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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.

Background: TSCP has shown its efficacy in vertigo control for intractable Meniere's disease. However, hearing impairment remains a problem and hampered the application of the surgery. Aims/objectives: To investigate the effect of dexamethasone on the hearing of Meniere's disease patients after TSCP to determine whether inflammation is involved in this process Material and methods: Meniere's disease patients who received TSCP surgeries were treated with or without dexamethasone postoperatively. All patients' hearing function were evaluated during a follow up of 2 years after surgery and compared between the two groups. Results: Hearing worsening and word recognition score loss were milder in the dexamethasone group than in the non-dexamethasone group. The rates of profound hearing worsening and word recognition score loss remained significantly lower in the dexamethasone group than in the non-dexamethasone group even 2 years after surgery. Conclusions: Dexamethasone protects the hearing of Meniere's patients after TSCP. Inflammation may be involved in the mechanism by which TSCP causes hearing impairment in these patients. Significance: This finding suggests that steroids should be used routinely after TSCP for hearing preservation, and operative precedures need to be modified to minimize inflammation in the inner ear.

Background: Betahistine is used worldwide to treat patients with Menière's disease. However, despite it being used for decades, diverging opinions on the effect of betahistine on Menière's symptomatology still exist. Aims: The objective of this systematic review was to provide an overview and rate the certainty of the current evidence base regarding the use of betahistine to treat patients with Menière's disease. Materials and methods: A systematic literature search was conducted in October 2019. The search strategy was subdivided into searches for existing guidelines, systematic reviews and individual randomized controlled trials (RCT) investigating the usage of betahistine as compared to placebo, in patients with Ménière's disease. The primary outcome was the frequency of vertigo attack(s) and occurrence of serious adverse events. Results: We identified three relevant guidelines and three systematic reviews: however, neither included any relevant trials matching our inclusion criteria. An individual search for RCTs identified one trial. The results from this particular trial showed no difference in effects on symptoms following treatment with betahistine. Conclusions and Significance: There is a need for further well-conducted placebo RCTs. Currently, there is still a lack of substantial evidence supporting betahistine as a significant and adequate treatment for patients diagnosed with Menière's disease. Trial registration number: The protocol is registered in PROSPERO. Registration number: CRD42018110127 Accepted 11.10.2018.

Background: Meniere's disease (MD) is a chronic condition of the inner ear consisting of symptoms that include vertigo attacks, fluctuating sensorineural hearing loss, tinnitus and aural fullness. Despite availability of various interventions, there is uncertainty surrounding their relative efficacy, thus making it difficult to select the appropriate treatments for MD. The objective of this systematic review was to assess the relative effects of the available pharmacologic and surgical interventions in patients with MD with regard to vertigo and other key patient outcomes based on data from randomized clinical trials (RCTs)., Methods: Our published protocol registered with PROSPERO (CRD42019119129) provides details on eligibility criteria and methods. We searched various databases including MEDLINE, Embase and the Cochrane Library from inception to December 10th, 2018. Screening at citation and full-text levels and risk of bias assessment were performed by two independent reviewers in duplicate, with discrepancies resolved by consensus or third-party adjudication. Bayesian network meta-analyses (NMA) were performed for hearing change and vertigo control outcomes, along with pairwise meta-analyses for these and additional outcomes., Results: We identified 2,889 unique citations, that yielded 23 relevant publications describing 18 unique RCTs (n = 1,231 patients). Overall, risk-of bias appraisal suggested the evidence base to be at unclear or high risk of bias. Amongst pharmacologics, we constructed treatment networks of five intervention groups that included placebo, intratympanic (IT) gentamicin, oral high-dose betahistine, IT steroid and IT steroid plus high-dose betahistine for NMAs of hearing change (improvement or deterioration) and complete vertigo control. IT steroid plus high-dose betahistine was associated with the largest difference in hearing improvement compared to placebo, followed by high-dose betahistine and IT steroid (though 95% credible intervals failed to rule out the possibility of no difference), while IT gentamicin was worse than IT steroid. The NMA of complete vertigo control suggested IT gentamicin was associated with the highest probability of achieving better complete vertigo control compared to placebo, followed by IT steroid plus high-dose betahistine. Only two studies related to surgical interventions were found, and data suggested no statistically significant difference in hearing changes between endolymphatic duct blockage (EDB) versus endolymphatic sac decompression (ESD), and ESD with or without steroid injection. One trial reported that 96.5% of patients in EDB group compared to 37.5% of the patients in ESD group achieved complete vertigo control 24 months after surgery (p = 0.002)., Conclusion: To achieve both hearing preservation and vertigo control, the best treatment option among the pharmacologic interventions compared may be IT steroid plus high-dose betahistine, considering that IT gentamicin may have good performance to control vertigo but may be detrimental to hearing preservation with high cumulative dosage and short interval between injections. However, IT steroid plus high-dose betahistine has not been compared in head-to-head trials against other interventions except for IT steroid alone in one trial, thus future trials that compare it with other interventions will help establish comparative effectiveness with direct evidence., Competing Interests: We have read the journal's policy and the authors of this manuscript have the following competing interests: BH has received consultancy fees from Eversana (previously Cornerstone Research Group) for methodologic advice related to systematic reviews and meta-analysis. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The remaining authors declare that they have no competing interests.

Purpose: Osmotic diuretics such as glycerol are used for diagnostic purposes in patients with a suspect of Meniere's disease (MD). Scientific evidence in the animal model and in humans has shown that glycerol can induce a reduction in endolymphatic hydrops; however, its use for therapeutic purposes in MD has never been reported. The aim of this study was to evaluate the effectiveness on symptom control of intravenous glycerol in a sample of patients with definite unilateral MD not responsive to dietary restrictions., Materials and Methods: Forty patients with unilateral intractable MD were included in the study. After audio-vestibular evaluation, patients were treated with intravenous 10% glycerol with 0.9% sodium chloride, 0.5 g/kg ml once a day for 2 consecutive days every fifteen days for six months. Vertigo attacks were evaluated before and after therapy and categorized into classes A-F according to the 2015 Equilibrium Committee criteria. Tinnitus and quality of life were evaluated through the Tinnitus Handicap Inventory and the Functionality Level Scale questionnaires., Results: Before treatment, patients had an average of 3.2 vertigo attacks/month; during the six months after treatment the average number of attacks/month decreased to 1.2 (p < 0.0001). At the end of the study period, 25 patients (62.5%) were in Class B vertigo control; 10 patients (25%) in Class C; and 5 patients (12.5%) in Class D. No patients were in Class A, E and F. No hearing deterioration was found in all treated patients. Quality of life according to administered questionnaires improved after treatment., Conclusions: In our sample, intravenous infusion of glycerol for two consecutive days every fifteen days for six months based on the patient's weight improved vertigo attacks and reduced the discomfort generated by tinnitus raising quality of life in patients with unilateral MD unresponsive to dietary restrictions., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

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.

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.

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.

Gel nails are a common artificial nail option. Ultraviolet (UV) nail lamps are commonly used to cure gel nails. Ultraviolet A radiation is a known mutagen that penetrates into the nail bed. Although previously reported, the role of UV nail lamps in the carcinogenesis of both keratinocyte carcinoma and melanoma remains controversial. Herein, we report a patient taking the photosensitizing agent hydrochlorothiazide who developed numerous squamous cell carcinomas on the dorsal hands and feet with a 10-year history of UV nail light exposure every 2-3 weeks.

: There are multiple treatment options for Ménière's disease (MD), including dietary modifications, aminoglycoside therapy, and surgery. All have limitations, ranging from limited effectiveness to permanent hearing loss. Corticosteroids have long been used to manage MD due to their relative efficacy and tolerability, but the exact mechanism for disease alleviation is uncertain. Until recently, the precise distribution and role that glucocorticoid receptors play in inner ear diseases have remained largely uninvestigated. Several studies propose they influence mechanisms of fluid regulation through ion and water homeostasis. This review will provide an update on the basic science literature describing the activity of endogenous glucocorticoids and exogenous corticosteroids in the inner ear and the relevance to MD, as well as early clinical trial data pertaining to the application of novel technologies for more effective administration of corticosteroids for the treatment of MD.

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.

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 compare the functional outcomes and complications of intratympanic gentamicin (ITG) versus intratympanic corticosteroids (ITC) in Menière's disease., Data Sources: An electronic search was conducted in the Cochrane Library, PubMed, and Embase databases on February 3, 2019. Articles written in English, Dutch, German, French, or Turkish language were included., Study Selection: Study inclusion criteria were: 1) patients diagnosed with definite Menière's disease according to the criteria of the American Academy of Otolaryngology-Head and Neck Surgery, 2) treated with ITG or ITC in a comparison study, and 3) reported subjective and objective outcomes concerning Menière's disease., Data Extraction: The quality of eligible studies was assessed according to an adjusted version of the Cochrane Risk of Bias tool. The extracted data were study characteristics (study design, publication year, and number of relevant patients), patient's characteristics (sex and age), disease characteristics (uni or bilateral and duration of Menière's disease), treatment protocol, and different therapeutic outcomes (vertigo, tinnitus, aural fullness, and hearing loss)., Data Synthesis: A total of eight articles were included for data extraction and analysis. For subjective outcomes, ITG was slightly favored compared to intratympanic corticosteroids. This was significant only in three studies (p < 0.05). For objective outcomes and complications, no significant differences were seen., Conclusions: The result of this systematic review shows some benefit of ITG over ITC for subjective outcomes and no difference regarding objective outcomes or complication rate. However, this superiority of ITG is rather weak. Both interventions can be effectively and safely used in controlling Menière's disease in acute situations.

Meniere's disease (MD) represents a clinical syndrome characterized by episodes of spontaneous vertigo, associated with fluctuating, low to medium frequencies sensorineural hearing loss (SNHL), tinnitus, and aural fullness affecting one or both ears. To date, the cause of MD remains substantially unknown, despite increasing evidence suggesting that oxidative stress and neuroinflammation may be central to the development of endolymphatic hydrops and consequent otholitic degeneration and displacement in the reuniting duct, thus originating the otolithic crisis from vestibular otolithic organs utricle or saccule. As a starting point to withstand pathological consequences, cellular pathways conferring protection against oxidative stress, such as vitagenes, are also induced, but at a level not sufficient to prevent full neuroprotection, which can be reinforced by exogenous nutritional approaches. One emerging strategy is supplementation with mushrooms. Mushroom preparations, used in traditional medicine for thousands of years, are endowed with various biological actions, including antioxidant, immunostimulatory, hepatoprotective, anticancer, as well as antiviral effects. For example, therapeutic polysaccharopeptides obtained from Coriolus versicolor are commercially well established. In this study, we examined the hypothesis that neurotoxic insult represents a critical primary mediator operating in MD pathogenesis, reflected by quantitative increases of markers of oxidative stress and cellular stress response in the peripheral blood of MD patients. We evaluated systemic oxidative stress and cellular stress response in MD patients in the absence and in the presence of treatment with a biomass preparation from Coriolus . Systemic oxidative stress was estimated by measuring, in plasma, protein carbonyls, hydroxynonenals (HNE), and ultraweak luminescence, as well as by lipidomics analysis of active biolipids, such as lipoxin A4 and F2-isoprostanes, whereas in lymphocytes we determined heat shock proteins 70 (Hsp72), heme oxygenase-1 (HO-1), thioredoxin (Trx), and γ-GC liase to evaluate the systemic cellular stress response. Increased levels of carbonyls, HNE, luminescence, and F2-isoprostanes were found in MD patients with respect to the MD plus Coriolus -treated group. This was paralleled by a significant ( p < 0.01) induction, after Coriolus treatment, of vitagenes such as HO-1, Hsp70, Trx, sirtuin-1, and γ-GC liase in lymphocyte and by a significant ( p < 0.05) increase in the plasma ratio-reduced glutathione (GSH) vs. oxidized glutathione (GSSG). In conclusion, patients affected by MD are under conditions of systemic oxidative stress, and the induction of vitagenes after mushroom supplementation indicates a maintained response to counteract intracellular pro-oxidant status. The present study also highlights the importance of investigating MD as a convenient model of cochlear neurodegenerative disease. Thus, searching innovative and more potent inducers of the vitagene system can allow the development of pharmacological strategies capable of enhancing the intrinsic reserve of vulnerable neurons, such as ganglion cells to maximize antidegenerative stress responses and thus providing neuroprotection.

Background: Hearing loss is one of the leading causes of disability in Canada and worldwide, with more than one million Canadians enduring a hearing-related disability. Meniere's disease (MD) is a chronic condition of the inner ear, manifesting as a triad of disabling symptoms, including attacks of vertigo, fluctuating sensorineural hearing loss (SNHL), and tinnitus. Impacts on quality of life are severe, particularly with respect to restrictions in social participation and physical activity, fatigue, and reduced capacity to work. Anxiety and other psychological disorders may result from the restrictions imposed on life, the constant uncertainty of vertigo attacks, and fluctuating SNHL, with neuroses and depression affecting 40 to 60% of sufferers of intractable MD. There is a need to establish the benefits of previously studied interventions with greater certainty. The planned systematic review and meta-analyses/network meta-analyses (NMAs) will assess the relative effects of competing pharmacologic and surgical interventions for management of MD in adults., Methods: An experienced medical information specialist in consultation with the review team will develop the electronic search strategies. We will search various databases including MEDLINE, Embase, and the Cochrane Library with no date or language restrictions for published literature, and key clinical trial registries for in-progress and completed trials. Screening of the literature will be performed by two reviewers independently using pre-specified eligibility criteria, and quality of the included studies will be assessed using the Cochrane Risk of Bias tool. We will resolve disagreements through consensus or third-party adjudication. When applicable, meta-analyses and NMAs will be pursued to compare interventions in terms of their effects on outcomes, including frequency and severity of vertigo, occurrence and intensity of tinnitus, changes in hearing and speech recognition, quality of life, and harms. Separate analyses exploring the effects of pharmacologic and surgical approaches will be performed., Discussion: Our planned systematic review will provide informative evaluations of existing treatments for management of Meniere's disease. The findings will inform practitioners as to the relative benefits and harms of the existing competing interventions for MD, offer optimal clinical treatment strategies, identify evidence gaps, and determine promising therapies for evaluation in future trials., Systematic Review Registration: PROSPERO CRD42019119129.

Objective: The purpose of the research is to test the measurement of the total urinary volume, induced by the diuretic osmotic action of mannitol, in a group of symptomatic MD patients and in healthy controls., Results: An altered excretory urinary volume after mannitol challenge was observed in symptomatic MD (874.3 ± 302.1) compared to healthy volunteers (361.7 ± 181.6) (p = 0.0001). This easy and self-administered method might be proposed to replace the analysis of the urinary sugars' concentration in symptomatic MD patients.

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.

Purpose: There are many therapeutic options for Meniere's disease (MD); intratympanic (IT) gentamicin has been proposed for intractable cases although controversy about dosage and method exists. 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 in which administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections., Materials and Methods: Forty-eight patients with unilateral intractable MD were included in the study. 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 assessment with pure tone audiometry, vestibular bed-side examination and video head impulse test was performed., Results: Before treatment patients had an average of 4.4 vertigo attacks/month; after treatment the average number decreased to 0.52. The majority of patients (77%) reached Class A vertigo control with 5 or less gentamicin injections. VOR gain was unaffected in the healthy side and significantly reduced in the affected side. No hearing deterioration was found in all treated patients., Conclusions: Low-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment; such protocol had an effect mainly on the vestibular function as demonstrated by the significant reduction in VOR gain in the affected side avoiding a cochlear damage., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Objective: This study aimed to determine the effectiveness of an intratympanic (IT) injection of a mixture of gentamicin and dexamethasone compared with intratympanic dexamethasone (ITD) for controlling vertigo and protecting the hearing level of Meniere's disease patients who have persistent vertigo attacks, despite medical treatment., Methods: Thirty eight patients with intractable Meniere's disease were included in this study. Twenty-one patients were treated with IT mixture gentamicin and dexamethasone injection; seventeen patients were treated with ITD. Pre- and post-treatment audiograms were compared with pure-tone averages. Control of vertigo was classified according to the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) vertigo control index., Results: In the mixture group single IT injection was administered in 18 patients (85.7%), 2 injections were administered in 2 patients (9.5%) and 3 injections were administered in one patient (4.8%). In the ITD group IT injection was performed 3 times (days 1,3,5) at intervals. The mean number of intervals per patient was 3,41 (range 1-6). Two years after IT treatment there was better control of vertigo in mixture group than in ITD group; 81% of mixture group and 70,6% of the ITD group achieved satisfactory control of vertigo (p = 0,0286). Audiology results of mixture group showed 20 patients (95,24%) with unchanged hearing and 1 patient (4,76%) with only 10-decibel deteriorated hearing. There was no worsening of hearing in the ITD group., Conclusion: The results of this study showed that an IT injection of a mixture of gentamicin and dexamethasone in intractable Meniere's disease cases is more effective than ITD for vertigo control., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: Ménière's disease (MD) is an inner ear disorder of unknown etiology, whose pathological substrate is the endolymphatic hydrops. Different treatments have been proposed; however, evidence of their effectiveness is lacking. The aim of this study was to evaluate by a questionnaire which medical and surgical treatments are used in Italy for the treatment of MD and to compare them with those proposed in other countries., Methods: An electronic questionnaire of 40 questions was formulated and sent to Italian otolaryngologist (ENT) divided into two groups: Group 1 ("generalists" 60.8%) and Group 2 ("neurotologist- NO" 39.2%)., Results: One hundred and twenty five ENT replied. Treatment of the acute phase, apart from symptomatics, was based on diuretics that are prescribed by 83.5% of respondents, steroids, prescribed by 66.7%, and vasodilators, prescribed by 22%. In the intercritical phase, 87.2% of respondents recommended low-salt diet, 78.4% of respondents prescribed betahistine, and 52.8% diuretics. Statistical analysis did not show correlation neither with the declared specialization nor with the number of patients treated. In case of failure of medical treatment, IT gentamicin was suggested by 48.8% of the respondents and IT steroids by 40.8%. Statistical analysis showed that generalists prefer IT steroids and NO IT gentamicin (p 0.019). In case of failure of both medical treatment and IT treatment, vestibular neurectomy was indicated by 58.4% of the respondents, 6.4% indicated endolymphatic sac surgery, and 2.4% surgical labyrinthectomy., Conclusion: In Italy, the treatment of MD stand on a gradual approach that starts from the dietary-behavioral changes and a pharmacological therapy based on betahistine. In refractory cases, IT treatment initially with steroids and, therefore, with gentamicin allows the control in vertigo in the majority of cases. In case of failure of IT treatment, VNS is the surgery of choice.

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: It is generally accepted that intratympanic injection provides an effective approach to manage severe vertigo in Ménière's disease. Although there are several medications available, that which is the most effective is still subject to debate., Objective: To assess the effectiveness and safety of the different medications used in the treatment of Ménière's disease by intratympanic injection using a network meta-analysis., Methods: PubMed, EMBASE, CINAHL and CENTRAL were searched. Only randomised controlled trials that compared the effectiveness of medications used for intratympanic injection to treat Ménière's disease with each other or a placebo were included. The primary outcome assessed was the effectiveness of medication in the management of vertigo symptoms. The effectiveness was expressed in terms of risk ratio (RR) with a 95% credible interval (CrI) for individual studies analysed. Network meta-analyses were performed by Stata version 15.0 using the network package., Results: Nine studies involving 314 patients treated with five different medications were included in the present analysis. A number of injections given varied from 1 to 10 and the follow-up time from 3 to 28 months. When compared to each other or to a placebo, Gentamicin was found to be the most efficacious medication, followed by Methylprednisolone, Latanoprost, Dexamethasone and Ganciclovir in order of effectiveness. However, no significant difference in efficacy was found between Gentamicin and Methylprednisolone when outcomes from studies with a follow-up time equal to or more than 24 months were analysed. It was not possible to conduct subgroup and sensitivity analysis because of the limited number of studies that were included., Conclusion: All medications are more effective than a placebo in the treatment of Ménière's disease by intratympanic injection. According to the SUCRA, Gentamicin ranked the most effective, with Gentamicin and Methylprednisolone equally effective in the long-term effect. When the potential risk of hearing loss induced by Gentamicin is taken into consideration, Methylprednisolone may be the best choice for the treatment of Ménière's disease by intratympanic injection., (© 2019 John Wiley & Sons Ltd.)

Vestibular migraine probably represents the second most common cause of vertigo after benign positional vertigo, by far exceeding Ménière disease. There are still relatively few published reports on vestibular migraine management, despite its enormous importance in daily practice. In 2003 the first clinical definition of vestibular migraine was proposed. Studies published before 2003 used variable terms for vestibular migraine. Some authors recommend treating vestibular migraine using multiple drugs; others have focused on using only one drug. Although at present it is not possible to quantify the effects of the treatments proposed, some recommendations can be made.

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.

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: In recent decades, intratympanic gentamicin (ITG) has increasingly been used to treat intractable Menière's disease (MD). We performed a meta-analysis of pooled clinical outcomes, exploring whether ITG was effective and safe., Data Sources: Cochrane Library database, Embase, and Medline., Study Selection: We searched scientific and medical databases to March 2018 for articles evaluating clinical outcomes after ITG treatment of intractable MD according to the American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) guidelines., Data Extraction: We performed a meta-analysis to evaluate treatment efficacy and safety. Quantitative and descriptive information of included RCTs was obtained., Data Synthesis: We ultimately evaluated 49 of the initially retrieved 1,062 citations (the 49 articles included data from a total of 2,344 MD patients). In almost all studies, patients served as their own controls; "before-and-after" clinical outcomes were reported. The I metric was used to explore heterogeneity., Conclusion: Overall, our results seem to provide the limited evidence about efficacy and toxicity effects of ITG. However, clinical outcomes require further confirmation; many included studies were poorly designed, less than 2 years for reporting results in MD are in the majority of patients. More long-term prospective follow-up, high-quality, large-scale, randomized controlled trials are needed to confirm that ITG is safe and effective when used to treat intractable MD.

Background: Platelet rich plasma procedure (PRP) is considered to be one of the safest aesthetic procedures. Adverse reactions after PRP administration are extreme rare., Purpose: We present the patient with serum sickness disease (SSD) after PRP procedure., Objective and Methods: 41 years old female suffers from alopecia areata for 5 years with frequent relapses and she has been suffering from Menier's disease recurrent symptoms for 6 years. The patient developed SSD after third PRP rejuvenating procedure and she has also noticed new alopecia areata lesions, but without Menier's disease symptoms. After SSD, 4 months later, she developed severe symptoms of Menier's disease with an episode of sudden sensorineural hearing loss. It alleviated only after intravenous administration of methylprednisolone. In our opinion, significant contraindication of PRP procedure is an autoimmune disease in the active phase., (© 2018 Wiley Periodicals, Inc.)

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.

Objective: To evaluate outcomes of intratympanic (IT) dexamethasone and gentamicin in Ménière Disease (MD)., Methods: Charts of adult patients with unilateral definite MD receiving IT gentamicin or dexamethasone from 2005 to 2017 were retrospectively reviewed. All patients had at least 6 months follow-up. Failure in each group was defined as the need for more aggressive therapy. Prior to 2011, all patient received IT gentamicin, administered as primary therapy after failure of conservative treatment measures. Gentamicin was administered every 2 weeks, up to three injections, until vertigo control was achieved. Beginning in 2011, the treatment protocol shifted to IT dexamethasone as initial treatment, with gentamicin used for dexamethasone failures. Dexamethasone was administered weekly for up to three injections. Treatments could be repeated if symptoms recurred., Results: Thirty-three patients received IT dexamethasone, and 70 patients received IT gentamicin. Dexamethasone patients received a mean of 3.3 injections compared to 2.7 in the gentamicin group (P = 0.011). There were 12 (38%) failures in the dexamethasone group and only seven (10%) gentamicin failures (P = 0.025). No patients failed both treatments. The mean time to failure in the dexamethasone group was 5 months, whereas in the gentamicin group it was 27 months. Change in pure tone audiometry from baseline was not different between treatment groups (P = 0.30)., Conclusion: Subjects receiving IT gentamicin required fewer injections and had a significantly longer time to failure than IT dexamethasone. Audiometric outcomes were similar between the groups. The use of IT gentamicin as initial therapy for early and long-term control of MD is safe and effective., Level of Evidence: 3 Laryngoscope, 129:216-221, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: This study aimed to evaluate the changes in the VOR gain after intratympanic gentamicin therapy and to correlate them with the mid-term effects on the control of vertigo, in a population of Menière's disease patients., Study Design: The study design was a prospective "Outcomes research.", Setting: Tertiary referral center., Patients: This study included 20 patients with unilateral Menière's disease refractory to medical therapy for at least 1 year, and treated with an on demand intratympanic gentamicin protocol., Intervention: Therapeutic., Main Outcome Measure: Audiometry, caloric testing, and a vHIT before beginning the protocol were performed. Patients underwent weekly vHIT assessments until a significant gain reduction was observed. Subsequently we performed vHIT tests 1 month after the therapy completion, and then every 3 months for at least 1 year., Results: Complete vertigo control (class A) was achieved in 14 patients at the 12-month follow-up assessment. We observed a significant reduction in VOR gain values at the 3-week follow-up assessment. We found a significant correlation between the 1-month posttreatment ipsilateral hVOR gain and the rate of vertigo recurrence after the first IT gentamicin treatment (p = 0.012; r = 0.400). At the mid-term assessment, 10 patients exhibited a significant partial recovery of the hVOR gain., Conclusions: The delayed effect of intratympanic gentamicin and the subsequent gain restoration are factors that may influence the patients' outcome. The feasibility of the vHIT system makes it a useful tool to monitorize the VOR changes.

Objective:: To evaluate the change in quality of life (QOL) of patients with Meniere's disease (MD) after treatment with migraine prophylaxis therapy., Methods:: Patients with definite MD were given the Meniere's Disease Outcomes Questionnaire-Retrospective (MDOQ-R) after migraine prophylactic therapy to assess QOL. Changes in physical, emotional, and social parameters affected by MD were calculated, along with a global pre- and posttreatment QOL scores., Results:: The MDOQ-R was given to 27 consecutive patients with definite MD. Patients who had at least an 18-month follow-up were included, resulting in 25 questionnaires. The mean change in QOL score was 25 ± 16 (range, -3 to 55), P = .02. Quality of life was improved in 23 (92%) of the respondents in every metric measured, unchanged in 1 (4%), and poorer in 1 (4%) of patients after migraine prophylaxis treatment., Conclusions:: Majority of MD patients who had all failed diuretic therapy responded positively to medications used for migraine prophylaxis, as indicated by a significant improvement in QOL. This study may further suggest a correlation between the pathophysiologic basis of disease in MD and vestibular migraine. Patients with MD may be successfully managed with medications intended to treat migraine.

Introduction: Middle ear application of gentamicin is a common medical treatment for uncontrolled Ménière's disease. The objective of the study was to evaluate the impact of endolymphatic hydrops on inner ear delivery., Methods: Perilymph gentamicin concentrations and correlation with endolymphatic hydrops in an animal model were assessed. A group of 24 guinea pigs was submitted to surgical obstruction of the endolymphatic sac and duct of the right ear. Gentamicin was applied either to the right ear's round window niche or through a transtympanic injection. Perilymph specimens were collected at different times. Histologic morphometry was used to evaluate both turn-specific and overall hydrops degree., Results: In animals with endolymphatic hydrops, lower concentrations of gentamicin were observed after 20 or 120 minutes of exposure and in both types of administration, when compared to controls. This difference reached statistical significance in the round window niche application group (Mann-Whitney, p = 0,007). A negative correlation between perilymphatic gentamicin concentration and hydrops degree could be observed in both groups, after 120 minutes of exposure (Spearman correlation, round window niche p<0,001; TT p = 0,005)., Conclusions: The study indicates that the endolymphatic hydrops degree has a negative interference on the delivery of gentamicin into the inner ear following middle ear application., Competing Interests: The authors have declared that no competing interests exist.

Intratympanic gentamicin (ITG) has been used to treat refractory Ménière's disease. Disequilibrium after ITG was still a challenge for some patients, and the underlying mechanism is poorly understood. Our previous study demonstrated that gentamicin distributed in the bilateral vestibular efferent neurons (VEN) after ITG; however, does it lead to VEN damage and cause further disequilibrium in patients following ITG? In this study, we observed severe damaged gentamicin-positive neurons of VEN and severe fractured myelin layer plates around neural fibers when viewed under transmission electron microscopy at day 3 after ITG. At day 30, neurons of VEN presented with relatively normal structures. Compared with the control group, the total number of choline acetyltransferase (CHAT) immunolabeling neurons in bilateral VEN showed a significant decrease both at day 3 and day 30. However, there was no significant difference in the total number of CHAT immunolabeling neurons between day 3 and day 30. It indicates that gentamicin is not only retrogradely transported into bilateral VEN, but also results in the degeneration of VEN after ITG. These findings may be related to patients' disequilibrium symptom after ITG. Furthermore, we speculate that VEN may play a role in vestibular compensation.

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.

Objective: To estimate how much could intratympanic gentamicin (ITG) interfere with the vestibular-ocular reflex (VOR) parameters on instrumental head impulse test (HIT), either with scleral search coil or video head impulse test and, eventually, foresee the control of vertigo crisis in unilateral intractable Ménière's disease (MD)., Methods: A literature search was conducted in PubMed, Scopus, Web of Science and Cochrane search engines. The search terms used were "vestibular ocular reflex", "head impulse test", "gentamicin," and "Meniere's disease". Limitations included text availability to be full text, species to be humans and language to be English. All study types were included. 89 articles were screened identifying four eligible studies were identified. Studies were included after consensus of the authors. Meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data was analysed using Review Manager software., Results: Instrumental HIT, after ITG for MD, demonstrated, in the treated ear, a decreased gain in the horizontal, posterior and superior semicircular canals (SCC), of 0.36 (0.26; 0.47; 95% CI), 0.35 (0.22; 0.48; 95% CI) and 0.28 (0.21; 0.35; 95% CI), respectively. Gain asymmetry increases between the treated and non-treated ear of 23.78 (7.22; 40.35; 95% CI), 32.01 (12.27; 51.76; 95% CI) and 17.49 (9.99; 24.99; 95% CI), were similarly detected in the horizontal, posterior and superior SCC, respectively. Significantly smaller gain values after the first treatment were observed for a single injection group versus multiple injection group in the horizontal (p=0.002) and superior SCCs (p=0.016)., Conclusions: Instrumental HIT is effective in evaluating the SCC function after ITG for intractable unilateral MD. VOR gain changes in the direction of the treated ear in the three SCC have been clearly registered. An increased reduction of the VOR gain in the horizontal and anterior SCC also seemed to foresee the control of vertigo crisis. Still, after meta-analysis, the small number of patients' data available did not allow to define a treatment end-point value. This review also indicated that further and better-designed studies are warranted., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Ménière's disease is a disorder of the inner ear that causes vertigo, tinnitus, fullness and hearing loss. Although several treatments are available, the success rate is reported to be around 70%, similar to placebo. Betahistine, a weak H1 receptor agonist and an effective H3 receptor antagonist, is frequently prescribed for Ménière's disease, especially to reduce recurrent vertigo attacks. The effects of this drug on hearing and other audiological symptoms remains unclear. Given the inconclusive reports in the literature, we proposed a consensus conference on the use of betahistine in Ménière's disease. The aim was to define best practice criteria for therapy for Ménière's disease, improve clinical suitability and reduce heterogeneity of the therapeutic approach. The consensus conference on betahistine for Ménière's disease involved a group of Italian experts in vestibular disorders who were asked a series of questions prepared by opinion leaders. The Delphi method, an iterative investigation method, was used to increase consensus. Via a tele-voting system, each participant anonymously evaluated all statements using a Likert 5-point scale. Betahistine was considered useful for the treatment of dizziness and vertigo during the intercritical phase of the disease (87% agreeing answers). However, during the acute phase of the disease betahistine was considered less effective and useful only when associated with other drugs (71% agreement). Similarly, the efficacy of the drug was considered low when used to reduce progressive hearing loss, tinnitus, and ear fullness. The experts advocated the use of betahistine during the intercritical phase of Ménière's disease to reduce the number and severity of vertigo attacks. Its use seems to be at low risk of major side effects., (Copyright © 2018 Società Italiana di Otorinolaringologia e Chirurgia Cervico-Facciale, Rome, Italy.)

Purpose: The uses of nimodipine for otolaryngic indications are reviewed, and recommendations for its use in clinical practice are provided., Summary: Nimodipine is currently indicated for the improvement of neurologic outcomes in adult patients with aneurysmal subarachnoid hemorrhage (aSAH). However, other oral and i.v. calcium channel blockers have not exhibited the same beneficial effects in patients with aSAH, leading clinicians to believe that nimodipine possesses unique neuroprotective effects in addition to its calcium channel-blocking and vasodilatory properties. Consequently, clinical investigations of nimodipine have been conducted for cochlear and facial nerve preservation after vestibular schwannoma (VS) surgery, symptomatic management of Ménière's disease and peripheral vertigo, and recovery of vocal cord paralysis after laryngeal nerve injury. Three prospective randomized studies have investigated nimodipine for hearing and/or nerve preservation in patients undergoing VS resection, the results of which have suggested a potential benefit of initiating nimodipine during the perioperative period. Several studies of Ménière's disease and/or peripheral vertigo have reported improved symptom control with nimodipine. For vocal fold paralysis associated with recurrent laryngeal nerve (RLN) injury, nimodipine may increase the recovery rate based on the results of 1 nonrandomized prospective study that used nimodipine in a protocolized manner. One small pilot study found that nimodipine improved facial nerve function after maxillofacial surgery., Conclusion: Due to its proposed vasoactive and neuroprotective effects, nimodipine may play a role in the treatment of a number of otolaryngic pathologies including VS, Ménière's disease, peripheral vertigo, RLN injury, and facial weakness after maxillofacial surgery. Small studies have shown improved symptom control and recovery after surgery. Since all of the aforementioned indications are still considered off label, clinicians and patients should collaboratively assess the risks and benefits before initiating treatment., Competing Interests: DisclosuresThe authors have declared no potential conflicts of interest., (Copyright © 2018 by the American Society of Health-System Pharmacists, Inc. All rights reserved.)

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.

Meniere Disease keeps challenges in its diagnosis and treatment since was defined by Prosper Meniere at the beginning of 19th Century. Several classifications and definition were made until now and speculations still exist on its etiology. As the etiology remains speculative the treatment models remain in discussion also. The European Academy of Otology and Neurotology Vertigo Guidelines Study Group intended to work on the diagnosis and treatment of Meniere's disease and created the European Positional Statement Document also by resuming the consensus studies on it. The new techniques on diagnosis are emphasized as well as the treatment models for each stage of the disease are clarified by disregarding the dilemmas on its treatment. The conservative, noninvasive and invasive therapeutic models are highlighted.

The role of immunological factors in the pathophysiology of Meniere's disease (MD) has been hypothesized. In order to evaluate the current level of evidence on autoimmunity in MD, original articles relevant to the matter (1970-2016) were reviewed. The following has been considered to support the theory of autoimmunity in MD (1) the increased prevalence of autoimmune diseases among MD patients, (2) the elevated levels of antibodies and immunocomplexes in MD patients, (3) the association of MD with HLA-types and genetic polymorphisms and (4) the positive corticosteroid-responsiveness detected in some MD patients. However, all studies have been small and lack positive replication. Studies concerning antibodies, HLA types and genetic polymorphisms have produced conflicting results and no single antibody, HLA type or polymorphism has been found in all or even in a significant subpopulation of MD patients. No convincing basic research evidence of autoimmunity in MD exists hence the field needs further study., (Copyright © 2017 Elsevier B.V. All rights reserved.)

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.