The clinical features and prognosis of mumps-associated hearing loss: a retrospective, multi-institutional investigation in Japan

Abstract

Conclusions: The majority of hearing loss due to mumps presents as unilateral profound sensorineural hearing loss, which is refractory to treatment. In rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is recommended to prevent mumps-associated hearing loss.

Objective: The objective of this study is to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes.

Subjects and methods: The clinical parameters were analyzed under a retrospective multi-institutional study design in patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016.

Results: Sixty-seven patients with hearing loss due to mumps were enrolled. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three patients presented with unilateral, and 4 with bilateral hearing loss. Profound hearing loss was observed in 65 ears. Only one ear with severe hearing loss showed complete recovery. Four patients with bilateral hearing loss received cochlear implant surgery. Most of the patients with hearing loss due to mumps had no history of vaccination.

Chinese abstract

结论 因腮腺炎引起的大多数听力损失表现为单侧深度感觉神经性听力损失, 对治疗没有反应。在罕见的双侧全聋的情况下, 耳蜗植入物有益于语音感知。建议接种腮腺炎疫苗以防止腮腺炎相关的听力损失。

目的 调查腮腺炎引起的听力损失的临床特征, 并评估听力结果。

对象和方法 在回顾性多机构研究设计下, 对1987年至2016年间在19家医院的耳鼻喉科部门诊断患有腮腺炎的听力损失患者进行临床参数分析。

结果 征收67名由腮腺炎引起的听力损失患者。研究人群包括35名男性和32名女性, 年龄从1至54岁, 中位年龄为9.5岁。 63例患者出现单侧、4例出现双侧听力损失。在65个耳中观察到严重的听力损失。只有一个严重听力损失的耳朵显示完全恢复。 4例双侧听力损失患者接受了人工耳蜗植入手术。大多数由于腮腺炎引起的听力损失患者没有接种疫苗的历史。

Keywords:

• Mumps
• hearing loss
• deafness
• outcome
• cochlear implant

Introduction

Mumps is an enveloped, single-stranded RNA virus belonging to the family paramyxoviridae, and causes an acute infectious disease mainly in children and young adults [1]. Transmission is by droplet spread, and humans are the only known host. The most common clinical manifestations of infection include a flu-like illness and bilateral swelling of the parotid glands [2,3]. However, subclinical infection is known to be common, and approximately 30% of patients with mumps may not experience parotid swelling [1]. Mumps infection occasionally induces the potential for complications such as pancreatitis, orchitis, oophoritis, aseptic meningitis, encephalitis and sensorineural hearing loss [1–3]. Hearing loss due to mumps is thought to be unilateral and profound with rapid onset [4–6]. Although steroids have been clinically administered in cases of mumps deafness according to the treatments for idiopathic sudden sensorineural hearing loss, the prognosis for patients with profound impairment is generally poor [4–6]. Meanwhile, spontaneous recovery in cases with mild hearing loss has been reported [7]. Thus, otological examination might not be performed in mild cases, resulting in possible underestimation of hearing loss due to mumps. The precise clinical course of hearing loss due to mumps, therefore, remains unclear.

There is no specific antiviral therapy for mumps. The effectiveness of vaccination for mumps has been widely confirmed, and WHO recommends immunization coverage of 90% to prevent mumps outbreaks [8]. Despite the usage of measles–mumps–rubella (MMR) vaccine in many countries, routine vaccination against mumps in Japan has not yet been performed for historical reasons [4]. In Japan, a voluntary mumps vaccination program was begun in 1981 and MMR vaccination has been provided as an option instead of monovalent measles vaccine for routine immunization since April 1989. However, these vaccinations were suspended due to a large number of vaccine-induced complications including aseptic meningitis in 1993. Thereafter, outbreaks of mumps have remained uncontrolled in Japan, and the number of patients with mumps deafness is expected to increase. Thus, details regarding the clinical features of this condition should be clarified to allow appropriate treatment of the associated hearing impairment.

In this retrospective study, we aimed to investigate the clinical characteristics of hearing loss due to mumps and to evaluate hearing outcomes.

Subjects and methods

Subjects

This study was conducted under a retrospective multi-institutional design with patients diagnosed with hearing loss due to mumps at the Otolaryngology departments of 19 hospitals between 1987 and 2016. This study design adhered to the tenets of the Declaration of Helsinki and was approved by the Institutional Review Board of each hospital.

We used the diagnostic criteria for mumps deafness proposed by the Acute Severe Hearing Loss Study Group, the Ministry of Health, Labor and Welfare of Japan in 1987, and revised in 2013 (Table 1) [9]. Patients underwent a thorough history-taking, physical examination, otoscopic examination, pure-tone audiometry, speech audiometry, impedance audiometry, distortion product otoacoustic emissions, equilibrium function test, serological tests including anti-mumps immunoglobulin M (IgM) and immunoglobulin G (IgG) antibody levels measured by enzyme-linked immunosorbent assay, computed tomography and/or magnetic resonance imaging. Patients with referent mumps deafness or insufficient clinical data were excluded from this analysis. The clinical parameters, such as age, affected side, severity of hearing loss, anti-mumps IgM and IgG antibody levels, administration of mumps vaccine, treatment and hearing outcomes, were analyzed.

Table 1. Criteria for the diagnosis of mumps deafness (revised in 2013).

Definite 1. Patients with evident clinical signs of mumps, such as swelling of the parotid gland and submandibular gland, and acute severe hearing loss during the period from 4 d before to 18 d after the appearance of such swelling 2. Patients without evident clinical signs of mumps, but IgM antibodies against mumps virus are detected within 3 months after the onset of acute severe hearing loss

Referent case: Patients in whom mumps deafness is suspected clinically 1. Patients whose family members or friends have mumps infection 2. Patients who have different periods to Definite Criterion 1

Audiometric data

Audiometry was performed using a pure-tone audiometer in a sound-proof booth. The pure-tone thresholds for each ear were determined at frequencies of 125, 250, 500, 1000, 2000, 4000 and 8000 Hz for air conduction, and at 250, 500, 1000, 2000 and 4000 Hz for bone conduction with masking as appropriate.

The severity of hearing loss was categorized into four grades based on the initial pure-tone audiogram using the criteria proposed by the Acute Severe Hearing Loss Study Group, the Ministry of Health, Labor and Welfare of Japan (Table 2) [10]. The audiological data used for the evaluation of hearing recovery included the initial and final pure-tone audiograms, according to the hearing outcome criteria proposed by the Acute Severe Hearing Loss Study Group, the Ministry of Health, Labor and Welfare of Japan (Table 3) [10]. In this study, complete or marked recovery was defined as hearing loss recovery.

Table 2. Criteria for the grading of hearing loss in idiopathic sudden sensorineural hearing loss.

Grade 1	PTA <40 dB
Grade 2	40 dB ≤ PTA <60 dB
Grade 3	60 dB ≤ PTA <90
Grade 4	90 dB ≤ PTA

PTA: pure-tone average. PTA was calculated based on pure-tone thresholds at 250, 500, 1000, 2000 and 4000 Hz.

Table 3. Criteria for the evaluation of hearing recovery in sudden deafness.

Complete recovery	All five frequencies at 250, 500, 1000, 2000 and 4000 Hz of final audiograms are 20 dB or less, or improvement to the same degree of hearing in the unaffected ear
Marked recovery	30 dB ≤ PTA improvement
Slight recovery	10 dB ≤ PTA improvement <30
No response	PTA improvement <10

PTA: pure-tone average. PTA was calculated based on pure-tone thresholds at 250, 500, 1000, 2000 and 4000 Hz.

Results

Subject profiles

One hundred and one patients were suspected of hearing loss due to mumps. Of these, 34 patients were excluded as ‘referent cases’ or due to insufficient clinical data. Finally, a total of 67 patients with ‘definite’ hearing loss due to mumps were enrolled in this study. Patient profiles are summarized in Table 4. The study population consisted of 35 males and 32 females, ranging in age from 1 to 54, with a median age of 9.5 years. Sixty-three (94.0%) of the 67 patients presented with unilateral, and 4 (6.0%) with bilateral hearing loss. Grade 4 hearing loss were observed in 65 (91.5%) of the 71 ears. Fifteen patients (22.4%) were diagnosed with hearing loss due to asymptomatic mumps infection based on serological examinations. Twenty-one patients (31.3%) experienced dizziness or vertigo. Nystagmus was observed in 14 patients (20.9%) at the initial examination.

Table 4. Characteristics of subjects with ‘definite’ hearing loss due to mumps.

Total number (n)	67
Age (years)
Range	1–54
Median	9.5
Gender (n, %)
Male	35 (52.2)
Female	32 (47.8)
Affected ear (n, %)
Unilateral	63 (94.0)
Bilateral	4 (6.0)
Severity (n, %)
Grade 1	0 (0)
Grade 2	2 (2.8)
Grade 3	4 (5.6)
Grade 4	65 (91.5)
Asymptomatic mumps infection	15 (22.4)
Dizziness or vertigo (n, %)	21 (31.3)
Nystagmus (n, %)	14 (20.9)

Treatment and hearing outcomes

Thirty-six patients with hearing loss due to mumps were treated with steroids (prednisolone, hydrocortisone, dexamethasone and betamethasone), 10 with vitamin B₁₂ and adenosine triphosphate disodium, and four with hyperbaric oxygen therapy. Twenty-nine of the 36 patients treated with steroids had both the pre- and post-treatment audiogram data available. With regard to hearing outcomes, 28 of these 29 patients showed no response (96.6%) according to the above-mentioned hearing outcome criteria. Only one case (3.4%) with Grade 3 hearing loss showed a complete recovery (Table 5). One patient with no recovery from unilateral deafness due to mumps was implanted bone-anchored hearing aids to improve directional hearing and performance in noise. Four patients with bilateral total deafness received cochlear implant surgery, and achieved good results for speech-sound perception.

Table 5. Hearing prognosis of mumps-associated hearing loss.

	Pre-steroid treatment hearing severity
Degree of hearing recovery	Grade 2 (%)	Grade 3 (%)	Grade 4 (%)	Total (%)
Complete recovery	0/1 (0)	1/3 (33.3)	0/25 (0)	1/29 (3.4)
Marked recovery	0/1 (0)	0/3 (0)	0/25 (0)	0/29 (0)
Slight recovery	0/1 (0)	0/3 (0)	0/25 (0)	0/29 (0)
No response	1/1 (100)	2/3 (66.7)	25/25 (100)	28/29 (96.6)

Vaccination

Two patients received only the first dose of the mumps vaccine. Although one patient was vaccinated against mumps, the number of doses was unknown. Thirty-seven patients were previously unvaccinated. Vaccination history in 27 patients was unclear.

Discussion

Sensorineural hearing loss is a well-known complication of mumps infection. It has been estimated that the incidence of hearing loss due to mumps ranges from approximately 1 per 1000 to 1 per 20,000 mumps cases [6,11]. In the previous epidemiological study of mumps deafness in Japan, there was a definite peak in the age distribution at 5–9 years old [4]. Thus, it may not be immediately recognized by the patients’ guardians or even the patients themselves if hearing impairment is unilateral. Furthermore, previous studies demonstrated that the anti-mumps IgM antibody level is elevated in 5–7% of patients with idiopathic sudden sensorineural hearing loss [12–14]. Fifteen patients were diagnosed with hearing loss due to asymptomatic mumps infection based on serological examinations in this study. Serological tests for patients with sudden sensorineural hearing loss should be performed to detect mump deafness, even though the possibilities of false-positive cases and discrepancies between the results of serum- and saliva-based examinations exist [15].

This study confirmed that the majority of hearing loss due to mumps presented as unilateral profound sensorineural hearing loss, and was refractory to various treatments, such as steroids, vasodilators, vitamin B₁₂ and hyperbaric oxygen therapy. Our results concerning the hearing prognosis are consistent with those reported in the previous published literature [4–6]. Meanwhile, one patient with severe hearing loss showed improvement. Spontaneous recovery in cases with mild to moderate impairment is possible, and this can lead to some cases of hearing loss associated with mumps being overlooked [7]. A high index of suspicion for hearing loss and adequate otological examination are required.

A small portion of cases of hearing loss due to mumps appear as bilateral hearing impairment, which remarkably reduces the patients’ quality of life [4]. Noda et al. reported two cases who received cochlear implants for bilateral mumps deafness, with a good result obtained in one case. The other case, who might have had central nervous damage involvement, did not achieve good results for speech perception [16]. Lindsay et al. [17] reported degeneration of the organ of Corti and the stria vascularis in a histopathological study of mumps deafness. Westmore et al. [18] isolated mumps virus from the perilymph of a patient with sudden deafness following mumps infection. Thus, the labyrinth might be a site of lesions following mumps in the majority of patients. It is thought that patients with mumps deafness are good candidates for cochlear implantation, although central nervous damage associated with meningitis and encephalitis should be carefully evaluated. In the present study, cochlear implants were installed in four patients with bilateral total deafness patients, and good results for speech perception were observed.

In the current study, only three patients were administrated a mumps vaccine, and the majority of patients with hearing loss caused by mumps had no history of vaccination. As mentioned above, there is no effective treatment for mumps deafness and the importance of prophylaxis by vaccination should be emphasized. A report from WHO stated that the countries that have achieved high vaccine coverage have shown a rapid decline in mumps morbidity, and encephalitis and deafness associated with mumps have nearly vanished [8]. Additionally, a second dose of mumps vaccine for children is recommended to eliminate mumps infection, starting with the first dose at 12–18 months of age, and the second dose at 4–6 years of age. Although a case of sudden unilateral total loss of cochleovestibular function following administration of a mumps vaccine has been reported [19], the incidence of vaccine-induced hearing loss is considered to be lower than that from natural infection. Plotkin postulated that the absence of prophylactic vaccination against mumps is surprising for a developed country [20]. Routine vaccination against mumps should be reconsidered to reduce the incidence of mumps deafness in Japan.

In conclusion, unilateral profound sensorineural hearing loss due to mumps was found to be common and refractory to treatment. In the rare cases of bilateral total deafness, cochlear implants were beneficial for speech perception. Vaccination against mumps is safe and effective, and is recommended to prevent hearing loss associated with mumps.

Disclosure statement

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.

Additional information

Funding

This study was supported by a Health and Labour Sciences Research Grant for Comprehensive Research on Disability Health and Welfare from the Ministry of Health, Labour and Welfare, Japan (http://www.mhlw.go.jp/english/) (S. U.).