Treatment of Meniere’s disease with Intratympanic Dexamethazone plus High
Dosage of Betahistine

Silviu Albu MD, Alina Nagy, Caius Doros, Luigi Marceanu, Sebastian
Cozma, Gabriela Musat, Franco Trabalzini

PII: S0196-0709(15)00247-1
DOI: doi: 10.1016/j.amjoto.2015.12.007
Reference: YAJOT 1664

To appear in: American Journal of Otolaryngology–Head and Neck Medicine and Surgery

Received date: 14 September 2015

Please cite this article as: Albu Silviu, Nagy Alina, Doros Caius, Marceanu Luigi,
Cozma Sebastian, Musat Gabriela, Trabalzini Franco, Treatment of Meniere’s dis-
ease with Intratympanic Dexamethazone plus High Dosage of Betahistine, Amer-
ican Journal of Otolaryngology–Head and Neck Medicine and Surgery (2015), doi:
10.1016/j.amjoto.2015.12.007

This is a PDF file of an unedited manuscript that has been accepted for publication.
As a service to our customers we are providing this early version of the manuscript.
The manuscript will undergo copyediting, typesetting, and review of the resulting proof
before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that
apply to the journal pertain.
 ACCEPTED MANUSCRIPT

Treatment of Meniere’s disease with Intratympanic Dexamethazone plus

High Dosage of Betahistine.

P T
RI
1, 2
Silviu Albu , Alina Nagy 2, Caius Doros 3, Luigi Marceanu 4, Sebastian Cozma 5, Gabriela

SC
Musat 6 and Franco Trabalzini 7

NU
MA
1
II-nd Department of Otolaryngology, Iuliu Hatieganu University of Medicine and Pharmacy
ED

Cluj-Napoca, Cluj-Napoca, Romania.

2
RoNeuro Institute for Neurological Research and Diagnostic, Cluj-Napoca, Romania.
PT

3
Department of Otolaryngology, Victor Babes University of Medicine and Pharmacy Timisoara,
CE

Timisoara, Romania.
AC

4
Transilvania University Brasov, Brasov, Romania.

5
Department of Otolaryngology, Grigore T. Popa University of Medicine and Pharmacy Iasi,

Iasi, Romania.

6
Department of Otolaryngology, Sf. Maria Hospital Bucuresti, Romania

7
Otology and Skull Base Surgery Unit, Siena University Hospital, Siena, Italy.

1
 ACCEPTED MANUSCRIPT

Corresponding author:

Silviu Albu, MD, Professor, II-nd Department of Otolaryngology

T
Iuliu Hatieganu University of Medicine and Pharmacy Cluj-Napoca,

P
Str. Republicii nr. 18

RI
SC
400015 Cluj-Napoca, Romania,

Fax: 0040 264 598278, E-mail: silviualbu63@gmail.com

NU
MA
ED
PT

Sponsorship: no funding was received for this study

Conflict of interest: nothing to declare

CE
AC

2
 ACCEPTED MANUSCRIPT

Abstract.

Purpose. The aim of the present study was to assess if the combined therapy of intratympanic

dexamethasone (ITD) and high dosage of betahistine (HDBH) is able to provide increased

T
vertigo control compared to ITD alone in patients suffering from definite unilateral Meniere’s

P
RI
disease (MD).

Materials and Methods. Consecutive MD patients were enrolled and randomly divided in two

SC
groups, each comprising 33 cases. Group A received a combination of ITD and identical-

NU
appearing placebo pills while Group B received a combination of ITD and HDBH. ITD protocol

consisted of three consecutive daily injections. HDBH comprised 144mg/day (48 mg tid). The
MA
main outcome measures were: 1) vertigo class, pure tone average (PTA), speech discrimination

score (SDS) and Functional Level Score (FLS) according to the American Academy of
ED

Otolaryngology-Head and Neck Surgery criteria; 2) complete and substantial vertigo control
PT

according to the Kaplan-Meier survival method.

Results. Sixty two patients completed the 24 months follow-up. A complete vertigo control was
CE

achieved in 14 patients (44%) from Group A and in 22 patients (73.3%) from Group B,
AC

statistically significant (p=0.01). Complete vertigo relief is also significant according to the

Kaplan-Meier method: p=0.027, log rank test. Substantial vertigo control was obtained in 21

patients (65.6%) in Group A and 27 patients (90%) in Group B. The difference is statistically

significant, p=0.02. The difference is significant according to the Kaplan Meier method:

p=0.035, log rank test. No significant differences between hearing levels and tinnitus scores were

demonstrated between the groups.

Conclusions. Our preliminary results demonstrate that complete and substantial vertigo control

is significantly higher in patients treated with a combination of HDBH and ITD.

3
 ACCEPTED MANUSCRIPT

Key words: Meniere disease, intratympanic dexamethasone, high-dosage of betahistine,

complete vertigo control, substantial vertigo control, survival methods.

P T
RI
SC
NU
MA
ED
PT
CE
AC

4
 ACCEPTED MANUSCRIPT

Introduction. Meniere’s disease (MD) is pathophysiologically regarded as an endolymphatic

hydrops of unknown etiology 1. It is estimated that 50.000 to 100.000 new cases occur each year

in the United States 2. Clinical diagnosis is established on a history of spontaneous vertigo spells,

T
2, 3
fluctuating sensorineural hearing loss, tinnitus, and aural fullness . Most often, vertigo is

P
RI
incapacitating, and thus, management is primarily intended to decrease the incidence and

severity of vertigo. The management protocol typically comprises dietary recommendations such

SC
as a low sodium diet and restriction of caffeine, nicotine, medications and, as a last remedy,

NU
surgical approaches 4. Medical treatment includes diuretics, betahistine, intratympanic (IT)
1, 3
injection of gentamicin or corticosteroids . Quite a lot of papers on betahistine for MD have
MA
been issued presenting conflicting results 5, 6, 7. However, an open trial proved that higher-dosage

of betahistine (144mg/day) is capable to significantly decrease incapacitating vertigo spells in

ED

MD 8. Recently, IT corticoids injections become widespread in clinical practice mainly because

PT

9-15
minimal side effects were reported in relationship to their use . IT corticosteroids achieve

greater inner ear concentrations than those acquired through systemic administration 16. Although
CE

IT gentamicin affords superior vertigo control compared with IT corticoids, it carries a greater
AC

risk of hearing loss and imbalance 17. This is why in clinical practice it appears that IT corticoid

injections are extensively prescribed 15. Some studies have presented encouraging results, while

others reported unsatisfactory outcomes associated with IT corticoids 9-17.

The aim of the present study was to assess if the combined therapy of IT dexamethasone (ITD)

and high dosage of betahistine (HDBH) is able to provide increased vertigo control rates

compared to ITD alone.

5
 ACCEPTED MANUSCRIPT

Materials and Methods. A multicenter, prospective study assessing the effectiveness of the

combined HDBH and ITD in decreasing vertigo spells in MD was performed between January

2009 and June 2013. Five departments with extensive experience in vestibular pathology were

T
involved, including the Departments of Otolaryngology from the Universities of Cluj-Napoca,

P
RI
Timisoara, Iasi, Bucuresti (all clinics from Romania), as well as the Otology and Skull Base

Surgery Unit in Siena, Italy. All studies were approved by the respective Institutional Review

SC
Boards in accordance with the Guidelines for Protection of Human Subjects. All patients signed

NU
an informed consent form before entering the study. Inclusion criteria were adult patients with

unilateral definite MD according to the guidelines of the American Academy of Otolaryngology–

MA
Head and Neck Surgery (AAO-HNS) 18. According to prior recommendations 3, 18, were included

patients with episodes of spontaneous vertigo lasting between 20 minutes and 12 hours. Further,
ED

as previously suggested 8 included patients had to suffer a mean of four or more vertigo spells per
PT

month during the 3 months foregoing management. All these patients failed a trial of 6 months of

low-salt diet, dietary restrictions such as caffeine and nicotine avoidance. According to previous
CE

8, 19
studies , exclusion criteria were: bilateral MD, other peripheral or central vestibular
AC

syndromes, middle ear pathology, noise-induced hearing loss, previous IT gentamicin or

corticosteroid or preceding ablative ear surgery and allergy to betahistine.

Patients underwent a complete neuro-otologic examination. Acoustic neuroma was ruled-out

using MRI. Auditory testing comprised pure tone audiometry (PTA) with 4 frequency average

(0.5, 1, 2, and 3 kHz) and speech discrimination score (SDS). The Functional Level Score (FLS),
18
Class and vertigo control (class A-F) were defined according to the AAO-HNS criteria .A

change of 10 dB or more in PTA or a change of 15% in SDS were considered clinically

20
significant. The Tinnitus Handicap Inventory (THI) was completed in each patient . THI is a

6
 ACCEPTED MANUSCRIPT

25-item questionnaire designed to assess the severity of tinnitus. Each item was completed with

―yes‖ scoring 4, ―sometimes‖ scoring 2, and ―no‖ scoring 0. The lower the total score, the less

was the tinnitus handicap. All of these parameters were obtained before the treatment and at the

T
end of the follow-up.

P
RI
Patients with definite MD were offered different therapeutic alternatives: IT injection of

corticoid or IT injection of gentamicin and vestibular neurectomy. Patients elected ITD injection

SC
with or without HDBH as an opportunity that might provide transitory cessation of vertigo spells

NU
without the destruction of vestibular system. If complete or substantial vertigo control was not

accomplished, another sequence of ITD was offered. In patients with persistent vertigo, despite
MA
repeated ITD injections, IT gentamicin injection or ablative surgery was offered.

Enrolled patients were randomly divided in two distinct groups (Group A and B), each
ED

comprising 33 patients. For random assignment of patients, a computer-generated list of random

PT

numbers was employed. Randomization was performed by an only investigator (LM) one day

before the injection. Both the surgeons and the patients were blinded to the treatment. Group A
CE

received a combination of ITD and identical-appearing placebo pills while Group B received a
AC

combination of ITD and HDBH. Dexamethasone was injected under the microscope according to
9-15
the guidelines : in the supine position, the patient turned the head 45° toward the unaffected

ear. Local anesthesia of the tympanic membrane was achieved and dexamethasone (4mg/mL)

was injected through a 22-gauge spinal needle and 1-mL syringe to fill the middle ear. Patients

were instructed to keep the supine position with the treated ear facing upward for 30 minutes

avoiding swallowing or talking. The ITD protocol consisted of three consecutive daily injections.

HDBH consisted in 144mg/day (48 mg tid).

7
 ACCEPTED MANUSCRIPT

Audiometric testing and completion of questionnaires were performed by researchers blinded to

the surgeons. Throughout the study, all patients kept a diary recording monthly the occurrence of

every vertiginous attack. At the follow-up visit, investigators reviewed these diaries. Patients

T
were monitored at 2-month intervals throughout the study. Every patient was monitored for at

P
RI
least 2 years. Both in Romania and Italy betahistine is the most prescribed drug in MD patients.

Nevertheless, betahisitne is a costly medication in both countries, therefore the tablets were

SC
supplied free of charge by the University hospitals involved in the study. Compliance to

NU
treatment was tested through regular weekly telephone calls. Moreover, at each intervening visit,

patients from both groups had to return the empty medication packages. Treatment side-effects
MA
were also recorded.

Sample size was computed with the software available from DSS Research Tools (http://
ED

www.dssresearch.com/toolkit.). Samples were planned to detect differences of 15% in the

PT

probability of primary endpoint (the probability of success for Group A was expected to be 50%,

whereas for Group B it was presumed to be 75%) with a Type I error of 5% and a statistic power
CE

of 80%. For each group, 30 subjects were required. In order to compensate for potential drop-
AC

outs, the number was raised to 33 patients.

Statistical analysis was performed using SPSS ver. 20.0 (SPSS Inc, Chicago, IL). The Student t-

test was used to detect significant differences between groups while differences between

categorical variables were evaluated using the chi square test. Data were expressed as mean ±

standard deviation (SD). A p value of less than 0.05 was considered significant. Differences

between groups regarding complete and substantial vertigo control were also analyzed according

to the Kaplan-Meier survival method. We used censored observation – if failure did not occur

during follow-up, the case was censored. In class A (complete vertigo control) plot, survival was

8
 ACCEPTED MANUSCRIPT

defined as the absence of vertigo spells and failure as recurrent vertigo. In class A + B

(substantial vertigo control) plot, survival was defined as substantial vertigo control and failure

when vertigo recurred with an incidence greater than 40% of the pre-treatment frequency. The

T
log-rank test was employed to compare survival between groups.

P
RI
SC
NU
MA
ED
PT
CE
AC

9
 ACCEPTED MANUSCRIPT

Results. Sixty six patients with unilateral definite MD were included in the present investigation.

The baseline features of two distinct groups are presented in Table 1. No statistically significant

differences were observed between the demographic and functional characteristics. Patients with

T
possible and probable MD were excluded, since our patients presented with MD stage over 2

P
RI
and/or FLS over 3. The mean number of vertigo attacks per month did not differ between the two

groups at baseline: in group A patients suffered a mean of 7.5 vertigo spells per month compared

SC
to 6.7 vertigo attacks per month in group B. The difference is not statistically significant.

NU
Sixty two patients completed the 24 months follow-up, while 3 patients (1 in Group A and 3 in
MA
Group B) were lost to follow-up. In Group A five patients (15%) received 1 ITD re-injection and

6 patients (18%) received 2 re-injections. In Group B four patients (12%) got 1 re-treatment
ED

comprising ITD injections and 3 patients got 2 re-treatments comprising ITD injections.

Vertigo control in the two groups is displayed in Table 2. Regarding vertigo class distribution
PT

among the two groups, the difference is not significant, p=0.11 chi square test. However,
CE

complete vertigo control was attained in 14 patients (44%) in Group A and in 22 patients
AC

(73.3%) in Group B. The difference is statistically significant, p=0.01 chi square test. The

difference between the groups in attaining complete vertigo relief is further demonstrated

employing the Kaplan-Meier plot specific to class A: according to log rank test (p=0.027) the

difference is statistically significant (see Figure 1). Substantial vertigo control (class A + B) was

obtained in 21 patients (65.6%) in Group A and 27 patients (90%) in Group B. The difference is

statistically significant, p=0.02 chi square test. The Kaplan Meier plot specific to class A + B

validates the significant difference: p=0.035 log rank test (see Figure 2). In Group A, despite 1 or

2 re-treatments, 10 patients reported limited control (class C and D) and one patient had no

control of vertigo (class E). In Group B, 2 patients had limited control (class C and D), while

10
 ACCEPTED MANUSCRIPT

failure was reported in 1 case (class E). Failures in both treatment groups were programmed for

IT gentamicin. At 24 months follow-up, level one of FLS was reached in 15 patients and level 2

in 8 cases in Group A, while in Group B 22 patients achieved level one and 7 patients level 2.

T
The difference is significant, p=0.04 chi square test.

P
RI
Hearing outcomes are listed in Table 3. According to our results at the end of the study there

SC
were no statistically significant variations within and between the groups. According to the 1995

AAO-HNS guidelines, in Group A hearing was unchanged in 15 patients, improved in 3 patients

NU
and worsened in 14 patients. Following the same guidelines, in Group B hearing was unchanged
MA
in 16 patients, improved in 2 patients and declined in 12 patients. No difference between the

groups in tinnitus awareness was noted during the follow-up.

ED

Side-effects associated with HDBH were not significant. HDBH caused nausea in 2 patients,

headache in 5 cases, diarrhea in 8 cases. Nevertheless, these adverse effects did not cause
PT

disruption of therapy.
CE
AC

11
 ACCEPTED MANUSCRIPT

Discussion.

According to animal experiments, betahistine is a H1 receptor agonist and a H3 receptor

21
antagonist and thus modulates synaptic transmission . Furthermore, betahistine increases in a

P T
22, 23
concentration-dependent mode the blood flow in the cochlea and in the brain . It was

RI
additional demonstrated a dose-dependent inhibitory action on spike generation within the

SC
neurons located in the medial and lateral vestibular nuclei 24. It is also suggested that betahistine

enhances significantly behavioral recovery and vestibular compensation in MD 7, 8, 25.

NU
The most recent meta-analysis of 12 randomized, double-blind, placebo-controlled clinical
MA
studies, clearly demonstrated a favorable outcome in MD patients treated with betahistine 7.

Additionally, Strupp et al 8 established that in MD, HDBH is more powerful than low dosage in
ED

decreasing the number of vertigo spells.

Advantageous effects of IT corticoids in MD are related to their immunosuppressive effects,

PT

adjustments in water and potassium transportation, modification in the expression of

CE

15-17
mineralocorticoid receptor-mediated genes and regulation of the aquaporines . According to

previous clinical recommendations 15-17, we have employed ITD in our trial. Generally speaking,
AC

12, 14, 17
the efficacy of ITD in controlling vertigo in MD patients is disappointingly low . Better

outcomes with ITD might be related to higher dosage (16 mg/mL) than the dosage commonly
17
used (4 mg/mL) or to the use of round window constant delivery systems . Despite these

results, patients select to continue with repeated IT injections as an alternative to ablative

procedures. The choice for ITD might be also related to the enhanced risk of hearing loss and
15
imbalance associated with IT gentamicin . It was assumed that ITD affords only temporary

symptomatic relief and thus needs to be repetitive until the occurrence of spontaneous

12
 ACCEPTED MANUSCRIPT

remission15, 17. Other factors supporting ITD are the patient’s awareness as an easy treatment,

placebo effect and preference on the part of the physician 15.

In an attempt to improve vertigo control related to ITD, we used HDBH in combination with

T
ITD. Since ITD is a repetitive treatment, it was previously suggested that Kaplan-Meier method

P
15

RI
provided a perfect exemplification of the clinical course of ITD . This is why we reported our

results according to both the AAO-HNS criteria 18 and Kaplan-Meier survival method. We were

SC
able to demonstrate that complete vertigo control is significantly higher in patients treated with

NU
18
HDBH and ITD. The difference is significant according to both AAO-HNS criteria and

Kaplan-Meier survival plot. Additionally, the number of patients attaining substantial vertigo
MA
control (class A + B) is statistically higher with the combined treatment. The two medications

used have different mechanisms in vertigo control and the effect of ITD is immediate while
ED

26
HDBH needs longer time to achieve decrease in vertigo spells . However, there are current
PT

treatment protocols demonstrating improved hearing and vertigo control when higher doses of IT
27
steroids are used. Recent literature suggests the dose should be 24 mg/ml . This is not
CE

commercially available in the United States and in Europe and must be compounded. As
AC

previously stated, we were using a low concentration steroid dosing (4mg/ml) and that may

account for the difference in treatment outcomes. We can conclude that in the lack of high doses

of ITD, using the treatment protocol concentration, betahistine added to improved outcomes.

As previously reported, there were no significantly effects on hearing levels and tinnitus scores

with this combination 6, 9-17.

As earlier stated, we lost only 3 patients to follow-up. This represents a very good retention rate,

since most studies have a much higher drop-out rate 9-17. Inasmuch as betahistine is an expensive

drug especially in Romania, the University hospitals involved in the study supplied the patients

13
 ACCEPTED MANUSCRIPT

free of charge with the medication. This is why our patients were adherent to the study, despite

the long two-year follow-up.

Despite these preliminary favorable results, a larger sample should support our initial results.

P T
RI
SC
NU
MA
ED
PT
CE
AC

14
 ACCEPTED MANUSCRIPT

References.

1. Sajjadi H, Paparella MM. Meniere’s disease. Lancet 2008; 372: 406-14.

2. Minor LB, Schessel DA, Carey JP. Meniere’s disease. Curr Opin Neurol 2004;/17:/9-16.

P T
3. Merchant SN, Adams JC, and Nadol JB Jr. Pathophysiology of Meniere ’s syndrome: are

RI
symptoms caused by endolymphatic hydrops? Otol Neurotol 2005;/26:/74-81.

SC
4. Coelho DH, Lalwani AK. Medical management of Meniere’s disease. Laryngoscope.

2008; 118:1099-1108.

NU
5. Jeck-Thole S, Wagner W (2006) Betahistine: a retrospective synopsis of safety data.
MA
Drug Saf 29(11):1049–1059.

6. James A, Burton MJ. Betahistine for Meniere’s disease or syndrome. Cochrane Database
ED

Syst Rev 2001;(1):CD001873.

7. Nauta JJP. Meta-analysis of clinical studies with betahistine in Ménière's disease and
PT

vestibular vertigo. Eur Arch Otorhinolaryngol. 2014 May; 271(5):887-97.

CE

8. Strupp M, Hupert D, Frenzel C, Wagner J, Hahn A, Jahn K et al. Long-term prophylactic

treatment of attacks of vertigo in Meniere’s disease—comparison of a high with a low

AC

dosage of betahistine in an open trial. Acta Otolaryngol. 2008; 128(5):520–524.

9. Itoh A, Sakata E. Treatment of vestibular disorders. Acta Otolaryngol Suppl.

1991;481:617-623.

10. Shea JJ Jr., Ge X. Dexamethasone perfusion of the labyrinth plus intravenous

dexamethasone for Me´nie`re’s disease. Otolaryngol Clin North Am. 1996; 29:353-358.

11. Garduno-Anaya MA, Couthino DT, Hinojosa-Gonzalez R, Pane-Pianese C, Rios-

Castaneda LC. Dexamethasone inner ear perfusion by intratympanic injection in

15
 ACCEPTED MANUSCRIPT

unilateral Meniere’s disease: a two-year prospective, placebo-controlled, double blind,

randomized trial. Otolaryngol Head Neck Surg. 2005; 133:285-294.

12. Silverstein H, Isaacson JE, Olds MJ, Rowan PT, Rosenberg S. Dexamethasone inner ear

T
perfusion for the treatment of Meniere’s disease: a prospective, randomized, double-

P
RI
blind, crossover trial. Am J Otol. 1998; 19:196-201.

13. Barrs DM, Keyser JS, Stallworth C, McElveen JT Jr. Intratympanic steroid injections for

SC
intractable Meniere’s disease. Laryngoscope. 2001; 111:2100-2104.

NU
14. Barrs DM. Intratympanic injections of dexamethasone for long-term control of vertigo.

Laryngoscope. 2004; 114:1910-1914.

MA
15. Boleas-Aguirre MS, Della Lin FR, Santina CC, Minor LB, Carey JP. Longitudinal results

with intratympanic dexamethasone in the treatment of Meniere’s disease. Otol Neurotol.

ED

2008;29:33-38.
PT

16. Parnes LS, Sun AH, Freeman DJ. Corticosteroid pharmacokinetics in the inner ear fluids:

an animal study followed by clinical application. Laryngoscope. 1999;109:1-17.

CE

17. Casani AP, Piaggi P, Cerchiai N, et al. Intratympanic treatment of intractable unilateral
AC

Meniere disease: gentamicin or dexamethasone? A randomized controlled trial.

Otolaryngol Head Neck Surg. 2012; 146 (3): 430-7.

18. Committee on Hearing and Equilibrium guidelines for the diagnosis and evaluation of

therapy in Meniere’s disease. Otolaryngol Head Neck Surg. 1995; 113:181-185.

19. Lezius F, Adrion C, Mansmann U, et al. High-dosage betahistine dihydrochloride

between 288 and 480 mg/day in patients with severe Menière’s disease: a case series. Eur

Arch Otorhinolaryngol 2011; 268:1237-40.

16
 ACCEPTED MANUSCRIPT

20. Newman CW, Jacobson GP, Spitzer JB. Development of the Tinnitus Handicap

Inventory. Arch Otolaryngol Head Neck Surg 1996; 122:143-8.

21. Lacour M, van de Heyning PH, Novotny M, et al. Betahistine in the treatment of

T
Ménière’s disease. Neuropsychiatr Dis Treat 2007; 3:429-40.

P
RI
22. Laurikainen E, Miller JM, Nuttall AL, Quirk WS. The vascular mechanism of action of

betahistine in the inner ear of the guinea pig. Eur Arch Otorhinolaryngol.1998; 255:119–

SC
123

NU
23. Ihler F, Bertlich M, Sharaf K, Strieth S, Strupp M, Canis M (2012) Betahistine exerts a

dose-dependent effect on cochlear stria vascularis blood flow in Guinea Pigs in vivo.
MA
PLoS ONE 7:e39086

24. Valli P. Betahistine reduces the resting firing rate of vestibular receptors in the frog. Acta
ED

Otolaryngol Suppl. 2000; 544:8–10.

PT

25. Lacour M. Betahistine treatment in managing vertigo and improving vestibular

compensation: clarification. J Vestib Res. 2013; 23(3):139-51.

CE

26. Albu S, Chirtes F, Trombitas V, Nagy A, et al. Intratympanic dexamethasone versus high
AC

dosage of betahistine in the treatment of intractable unilateral Meniere disease. Am J

Otolaryngol. 2014 Oct 30. doi: 10.1016/j.amjoto.2014.

27. McRackan TR, Best J, Pearce EC, Bennett ML, Dietrich M, Wanna GB, Haynes DS,

Labadie RF. Intratympanic dexamethasone as a symptomatic treatment for Ménière's

disease. Otol Neurotol. 2014 Oct; 35(9):1638-40

17
 ACCEPTED MANUSCRIPT

Table 1.

T
Distribution of baseline features in the two groups.

P
RI
Group A Group B p value

SC
N=33 N=33

Gender

NU
Males/Females 12/21 15/18 0.46*

Stage 2 3 4 2 3 4
MA
Patients (N) 6 18 9 7 19 7 0.83*

FLS 3 4 5 3 4 5
ED

Patients (N) 4 17 12 5 15 13 0.87*

PT

PTA (Mean ± SD) 51.4 ± 13.6 54.6 ± 15.2 0.47**

CE

SDS (Mean ± SD) 65.2 ± 18.6 68.4 ± 17.7 0.73**

THI (Mean ± SD) 27.7 ± 16.7 28.3 ± 14.8 0.81**

AC

Group A: IT dexamethasone

Group B: IT dexamethasone plus betahistine

FLS: functional level score

PTA: pure tone audiometry

SDS: speech discrimination score

18
 ACCEPTED MANUSCRIPT

THI: Tinnitus Handicap Inventory

* chi square test

T
** Student t test

P
RI
SC
NU
MA
ED
PT
CE
AC

19
 ACCEPTED MANUSCRIPT

Table 2.

Vertigo class and functional level in the two groups of patients following treatment.

T
Group A Group B p value

P
N=32 (%) N=30 (%) chi square test

RI
Class

SC
A 14 (44%) 22 (73.3%)

NU
B 7 (22%) 5 (16.6%)

C 6 (19%) MA 1 (3.3%) 0.11

D 4 (12%) 1 (3.3%)

E 1 (3%) 1 (3.3%)
ED

FLS
PT

1 15 (47%) 22 (73.3%)

2 8 (25%) 7 (23.3%)
CE

3 7 (22%) 1 (3.3%) 0.04

AC

4 2 (6%) 0 (0%)

Group A: IT dexamethasone

Group B: IT dexamethasone plus betahistine

20
 ACCEPTED MANUSCRIPT

Table 3.

PTA, SDS and THI scores before treatment and at the end of the study in the two groups.

P T
RI
Group A Group B p value

SC
N=32 N=30 student t test

PTA (Mean ± SD)

NU
Before treatment 51.4 ± 13.6 54.6 ± 15.2 0.47
MA
After treatment 49.8 ± 16.7 51.2 ± 17.4 0.65

p value 0.38 0.73

ED

SDS (Mean ± SD)

Before treatment 65.2 ± 18.6 68.4 ± 17.7 0.73

PT

After treatment 63.6 ± 19.8 66.4 ± 20.2 0.68

CE

p value 0.73 0.54

THI (Mean ± SD)

AC

Before treatment 27.7 ± 16.7 28.3 ± 14.8 0.81

After treatment 25.4 ± 13.2 26.3 ± 12.7 0.72

p value 0.31 0.46

Group A: IT dexamethasone

Group B: IT dexamethasone and betahistine

PTA: pure tone audiometry

21
 ACCEPTED MANUSCRIPT

SDS: speech discrimination score

THI: Tinnitus Handicap Inventory

PT
RI
SC
NU
MA
ED
PT
CE
AC

22
 ACCEPTED MANUSCRIPT

Figure 1.

T
The Kaplan-Meier survival curves for the likelihood of achieving complete (class A) vertigo

P
control in the two groups throughout the study period.

RI
SC
NU
MA Figure 2.

The Kaplan-Meier survival curves for the likelihood of achieving substantial (class A+B) vertigo
ED

control in the two groups throughout the study period.

PT
CE
AC

23
 ACCEPTED MANUSCRIPT

Figure 1

TP
RI
SC
NU
MA
ED
PT
CE
AC

Group A: IT dexamethasone

Group B: IT dexamethasone plus betahistine

24
 ACCEPTED MANUSCRIPT

Figure 2

TP
RI
SC
NU
MA
ED
PT
CE
AC

Group A: IT dexamethasone

Group B: IT dexamethasone plus betahistine

25