Intratympanic Gentamicin Treatment Research Articles

Results of Electrocochleography in Ménière’s Disease after Successful Vertigo Control by Single Intratympanic Gentamicin Injection

In the last several years, a promising new approach has been suggested in the therapy of Ménière’s disease (MD): the low-dose intratympanic gentamicin therapy. By titrating the desired vestibular inhibition by single injections and infrequent administration, side effects concerning hearing can be held on an acceptably low level, while disease-related symptoms are often successfully eliminated. However, it is still unclear if endolymphatic hydrops actually decreases when the patients become symptom free. In the literature, hydrops is significantly associated with an enhanced ratio of summating potential/action potential (SP/AP). Our aim in this retrospective study was to answer the question if pathologically high SP/AP ratios normalize after successful low-dose intratympanic gentamicin treatment. Twenty-eight patients with MD received one, two or three intratympanic gentamicin injections. These injections inhibited vertigo spells without causing additional hearing loss. SP/AP ratios measured by noninvasive electrocochleography did not improve statistically when patients became symptom free. This indicates that the beneficial effect of gentamicin does not depend on the improvement of SP/AP ratios. Considering the well-established correlation between increased SP/AP and active MD, it thus seems unlikely that gentamicin treatment significantly reduces hydrops.

Outcomes of Endolymphatic Shunt Surgery for Ménière's Disease

To compare proportions of the combined outcome of vertigo control and hearing preservation between intratympanic gentamicin injections and endolymphatic sac shunt surgery for intractable vertigo in Ménière's disease patients. Analysis of published data and retrospective review. Tertiary otologic referral center. Patients with Ménière's disease who had failed medical management: 183 surgical patients (shunt group) and 203 patients obtained from 6 published gentamicin treatment studies (gentamicin group). Cases were included if hearing and vertigo data were available before and after treatment with no previous surgical or injection treatment. Average patient age ranged from 45 to 59 years across studies. Gentamicin studies had nearly equal female to male subjects, whereas the shunt group was 60% female. Endolymphatic sac shunt surgery or intratympanic gentamicin treatment of differing doses and injection schedules. Proportion of patients with best combined vertigo control/hearing preservation. Hearing preservation is 10 dB or less increase in pure-tone average. Outcomes were categorized as follows: complete vertigo control/hearing preservation (best), complete vertigo control/hearing loss, incomplete vertigo control/hearing preservation, and incomplete vertigo control/hearing loss (worst). The shunt group showed a significantly higher percentage of the best outcome (62%) than the gentamicin group (56%, p <or= 0.003), as well as a higher rate of complete vertigo control (86% versus 71%; p <or= 0.001). A higher percentage of patients undergoing shunt surgery attained complete vertigo control/hearing preservation relative to intratympanic gentamicin. There continues to be significant variability in gentamicin outcomes, suggesting that the technique requires additional refinement before consistently producing good outcomes.

Intratympanic gentamicin treatment of patients with Ménière's disease with normal hearing

Objective Understand the safety and outcomes of intratympanic gentamicin treatment in patients with Ménière's disease with normal hearing. Study Design Case series with chart review. Setting Tertiary referral center. Subjects and Methods A total of 224 patients with disabling Ménière's disease treated between May 1996 and June 2007 were grouped according to the American Academy of Otolaryngology–Head and Neck Surgery (AAO-HNS) 1995 Committee on Hearing and Equilibrium staging guidelines: stage 1 (<25 dB pure-tone average [PTA]); stage 2 through 4 (>25 dB PTA). Patients underwent self-treatment with intratympanic gentamicin (10 mg/mL) three times daily for one to eight weeks. Outcome measures included pre- and post-treatment speech discrimination score (SDS), PTA, electronystagmography, vertigo relief, and statistical analysis utilizing the Pearson χ 2 test. Results Twenty-two (88%) of 24 patients with stage 1 Ménière's disease showed unchanged or improved SDS. All 24 patients showed a mean PTA loss of 8 dB. Seventeen (71%) patients reported complete or improved vertigo control. One hundred sixteen (59%) of 200 patients with stage 2 through 4 Ménière's disease showed unchanged or improved SDS. All 200 patients showed a mean PTA loss of 11 dB. One hundred forty-eight (74%) patients reported complete or improved vertigo control. Conclusions Patients with stage 1 Ménière's disease appear to have similar vertigo control with better hearing preservation than patients with advanced disease when treated with low-dose intratympanic gentamicin (10 mg/mL).

Intratympanic dilute gentamicin treatment of Ménière's disease

Intratympanic dilute gentamicin treatment of Ménière's disease

Case report: a case of intractable Meniere's disease treated with autogenic training

BackgroundPsychological stress plays an important role in the onset and course of Meniere's disease. Surgical therapy and intratympanic gentamicin treatment are options for cases that are intractable to conventional medical therapy. Psychotherapy, however, including autogenic training (AT), which can be used for general relaxation, is not widely accepted. This paper describes the successful administration of AT in a subject suffering from intractable Meniere's disease.Case presentationA 51-year-old male patient has suffered from fluctuating right sensorineural hearing loss with vertigo since 1994. In May 2002, he was first admitted to our hospital due to a severe vertigo attack accompanied by right sensorineural hearing loss. Spontaneous nystagmus toward the right side was observed. Since April 2004, he has experienced vertigo spells with right-sided tinnitus a few times per month that are intractable to conventional medical therapy. After four months, tympanic tube insertion was preformed in the right tympanic membrane. Intratympanic injection of dexamethasone was ineffective. He refused Meniett therapy and intratympanic gentamicin injection. In addition to his vertigo spells, he suffered from insomnia, tinnitus, and anxiety. Tranquilizers such as benzodiazepines and antidepressants such as serotonin selective re-uptake inhibitors (SSRIs) failed to stop the vertigo and only slightly improved his insomnia. In December 2006, the patient began psychological counseling with a psychotherapist. After brief psychological counseling along with cognitive behavior therapy (CBT), he began AT. He diligently and regularly continued his AT training in his home according to a written timetable. His insomnia, tinnitus, and vertigo spells disappeared within a few weeks after only four psychotherapy sessions. In order to master the six standard formulas of AT, he underwent two more sessions. Thereafter, he underwent follow-up for 9 months with no additional treatment. He is now free from drugs, including tranquilizers, and has continued AT. No additional treatment was performed. When we examined him six and nine months later for follow-up, he was free of vertigo and insomnia.ConclusionAT together with CBT can be a viable and palatable treatment option for Meniere's disease patients who are not responsive to other therapies.

Reliability of the vestibular evoked myogenic potential test in assessing intratympanic gentamicin therapy in Meniere's disease

Conclusions. The results of this preliminary study demonstrate that with regard to determining the efficacy of intratympanic (IT) gentamicin treatment in patients with Meniere's disease, the reliability of testing for vestibular evoked myogenic potentials (VEMPs) is comparable to that of caloric tests. Compared with caloric tests, VEMP measurements are more comfortable and take less time. The results of VEMP and caloric testing do not correlate with the results of hearing tests. Objective. To test the reliability of VEMP testing to monitor the results of IT gentamicin therapy in patients with Meniere's disease. Subjects and methods. Twelve patients with unilateral Meniere's disease were evaluated with pure tone audiometry (PTA), bithermal caloric tests, and VEMP tests. Patients with measurable caloric and VEMP results before IT gentamicin treatment were included in the study. IT gentamicin (0.5 ml) at a concentration of 40 mg/ml was administered to the patients. Reinjection was performed 10 days later depending on patients’ complaints. Patients were re-evaluated with short- and long-term VEMP, hearing, and caloric test results. Results. Caloric responses and VEMPs changed following gentamicin therapy in 9 patients and 12 patients, respectively. Long-term results of caloric and VEMP tests in patients receiving IT gentamicin treatment changed in 7 patients and 10 patients, respectively.

Intratympanic gentamicin therapy for control of vertigo in unilateral Menière's disease: a prospective, double-blind, randomized, placebo-controlled trial

Conclusions. Intratympanic application of gentamicin is a relatively safe and efficient treatment for the reduction of complaints of vertigo attacks associated with Menière's disease. The treatment also reduces the severity of the perceived aural fullness. Objective. To investigate the effectiveness of intratympanic gentamicin treatment in patients with unilateral Menière's disease. Subjects and methods. In a prospective, double-blind, randomized, placebo-controlled clinical trial subjects scored vertigo complaints, aural fullness and tinnitus, before, during and up to 1 year after treatment. Hearing loss was monitored with pure tone audiometry. Results. Gentamicin treatment resulted in a significant reduction of the score for vertigo complaints and the score for perceived aural fullness. A small increase in hearing loss (average 8 dB) was measured in the gentamicin group.

Gentamicin is Primarily Localized in Vestibular Type I Hair Cells after Intratympanic Administration

Intratympanic (IT) gentamicin injections are effective in the control of episodic vertigo due to Ménière's disease. Histological studies in animals have found that the loss of type I vestibular hair cells far exceeds that of type II cells after IT gentamicin treatment. The objective of this study was to determine whether this selective toxicity for type I hair cells might be due to selective concentration of the drug by these cells. Gentamicin was localized within the vestibular epithelium by both direct and indirect methods. Gentamicin conjugated to Texas Red(R) was used as a direct tracer, and anti-gentamicin antibody provided an indirect means of localization. Conjugated or unconjugated gentamicin was injected into the left tympanic space of chinchillas. The animals were killed and fixed 1 or 3 weeks post-treatment. Confocal fluorescence microscopy was used to determine the localization of gentamicin in semicircular canal cristae. Results from the animals killed within 1 week of administration showed that numerous type I hair cells still remained throughout the epithelium. The mean intensity in grayscale units (0-255) of anti-gentamicin labeling for type I hair cells was 28.14 (95% CI 24.60-31.69), for type II hair cells was 17.09 (14.99-19.20), and for support cells was 5.35 (5.34-5.46; p < 0.001, ANOVA). Anti-gentamicin antibody labeling appeared in the majority of type I hair cells throughout their cytoplasm, but with greater intensity at the apex (p < 0.001). Intensity of fluorescence with Texas-Red conjugated gentamicin was 25.38 (22.83-27.94) in type I hair cells, 15.60 (14.73-16.48) in type II cells, and 12.62 (12.06-13.17) in support cells (p < 0.001, ANOVA). These results suggest that type I hair cells are more susceptible to gentamicin because they more avidly take up or retain the drug in the early period after administration.

Long‐Term Disability of Class A Patients With Ménière's Disease After Treatment With Intratympanic Gentamicin

The main objective of this study was to characterize the residual vestibular symptoms and disability in patients with Ménière's disease who had achieved complete control of vertigo through intratympanic gentamicin treatment. Furthermore, we assessed whether the Functional Level Score prior to treatment reflected the posttreatment symptoms and disability. Prospective. Tertiary medical center. This study involved 103 patients with Ménière's disease treated with intratympanic gentamicin who, after a long-term follow up, have not suffered new vertigo spells and were not subject to any major modification in their treatment. At inclusion and at the last follow-up visit after a minimum of 3 years of ending the treatment, the clinical status (number of vertigo spells), the unsteadiness as well as the disability produced by the disease, symptoms of anxiety, and compensation were asked using specific questionnaires. The results before and after treatment were analyzed using nonparametric tests. After a 5-year follow-up, complete control of vertigo was obtained in 81% of the patients with Ménière's disease who were treated with intratympanic gentamicin. Of them, 15.5% still complained of unsteadiness. A functional level of 6 or unsteadiness after treatment are related with a nonreduction in disability after long-term control of vertigo spells. The efficacy of gentamicin administered intratympanically is high after long-term follow-up as shown by the disappearance of vertigo spells and by the reduction in disability, increase in perception of quality of life, and reduction in anxiety related to vestibular symptoms. Unsteadiness, although an infrequent complaint, determines a level of almost similar severity in those issues. Special care must be taken with patients with a Functional Level Scale score of 6 at the time of beginning treatment.

Intratympanic gentamicin treatment in Meniere's disease: Patients' experiences and outcomes

Intratympanic gentamicin treatment in Meniere's disease: Patients' experiences and outcomes

Intratympanic gentamicin therapy for intractable Ménière's disease

Conclusions. Intratympanic gentamicin treatment using a low dose of gentamicin (∼21–24 mg per injection) applied at intervals of a minimum of 27 days, has been shown to be a successful treatment of vertigo. Objectives. The objective of this analysis was to evaluate the efficacy and side effects of intratympanic injections of gentamicin as treatment of intractable unilateral Ménière's disease. Patients and methods. This was a retrospective study in which 57 patients treated with intratympanic gentamicin for Ménière's disease were analysed. Patients received between 1 and 10 intratympanic injections of gentamicin in an outpatient setting. Results. Six months after treatment, overall complete or substantial vertigo control was reported by 80.7% of our patients (VCC class A, 61.4%; class B, 19.3%). Unilateral caloric weakness increased from 50.1% to 79.8% after treatment, and complete caloric areflexia (30°C and 44°C) was induced in 38.6%. In this study hearing worsened (>10dB = SNHL) in only 15.8% of our patients (range 10–29 dB) and loss of word recognition (WR) scores worsened (>15%) in 31% of the patients. Only 1 injection was necessary in 49.1% of the patients, the remaining 50.9% needed 2, 3, 4, 6 or 10 injections, always with a time interval of a minimum of 27 days.

Intratympanic gentamicin treatment in Meniere's disease: Patients' experiences and outcomes

The aim of this study was to assess the experiences and outcomes of patients receiving intratympanic gentamicin treatment for Ménière's disease in Norfolk, UK. This study was based on a retrospective questionnaire survey and a review of patients' medical records. Two district hospitals. All 29 patients treated between 1999 and 2001, with a minimum follow up of two years post-treatment, were included in the study. Twenty-three patients completed the questionnaires (79 per cent response rate). Glasgow benefit inventory (GBI) and vertigo symptom scale (VSS) scores, plus change in hearing thresholds. The mean GBI total score was +36, indicating substantial improvement in patients' overall quality of life following gentamicin treatment. The VSS scores demonstrated low levels of vertigo or unsteadiness in treated patients. Three patients suffered deterioration in their hearing thresholds following a single injection of gentamicin. However, 96 per cent of responders stated that they would be willing to have such treatment again, if necessary. Intratympanic gentamicin treatment ought to be offered to Ménière's patients suffering from disabling vertigo, with the proviso that they be made aware of the possibility of hearing deterioration.

Outcomes in the use of intra-tympanic gentamicin in the treatment of Ménière's disease

The pathogenesis of Ménière's disease is associated with a disorder of ionic homeostasis, with the pathologic correlate being endolymphatic hydrops. Despite uncertainty as to its particular mode of action, it is accepted wisdom that intra-tympanic gentamicin has a definite therapeutic role in the control of symptoms in patients who fail to respond to medical therapy. This study reports an evaluation of the efficacy of intra-tympanic gentamicin in the treatment of Ménière's disease and also presents a simple, reliable, safe method of administering gentamicin for this purpose. A retrospective review of 56 patients undergoing intra-tympanic gentamicin treatment for Ménière's disease was conducted. Response to treatment was analysed using a patient survey and examination of pure-tone averages. An overall significant improvement in vertigo symptoms of 81.3 per cent was found. There was a 21.4 per cent rate of significant hearing loss, defined as greater than 10 dB, with an average loss in this group of 18.5 dB. A single dose of gentamicin applied directly to the round window resulted in a high rate of control of vertigo, with acceptably low rates of hearing loss.

Angular Vestibulo-Ocular Reflex Gains Correlate with Vertigo Control after Intratympanic Gentamicin Treatment for Meniere's Disease

The objective of our study was to determine whether angular vestibulo-ocular reflex (aVOR) gains correlated with vertigo control after intratympanic gentamicin treatment for Meniere's disease. We conducted a prospective study of 18 subjects with unilateral Meniere's disease treated with intratympanic gentamicin injection and followed all subjects for 1 year. We measured the gain of the aVOR elicited by rapid rotary head thrusts in each of the canal planes for each subject before and after treatment with intratympanic gentamicin by using magnetic search coils to record eye movements. During the follow-up period, 11 subjects ("single-treatment group"; 61%) had control of their vertigo with a single gentamicin injection. The remaining 7 subjects ("multiple-treatment group"; 39%) experienced recurrent vertigo that required a second injection of gentamicin at a mean of 6 months after the first treatment. The 11 subjects in the single-treatment group had significantly greater reduction of labyrinthine function after the first treatment, as measured by change in ipsilateral horizontal canal gain, than did the 7 subjects with vertigo recurrence. Changes in caloric asymmetry did not correlate with vertigo control. Our results suggest that successful treatment of Meniere's disease is closely related to attenuation of semicircular canal function as measured by horizontal canal aVOR gains.

Distortion Product Otoacoustic Emissions after Intratympanic Gentamicin Therapy for Unilateral Ménière’s Disease

The treatment of patients with Ménière’s disease that do not respond to conventional therapy becomes complicated, particularly when taking into account the issue of hearing damage as well as the control of vertigo. Treatment often involves the intratympanic administration of gentamicin, for which different protocols are used. Hence, it is important that we better understand how this treatment influences hearing, beyond mere audiometric assessments. The aim of this prospective study was to evaluate the effect of intratympanic gentamicin treatment for Ménière’s disease on cochlear function, as assessed by otoacoustic emissions. The 41 patients included in the study had been diagnosed with unilateral Ménière’s disease as defined by the American Academy of Otolaryngology-Head and Neck Surgery guidelines (1995), and had been refractory to medical treatment for at least 1 year. Intratympanic injections of gentamicin at a concentration of 27 mg/ml were performed at weekly intervals until indications of vestibular hypofunction appeared in the treated ear. Before beginning the treatment and 3 months after ending it, pure tone and speech audiometry tests were performed and the results are expressed in terms of the pure tone average (0.5, 1, 2, and 3 kHz) and the speech discrimination score, respectively. At the same time, a distortion product otoacoustic emission (DPOAE) study was performed and the results are expressed in terms of its presence or absence, and as the amplitude and threshold of the emission. When analyzed 3 months after the treatment had terminated, hearing loss was seen in 13 patients (31.7%). However, no significant change in the threshold and/or amplitude of otoacoustic emissions was observed in any of the patients. Neither were changes in the audiometric stage, number of injections required or the existence of DPOAE before treatment detected. Hence, the treatment method used here for patients with intractable unilateral Ménière’s disease can be considered as having a low risk on auditory function, as assessed both audiometrically and with otoacoustic emissions, and can be considered as subablative for hearing function.

Vestibular function at the end of intratympanic gentamicin treatment of patients with Ménière's disease

The aim of this study is to analyze the effects of intratympanic gentamicin injections on vestibular function in 33 patients with unilateral Meniere's Disease (according to AAO-HNS guidelines 1995) that had been unresponsive to medical therapy for at least one year. In such patients, the results of bedside examination of vestibular function vestibular examination is compared to those from laboratory tests. Intratympanic gentamicin injections (27 mg/ml) were performed at weekly intervals until symptoms or signs of vestibular hypofunction developed in the treated ear. Vestibular function was evaluated in two different rotatory chair tests. The parameters that were specifically considered were the time constant of the vestibulo-ocular reflex (VOR) after impulse rotation with a peak chair velocity of 100 degrees s(-1), and the phase and gain of the VOR after the sinusoidal harmonic acceleration (SHA) test with a peak chair velocity of 50 degrees s(-1). After treatment, both the time constant of the VOR after rotation towards the treated side and the gain in the SHA test were significantly reduced. These reductions were in accordance with the number of additional signs observed upon bedside examination at the end of the treatment. The changes observed in the VOR correlate well with the results of bedside examination of vestibular function, which in turn reflects the damage induced by intratympanic gentamicin injection.

Intratympanic gentamicin treatment after endolymphatic sac surgery

Conclusions. Interval treatment with up to three intratympanic gentamicin injections once weekly effectively controlled vertigo while preserving hearing in patients with Ménière's disease and recurrent or resistant vertigo after saccotomy. Objectives. Recurrent or resistant incapacitating vertigo may occur after endolymphatic sac surgery (saccotomy) in patients with Ménière's disease. In these patients, revision saccotomy, vestibular nerve section or labyrinthectomy are the established treatment options. We advocate a once-weekly application of intratympanic gentamicin (12 mg) as an effective alternative in this group of patients. Material and methods. Five patients (age range 39–65 years) with definite Ménière's disease according to the 1995 American Academy of Otolaryngology—Head and Neck Surgery (AAO—HNS) criteria and incapacitating vertigo underwent gentamicin treatment after saccotomy. Control of vertigo and hearing preservation were the aims of treatment. The follow-up period ranged from 26 to 59 months. History and pure-tone audiometry were used to assess vertigo control and hearing, respectively. The frequency of vertigo in the 6-month period before gentamicin treatment ranged between 0.5 and four definitive episodes per month. Hearing stage (AAO—HNS criteria) before gentamicin treatment ranged between 2 and 4. Pre- and post-treatment pure-tone hearing thresholds at 0.5, 1, 2 and 3 kHz were compared by means of the Mann–Whitney U-test. Results. Complete vertigo control (class A; AAO—HNS) and hearing preservation at 0.5, 1, 2 and 3 kHz were achieved.

Meniett therapy: rescue treatment in severe drug-resistant Ménière's disease?

Conclusion. Our data indicate that Meniett therapy is unlikely to be helpful in the long-term treatment of patients with severe, drug-resistant Ménière's disease (MD) in whom injection of intratympanic gentamicin (ITG) or another destructive procedure would otherwise be performed. Objective. To investigate the value of Meniett therapy in patients with drug-resistant MD referred for injection of ITG. Material and methods. Twelve patients referred for ITG treatment were followed during a 2-month period of Meniett therapy. Symptoms, functional level and hearing status were evaluated using a standardized staging system. Disease-specific quality-of-life measures were obtained before and after Meniett therapy. At the end of the study period, patients were followed for a mean of 37 months, thus providing long-term outcome data. Results. In two patients, Meniett treatment was interrupted after 1 month because of persistent severe vertigo. In the remaining 10 subjects, we found a significant decrease in the median number of vertigo spells from 10.0/month (25th–75th percentile 4.0–19.0) prior to treatment to 3.0/month (25th–75th percentile 1.5–4.5) after treatment (p=0.02). There was, however, no improvement in hearing status, tinnitus, functional level or self-perceived dizziness handicap. Long-term (>1 year) follow-up data revealed that only 2 subjects preferred to continue Meniett therapy and that ablative surgery had to be performed in 6/12 study patients.

Intratympanic Gentamicin for Menière's Disease: a Meta‐Analysis

To systematically review the published experience on intratympanic gentamicin treatment for intractable Menière's disease. Meta-analysis using a random effect model. A comprehensive literature search was performed for articles using intratympanic gentamicin as a sole treatment modality with reporting of results according to the American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) guidelines for Menière's disease. Two reviewers independently assessed trial quality and extracted data. Fifteen trials with 627 patients met the inclusion criteria. All trials reported "before-after" outcome measures, using patients as their own controls. No double-blind or blinded prospective control trials were identified. Complete (class A) vertigo control was achieved in 74.7% (confidence interval [CI]95% 67.8-81.5%) of patients, and complete or substantial (class B) control was achieved in 92.7% (CI95% 89.5-96.0%). The success rate was not affected by gentamicin treatment regimen (fixed vs. titration). Hearing level and word recognition were not adversely affected, regardless of gentamicin treatment regimen. Analysis of functional level was not performed because of lack of data in the selected articles. Intratympanic gentamicin treatment for intractable Menière's disease appears to be effective in the relief of vertigo. Cochleotoxicity and ototoxicity is unlikely to be a major side effect. However, the level of evidence reflected from the eligible articles is insufficient, especially because of relatively poor study design. Therefore, it is prudent that patients eligible for this type of treatment should be selected carefully and titrated with low-dose gentamicin. Further investigation with this treatment modality with control subjects is warranted.

Selective vestibular ablation by intratympanic gentamicin in patients with unilateral active ménière's disease: a prospective, double-blind, placebo-controlled, randomized clinical trial

ObjectiveTo establish the efficacy of intratympanic gentamicin treatment in patients with unilateral Ménière's disease.Material and MethodsThis was a prospective, double-blind, randomized clinical trial of intratympanic gentamicin versus intratympanic buffer solution (placebo) in patients with established active Ménière's disease in the affected ear. Outcome measures included the number of vertiginous spells, degree of sensorineural hearing loss, labyrinthine function and labyrinthine asymmetry.ResultsTopical gentamicin provided a significant reduction in the number of vertiginous spells, although a “placebo effect” was also observed. Sensorineural hearing loss did not occur in the gentamicin group, although some deterioration occurred in the placebo group.ConclusionsIntratympanic gentamicin is a safe and efficient treatment for the vertiginous spells associated with Ménière's disease. When applied early in the course of the disease, it may prevent some of the sensorineural hearing deterioration associated with it.