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)

Management of vestibular dysfunction and hearing loss in intralabyrinthine schwannomas.

PURPOSE: Intralabyrinthine schwannomas (ILS) are rare, benign, slow-growing tumors arising from schwann cells of the cochlear or vestibular nerves within the bony labyrinth. This study provides insight into the management of this rare tumor through a large case series. MATERIALS AND METHODS: After Institutional Review Board approval, a retrospective chart review was performed of all ILS patients treated at our institution between 2007 and 2019. RESULTS: 20 patients (9 male, 11 female) with ILS were managed at our institution. The right ear was affected in 9 patients (45%) and the left in 11 (55%). Subjective hearing loss was endorsed by all 20 patients. Average pure tone average at presentation was 72 dB nHL. Nine tumors (45%) were intravestibular, 6 (30%) were intracochlear, 4 (20%) were transmodiolar and 1 (5%) was intravestibulocochlear. Hearings aids were used in 3 patients (15%), BiCROS in 2 (10%), CI in 2 (10%), and bone conduction implant in 1 (5%). Vestibular rehabilitation was pursued in 5 patients. Surgical excision was performed for one patient (5%) via translabyrinthine approach due to intractable vertigo. No patients received radiotherapy or intratympanic gentamicin injections. CONCLUSION: ILS presents a diagnostic and management challenge given the similarity of symptoms with other disorders and limited treatment options. Hearing loss may be managed on a case-by-case basis according to patient symptoms while vestibular loss may be mitigated with vestibular therapy. Surgical excision may be considered in patients with intractable vertigo, severe hearing loss with concurrent CI placement, or in other case-by-case situations.

Adeno-associated virus gene replacement for recessive inner ear dysfunction: Progress and challenges.

Approximately 3 in 1000 children in the US under 4 years of age are affected by hearing loss. Currently, cochlear implants represent the only line of treatment for patients with severe to profound hearing loss, and there are no targeted drug or biological based therapies available. Gene replacement is a promising therapeutic approach for hereditary hearing loss, where viral vectors are used to deliver functional cDNA to "replace" defective genes in dysfunctional cells in the inner ear. Proof-of-concept studies have successfully used this approach to improve auditory function in mouse models of hereditary hearing loss, and human clinical trials are on the immediate horizon. The success of this method is ultimately determined by the underlying biology of the defective gene and design of the treatment strategy, relying on intervention before degeneration of the sensory structures occurs. A challenge will be the delivery of a corrective gene to the proper target within the therapeutic window of opportunity, which may be unique for each specific defective gene. Although rescue of pre-lingual forms of recessive deafness have been explored in animal models thus far, future identification of genes with post-lingual onset that are amenable to gene replacement holds even greater promise for treatment, since the therapeutic window is likely open for a much longer period of time. This review summarizes the current state of adeno-associated virus (AAV) gene replacement therapy for recessive hereditary hearing loss and discusses potential challenges and opportunities for translating inner ear gene replacement therapy for patients with hereditary hearing loss.

Practical aspects of inner ear gene delivery for research and clinical applications.

The application of gene therapy is widely expanding in research and continuously improving in preparation for clinical applications. The inner ear is an attractive target for gene therapy for treating environmental and genetic diseases in both the auditory and vestibular systems. With the lack of spontaneous cochlear hair cell replacement, hair cell regeneration in adult mammals is among the most important goals of gene therapy. In addition, correcting gene defects can open up a new era for treating inner ear diseases. The relative isolation and small size of the inner ear dictate local administration routes and carefully calculated small volumes of reagents. In the current review, we will cover effective timing, injection routes and types of vectors for successful gene delivery to specific target cells within the inner ear. Differences between research purposes and clinical applications are also discussed.

Children with posterior semicircular canal dehiscence: A case series.

Posterior semicircular canal dehiscence is a rare condition and can cause a variety of symptoms. We report three cases of children between 5 and 12 years of age with a PSCD. They all presented with different complaints as follows: Tullio phenomenon in the first case, conductive hearing loss in the second and, conductive hearing loss and pulsatile tinnitus in the third. Imaging showed in all cases a PSCD on the right side, caused by a prominent jugular bulb (high riding bulb). We describe the clinical, audiometric and radiological findings, and discuss the management and therapy. A conservative "wait and see" approach is recommended, especially with children, because of the possible complications of surgery and the possibility that the symptoms will lessen with the skull base osseous maturation.

Recovery of ocular and cervical vestibular evoked myogenic potentials after treatment of inner ear diseases.

Purpose: This study aimed to assess the clinical value of ocular vestibular evoked myogenic potential (oVEMP) and cervical vestibular evoked myogenic potential (cVEMP) for monitoring the rehabilitation of vestibular function in patients treated for peripheral vertigo. Materials and methods: Fifteen patients who had been diagnosed with peripheral vertigo and showed no VEMP response on the affected side but exhibited symptom alleviation and VEMP responses after therapies were retrospectively enrolled. We analyzed the restoration and parameters of their VEMP response. Results: After treatment, six patients with sudden sensorineural hearing loss showed VEMP recovery, including two with both oVEMP and cVEMP recovery, three with oVEMP recovery only, and one with cVEMP recovery only. Two patients with Meniere's disease (MD) showed cVEMP recovery, while the other three MD patients showed oVEMP recovery. Three patients with herpes zoster oticus exhibited cVEMP recovery. One patient with vestibular neuritis exhibited cVEMP recovery. Among the patients with cVEMP and/or oVEMP restoration, most patients presented normal VEMP parameters; however, some patients showed abnormal VEMP parameters after treatment. Conclusion: Combined oVEMP and cVEMP are objective tools for assessing vestibular otolithic end organ function during dynamic functional recovery from vestibular diseases.

Perilymphatic Fistulas and Superior Semi-Circular Canal Dehiscence Syndrome.

Perilymphatic fistulas (PLF) and superior semi-circular canal dehiscence syndrome (SCDS) are 2 conditions that can present with sound and/or pressure-induced vertigo. PLF should be suspected in cases of trauma or surgery, while a spontaneous PLF is a diagnosis of exclusion. Research is ongoing to identify an ideal biomarker for perilymph. The diagnosis of SCDS continues to evolve with further research into vestibular-evoked myogenic potentials, electrocochleography, and higher resolution CT imaging. Treatment advances include the transmastoid approach, smaller middle fossa craniotomies, and usage of endoscopes. Temporal bone studies have furthered the understanding of pressure dynamics within the ear and how this relates to recommendations for repair versus alternative treatments such as round window plugging.

Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches / Enfermedad inmunomediada del oído interno: diagnóstico y enfoques terapéuticos

Introduction: Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. Methods: A review of articles on IMIED from the last 10 years was conducted using PubMed(R) database. Results: IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. Conclusion: Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome

Introducción: La enfermedad inmunomediada del oído interno (EIMOI) es una forma rara de pérdida auditiva bilateral sensorineural, que progresa generalmente en semanas a meses y responde al tratamiento inmunosupresor. A pesar de los recientes avances, no hay consenso sobre el diagnóstico y el tratamiento óptimo. Métodos: Se realizó una revisión de artículos sobre la EAOI de los últimos 10 años utilizando la base de datos PubMed(R). Resultados: La EIMOI es una enfermedad rara que afecta principalmente a las mujeres de 2 a 50 años de edad. Puede ser una enfermedad del oído primaria o secundaria a una enfermedad sistémica autoinmune. Parece estar involucrada una respuesta inmune dual (tanto celular como humoral). La coclina parece ser la proteína del oído interno diana en esta enfermedad. La distinción de otras formas de pérdida de audición neurosensorial es un desafío. El examen físico es obligatorio para la exclusión de otras causas de pérdida de la audición; la audiometría identifica curvas características de pérdida de audición. Los estudios de laboratorio y de imágenes son controvertidos, ya que no hay marcador diagnóstico disponible. Conclusión: A pesar de la investigación reciente, el diagnóstico de la EAOI sigue siendo de exclusión. Los esteroides siguen siendo el pilar del tratamiento; otras terapéuticas necesitan más investigación. Para los casos refractarios, la implantación coclear es una opción con buen resultado relativo

Improved TMC1 gene therapy restores hearing and balance in mice with genetic inner ear disorders.

Fifty percent of inner ear disorders are caused by genetic mutations. To develop treatments for genetic inner ear disorders, we designed gene replacement therapies using synthetic adeno-associated viral vectors to deliver the coding sequence for Transmembrane Channel-Like (Tmc) 1 or 2 into sensory hair cells of mice with hearing and balance deficits due to mutations in Tmc1 and closely related Tmc2. Here we report restoration of function in inner and outer hair cells, enhanced hair cell survival, restoration of cochlear and vestibular function, restoration of neural responses in auditory cortex and recovery of behavioral responses to auditory and vestibular stimulation. Secondarily, we find that inner ear Tmc gene therapy restores breeding efficiency, litter survival and normal growth rates in mouse models of genetic inner ear dysfunction. Although challenges remain, the data suggest that Tmc gene therapy may be well suited for further development and perhaps translation to clinical application.

Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches.

INTRODUCTION: Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. METHODS: A review of articles on IMIED from the last 10 years was conducted using PubMed® database. RESULTS: IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. CONCLUSION: Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome.

Update on Vertigo in Autoimmune Disorders, from Diagnosis to Treatment.

The prevalence of autoimmune diseases has been increasing over the last 20 years. The clinical presentation of this large and heterogeneous group of disorders depends on whether the involvement is organ-specific or non-organ-specific. Dizziness, vertigo, and disequilibrium are common symptoms reported by patients with vestibulocochlear involvement. The association of vertigo and autoimmune diseases has been largely documented, suggesting that autoimmune disorders could be overrepresented in patients with vertigo in comparison to the general population. The aim of this review is to present the recent literature findings in the field of autoimmune-mediated diseases with cochleovestibular involvement, focusing on the clinical presentation, diagnosis, and treatment of immune-mediated inner ear diseases including autoimmune inner ear disease (AIED), Meniere's disease, and bilateral vestibulopathy, as well as of systemic autoimmune diseases with audiovestibular disorders, namely, Behçet's disease, Cogan's syndrome, sarcoidosis, autoimmune thyroid disease, Vogt-Koyanagi-Harada syndrome, relapsing polychondritis, systemic lupus erythematosus, antiphospholipid syndrome, IgG4-related disease, and ANCA-associated vasculitides.

Autoimmune Inner Ear Disease: Immune Biomarkers, Audiovestibular Aspects, and Therapeutic Modalities of Cogan's Syndrome.

Cogan's syndrome (CS) is a rare autoimmune disorder characterized by audiovestibular dysfunction and ocular inflammation. Currently, there is no specific serum autoantibody used in the diagnostic workup of CS. Treatment is based on immunosuppressive agents, mainly corticosteroids as first-line choice. Recently, novel therapeutic modalities in CS have emerged. These include tumor necrosis factor-α inhibitors and other biologicals. Despite medical treatment, hearing loss may progress to irreversible bilateral profound SNHL in approximately half of CS patients resulting in candidacy for cochlear implantation (CI). Due to the inflammatory nature of the disease that is causing endosteal reaction with partial obliteration or complete neoossification of the intracochlear ducts, early CI is recommended. CI provides excellent and stable hearing rehabilitation with high score of word and sentence recognition. In this review, we will discuss different aspects of CS including clinical presentation, diagnosis, treatment, and future directives.

Diagnosis and Treatment of Perilymphatic Fistula.

Perilymphatic fistula (PLF) is defined as an abnormal communication between the fluid (perilymph)-filled space of the inner ear and the air-filled space of the middle ear and mastoid, or cranial spaces. PLF is located in the round or oval window, fractured bony labyrinth, microfissures, anomalous footplate, and can occur after head trauma or barotrauma, chronic inflammation, or in otic capsule dehiscence. This clinical entity was initially proposed more than a century ago, yet it has remained a topic of controversy for more than 50 years. The difficulty of making a definitive diagnosis of PLF has caused a long-standing debate regarding its prevalence, natural history, management and even its very existence. In this present study, we will discuss the symptoms, physiological tests (focusing on vestibular assessment) and imaging studies. Referring to a previous criticism, we will share our classification of PLF into 4 categories. Furthermore, we will summarize a nationwide survey using a novel and widely used biomarker (Cochlin-tomoprotein [CTP]) for PLF diagnosis in Japan and present the results of the new diagnostic criteria. PLF is surgically correctable by sealing the fistula, and appropriate recognition and treatment of PLF can improve hearing and balance, and in turn, improve the quality of life of afflicted patients. Therefore, PLF is an especially important treatable disease for otologists.

Outlook and future of inner ear therapy.

Drug delivery to the inner ear is an ideal method to treat a wide variety of otologic conditions. A broad range of potential applications is just beginning to be explored. New approaches combine principles of inner ear pharmacokinetics with emerging technologies of drug delivery including novel delivery systems, drug-device combinations, and new categories of drugs. Strategies include cell-specific targeting, manipulation of gene expression, local activation following systemic delivery, and use of stem cells, viral vectors, and gene editing systems. Translation of these therapies to the clinic remains challenging given the potential risks of intracochlear and intralabyrinthine trauma, our limited understanding of the etiologies of particular inner ear disorders, and paucity of accurate diagnostic tools at the cellular level. This review provides an overview of future methods, delivery systems, disease targets, and clinical considerations required for translation to clinical medicine.

Superior semicircular canal dehiscence: Diagnosis and management.

The authors provide an update on the clinical manifestations, diagnosis and various approaches to the treatment of superior semicircular canal dehiscence (SSCD). SSCD is a rare condition where the bone overlying the superior semicircular canal thins or dehisces causing characteristic clinical findings. Since this was first reported in 1998 by Minor and colleagues, there has been much advancement made in terms of diagnosis and treatment. Signs and symptoms include a wide variation of both vestibular and auditory manifestations. Diagnosis made solely on clinical signs is difficult due to how varied the presentations can be and the overlap with other otologic pathologies. High-resolution CT temporal scans have been the standard in confirming superior semicircular canal dehiscence, however, MRI FIESTA scans have recently been used to image SSCD. Additionally, audiometry and vestibular evoked myogenic potential (VEMP) testing are useful screening tools. Currently, the middle fossa approach is the most common and standard surgical approach to repair SSCD. The transmastoid, endoscopic and transcanal or endaural approaches have also been recently utilized. Presently, there is no consensus as to the best approach, material or technique for repair of SSCD. As we learn more, newer and less invasive approaches and techniques are being used to treat SSCD. We present a comprehensive review of SSCD, including clinical symptoms and presentation, histopathology, diagnosis, treatment strategies and outcomes of intervention.

Delivery of Adeno-Associated Virus Vectors in Adult Mammalian Inner-Ear Cell Subtypes Without Auditory Dysfunction.

Hearing loss, including genetic hearing loss, is one of the most common forms of sensory deficits in humans with limited options of treatment. Adeno-associated virus (AAV)-mediated gene transfer has been shown to recover auditory functions effectively in mouse models of genetic deafness when delivered at neonatal stages. However, the mouse cochlea is still developing at those time points, whereas in humans, the newborn inner ears are already fully mature. For effective gene therapy to treat genetic deafness, it is necessary to determine whether AAV-mediated therapy can be equally effective in the fully mature mouse inner ear without causing damage to the inner ear. This study tested several AAV serotypes by canalostomy in adult mice. It is shown that most AAVs transduce the sensory inner hair cells efficiently, but are less efficient at transducing outer hair cells. A subset of AAVs also transduces non-sensory cochlear cell types. Neither the surgical procedure of canalostomy nor the AAV serotypes damage hair cells or impair normal hearing. The studies indicate that canalostomy can be a viable route for safe and efficient gene delivery, and they expand the repertoire of AAVs to target diverse cell types in the adult inner ear.

Nanomedicine for Inner Ear Diseases: A Review of Recent In Vivo Studies.

Nanoparticles are promising therapeutic options for inner ear disease. In this report, we review in vivo animal studies in the otologic field using nanoparticles over the past 5 years. Many studies have used nanoparticles to deliver drugs, genes, and growth factors, and functional and morphological changes have been observed. The constituents of nanoparticles are also diversifying into various biocompatible materials, including poly(lactic-co-glycolic acid) (PLGA). The safe and effective delivery of drugs or genes in the inner ear will be a breakthrough for the treatment of inner ear diseases, including age-related hearing loss.