Patient-Reported Outcomes After Vestibular Implantation for Bilateral Vestibular Hypofunction.

Importance: Standard-of-care treatment proves inadequate for many patients with bilateral vestibular hypofunction (BVH). Vestibular implantation is an emerging alternative. Objective: To examine patient-reported outcomes from prosthetic vestibular stimulation. Design, Setting, and Participants: The Multichannel Vestibular Implant (MVI) Early Feasibility Study is an ongoing prospective, nonrandomized, single-group, single-center cohort study conducted at Johns Hopkins Hospital that has been active since 2016 in which participants serve as their own controls. The study includes adults with severe or profound adult-onset BVH for at least 1 year and inadequate compensation despite standard-of-care treatment. As of March 2023, 12 candidates completed the eligibility screening process. Intervention: The MVI system electrically stimulates semicircular canal branches of the vestibular nerve to convey head rotation. Main Outcomes and Measures: Patient-reported outcome instruments assessing dizziness (Dizziness Handicap Inventory [DHI]) and vestibular-related disability (Vestibular Disorders-Activities of Daily Living [VADL]). Health-related quality of life (HRQOL) assessed using the Short Form-36 Utility (SF36U) and Health Utilities Index Mark 3 (HUI3), from which quality-adjusted life-years were computed. Results: Ten individuals (5 female [50%]; mean [SD] age, 58.5 [5.0] years; range, 51-66 years) underwent unilateral implantation. A control group of 10 trial applicants (5 female [50%]; mean [SD] age, 55.1 [8.5] years; range, 42-73 years) completed 6-month follow-up surveys after the initial application. After 0.5 years of continuous MVI use, a pooled mean (95% CI) of within-participant changes showed improvements in dizziness (DHI, -36; 95% CI, -55 to -18), vestibular disability (VADL, -1.7; 95% CI, -2.6 to -0.7), and HRQOL by SF36U (0.12; 95% CI, 0.07-0.17) but not HUI3 (0.02; 95% CI, -0.22 to 0.27). Improvements exceeded minimally important differences in the direction of benefit (exceeding 18, 0.65, and 0.03, respectively, for DHI, VADL, and SF36U). The control group reported no mean change in dizziness (DHI, -4; 95% CI, -10 to 2), vestibular disability (VADL, 0.1; 95% CI, -0.9 to 1.1) or HRQOL per SF36U (0; 95% CI, -0.06 to 0.05) but an increase in HRQOL per HUI3 (0.10; 95% CI, 0.04-0.16). Lifetime HRQOL gain for MVI users was estimated to be 1.7 quality-adjusted life-years (95% CI, 0.6-2.8) using SF36U and 1.4 (95% CI, -1.2 to 4.0) using HUI3. Conclusions and Relevance: This cohort study found that vestibular implant recipients report vestibular symptom improvements not reported by a control group. These patient-reported benefits support the use of vestibular implantation as a treatment for bilateral vestibular hypofunction.

Cochlear Implant Revisions Over Three Decades of Experience.

IMPORTANCE: The indications, technology, and surgical technique for cochlear implantation have evolved over the last three decades. Understanding the risk of cochlear implant revision (CIR) is important for patient counseling. OBJECTIVE: The objective of this study was to analyze the rates, indications, and audiologic outcomes for CIR over three decades of experience at a single academic medical center. DESIGN: A retrospective chart review was performed at a single academic medical center for individuals who underwent cochlear implantation between 1985 and 2022. SETTING: Single academic medical center. PARTICIPANTS: Three thousand twenty-five individuals who underwent 3,934 cochlear implant operations from 1985 to 2022. EXPOSURE: Cochlear implantation. MAIN OUTCOMES AND MEASURES: Rates, indications, risk factors, and audiologic outcomes for CIR. RESULTS: There were 276 cases of CIR after primary implantation and an overall revision rate of 7.6% (95% confidence interval, 6.8-8.5%) over 37 years of follow-up with many cases of CIR secondary to Advanced Bionics vendor B and field action failure groups. CIR rates increased sharply through the early and mid-2000s and have since remained stable. Hard or soft device failure was the most common indication for CIR, accounting for 73% of cases. Pediatric patient status and previous CIR were associated with an increased risk of CIR. Audiologic outcomes after CIR were similar to those before device failure. CONCLUSIONS AND RELEVANCE: CIR remains a common procedure most often performed for device failure. Pediatric patients and those who have undergone previous CIR are at the highest risk for future CIR. Audiologic outcomes remain stable after CIR, and these data will help providers counsel patients at the risk of future CIR and understand the risk factors associated with CIR.

Binocular 3-D otolith-ocular reflexes: responses of chinchillas to natural and prosthetic stimulation after ototoxic injury and vestibular implantation.

The otolith end organs inform the brain about gravitational and linear accelerations, driving the otolith-ocular reflex (OOR) to stabilize the eyes during translational motion (e.g., moving forward without rotating) and head tilt with respect to gravity. We previously characterized OOR responses of normal chinchillas to whole body tilt and translation and to prosthetic electrical stimulation targeting the utricle and saccule via electrodes implanted in otherwise normal ears. Here we extend that work to examine OOR responses to tilt and translation stimuli after unilateral intratympanic gentamicin injection and to natural/mechanical and prosthetic/electrical stimulation delivered separately or in combination to animals with bilateral vestibular hypofunction after right ear intratympanic gentamicin injection followed by surgical disruption of the left labyrinth at the time of electrode implantation. Unilateral intratympanic gentamicin injection decreased natural OOR response magnitude to about half of normal, without markedly changing OOR response direction or symmetry. Subsequent surgical disruption of the contralateral labyrinth at the time of electrode implantation surgery further decreased OOR magnitude during natural stimulation, consistent with bimodal-bilateral otolith end organ hypofunction (ototoxic on the right ear, surgical on the left ear). Delivery of pulse frequency- or pulse amplitude-modulated prosthetic/electrical stimulation targeting the left utricle and saccule in phase with whole body tilt and translation motion stimuli yielded responses closer to normal than the deficient OOR responses of those same animals in response to head tilt and translation alone.NEW & NOTEWORTHY Previous studies to expand the scope of prosthetic stimulation of the otolith end organs showed that selective stimulation of the utricle and saccule is possible. This article further defines those possibilities by characterizing a diseased animal model and subsequently studying its responses to electrical stimulation alone and in combination with mechanical motion. We show that we can partially restore responses to tilt and translation in animals with unilateral gentamicin ototoxic injury and contralateral surgical disruption.

Outcomes after revision of Advanced Bionics Clarion 1.2 cochlear implants.

INTRODUCTION: Cochlear implant reimplantation (CIR) for external processor upgrade or device failure is becoming increasingly common as the population of cochlear implant recipients ages. Patients with Advanced Bionics (AB) Clarion 1.2 cochlear implants may undergo CIR for device age/failure or desired technology upgrade so that they may use newer external processors that have improved connectivity features. The objective of this study was to evaluate audiologic outcomes for patients who were initially implanted with an AB Clarion 1.2 internal device and underwent CIR for technology upgrade or device failure. METHODS: Retrospective chart review was performed at a single academic medical center for patients (pediatric and adult) with an AB Clarion 1.2 internal device who underwent CIR to a later generation AB internal device and had available audiologic data. RESULTS: Forty-eight individuals with a Clarion 1.2 implant underwent CIR. Pre- and post-CIR speech understanding did not change for AzBio (p-value = 0.11, mean change = 12.1%, 95% CI = -2.9-27.2%), CNCw (p-value = 0.74, mean change = -1%, 95% CI = -10.4-12.4%), or HINT (p-value = 0.12, mean change = 19.9%, 95% CI = -2.6-42.4%) scores. Pure-tone averages improved following CIR (p-value < 0.01, mean change = 4.3 dB, 95% CI = 1.5-7.1 dB). CONCLUSIONS: Revision of AB Clarion 1.2 cochlear implants does not significantly worsen audiologic outcomes and may improve hearing in some individuals, but individual patient-level outcomes are variable.

Vestibular Implantation Can Work Even After More Than 20 Years of Bilateral Vestibular Hypofunction.

OBJECTIVE: To determine whether prosthetic stimulation delivered via a vestibular implant can elicit artificial sensation of head movement despite long (23-yr) duration adult-onset ototoxic bilateral vestibular hypofunction (BVH). STUDY DESIGN: Case report. SETTING: Tertiary care center as part of a first-in-human clinical trial. PATIENTS: One. INTERVENTIONS: Unilateral vestibular implantation with an investigational multichannel vestibular implant in a 55-year-old man with a well-documented 23-year history of aminoglycoside-induced BVH. MAIN OUTCOME MEASURES: Electrically evoked vestibulo-ocular reflexes (eeVOR). RESULTS: Vestibular implant stimulation can drive stimulus-aligned eeVOR and elicit a vestibular percept 23 years after the onset of bilateral vestibulopathy. Prosthetic stimulation targeting individual semicircular canals elicited eye movements that approximately aligned with each targeted canal's axis. The magnitude of the eeVOR response increased with increasing stimulus current amplitude. Response alignment and magnitude were similar to those observed for implant recipients who underwent vestibular implantation less than 10 years after BVH onset. Responses were approximately stable for 18 months of continuous device use (24 h/d except during sleep). CONCLUSIONS: Vestibular implantation and prosthetic electrical stimulation of semicircular canal afferent nerves can drive canal-specific eye movement responses more than 20 years after the onset of ototoxic vestibular hypofunction.

Sudden Sensorineural Hearing and Vestibular Loss in a Case of Relapsing Polychondritis.

OBJECTIVES: To report a case of profound bilateral sensorineural hearing and vestibular loss from relapsing polychondritis and hearing outcomes after cochlear implantation. METHODS: Case report and literature review. RESULTS: A 43 year-old woman developed sudden loss of hearing and balance that progressed over several weeks to bilateral, profound hearing and vestibular loss. Steroid treatments were ineffective. She underwent vestibular physical therapy and left cochlear implantation. About 10 months after her initial presentation, she developed erythema, warmth, swelling, and pain of the left auricle sparing the lobule, flattening of the bridge of her nose, and right ankle swelling, warmth, and skin erythema. A biopsy of the left auricle revealed histopathologic findings consistent with relapsing polychondritis. She was treated with high dose prednisolone. The ear inflammation resolved, however, despite excellent auditory response to pure tone thresholds, the patient reported no improvement in speech perception after cochlear implantation. CONCLUSIONS: Relapsing polychondritis can present with rapidly progressive, profound loss of hearing and vestibular function. Hearing outcomes after cochlear implantation can include poor speech discrimination despite good pure tone detection thresholds.

Continuous vestibular implant stimulation partially restores eye-stabilizing reflexes.

BACKGROUNDBilateral loss of vestibular (inner ear inertial) sensation causes chronically blurred vision during head movement, postural instability, and increased fall risk. Individuals who fail to compensate despite rehabilitation therapy have no adequate treatment options. Analogous to hearing restoration via cochlear implants, prosthetic electrical stimulation of vestibular nerve branches to encode head motion has garnered interest as a potential treatment, but prior studies in humans have not included continuous long-term stimulation or 3D binocular vestibulo-ocular reflex (VOR) oculography, without which one cannot determine whether an implant selectively stimulates the implanted ear's 3 semicircular canals.METHODSWe report binocular 3D VOR responses of 4 human subjects with ototoxic bilateral vestibular loss unilaterally implanted with a Labyrinth Devices Multichannel Vestibular Implant System vestibular implant, which provides continuous, long-term, motion-modulated prosthetic stimulation via electrodes in 3 semicircular canals.RESULTSInitiation of prosthetic stimulation evoked nystagmus that decayed within 30 minutes. Stimulation targeting 1 canal produced 3D VOR responses approximately aligned with that canal's anatomic axis. Targeting multiple canals yielded responses aligned with a vector sum of individual responses. Over 350-812 days of continuous 24 h/d use, modulated electrical stimulation produced stable VOR responses that grew with stimulus intensity and aligned approximately with any specified 3D head rotation axis.CONCLUSIONThese results demonstrate that a vestibular implant can selectively, continuously, and chronically provide artificial sensory input to all 3 implanted semicircular canals in individuals disabled by bilateral vestibular loss, driving reflexive VOR eye movements that approximately align in 3D with the head motion axis encoded by the implant.TRIAL REGISTRATIONClinicalTrials.gov: NCT02725463.FUNDINGNIH/National Institute on Deafness and Other Communication Disorders: R01DC013536 and 2T32DC000023; Labyrinth Devices, LLC; and Med-El GmbH.

Clinical and Physiologic Predictors and Postoperative Outcomes of Near Dehiscence Syndrome.

OBJECTIVE: To identify predictors of near dehiscence (ND) or thin rather than dehiscent bone overlying the superior semicircular canal in patients with signs and symptoms suggestive of superior semicircular canal dehiscence syndrome (SCDS), as well as postoperative outcomes. STUDY DESIGN: Retrospective case-control study. SETTING: Tertiary referral center. PATIENTS: All 288 patients who underwent middle cranial fossa approach for repair of SCDS (1998-2018) were reviewed for cases of ND. Demographics, symptoms, and clinical signs including nystagmus, ocular vestibular-evoked myogenic potential (oVEMP) amplitude, cervical vestibular-evoked myogenic potential (cVEMP) thresholds, and low-frequency air-bone gap were compared before and after surgery. MAIN OUTCOME MEASURE: Presence of preoperative ND and postoperative symptoms and physiologic measures. RESULTS: Seventeen cases of ND (16 patients, 17 ears) and 34 cases (34 ears) of frank SCDS were identified. ND cases differed from frank dehiscence cases in that they were less likely to have nystagmus in response to ear canal pressure or loud sounds, OR = 0.05 (95% CI 0.01-0.25) and Valsalva, OR = 0.08 (0.01-0.67), smaller peak-to-peak oVEMP amplitudes, OR = 0.84 (0.75-0.95), and higher cVEMP thresholds, OR = 1.21 (1.07-1.37). Patients with ND had similar symptoms to those with frank SCDS before surgery, and after surgery had outcomes similar to patients with frank SCDS. CONCLUSIONS: In patients with symptoms consistent with SCDS, predictors of ND include absence of nystagmus in response to pressure/loud sounds, greater cVEMP thresholds, and smaller oVEMP amplitudes. We propose ND is on a spectrum of dehiscence that partially accounts for the diversity of clinical presentations of patients with SCDS.

Bilateral vestibulopathy: Diagnostic criteria Consensus document of the Classification Committee of the Bárány Society.

This paper describes the diagnostic criteria for bilateral vestibulopathy (BVP) by the Classification Committee of the Bárány Society. The diagnosis of BVP is based on the patient history, bedside examination and laboratory evaluation. Bilateral vestibulopathy is a chronic vestibular syndrome which is characterized by unsteadiness when walking or standing, which worsen in darkness and/or on uneven ground, or during head motion. Additionally, patients may describe head or body movement-induced blurred vision or oscillopsia. There are typically no symptoms while sitting or lying down under static conditions.The diagnosis of BVP requires bilaterally significantly impaired or absent function of the vestibulo-ocular reflex (VOR). This can be diagnosed for the high frequency range of the angular VOR by the head impulse test (HIT), the video-HIT (vHIT) and the scleral coil technique and for the low frequency range by caloric testing. The moderate range can be examined by the sinusoidal or step profile rotational chair test.For the diagnosis of BVP, the horizontal angular VOR gain on both sides should be <0.6 (angular velocity 150-300°/s) and/or the sum of the maximal peak velocities of the slow phase caloric-induced nystagmus for stimulation with warm and cold water on each side <6°/s and/or the horizontal angular VOR gain <0.1 upon sinusoidal stimulation on a rotatory chair (0.1 Hz, Vmax = 50°/sec) and/or a phase lead >68 degrees (time constant of <5 seconds). For the diagnosis of probable BVP the above mentioned symptoms and a bilaterally pathological bedside HIT are required.Complementary tests that may be used but are currently not included in the definition are: a) dynamic visual acuity (a decrease of ≥0.2 logMAR is considered pathological); b) Romberg (indicating a sensory deficit of the vestibular or somatosensory system and therefore not specific); and c) abnormal cervical and ocular vestibular-evoked myogenic potentials for otolith function.At present the scientific basis for further subdivisions into subtypes of BVP is not sufficient to put forward reliable or clinically meaningful definitions. Depending on the affected anatomical structure and frequency range, different subtypes may be better identified in the future: impaired canal function in the low- or high-frequency VOR range only and/or impaired otolith function only; the latter is evidently very rare.Bilateral vestibulopathy is a clinical syndrome and, if known, the etiology (e.g., due to ototoxicity, bilateral Menière's disease, bilateral vestibular schwannoma) should be added to the diagnosis. Synonyms include bilateral vestibular failure, deficiency, areflexia, hypofunction and loss.

Rhesus Cochlear and Vestibular Functions Are Preserved After Inner Ear Injection of Saline Volume Sufficient for Gene Therapy Delivery.

Sensorineural losses of hearing and vestibular sensation due to hair cell dysfunction are among the most common disabilities. Recent preclinical research demonstrates that treatment of the inner ear with a variety of compounds, including gene therapy agents, may elicit regeneration and/or repair of hair cells in animals exposed to ototoxic medications or other insults to the inner ear. Delivery of gene therapy may also offer a means for treatment of hereditary hearing loss. However, injection of a fluid volume sufficient to deliver an adequate dose of a pharmacologic agent could, in theory, cause inner ear trauma that compromises functional outcome. The primary goal of the present study was to assess that risk in rhesus monkeys, which closely approximates humans with regard to middle and inner ear anatomy. Secondary goals were to identify the best delivery route into the primate ear from among two common surgical approaches (i.e., via an oval window stapedotomy and via the round window) and to determine the relative volumes of rhesus, rodent, and human labyrinths for extrapolation of results to other species. We measured hearing and vestibular functions before and 2, 4, and 8 weeks after unilateral injection of phosphate-buffered saline vehicle (PBSV) into the perilymphatic space of normal rhesus monkeys at volumes sufficient to deliver an atoh1 gene therapy vector. To isolate effects of injection, PBSV without vector was used. Assays included behavioral observation, auditory brainstem responses, distortion product otoacoustic emissions, and scleral coil measurement of vestibulo-ocular reflexes during whole-body rotation in darkness. Three groups (N = 3 each) were studied. Group A received a 10 µL transmastoid/trans-stapes injection via a laser stapedotomy. Group B received a 10 µL transmastoid/trans-round window injection. Group C received a 30 µL transmastoid/trans-round window injection. We also measured inner ear fluid space volume via 3D reconstruction of computed tomography (CT) images of adult C57BL6 mouse, rat, rhesus macaque, and human temporal bones (N = 3 each). Injection was well tolerated by all animals, with eight of nine exhibiting no signs of disequilibrium and one animal exhibiting transient disequilibrium that resolved spontaneously by 24 h after surgery. Physiologic results at the final, 8-week post-injection measurement showed that injection was well tolerated. Compared to its pretreatment values, no treated ear's ABR threshold had worsened by more than 5 dB at any stimulus frequency; distortion product otoacoustic emissions remained detectable above the noise floor for every treated ear (mean, SD and maximum deviation from baseline: -1.3, 9.0, and -18 dB, respectively); and no animal exhibited a reduction of more than 3 % in vestibulo-ocular reflex gain during high-acceleration, whole-body, passive yaw rotations in darkness toward the treated side. All control ears and all operated ears with definite histologic evidence of injection through the intended site showed similar findings, with intact hair cells in all five inner ear sensory epithelia and intact auditory/vestibular neurons. The relative volumes of mouse, rat, rhesus, and human inner ears as measured by CT were (mean ± SD) 2.5 ± 0.1, 5.5 ± 0.4, 59.4 ± 4.7 and 191.1 ± 4.7 µL. These results indicate that injection of PBSV at volumes sufficient for gene therapy delivery can be accomplished without destruction of inner ear structures required for hearing and vestibular sensation.

Heat pulse excitability of vestibular hair cells and afferent neurons.

In the present study we combined electrophysiology with optical heat pulse stimuli to examine thermodynamics of membrane electrical excitability in mammalian vestibular hair cells and afferent neurons. We recorded whole cell currents in mammalian type II vestibular hair cells using an excised preparation (mouse) and action potentials (APs) in afferent neurons in vivo (chinchilla) in response to optical heat pulses applied to the crista (ΔT ≈ 0.25°C per pulse). Afferent spike trains evoked by heat pulse stimuli were diverse and included asynchronous inhibition, asynchronous excitation, and/or phase-locked APs synchronized to each infrared heat pulse. Thermal responses of membrane currents responsible for APs in ganglion neurons were strictly excitatory, with Q10 ≈ 2. In contrast, hair cells responded with a mix of excitatory and inhibitory currents. Excitatory hair cell membrane currents included a thermoelectric capacitive current proportional to the rate of temperature rise (dT/dt) and an inward conduction current driven by ΔT An iberiotoxin-sensitive inhibitory conduction current was also evoked by ΔT, rising in <3 ms and decaying with a time constant of ∼24 ms. The inhibitory component dominated whole cell currents in 50% of hair cells at -68 mV and in 67% of hair cells at -60 mV. Responses were quantified and described on the basis of first principles of thermodynamics. Results identify key molecular targets underlying heat pulse excitability in vestibular sensory organs and provide quantitative methods for rational application of optical heat pulses to examine protein biophysics and manipulate cellular excitability.

Characterization of Vestibulopathy in Individuals with Type 2 Diabetes Mellitus.

OBJECTIVE: Previous observational studies suggest higher rates of vestibular dysfunction among patients with type 2 diabetes mellitus (DM) compared with those without diabetes. This study aims to functionally localize vestibular dysfunction in adults with type 2 DM. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary academic medical center. SUBJECTS AND METHODS: Adults 50 years of age and older with ≥10-year history of type 2 DM were recruited (December 2011-February 2013, n = 25). Vestibular function was assessed by cervical and ocular vestibular-evoked myogenic potentials (VEMPs), testing the saccule and utricle, respectively. Head thrust dynamic visual acuity testing assessed semicircular canal (SCC) function in all canal planes. Results were compared with nondiabetic age-matched controls (n = 25). RESULTS: Subjects were 64.7 ± 7.6 years old, were 40% female, and had a mean hemoglobin A1c of 8.3% ± 1.7%. SCC dysfunction was more common than otoconial organ dysfunction, with 70% of subjects with DM demonstrating impaired performance of at least 1 SCC (ΔlogMAR ≥0.18) and 50% demonstrating otoconial organ impairment (absent ocular VEMP and/or cervical VEMP). Adults with type 2 DM had poorer lateral and superior SCC performance (P < .05) but similar posterior SCC performance compared with controls (P = .16). Both cervical VEMP peak-to-peak amplitude and ocular VEMP n1 amplitude were also decreased with diabetes (P < .01). CONCLUSION: Adults with type 2 DM have poorer performance on tests of vestibular function related to both SCC and otoconial organ function compared with nondiabetic age-matched adults. Future studies are needed to better understand the relationship between vestibular function and functional disability in persons with diabetes.

Intraoperative neuromonitoring for superior semicircular canal dehiscence and hearing outcomes.

BACKGROUND: Recent findings in patients with superior semicircular canal dehiscence (SCD) have shown an elevated ratio of summating potential (SP) to action potential (AP), as measured by electrocochleography (ECochG). Changes in this ratio can be seen during surgical intervention. The objective of this study was to evaluate the utility of intraoperative ECochG and auditory brainstem response (ABR) as predictive tools for postoperative hearing outcomes after surgical plugging via middle cranial fossa approach for SCD syndrome (SCDS). METHODS: This was a review of 34 cases (33 patients) in which reproducible intraoperative ECochG recordings were obtained during surgery. Diagnosis of SCDS was based on history, physical examination, vestibular function testing, and computed tomography imaging. Simultaneous intraoperative ECochG and ABR were performed. Pure-tone audiometry was performed preoperatively and at least 1 month postoperatively, and air-bone gap (ABG) was calculated. Changes in SP/AP ratio, SP amplitude, and ABR wave I latency were compared with changes in pure-tone average and ABG before and after surgery. RESULTS: Median SP/AP ratio of affected ears was 0.62 (interquartile range [IQR], 0.45-0.74) and decreased immediately after surgical plugging of the affected canal to 0.42 (IQR, 0.29-0.52; p < 0.01). Contralateral SP/AP ratio before plugging was 0.33 (IQR, 0.25-0.42) and remained unchanged at the conclusion of surgery (0.30; IQR, 0.25-0.35; p = 0.32). Intraoperative changes in ABR wave I latency and SP amplitude did not predict changes in pure-tone average or ABG after surgery (p > 0.05). CONCLUSION: This study confirmed the presence of an elevated SP/AP ratio in ears with SCDS. The SP/AP ratio commonly decreases during plugging. However, an intraoperative decrease in SP/AP does not appear to be sensitive to either the beneficial decrease in ABGs or the mild high-frequency sensory loss that can occur in patients undergoing surgical plugging of the superior semicircular canal. Future work will determine the value of intraoperative ECochG in predicting changes in vestibular function.

Bilateral Vestibular Deficiency: Quality of Life and Economic Implications.

IMPORTANCE: Bilateral vestibular deficiency (BVD) causes chronic imbalance and unsteady vision and greatly increases the risk of falls; however, its effects on quality of life and economic impact are not well defined. OBJECTIVE: To quantify disease-specific and health-related quality of life, health care utilization, and economic impact on individuals with BVD in comparison with those with unilateral vestibular deficiency (UVD). DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional survey study of patients with BVD or UVD and healthy controls at an academic medical center. Vestibular dysfunction was diagnosed by means of caloric nystagmography. INTERVENTIONS: Survey questionnaire. MAIN OUTCOMES AND MEASURES: Health status was measured using the Dizziness Handicap Index (DHI) and Health Utility Index Mark 3 (HUI3). Economic burden was estimated using participant responses to questions on disease-specific health care utilization and lost productivity. RESULTS: Fifteen patients with BVD, 22 with UVD, and 23 healthy controls participated. In comparison with patients with UVD and controls, patients with BVD had significantly worse DHI (P < .001) and HUI3 scores. Statistically significant between-group differences were observed for overall HUI3 score (P < .001) and for specific attributes including vision, hearing, ambulation, emotion, and pain (P < .001 for all). Generalized linear model analysis of clinical variables associated with HUI3 scores after adjustment for other variables (including sex, race, education, age, and frequency of dizziness-related outpatient clinic visits) showed that the presence of UVD (P < .001) or BVD (P < .001), increased dizziness-related emergency room visits (P = .002), and increased dizziness-related missed work days (P < .001) were independently associated with worse HUI3 scores. Patients with BVD and UVD incurred estimated mean (range) annual economic burdens of $13,019 ($0-$48,830) and $3531 ($0-$48,442) per patient, respectively. CONCLUSIONS AND RELEVANCE: Bilateral vestibular deficiency significantly decreases quality of life and imposes substantial economic burdens on individuals and society. These results underscore the limits of adaptation and compensation in BVD. Furthermore, they quantify the potential benefits of prosthetic restoration of vestibular function both to these individuals and to society.

Prevalence and impact of bilateral vestibular hypofunction: results from the 2008 US National Health Interview Survey.

IMPORTANCE: Profound bilateral vestibular hypofunction (BVH) causes disabling oscillopsia, chronic disequilibrium, and postural instability, but little is known about its epidemiology and impact. OBJECTIVE: To assess prevalence and functional impact of BVH in the US adult population. DESIGN AND SETTING: National cross-sectional survey using a national database and corollary validation study. PATIENTS: Adult respondents to the 2008 Balance and Dizziness Supplement to the US National Health Interview Survey (N = 21 782). MAIN OUTCOMES AND MEASURES: Prevalence of BVH, socioeconomic and quality-of-life impact of BVH, and fall risk. Criteria for the survey-based diagnosis of BVH included all of the following: presence of visual blurring with head movement; unsteadiness; difficulty walking in darkness or unsteady surfaces and in a straight path; and symptoms being at least "a big problem" and present for at least 1 year, in the absence of other neurologic conditions or eye pathologic conditions affecting vision. RESULTS: Adjusted national estimates from this survey indicate the prevalence of BVH in 2008 was 28 per 100 000 US adults (64 046 Americans). Of the participants with BVH, 44% reported changing their driving habits because of their symptoms, 56% reported reduced participation in social activities, and 58% reported difficulties with activities of daily living. Respondents with BVH had a 31-fold increase in the odds of falling in multivariate analyses compared with all respondents, with 25% reporting a recent fall-related injury. CONCLUSIONS AND RELEVANCE: As estimated by the presence of specific symptoms in a nationally representative survey, BVH has considerable socioeconomic and quality-of-life impacts and significantly increases fall risk. These data support the need for new therapeutic strategies for BVH, including vestibular rehabilitation and implantable vestibular prostheses.

Near-dehiscence: clinical findings in patients with thin bone over the superior semicircular canal.

OBJECTIVE: To determine whether patients with thin bone over the superior semicircular canal can develop signs or symptoms of superior canal dehiscence syndrome (SCDS). STUDY DESIGN: Retrospective case series. SETTING: Tertiary referral center. PATIENTS: All patients from our institution found to have thin but not frankly dehiscent bone over the superior canal despite symptoms and signs of SCDS. MAIN OUTCOME MEASURES: Preoperative CT imaging, symptoms, audiometry, vestibular evoked myogenic potentials (VEMP), and intraoperative electrocochleography (ECochG) results were reviewed. Symptoms were assessed at least 1 month postoperatively in all patients, and postoperative physiologic data are presented when available. RESULTS: Ten patients (11 ears) had thin bone over the superior semicircular canal at surgery. All presented with autophony or sound- and/or pressure-induced vertigo, in addition to at least 1 physiologic measure consistent with SCDS. CT imaging was read as showing either dehiscence (36%) or marked thinning of bone overlying the affected canal (64%). Preoperative median low-frequency air-bone gap (ABG) was elevated (10.9 dB; interquartile range [IQR], 8.8-12.5), with 4 patients demonstrating negative bone conduction thresholds. Patients had elevated oVEMP amplitude (median, 20.7; IQR, 6.7-22.1) µV and ECochG SP/AP ratios (median, 0.59; IQR, 0.54-0.67). Postoperative ABG and SP/AP ratio decreased significantly compared with preoperative values (p < 0.05), and all patients reported symptomatic improvement. CONCLUSION: Symptoms typical of SCDS can occur in cases with thin but not dehiscent bone. Surgical plugging or resurfacing can reduce symptoms in such cases.

Hearing outcomes after surgical plugging of the superior semicircular canal by a middle cranial fossa approach.

OBJECTIVE: To determine postoperative hearing outcomes after surgical plugging via middle cranial fossa approach for superior semicircular canal dehiscence syndrome (SCDS). STUDY DESIGN: Clinical review. SETTING: Tertiary care medical center. PATIENTS: Forty-three cases of SCDS based on history, physical examination, vestibular function testing, and computed tomography imaging confirming the presence of a dehiscence. All patients underwent surgical plugging of the superior semicircular canal via middle cranial fossa approach. INTERVENTION: Pure tone audiometry was performed preoperatively and at 7 days and at least 1 month postoperatively. MAIN OUTCOME MEASURES: Change in air-bone gap (ABG) and pure tone average (PTA). RESULTS: Preoperative average ABG across 0.25, 0.5, 1, and 2 kHz was 16.0 dB (standard deviation [SD], 7.5 dB). At 7 days postoperatively, average ABG was 16.5 dB (SD, 11.1; p = 0.42), and at greater than 1 month was 8.1 dB (SD, 8.4; p < 0.001). 53% (95% confidence interval, 33-69) of affected ears had greater than 10 dB increase in their 4-frequency (0.5, 1, 2, and 4 kHz) PTA measured by bone-conduction (BC) threshold 7 days postoperatively and 25% (95% confidence interval, 8-39) at greater than 1 month postoperatively. Mean BC PTA of affected ears was 8.4 dB hearing loss (HL) (SD, 10.4) preoperatively. Compared with baseline, this declined to 19.2 dB HL (SD, 12.6; p < 0.001) at 7 days postoperatively and 16.4 dB HL (SD, 18.8; p = 0.01) at greater than 1 month. No significant differences in speech discrimination score were noted (F = 0.17). CONCLUSION: Low-frequency air-bone gap decreases after surgical plugging and seems to be due to both increased BC thresholds and decreased AC thresholds. Surgical plugging via a middle cranial fossa approach in SCDS is associated with mild high-frequency sensorineural hearing loss that persists in 25% but no change in speech discrimination.

Functional variants in NOS1 and NOS2A are not associated with progressive hearing loss in Ménière's disease in a European Caucasian population.

Hearing loss in Ménière's disease (MD) is associated with loss of spiral ganglion neurons and hair cells. In a guinea pig model of endolymphatic hydrops, nitric oxide synthases (NOS) and oxidative stress mediate loss of spiral ganglion neurons. To test the hypothesis that functional variants of NOS1 and NOS2A are associated with MD, we genotyped three functional variants of NOS1 (rs41279104, rs2682826, and a cytosine-adenosine microsatellite repeat in exon 1f) and the CCTTT repeat in the promoter of NOS2A gene (rs3833912) in two independent MD sets (273 patients in total) and 550 controls. A third cohort of American patients was genotyped as replication cohort for the CCTTT repeat. Neither allele nor genotype frequencies of rs41279104 and rs2682826 were associated with MD, although longer alleles of the cytosine-adenosine microsatellite repeat were marginally significant (corrected p = 0.05) in the Mediterranean cohort but not in a second Galicia cohort. Shorter numbers of the CCTTT repeat in NOS2A were significantly more frequent in Galicia controls (OR = 0.37 [CI, 0.18-0.76], corrected p = 0.04), but this finding could not be replicated in Mediterranean or American case-control populations. Meta-analysis did not support an association between CCTTT repeats and risk for MD. Severe hearing loss (>75 dB) was also not associated with any functional variants studied. Functional variants of NOS1 and NOS2A do not confer susceptibility for MD.

Complementary gain modifications of the cervico-ocular (COR) and angular vestibulo-ocular (aVOR) reflexes after canal plugging.

To determine whether the COR compensates for the loss of aVOR gain, independent of species, we studied cynomolgus and rhesus monkeys in which all six semicircular canals were plugged. Gains and phases of the aVOR and COR were determined at frequencies ranging from 0.02 to 6 Hz and fit with model-based transfer functions. Following canal plugging in a rhesus monkey, the acute stage aVOR gain was small and there were absent responses to thrusts of yaw rotation. In the chronic state, aVOR behavior was characterized by a cupula/endolymph time constant of ≈ 0.07 s, responding only to high frequencies of head rotation. COR gains were ≈ 0 before surgery but increased to ≈ 0.15 at low frequencies just after surgery; the COR gains increased to ≈ 0.4 over the next 12 weeks. Nine weeks after surgery, the summated aVOR + COR responses compensated for head velocity in space in the 0.5-3 Hz frequency range. The gains and phases continued to improve until the 35th week, where the combined aVOR + COR stabilized with gains of ≈ 0.5-0.6 and the phases were compensatory over all frequencies. Two cynomolgus monkeys operated 3-12 years earlier had similar frequency characteristics of the aVOR and COR. The combined aVOR + COR gains were ≈ 0.4-0.8 with compensatory phases. To achieve gains close to 1.0, other mechanisms may contribute to gaze compensation, especially with the head free. Thus, while there are individual variations in the time of adaptation of the gain and phase parameters, the essential functional organization of the adaption to vestibular lesions is uniform across these species.