Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

BACKGROUND: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining. AIM: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes. METHODS: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments. OUTCOMES: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement. RESULTS: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity. CLINICAL IMPLICATIONS: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging. STRENGTHS AND LIMITATIONS: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues. CONCLUSIONS: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge.

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans.

Hair cell (HC) loss by epithelial extrusion has been described to occur in the rodent vestibular system during chronic 3,3'-iminodipropionitrile (IDPN) ototoxicity. This is preceded by dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals. Here, we evaluated whether these phenomena have wider significance. First, we studied rats receiving seven different doses of streptomycin, ranging from 100 to 800 mg/kg/day, for 3-8 weeks. Streptomycin caused loss of vestibular function associated with partial loss of HCI and decreased expression of contactin-associated protein (CASPR1), denoting calyceal junction dismantlement, in the calyces encasing the surviving HCI. Additional molecular and ultrastructural data supported the conclusion that HC-calyx detachment precede HCI loss by extrusion. Animals allowed to survive after the treatment showed functional recuperation and rebuilding of the calyceal junction. Second, we evaluated human sensory epithelia obtained during therapeutic labyrinthectomies and trans-labyrinthine tumour excisions. Some samples showed abnormal CASPR1 label strongly suggestive of calyceal junction dismantlement. Therefore, reversible dismantlement of the vestibular calyceal junction may be a common response triggered by chronic stress, including ototoxic stress, before HCI loss. This may partly explain clinical observations of reversion in function loss after aminoglycoside exposure.

Resection of Intracochlear Schwannomas With Immediate Cochlear Implantation.

INTRODUCTION: Intralabyrinthine schwannomas, including the intracochlear variety, are rare benign tumors. They can cause a number of symptoms and have the potential to grow to involve other critical structures of the inner ear and skull base. While surgical resection is feasible, there is typically permanent hearing dysfunction as a result of resection and subsequent fibrosis. Here, we present 2 cases of intracochlear schwannomas (ICS) that were successfully resected with simultaneous cochlear implant placement. METHODS: Patient 1 presented with an intravestibulocochlear schwannoma. This patient underwent a translabyrinthine approach. Endoscopic assistance was used to dissect the tumor from the vestibule and basal turn of the cochlea, through an enlarged round window approach. A cochlear implant was placed via a round window cochleostomy. Patient 2 presented with an intracochlear schwannoma involving the basal and middle turns of the cochlea. The patient underwent a trans-otic approach for resection. A large portion of the cochlear promontory required unroofing for complete exposure of the tumor. A cochlear implant was then placed via a round window cochleostomy. RESULTS: Upon cochlear implant activation, Patient 1's sound field thresholds using the implant were near the normal range of hearing, ranging from 25 to 50 dB HL from 250 to 6000 Hz. Patient 2's 6-month post-operative cochlear implant sound field testing ranged from 20 to 30 dB HL from 250 to 6000 Hz and speech recognition testing revealed 59% on AZ Bio sentences compared to 0% pre-operatively. CONCLUSION: Simultaneous cochlear implantation after resection of intracochlear schwannomas is safe and successful in restoring hearing. Attention to adequate exposure and endoscopic assistance, when required, allow for gross total resection while minimizing trauma to cochlear structures. In such cases, immediate cochlear implantation allows for hearing rehabilitation before likely cochlear fibrosis can occur.

Sindrome Vestibular Agudo posterior a la infección por SARS-COV2 / Acute Vestibular Syndrome after SARS-COV2 infection

Introducción: El Sars-CoV 2 puede afectar al nervio vestibulococlear debido a su neurotropismo. Este trabajo tiene como objetivo reportar el caso de un paciente con vértigo agudo posterior a la infección por COVID-19. Materiales y Métodos: Paciente masculino de 64 años que consultó por un ataque de vértigo agudo, de predominio en el lado izquierdo, quince días después de su convalecencia por una infección por COVID-19. Se realizaron estudios neurootológicos y de resonancia magnética. Resultados: La resonancia magnética descartó la presencia de lesiones que pudieran explicar las manifestaciones clínicas. A altas frecuencias, la audiometría tonal reveló una pérdida auditiva neurosensorial en ambos lados. vHIT (video Head Impulse Test) y VEMP cervical (potenciales miogénicos evocados vestibulares) mostraron afectación del lado izquierdo. Los VEMP oculares mostraron afectación bilateral. El paciente mejoró con rehabilitación vestibular, pero las manifestaciones de vHIT persistieron a los 6 y 12 meses. Discusión: El vértigo agudo en este paciente podría haber sido el resultado de una neuronitis vestibular, secundaria a la infección previa por Sars-CoV2. Sin embargo, no se deben descartar diferentes mecanismos virales directos

: Sars-CoV 2 may affect the vestibulocochlear nerve due to its neurotropism. This work aims to report the case of a patient with acute vertigo following COVID-19 infection. Materials and Methods: A 64-year-old male patient consulted for an acute vertigo attack, predominantly to the left side, fifteen days after his convalescence due to a COVID-19 infection. Neuro-otological and MRI studies were carried out. Results: MRI ruled out the presence of lesions that could explain clinical manifestations. At high frequencies, tonal audiometry revealed a sensorineural hearing loss on both sides. vHIT (video Head Impulse Test) and cervical VEMP (Vestibular Evoked Myogenic Potentials) showed left side involvement. Ocular VEMP showed bilateral involvement. The patient improved with vestibular rehabilitation, but vHIT manifestations persisted at 6 and 12 months. Discussion: Acute vertigo in this patient might have been the result of vestibular neuronitis, secondary to the previous Sars-CoV2 infection. However, different direct viral mechanisms should not be ruled out

Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease.

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

An in vitro model to assess the peripheral vestibulotoxicity of aromatic solvents.

Epidemiological and experimental studies indicate that a number of aromatic solvents widely used in the industry can affect hearing and balance following chronic exposure. Animal studies demonstrated that long-term exposure to aromatic solvents directly damages the auditory receptor within the inner ear: the cochlea. However, no information is available on their effect on the vestibular receptor, which shares many structural features with the cochlea and is also localized in inner ear. The aim of this study was to use an in vitro approach to assess and compare the vestibular toxicity of different aromatic solvents (toluene, ethylbenzene, styrene and ortho-, meta-, para-xylene), all of which have well known cochleotoxic properties. We used a three-dimensional culture model of rat utricles ("cysts") with preserved functional sensory and secretory epithelia, and containing a potassium-rich (K+) endolymph-like fluid for this study. Variations in K+ concentrations in this model were considered as biomarkers of toxicity of the substances tested. After 72 h exposure, o-xylene, ethylbenzene and styrene decreased the K+ concentration by 78 %, 37 % and 28 %, respectively. O- xylene and styrene both caused histopathological alterations in secretory and sensory epithelial areas after 72 h exposure, whereas no anomalies were observed in ethylbenzene-exposed samples. These in vitro results suggest that some widely used aromatic solvents might have vestibulotoxic properties (o-xylene, styrene and ethylbenzene), whereas others may not (p-xylene, m-xylene, toluene). Our results also indicate that variations in endolymphatic K+ concentration may be a more sensitive marker of vestibular toxicity than histopathological events. Finally, this study suggests that cochleotoxic solvents might not be necessarily vestibulotoxic, and vice versa.

Cellular origin and response of flat epithelium in the vestibular end organs of mice to Atoh1 overexpression.

A flat epithelium (FE) may be found in the vestibular end organs of humans and mice with vestibular dysfunction. However, the pathogenesis of FE is unclear and inducing hair cell (HC) regeneration is challenging, as both HCs and supporting cells (SCs) in vestibular FE are damaged. To determine the cellular origin of vestibular FE and examine its response to Atoh1 overexpression, we fate-mapped vestibular epithelial cells in three transgenic mouse lines (vGlut3-iCreERT2:Rosa26tdTomato, GLAST-CreERT2:Rosa26tdTomato, and Plp-CreERT2:Rosa26tdTomato) after inducing a lesion by administering a high dose of streptomycin. Atoh1 overexpression in vestibular FE was mediated by an adeno-associated virus serotype 8 (AAV8) vector. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, was administered with AAV8 to enhance Atoh1 overexpression. The transduction efficiency and population of myosin VIIa-positive cells were analyzed. A small number of HCs were present in vestibular FE. FE did not show broad GLAST-Cre or Plp-Cre expression, unlike the original SCs. SAHA dramatically enhanced AAV8-mediated exogenous gene overexpression, and Atoh1 overexpression plus SAHA promoted myosin VIIa expression in FE cells. Our data provide insight into FE formation and will facilitate studies of gene therapy for vestibular FE.

c-Fos Expression after Stochastic Vestibular Stimulation and Levodopa in 6-OHDA Hemilesioned Rats.

Near threshold stochastic vestibular stimulation (SVS) enhances postural control and improves other symptoms in neurodegenerative disorders like Parkinson's disease (PD). Improvement of postural control can tentatively be explained by increased responsivity of the vestibular system, but the mechanism behind other effects of near threshold SVS, like improved motor symptoms and cognitive responsiveness in PD, are not known. To better understand the effect of vestibular stimulation on brain activity in PD, c-Fos expression was used as a marker of change in functional activity following SVS in 6-hydroxydopamine (6-OHDA) hemi-lesioned and in sham-lesioned rats. The results were compared with the effect of a single levodopa injection in 6-OHDA hemi-lesioned or saline in sham-lesioned rats. SVS was found to increase c-Fos expression more than levodopa as well as saline in the parvocellular medial vestibular nucleus (MVePC) and more in 6-OHDA hemi-lesioned than in sham-lesioned animals. Furthermore, c-Fos expression increased more in the habenula nucleus (LHb) after SVS than it did after levodopa in 6-OHDA hemilesioned animals and after saline in the sham-lesioned animals. SVS and levodopa induced similar c-Fos expression in several regions, e.g. the caudate putamen (CPu), where saline had no effect. In conclusion there was overlap between SVS-activated areas and levodopa-activated areas, but activation was more pronounced following SVS in the MVePC of 6-OHDA lesioned and in the LHb in both lesioned and sham-lesioned rats.

Density of Macrophages Immunostained With Anti-iba1 Antibody in the Vestibular Endorgans After Cochlear Implantation in the Human.

HYPOTHESIS: Cochlear implantation may result in an increase in the density of macrophages in vestibular endorgans in the human. BACKGROUND: Vestibular symptoms are a common complication of cochlear implantation. In a previous study, we demonstrated histological evidence of a foreign-body response caused by silicon and platinum in the human cochlea following cochlear implantation. The objective of the current study was to seek evidence of a possible immune response in vestibular endorgans after cochlear implantation. METHODS: The density of macrophages immunostained with anti-Iba1 antibody in the vestibular endorgans (lateral and posterior semicircular canals, utricle and saccule) in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy. The densities of macrophages in the neuroepithelium, subepithelial stroma, and among dendritic processes in the mid-stromal zone in four vestibular endorgans in the implanted and the opposite unimplanted ears were compared. The distributions of macrophage morphology (amoeboid, transitional and ramified) were also compared. RESULTS: The densities of macrophages in implanted ears in four vestibular endorgans were significantly greater than that in opposite unimplanted ears except in the subepithelial zone of the utricle and posterior semicircular canal. In contrast to the neuroepithelium, the subepithelial distribution of amoeboid macrophages in implanted ears was significantly less than in unimplanted ears. CONCLUSION: An increase in the density of macrophages in four vestibular endorgans after implantation was demonstrated. The transition among phenotype of macrophages suggested possible migration of amoeboid macrophages from the subepithelial stroma into the neuroepithelium.

A new immunohistochemical method to evaluate the development of vestibular compensation after unilateral labyrinthectomy in rats.

BACKGROUND: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC. OBJECTIVE: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC. MATERIALS AND METHODS: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL rats was used as an index. RESULTS: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL rats. CONCLUSION: These findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC.

Sensorineural Hearing Loss in Leukemia: A Case Report Showing Intravascular Coagulation in the Cochlea and Vestibular Labyrinth.

INTRODUCTION: Sensorineural hearing loss frequently has been described in patients with leukemia, and in fact, hearing loss may be the presenting symptom of this disease. However, the pathogenesis of sensorineural hearing loss in leukemia is not well understood. OBJECTIVE: To describe the temporal bone histopathology in 1 patient with leukemia and sensorineural hearing loss. METHODS: The histopathology of the temporal bones of 1 patient with chronic myelomonocytic leukemia who suffered well-documented bilateral sequential profound sensorineural hearing loss 4 months before death was investigated using light microscopy. RESULT: There was evidence of ischemic necrosis of the neuroepithelium and intravascular fibrin micro-thrombi suggestive of intravascular coagulation in the cochlea and vestibular labyrinth. CONCLUSION: Intravascular coagulation may be a contributing factor in the commonly reported finding of hemorrhage in the cochlea in leukemia and may play a role in the pathogenesis of sensorineural loss in some cases of leukemia.

Peripheral Vestibular System Histopathologic Changes following Head Injury without Temporal Bone Fracture.

OBJECTIVE: Vestibular symptoms such as dizziness and vertigo are common after head injury and may be due to trauma to the peripheral vestibular system. The pathophysiology of peripheral vestibular symptoms following head injury without temporal bone (TB) fracture, however, is not well understood. Herein, we investigate the histopathology of the peripheral vestibular system of patients who sustained head injury without a TB fracture. STUDY DESIGN: Otopathology study. SETTING: Otopathology laboratory. SUBJECTS AND METHODS: TB of subjects with a history of head injury without TB fractures were included and evaluated by light microscopy. Specimens were assessed for qualitative and quantitative characteristics, such as number of Scarpa's ganglion cells in the superior and inferior vestibular nerves, vestibular hair cell and/or dendrite degeneration in vestibular end organs, presence of vestibular hydrops, and obstruction of the endolymphatic duct. RESULTS: Five cases (n = 5 TBs) had evidence of vestibular pathology. There was a decrease of 48.6% (range, 40%-59%) in the mean count of Scarpa's ganglion cells as compared with that of normative historical age-matched controls. Moderate to severe degeneration of the vestibular membranous labyrinth was identified in the posterior, superior, and lateral canals in several cases (50%, n = 4 TBs). The maculae utriculi and sacculi showed mild to severe degeneration in 2 cases. Additional findings include vestibular hydrops (25%, n = 2 TBs) and blockage of the endolymphatic duct (n = 1 TB). CONCLUSIONS: Otopathologic analysis of patients with a history of head injury without TB fracture demonstrated peripheral vestibular otopathology. Future studies are necessary to determine if otopathology findings are directly attributable to head injury.

Assessment of a Statistical Algorithm for the Prediction of Benign Paroxysmal Positional Vertigo.

Importance: Benign paroxysmal positional vertigo (BPPV) is an otologic pathologic condition defined as a sensation of spinning triggered by changes in head position relative to gravity and caused by an entrapment of fragmented endolymph debris most commonly in the posterior semicircular canal. Confirmation of diagnosis requires experience with procedures that are poorly known by those other than practitioners with advanced otologic training. The complexity in the diagnosis of BPPV inspired the design of a questionnaire-based algorithm that would be useful for determining a vestibular diagnosis and treatment options. Objective: To assess a statistical algorithm for the diagnosis of BPPV in a busy tertiary care setting, with the long-term goal of implementing a clinical pathway to efficiently diagnose and treat patients with dizziness. Design, Setting, and Participants: In this retrospective case series, 200 patients who visited the Department of Otolaryngology-Head and Neck Surgery at Johns Hopkins University School of Medicine for their initial vertigo symptoms from September 1, 2016, to December 31, 2016, were assessed. Interventions: Use of a validated patient questionnaire as a tool to differentiate patients with dizziness in an electronic medical record review. Main Outcomes and Measures: Linear predictor (LP) value based on the questionnaire for the diagnosis of BPPV. Results: Of the 200 patient visits reviewed (132 [66%] female), 106 (53.0%; 68 [64%] female) had the information necessary to calculate the LP value and had a confirmed final diagnosis. On the basis of an LP value of 0.2 or greater, the sensitivity for a diagnosis of BPPV was 0.75 and the specificity was 1.0. The positive predictive value was 1.0, whereas the negative predictive value was 0.96. Patients with BPPV had a statistically significantly different LP value (odds ratio, 5.92; 95% CI, 2.73-12.83) than did patients without BPPV. Conclusions and Relevance: The findings of this study suggest that the algorithm is efficient for the diagnosis of BPPV in a clinical care setting.

Potenciales evocados miogénicos vestibulares con clicks y estímulos galvánicos / Vestibular evoked myogenic potentials with clicks and galvaric stimulation

El análisis del reflejo vestíbulo-cólico, que consiste en la activación de los vestibulares primarios, aporta una una valiosa información sobre la fisiología vestibular y es una herramienta útil para la evaluación de pacientes con alteraciones vestibulares. El objetivo de este trabajo es determinar las respuestas vestíbulo-cólicas mediante los estímulos con clicks de alta intensidad y mediante estímulos eléctricos transmastoideos (estimulación galvánica), establecer los valores de referencia y evaluar los parámetros según la edad. Se evaluaron a 20 personas sanas asintomáticas: en cada uno de ellos se evaluó la respuesta vestíbulo-cólica ante la estimulación con clicks, donde se registró una respuesta bifásica p13-n23 y ante la estimulación galvánica, donde se obtuvo una respuesta positivo-negativa p1-n1. Se utilizaron dos electrodos de registro, uno activo, ubicado en el tercio superior del músculo esternocleidomastoideo y otro de referencia ubicado en la unión esternoclavicular ipsilateral. Se analizaron las latencias, las amplitudes de los componentes y los índices de asimetría de amplitudes;las medianas de las latencias de los componentes p13 y n23 fueron significativamente menores que las de los componentes p1-n1; las amplitudes, tras la estimulación galvánica fueron menores que las obtenidas con clicks. Asimismo, se halló una correlación negativa entre la amplitud de la respuestas y la edad de los sujetos. El índice de asimetría de amplitudes fue similar en ambos paradigmas. El empleo de ambos tipos de estímulo es complementario para el estudio de la fisiología vestibular

The assessment of the vestibulocollic reflex consists of the activation of primary vestibular afferents; it also provides valuable information about vestibular physiology, and thus, can be used as a diagnostic tool in vestibular disorders. The aim of this research work is to evaluate this vestibule-collic response by using high intensity auditory as well as galvanic stimuli in order to provide normal referente values and search a correlation between each parameter and the age of individuals. Twenty healthy individuals of both sexes were subjetct to an assessment and after high intensity clicks a p13-n23 a response was obtained; furthermore, after galvanic stimuli a p1-n1 response was obtained. Two surface electrodes (active and reference) were used to read the responses obtained. Latency and amplitudes of p13-n23 and p1-n1 responses and asymmetry indexes were analyzed. Median latencies of p13-n23 responses were shorter than those of p1-n1 responses; and amplitudes of p1-n1 were smaller than those of p13-n23. It was observed a negative correlation between amplitudes of responses and age of the subjets. Asymmetry indexes were similar in both paradigms. The assessment of the vestibulo-collic reflex by using both clicks and galvanic stimulation gives valuable information about vestibular physiology

[Etiology analysis and vestibular assessment of bilateral vestibular vestibulopathy].

Objective:To define clinical and laboratory characteristics of bilateral vestibulopathy(BVP) and to propose diagnostic criteria of this disorder based on clinical and laboratory vestibular function test findings.Method:Forty-two case series with a clinical suspicion of BVP were retrospectively analyzed, in an attempt to determine etiology. Presenting auditory-vestibular symptoms, bedside dynamic visual acuity tests and laboratory test were reviewed, including bithermal caloric test, rotatory chair tests, video head impulse test (vHIT), vestibular-evoked myogenic potentials (VEMP).Result:Among these 42 patients, dizziness was seen in 42 cases(100%), oscillopsia was seen in 21 cases(50%), hearing loss was seen in 30(71.4%). Eight cases(19%) had tinnitus. Twenty-five cases showed vestibular loss in dynamic visual acuity test (69.4%). Definite diagnosis of complete BVP was made in 36 patients when the patients showed abnormal findings on caloric test, rotatory chair test and vHIT in addition to the symptoms. Whereas probable diagnosis of partial BVP was obtained in 6 patients with abnormal caloric test and rotatory chair test but no pathological vHIT. VEMP (ocular or cervical) could be recorded in 20 patients. Fourteen cases were caused by ototoxic drugs while no causes could be determined in 6 cases among these 42 cases.Conclusion:The diagnosis of BVP is a challenge. Vestibular laboratory test battery which reflect full frequency function of VOR has great value to confirming the diagnosis and differentiate complete BVP to partial BVP. Diagnosis standard shall be made combining clinical history, characteristic symptoms and the results of auditory-vestibular function testing. Ototoxic drugs contribute most considering etiology.

Comparison among ultrasonic, electrical apparatus, and toxic chemicals for vestibular lesion in mice.

BACKGROUND: The vestibular lesion (VL) is required to examine the physiological function of the vestibular system in animals. Toxic chemicals or electrical apparatus have been used for the VL, however, they are not ideal as they have low specificity, and can result in unintended damage, and systemic toxic effect. NEW METHOD: Localized vibration-induced VL, using an ultrasonicator, is expected to overcome the problems associated with chemical and electrical lesions. Thus, we examined the effect of the ultrasonication on the VL from the aspects of both the physiological function and histology in the present study. RESULTS: and Comparison with Existing Method(s) Complete VL, which was evaluated by deterioration of swimming skills, righting reflex, and body stability, was induced using an ultrasonicator or electrical apparatus. Histological evaluation shows that hair cell layers in the saccule and utricle were completely destroyed in both methods Furthermore, significant drop in body mass was observed in VL. However, abscess at the cranial base was observed in VL induced by the electrical apparatus in ICR mice. Complete chemically-induced VL was observed in C57BL/6J but not ICR mice, and systemic leakage of the toxic chemicals (arsenic) was not detectable even 1day after surgery. CONCLUSIONS: Compared to the electrical apparatus, the ultrasonicator is useful for inducing VL in ICR and C57BL/6J mice, as it results in less non-specific damage. Toxic chemicals can be used for inducing VL in C57BL/6J mice; however, this method does not ensure complete disruption of the hair cells in the saccule and utricle.

Local gene therapy durably restores vestibular function in a mouse model of Usher syndrome type 1G.

Our understanding of the mechanisms underlying inherited forms of inner ear deficits has considerably improved during the past 20 y, but we are still far from curative treatments. We investigated gene replacement as a strategy for restoring inner ear functions in a mouse model of Usher syndrome type 1G, characterized by congenital profound deafness and balance disorders. These mice lack the scaffold protein sans, which is involved both in the morphogenesis of the stereociliary bundle, the sensory antenna of inner ear hair cells, and in the mechanoelectrical transduction process. We show that a single delivery of the sans cDNA by the adenoassociated virus 8 to the inner ear of newborn mutant mice reestablishes the expression and targeting of the protein to the tips of stereocilia. The therapeutic gene restores the architecture and mechanosensitivity of stereociliary bundles, improves hearing thresholds, and durably rescues these mice from the balance defects. Our results open up new perspectives for efficient gene therapy of cochlear and vestibular disorders by showing that even severe dysmorphogenesis of stereociliary bundles can be corrected.

Unique Case of Hearing Recovery After Otic Capsule Destruction and Complete Sensorineural Hearing Loss Caused by Langerhans Cell Histiocytosis.

: A 14-year-old woman presented with right-sided otologic and vestibular symptoms after presenting with hormonal disturbances earlier that year. Imaging showed a gross destruction of the temporal bone, mastoid air cells, and external acoustic meatus with invasion into the otic capsule. The patient experienced complete sensorineural hearing loss in the right ear. Biopsy diagnosed Langerhans cell histiocytosis (LCH) and the patient was treated with chemotherapy. After 1 year of treatment, the patient's hearing partially recovered and imaging showed reconstitution of the temporal bone including the otic capsule. Our case is the first report of complete sensorineural hearing loss with partial recovery after LCH treatment.

[Benign paroxysmal positional vertigo: modern concepts of its etiology and pathogenesis]. / Dobrokachestvennoe paroksizmal'noe pozitsionnoe golovokruzhenie: sovremennye predstavleniia ob étiologii i patogeneze.

The objective of the present review of the literature is the analysis of the currently available data concerning etiology and pathogenesis of benign paroxysmal positional vertigo (BPPV). The special emphasis is placed on the modern hypotheses of BPPV formation that collectively account for not more than 15% of all known cases of this condition. The best explored are the following causes of benign paroxysmal positional vertigo: vestibular neuronitis, head injuries, and disorders in the middle ear. During the recent years, much attention has been given to the role of disturbances of calcium metabolism and osteoporosis in etiology of benign paroxysmal positional vertigo. It is supposed that pathogenesis of vertiginous attacks can be explained in terms of the canalolithiasis and cupulolithiasis theories.