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.

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.

Estudio de la audición (128-20.000 Hz) en mujeres con tiroiditis autoinmune: papel de los anticuerpos frente al déficit de hormona tiroidea / Audiological evaluation (128-20.000 Hz) in women with autoinmune thyroiditis: The role of antibodies vs. l-thyroxine deficiency

Antecedentes y objetivo: Hay muchas causas de hipoacusia neurosensorial, entre las que tiene especial interés la patología autoinmune del oído interno por su posible reversibilidad con tratamiento esteroideo, a veces asociada a enfermedades sistémicas autoinmunes. La tiroiditis crónica autoinmune o de Hashimoto (TA) presenta anticuerpos que podrían afectar al oído interno independientemente del hipotiroidismo, efecto que no ha sido suficientemente estudiado y nunca mediante audiometría con extensión en altas frecuencias.El objetivo de este trabajo es estudiar si existe afectación de los umbrales auditivos en pacientes de TA, sin hipotiroidismo, en la totalidad del espectro auditivo humano (128 Hz – 20 kHz) distribuido por grupos de edad.Materiales y métodosSe han seleccionado 128 pacientes divididos en dos grupos. El primer grupo de pacientes presenta anticuerpos antitiroideos elevados sin necesitar tratamiento sustitutivo con tiroxina. El segundo grupo con tratamiento sustitutivo con tiroxina, bien controlados. Se comparan con el grupo control (GC) de 209 pacientes. En todos se realizó historia clínica, exploración otológica, estudio de niveles de anticuerpos antitiroideos, TSH (thyroid-stimulating hormone), T3 y T4 libres, timpanograma, estudio audiométrico convencional y con extensión en altas frecuencias.ResultadosTodos los pacientes fueron mujeres. Ambos grupos mostraron peor audición que los controles, siendo la diferencia estadísticamente significativa en todas las frecuencias; en el rango de frecuencias de 8 – 20 kHz con una diferencia de más de 10 dB, y en los rangos de 9-16 kHz y de 20 kHz de más de 20 dB. (AU)

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 to 20.000 Hz) are affected in Hashimoto's disease.Materials and methodsTwo 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.ResultsAll 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 8-20 kHz frequency range this difference was more than 10 dB, and in the 9-16 kHz and 20 kHz range this difference was more than 20 dB. When separated by age groups, in younger subjects (20-29 years) these differences were found in all frequencies, except for conversational frequencies (500 - 4,000 Hz); 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. (AU)

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.

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.

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.

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.

Prevalence of presbycusis in an otologically normal population / Prevalencia de presbiacusia en una población otológicamente norma

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 (≥ 41 dB) 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

ANTECEDENTES Y OBJETIVO: La presbiacusia o pérdida auditiva relacionada con la edad, es una hipoacusia neurosensorial bilateral y simétrica asociada exclusivamente a la edad. La presbiacusia es muy relevante debido a su alta prevalencia y sus consecuencias (alteraciones en la comunicación, aislamiento social, depresión, demencia) y el impacto económico. Este es el primer trabajo que aporta datos sobre la prevalencia de la presbiacusia en una población otológicamente normal, es decir, sin enfermedad auditiva previa, exposición a ruido o sustancias potencialmente ototóxicas o pérdida de audición familiar. MATERIAL Y MÉTODOS: Un total de 4.290 sujetos de 5 a 90 años de edad fueron incluidos en el estudio. RESULTADOS: No se encontraron diferencias entre el oído derecho y el izquierdo, ni entre varones y mujeres. La presbiacusia se detectó a partir de los 60 años siguiendo la clasificación de la OMS, aunque los resultados varían dependiendo de la clasificación utilizada. Se detectó hipoacusia moderada (≥ 41dB) en la población mayor de 72 años. Ninguno de los sujetos tenía hipoacusia grave o profunda. La prevalencia de presbiacusia aumentó con la edad, siendo del 100% en individuos de 80 años o más. La prevalencia de la presbiacusia es altamente variable dependiendo de las frecuencias promediadas y del sistema de clasificación utilizado; por lo tanto, debería utilizarse un sistema de clasificación común. CONCLUSIONES: Para establecer la prevalencia de la presbiacusia se necesita una población otológicamente normal ya que, si la población no está cribada, lo que se mide es la hipoacusia que incluye todos los tipos de pérdida auditiva, pero no la presbiacusia de forma aislada

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.

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

Introducción: La sordera súbita idiopática (SSI) es aquella hipoacusia neurosensorial de inicio súbito de causa desconocida. Objetivos: Actualización del consenso sobre el diagnóstico, tratamiento y seguimiento de la SSI. Material y métodos: Presentamos una tercera actualización del consenso de SSI, mediante revisión sistemática de la literatura sobre la SSI desde 1966 hasta marzo de 2018, sobre los términos MESH "(acute or sudden) hearing loss or deafness", con 1.508 artículos relevantes. Resultados: En cuanto al diagnóstico, ante una sospecha clínica de SSI, las pruebas diagnósticas que se consideran necesarias son las siguientes: otoscopia, acumetría, audiometría tonal, audiometría verbal y timpanograma para descartar causas transmisivas de sordera. Una vez hecho el diagnóstico clínico de SSI, antes de comenzar el tratamiento, se solicitará una batería analítica. Deberá completarse más tarde el estudio con RM de oído interno, idealmente en los primeros 15 días, para descartar causas específicas de sordera súbita neurosensorial y para contribuir a elucidar posibles mecanismos fisiopatológicos. A pesar de la controversia en cuanto al tratamiento de SSI, se recomienda, por los efectos en la calidad de vida de la SSI y los raros eventos indeseables con esteroides a corto plazo, que el tratamiento de la SSI esté basado fundamentalmente en los corticoides, que pueden utilizarse por vía oral o intratimpánica, en función del paciente. En caso de fracaso de la vía sistémica, se recomienda usar corticoides intratimpánicos como rescate. Respecto al seguimiento, se realizará un control a la semana del inicio, a los 7 días y hasta los 12 meses. Conclusiones: Como consenso, el resultado de los tratamientos aplicados debería presentarse tanto en cantidad de decibelios recuperados en el umbral auditivo tonal como con parámetros de audiometría verbal

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 deafness", 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

l-Thyroxine does not prevent immunemediated sensorineural hearing loss in autoimmune thyroid diseases / l-Tiroxina no previene la hipoacusia neurosensorial inmuno-mediada en enfermedades tiroideas autoinmunes

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 10 dB 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

Objetivo: Este es el primer trabajo que trata la hipoacusia por enfermedad inmune-mediada del oído interno (IMIED) en un grupo de pacientes afectados de tiroiditis autoinmune (AITD), cuyo tratamiento requirió corticosteroides, a pesar de haber sido tratados con levotiroxina. También se presenta la inmunopatología que vincula el oído interno y la glándula tiroides. Pacientes: Se seleccionó un total de 220 pacientes con hipoacusia neurosensorial (SNHL) por causas diferentes a presbiacusia. A todos los pacientes se les realizó una audiometría, calculándose la media de tonos puros antes y después del tratamiento con corticosteroides. Resultados: Ochenta y cuatro (84) pacientes tenían SNHL de origen autoinmune, y 15 pacientes fueron diagnosticados de AITD (Enfermedad de Hashimoto). Se observó hipoacusia bilateral en 10 pacientes (66,5%). La sordera súbita fue la forma de presentación clínica más frecuente. Nueve pacientes presentaron una recuperación auditiva superior a 10 dB tras el tratamiento con corticosteroides. Conclusiones: Se piensa que el hipotiroidismo adquirido afecta a la audición por diferentes mecanismos. Aunque la terapia hormonal específica puede mejorar los trastornos auditivos periféricos o centrales asociados al hipotiroidismo, la presencia de IMIED en los pacientes de AITD requiere otro abordaje. Se ha sugerido una alteración de los mecanismos reguladores de la respuesta inmune que implica a las células de Treg y a las células CD4+CD45RO en los pacientes con AITD e IMIED. En el presente estudio, a pesar de que todos los pacientes con hipotiroidismo e hipotiroidismo subclínico estaban siendo tratados con levotiroxina, se observó hipoacusia inmuno-mediada. La terapia con corticosteroides podría lograr una recuperación auditiva. Dado que el oído interno y la glándula tiroides comparten posibles antígenos diana, destacamos la existencia de IMIED en los pacientes de AITD, y la instauración de una terapia adecuada con corticosteroides

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.

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

INTRODUCCIÓN: Los esquemas actuales de tratamiento de la hipoacusia inmunomediada con corticoides, dosis baja y pauta corta, son insuficientes. MÉTODOS: Para determinar el papel de la azatioprina en el control del deterioro auditivo se ha llevado a cabo un estudio observacional descriptivo longitudinal con 20 pacientes tratados con azatioprina por vía oral (1,5-2,5 mg/kg/día en dos dosis) durante 1año. Se consideró recaída la pérdida de 10 dB en dos frecuencias consecutivas o de 15 dB en una frecuencia aislada. RESULTADOS: La edad media de los pacientes fue de 52,50 años (IC 95%: 46,91-58,17), y la mitad fueron mujeres. La afectación bilateral fue del 65%. Un 75% presentaban enfermedad organoespecífica y un 25%, enfermedad autoinmune sistémica. La diferencia entre la PTA basal (46,49 dB; DE18,90) y la PTA a los 12meses (45,47 dB; DE 18,88) no alcanzó significación estadística (p = 0,799). Existía una correlación positiva moderada entre sexo femenino y presencia de enfermedad sistémica (R = 0,577). Aplicando t de Student para datos apareados se obtuvo una diferencia significativa (p = 0,042) entre el descenso de la PTA en frecuencias hasta 1.000Hz (PTA125-1.000Hz). La tasa relativa de incidencia de recaída por año fue de 0,52 recaídas/año (IC 95%: 0,19-1,14). El tiempo medio de supervivencia libre de recaída audiométrica fue de 9,70 meses (DE 1,03). CONCLUSIONES: La azatioprina mantiene el umbral de audición, disminuye el riesgo de recaída y frena la velocidad con la que los pacientes recaen, alterando el curso de la enfermedad inmunomediada del oído interno

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 (1.5-2.5 mg/kg/day into two doses) for 1year. The loss of 10 dB on two consecutive frequencies or 15 dB on an isolated frequency was considered as relapse. RESULTS: The mean age of the patients was 52.50 years (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 (46.49 dB; DS 18.90) and PTA at 12 months (45.47dB; DS 18.88) 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 9.70 months (DS 1.03). 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

Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides / Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids

OBJETIVO: Describir los resultados en términos de supervivencia libre de recaída audiométrica y el ritmo de recaída en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides. MÉTODO: Estudio retrospectivo de pacientes, con recaídas audiométricas, en seguimiento desde 1995 hasta 2014, en 2 centros de la Comunidad de Madrid. RESULTADOS: Se evaluaron 31 pacientes con una media de edad de 48,52 años (14,67 DE) de los cuales el 61,3% fueron mujeres. La mayoría de las hipoacusias fueron fluctuantes (48,4%). Solo el 16,1% de los pacientes presentaban enfermedad autoinmune sistémica. Existe una correlación positiva moderada entre ser mujer y presentar afectación sistémica (coeficiente de correlación de Spearman = 0,356). La tasa relativa de incidencia de recaída en el primer año en nuestra serie fue de 2,01 recaídas/año con un IC95% (1,32-2,92). El tiempo de supervivencia medio del evento (recaída audiométrica) fue de 5,25 meses (DE 0,756). Con el análisis multivariante, la única variable que consiguió significación estadística fue la edad, con una hazard ratio de 1,032 (IC95%; 1,001-1,063, p = 0,043). CONCLUSIONES: La enfermedad inmunomediada del oído interno es una enfermedad crónica con recaídas. La mitad de los pacientes tratados exclusivamente con corticoides recaen antes de los 6 meses de seguimiento. Además, si un paciente no ha presentado recaída, tiene más riesgo de recaer cada año que pasa. El análisis de la supervivencia libre de recaída audiométrica permitirá comparar el efecto de tratamientos futuros y su capacidad para reducir el ritmo de recaídas

OBJECTIVE: To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. METHOD: Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. RESULTS: We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient = 0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P = .043). CONCLUSIONS: Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses

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.

Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids. / Análisis de supervivencia libre de recaída audiométrica en pacientes con hipoacusia inmunomediada tratados exclusivamente con corticoides.

OBJECTIVE: To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. METHOD: Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. RESULTS: We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). CONCLUSIONS: Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses.

Extended high frequency audiometry can diagnose sub-clinic involvement in a seemingly normal hearing systemic lupus erythematosus population.

CONCLUSIONS: Sensorineural hearing loss must be considered within the clinical picture of systemic lupus erythematosus. The results confirm the usefulness of extended high-frequency audiometry in the audiologic testing of these patients, enabling the possibility of modifying or applying a preventive treatment for a possible hearing loss. OBJECTIVES: Hearing involvement is usually under-diagnosed with routine auditory examination. This study proposes the use of extended high-frequency audiometry to achieve a correct detection of a possible asymptomatic hypoacusis in early stages of the disease. The aim of this study is to analyze the hearing levels in extended high-frequencies in these patients and to correlate the hearing loss with the severity of the disease and the immunological parameters. METHODS: A descriptive cross-sectional study was performed. Fifty-five patients with systemic lupus erythematosus were included in the study. The control group consisted of 71 patients paired by age and sex with the study population. Both a pure tone audiometry and an extended high-frequency audiometry (8-18 KHz) were performed. RESULTS: In total, 70% were diagnosed with sensorineural hearing loss with extended high-frequency audiometry, overcoming the results obtained with pure tone audiometry (30.9%). Statistically significant correlations were found within the patients regarding sensorineural hearing loss related with age, disease activity and cryoglobulinemia.

Spontaneous Cannabinoid Receptor 2 (CB2) Expression in the Cochlea of Adult Albino Rat and Its Up-Regulation after Cisplatin Treatment.

We provide evidence for the presence of cannabinoid CB2 receptors in some cellular types of the cochlea of the adult albino rat. Cannabinoids and their receptors are increasingly being studied because of their high potential for clinical use. As a hyperspecialized portion of the peripheral nervous system, study of the expression and function of cannabinoid receptors in the hearing organ is of high interest. Stria vascularis and inner hair cells express CB2 receptor, as well as neurites and cell bodies of the spiral ganglion. Cellular types such as supporting cells and outer hair cells, in which the expression of other types of functional receptors has been reported, do not significantly express CB2 receptors in this study. An up-regulation of CB2 gene expression was detected after an ototoxic event such as cisplatin treatment, probably due to pro-inflammatory events triggered by the drug. That fact suggests promising potential of CB2 receptor as a therapeutic target for new treatments to palliate cisplatin-induced hearing loss and other ototoxic events which triggers inflammatory pathways.