Joseph B. Nadol

Survival of Spiral Ganglion Cells in Profound Sensorineural Hearing Loss: Implications for Cochlear Implantation

Ninety-three temporal bones from 66 patients who were profoundly deaf during life were reconstructed by analysis of serial light microscopic sections. The correlations of total and segmental spiral ganglion cell counts with age, duration of hearing loss and profound deafness, and cause of hearing loss were evaluated. Bivariate analysis demonstrated that total spiral ganglion cell count tended to be lower in older than in younger deaf individuals and lower with longer duration of hearing loss and total deafness. However, multiple regression analysis demonstrated that the cause of hearing loss was the single most significant determinant of total spiral ganglion cell count. Patients with deafness due to aminoglycoside toxicity or sudden idiopathic deafness had the highest residual spiral ganglion cell count and patients with deafness due to presumptive postnatal viral labyrinthitis, bacterial labyrinthitis, and congenital or genetic causes had the lowest numbers of residual spiral ganglion cells.

Pathophysiology of Meniere's syndrome: are symptoms caused by endolymphatic hydrops?

Background: The association of Ménières syndrome with endolymphatic hydrops has led to the formation of a central hypothesis: many possible etiologic factors lead to hydrops, and hydrops in turn generates the symptoms. However, this hypothesis of hydrops as being the final common pathway has not been proven conclusively. Specific Aim: To examine human temporal bones with respect to the role of hydrops in causing symptoms in Ménières syndrome. If the central hypothesis were true, every case of Ménières syndrome should have hydrops and every case of hydrops should show the typical symptoms. Methods: Review of archival temporal bone cases with a clinical diagnosis of Ménières syndrome (28 cases) or a histopathologic diagnosis of hydrops (79 cases). Results: All 28 cases with classical symptoms of Ménières syndrome showed hydrops in at least one ear. However, the reverse was not true. There were 9 cases with idiopathic hydrops and 10 cases with secondary hydrops, but the patients did not exhibit the classic symptoms of Ménières syndrome. A review of the literature revealed cases with asymptomatic hydrops (similar to the current study), as well as cases where symptoms of Ménières syndrome existed during life but no hydrops was observed on histology. We also review recent experimental data where obstruction of the endolymphatic duct in guinea pigs resulted in cytochemical abnormalities within fibrocytes of the spiral ligament before development of hydrops. This result is consistent with the hypothesis that hydrops resulted from disordered fluid homeostasis caused by disruption of regulatory elements within the spiral ligament. Conclusion: Endolymphatic hydrops should be considered as a histologic marker for Ménières syndrome rather than being directly responsible for its symptoms.

Mutations in a novel cochlear gene cause DFNA9, a human nonsyndromic deafness with vestibular dysfunction

DFNA9 is an autosomal dominant, nonsyndromic, progressive sensorineural hearing loss with vestibular pathology. Here we report three missense mutations in human COCH (previously described as Coch5b2), a novel cochlear gene, in three unrelated kindreds with DFNA9. All three residues mutated in DFNA9 are conserved in mouse and chicken Coch, and are found in a region containing four conserved cysteines with homology to a domain in factor C, a lipopolysaccharide-binding coagulation factor in Limulus polyphemus. COCH message, found at high levels in human cochlear and vestibular organs, occurs in the chicken inner ear in the regions of the auditory and vestibular nerve fibres, the neural and abneural limbs adjacent to the cochlear sensory epithelium and the stroma of the crista ampullaris of the vestibular labyrinth. These areas correspond to human inner ear structures which show histopathological findings of acidophilic ground substance in DFNA9 patients.

Patterns of Neural Degeneration in the Human Cochlea and Auditory Nerve: Implications for Cochlear Implantation

Although the identity of all the variables that may influence speech recognition after cochlear implantation is unknown, the degree of preservation of spiral ganglion cells is generally considered to be of primary importance. A series of experiments in our laboratories, directed at quantification of surviving spiral ganglion cells in the profoundly deaf, evaluation of the predictive value of a variety of clinical parameters, and the evaluation of the consequences of implantation in the inner ear, is summarized. Histologic study of the inner ears of patients who were deafened during life demonstrated that the cause of deafness accounted for 57% of the variability of spiral ganglion cell counts. Spiral ganglion cell counts were highest in individuals deafened by aminoglycoside toxicity or sudden idiopathic deafness and lowest in those deafened by postnatal viral labyrinthitis, congenital or genetic deafness, or bacterial meningitis. Study of the determinants of degeneration of the spiral ganglion revealed that degeneration is most severe in the basal compared with the apical turn and more severe when both inner and outer hair cells are absent. Unlike the findings in some experimental animal studies, no survival advantage of type II ganglion cells could be identified. There was a strong negative correlation between the degree of bony occlusion of the cochlea and the normality of the spiral ganglion cell count. However, even in specimens in which there was severe bony occlusion, significant numbers of spiral ganglion cells survived. A strong positive correlation between the diameter of the cochlear, vestibular, and eighth cranial nerves with the total spiral ganglion cell count (p < 0.001) was found. This would suggest that modern imaging techniques may be used to predict residual spiral ganglion cell population in cochlear implant candidates. Trauma from implantation of the electrode array was studied in both cadaveric human temporal bone models and temporal bones from individuals who received implants during life. A characteristic pattern of damage to the lateral cochlear wall and basilar membrane was identified in the upper basal turn. New bone formation and perielectrode fibrosis was common after cochlear implantation. Despite this significant trauma and reaction, there is no firm evidence that further degeneration of the spiral ganglion can be predicted as a consequence.

Histopathology of Cochlear Implants in Humans

The insertion of an intrascalar electrode array during cochlear implantation causes immediate damage to the inner ear and may result in delayed onset of additional damage that may interfere with neuronal stimulation. To date, there have been reports on fewer than 50 temporal bone specimens from patients who had undergone implantation during life. The majority of these were single-channel implants, whereas the majority of implants inserted today are multichannel systems. This report presents the histopathologic findings in temporal bones from 8 individuals who in life had undergone multichannel cochlear implantation, with particular attention to the type and location of trauma and to long-term changes within the cochlea. The effect of these changes on spiral ganglion cell counts and the correlation between speech comprehension and spiral ganglion cell counts were calculated. In 4 of the 8 cases, the opposite, unimplanted ear was available for comparison. In 3 of the 4 cases, there was no significant difference between the spiral ganglion cell counts on the implanted and unimplanted sides. In addition, in this series of 8 cases, there was an apparent negative correlation between residual spiral ganglion cell count and hearing performance during life as measured by single-syllable word recognition. This finding suggests that abnormalities in the central auditory pathways are at least as important as spiral ganglion cell loss in limiting the performance of implant users.

Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss.

Background: The cause and pathogenesis of idiopathic sudden sensorineural hearing loss remain unknown. Proposed theories include vascular occlusion, membrane breaks, and viral cochleitis. Aims: To describe the temporal bone histopathology in 17 ears (aged 45-94 yr) with idiopathic sudden sensorineural hearing loss in our temporal bone collection and to discuss the implications of the histopathologic findings with respect to the pathophysiology of idiopathic sudden sensorineural hearing loss. Methods: Standard light microscopy using hematoxylin and eosin-stained sections was used to assess the otologic abnormalities. Results: Hearing had recovered in two ears and no histologic correlates were found for the hearing loss in both ears. In the remaining 15 ears, the predominant abnormalities were as follows: 1) loss of hair cells and supporting cells of the organ of Corti (with or without atrophy of the tectorial membrane, stria vascularis, spiral limbus, and cochlear neurons) (13 ears); 2) loss of the tectorial membrane, supporting cells, and stria vascularis (1 ear); and 3) loss of cochlear neurons only (1 ear). Evidence of a possible vascular cause for the idiopathic sudden sensorineural hearing loss was observed in only one ear. No membrane breaks were observed in any ear. Only 1 of the 17 temporal bones was acquired acutely during idiopathic sudden sensorineural hearing loss, and this ear did not demonstrate any leukocytic invasion, hypervascularity, or hemorrhage within the labyrinth, as might be expected with a viral cochleitis. Discussion: The temporal bone findings do not support the concept of membrane breaks, perilymphatic fistulae, or vascular occlusion as common causes for idiopathic sudden sensorineural hearing loss. The finding in our one case acquired acutely during idiopathic sudden sensorineural hearing loss as well as other clinical and experimental observations do not strongly support the theory of viral cochleitis. Conclusion: We put forth the hypothesis that idiopathic sudden sensorineural hearing loss may be the result of pathologic activation of cellular stress pathways involving nuclear factor-κB within the cochlea.

Postnatal Growth of the Human Temporal Bone Implications for Cochlear Implants in Children

Recent interest in cochlear implantation for children has made it important to understand how postnatal growth of the ear will affect such devices. In this study, the postnatal growth of the labyrinth, middle ear, and mastoid was measured in three dimensions using radiographic and temporal bone data. Measurements were made from histologic sections of 48 temporal bones from children and compared to adult temporal bones. Radiographic measurements were made from 253 sets of skull radiographs of children and compared to adult skull series. In the three dimensions measured, there was no postnatal growth of the labyrinth and little variation in size between individuals. Measurements of the middle ear showed greater variation between individuals than measurements of the inner ear, but growth only in the distance from stapes footplate to the tympanic membrane. The mastoid showed growth in all three dimensions: length, width, and depth. The pattern of growth for mastoid length and width appears to follow a double logistic model, with differences between males and females. The growth in mastoid depth is smaller and appears to follow a single exponential curve. The implications for cochlear implantation in children are discussed.

Is Word Recognition Correlated With the Number of Surviving Spiral Ganglion Cells and Electrode Insertion Depth in Human Subjects With Cochlear Implants

Objectives/Hypothesis: Speech perception scores using cochlear implants have ranged widely in all published series. The underlying determinants of success in word recognition are incompletely defined. Although it has been assumed that residual spiral ganglion cell population in the deaf ear may play a critical role, published data from temporal bone specimens from patients have not supported this hypothesis. The depth of insertion of a multichannel cochlear implant has also been suggested as a clinical variable that may be correlated with word recognition. In the current study these correlations were evaluated in 15 human subjects.

Preservation of hearing in surgical removal of acoustic neuromas of the internal auditory canal and cerebellar pontine angle

The surgical results in 69 patients with unilateral tumors of the cerebellopontine angle or internal auditory canal in whom total tumor removal was accomplished, and in whom an attempt was made to preserve hearing, are presented. The success rate of preservation of hearing and facial nerve function was correlated with the size of the tumor. Useful hearing, as defined by speech reception threshold no poorer than 70 dB and a discrimination score of at least 15%, was preserved in 73% of cases in which the tumor extension to the posterior fossa was no greater than 0.5 cm. In contrast, useful hearing was preserved in 22% of cases in which posterior fossa extension was greater than 2.5 cm. No significant correlation was found between preoperative evoked responses and success in preservation of hearing. The techniques and value of intraoperative monitoring of electrocochleogram (ECoG) and brain stem evoked response are discussed. A theory of pathogenesis of intraoperative hearing loss, based on correlation of changes in evoked responses and simultaneous surgical events, is presented.

Vertigo of Delayed Onset after Sudden Deafness

An entity of episodic true vertigo of delayed onset following sudden and profound sensorineural hearing loss is described. Data on 12 patients and three case reports are presented. The latency between sudden deafness and the onset of the vertigo varied from 1 to 68 years. The vestibular symptoms are identical to the vestibular symptoms of Ménières disease, and there is some evidence that endolymphatic hydrops in the previously deafened ear represents at least part of the labyrinthine pathology. Labyrinthectomy in the deaf ear was curative. Tentatively, this entity is best considered a variant of Ménières disease.