The Controversial Role of Folic Acid on Diabetic Auditory Neuropathy

PurposeDiabetic auditory neuropathy(DAN) is a common complication of diabetes that seriously affects the quality of life in patients. In this study, we investigate the role of folic acid in the treatment of DAN in an experimental rat model.MethodsThirty-two Sprague-Dawley rats were equally divided into 4 groups: group 1, normal; group 2, diabetic rats; group 3and 4, rats treated with folic acid (40 and 80 mg/kg, respectively). The tools we used in this study to investigate the effect of folic acid on DAN were auditory brain stem response, stereology methodfor estimation ofthe volume and number ofspiral ganglion,volume of stria vascularis, and spiral ligament, and measurement of homocysteine (HCY), malondealdehyde(MDA) and superoxide dismutase.ResultsOur study showed that folic acid treatment was not significantly effective in improving structural and functional disorders in DAN, despite its effect in reducing HCY and MDA as oxidative biomarkers.ConclusionFolic acid is not effective in relieving morphological and functional disorders in DAN.

Auditory Brain Stem Response Predictors of Hearing Outcomes after Middle Fossa Resection of Vestibular Schwannomas

Objectives To analyze the relationship between preoperative and intraoperative auditory brain stem response (ABR) characteristics and hearing outcomes in patients with vestibular schwannomas (VS) undergoing hearing preservation (HP) surgery via a middle cranial fossa (MCF) approach. Design Prospective study. Setting Academic tertiary skull base referral center. Methods Pre- and postoperative pure-tone average (PTA) and word recognition score (WRS) were examined. Intraoperative ABR wave III latency, wave V latency, and amplitude were recorded. HP was defined as postoperative WRS ≥50%. Participants Adult patients with VS and WRS ≥50% who underwent MCF tumor resection between November 2017 and September 2019. Main Outcome Measures Postoperative hearing outcomes. Results Sixty patients were included. Mean tumor size was 9.2 mm (range, 3–17). HP rates were 56.7% for the cohort and 69.7% for tumors <10 mm. A complete loss of wave V was associated with an 82.9% increase in postoperative PTA (p < 0.001) and 97.2% decrease in WRS (p < 0.001), whereas a diminished wave V was correlated with 62.7% increase in PTA (p < 0.001) and 55.7% decrease in WRS (p = 0.006). A diminished or absent wave V, but not increased wave III/V latency or decreased wave V amplitude, was correlated with a decline in postoperative hearing class (r = 0.735, p < 0.001). Receiver-operating characteristic analysis demonstrated that a stable wave V has the highest accuracy in predicting HP (sensitivity of 82.6%, specificity of 84.8%). Conclusion Of the examined preoperative and intraoperative ABR characteristics, a stable wave V intraoperatively was the strongest predictor of HP after MCF resection of VS. Level of Evidence Level III.

Can auditory brain stem response accurately reflect the cochlear function?

Auditory brain stem response (ABR) is more commonly used to evaluate cochlear lesions than cochlear compound action potential (CAP). In a noise-induced cochlear damage model, we found that the reduced CAP and enhanced ABR caused the threshold difference. In a unilateral cochlear destruction model, a shadow curve of the ABR from the contralateral healthy ear masked the hearing loss in the destroyed ear.

Mechanisms of hearing loss and cell death in the cochlea of connexin mutant mice

Mutations in connexin 30 (Cx30) are known to cause severe congenital hearing impairment; however, the mechanism by which Cx30 mediates homeostasis of endocochlear gap junctions is unclear. We used a gene deletion mouse model to explore the mechanisms of Cx30 in preventing hearing loss. Our results suggest that despite severe loss of the auditory brain-stem response and endocochlear potential at postnatal day 18, Cx30−/− mice only show sporadic loss of the outer hair cells. This inconsistency in the time course and severity of hearing and hair cell losses in Cx30−/− mice might be explained, in part, by an increase in reactive oxygen species generation beginning at postnatal day 10. The expression of oxidative stress genes was increased in Cx30−/− mice in the stria vascularis, spiral ligament, and organ of Corti. Furthermore, Cx30 deficiency caused mitochondrial dysfunction at postnatal day 18, as assessed by decreased ATP levels and decreased expression of mitochondrial complex I proteins, especially in the stria vascularis. Proteomic analysis further identified 444 proteins that were dysregulated in Cx30−/− mice, including several that are involved in mitochondria electron transport, ATP synthesis, or ion transport. Additionally, proapoptotic proteins, including Bax, Bad, and caspase-3, were upregulated at postnatal day 18, providing a molecular basis to explain the loss of hearing that occurs before hair cell loss. Therefore, our results are consistent with an environment of oxidative stress and mitochondrial damage in the cochlea of Cx30−/− mice that is coincident with hearing loss but precedes hair cell loss.

Evaluation of a Model of Long-Term Middle Ear Catheterization for Repeat Infusion Administration and Cochlear Hair Cell Injury in Guinea Pigs

Middle ear administration has numerous applications, including antibiotherapy and gene therapy, and is increasingly used to target the auditory and vestibular systems. In animal studies, investigating repeated exposure that mimics clinical dosing regimens has remained a challenge due to the lack of suitable models. Intratympanic injections are not suitable for long-term studies due to the increased risk related to tympanic membrane rupture or scarring and repeat anesthesia events. Surgical models of middle ear catheterization previously used have not been reliable for longer than 4 weeks, resulted in elevated stress levels, and have been associated with significant changes related to the surgery and/or the presence of the catheter such as local trauma and inflammatory and degenerative processes. These complications cause decreased hearing/deafness and greatly diminish the value and accuracy of ototoxicity studies. We describe here a procedure that permits repeat dosing into the middle ear of guinea pigs and can be used to produce a model of aminoglycoside-induced hair cell injury. The innocuity of the procedures and the efficacy of the ototoxicity model were confirmed using auditory brain stem response assessment, histopathological evaluation, and cytocochleograms. Procedure-related changes were limited to minimal inflammation in the middle ear.

Auditory Brainstem Evoked Response Patterns in the Neonatal Intensive Care Unit

Objective Delayed maturation of auditory brainstem pathway in neonates admitted to the neonatal intensive care unit (NICU) may lead to misdiagnosis of children with normal peripheral hearing and inappropriate use of amplification devices. The aim of this study is to determine the pattern of auditory brain stem response in neonates admitted to the NICU for proper hearing assessment in this high-risk population. Study Design This prospective study was conducted on 1,469 infants who were admitted to the NICU, of which 1,423 had one or more risk factors for permanent congenital hearing loss and were screened with automated auditory brain stem response (AABR). A total of 60 infants were referred for diagnostic ABR analysis after failure on AABR screening. The control group comprised 60 well-baby nursery neonates with no risk factors for PCHL. Results Mean values of absolute latencies of waves III and V; interpeak latencies I–III, III–V, and I–V; amplitude of waves I, and V; and I/V amplitude ratio at 90 dBnHL measured for the right and left ears at 1 and 3 months of age show significant difference in NICU neonates compared with controls (p < 0.05). All the diagnostic ABR measurements significantly improved at the age of 3 months (p < 0.001) except wave I absolute latency of both groups (p > 0.05). Significant correlations were found between ABR readings at the age of 1 and 3 months and the gestational age of the NICU neonates (p < 0.05). Conclusion Diagnostic ABR findings in NICU neonates suggested delayed maturation of the auditory brainstem pathway with a great impact of gestational age on this maturation. Auditory maturational changes were observed at 3 months of age of patient and control groups.

Within-Subject Analysis of Auditory Brain Stem Responses in Adults With Unilateral Tinnitus

Tinnitus affects about 10% of population worldwide. Most patients present with some degrees of hearing impairment, while others remain normal. The aim of this study was to analyze the latency and amplitude of auditory brain stem response (ABR) waveforms in patients with unilateral tinnitus. The tinnitus ears and non-tinnitus ears were compared for each patient. Sixty-seven patients with single-sided tinnitus were enrolled, including 26 male and 41 female patients with a mean age of 54.4 (age ranged from 22 to 79). Eighteen patients had bilateral normal hearing, while 49 patients had some degree of sensorineural hearing. The ABR waveforms were retrospectively analyzed in terms of waves I, III, and V absolute latency, as well as waves I-III, waves II-V, and waves I-V latency intervals, amplitude, and amplitude ratio (III/I, V/I). Statistical analyses were performed within patients. There was no significant ABR difference between the tinnitus and non-tinnitus ears with regard to all the wave latencies and amplitudes in our patients (all P values >0.1). Our result that ABR changes were not found between tinnitus and non-tinnitus ears implies that tinnitus does not simply originate from the defect of the peripheral auditory system. It conforms to the contemporary theory that a higher level of the brain is involved in the generation of tinnitus.

Audiological manifestations in patients of upper airway allergy

<p class="abstract"><strong>Background:</strong> The pathophysiology of involvement of inner ear in patients of upper airway allergy is poorly understood. The endolymphatic sac may be the likely seat of involvement in these patients as it can process antigens and produce its own local immune response. The aim of study was to assess the audiological profile of these patients.</p><p class="abstract"><strong>Methods:</strong> 53 patients of upper airway allergy (33 females and 20 males with mean age 25.77 years) and 20 control subjects (9 females and 11 males with mean age of 35.65 years) underwent haematological and audiological assessment. </p><p class="abstract"><strong>Results:</strong> The study group had sensorineural hearing loss at 4000 and 8000 Hz frequencies. Abnormal distortion product otoacoustic emissions (DPOAEs) were noted in the study group as compared with the controls. On auditory brain stem response testing, no statistically significant difference was noted in the absolute latencies of waves I, III and V between study and control groups. Also no statistically significant difference was noted in the wave I-III and wave I-V inter peak latencies between the two groups.</p><p class="abstract"><strong>Conclusions:</strong> We found higher prevalence of high frequency sensorineural hearing loss and abnormalities of DPOAEs in patients having upper airway allergy. The likely seat of damage appears to be the inner ear as evidenced by abnormalities of DPOAEs. However the exact pathophysiology of inner ear damage in patients of upper airway allergy is poorly understood and needs further research.</p>