Intratympanic steroid treatment: a review.

OBJECTIVE: To review published literature regarding the use of intratympanic steroids in the treatment of Meniere's disease and sudden sensorineural hearing loss and to make recommendations regarding their use based on the literature review. DATA SOURCES: Literature review from 1996 to 2003, PubMed, Medline Plus, and Web of Science. STUDY SELECTION: Retrospective case series and uncontrolled prospective cohort studies were the only types of studies available for review. CONCLUSION: On the basis of the available literature, a weak recommendation is made to use intratympanic steroid treatment of sudden hearing loss if oral steroid therapy fails or is contraindicated. The available studies regarding intratympanic steroid treatment of Meniere's disease and tinnitus are inadequate to answer the question of the efficacy of this treatment for these conditions. Higher quality studies are needed.     

Chemical perfusion of the inner ear

In general, chemical perfusion therapy of inner ear disease is safe, inexpensive, and easy to perform. High inner ear medication concentrations can be achieved while minimizing systemic side effects. Most delivery methods are minimally invasive and can be performed in the office. The treatment is usually well accepted by patients. Vertigo control rates for Meniere's disease have been excellent--rivaling other prominent surgical treatments--allowing intratympanic therapy to become the most prominent first-line treatment for Meniere's disease. Side effects of ototoxicity occurring in approximately 30% of patients remain as one of the primary hurdles to overcome. Most patients who experience hearing loss, however, do not complain of the loss and are simply happy to be free of their vertigo attacks. The use of oral steroids to rescue and preserve hearing during gentamicin perfusion remain promising, and complete recovery and even hearing improvement have been observed [30]. Steroid perfusion of the inner ear also is variably effective for the treatment of SSHL, and is particularly indicated when oral steroids fail or are contraindicated due to other health reasons. Many inner ear perfusion methods and philosophies of treatment exist. Each technique has its associated advantages and disadvantages, and the individual surgeon must decide which technique to use in concordance with the patient's disease and expectations. In the future, new medications likely will be developed to treat certain types of inner ear disease, including SSHL, tinnitus, and various forms of vertigo. These medications can be administered by direct chemical perfusion of the inner ear.     

小剂量庆大霉素鼓室内注射治疗难治性梅尼埃病眩晕的临床研究

目的：分析小剂量庆大霉素鼓室内注射治疗难治性梅尼埃病眩晕的疗效。方法：19例单侧难治性梅尼埃病患者显微镜下鼓室内注射庆大霉素,根据床旁试验（自发性眼震、摇头实验、甩头试验）,听力变化或患者主观症状来决定3周后是否需要再次注射。结果：19例患者中17例眩晕能得到控制,眩晕控制率89％,其中5例患者经1次注射后眩晕就得到控制;8例患者2次注射后眩晕达到控制,其中1例患者因不能忍受耳内肿胀感,要求进一步治疗,行内淋巴囊减压后,症状缓减;有4例患者经3次注射后眩晕得到控制;另外2例患者注射2次后眩晕无改善,要求终止治疗。2例患者注射后听力好转,14例患者注射后听力无变化,3例患者（15％）注射后听力进一步下降。结论：运用小剂量鼓室内庆大霉素注射治疗难治性梅尼埃病眩晕,1次注射后观察3周决定再次注射的必要性,结果显示这一治疗方案既能有效控制眩晕的发作,又能降低听力损伤的风险。     

Intratympanic dexamethasone for sudden sensorineural hearing loss after failure of systemic therapy

OBJECTIVE: Intratympanic steroids are increasingly used in the treatment of inner ear disorders, especially in patients with sudden sensorineural hearing loss (SNHL) who have failed systemic therapy. We reviewed our experience with intratympanic steroids in the treatment of patients with sudden SNHL to determine overall success, morbidity, and prognostic factors. HYPOTHESIS: Intratympanic steroids have minimal morbidity and the potential to have a positive effect on hearing recovery in patients with sudden SNHL who have failed systemic therapy. STUDY DESIGN: The authors conducted a retrospective review. METHODS: Patients presenting with sudden SNHL defined as a rapid decline in hearing over 3 days or less affecting 3 or more frequencies by 30 dB or greater who underwent intratympanic steroids therapy (24 mg/mL dexamethasone) were reviewed. Excluded were patients with Meniere disease, retrocochlear disease, autoimmune HL, trauma, fluctuating HL, radiation-induced HL, noise-induced HL, or any other identifiable etiology for sudden HL. Patients who showed signs of fluctuation of hearing after injection were excluded. Pretreatment and posttreatment audiometric evaluations including pure-tone average (PTA) and speech reception threshold (SRT) were analyzed. Patient variables as they related to recovery were studied and included patient age, time to onset of therapy, status of the contralateral ear, presence of diabetes, severity of HL, and presence of associated symptoms (tinnitus, vertigo). A 20-dB gain in PTA or a 20% improvement in SDS was considered significant. RESULTS:: Forty patients fit the criteria for inclusion in the study. The mean age of the patients was 54.8 years with a range from 17 to 84 years of age. Overall, 40% (n = 16) showed any improvement in PTA or SDS. Fourteen (35%) men and 26 (65%) women were included. Using the criteria of 20-dB improvement in PTA or 20% improvement in SDS for success, 27.5% (n = 11) showed improvement. The mean number of days from onset of symptoms to intratympanic therapy was 40 days with a range of 7 days to 310 days. A statistically significant difference was noted in those patients who received earlier injection (P = .0008, rank sum test). No patient receiving intratympanic dexamethasone after 36 days recovered hearing using 20-dB PTA decrease or a 20% increase in discrimination as criteria for recovery. Twelve percent (n = 5) of patients in the study had diabetes with 20% recovering after intratympanic dexamethasone (not significantly different from nondiabetics at 28.6%, Fisher exact test, P = 1.0). Comparison to other studies that used differing steroid type, concentration, dosing schedule, inclusion criteria, and criteria for success revealed, in many instances, a similar overall recovery rate. CONCLUSIONS: Difficulty in proving efficacy of a single modality is present in all studies on SNHL secondary to multiple treatment protocols, variable rates of recovery, and a high rate of spontaneous recovery. Forty percent of patients showed some improvement in SDS or PTA after treatment failure. When criteria of 20-dB PTA or 20% is considered to define improvement, the recovery rate was 27.5%. Modest improvement is seen with the current protocol of a single intratympanic steroid injection of 24 mg/mL dexamethasone in patients who failed systemic therapy. Dramatic hearing recovery in treatment failures was rarely encountered. No patient showed significant benefit from intratympanic steroids after 36 days when using this protocol for idiopathic sudden SNHL. If patients injected after 6 weeks are excluded from the study, the improvement rate increases from 26.9% to 39.3%. Earlier intratympanic injection had a significant impact on hearing recovery, although with any therapeutic intervention for sudden SNHL, early success may be attributed to natural history. If we further exclude seven patients treated with intratympanic steroids within 2 weeks of the onset of symptoms (i.e., study only those patients treated with intratympanic dexamethasone between 2 and 6 weeks after onset of symptoms), still, 26% improved by 20 dB or 20% SDS. The recovery rates after initial systemic failure are higher than would be expected in this treatment failure group given our control group (9.1%) and literature review. These findings indicate a positive effect from steroid perfusion in this patient population.     

Intratympanic gentamicin for unilateral Meniere's disease: results of therapy

Patients with Meniere's disease that remains refractory to conservative treatment have traditionally been subjected to ablative surgery. The purpose of this prospective study was to evaluate the use of intratympanic gentamicin in eliminating incapacitating vertigo, while preserving hearing. Over the past 8 years, 83 patients have received between 1 and 6 intratympanic injections of gentamicin in an out-patient setting, with duration of therapy titrated to individual symptom response and effect on hearing. Using established AAO-HNS guidelines, we present data on 50 patients who have a minimum of 2 years follow-up. Control or significant improvement of definitive Meniere's attacks was achieved in 92% of patients and hearing preserved or improved in 76%. Only one patient experienced profound sensorineural hearing loss. We feel this treatment option should be considered and offered to patients in whom medical treatment has failed.     

Intratympanic Methylprednisolone as Rescue Therapy in Sudden Sensorineural Hearing Loss

Treatment in sudden sensorineural hearing loss is a contentious issue, today, oral steroids are the most common choice and considered the best treatment option, but the use of intratympanic steroids has become an attractive alternative, especially in cases when systemic therapy fails, or to avoid the side effects of the systemic use of steroids.AimTo describe the results of intratympanic methylprednisolone in idiopathic sudden sensorineural hearing loss after failure of oral prednisolone.MethodsIn a prospective study fourteen patients with idiopathic sudden sensorineural hearing loss were treated with intratympanic methylprednisolone after failing in the treatment with systemic steroids. Pretreatment and post-treatment audiometric evaluations including pure tone average (PTA) and speech reception thresholds (SRT) were analyzed.ResultsTen from 14 patients treated with intra-tympanic methylprednisolone presented with hearing recovery > 20 dB in PTA or 20% in SRT.ConclusionThree intratympanic injections of methylprednisolone improved pure-tone average or speech discrimination scores for a subset of sudden hearing loss subjects that failed to benefit from oral steroids.     

梅尼埃病的个体化治疗及疗效评估

目的:探讨梅尼埃病的个性化临床治疗方法,评估梅尼埃病的非手术及手术疗效.方法:将所有梅尼埃病患者根据听力及生活质量情况进行分期;根据分期情况予以非手术治疗(改变生活方式、口服药物以及鼓室内注射地塞米松)、内淋巴囊减压或引流术、前庭神经切断术或迷路切除术.分析手术治疗梅尼埃病患者病史特点和手术情况;对于手术满1年以上的梅...     

Definition of fluctuant hearing loss.

In summary, fluctuant hearing loss is defined as a disorder of the inner ear characterized by fullness, roaring tinnitus, and fluctuations in hearing. It is believed to be caused by an inadequate absorption of endolymph from the endolymphatic sac, with or without one or more metabolic disorders, that interferes with the delicate balance between the production and absorption of endolymph and thus produces cochlear hydrops. This triad of fullness, roaring tinnitus, and fluctuant hearing loss resulting from cochlear hydrops is much more common than the quadrad of true turning vertigo, fullness, roaring tinnitus, and fluctuant hearing loss due to vestibular and cochlear hydrops known as Meniere's disease. Although patients with fluctuant hearing loss only may eventually develop vertigo as the chief complaint and then be said to have Meniere's disease, it is remarkable how many patients continue to suffer mainly from cochlear symptoms at all times. It would appear, because of the greater frequency of fluctuant hearing loss than in Meniere's disease, that the cochlear labyrinth is more susceptible to hydrops than the vestibular labyrinth. For the purposes of diagnosis and treatment it is very useful to separate patients into those with fluctuant hearing loss and those with Meniere's disease.     

经鼓室应用类固醇激素治疗内耳疾病进展

类固醇激素可以改善内淋巴积水和耳蜗循环功能、减轻内耳炎症水肿,是治疗内耳疾病比较公认且临床普遍应用的制剂。近年来经鼓室应用类固醇激素治疗内耳疾病以其给药后耳蜗淋巴液中药物浓度高、疗效可靠、副作用极少等优点,越来越受到重视。本文回顾了近十几年国内外学者关于经鼓室应用类固醇激素治疗梅尼埃病、突发性聋、耳鸣等疾病的相关文献,对鼓室内类固醇激素治疗的优势、疗效等进行综述。尽管目前最佳的药物类型、剂量、疗程、持续时间等都未确定,但经鼓室应用类固醇激素的前景十分乐观,是否可以成为全身激素治疗的一种替代疗法,仍需进一步深入的实验研究和调查。     

Use of intratympanic gentamycin for the treatment of Meniere's disease

The ablation treatment of Meniere's disease by intratympanic streptomycin applications was first reported by Schuknecht in 1957. Streptomycin and gentamycin are the most frequent aminoglycosides used for the Meniere's disease treatment. Gentamycin is responsible for the damage of vestibular dark cells causing the impairment of endolymph production. This method gives the possibility for the control of the vertigo with a potential hearing preservation. Fifteen patients with unilateral Meniere's disease who had not responded to conventional therapy, were treated by intratympanic gentamycin injections. The hearing status and the caloric test were staged before and after treatment according to the AAO-HNS guidelines. Overall results after minimum 1 year follow-up in this group were as shown below: complete vertigo control--5 patients, substantial vertigo control--8 patients, complete relief of tinnitus--10, relief of aural fullness--12 patients, hearing loss--none. According to presented results, intratympanic injections of gentamycin is the useful alternative to the surgery. This method should be consider in every patient with the unilateral Meniere's disease, who had not responded to the conventional treatment.     

Pediatric and Geriatric Tinnitus

The subject of tinnitus in the population extremes-children and the elderly-is ignored by the literature, probably because children do not complain of tinnitus spontaneously, whereas it is only one challenge among other major health problems in the elderly. A short review of the literature on this subject is presented. Presbytinnitus, defined as tinnitus that accompanies the progressive hearing loss of presbycusis is classified as: type 1 (normal aging affecting the cochlea), and type II (preexistent sensorineural hearing loss accompanied by multiple systemic complaints, especially of sensory ones). The incidence of tinnitus in presbycusis is 11%. Like in other age groups, there is no significant gender predilection in the prevalence of tinnitus, but a correlation was demonstrated between the severity of tinnitus and exposure to noise. Hypertension was associated with a lower incidence of tinnitus, as compared to normotension and hypotension. Several treatment modalities of geriatric tinnitus are reviewed: the superiority of the band-noise masker in patients with presbycusis, as compared to electrical promontory stimulation; amino-oxyacetic in presbycusis and Meniere's disease; zinc supplementation in marginally zinc-deficient elderly patients in improving sensorineural hearing loss and tinnitus; aeration of the middle ear in presbycusis caused by secretory otitis media. Pediatric tinnitus has an incidence of 13% in children who passed an audiometric screening test, and 23-60% in those with hearing loss, 44% in secretory otitis media, but only 3% complain spontaneously because that the child considers tinnitus to be a normal event. There is no significant difference between children with tinnitus and those without in terms of hearing level, age, gender, or etiology of the deafness. Despite the fact that often children do not mention it, tinnitus may incite behavioral problems.     

Treatment of Meniere's disease by intratympanic injection with lidocaine

Intratympanic injection of lidocaine hydrochloride was used to alleviate distressing symptoms of tinnitus and vertigo in 28 patients with Meniere's disease. Of the 28 patients, 82% found an immediate improvement in vertigo, and there was an improvement in tinnitus in 67.8%. There was no change in complaints of tinnitus or vertigo in five patients with Meniere's disease who were each injected with a similar amount of saline into the middle ear, and who acted as a control group. An intratympanic injection of lidocaine alleviated the disabling symptoms of tinnitus and vertigo in some of the patients with Meniere's disease who had not reacted well to medical treatment. The procedure is without the hazards of the intravenous injection of lidocaine, and can be done by every otologist, even in clinic practice.     

Systematic review of intratympanic gentamicin in Meniere's disease

OBJECTIVES: To assess and summarize the best available evidence for the use of intratympanic gentamicin in patients with Meniere's disease with respect to improvement of vertigo, tinnitus, and change in hearing. METHODS: Comprehensive electronic searches were conducted on the databases of MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. All generated titles were reviewed, and potentially relevant articles were assessed for inclusion. Data from included articles were extracted and summarized. RESULTS: Overall pooled results on vertigo control revealed complete or substantial control in 89% of patients (study range 73-100%). Hearing was worsened in 26% (0-90%). Subjective improvement in tinnitus was seen in 57% of patients (0-82%). Different treatment protocols all resulted in similar rates of vertigo control. CONCLUSIONS: Intratympanic gentamicin appears effective in controlling the symptoms of Meniere's disease, regardless of the protocol used. Although the literature on this treatment is extensive, there is a likelihood of significant bias in many currently published reports. There is a clear need for a prospective, randomized, blinded, placebo-controlled trial to assess the true effectiveness of this treatment.     

Autoimmune reactivity in Ménière's disease: a preliminary report

Autoimmune inner ear disease was first described by McCabe in 1979. The diagnosis is supported by cell mediated immune responses to inner ear membrane antigen stimulation. Meniere's disease consists of episodic vertigo, fluctuating sensorineural hearing loss, tinnitus and often aural pressure. Although most clinicians feel that Meniere's disease has no known cause, recently several researchers have suggested that some cases of Meniere's disease may be autoimmune in origin. In the present study, 10 patients with bilateral Meniere's disease were studied prospectively for autoimmune inner ear disease using both cellular and humoral immune tests. Results were compared with normal control subjects. One additional patient with Meniere's disease was identified retrospectively to have positive autoimmune test results. Preliminary conclusions suggest that at least some cases of presumed idiopathic Meniere's disease are autoimmune in origin. Therapeutic implications are significant: the addition of steroids, cytotoxic drugs and/or apheresis to conventional treatment may help prevent total deafness which otherwise might be inevitable.     

Visualization of endolymphatic hydrops in patients with Meniere's disease

OBJECTIVE: Recently, there have been many reports of intratympanic gentamicin therapy for the treatment of intractable Meniere's disease. Intratympanic administration of steroids has also been used to treat sudden sensorineural hearing loss. We attempted to visualize how the intratympanically administered drug enters the inner ear. METHODS: Gadolinium hydrate diluted eightfold with saline was injected intratympanically through the tympanic membrane using a 23 G needle in nine patients with inner ear diseases. With a 3 Tesla magnetic resonance imaging (MRI) unit, three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) imaging was performed. RESULTS: 3D-FLAIR MRI clearly revealed that the gadolinium entered the perilymphatic space and delineated the perilymphatic and endolymphatic spaces of the inner ear. In patients with endolymphatic hydrops, the perilymphatic space surrounding the endolymph was small or had disappeared. Gadolinium appeared first in the scala tympani of the basal turn of the cochlea and the perilymphatic space of the vestibule. One day after the intratympanic injection of gadolinium, the gadolinium was observed in almost all parts of the perilymph. Six days after the intratympanic injection, the gadolinium had almost disappeared from the inner ear. CONCLUSION: We reported the first visualization of endolymphatic hydrops in patients with Meniere's disease. The relationship between the image of the endolymphatic space and functional tests, such as electrocochleography and vestibular-evoked myogenic potential, must be examined in the near future. It is important for the development of intratympanic drug therapies for inner-ear diseases to investigate how the drugs enter and leave the inner ear.     

Chemical and physical labyrinthectomy for Meniere's disease

The use of intratympanic gentamicin is currently a popular and easily performed office procedure for the conservative treatment of the Meniere's disease patient who has failed medical therapy or who is not a candidate for surgical therapy. The procedure provides excellent control for the symptom of vertigo. Despite this success, there remains a significant risk of hearing loss irrespective of administered dose. In the future, antioxidant [42,43] or salicylate therapy may prevent aminoglycoside toxicity [44]. These prophylaxis methods have shown promise in the laboratory. Current methods do not allow for accurate drug delivery to the inner ear. Middle ear mucosal status, round window thickness or adhesion, patency of eustachian tube, and the effect of endolymphatic hydrops on ototoxicity are factors simply out of the control of the operator's hands. Judging by the number of recent articles, intratympanic gentamicin instillation will continue to be an area of interest for the otologist. Users should be encouraged to be consistent and conservative in gentamicin dosing. It is clear that vestibular ablation is not necessary for adequate control of vestibular symptoms and that larger doses may increase the risk of hearing loss. American Academy of Otolaryngology-Head and Neck Surgery guidelines [45] should be used and adhered to for reporting on the treatment of Meniere's disease, so that the literature may be more comparable. In the same light, a prospective standardized trial would be helpful in determining ultimate efficacy and risk to the patient. Transmastoid labyrinthectomy remains the surgical standard for extirpating the offending labyrinth when hearing preservation is not an issue. In appropriate patients, the procedure is a safe and effective method for relieving patients of vertiginous attacks. Most patients tolerate the procedure very well and are able to compensate fairly well over the course of several weeks to months.     

两种激素鼓室内灌注治疗主观性耳鸣的近期临床观察

目的:探讨鼓室内灌注醋酸泼尼松龙和地塞米松治疗主观性耳鸣的疗效。方法:选择病史在1个月以上已接受过口服药物治疗的主观性耳鸣患者73例(78耳),醋酸泼尼松龙组鼓室灌注醋酸泼尼松龙注射液,地塞米松组鼓室灌注地塞米松注射液,对照组口服卡马西平。3组均同时口服甲磺酸倍他司汀片、维生素B1片和甲钴胺片。所有患者在治疗前、治疗结束时再次行纯音测听和耳鸣匹配测试,随访6个月。结果:73例患者(78耳)均完成全部的治疗及随访。治疗结束时,醋酸泼尼松龙组、地塞米松组、对照组耳鸣治疗有效率分别为48.6%、33.3%、44.0%;6个月后3组的耳鸣控制率分别是45.7%、27.8%、36.0%。结论:鼓室内应用激素能改善主观性耳鸣,对口服药物无效的患者可以选用鼓室灌注类固醇激素。     

Intratympanic dexamethasone injections as a treatment for severe, disabling tinnitus: does it work?

OBJECTIVE: To test the effectiveness of intratympanic dexamethasone injections as a treatment for severe disabling cochlear tinnitus. DESIGN: Randomized, prospective, single-blind study. SETTING: Academic tertiary referral hospital. PATIENTS: Thirty-six patients with severe disabling tinnitus predominantly of cochlear origin were randomly assigned to receive intratympanic injections of a dexamethasone solution or isotonic sodium chloride (saline) solution. INTERVENTIONS: Under topical anesthesia and after randomization, 36 patients received 0.5-mL intratympanic injections once per week for 4 weeks of either a 4-mg/mL dexamethasone solution or saline solution. Five patients were excluded from analysis because they did not complete the treatment or did not return for follow-up. MAIN OUTCOME MEASURE: Improvement of tinnitus measured with a visual analog scale. RESULTS: The 2 groups were similar in age, sex, tinnitus laterality, measurement of tinnitus intensity on the visual analog scale, and main otologic diagnosis. We considered a 2-point improvement on the visual analog scale to be significant. Twenty-nine percent of the ears in the saline group and 33% of the ears in the dexamethasone group showed significant improvement immediately after completion of treatment. These measurements were not significantly different from each other. Follow-up varied from 13 to 31 months, and the patients with improved tinnitus returned to the initial measurements over time. CONCLUSIONS: There was no advantage in intratympanic injections of dexamethasone over saline solution in the treatment of severe, disabling tinnitus. Both solutions produced a placebolike improvement.     

Intratympanic gentamicin titration therapy for intractable Meniere's disease.

OBJECTIVE: This study aimed to assess the efficacy and morbidity of intratympanic gentamicin titration therapy on patients with intractable unilateral Meniere's disease. STUDY DESIGN: The study design was a retrospective chart review and patient interviews. SETTING: The study was conducted at a tertiary referral ambulatory dizziness clinic at the London Health Sciences Centre, University Campus, from July 1992 to June 1997. INTERVENTION: Eighty-three patients received weekly intratympanic gentamicin injections in their diseased ear. Treatments were terminated after four injections or sooner if patients met clinical or audiologic criteria. Sixty-eight patients were available for detailed follow-up. MAIN OUTCOME MEASURES: Vertigo frequency, hearing status, personal disability ratings, tinnitus level, and caloric responses before and after gentamicin therapy were measured. RESULTS: Eighty-four percent of patients showed complete, and an additional 6% showed substantial, vertigo control. At 24 months, 17% of patients demonstrated a clinically significant (10-dB) reduction in hearing, but 26% showed a significant hearing improvement. Overall, the group showed no combined statistically significant changes in any of the hearing parameters. No patients had an "extreme" drop in hearing (>30 dB). CONCLUSIONS: Intratympanic gentamicin titration therapy provides excellent vertigo control with a low incidence of hearing loss.     

Low-dose intratympanic gentamicin treatment of Meniere's disease

To control attacks of vertigo while preserving both hearing and labyrinthine function, low doses of gentamicin were instilled intratympanically in nine patients with intractable unilateral Meniere's disease. Each patient received six instillations of antibiotic of 4 mg each (total dose, 24 mg). Patients were then followed for 2–4 years. Long-term results of treatment are reported according to the American Academy of Otolaryngology-Head and Neck Surgery 1985 criteria. Of the nine cases, three experienced complete control of vertiginous attacks, while six received substantial control. Post-treatment hearing acuity was unaffected, although disability following treatment became worse in one patient, a 66-year-old man. Caloric responses after therapy were absent or severely reduced in three ears, moderately reduced in two ears and unchanged in four ears. In three patients, labyrinthine function was found damaged 4–8 days after administration of the last dose of drug. Overall, intratympanic instillations of low doses of gentamicin in patients with intractable Meniere's disease were found to control vertiginous attacks with less damage to the inner ear function than that reported in the literature.