**2. Methods**

**1. Introduction**

176 Up to Date on Meniere's Disease

disabling tinnitus—SDT).

1 year [2]. They did not use a control group.

effective for the treatment of chronic SDT.

Tinnitus is a complex disorder and is presented as a hearing sensation, which is not associated with an external sound stimulus [1]. It probably arises initially in the cochlea and later reaches higher structures of the auditory system where it becomes sometimes very annoying (severe

One study showed 10 patients with "predominantly cochlear tinnitus" treated using intratympanic dexamethasone injections and described 5 patients with tinnitus control for at least

The effectiveness of intratympanic dexamethasone injections as a treatment for SDT was studied [3]. A control group was treated with saline solution and a study group with dexamethasone solution, both using intratympanic injections. There was no statistic significant difference between saline and dexamethasone solution regarding tinnitus improvement measured with visual analog scale (VAS). They concluded that intratympanic injections of steroids are not

For acute tinnitus, interventions such as intratympanic AM‐101 (a cochlear N‐methyl‐D‐aspartate receptor antagonist) were tested. However, there is insufficient evidence to support the safety and efficacy of this intervention [4]. A second phase study was carried out, randomized, and placebo controlled using AM‐101 intratympanic injections and concluded that the duration of symptoms affected the cure rate of intratympanic therapy for acute subjective tinnitus [5].

The management of subjective tinnitus associated with idiopathic sudden sensorineural hearing loss (ISSHL) includes oral, intravenous, and/or intratympanic administration of corticosteroids as initial therapy [6]. Intratympanic corticosteroids were effective for the treatment of idiopathic sudden sensorineural hearing loss (ISSHL) in controlled trials when used as primary therapy [7] or as rescue therapy after failure of initial oral steroids therapy [6].

The sudden sensorineural hearing loss (SSHL) is a hearing loss of at least 30 dB at three consecutive frequencies occurring in the period of 3 days or less [8] may occur in frequencies and

SSHL is often accompanied by tinnitus and there are few theories trying to explain its mechanism. One of them associates this symptom to a maladaptive attempt at cortical reorganiza-

Many of these patients with tinnitus and SHL remain with residual buzz even if the treatment for SHL has been effective. The treatment of sudden sensorineural hearing loss is based on its etiology. In idiopathic sudden sensorineural hearing loss (ISSHL), the oral corticosteroids are widely used, although the supporting evidence is weak. Injection intratympanic dexamethasone has been tried in patients with idiopathic sudden sensorineural hearing loss because it provides a high concentration of steroids in the labyrinth in animal models [8]. In addition, there are several advantages to intratympanic treatment. The procedure is well tolerated, relatively easy to perform as outpatient. Most patients understand the concept of intratympanic

intensities varying from a mild hearing loss to a total loss of hearing [9, 10].

tion process due to peripheral deafferentation [7].

treatment and easily accept this therapy [3].

The study protocol and procedures were approved by the Research Ethics Committee (REC) University of Brasilia (Opinion number 132/2012). All patients received information about the risks and expectations of therapy and signed a free informed consent form (FICF) accepting their participation in the study.

This is an analytical, prospective and longitudinal study, and the data were analyzed between January (2014) and June (2015).

Patients with middle ear diseases; presence of air type tympanogram, Ad, Ar, B, or C; prior ear surgery; signs of acute or chronic otitis media; history of Meniere's syndrome or fluctuating hearing; and history of prior sensorineural hearing loss were excluded (**Figure 1**).

From the initial sample of 38 patients with acute tinnitus and idiopathic sudden hearing loss, 23 were enrolled, 13 in the oral steroid therapy group (Group 1/oral therapy) and 10 in the intratympanic corticosteroids group after failure of oral therapy (Group 2/rescue therapy).

Tinnitus handicap inventory (THI) [11] and visual analog scale (VAS) were used for evaluation of tinnitus annoyance. For audiological assessment, tonal and vocal audiometry were used. (Diagnostic audiometer Madson Itera II) and for distortion products otoacoustic emission (DPOAE) measurements OtoRead Portable Interacoustic device was used.

A detailed clinical history was taken, followed by an otoneurological examination and audiological assessment by tonal and vocal audiometry. DPOAE measurements and application of THI [11] and VAS were carried out before onset of therapy and 3 months later [6].

All patients underwent pure‐tone audiometry (PTA) and speech audiometry carried out by the same audiologist before and after treatment. The mean was calculated based on pure‐tone average at 500, 1000, 2000, and 4000 Hz [12].

For DPOAEs, primary tones f1 and f2 were presented at 55 and 65 dBSPL (sound pressure levels). The f2/f1 ratio was kept at approximately 1.2. The levels of the DPOAE at 2fi–f2 were recorded in four different frequencies (ranging between 2000 and 5000 Hz), DP‐gram showed DP1 level (dB) and DP1 signal‐to‐noise ratio (dB).

All patients were treated with systemic oral therapy according to the local protocol (1 mg/kg/ day prednisolone for 10 days, followed by decreasing doses thereafter). Next, rescue therapy with intratympanic methylprednisolone was offered after systemic therapy failed and no improvements were demonstrated audiometrically in 10 patients (Group 2).

**Figure 1.** Schematic diagram.

Initially, EMLA cream was applied (AstraZeneca, Wilmington DE) for topical anesthesia in the external auditory canal and the tympanic membrane and left for 30–45 minutes. Then, the patient's head was placed at 45° in the direction of the affected ear. A solution of 40 mg of methylprednisolone/ml was warmed to body temperature. About 0.3–0.5 ml of the solution was injected into the middle ear; two holes were made with the application of needle (Gelco N.22), one just below the umbo (where the drug was administered) and another in the upper posterior region (vent). After intratympanic application of the steroid, the patient remained in the injection position with head turned 45° for 30 minutes to maximize exposure of the round window membrane to the solution and were applied three injections every 48 hours.

The criteria for defining successful recovery after therapy vary in the literature on intratympanic therapy. The hearing recovery was analyzed in three categories: (A) complete recovery when there was improvement ≥ 30 dBHL (hearing loss) in the affected frequencies; (B) partial recovery, when there was improvement ≥ 10 dBHL and ≤ 30 dBHL in the affected frequencies; (C) no recovery when there is an improvement of ≤ 9 dBHL [13]. Failure of oral prednisolone therapy was absence of improvement, as just described, after 14 days of treatment [14].

All patients answered the THI [11] and the VAS to assess quantitatively and qualitatively the therapeutic response in relation to tinnitus. In the VAS, score ranges from 1 to 10, where 10 represents the highest degree of tinnitus severity. Scores measured the intensity and discomfort of tinnitus. Two points in the VAS were considered significant change [3]. The THI questionnaire was considered improved when there was change of category of tinnitus severity in the following scale: Grade 1 negligible (0–16), Grade 2 light (18–36), Grade 3 moderate (38–56), Grade 4 severe (58–76), and Grade 5 catastrophic (78–100) [11].

The average posttreatment for some measures were compared between types of treatment (oral therapy and intratympanic corticosteroids after failure of oral therapy) using an analysis of covariance model (ANCOVA). In the ANCOVA model, the measurement obtained after treatment was considered the dependent variable, the type of treatment as the independent variable and the measures at baseline as the covariate. Mean comparisons were made with the intragroup test employing Student *t‐*test for paired samples. Note that *p* < 0.05 was considered significant. The analysis was performed using SAS v 9.4 (SAS Institute, Inc., 2012).
