Original Research—Otology and Neurotology
Otolaryngology–
The Effect of Intratympanic
Methylprednisolone and Gentamicin
Injection on Ménière’s Disease
Nathalie Gabra1, and Issam Saliba, MD, FRCS1
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objectives. To compare the efficacy of intratympanic injec-
tions of methylprednisolone (ITMP) and intratympanic
injections of gentamicin (ITG) to control the symptoms of
Ménière’s disease and to evaluate their effect on hearing
level.
Study Design. A historical cohort study.
Setting. Tertiary referral center.
Subjects and Methods. Eighty-nine patients affected by
Ménière’s disease were included in this study, of whom 47
were treated with ITG and 42 were treated with ITMP. Two
periods of follow-up were considered: 0 to 6 months and 6
to 12 months after the intratympanic injections (ITI). Mean
outcome measurements consisted of control of vertigo
attacks, tinnitus, and aural fullness; pure-tone average (PTA);
and speech discrimination score (SDS).
Results. The 2 groups had the same number of vertigo
spells per month before ITI (P = .883). Six to 12 months
after ITI, 82.9% of the ITG group and 48.1% of the ITMP
group achieved complete control of vertigo (P = .004).
There was better control of tinnitus and aural fullness with
ITG than with ITMP (P  .002). The 2 groups had a statisti-
cally significant difference in hearing level before ITI (P 
.001). This difference was no longer present 6 to 12
months after ITI (P . .05).
Conclusion. Intratympanic injections of gentamicin are more
efficient than ITMP in controlling the symptoms of Ménière’s
disease. The 2 groups ended up without a difference in hear-
ing level after ITI. According to these findings, administrating
ITMP to control Ménière’s disease seems to be less benefi-
cial than ITG.
Keywords
methylprednisolone, gentamicin, Ménière, intratympanic
injection, vertigo, hearing loss, ear fullness
Received September 20, 2012; revised September 21, 2012; accepted
July 7, 2012.
Head and Neck Surgery
148(4) 642–647
Ó American Academy of
Otolaryngology—Head and Neck
Surgery Foundation 2013
Reprints and permission:
sagepub.com/journalsPermissions.nav
DOI: 10.1177/0194599812472882
http://otojournal.org
M
énière’s disease is an idiopathic condition charac-
terized by the presence of fluctuating hearing loss,
episodic vertigo, unilateral tinnitus, and aural full-
ness related to an endolymphatic hydrops. Although symp-
toms manifestation was well described by Prosper Ménière in
1864, the underlying cause of this endolymphatic hydrops
remains unknown. Thus, its therapy is symptomatic and
empirical, mainly against the vertigo attacks, which can be
very disabling.
Medical treatment consisting of salt restriction, vasodila-
tors, diuretics, and symptomatic therapy for the nausea and
diaphoresis associated with spells of vertigo allows control-
ling the disease in as many as two-thirds of the patients.1
When medical therapy fails to reduce the recurrent spells of
vertigo, other treatment options should be considered. In 1927,
Guild2 described in his study of guinea pigs the endolymphatic
sac as the site of ‘‘outflow of the endolymph,’’ which was a
major discovery in the mechanics of the endolymphatic flow
in the middle ear. Later the same year, Portmann3 described
his first endolymphatic surgery for Ménière’s disease. One year
later, Dandy4 proceeded with the first vestibular neurectomy.
These procedures preserve hearing and are used for patients
with functional hearing level. For those with nonserviceable
hearing, labyrinthectomy is most commonly performed. These
procedures are efficient to treat vertigo but have a high risk of
postoperative complications.5
In 1948, Fowler6 introduced the concept of ‘‘chemical
labyrinthectomy’’ by using intramuscular injections of strep-
tomycin, a vestibulotoxic bactericidal antibiotic, to control
vertigo. In fact, aminoglycosides have shown to be more
vestibulotoxic than cochleotoxic.7,8 In addition, some stud-
ies have suggested that at low dose, aminoglycosides cause
ototoxic damage to the dark cells that produce endolymph and
therefore would reduce endolymphatic volume.9 To avoid the
systemic complications associated with these intramuscular
1
Division of Otolaryngology–Head and Neck Surgery, Montreal University
Hospital Center, University of Montreal, Montreal, Quebec, Canada
Corresponding Author:
Issam Saliba, MD, FRCS, Division of Otolaryngology–Head and Neck
Surgery, Montreal University Hospital Center, University of Montreal, 1560,
rue Sherbrooke East, Montreal-Qc, H2L 4M1, Canada
Email: issam.saliba@umontreal.ca
Gabra and Saliba
injections, Schuknecht7 introduced the concept of intratympa-
nic injections in 1957.
Furthermore, some investigations demonstrated immunolo-
gical abnormalities in Ménière’s disease: elevated levels of
IgG circulating immune complexes,10-12 autoimmune
responses to type II collagen,13,14 focal inflammation with
intraepithelial invasion of mononuclear cells (endolymphatic
sacitis),15 and IgG and autoantibody deposits in the endolym-
phatic sac.16 Therefore, the beneficial effects of intratympanic
steroids could be due to their anti-inflammatory and immuno-
suppressive effects. They also have an effect on ionic hemosta-
sis regulation through modifications in the potassium transport,
which reduces the damage to the intracochlear barrier involved
in Ménière’s disease.17 Finally, the protective role of the aqua-
porines contributes to the water balance in the inner ear.18 In
addition, it has been shown that steroids applied to the round
window have higher drug concentration in the inner ear fluids
than systemic injections, which also have many undesirable
side effects.19
In our institution, intratympanic injections of methylpred-
nisolone (ITMP) are used in patients with Ménière’s disease
who have intractable vertigo and functional hearing, whereas
intratympanic injections of gentamicin (ITG) are used to
ablate vestibular function in patients with an intractable ver-
tigo and nonserviceable hearing because of its potential
ototoxicity.
The purpose of this study is to compare the efficacy of
ITMP with ITG to control vertigo attacks, tinnitus, and aural
fullness, as well as evaluate the ability of ITMP to preserve
functional hearing in patients with Ménière’s disease.
Methods
This is a historical cohort study including patients seen in
our tertiary care center and diagnosed with Ménière’s dis-
ease according to criteria of the American Academy of
Otolaryngology—Head and Neck Surgery (AAO-HNS).20
Patients who had undergone medical therapy and caf-
feine, alcohol, theine, and salt (CATS) restriction for at
least 6 months without further benefit and who had more
than 1 vertigo attack per month before intratympanic injec-
tions (ITI) were included in the study. In CATS restriction
therapy, both caffeine and theine have the same effect on
Ménière’s disease, but caffeine refers to coffee and theine
refers to tea restrictions. Both have to be mentioned to the
patient. The study was approved by our institutional research
ethics board and follows the standards of our institutional
ethics committee.
Eighty-nine patients met our study’s inclusion criteria,
among whom 47 with nonserviceable hearing had received
ITG and 42 with functional hearing had received ITMP.
Functional hearing is defined as class A or B in the AAO-
HNS criteria.21 Patients received 1 intratympanic injection of
gentamicin (26.7 mg/mL) or methylprednisolone (62.5 mg/mL)
per week for 3 weeks.
Data gathering was based on consultations and follow-up
per period: 0 to 6 months before and then 0 to 6 months and
6 to 12 months after ITI.
643
Vertigo was evaluated by the number of attacks the
patient reported per period. We assessed the number of
attacks per month in the last 6 months before ITI and the
total number of attacks that occurred 0 to 6 months and 6 to
12 months after ITI. Aural fullness and tinnitus were evalu-
ated by their presence or absence at each control visit.
Hearing impairment was assessed according to the pure-
tone average (PTA) at 0.5-, 1-, 2-, and 4-kHz frequencies and
speech discrimination score (SDS). A change of 10 dB or
more in the PTA or a change of 15% in SDS was considered
clinically significant. In patients with bilateral Ménière’s dis-
ease, only data concerning the first affected ear were consid-
ered in the study.
Statistical Analysis
Statistical study was performed using SPSS (version 20)
software (SPSS, Inc, an IBM Company, Chicago, Illinois).
The comparisons of the 2 groups were studied using the
Student t test and x2 test. For the ‘‘number of spells,’’ PTA,
and SDS, we used a Student t test to compare the changes
from baseline at 6 months and from 6 months at 12 months.
The error bars represent the standard deviation of the mean.
P \ .05 is considered statistically significant.
Results
Patients’ characteristics are given in Table 1; the 2 groups of
patients were homogeneous in number and age (P . .05).
They were also comparable in terms of sex repartition (P =
.156). The results were regrouped according to symptoms.
Vertigo, Tinnitus, Aural Fullness, and Hearing loss
Vertigo Control. The mean 6 SD number of spells per
month before ITI was 5.5 6 7.10 (n = 47) in the ITG group
and 5.3 6 6.41 (n = 42) in the ITMP group with no signifi-
cant difference between the 2 groups (P = .883). In 0 to 6
months after the ITI, the number of spells decreased to 0.5 6
1.19 (n = 42) in the ITG group and 2.3 6 3.20 (n = 41) in
the ITMP group. Finally, 6 to 12 months after ITI, there were
0.4 6 1.38 (n = 35) spells in the ITG group and 1.4 6 1.87
(n = 27) in the ITMP group. There was a statistically signifi-
cant difference between the ITG and ITMP groups in 0 to
6 months and 6 to 12 months after ITI (P = .001 and P =
.025, respectively) (Figure 1).
In the first period after treatment, 78.6% of the ITG
group achieved complete control of vertigo compared with
41.5% of the ITMP group, with a statistically significant
difference (P = .001). In the second period after treatment,
82.9% of the ITG group and 48.1% of the ITMP group
achieved complete control of vertigo with a statistically sig-
nificant difference (P = .004). These results are represented
in Table 2.
Moreover, within the ITG group, there was a statistically
significant decrease in the number of spells between the
pre-ITI period and the 0- to 6-month period after ITI (P \
.0001). There was no statistically significant difference
between the 0- to 6-month and 6- to 12-month periods after
644 Otolaryngology–Head and Neck Surgery 148(4)

Table 1. Patients Characteristics in the Intratympanic Injections of Gentamicin (ITG) and Intratympanic Injections of Methylprednisolone
(ITMP) Groups
Group ITG ITMP P Value

Number 47 42 .711
Sex, No. (%) Male 19 (40 %) 11 (26 %) .156
Female 28 (60 %) 31 (74 %)
Age, y 54.3 53 .824

10 Table 2. Evolution of Vertigo Spells after Treatment in the

Number of spells in each period

9
Intratympanic Injections of Gentamicin (ITG) and Intratympanic
8
7 Injections of Methylprednisolone (ITMP) Groups
6
5
Vertigo Spells ITG ITMP P Value
4 * P = 0.001 * P = 0.025
3 No. of patients 42 41
2
1
0-6 months after ITI, %
0 None 78.6 41.5 .001
Period
Per month in the last 6 0 - 6 months 6 - 12 months At least 1 21.4 58.5
months before ITI aer ITI aer ITI
No. of patients 35 27
Intratympanic injecons of Gentamicin
Intratympanic injecons of Methylprednisolone
6-12 months after ITI, %
None 82.9 48.1 .004
Figure 1. Mean number of vertigo attacks before and after intra-
At least 1 17.1 51.9
tympanic injections (ITI). We considered the number of spells per
month in the last 6 months before ITI and the total number of Abbreviation: ITI, intratympanic injections.
spells 0 to 6 months and 6 to 12 months after ITI. *Statistically sig-
nificant difference; error bars represent the standard deviation.
Table 3. Tinnitus Control in the Intratympanic Injections of
Gentamicin (ITG) and Intratympanic Injections of
ITI (P = .907). The same phenomenon was observed with Methylprednisolone (ITMP) Groups
the ITMP group: there was a statistically significant
Presence of Tinnitus ITG, No. (%) ITMP, No. (%) P Value
decrease in the number of vertigo spells in the first period
(P = .025) and no difference between the 0- to 6-month and Before ITI 47 (100) 42 (100) —
6- to 12-month periods after ITI (P = .95) (Figure 1). 0-6 months after ITI 43 (30.2) 41 (78) \.001
6-12 months after ITI 33 (27.3) 25 (68) .002
Tinnitus Control. In total, 30.2% of the ITG group and 78%
of the ITMP group had refractory tinnitus 0 to 6 months after Abbreviation: ITI, intratympanic injections; —, not applicable.
ITI (P  .001), whereas in the 6- to 12-month period, these
values were 27.3% and 68%, respectively (P = .002). Results
are represented in Table 3.
difference in the evolution of the 2 groups from before to
Aural Fullness. In the ITG group, 93.6% of patients had after treatment (P = .456 for the 0- to 6-month period and
aural fullness before ITI and 16.3% still had it after ITI. In P = .06 for the 6- to 12-month period). However, the statis-
the ITPM group, 95.2% had aural fullness before ITI and tically significant difference in PTA between the 2 groups
65% after ITI. Although there was no statistically significant before ITI (P  .001) was no longer present 6 to 12
difference before ITI (P = .634), there was a statistically sig- months after ITI (P = .668) (Figure 2).
nificant difference between the 2 groups (P  .001) after ITI.
Speech Discrimination Score. In the first 0 to 6 months,
Pure-Tone Average. Before ITI, the mean PTA was 59.27 there was a decrease in the SDS followed by an increase in
6 17.41 dB and 41.89 6 14.92 dB for the ITG and ITMP the next 6 to 12 months in the ITG group. As for the ITMP
groups, respectively. There was a slight increase in PTA at 6 group, the SDS decreased in the first period and remained
months in the 2 groups. This was followed by a decrease in stable in the second period. There was no statistically signif-
PTA in the ITG group and an increase in PTA in the ITMP icant difference in the evolution of SDS between the 2
group so that 12 months after ITI, the mean PTA was 52.63 groups after ITI. However, the 2 groups had a different SDS
6 14.18 dB and 49.51 6 17.9 dB for the ITG and ITMP before ITI (P  .001) but ended up without a difference in
groups, respectively. There was no statistically significant SDS 6 to 12 months after ITI (P = .181) (Figure 3).
Gabra and Saliba 645

PTA (dB)
ITMP treatments, ITG shows a higher efficiency to control
0
Ménière’s disease symptoms when compared with ITMP. In
10
p<0.001 p<0.001 p=0.668 addition, both ITI treatments reveal a stability of vertigo
20
control 0 to 6 months and 6 to 12 months after ITI.
30
However, at 1-year follow-up, 82.9% of patients in the ITG
40 ITG
group had complete control of vertigo with a statistically
50
ITMP significant difference when compared with the ITMP group,
60 in which only 48.1% achieved complete control.
70 Moreover, ITG was associated with better aural fullness
80 and tinnitus control than ITMP, with a statistically signifi-
90
Period cant difference.
0 - 6 months 0 - 6 months 6 - 12 months
before ITI aer ITI aer ITI
Regarding the hearing outcome, there was no statistically
significant difference between the 2 groups in terms of PTA
Figure 2. Evolution of the pure-tone average (PTA) in the intra-
evolution. The changes in the 2 groups over 1 year were
tympanic injections of gentamicin (ITG) group and the intratympa-
nic injections of methylprednisolone (ITMP) group. ITI, less than 10 dB, which is not considered clinically signifi-
intratympanic injections; error bars represent the standard cant. We could see a tendency toward deterioration in the
deviation. ITMP group and a tendency toward improvement in the
ITG group after 1 year of follow-up.
Concerning SDS, there was less than 15% change in the
2 groups, which cannot be considered clinically significant.
100
However, we could see once again a tendency toward dete-
90
rioration in the ITMP group and a tendency toward an
80
improvement in the ITG group.
70
60
Even though the 2 groups had a significantly different
50 ITG
hearing level before ITI, they ended up with no difference
40 in hearing level 12 months after ITI. It is known that genta-
ITMP
30 micin affects the dark cells of the ear that produce the endo-
p<0.001 p<0.001 p=0.181
20 lymph. With ITG, the endolymph secretion diminishes, and
10 therefore the hydrops decreases, and this can explain the
0 hearing improvement with ITG.
Period
Furthermore, 5 patients in the ITMP group had recurrent
disabling episodes of Ménière’s disease after the treatment
Figure 3. Evolution of the speech discrimination score (SDS) in
and had to receive a series of more methylprednisolone
the intratympanic injections of gentamicin (ITG) group and the
intratympanic injections of methylprednisolone (ITMP) group. ITI,
injections when hearing was still functional (2/5 patients) or
intratympanic injections; error bars represent the standard gentamicin injections (3/5 patients) when hearing was no
deviation. longer functional to achieve complete vertigo control.
Only 2 prospective randomized controlled studies with 2
years of follow-up have compared the effect of ITG with
intratympanic steroids (dexamethasone, ITD) in Ménière’s
Discussion disease.22,23 Casani and Piaggi22 reported a complete vertigo
control rate of 81% and 43% in the ITG and ITD groups,
The underlying cause of Ménière’s disease has not been respectively. Sennaroglu et al23 reported satisfactory control
identified; therefore, this disease has no cure, and treatment of vertigo in 75% and 72% of the ITG and ITD groups,
is symptomatic mainly against vertigo attacks. At our insti- respectively. Parnes et al24 studied the pharmacokinetics of
tution, the algorithm is based on hearing level: patients fail- 3 intratympanic injections of corticosteroids: hydrocorti-
ing to respond to medical therapy and CATS restriction for sone, methylprednisolone, and dexamethasone (short-acting,
at least 6 months and presenting at least 1 vertigo attack per intermediate-acting, and long-acting steroids, respectively).
month are treated with ITI. Those who have nonserviceable They found that the highest inner ear concentrations were
hearing receive ITG, and those with functional hearing reached with the intratympanic methylprednisolone injec-
receive ITMP. tions: they reached their highest concentration 2 hours after
However, since our aim is to eradicate vertigo attacks the injections, remained at high levels for 6 hours, and
while minimizing side effects and since ITG is associated declined over 24 hours. Whereas for dexamethasone, the
with a potential ototoxicity, we found it important to evalu- highest concentration was reached after 2 hours but was
ate the efficiency of ITMP to control Ménière’s disease null after 6 hours.
symptoms while preserving hearing. Regarding hearing outcomes, these 2 studies did not use
Even though our study demonstrates a decrease in the ITG for patients with severe hearing loss only; therefore,
number of vertigo spells 0 to 6 months after the ITG and the comparison with our study is not appropriate for this
646
group. However, in the ITD group, Casani et al22 reported
that 46% of the patients had an unchanged hearing level and
43.3% of the patients showed a worsening of their hearing,
and Sennaroglu et al23 reported that 46% of the patients had
an unchanged hearing level and 16% showed a worsening
hearing level. Another study conducted by Selivanova et
al25 reported a 71% decreased hearing level with ITD.
The remaining articles evaluate the efficiency of each
treatment separately, with a wide range of results concern-
ing vertigo control with ITD: Itoh and Sakata,26 78%;
Hirvonen et al,27 76%; Barrs et al,28 60%; Barrs,29 47%;
and Dodson et al,30 54%. These results show the lower effi-
ciency of ITD to achieve complete vertigo control. As for
ITG, 2 recent meta-analyses31,32 have reported complete or
substantial vertigo control in almost 90% of patients.
The meta-analysis done by Chia et al31 compared 5 dif-
ferent delivery methods of gentamicin. The high-dose or
multiple-dose technique (3 doses of gentamicin per day for
4 days) was associated with the highest rate of hearing loss
(34.7%) with a vertigo control rate comparable to the other
methods. The low-dose technique (1 or 2 doses on consecu-
tive days or weeks repeated only if symptoms occurred) was
associated with a hearing loss rate comparable to other
methods (23%) but with the lowest rate of vertigo control
(66.7%). The weekly method of administration (a single
dose once a week for 4 weeks), which is similar to our
method of administration, demonstrated the lowest rate of
hearing loss (13.1%) and a complete vertigo control in 75%
of the patients. Finally, the titration method (termination of
treatment with onset of symptoms of inner ear disturbance
regardless of the administration frequency) was associated
with the best vertigo control rate (81.7%) and a hearing loss
rate comparable to other methods (24%).
Moreover, as shown in animal studies, the elimination
half-time of gentamicin is considerably shorter in the blood
(hours) than in the inner ear tissue (30 days). Therefore,
administration of gentamicin doses over a prolonged time
frame increases its accumulation in the inner ear tissue and
therefore its toxicity.33,34
In addition, several studies showed a correlation between
genetic mutations and aminoglycoside ototoxicity.35,36 The
most common mutation associated with deafness related to
aminoglycosides is the A 1555 G mutation in mitochondrial
12S rRNA, which has been detected in patients with differ-
ent ethnic backgrounds: ranging from 0.6% of spontaneous
hearing loss in the United States37 to 20% of spontaneous
hearing loss in Spain38 and up to 33% of aminoglycoside-
related hearing loss in Japan.39
Therefore, titration administration method, which takes
into account the interindividual variability in drug response,
appears to be a good approach to maximize the vertigo con-
trol rate while minimizing cochlear side effects. However,
monitoring patients is not always easy and practical.
Our study has several limitations. First, because of its his-
torical character, it is more difficult to analyze qualitative
data such as disability score and quality-of-life assessment. In
addition, only a 12-month follow-up was considered since
Otolaryngology–Head and Neck Surgery 148(4)
many patients did not present at their appointments later on,
which narrows our observations. For the ‘‘number of spells,’’
PTA, and SDS, the evolution of the groups was not studied
using analysis of variance for repeated measures with 2 factors
(time and group) because the loss of follow-up was too impor-
tant. We had 89 subjects at baseline, 42 subjects at 6 months,
and 35 subjects at 12 months for the ITG group and 41 sub-
jects at 6 months and 27 subjects at 12 months for the ITMP
group. Therefore, we used a Student t test to compare the
changes from baseline at 6 months and from 6 months at
12 months. This approach is more powerful, but the possi-
bility of type I error is bigger. The results are sufficiently
clear that even if we had used a Bonferroni correction, we
would have had the same conclusion.
Although ITG and ITI of steroids were largely evaluated
separately, this is the first study in the literature to compare
methylprednisolone as an intratympanic steroid injection with
ITG in the treatment of Ménière’s disease. Since all treat-
ments used in Ménière’s disease are empirical, this approach
is clinically relevant so as to establish an algorithm adapted
to each case.
Conclusion
Our study demonstrated that ITG achieves a better control
of the symptoms related to Ménière’s disease (vertigo, aural
fullness, and tinnitus) than does ITMP. Patients treated with
ITMP and patients treated with ITG ended up without a dif-
ference in hearing level 12 months later. According to these
findings, administrating ITMP to control Ménière’s disease
seems to be less beneficial than administering ITG.
Author Contributions
Nathalie Gabra, substantial contributions to conception and
design, acquisition, analysis and interpretation of data, drafting the
article, final approval of the version to be published; Issam Saliba,
substantial contributions to conception and design, acquisition,
analysis and interpretation of data, drafting the article, final
approval of the version to be published.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None.
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