Barbara J. Burgess

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.

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.

Patterns of degeneration in the human cochlear nerve

The patterns of neural degeneration of the spiral ganglion were studied in 12 human pathologic specimens and 2 normal neonatal specimens. Morphometric analysis of spiral ganglion cells included the maximum cross-sectional areas of both large (type 1) and small (type II) spiral ganglion cells. The organ of Corti in segments corresponding to the spiral ganglion, was evaluated for the presence or absence of inner (IHC) and outer (OHC) hair cells and supporting cells. The relationship between degeneration of spiral ganglion cells and degeneration in the organ of Corti, the age, sex, duration of deafness, cochlear location and delay between death and fixation was evaluated statistically. Both primary and secondary degeneration of the spiral ganglion were more severe in the basal than apical half of the cochlea. Degeneration of the spiral ganglion was most severe when both IHCs and OHCs were absent in the organ of Corti. No survival advantage was identified for type II ganglion cells as has been previously reported. That is, there was no correlation between the degree of degeneration of the spiral ganglion and the prevalence of type II ganglion cells. In fact, there was more severe degeneration of type II cells when the corresponding organ of Corti was severely degenerated. These findings in the human were compared with animal models of degeneration of the spiral ganglion, and the implications for cochlear implantation were discussed.

Histopathology of the peripheral vestibular system after cochlear implantation in the human.

Objectives: The objective of this study was to describe the histology of the peripheral vestibular system in temporal bones from patients who in life had undergone cochlear implantation and to correlate the findings with previous reports of vestibular dysfunction after cochlear implantation. This is the first quantitative report of the impact of implantation on the vestibular neuronal end organ. Methods: There were 19 temporal bones available for histologic study. Of these, 17 were suitable for the description of the morphology of the membranous labyrinth, 8 for counting Scarpas ganglion cells, and 6 for measuring the densities of vestibular hair cells. The bones were fixed, cut, and stained according to previously published methods. Preferably, the implanted electrode was left in situ. Vestibular hair cells were counted with Nomarskis optics. Results: Differences in Scarpas ganglion cell counts and hair cell densities between the implanted and nonimplanted sides were not statistically significant. In 59% of the implanted bones, the cochlea was hydropic, and in the majority of these bones the saccule was collapsed. Conclusion: Cochlear implantation does not cause deafferentation of the peripheral vestibular system. Cochlear hydrops accompanied by saccular collapse is common and may cause attacks of vertigo of delayed onset, similar to Ménières syndrome as previously reported in several clinical series. Hydrops could be caused by obstruction of endolymphatic flow in the ductus reuniens or in the hook portion of the cochlea or by damage to the lateral cochlear wall caused by implantation.

Pattern of degeneration of the spiral ganglion cell and its processes in the C57BL/6J mouse.

Although degeneration of spiral ganglion cells has been described as a histopathologic correlate of hearing loss both in animals and humans, the pattern and sequence of this degeneration remain controversial. Degeneration of hair cells and of spiral ganglion cells and their dendritic processes was evaluated in the C57BL/6J mouse, in which there is a genetically determined progressive sensorineural loss starting in the high frequencies that is similar to the pattern commonly seen in the human. Auditory function was evaluated by brainstem evoked responses, and degeneration of hair cells, ganglion cells and their dendrites was evaluated histologically at 3, 8, 12 and 18 months of age. Progressive loss of auditory sensitivity was correlated with the loss of outer and inner hair cells and spiral ganglion cells and their dendritic processes. In addition, dendritic counts were consistently lower at a distal location in the osseous spiral lamina (i.e. near the organ of Corti) than at a proximal location (i.e. near the spiral ganglion), and the difference between the number of distal dendrites and the number of proximal dendrites tended to be greater with advancing age. These observations suggest an age-related progressive retrograde degeneration of spiral ganglion cells. Thus, in degenerating cochleas, some remaining spiral ganglion cells may have no distal dendritic processes near the organ of Corti. This may have implications for successful stimulation of the cochlear neuron in cochlear implantation.

Morphometric Analysis of Normal Human Spiral Ganglion Cells

A morphometric analysis of the human spiral ganglion was performed at an ultrastructural level. Cells of the basal, middle, and upper middle turns were evaluated by serial section. The following parameters were evaluated: Myelinization, area, diameter, circumference, and degree of roundness of the cell body and nucleus; diameter of the axon and dendrite in their initial segments; and process configuration. Analysis of variance suggested there were at least two types of cell bodies within the human spiral ganglion, best delineated by the dimensions of the cell body and nucleus and the ratio of diameter of the initial segments of axonic and dendritic processes. Myelinization and degree of roundness were relatively unimportant differential parameters. Cluster (multivariate) analysis of the six most important differential parameters suggested the possibility of five subgroups among the groups of large and small cells. For the middle and upper middle turns, cluster analysis suggested that there may be as many as three groups of cells based on morphometric analysis. These results are discussed in relation to other morphologic and physiologic data in the mammalian spiral ganglion.

Otopathology in a Case of Multichannel Cochlear Implantation

The histopathology of the temporal bones of a patient who died of unrelated causes 10 weeks following cochlear implantation using a Richards Ineraid® device is presented. Deafness was caused by a prolonged course of intravenous gentamycin therapy 5 years prior to implantation.

Temporal bone histopathology in alport syndrome.

Objective: To determine the histopathologic abnormalities within the cochlea in Alport syndrome.

Effects of Fixative and Embedding Medium on Morphology and Immunostaining of the Cochlea

The localization of proteins by immunostaining is a powerful method to investigate otologic disorders. However, the use of fixatives and embedding media (necessary for the preservation of morphology) can obscure antigens, making it difficult to perform immunoassays. We performed a systematic investigation of the effects of fixative and embedding medium on morphology and immunostaining of the mouse cochlea. Three different fixative solutions [4% formaldehyde (F), 4% formaldehyde + 1% acetic acid (FA), and 4% formaldehyde + 1% acetic acid + 0.1% glutaraldehyde (FGA)] and 3 different embedding media (paraffin, polyester wax, and celloidin) were used. Morphology was assessed using light microscopy. Immunostaining was studied using a panel of 6 antibodies (to prostaglandin D synthase, aquaporin 1, connective tissue growth factor, 200-kDa neurofilament, tubulin and Na+,K+-ATPase). Preservation of morphology was suboptimal with paraffin, adequate with polyester wax and superb with celloidin. Immunostaining was successful using all 6 antibodies in all 3 fixatives and all 3 embedding media. While there were differences in strength of signal and localization of antigen between the 3 fixatives, overall, FA and FGA gave the most uniform results. For a given fixative and antibody, there was surprisingly little difference in the quality of immunostaining between celloidin and paraffin, while results in polyester wax were not as good in some cases. These results suggest that celloidin may be the embedding medium of choice for both morphological and pathological studies, including immunostaining when morphology must be optimized.

Morphologic evidence for three cell types in the human spiral ganglion

Although two types of spiral ganglion cells (large type I and smaller type II) have classically been described by anatomic studies in both animal and human spiral ganglion, there is physiologic and morphologic evidence for subtypes of the large type I ganglion cell. In addition, in the animal and human, a variety of morphologic differences based on cytoplasmic content, myelinization, immunostaining and morphometric analysis have suggested more than one variety of type I ganglion cell. Light and electron microscopic serial sections of the spiral ganglion in two human specimens in the basal, middle and upper middle turns were pooled for morphometric analysis of the cell area, nuclear area and axon diameter. Analysis of variance, bivariate scatter plots and multivariate cluster analysis provided evidence for 3 types of ganglion cells in the human spiral ganglion: large, intermediate and small, varying from each other significantly on the basis of cell area. It was suggested, based on the morphologic findings and prevalence of the cell types, that the large and intermediate cells were subtypes of the classic type I spiral ganglion cell, whereas the small ganglion cell was consistent with the classically described type II ganglion cell.