Abstract
Objectives
The aim of this study was to assess whether gadolinium-based contrast agent influences short-term hearing function in patients with Ménière’s disease undergoing intratympanically enhanced inner-ear magnetic resonance imaging.
Design
This is a prospective cohort study.
Setting
This study was conducted a tertiary referral university hospital, ENT department.
Participants
In this study, 21 adult patients with definite, unilateral Ménière’s disease were included. According to the criteria of the Committee on Hearing and Equilibrium, all patients were in stage 1 or 2 of the disease, with largely preserved hearing function.
Outcomes
All patients underwent clinical and audiologic testing before and 24 hours after intratympanic application of gadolinium-based contrast agent. The effects of the contrast medium on the hearing function were assessed by analysis of frequency thresholds, pure-tone average from 500 Hz to 3 kHz, and speech audiometry.
Results
Pure-tone average and single-frequency thresholds in audiometry showed no statistically significant difference after the application of intratympanic gadolinium-based contrast agent. Furthermore, speech audiometry scores remained stable after the application of the contrast agent.
Conclusions
This study did not demonstrate clinically significant short-term effects of intratympanic application of gadolinium-based contrast agent on hearing function in patients with Ménière’s disease in initial stages.
1
Introduction
For 150 years, the diagnosis of Ménière’s disease was based on a combination of the symptoms vertigo, hearing loss, aural fullness, and/or tinnitus. Certain diagnosis was only possible by histopathologic investigation of postmortem temporal bone specimens. The first description of the successful use of magnetic resonance imaging to visualize the endolymphatic hydrops in living patients with Ménière’s disease was achieved in 2007 by Nakashima and colleagues . The clear visualization of the endolymphatic hydrops was rendered possible by applying gadolinium-based contrast agent (GBCA) intratympanically instead of intravenously. Their study showed that intratympanically administered GBCA entered the perilymphatic space in a higher concentration than after intravenous application and, therefore, delineated the endolymphatic hydrops in the inner ear as a hypointense area bulging toward the contrasted perilymphatic space. From 9 patients, 7 had good distribution of GBCA in the inner ear 1 day after the application. They did not describe any adverse effects from this new route of application.
Gadolinium-based contrast agent is a widely used and safe intravenous contrast medium for magnetic resonance imaging. Gadolinium is a metal and, alone, can form gadolinium ions (Gd 3+ ), which are in this form highly toxic. Therefore, the only possible use of gadolinium-based media is in form of chelates, as for example, gadodiamide or Gd-diethylenetriaminepentaacetic acid. In this form, only a very small proportion of gadolinium exists as free Gd 3+ . The use of GBCA as an intravenous contrast medium is very safe and causes fewer adverse reactions than, for example, iodine-based contrast mediums. Some of the frequent adverse reactions (<3%) described by the pharmaceutical industry are nausea, dizziness, and headache . A very rare but serious risk related to the intravenous use of GBCAs is the development of nephrogenic systemic fibrosis in patients with chronic or acute renal failure. In these cases or in patients with renal dysfunction, the use of GBCA should be avoided .
The intratympanic route of application of drugs uses the transport capacity through the round window into the perilymph system. Like other drugs, GBCA can also move into the perilymph system, remaining in the inner ear for some time . Only a few studies with animal models have, until now, analyzed the effects of GBCA on the inner ear . Nevertheless, the use of intratympanic GBCA to visualize the endolymphatic hydrops typical of Ménière’s disease is increasing in the last few years. As described by Pyykö et al , until now, more than 100 inner-ear magnetic resonance scans have been performed, and in almost all patients with probable or definite Ménière’s disease, endolymphatic hydrops could be detected. Another publication from Colletti et al compares different application forms of GBCA into the inner ear, including the intratympanic route and direct injection into the endolymphatic sac. They demonstrated good magnetic resonance visualization of the endolymphatic space by the direct endolymph space injection and exclusive enhancement of the perilymphatic space by the intratympanic application. Furthermore, they did not find any adverse effects in any of the participants. Besides the visualization of the endolymphatic space by using intratympanic GBCA in magnetic resonance, Gürkov et al also showed a positive correlation between the degree of the endolymphatic hydrops and the loss of audiovestibular function in Ménière’s disease.
The objective of this study is to analyze the possible short-term adverse effects of intratympanic GBCA on the auditory function in patients with Ménière’s disease with serviceable hearing undergoing intratympanically enhanced inner-ear magnetic resonance imaging.
2
Materials and methods
This prospective clinical study was conducted at the ENT department of a tertiary referral university hospital. The study protocol was approved by the local institutional ethics committee. All patients gave their written informed consent to participate in the study.
2.1
Patient collective
Inclusion criteria were a definite diagnosis of unilateral Ménière’s disease in the stages 1 and 2 according to the guidelines of the Committee on Hearing and Equilibrium . Therefore, the study population consisted of patients with largely preserved hearing function. Furthermore, patients with frequently fluctuating hearing loss were not included, for reasons of better comparability. Patients underwent clinical and neuro-otologic evaluation before inclusion in the study. Exclusion criteria were previous otologic surgery or ablative therapy (eg, gentamicin), presence of a ventilation tube, subjective fluctuation of hearing loss during the last 3 days, and any form of middle ear disease. Twenty-one adult patients, between November 2009 and December 2010, with unilateral definite Ménière’s disease were included. Seven patients were male, and 14 were female; patients’ age was 28 to 76 years (48.2 ± 13.4 years). The affected side distribution was almost equal, with a right/left ratio of 12:9. The duration of the symptoms was from 1 to 540 months (77.0 ± 126.6 months). About 60% of the patients were in stage 1 of the disease based on the 4-tone average classification for the hearing thresholds at 500 Hz and at 1, 2, and 3 kHz. Basic clinical details are presented in Table 1 .
| Sex, n (%) | Side, n (%) | Age (y) | Disease duration (mo) | Disease stage, n (%) |
|---|---|---|---|---|
| Male, 7 (33) | Right, 12 (57%) | Mean, 48.2 | Mean, 77.0 | Stage 1, 12 (57) |
| Female, 14 (67) | Left, 9 (42) | Range, 28–76 | Range, 1–540 | Stage 2, 9 (43) |
| SD, 13.4 | SD, 126.6 |
2.2
Study design
One day before the magnetic resonance scan, that is, immediately before the contrast medium application, all patients underwent a clinical and audiologic evaluation. After the contrast medium application, the patients stayed in the hospital overnight under observation. A second audiologic evaluation was done 20 to 24 hours after the application, that is, shortly before the magnetic resonance examination.
2.3
Intratympanic GBCA injection
Gadolinium-based contrast agent was used in gadodiamide form (Omniscan; Daiich Pharmaceutical Co Ltd, Tokyo, Japan), diluted 8-fold in saline solution. The patient was lying in a supine position with the head turned 45° to the healthy side, so that under microscopic control, 0.4 mL of the solution was injected through the tympanic membrane with a 27-gauge needle, using one puncture in the anterosuperior quadrant for the air to escape and another puncture in the anteroinferior quadrant for injection of the GBCA. After the injection, the patient remained 30 minutes with the head in the same position and was instructed not to speak or chew during this period.
2.4
Audiologic evaluation
Before and after intratympanic GBCA application, all patients underwent audiologic testing with pure-tone audiometry and speech audiometry. The postinjection tests were performed between 20 and 24 hours after injection. Before the postinjection audiometry, the tympanic membranes were checked for regular healing by otomicroscopy. Tympanometry was performed to ensure a normal middle ear function.
Measurements for pure-tone audiometry were performed at frequencies from 250 Hz to 6 kHz. The contralateral ear was masked by adequate noise. All audiometric equipment has been checked every 6 months according to the standard national specification. The audiologic tests were performed by experienced audiometrists in a double-walled sound-proof room. Pure-tone average (PTA) was then calculated for each patient regarding the specifications of the Committee on Hearing and Equilibrium as a 4-tone average from 500 Hz to 3 kHz.
Speech audiometry was performed using the Freiburger monosyllabic word test. The words were presented via earphones at 60, 80, and 100 dB hearing level (HL), and the percentage of words correctly repeated by the patient was calculated. The healthy ear was masked by adequate noise during the whole test.
2.5
Documentation and statistics
All patient data were stored and analyzed on the SPSS spreadsheets (PASW Statistics 18, version 18.0.0; SPSS, Chicago, IL). Descriptive statistics, t test for paired samples, and Pearson correlations were used. A P value of.05 or less was chosen as the level of significance.
2
Materials and methods
This prospective clinical study was conducted at the ENT department of a tertiary referral university hospital. The study protocol was approved by the local institutional ethics committee. All patients gave their written informed consent to participate in the study.
2.1
Patient collective
Inclusion criteria were a definite diagnosis of unilateral Ménière’s disease in the stages 1 and 2 according to the guidelines of the Committee on Hearing and Equilibrium . Therefore, the study population consisted of patients with largely preserved hearing function. Furthermore, patients with frequently fluctuating hearing loss were not included, for reasons of better comparability. Patients underwent clinical and neuro-otologic evaluation before inclusion in the study. Exclusion criteria were previous otologic surgery or ablative therapy (eg, gentamicin), presence of a ventilation tube, subjective fluctuation of hearing loss during the last 3 days, and any form of middle ear disease. Twenty-one adult patients, between November 2009 and December 2010, with unilateral definite Ménière’s disease were included. Seven patients were male, and 14 were female; patients’ age was 28 to 76 years (48.2 ± 13.4 years). The affected side distribution was almost equal, with a right/left ratio of 12:9. The duration of the symptoms was from 1 to 540 months (77.0 ± 126.6 months). About 60% of the patients were in stage 1 of the disease based on the 4-tone average classification for the hearing thresholds at 500 Hz and at 1, 2, and 3 kHz. Basic clinical details are presented in Table 1 .
| Sex, n (%) | Side, n (%) | Age (y) | Disease duration (mo) | Disease stage, n (%) |
|---|---|---|---|---|
| Male, 7 (33) | Right, 12 (57%) | Mean, 48.2 | Mean, 77.0 | Stage 1, 12 (57) |
| Female, 14 (67) | Left, 9 (42) | Range, 28–76 | Range, 1–540 | Stage 2, 9 (43) |
| SD, 13.4 | SD, 126.6 |
2.2
Study design
One day before the magnetic resonance scan, that is, immediately before the contrast medium application, all patients underwent a clinical and audiologic evaluation. After the contrast medium application, the patients stayed in the hospital overnight under observation. A second audiologic evaluation was done 20 to 24 hours after the application, that is, shortly before the magnetic resonance examination.
2.3
Intratympanic GBCA injection
Gadolinium-based contrast agent was used in gadodiamide form (Omniscan; Daiich Pharmaceutical Co Ltd, Tokyo, Japan), diluted 8-fold in saline solution. The patient was lying in a supine position with the head turned 45° to the healthy side, so that under microscopic control, 0.4 mL of the solution was injected through the tympanic membrane with a 27-gauge needle, using one puncture in the anterosuperior quadrant for the air to escape and another puncture in the anteroinferior quadrant for injection of the GBCA. After the injection, the patient remained 30 minutes with the head in the same position and was instructed not to speak or chew during this period.
2.4
Audiologic evaluation
Before and after intratympanic GBCA application, all patients underwent audiologic testing with pure-tone audiometry and speech audiometry. The postinjection tests were performed between 20 and 24 hours after injection. Before the postinjection audiometry, the tympanic membranes were checked for regular healing by otomicroscopy. Tympanometry was performed to ensure a normal middle ear function.
Measurements for pure-tone audiometry were performed at frequencies from 250 Hz to 6 kHz. The contralateral ear was masked by adequate noise. All audiometric equipment has been checked every 6 months according to the standard national specification. The audiologic tests were performed by experienced audiometrists in a double-walled sound-proof room. Pure-tone average (PTA) was then calculated for each patient regarding the specifications of the Committee on Hearing and Equilibrium as a 4-tone average from 500 Hz to 3 kHz.
Speech audiometry was performed using the Freiburger monosyllabic word test. The words were presented via earphones at 60, 80, and 100 dB hearing level (HL), and the percentage of words correctly repeated by the patient was calculated. The healthy ear was masked by adequate noise during the whole test.
2.5
Documentation and statistics
All patient data were stored and analyzed on the SPSS spreadsheets (PASW Statistics 18, version 18.0.0; SPSS, Chicago, IL). Descriptive statistics, t test for paired samples, and Pearson correlations were used. A P value of.05 or less was chosen as the level of significance.
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