Utility and limitations of metabolic parameters in head and neck cancer: finding a practical segmentation method.

PURPOSE: Although metabolic tumor volume (MTV) and total lesion glycolysis (TLG) have shown good prognostic value in head and neck cancer (HNC), there are still many issues to resolve before their potential application in standard clinical practice. The purpose of this study was to compare the discrimination ability of two relevant segmentation methods in HNC and to evaluate the potential benefit of adding lymph nodes' metabolism (LNM) to the measurements. METHODS: We retrospectively analyzed a recently published database of 62 patients with HNC treated with chemoradiotherapy. MTV and TLG were measured using an absolute threshold of SUV2.5. Comparison analysis with previously published background-level threshold (BLT) results was done through Concordance index (C-index) in eight prognostic models. RESULTS: BLT obtained better C-index values in five out of the eight models. The addition of LNM improved C-index values in six of the prognostic models. CONCLUSION: We found a potential benefit in adding LNM to the main tumor measurements, as well as in using a BLT for MTV segmentation compared to the most commonly used SUV2.5 threshold. Despite its limitations, this study suggests a practical and simple manner to use these parameters in standard clinical practice, aiming to help elaborate a general consensus.

Hemangiopericytoma of the parapharyngeal space: a diagnostic challenge.

Parapharyngeal space tumors are known for having a difficult approach, misleading diagnosis and for representing a treatment challenge. Hemangiopericytomas account for less than 1% of all vascular neoplasms and 3% of all soft tissue sarcomas. Only 14 cases have been reported in the worldwide literature in this location. We present a case of a 44-year-old male who was referred for evaluation. A CT scan and MRI showed a large parapharyngeal mass of a possible salivary gland origin. The patient underwent a lateral cervicotomy associated with a transparotid-transmandibular approach, obtaining a vimentin-positive immunostaining tumor defining the diagnosis. The accurate management and prognosis of this type of neoplasm are provided by the definite diagnosis obtained by a correct histopathologic assessment. A high clinical suspicion is essential.

Audiological evaluation (128-20,000Hz) in women with autoimmune thyroiditis: The role of antibodies vs. l-thyroxine deficiency.

BACKGROUND AND AIM: Although sensorineural hearing loss may have different aetiologies, we focused on autoimmune hearing loss since it may be reversible with corticosteroid therapy; this entity is sometimes associated with systemic autoimmune diseases. Hashimoto's thyroiditis or chronic autoimmune thyroiditis shows antibodies and may be harmful to hearing thresholds regardless of hypothyroidism effect. To date this effect has not been sufficiently studied and never with extended high frequencies. The aim of this work is to study by age groups whether hearing thresholds in the human auditory range (128-20,000Hz) are affected in Hashimoto's disease. MATERIALS AND METHODS: Two groups of 128 patients affected by Hashimoto's thyroiditis were included. First group: patients with pathological antithyroid antibodies who do not need L-thyroxine treatment. Second group: patients controlled with L-thyroxine substitutive treatment. Audiometric threshold study comparing between the groups of patients and a group of 209 controls was performed. All patients underwent complete otorhinolaryngological examination, antithyroid antibodies, TSH, T3 and T4 blood levels, tympanometry, conventional pure-tone audiometry, and extended-high-frequency audiometry. RESULTS: All patients were women. Both groups showed worst audiometric thresholds than the control group; both study groups showed worse hearing than controls, this difference was statistically significant in all frequencies. In the 8-20kHz frequency range, this difference was more than 10dB, and in the 9-16kHz and 20kHz range this difference was more than 20dB. When separated by age groups, in younger subjects (20-29 years) these differences were found in all frequencies, except for conversational frequencies (500-4,000Hz); between 30 and 49 years the difference is statistically significant in all frequencies; and from 50 to 69 years differences are found, especially in the conversational frequencies. CONCLUSIONS: This first work studying the human auditory range in the chronic autoimmune thyroiditis or Hashimoto's thyroiditis confirms that hearing loss related to the autoimmune disorder predominates at extended-high-frequencies initially. But ends up involving all frequencies in pure-tone conventional audiometry, then it may be detected in routine clinical tests. These results support the role of extended-high-frequencies audiometry to diagnose subclinical hearing loss in patients affected by Hashimoto's thyroiditis.

Chronic cough in post-COVID syndrome: Laryngeal electromyography findings in vagus nerve neuropathy.

BACKGROUND: Despite being a new entity, there is a large amount of information on the characteristics of SARS-CoV-2 infection and the symptoms of the acute phase; however, there are still many unknowns about the clinical features and pathophysiology of post-COVID syndrome. Refractory chronic cough is one of the most prevalent symptoms and carries both a medical problem and a social stigma. Many recent studies have highlighted the role of SARS-CoV-2 neurotropism, but no studies have demonstrated vagus nerve neuropathy as a cause of persistent chronic cough or other COVID-19 long-term effects. OBJECTIVE: The main objective was to assess the involvement of the vagus nerve neuropathy as a cause of chronic cough and other post-COVID syndrome symptoms. MATERIAL AND METHODS: This was a single-center observational study with prospective clinical data collected from 38 patients with chronic cough and post-COVID-19 syndrome. Clinical characteristics and laryngeal electromyographic findings were analyzed. RESULTS: Clinical data from 38 patients with chronic cough after 12 weeks of the acute phase of COVID-19 infection were analyzed. Of these patients, 81.6% suffered from other post-COVID conditions and, 73.6% reported fluctuating evolution of symptoms. Laryngeal electromyography (LEMG) of the thyroarytenoid (TA) muscles and cricothyroid (CT) muscles was pathological in 76.3% of the patients. Of the patients with abnormal LEMG, chronic denervation was the most frequent finding (82.8%), 10.3% presented acute denervation signs, and 6.9% presented myopathic pattern in LEMG. CONCLUSIONS: LEMG studies suggest the existence of postviral vagus nerve neuropathy after SARS-CoV-2 infection that could explain chronic cough in post-COVID syndrome.

Reactive oxygen species in apoptosis induced by cisplatin: review of physiopathological mechanisms in animal models.

Cisplatin is a highly effective chemotherapeutic agent but displays significant ototoxic side effects. The most prominent change seen in the cochlea after cisplatin administration consists of loss of outer hair cells. Several mechanisms are believed to mediate cisplatin-induced apoptosis: binding of cisplatin to guanine bases on DNA and the formation of inter- and intra-strand chain cross-linking, generation of reactive oxygen species (ROS) with increased lipid peroxidation and Ca(2+) influx and, finally, inflammation mediated by cisplatin. The aim of the present review is to analyze the role of ROS in the mechanisms causing cisplatin-mediated apoptosis in the inner ear and the contribution of the different pathways involved, emphasizing the main strategies to blockade events leading to apoptosis of cochlear cells.

Phenotypic Characterization of Laryngospasm: The Utility of Laryngeal Neurophysiological Studies.

OBJECTIVE: To determine the existence of laryngeal neuropathy and the influence of gastroesophageal reflux in patients with episodic laryngospasm. STUDY DESIGN: Single -center, observational study with prospective clinical collection. STUDY SETTING: Prospective analysis of 18 Spanish patients with episodic laryngospasm in a Spanish Public Center collected by otolaryngologist. The recruitment dates were from January 2019 to December 2019. METHODS: Data collection of 18 patients with episodic laryngospasm. Clinical characteristics, laryngeal neurophysiological studies and reflux esophageal testing were analyzed. RESULTS: All patients have a trigger for the laryngospasms, being the most prevalent adopting the supine position (27.7%). EMG and ENG were pathological in 83.3 and 63.6 % respectively. Chronic bilateral denervation (increased amplitude and duration of potentials) with signs of reinnervation in the non-active chronic phase (large polyphasia), was the most prevalent finding. Evidence of gastroesophageal reflux either by pH meter, Gastroscopy or both was found in 38.8 % of patients. CONCLUSIONS: Neurophysiological studies have confirmed the existence of laryngeal neuropathy in the majority of patients with laryngospasm. A substantial percentage of patients (38.8%) with laryngospasm had objective GERD and improved with PPIs. Laryngeal EMG and ENG can establish a more accurate diagnostic for episodic laryngospams and may supports treatment with neuromodulators.

Adding value to tumor staging in head and neck cancer: The role of metabolic parameters as prognostic factors.

BACKGROUND: Validated biomarkers in head and neck squamous cell carcinoma (HNSCC) are scarce. METHODS: We retrospectively analyzed 62 patients with HNSCC treated with radiotherapy +/- concurrent chemotherapy. Pretreatment metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were measured in a 18 F-FDG positron emission tomography using a liver dependent standardized uptake value threshold. Cox regression analyses were performed to find associations with disease-free survival (DFS) and overall survival (OS). RESULTS: High values of MTV (>37 ml) were independently associated with a worse DFS (hazard ratio [HR] = 3.45; 95% confidence interval [CI], 1.52-7.84) and OS (HR = 3.27; 95% CI, 1.41-7.57). Similar results were found for high values of TLG (>247 g) for DFS (HR = 3.32; 95% CI, 1.44-7.65) and OS (HR = 3.42; 95% CI, 1.45-8.07). CONCLUSIONS: MTV and TLG can be considered as independent prognostic factors for DFS and OS in patients with HNSCC. Considering how easily obtainable they are, they may be useful for predicting clinical outcomes in these patients.

Cerebellar gangliocytoma as a cause of fluctuating hearing loss.

Cerebellar lesions could be a cause of fluctuating hearing loss, due to the increase of intracranial pressure by partially or complete blocking of the Foramen of Luschka. Patients with intracranial hypertension may present audio-vestibular symptoms. Fluctuating sensorineural hearing loss may be the manifestation of different inner ear disorders such as Meniere's disease (MD), immune-mediated inner ear disease (IMIED), otosyphilis, and labyrinthine fistula including semicircular canal dehiscence. A rare mechanism involved in the fluctuating hearing loss is the increase in cerebrospinal fluid (CSF) pressure, that may be caused by a cerebellar tumor. A 51-year-old female presented a 2-year history of left ear fluctuating hearing loss and tinnitus, with fluctuations among the day, and normal otoscopy. Several audiometries showed a left ear moderate sensorineural hearing loss in low frequencies (Figure 1). The patient underwent a cerebral magnetic resonance imaging (MRI) (Figure 2). She was treated with three courses of systemic steroids showing improvement of symptoms during the treatment. However, the symptoms always returned when corticotherapy was interrupted. The patient was given two intratympanic steroids cycles combined with hydrochlorothiazide/ amiloride hydrochloride. The cerebral MRI described a left cerebellar focal lesion diagnosed as a cerebellar gangliocytoma. After receiving the second intratympanic steroids, cycle combined with systemic ameride showed a significant improvement of audition. Between the several causes of fluctuating hearing loss, a cerebellar gangliocytoma is a very rare disease, which needs a high degree of suspicion and otorhinolaryngologists should be familiar with this entity since patients may present with audiological and vestibular symptoms.

Prevalence of presbycusis in an otologically normal population.

OBJECTIVE: Presbycusis or age-related hearing loss is a bilaterally symmetric sensorineural hearing loss associated exclusively with age, excluding any other causes of hearing loss. Presbycusis is very relevant because of its high prevalence, and its consequences (e.g., alterations in communication, social isolation, depression, dementia), and the economic impact. This paper reports the first attempt to estimate the prevalence of presbycusis in an otologically normal population, i.e., without previous ear disease, exposure to noise, or potentially ototoxic substances, or familial hearing loss. METHODS: A total of 4290 subjects from 5 to 90 years old were included in the study. RESULTS: No statistically significant differences were found between right and left ear, nor between males and females, in any of the age groups. Presbycusis was detected over 60 years following the WHO classification; although the results vary depending on the classification used. Moderate hearing loss (≥ 41dB) was detected in the population over 72 years. None of the subjects had severe or profound hearing impairment. The prevalence of presbycusis increased with age, being 100% in individuals aged 80 years and older. The prevalence of presbycusis is highly variable depending on the pure-tone averaged frequencies and the classification system used; therefore, a common classification system should be used. CONCLUSIONS: An otologically normal population is needed to establish the prevalence of presbycusis as in non-screened populations it is the hearing level including all types of hearing loss that is measured, but not presbycusis itself.

Metabolic tumor volume and total lesion glycolysis as prognostic factors in head and neck cancer: Systematic review and meta-analysis.

The role of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) in head and neck cancer (HNC) prognosis is not well established. We conducted a systematic review focusing on MTV and TLG measured by 18 F-FDG positron-emission tomography in HNC. Meta-analyses were developed, estimating hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS). Eighteen studies were found with a total of 1512 patients. MTV-adjusted analysis had an HR of 4.65 (95% CI = 2.04-10.6) for DFS and 3.89 (95% CI = 1.47-10.30) for OS. TLG-unadjusted analysis had an HR of 3.19 (95% CI = 2.33-4.37) for DFS and 2.48 (95% CI = 1.82-3.39) for OS. TLG-adjusted analysis for DFS obtained an HR of 2.05 (95% CI = 0.96-4.39). MTV and TLG are good prognostic factors in HNC, as high values predict a worse OS and DFS. Given the important information they provide, these parameters may be considered in clinical practice, as they are easily obtainable with current technology.

[Radiological diagnostic of the non-pathological conditions of the petrous apex]. / Diagnóstico radiológico de las condiciones no patológicas del ápex petroso.

Many patients with otological symptoms are remitted to the otolaryngology outpatient clinics every day. These patients commonly undergo imaging studies, generally magnetic resonance imaging (MRI). In some cases, a positive unilateral result is found in the form of a potentially pathological signal that can be observed in the petrous apex region. We present the cases of 6 patients (aged between 26 and 62 years) with asymmetric bone marrow distribution or trapped mucous fluid secretions in the petrous apex, collected over a 6-year period. Diagnosis was made with the use of CT scans and MRI. All of the patients were referred for skull base surgery. In all cases a non-pathologic asymmetry was diagnosed in the petrous apex. Certain non-pathologic conditions of the petrous apex must be treated expectantly without any surgery.

[Designing a new tool for hearing exploration]. / Diseño de una nueva herramienta para la exploración auditiva.

INTRODUCTION: Many presbycusic patients have difficulty in understanding certain words. This could be justified because certain sounds in Spanish are more difficult to perceive, particularly the sounds with energy in the high frequencies. We propose to use a sentence as a tool to check this theory. MATERIALS AND METHOD: All the Spanish sounds were analyzed, measuring the degree of acoustic energy in all the frequencies. The conclusions drawn from the comparison of the results allowed the design of the tool that is proposed here. RESULTS: We established a gradient of perception difficulty, occlusive consonants being the least perceptible, followed by fricative, and finally all those segments with harmony and a clear formant structure. The Spanish sentence "Ana vio ese coche rojizo fino" is proposed as the tool for this study. This sentence has some as it comprises certain peculiarities that makes it particularly useful for this purpose. It will allow us to check whether understanding deteriorates as we move from beginning to end, helping evaluate the importance of high frequencies for intelligibility. CONCLUSIONS: A positive result could help in the design of amplification systems to improve speech intelligibility. In addition, the exploratory tool could allow neuro-acoustic exploration, useful in the central auditory pathology studies.

l-Thyroxine does not prevent immunemediated sensorineural hearing loss in autoimmune thyroid diseases.

OBJECTIVE: This is the first report dealing with immune-mediated inner ear disease (IMIED) hearing loss in a group of patients affected with autoimmune thyroid disease (AITD), whose treatment required corticosteroids, despite being treated with levothyroxine. Immunopathology linking the inner ear and the thyroid gland is also presented. PATIENTS: A total of 220 patients were selected with sensorineural hearing loss (SNHL) of causes other than presbycusis. Audiometry was performed and pure tone average was calculated before and after treatment with corticosteroids. RESULTS: Eighty-four (84) patients had SNHL of autoimmune origin, and 15 patients were diagnosed with AITD (Hashimoto's disease). Bilateral hearing loss was observed in 10 patients (66.5%). Sudden sensorineural hearing loss was the most frequent clinical form of presentation. Nine patients showed a hearing recovery greater than 10dB after corticosteroid treatment. CONCLUSIONS: Acquired hypothyroidism is thought to affect hearing due to different mechanisms. Although specific hormonal therapy may improve peripheral or central auditory disorders associated with hypothyroidism, the presence of IMIED in AITD patients requires another approach. Altered immune regulatory mechanisms involving Treg cells and CD4+CD45RO cells have been suggested in patients with AITD and IMIED. In the present study, although all the patients with hypothyroidism and subclinical hypothyroidism were being treated with levothyroxine, immune-mediated hearing loss was observed. Therapy with corticosteroids could achieve hearing recovery. Since inner ear and thyroid gland share possible antigen targets, we highlight the existence of IMIED in AITD patients and the importance of implementing appropriate therapy with corticosteroids.

Update on consensus on diagnosis and treatment of idiopathic sudden sensorineural hearing loss. / Actualización del consenso sobre el diagnóstico y tratamiento de la sordera súbita idiopática.

INTRODUCTION: Idiopathic sudden sensorineural hearing loss (ISSNHL) is a sudden, unexplained unilateral hearing loss. OBJECTIVES: To update the Spanish Consensus on the diagnosis, treatment and follow-up of ISSNHL. MATERIAL AND METHODS: After a systematic review of the literature from 1966 to March 2018, on MESH terms «(acute or sudden) hearing loss or deafness¼, a third update was performed, including 1508 relevant papers. RESULTS: Regarding diagnosis, 11ISSNHL is clinically suspected, the following diagnostic tests are mandatory: otoscopy, acumetry, tonal audiometry, speech audiometry, and tympanometry, to discount conductive causes. After clinical diagnosis has been established, and before treatment is started, a full analysis should be performed. An MRI should then be requested, ideally performed during the first 15 days after diagnosis, to discount specific causes and to help to understand the physiopathological mechanisms in each case. Although treatment is very controversial, due to its effect on quality of life after ISSNHL and the few rare adverse effects associated with short-term steroid treatment, this consensus recommends that all patients should be treated with steroids, orally and/or intratympanically, depending on each patient. In the event of failure of systemic steroids, intratympanic rescue is also recommended. Follow-up should be at day 7, and after 12 months. CONCLUSION: By consensus, results after treatment should be reported as absolute decibels recovered in pure tonal audiometry and as improvement in speech audiometry.

Does the serological study for viral infection in autoimmune inner ear disease make sense?

Viral infections of the labyrinth have been considered a major source of auditory and vestibular system pathology. However, the involvement of virus in the development of immune reactions responsible for immunomediated inner ear disease has not been studied enough. Following viral infection, an effector immune response, humoral (B cell) and/or cytotoxic (T cell) is directed against a virus and it might cross-react with self-protein or autoantigen, evoking an autoimmune response. Since clinically it can be very difficult to establish a viral etiology for such disorders, serologic studies can be used to confirm the suspected diagnosis. Patients affected by immunomediated inner ear disease that had presented an upper respiratory tract infection underwent an immunologic workup study including microbiological study. After the application of this diagnostic protocol, only one patient, that was subsequently diagnosed with Cogan's syndrome, showed a positive serological test for viral infection. On the basis of the low efficacy of serological testing and due to the lack of evidence, we do not recommend to carry out serologic studies for viral infection.

Adverse effects of glucocorticoid therapy for inner ear disorders.

BACKGROUND: Because of their anti-inflammatory effects and suppression of the immune system, glucocorticoids have been widely used in otolaryngologic disorders and perioperative conditions. OBJECTIVE: The objective of the present study was to determine the incidence of adverse effects after the administration of glucocorticosteroids in patients affected by diverse inner ear disorders. METHODS: One hundred and sixty-three patients affected by sudden sensorineural hearing loss, 39 with progressive sensorineural hearing loss and 16 with fluctuating sensorineural hearing loss were subjected to glucocorticosteroid therapy with 6-methylprednisolone at a starting dose of 1 mg/kg body weight per day; this therapy was tapered during the next 21-28 days. In 20 patients with profound hearing loss (>70 dB), 3 boluses of prednisolone-21-hydrogen-succinate (500 mg per day) were administered. After receiving the boluses, these patients continued with the oral 6-methylprednisolone scheme. RESULTS: Mild adverse effects were observed in 16 patients (7.01%). Only 2 patients (0.9%) with sudden sensorineural hearing loss showed severe complications: peptic ulcer and avascular necrosis of the femoral heads. CONCLUSIONS: The low percentage of severe adverse effects observed in the present study validates the use of corticosteroids for the treatment of inner ear disorders although we should not underestimate these rare complications.

[Intervention of spiral ligament fibrocytes in the metabolic regulation of the inner ear]. / Intervención de los fibrocitos del ligamento espiral en la regulación metabólica del oído interno.

Maintenance of the K(+) gradient between endolymph and perilymph is essential for normal hearing and depends primarily on the activity of the stria vascularis. Abundant Na-K-ATPase in marginal strial cells provides a pumping mechanism for preserving the K(+) level of the endolymph and consequently, the endocochlear potential. Fibrocytes in the lateral wall of the cochlea supply K(+) to the strial pump, via gap junctions, by recycling back into the stria the ions that efflux from the scala media during auditory transduction. The lateral wall of the cochlea encloses five types of fibrocytes, differentiated by their location, structural features and content of enzymes mediating or energizing ion transport. The disruption of the gap junction bonds by connexin mutations and other pathologies leads to an interruption of K(+) recirculation pathways. The expression of cochlin and otoraplin, proteins that participate in structural or regulatory functions in the inner ear, suggests more diversity and complexity of the mesenchymal tissues than envisioned previously. The presence of otospiralin, a novel protein found in fibrocytes of spiral limbus, spiral ligament and subepithelial regions of the vestibule, represent a critical finding since that protein has been shown to be essential for the survival of the hair cells and supporting cells of the inner ear. A more profound knowledge and understanding of the function of inner ear fibrocytes will provide a new and promising aetiopathogenic approach to the treatment of inner ear disorders.

[Environmental scanning electron microscopy for biofilm detection in tonsils]. / Microscopia electrónica de barrido ambiental para la detección de biopelículas en las amígdalas.

INTRODUCTION AND OBJECTIVE: To describe an environmental scanning electron microscopic method for the study of biofilms in clinical samples. A comparison with standard scanning electron microscopy is performed. PATIENTS AND METHOD: Nine patients with a past history of recurrent tonsillitis underwent tonsillectomy. Samples from each patient were obtained for both conventional and environmental scanning electron microscopy. The tonsils removed from 2 patients with sleep apnoea syndrome were used as controls. RESULTS: Eight of nine tonsils had biofilms on their surface. Scanning electron microscopy showed accumulations of bacteria covered by fibrillar structures resulting from the sample dehydration process. Environmental scanning electron microscopy provided a view of bacteria embedded in a homogeneous, amorphous substance that was preserved during the examination. CONCLUSIONS: Environmental scanning electron microscopy permits the imaging of wet systems at different degrees of dehydration. It therefore allows researchers to observe biofilms in their natural hydrated state.

[Ultra-structural study of the lateral portion of the auditory sensorial organ using a decalcification-free method]. / Estudio ultraestructural de la porción lateral del órgano sensorial auditivo mediante un método sin descalcificación.

OBJECTIVE: To explain the development of a new personal technique to study the spiral ligament and stria vascularis in Guinea pig cochleae by obtaining sample tissue without decalcification and to assess its validity for electron microscopy analysis. MATERIAL AND METHOD: Samples were taken from five female Guinea pigs weighing 200-250 g and were fixed in glutaraldehyde and paraformaldehyde for analysis of the spiral ligament and stria vascularis ultrastructure by transmission electron microscopy. RESULTS: All of the ultrastructure components in the spiral ligament and stria vascularis could be examined without the need for decalcification. CONCLUSIONS: Our method to obtain and analyze samples of cochlea side wall is valid, easy and faster.

Azathioprine reduces the risk of audiometric relapse in immune-mediated hearing loss. / La azatioprina reduce el riesgo de recaída audiométrica en hipoacusia inmunomediada.

INTRODUCTION: Current schemes for treatment of immune-mediated hearing loss with sporadic short-course, low-dose corticosteroids, are insufficient. METHODS: To determine the role of azathioprine in the control of auditory impairment, a longitudinal, observational, descriptive study was performed with 20 patients treated with azathioprine (1.5-2.5mg/kg/day into two doses) for 1year. The loss of 10dB on two consecutive frequencies or 15dB on an isolated frequency was considered as relapse. RESULTS: The mean age of the patients was 52.50years (95%CI: 46.91-58.17), half were women. Bilateral affectation was 65%. 75% had organ specific disease and 25% had systemic autoimmune disease. The difference between baseline PTA (46.49dB; DS18.90) and PTA at 12months (45.47dB; DS18.88) did not reach statistical significance (P=.799). There was a moderate positive correlation between female sex and the presence of systemic disease (R=.577). By applying Student's t for paired data, a significant difference (P=.042) was obtained between the PTA in frequencies up to 1000 Hz (PTA125-1000Hz). The relative incidence rate of relapse per year was .52 relapses/year (95%CI: .19-1.14]). The median time to audiometric relapse-free was 9.70months (DS1.03). CONCLUSIONS: Azathioprine maintains the hearing threshold, decreases the risk of relapse, and slows down the rate at which patients relapse, altering the course of immune-mediated inner ear disease.