Clinical course of five patients definitively diagnosed with idiopathic perilymphatic fistula treated with transcanal endoscopic ear surgery.

Objectives: An idiopathic perilymphatic fistula (PLF) can be difficult to diagnose because patients present with sudden sensorineural hearing loss (SSHL) and/or vestibular symptoms without any preceding events. In such cases, we currently test for cochlin-tomoprotein (CTP) to confirm the diagnosis of idiopathic PLF because CTP is only detected in the perilymph. In this study, we report the clinical course of five patients definitively diagnosed with idiopathic PLF who underwent PLF repair surgery using transcanal endoscopic ear surgery (TEES). Patients and methods: Five patients were initially treated with intratympanic dexamethasone for SSHL, at which time a CTP test was also performed (preoperative CTP test). Due to refractory hearing loss and/or fluctuating disequilibrium, PLF repair surgery using TEES was performed to seal the oval and round windows using connective tissue and fibrin glue. These patients were diagnosed with definite idiopathic PLF based on pre- or intra-operative CTP test results (negative, < 0.4 ng/mL; intermediate, 0.4-< 0.8 ng/mL; and positive, > 0.8 ng/mL). We evaluated pre- and intra-operative CTP values, intraoperative surgical findings via a magnified endoscopic view, and pre- and post-operative changes in averaged hearing level and vestibular symptoms. Results: Pre- and intra-operative CTP values were positive and intermediate in three patients, positive and negative in one patient, and negative and positive in one patient. None of the patients had intraoperative findings consistent with a fistula between the inner and middle ears or leakage of perilymph. Only two patients showed a slight postoperative recovery in hearing. Four patients complained of disequilibrium preoperatively, of whom two had resolution of disequilibrium postoperatively. Conclusion: A positive CTP test confirms PLF in patients without obvious intraoperative findings. The CTP test is considered more sensitive than endoscopic fistula confirmation. We consider that CTP test results are important indicators to decide the surgical indication for idiopathic PLF repair surgery. In our experience with the five cases, two of them showed improvements in both hearing and vestibular symptoms.

The use of basic fibroblast growth factor to treat intractable Bell's palsy administered via transcanal endoscopic ear surgery.

PURPOSE: Facial nerve decompression surgery is an invasive procedure which has hitherto been the main option for patients with severe intractable Bell's palsy which is resistant to drug treatment. We have developed a new salvage treatment for such patients by using minimally invasive transcanal endoscopic ear surgery (TEES) to deliver the biological regenerative agent, basic fibroblast growth factor (bFGF), to the damaged facial nerve. MATERIALS AND METHODS: An endoscopic salvage treatment group was studied prospectively and was made up of severe intractable Bell's palsy patients who did not respond to high dose steroid treatment and had an ENoG value of 5 % or less. This surgery group was retrospectively compared to a similar control group who had received high dose steroid only. RESULTS: Complete recovery to House-Brackmann (HB) Grade I was achieved by 44.8 % of the endoscopic salvage treatment group which was significantly higher than the 21.2 % of the control group at one-year follow up. Patients with an ENoG value of 1 % to 5 % exhibited a significantly higher complete recovery rate of 71.4 % in the endoscopic salvage treatment group than the 28.6 % of the control group. In addition, no complications were observed including hearing loss. CONCLUSIONS: bFGF delivered via TEES shows considerable promise as a new salvage treatment of severe intractable Bell's palsy that is resistant to high dose steroid treatment without the risks presented by facial nerve decompression surgery.

Benefits of High-Dose Corticosteroid and Antiviral Agent Combination Therapy in the Treatment of House-Brackman Grade VI Ramsay Hunt Syndrome.

OBJECTIVE: Few large-scale investigations have been conducted on treatment of House-Brackmann grade VI (HB grade VI) Ramsay Hunt syndrome (RHS) patients. We compared recovery rates among patients receiving a normal-dose corticosteroid (prednisolone [PSL] 60 mg/d) or high-dose corticosteroid (PSL 200 mg/d), both with or without an antiviral agents. Recovery rates were also examined based on the order of presentation of herpetic vesicles versus facial palsy. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: A total of 128 patients with HB grade VI RHS were treated in our department between 1995 and 2017. These patients were divided into four treatment groups based on corticosteroid dosage and use of an antiviral agent. METHODS: We assessed treatment outcomes for HB grade VI patients together with logistic regression analysis to investigate factors that can impact treatment outcomes, that is, sex, age, days to start of treatment, PSL dosage, and antiviral agent administration. RESULTS: Recovery rates were best in the high-dose corticosteroid group with an antiviral agent (71.1%) in comparison with the normal-dose corticosteroid group with an antiviral agent (60.0%) or high-dose corticosteroid alone (57.1%). Significant factors for treatment outcomes were high-dose corticosteroid administration and early initiation of treatment. A better recovery rate was also found when the herpetic vesicles appeared before facial palsy. CONCLUSION: We showed that a combination of a high-dose corticosteroid and antiviral agent produced the best outcomes for patients with HB grade VI RHS. However, our results were not statistically significant because of small sample size.

The Feasibility and Treatment Results of Transcanal Endoscopic Myringoplasty.

OBJECTIVE: We reported on transcanal endoscopic myringoplasty in 25 cases preliminarily in 2014. Now our number of transcanal endoscopic myringoplasty reached to 209 ears and allowed us to adequately investigate the visibility, necessity of canalplasty, treatment results, and multivariate analysis. STUDY DESIGN: A prospective case series. SETTING: Tertiary referral center. PATIENTS: Transcanal endoscopic myringoplasty was performed on 209 ears in 201 patients between 2011 and 2019 and followed up over 1 year. METHODS: Preoperative endoscopic and microscopic views for the same patient were compared. We examined success rates at 1 year after surgery according to operation type, perforation size, operation side, gender, cause of perforation, and age, and also examined hearing results. Logistic regression analysis was performed to investigate the basic demographic and clinical characteristics of the patients associated with perforation closure. RESULTS: The anterior edge of the preoperative perforation was not visible under microscopy in 14.4% of patients. In contrast, endoscopic views revealed the entire tympanic membrane in one field. However, canalplasty was required in 2.4% of tympanic procedures due to difficulty of manipulation. The overall closure rate for perforations was 90.4%. Logistic regression analysis revealed that age > 11 was the only significant factor associated with perforation closure. The average reduction in air-bone gap was 12.1 dB. CONCLUSION: The endoscopic myringoplasty produced better visualization, the same or better closure rates, and the same or lower complication rates as compared with traditional microscopic techniques.

Adverse reactions to BNT162b2 mRNA COVID-19 vaccine in medical staff with a history of allergy.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) vaccination is progressing globally. Several adverse reactions have been reported with vaccination against COVID-19. It is unknown whether adverse reactions to COVID-19 vaccination are severe in individuals with allergies. METHODS: We administered the COVID-19 vaccine to the medical staff at Yamagata University Hospital from March to August 2021. Subsequently, we conducted an online questionnaire-based survey to investigate the presence of allergy and adverse reactions after vaccination and examine the association between allergy and adverse reactions after immunization. RESULTS: Responses were collected from 1586 to 1306 participants after the first and second administration of the BNT162b2 mRNA COVID-19 vaccine, respectively. Adverse reactions included injection site pain, injection site swelling, fever, fatigue or malaise, headache, chills, nausea, muscle pain outside the injection site, and arthralgia. The frequency of some adverse reactions and their severity were higher, and the duration of symptoms was longer in participants with allergies than in those without allergies. Although several participants visited the emergency room for treatment after the first and second vaccinations, no participant was diagnosed with anaphylaxis. CONCLUSIONS: This study suggests that the frequency and severity of adverse reactions after injection of BNT162b2 mRNA COVID-19 vaccine were higher in individuals with allergy; however, no severe adverse reactions such as anaphylaxis or death were observed. These results indicate that individuals with allergic histories may tolerate the BNT162b2 mRNA COVID-19 vaccine.

International Survey of Operative Practices for Otologists and Neurotologists During the COVID-19 Crisis.

OBJECTIVE: To investigate the influence of the COVID-19 pandemic on operative practices of otology and neurotology providers internationally. STUDY DESIGN: Cross-sectional survey. METHODS: A 78-question survey was distributed to otologists and neurotologists between May 12, 2020 and June 8, 2020 to assess the impact of the pandemic on surgical practices. Sections within the survey delineated time periods: prior to the crisis, onset of the crisis, during the crisis, postcrisis transition. RESULTS: Of 396 survey respondents, 284 participants from 38 countries met inclusion criteria.Respondents were 16.9% female and 82.4% male, with a most common age range of 40 to 49 years (36.3%). 69.8% of participants had been in practice for over 10 years and most respondents worked in an academic medical center (79.2%). The average operative weekly caseload was 5.3 (SD 3.9) per surgeon prior to the crisis, 0.7 (SD 1.2) during the COVID-19 crisis, and 3.5 (SD 3.3) for those who had begun a postcrisis transition at the time of survey administration (p < 0.001). 71.5% of providers did not perform an elective otologic or neurotologic operative procedure during the initial crisis period. 49.8% reported modifying their surgical technique due to the COVID-19 pandemic. Use of powered air-purifying respirators and filtering facepiece 2 or 3 (FFP2/FFP3) respirators were in minimal supply for 66.9% and 62.3% of respondents, respectively. CONCLUSION: The COVID-19 pandemic impacted the otology and neurotology community globally, resulting in significant changes in operative volume and case selection. Modification of surgical technique and shortages of personal protective equipment were frequently reported.

Y-27632, a ROCK inhibitor, improved laser-induced shock wave (LISW)-induced cochlear synaptopathy in mice.

Recently, a pathological condition called cochlear synaptopathy has been clarified, and as a disorder of the auditory nerve synapses that occurs prior to failure of hair cells, it has been recognized as a major cause of sensorineural hearing loss. However, cochlear synaptopathy is untreatable. Inhibition of rho-associated coiled-coil containing protein kinase (ROCK), a serine-threonine protein kinase, has been reported to have neuroprotective and regenerative effects on synaptic pathways in the nervous system, including those in the inner ear. We previously demonstrated the regenerative effect of the ROCK inhibitor, Y-27632, on an excitotoxic cochlear nerve damage model in vitro. In this study, we aimed to validate the effect of ROCK inhibition on mice with cochlear synaptopathy induced by laser-induced shock wave (LISW) in vivo. After the elevation of ROCK1/2 expression in the damaged cochlea was confirmed, we administered Y-27632 locally via the middle ear. The amplitude of wave I in the auditory brainstem response and the number of synapses in the Y-27632-treated cochlea increased significantly. These results clearly demonstrate that ROCK inhibition has a promising clinical application in the treatment of cochlear synaptopathy, which is the major pathology of sensorineural hearing loss.

Multicenter phase III trial of regenerative treatment for chronic tympanic membrane perforation.

OBJECTIVE: To evaluate the efficacy and safety of regenerative treatment for tympanic membrane perforation (TMP) using gelatin sponge, basic fibroblast growth factor (bFGF), and fibrin glue. METHODS: This was a multicenter, non-randomized, single-arm study conducted at tertiary referral centers. Twenty patients with chronic TMP (age 23-78 years, 6 males, 14 females) were registered from three institutions. All treated patients were included in the safety analysis population. The edges of the TMP were disrupted mechanically by myringotomy and several pieces of gelatin sponge immersed in bFGF were placed and fixed with fibrin glue to cover the perforation. The TMP was examined 4 ± 1 weeks later. The protocol was repeated up to four times until closure was complete. The main outcome measures were closure or a decrease in size of the TMP, hearing improvement, and air-bone gap evaluated 16 weeks after the final regenerative procedure (FRP). Adverse events (AEs) were monitored throughout the study. RESULTS: Total closure of the TMP at 16 weeks was achieved in 15 out of 20 patients (75.0%, 95% confidence interval [CI]: 50.9%-91.3%) and the mean decrease in size was 92.2% (95%CI: 82.9%-100.0%). The ratio of hearing improvement and the air-bone gap at 16 weeks after FRP were 100% (20/20; 95%CI: 83.2%-100%) and 5.3 ± 4.2 dB (p <0.0001), respectively. Thirteen out of 20 patients (65.0%) experienced at least one AE, but no serious AEs occurred. CONCLUSION: The results indicate that the current regenerative treatment for TMP using gelatin sponge, bFGF, and fibrin glue is safe and effective.

Consistent removal of hair cells in vestibular end organs by time-dependent transtympanic administration of gentamicin in guinea pigs.

BACKGROUND: Vestibular hair cell loss and its role in balance disorders are not yet completely understood due largely to the lack of precise hair cell damage protocols. NEW METHOD: Our damage protocol aims to selectively remove type I hair cells in a way that produces consistent and predictable lesions that can be used for reliable inter-animal and inter-group comparison in balance research. This objective is achieved by transtympanic injection of gentamicin on both the round window membrane and oval window over a fixed time period followed by thorough washing. RESULTS: We achieved nearly total and consistent loss of type I hair cells at 94 % for the crista ampullaris of the lateral semicircular canal (LSC) and 86 % for the utricular macula with negligible loss of type II hair cells at 4% for the crista ampullaris of the LSC and 6% for the utricular macula. While the vestibular function was compromised in the relevant study group, this group had a zero mortality rate with no significant suppression of body weight gain. COMPARISON WITH EXISTING METHODS: Gentamicin is typically administered via intraperitoneal systemic injection or, more recently, transtympanic injection. The intraperitoneal method is simple, but mortality rate is high. The transtympanic injection method produces ototoxic damage but with inconsistent lesion size. This inconsistency prevents reliable comparisons among animals. CONCLUSIONS: This protocol employs a transtympanic injection method which selectively targets type I hair cells for removal in the vestibular epithelia in a time-dependent manner, uniformly damages vestibular function, and causes uniform hair cell loss.

Regenerative Effect of a ROCK Inhibitor, Y-27632, on Excitotoxic Trauma in an Organotypic Culture of the Cochlea.

In the past, most inner ear diseases were thought to start with the impairment of the sensory epithelium of the cochlea before subsequently progressing to secondary neural degeneration. However, recent studies show that loss of primary synapses accompanied by excitotoxic degeneration of peripheral axons is likely to be the underlying pathology in sensorineural hearing loss. Rho-associated coiled-coil containing protein kinase (ROCK) inhibition has been reported to have neuroprotective and regenerative effects on synaptic pathways. Therefore, we analyzed the effect of ROCK inhibition using Y-27632 in a model of peripheral axonal damage in the spiral ganglion neurons created using the glutamate agonists, N-methyl-D-aspartate (NMDA) and kainic acid, to induce excitotoxic trauma in the explanted cochlea. The number of axons projecting to hair cells in the cochlea treated with Y-27632 was significantly greater than those in the cochlea treated only with NMDA + kainic acid. Furthermore, there was a significant increase in synapses between the spiral ganglion and the inner hair cells in the cochlea treated with Y-27632. The findings of this study suggest that ROCK inhibition could be a potential strategy for the regeneration of peripheral axons in the spiral ganglion and synapse formation in the inner hair cells of a cochlea that has sustained excitotoxic injury, which is one of the primary etiologies of inner ear disease.

The iArmS Robotic Armrest Prolongs Endoscope Lens-Wiping Intervals in Endoscopic Sinus Surgery.

Objective. Fouling of the endoscope lens is a major problem in endoscopic sinus surgery (ESS). We examined whether the use of the intelligent arm support system (iArmS), a robotic armrest, could prolong endoscope lens-wiping intervals in ESS and thus allow for continuously clear endoscopic images. Study Design. This study is a prospective, nonrandomized crossover study. Methods. Three surgeons who performed ESS at 2 centers each conducted 3 operations with the iArmS and 3 operations without the iArmS; thus, 18 operations were assessed. To blind the assessments, we performed them prospectively without informing subjects of the endpoints. We recorded the operations and observed the recordings at a later date; endoscope lens-wiping times were noted in seconds to determine the endoscope lens-wiping intervals. Our examination was based on the null hypothesis that endoscope lens-wiping intervals would not differ according to the use or nonuse of the iArmS. Results. The median endoscope lens-wiping intervals with and without using the iArmS were 361 seconds and 135 seconds, respectively. Based on the Wilcoxon rank-sum test, this difference was significant (P = 0.001); thus, the null hypothesis was rejected. This result indicated that endoscope lens-wiping intervals are greatly prolonged by the use of the iArmS. Conclusion. The iArmS robotic armrest is suitable for ESS, prolongs endoscope lens-wiping intervals, and facilitates obtaining continuous clear endoscopic images.

The effect of insulin-like growth factor 1 on the recovery of facial nerve function in a guinea pig model of facial palsy.

The efficacy of insulin-like growth factor 1 (IGF-1) in the treatment of peripheral facial nerve palsy was investigated using an animal model. The facial nerve within the temporal bone was exposed and compressed by clamping. The animals were treated with either IGF-1 or saline which was topically administered by a gelatin-based sustained-release hydrogel via an intratemporal route. The recovery from facial nerve palsy was evaluated at 8 weeks postoperatively based on eyelid closure, complete recovery rate, electroneurography and number of axons found on the facial nerve. IGF-1 treatment resulted in significant improvement in the changes of the degree of eyelid closure over the total time period and complete recovery rate. A separate study showed that IGF-1 receptor mRNA was expressed in facial nerves up to 14 days after the nerve-clamping procedure. IGF-1 was thus found to be effective in the treatment of peripheral facial nerve palsy when topically applied using a sustained-release gelatin-based hydrogel via an intratemporal route.

Measurement of the Pediatric and Adult Osseous External Auditory Canal: Implications for Transcanal Endoscopic Ear Surgery.

OBJECTIVE: To develop a method for measuring the diameter of the osseous external auditory canal (OEAC) in pediatric and adult patients. STUDY DESIGN: Retrospective analysis of imaging data from patients with a cholesteatoma who underwent transcanal endoscopic ear surgery (TEES) to remove the cholesteatoma by analyzing preoperative sagittal cone beam computed tomography (CBCT) images using ImageJ. METHODS: Pediatric and adult patients were included who underwent TEES for a cholesteatoma between December 2011 and March 2015 and had available preoperative CBCT scans. Sagittal CT imaging data were analyzed by ImageJ to measure the maximum and minimum Feret diameters along the OEAC. The output data were then analyzed to determine the smallest maximum and smallest minimum Feret diameters for each patient. RESULTS: Fifty-one patients ranging in age from 3 to 83 years old were included in this study. The smallest maximum Feret diameter ranged from 6.5 to 10.1 mm (mean: 8.0 mm) for pediatric patients (<16 years of age) and 6.9 to 15.0 mm (mean: 8.9 mm) for adult patients, while the smallest minimum Feret diameter ranged from 3.6 to 5.9 mm (mean: 5.1 mm) for pediatric patients and 3.4 to 6.4 mm (mean: 5.4 mm) for adult patients. Moreover, the smallest maximum Feret diameters of children were significantly smaller than those of adults. CONCLUSION: We have developed a novel method for measuring the diameter along the OEAC and determining its narrowest site. This method can be incorporated into the preoperative evaluation of patients who are candidates for TEES.

Brain Abscess as a Rare Complication of Primary Extranodal Nasal-type Natural Killer/T-cell Lymphoma.

We present the case of a 58-year-old Japanese woman with a natural killer T (NK/T)-cell lymphoma complicated by brain abscess. NK/T-cell lymphomas represent a rare type of lymphoma derived from either activated NK cells or, rarely, cytotoxic T cells. They are aggressive Epstein-Barr virus (EBV)-associated lymphomas that involve mainly the nasal cavity. Brain abscess associated with primary extranodal nasal-type NK/T-cell lymphoma is extremely uncommon: to our knowledge, this is the first reported case of this lymphoma with brain abscess as the initial clinical manifestation. Endoscopic surgery was performed for definitive diagnosis under intraoperative navigation system. Chemotherapy followed by radiotherapy was performed and was effective: 72 months later the tumor has not recurred. Recommendations of endoscopic management for diagnosis and treatment of this rare neoplasm are discussed.

Facial nerve and chorda tympani schwannomas: Case series, and advantages of using non-rigid registration of post-enhanced 3D-T1 Turbo Field Echo and CT images (TURFECT) in their diagnosis and surgical treatment.

OBJECTIVE: Facial nerve schwannomas (FNSs) and chorda tympani schwannomas are very rare. Diagnosis of these tumors is sometimes difficult, and treatment consensus has not yet been reached. We report here a series of cases of FNS and chorda tympani schwannoma and highlight the usefulness of our newly developed technique of non-rigid registration of post-enhanced 3D-T1 Turbo Field Echo and CT images (TURFECT) in their diagnosis and treatment. METHODS: MRI images were adjusted with the corresponding CT images in terms of angle and position in order to index the anatomical structures. The well-enhanced T1-Gd+ lesions of tumors having good blood flow show up as bright red after color mapping. RESULTS: Between 2014 and 2018, five patients were diagnosed with schwannomas in the temporal bone: three with FNS and two with chorda tympani schwannoma. Gd-enhanced MRI showed only a high-intensity mass, and we could not detect the relationship between tumor-like mass and bone (including the ossicles) by MRI only. In contrast, TURFECT was very useful for diagnosing the precise location, allowing us to decide on an endoscopic surgical plan in some of our cases. An endoscope enabled visualization of the medial wall of the tympanic cavity and the status of the tumors, thus we could successfully perform transcanal endoscopic biopsy and resections. CONCLUSION: TURFECT can be very useful for diagnosis of FNSs and chorda tympani schwannomas and for deciding surgical treatments such as a transcanal endoscopic approach.

Malignancies in Patients with IgG4-Related Diseases in Head and Neck Regions.

Immunoglobulin G4-related disease (IgG4-RD) is a recently recognized disease, characterized by high serum IgG4 concentrations and IgG4-producing plasma cell expansion with fibrotic or sclerotic changes in affected organs. Recent work has focused on the relationship between IgG4-RD and malignancies, but there is no report of malignancies associated with IgG4-RD in head and neck regions. The aim of this study was to analyze the clinicopathological characteristics of malignancies in patients with IgG4-RD in head and neck regions. We retrospectively analyzed 26 patients with IgG4-RD (12 men and 14 women aged 60.6 ± 11.6 years). The mean follow-up period was 26.6 months (from 12 to 96 months). These patients were divided into single-lesion group (n = 12) with IgG4-RD only in head and neck regions and multiple-lesion group (n = 14) with IgG4-RD in other regions. There was no significant difference in serum IgG4 concentrations between the single-lesion group (459.4 ± 336.4 mg/dL) and the multiple-lesion group (908.0 ± 739.2 mg/dL) (P = 0.07), whereas the IgG4/IgG ratio was significantly lower in the single-lesion group (22.8 ± 11.0%; n = 11) compared with the multiple-lesion group (31.7 ± 15.0%; n = 11, P = 0.02). Among the 26 patients, two patients (7.7%), both in the multiple-lesion group, developed life-threatening malignancies (salivary duct carcinoma in the submandibular gland and lymphoma in the orbital tissue). All physicians need to keep in mind the possible coexistence of malignancies in patients with IgG4-RD with high IgG4/IgG ratio and multiple lesions at the time of diagnosis.

Transcanal Endoscopic Ear Surgery for Congenital Middle Ear Anomalies.

OBJECTIVE: To demonstrate the efficacy of transcanal endoscopic ear surgery (TEES) for congenital middle ear anomalies. STUDY DESIGN: Retrospective case review. SETTING: Tertiary referral center. PATIENTS: Twenty-one patients ranging in age from 4 to 62 years old (median: 15 yr) who underwent TEES between 2011 and 2017 were compared with 19 patients ranging in age from 3 to 49 years old (median: 11 yr) who underwent microscopic ear surgery (MES) between 2000 and 2011. INTERVENTION: Ossiculoplasty or stapes surgeries were performed with TEES or MES. TEES was performed using a rigid endoscope with an outer diameter of 2.7-mm coupled with a full high-definition video system. MES was performed via a transcanal approach with a retroauricular incision. MAIN OUTCOME MEASURE: Middle ear anomaly classification, operating time, and hearing outcomes based on the American Academy of Otolaryngology and Head and Neck Surgery criteria were evaluated and compared between the TEES and MES groups. RESULTS: For Teunissen and Cremers class III anomalies, defined as ossicular chain malformations with a mobile stapes footplate, postoperative air-bone gap closure to 10 dB or less was achieved in 50% of the TEES group and 47% of the MES group. Postoperative air-bone gap closure to 20 dB or less was achieved in 86% of the TEES group and 100% of the MES group. No significant difference was found in the operating time between the two groups. All MES procedures required a retroauricular incision. CONCLUSION: Our results indicate that TEES has similar auditory outcomes compared with MES while avoiding a retroauricular incision.

Expression and localization of diacylglycerol kinase ζ in guinea pig cochlea and its functional implication under noise-exposure stress conditions.

Cochlear hair cells are essential for the mechanotransduction of hearing. Sensorineural hearing loss can be irreversible because hair cells have a minimal ability to repair or regenerate themselves once damaged. In order to develop therapeutic interventions to prevent hair cell loss, it is necessary to understand the signaling pathway operating in cochlear hair cells and its alteration upon damage. Diacylglycerol kinase (DGK) regulates intracellular signal transduction through phosphorylation of lipidic second messenger diacylglycerol. We have previously reported characteristic expression and localization patterns of DGKs in various organs under pathophysiological conditions. Nevertheless, little is known about morphological and functional aspects of this enzyme family in the cochlea. First RT-PCR analysis reveals predominant mRNA expression of DGKα, DGKε and DGKζ. Immunohistochemical analysis shows that DGKζ localizes to the nuclei of inner hair cells (IHCs), outer hair cells (OHCs), supporting cells and spiral ganglion neurons in guinea pig cochlea under normal conditions. It is well known that loud noise exposure induces cochlear damage, thereby resulting in hair cell loss. In particular, OHCs are highly vulnerable to noise exposure than IHCs. We found that after 1 week of noise exposure DGKζ translocates from the nucleus to the cytoplasm in damage-sensitive OHCs and gradually disappears thereafter. In sharp contrast, DGKζ remains to the nucleus in damage-resistant IHCs. These results suggest that DGKζ cytoplasmic translocation is well correlated with cellular damage under noise-exposure stress conditions and is involved in delayed cell death in cochlear outer hair cells.

Detecting the recruitment phenomenon in adults using 80-Hz auditory steady-state response.

OBJECTIVES: The ASSR is used widely as an objective measurement of hearing in clinical settings because of its high frequency specificity. The recruitment phenomenon is generally detected using subjective evaluations which require direct communication with the patient. If the recruitment phenomenon can be detected with ASSR, it would facilitate diagnosis in patients with developmental disorders and infants. SUBJECTS AND METHODS: We examined 2 groups of subjects: 10 subjects with unilateral hearing impairment in whom the recruitment phenomenon was detected by the alternate binaural loudness balance test and 12 normal subjects. We compared the relationships between the ASSR response and the stimulus sound pressure level in the 2 groups using the 80-Hz ASSR. RESULTS: The amplitude of ASSR was significantly higher in the impaired ear in hearing-impaired subjects compared to a normal ear in normal subjects. The latency of ASSR was significantly shorter in the impaired ear in hearing-impaired subjects than in the normal ear in the normal subjects. CONCLUSION: This study showed that the recruitment phenomenon caused the higher amplitude and the shorter latency observed in hearing-impaired subjects in the 80-Hz auditory steady-state response (ASSR) in comparison with normal subjects.