Dynamic Molecular Markers of Otosclerosis in the Human Cochlea.

OBJECTIVE: To investigate the role and distribution of various molecular markers using immunohistochemistry and immunofluorescence to further elucidate and understand the pathogenesis of otosclerosis. METHODS: Archival celloidin formalin-fixed 20-micron thick histologic sections from 7 patients diagnosed with otosclerosis were studied and compared to controls. Sections in the mid-modiolar region were immunoreacted with rabbit polyclonal antibodies against nidogen-1, ß2-laminin, collagen-IX, BSP, and monoclonal antibodies against TGF ß-1 and ubiquitin. Digital images were acquired using a high-resolution light and laser confocal microscope. RESULTS: Nidogen-1, BSP, and collagen-IX were expressed in the otospongiotic regions, and to lesser extent, in the otosclerotic regions, the latter previously believed to be inactive. ß2-laminin and ubiquitin were uniformly expressed in both otospongiotic and otosclerotic regions. There was a basal level of expression of all of these markers in the normal hearing and sensorineural hearing loss specimens utilized as control. TGF ß -1, however, though present in the otosclerosis bones, was absent in the normal hearing and sensorineural hearing loss controls. CONCLUSIONS: Our results propose that the activity and function of TGF-1 may play a key role in the development and pathogenesis of otosclerosis. Further studies utilizing a higher number of temporal bone specimens will be helpful for future analysis and to help decipher its role as a potential target in therapeutic interventions.

Expression of Brain-Derived Neurotrophic Factor in Human Spiral Ganglia Neurons after Cochlear Implantation.

BACKGROUND: Brain-derived neurotrophic factor (BDNF) is an important factor in the development and neuroprotection of afferent auditory pathways. In this study, we investigated the expression of BDNF in the afferent auditory pathway after cochlear implantation (CI), hypothesizing that electrical stimulation after CI stimulates BDNF expression in the afferent auditory pathway. METHODS: Archival human temporal bones from eight patients with a history of CI and five patients with normal hearing (ages 65-93 years old) were studied. Temporal bone specimens were immunoreacted with rabbit polyclonal antibodies against BDNF and mouse monoclonal antibodies against pan-neurofilaments. In cases of unilateral CI, the BDNF expression was compared with the contralateral unimplanted ear and normal temporal bones without hearing loss. RESULTS: BDNF immunoreactivity (IR) localized to the spiral ganglion neurons (SGNs) somata and the surrounding satellite cells. BDNF-IR in the spiral ganglia was similar in the apical, middle, and basal hook regions. Neurofilament IR localized to SGN nerve fibers in both implanted and unimplanted cochleae. BDNF-IR in the SGN and satellite cells was significantly increased in the implanted specimens compared with the unimplanted specimens ( p < 0.05) and the normal hearing specimens ( p < 0.05). BDNF-IR expression was similar in the unimplanted cochlea and in the normal cochlea. BDNF protein expression was increased despite complete loss of the organ of Corti hair cells and supporting cells. Even in the cases of CI with a 6-mm first-generation electrode, BDNF expression was upregulated throughout the cochlea. CONCLUSIONS: BDNF expression in the SGN appears to be upregulated by the electrical stimulation from CI. This study provides evidence that the electrical stimulation from CI may stimulate the expression of BDNF, playing a neuroprotective role in the rehabilitation of hearing in the deafened ear.

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.

Immunohistochemical localization of glucocorticoid receptors in the human cochlea.

In the present study we investigated the localization of glucocorticoid receptors (GCR) in the human inner ear using immunohistochemistry. Celloidin-embedded cochlear sections of patients with normal hearing (n = 5), patients diagnosed with MD (n = 5), and noise induced hearing loss (n = 5) were immunostained using GCR rabbit affinity-purified polyclonal antibodies and secondary fluorescent or HRP labeled antibodies. Digital fluorescent images were acquired using a light sheet laser confocal microscope. In celloidin-embedded sections GCR-IF was present in the cell nuclei of hair cells and supporting cells of the organ of Corti. GCR-IF was detected in cell nuclei of the Reisner's membrane. GCR-IF was seen in cell nuclei of the stria vascularis and the spiral ligament. GCR-IF was found in the spiral ganglia cell nuclei, however, spiral ganglia neurons showed no GCR-IF. Although GCRs were found in most cell nuclei of the cochlea, the intensity of IF was differential among the different cell types being more intense in supporting cells than in sensory hair cells. The differential expression of GCR receptors found in the human cochlea may help to understand the site of action of glucocorticoids in different ear diseases.

Morphometric Analysis and Linear Measurements of the Scala Tympani and Implications in Cochlear Implant Electrodes.

HYPOTHESIS: The objective of this study was to perform detailed height and cross-sectional area measurements of the scala tympani in histologic sections of nondiseased human temporal bones and correlate them with cochlear implant electrode dimensions. BACKGROUND: Previous investigations in scala tympani dimensions have used microcomputed tomography or casting modalities, which cannot be correlated directly with microanatomy visible on histologic specimens. METHODS: Three-dimensional reconstructions of 10 archival human temporal bone specimens with no history of middle or inner ear disease were generated using hematoxylin and eosin histopathologic slides. At 90-degree intervals, the heights of the scala tympani at lateral wall, midscala, and perimodiolar locations were measured, along with cross-sectional area. RESULTS: The vertical height of the scala tympani at its lateral wall significantly decreased from 1.28 to 0.88 mm from 0 to 180 degrees, and the perimodiolar height decreased from 1.20 to 0.85 mm. The cross-sectional area decreased from 2.29 (standard deviation, 0.60) mm 2 to 1.38 (standard deviation, 0.13) mm 2 from 0 to 180 degrees ( p = 0.001). After 360 degrees, the scala tympani shape transitioned from an ovoid to triangular shape, corresponding with a significantly decreased lateral height relative to perimodiolar height. Wide variability was observed among the cochlear implant electrode sizes relative to scala tympani measurements. CONCLUSION: The present study is the first to conduct detailed measurements of heights and cross-sectional area of the scala tympani and the first to statistically characterize the change in its shape after the basal turn. These measurements have important implications in understanding locations of intracochlear trauma during insertion and electrode design.

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.

Archival Human Temporal Bone: Anatomical and Histopathological Studies of Cochlear Implantation.

Since being FDA approved in 1984, cochlear implantation has been used successfully to restore hearing in those with severe to profound hearing loss with broader applications including single-sided deafness, the use of hybrid electroacoustic stimulation, and implantation at all extremes of age. Cochlear implants have undergone multiple changes in the design aimed at improving the processing technology, while simultaneously minimizing the surgical trauma and foreign body reaction. The following review examines the human temporal bone studies regarding the anatomy of the human cochlea and how the anatomy relates to cochlear implant design, the factors related to complications after implantation, and the predictors of new tissue formation and osteoneogenesis. Histopathological studies are reviewed which aim to understand the potential implications of the effects of new tissue formation and inflammation following implantation.

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.

Relationship Between the Onset of Ménière's Disease and Sympathetic Hyperactivity.

Objective: The pathogenesis of Ménière's disease is still largely unknown; however, it is known to be strongly associated with stress. Excessive stress can cause hyperactivity of the sympathetic autonomic nervous system. With the aim of understanding changes in sympathetic hyperactivity before and after Ménière's disease, we compared autonomic nervous function in patients in a stable phase of Ménière's disease and that in healthy adults. We also gathered data over about 10 years on autonomic nervous function immediately before a Ménière's attack. Study Design: Prospective study. Patients: Autonomic nervous function was analyzed in 129 patients in a stable phase of Ménière's disease 31 healthy adult volunteers. In nine patients, autonomic nervous function was also measured immediately before and after treatment of a vertigo attack. Main Outcome Measure: Power spectrum analysis of heart rate variability (HRV) of EEG/ECG and an infrared electronic pupillometer were used. Sympathetic and parasympathetic nervous function was measured. Results: There were no statistically significant differences in autonomic nervous function determined by HRV and electronic pupillometry between patients in a stable phase of Ménière's disease and healthy adults. Sympathetic function as measured by electronic pupillometry parameters VD and T5 showed no difference between the affected and unaffected sides in the baseline data measured in the stable phase (VD: affected side is 31.02 ± 6.16 mm/sec, unaffected side is 29.25 ± 5.73 mm/sec; T5: affected side is 3.37 ± 0.43 msec, unaffected side is 3.25 ± 0.39 msec). In contrast, all nine patients whose HRV data had been obtained just before an attack showed marked suppression of the parasympathetic nervous system and activation of the sympathetic nervous system. Electronic pupillometry also revealed an overactivation of the sympathetic nervous system on the affected side, just before the attacks. Analysis of sequential changes after the onset of an attack revealed that overactivation on the affected side was reduced after treatment, and no difference between affected and unaffected sides was observed 3 days after treatment. Conclusion: Detailed analysis of autonomic nervous function showed that immediately before an attack of Ménière's disease, the sympathetic nervous system on the affected side was strongly overactivated.

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.

Predictors of Fibrotic and Bone Tissue Formation With 3-D Reconstructions of Post-implantation Human Temporal Bones.

HYPOTHESIS: Years of implantation, surgical insertion approach, and electrode length will impact the volume of new tissue formation secondary to cochlear implantation. BACKGROUND: New tissue formation, fibrosis, and osteoneogenesis after cochlear implantation have been implicated in increasing impedance and affecting performance of the cochlear implant. METHODS: 3-D reconstructions of 15 archival human temporal bones from patients with a history of cochlear implantation (CI) were generated from H&E histopathologic slides to study factors which affect volume of tissue formation. RESULTS: Years of implantation was a predictor of osteoneogenesis (r = 0.638, p-value = 0.011) and total new tissue formation (r = 0.588, p-value = 0.021), however not of fibrosis (r = 0.235, p-value = 0.399). Median total tissue formation differed between cochleostomy and round window insertions, 25.98 and 10.34%, respectively (Mann-Whitney U = 7, p = 0.018). No correlations were found between electrode length or angular insertion depth and total new tissue (p = 0.192, p = 0.35), osteoneogenesis (p = 0.193, p = 0.27), and fibrosis (p = 0.498, p = 0.83), respectively. However, the type II error for electrode length and angular insertion depth ranged from 0.73 to 0.90, largely due to small numbers of the shorter electrodes. CONCLUSIONS: With numbers of cochlear implant recipients increasing worldwide, an understanding of how to minimize intracochlear changes from implantation is important. The present study demonstrates that increasing years of implantation and inserting electrodes via a cochleostomy compared with a round window approach are associated with significantly greater degree of new tissue volume formation. While previous studies have demonstrated increased intracochlear damage in the setting of translocation with longer electrodes, length, and angular insertion depth of CI electrodes were not associated with increased tissue formation.

Isolated Saccular Hydrops on High-resolution MRI Is Associated With Full Spectrum Menière's Disease.

OBJECTIVE: To describe the clinical presentation of patients with isolated saccular endolymphathic hydrops (EH) detected. STUDY DESIGN: Clinical case series. SETTING: University-based tertiary referral center. PATIENTS: All subjects presenting with vertigo or hearing loss who had isolated saccular EH detected. INTERVENTION: High-resolution delayed-contrast magnetic resonance imaging (MRI) conducted between November 2015 and November 2016. MAIN OUTCOME MEASURES: Audiovestibular testing results and analysis of clinical histories. RESULTS: Isolated saccular EH was detected in 18 subjects. Sixteen met criteria for definite Menière's disease (MD, n = 12) or delayed endolymphatic hydrops (DEH, n = 4). One had a history of sudden sensorineural hearing loss (SSNHL) and 3 years after MRI developed recurrent vertigo characteristic of DEH. One patient had a history of atypical DEH (Tumarkin falls without vertigo following SSNHL). Four patients had Tumarkin falls. Most (83%) demonstrated mild-to-severe low-frequency fluctuating loss, and six (33.3%) had a history of ipsilateral sudden profound SNHL. Nine of the 17 (53%) patients tested had an ipsilateral caloric paresis ranging from 26 to 67%. Ipsilateral vestibular-evoked myogenic potentials showed reduced or absent responses in 5 of the 17 tested (29%). CONCLUSIONS: The full spectrum of MD may be associated with saccular hydrops. We propose that MD and DEH often begin in the saccule, and MRI may provide clues to the pathophysiology of MD. Saccular hydrops was present in one patient with SSNHL who did not develop vertigo spells until 3 years after MRI, indicating that saccular hydrops may be the first manifestation of MD or DEH.

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.

Human Temporal Bone Study of Vestibular Histopathology in Cochlear Implant Patients With Cochlear Hydrops.

HYPOTHESIS: Endolymphatic hydrops (EH) associated with cochlear implantation are associated with vestibular dysfunction. BACKGROUND: Vestibular dysfunction is a known risk after cochlear implantation (CI). CI has been shown to cause cochlear hydrops due to fibrosis surrounding the ductus reuniens. However, the association of cochlear hydrops with vestibular hydrops and the relationship to vestibular symptoms remain unknown. METHODS: Histopathological analysis and clinical evaluation of the vestibular end organs of 17 human temporal bones (HTB)s exhibiting cochlear hydrops from 15 CI recipients. RESULTS: Eight of 15 patients with cochlear hydrops due to CI had complaints of dizziness, vertigo, or imbalance following CI. In all 17 HTBs with cochlear hydrops, there was fibrosis, atrophy, or obstruction of the ductus reuniens, and all had straight electrode CI via cochleostomy. In one of the eight reporting postoperative dizziness, labyrinthitis ossificans was deemed causative. Six of the seven remaining patients had EH of both the saccule and utricle. Fifteen of 17 HTBs (88.2%) had saccular EH. In contrast, 8 of 17 HTBs (47.0%) in 7 patients had utricular EH, of which 6 patients had postoperative vertigo spells. It seems that hydrops of the utricle closely corresponds to postoperative vertigo spells and vestibular complaints. CONCLUSION: Implantation of the CI, when complicated by ductus reuniens fibrosis, may cause both cochlear hydrops and vestibular endolymphatic hydrops. Hydrops of the vestibular periphery when involving the utricle seems to be more likely associated with disabling vertigo symptoms. This study supports the round window technique of insertion rather than cochleostomy.