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.

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.

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.

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.

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.

Examination of Hearing in a Rheumatoid Arthritis Population: Role of Extended-High-Frequency Audiometry in the Diagnosis of Subclinical Involvement.

Objective. The aim of this study is to analyze the high-frequency hearing levels in patients with rheumatoid arthritis and to determine the relationship between hearing loss, disease duration, and immunological parameters. Materials and Methods. A descriptive cross-sectional study including fifty-three patients with rheumatoid arthritis was performed. The control group consisted of 71 age- and sex-matched patients from the study population (consecutively recruited in Madrid "Area 9," from January 2010 to February 2011). Both a pure tone audiometry and an extended-high-frequency audiometry were performed. Results. Extended-high-frequency audiometry diagnosed sensorineural hearing loss in 69.8% of the patients which exceeded the results obtained with pure tone audiometry (43% of the patients). This study found significant correlations in patients with sensorineural hearing loss related to age, sex, and serum anti-cardiolipin (aCL) antibody levels. Conclusion. Sensorineural hearing loss must be considered within the clinical context of rheumatoid arthritis. Our results demonstrated that an extended-high-frequency audiometry is a useful audiological test that must be performed within the diagnostic and follow-up testing of patients with rheumatoid arthritis, providing further insight into a disease-modifying treatment or a hearing loss preventive treatment.

Sudden hearing loss: National survey in Spain.

INTRODUCTION: The objective of our study was to identify the diagnostic and therapeutic approaches in the different ENT Departments of Spain with respect to sudden deafness. We wanted to establish a basis to help to create a new nation-wide consensus, unifying treatment, diagnostic and follow-up criteria for this disease. METHODS: We carried out an anonymous Internet survey, addressing Spanish ENT doctors nation-wide (n=2,029), gathering in 33 questions different aspects about diagnostic criteria, additional tests, treatment procedures and prognostic factors in sudden deafness, according to the different protocols and experience of the participants in the survey. RESULTS: A total of 293 Spanish ENT doctors (14%) took part anonymously. In relation to diagnostic criteria, is the most noteworthy was the requisite of a confirmed neurosensorial loss (91.1%) followed by "initiated in less than three days" (75%) and 3 consecutive frequencies affected (76.4%). More than half of the participants requested an MRI of the IAC/CPA (68.7%) and 88.2% used gadolinium in this test. The prognostic factor most frequently considered was delay in commencement of treatment onset (84.8%). As far as treatment of primary cases, most of the responders agreed on the use of corticosteroids (99.7%). Oral administration was the most widely used (66%), followed by intravenous (29.6%) and intratympanic (1.4%) administration. Ninety-two percent had not had any major complications with systemic steroids. Intratympanic treatments were used by 70% of responders for rescue in failure. CONCLUSIONS: In Spain there is currently a significant disparity of concepts regarding the diagnosis of sudden deafness, and more agreement as to using steroids as their treatment. This highlights the need to implement measures to promote a better approach, which would be homogeneous and consensual, to this condition.

Promising Technique for Facial Nerve Reconstruction in Extended Parotidectomy.

INTRODUCTION: Malignant tumors of the parotid gland account scarcely for 5% of all head and neck tumors. Most of these neoplasms have a high tendency for recurrence, local infiltration, perineural extension, and metastasis. Although uncommon, these malignant tumors require complex surgical treatment sometimes involving a total parotidectomy including a complete facial nerve resection. Severe functional and aesthetic facial defects are the result of a complete sacrifice or injury to isolated branches becoming an uncomfortable distress for patients and a major challenge for reconstructive surgeons. CASE REPORT: A case of a 54-year-old, systemically healthy male patient with a 4 month complaint of pain and swelling on the right side of the face is presented. The patient reported a rapid increase in the size of the lesion over the past 2 months. Imaging tests and histopathological analysis reported an adenoid cystic carcinoma. A complete parotidectomy was carried out with an intraoperative notice of facial nerve infiltration requiring a second intervention for nerve and defect reconstruction. A free ALT flap with vascularized nerve grafts was the surgical choice. A 6 month follow-up showed partial facial movement recovery and the facial defect mended. CONCLUSION: It is of critical importance to restore function to patients with facial nerve injury. Vascularized nerve grafts, in many clinical and experimental studies, have shown to result in better nerve regeneration than conventional non-vascularized nerve grafts. Nevertheless, there are factors that may affect the degree, speed and regeneration rate regarding the free fasciocutaneous flap. In complex head and neck defects following a total parotidectomy, the extended free fasciocutaneous ALT (anterior-lateral thigh) flap with a vascularized nerve graft is ideally suited for the reconstruction of the injured site. Donor-site morbidity is low and additional surgical time is minimal compared with the time of a single ALT flap transfer.

New prospects in the diagnosis and treatment of immune-mediated inner ear disease.

Autoimmune inner ear disease (AIED) represents a very fertile research field and the advancements in the understanding of this disease have a direct application not only in patients affected with this condition but also in other inner ear disorders that share the same injury mechanism, damage to the inner ear hair cells. AIED also presents many challenges that have still to be overcome. Firstly, access to the inner ear is limited, as many interventions such as biopsies can result in great irreversible damage. Secondly, there are no completely specific markers for AIED. Lack of a definitive diagnosis can result in the treatment of patients not affected with the disease and, therefore, no response. Finally, some patients become refractory to glucocorticoids and new therapies are needed. This review offers an overview of the animal models that have contributed to the understanding of AIED pathophysiology, the value of currently available diagnostic tests, and therapeutic options, with a special focus on new therapies for non responders or patients refractory to glucocorticoids. Among these new options for therapy, biological agents have been tested recently, whereas gene and stem cell therapy may have a role in the future. The intratympanic route of administration avoids the systemic side effects associated with currently used drugs, and may become a more frequent approach in the future.

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.

Patient-derived olfactory mucosa cells but not lung or skin fibroblasts mediate axonal regeneration of retinal ganglion neurons.

Although human olfactory mucosa derived cells (OMC) have been used in animal models and clinical trials with CNS repair purposes, the exact identity of these cells in culture with respect to their tissue of origin is not fully understood and their neuroregenerative capacity in vitro has not yet been demonstrated. In this study we have compared human OMC with human ensheathing glia from olfactory bulb (OB) and human fibroblasts from skin and lung. Our results indicate that these different cultured cell types exhibit considerable overlap of antigenic markers such that it is presently not possible to distinguish them immunocytochemically. However, in rat retinal ganglion neuron coculture assays the axonal regenerative activity of OMC and OB ensheathing glia was dramatically higher than that exhibited by all fibroblast samples, confirming neuroregenerative activity as a unique property shared by cultured cells derived from the human olfactory system.