: 0.4 to 0.5 ml of buffered gentamicin were administered through an intratympanic route. A total of 5 mg in case of low dose and 20 mg as a standard dose., Main Outcome Measures: Vertigo control, Meniere's Disease Functional Level Scale (MDFLS), Dizziness Handicap Inventory (DHI), and pure tone audiometry pre and posttreatment., Results: Thirty-one patients, 16 women and 15 men with a mean age of 52.81 (22-79) years were included. The number of ITG injections ranged from 1 to 7, with a mean of 2.52 applications per patient. Mean interval between doses was 212.15 (21-1442) days. Average follow-up was 24.03 months. An improvement on MDFLS was seen on 77.4% (n = 24) patients. DHI score improved after gentamicin treatment (mean 55.23 versus 24.06, p ≤ 0.001). Thirty patients (96.8%) reached complete or substantial vertigo control. Only one patient did not achieve control. Hearing was preserved in 43.5% (n = 10) of analyzed audiograms, whereas 17.4% (n = 4) developed hearing loss greater than 20 dB, which was not statistically significant (p = 0.099)., Conclusions: In our study, on demand and low dose ITG was effective for vertigo control in patients with intractable MD. Individualized therapy is recommended in all patients to minimize vestibular and cochlear toxicity.

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere's disease (MD). Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gain and pure-tone threshold after low-dose ITG for MD. Methods: Sixteen patients with definite MD who were treated by low-dose ITG were retrospectively reviewed. We defined VOR gain difference as an amount of decreased gain in video head impulse test one month after ITG. Patients were classified into two groups: single injection vs. multiple injections. Multiple injections group was composed of patients with poor vertigo control after initial ITG who required second or third ITG later in follow up period. Results: VOR gain differences of both horizontal and posterior canal plane were higher than those of anterior canal plane. Between two groups, mean VOR gain difference of horizontal canal plane in multiple injections group was lower than that in single injection group. Only two patients showed increased pure-tone threshold more than 10 dB. Conclusion and significance: Our results suggest that ITG appears to cause a differential loss of function across three semicircular canals. Furthermore, if VOR gain difference of horizontal canal is relatively low after initial ITG, patient might have poor vertigo control and be required another ITG.

Background: Endolymphatic sac decompression surgery (ESDS) is commonly used for intractable Meniere's disease, but its effect remains controversial because of the low rate of vertigo control. Objectives: In the present study, we examined ESDS combined with posterior tympanotomy with local steroids as a new therapeutic strategy for intractable Meniere's disease. Materials and methods: This retrospective study enrolled 19 patients with Meniere's disease using ESDS combined with posterior tympanotomy with local steroids between 2015 and 2018. Postoperatively we recorded and evaluated changes in vertigo attack frequency and hearing level. Results: Vertigo episodes decreased from 3.6 ± 3.2 times preoperatively to 0.2 ± 0.5 times postoperatively, with 89.5% complete vertigo control rate. Mean PTA decreased from 40.5 ± 21.3 dB to 39.5 ± 17.5 dB postoperatively, with 21.1% improvement rate. Conclusions and significance: The present findings suggest that ESDS combined with posterior tympanotomy with local steroids could improve clinical results of hearing as well as vertigo control for intractable Meniere's disease.

Purpose: Specially processed cereals (SPC) that increase endogenous antisecretory factor (AF) synthesis have been proposed to improve symptoms of Meniere's disease (MD) with controversial results. The aim of this study was to evaluate the effects of SPC in patients with definite unilateral MD and compare the results to a treatment protocol with intravenous glycerol and dexamethasone., Methods: Thirteen patients with unilateral MD were treated with SPC and 13 patients were treated with intravenous glycerol and dexamethasone for 12 months. Audio-vestibular evaluation was performed before (T0) and at the end of the treatments (T12). The number of vertigo spells were evaluated before and after therapy and the Efficacy Index (EI) was calculated. Questionnaires for hearing loss (HHIA), tinnitus (THI) and quality of life (TFL) were administered., Results: EI decreased in the SPC group in the second semester compared to the first although not significantly (p = 0.6323). There was a significant reduction for THI score in the SPC group at T12 (p = 0.0325). No significant differences were found between the two groups at T0 (p = 0.4723), while a significant difference was found at T12 (p = 0.0041). Quality of life showed an improvement in daily activities in the SPC group compared to infusion therapy group., Conclusion: Our study shows a reduced number of vertigo attacks and a positive effect on the discomfort generated by tinnitus and quality of life in patients with unilateral MD treated with SPC and when compared to patients treated with intravenous glycerol and dexamethasone. No effects on hearing thresholds were noted in both groups.

Objective: To evaluate the efficacy and safety of modified-release (MR) betahistine (48 mg once daily) versus betaserc (24 mg twice daily) in patients with Meniere's disease or vestibular vertigo., Material and Methods: A multicentre, double-blind, randomized clinical study in patients with an established diagnosis of Meniere's disease (35%) or vestibular vertigo (65%) was carried out. A total of 264 patients were randomized (132 in each group).The inclusion criteria were a Dizziness Handicap Inventory (DHI) total score of more than 30 points and at least 2 vertigo attacks within the previous 4 weeks. The primary efficacy variable was the change in the DHI total score from baseline to after 12 weeks of treatment. The predefined non-inferiority margin was set at 9 points for the DHI total score., Results: After 12 weeks of treatment, the DHI total score was significantly ( p <0.001) decreased compared with baseline, by 32.0±20.7 in the betahistine MR group and by 31.8±19.8 in the betaserc group. The adjusted difference in the change in the DHI total score with a one-sided 97.5% CI was 0.9 (--; 5.3) points, the upper confidence limit (+5.3) fell below the predefined margin of non-inferiority of 9 points, and the non-inferiority of betahistine MR to betaserc was established. The treatment groups were comparable in terms of reduced scores for the functional, emotional and physical subdomains of DHI; reduced frequency, intensity and duration of vertigo attacks; decreased proportion of patients with prolonged attacks and severe symptoms during attacks; and scores on the Clinical Global Impression - Improvement scale. The safety profile of betahistine MR was comparable to that of betaserc, the most frequently reported adverse event was headache in both treatment groups., Conclusion: Betahistine MR (48 mg once daily) is non-inferior to betaserc (24 mg twice daily) in patients with Meniere's disease or vestibular vertigo and has a comparable safety profile.

Introduction: Menière's disease (MD) is an uncommon cause of sudden profound vertigo. A variety of medical and surgical treatments have been used to manage this condition. This study reviewed the outcomes of patients treated with grommet insertion and transtympanic steroid injection., Methods: Patients diagnosed with MD between 2007 and 2017 were identified, and case notes and audiological data were retrieved for those managed by grommet (ventilation tube) insertion with and without transtympanic steroid injection., Results: Thirty-three patients were identified as being diagnosed with MD. Grommet insertion resulted in cessation or improvement of attacks in 91% of cases. The mean follow-up duration was 33.8 months (median: 29 months). The mean hearing threshold across the low frequencies improved from 57.2dBHL to 49.4dBHL ( p =0.031). Following the intervention, improved tinnitus was reported in 80% of cases. Twelve patients (36%) reported aural fullness prior to grommet insertion; all reported improved symptoms following the procedure., Conclusions: Early grommet insertion with transtympanic steroid injection, combined with customised vestibular physiotherapy, may provide an alternative first-line strategy for MD, preventing further true MD attacks. In some patients, it may significantly improve hearing thresholds.

Objectives: To investigate the beneficial effects and safety of intratympanic steroid installation compared with placebo in patients with Menière's disease., Methods: We performed a systematic literature search in MEDLINE and EMBASE for existing systematic reviews and individual randomized controlled trials (RCTs). Studies were included if they investigated the usage intratympanic steroids in patients aged 18 and above, with definite or probable Menière's disease. The quality of the identified existing reviews was assessed using the AMSTAR tool. The risk of bias in RCTs was assessed using the Cochrane Risk of Bias Tool and overall quality of the individual outcomes was evaluated using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) method., Results: The literature search provided four systematic reviews, from which one yielded a sufficient AMSTAR evaluation and subsequently provided three RCTs relevant for inclusion. Due to the lack of sufficient reporting of the data, quantitative synthesis was not applicable. In the qualitative synthesis for the primary outcome, the results from the RCTs showed that there was a slight indication of steroid treatment reducing the frequency of vertiginous attacks. No serious adverse events were reported. Based on the GRADE approach the quality for both findings is very low. No studies reported on the secondary outcomes., Conclusion: The effect of intratympanic steroid treatment in Menière's disease is questionable. There is a great need for further research to sufficiently assess whether steroid treatment may be considered as a safe and effective treatment for patients with Menière's disease.

Background: Ménière's disease (MD) is a disorder of the inner ear, causing episodes of vertigo. Although surgery is reserved for intractable MD, intratympanic gentamicin (ITG) injection has become an alternative for controlling vertigo., Aims/objectives: To investigate the genetic basis of ITG efficacy., Material and Methods: We hypothesized that single nucleotide polymorphisms (SNPs) affect outcomes in patients with MD who receive ITG injections. Whole-exome sequencing was used to determine variations in coding regions., Results: Multivariate analysis revealed two SNPs, rs1052571 in caspase 9 (CASP9; p = .017) and rs3745274 in cytochrome P450 2B6 (p = .053), which were associated with susceptibility to ITG injections. Only the C-allele in the rs1052571 SNP was significantly associated with susceptibility (p = .027; odds ratio: 5.95; 95% confidence interval: 1.26-28.57, by Fisher's exact test)., Conclusions and Significance: Our results elucidated the role of the rs1052571 SNP and provide a genetic perspective on gentamicin efficacy (susceptibility) in treating intractable MD.

Objectives: The aim of the present study was to investigate current treatment practices and self-reported effectiveness in Ménière's disease., Materials and Methods: Members of two Italian Ménière's disease support (n=170) with ≥6-month history of Ménière's disease were administered an online survey about recent treatments. Vertigo episode count, work absenteeism, and limitations in family life, social life, work, or travel as included in the Social Life and Work Impact of Dizziness Questionnaire before and after recent treatments were queried., Results: Twenty-four different treatments were reported for Ménière's disease, with dietary modifications (55%), diuretics (47%), and betahistine (41%) being the most common. The majority (71%) received multiple simultaneous treatments. Prior to the most recent treatments, 78%-89% of respondents indicated limitations in family or social life, work, or traveling. After their most recent treatment, respondents reported improvements in mean vertigo episode counts (5.7±7.6 vs. 2.6±4.6, p<0.001), days off work per month (10.1±9.2 vs. 4.2±6.7, p<0.001), and proportions indicating limitations in any functional measure assessed (p<0.05). These findings were consistent regardless of treatment approach (p<0.05 for all). Intratympanic gentamicin provided the greatest reductions in vertigo count, functional limitations, and work absenteeism (p<0.01 for all), as well as the fewest respondents reporting post-treatment functional limitations (16%-37%)., Conclusion: Despite many treatment approaches targeting different proposed pathophysiology for Ménière's disease in this cross-sectional survey, all treatments are reported as effective by patients. These findings support a prominent placebo effect in Ménière's disease and highlight challenges in studying treatment outcomes; there is a critical need to better understand Ménière'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.

Objective: To describe the long-term clinical vertigo control along with measured lateral canal vestibular function in patients with unilateral refractory Menière's disease (MD) treated with gentamicin transtympanic injections (TTI)., Study Design: Retrospective analytic study., Setting: Tertiary referral center., Patients: Thirty-eight patients treated by TTI for medically refractory unilateral MD, defined by the 1995 AAO-HNS criteria, between May 2006 and December 2012., Intervention(s): One-year course of treatment with gentamicin TTI following a low dose on-demand protocol. TTI were repeated in new courses of treatment when MD recurrence occurred., Main Outcome Measure(s): AAO-HNS class of control, caloric tests (CalT), recurrence rate., Results: After an average clinical follow-up of 71 months, all patients entered a class of control A (78%) or B (22%), with an average of 2.3 TTI received. The mean maximal obtained deficit was 88.5%, and the mean long-term deficit was 85.5%. Ten (26%) patients had disease recurrence requiring a new course of treatment. A value of the first CalT in the 3 months following the first TTI strictly higher than 78% was significantly associated with disease control and the absence of symptom recurrence (p≤0.01). In the "recurrence" group, four patients had a significantly lower mean value of all CalT performed after the first TTI when compared with other patients (p≤0.001), indicating gentamicin resistance CONCLUSION:: Achieving a sustainable vestibular deficit on caloric testing is key for MD symptom control after gentamicin TTI. Gentamicin resistance must be diagnosed early to adapt therapeutic strategies.

Objectives: Since oral betahistine has a very high first-pass effect (ca. 99%), metabolized by monoamine oxidases (MAO), the benefits of a high-dosage betahistine monotherapy were compared with those of a lower dosage of betahistine in combination with the MAO-B inhibitor (MAO-B) selegiline on the frequency of acute attacks of vertigo in patients with Menière's disease (MD)., Methods: Thirteen adults aged 40-75 years (mean 58.9 years; six females) had initially been treated with a high dosage of betahistine dihydrochloride for at least 1 year. Under this therapy, all of them had ≤ 1 attack for ≥ 3 months prior to the combination pharmacotherapy. Subsequently, they received 5 mg/day selegiline and the dosage of betahistine was reduced to about one tenth and then individually adjusted to the dosage needed to achieve the same treatment response (≤ 1 per 3 months, observational period of at least 6 months)., Results: The initial dosage for the long-term "titration" of the attacks of vertigo was 9-80 24-mg tablets/day (mean 37.3), i.e. 216-1920 mg/day (mean 895.4 mg/day). After the combination with selegiline, the dosage needed to achieve the same benefit for ≥ 3 months was 3-36 24-mg tablets (mean 8.5), i.e., 72-864 mg/day [mean 204.9 mg/day, p < 0.001 (paired t test)]. One patient transiently stopped the treatment with selegiline, another one reduced the dosage to 2.5 mg/day and the attacks re-occurred after 2-4 weeks. Six out of 13 patients reported transient fullness of the head during the combined treatment; in 2 of them this went away when they switched to 2.5 mg bid. In the longer term (> 9 months), one patient had to increase the selegiline dosage to 5 mg bd, one patient stopped the treatment with selegiline., Conclusions: The achievement of the same clinical effect with a significantly lower (about 1/5) dosage of betahistine can be explained by the inhibition of the MAO-B by selegiline leading to higher serum concentrations of betahistine. This approach is in line with recent developments to bypass the first-pass effect of betahistine by transbuccal or intranasal application. Despite the substantial methodological limitations of such an observational study, this combined pharmacotherapy could be an alternative to a high-dosage monotherapy with betahistine of MD.

Background: Intra-tympanic injections of gentamicin (ITG), a known ototoxic agent, have been proven to be effective in controlling Menière's disease (MD) symptoms, in patients who did not respond to conservative therapy, although its safety was questionable., Objectives: To study whether low-concentration ITG, in refractory MD, had an effect on the ipsilateral hearing, in comparison to the contralateral ear, and to study the effectiveness of such treatment., Methods: A comparative, retrospective cohort study was conducted between 2003 and 2015, and compared the change in the hearing level between the injected ear and the contralateral, untreated ear., Outcomes: In 20 of 27 patients (74.1%), one course of ITG treatment was considered as successful. In the short-term, there was improvement of hearing level at 1000 Hz (p = 0.014), and deterioration of hearing level at 8000 Hz (p = 0.039), both in comparison to the control ear. In the long-term and after confounders adjustment, we found there were no differences in the hearing levels between the treated ear and the untreated contralateral ear., Conclusions: A high success rates of treating vertigo attacks with low concentration ITG in refractory unilateral MD patients is herein reported, while a significant difference was not observed in the hearing threshold compared with the healthy contralateral ear.

Introduction: Ménière`s disease is an inner ear disorder characterized by episodes of spontaneous vertigo, fluctuating hearing loss and tinnitus. Diuretics have been widely used for the treatment of attacks, but there is controversy about their effectiveness., Methods: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified three systematic reviews including nineteen studies overall, of which four were randomized trials. We concluded it is not clear whether diuretics lead to a symptomatic improvement of vertigo or an objective decrease in hearing loss in patients with Ménière`s disease, because the certainty of the evidence is very low.

Objective: In this retrospective study the aim of the authors was to examine the effect of gentamicin on the individual semicircular canals after low dose, single injection intratympanal gentamicin therapy in Meniere's disease., Methods: Data of 32 patients treated between 2011 and 2015 were collected. The high frequency, high acceleration vestibuloocular reflex (VOR) gain was measured in the individual semicircular canals using video head impulse test immediately before the first intratympanal gentamicin instillation and approximately two months later., Results: In all cases 'AAO-HNS Class A' vertigo control could be attained at least for several months. In 13 cases only one instillation was necessary. In the other 19 cases the attacks returned after a few months. In 11 cases the injection had to be repeated a second time, in 4 cases 3 injections, in 2 cases 4, in 1 case 5 injections and in another 6 injections were necessary. The initial VOR gain was normal in all cases and two months after one injection it decreased in average by 40% in a highly significant manner. However, there were cases in which, although the patients became free of attacks, the gain values remained normal., Conclusion: It was possible to demonstrate a significant correlation between the gain decrease of the individual canals. There was no prognostic correlation between the initial gain decrease after the first injection and the necessity of further injections. Gain values also decreased slightly but significantly in the lateral and posteriors canals on the contralateral, untreated side, possibly because of the missing disfacilitation from the treated side., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Despite some proposed roles for the diagnostic impact of the cervical vestibular evoked myogenic potential test in the patients with Meniere's disease, the role of this test as an objective instrument in following up the patients with Meniere's disease who underwent. Intratympanic steroid injection is not cleared. In a prospective study, thirty-one adult patients with definite one-sided Meniere's disease with vertigo as main complaint refractory to medical treatments for three months, were selected. Patients underwent three times of intratympanic dexamethasone injection with one-week intervals. We performed cervical vestibular evoked myogenic potential test at first and four weeks after the last injection for all participants. We followed the patients for one year. The study results were analyzed with the chi-square test. Cervical vestibular evoked myogenic potential test could not be recorded in 26 patients (83.9%), and the test results were abnormal in the remaining 5 patients. The results were abnormal in the healthy ear of 32.3% of the patients. Despite the clinical improvement of the symptoms after intratympanic injection, the test results were not changed. Cervical vestibular evoked myogenic potential test could not be recorded in the majority of the patients with Meniere's disease; while it is usually recorded in normal ears. On the other hand, results of the cervical vestibular evoked myogenic potential test do not change during the early phase after treatment and could not be a good option for follow up and evaluating the response in this situation.

Problem: Meniere’s disease is an inner ear disorder characterized by episodes of spontaneous vertigo, fluctuating hearing loss and tinnitus. Betahistine has been used to reduce intensity and frecuency of vertigo attacks, but there is controversy regarding its effectiveness., Methods: To answer this question we used Epistemonikos, the largest database of systematic reviews in health, which is maintained by screening multiple information sources, including MEDLINE, EMBASE, Cochrane, among others. We extracted data from the systematic reviews, reanalyzed data of primary studies, conducted a meta-analysis and generated a summary of findings table using the GRADE approach., Results and Conclusions: We identified four systematic reviews including 12 trials overall. We concluded betahistine might reduce the number of attacks, vertigo intensity and lead to a symptomatic improvement according to global judgement in patients with Meniere’s disease, but the certainty of evidence is low. On the other hand, it probably does not have significant adverse effects.

Objective: To compare the efficacy of intratympanic gentamicin injection (ITG) on vertigo control, drop attacks, and functional level in Menière's disease patients with and without a history of migraine., Patients: Menière's disease patients (patients with migraine and age- and sex-matched control patients without migraine) treated from 2002 to 2012 who failed medical management and received ITG, with a minimum 2-year follow up., Intervention: ITG., Main Outcome Measures: Vertigo control, drop attack prevalence, and change in functional level., Results: Twenty-eight Menière's disease patients were included in this study (14 with migraine and 14 matched patients without migraine). There were three men and 11 women in each groups, with a mean age of 53 ± 8.9 years. Baseline characteristics (Menière's stage, vertigo frequency, drop attack prevalence, and functional level) before ITG were not significantly different between the two groups. Two years after ITG, 71% of Menière's disease with migraine patients and 78% of Menière's disease without migraine patients had class A, B, or C vertigo control (p > 0.999). Change in prevalence of drop attacks (43-7% versus 50-0%, respectively) was also similar (p > 0.999). However, significantly fewer vertigo control class A, B, and C migraine patients achieved functional level 1 or 2 (40%) compared with non-migraine patients (91%) (p = 0.007)., Conclusions: Although ITG appears equally effective in treating vertigo and drop attacks in Menière's disease with and without migraine, patients with migraine derive significantly less benefit in terms of functional improvement.

Objective: To assess the efficacy and safety of two different intratympanic dexamethasone (IT Dex) injection protocols for intractable unilateral Ménière's disease., Study Design: Prospective case series., Setting: Tertiary neurotology clinic., Patients: One hundred six consecutive adult patients with definite unilateral Ménière's disease who had failed medical management were studied for an average of 1,061 days. None had previous oral steroid, IT steroid, or ablative treatment., Interventions: Two different IT Dex regimes, either a single injection or a series of four injections, that were subsequently repeated as indicated., Main Outcome Measure: Requirement for subsequent ablative therapy in the form of intratympanic gentamicin, vestibular nerve section, or labyrinthectomy. Hearing outcomes were measured using pure-tone average of 0.5, 1, 2, and 3 kHz on standard audiometry., Results: The number of intratympanic dexamethasone injections per patient ranged from 1 to 29 (median = 4). Using the Kaplan-Meier method, predicted survival (patients not requiring ablative therapy) at 2 and 4 years after initial treatment was 83.9 and 79.3%, respectively. The injection series protocol ultimately yielded 5% better survival than the single injection protocol, but this was not statistically significant. Injections did not protect against hearing loss, and the most recent pure-tone averages declined compared with pretreatment values by an average of 8.27 dB (p < 0.05). The treatments did not result in any acute hearing losses, permanent tympanic membrane perforations, or other significant adverse events., Conclusion: Intratympanic dexamethasone injections were successful in controlling vertigo insofar as they were able to obviate ablative therapy in the majority of Ménière's disease patients in this study. The injection series protocol may have been more beneficial compared with the single injection, although the difference between the two protocols was nonsignificant. Hearing mildly declined over the treatment course, which likely represents natural disease progression. The lack of adverse events suggests that IT Dex may be a nonablative option for patients with bilateral disease or only hearing/vestibular ears.

Ménière’s disease affects the inner ear and its main symptoms are vertigo, hearing loss and fluctuating aural symptoms. Nowadays, there are many therapeutic alternatives, being the use of intratympanic corticosteroids one that has become popular. To answer this question, we searched in Epistemonikos database, which is maintained by screening multiple databases. We identified four systematic reviews including 15 studies overall, of which seven were randomized trials. We extracted data and generated a summary of findings table using the GRADE approach. We concluded intratympanic corticosteroids probably do not decrease tinnitus, and might not decrease vertigo, hearing loss or aural fullness sensation in Ménière’s disease. Intratympanic corticosteroids probably do not cause important adverse effects.