Intraoperative assessment of cochlear nerve functionality in various vestibular schwannoma scenarios: Lessons learned.

The use of cochlear implants (CIs) is on the rise for patients with vestibular schwannoma (VS). Besides CI following tumor resection, new scenarios such as implantation in observed and/or irradiated tumors are becoming increasingly common. A significant emerging trend is the need of intraoperative evaluation of the functionality of the cochlear nerve in order to decide if a CI would be placed. The purpose of this paper is to explore the experience of a tertiary center with the application of the Auditory Nerve Test System (ANTS) in various scenarios regarding VS patients. The results are compared to that of the studies that have previously used the ANTS in this condition. Patients with unilateral or bilateral VS (NF2) who were evaluated with the ANTS prior to considering CI in a tertiary center between 2021 and 2023 were analyzed. The presence of a robust wave V was chosen to define a positive electrical auditory brainstem response (EABR). Two patients underwent promontory stimulation (PromStim) EABR previous to ANTS evaluation. Seven patients, 2 NF-2 and 5 with sporadic VS were included. The initial scenario was simultaneous translabyrinthine (TL) tumor resection and CI in 3 cases while a CI placement without tumor resection was planned in 4 cases. The ANTS was positive in 4 cases, negative in 2 cases, and uncertain in one case. Two patients underwent simultaneous TL and CI, 1 patient simultaneous TL and auditory brainstem implant, 3 patients posterior tympanotomy with CI, and 1 patient had no implant placement. In the 5 patients undergoing CI, sound detection was present. There was a good correlation between the PromStim and ANTS EABR. The literature research yielded 35 patients with complete information about EABR response. There was one false negative and one false positive case; that is, the 28 implanted cases with a present wave V following tumor resection had some degree of auditory perception in all but one case. The ANTS is a useful intraoperative tool to asses CI candidacy in VS patients undergoing observation, irradiation or surgery. A positive strongly predicts at least sound detection with the CI.

Cochlear implantation after radiosurgery for vestibular schwannoma.

OBJECTIVE: The object of this study was to ascertain outcomes of cochlear implantation (CI) following stereotactic radiosurgery (SRS) for vestibular schwannoma (VS). METHODS: The authors conducted a retrospective chart review of adult patients with VS treated with SRS who underwent CI between 1990 and 2019 at a single tertiary care referral center. Patient demographics, tumor features, treatment parameters, and pre- and postimplantation audiometric and clinical outcomes are presented. RESULTS: Seventeen patients (18 ears) underwent SRS and ipsilateral CI during the study period. Thirteen patients (76%) had neurofibromatosis type 2 (NF2). Median age at SRS and CI were 44 and 48 years, respectively. Median time from SRS to CI was 60 days, but notably, 4 patients underwent SRS and CI within 1 day and 5 patients underwent CI more than 7 years after SRS. Median marginal dose was 13 Gy. Median treatment volume at the time of SRS was 1400 mm3 (range 84-6080 mm3, n = 15 patients). Median post-CI PTA was 28 dB HL, improved from 101 dB HL preoperatively (p < 0.001). Overall, 11 patients (12 ears) exhibited open-set speech understanding. Sentence testing was performed at a median of 10 months (range 1-143 months) post-CI. The median AzBio sentence score for patients with open-set speech understanding was 76% (range 19%-95%, n = 10 ears). Two ears exhibited Hearing in Noise Test (HINT) sentence scores of 49% and 95%, respectively. Four patients achieved environmental sound awareness without open-set speech recognition. Two had no detectable auditory percepts. CONCLUSIONS: Most patients who underwent CI following SRS for VS enjoyed access to sound at near-normal levels, with the majority achieving good open-set speech understanding. Implantation can be performed immediately following SRS or in a delayed fashion, depending on hearing status as well as other factors. This strategy may be applied to cases of sporadic or NF2-associated VS. ABBREVIATIONS: AAO-HNS = American Academy of Otolaryngology-Head and Neck Surgery; ABI = auditory brainstem implant; CI = cochlear implantation; CN = cranial nerve; CNC = consonant-nucleus-consonant; CPA = cerebellopontine angle; EPS = electrical promontory stimulation; ESA = environmental sound awareness; HINT = Hearing in Noise Test; IAC = internal auditory canal; NF2 = neurofibromatosis type 2; OSP = open-set speech perception; PTA = pure tone average; SRS = stereotactic radiosurgery; VS = vestibular schwannoma; WRS = word recognition score.

Transplantation of adipose-derived stromal cells protects functional and morphological auditory nerve integrity in a model of cochlear implantation.

Cochlear implants are considered the gold standard therapy for subjects with severe hearing loss and deafness. Cochlear implants bypass the damaged hair cells and directly stimulate spiral ganglion neurons (SGNs) of the auditory nerve. Hence, the presence of functional SGNs is crucial for speech perception in electric hearing with a cochlear implant. In deaf individuals, SGNs progressively degenerate due to the lack of neurotrophic support, normally provided by sensory cells of the inner ear. Adipose-derived stromal cells (ASCs) are known to produce neurotrophic factors. In a guinea pig model of sensory hearing loss and cochlear implantation, ASCs were autologously transplanted into the scala tympani prior to insertion of a cochlear implant on one side. Electrically evoked auditory brain stem responses (eABR) were recorded 8 weeks after cochlear implantation. At conclusion of the experiment, the cochleae were histologically evaluated. Compared to untreated control animals, transplantation of ASCs resulted in an increased number of SGNs and their peripheral neurites. In ASC-transplanted animals, mean eABR thresholds were lower and suprathreshold amplitudes larger, suggesting a larger population of intact auditory nerve fibers. Moreover, when compared to controls, amplitude-level functions of eABRs in ASC transplanted animals demonstrated steeper slopes in response to increasing interphase gaps (IPGs), indicative of better functionality of the auditory nerve. In summary, results suggest that transplantation of autologous ASCs into the deaf inner ear may have protective effects on the survival of SGNs and their peripheral processes and may thus contribute to long-term benefits in speech discrimination performance in cochlear implant subjects.

Cervical and ocular vestibular evoked myogenic potentials in determining nerve division involvement in patients with a tumor located in the internal auditory canal.

OBJECTIVES: The study aimed at the analysis of the parameters of acoustic cervical and ocular vestibular evoked myogenic potentials (AC-cVEMP and AC-oVEMP) response in patients with a confirmed tumor located in the internal auditory canal. It also aimed to assess to what degree a combination of these tests may be of benefit in the preoperative indication of the affected nerve division via preoperative determination whether the tumor originated from the superior or inferior division of the vestibular nerve, both divisions, or if it originated from a different nerve in the internal auditory canal. METHODS: The study group included 50 patients. Preoperative MRI scans were used to measure tumor diameter. AC-cVEMP and AC-oVEMP testing were performed before tumor resection. The surgeon was asked for a detailed description of the tumor origin. RESULTS: The corrected amplitude of cVEMP was significantly lower on the tumor side than on the non-affected side and in the control group. The corrected Asymmetry Ratio (AR) of cVEMPs in patients with the tumor was significantly elevated above the reference values with the mean being 58.29% and the mean AR of oVEMPs in patients the tumor was 71.78% which made both results significantly higher than in the control group. Neither cVEMP nor oVEMP latency was significantly correlated with tumor size. Data obtained from cVEMP and oVEMP tests was an effective indicator of tumor origin in 74% of patients showing which division (or both divisions) of the VIIIth nerve was affected in comparison with information obtained from the surgeon. CONCLUSIONS: The combined use of AC-cVEMP and AC-oVEMP tests may be useful in surgical planning in patients the tumor located in the internal auditory canal, providing a highly probable determination of the division of the affected nerve. Such information is valuable for the surgeon as it offers additional knowledge about the tumor before the procedure. cVEMP and oVEMP results may not be used as the basis for the calculation of tumor size in patients.

Detailed insight into transtympanic electrocochleography (TT-ECochG) and direct cochlear nerve action potential (CNAP) for intraoperative hearing monitoring in patients with vestibular schwannoma - methodology of measurements and interpretation of results.

<b>Background:</b> The aim was to present the methodology and interpretation of intraoperative hearing monitoring with simultaneous Transtympanic Electrocochleography (TT-ECochG) and direct Cochlear Nerve Action Potential (CNAP) measurements during vestibular schwannoma removal. <br><b>Materials and Methods:</b> Detailed methodology of measurements and interpretation of results are presented in three exemplary patients who underwent tumor removal via middle fossa approach (MFA) with the use of intraoperative monitoring of hearing with TT-ECochG and direct CNAP performed in real time. In addition, all responses were automatically recorded and stored along with surgical information and subjected to detailed analyses and calculation after surgery. <br><b>Results:</b> The following changes in TT-ECochG and direct CNAP responses were observed: Patient #1 - TT-ECochG and CNAP responses with minor, but transient, morphology changes (hearing was preserved); Patient #2 - CNAP responses changed significantly but, temporarily, from triphasic into biphasic responses later, with marked but partially reversible desynchronization of CNAP; changes in TT-ECochG responses were also observed but, at the end, returned to baseline (surgery-related deterioration of hearing); Patient #3 - irreversible changes of TT-ECochG and direct CNAP (complete loss of hearing). <br><b>Conclusions:</b> A combination of TT-ECochG and direct CNAP allows for real-time monitoring of auditory function during vestibular schwannoma resection and surgical manipulation which contribute to the risk of hearing loss. Therefore, the surgeon can be instantly informed about changes which could increase the possibility of preserving the patient's hearing.

A review of auditory gain, low-level noise and sound therapy for tinnitus and hyperacusis.

Objective: This article reviews: (1) the evidence related to enhanced central gain as a potential mechanism for the generation of tinnitus and hyperacusis, (2) the neuroplastic changes induced by prolonged, low-level sound stimulation and (3) the clinical effectiveness of various sound therapies and amplification for the treatment of tinnitus and hyperacusis.Design: General literature review.Study sample: Peer-reviewed articles related to auditory neural gain, prolonged low-level noise exposure and effectiveness of sound therapy.Results: A large body of literature exists supporting the enhanced neural gain model of tinnitus and hyperacusis. Neuroplastic changes associated with prolonged low-level noise show evidence of reversing enhanced neural gain, which should theoretically reduce percepts of tinnitus and/or hyperacusis. However, the available clinical evidence assessing the efficacy of sound therapy to reduce tinnitus or hyperacusis lacks controlled clinical trials to accurately assess the effectiveness of sound therapy.Conclusions: The available literature from basic science studies supports the neural gain model of tinnitus and hyperacusis, which conceivably should be effectively managed with sound therapy. However, well-controlled clinical trials are needed before conclusions can be made on the effectiveness of sound therapy for tinnitus and hyperacusis.

[Preoperative imaging and electrophysiological evaluation of cochlear implantation in children with cochlear nerve dysplasia].

Objective:The aim of this study is to investigate the use of CT, magnetic resonance imaging （MRI）, functional magnetic resonance （fMRI） and electrical evoked auditory brainstem response in children with cochlear nerve deficiency （CND） before cochlear implantation （CI） （electrically evoked auditory brain stem response, EABR） evaluated auditory pathway, auditory cortex function, and cochlear nerve function. Method:Of 6 children with bilateral profound sensorineural hearing loss, bilateral internal auditory meatus stenosis was diagnosed by CT as in 4 cases and unilateral internal auditory meatus stenosis in 1 case. In 3 cases, oblique sagittal MRI reconstruction of the internal auditory meatus showed only facial nerve and vestibular nerve existence. 6 cases were diagnosed as CND by imaging, among which underwent fMRI and EABR in 3 cases, respectively. All the children received unilateral CI and were followed up for at least 1 year after hearing and speech rehabilitation. Result:fMRI was examed in 3 cases with CND. It showed that the right auditory cortex was activated in 1 case after sound given to the left ear but no activation was found in the left cortex when sound given to the right ear. 1 case showed activation in bilateral transverse temporal gyrus while sound was given to the left, right and both ears at 2000Hz. Another case had no activation in both auditory cortex. EABR detection elicited V wave in 2 of 3 cases. 6 children received audiological and speech evaluation 1 month, 6 and 12 months after CI. Among them, the hearing level was improved within 6 months after surgery in 4 cases, and the threshold of sound field was （48.15±6.60） dB HL, MAIS and CAP scores were improved. However, SIR score improvement is limited in 3 cases. The hearing level was improved in 1 case, but speech rehabilitation was poor mainly due to the older age. Conclusion:Preoperative comprehensive application of imaging and electrophysiological evaluation of children with CND can more accurately assess the integrity of the auditory pathway and understand the function of the cochlear nerve. It has important reference significance for whether or not to perform surgery. There was a significant difference in auditory speech rehabilitation after CND in children with CND.

[The molecular mechanisms underpinning auditory neuropathy].

Auditory neuropathy (AN) is a hearing disorder where cochlear inner hair cell and/or the auditory nerve function is disrupted while outer hair cell function is normal. It can affect people of all ages, from infancy to adulthood. People with auditory neuropathy may have normal hearing threshold, or hearing loss ranging from mild to severe; they always have poor speech-perception abilities. It is a heterogeneous disorder which can have either congenital or acquired causes. AN may result from specific loss of cochlear inner hair cells, disordered release of neurotransmitters by inner hair cell ribbon synapses, deafferentation accompanying loss of auditory nerve fibers, neural dys-synchrony or conduction block as a result of demyelination of nerve fibers and auditory nerve hypoplasia. Although the definition of AN includes the central part, its incidence is low, and the etiology and pathology are not clear. The present review aimed to provide an overview of the genetic conditions associated with AN and highlight the neural and synaptic mechanism of AN. Possible strategy for treatments of AN was also discussed.

Extracochlear Stimulation of Electrically Evoked Auditory Brainstem Responses (eABRs) Remains the Preferred Pre-implant Auditory Nerve Function Test in an Assessor-blinded Comparison.

OBJECTIVE: Electrically evoked auditory brainstem responses (eABRs) can be recorded before cochlear implant (CI) surgery to verify auditory nerve function, and is particularly helpful in to assess the function of the auditory nerve in cases of auditory nerve hypoplasia. This is the first study to compare three preimplant eABRs recording techniques: 1) standard extracochlear, 2) novel intracochlear, and 3) conventional intracochlear with the CI. STUDY DESIGN: A within-participants design was used where eABRs were sequentially measured during CI surgery using three methods with stimulation from: 1) an extracochlear electrode placed at the round window niche, 2) two different electrodes on a recently developed Intracochlear Test Array (ITA), and 3) two different electrodes on a CI electrode array. SETTING: New adults implantees (n = 16) were recruited through the Manchester Auditory Implant Centre and eABR measurements were made in theater at the time of CI surgery. PATIENTS: All participants met the clinical criteria for cochlear implantation. Only participants with radiologically normal auditory nerves were recruited to the study. All participants were surgically listed for either a MED-EL Synchrony implant or a Cochlear Nucleus Profile implant, per standard practice in the implant centre. OUTCOME MEASURES: Primary outcome measures were: 1) charge (µC) required to elicit a threshold response, and 2) latencies (ms) in the threshold waveforms. Secondary outcome measures were: 1) morphologies of responses at suprathreshold stimulation levels and 2) wave V growth patterns. RESULTS: eABRs were successfully measured from 15 participants. In terms of primary outcome measures, the charge required to elicit a response using the extracochlear electrode (median = 0.075 µC) was approximately six times larger than all other electrodes and the latency of wave V was approximately 0.5 ms longer when using the extracochlear electrode (mean = 5.1 ms). In terms of secondary outcomes, there were some minor quantitative differences in responses between extracochlear and intracochlear stimulation; in particular, ITA responses were highly variable in quality. The ITA responses were rated poor quality in 33% of recordings and in two instances did not allow for data collection. When not disrupted by open circuits, the median ITA response contained one more waveform than the median extracochlear response. CONCLUSIONS: In this first study comparing intracochlear and extracochlear stimulation, the results show that both can be used to produce an eABR that is representative of the one elicited by the CI. In the majority of cases, extracochlear stimulation was the preferred approach for preimplant auditory nerve function testing because of consistency, recordings that could be analyzed, and because extracochlear placement of the electrode does not require a cochleostomy to insert an electrode.

Perioperative Recording of Cochlear Implant Evoked Brain Stem Responses After Removal of the Intralabyrinthine Portion of a Vestibular Schwannoma in a Patient with NF2.

OBJECTIVE: To predict and optimize hearing outcomes with a cochlear implant (CI) in patients with intracochlear schwannoma and neurofibromatosis type 2 (NF2). PATIENT: A patient with NF2 and bilateral deafness. INTERVENTIONS: The intracochlear portion of a vestibular schwannoma was removed with a partial cochleoectomy. During the procedure, a CI was implanted. MAIN OUTCOME MEASURES: Perioperatively, electrically evoked auditory brainstem responses (eABRs) were recorded with a novel intracochlear, CI-evoked, broad band stimulus to support the decision to implant a CI. RESULTS: We found positive eABR responses, with thresholds at around the 200 current level. The eV wave was discernible at all stimulated electrodes, with a prolonged latency of about 6.5 ms. The eIII wave was detected at electrodes 9 and 13, with a latency of 4.5 ms. The acoustic reflex was detectable at all stimulated electrodes. Subjective auditory perception could be achieved by stimulating 3 days after surgery. In open-set word recognition, the patient achieved 60% recognition of monosyllables after the first audio processor fitting and 100% 1 month later. CONCLUSIONS: After a partial cochleoectomy, this method may serve as a peri-operative, objective assessment of cochlear nerve integrity that could potentially impact the prediction of CI performance. Potential future applications might be assessments of cochlear nerve integrity in patients with inner ear malformations, radiologically suspected cochlear nerve deficiencies, and resected or irradiated spontaneous vestibular schwannomas or NF2.

[Preoperative diagnosis and evaluation of cochlear implantation in patients with cochlear nerve deficiency].

Cochlear nerve deficiency (CND) refers to a small or absent cochlear branch of the vestibulocochlear nerve (VCN) or cochlear nerve (CN). Congenitally deaf children with CND who received cochlear implants (CIs) generally exhibit poorer auditory performance than CI children without CND. It is important to confirm the integrity of the auditory pathway before surgery. High-resolution computed tomography (HRCT) and three-dimensional magnetic resonance imaging (3D MRI) are major techniques used to diagnosis CND. In this paper, we reviewed the methods of preoperative evaluation, cochlear nerve embryonic development, techniques for diagnosis and outcomes of cochlear implantation.

How Well Does Intraoperative Audiologic Monitoring Predict Hearing Outcome During Middle Fossa Vestibular Schwannoma Resection?

OBJECTIVE: To evaluate the association between signal changes during intraoperative audiologic monitoring and postoperative audiometric outcome in patients undergoing vestibular schwannoma (VS) resection via middle cranial fossa (MCF) approach. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary referral center. PATIENTS: One hundred twenty-six consecutive patients (mean age 48.6 yrs, range 16-67; mean tumor size 9.9 mm, range 1.8-18.9 mm) who underwent MCF VS resection. INTERVENTIONS: Intraoperative audiologic monitoring using auditory brainstem response (ABR) and direct cochlear nerve action potential (CNAP). MAIN OUTCOME MEASURES: Intraoperative ABR wave V and CNAP N1 amplitudes and postoperative pure-tone average (PTA) and word recognition score (WRS). RESULTS: On ABR, absent wave V amplitude was associated with an 81.1% increase and 82.3% decrease in postoperative PTA and WRS, respectively. On CNAP, decreased or absent N1 amplitude was associated with 47.3 and 100% increase, respectively, in postoperative PTA, and 45.3% and 100% decrease, respectively, in postoperative WRS. Receiver-operating curve analysis showed that ABR combined with CNAP using a Cueva electrode achieved the highest diagnostic accuracy in predicting postoperative hearing decline when measured by WRS class (sensitivity 83.3%, specificity 100%), and performed better compared with each modality alone. CONCLUSION: Intraoperative ABR wave V and CNAP amplitude changes are associated with changes in postoperative hearing, and dual modality monitoring was more diagnostic of postoperative hearing decline compared with each modality alone during MCF VS resection. Overall, intraoperative ABR and CNAP were more specific than sensitive for postoperative hearing decline.

Intraoperative Auditory System Monitoring.

A new electrophysiological system for intraoperative, continuous, near-real time monitoring of cochlear nerve function through acoustic stimulation in the ear canal and recording of the evoked dorsal cochlear nucleus potentials (DNAPs) by a specially designed DNAP electrode placed directly on the brainstem is described. The system is denominated "(cerebellopontine angle) CPA Master" and is designed for hearing preservation surgery in the cerebello-pontine angle, through the retro-sigmoid or the retro-labyrinthine approach. As an additional novelty within the field, the system allows intraoperative mapping and thus precise localization of the cochlear nerve in its entire trajectory from the brainstem to the fundus of the internal auditory canal, which is a major advance in relation to atraumatic dissection of the nerve. The system can be used for surgery of all types of CPA tumors, for example, vestibular schwannomas, meningiomas and epidermoid cysts, but also for vestibular nerve section and vascular decompression. The system also allows evaluation of the electrical functionality of an anatomically intact cochlear nerve in translabyrinthine surgery, thus predicting the benefit of optional cochlear implantation.

[An analysis of electrocochleography in patients with OSAHS].

Objective:To investigate the values of electrocochleograph（ECochG）in patients with OSAHS. Method:ECochG was performed in 31 (62 ears) OSAHS patients (moderately 5 cases, severely 26 cases) and 28 healthy adults (56 ears). AP latency ，AP amplitude and SP/AP were measured and analyzed. Result:There was no difference between the two groups in SP/AP amplitude ratio（P>0.05） while both AP latency（P<0.05） and AP amplitude（P<0.05） were significantly different. Conclusion:ECochG can confirm the damage of cochlear and auditory nerve near the cochlear segment in patients with moderate to severe OSAHS.

Plasticity after pediatric cochlear implantation: Implication from changes in peripheral plasma level of BDNF and auditory nerve responses.

INTRODUCTION: Sensory neural hearing loss could lead to some structural and physiological changes in the auditory pathways, such as alteration in the expression of neurotrophins. These factors, especially Brain-Derived Neurotrophic Factor (BDNF), play an important role in synaptic functions and experience-related plasticity. Restoring cochlear function after hearing loss is possible through cochlear implantation (CI). Evaluation of the blood concentration changes of neurotrophins as prerequisites of plasticity could help scientists to determine the prognosis of CI as in the candidacy procedure or enhancing prosthesis function by adding the exact needed amount of BDNF to the electrode array. METHODS: Here we have studied the plasma BDNF concentration before CI surgery and 6 months after using CI device in 15 pediatric CI recipients and compared this level with changes of BDNF concentration in 10 children who were using hearing aid (H.A). In addition, we searched for a possible correlation between post-surgery plasma BDNF concentration and electrical compound action potential (ECAP) and comfort-level (C-level) thresholds. RESULTS: Plasma BDNF concentration in children with CI increased significantly after CI surgery, while this difference in H.A group was not significant. Analysis of repeated measures of ECAP and C-level thresholds in CI group showed that there were some kinds of steadiness during follow- up sessions for ECAP thresholds in basal and E16 of middle electrodes, whereas C-level thresholds for all selected electrodes increased significantly up to six months follow-up. Interestingly, we did not find any significant correlation between post-surgery plasma BDNF concentration and ECAP or C-level threshold changes. CONCLUSION: It is concluded that changes in C-level threshold and steady state of ECAP thresholds and significant changes in BDNF concentration could be regarded as an indicator of experienced-related plasticity after CI stimulation.

Electrophysiology of Cranial Nerve Testing: Auditory Nerve.

The electrocochleogram and brainstem auditory evoked potentials (BAEPs) are electrophysiologic signals used to assess the auditory nerve. The electrocohleogram includes the cochlear microphonic, the cochlear summating potential, and the eighth nerve compound action potential. It is used predominantly for hearing assessment and for diagnosis of Ménière disease and auditory neuropathy. Brainstem auditory evoked potentials are used for hearing assessment, diagnosis of dysfunction within the cochlea, the auditory nerve, and the brainstem auditory pathways up to the level of the mesencephalon, and intraoperative monitoring of these structures. The earliest BAEP component, wave I, and the eighth nerve compound action potential reflect the same process-the initial depolarization in the distal auditory nerve. Brainstem auditory evoked potential wave II receives contributions from the region of the cochlear nucleus and from the second depolarization in the distal auditory nerve. Wave III and later components are entirely generated rostral to the auditory nerve. Interpretation of BAEP studies is based on waves I, III, and V; auditory nerve dysfunction is manifested as prolongation of the I-III interpeak interval or absence of waves III and V. Eighth nerve tumors can cause a variety of BAEP abnormalities depending on which structures they affect. Adverse intraoperative BAEP changes can have many etiologies, including direct mechanical or thermal injury of tissue, ischemia (including cochlear ischemia or infarction due to compromise of the internal auditory artery), eighth nerve stretch, systemic or localized hypothermia, and artifactual BAEP changes due to technical factors.

Effect of granulocyte colony-stimulating factor on the cochlear nuclei after creation of a partial nerve lesion: an experimental study in rats.

OBJECTIVE The risk of injury of the cochlear nerve during angle (CPA) surgery is high. Granulocyte colony-stimulating factor (G-CSF) has been found in various experimental models of peripheral and CNS injury to have a neuroprotective effect by inhibiting apoptosis and inflammation. However, to the authors' knowledge, the influence of G-CSF on cochlear nerve regeneration has not been reported. This study investigated the neuroprotective effect of G-CSF after a partial cochlear nerve lesion in rats. METHODS A lesion of the right cochlear nerve in adult male Sprague-Dawley rats was created using a water-jet dissector with a pressure of 8 bar. In the first group (G-CSF-post), G-CSF was administrated on Days 1, 3, and 5 after the surgery. The second group (G-CSF-pre/post) was treated with G-CSF 1 day before and 1, 3, and 5 days after applying the nerve injury. The control group received sodium chloride after nerve injury at the various time points. Brainstem auditory evoked potentials (BAEPs) were measured directly before and after nerve injury and on Days 1 and 7 to evaluate the acoustic function of the cochlear nerve. The animals were sacrificed 1 week after the operation, and their brains were fixed in formalin. Nissl staining of the cochlear nuclei was performed, and histological sections were analyzed with a light microscope and an image-processing program. The numbers of neurons in the cochlear nuclei were assessed. RESULTS The values for Waves 2 and 4 of the BAEPs decreased abruptly in all 3 groups in the direct postoperative measurement. Although the amplitude in the control group did not recover, it increased in both treatment groups. According to 2-way ANOVA, groups treated with G-CSF had a significant increase in BAEP Wave II amplitudes on the right side (p = 0.0401) after the applied cochlear nerve injury. With respect to Wave IV, a trend toward better recovery in the G-CSF groups was found, but this difference did not reach statistical significance. In the histological analysis, higher numbers of neurons were found in the G-CSF groups. In the statistical analysis, the difference in the numbers of neurons between the control and G-CSF-post groups reached significance (p = 0.0086). The difference in the numbers of neurons between the control and G-CSF-pre/post groups and between the G-CSF-post and G-CSF-pre/post groups did not reach statistical significance. CONCLUSIONS The use of G-CSF improved the function of the eighth cranial nerve and protected cochlear nucleus cells from destruction after a controlled partial injury of the nerve. These findings might be relevant for surgery that involves CPA tumors. The use of G-CSF in patients with a lesion in the CPA might improve postoperative outcomes.

The effect of progressive hearing loss on the morphology of endbulbs of Held and bushy cells.

Studies of congenital and early-onset deafness have demonstrated that an absence of peripheral sound-evoked activity in the auditory nerve causes pathological changes in central auditory structures. The aim of this study was to establish whether progressive acquired hearing loss could lead to similar brain changes that would degrade the precision of signal transmission. We used complementary physiologic hearing tests and microscopic techniques to study the combined effect of both magnitude and duration of hearing loss on one of the first auditory synapses in the brain, the endbulb of Held (EB), along with its bushy cell (BC) target in the anteroventral cochlear nucleus. We compared two hearing mouse strains (CBA/Ca and heterozygous shaker-2+/-) against a model of early-onset progressive hearing loss (DBA/2) and a model of congenital deafness (homozygous shaker-2-/-), examining each strain at 1, 3, and 6 months of age. Furthermore, we employed a frequency model of the mouse cochlear nucleus to constrain our analyses to regions most likely to exhibit graded changes in hearing function with time. No significant differences in the gross morphology of EB or BC structure were observed in 1-month-old animals, indicating uninterrupted development. However, in animals with hearing loss, both EBs and BCs exhibited a graded reduction in size that paralleled the hearing loss, with the most severe pathology seen in deaf 6-month-old shaker-2-/- mice. Ultrastructural pathologies associated with hearing loss were less dramatic: minor changes were observed in terminal size but mitochondrial fraction and postsynaptic densities remained relatively stable. These results indicate that acquired progressive hearing loss can have consequences on auditory brain structure, with prolonged loss leading to greater pathologies. Our findings suggest a role for early intervention with assistive devices in order to mitigate long-term pathology and loss of function.