1

Introduction

Intratympanic gentamicin has become an important treatment modality in the management of unilateral Ménière disease (MD) over the past decade . However, there are controversies on the drug concentration, application methods, and dosing protocols of the treatment . Vertigo attacks associated with MD can be controlled by using local gentamicin injections to achieve a chemical labyrinthectomy. Low-dose gentamicin destroys the vestibular but not auditory hair cells .

Caloric tests assessing the function of the lateral canal at low frequencies is generally used in clinical studies about chemical labyrinthectomy . The effect on otolith function has rarely been studied by vestibular-evoked myogenic potentials (VEMPs) . Bickford et al were the first to record these electromyographic (EMG) potentials. Colebatch et al reinvestigated the effects of loud clicks. They defined a biphasic, initially positive response (p13n23) recorded from averaged EMG, which occurred at short latency and ipsilateral to the ear stimulated. The short-onset latency of the VEMP indicates the likelihood of a response mediated by an oligosynaptic pathway including the saccule, inferior vestibular nerve, vestibular nucleus, and medial vestibulospinal tractus to the accessory nucleus . The caloric test, on the other hand, examines the function of the lateral semicircular canal and the superior vestibular nerve.

The aims of the study were to assess the efficacy and safety of single and low-dose intratympanic gentamicin therapy in MD patients who were monitored both with caloric tests and VEMPs and to investigate whether VEMPs have an additional role in predicting the efficacy of the drug or not.

2

Methods

The study was conducted in Ege University Medical School, Departments of Otolaryngology and Neurology. Twenty-five patients (10 males, 15 females) with unilateral MD diagnosed according to the criteria of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology and Head-Neck Surgery Foundation (AAO-HNS) were included as the study group . All patients were evaluated by a special referral council that comprises specialists from otolaryngology, neurology, and physical medicine departments. Average vertigo episode, defined as the exact sensation of illusion of rotation, was at least 2 per month for all patients in whom vertigo attacks could not be controlled despite systemic medical treatment. Forty healthy subjects (14 male, 26 females) who had no conductive or sensorineural hearing loss and no known history of a cochleovestibular disorder constituted the control group. A signed informed consent was taken from all patients and controls, and the study protocol was approved by Ege University Ethics Committee.

All patients underwent systemic and neuro-otologic examinations at each visit. Tonal audiometry, caloric tests, and VEMPs were evaluated before the initial application of gentamicin therapy and 2 weeks later. Patients with any otoscopic abnormalities, including previous history of otitis media and conducting type hearing loss, were excluded from the study.

Low-dose (16 mg/mL) gentamicin buffered with HCO ₃ was injected intratympanically to all patients by a 22-gauge fine needle. The application was performed through posteroinferior quadrant of tympanic membrane, and the total amount of given medication was 1 mL. The patients were asked to lie in supine position with the effected ear up for 30 minutes and were encouraged not to swallow.

Effectiveness of the protocol was assessed at the end of the 6-month follow-up period. Patients were questioned about ongoing vertigo episodes and general dizziness status. The latter was evaluated with visual analog scales (VAS) measured in millimeters from 0 to 100; higher results indicating a better outcome.

Caloric tests were performed by means of Nystar software (Nicolet Instrument Inc, Madison, WI). Caloric irrigations were performed by using 200-mL tap water at a temperature of 44°C (warm) and 30°C (cold). Ice-water caloric test (2–4°C, 10 mL) was used in patients without a caloric response to warm and cold water to confirm caloric areflexia. VEMPs were recorded by using a Synergy device (Medelec; Oxford Instruments Medical Inc, UK). To record the surface EMG activity, an active electrode was placed on the upper half of the sternocleidomastoid muscle ipsilateral to the stimulation, with the reference electrode placed on the upper third of sternum and the ground electrode on the middle of the forehead. Patients were seated on an armchair and were asked to turn their head contralaterally to the ear being tested to achieve maximal activation of the sternocleidomastoid. Two stimulation consequences consisting of 100 sound stimuli were given. The acoustic stimuli were clicks at an intensity of 100 dBnHL of 0.1-millisecond duration, delivered at a frequency of 5 Hz through a headphone unilaterally to each ear. The EMG signal was bandpass filtered from 10 to 1000 Hz and averaged during a 100-millisecond interval. The initial positive/negative polarity of the waveform with peaks was termed p13 and n23 on the basis of respective latencies. The latencies of peaks p13 and n23 and peak-to-peak amplitude of p13–n23 were measured.

Canal paresis in caloric test was defined as a side difference of more than %25 for the maximal slow-phase velocity (SPVmax) of nystagmus between the 2 ears. Side-to-side differences of VEMP amplitude were expressed as percent VEMP asymmetry . The upper limit of percent VEMP asymmetry was set based on the data of 40 healthy subjects as mean ± 2 SD. Posttreatment VEMPs decreasing beyond this limit were regarded as deteriorated VEMPs.

Patients were divided into 3 groups according to their posttreatment VEMPs and caloric responses separately. These groups comprised normal, deteriorated and absent VEMPs, and caloric responses. General dizziness status, assessed by VAS, was evaluated and compared according to these groups. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS v17.0; SPSS, Chicago, IL) software.

2

Methods

The study was conducted in Ege University Medical School, Departments of Otolaryngology and Neurology. Twenty-five patients (10 males, 15 females) with unilateral MD diagnosed according to the criteria of the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology and Head-Neck Surgery Foundation (AAO-HNS) were included as the study group . All patients were evaluated by a special referral council that comprises specialists from otolaryngology, neurology, and physical medicine departments. Average vertigo episode, defined as the exact sensation of illusion of rotation, was at least 2 per month for all patients in whom vertigo attacks could not be controlled despite systemic medical treatment. Forty healthy subjects (14 male, 26 females) who had no conductive or sensorineural hearing loss and no known history of a cochleovestibular disorder constituted the control group. A signed informed consent was taken from all patients and controls, and the study protocol was approved by Ege University Ethics Committee.

All patients underwent systemic and neuro-otologic examinations at each visit. Tonal audiometry, caloric tests, and VEMPs were evaluated before the initial application of gentamicin therapy and 2 weeks later. Patients with any otoscopic abnormalities, including previous history of otitis media and conducting type hearing loss, were excluded from the study.

Low-dose (16 mg/mL) gentamicin buffered with HCO ₃ was injected intratympanically to all patients by a 22-gauge fine needle. The application was performed through posteroinferior quadrant of tympanic membrane, and the total amount of given medication was 1 mL. The patients were asked to lie in supine position with the effected ear up for 30 minutes and were encouraged not to swallow.

Effectiveness of the protocol was assessed at the end of the 6-month follow-up period. Patients were questioned about ongoing vertigo episodes and general dizziness status. The latter was evaluated with visual analog scales (VAS) measured in millimeters from 0 to 100; higher results indicating a better outcome.

Caloric tests were performed by means of Nystar software (Nicolet Instrument Inc, Madison, WI). Caloric irrigations were performed by using 200-mL tap water at a temperature of 44°C (warm) and 30°C (cold). Ice-water caloric test (2–4°C, 10 mL) was used in patients without a caloric response to warm and cold water to confirm caloric areflexia. VEMPs were recorded by using a Synergy device (Medelec; Oxford Instruments Medical Inc, UK). To record the surface EMG activity, an active electrode was placed on the upper half of the sternocleidomastoid muscle ipsilateral to the stimulation, with the reference electrode placed on the upper third of sternum and the ground electrode on the middle of the forehead. Patients were seated on an armchair and were asked to turn their head contralaterally to the ear being tested to achieve maximal activation of the sternocleidomastoid. Two stimulation consequences consisting of 100 sound stimuli were given. The acoustic stimuli were clicks at an intensity of 100 dBnHL of 0.1-millisecond duration, delivered at a frequency of 5 Hz through a headphone unilaterally to each ear. The EMG signal was bandpass filtered from 10 to 1000 Hz and averaged during a 100-millisecond interval. The initial positive/negative polarity of the waveform with peaks was termed p13 and n23 on the basis of respective latencies. The latencies of peaks p13 and n23 and peak-to-peak amplitude of p13–n23 were measured.

Canal paresis in caloric test was defined as a side difference of more than %25 for the maximal slow-phase velocity (SPVmax) of nystagmus between the 2 ears. Side-to-side differences of VEMP amplitude were expressed as percent VEMP asymmetry . The upper limit of percent VEMP asymmetry was set based on the data of 40 healthy subjects as mean ± 2 SD. Posttreatment VEMPs decreasing beyond this limit were regarded as deteriorated VEMPs.

Patients were divided into 3 groups according to their posttreatment VEMPs and caloric responses separately. These groups comprised normal, deteriorated and absent VEMPs, and caloric responses. General dizziness status, assessed by VAS, was evaluated and compared according to these groups. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS v17.0; SPSS, Chicago, IL) software.