Audiological characteristics and exploratory treatment of a rare condition of acute-otitis-media-associated sudden sensorineural hearing loss.

BACKGROUND: Acute otitis media (AOM) is a common disease that is more prevalent in children. Most studies concerning AOM-associated sudden sensorineural hearing loss are case reports and retrospective in nature, hence the etiology of AOM-associated sudden hearing loss has not been fully established. AIM: To analyze audiological characteristics of AOM-associated sudden hearing loss and evaluate efficacy of combined tympanostomy tube placement (TTP) and intratympanic methylprednisolone.
METHODS: Eight adult patients who were diagnosed with AOM-associated sudden hearing loss and ineffectively treated by conventional medical therapy were enrolled in this study. Basic data were collected, and pure tone audiometry was performed to assess the audiological characteristics. Combination therapy with TTP and intratympanic methylprednisolone injection was given to the patients.
RESULTS: Mixed or sensorineural hearing loss was observed at high frequencies (2-4 kHz). All the cases in this study were cured after TTP and intratympanic methylprednisolone. After treatment, the average hearing threshold at affected frequencies was significantly lower than those in the pretreatment group (P < 0.05) and was similar to that in the healthy ears (P > 0.05).
CONCLUSION: AOM rarely induces sudden sensorineural hearing loss. Combination therapy with TTP and intratympanic methylprednisolone injection may be effective after failure of conventional medical treatment. ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.

Core Tip: Acute otitis media (AOM)-associated sudden sensorineural hearing loss is a rare otological condition and the mechanism and treatment methods have not been defined. This study described the audiological features of the patients with AOM-associated sudden hearing loss and evaluated the clinical efficacy of tympanostomy tube placement and intratympanic methylprednisolone injection after failure of conventional medical therapy.

INTRODUCTION

Acute otitis media (AOM) is a common disease that is more prevalent in children, affecting > 80% of children before the age of 3 years[1]. Globally, there are > 709 million new cases reported every year[2,3]. AOM is mainly caused by acute viral infection of the upper respiratory tract, which alters eustachian tube function and exposes the middle ear to bacterial infiltration[4]. There may be a conductive hearing loss if the patient also has tympanic effusion, and the degree of hearing loss can vary from negligible to 60 dB[5-8]. In the clinic, antibiotics and early myringotomy are the only two treatment options currently available for AOM patients[9]. Sudden sensorineural hearing loss is a frightening symptom that affects about 5–27 per 100000 people annually, with around 66000 new cases per year in the United States[10]. Most of these cases received corticosteroids as initial therapy[11]. Furthermore, intratympanic steroid administration is suggested as salvage therapy when initial therapy fails[11,12]. However, AOM-associated sudden sensorineural hearing loss is a rare otological condition and the mechanism and treatment methods have not been defined.

Most studies concerning AOM-associated sudden sensorineural hearing loss are case reports and retrospective in nature[12-14], hence, the etiology of AOM-associated sudden hearing loss has not been fully established. One of the hypotheses is that effusion in the middle ear causes vibration limitation and hypoxia of two windows, which leads to bone conduction hearing loss[15]. Another hypothesis for the sudden deafness is that the toxins released by infection enter the inner ear through the round window membrane (RWM)[16]. Since absorbing the effusion in the middle ear does not completely restore sensorineural hearing loss, the latter hypothesis currently seems more acceptable. Even though AOM-associated sudden hearing loss is a rare otological disorder, if not treated on time, it might cause permanent hearing loss. Therefore, it is important that the disorder is diagnosed early and treated immediately. This study described the audiological features of patients with AOM-associated sudden hearing loss and evaluated the clinical efficacy of tympanostomy tube placement (TTP) and intratympanic methylprednisolone injection after failure of conventional medical therapy.

MATERIALS AND METHODS

Subjects

Patients with AOM-associated sudden hearing loss who visited the Department of Otolaryngology of Beijing Tsinghua Changgung Hospital between October 1, 2018 and June 1, 2020 were enrolled for this retrospective study. Written consent was signed by all the subjects, and this study was approved by the Human Research Ethics Committee of Beijing Tsinghua Changgung Hospital.

The patients were chosen based on following criteria: (1) Age 18–70 years; (2) AOM was diagnosed based on clinical symptoms, pneumatic otoscopy, pure-tone audiometry (PTA) and tympanometry; (3) Sudden hearing loss was diagnosed according to the Guidelines for Diagnosis and Management of Sudden Hearing Loss (2015), if PTA showed a decrease in hearing threshold ≥ 20 dB, for at least two consecutive frequencies from 0.25 to 4 kHz[17]; and (4) Conventional medical therapy was ineffective.

Exclusion criteria were as follows: (1) Current administration of oral or topical antibiotics for the affected ear; (2) Steroid treatment within 10 d before enrollment; (3) Previous perforation in the affected ear; (4) Allergic to cefuroxime axetil, cefdinir or moxifloxacin; and (5) Grommet (ventilation tube) i in the affected ear.

Intervention

All patients underwent myringotomy under local anesthesia, a ventilation tube was placed, and intratympanic injection of methylprednisolone (approximate 0.4 mL, 40 mg/mL) was given once every 3–4 d. The surgical procedures were performed by an experienced physician. The injection was given at most four times and PTA was performed 2 d after the last treatment or when hearing improvement was reported by the subjects.

Audiometric evaluation

Pure-tone test: It was conducted by using audiometry (TDH-39P Telephonics headset; Clinical Audiometer AC40, Interacoustics Company, Assens, Denmark, and the B-71 bone vibrator) in a sound-insulated cabin. The frequency-specific threshold was determined as the lowest sound intensity that the patient could hear at the specific frequency. The air conduction thresholds at 0.25, 0.5, 1, 2 and 4 kHz were determined.

Measurement of bone conduction thresholds: A B-71 bone vibrator was placed on the mastoid protrusion of the temporal bone of the subjects. The BC threshold values were determined at 0.25, 0.5, 1, 2 and 4 kHz.

Air–bone gap: The air–bone gap (ABG) was calculated as the difference between the pure-tone bone conduction and air conduction thresholds.

Average hearing at affected frequencies When the bone conduction threshold was ≥ 20 dB over two or more consecutive frequencies, these frequencies were determined as affected frequencies. An average hearing at the affected frequencies was determined as the average hearing threshold at the corresponding frequencies.

Evaluation of efficacy

An improvement of ≥ 15 dB of the average hearing threshold at the affected frequencies after treatment was identified as effective, whereas an improvement of < 15 dB was identified as ineffective. A cure was defined as restoring the average hearing threshold at the affected frequencies to the normal hearing levels or the contralateral hearing levels after treatment.

Statistical analysis

The data were evaluated by using SPSS version 26.0 (Chicago, IL, United States). The data were expressed as mean ± SD. The changes in the hearing threshold values before and after treatment were analyzed by nonparametric test, and the difference was considered statistically significant if P was < 0.05.

RESULTS

Demographics

Eight patients who met the inclusion criteria were included in the study (Table 1), with an average age of 51.1 ± 13.60 years. All of them were affected in one ear with different degrees of bone conduction hearing loss.

Table 1

Demographics of the enrolled patients (n = 8, mean ± SD)

Case No.	Side of the affected ear		Gender		Age (yr)	Hearing loss		Tinnitus				Curve type
	Left	Right	Male	Female		Yes	No	No	Light	Middle	Severe	A	B	C
1	√			√	37	√		√					√
2		√		√	38	√		√				√
3	√		√		47	√		√					√
4	√			√	63	√		√					√
5	√			√	59	√		√					√
6		√	√		67	√				√			√
7	√			√	34	√				√			√
8	√			√	64	√		√					√
Total	6	2	2	6	51.1 ± 13.60	8	0	6	0	2	0	1	7	0

Audiological characteristics pretreatment

The bone conduction and air conduction threshold values of the affected ears and healthy ears at different frequencies are listed in Table 2. Table 2 shows that the hearing threshold values of the affected ears were significantly higher than those of the contralateral healthy ears over 0.5, 1, 2 and 4 kHz for bone conduction (P < 0.05) and at all frequencies for air conduction. The audiogram data clearly showed that conductive hearing loss was observed at low frequencies, and mixed or sensorineural hearing loss was seen at high frequencies (Figure 1). Bone conduction hearing was impaired at 2 kHz in all patients, i.e., an incidence rate of 100%. The average hearing threshold of the affected frequencies was 37.19 ± 9.49 dB.

Table 2

Comparison of bone conduction and air conduction thresholds between the affected and contralateral heathy ears (dB HL, mean ± SD)

Group	No.	0.25 kHz, BC	0.5 kHz, BC	1 kHz, BC	2 kHz, BC	4 kHz, BC
Affected ears	8	9.38 ± 5.60	17.50 ± 9.63	18.75 ± 9.16	33.12 ± 12.51	39.38 ± 17.41
Healthy ears	8	8.13 ± 5.30	13.13 ± 5.30	11.25 ± 6.40	17.50 ± 8.86	22.50 ± 11.34
Z		-0.220	-1.282	-1.973	-2.570	-2.161
P		0.826	0.200	0.048	0.010	0.031
Group	No.	0.25 kHz, AC	0.5 kHz, AC	1 kHz, AC	2 kHz, AC	4 kHz, AC
Affected ears	8	28.13 ± 11.63	31.88 ± 15.34	38.75 ± 18.27	38.75 ± 16.42	56.25 ± 22.16
Healthy ears	8	8.13 ± 5.30	13.13 ± 5.30	11.25 ± 6.40	17.50 ± 8.86	22.50 ± 11.34
Z		-2.965	-2.971	-3.242	-2.797	-2.905
P value		0.003	0.003	0.001	0.005	0.004

AC: Air conduction; BC: Bone conduction.

Figure 1

Audiogram. Audiogram pretreatment: conductive hearing loss was observed at low frequencies of 0.25–1 kHz, and sensorineural hearing loss was seen at high frequencies of 2–4 kHz; the hearing threshold of the left ear was normal. [: Bone conduction of right ear with sheltering; <: Bone conduction of left ear; O: Air conduction of right ear; ∆: Air conduction of right ear with sheltering; ×: Air conduction of left ear; blue markers = left ear; red markers = right ear.

The frequency ranges of 0.25–1 kHz and 2–4 kHz were defined as low and high frequencies, respectively. The bone conduction threshold values at low frequencies were close to normal, and hearing loss was observed at high frequencies, with significant difference (P < 0.05) (Table 3). The average ABG was greater in the low frequency group, but the difference between the two groups was not statistically significant (Table 3).

Table 3

Comparison of average bone conduction thresholds and air-bone gap at low and high frequency

Group	0.25-1 kHz	2-4 kHz	Z	P value
Average BC threshold	15.25 ± 6.52	36.25 ± 6.52	-2.897	0.004
Air-bone gap	16.25 ± 11.64	11.56 ± 6.80	-0.527	0.598

BC: Bone conduction.

Audiological characteristics and efficacy after treatment

The average interval from disease onset to the start of treatment was 8.63 ± 10.60 d (range, 3–30 d). All eight patients received TTP and intratympanic methylprednisolone injection (the average number of injections was 2), and were cured after treatment. The average hearing threshold value at the affected frequencies post-treatment was significantly lower than the pre-treatment value (P < 0.05), whereas it was not significantly different from that of the healthy ears (P > 0.05) (Table 4). The audiological changes observed after the treatment were shown in a post-treatment audiogram (Figure 2). The average ABG was significantly improved (P < 0.05) (Table 5). These results indicated that the combination of TTP and intratympanic methylprednisolone injection was a good salvage treatment regimen for patients suffering from AOM associated sudden hearing loss after failure of the conventional treatment.

Table 4

Comparison of the average hearing threshold at affected frequencies pre- and post-treatment with healthy ears

Group	Mean hearing threshold at affected frequencies (dB HL)	Z	P value
Pre-treatment	37.19 ± 9.49	-2.804	0.005
Healthy ears	19.69 ± 7.95
Post-treatment	21.66 ± 9.14	-0.370	0.712

Figure 2

Audiogram. Audiogram after treatment: Conductive hearing loss at low frequencies of the same patient disappeared and sensorineural hearing loss observed at high frequencies of 2–4kHz was restored to the hearing level of the healthy ear; the hearing threshold of the left ear was normal. O: Air conduction of right ear = bone conduction of right ear; ×: Air conduction of left ear = bone conduction of left ear; blue markers = left ear; red markers = right ear.

Table 5

Comparison of the pre-treatment air-bone gap with post-treatment values

Group	Air-bone gap (dB HL)	Z	P value
Pre-treatment	14.38 ± 9.40	-3.165	0.002
Post-treatment	3.25 ± 2.71

DISCUSSION

The pathogenesis of sensorineural hearing loss in patients with AOM has been investigated, and the leading proposed theory is that an inflammation induces increased permeability of RWM, which allows the entry of endotoxins and ionic disequilibrium in the cochlea[17]. The bacterial (e.g., Streptococcus pneumoniae) byproducts and inflammatory mediators associated with AOM have been proven to enhance the permeability of RWM and cause subsequent cochlear damage[16,18,19]. It was found that the resulting hearing loss predominantly affected the hearing threshold values at high frequencies, which supports the above-mentioned theory[20]. In this study, it was found that the audiological characteristics of the patients with AOM-associated sudden hearing loss were as follows: ABG at low frequencies and bone conduction hearing loss at high frequencies. These results were in accordance with a previous case report, in which a female patient who was diagnosed with AOM-associated bilateral sudden hearing loss presented with higher hearing threshold values for both bone and air conduction at 2 and 4 kHz frequencies[13]. Despite the similar results reported in several studies, the pathological explanation for the elevation in hearing thresholds at high frequencies following AOM with effusion has not been fully elucidated. It is noteworthy that the prognosis of low frequency hearing loss was demonstrated to be better than that of high frequency. Patients with low frequency hearing loss showed a significantly higher recovery rate (74.1%, 40/54) than those with high frequency hearing loss (45.6%, 26/57) (P < 0.001)[21]. High-frequency hearing loss has also been associated with various symptoms such as deterioration in music perception[22]. In addition, a longitudinal cohort study showed that patients who had chronic suppurative otitis media and hearing loss after recurrent AOM are more likely to suffer from dizziness in adulthood[23], indicating that AOM-associated high frequency hearing loss in childhood may influence the hearing and quality of life in the long term. Therefore, high-frequency audiometry should be considered for AOM patients to detect early changes in the auditory thresholds, and early intervention should be planned when plausible. To the best of our knowledge, this study is the largest case study that has investigated the audiological characteristics of patients with AOM-associated sudden deafness.

Currently, the front-line treatment choices for AOM, according to the guidelines and clinicians, are antibiotics and myringotomy, alone or in combination with ventilation tube placement. Song et al[9] suggested that early myringotomy (with or without placing ventilation tubes) and antibiotics significantly improved clinical outcomes of eight patients with AOM. As for the sudden sensorineural hearing loss, it was recommended by the American Academy of Otolaryngology guidelines that systemic corticosteroids and/or hyperbaric oxygen therapy should be adopted as soon as the diagnosis was made, if needed an intratympanic steroid injection was recommended as a possible salvage therapy[11].

However, there is no standard treatment modality for patients with AOM-associated sudden deafness due to limited evidence and rarity of the disease. In the current study, antibiotics and intravenous methylprednisolone were administered in all eight patients; however, the treatment was ineffective. A combination treatment of TTP and intratympanic methylprednisolone injection was applied as a salvage and exploratory therapy. All the patients in this study showed improvement in BC threshold values at the affected frequencies and showed improvement in ABG. The results were in accordance with a previous study. Seven patients with sensorineural hearing loss associated with AOM were offered intratympanic steroids after oral antibiotics and oral prednisolone failed to improve hearing. Hearing improvement was achieved in 57% of patients (4/7) after intratympanic injections of methylprednisolone. A possible reason is that intratympanic methylprednisolone injection can provide a concentrated local steroid effect in nonresponders to antibiotics. The results clearly indicated that the combination therapy of TTP and intratympanic glucocorticoid injection was a good choice for treating patients with AOM-associated sudden deafness after failure of conventional medical treatment.

However, further well-designed studies are needed to verify the findings of the current study as there were some limitations to this study. Firstly, AOM-associated sudden hearing loss is a rare disease in adults, thus, the sample size of this study was too small. Secondly, a control group in which no further treatment was provided after failure of the first treatment was not accommodated in this study. Hence in the future, well-designed studies with a larger sample size are required to further corroborate findings of this study.

CONCLUSION

In summary, the current case study indicated that AOM may rarely induce sudden sensorineural hearing loss, and high frequencies (2–4 kHz) are often involved. Combination therapy with TTP and intratympanic methylprednisolone injection may be a good salvage treatment modality for patients with AOM-associated sudden hearing loss after failure of conventional treatment.

ARTICLE HIGHLIGHTS

Research background

Acute otitis media (AOM) is a common disease in children, affecting > 80% of children before the age of 3 years. AOM-associated sudden sensorineural hearing loss is a rare otological disorder, and the mechanism and treatment methods remain to be investigated.

Research motivation

If AOM-associated sudden hearing loss is not treated on time, it might cause permanent hearing loss. Therefore, early diagnosis and treatment of AOM-associated sudden hearing loss are important.

Research objectives

This study aimed to describe the audiological features of the patients with AOM-associated sudden hearing loss and evaluate the clinical efficacy of tympanostomy tube placement (TTP) and intratympanic methylprednisolone injection after failure of conventional medical therapy.

Research methods

Patients with AOM-associated sudden hearing loss who visited the Department of Otolaryngology of Beijing Tsinghua Changgung Hospital between October 1, 2018 and June 1, 2020 and were ineffectively treated by conventional medical therapy were enrolled in this study. Basic data were collected, and pure-tone audiometry was performed to assess the audiological characteristics. Combination therapy with TTP and intratympanic methylprednisolone injection was given to the patients.

Research results

Mixed or sensorineural hearing loss was observed at high frequencies (2–4 kHz). All the patients in this study were cured after TTP and intratympanic methylprednisolone. After treatment, the average hearing threshold at affected frequencies was significantly lower than those in the pretreatment group and was similar to those in the healthy ears.

Research conclusions

Our study indicated that AOM may rarely induce sudden sensorineural hearing loss, and high frequencies (2–4 kHz) are often involved. Combination therapy with TTP and intratympanic methylprednisolone injection may be a good salvage treatment modality for patients with AOM-associated sudden hearing loss after failure of conventional treatment.

Research perspectives

Our study may bring more chances for recovery of patients with AOM-associated sudden hearing loss after failure of conventional treatment. However, our findings remain to be verified by well-designed studies with a large sample size.