Natural History of Untreated Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: Although corticosteroids and other treatments for idiopathic sudden sensorineural hearing loss (ISSNHL) have been described, understanding its prognosis without intervention provides valuable information for patient management. The objective of this study is to provide a comprehensive, quantitative statistical analysis of the natural history of untreated idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY TYPE AND DESIGN: A systematic review and meta-analyses. METHODS: Two independent searches of PubMed, Scopus, Web of Science, and Cochrane Library databases up to June 30, 2022, were performed. Adults with idiopathic sudden sensorineural hearing loss who received placebo or were untreated and had audiometric outcome measures in all study types were reviewed. These data indicative of the natural history of ISSNHL were analyzed, as were study characteristics related to risk of bias. Heterogeneity as assessed via I2 and random effects analyses were performed. RESULTS: Six studies meeting the inclusion criteria yielded 319 untreated patients whose natural history could be assessed. Heterogeneity among studies was moderate, with a variety of reported outcomes. A hearing improvement of at least 30 dB HL was observed in 36% (95% CI 0.28-0.44) of untreated patients, and of at least 10 dB HL was observed in 70% (95% CI 0.57-0.82) of untreated patients at 3 months. The mean hearing gain among untreated patients was 24.0 dB HL (95% CI 2.65-45.37) at 2-3 months. CONCLUSIONS: The observed natural history of ISSNHL suggests that patients can regain some hearing without active treatment. In the absence of future studies collecting prospective natural history data from untreated or placebo-treated ISSNHL patients, the data presented here provide the best available historical control data for reconsideration of results in past ISSNHL studies, as well as a roadmap for design and interpretation of future ISSNHL treatment clinical trials. Furthermore, knowing there is a statistically significant mean hearing gain of 24.0 dB HL in the untreated/placebo group provides an ethical basis for future placebo study of ISSNHL. The current status on ISSNHL management calls for a multi-institutional, randomized, double-blind placebo-controlled trial with validated outcome measures to provide science-based treatment guidance. Laryngoscope, 2024.

Inner ear therapeutics and the war on hearing loss: systemic barriers to success.

Despite over 20 years of effort in academic research centers, start-up companies, and established pharmaceutical companies, there are no FDA-approved inner ear therapeutics for treatment of sensorineural hearing loss. There are a number of systemic barriers to creation of this new field of inner ear therapeutics. These include insufficient understanding of the particularity of different causes of hearing loss at the cellular and molecular level, lack of diagnostics of adequate sensitivity and specificity to discern these differences in vivo, a tendency for start-up biotech/pharma companies to prioritize competition over collaboration, and a drug development ecosystem that is really in the "pre-competitive" phase and a lack of infrastructure to develop, validate, gain regulatory approval, and successfully market an inner ear therapeutic. These issues will be discussed in this perspective article and a proposed remedy in the form of an inner ear therapeutics "moon shot" will be offered.

Assessment of Sudden Sensorineural Hearing Loss After COVID-19 Vaccination.

IMPORTANCE: Emerging reports of sudden sensorineural hearing loss (SSNHL) after COVID-19 vaccination within the otolaryngological community and the public have raised concern about a possible association between COVID-19 vaccination and the development of SSNHL. OBJECTIVE: To examine the potential association between COVID-19 vaccination and SSNHL. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study and case series involved an up-to-date population-based analysis of 555 incident reports of probable SSNHL in the Centers for Disease Control and Prevention Vaccine Adverse Events Reporting System (VAERS) over the first 7 months of the US vaccination campaign (December 14, 2020, through July 16, 2021). In addition, data from a multi-institutional retrospective case series of 21 patients who developed SSNHL after COVID-19 vaccination were analyzed. The study included all adults experiencing SSNHL within 3 weeks of COVID-19 vaccination who submitted reports to VAERS and consecutive adult patients presenting to 2 tertiary care centers and 1 community practice in the US who were diagnosed with SSNHL within 3 weeks of COVID-19 vaccination. EXPOSURES: Receipt of a COVID-19 vaccine produced by any of the 3 vaccine manufacturers (Pfizer-BioNTech, Moderna, or Janssen/Johnson & Johnson) used in the US. MAIN OUTCOMES AND MEASURES: Incidence of reports of SSNHL after COVID-19 vaccination recorded in VAERS and clinical characteristics of adult patients presenting with SSNHL after COVID-19 vaccination. RESULTS: A total of 555 incident reports in VAERS (mean patient age, 54 years [range, 15-93 years]; 305 women [55.0%]; data on race and ethnicity not available in VAERS) met the definition of probable SSNHL (mean time to onset, 6 days [range, 0-21 days]) over the period investigated, representing an annualized incidence estimate of 0.6 to 28.0 cases of SSNHL per 100 000 people per year. The rate of incident reports of SSNHL was similar across all 3 vaccine manufacturers (0.16 cases per 100 000 doses for both Pfizer-BioNTech and Moderna vaccines, and 0.22 cases per 100 000 doses for Janssen/Johnson & Johnson vaccine). The case series included 21 patients (mean age, 61 years [range, 23-92 years]; 13 women [61.9%]) with SSNHL, with a mean time to onset of 6 days (range, 0-15 days). Patients were heterogeneous with respect to clinical and demographic characteristics. Preexisting autoimmune disease was present in 6 patients (28.6%). Of the 14 patients with posttreatment audiometric data, 8 (57.1%) experienced improvement after receiving treatment. One patient experienced SSNHL 14 days after receiving each dose of the Pfizer-BioNTech vaccine. CONCLUSIONS AND RELEVANCE: In this cross-sectional study, findings from an updated analysis of VAERS data and a case series of patients who experienced SSNHL after COVID-19 vaccination did not suggest an association between COVID-19 vaccination and an increased incidence of hearing loss compared with the expected incidence in the general population.

A Systematic Review of Clinical Vestibular Symptom Triage, Tools, and Algorithms.

OBJECTIVE: The evaluation of peripheral vestibular disorders in clinical practice is an especially difficult endeavor, particularly for the inexperienced clinician. The goal of this systematic review is thus to evaluate the design, approaches, and outcomes for clinical vestibular symptom triage and decision support tools reported in contemporary published literature. DATA SOURCES: A comprehensive search of existing literature in August 2020 was conducted using MEDLINE, CINAHL, and EMBASE using terms of desired diagnostic tools such as algorithm, protocol, and questionnaire as well as an exhaustive set of terms to encompass vestibular disorders. REVIEW METHODS: Study characteristics, tool metrics, and performance were extracted using a standardized form. Quality assessment was conducted using a modified version of the Quality of Diagnostic Accuracy Studies 2 (QUADAS-2) assessment tool. RESULTS: A total of 18 articles each reporting a novel tool for the evaluation of vestibular disorders were identified. Tools were organized into 3 discrete categories, including self-administered questionnaires, health care professional administered tools, and decision support systems. Most tools could differentiate between specific vestibular pathologies, with outcome measures including sensitivity, specificity, and accuracy. CONCLUSION: A multitude of tools have been published to aid with the evaluation of vertiginous patients. Our systematic review identified several low-evidence reports of triage and decision support tools for the evaluation of vestibular disorders.

Cochlear Implantation Hearing Outcome in Ménière's Disease.

OBJECTIVE: The aim of this study was to evaluate the hearing outcome of cochlear implantation in patients deafened by Ménière's disease. STUDY DESIGN: Retrospective single-institution study. SETTING: Tertiary medical center. METHODS: Our institutional database of 1400 patients with cochlear implants was reviewed to identify cases with deafness due to Ménière's disease. Twenty-nine patients were identified: 24 with unilateral and 5 with sequential bilateral cochlear implants. Pre- and postoperative speech recognition scores and medical data were extracted from the medical record and analyzed. RESULTS: Overall the mean difference between pre- and postoperative speech recognition after >1 year was 56% (95% CI, 47.08%-64.92%). The mean preoperative monosyllabic word score was 9.5%, and the mean postoperative scores at 1 month, 3 months, 6 months, 1 year, and >1 year were 37.1%, 46.1%, 54.1%, 59.1%, and 66.8%, respectively. Cochlear implantation resulted in improved word scores in all patients regardless of prior medical or surgical treatment (endolymphatic sac, labyrinthectomy). The mean postoperative hearing improvement in patients aged <70 and ≥70 years was 65.26% (95% CI, 54.79%-75.73%) and 40.00% (95% CI, 27.22%-52.77%). Postoperative word scores in patients with bilateral cochlear implants were not significantly different between the first and second implanted ears or between the monoaural and binaural testing conditions. CONCLUSION: Cochlear implant in patients deafened by Ménière's disease significantly improves word recognition scores regardless of whether medical or surgical treatment is used prior to implantation. The potential improvement in word recognition scores decreases after age 70 years.

Efficacy and Durability of Intratympanic Gentamicin Treatment for Meniere's Disease.

Objective: To study the success of intratympanic gentamicin (ITG) treatment in reducing vertigo attacks in Meniere's disease (MD) and the value of the Halmagyi head thrust test (HTT) in predicting treatment durability. Study Design: Retrospective cohort study. Setting: Tertiary care vestibular clinic. Patients: Unilateral MD patients treated with ITG from 2006-2019 with ≥6 months follow-up. Main Outcome Measures: Demographics, audiometric data, subjective symptomatology, and HTT results were collected. Treatment success was defined as sufficient symptom relief. Treatment failure indicated vertigo control of less than 6 months duration. Treatment relapse indicated vertigo recurrence after 6 months. Results: Of 255 patients, treatment success, failure, and relapse occurred in 226 (88.6%), 29 (11.4%), and 121 (47.1%) patients, respectively. 48 (18.8%) patients who failed to respond or relapsed underwent labyrinthectomy. Mean follow-up time was 3.7 yrs (range 0.5-12.8). After ITG treatment, 25% patients reported worse hearing; mean pure tone average (PTA) increased by 18.6 ± 11.3 dB and mean word recognition score (WRS) decreased by 33 ± 21%. Of the 148 patients with negative pre-treatment HHT, 103 (69.6%) converted to positive after ITG treatment. Mean time-to-relapse in the converted and non-converted HTT cohorts was significantly different (49.7 vs. 27.0 months, p = 0.009) even after adjusting for gender, age, laterality, duration of symptoms, and number of ITG treatments. There were no significant differences between the two groups in hearing outcomes or subjective symptoms (e.g. lingering disequilibrium). Conclusions: ITG treatment effectively reduces the number of vertigo attacks in MD. HTT is valuable in predicting durability of treatment benefit.

The Efficient Dizziness History and Exam.

Dizziness is a common complaint in otolaryngology clinics and can present a diagnostic challenge. A thorough history including onset, duration, and exacerbating and alleviating factors, along with physician persistence, can help differentiate between otologic and nonotologic forms of dizziness. An otologic and neurotologic physical examination, including vestibulo-ocular reflex and cranial nerve function evaluation and postural examination, can shed further light on symptom etiology. Otologic forms of dizziness often result in vertigo and may be associated with unilateral symptoms of hearing loss, aural fullness, or tinnitus. Primary causes of dizziness are more often constant and insidious in onset.

Optimized Diagnostic Approach to Patients Suspected of Superior Semicircular Canal Dehiscence.

OBJECTIVES: Current methods of diagnosing superior semicircular canal dehiscence syndrome (SCDS) include a clinical exam, audiometric testing, temporal bone computer tomography (CT) imaging, and vestibular evoked myogenic potential (VEMP) testing. The main objective of this study was to develop an improved diagnostic approach to SCDS optimized for accuracy, efficiency, and safety that utilizes clinical presentation, audiometric testing, CT imaging, high-frequency cervical VEMP (cVEMP) testing, and patient treatment preference. A secondary aim was to investigate the cost associated with the current versus proposed diagnostic paradigms. DESIGN: All patients who underwent cVEMP testing since introduction of the 2 kHz cVEMP in our clinical protocol in July 2018 were screened. Patients suspected of SCDS based upon symptoms who also had available audiogram, CT scan, and 2 kHz cVEMP were included (58 ears). Patients were categorized as dehiscent, thin, or not dehiscent based on their CT scan. Symptom prevalence and cVEMP outcomes were analyzed and compared for all groups. The accuracy of the 2 kHz cVEMP was calculated using CT imaging as the standard. Using a combination of patient symptomatology, audiometric, CT and 2 kHz cVEMP data, as well as patient preference, a best clinical practice approach was developed. The cost associated with this approach was calculated and compared with cost of the current SCDS diagnostic workup using Medicare reimbursement rates. RESULTS: In the overall patient population suspected of SCDS based on clinical presentation, the sensitivity and specificity of 2 kHz cVEMP were 76% and 100%, respectively, while the positive and negative predictive values were 100% and 84.6%, assuming that the CT scan finding was correct. Autophony was the most common symptom in patients who had both superior semicircular canal dehiscence on CT imaging plus abnormal 2 kHz cVEMP (p < 0.001). Combining patient symptomatology, 2 kHz normalized peak to peak cVEMP amplitude, and patient treatment preference to determine, which patients should undergo CT scanning resulted in a potential cost reduction between 45% and 61%. CONCLUSION: In patients suspected of SCDS based on their clinical presentation, the combination of symptomatology, 2 kHz cVEMP data, and patient preference can be used to determine which patients should undergo CT scanning, resulting in a diagnostic cost reduction and reduced patient radiation exposure.

Improved Speech Intelligibility in Subjects With Stable Sensorineural Hearing Loss Following Intratympanic Dosing of FX-322 in a Phase 1b Study.

OBJECTIVES: There are no approved pharmacologic therapies for chronic sensorineural hearing loss (SNHL). The combination of CHIR99021+valproic acid (CV, FX-322) has been shown to regenerate mammalian cochlear hair cells ex vivo. The objectives were to characterize the cochlear pharmacokinetic profile of CV in guinea pigs, then measure FX-322 in human perilymph samples, and finally assess safety and audiometric effects of FX-322 in humans with chronic SNHL. STUDY DESIGNS: Middle ear residence, cochlear distribution, and elimination profiles of FX-322 were assessed in guinea pigs. Human perilymph sampling following intratympanic FX-322 dosing was performed in an open-label study in cochlear implant subjects. Unilateral intratympanic FX-322 was assessed in a Phase 1b prospective, randomized, double-blinded, placebo-controlled clinical trial. SETTING: Three private otolaryngology practices in the US. PATIENTS: Individuals diagnosed with mild to moderately severe chronic SNHL (≤70 dB standard pure-tone average) in one or both ears that was stable for ≥6 months, medical histories consistent with noise-induced or idiopathic sudden SNHL, and no significant vestibular symptoms. INTERVENTIONS: Intratympanic FX-322. MAIN OUTCOME MEASURES: Pharmacokinetics of FX-322 in perilymph and safety and audiometric effects. RESULTS: After intratympanic delivery in guinea pigs and humans, FX-322 levels in the cochlear extended high-frequency region were observed and projected to be pharmacologically active in humans. A single dose of FX-322 in SNHL subjects was well tolerated with mild, transient treatment-related adverse events (n = 15 FX-322 vs 8 placebo). Of the six patients treated with FX-322 who had baseline word recognition in quiet scores below 90%, four showed clinically meaningful improvements (absolute word recognition improved 18-42%, exceeding the 95% confidence interval determined by previously published criteria). No significant changes in placebo-injected ears were observed. At the group level, FX-322 subjects outperformed placebo group in word recognition in quiet when averaged across all time points, with a mean improvement from baseline of 18.9% (p = 0.029). For words in noise, the treated group showed a mean 1.3 dB signal-to-noise ratio improvement (p = 0.012) relative to their baseline scores while placebo-treated subjects did not (-0.21 dB, p = 0.71). CONCLUSIONS: Delivery of FX-322 to the extended high-frequency region of the cochlea is well tolerated and enhances speech recognition performance in multiple subjects with stable chronic hearing loss.

Subjective Cognitive Symptoms and Dizziness Handicap Inventory (DHI) Performance in Patients With Vestibular Migraine and Menière's Disease.

OBJECTIVE: Cognitive symptoms in patients with vestibular disorders are far from rare, but identification of patients at risk for cognitive impairment remains poor. The Dizziness Handicap Inventory (DHI) is a widely used patient-reported outcome questionnaire for dizzy patients with several questions that address cognitive function. However, the relationship between subjective cognitive symptomatology in patients with vestibular disorders and performance on DHI is poorly characterized. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care vestibular clinic. SUBJECTS: Individuals with diagnoses of vestibular migraine (VM), Menière's disease (MD), and concomitant vestibular migraine and Menière's disease (VMMD) presenting to clinic between January 2007 and December 2019. RESULTS: Of 761 subjects, 365 had VM, 311 had MD, and 85 had VMMD. Symptoms of brain fog and chronic fatigue occurred more frequently in the VM and VMMD groups compared with the MD group (χ2 (df = 2, n = 761) = 67.8, 20.9, respectively, p < 0.0001). DHI scores were significantly higher in patients with VM and VMMD compared with those with MD (F[2,758] = 63.5, p < 0.001). A DHI score ≥ 13 suggested that the patient suffered from brain fog (sensitivity = 47.4%, specificity = 72.3%), whereas a score ≥ 15 indicated that the patient complained of chronic fatigue (sensitivity = 81.5%, specificity = 57.7%). CONCLUSION: Our results indicate a high prevalence of interictal cognitive symptoms in patients with episodic vestibular disorders. The DHI cannot be reliably used to differentiate between vestibular disorders nor detect cognitive impairment in these patient populations. Alternative methods must be used to identify vestibulopathic patients with cognitive symptoms to initiate strategies for prevention and treatment.

Vestibular Evoked Myogenic Potential (VEMP) Testing for Diagnosis of Superior Semicircular Canal Dehiscence.

Superior semicircular canal dehiscence is a bony defect of the superior semicircular canal, which can lead to a variety of auditory and vestibular symptoms. The diagnosis of superior semicircular canal dehiscence (SCD) can be challenging, time consuming, and costly. The clinical presentation of SCD patients resembles that of other otologic disease, necessitating objective diagnostics. Although temporal bone CT imaging provides excellent sensitivity for SCD detection, it lacks specificity. Because the treatment of SCD is surgical, it is crucial to use a highly specific test to confirm the diagnosis and avoid false positives and subsequent unnecessary surgery. This review provides an update on recent improvements in vestibular evoked myogenic potential (VEMP) testing for SCD diagnosis. Combining audiometric and conventional cervical VEMP results improves SCD diagnostic accuracy. High frequency VEMP testing is superior to all other methods described to date. It is highly specific for the detection of SCD and may be used to guide decision-making regarding the need for subsequent CT imaging. This algorithmic sequential use of testing can substantially reduce radiation exposure as well as cost associated with SCD diagnosis.

Transmastoid Labyrinthectomy for Menière's Disease: Experience and Outcomes.

OBJECTIVE: To characterize presurgical symptoms and treatment history and postoperative course in patients with medically recalcitrant Menière's disease undergoing transmastoid labyrinthectomy in the post-intratympanic gentamicin era. STUDY DESIGN: Retrospective case series. SETTING: Tertiary academic medical center. PATIENTS: All patients who underwent transmastoid labyrinthectomy for medically recalcitrant Menière's disease in 2003 to 2019 by the senior author. INTERVENTIONS: Review of patients' medical records for: preoperative history of drop attacks, gentamicin injections, endolymphatic sac decompression or vestibular neurectomy, preoperative audiograms, length of hospital stay, postoperative complications, and persistent symptoms or challenging recovery. MAIN OUTCOME MEASURES: Presurgical clinical history and proximal postoperative outcomes. RESULTS: Seventy-two patients with a mean age of 56.7 (standard deviation [SD] 10.7) were included. All cases were unilateral. Forty-three patients (59.7%) suffered from drop attacks. Sixty-two (86.1%) had failed sufficient symptom control with gentamicin injections. The mean preoperative word recognition score was 36.4% (SD 23.7) versus 95.1% (SD 8.5) in the contralateral ear. The mean pure-tone average (PTA) of the ipsilateral ear before surgery was 65.5 dB (SD 18.0) versus 16.2 (SD 13.5) for the contralateral ear. Mean hospital stay was 2.0 days (SD 0.87 days, range of 1-5 d). Three patients (4.2%) had prolonged postoperative vertigo. CONCLUSIONS: Transmastoid labyrinthectomy at our center is performed for unilateral Menière's disease, generally when intratympanic gentamicin has failed. A majority of surgical patients suffer from drop attacks preoperatively. Hospital stay is typically brief.

Telemedicine Algorithm for the Management of Dizzy Patients.

As a result of the COVID-19 pandemic, telemedicine has been thrust to the forefront of health care. Despite its inherent limitations, telemedicine offers many advantages to both patient and physician as an alternative to in-person evaluation of select patients. In the near term, telemedicine allows nonpandemic care to proceed while observing appropriate public health concerns to minimize the spread of pandemic pathogens. Thus, it behooves practitioners to use telemedicine consultations for common otolaryngology complaints. Assessment of the dizzy patient is well-suited to an algorithmic approach that can be adapted to a telemedicine setting. As best practices for telemedicine have yet to be defined, we present herein a practical approach to the history and limited physical examination of the dizzy patient in the telemedicine setting for the general otolaryngologist. Indeed, once the acute crisis has abated, we suspect that this approach will continue to be an effective way to manage dizzy patients.

Peripheral Vestibular Organ Degeneration After Temporal Bone Fracture: A Human Otopathology Study.

OBJECTIVES/HYPOTHESIS: Vestibular symptoms are a common sequela of temporal bone fractures (TBFs). The mechanisms of injury to the peripheral vestibular system following TBF, however, are not well described. Herein, we aimed to investigate the histopathology of the peripheral vestibular system in patients who sustained TBFs. STUDY DESIGN: Retrospective human specimen analysis. METHODS: Specimens from the National Temporal Bone Pathology Registry with (cases) and without (controls) TBFs were evaluated. Specimens were analyzed by light microscopy for vestibular hair cell and/or dendritic degeneration, presence of endolymphatic hydrops, blockage of the endolymphatic duct, and number of Scarpa ganglion cells (ScGCs) in the superior and inferior vestibular nerves. RESULTS: Seven temporal bones (TBs) from five individuals with TBFs, and seven TBs from six age-matched individuals without a history of head injury met inclusion and exclusion criteria. All fractures involved the otic capsule. Severe degeneration of the cristae was identified in the semicircular canals in all TBF cases. The utricular and saccular maculae showed mild to severe degeneration in the TBF cases. Vestibular hydrops (n = 2 TBs) and blockage of the endolymphatic duct (n = 3 TBs) were also present in the TBF cases. There was a decrease of 52.6% in the mean total ScGC count in the TBF cases (n = 3 TBs) compared to age-matched controls (n = 7 TBs, P = .015). There was a mean loss of 53% of the ScGCs in the superior vestibular nerve and a mean loss of 52.3% of the ScGCs in the inferior vestibular nerve compared to age-matched controls (P = .033 and P = .021, respectively). CONCLUSIONS: In a cohort of patients with TBFs, there were distinct peripheral vestibular changes including reduction of ScGCs. LEVEL OF EVIDENCE: NA Laryngoscope, 130:752-760, 2020.

Patient-reported auditory handicap measures following mild traumatic brain injury.

OBJECTIVES/HYPOTHESIS: Few studies have specifically addressed auditory complaints in patients with nonblast mild traumatic brain injury (mTBI). Herein, we aimed to investigate auditory symptoms in patients following mTBI using patient-reported outcome measures. STUDY DESIGN: Retrospective analysis of prospectively collected data in a tertiary-care hospital. METHODS: The patients included those with mTBI (cases) and those without mTBI (controls). Individuals (≥18 years old) with and without mTBI were screened. Exclusion criteria included history of otologic disorders, blast injury, or occupational noise exposure. Primary outcomes included the Hearing Handicap Inventory for Adults (HHIA), Tinnitus Handicap Inventory (THI), and Hyperacusis Questionnaire (HQ). Secondary outcomes included subjective auditory complaints. RESULTS: From September 2017 to September 2018, 52 patients with mTBI and 55 controls met inclusion and exclusion criteria. The mean time between mTBI and survey intake was 70.6 months. The mean age and gender were 51.5 years old and 73% female in the mTBI group, and 46.1 years old and 56.3% female in the control group (P = .112 and P = .105, respectively). Patients with mTBI reported hyperacusis (67.3% of all mTBI patients), hearing loss (61.5%), and tinnitus (61.5%), compared to 8.3%, 12.7%, and 16.4%, respectively, for control subjects (P < .0001). The mean HHIA score in the mTBI group was 38.3 versus 8.5 in controls (P = .002). The mean THI score was 27.4 in the mTBI group and 3.1 in controls (P < .0001). The mean HQ score was 26.5 in mTBI group and 7.3 in controls (P = .001). CONCLUSIONS: Auditory symptoms and associated handicap were common in patients with nonblast mTBI compared to age-matched controls. Findings have implications for the pathophysiology and management of symptoms in this patient population. LEVEL OF EVIDENCE: 3 Laryngoscope, 130:761-767, 2020.

Predicting Development of Bilateral Menière's Disease Based on cVEMP Threshold and Tuning.

OBJECTIVE: To investigate if the cervical vestibular evoked myogenic potential (cVEMP) is predictive for developing bilateral Menière's disease (MD). STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care center. PATIENTS: Records of 71 patients previously diagnosed with unilateral MD at our institution who underwent cVEMP testing between 2002 and 2011 were screened. INTERVENTION: Patients were contacted to answer a questionnaire to identify which patients had developed bilateral disease. Based on questionnaires and medical charts, 49 patients with a follow-up time of at least 5 years were included. The 49 originally asymptomatic ears are referred to as "study ears." Previously reported cVEMP criteria (original criteria) applied to study-ear cVEMPs separated them into Menière-like and normal-like groups. MAIN OUTCOME MEASURE: The main purpose was to determine if previously obtained cVEMP thresholds and tuning ratios of unilateral MD patients could predict who develops bilateral disease. RESULTS: From the 49 included patients, 12 developed bilateral disease (24.5%). The study ears characterized by original cVEMP criteria as Menière-like were significantly more likely to develop bilateral disease compared with the normal-like study ears. The original criteria predicted development of bilateral disease with a positive predictive value (PPV) and negative predictive value (NPV) of 58.3% and 86.5% respectively. ROC curves were used to revise cVEMP criteria for predicting the progression to bilateral disease. A revised criterion combining three cVEMP metrics, reached a PPV and NPV of 85.7% and 93.7%. CONCLUSION: cVEMP threshold and tuning in unilateral MD patients are predictive of which patients will develop bilateral disease.

Vestibular Aqueduct Morphology Correlates With Endolymphatic Sac Pathologies in Menière's Disease-A Correlative Histology and Computed Tomography Study.

HYPOTHESIS: The vestibular aqueduct (VA) in Menière's disease (MD) exhibits different angular trajectories depending on the presenting endolymphatic sac (ES) pathology, i.e., 1) ES hypoplasia or 2) ES degeneration. BACKGROUND: Hypoplasia or degeneration of the ES was consistently found in inner ears affected by MD. The two etiologically distinct ES pathologies presumably represent two disease "endotypes," which may be associated with different clinical traits ("phenotypes") of MD. Recognizing these endotypes in the clinical setting requires a diagnostic tool. METHODS: 1) Defining the angular trajectory of the VA (ATVA) in the axial plane. 2) Measuring age-dependent normative data for the ATVA in postmortem temporal bone histology material from normal adults and fetuses. 3) Validating ATVA measurements from normative CT imaging data. 4) Correlating the ATVA with different ES pathologies in histological materials and CT imaging data from MD patients. RESULTS: 1) The ATVA differed significantly between normal adults and MD cases with ES degeneration, as well as between fetuses and MD cases with ES hypoplasia; 2) a strong correlation between ATVA measurements in histological sections and CT imaging data was found; 3) a correlation between the ATVA, in particular its axial trajectory in the opercular region (angle αexit), with degenerative (αexit < 120°) and hypoplastic ES pathology (αexit > 140°) was demonstrated. CONCLUSION: We established the ATVA as a radiographic surrogate marker for ES pathologies. CT-imaging-based determination of the ATVA enables endotyping of MD patients according to ES pathology. Future studies will apply this method to investigate whether ES endotypes distinguish clinically meaningful subgroups of MD patients.

Cervical Vestibular Evoked Myogenic Potentials in Menière's Disease: A Comparison of Response Metrics.

OBJECTIVE: The cervical vestibular evoked myogenic potential (cVEMP) has been used to evaluate patients with Menière's disease (MD). Studied cVEMP metrics include: amplitude, threshold, frequency tuning, and interaural asymmetry ratio (IAR). However, few studies compared these metrics in the same set of MD patients, and methodological differences prevent such a comparison across studies. This study investigates the value of different cVEMP metrics in distinguishing one set of MD patients from age-matched controls. STUDY DESIGN: Prospective study. SETTING: Tertiary care center. PATIENTS: Thirty patients with definite unilateral MD and 23 age-matched controls were prospectively included. All underwent cVEMP testing at 500, 750, 1000, and 2000 Hz on each side. Ears were separated into three groups: affected MD, unaffected MD, and control. MAIN OUTCOME MEASURES: Sound level functions were obtained at each frequency, and normalized peak-to-peak amplitude (VEMPn), VEMP inhibition depth (VEMPid), threshold, frequency-tuning ratio, and IAR were calculated. For all metrics, the differentiation between MD and control ears was compared using receiver operating characteristic (ROC) curves. RESULTS: 500 Hz cVEMP threshold, VEMPn, and VEMPid were similarly good at distinguishing affected MD ears from healthy ears, with ROC area under the curves (AUCs) of more than 0.828 and optimal sensitivities and specificities of at least 80 and 70%. Combinations of these three metrics yielded slightly larger AUCs (>0.880). Tuning ratios and IAR were less effective in separating healthy from affected ears with AUCs ranging from 0.529 to 0.720. CONCLUSION: The cVEMP metrics most useful in distinguishing MD patients from healthy controls are threshold, VEMPn, and VEMPid, using 500 Hz stimuli.

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.

Inner ear pathologies impair sodium-regulated ion transport in Meniere's disease.

Meniere's disease (MD), a syndromal inner ear disease, is commonly associated with a pathological accumulation of endolymphatic fluid in the inner ear, termed "idiopathic" endolymphatic hydrops (iEH). Although numerous precipitating/exacerbating factors have been proposed for MD, its etiology remains elusive. Here, using immunohistochemistry and in situ protein-protein interaction detection assays, we demonstrate mineralocorticoid-controlled sodium transport mechanisms in the epithelium of the extraosseous portion of the endolymphatic sac (eES) in the murine and human inner ears. Histological analysis of the eES in an extensive series of human temporal bones consistently revealed pathological changes in the eES in cases with iEH and a clinical history of MD, but no such changes were found in cases with "secondary" EH due to other otological diseases or in healthy controls. Notably, two etiologically different pathologies-degeneration and developmental hypoplasia-that selectively affect the eES in MD were distinguished. Clinical records from MD cases with degenerative and hypoplastic eES pathology revealed distinct intergroup differences in clinical disease presentation. Overall, we have identified for the first time two inner ear pathologies that are consistently present in MD and can be directly linked to the pathogenesis of EH, and which potentially affect the phenotypical presentation of MD.