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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.)

Objective: The main objective was to assess the efficacy of intratympanic dexamethasone injection in controlling vertigo in unilateral Ménière's disease refractory to medical treatment., Materials and Methods: A retrospective study included 25 patients with disabling unilateral Ménière's disease, defined according to the American Academy of Otorhinolaryngology-Head and Neck Surgery (AAO-HNS) criteria. Patients received intratympanic dexamethasone during the monitoring period. Control of vertigo was classified according to AAO-HNS vertigo control index, at 6 months, 1 year, and 2 years after treatment initiation. Complications and progression of hearing were also assessed., Results: Satisfactory control (class A or B) was obtained in 92% of patients (n=23/25) at 6 months, 68% (n=17/25) at 1 year, and 70% (n=16/23) at 2 years. There was no worsening of hearing in those patients who were well-controlled by this therapeutic strategy. No local or systemic complications were observed during follow-up., Conclusion: Dexamethasone is part of the management strategy for patients with Ménière's disease refractory to conventional treatment, implemented before destructive treatment. It achieves control of vertigo in 70% of patients at 2 years., (Copyright © 2017 Elsevier Masson SAS. 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.

The objective of the present study was to elucidate the dynamics of the hormonal status of the adrenal glands in the patients suffering from Menière's disease in its different clinical forms. We examined a total of 26 patients at the age from 29 to 47 years presenting with this condition. All the patients were divided into two groups depending on the character of the disease. Group 1 was comprised of 20 patients experiencing the crises from 2 to 6 times during a year. Group 2 was composed of six patients in whom the crises occurred with a frequency of 2-4 times per week within at least two weeks. The serum levels of cortisol and aldosterone were measured both during the crises and between them with the use of the proper immunoenzyme assays. The control group was formed of 20 practically healthy volunteers. It was shown that the blood cortisol level during a fit of dizziness in the patients of group 1 increased in comparison with that in the control subjects (798.7±71.2 nmol/l and 453.68±49.39 nmol/l respectively; p<0.05). The patients having recurrent crises (group 2) experienced a significant decrease in the blood cortisol levels down to 293.5±38.1 nmol/l during a crisis in comparison with the control subjects (453.68±49.39 nmol/l; p<0.05). During the inter-crisis periods , the blood cortisol level in the patients of the first group remained within normal bounds whereas in the patients of the second group its mean value was 18.7% lower (p>0.05). The serum aldosterone level in the patients of the first group was not significantly different from that in the second group both during crises and in the periods of remission. It is concluded that the results of the study provide the data for the pathogenetic substantiation of the possibility for the use of corticosteroids in the treatment of the patients suffering from frequent crisis of Menière's disease.

Meniere's disease is an inner ear pathology characterized by periodic fits of systemic dizziness, fluctuating low-frequency sensorineural loss of hearing, stuffiness in the ear and tympanophonia. The objective of the present study was to evaluate the effectiveness of the intra-tympanic administration of methyl prednisolone in the combination with gentamycin used to treat the patients presenting with Meniere's disease. The study included 18 patients at the age varying from 18 to 70 years presenting with this condition. Group 1 was formed to treat the patients with gentamycin, group 2 was comprised of the patients treated with methyl prednisolone. Special emphasis was placed on the recording of dynamics of the parameters of tonal threshold audiometry and cervical evoked vestibular myogenic potentials. The episodes of dizziness were characterized based on the results of comparison of the number of systemic dizziness episodes within the first 6 months after the first injection of methyl prednisolone or gentamycin with the number of such episodes during one month prior to the onset of the treatment. The results were estimated based on the Dizziness Handicap Inventory (DHI scale). It was shown that the patients comprising group 2 experienced a more pronounced reduction in the number of dizziness episodes compared with those in group 1 (91.56 and 69.81% decrease respectively). Moreover, hearing improved by 35% in the patients of group 2, whereas the improvement was altogether absent the patients of group 1. The patients of both groups reported comparable reduction of subjective tympanophonia estimated based on the DHI scale. The results of the comparison were evaluated based on the DHI scale (54.9% in group 2 and 53.8% in group 1).

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.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

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.

Objectives (1) Describe the prevalence of radiographic signs of intracranial hypertension (ICH) in Ménière's disease (MD) and (2) compare the prevalence of radiographic signs of ICH in MD patients managed medically to those managed surgically. Study Design Case-control study. Setting Academic neurotologic practice. Subjects and Methods Adult MD patients (aged ≥17 years) treated from 2011 to 2015 were reviewed. Inclusion required magnetic resonance imaging (MRI) of the head and follow-up >6 months. Patients with intracranial tumors, mass effect, trauma, previous intracranial surgery, and glaucoma were excluded. MD patients were separated by administered treatment into medical and surgical subgroups. Cochlear implant (CI) recipients served as radiographic controls. Eighty-four MD patients (46 surgical, 38 medical) and 37 CI controls were assessed. MRI measurements assessed for empty/partial sella (ES/PS), dilated/tortuous optic nerve sheath (ONS), and posterior globe flattening (PGF). Results Mean age was 53.8 ± 1.3 years and median body mass index (BMI) was 28.2 kg/m 2 . Of the patients, 64% were female and 92% were white. MRI findings in the MD cohort were as follows: ES/PS, 46.4%; ONS change, 42.8%; and PGF, 8.3%. The prevalence of ONS change was higher in MD patients than in controls (42.8% vs 13.5%, P = .003). The surgical MD group had higher prevalence of ONS change (52%) compared with the medical group (31.5%, P = .05) and controls (13.5%, P = .0004). The surgical group had a higher prevalence of ≥2 simultaneous MRI findings compared with medical MD patients (39% vs 10%, P = .01) and controls (14%, P = .01). Conclusion MD patients demonstrate a high prevalence of radiographic signs of ICH. MD patients who required surgery had a greater prevalence of radiographic signs of ICH compared with non-MD patients and medically managed MD patients.

Objective: To evaluate the effects of selective serotonin re-uptake inhibitors (SSRIs) on Meniere's disease (MD) on patients who have both MD and generalized anxiety disorder., Materials and Methods: All patients were evaluated with neurotologic examination, videonystagmography, audiological tests, and inner ear magnetic resonance imaging. Characteristic history and the evaluation of the patients' vertigo attacks during the attacks were the primary criteria for the diagnosis of MD. According to these parameters, 12 patients were diagnosed with definite MD and also symptoms of generalized anxiety disorder. Escitalopram 10 mg was prescribed to the patients. The clinical records of these patients were reviewed., Results: Eight female and 4 male patients with MD and generalized anxiety disorder were included. The average age was found to be 46.25 years (34-63 years). Magnetic resonance imaging of patients was reported as normal. All patients had unilateral MD. The patients were diagnosed with MD for 2-12 years (mean: 5 years). All patients used betahistine and diuretics before escitalopram. Intratympanic gentamicin was also applied to one patient. After escitalopram medication, no vertigo attack was observed in any of the patients., Conclusion: SSRIs may have a central balancing effect on vertigo attacks of MD. Escitalopram can control vertigo attacks in MD. Further studies are needed to support this effect.

The BEMED study (BMJ 2016; 352: DOI 10.1136) was designed as multi-centric, double-blind, plaebo-controlled study in patients with Menière's disease. It should compare a low-level (2 × 24 mg/d) vs. high-level (3 × 48 mg/d) betahstine intake vs. placebo. The primary endpoint was the "number of vertigo attacks lasting longer than 20 min as documented in a patient's diary". The main finding of the study was that betahistine did not significantly better reduced the number of vertigo attacks than placebo. Therefore, the BEMED study should be critically discussed in the present paper., Competing Interests: Disclosure The authors report no conflicts of interest in this work., (Georg Thieme Verlag KG Stuttgart · New York.)

Objective: The purpose of the study is to prevent hearing loss when using intratympanic (IT) gentamicin for intractable Meniere's disease., Materials and Methods: It is a retrospective case review study. Twenty five patients who had definite Meniere's disease and had either selective window application or weekly IT gentamicin were included into the study. First group (selective) had dexamethasone on the round window and gentamicin on oval window during exploratory tympanotomy procedure. The second group had IT gentamicin at weekly intervals. The degree of caloric weakness (CW), average hearing level in low pitch (HLP) (250, 500, 1000, 2000 Hz) and high pitch (HHP) (4000, 6000, 8000 Hz) were compared before and after treatment. The need for further treatment was noted., Results: In the first group, the average HLP was increased from 51.6±7dB to 52.2±5.6 dB. The average HHP was increased 41.96±20.2 dB to 47.2±18.3 dB after treatment. The CW changed from 37.6±23.9 % to 54.6±30.6 %. In the second group, the average HLP was increased from 56.3±10.5 dB to 61.65±18.3 dB. The average HHP was increased 59.05±17.4 dB to 69.4±21.98 dB after treatment. The CW changed from 45.8±22.3% to 71.53±29.63 %. Both methods had statisticaly significant increase in caloric weakness. But only IT gentamicin led a significant hearing loss in HHP., Conclusion: The use of dexamethasone and gentamycin via different windows in the middle ear is safe and effective method for Meniere's disease in the short term. Application of dexamethasone protects not only the hearing cells but vestibular cells also.

Objective: Mal de debarquement syndrome (MdDS) is a balance disorder that typically starts after an extended exposure to passive motion, such as a boat or plane ride. Management is typically supportive (e.g. physical therapy), and symptoms that persist beyond 6 months have been described as unlikely to remit. This study was conducted to evaluate the response of patients with MdDS to management with migraine prophylaxis, including lifestyle changes and medical therapy., Study Design: Prospective review., Setting: Ambulatory setting at a tertiary care medical center., Methods: Clinical history, detailed questionnaires, and audiograms were used to diagnose patients with MdDS. Those patients with the diagnosis of the MdDS were placed on our institutional vestibular migraine management protocol. Treatment response was assessed with a quality-of-life (QOL) survey and visual analog scale., Results: Fifteen patients were diagnosed with MdDS, with a predominance of females (73%) and a mean age of 50 ± 13 years. Eleven patients (73%) responded well to management with a vestibular migraine protocol, which included lifestyle changes, as well as pharmacotherapy with verapamil, nortriptyline, topiramate, or a combination thereof. In comparison, a retrospective control group of 17 patients demonstrated a lower rate of improvement when treated with vestibular rehabilitation and physical therapy., Conclusion: Management of MdDS as vestibular migraine can improve patients' symptoms and increase the QOL. Nearly all the patients suffering from MdDS had a personal or family history of migraine headaches or had signs or symptoms suggestive of atypical migraine., Level of Evidence: 4 Laryngoscope, 127:1670-1675, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

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.

Introduction: The role of this study was to evaluate the effectiveness of intra tympanic administration of Gentamicin(40 mgs/ml) and Dexamethasone 0.5 ml(4 mgs/ml) on hearing and tinnitus of patients who had recurrent acute attacks of vertigo, tinnitus and hearing loss., Study Design: 60 consecutive patients of Meniere's disease were randomly divided into 3 groups of twenty patients each. Group A included 20 patients who received intra tympanic gentamicin, Group B included 20 patients who received intra tympanic dexamethasone and Group C included 20 patients who received intra tympanic normal saline 0.5 ml. The mean pure tone thresholds at speech frequencies were noted before treatment and 2 weeks, 3 months and 6 months after treatment. Tinnitus was surveyed with a set questionnaire (Tinnitus Handicap Inventory)., Results: The mean PTA at speech frequencies for Group A worsened from 50 dB to 62 dB which was statistically significant. Two ears developed profound sensorineural hearing loss. The mean tinnitus handicap inventory grade of group A was 4. Mean was 2 at the end of 6 months which indicates significant reduction of the tinnitus score. Group B patients had a mean PTA at speech frequencies of 42 dB. There was no gain in 12 patients and less than 10 dB in the remaining eight patients and no worsening of hearing was seen. The mean tinnitus handicap inventory grade in Group B was 2.5 and was 2 at 6 months after treatment. Group C patients had a mean PTA of 48 dB before treatment and were same after treatment however the tinnitus handicap grade was 2.5 before the treatment and 2.0 after treatment., Conclusion: Intra tympanic gentamicin is more effective in controlling tinnitus as compared to dexamethasone and placebo and there was no marked difference in control of tinnitus between placebo and steroids. There is significant hearing loss with IT Gentamicin and no marked difference between steroid and placebo on hearing.

Conclusion: Gastric type H + ,K + -ATPase in the vestibular end organs may be of importance for K + circulation and may also be related to pH regulation in vestibular end organs and endolymphatic sac., Objective: To analyze the expression of gastric-type H + ,K + -ATPase in normal mouse vestibular end organs., Methods: 8 weeks old CBA/J mice were used in this study. The presence of gastric-type H + ,K + -ATPase α and β in the vestibular end organs, viz. utricle, saccule, ampulla, vestibular ganglion, and endolymphatic sac, was investigated using immunohistochemistry., Results: In the vestibular end organs, H + ,K + -ATPase α and β were almost identical. H + ,K + -ATPase was expressed in sensory cells, the basolateral surface of dark cells, fibrocytes, in vestibular ganglion cells, and in the upper region of the endolymphatic sac epithelial cells.

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.

Objective: To describe the safety and potential efficacy of intratympanic administration of triamcinolone (40 mg/mL) in the treatment of unilateral Ménière's syndrome., Study Design: Single-institution retrospective analysis., Setting: Tertiary referral neurotology clinic., Patients: Eighteen patients diagnosed with unilateral Ménière's syndrome with vertigo refractory to medical management., Intervention(s): Intratympanic injection of triamcinolone or dexamethasone., Outcome Measure(s): Kaplan-Meier analysis was implemented to determine the rate of successful vertigo control. Responders were defined as patients who achieved sufficient vertigo control to decline ablative therapy. Nonresponders were defined as those who did not achieve satisfactory vertigo control and required ablative or surgical therapy. Pre- and posttreatment audiogram data was used to evaluate changes in hearing. Patient follow-up data was assessed for complications potentially resulting from intratympanic therapy., Results: No patient experienced profound hearing loss or other serious adverse events as a result of intratympanic triamcinolone therapy. Tympanic membrane perforation occurred in three (18%) patients, all of whom had received three or more previous intratympanic injections. Satisfactory vertigo control with intratympanic triamcinolone therapy was achieved in 14 (78%) of 18 subjects., Conclusion: Our results suggest that intratympanic triamcinolone therapy on an as-needed basis is a safe and potentially effective procedure for vertigo control in patients with Ménière's syndrome. These findings warrant the implementation of prospective, controlled trials to investigate its safety and efficacy further.

The aim of this study is to review the literature on sustained-release vehicles delivering gentamycin in the inner ear of patients suffering from Meniere's disease (MD), and critically assess their respective clinical effectiveness and safety. A systematic literature review was conducted in Medline and other database sources until January 2016, along with critical analysis of pooled data. Overall, six prospective and four retrospective studies were systematically analyzed. The total number of treated patients was 320. A 2 year patient follow up was only reported in 40 % of studies. Inner ear gentamycin delivery using sustained-release vehicles is associated with improved vertigo control (strength of recommendation B), and quality of life (strength of recommendation B) in MD sufferers. In addition, dynamic-release devices seem to achieve high rates of improvement in the appearance of tinnitus (65.4 %) and aural pressure (76.2 %). By contrast, percentages of complete and partial hearing loss appear unacceptably high (31.08 and 23.38 % of patients, respectively), compared to historical data involving simple intratympanic gentamycin injections. Sustained-release vehicles for gentamycin delivery may have a role in the management of MD patients who have previously failed intratympanic gentamycin injections, or those who have already lost serviceable hearing. Their use as first line treatment over single intratympanic injections for all MD patients, who do not respond to conservative treatment should be discouraged.

Introduction: Inner ear disorders such as hearing loss, tinnitus, and Ménière's disease significantly impact the quality of life of affected individuals. Treatment of such disorders is an ongoing challenge. Current clinical approaches relieve symptoms but do not fully restore hearing, and the search for more effective therapeutic methods represents an area of urgent current interest. Areas covered: Thirty four patents and patent applications published from 2011 to 2015 were selected from the database of the U.S. Patent and Trademark Office (USPTO) and World Intellectual Property Organization (WIPO), covering new approaches for the treatment of inner ear disorders described in the patent literature: 1) identification of new therapeutic agents, 2) development of sustained release formulations, and 3) medical devices that facilitate delivery of such agents to the inner ear. Expert opinion: The search for effective treatments of inner ear disorders is ongoing. Increased understanding of the molecular mechanisms of hearing loss, Ménière's disease, and tinnitus is driving development of new therapeutic agents. However, delivery of these agents to the inner ear is a continuing challenge. At present, combination of a suitable drug with an appropriate mode of drug delivery is the key focus of innovative research to cure inner ear disorders.

Conclusions: One-shot, low-dose intra-tympanic gentamicin (ITG) treatment was effective and safe for Ménière's disease (MD) patients. Head thrust test (HTT) and vestibular evoked myogenic potentials (VEMPs) test could be used as endpoint indicators for vertigo control in MD patients., Objectives: The present study is to explore end-point indicators of ITG injection in MD., Methods: Patients with MD were reviewed from June 2012 to March 2014. Single-shot ITG at a concentration of 30 mg/ml was administered to patients. The sensitivity and specificity of HTT and VEMPs for vertigo control were measured., Results: All 37 patients with a median follow-up of 26 months were included. Of those 37 patients, 24 patients (64.9%) obtained class A vertigo control and seven patients (18.9%) obtained class B vertigo control. Only six patients had class C control (16.2%). The sensitivity and specificity of HTT for vertigo control were 74.2% and 50.0%. Meanwhile, the sensitivity and specificity of VEMPs threshold were 83.9% and 33.3%. When combined HTT and VEMPs, sensitivity and specificity were 93.5% and 66.7%. Based on the four-tone average thresholds at 0.5, 1, 2, 3 kHz, 78.4% patients had no significant change in PTA and 16.2% patients experienced significant improvement.

Conclusion: Intra-tympanic dexamethasone injection (ITD) could serve as a first-line intra-tympanic (IT) treatment for Meniere's disease (MD), regardless of hearing level. Even if the response to initial ITD course was unsatisfactory, a repeated course may be beneficial with some patients., Objectives: This study examined the effect of repeated courses of ITD administered on demand and investigated the possibility of ITD as an initial IT treatment for medically intractable MD patients., Method: Fifty-one patients who had been diagnosed with definite MD and given course(s) of ITD treatment were included. Vertigo control, pure tone average and functional disability scores were evaluated against the American Academy of Otolaryngology-Head and Neck Surgery guidelines for MD., Results: Vertigo disappeared or was substantially controlled in 58.8% and 23.5% of the patients, respectively, after the first ITD course. A repeated course further raised the complete vertigo control rate by 15.7% and intra-tympanic gentamycin injection could be postponed or avoided in 78.6% of the patients who required repeated IT treatment. Hearing was unchanged after the first course of ITD (p > .05). No significant differences were detected in the clinical profiles or laboratory findings between patients receiving single course of ITD and those on multiple courses (p > .05).

Objective: To investigate the efficacy and safety of low-dose intratympanic gentamicin (ITG) compared with intratympanic dexamethasone (ITD) in patients with intractable Meniere's disease (MD). Method: Seventy patients affected by definite unilateral MD were enrolled. 1 ml of gentamicin sulfate(40 g/L) was buffered with 0.5 ml of sodium bicarbonate to obtain a 6.4 pH solution with 26.7 g/L concentration. Thirty-five patients were treated with the buffered gentamicin solution on every week for 2 times. Thirty-five patients were treated with ITD (5 mg) in the first two days, and then every week for 4 weeks. At 2-year follow-up, mean outcome measurements consisted of control of vertigo attacks, pure tone average (PTA), dizziness handicap inventory and tinnitus handicap inventory. Result: Among 34 cases with complete follow-up data in the ITG group, complete control of vertigo (class A) was achieved in 27 patients and substantial control of vertigo (class B) in 5 patients. Among 32 cases with complete follow-up data in the ITD group, class A and B were achieved in 13 and 6 patients respectively ( P < 0.05). There were no statistically significant variations between the two groups in PTA and THI ( t = 1.737 and t =－0.197, P > 0.05). Conclusion: Low-dose ITG achieves better outcome than ITD in the control of vertigo attacks in patients suffering from unilateral intractable MD, with a very low incidence of hearing deterioration., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background and Objective: Ménière's disease (MD) is a disorder of the inner ear typically showing recurrent acute episodes of vertigo, hearing loss, and tinnitus. Epidemiologic studies on MD are scarce. We assessed the incidence rates (IRs) of MD and describe the characteristics of MD cases, comparing them to control patients without recorded evidence of MD., Study Design: We conducted a retrospective population-based follow-up study and a nested case-control analysis using data from the UK-based Clinical Practice Research Datalink., Methods: We identified patients between 18 and 79 years of age with an incident MD diagnosis between January 1993 and December 2014. We assessed the IRs of betahistine-treated MD. In the nested case-control analysis, we matched 4 controls to each MD case on sex, age, general practice, years of active history in the database, and calendar time. We conducted a χ2 test to present p values in order to compare the prevalence of demographics, comorbidities, and co-medication between cases and controls., Results: We identified 5,508 MD cases and 22,032 MD-free controls (65.4% females). The overall IR for MD in the UK was 13.1 per 100,000 person-years. More cases were female, and the mean age at diagnosis was 55.4 ± 13.7 years. Smoking and alcohol consumption were less prevalent among MD cases. Depression, other affective disorders, sleeping disorders, anxiety, and migraine were more prevalent among MD cases than among controls., Conclusions: MD is uncommon in primary care in the UK with a preponderance among females., (© 2017 S. Karger AG, Basel.)

Purpose: To determine the rate of persistent tympanic membrane perforation after intratympanic steroid injection. To determine which comorbid conditions and risk factors are associated with prolonged time to perforation closure following intratympanic steroid injection., Materials and Methods: Clinical data were gathered for patients who had undergone intratympanic steroid injection to treat sudden sensorineural hearing loss or Ménière's disease. Primary outcomes analysis included rate of persistent tympanic membrane perforation, defined as perforation at least 90days following last injection, and time to perforation healing. Age, sex, number of injections, smoking status, diabetes mellitus, previous head and neck irradiation, and concurrent oral steroids, were analyzed as potential predictors of persistent perforation., Results: One hundred ninety two patients were included in this study. Three patients (1.6%) had persistent tympanic membrane perforations. All three patients received multiple injections. One patient underwent tympanoplasty for repair of persistent perforation. The median time to perforation healing was 18days. There was no statistically significant variable associated with time to perforation healing. However, patients with prior history of head and neck radiation averaged 36.5days for perforation healing compared to 17.5days with no prior history of radiation and this approached statistical significance (p=0.078)., Conclusions: The rate of persistent tympanic membrane perforation following intratympanic steroid injection is low. Patients with a history of radiation to the head and neck may be at increased risk for prolonged time for closure of perforation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Drop attack (DA) associated with Ménière's disease (MD) and delayed endolymphatic hydrops (DEH) is not common and may cause life-threatening clinical problems. The intratympanic dexamethasone (ITD) is one of primary treatments for MD or DEH. Our study investigated the effect of ITD on the DA associated with endolymphatic hydrops (EH).We retrospectively reviewed 10 patients with MD- and DEH-associated DA between January 2009 and December 2013 in Outpatient Department of Otolaryngology, Union Hospital, Wuhan, China. Among them, 7 patients (5 cases with MD, 2 cases of DEH) received ITD (4 times, on weekly basis). Further repeated ITD courses or intratympanic gentamicin (ITG) were given if the vertigo was not satisfactorily controlled. The number of DA and status of vertigo control after intratympanic injection were evaluated. After a follow-up study lasting from 19 to 35 months, DA in 5 cases (71.4%) disappeared after initial ITD course. In 2 cases, DA was altogether controlled after an additional intratympanic injection (repeated ITD or/and ITG).This study showed that ITD promises to be a first-line conservative treatment for MD- or DEH-related DA since the steroid possesses no inner-ear toxicity. Furthermore, for MD- or DEH-related DA refractory to ITD, ITG can be an effective alternative., Competing Interests: The authors have no conflicts of interest to disclose.

Intratympanic gentamicin therapy is widely used clinically to suppress the vestibular symptoms of Meniere's disease. Dosing in humans was empirically established and we still know remarkably little about where gentamicin enters the inner ear, where it reaches in the inner ear and what time course it follows after local applications. In this study, gentamicin was applied to the round window niche as a 20 μL bolus of 40 mg/ml solution. Ten 2 μL samples of perilymph were collected sequentially from the lateral semi-circular canal (LSCC) at times from 1 to 4 h after application. Gentamicin concentration was typically highest in samples originating from the vestibule and was lower in samples originating from scala tympani. To interpret these results, perilymph elimination kinetics for gentamicin was quantified by loading the entire perilymph space by injection at the LSCC with a 500 μg/ml gentamicin solution followed by sequential perilymph sampling from the LSCC after different delay times. This allowed concentration decline in perilymph to be followed with time. Gentamicin was retained well in scala vestibuli and the vestibule but declined rapidly at the base of scala tympani, dominated by interactions of perilymph with CSF, as reported for other substances. Quantitative analysis, taking into account perilymph kinetics for gentamicin, showed that more gentamicin entered at the round window membrane (57%) than at the stapes (35%) but the lower concentrations found in scala tympani were due to greater losses there. The gentamicin levels found in perilymph of the vestibule, which are higher than would be expected from round window entry alone, undoubtedly contribute to the vestibulotoxic effects of the drug. Furthermore, calculations of gentamicin distribution following targeted applications to the RW or stapes are more consistent with cochleotoxicity depending on the gentamicin concentration in scala vestibuli rather than that in scala tympani., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: To evaluate safety and efficacy of a single intratympanic injection of OTO-104, sustained-exposure dexamethasone, in patients with unilateral Ménière's disease., Study Design: Randomized, double-blind, placebo-controlled, Phase 2b study over 5 months., Setting: Fifty-two academic and community otolaryngology centers., Patients: One hundred fifty four patients (77 per group) aged 18 to 85 years inclusive., Intervention: Single intratympanic injection of OTO-104 (12 mg dexamethasone) or placebo., Main Outcome Measures: Efficacy (vertigo) and safety (adverse events, otoscopy, audiometry, tympanometry)., Results: Primary endpoint (change from baseline in vertigo rate at Month 3) was not statistically significant (placebo [-43%], OTO-104 [-61%], P = 0.067). Improvements with OTO-104 were observed in prospectively defined secondary endpoints number of days with definitive vertigo, (Month 2 [P = 0.035], Month 3 [P = 0.030]), vertigo severity (Months 2-3, P = 0.046) and daily vertigo counts (Month 2, P = 0.042), and in some Short Form-36 (SF-36) subscales (Month 2 bodily pain P = 0.039, vitality P = 0.045, social functioning P = 0.025). No difference in tinnitus loudness or tinnitus handicap inventory (THI-25) was observed. OTO-104 was well tolerated; no negative impact on safety compared with placebo. Persistent tympanic membrane perforation was observed in two OTO-104 treated patients at study end., Conclusion: OTO-104 was well-tolerated, did not significantly affect change from baseline in vertigo rate, but did reduce number definitive vertigo days, vertigo severity, and average daily vertigo count compared with placebo during Month 3. Results provide insight into analyzing for a vertigo treatment effect and support advancing OTO-104 into Phase 3 clinical trials for the treatment of Ménière's disease symptoms.

Introduction: Even today, the treatment of intractable vertigo remains a challenge. Vestibular ablation with intratympanic gentamicin stands as a good alternative in the management of refractory vertigo patients., Objective: To control intractable vertigo through complete saccular and horizontal canal vestibular ablation with intratympanic gentamicin treatment., Methods: Patients with refractory episodic vertigo were included. The inclusion criteria were: unilateral ear disease, moderate to profound sensorineural hearing loss, and failure to other treatments. Included patients underwent 0.5-0.8mL of gentamicin intratympanic application at a 30mg/mL concentration. Vestibular ablation was confirmed by the absence of response on cervical vestibular evoked myogenic potentials and no response on caloric tests. Audiometry, electronystagmography with iced water, and vestibular evoked myogenic potentials were performed in all patients., Results: Ten patients were included; nine patients with Meniere's disease and one patient with (late onset) delayed hydrops. Nine patients showed an absent response on vestibular evoked myogenic potentials and no response on caloric tests. The only patient with low amplitude on cervical vestibular evoked myogenic potentials had vertigo recurrence. Vertigo control was achieved in 90% of the patients. One patient developed hearing loss >30dB., Conclusions: Cervical vestibular evoked myogenic potentials confirmed vestibular ablation in patients treated with intratympanic gentamicin. High-grade vertigo control was due to complete saccular and horizontal canal ablation (no response to iced water in electronystagmography and no response on cervical vestibular evoked myogenic potentials)., (Copyright © 2016 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

Conclusion: The dehydration test using isosorbide is well tolerated when used to detect endolymphatic hydrops and may also be used to improve the sensitivity of ECoG performed on patients with MD, especially in poor hearing at low-frequency., Objective: This prospective study was to explore the diagnostic utility of a dehydration test, administering oral isosorbide, which has been used to treat Meniere's disease (MD)., Method: Electrocochleography (ECoG) and the dehydration test with isosorbide were performed on 32 patients diagnosed with definite diagnosed MD. Isosorbide (120 mL) was orally administered after baseline audiometric testing, and the testing was repeated 3 h later. The dehydration test was considered positive when improvements in hearing thresholds of 10 dB or more were evident at two or more frequencies, or the speech discrimination score increased by 12% or more. An abnormal ECoG finding was defined as an SP/AP (summating potential/action potential) ratio ≥0.4., Results: The dehydration test using isosorbide was positive in 10 of 32 patients (31.3%). The test was not associated with development of any serious side-effect. Abnormal ECoG findings were noted in 14 of 32 patients (43.8%). When endolymphatic hydrops was defined as an abnormal ECoG or a positive dehydration test, the condition was detected in 21 of 32 patients (65.6%). The positive result in dehydration test was significantly higher in patients with above moderate hearing loss at low-frequency.

Intratympanic injection of gentamicin is increasingly used in the treatment of unilateral disabling Menière's disease (MD). Several objective functional and subjective tests have been developed to assess the control of vertigo after gentamicin treatment. The aim of this study was to show that subjective results require a vestibular deafferentation as profound as possible, evidenced with multifrequency vestibular assessment. Sixty four patients with intractable MD in situation of medical treatment failure longer than 6 months were included between 1998 and 2013 in this case control study. A 2-year follow-up was performed after the last intratympanic gentamicin performed with the titration technique. A vestibular assessment was applied before and after 2 years of treatment with a functional level score using the AAOHNS vertigo scale and multifrequency vestibular assessment: skull vibration-induced nystagmus test (SVINT), head-shaking test (HST) and caloric test (CaTe). The correlation between the results of the questionnaire and the level of the deafferentation as evaluated by the tests was analyzed with the Spearman test. Among the 64 included patients, 56 (87.5 %) described vertigo control. There was a correlation (=-0.33 [-0.53; -0.09], p = 0.008) between subjective improvement (AAO -HNS 1 or 2) and the degree of vestibular deafferentation as evidenced by a destructive nystagmus (beating toward the safe side) with the HST and the SVINT, as well as a caloric hypofunction >90 % with the CaTe. The present study demonstrates that a profound vestibular deafferentation confirmed with multifrequency test evaluation is needed to have a subjective improvement in the treatment of unilateral disabling MD with intratympanic gentamicin.

Multiple options exist to manage Ménière's disease (MD), ranging from dietary modifications to ablative surgery. Corticosteroids (CS) have long been used to manage MD, but their exact mechanism for disease alleviation is relatively uncertain. Glucocorticoid receptors have been shown to exist in the human inner ear and several studies propose they influence mechanisms of blood flow, fluid regulation, and ion regulation, with recent evidence describing the latter two. Corticosteroids have been shown to upregulate aquaporins and ion channels in the inner ear, and may have a positive effect on labyrinthine blood flow. Additionally, processes have been described in genomic and non-genomic manners. This text will review the literature on the actions of CS on the inner ear relevant to MD., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Preventing or reversing hearing loss is challenging in Ménière's disease. Betahistine, as a histamine agonist, has been tried in controlling vertigo in patients with Ménière's disease, but its effectiveness on hearing problems is not known., Objective: To examine the effect of betahistine on hearing function in not-previously-treated patients with Ménière's disease and to define possible contributors in this regard., Methods: A total of 200 not-previously-treated patients with definite unilateral Ménière's disease received betahistine by mouth (initial dose, 16mg three times a day; maintenance dose, 24-48mg daily in divided doses). Changes in indicators of hearing status before and six months after treatment were documented. Hearing loss was considered as the mean hearing level >25dB HL at five frequencies., Results: The mean duration of disease was 3.37 years. Six months after treatment the mean hearing level decreased by 6.35dB compared to that at the baseline (p<0.001). Both patients' age and the duration of disease correlated negatively with the improvement in hearing function. Post treatment hearing loss was independently associated with age, the initial hearing level and the chronicity of disease. The corresponding optimal cut-off points for predicating a persistent hearing loss 6 months after treatment were 47 years, 38dB HL, and 1.4 years, respectively., Conclusion: Oral betahistine was significantly effective in preventing/reversing hearing deterioration in patients with Ménière's disease. Age, the hearing level on admission, and the disease duration were independent predictors of hearing status after treatment., (Copyright © 2015 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

The objective of the study was to determine the evidence of intratympanic steroids injections (ITSI) for efficacy in the management of the following inner ear diseases: Ménière's disease, tinnitus, noise-induced hearing loss (NIHL) and idiopathic sudden sensorineural hearing loss (ISSNHL). The data sources were literature review from 1946 to December 2014, PubMed and Medline. A systematic review of the existing literature was performed. Databases were searched for all human prospective randomized clinical trials using ITSI in at least one treatment group. The authors identified 29 prospective randomized clinical trials investigating the benefits of an intratympanic delivery of steroids. Six articles on Ménière's disease were identified, of which one favored ITSI over placebo in vertigo control. Of the five randomized clinical trials on tinnitus therapy, one study found better tinnitus control with ITSI. The only available trial on NIHL showed significant hearing recovery with combination therapy (ITSI and oral steroids therapy). Seventeen studies were identified on ISSNHL, of which 10 investigated ITSI as a first-line therapy and 7 as a salvage therapy. Studies analysis found benefits in hearing recovery in both settings. Due to heterogeneity in treatment protocols and follow-up, a meta-analysis was not performed. Given the low adverse effects rates of ITSI therapy and good patient tolerability, local delivery should be considered as an interesting adjunct to the therapy of the ISSNHL and NIHL. Only one article over six where ITSI therapy offers potential benefits to patients with Ménière's disease in the control of tinnitus and vertigo was found. ITSI does not seem to be effective in the treatment of tinnitus.

Background The intratympanic application of the ototoxic aminoglycoside gentamicin has shown promising results as an ablative treatment for vertigo associated with Ménière's disease. Objective To evaluate the efficacy and safety of intratympanic gentamicin and to specifically analyse the effect of this treatment on high and low hearing frequencies in patients with unilateral definite Ménière's disease. Method Subjects were treated with intratympanic gentamicin and were evaluated on vertigo, tinnitus, mean pure tone audiometry threshold and speech discrimination score. Subjects were followed for evaluation for up to 2 years after treatment. Results The number of vertigo spells per month decreased and subjects experienced less tinnitus. During follow up there was an increase of hearing loss in the low (0.25-, 0.5-, 1-kHz) frequency range (13.3 dB; p = 0.03). There was no significant increase of hearing loss in the high (2-, 4-, 8-kHz) frequency range. A clinically significant change in speech discrimination score was found in 50 % of the subjects. Conclusion Our results indicate that intratympanic gentamicin especially affects the mean pure tone audiometry threshold in the low frequency range, which may have clinical implications. Though many of our results are (statistically) substantial the study was limited by the small cohort size.

Purpose: Increased cochlear lymph fluid signals on three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) images obtained several minutes after intravenous administration of a single dose of gadolinium-based contrast agent (IV-SD-GBCA) in a patient with severe retrofenestral type otosclerosis had been reported. This increase was thought to represent breakdown of the blood-labyrinthine barrier. The purpose of this study was to evaluate cochlear lymph signal on heavily T2-weighted 3D-FLAIR (HF) images obtained 4 hours after IV-SD-GBCA in patients with otosclerosis, Ménière's disease, and healthy subjects., Materials and Methods: Twenty-two ears from 12 patients with otosclerotic plaques determined by computed tomography (CT), 16 ears from 8 healthy volunteers, and 10 ears from 9 Ménière's disease patients with significant endolymphatic hydrops on magnetic resonance (MR) images were retrospectively analyzed. Images were obtained 4 hours after IV-SD-GBCA. Patients and healthy volunteers underwent MR cisternography (MRC) for anatomical reference of the fluid space and HF at 3T. The region of interest (ROI) was manually drawn on MRC images around the scala tympani in the basal cochlear turn. The reference ROI was set in the cerebellum. ROIs were copied onto HF images and the signal intensity ratio (SIR) of cochlear perilymph to cerebellum was measured. Differences in the SIR on HF images among the three groups were tested by one-way analysis of variance (ANOVA)., Results: The mean SIR was 24.0 ± 10.1 in otosclerosis patients, 7.9 ± 1.5 in volunteers, and 11.6 ± 3.9 in Ménière's disease patients. The mean SIR was significantly higher in the otosclerosis group than in the other groups (P < 0.001). In the otosclerosis group, there was a significant difference in the SIR between the retrofenestral type and the fenestral type (P = 0.033)., Conclusions: In patients with otosclerosis, the SIR was higher than in Ménière's disease patients or in healthy volunteers. The SIR was higher in the retrofenestral type than in the fenestral type.

The human endolymphatic sac (ES) is situated in a duplicature of the dura in the posterior cranial fossa and constitutes a part of the inner ear. The sac possesses immunological capacities and is responsible for a major part of the trans-epithelial ion transport occurring within the inner ear, via molecular mechanisms similar to that of the kidney collecting duct epithelia. Dysfunction of the trans-epithelial ion transport has been hypothesized as the reason for the endolymphatic hydrops occurring in Menieres diseases. Thus, candidate drug selection for medical treatment of Menieres disease has been based on a potential capability of improving trans-epithelial ion transport. However, recent human studies seems to rule out diuretic therapy and The Committee for Medicinal Products for Human Use redrew the recommendation for trimetazidine (Vastarel) treatment in the management of Meniere disease in 2012. This leaves betahistine (Betaserc) as the only drug for potential prevention of the incapacitating attacks of dizziness, tinnitus and hearing loss. However, the histamine receptors targeted by betahistine have never been demonstrated in the human ES. Accordingly, this study aims to investigate the expression of histamine receptors of the human ES epithelium and sub-epithelial stroma. Following sampling of human endolymphatic sac tissue during translabyrinthine surgery, the expression of histamine receptor genes was determined by cDNA microarray analysis. Results were subsequently verified by immuno-histochemistry. The combined results of microarrays and immuno-histochemistry showed expression of the histamine receptor HRH1 in the epithelial lining of the ES, whereas HRH3 was expressed exclusively in the sub-epithelial capillary network. Receptors HRH2 and -4 were not expressed. The present data provide the first direct evidence of a molecular rationale for betahistine treatment in Menieres disease. A potential betahistine effect in Menieres disease may primarily be through the H3-receptor antagonism, leading to inhibition of vestibular neuro-transmission and central vaso-dilation. The H1-receptor localization in the ES epithelium suggests an immuno-regulatory effect.

Objective: To investigate the history,audiology,imaging,and operative characteristics of tympanosclerosis patients with intact tympanic membranes,and to provide theoretical reference for preoperative diagnosis and treatment. Method: A retrospective study was carried out among 9 tympanosclerosis patients (16 ears) with intact tympanic membranes who underwent exploratory tympanotomy.For different patients,the different reconstruction of ossicular chain are in selection.We compared the pre-operative outcomes of pure tone audiometry and otoscope with the post-operative outcomes,and calculated their air-bone gap and improvement value. Result: At 3 month after operation,otoscope showed that the tympanic membrane of all patiens were integrity.Tinnitus disappeared or improved in 5 cases.The mean thresholds of air conduction,bone conduction and air-bone gap were(40.33±11.48)dB,(27.34±8.46)dB,(13.16±9.85)dB respectively.The air-bone gap in 3 months after the operation was significantly smaller than that before operation( P <0.05). Conclusion: Most of the patients with tympanosclerosis suffer mixed hearing loss.In addition to chronic inflammatory stimulation,tympanic membrane incision catheter may be one of the important pathogenic factors.Morphology and imaging are more useful in differentiation of otosclerosis.Early and active surgery interference would attain good effect., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: To study the effect of low-dose gentamicin intratympanic therapy on intractable Meniere's disease on hearing. Method: One hundred and forty cases of patients with ENT intractable Meniere's disease were selected in this clinical trial study,all patients were enrolled in the drum line intraventricular injection of low-dose gentamicin treatment.After two weeks' treatment in hospital,the patients followed-up for 1 years,all patients did pure tone audiometry,speech audiometry and on hearing threshold changes before and after treatment were comparatively analyzed; continu followed-up for 1 year and the patients' Meniere's disease therapeutic effect were analyzed. Result: After treatment,the follow up within a year of 120 patients(140 cases,20 cases were lost),36 cases never attack of vertigo symptoms,the total effective rate was 91.7%; all patients before treatment speech frequency was(67.2±2.1) dB after treatment(65.5±2.0) dB,the difference was not statistically significant( P >0.05); In the group of gentamicin treatment,all patients 1-3 kHz compare hearing thresholds and changes of 8 kHz before and after injection,the difference was not statistically significant( P >0.05); tinnitus,ear fullness episodes of a significant reduction in the overall incidence rate dropped to 2% from 7% after treatment,the difference was statistically significant( P <0.05) . Conclusion: For intractable Meniere's disease,a small dose of gentamicin intratympanic have a positive clinical effect,and no significant effect on hearing Thus,it is a worthy of promotion and application for low dose gentamincin intratympanic injection in intractable Meniere's disease., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: (1) Review evidence for the use of oral diuretic medications in the management of Ménière's disease. (2) Analyze therapy-related hearing and vertigo outcomes., Data Sources: Literature was obtained through directed searches of MEDLINE, EMBASE, Web of Science, EBSCO Host, Cochrane Reviews, and linked citations through seminal papers. We searched independent electronic databases for articles that reported the use of diuretics in patients with Ménière's disease., Review Methods: All articles of level 4 evidence or higher, per the Oxford Centre for Evidence-Based Medicine, were included with no limit for number of patients, duration of therapy, or follow-up period. Two independent investigators reviewed the articles for inclusion eligibility. Outcomes were tabulated, including subjective or quantitative measures of hearing, tinnitus, vertigo episode frequency, and medication adverse effects., Results: Nineteen articles were included from 1962 to 2012 from 11 countries. Twelve retrospective case series, 4 randomized controlled trials, 2 case-control trials, and 1 prospective case series were identified. Six studies investigated isosorbide; 5, hydrochlorothiazide; 2, acetazolamide; 2, chlorthalidone; and 1 each of betahistine, hydrochlorothiazide, chlorthalidone, acetazolamide, hydrochlorothiazide-triamterene, and nimodipine. Eight (42.1%) studies reported hearing outcomes improvement. Fifteen (79.0%) studies reported vertigo outcomes improvement. Ten (52.6%) studies reported no side effects, and 4 studies (21.1%) reported abdominal discomfort. No significant morbidity or mortality was reported in any study., Conclusion: Multiple low evidence-level studies report that oral diuretic therapy may be beneficial in the medical management of Ménière's disease. Improvement in vertigo episode frequency was consistently reported, with less convincing evidence for improvement in hearing outcomes., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

Objective: To assess the effectiveness and response over time of intratympanic dexamethasone on the symptoms of Meniere's disease., Materials and Methods: We performed a matched cohort study of 24 patients with Meniere's disease who were unresponsive to initial treatment and underwent 3 sessions of weekly intratympanic dexamethasone injections using a concentration of 16 mg/mL and 24 matched controls with the same characteristics with regard to vertigo spells., Results: Compared with control subjects, intratympanic dexamethasone injections resulted in a decrease in the frequency of vertigo spells in the first 6-month period. In the dexamethasone-treated group, a ≥60% decrease in vertigo spells was achieved by 70.8% of patients in the first 6 months. Total remission was achieved by 20.8% of patients in the first 8 months, but after this, the effect tapered. A slight improvement in Tinnitus loudness and no changes in hearing levels were found. The stage of Meniere's disease, years from disease onset, and mean number of vertigo spells per month did not have any effects on the percentage of decrease in vertigo spells., Conclusion: Intratympanic dexamethasone temporarily reduces the frequency of vertigo spells during the initial months but does not remove the probability of having further spells in the future. This therapy provides a valuable tool to accomplish a rapid decrease in vertigo spells in subjects with Meniere's disease, and it is considered an alternative to chemical or surgical labyrinthectomy.

While many high quality studies are available for the specific immunotherapy of the allergic rhinitis and limited for the angiotensin-converting enzyme inhibitor induced angioedema available, the evidence is very low for Ménière's disease or for the medicinal treatment of post-surgery laryngeal edema. This paper discusses the study data and evidence of the respective diseases., (© Georg Thieme Verlag KG Stuttgart · New York.)

Objective: To verify the hypothesis that intravenous frusemide reduces endolymphatic hydrops, as evaluated by three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging following intratympanic gadolinium administration., Methods: The study comprised 12 patients (7 females and 5 males, aged 19-74 years) with Ménière's disease. Disease duration ranged from 0.5 to 8 years, with a frequency of 0.5 to 6 vertigo spells per month, as calculated in the last 6 months. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging was performed 24 hours after intratympanic injection of gadobutrol diluted eight-fold. Frusemide 20 mg was given intravenously immediately after imaging. Magnetic resonance imaging was repeated after 1 hour, using the same parameters and sequence., Results: All patients showed enhancement defects, indicating endolymphatic hydrops of variable degrees. No modifications occurred at the second magnetic resonance imaging performed 1 hour after frusemide administration., Conclusion: There was no evidence of endolymphatic hydrops modification 1 hour after intravenously administered frusemide. Therefore, loop diuretics in Ménière's disease, which are today used on an empirical basis, must be reconsidered. Implications of these outcomes are discussed and related to the role of endolymphatic hydrops in the development of Ménière's disease.

We investigated the influence of vasopressin type 2 receptor antagonist (OPC-41061; Tolvaptan) on experimentally induced endolymphatic hydrops (EH) in guinea pigs. In the first series, the endolymphatic sac (ES) of the left ear of all animals was electrocauterized. Four weeks after surgery, the animals were allocated to four groups: three systemic applications groups (saline, OPC 10 and 100 mg/kg) and a local round window (RW) OPC 1 mg/body application group. We examined the histopathology of the temporal bones and assessed volumetric changes of the endolymphatic space in the cochlea and saccule. In the second series, we investigated the effects of systemic and topical applications of OPC on plasma vasopressin (p-VP) concentrations and plasma osmolality (p-OSM). In the first series, we found that EH was reduced in the OPC 10 mg/kg systemic and OPC RW application groups. In contrast, EH increased in the OPC 100 mg/kg systemic application group. In the second series, neither p-VP levels nor p-OSM were significantly different among the non-OPC, OPC 10 mg/kg systemic, and OPC RW application groups. However, in the OPC 100 mg/kg systemic application group, the p-VP level was significantly higher than that in other groups, and p-OSM was higher than that in the non-OPC group. The systemic application of a low dose of OPC and topical application of OPC resulted in reduced EH in the face of minimal systemic effects (p-VP and p-OSM). These findings suggest that OPC-41061 may be one useful treatment option for EH., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Study Question: What is the long term efficacy of betahistine dihydrochloride on the incidence of vertigo attacks in patients with Meniere's disease, compared with placebo?, Methods: The BEMED trial is a multicentre, double blind, randomised, placebo controlled, three arm, parallel group, phase III, dose defining superiority trial conducted in 14 German tertiary referral centres (for neurology or ear, nose, and throat). Adults aged 21-80 years (mean age 56 years) with definite unilateral or bilateral Meniere's disease were recruited from March 2008 to November 2012. Participants received placebo (n=74), low dose betahistine (2 × 24 mg daily, (n=73)), or high dose betahistine (3 × 48 mg daily, (n=74)) over nine months. The primary outcome was the number of attacks per 30 days, based on patients' diaries during a three month assessment period at months seven to nine. An internet based randomisation schedule performed a concealed 1:1:1 allocation, stratified by study site. Secondary outcomes included the duration and severity of attacks, change in quality of life scores, and several observer-reported parameters to assess changes in audiological and vestibular function., Study Answer and Limitations: Incidence of attacks related to Meniere's disease did not differ between the three treatment groups (P=0.759). Compared with placebo, attack rate ratios were 1.036 (95% confidence interval 0.942 to 1.140) and 1.012 (0.919 to 1.114) for low dose and high dose betahistine, respectively. The overall monthly attack rate fell significantly by the factor 0.758 (0.705 to 0.816; P<0.001). The population based, mean monthly incidence averaged over the assessment period was 2.722 (1.304 to 6.309), 3.204 (1.345 to 7.929), and 3.258 (1.685 to 7.266) for the placebo, low dose betahistine, and high dose betahistine groups, respectively. Results were consistent for all secondary outcomes. Treatment was well tolerated with no unexpected safety findings. Without a control group of patients who did not receive any intervention to follow the natural course of the disease, the placebo effect could not be accurately assessed and differentiated from spontaneous remission and fluctuation of symptoms., What This Study Adds: Current evidence is limited as to whether betahistine prevents vertigo attacks caused by Meniere's disease, compared with placebo. The trial provides information on symptom relief on placebo intervention which is relevant for the design of future studies on potential disease modifying treatments in patients with Meniere's disease., Funding, Competing Interests, Data Sharing: Support from the German Federal Ministry of Education and Research (BMBF support code 01KG0708). Potential competing interests have been reported in full at the end of the paper on thebmj.com. Data are available from the corresponding author (Michael.Strupp@med.uni-muenchen.de) or biostatistician (mansmann@ibe.med.uni-muenchen.de). Study registration EudraCT no 2005-000752-32; ISRCTN no ISRCTN44359668., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: The aim of this study is to prove the involvement of the immune response in the etiopathogenesis of some cochleovestibular disorders by a demonstration of antibodies against inner ear antigens and identify the benefits of immunosuppressive therapy., Background: McCabe in 1979 postulated the hypothesis of autoimmune inner ear disease., Methods: Sodium dodecyl sulfate polyacrylamid gel electrophoresis and immunoblotting were used to examine the serum of 74 subjects for the presence of antibodies against inner ear antigens. The subjects were divided into three groups: A--subjects with idiopathic progressive sensorineural hearing loss, B--subjects with Menière´s disease, C--healthy subjects. Individuals with proven antibodies received immunosuppressive therapy., Results: We detected antibodies against inner ear antigens with molecular weight of 30, 50, 60, 80, 100 kDa. In group A they were found in 52% of 25 subjects, in group B in 44% of 25 subjects and they were not detected in group C. An improvement of hearing was recorded in 69% of subjects in group A. An improvement of hearing was observed in 72%, significant relief of vertigo in 81% of subjects in group B., Conclusion: The present study supports the hypothesis of immune-mediated cochleovestibular disease (Tab. 3, Ref. 15).

Background: Meniere's syndrome or disease (MS/D) is typically characterised by episodic vertigo, aural fullness, tinnitus and fluctuating hearing loss. There are multiple options available for treatment with variation in consensus on the best intervention., Objective: To evaluate the evidence on the efficacy of intratympanic therapies [steroids, gentamicin, antivirals and other therapies] on the frequency and severity of vertigo and other symptoms of MS/D., Search Strategy: A literature search was performed on AMED, EMBASE, HMIC, MEDLINE, PsycINFO, BNI, CINAHL, HEALTH BUSINESS ELITE, CENTRAL and Cochrane Ear, Nose and Throat disorders group trials register using various MeSH. The search was restricted to English and human subjects, and the last date of search was December 2014., Selection Criteria: Randomised controlled trials of intratympanic therapies [steroids, gentamicin antivirals and latanoprost] versus a placebo or another treatment., Results: We analysed 8 RCT's comparing intratympanic steroids, gentamicin, ganciclovir (antiviral) and latanoprost versus another form of intratympanic treatment or placebo., Conclusions: On the basis of 6 RCT's (n = 242), there is evidence to support the effectiveness of intratympanic steroids and gentamicin to control symptoms of vertigo in MS/D albeit with a risk of hearing loss with gentamicin. However, there was no consensus found on doses or treatment protocols. There was no evidence to support the use of other forms of intratympanic therapy (antivirals and latanoprost) in MS/D., (© 2015 John Wiley & Sons Ltd.)