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.     

Long-term disability of class A patients with Ménière's disease after treatment with intratympanic gentamicin

OBJECTIVE: 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. STUDY DESIGN: Prospective. SETTING: Tertiary medical center. PATIENTS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Follow-up assessment of intratympanic gentamicin therapy and Saccotomia in Menière's Disease

BACKGROUND: The intratympanic application of ototoxic antibiotics and saccotomia have been well documented in severe cases of one-sided Menière's disease for 30 years now. Both treatment methods are still subject to controversial discussion. PATIENTS AND MATERIAL: This study includes 8 patients suffering from persistent one-sided Menière's disease after treatment with gentamicin application and additional saccotomia (n=2). We performed follow-up visits including the assessment of hearing ability, vestibular function and cranial MRI, 2-10 years after onset of treatment. RESULTS: After therapeutic interventions 7 patients reported to be healed of their symptom vertigo. In 4 patients the gentamicin-treated vestibular organ did not respond to thermic stimulus at the time of follow-up examination. Auditory threshold shift was observed in 3 patients (1 permanent, 2 temporary), whereas hearing threshold improved in 2 patients. Tinnitus was attenuated in 3 patients, while 1 patient suffered from posttherapeutic onset of tinnitus. Morphological and structural changes due to Menière's disease and treatment procedures were ruled out by cranial MRI. CONCLUSION: The intratympanic application of ototoxic medication is a safe and effective treatment method in severe cases of Menière's disease. Saccotomia should be considered as therapeutic regimen for persistent symptoms after repeated application of gentamicin.     

Intratympanic gentamicin for Menière's disease: a meta-analysis

OBJECTIVES: To systematically review the published experience on intratympanic gentamicin treatment for intractable Menière's disease. STUDY DESIGN: Meta-analysis using a random effect model. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Long-term hearing outcome in patients receiving intratympanic gentamicin for Ménière's disease

OBJECTIVE: To determine the long-term hearing outcome in patients with intractable vertigo caused by unilateral Ménière's disease who were treated with intratympanic injection of gentamicin. STUDY DESIGN: The study was a longitudinal analysis of hearing and control of vertigo in patients with unilateral Ménière's disease who received intratympanic gentamicin. METHODS: Pure-tone thresholds and speech discrimination scores on audiometry were analyzed, along with the control of vertigo. Criteria described in 1995 by the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) were used. Patients treated with intratympanic gentamicin had "definite" Ménière's disease and had intractable vertigo despite optimal medical therapy, no symptoms suggestive of Ménière's disease in the contralateral ear, and serviceable hearing in the contralateral ear. The study analyzed the outcomes of 34 patients for whom follow-up data were available for periods greater than 24 months after intratympanic gentamicin. RESULTS: Complete control of vertigo (AAOHNS Class A) was obtained in 90% of the patients. Profound sensorineural hearing loss occurred as a result of gentamicin injection in 1 of the 34 patients (3%). When data from all patients were grouped together, hearing was improved in 5 (15%), unchanged in 23 (68%), and worse in 6 (17%) patients. This distribution of hearing outcome is similar to that in patients whose symptoms of Ménière's disease were managed with medical measures. Recurrent vertigo developed in 10 patients (29%) at an interval of 4 to 15 months after initially complete control. Treatment with additional intratympanic injection(s) of gentamicin did not result in a change in hearing. CONCLUSION: The risk of hearing loss in patients treated with infrequent intratympanic injection(s) of gentamicin is low.     

VEMPs and dynamic posturography after intratympanic gentamycin in Menière's disease

In this study, we investigated whether vestibular evoked myogenic potentials (VEMPs) and dynamic posturography (DP) are useful in the evaluation of the vestibular function in patients affected by active monoaural Menière's disease (MD) treated with intratympanic gentamycin. Twelve subjects affected by monoaural MD were treated with weekly intratympanic injections of 0.5 ml of gentamycin at a concentration of 20 mg/ml. VEMPs were used to test saccular function, while postural control was analyzed by DP. The results obtained with these two techniques were compared with those obtained by using bithermal caloric test. The mean follow-up was 15.3 months (6--28 months). Therapy resulted in complete absence of the caloric response in six subjects (50) and in caloric test-induced asymmetry in the remaining individuals, ranging from 83 to 27. At follow-up, eleven patients (91.6%) were free of vertigo, while one patient had two vertigo spells 9 months after treatment. Before treatment, VEMPs were present in the affected ear of eleven patients. After treatment VEMPs were absent in all the patients. At the end of follow-up, reappearance of VEMPs was observed in two patients, with no changes in latency values and amplitude ratio. DP demonstrated a reduction of the Composite Score (CS) one week after therapy, with a prevalent reduction of the vestibular component. After 6 months, there was an improvement of the CS and, in particular, of the vestibular component. The present study demonstrates that bithermal caloric test and VEMPs allow for the functional evaluation of both the horizontal semicircular canal and the sacculus, suggesting that these techniques might be used together to monitor the efficacy of intratympanic gentamycin therapy. In addition, our data indicate that DP might provide important information on compensation phenomena and show that intratympanic gentamycin can improve postural control in MD patients.     

Low-dose intratympanic gentamicin treatment for dizziness in Ménière's disease

OBJECTIVE: Intratympanic gentamicin is used to control dizziness of Ménière's disease, with a low rate of morbidity and a high success rate. We aimed to develop a new technique and schedule of therapy using a lower dose. DESIGN: A retrospective chart review in Ménière's disease patients treated for intractable dizziness. SETTING: A tertiary/quaternary care outpatient setting. METHODS: Patients were administered intratympanic gentamicin using a low-dose protocol on 2 successive days and evaluated with pre- and post-treatment audiovestibular assessment. MAIN OUTCOME MEASURES: Standard evaluation methods of audiovestibular function measured pre- and postfunction of hearing and balance to determine the effects of treatment and morbidity in the form of hearing loss. A telephone follow-up survey was also undertaken. RESULTS: Patients reported satisfactory control of dizziness, with little morbidity in the form of hearing loss. We also found that the use of a myringotomy tube could be precluded. Post-treatment symptoms of imbalance reported by patients settled as patients compensated. In a telephone survey conducted some years after treatment, patient satisfaction was found to be high. CONCLUSIONS: This two-dose regime was shown to be effective in controlling dizzy spells. In patients refractory to the initial two-dose treatment, a follow-up course of treatment usually proved effective. Long-term follow-up of patients seems to show that failure of treatment usually occurs within the first few months, and that symptoms, once controlled, rarely recur.     

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.     

Class A results in Menière's disease.

A series of 101 patients with Menière's disease treated surgically with an intramastoid endolymphatic shunt operation and with a minimum follow-up of 2 years is reported. The results included success in 76 percent and failure in 22 percent. Thirteen of these patients maintained a hearing level of 15 dB or better, while 11 patients experienced hearing gains of 25 dB or better. These results are compared to other reports, and the difficulty of making such comparisons is illustrated. A derived "efficacy ratio" is defined, and its use is suggested to aid in making statistical inference. The conclusion is reached that more knowledge is required about the natural history of Menière's disease so that appropriate staging may be carried out on these study populations.     

Intratympanic gentamicin therapy for intractable Ménière's disease

CONCLUSIONS: Intratympanic gentamicin treatment using a low dose of gentamicin (approximately 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 degrees C and 44 degrees C) was induced in 38.6%. In this study hearing worsened (> 10 dB = 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.     

Long-term results of gentamicin inner ear perfusion in Ménière's disease

Chemical perfusion of the inner ear is an increasingly popular treatment for Ménière's disease. The authors report on the long-term results of 22 patients treated with gentamicin delivered via a round window micro-catheter. Patients with Ménière's disease underwent continuous, low dose (10 mg/ml) gentamicin infusion at 5 microlitre per hour for 10 days, through a micro-catheter placed into the round window niche. Vertigo was controlled in 95 per cent, whilst preserving hearing in 77 per cent. Hearing improved in three patients. Three patients with pre-operative serviceable hearing (PTA < 50 db) demonstrated reduced hearing; two patients with pre-operative non-serviceable hearing developed a dead ear. Tinnitus and aural fullness remained unchanged or improved in 86 per cent and 68 per cent respectively. Long-term vertigo control can be achieved using low dose gentamicin, whilst preserving hearing and vestibular function in the majority of patients. This procedure appears to stabilize the vestibular function, enhancing the chance of effective vestibular rehabilitation.     

Treatment of Ménière's disease by intratympanic gentamicin application

Ménière's disease is a vestibular disorder characterized by episodic vertigo, tinnitus, fluctuant hearing loss, and ear fullness, with vertiginous attacks being the most disabling complaint. The effectiveness of conservative treatment has been variable, while surgical techniques provide more permanent relief from vertigo, but pose possible morbidity and cochlear risk. Intratympanic administration of gentamicin has been proposed as an alternative for patients with debilitating Ménière's disease who have failed to respond to standard medical treatment. The goal of such treatment is to control vertigo by partially or completely destroying the vestibular system, while at the same time maintaining hearing. In this review we present the current medical literature on pathophysiology, pharmacokinetics, administration methods, dosage, treatment protocols, and problems related to intratympanic administration of gentamicin for patients with MD. Intratympanic gentamicin administration is a simple medical modality for treatment of persistent vertigo in patients with Ménière's disease. According to recent world research protocols, we propose the instillation of gentamicin by transtympanic injection, as a quick, easy, well-tolerated, ambulatory and cost-effective technique. Drug solution concentrations should be dependent on the frequency, intensity and duration of vertigo spells, as well as the degree of existing hearing loss, thus providing progressive vertigo relief with a low possibility of secondary deafness.     

Intratympanic gentamicin in Menière's disease: the impact on tinnitus

Intratympanic administration of gentamicin for the treatment of intractable Menière's disease can achieve relief of vertigo. However, the effect of gentamicin on tinnitus has been less well identified. and conflicting results have been reported. Intratympanic gentamicin therapy was given to 25 patients with Menière's disease for the control of vertigo, and the effect of the therapy on tinnitus was evaluated by a 10-point scale and a modified tinnitus questionnaire. It was found that the tinnitus decreased in four patients (16%) and disappeared in three patients (12%) at follow-up. The effect of gentamicin on tinnitus presented intersubject variability, and no correlation was found between the amount of gentamicin injected and its effect on tinnitus.     

Psychological assessment of patients with Menière's disease

The objective of this study was to evaluate daily stressors, coping, personality, physical and mental health, and quality of life in Menière patients. 110 consecutive patients with definite Menière's disease were assessed using the Dutch Daily Hassles List, Coping Inventory for Stressful Situations (CISS), Symptoms Checklist 90 (SCL-90), NEO Five Factor Inventory (NEO-FFI), General Health Questionnaire (GHQ-12), and the Short Form Health Survey 36 (SF-36). Duration and subjective severity of symptoms were scored using a self-report questionnaire. It was shown that Menière patients had more daily stressors, used certain coping strategies less often, and had more psychopathology (e.g. anxiety and depression), and a worse quality of life compared to healthy reference groups. No abnormalities in personality were found. Patients with more severe symptoms had more psychopathology and a worse quality of life than patients with mild symptoms. The psychological profile of Menière patients seems comparable to patients with other chronic diseases. The outcomes should be used to intensify psychological support in patients with this disabling disease.

Sumario

El objetivo de este estudio fue evaluar los factores de estrés cotidiano, la capacidad de manejo de problemas, personalidad, salud física y mental, y calidad de vida en pacientes con Menière. Se evaluaron 110 pacientes con enfermedad de Menière confirmada utilizando la Lista Holandesa de Problemas Diarios, el Inventario de Manejo de Situaciones Tensinógenas (CISS), el Listado 90 de Síntomas (SCL-90), el Inventario NEO de Cinco Factores (NEO-FFI), el Cuestionario General de Salud (GHQ-12) y la Encuesta de Salud de Fórmula Corta 36 (SF-36). Se anotó la duración y la severidad relativa de los síntomas usando un cuestionario de auto-reporte. Se mostró que los pacientes con Menière tenían más factores cotidianos de estrés, utilizaban menos a menudo ciertas estrategias para enfrentar dificultades, y tenían más psico-patología (p.e., ansiedad y depresión) y una peor calidad de vida que los grupos saludables de referencia. No se encontraron anormalidades de personalidad. Los pacientes con síntomas más severos tenían más psico-patología y peor calidad de vida que los pacientes con síntomas leves. El perfil psicológico de los pacientes con Menière parece comparable el de pacientes con otras enfermedades crónicas. Los resultados pueden utilizarse para intensificar el apoyo psicológico a los pacientes con esta enfermedad tan discapacitante.     

Aldosterone assessment in patients with Menière's disease

Since 1938 endolymphatic hydrops has generally been accepted as the basic histopathological substrate of Menière's disease. In animal studies it has been found that exogenous administration of aldosterone resulted in endolymphatic hydrops. Manifestations of Menière's disease are frequently observed in times of emotional stress. Mediated through the hypothalamus, stress leads to an increased secretion of adrenocorticotropic hormone from the anterior pituitary gland, followed by an increased adrenocortical production of glucocorticoids (cortisol and corticosterone) and mineralocorticoids (aldosterone). We addressed the question whether plasma aldosterone levels, like in guinea pigs, would be increased in patients with Menière's disease. As part of a diagnostic protocol a clinical prospective cohort study was therefore performed on 89 patients with Menière's disease to assess plasma aldosterone levels. Plasma aldosterone was not elevated in Menière patients compared to plasma aldosterone in a control group of 27 normal subjects. No statistically significant differences were found in plasma aldosterone between uni- and bilateral Menière's disease. Plasma aldosterone levels did not correlate with age, average hearing loss, duration or perceived severity of subjective complaints (vertigo, hearing loss, tinnitus and aural pressure). In this study plasma aldosterone was not elevated in patients with Menière's disease compared to normal subjects. Plasma aldosterone can thus not be used as a diagnostic tool for Menière's disease. In conclusion: No anomalous plasma aldosterone levels were found in Menière patients during an attack-free period. The question whether plasma aldosterone and cortisol levels show variations before, during and after an attack remains to be answered. If so, this might contribute to a better understanding of the pathophysiological mechanism of Menière's disease.