Supporting cell survival after cochlear implant surgery.

Supporting cells (SCs) provide structure and maintain an environment that allows hair cells to receive and transmit signals in the auditory pathway. After insult to hair cells and ganglion cells, SCs respond by marking unsalvageable cells for death and maintain structural integrity. Although the histopathology after cochlear implantation has been described regarding hair cells and neural structures, surviving SCs in the implanted ear have not. We present a patient whose posthumous examination of an implanted cochlea demonstrated SC survival. This finding has implications for SC function in maintaining electrical hearing and candidacy for future hair cell regeneration therapies. Laryngoscope, 129:E36-E40, 2019.

Cochlear Dysfunction is not Common in Human Meningioma of the Internal Auditory Canal.

HYPOTHESIS: Cochlear dysfunction is not common in human meningioma of the internal auditory canal. BACKGROUND: Meningiomas arising from the cerebellopontine angle and internal auditory canal typically cause hearing loss. Cochlear dysfunction is known to contribute to sensorineural hearing loss induced by vestibular schwannoma, the most common tumor of the internal auditory canal. Detailed cochlear histopathology in meningioma has not been reported. METHODS: Retrospective analysis of cochlear histopathology in five unoperated and five operated meningiomas of the internal auditory canal identified after screening human temporal bone collections from three academic medical centers. RESULTS: While some dysfunction of all analyzed cochlear cell types was identified, a predominant or exclusive loss of hair cells was not observed in any meningioma. Only 14.3% of temporal bones showed significantly more hair cell damage on the side of the tumor when compared with the contralateral ear; cochlear neuronal damage was more prevalent in meningiomas. The incidence of hydrops, perilymphatic precipitate, or endolymphatic precipitate was low. CONCLUSIONS: Substantial cochlear damage in human meningioma of the internal auditory canal is not common. This may explain the anecdotal hearing improvement observed after surgical resection of meningioma. Our findings underline the importance of developing therapeutic strategies to prevent cochlear neuronal degeneration due to tumors of the internal auditory canal.

Cochlear implant histopathology.

The microscopic examination of fifty-five serially sectioned implanted temporal bones has provided insight into what is being stimulated; and the changes that are the result of the insertion and presence of the implant. The ganglion cell bodies (neurons) are structures being stimulated (two laboratories have reported an inverse relationship of the number of neurons and performance). Insertion through the round window, verses a cochleostomy, produces the least fibrosis and new bone. Fibrosis and new bone do not affect the implant function unless they form in the scala vestibuli in the region of the ductus reuniens, and, block it; and produce cochlear hydrops resulting in a delayed low tone loss of hearing in hybrid implants. Animal models cannot be applied to humans because of the difference in size and myelination of the neurons.

Empirical Derivation of Correction Factors for Human Spiral Ganglion Cell Nucleus and Nucleolus Count Units.

OBJECTIVE: Profile count method for estimating cell number in sectioned tissue applies a correction factor for double count (resulting from transection during sectioning) of count units selected to represent the cell. For human spiral ganglion cell counts, we attempted to address apparent confusion between published correction factors for nucleus and nucleolus count units that are identical despite the role of count unit diameter in a commonly used correction factor formula. STUDY DESIGN: We examined a portion of human cochlea to empirically derive correction factors for the 2 count units, using 3-dimensional reconstruction software to identify double counts. SETTING: The Neurotology and House Histological Temporal Bone Laboratory at University of California at Los Angeles. SUBJECTS AND METHODS: Using a fully sectioned and stained human temporal bone, we identified and generated digital images of sections of the modiolar region of the lower first turn of cochlea, identified count units with a light microscope, labeled them on corresponding digital sections, and used 3-dimensional reconstruction software to identify double-counted count units. RESULTS: For 25 consecutive sections, we determined that double-count correction factors for nucleus count unit (0.91) and nucleolus count unit (0.92) matched the published factors. We discovered that nuclei and, therefore, spiral ganglion cells were undercounted by 6.3% when using nucleolus count units. CONCLUSION: We determined that correction factors for count units must include an element for undercounting spiral ganglion cells as well as the double-count element. We recommend a correction factor of 0.91 for the nucleus count unit and 0.98 for the nucleolus count unit when using 20-µm sections.

Neurofibromatosis 2 invasion of the internal auditory canal wall: clinical significance.

OBJECTIVE: To describe the infiltration of severe phenotype ("Wishart") neurofibromatosis type 2 (NF2)-related vestibular nerve schwannomas (VSs) into the internal auditory canal wall in contrast to sporadic VS and the milder ("Gardner") phenotype NF2-related VS. STUDY DESIGN: Retrospective case series involving microscopic examination and review of clinical history. SETTING: Temporal bone laboratory, harboring 849 documented pairs of decalcified, formalin-fixed, celloidin-embedded, sectioned human temporal bones (hTBs) with clinical history. SUBJECTS AND METHODS: Histologic sections from 56 patients who had been treated by the House Clinic for VS and who had pledged their temporal bones were identified in the data base of the laboratory. Twenty-four hTBs were from individuals with NF2.Each series of sections was examined microscopically for evidence of invasion of the walls of the internal auditory canal (IAC), hearing thresholds, speech discrimination, score (SDS), and tumor recurrence. RESULTS: Infiltration of the walls of the IAC by small buds of VS was found in 17 of the 24 NF2 hTBs. The only 2 NF2 without invasion were from an elderly patient with the milder (Gardner) form of NF2. Ten of the 12 NF2 patients had undergone surgery for the removal of their tumor, but residual tumor remained in the bone surrounding the IAC. Invasive VS were associated with poorer hearing thresholds at 250, 500, 1,000, and 2,000 Hz and lower SDS score. A relationship between invasion and recurrence was not statistically significant. CONCLUSION: The majority of IAC tumors associated with the severe "Wishart" phenotype demonstrate bone invasion within the IAC. Invasion of bone was associated with poorer hearing. The invasive nature of NF2-associated tumors may partially explain their higher recurrence rate after resection. Surgeons managing NF2-related VS should be aware of the small infiltrations of the wall of the IAC when removing these tumors to minimize recurrence.

The periductal channels of the endolymphatic duct, hydrodynamic implications.

OBJECTIVE: To describe the anatomy of a small network of channels surrounding the human endolymphatic duct. STUDY DESIGN: Archival temporal bone sections and a surgical specimen were studied using a variety of techniques. SETTING: Temporal bone laboratory of the House Research Institute. SUBJECTS AND METHODS: Archival temporal bone sections were examined by light microscopy, 3D reconstruction, and immunohistochemical labeling. A surgical specimen was examined using electron microscopy. Sections from temporal bones with blocked endolymphatic ducts or amputated sacs were examined for the manifestations of endolymphatic hydrops. RESULTS: Peri-endolymphatic duct channels were found to extend from the proximal cisternal part of the endolymphatic sac to the supporting tissue of the saccule and utricle. Tissue in the channels, as seen by conventional and electron microscopy, is continuous with and identical with the tissue surrounding the endolymphatic duct. Tissue in the channels labels with the S100 antibody similar to the spiral ligament and supporting tissue of the vestibular end organs and suggests a neural crest origin, as did the presence of melanocytes. Obstruction of the endolymphatic duct resulted in endolymphatic hydrops whereas amputation of the sac did not. CONCLUSION: Endolymph is probably absorbed in the endolymphatic duct. The peri-endolymphatic duct channels that extend from the proximal sac to the supporting tissue of the saccule label with the S100 antibody and contain melanocytes suggest a neural crest origin and involvement in fluid and potassium hydrodynamics similar to those described for the similarly staining spiral ligament of the cochlea.

Idiopathic sudden sensorineural hearing loss: vascular or viral?

OBJECTIVE: To demonstrate that sudden sensorineural hearing loss is possibly of viral origin rather than vascular. STUDY DESIGN: The histopathologic morphology in 7 temporal bones with known vascular impairment due to surgical interventions was compared with that of 11 bones with a history of idiopathic sudden sensorineural hearing loss (ISSNHL). Attention was paid to the spiral ligament, stria vascularis, organ of Corti hair cells, tectorial membrane, ganglion cell population, and degree of perilymph fibrosis and the auditory nerve. SETTING: A temporal bone laboratory that has been in operation for more than 50 years and includes a database consisting of clinical and histopathological information that facilitates quantitative and qualitative analysis. SUBJECTS: Eight hundred forty-nine individuals who pledged their temporal bones for scientific study, of which 18 were selected for this study by means of the database criteria of sudden sensorineural hearing loss and postmiddle fossa and retro sigmoid sinus tumor removal or vestibular nerve section. RESULTS: Sudden sensorineural hearing loss bones exhibited no perilymph fibrosis compared with 6 of 7 vascular cases with fibrosis (P ≤ .001), exhibited less loss of ganglion cells (P ≤ .026), exhibited greater survival of spiral ligament (P ≤ .029), and averaged twice the survival of hair cells and more widespread tectorial membrane abnormalities. CONCLUSION: Analysis of human temporal bones from patients with a sudden sensorineural hearing loss does not support a vascular insufficiency but is more suggestive of a viral etiology.

Petrous apex cholesterol granuloma: maintenance of drainage pathway, the histopathology of surgical management and histopathologic evidence for the exposed marrow theory.

OBJECTIVES: (1) To assess the maintenance of drainage pathway patency in patients who undergo surgical management of cholesterol granulomas, (2) to review the histopathologic and radiologic changes associated with surgical drainage of petrous apex (PA) cholesterol granulomas, and (3) to provide histopathologic evidence regarding the exposed marrow theory of PA cholesterol granulomas. STUDY DESIGN: Retrospective case review and histopathologic analysis. SETTING: Tertiary referral center. PATIENTS: Records of 17 patients with surgically managed PA cholesterol granulomas were reviewed. Histopathologic analysis was performed on temporal bones of 11 patients with PA cholesterol granulomas from the Temporal Bone repository at the House Research Institute. INTERVENTIONS: Surgical drainage of PA cholesterol granulomas; follow-up radiologic imaging (computed tomography or magnetic resonance imaging), when available. MAIN OUTCOME MEASURES: Primary outcome is demonstrated maintenance of a PA outflow drainage pathway after the surgical drainage procedure as assessed by radiologic imaging, available histopathology, and/or recurrence of symptoms indicating failure of maintenance. Other measures include need for revision surgery and histopathology findings. RESULTS: A majority (65%) of patients exhibited maintenance of their PA drainage pathway. Histopathologic evidence suggests that the PA drainage pathway can be maintained for many years after surgical drainage. Recurrence of symptoms was related to obstruction of the drainage pathway by fibrous tissue and/or granulomatous tissue. Placement of a stent improved the patient's chance of remaining symptom-free, with recurrence of symptoms and revision surgery required in only 2 stent cases (18%) as compared with 83% of those with no stent (p ≤ 0.035). Histopathologic evidence for the exposed marrow theory of PA cholesterol granulomas was found. CONCLUSION: The majority of patients who undergo surgical drainage of PA cholesterol granulomas remain symptom-free after surgical drainage. Histopathologic analysis of temporal bone specimens provides evidence supporting the exposed marrow theory of PA cholesterol granuloma formation. Loss of patency of the PA drainage pathway may be an important predictor for symptomatic recurrence of PA cholesterol granulomas. Placement of a stent may decrease the likelihood of symptomatic recurrence.

Dysfunction of the cochlea contributing to hearing loss in acoustic neuromas: an underappreciated entity.

OBJECTIVE: Hearing loss is a common symptom in patients with cochleovestibular schwannoma. Clinical and histologic observations have suggested that the hearing loss may be caused by both retrocochlear and cochlear mechanisms. Our goal was to perform a detailed assessment of cochlear pathology in patients with vestibular schwannoma (VS). STUDY DESIGN: Retrospective analysis of temporal bone histopathology. SETTING: Multi-center study. MATERIAL: Temporal bones from 32 patients with unilateral, sporadic VS within the internal auditory canal. MAIN OUTCOME MEASURES: Sections through the cochleae on the VS side and opposite (control) ear were evaluated for loss of inner and outer hair cells, atrophy of the stria vascularis, loss of cochlear neurons, and presence of endolymphatic hydrops and precipitate within the endolymph or perilymph. Observed pathologies were correlated to nerve of origin, VS volume, and distance of VS from the cochlea. Hearing thresholds also were assessed. RESULTS: VS caused significantly more inner and outer hair cell loss, cochlear neuronal loss, precipitate in endolymph and perilymph, and decreased pure tone average, when compared with the opposite ear. Tumor size, distance from the cochlea, and nerve of origin did not correlate with structural changes in the cochlea or the hearing threshold. CONCLUSION: There is significant degeneration of cochlear structures in ears with VS. Cochlear dysfunction may be an important contributor to the hearing loss caused by VS and can explain certain clinically observed phenomena in patients with VS.

What is the site of origin of cochleovestibular schwannomas?

The belief that cochleovestibular schwannomas arise from the glial-Schwann cell junction has repeatedly been quoted in the literature, although there is no published evidence that supports this statement. A systematic evaluation of the nerve of origin and the precise location of cochleovestibular schwannomas using our respective archival temporal bone collections was conducted. Forty tumors were within the internal auditory canal (IAC), while 10 were intralabyrinthine neoplasms. Of the 40 IAC schwannomas, 4 arose from the cochlear nerve, and 36 from the vestibular nerve. Twenty-one tumors clearly arose lateral to the glial-Schwann cell junction, while 16 tumors filled at least two thirds of the IAC, with the epicenter of the neoplasm located in the mid part or the lateral part of the IAC. Only 3 schwannomas were located in the medial one third of the IAC in the area of the glial-Schwann cell junction. We concluded that cochleovestibular schwannomas may arise anywhere along the course of the axons of the eighth cranial nerve from the glial-Schwann sheath junction up until their terminations within the auditory and vestibular end organs.

Histopathologic markers of hearing loss in intralabyrinthine schwannomas: implications for management.

OBJECTIVE: This study aimed to review the clinical history and management of patients with intralabyrinthine schwannomas and evaluate the histopathologic features of these tumors. STUDY DESIGN: A retrospective case review of 24 patients and 7 temporal bone specimens. SETTING: An otologic tertiary referral private practice. PATIENTS: Patients with magnetic resonance imaging-confirmed intralabyrinthine schwannoma diagnosed after 1995 and non-Neurofibromatosis type 2 temporal bone specimens with schwannomas confined to the bony labyrinth. MAIN OUTCOME MEASURES: Clinical data including history, imaging and audiometry were evaluated. The histopathologic features of temporal bone specimens including tumor location and degenerative changes were analyzed. RESULTS: The intralabyrinthine location of the tumor does not predict the degree or time to progression of hearing loss. Both sensorineural and conductive hearing loss can occur. Mechanisms of hearing loss include hair cell, spiral ganglion, and stria vascularis degeneration in addition to mechanical obstruction. CONCLUSION: Hearing loss is the most common symptom with intralabyrinthine schwannomas. Histopathology reveals that multiple mechanisms of degeneration may occur within the labyrinth to induce hearing loss. Observation provides the most reliable hearing preservation strategy.

Temporal bone histopathology in neurofibromatosis type 2.

OBJECTIVES/HYPOTHESIS: To describe the histopathologic findings in the temporal bone in patients with neurofibromatosis type 2 (NF2). The literature contains limited data on otopathology of NF2. STUDY DESIGN: Basic science study. METHODS: Twenty-six temporal bones from 16 patients with NF2 were examined by light microscopy. The diagnosis of NF2 was made on the basis of bilateral cochleovestibular schwannomas. Clinical information was obtained from review of the medical records. RESULTS: The tumors were multicentric in origin in 19 of 26 (73%) ears. Typically, tumors were seen arising within the internal auditory canal and from various locations within the labyrinth. The majority of schwannomas showed high cellularity with involvement of the labyrinth. Most cases showed significant degrees of degeneration of sensory and neural elements within the cochlea. Fusion tumors were sometimes seen as a result of a schwannoma merging with an adjacent meningioma. Fifteen of 26 (58%) ears showed facial nerve involvement by schwannoma. CONCLUSIONS: Cochleovestibular schwannomas in NF2 are aggressive neoplasms; they are often multicentric and demonstrate a propensity to involve the labyrinth. There is often associated secondary degeneration within the cochlea. These features make total removal of these tumors and their removal with preservation of hearing more difficult than with sporadic unilateral cochleovestibular schwannoma.