Temporal Trends in Early Pediatric Cochlear Implantations in California from 2018 to 2020.

OBJECTIVE: To characterize the demographics of children receiving cochlear implantations, identify factors associated with delayed implantations, and trend these factors over time. DESIGN: Retrospective cross-sectional study. SETTING: Healthcare Cost and Utilization Project California State Ambulatory Surgery Database for calendar years 2018-2020. PATIENTS: Children 5 years or younger undergoing cochlear implantation. INTERVENTIONS: Cochlear implantation. MAIN OUTCOMES MEASURES: The population-controlled number of cochlear implantations was calculated and stratified by race and insurance. Early implantation was defined as implantation at age 2 years or younger. A mixed-effects logistic regression model was generated to identify factors associated with early implantation and how that association changed from 2018 to 2020. RESULTS: The final cohort included 467 children. The number of implantations increased from 141 to 175 implants from 2018 to 2020 (24.1% increase); 229 (49.0%) children were implanted at 2 years or younger. Medicaid insurance was associated with decreased odds of early implantation (odds ratio, 0.18 [95% confidence interval, 0.15-0.23], p < 0.001); this association with Medicaid insurance was significant when stratified across all racial groups. The percentage of children with Medicaid who were implanted at 2 years or younger increased from 20.9 to 62.0% from 2018 to 2020. CONCLUSIONS AND RELEVANCE: Among children in California, socioeconomic factors, in particular public insurance, are correlated with age of cochlear implantation. These disparities improved significantly from 2018 to 2020. Further investigation into changes and initiatives in California during this time frame may aid in directing national efforts to improve pediatric cochlear implantation access.

Temporal bone histopathology in revision cochlear implantation.

An increasing number of young infants, as early as six months of age with congenital hearing loss receive cochlear implantation, and it is probable that many of these patients will require revision surgery later in life. The possibility of explantation of the cochlear electrode and reimplantation may cause damage to the cochlea, compromising the speech perception outcome in revision implant is of concern. There is only one prior temporal bone histopathology study to look at the outcome of revision surgery and no prior study evaluating revision cochlear implantation that used the round window approach. We conducted a histopathological study of four temporal bone specimens from four patients who underwent revision cochlear implantation and when available post-operative speech perception tests were evaluated. In all cases, the reimplanted electrode followed into the same fibrous sheath without evidence of additional intracochlear damage due to revision surgery. The intracochlear damage from the initial cochlear implantation appears to be a more important factor in outcomes rather than changes associated with explantation and reimplantation.

Differential Expression of Na/K-ATPase in the Human Saccule of Patients With and Without Otologic Disease.

HYPOTHESIS: Na + , K + -ATPase (Na/K-ATPase) α1 subunit expression in the saccule of patients diagnosed with otologic disease is different compared with normal controls. BACKGROUND: We have recently characterized changes in the expression of Na/K-ATPase α1 subunit in the normal and pathological cochlea; however, no studies have determined the distribution Na/K-ATPase α1 subunit in the human saccule. The present study uses archival temporal bones to study the expression Na/K-ATPase α1 subunit in the human saccule. METHODS: Archival celloidin formalin fixed 20-micron thick sections of the vestibule from patients diagnosed with Menière's disease (n = 5), otosclerosis (n = 5), sensorineural hearing loss, and normal hearing and balance (n = 5) were analyzed. Sections containing the saccular macula were immunoreacted with mouse monoclonal antibodies against Na/K-ATPase α1 subunit. Micrographs were acquired using a high-resolution digital camera coupled to a light inverted microscope. RESULTS: In the normal human saccule vestibular sensory epithelium, Na/K-ATPase α1 immunoreactivity (IR) was present in nerve fibers and calyces that surround type I vestibular hair cells and nerve terminals. The transition epithelium cells were also Na/K-ATPase α1 immunoreactive. Comparison between normal and pathological specimens showed that there was a significant reduction of Na/K-ATPase α1 IR in the saccule vestibular sensory epithelium from patients with Menière's disease, otosclerosis, and sensorineural hearing loss. CONCLUSIONS: The decrease of Na/K-ATPase-IR α1 in the saccule vestibular sensory epithelium from patients with otopathologies suggests its critical role in inner ear homeostasis and pathology.

Cochlear implants: Causes, effects and mitigation strategies for the foreign body response and inflammation.

Cochlear implants provide effective auditory rehabilitation for patients with severe to profound sensorineural hearing loss. Recent advances in cochlear implant technology and surgical approaches have enabled a greater number of patients to benefit from this technology, including those with significant residual low frequency acoustic hearing. Nearly all cochleae implanted with a cochlear implant electrode array develop an inflammatory and fibrotic response. This tissue reaction can have deleterious consequences for implant function, residual acoustic hearing, and the development of the next generation of cochlear prosthetics. This article reviews the current understanding of the inflammatory/foreign body response (FBR) after cochlear implant surgery, its impact on clinical outcome, and therapeutic strategies to mitigate this response. Findings from both in human subjects and animal models across a variety of species are highlighted. Electrode array design, surgical techniques, implant materials, and the degree and type of electrical stimulation are some critical factors that affect the FBR and inflammation. Modification of these factors and various anti-inflammatory pharmacological interventions have been shown to mitigate the inflammatory/FBR response. Ongoing and future approaches that seek to limit surgical trauma and curb the FBR to the implanted biomaterials of the electrode array are discussed. A better understanding of the anatomical, cellular and molecular basis of the inflammatory/FBR response after cochlear implantation has the potential to improve the outcome of current cochlear implants and also facilitate the development of the next generation of neural prostheses.

Association of Socioeconomic Characteristics With Receipt of Pediatric Cochlear Implantations in California.

Importance: Earlier cochlear implantation among children with bilateral severe to profound sensorineural hearing loss is associated with improved language outcomes. More work is necessary to identify patients at risk for delayed cochlear implantation and understand targets for interventions to improve cochlear implantation rates among children. Objective: To describe the demographics among children receiving cochlear implantations and variability in implantation rates in California and to investigate sociodemographic and parental factors associated with early pediatric cochlear implantation. Design, Setting, and Participants: This retrospective cross-sectional study was conducted using data from the Healthcare Cost and Utilization Project California State Ambulatory Surgery Database in calendar year 2018. Included patients were children aged 9 years old or younger undergoing cochlear implantation. Sociodemographic factors, location of treatment, and parental factors were collected. Data were analyzed from March through August 2021. Main Outcomes and Measures: Binary logistic regression was performed to investigate sociodemographic factors associated with early cochlear implantation (ie, before age 2 years). Geographic variability in pediatric cochlear implantation across hospital referral regions in California was described, and various parental factors associated with implantation before age 2 years were analyzed. Results: Among 182 children receiving cochlear implantations, the median (IQR) age was 3 (1-5) years and 58 children (31.9%) received implantations at ages 2 years or younger. There were 90 girls (49.5%) and 92 boys (50.5%), and among 170 children with race and ethnicity data, there were 27 Asian or Pacific Islander children (15.9%), 63 Hispanic children (37.1%), and 55 White children (32.4%). The risk of CI was significantly decreased among Black children compared with Asian or Pacific Islander children (relative risk [RR], 0.18 [95% CI, 0.07-0.47]; P = .001) and White children (RR, 0.24 [95% CI, 0.10-0.59]; P = .002) and among Hispanic children compared with Asian or Pacific Islander children (RR, 0.32 [95% CI, 0.21-0.50]; P < .001) and White children (RR, 0.42 [95% CI, 0.29-0.59; P < .001). Compared with private insurance, Medicaid insurance was associated with decreased odds of implantation at ages 2 years or younger (odds ratio [OR], 0.19 [95% CI, 0.06-0.64]; P = .007), and every 1 percentage point increase in maternal high school completion percentage in a given California hospital referral region was correlated with a 5-percentage point increase in percentage of cochlear implants performed at age 2 years or younger (b = 5.18 [95% CI, 1.34-9.02]; P = .008). There were no significant differences in rates of early implantation by race or ethnicity. Conclusions and Relevance: This study found significant variability in pediatric cochlear implantation rates in California. These findings suggest that socioeconomic and parental factors may be associated with differences in access to early cochlear implantation and suggest the need to invest in initiatives to address barriers to appropriate and timely access to care.

Histopathologic Analysis of Temporal Bones With Otosclerosis Following Cochlear Implantation.

OBJECTIVE: Analyze changes in osteoneogenesis and fibrosis following cochlear implant (CI) surgery in patients with otosclerosis and compare differences based on insertion technique. BACKGROUND: When advanced otosclerotic disease extends to the otic capsule, severe and profound sensorineural hearing loss necessitates consideration of a cochlear implant. Histopathological analysis of the human temporal bone after implantation in the patient with otosclerosis may reveal important variables that predict CI success. METHODS: Histopathological evaluation of archival human temporal bones from subjects with a history of CI for cochlear otosclerosis. A total of 17 human temporal bones (HTB) were analyzed, 13 implanted, and 4 contralateral non-implanted controls. RESULTS: Histopathological studies revealed extensive osteoneogenesis and fibrosis which was more prominent at the cochleostomy insertion site in the basal turn of the cochlea often obliterating the scala tympani in the basal turn, and in some cases extending to the scala media and scala vestibuli. Cochlear hydrops was nearly universal in these cases. This contrasted with the round window insertion, which exhibited minimal osteoneogenesis within the cochlear duct. In addition, in the contralateral, unimplanted control ears, there was otosclerosis at the stapes footplate, fissula ante fenestrum but no osteoneogenesis within the cochlear duct. CONCLUSION: Cochleostomy approach to CI insertion in otosclerosis patients is associated with significant fibrosis, osteoneogenesis, and cochlear hydrops. A round window insertion technique can be utilized to help minimize these histopathologic findings whenever feasible.

Selected Otologic Disorders Causing Dizziness.

PURPOSE OF REVIEW: This article details updated clinical presentations and current treatment paradigms of the common otologic disorders that may present to the neurologist for vertigo, including Ménière disease, superior semicircular canal dehiscence syndrome, perilymphatic fistula, barotrauma, cholesteatoma, Ramsay Hunt syndrome, enlarged vestibular aqueduct syndrome, and autoimmune inner ear disease including Cogan syndrome. RECENT FINDINGS: The recent data on modern imaging techniques with three-dimensional delayed IV contrast in Ménière disease, findings on the clinical and testing parameters to diagnose semicircular canal dehiscence and barotrauma, and clinical findings in Ramsay Hunt syndrome, cholesteatoma, and enlarged vestibular aqueduct syndrome are discussed in the article. The most recent findings on the treatment and evaluation of autoimmune inner ear disease and Cogan syndrome are also covered. SUMMARY: This article discusses the common clinical otologic entities in patients who may present to the neurologist for vertigo, and it can be used as a guide in the diagnosis of these conditions with the use of auditory, vestibular, and imaging results.

Cisplatin ototoxicity histopathology.

This study investigates the histopathological changes of the cochlea and vestibular end organs of a patient who received cisplatin for Hodgkin's lymphoma. He experienced acute high-frequency sensorineural hearing loss and tinnitus after receiving treatment. Using histopathological analysis of his temporal bones after he unfortunately succumbed to his disease, we found that the ototoxic effect of cisplatin is primarily within the cochlea, with significant damage located at the organ of Corti at the base-hook region, consistent with findings in animal models. The effects of cisplatin were minimal when reviewing the vestibular end organs.

Cochlear Meniere's: A Distinct Clinical Entity With Isolated Cochlear Hydrops on High-Resolution MRI?

Objective: Describe the clinical characteristics of patients with isolated cochlear endolymphatic hydrops (EH). Study design: Clinical case series. Setting: Tertiary Neurotology referral clinic. Patients: All subjects presenting to a University Neurotology clinic during a 1-year period from July 2015 until August 2016 who had isolated cochlear EH on MRI. Patients with a history of temporal bone surgery prior to the MRI were excluded. Intervention: High-resolution delayed-intravenous contrast MRI. Main outcome measures: Audiometric and vestibular testing, clinical history analysis. Results: 10 subjects demonstrated isolated, unilateral cochlear hydrops on MRI. None of these patients met the criteria for Meniere's disease. Mean age of the group was 66.4 years and most were males (70%). Unilateral aural fullness (70%), tinnitus (80%), and hearing loss (90%) were frequently observed. Only one patient presented with unsteadiness (10%) and one patient had a single isolated spell of positional vertigo 1 month prior to the MRI (10%) but no further vertigo spells in the 4 years following the MRI. The mean PTA was 37.8 dB which was significantly decreased from the non-affected ear with PTA of 17.9 (p < 0.001). One patient developed vertiginous spells and unsteadiness 4 years after initial presentation and a repeat MRI revealed progression to utricular, saccular and cochlear hydrops. Vestibular testing was obtained in five patients with one patient presenting with 50% caloric paresis and all others normal. The most common treatment tried was acetazolamide in seven patients with 86% reporting subjective clinical improvement. Two out of the 10 patients had a history of migraine (20%). Conclusions: Patients with MRI exhibiting isolated cochlear EH present with predominantly auditory symptoms: mild to moderate low-frequency hearing loss, aural fullness, tinnitus without significant vertigo. Isolated cochlear hydrops is more common in males, average age in mid-60's and there is a low comorbidity of migraine headaches. This contrasts significantly with patients with isolated saccular hydrops on MRI from our prior studies. We believe that isolated cochlear EH with hearing loss but no vertigo is distinct from Meniere's disease or its variant delayed endolymphatic hydrops. We propose that cochlear Meniere's disease represents a distinct clinical entity that could be a variant of Meniere's disease.

Immunohistochemical location of Na+, K+-ATPase α1 subunit in the human inner ear.

Na+, K+-ATPase (Na,K-ATPase) is an ubiquitous enzyme in the inner ear and a key factor in the maintenance of the osmotic gradient of the endolymph. This study uses Na,K-ATPase α1 subunit immunoreactivity (IR) to identify cellular structures in the normal and disease human cochlea. Formalin-fixed celloidin-embedded (FFCE) human temporal bone sections were immunoreacted with mouse monoclonal antibodies against Na,K-ATPase α1 subunit. Na,K-ATPase α1 IR was examined in the cochlea of 30 patients: four with normal hearing, 5 with Meniere's disease, and 21 with other inner ear diseases: 11 male, 19 female; ages 42 to 96 years-old (yo), average age of 77 yo. Na,K-ATPase α1 IR area was quantified using the ImageJ software program. Na,K-ATPase α1 IR was located in the stria vascularis, and in type I, II and IV fibrocytes of the spiral ligament in the cochlea from patients with normal hearing. Na,K-ATPase α1 IR was seen in Deiters's cells and inner phalangeal cells of the organ of Corti. Na,K-ATPase α1 IR was present in satellite cells that surround the neurons of the spiral ganglia. In the inner ear of pathological specimens, Na,K-ATPase IR area was decreased (compared to the normal) in the stria vascularis, supporting cells in the organ of Corti and satellite cells of the spiral ganglia. These results show that Na,K-ATPase α1 IR is a good marker to identify cellular structures of the human inner ear and may be used to study cellular changes in the cochlea associated with aging and disease. The ubiquitous localization of Na,K-ATPase α1 in the human cochlea is consistent with the Na,K-ATPase role in ionic homeostasis and osmolarity, similar to that seen in animal models.

Immune Response of Macrophage Population to Cochlear Implantation: Cochlea Immune Cells.

HYPOTHESIS: The presence and distribution of ionized calcium binding adaptor 1 and CD68 macrophages in the human cochlea is altered in cochlear implantation (CI) compared with the normative or nonimplanted cochlea. BACKGROUND: It has been hypothesized that CI induces an immunological response in macrophages leading to implant failure or reduced hearing. Macrophages are resident immune cells in human cochlea and have been shown to phagocytize implant material. In animal models, macrophage populations increase with surgical stress and with the introduction of a foreign body. However, the function and response of inner ear macrophages to CI are only beginning to be understood. This study seeks to investigate the inflammatory response to CI by comparing cochlear macrophages in implanted and nonimplanted human temporal bones. METHODS: Nineteen temporal bones from nine implanted ears, seven contralateral controls, and three normal control ears were evaluated for the presence and distribution of CD68 and Iba1 expressing positive macrophages. RESULTS: Three types of macrophage populations were detected 1) CD68 positive macrophages, 2) Iba1 positive macrophages, and 3) CD68 and Iba1 colocalizing macrophages. Macrophage distribution was ubiquitous: the stria vascularis, Rosenthal canal, and the mid-modiolus intermingled in the spiral ganglia. Iba1 and CD68 macrophages were found in the CI and non-CI contralateral and normal human cochlea. Most ionized calcium binding adaptor 1 expressing macrophages were ramified/amoeboid cells, while CD68 expressing macrophages were round shaped with foamy appearance in some areas. In the CI cochlea, both types of macrophages were detected in the fibrous sheath surrounding the CI path and within fibrotic areas within the scala tympani and the scala vestibuli in the case of CI translocation. In four cases, the density of macrophages was unchanged in the CI compared with the contralateral nonimplanted side, and in three cases, there was an increased number of macrophages in the implanted CI side compared with the nonimplanted side. CONCLUSION: Multiple populations of macrophages exist within the cochlea which are present at baseline and in response to trauma from CI. These results further support evidence for a macrophage response to cochlear implantation. Further studies are indicated to evaluate whether these macrophages have a beneficial, detrimental, or a mixed effect in CI patients.

Investigations of the Microvasculature of the Human Macula Utricle in Meniere's Disease.

The integrity and permeability of the blood labyrinthine barrier (BLB) in the inner ear is important to maintain adequate blood supply, and to control the passage of fluids, molecules and ions. Identifying the cellular and structural components of the BLB, the vascular endothelial cells (VECs), pericytes, and the perivascular basement membrane, is critical to understand the pathophysiology of the inner ear microvasculature and to design efficient delivery of therapeutics across the BLB. A recent study of the normal and pathological ultrastructural changes in the human macula utricle microvasculature demonstrated that the VECs are damaged in Meniere's disease (MD), and further studies identified oxidative stress markers (iNOS and nitrotyrosine) in the VECs. Using fluorescence microscopy, the microvasculature was studied in the macula utricle of patients diagnosed with MD that required transmastoid labyrinthectomy for intractable vertigo (n = 5), and patients who required a translabyrinthine approach for vestibular schwannoma (VS) resection (n = 3). Normal utricles (controls) were also included (n = 3). VECs were identified using rabbit polyclonal antibodies against the glucose transporter-1 (GLUT-1) and pericytes were identified using mouse monoclonal antibodies against alpha-smooth muscle actin (α-SMA). Immunofluorescence (IF) staining was made in half of the utricle and flat mounted. The other half was used to study the integrity of the BLB using transmission electron microscopy (TEM). GLUT-1-IF, allowed delineation of the macula utricle microvasculature (located in the stroma underneath the sensory epithelia) in both MD and VS specimens. Three sizes of vessels were present in the utricle vasculature: Small size (<15 µm), medium size (15-25 µm) and large size >25 µm. α-SMA-IF was present in pericytes that surround the VECS in medium and thick size vessels. Thin size vessels showed almost no α-SMA-IF. AngioTool software was used for quantitative analysis. A significant decreased number of junctions, total vessel length, and average vessel length was detected in the microvasculature in MD specimens compared with VS and control specimens. The deeper understanding of the anatomy of the BLB in the human vestibular periphery and its pathological changes in disease will enable the development of non-invasive delivery strategy for the treatment of hearing and balance disorders.

Otopetrin-2 Immunolocalization in the Human Macula Utricle.

BACKGROUND: In the present study, we investigated the localization of otopetrin-2-a member of the otopetrin family that encodes proton-selective ion channels-in the human macula utricle using immunohistochemistry. METHODS: Macula utricle were acquired at surgery from patients who required transmastoid labyrinthectomy for intractable vertigo due to Meniere's disease (MD; n = 3) and/or vestibular drops attacks (VDA; n = 2) and from temporal bones (n = 2) acquired at autopsy from individuals with no balance disorders. Immunofluorescence staining with otopetrin-2 (rabbit affinity purified polyclonal antibody) and GFAP (mouse monoclonal antibody) to identify vestibular supporting cells was made in formalin fixed cryostat sections or whole microdissected utricle (for flat mount preparations). Secondary antibodies against rabbit and mouse were used for the identification of both proteins. Digital fluorescent images were obtained using a high-resolution laser confocal microscope. RESULTS: Using cryostat sections and flat mount preparations otopetrin-2 immunofluorescence was seen as punctated signal throughout the supporting cells cytoplasm. GFAP immunofluorescence was present in the supporting cell cytoplasm. The distribution of otopetrin-2 was similar in the macula utricle obtained from MD, VDA, or autopsy normative patients. CONCLUSIONS: Otopetrin-2 was localized in supporting cells in a similar fashion that otopetrin-1 previously reported in the mouse macula utricle. The differential expression of otopetrin-2 in the supporting cells of the human macula utricle suggest an important role in the vestibular sensory periphery homeostasis and otolith maintenance.

Oxidative Stress in the Blood Labyrinthine Barrier in the Macula Utricle of Meniere's Disease Patients.

The blood labyrinthine barrier (BLB) is critical in the maintenance of inner ear ionic and fluid homeostasis. Recent studies using imaging and histopathology demonstrate loss of integrity of the BLB in the affected inner ear of Meniere's disease (MD) patients. We hypothesized that oxidative stress is involved in the pathogenesis of BLB degeneration, and to date there are no studies of oxidative stress proteins in the human BLB. We investigated the ultrastructural and immunohistochemical changes of the BLB in the vestibular endorgan, the macula utricle, from patients with MD (n = 10), acoustic neuroma (AN) (n = 6) and normative autopsy specimens (n = 3) with no inner ear disease. Each subject had a well-documented clinical history and audiovestibular testing. Utricular maculae were studied using light and transmission electron microscopy and double labeling immunofluorescence. Vascular endothelial cells (VECs) were identified using isolectin B4 (IB4) and glucose-transporter-1 (GLUT-1). Pericytes were identified using alpha smooth muscle actin (αSMA) and phalloidin. IB4 staining of VECS was consistently seen in both AN and normative. In contrast, IB4 was nearly undetectable in all MD specimens, consistent with the significant VEC damage confirmed on transmission electron microscopy. GLUT-1 was present in MD, AN, and normative. αSMA and phalloidin were expressed consistently in the BLB pericytes in normative, AN specimen, and Meniere's specimens. Endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), and nitrotyrosine were used as markers of oxidative stress. The VECs of the BLB in Meniere's had significantly higher levels of expression of iNOS and nitrotyrosine compared with normative and AN specimen. eNOS-IF staining showed similar patterns in normative and Meniere's specimens. Microarray-based gene expression profiling confirmed upregulation of iNOS mRNA from the macula utricle of Meniere's patients compared with AN. Nitrotyrosine, a marker recognized as a hallmark of inflammation, especially when seen in association with an upregulation of iNOS, was detected in the epithelial and stromal cells in addition to VECs in MD. Immunohistochemical and ultrastructural degenerative changes of the VEC suggest that these cells are the primary targets of oxidative stress, and pericyte pathology including degeneration and migration, likely also plays a role in the loss of integrity of the BLB and triggering of inflammatory pathways in MD. These studies advance our scientific understanding of oxidative stress in the human inner ear BLB and otopathology.

Immunohistochemical localization of megalin and cubilin in the human inner ear.

Megalin and cubilin are endocytic receptors expressed in many absorptive polarized epithelia. These receptors have been implicated in the transport of gentamicin in the inner ear as possible contributors to ototoxic damage. Megalin and cubilin have been characterized in detail in the mouse and rat inner ear, but not in the human inner ear. In this study, megalin and cubilin were localized by immunohistochemistry using affinity-purified antibodies in formalin fixed frozen cryostat and celloidin embedded sections of the human inner ear. In the cochlea megalin and cubilin were localized in marginal cells of the stria vascularis, epithelial cells of the spiral prominence and the Reissner's membrane. In the macula utricle and cristae ampullaris, megalin and cubilin were localized in transitional and dark cells, but not in vestibular hair cells and supporting cells. In the endolymphatic duct megalin and cubilin were localized in the epithelial cells. The localization of megalin and cubilin in the human inner ear is consistent with previous reports in the inner ear of animal models and suggest that these receptors may play an important role in the inner ear endocytic transport, and maybe potential targets for prevention of ototoxic damage or the delivery of medications.

Immunohistochemical localization of Nrf2 in the human cochlea.

Oxidative stress plays an important role in several inner ear diseases and normal aging. Nuclear (erythroid-derived 2)-like 2, also known as Nrf2, is a transcription factor encoded by the NFE2L2 gene that controls the expression of genes necessary to reduce oxidative stress. There are no studies to the date on the localization of Nrf2 in the human inner ear in normal or pathological conditions. Therefore, we investigated the immunohistochemical localization of Nrf2 in the human cochlea and vestibule using formalin-fixed celloidin-embedded human temporal bone sections. Nrf2 immunoreactivity (IR) was found in the inner and outer hair cells and supporting cells of the organ of Corti throughout the cochlea. Nfr2-IR was also found in hair cells and supporting cells of the maculae and cristae vestibular sensory epithelia. Nrf2-IR was decreased in the organ of Corti of older age individuals. The immunolocalization of Nrf2 in both auditory and vestibular sensory epithelia suggest that this transcription factor may play a relevant role in protecting sensory hair cells from oxidative stress.

High Resolution Three-Dimensional Delayed Contrast MRI Detects Endolymphatic Hydrops in Patients With Vertigo and Vestibular Schwannoma.

OBJECTIVE: Advances in high resolution magnetic resonance imaging (MRI) have enabled the detection of endolymphatic hydrops (EH), a pathological ballooning of the endolymphatic fluid system, known to be associated with Menière's disease. When a patient has a known diagnosis of vestibular schwannoma and develops recurrent episodic vertigo spells, many surgeons recommend surgical intervention, attributing the vestibular symptoms to the vestibular schwannoma. The aim of this study is to evaluate the clinical outcome in patients with vestibular schwannoma and EH, treated medically, for recurrent spells of vertigo. PATIENTS: Two patients with EH and vestibular schwannoma who presented with recurrent spells of vertigo are included. Both had characteristic low frequency hearing loss ipsilateral to the schwannoma. INTERVENTION: MRI sequences with 3T scanner (Skyra, Siemens Healthcare, Erlangen, Germany) using high resolution three-dimensional delayed postcontrast protocol included "cisternographic" T2 and delayed intravenous-enhanced three-dimensional fluid-attenuation inversion recovery (DIVE-3D-FLAIR) sequences, performed with 2350 ms (bright perilymph) and 2050 ms (bright endolymph) inversion times and with subtracted images. MAIN OUTCOME MEASURE: MRI FLAIR evaluation of EH and presence or absence of vestibular symptoms. RESULTS: Both patients had resolution of the disabling vertigo spells with a diuretic, and Patient 1 had unchanged EH, while Patient 2 had partial resolution of the EH and the FLAIR hyperintensity. CONCLUSION: When EH coexists with vestibular schwannoma in a patient presenting with recurrent vertigo spells, medical treatments for EH may alleviate the vestibular symptoms. We recommend that patients with small vestibular schwannomas who present with vertigo spells undergo high resolution MRI to evaluate for EH and undergo a trial of medical treatment with diuretics.

High Resolution MRI Shows Presence of Endolymphatic Hydrops in Patients Still Symptomatic After Endolymphatic Shunt Surgery.

OBJECTIVE: Endolymphatic hydrops has been well described in patients with Ménière's syndrome; however, causation has not been established. Decompression of the endolymphatic sac has been proposed as a means to relieve hydrops and improve vertigo symptoms, but the efficacy of the surgery is debated. Until recently, there have been few objective measures of efficacy other than patients' subjective symptoms. Recent archival human temporal bone studies have shown that patients continue to have hydrops after shunt surgery. We propose using high-resolution magnetic resonance imaging (MRI) to determine the efficacy of endolymphatic shunt surgery (ELS) in patients who continue to experience vertigo. PATIENTS: Four patients presented with continued vertigo after ELS. INTERVENTIONS: Magnetic resonance imaging sequences included "cisternographic" three-dimensional T2, and delayed intravenous-enhanced three-dimensional fluid-attenuation inversion recovery (DIVE-3D-FLAIR) sequences, performed with 2350 ms (bright perilymph) and 2050 ms (bright endolymph) inversion times. The bright endolymph images were subtracted from bright perilymph images to create a composite image with bright perilymph, dark endolymph, and intermediate bone signals. MAIN OUTCOME MEASURES: MRI finding of endolymphatic hydrops. RESULTS: In all five affected ears in four patients who continued to experience severe vertigo, hydrops was found on high resolution MRI on the operated ear. The appearance on MRI was no different than in patients with endolymphatic hydrops (EH) who have not had surgery. CONCLUSIONS: The present study demonstrates the persistence of endolymphatic hydrops in patients who have failed ELS. Future studies evaluating for the presence or absence of endolymphatic hydrops in patients who claim to obtain relief from ELS.

The expression of glutamate aspartate transporter (GLAST) within the human cochlea and its distribution in various patient populations.

Glutamate plays an important role in the central nervous system as an excitatory neurotransmitter. However, its abundance can lead to excitotoxicity which necessitates the proper function of active glutamate transporters. The glutamate-aspartate transporter (GLAST) has been shown to exist and function within non-human cochlear specimens regulating the inner ear glutamate concentration. In this study, we examined human cochleas from formalin-fixed celloidin-embedded temporal bone specimens of three different types of patients (Meniere's disease, normal controls, and other otopathologic conditions) and examined the differential expression of GLAST in the spiral ligament of the basal, middle, and apical turns of the cochlea. Immunohistochemical staining was performed with polyclonal antibodies against GLAST and image analysis was carried out with the Image J analysis software. In contrast to other studies with non-human specimens, GLAST was expressed in the spiral ligament fibrocytes but was not detected in the satellite cells of the spiral ganglia or supporting cells of the Organ of Corti in the human cochlea. Our data also showed that GLAST expression significantly differs in the basal and apical turns of the cochlea. Lastly, post-hoc analysis showed a difference in the GLAST immunoreactive area of patients with Meniere's disease when compared to that of patients with other otopathologic conditions-such as presbycusis or ototoxicity. These results may potentially lead to further understanding of different disease states that affect hearing.

Otolithic membrane damage in patients with endolymphatic hydrops and drop attacks.

OBJECTIVES: 1. Evaluate the otolithic membrane in patients with endolymphatic hydrops (EH) and vestibular drop attacks (VDA) undergoing ablative labyrinthectomy. 2. Correlate intraoperative findings to archival temporal bone specimens of patients with EH. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. SPECIMEN SOURCE: 1. Patients undergoing labyrinthectomy for incapacitating Ménière's disease (MD), delayed EH, VDA, or acoustic neuroma (AN) between 2004 and 2011. 2. Archival temporal bone specimens of patients with MD. INTERVENTIONS: Ablative labyrinthectomy. MAIN OUTCOME MEASURES: Examination of the utricular otolithic membrane. RESULTS: The otolithic membrane of the utricle was evaluated intraoperatively in 28 patients undergoing labyrinthectomy. Seven (25%) had a history of VDA, 6 (21%) had delayed EH, 9 (32%) had MD, and 6 (21%) had AN. All patients with VDA showed evidence of a disrupted utricular otolithic membrane, whereas only 50% and 56% of patients with delayed EH and MD, respectively, demonstrated otolithic membrane disruption (p = 0.051). None of the patients with AN showed otolithic membrane disruption (p = 0.004). The mean thickness of the otolithic membrane in 5 archival temporal bone MD specimens was 11.45 micrometers versus 38 micrometers in normal specimens (p = 0.001). CONCLUSION: The otolithic membrane is consistently damaged in patients with VDA. In addition, there is a significantly higher incidence of otolithic membrane injury in patients with MD and delayed EH compared with patients without hydrops, suggesting that the underlying pathophysiology in VDA results from injury to the otolithic membrane of the saccule and utricle, resulting in free-floating otoliths and atrophy.