Auditory-nerve responses in mice with noise-induced cochlear synaptopathy.

Cochlear synaptopathy is the noise-induced or age-related loss of ribbon synapses between inner hair cells (IHCs) and auditory-nerve fibers (ANFs), first reported in CBA/CaJ mice. Recordings from single ANFs in anesthetized, noise-exposed guinea pigs suggested that neurons with low spontaneous rates (SRs) and high thresholds are more vulnerable than low-threshold, high-SR fibers. However, there is extensive postexposure regeneration of ANFs in guinea pigs but not in mice. Here, we exposed CBA/CaJ mice to octave-band noise and recorded sound-evoked and spontaneous activity from single ANFs at least 2 wk later. Confocal analysis of cochleae immunostained for pre- and postsynaptic markers confirmed the expected loss of 40%-50% of ANF synapses in the basal half of the cochlea; however, our data were not consistent with a selective loss of low-SR fibers. Rather they suggested a loss of both SR groups in synaptopathic regions. Single-fiber thresholds and frequency tuning recovered to pre-exposure levels; however, response to tone bursts showed increased peak and steady-state firing rates, as well as decreased jitter in first-spike latencies. This apparent gain-of-function increased the robustness of tone-burst responses in the presence of continuous masking noise. This study suggests that the nature of noise-induced synaptic damage varies between different species and that, in mouse, the noise-induced hyperexcitability seen in central auditory circuits is also observed at the level of the auditory nerve.NEW & NOTEWORTHY Noise-induced damage to synapses between inner hair cells and auditory-nerve fibers (ANFs) can occur without permanent hair cell damage, resulting in pathophysiology that "hides" behind normal thresholds. Prior single-fiber neurophysiology in guinea pig suggested that noise selectively targets high-threshold ANFs. Here, we show that the lingering pathophysiology differs in mouse, with both ANF groups affected and a paradoxical gain-of-function in surviving low-threshold fibers, including increased onset rate, decreased onset jitter, and reduced maskability.

CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects.

BACKGROUND: Primary hereditary microcephaly (MCPH) comprises a large group of autosomal recessive disorders mainly affecting cortical development and resulting in a congenital impairment of brain growth. Despite the identification of >25 causal genes so far, it remains a challenge to distinguish between different MCPH forms at the clinical level. METHODS: 7 patients with newly identified mutations in CDK5RAP2 (MCPH3) were investigated by performing prospective, extensive and systematic clinical, MRI, psychomotor, neurosensory and cognitive examinations under similar conditions. RESULTS: All patients displayed neurosensory defects in addition to microcephaly. Small cochlea with incomplete partition type II was found in all cases and was associated with progressive deafness in 4 of them. Furthermore, the CDK5RAP2 protein was specifically identified in the developing cochlea from human fetal tissues. Microphthalmia was also present in all patients along with retinal pigmentation changes and lipofuscin deposits. Finally, hypothalamic anomalies consisting of interhypothalamic adhesions, a congenital midline defect usually associated with holoprosencephaly, was detected in 5 cases. CONCLUSION: This is the first report indicating that CDK5RAP2 not only governs brain size but also plays a role in ocular and cochlear development and is necessary for hypothalamic nuclear separation at the midline. Our data indicate that CDK5RAP2 should be considered as a potential gene associated with deafness and forme fruste of holoprosencephaly. These children should be given neurosensory follow-up to prevent additional comorbidities and allow them reaching their full educational potential. TRIAL REGISTRATION NUMBER: NCT01565005.

Osmotic stabilization prevents cochlear synaptopathy after blast trauma.

Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.

Umbilical Cord Mesenchymal Stromal Cell-Derived Exosomes Rescue the Loss of Outer Hair Cells and Repair Cochlear Damage in Cisplatin-Injected Mice.

Umbilical cord-derived mesenchymal stromal cells (UCMSCs) have potential applications in regenerative medicine. UCMSCs have been demonstrated to repair tissue damage in many inflammatory and degenerative diseases. We have previously shown that UCMSC exosomes reduce nerve injury-induced pain in rats. In this study, we characterized UCMSC exosomes using RNA sequencing and proteomic analyses and investigated their protective effects on cisplatin-induced hearing loss in mice. Two independent experiments were designed to investigate the protective effects on cisplatin-induced hearing loss in mice: (i) chronic intraperitoneal cisplatin administration (4 mg/kg) once per day for 5 consecutive days and intraperitoneal UCMSC exosome (1.2 µg/µL) injection at the same time point; and (ii) UCMSC exosome (1.2 µg/µL) injection through a round window niche 3 days after chronic cisplatin administration. Our data suggest that UCMSC exosomes exert protective effects in vivo. The post-traumatic administration of UCMSC exosomes significantly improved hearing loss and rescued the loss of cochlear hair cells in mice receiving chronic cisplatin injection. Neuropathological gene panel analyses further revealed the UCMSC exosomes treatment led to beneficial changes in the expression levels of many genes in the cochlear tissues of cisplatin-injected mice. In conclusion, UCMSC exosomes exerted protective effects in treating ototoxicity-induced hearing loss by promoting tissue remodeling and repair.

Embryology, Malformations, and Rare Diseases of the Cochlea. / Embryologie, Fehlbildungen und seltene Erkrankungen der Cochlea.

Despite the low overall prevalence of individual rare diseases, cochlear dysfunction leading to hearing loss represents a symptom in a large proportion. The aim of this work was to provide a clear overview of rare cochlear diseases, taking into account the embryonic development of the cochlea and the systematic presentation of the different disorders. Although rapid biotechnological and bioinformatic advances may facilitate the diagnosis of a rare disease, an interdisciplinary exchange is often required to raise the suspicion of a rare disease. It is important to recognize that the phenotype of rare inner ear diseases can vary greatly not only in non-syndromic but also in syndromic hearing disorders. Finally, it becomes clear that the phenotype of the individual rare diseases cannot be determined exclusively by classical genetics even in monogenetic disorders.

Association between speech perception in noise and electrophysiological measures: an exploratory study of possible techniques to evaluate cochlear synaptopathy in humans.

Objective: The primary aim of this study was to investigate whether scores for a speech-in-noise test were associated with the results of two electrophysiological techniques mainly targeting low spontaneous rate, high-threshold auditory fibres.Design: Cross-sectional study. Participants were evaluated with the hearing-in-noise test (HINT), along with the Auditory Brainstem Response (ABR) with and without ipsilateral noise. The wave V/I amplitude ratio for the ABR without ipsilateral noise and ABR wave V latency shift in the presence of ipsilateral noise were obtained.Study sample: Twenty adults aged between 20 and 34 years (10 females) who did not report occupational exposure to noise were selected. All participants presented with normal hearing thresholds (0.250-8 kHz) and the presence of distortion product otoacoustic emissions, bilaterally.Results: A significant association between the wave V/I amplitude ratio for the left ear and the HINT scores for the left ear was found.Conclusions: Based on the results of this study, in normal-hearing listeners, the wave V/I ratio is associated with speech-in-noise performance, specifically in the left ear. This non-invasive procedure has the potential to be used in clinical populations who present with speech-in-noise difficulties despite having normal audiograms.

A long-term follow-up study on otoacoustic emissions testing in paediatric patients with severe malaria in Gabon.

BACKGROUND: In a previous study, severe and cerebral malaria have been connected with acute cochlear malfunction in children, demonstrated by a decrease of transitory evoked otoacoustic emissions (TEOAEs) reproducibility. This study aims to determine whether cochlear malfunction persists for 4 years after recovery from severe malaria in a subset of the previous study's collective. Follow-up TEOAEs were performed on site (CERMEL, Hôpital Albert Schweitzer, Lambaréné, Gabon) or at the participants' homes; 33 out of 90 participants included in the initial investigation by Schmutzhard et al. could be retrieved and were re-examined, 31/33 could be included. Of the 57 missing participants, 51 could not be contacted, 1 had moved away, 4 refused to cooperate, and 1 had died. METHODS: As in the initial investigation, participants of this prospective follow-up study were subjected to TEOAE examination on both ears separately. A wave correlation rate of > 60% on both ears was considered a "pass"; if one ear failed to pass, the examination was considered a "fail". The results were compared to the primary control group. Additionally, a questionnaire has been applied focusing on subsequent malaria infections between the primary inclusion and follow-up and subjective impairment of hearing and/or understanding. RESULTS: The cohort's mean age was 9 years, 14 children were female, 18 male. 31 had been originally admitted with severe, one with cerebral malaria. 83.8% of participants (n = 26) presented with a TEOAE correlation rate of > 60% on both ears (the cut-off for good cochlear function); in the control group, 92.2% (n = 83) had passed TEOAE examination on both ears. Recurrent severe malaria was associated with a worse TEOAE correlation rate. Age at infection and gender had no influence on the outcome. CONCLUSIONS: Cochlear malfunction seems to be persistent after 4 years in more than 16% of children hospitalized for malaria. In a healthy control group, this proportion was 7.8%. Yet, the severity of the initial TEOAE-decrease did not predict a worse outcome.

Cochlear implantation in patients with ossified cochleas.

PURPOSE: The timing of CI for postmeningitic deafness is controversial and differential outcomes have been reported. To review and share our surgical and auditory outcomes. MATERIALS AND METHODS: 17 patients with ossified cochleas who received CI were enrolled. Clinical data including the cause of cochlear ossification, preoperative examination, onset of deafness, age at implantation, surgical findings, and relevant auditory outcomes was analysed. RESULTS: Cochlear ossification was observed in 53% of patients with HRCT, whereas the corresponding value for MRI was 59%. Patients in both stage I and II received complete insertion of the electrode array, however, stage III patients only received partial insertion. 1 patient in stage II received bilateral CI. Hearing tests showed increased average hearing threshold for stage III patients than those in stage I and II (P < 0.05). CAP scores were much lower for stage III patients than those in stage I and II (P < 0.05). Postlingual deafness patients showed higher SIR scores than prelingual deafness children (P < 0.05). CONCLUSIONS: HRCT and MRI have comparable value in predicting the occurrence of ossification in cochleas. We recommend fast surgical intervention in the patients with bilateral profound postmeningitic deafness. If possible, bilateral cochlear implantation is recommended.

Is there a relation between sudden sensorineural hearing loss and white matter lesions?

PURPOSE: Sudden sensorineural hearing loss (SSNHL) has similarities to conditions with vascular etiologies such as myocardial infarction and cerebral stroke. Thus, it could be considered as an early sign of a vascular disease and not only a specific local condition. Chronic hypoperfusion in the brain districts leads to a chronic ischemic damage, called cerebral small vessel disease (CSVD), detectable with brain magnetic resonance imaging (MRI). METHODS: The authors used CSVD to establish the presence of vascular risk factors in individuals with SSNHL and used the Fazekas score scale to classify them. RESULTS: Our study showed that individuals with SSNHL aged between 48 and 60 years have 26% more probability to have a Fazekas score higher than 1 compared to the general population. Individuals younger than 28 years showed a statistically significant negative correlation to have a Fazekas score higher than 0. The higher is the Fazekas score, the less is the probability of hearing recovery. The medium hearing-recovery probability is 46%. This decreases by 16% for every increase of score in the Fazekas scale. In the present study, the recovery probability decreased from 80% in individuals younger than 48 years with a score of 0 to 14% in individuals with a Fazekas scores of 3 and 4. CONCLUSIONS: The authors assessed a higher prevalence of CSVD compared to the general population in patients aged between 48 and 60 years with SSNHL. Moreover, they assessed that the presence of CSVD is related to a decreased probability of recovery, as it has already been demonstrated for stroke.

Purinergic Signaling and Cochlear Injury-Targeting the Immune System?

Hearing impairment is the most common sensory deficit, affecting more than 400 million people worldwide. Sensorineural hearing losses currently lack any specific or efficient pharmacotherapy largely due to the insufficient knowledge of the pathomechanism. Purinergic signaling plays a substantial role in cochlear (patho)physiology. P2 (ionotropic P2X and the metabotropic P2Y) as well as adenosine receptors expressed on cochlear sensory and non-sensory cells are involved mostly in protective mechanisms of the cochlea. They are implicated in the sensitivity adjustment of the receptor cells by a K+ shunt and can attenuate the cochlear amplification by modifying cochlear micromechanics. Cochlear blood flow is also regulated by purines. Here, we propose to comprehend this field with the purine-immune interactions in the cochlea. The role of harmful immune mechanisms in sensorineural hearing losses has been emerging in the horizon of cochlear pathologies. In addition to decreasing hearing sensitivity and increasing cochlear blood supply, influencing the immune system can be the additional avenue for pharmacological targeting of purinergic signaling in the cochlea. Elucidating this complexity of purinergic effects on cochlear functions is necessary and it can result in development of new therapeutic approaches in hearing disabilities, especially in the noise-induced ones.

Hidden hearing deficits in military service members with persistent post concussive symptoms.

INTRODUCTION: Individuals with persistent symptoms after mild traumatic brain injury (mTBI) often have auditory complaints. In this study, we used the auditory brainstem response (ABR) to determine whether cochlear synaptopathy could explain auditory symptoms. METHODS: 69 adult military service members with mTBI and 25 adults without brain injury (NCT01611194 and NCT01925963) completed pure-tone audiometry, ABR, and central auditory processing tests. All participants were male, ages 21-50. RESULTS: 37/69 mTBI participants had measurable hearing loss, while another 20%-30% had hearing complaints or tinnitus. While mTBI participants with measurable hearing loss had reduced wave I and III amplitude and decreased III-V interpeak latency, those with no measurable hearing loss did not significantly differ from controls on any ABR parameter. Those with measurable hearing loss were also more likely to have abnormal central auditory processing. mTBI participants with no measurable hearing loss but who reported hearing concerns had some ABR findings (III-V interpeak latency, I and V amplitudes, V/I amplitude ratio) more like the measurable hearing loss mTBI group than normative controls. CONCLUSION: Cochlear synaptopathy may have contributed to some of the auditory impairment in service members with mTBI with measurable hearing loss. However, these results are likely confounded by cochlear hair cell damage.

Severe obstructive sleep apnea is associated with cochlear function impairment.

PURPOSE: The purpose of this study is to investigate the association between obstructive sleep apnea (OSA) with middle ear acoustic transference and cochlear function. METHODS: Male individuals with and without mild, moderate, and severe OSA according to standard criteria of full polysomnography and no co-morbidities were studied. Subjects with BMI ≥40 kg/m2, present or past treatment for OSA, with heart failure, diabetes, hypertension, dyslipidemia, stroke, use of chronic medications, and previous history of risk for hearing loss were excluded. All subjects were submitted to full polysomnography, evaluation of wideband acoustic immittance by energy of absorbance (EA), and distortion product otoacoustic emissions (DPOAE). RESULTS: We studied 38 subjects (age 35.8 ± 7.2 years, BMI 28.8 ± 3.8 kg/m2) divided into no OSA (n = 10, age 33.6 ± 6.4 years, BMI 26.9 ± 4.1 kg/m2), mild (n = 11, age 32.8 ± 2.9 years, BMI 28.5 ± 3.5 kg/m2), moderate (n = 8, age 34.1 ± 6.8 years, BMI 29.6 ± 3.3 kg/m2), and severe OSA (n = 9, age 41.2 ± 9.2 years, BMI 30.5 ± 3.8 kg/m2). EA was similar between groups. In contrast, patients with severe OSA presented significantly lower DPOAE amplitudes when compared to the control, mild, and moderate OSA groups (p ≤ 0.03, for all comparisons). CONCLUSIONS: Acoustic transference function of middle ear is similar in adults with and without OSA. Severe OSA is independently associated with cochlear function impairment in patients with no significant co-morbidities.

Utilizing prestin as a predictive marker for the early detection of outer hair cell damage.

PURPOSE: To evaluate prestin as a biomarker for the identification of early ototoxicity. MATERIALS AND METHODS: Rats (n = 47) were randomly assigned to five groups: low-dose (LAG) or high-dose (HAG) amikacin (200 and 600 mg/kg/day, respectively, for 10 days), low-dose (LCIS)or high-dose (HCIS) cisplatin (single doses of 5 and 15 mg/kg, respectively, for 3 days), and control (n = 8). At the end of the experiment, measurement of distortion product-evoked otoacoustic emissions (DPOAE) were performed to evaluate hearing, then blood samples and both ear tissues were collected under anesthesia. Prestin levels were determined by ELISA. Cochlear damage was evaluated histologically using a 4-point scoring system. RESULTS: The mean serum prestin levels were 377.0 ±â€¯135.3, 411.3 ±â€¯73.1, 512.6 ±â€¯106.0, 455.0 ±â€¯74.2 and 555.3 ±â€¯47.9 pg/ml for control, LCIS, HCIS, LAG and HAG groups, respectively. There was significant difference between prestin levels of Control-LCIS-HCIS groups (p = 0.031) and prestin levels of Control-LAG-HAG groups (p = 0.003). There were also significant differences in prestin levels between the low- and high-dose cisplatin and amikacin groups (p = 0.028 and p = 0.011, respectively). Each group had significantly lower DPOAE results at 4, 6 and 8 kHz than control groups (p < 0.001). The LAG, HAG, LCIS and HCIS groups had significantly higher cochlear damage scores than the control group (p < 0.05). CONCLUSIONS: Higher doses of cisplatin and amikacin were associated with the greatest increases in serum prestin level and cochlear damage score. The results of this study suggest that prestin is a promising early indicator of cochlear damage.

Auditory and audio-visual processing in patients with cochlear, auditory brainstem, and auditory midbrain implants: An EEG study.

There is substantial variability in speech recognition ability across patients with cochlear implants (CIs), auditory brainstem implants (ABIs), and auditory midbrain implants (AMIs). To better understand how this variability is related to central processing differences, the current electroencephalography (EEG) study compared hearing abilities and auditory-cortex activation in patients with electrical stimulation at different sites of the auditory pathway. Three different groups of patients with auditory implants (Hannover Medical School; ABI: n = 6, CI: n = 6; AMI: n = 2) performed a speeded response task and a speech recognition test with auditory, visual, and audio-visual stimuli. Behavioral performance and cortical processing of auditory and audio-visual stimuli were compared between groups. ABI and AMI patients showed prolonged response times on auditory and audio-visual stimuli compared with NH listeners and CI patients. This was confirmed by prolonged N1 latencies and reduced N1 amplitudes in ABI and AMI patients. However, patients with central auditory implants showed a remarkable gain in performance when visual and auditory input was combined, in both speech and non-speech conditions, which was reflected by a strong visual modulation of auditory-cortex activation in these individuals. In sum, the results suggest that the behavioral improvement for audio-visual conditions in central auditory implant patients is based on enhanced audio-visual interactions in the auditory cortex. Their findings may provide important implications for the optimization of electrical stimulation and rehabilitation strategies in patients with central auditory prostheses. Hum Brain Mapp 38:2206-2225, 2017. © 2017 Wiley Periodicals, Inc.

IL-10/HMOX1 signaling modulates cochlear inflammation via negative regulation of MCP-1/CCL2 expression in cochlear fibrocytes.

Cochlear inflammatory diseases, such as tympanogenic labyrinthitis, are associated with acquired sensorineural hearing loss. Although otitis media is extremely frequent in children, tympanogenic labyrinthitis is not commonly observed, which suggests the existence of a potent anti-inflammatory mechanism modulating cochlear inflammation. In this study, we aimed to determine the molecular mechanism involved in cochlear protection from inflammation-mediated tissue damage, focusing on IL-10 and hemoxygenase-1 (HMOX1) signaling. We demonstrated that IL-10Rs are expressed in the cochlear lateral wall of mice and rats, particularly in the spiral ligament fibrocytes (SLFs). The rat SLF cell line was found to inhibit nontypeable Haemophilus influenzae (NTHi)-induced upregulation of monocyte chemotactic protein-1 (MCP-1; CCL2) in response to IL-10. This inhibition was suppressed by silencing IL-10R1 and was mimicked by cobalt Protoporphyrin IX and CO-releasing molecule-2. In addition, IL-10 appeared to suppress monocyte recruitment through reduction of NTHi-induced rat SLF cell line-derived chemoattractants. Silencing of HMOX1 was found to attenuate the inhibitory effect of IL-10 on NTHi-induced MCP-1/CCL2 upregulation. Chromatin immunoprecipitation assays showed that IL-10 inhibits NTHi-induced binding of p65 NF-κB to the distal motif in the promoter region of MCP-1/CCL2, resulting in suppression of NTHi-induced NF-κB activation. Furthermore, IL-10 deficiency appeared to significantly affect cochlear inflammation induced by intratympanic injections of NTHi. Taken together, our results suggest that IL-10/HMOX1 signaling is involved in modulation of cochlear inflammation through inhibition of MCP-1/CCL2 regulation in SLFs, implying a therapeutic potential for a CO-based approach for inflammation-associated cochlear diseases.

Ozone Prevents Cochlear Damage From Ischemia-Reperfusion Injury in Guinea Pigs.

The cochlea is an end organ, which is metabolically dependent on a nutrient and oxygen supply to maintain its normal physiological function. Cochlear ischemia and reperfusion (IR) injury is considered one of the most important causes of human idiopathic sudden sensorineural hearing loss. The aim of the present study was to study the efficacy of ozone therapy against cochlear damage caused by IR injury and to investigate the potential clinical use of this treatment for sudden deafness. Twenty-eight guinea pigs were randomized into four groups. The sham group (S) (n = 7) was administered physiological saline intraperitoneally (i.p.) for 7 days. The ozone group (O) (n = 7) was administered 1 mg/kg of ozone i.p. for 7 days. In the IR + O group (n = 7), 1 mg/kg of ozone was administered i.p. for 7 days before IR injury. On the eighth day, the IR + O group was subjected to cochlear ischemia for 15 min by occluding the bilateral vertebral artery and vein with a nontraumatic clamp and then reperfusion for 2 h. The IR group was subjected to cochlear IR injury. After the IR procedure, the guinea pigs were sacrificed on the same day. In a general histological evaluation, cochlear and spiral ganglionic tissues were examined with a light microscope, and apoptotic cells were counted by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining. The apoptotic index (AI) was then calculated. Blood samples were sent for analyses of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase, malondialdehyde (MDA), the total oxidant score (TOS), and total antioxidant capacity (TAC). Data were evaluated statistically using the Kruskal-Wallis test. The AI was highest in the IR group. The AI of the IR + O group was lower than that of the IR group. The biochemical antioxidant parameters SOD and GSH-Px and the TAC values were highest in the O group and lowest in the IR group. The MDA level and TOS were highest in the IR group and lowest in the O group. Controlled ozone administration stimulated endogenous antioxidant defense systems, thereby helping the body to combat IR injury. Although this study revealed a statistically significant decrease in cochlear IR damage following ozone therapy, further studies will be necessary to explain the protective mechanisms of ozone therapy in cochlear IR injury.

A systematic review of stimulus parameters for eliciting distortion product otoacoustic emissions from adult humans.

OBJECTIVE: The objective of this study is to review the scientific literature to determine if a set of stimulus parameters can be described to elicit distortion product otoacoustic emissions (DPOAEs) of higher absolute level and/or greater reliability in healthy adult humans and higher sensitivity and specificity in adults with cochlear lesions. DESIGN: Systematic review. STUDY SAMPLE: Searches of four electronic databases yielded 47 studies that had used different parameters to elicit DPOAEs from within or between-groups of adult humans. RESULTS: The wide range of stimulus parameters used in the reviewed studies saw a wide range of reported values for DPOAE level, reliability, and sensitivity and specificity to cochlear lesions. CONCLUSION: The most commonly used stimulus parameters for eliciting DPOAEs from adult humans have included frequency ratios for the two primary tones (f2/f1) of between 1.04 and 1.4 and levels (L1/L2) of 65/55 dB SPL. The most commonly used parameters for eliciting DPOAEs of higher level in healthy adults appear to be linked to f2/f1 values between 1.20 and 1.22 and L1/L2 levels of 75/75 dB SPL. The stimulus parameters for eliciting DPOAEs of greater reliability in healthy adults and higher sensitivity and specificity in adults with cochlear lesions have yet to be clearly determined.

[The fistula of the round window of the cochlea]. / Fistula okna ulitki.

This article presents the data on the frequency, diagnostics, and variants of the surgical treatment of the fistula of the round window of the cochlea. A case of this pathology is reported with the special emphasis placed on the approaches to the diagnostics and surgical management of this condition.

[The results of bilateral cochlear implantation in the children who survived meningitis]. / Rezul'taty bilateral'noi kokhlearnoi implantatsii u detei, perenesshikh meningit.

The objective of the present study was the prospective analysis of the results of bilateral cochlear implantation (CI) in the children presenting with bilateral ossification of the cochlea after they had survived meningitis. A total of 15 patients underwent the surgical intervention. In those exhibiting bilateral ossification of the basal cochlear helix over the 5 mm segment (up to first bend of the cochlear turn) and partial ossification of the second helix (in 6 children), the affected portions were removed with the placement of two choleostomies, the lower one (from the ossified membrane of the cochlear window) and the upper one (toward the second helix). Activation of the speech processors of the CI systems was carried out within 4-6 weeks after surgery. The hearing abilities of the children were evaluated in accordance with the 'Estimation of the auditory perception categories', 'Estimation of the child's apprehension capacity', and 'Analysis of speech intelligibility rating' guidelines. In all the children with ossification over less than 5 mm of the basal cochlear helix, it proved possible to introduce the whole intracochlear electrode grid whereas only half of the electrode array was implanted in the cases of overall ossification of the basal helix. The first results obtained by telemetry and surdopedagogical testing gave evidence of the possibility of identifying various sources of non-verbal and speech stimuli in all the treated children at a small (up to 3 meters) distance.