Accepted Manuscript

Intratympanic injection of dexamethasone after failure of

intravenous prednisolone in simultaneous bilateral sudden
sensorineural hearing loss

Daowen Wang, Peng Xu

PII: S0196-0709(18)30607-0
DOI: doi:10.1016/j.amjoto.2018.07.008
Reference: YAJOT 2064
American Journal of Otolaryngology--Head and Neck Medicine and
To appear in:
Surgery
Received
8 July 2018
date:

Please cite this article as: Daowen Wang, Peng Xu , Intratympanic injection of
dexamethasone after failure of intravenous prednisolone in simultaneous bilateral sudden
sensorineural hearing loss. Yajot (2018), doi:10.1016/j.amjoto.2018.07.008

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Intratympanic injection of dexamethasone after failure of intravenous

prednisolone in simultaneous bilateral sudden sensorineural hearing loss

Daowen Wang1, MD

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Department of Otolaryngology, Peking University Health Science Center, Beijing

100191, P.R.C.

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Correspondence to: Peng Xu, Department of Otolaryngology, Peking University

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Health Science Center, Beijing 100191, P.R.C. Email: daowen007@sina.com.

Declarations of interest: none.

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Abstract

Purpose: This study aimed to analyze outcomes of intratympanic injection of

dexamethasone after failure of intravenous prednisolone in simultaneous bilateral

sudden sensorineural hearing loss (SSNHL).

Materials and Methods: The cases of simultaneous bilateral SSNHL treated in our

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hospital from March 2007 to March 2018 were retrospectively analyzed. During the

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earlier period (March 2007 to February 2012), the cases were treated by intravenous

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prednisolone only, and classified into group A. During the late period (February 2012

to March 2018), intratympanic injection of dexamethasone after failure of intravenous

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prednisolone therapy was employed to treat simultaneous bilateral SSNHL, and these
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patients were enrolled in group B. Effective rates of the two treatment modalities in

group A and B were compared.

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Results: In group A, 3 of 40 ears obtained complete recovery, and 4 ears achieved

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partial recovery after intravenous prednisolone treatment, with the effective rate of
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only 17.5% (7/40 ears). In contrast, 6 of 44 ears in group B achieved complete

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recovery, and 10 ears got partial recovery, with the effective rate of 36.4% (16/44
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ears). There was significant difference in the effective rate between the two groups.

Conclusion: Intratympanic injection of dexamethasone after failure of intravenous

prednisolone therapy was a better choice for simultaneous bilateral SSNHL compared

to traditional intravenous prednisolone therapy.

Keywords: Sudden sensorineural hearing loss; bilateral; intratympanic injection;

prednisolone; dexamethasone
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Introduction

Sudden sensorineural hearing loss (SSNHL) is common, with an estimated

incidence of 5-20 per 100,000 each year in the USA [1]. It is usually unilateral, with

idiopathic etiology in most cases [2]. 32%-65% cases with unilateral SSNHL can

achieve spontaneous recovery [3, 4]. Systemic steroid is the main treatment modality

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for SSNHL, which significantly increases the recovery rate [3]. In contrast, bilateral

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SSNHL is rather rare, accounting for 0.4-4.9% of all SSNHL cases [5-8]. The

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prognosis of bilateral SSNHL is poor, especially simultaneous bilateral SSNHL.

Xenellis J et al. [9] compared outcomes of simultaneous bilateral SSNHL and

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sequential bilateral SSNHL as well as unilateral SSNHL treated by intravenous
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prednisolone, and it was found that meaningful improvement of hearing was observed

in only 27.2% cases with simultaneous bilateral SSNHL, which was significantly
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lower compared to 74.1% of cases with unilateral SSNHL and 71.4% of cases with
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sequential bilateral SSNHL. It was indicated that outcomes of simultaneous bilateral

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SSNHL treated by intravenous prednisolone were much poorer compared to

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sequential bilateral SSNHL and unilateral SSNHL.

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Intratympanic steroid therapy is increasingly employed to treat idiopathic SSNHL.

A higher level of intracochlear dexamethasone was noted for intratympanic infusion

compared to intravenous administration [10]. Moreover, lower plasma levels were

also found in intratympanic infusion group, indicating smaller possibility of systemic

side effects. Intratympanic injection has been recommended for salvage after failure

of systemic steroid therapy [11]. However, to our knowledge, application of

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intratympanic injection in simultaneous bilateral SSNHL has not been reported. In

order to maximize the outcomes of simultaneous bilateral SSNHL, we employed

intratympanic infiltration of dexamethasone after failure of intravenous steroid

therapy to treat simultaneous bilateral SSNHL, and analyzed the outcomes.

Materials and methods

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Subjects

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From March 2007 to March 2018, the cases of simultaneous bilateral SSNHL

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treated in our hospital were enrolled in the study and retrospectively analyzed.

Inclusion criteria: 1. SSNHL greater than 30dB in 3 consecutive frequencies in

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standard pure tone hearing thresholds (0.5, 1, 2 and 4 kHz) within 72h; 2. bilateral
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concurrent onset of hearing loss (the second ear was affected within 3 days of the first

ear). Exclusion criteria: 1. acoustic neuroma; 2. large vestibular aqueduct syndrome; 3.

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syphilis; 4. parotitis; 5. retrocochlear disease; 6. Meniere's disease; 7. autoimmune

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diseases; 8. ototoxic drug administration; 9. long-term noise exposure.

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Treatment modalities
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During the earlier period (March 2007 to February 2012), the cases were treated
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by intravenous prednisolone only. Prednisolone was provided intravenously for 15

days (60 mg for 7 days, followed by 40mg for 2 days, 30mg for 2 days, 20 mg for 2

days, and 10mg for 2 days). If the patients had diabetes, the plasma glucose levels

would be strictly monitored and controlled by insulin if necessary. These patients

were enrolled in group A (40 ears).

During the late period (February 2012 to March 2018), intratympanic injection of
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dexamethasone after failure of intravenous prednisolone therapy was employed to

treat simultaneous bilateral SSNHL, and these patients were enrolled in group B (44

ears). The intravenous prednisolone therapy was identical to group A. If there was no

recovery of hearing loss after 15-day prednisolone treatment revealed by pure tone

audiometry, intratympanic injection of dexamethasone would be recommended to the

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patients, and informed consent was signed by the patients. Briefly, after 75% alcohol

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disinfection, 1% lidocaine was used for local anesthesia with the patients in the supine

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position. Two perforations, 1 puncture for ventilation and the other for injection, were

made in the anterosuperior quadrant of the tympanic membrane under microscopic

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direction. Dexamethasone (5 mg/mL; about 0.3-0.4 mL) was injected into the middle
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cavity. The patient was told to avoid head motion during the procedure and keep the

other ear pointed down within 30 min, and both swallowing and speaking were
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forbidden. Intratympanic injection for the other ear was performed on the next day, if
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both ears were ineffective to systemic treatment. The procedure was done every two
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days, a total of 4 times for each ear.

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Hearing evaluation
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Standard pure tone audiometry was performed before treatment, after systemic

treatment, and after the last intratympanic injection. Average hearing thresholds were

defined as average air-conduction hearing thresholds at 0.5, 1, 2 and 4 kHz. The

audiogram shapes were divided into 4 subtypes: ascending type, descending type, flat

type, and profound deafness type [12].

Mild hearing loss indicated average hearing thresholds of 26-40dB, moderate

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hearing loss meant average hearing thresholds of 41-70dB, severe hearing loss

indicated average hearing thresholds of 71-90dB, and profound hearing loss was

defined if average hearing thresholds were more than 90dB.

Efficacy was defined according to pure-tone audiometric results after systemic

treatment or intratympanic injection. Recovery was defined as improved average

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hearing thresholds of at least 10dB. Complete recovery indicated average hearing

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thresholds ≤25dB or return to the hearing level before disease onset. Partial recovery

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referred to recovery but not reaching the standard of complete recovery. No recovery

meant hearing gain less than 10dB.

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Statistical analysis
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Means between two groups were compared by using the t-test. Effective rates

were compared by chi-square test. P<0.05 indicated significant difference.

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Results
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Baseline information
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A total of 42 cases (84 ears) with simultaneous bilateral SSNHL were enrolled in
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the study. There were 20 cases (40 ears) in group A, and 22 cases (44 ears) in group B.
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The detailed information is listed in Table 1. In group A, there were 8 males and 12

females, with an average age of 52.1±12.3 years. The mean interval between onset of

hearing loss and treatment was 5.7±3.4 days. Vertigo, aural fullness, and tinnitus were

presented by 30%, 20%, and 55% cases, respectively. Regarding to audiogram shapes,

10%, 30%, 15% and 45% ears were of ascending type, descending type, flat type and

profound deafness type, respectively. Before treatment, 5%, 15%, 20% and 60% ears
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were of mild hearing loss, moderate hearing loss, severe hearing loss and profound

hearing loss, respectively.

In group B, there were 10 males and 12 females, with an average age of

53.2±13.2 years. The mean interval between onset of hearing loss and treatment was

7.2±4.1 days. Vertigo, aural fullness, and tinnitus were presented by 31.8%, 27.3%,

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and 50% cases, respectively. Regarding to audiogram shapes, 9.1%, 22.7%, 18.2%

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and 50 % ears were of ascending type, descending type, flat type and profound

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deafness type, respectively. Before treatment, 4.5%, 13.6%, 27.3% and 54.6% ears

were of mild hearing loss, moderate hearing loss, severe hearing loss and profound
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hearing loss, respectively. Statistical analysis showed that there was no significant
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difference in the basic information (including age, gender, interval between onset and

treatment, vertigo, aural fullness, tinnitus, audiogram shapes, and hearing levels
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before treatment) between group A and group B.

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Efficacy
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In group A, 3 ears obtained complete recovery, and 4 ears achieved partial

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recovery after intravenous prednisolone treatment, with the effective rate of 17.5%
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(7/40 ears). In contrast, 6 ears in group B achieved complete recovery, and 10 ears got

partial recovery, with the effective rate of 36.4% (16/44 ears). There was significant

difference in the effective rate between the two groups (p<0.05). (Table 2)

Discussion

Bilateral SSNHL is a rare entity, and its pathophysiology remains largely

unknown. Bilateral SSNHL is considered as a group of symptoms associated with

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cochlear damage, rather than a single disease. Viral infection and cardiovascular

diseases are most proposed causes of bilateral SSNHL. Yanagita and Murahashi [6]

found high viral antibody titers in the patients in whom common cold and fever

seemed to trigger the onset of bilateral sudden deafness, which were more commonly

seen than the cases with unilateral deafness. Thus, they considered that viral infection

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was the primary cause of bilateral SSNHL. Oh JH et al. [8] assumed that

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cardiovascular diseases may cause peripheral circulation disorder and cochlear

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damage, and cardiovascular diseases are primary causes of bilateral SSNHL.

Consistently, Fetterman et al. [5] reported that among those with bilateral SSNHL, the
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incidence of cardiovascular diseases is three times of that among patients with
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unilateral SSNHL. This is an indirect evidence that cardiovascular diseases are among

the causes of bilateral SSNHL.

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The prognosis of bilateral SSNHL treated by either intravenous prednisolone or

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subperiosteum injection of methylprednisolone and lidocaine is poor. Xenellis J et al.

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[9] treated simultaneous bilateral SSNHL by intravenous prednisolone, and it was

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found that meaningful improvement of hearing was observed in only 27.2% cases.
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Wang Y et al. [13] injected methylprednisolone and lidocaine in the subperiosteum of

cribriform area posterior auricle of 14 cases with sequential bilateral SSNHL every 3

days, and found that improvement of hearing was noticed in only 28.57% of the

recently affected ear and 0% of the contralateral ear. In order to maximize the

therapeutic effect of bilateral SSNHL, intratympanic injection of dexamethasone after

failure of intravenous prednisolone therapy, was attempted in cases with simultaneous

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bilateral SSNHL since February 2012 in our hospital. Although the traditional therapy

of intravenous prednisolone in our study achieved hearing recovery in only 17.5%,

similar to the previous report [9], 36.4% cases achieved either complete recovery or

partial recovery of hearing after the novel treatment modality, with significant

difference (p<0.05). Moreover, there was no significant difference in terms of interval

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between onset and treatment, tinnitus, audiogram shapes, and hearing levels before

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treatment between the two groups, excluding the influencing of possible confounding

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factors. Given the results above, our study first demonstrated that intratympanic

injection of dexamethasone after failure of intravenous prednisolone therapy was a

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better choice for simultaneous bilateral SSNHL compared to traditional intravenous
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prednisolone therapy.

During the past 15 years, several studies [14-20] about intratympanic injection of
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glucocorticoids for idiopathic SSNHL have been published, and either dexamethasone
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or methylprednisolone was used as the primary or salvage therapy, with positive

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results. Haynes DS et al. applied intratympanic dexamethasone for SSNHL after

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failure of systemic therapy, and found 40% cases showed improvement of hearing
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compared to 9.1% in the control group [17]. Intratympanic injection has been

recommended for salvage after failure of systemic steroid therapy for idiopathic

SSNHL [11]. Our study was the first to apply intratympanic injection of

dexamethasone as a salvage after failure of systemic steroid therapy for simultaneous

bilateral SSNHL, and good results were achieved. Steroid is commonly used for

SSNHL, mainly because it is believed that steroid may induce suppression of the
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immune response, change microcirculation and decrease endolymphatic pressure [21].

A higher level of intracochlear dexamethasone was observed for intratympanic

infusion compared to intravenous administration [10]. This may explain the better

outcomes of intratympanic injection of dexamethasone after failure of intravenous

prednisolone therapy in our study.

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However, there are some limitations in this study. First, our study was

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retrospective, with the coherent short-comings of retrospective study. Second, the

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sample size was not large due to the rarity of bilateral SSNHL. Third, the mechanism

of better outcomes of the novel treatment modality was not further investigated in this
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study. Therefore, our results remain to be further confirmed by well-designed
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prospective study.

Compliance with Ethical Standards:

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Conflict of interests: We declare that there is no conflict of interest.

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Ethical approval: All procedures performed in studies involving human participants

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were in accordance with the ethical standards of the institutional and/or national
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research committee and with the 1964 Helsinki declaration and its later amendments
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or comparable ethical standards.

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Table 1 Clinical features of 20 cases (40 ears) in group A and 22 cases (44 ears) in

group B

Group A Group B

Age (years) 52.1±12.3 53.2±13.2

Sex (male /female) 8:12 10:12

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Interval (days) 5.7±3.4 7.2±4.1

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Associated symptoms (%)

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Vertigo 30% 31.8%

Aural fullness 20% 27.3%

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Tinnitus 55% 50%
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Audiogram shapes (%)

Ascending type 10% 9.1%

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Descending type 30% 22.7%

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Flat type 15% 18.2%

Profound deafness type 45% 50%

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Hearing levels before treatment (%)

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Mild hearing loss 5% 4.5%

Moderate hearing loss 15% 13.6%

Severe hearing loss 20% 27.3%

Profound hearing loss 60% 54.6%

Interval refers to interval between onset of hearing loss and treatment. No significant

difference was found between the two groups (p>0.05).

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Table 2 Effective rates of 40 ears in group A and 44 ears in group B

Group A Group B

Complete recovery 3 ears 6 ears

Partial recovery 4 ears 10 ears

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Effective rate 17.5% 36.4%

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The effective rate of group B was higher compared to group A (p=0.032).

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