Clinical outcomes of resecting scarpa's ganglion during vestibular schwannoma surgery.

Vestibular schwannomas are slow-growing tumors arising from the Schwann cells of the vestibular nerve. Scarpa's ganglion, the vestibular nerve ganglion, is located within the internal auditory meatus. Surgical treatment of vestibular schwannomas carries the potential of resecting Scarpa's ganglion along with the tumor. No prior studies have evaluated outcomes based on the presence of Scarpa's ganglion within tumor specimens. The neurosurgery patient records were queried for patients who underwent surgical resection of vestibular schwannomas at the University of Missouri Healthcare between January 1, 2008 and December 31, 2018. Inclusion criteria consisted of minimum age of 18, imaging demonstrating an eighth nerve tumor, surgical resection thereof, and a final pathological diagnosis of WHO grade I schwannoma. Data were collected retrospectively. The histological slides of the tumors were reviewed, and the presence or absence of the ganglion was noted. Outcomes analyzed included postoperative dizziness, hearing, and facial nerve function. Fifty-two patients met inclusion criteria. Ten (19%) resected tumors contained portions of the ganglion. No difference in risk of resection of ganglion occurred based on the surgical approach (p = 0.2454). Mean follow-up duration was 24.6 months ± 26.2 standard deviation. No differences in postoperative hearing or dizziness (p = 0.8483 and p = 0.3190 respectively) were present if Scarpa's ganglion was resected. House-Brackmann classification of facial nerve function at last follow-up was similar (p = 0.9190). Resection of Scarpa's ganglion with vestibular schwannomas does not increase risk of post-operative dizziness, facial nerve weakness, or hearing loss.

Protecting against electrode insertion trauma using dexamethasone.

OBJECTIVE: To compare the benefits of a dexamethasone-eluting array for hearing preservation and cochlear histopathology in low trauma (soft-surgery) and high trauma models of cochlear implant surgery. METHODS: Adult guinea pigs were implanted with an intra-cochlear array using two different surgical procedures: either a soft-surgery approach or following generation of electrode insertion trauma (high trauma). Two methods of dexamethasone delivery were evaluated: elution from an electrode array alone, and elution from a cochlear implant electrode array in combination with a pre-operative systemic injection. All electrode arrays were implanted for a period of 4 weeks. Outcome measures at 4 weeks post-implantation included auditory brainstem response (ABR) thresholds, histological analysis of spiral ganglion neuron density, fibrotic tissue, new bone growth, and cochlear damage. RESULTS: Animals exposed to high surgical trauma showed greater hearing loss than those in the low trauma model, irrespective of the presence of dexamethasone. Whilst the area of intra-cochlear fibrotic tissue growth post-implantation was also independent of dexamethasone administration, new bone growth was significantly reduced in its presence. Our high trauma model effectively obliterated the organ of Corti and significantly reduced spiral ganglion neuron densities in the lower basal turn. This trauma-induced reduction in spiral ganglion neuron survival decreased with the inclusion of a dexamethasone-eluting array. A pre-operative systemic injection of dexamethasone did not significantly improve any outcome measures beyond those provided with a dexamethasone-eluting array alone. CONCLUSION: Dexamethasone-eluting intra-cochlear arrays may inhibit osteoneogenesis, and reduce spiral ganglion neuron loss following traumatic cochlear implantation.

Microenvironmental support for cell delivery to the inner ear.

Transplantation of mesenchymal stromal cells (MSC) presents a promising approach not only for the replacement of lost or degenerated cells in diseased organs but also for local drug delivery. It can potentially be used to enhance the safety and efficacy of inner ear surgeries such as cochlear implantation. Options for enhancing the effects of MSC therapy include modulating cell behaviour with customized bio-matrixes or modulating their behaviour by ex vivo transfection of the cells with a variety of genes. In this study, we demonstrate that MSC delivered to the inner ear of guinea pigs or to decellularized cochleae preferentially bind to areas of high heparin concentration. This presents an opportunity for modulating cell behaviour ex vivo. We evaluated the effect of carboxymethylglucose sulfate (Cacicol®), a heparan sulfate analogue on spiral ganglion cells and MSC and demonstrated support of neuronal survival and support of stem cell proliferation.

Genetic variants in the peripheral auditory system significantly affect adult cochlear implant performance.

BACKGROUND: Cochlear implantation is an effective habilitation modality for adults with significant hearing loss. However, post-implant performance is variable. A portion of this variance in outcome can be attributed to clinical factors. Recent physiological studies suggest that the health of the spiral ganglion also impacts post-operative cochlear implant outcomes. The goal of this study was to determine whether genetic factors affecting spiral ganglion neurons may be associated with cochlear implant performance. METHODS: Adults with post-lingual deafness who underwent cochlear implantation at the University of Iowa were studied. Pre-implantation evaluation included comprehensive genetic testing for genetic diagnosis. A novel score of genetic variants affecting genes with functional effects in the spiral ganglion was calculated. A Z-scored average of up to three post-operative speech perception tests (CNC, HINT, and AzBio) was used to assess outcome. RESULTS: Genetically determined spiral ganglion health affects cochlear implant outcomes, and when considered in conjunction with clinically determined etiology of deafness, accounts for 18.3% of the variance in postoperative speech recognition outcomes. Cochlear implant recipients with deleterious genetic variants that affect the cochlear sensory organ perform significantly better on tests of speech perception than recipients with deleterious genetic variants that affect the spiral ganglion. CONCLUSION: Etiological diagnosis of deafness including genetic testing is the single largest predictor of postoperative speech outcomes in adult cochlear implant recipients. A detailed understanding of the genetic underpinning of hearing loss will better inform pre-implant counseling. The method presented here should serve as a guide for further research into the molecular physiology of the peripheral auditory system and cochlear implants.

Stem cell transplantation via the cochlear lateral wall for replacement of degenerated spiral ganglion neurons.

Spiral ganglion neurons (SGNs) are poorly regenerated in the mammalian inner ear. Because of this, stem cell transplantation has been used to replace injured SGNs, and several studies have addressed this approach. However, the difficulty of delivering stem cells into the cochlea and encouraging their migration to Rosenthal's canal (RC), where the SGNs are located, severely restricts this therapeutic strategy. In this study, we attempted to establish a new stem cell transplantation route into the cochlea via the cochlear lateral wall (CLW). First, we tested the precision of this route by injecting Fluorogold into the CLW and next assessed its safety by mock surgeries. Then, using a degenerated SGN animal model, we transplanted neural stem cells (NSCs), derived from the olfactory bulb of C57BL/6-green fluorescent protein (GFP) mice, via the CLW route and examined the cells' distribution in the cochlea. We found the CLW transplantation route is precise and safe. In addition, NSCs migrated into RC with a high efficiency and differentiated into neurons in a degenerated SGN rat model after the CLW transplantation. This result revealed that the basilar membrane (BM) may have crevices permitting the migration of NSCs. The result of this study demonstrates a novel route for cell transplantation to the inner ear, which is important for the replacement of degenerated SGNs and may contribute to the treatment of sensorineural hearing loss.

Transplantation of bone marrow-derived neurospheres into guinea pig cochlea.

OBJECTIVES/HYPOTHESIS: To investigate the potential of neurally induced bone marrow stromal cells (BMSCs) as transplants for replacement of spiral ganglion neurons. METHODS: BMSCs were harvested from the femurs and tibias of adult guinea pigs. BMSCs were cultured with neural induction media and formed spheres. The capacity of BMSC-derived spheres for neural differentiation was examined by immunocytochemistry in vitro. BMSC-derived spheres were injected into the modiolus of the intact cochleae or those locally damaged by ouabain, followed by histological and functional analyses. RESULTS: In vitro analysis revealed a high capacity of BMSC-derived spheres for neural differentiation. After transplantation into the cochlear modiolus, the survival and neural differentiation of BMSC-derived spheres was observed in both the intact and damaged cochleae. In intact cochleae, transplants settled in various portions of the cochlea, including the cochlear modiolus, whereas in damaged cochleae, transplants were predominantly observed in the internal auditory meatus. Transplantation of BMSC-derived spheres resulted in no functional recovery of the cochlea or protection of host spiral ganglion neurons. CONCLUSIONS: The present findings indicate that BMSC-derived spheres can be a source for replacement of spiral ganglion neurons, although further manipulations are required for functional recovery.

Surgical access to the mammalian cochlea for cell-based therapies.

Cochlear implants are dependent on functionally viable spiral ganglion neurons (SGNs) - the primary auditory neurons of the inner ear. Cell-based therapies are being used experimentally in an attempt to rescue SGNs from deafness-induced degeneration or to generate new neurons. The success of these therapies will be dependent on the development of surgical techniques designed to ensure precise cell placement while minimizing surgical trauma, adverse tissue reaction and cell dispersal. Using 24 normal adult guinea pigs we assessed three surgical procedures for cell delivery into the cochlea: (i) a cochleostomy into the scala tympani (ST); (ii) direct access to Rosenthal's canal - the site of the SGN soma - via a localized fracture of the osseous spiral lamina (RC); and (iii) direct access to the auditory nerve via a translabyrinthine surgical approach (TL). Half the cohort had surgery alone while the other half had surgery combined with the delivery of biocompatible microspheres designed to model implanted cells. Following a four week survival period the inflammatory response and SGN survival were measured for each cohort and the location of microspheres were determined. We observed a wide variability across the three surgical approaches examined, including the extent of the inflammatory tissue response (TL>>RC> or =ST) and the survival of SGNs (ST>RC>>TL). Importantly, microspheres were effectively retained at the implant site after all three surgical approaches. Direct access to Rosenthal's canal offered the most promising surgical approach to the SGNs, although the technique must be further refined to reduce the localized trauma associated with the procedure.

Engraftment of embryonic stem cell-derived neurons into the cochlear modiolus.

This study aimed to evaluate the potential of embryonic stem cell-derived neural progenitors for use as transplants for the replacement of the auditory primary neurons, spiral ganglion neurons. Mouse embryonic stem cell-derived neural progenitors were implanted into the base of the cochlear modiolus of normal or deafened guinea pigs, which contains spiral ganglion neurons and cochlear nerve fibers. Histological analysis demonstrated the survival and neural differentiation of transplants in the cochlear modiolus and active neurite outgrowth of transplants toward host peripheral or central auditory systems. Functional assessments indicated the potential of transplanted embryonic stem cell-derived neural progenitors to elicit the functional recovery of damaged cochleae. These findings support the hypothesis that transplantation of embryonic stem cell-derived neural progenitors can contribute to the functional restoration of spiral ganglion neurons.

Methods for providing therapeutic agents to treat damaged spiral ganglion neurons.

Sensorineural hearing loss, characterized by damage to sensory hair cells and/or associated nerve fibers is a leading cause of hearing disorders throughout the world. To date, treatment options are limited and there is no cure for damaged inner ear cells. Because the inner ear is a tiny organ housed in bone deep within the skull, access to the inner ear is limited, making delivery of therapeutic agents difficult. In recent years scientists have investigated a number of growth factors that have the potential to regulate survival or recovery of auditory neurons. Coinciding with the focus on molecules that may restore function are efforts to develop novel delivery methods. Researchers have been investigating the use of mini osmotic pumps, viral vectors and stem cells as a means of providing direct application of growth factors to the inner ear. This review summarizes recent findings regarding the molecules that may be useful for restoring damaged spiral ganglion neurons, as well as the advantages and disadvantages of various delivery systems.

Growth of postoperative remnants of unilateral vestibular nerve schwannoma: role of the vestibular ganglion.

Histopathological examination of seven temporal bones from patients who underwent a removal of vestibular nerve schwannomas by the translabyrithine or middle fossa approaches has demonstrated small tumor remnants that failed to grow as long as 25 years after surgery. In spite of the high incidence of residual tumors, the clinical recurrence rate of tumors operated at our institution by the translabyrinthine or middle fossa approaches is low (0.3%). Immunohistochemical labeling of dividing cells demonstrated that segments of tumor adjacent to the vestibular nerve and ganglion contained more dividing cells than were present in areas of the tumor at a distance from them.