[Research progress in targeted delivery of inner ear using nanocarriers].

Various inner ear diseases such as sensorineural deafness and Meniere's disease bring about problems such as speech communication disorders and decreased work efficiency, which seriously affect the life quality of patients. Due to the special anatomical structure and blood-labyrinth barrier in the inner ear, the current drug administration methods are often unable to achieve satisfactory results. Nanocarriers are the forefront and hot spot of nanotechnology research. In recent years, a lot of research progress has been made in the field of targeted delivery of the inner ear, which is expected to be eventually applied to the treatment of clinical diseases of the inner ear. This review focuses on the advantages, main research achievements and limitations of various nanocarriers in the targeted delivery of the inner ear, hoping to provide new ideas for related research.

A mouse model of autoimmune inner ear disease without endolymphatic hydrops.

Autoimmune inner ear disease (AIED) is an organ-specific disease characterized by irreversible, prolonged, and progressive hearing and equilibrium dysfunctions. The primary symptoms of AIED include asymmetric sensorineural hearing loss accompanied by vertigo, aural fullness, and tinnitus. AIED is divided into primary and secondary types. Research has been conducted using animal models of rheumatoid arthritis (RA), a cause of secondary AIED. However, current models are insufficient to accurately analyze vestibular function, and the mechanism underlying the onset of AIED has not yet been fully elucidated. Elucidation of the mechanism of AIED onset is urgently needed to develop effective treatments. In the present study, we analyzed the pathogenesis of vertigo in autoimmune diseases using a mouse model of type II collagen-induced RA. Auditory brain stem response analysis demonstrated that the RA mouse models exhibited hearing loss, which is the primary symptom of AIED. In addition, our vestibulo-oculomotor reflex analysis, which is an excellent vestibular function test, accurately captured vertigo symptoms in the RA mouse models. Moreover, our results revealed that the cause of hearing loss and vestibular dysfunction was not endolymphatic hydrops, but rather structural destruction of the organ of Corti and the lateral semicircular canal ampulla due to an autoimmune reaction against type II collagen. Overall, we were able to establish a mouse model of AIED without endolymphatic hydrops. Our findings will help elucidate the mechanisms of hearing loss and vertigo associated with AIED and facilitate the development of new therapeutic methods.

Intratympanic Gels for Inner Ear Disorders: A Scoping Review of Clinical Trials.

OBJECTIVE: Intratympanic injections are a safe, well tolerated procedure routinely performed by ENT's specialists. Intratympanic injections of gels have the potential to deliver therapeutics into the cochlea through the round window membrane prolonging the release of drugs in the inner ear compartment. Aim of the present review is to summarize clinical trials testing pharmacological treatments for inner ear pathologies through intratympanic gel formulations. DATA SOURCES: Online databases (Google scholar and PubMed) and registers (Clinicaltrials.gov and Euclinicaltrial) were used to identify clinical trials performed between 1990 and 2022. REVIEW METHODS: PRISMA criteria have been followed. Clinical trials testing gel formulations administered through local intratympanic injections and targeting inner ear disorders were included. All the reports were identified by the authors working in pairs sequentially selecting only studies respecting the inclusion criteria. RESULTS: A total of 45 clinical studies have been noticed; the gels for intratympanic injection are in the form of poloxamers or hyaluronic acid combinations; the trials found target different kind of inner ear disorders: acquired-stable SNHL, tinnitus, acute sudden SNHL, Meniere disease, cisplatin induced ototoxicity and hearing preservation in patients undergoing cochlear implant surgery. CONCLUSION: Few studies listed do not provide the specific kind of gel formulation used but only report the intratympanic delivery vehicle as "gel" or "thermogel". Multiple clinical studies have been targeting several forms of inner ear disorders by injecting different compounds through poloxamer and hyaluronic acid formulations. Larger and more advanced clinical stages are necessary to confirm the efficacy of these chemical compounds.

Post-operative vestibular and equilibrium evaluation in patients with cholesteatoma-induced labyrinthine fistulas.

OBJECTIVE: This study aimed to compare the pre- and post-operative vestibular and equilibrium functions of patients with cholesteatoma-induced labyrinthine fistulas who underwent different management methods. METHODS: Data from 49 patients with cholesteatoma-induced labyrinthine fistulas who underwent one of three surgical procedures were retrospectively analysed. The three management options were fistula repair, obliteration and canal occlusion. RESULTS: Patients underwent fistula repair (n = 8), canal occlusion (n = 18) or obliteration procedures (n = 23). Patients in the fistula repair and canal occlusion groups suffered from post-operative vertigo and imbalance, which persisted for longer than in those in the obliteration group. Despite receiving different management strategies, all patients achieved complete recovery of equilibrium functions through persistent efforts in rehabilitation exercises. CONCLUSION: Complete removal of the cholesteatoma matrix overlying the fistula is reliable for preventing iatrogenic hearing deterioration due to unremitting labyrinthitis. Thus, among the three fistula treatments, obliteration is the optimal method for preserving post-operative vestibular functions.

A Rare Case of Angiofibroma Presenting as an Endolymphatic Sac Tumor.

A 30-year-old man presented with minute-long episodes of vertigo and severe autophony. CVEMP showed a decreased threshold when testing the left side, potentially indicating SSCD. A subsequent MRI demonstrated a multi-lobulated, cystic mass in the temporal bone and the radiological diagnosis at that time was ELST. Tumor excision was performed, and microscopic examination of the excised material revealed fibrovascular tissue without signs of papillary or cystic projections. The conclusion of the histological assessment rendered a diagnosis of angiofibroma. We were unable to find a previous report of ENA originating around the endolymphatic sac. Laryngoscope, 134:1897-1900, 2024.

Third window lesions of the inner ear: A pictorial review.

PURPOSE: Radiographic review of pathologies that associate with third window syndrome. METHODS: Case series and literature review. RESULTS: Eight unique third window conditions are described and illustrated, including superior, lateral, and posterior semicircular canal dehiscence; carotid-cochlear, facial-cochlear, and internal auditory canal-cochlear dehiscence, labyrinthine erosion from endolymphatic sac tumor, and enlarged vestibular aqueduct. CONCLUSION: The present study highlights the characteristic imaging features and symptoms to differentiate third window pathologies for expedient diagnosis and management planning.

Intratympanic dexamethasone in Manières disease and symptom control.

BACKGROUND: Manières disease (MD) is a chronic inner ear disease characterized by recurrent vertigo and fluctuation in auditory symptoms. Vertigo spells have a sudden onset and are difficult for patients to handle. Therefore, treating a patient with MD is still a challenge for clinicians. AIMS: This study aims to analyse the short-term effects of intratympanic dexamethasone (ITD) on the various symptoms of unilateral MD. MATERIALS AND METHODS: The study comprised 27 patients with unilateral MD and severe vertigo who failed medication therapy. Treatment was with ITD as an alternative to destructive therapy. Treatment is evaluated after four months. RESULTS: Significant improvements were measured with Dizziness Handicap Inventory (DHI), Tinnitus Handicap Inventory (THI), frequency of vertigo attacks longer than 20 min, Functional Level Scale (FLS), and tinnitus sensation measured by the Analog Visual Scale (AVS). Patients with severe symptoms grading with DHI and THI experienced the most improvement. Patients have achieved substantial vertigo control in 73%. CONCLUSION: ITD application shows improvement in controlling vertigo and tinnitus in patients under exacerbation in MD. SIGNIFICANCE: It is a promising non-destructive addition to the 'stepwise treatment concept' in MD and can be used as a first-line treatment in vertigo control.

[A case report of middle ear cholesteatoma complicated with labyrinthine fistulaand delayed endolymphatic hydrops].

Delayed endolymphatic hydrops （DEH） is a rare disease that causes vertigo and is often misdiagnosed as other vertigo diseases. This article reports on a patient with vertigo who was easily misdiagnosed. The patient was a middle ear cholesteatoma complicated by labyrinthine fistula （LF）; however, his vertigo was episodic vertigo, which could not be explained solely by LF causing labyrinthitis. The possibility of endolymphatic hydrops was suspected, which was confirmed by inner ear magnetic resonance gadolinium imaging. This is the first reported case of middle ear cholesteatoma complicated by LF and DEH. The patient underwent surgical resection of the cholesteatoma and three semicircular canal obstructions at the same time. During two years postoperative follow-up, the patient did not experience a recurrence of vertigo. When diagnosing vertigo diseases, a careful history of vertigo is of utmost importance.

Comparação do nível de confiança para realização de atividades diárias pré e pós reabilitação vestibular em pacientes com disfunção vestibular / Comparison of the level of confidence to perform daily activities before and after vestibular rehabilitation in patients with vestibular dysfunction / Comparación del nivel de confianza para la realización de actividades diarias antes y después de la rehabilitación vestibular en pacientes con disfunción vestibular

Introdução: A reabilitação vestibular (RV) surge como uma opção terapêutica em casos de tontura e desequilíbrio postural. O The Activities-specific Balance Confidence Scale (ABC Scale) é um questionário utilizado para avaliar a interferência destes sintomas vestibulares por meio do nível de confiança dos indivíduos em realizar atividades diárias que envolvem o equilíbrio postural. Objetivo: comparar o nível de confiança na realização de atividades diárias relacionadas ao equilíbrio corporal, pré e pós reabilitação vestibular (RV) em pacientes com disfunção vestibular. Método: Estudo primário, intervencional, clínico, longitudinal, prospectivo, analítico, não controlado. Participaram 14 indivíduos, do sexo feminino e masculino, portadores de vestibulopatia periférica. Foi aplicado o Activities-specific Balance Confidance Scale (ABC Scale) nas condições pré e pós RV. Os dados foram analisados de forma descritiva e inferencial, pelos testes Exato de Fisher, t-Sudent e o modelo linear de efeitos mistos. Resultados: A amostra se caracterizou por 78.57% do sexo feminino e 21.43% do sexo masculino, com média de idade de 59.21 anos. Observou-se diferença estatística quando comparados os resultados do ABC Scale nas condições pré e pós RV (p<0.0001). Não foi verificada diferença estatística entre os escores deste instrumento com as variáveis sexo, idade e número de sessões terapêuticas. Conclusão: Foi possível concluir que o nível de confiança dos pacientes dessa amostra modificou de baixo, na fase pré reabilitação, para alto, na fase final da intervenção, o que consolida a ocorrência do aumento no nível de confiança que acarretou melhoria na qualidade de vida. (AU)

Introduction: Vestibular rehabilitation (VR) appears as a therapeutic option in cases of dizziness and postural imbalance. The Activities-specific Balance Confidence Scale (ABC Scale) is a questionnaire used to assess the interference of these vestibular symptoms with the individuals' level of confidence to carry out daily activities involving postural balance. Objective: to compare the level of confidence to carry out daily activities related to body balance, before and after VR, in patients with vestibular dysfunction. Method: Primary, interventional, clinical, longitudinal, prospective, analytical, and noncontrolled study. The sample comprised 14 male and female individuals with peripheral vestibulopathy. The ABC Scale was applied before and after VR. Descriptive and inferential data analysis were performed, using Fisher's Exact test, Student's t-test, and the linear mixed-effects model. Results: The sample had 78.57% females and 21.43% males, with a mean age of 59.21 years. There was a statistical difference in ABC Scale results before and after VR (p < 0.0001). There was no statistical difference between its scores and sex, age, or the number of therapy sessions. Conclusion: It was concluded that this study patients' confidence level changed from low in the pre-rehabilitation phase, to high in the final phase of the intervention, which consolidates the increase in confidence level that led to an improvement of quality of life. (AU)

Introducción: La rehabilitación vestibular (RV) aparece como una opción terapéutica en casos de mareos y desequilibrio postural. La Escala de Confianza en el Equilibrio Específica de Actividades (Escala ABC) es un cuestionario utilizado para evaluar la interferencia de estos síntomas vestibulares a través del nivel de confianza de los individuos en la realización de actividades diarias que involucran el equilibrio postural. Objetivo: comparar el nivel de confianza en la realización de actividades cotidianas relacionadas con el equilibrio corporal, pre y post rehabilitación vestibular (RV) en pacientes con disfunción vestibular. Método: Estudio primario, intervencionista, clínico, longitudinal, prospectivo, analítico, no controlado. Participaron 14 individuos, hombres y mujeres y con vestibulopatía periférica. La Escala de Confianza del Equilibrio Específica de Actividades (Escala ABC) se aplicó en condiciones previas y posteriores a la RV. Los datos fueron sometidos a análisis descriptivo e inferencial mediante la prueba exacta de Fisher, t-Sudent y el modelo lineal de efectos mixtos. Resultados: La muestra se caracterizó por 78,57% del sexo femenino y 21,43% del masculino, con una edad media de 59,21 años. Hubo diferencia estadística al comparar los resultados de la Escala ABC en condiciones pre y post RV (p<0,0001). No hubo diferencia estadística entre los puntajes de este instrumento con las variables sexo, edad y número de sesiones terapéuticas. Conclusión: Fue posible concluir que el nivel de confianza de los pacientes de esta muestra pasó de bajo, en la fase de pre-rehabilitación, a alto, en la fase final de la intervención, lo que consolida la ocurrencia del aumento en el nivel de confianza que llevó a una mejora en la calidad de vida. (AU)

A state-of-the-art analysis of pharmacological delivery and artificial intelligence techniques for inner ear disease treatment.

Over the last several decades, both the academic and therapeutic fields have seen significant progress in the delivery of drugs to the inner ear due to recent delivery methods established for the systemic administration of drugs in inner ear treatment. Novel technologies such as nanoparticles and hydrogels are being investigated, in addition to the traditional treatment methods. Intracochlear devices, which utilize current developments in microsystems technology, are on the horizon of inner ear drug delivery methods and are designed to provide medicine directly into the inner ear. These devices are used for stem cell treatment, RNA interference, and the delivery of neurotrophic factors and steroids during cochlear implantation. An in-depth analysis of artificial neural networks (ANNs) in pharmaceutical research may be found in ANNs for Drug Delivery, Design, and Disposition. This prediction tool has a great deal of promise to assist researchers in more successfully designing, developing, and delivering successful medications because of its capacity to learn and self-correct in a very complicated environment. ANN achieved a high level of accuracy exceeding 0.90, along with a sensitivity of 95% and a specificity of 100%, in accurately distinguishing illness. Additionally, the ANN model provided nearly perfect measures of 0.99%. Nanoparticles exhibit potential as a viable therapeutic approach for bacterial infections that are challenging to manage, such as otitis media. The utilization of ANNs has the potential to enhance the effectiveness of nanoparticle therapy, particularly in the realm of automated identification of otitis media. Polymeric nanoparticles have demonstrated effectiveness in the treatment of prevalent bacterial infections in pediatric patients, suggesting significant potential for forthcoming therapeutic interventions. Finally, this study is based on a research of how inner ear diseases have been treated in the last ten years (2012-2022) using machine learning.

[Method of registration of vestibular myogenic evoked potentials in the diagnosis of diseases of the inner ear]. / Metod registratsii vestibulyarnykh miogennykh vyzvannykh potentsialov v diagnostike zabolevanii vnutrennego ukha.

The literature review is devoted to the practical application of the method of recording vestibular evoked myogenic potentials (VEMPs) in the diagnosis of the inner ear diseases: superior semicircular canal dehiscence syndrome, Meniere's disease, benign paroxysmal positional vertigo (BPPV), vestibular neuritis. Registration of VMEP is an electrophysiological research method that allows to assess objectively the functional state of the otolith receptors (sacculus and utriculus) and their pathways, which expands the diagnostic capabilities in diagnosis of the inner ear diseases.

Relapsing autoimmune inner ear disease with significant response to methotrexate and azathioprine combination therapy: A case report and mini literature review.

RATIONALE: Autoimmune inner ear disease typically presents with bilateral hearing loss that progresses over weeks or months though its mechanisms are unknown. Corticosteroids are the first-line treatment, but their responses are variable and relapses are frequent. Thus, many experts have sought to replace corticosteroids with immunosuppressive agents. PATIENT CONCERNS: A 35-year-old woman experienced a progressive hearing impairment, initially on the left side and later becoming bilateral. Her response to corticosteroid monotherapy was temporary, and there have been two relapse episodes over several months. DIAGNOSES: Autoimmune inner ear disease was considered due to evidence of autoimmunity combined with a clinical course of bilateral and recurrent sensorineural hearing loss and a partial response to corticosteroid therapy. INTERVENTIONS: The patient received a 3-day mini-pulse of methylprednisolone at 250 mg/d, followed by 12 mg/d maintenance, and concurrently began an azathioprine regimen gradually increasing to 100 mg/day as a corticosteroid-sparing agent. OUTCOMES: Three weeks after immunosuppressive therapy, hearing and pure-tone audiometry improved, and after 7 weeks, methylprednisolone was tapered to 8 mg/d. The dosage was further reduced by adding methotrexate at 7.5 mg/week, resulting in a reduction to 4 mg/d as maintenance therapy after 4 weeks. LESSONS: For patients who are unresponsive to corticosteroids or experience difficulty tolerating them, a combination therapy of methotrexate and azathioprine is recommended as a viable alternative as this regimen is well-tolerated and yields positive outcomes.

[Endolymphatic sac tumor with intralabyrinthine hemorrhage: a case report].

A 27-year-old female patient suffering endolymphatic sac tumor with intralabyrinthine hemorrhage was reported. The patient had hearing loss in the left ear with continuous tinnitus, and MRI showed the soft tissue shadow of endolymphatic sac. Considering that the tumor involved semicircular canal and vestibule,endolymphatic cyst tumor resection was performed by labyrinth route. After surgery, there was no cerebrospinal fluid leakage and facial nerve function was normal. More importantly, enhanced MRI of temporal bone showed no tumor recurrence 1 year after surgery.

What is the most important factor to preserve hearing in lateral semicircular canal fistula surgeries, fistula size or bony structure?

PURPOSE: Cholesteatoma on lateral semicircular canal (LSCC) fistula > 2 mm in size is likely to be unmanipulated due to the risk of sensorineural hearing loss. However, the matrix can be successfully removed without hearing loss when it is > 2 mm. The purpose of the study was to evaluate surgical experience over the past 10 years and to suggest the important factor for the hearing preservation in LSCC fistula surgeries. METHODS: According to the fistula size and symptoms, 63 patients with LSCC fistula were grouped as follows: Type I (fistula < 2 mm), Type II (≥ 2 mm and < 4 mm without vertigo), Type III (≥ 2 mm and < 4 mm with vertigo), Type IV (≥ 4 mm), and Type V (any size fistula but with deafness at the initial visit). The cholesteatoma matrix was meticulously manipulated and removed by experienced surgeons. RESULTS: Only two patients completely lost their hearing after surgery (4.5%). However, the loss was inevitable because their cholesteatomas were highly invasive and there was also facial nerve canal involvement; thus, the bony structure of the LSCC was already destroyed by the cholesteatoma. Unlike these two Type IV patients, Type I-III patients, and those with a fistula size < 4 mm, did not lose their sensorineural hearing. If the structure of the LSCC was maintained, hearing loss did not occur even if the fistula size ≥ 4 mm. CONCLUSIONS: The preservation of the labyrinthine structure is more important than the defect size of the LSCC fistula. If the structure is intact, cholesteatoma matrices lying on the defect can be safely removed, even though the size of bony defect is large.

Prevalence of immune-mediated inner ear disease in non-segmental vitiligo: A cross-sectional study.

BACKGROUND: Sensorineural hearing loss (SNHL) is associated with non-segmental vitiligo (NSV); however, the aetiology of SNHL has not been explored. The concomitance of autoimmune disease in vitiligo patients demands the investigation of immune-mediated inner ear disease (IMIED) as a cause of SNHL in NSV. The anti-Hsp70 antibody is a serological marker of IMIED, which may help in the early diagnosis of this disease. OBJECTIVE: To evaluate the prevalence of IMIED in NSV patients. METHODS: Cross-sectional study involving NSV adult patients and a control group, evaluated through audiometry and serological dosage of the anti-Hsp70 antibody. RESULTS: In total, 112 cases and 23 controls were evaluated. Bilateral SNHL was found in 28 (25.0%; 95%CI 17.9%-32.1%) patients and in 1 (4.3%) control (p = 0.019). Six cases (5.4%; 95%CI 2.7%-8.0%) presented bilateral SNHL of unexplained aetiology, and anti-Hsp70 antibody positivity, fulfilling the diagnostic criteria for IMIED. No controls met the diagnostic criteria for IMIED. Serum anti-Hsp70 antibodies were higher in cases with IMIED: median 220.9 vs. 85.1 ng/ml (p = 0.001). CONCLUSION: The prevalence of IMIED is remarkable in NSV adult patients.