Hippocampal atrophy is associated with hearing loss in cognitively normal adults.

Objectives: A growing body of evidence suggests that age-related hearing loss (HL) is associated with morphological changes of the cerebral cortex, but the results have been drawn from a small amount of data in most studies. The aim of this study is to investigate the correlation between HL and gray matter volume (GMV) in a large number of subjects, strictly controlling for an extensive set of possible biases. Methods: Medical records of 576 subjects who underwent pure tone audiometry, brain magnetic resonance imaging (MRI), and the Korean Mini-Mental State Exam (K-MMSE) were reviewed. Among them, subjects with normal cognitive function and free of central nervous system disorders or coronary artery disease were included. Outliers were excluded after a sample homogeneity check. In the end, 405 subjects were enrolled. Pure tone hearing thresholds were determined at 0.5, 1, 2, and 4 kHz in the better ear. Enrolled subjects were divided into 3 groups according to pure tone average: normal hearing (NH), mild HL (MHL), and moderate-to-severe HL (MSHL) groups. Using voxel-based morphometry, we evaluated GMV changes that may be associated with HL. Sex, age, total intracranial volume, type of MRI scanner, education level, K-MMSE score, smoking status, and presence of hypertension, diabetes mellitus and dyslipidemia were used as covariates. Results: A statistically significant negative correlation between the hearing thresholds and GMV of the hippocampus was elucidated. Additionally, in group comparisons, the left hippocampal GMV of the MSHL group was significantly smaller than that of the NH and MHL groups. Conclusion: Based on the negative correlation between hearing thresholds and hippocampal GMV in cognitively normal old adults, the current study indicates that peripheral deafferentation could be a potential contributing factor to hippocampal atrophy.

Causes and outcomes of revision surgery in subjects with pulsatile tinnitus.

Introduction: Once the underlying pathology has been identified, pulsatile tinnitus (PT) can be treated successfully with surgical or interventional management. However, some patients experience residual or recurrent symptoms following initially successful surgical treatment, and require revision surgery or additional procedures. Here, we report a case series of patients who had undergone revision surgery or interventional treatment, and suggest possible ways of minimizing the need for revision. Methods: Between January 2014 and March 2023, a total of seven subjects underwent revision surgery or interventional treatment for persistent or recurrent PT after initial surgical treatment. Demographic data, reasons for revision, and changes in symptoms before and after revision were analyzed retrospectively. Temporal bone computed tomographic angiography images were reviewed to identify the causes and reasons for revision. Results: Of the seven subjects, six underwent sigmoid sinus (SS) resurfacing/reshaping due to ipsilateral diverticulum (Div) or dehiscence (Deh), and one underwent jugular bulb (JB) resurfacing due to a high-riding JB with bony Deh. Of the five subjects who underwent revision SS surgery due to recurrent SS-Div or SS-Deh, three showed marked resolution of PT, while the other two showed partial improvement of the symptoms. One subject who underwent revision JB resurfacing, and another who underwent additional transarterial embolization for a concurrent ipsilateral dural arteriovenous fistula, reported marked improvement of PT. Discussion: The possibility of recurrence should be taken into account when performing surgical intervention in patients with PT. The likelihood of recurrence can be minimized through a comprehensive evaluation to identify possible multiple etiologies, and through the use of durable materials and appropriate surgical methods.

Association between Chronic Kidney Disease and Sudden Sensorineural Hearing Loss: A Longitudinal Follow-Up Studies Using ICD-10 Codes in a National Health Screening Cohort.

This study aims to investigate the association between chronic kidney disease (CKD) and sudden sensorineural hearing loss (SSNHL) using a population-based cohort study. We used data from the Korean National Health Insurance Service-Health Screening Cohort. Participants were selected based on diagnosis and treatment codes, and CKD participants were 1:4 matched with control participants. Covariates, including demographic and lifestyle factors, and comorbidities were considered in the analysis. We calculated the incidence rate and hazards ratio of SSNHL. A total of 16,713 CKD participants and 66,852 matched controls were enrolled. The CKD group had a higher incidence rate of SSNHL compared to the control group at 2.16 and 1.74 per 1000 person-years, respectively. The CKD group exhibited a higher risk for SSNHL compared to the control group with adjusted HR 1.21. In the subgroup analysis, the presence of cardiovascular risk factors was associated with a diminished effect of CKD on the risk of developing SSNHL. This study provides strong evidence of an association between CKD per se and an increased risk of SSNHL even after adjusting for various demographic and comorbidity factors. The findings suggest that CKD patients may require more comprehensive monitoring for hearing loss.

The molecular etiology of deafness and auditory performance in the postlingually deafened cochlear implantees.

Recent advances in molecular genetic testing (MGT) have improved identification of genetic aetiology of candidates for cochlear implantation (CI). However, whether genetic information increases CI outcome predictability in post-lingual deafness remains unclear. Therefore, we evaluated the outcomes of CI with respect to genetic aetiology and clinical predictors by comparing the data of study subjects; those with an identified genetic aetiology (GD group), and those without identifiable variants (GUD group). First, we identified the genetic aetiology in 21 of 40 subjects and also observed genetic etiologic heterogeneity. The GD group demonstrated significantly greater improvement in speech perception scores over a 1-year period than did the GUD group. Further, inverse correlation between deafness duration and the 1-year improvement in speech perception scores was tighter in the GD group than in the GUD group. The weak correlation between deafness duration and CI outcomes in the GUD group might suggest the pathophysiology underlying GUD already significantly involves the cortex, leading to lesser sensitivity to further cortex issues such as deafness duration. Under our MGT protocol, the correlation between deafness duration and CI outcomes were found to rely on the presence of identifiable genetic aetiology, strongly advocating early CI in individual with proven genetic aetiologies.

Prognostic value of the posterior cricoarytenoid muscle atrophy in computerized tomography scans for unilateral vocal fold paralysis recovery.

OBJECTIVES: To evaluate the prognostic value of the posterior cricoarytenoid (PCA) muscle atrophy observed on neck computed tomography (CT) in patients with unilateral vocal fold paralysis. METHODS: CT images of 87 subjects with unilateral vocal fold paralysis (UVFP) were evaluated to analyze the PCA muscle atrophy and to measure the severity of the PCA muscle atrophy in semi-quantitative manner. The grading of the PCA muscle atrophy was compared with the recruitment pattern of laryngeal electromyography (LEMG) and restoration of vocal fold movement. RESULTS: The PCA muscle was identifiable on CT in 73 subjects. Using the PCA muscle atrophy as an indicator of UVFP, we correctly predicted the paralysis in 69 (94.5%). Grade of the PCA muscle atrophy is significantly correlated with recruitment pattern of LEMG. If the positive result is defined as the PCA muscle showed moderate to severe degree of atrophy, we could predict the persistent UVFP in 88% of patients. CONCLUSIONS: PCA muscle atrophy identified on CT scan in patients with UVFP, is associated with low rates of return of mobility in the affected vocal fold.

Neurocognition of Aged Patients With Chronic Tinnitus: Focus on Mild Cognitive Impairment.

OBJECTIVES: To investigate the neurocognition of aged patients with chronic tinnitus and reveal the possible association between tinnitus severity and cognitive function, with attention to mild cognitive impairment (MCI). METHODS: Fifty-eight elderly patients (≥65 years old) with chronic tinnitus (≥6 months) were prospectively enrolled in this study. All patients assessed the neurocognitive batteries including the Korean version of the patient health questionnaire-9 (K-PHQ-9), the Lawton instrumental activities of daily living scale (K-IADL), and the Montreal cognitive assessment (MoCA-K). After initial evaluation to exclude moderate or severe cognitive impairment by a psychiatrist, the patients were classified into two groups: MCI and non-MCI, according to the MoCA-K scores (cutoff value, 22/23). All patients underwent audiological examinations including psychoacoustic tests of tinnitus. RESULTS: Of 58 patients, 10 (17.2%) met the MCI criteria. The tinnitus handicap inventory (THI) score in the MCI group was significantly higher than that in the non-MCI group. Based on multivariate regression analysis, a significant association between tinnitus severity and MoCA-K score was also detected. Specifically, bothersome tinnitus (THI score ≥30) was closely linked to the presence of MCI. Meanwhile, the impact of MCI on both K-PHQ-9 and K-IADL scores was not evident in patients with chronic tinnitus. CONCLUSION: Tinnitus severity appears to be a potential independent determinant for predicting the MCI, suggesting the underlying mechanism between chronic tinnitus and cognitive deficit. Given that MCI highly links to dementia, the evaluation of cognitive functions in aged patients with chronic tinnitus need to be considered at the initial assessment of tinnitus.

Changes in the Resting-State Cortical Oscillatory Activity 6 Months After Modified Tinnitus Retraining Therapy.

Although tinnitus retraining therapy (TRT) based on Jastreboff's classical neurophysiological model is efficacious in most patients, its effects on the cortical activity changes responsible for the improvement of tinnitus are still unclear. In this study, we compared pre- and post-TRT resting-state quantitative electroencephalography (rs-qEEG) findings to identify power changes that could explain TRT-induced improvements. Thirty-seven patients with severe tinnitus were enrolled in the study, and rs-qEEG data recorded before the initial TRT sessions and 6 months after TRT were compared. In addition, associations between the changes in qEEG and percentage improvements in Tinnitus Handicap Inventory (THI) scores and numeric rating scale (NRS) scores of tinnitus loudness and tinnitus perception were examined. The mean THI score decreased significantly 6 months after the initial TRT session. Also, significant improvements were observed 6 months after the initial TRT session compared with the pre-treatment scores in NRS loudness, distress, and perception. As compared with the pre-TRT status, post-TRT 6 months status showed significantly decreased powers in the left primary and secondary auditory cortices for the gamma frequency band. Changes in the alpha 1 frequency band power in the right insula and orbitofrontal cortex (OFC) appeared to be positively correlated with the percentage changes in NRS distress. These results suggested that TRT improved tinnitus-related distress by reducing the power of the top-down autonomic response modulator or peripheral physiological responses to emotional experiences. That is, TRT induced habituation via modulation of functional connections between the auditory system and the limbic and autonomic nervous systems. Our results confer additional basis for understanding the neurophysiological model and the newly suggested integrative model of tinnitus by De Ridder et al. (2014) in the context of the long-term efficacy of TRT.

"Third Window" and "Single Window" Effects Impede Surgical Success: Analysis of Retrofenestral Otosclerosis Involving the Internal Auditory Canal or Round Window.

BACKGROUND AND OBJECTIVES: We aimed to identify prognostic computed tomography (CT) findings in retrofenestral otosclerosis, with particular attention paid to the role of otosclerotic lesion area in predicting post-stapedotomy outcome. MATERIALS AND METHODS: We included 17 subjects (23 ears) with retrofenestral otosclerosis who underwent stapedotomy. On preoperative CT, the presence of cavitating lesion and involvement of various subsites (cochlea, round window [RW], vestibule, and semicircular canal) were assessed. Pre- and post-stapedotomy audiometric results were compared according to the CT findings. The surgical outcomes were analyzed using logistic regression with Firth correction. RESULTS: Cavitating lesions were present in 15 of 23 ears (65.2%). Involvement of the RW was the strongest predictor of unsuccessful surgical outcome, followed by involvement of the internal auditory canal (IAC) and the cochlea. CONCLUSIONS: RW and IAC involvement in retrofenestral otosclerosis were shown to predict unsuccessful outcomes. While a "third window" effect caused by extension of a cavitating lesion into the IAC may dissipate sound energy and thus serve as a barrier to desirable postoperative audiological outcome, a "single window" effect due to an extension of retrofenestral otosclerosis into the RW may preclude a good surgical outcome, even after successful stapedotomy, due to less compressible cochlear fluid and thus decreased linear movement of the piston.

Involvement of the Internal Auditory Canal in Subjects With Cochlear Otosclerosis: A Less Acknowledged Third Window That Affects Surgical Outcome.

OBJECTIVE: To investigate the effects of cavitating lesions involving the internal auditory canal (IAC) in subjects with cochlear otosclerosis with regard to poststapedotomy hearing outcome. STUDY DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A retrospective chart review of 134 subjects with otosclerosis treated from January 2011 to June 2017 at Seoul National University Bundang Hospital was conducted. Sixteen subjects (23 ears) with temporal bone computed tomography (TBCT)-confirmed cochlear otosclerosis who underwent stapedotomy were included in the study. MAIN OUTCOME MEASURES: Pure tone audiometry (PTA) (i.e., air and bone conduction; AC and BC, respectively) thresholds and air-bone gap (ABG), measured at 6 months postoperatively were compared between cochlear otosclerosis with and without IAC involvement (IAC group and non-IAC group, respectively). RESULTS: A total of 14 of 23 ears showed involvement of the IAC. There were no significant differences in age, side of otosclerosis, or preoperative hearing threshold between the two groups. The mean postoperative AC and BC thresholds and ABG of the IAC group were significantly poorer (45.7 dB, 33.8 dB, and 11.8 dB, respectively) than those of the nonIAC group (24.1 dB, 20.0 dB, and 4.1 dB, respectively). CONCLUSIONS: Cochlear otosclerosis with cavitating lesions involving the IAC showed significantly poorer postoperative audiological outcomes than those without any cavitating lesion. Cavitation extending to the IAC may act as a third window providing a route for sound energy shunting, and thus precluding successful hearing outcome in some subjects with cavitating otosclerosis after stapedotomy.

Effect of Ginkgo Biloba Extract on N-Methyl-D-Aspartic Acid Receptor Subunit 2B Expression in a Salicylate-Induced Ototoxicity Model.

OBJECTIVES: Sodium salicylate (SS) is well known for its ototoxic properties that induce functional and morphological changes in the cochlea and brain. Ginkgo biloba extract (GBE) has been widely used for treatment of various neurodegenerative diseases; however, its effects on salicylate-induced ototoxicity remain unclear. Herein, we examined the effects of EGb 761 (EGb), a standard form of GBE, on the plasticity of the N-methyl-D-aspartate receptor subunit 2B (GluN2B) in the inferior colliculus (IC) following SS administration. METHODS: Seven-week-old Sprague Dawley rats (n=24) were randomly allocated to control, SS, EGb, and EGb+SS groups. The SS group received a single intraperitoneal SS injection (350 mg/kg), the EGb group received EGb orally for 5 consecutive days (40 mg/kg), and the EGb+SS group received EGb for 5 consecutive days, followed by an SS injection. The auditory brainstem responses (ABRs) were assessed at baseline and 2 hours after SS administration. GluN2B expression was examined by Western blot and immunohistochemistry. RESULTS: There were no significant differences in ABR threshold shifts among the groups. The expression of the GluN2B protein normalized by which of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was significantly lower in the EGb+SS group, as compared to the SS group (P=0.012). Weak and diffused GluN2B immunoreactivity was detected in the IC neural cells of the EGb+SS group, while those of the SS group exhibited strong and diffused GluN2B positivity. CONCLUSION: EGb may play a role in regulating the GluN2B expression in the IC of salicylate-induced ototoxicity model.

Inflammatory and Immune Proteins in Umbilical Cord Blood: Association with Hearing Screening Test Failure in Preterm Neonates.

OBJECTIVE: We aimed to determine whether elevated levels of various inflammatory and immune proteins in umbilical cord blood are associated with an increased risk of newborn hearing screening (NHS) test failure in preterm neonates. METHODS: This retrospective cohort study included 127 premature singleton infants who were born at ≤33.6 weeks. Umbilical cord plasma at birth was assayed for interleukin (IL)-6, complement C3a and C5a, matrix metalloproteinase (MMP)-9, macrophage colony-stimulating factor (M-CSF), and endostatin levels using ELISA kits. Neonatal blood C-reactive protein (CRP) levels were measured within 2 hours of birth. The primary outcome measure was a uni- or bilateral refer result on an NHS test. Univariate and multivariate analyses were applied. RESULTS: Fifteen (11.8%) infants failed the NHS test. In the univariate analyses, high IL-6 and low C3a levels in umbilical cord plasma, funisitis, and an elevated CRP level (>5 mg/L) in the immediate postnatal period were significantly associated with NHS test failure. However, the levels of umbilical cord plasma MMP-9, C5a, M-CSF, and endostatin were not significantly different between infants who passed and those who failed the NHS test. Multiple logistic regression analyses indicated that elevated umbilical cord plasma C3a levels were independently associated with a reduced risk of NHS test failure, whereas elevated levels of umbilical cord plasma IL-6 and high CRP levels in the immediate postnatal period were significantly associated with NHS test failure. CONCLUSIONS: Our data demonstrated that in preterm neonates, a systemic fetal inflammatory response reflected by umbilical cord plasma IL-6 and immediate postnatal CRP levels may contribute to the risk for NHS test failure, whereas the changes in complement activation fragments initiated in utero may have protective effect of hearing screen failure.

The Novel Peptide Vaccine GV1001 Protects Hearing in a Kanamycin-induced Ototoxicity Mouse Model.

HYPOTHESIS: We tested whether GV1001 has any ototoxic side effects at different doses and whether it protects hearing in an aminoglycoside-induced ototoxicity mouse model. BACKGROUND: GV1001, a novel peptide vaccine currently being examined in a Phase 3 clinical trial to treat pancreatic cancer, also has anti-inflammatory and antioxidant effects. METHODS: In the first experiment, C57/BL6 mice were injected with GV1001 preparations at concentrations of 0.1 to 100 mg/kg for 7 days to evaluate the toxicity of GV1001 on the inner ear and kidneys. In the second experiment, the protective effect of GV1001 was tested in an ototoxicity mouse model that was generated by injecting 800 mg/kg kanamycin (KM) for 2 weeks. The hearing threshold and hair cell loss were compared between the KM + GV1001 group (treated with 10 mg/kg GV1001 for 2 wk) and the KM + saline group. The hearing threshold was measured before, and 7, 14, and 21 days after the initial treatment. The blood urea nitrogen level was measured. RESULTS: No ototoxicity or renal toxicity was found following treatment with different doses of GV1001 (0.1-100 mg/kg). The KM + saline group showed impaired auditory function and markedly disoriented and missing cochlear hair cells, while the KM + GV1001 group showed significant hearing and hair cell preservation in comparison (p < 0.05). CONCLUSION: GV1001 itself did not have any detrimental effects on the inner ear or kidney. In the KM induced ototoxicity model, concomitant administration of GV1001 protected against cochlear hair cell damage and preserve hearing.

Correlation between olfactory severity ratings based on olfactory function test scores and self-reported severity rating of olfactory loss.

CONCLUSION: Olfactory test scores are significantly correlated with self-rated severity scales. However, the statistical rating based on olfactory tests did not strongly agree with the self-reported severity rating. This suggests that there is a discrepancy between olfactory test results and the severity described by patients themselves. OBJECTIVES: This study aimed to identify the correlation between statistical ratings based on test scores and self-rating of the severity of olfactory loss. METHOD: A total of 1555 subjects were asked to rate olfactory loss severity by one of five scales. Olfactory tests consist of the butanol threshold test (BTT) and cross-cultural smell identification test (CCSIT). RESULTS: There were significant correlations between BTT scores and self-rated severity scales (r = 0.619, p < 0.001) and between CCSIT scores and self-rated severity scales (r = 0.597, p < 0.001) after adjustment for age, sex, and medical conditions. Using discriminant analysis for both BTT and CCSIT, scores 0-4 could be statistically rated as anosmia, scores 5 and 6 as severe hyposmia, scores 7 and 8 as moderate hyposmia, and scores 9-12 as normosmia (Wilks's lambda = 0.605, p < 0.001 for BTT and Wilks's lambda = 0.597, p < 0.001 for CCSIT).

Is There Any Age Cutoff to Treat Elderly Patients with Head and Neck Cancer? Comparing with Septuagenarians and Octogenarians.

With the increase in life expectancy, age is no longer considered as a limitation for treatment. Nevertheless, the treatment of elderly patients with head and neck cancer (HNC) remains controversial. Here, we aimed to review our experience with the treatment for elderly patients, while particularly focusing on the differences among older old patients (septuagenarians vs. octogenarians). We retrospectively reviewed the records of 260 elderly patients who were assigned to 3 groups according to age: 70 years old ≤ group 1 < 75 years old, 75 years old ≤ group 2 < 80 years old, and group 3 ≥ 80 years old. The patients were assessed for comorbidities using the Adult Comorbidity Evaluation (ACE)-27, and the American Society of Anesthesia (ASA) physical status was also compared. Group 1, 2, and 3, consisted of 97, 102, and 61 patients, respectively. No significant difference in demographic data was noted among the groups. However, group 3 showed more comorbidities than groups 1 and 2. With regard to the initial treatment for HNC, radiation therapy (RT) was more frequently performed in group 3 than in groups 1 and 2. Among 7 patients of non-compliant to treatment in group 3, 6 patients had have performed RT. In group 3, a total of 18 patients underwent surgery, including microvascular free flap reconstruction and no significant difference in complications was observed postoperatively compared with group 1 and 2. Moreover, no significant difference was noted in overall survival between the groups, regardless of the treatment modality chosen. In conclusion, octogenarians with HNC should be more carefully managed than septuagenarians with HNC. Surgical treatment can be considered in octogenarians with HNC, if it can be tolerated.