Enlarged vestibular aqueduct: Audiological and genetical features in children and adolescents.

BACKGROUND: Enlarged Vestibular Aqueduct (EVA) is one of the most common congenital malformations associated with sensorineural or mixed hearing loss. The association between hearing loss and EVA is described in syndromic (i.e. Pendred Syndrome, BOR, Waardenburg) and non-syndromic disorders, as isolate or familiar mutations of the SLC26A4 gene. The audiological phenotype of the EVA syndrome is heterogeneous, the type and entity of hearing loss may vary and vertigo episodes might also be present. OBJECTIVE: The aim of this retrospective study was to describe the clinical and genetic features of a group of adolescent subjects presenting an EVA clinical profile, considering the presence of SLC26A4 gene mutations. METHODS: 14 Caucasian patients were assessed (24 ears in total; 4 patients presented a monolateral EVA), 10 females and 4 males. Their age at the time of diagnosis was between 1 and 6 years (mean age 2.5 years). Subjects were assessed by an ENT microscopy evaluation with a complete audiometric assessment, CT & MRI scans and genetic tests for the evaluation of the pendrin gene mutations (SLC26A4). RESULTS: Considering the presence of SLC26A4 mutations and thyroid function, we could identify three sub-groups of patients: group 1, non syndromic EVA (ns EVA, no SLC26A4 mutation and no thyroid dysfunction); group 2, EVA with DFNB4 (single SLC26A4 gene mutation and no thyroid dysfunction); group 3, EVA with Pendred Syndrome (two pathological mutation of SLC26A4 and thyromegaly with thyroid dysfunction). Patients of group 1 (ns-EVA) showed various degrees of hearing loss from mild (55%) to severe-profound (45%). In groups 2 (DFNB4) and 3 (PDS), the degree of hearing loss is severe to profound in 70-75% of the cases; middle and high frequencies are mainly involved. CONCLUSIONS: The phenotypic expressions associated with the EVA clinical profile are heterogeneous. From the available data, it was not possible to identify a representative audiological profile, in any of the three sub-groups. The data suggest that: (i) a later onset of hearing loss is usually related to EVA, in absence of SLC26A4 gene mutations; and (ii) hearing loss is more severe in patients with SLC26A4 gene mutations (groups 2 and 3 of this study).

Cochlear implant and inflammation reaction: Safety study of a new steroid-eluting electrode.

Dexamethasone is a common anti-inflammatory agent added to cochlear implants to reduce hearing loss due to electrode insertion trauma. We evaluated the safety of eluting silicone rods containing 10% dexamethasone in a Guinea pig model. Animals were implanted with a dexamethasone eluting silicone electrode (DER) or with a non-eluting electrode (NER). The control group only underwent a cochleostomy (CS). Prior to implantation and during the two weeks following implantation, the hearing status of the animals was assessed by means of Compound Action Potentials (CAPs) with an electrode placed near the round window. Two weeks after implantation, the mean click threshold shifts were 1 dB ± 10 dB in the DER group, 10 dB ± 10 dB in the NER group and -4 dB ± 10 dB in the control group. After two weeks the bullae of each animal were extracted to verify the presence of macrophages, the percent of tissue growth in the scala tympani and the tissue sealing around cochleostomy. Silicone electrodes samples were also explanted and examined for bacterial infection. Neither bacterial infection nor enhanced number of macrophages were observed. A limited, but not significant, tissue growth was found in the scala tympani between the experimental and the control group. The data suggest that, in the Guinea pig model, the use of DER is apparently safe as an anti-inflammatory slow-release additive to the cochlear implant.

Idiopathic sudden sensorineural hearing loss: cardiovascular risk factors do not influence hearing threshold recovery.

Previous studies have suggested that risk factors for ischaemic vascular disease, such as cigarette smoking, hypertension and hyperlipidaemia, can also be considered risk factors for the development of idiopathic sudden sensorineural hearing loss (ISSNHL). In this study, we have evaluated the hypothesis that these factors can influence hearing threshold recovery in patients affected by ISSNHL. A total of 141 subjects who suffered an episode of ISSNHL were included. All subjects were assessed with tonal audiometry, auditory brainstem responses and MRI to exclude retrocochlear pathology. Hearing tests were conducted at ISSNHL onset (t = 0) and after 30 days. Patients were divided into three classes according to the presence/absence of one or more cardiovascular risk factors including: history of smoking, total serum cholesterol/triglycerides, history of hypertension and diabetes mellitus. Values of hearing threshold recovery were estimated and comparisons were conducted across the three risk factor classes. 75% of patients affected by ISSNHL showed a threshold recovery. However, the threshold recovery was found to be class-independent (average recovery value of 18 dB HL per classes) and also independent of age and gender. Even if cardiovascular risk factors have been found to be involved in the pathogenesis of ISSNHL, the present study suggests that these factors do not have any significant influence on the threshold recovery in ISSNHL.

Genetics of presbycusis and presbystasis.

Presbycusis and presbystasis represent relevant problems of aging, caused by the increase in life expectancy in developed countries. As such, it is advantageous to better understand the physiopathological mechanisms of these age-related inner ear diseases. The hypothesis that presbycusis and presbystasis have a genetic background was proposed some years ago. Several studies (in humans and animals) are available in the literature, and possible genes involved in the physiopathology of both diseases have been identified. The aim of this paper is to present an overview of the information available in the current medical literature on presbycusis and presbystasis.

Identifying congenital hearing impairment: preliminary results from a comparative study using objective and subjective audiometric protocols.

To compare objective and subjective protocols assessing hearing loss in young children and evaluate frequency-specific hearing impairment through a comparison between auditory steady state responses (ASSR), auditory brainstem responses (ABR), transient otoacoustic emissions and conditioned orientation reflex responses (COR). Thirty-five hearing-impaired children (20 male and 15 female), aged between 14 months and 4 years, participated in the study. Hearing threshold levels and peripheral auditory function were assessed by measurements of ABR, ASSR, otoacoustic emissions and COR. The analysis of the COR and ASSR variables showed significant correlations in the majority of tested frequencies. The data highlight a characteristic of the COR procedure, which is an underestimation of the hearing threshold in comparison to the ASSR estimate. The data show that the COR threshold assessment follows the pattern of the other two established electrophysiological methods (ABR, ASSR). The correlation analyses did not permit evaluation of the precision of these estimates. Considering that the ASSR variables show a better relationship with ABR (higher correlation values) than COR, it might be advantageous to utilize the ASSR to gain frequency-specific information.

A comparison of audiometric and objective methods in hearing screening of school children. A preliminary study.

OBJECTIVE: In newborn hearing screening, one exclusively applies objective hearing testing methods--based on evoked potentials and/or on otoacoustic emissions. However, when testing school children, one can consider both audiometric and electrophysiological methods. The choice of methods is determined by the aims of the program. If one wants to detect conductive hearing losses, impedance audiometry seems to be the method of choice. METHODS: The aim of this study was to compare test performance measures from audiometric and objective methods (OAEs and impedance audiometry), in the hearing screening of school children. Screening protocols were applied on a group of 190 children of about 12 years of age (6th grade of primary school). RESULTS: For a single application of a screening procedure, the best performance was observed in the automated four-tone audiometry, followed by the tympanometry and the TEOAE-based procedures. Screening performance was enhanced using a combination of automated and impedance audiometry. A four-tone audiometry test combined with tympanometry gives a sensitivity of 65%, and the PPV of 46%, which are reasonable values, acceptable for practical use. The use of a TEOAE protocol degrades the overall performance of screening. CONCLUSIONS: Screening of school children is feasible with a combination of automated audiometry and tympanometry with time requirements equal to 3 min per subject.

Optimizing otoacoustic emission protocols for a UNHS program.

OBJECTIVE: To identify the optimal test protocol to screen for hearing problems in newborns, an evaluation of three distortion product otoacoustic emission (DPOAE) protocols was conducted in neonates, from a well-baby nursery (WBN) and from a neonatal intensive care unit (NICU) and compared to the performance in newborns of a more standard protocol based on transient-evoked OAEs (TEOAEs). METHODS: The DPOAE protocols used asymmetrical stimulus intensities (L(1) > L(2)) with a frequency ratio of 1.22, in the following format: (P1), L(1) = 60, L(2) = 50 dB SPL; (P2), L(1) = 65, L(2) = 55 dB SPL, and (P3), L(1) = 75, L(2) = 65 dB SPL. Linear TEOAE responses, evoked by click stimuli of 75 dB peSPL, were used as controls of normal cochlear function. Five frequencies at 1.5, 2.0, 3.0, 4.0 and 5.0 kHz were tested with a common commercially available macro-based software subroutine (Otodynamics Corp, ILO-92). The project evaluated the responses from 1200 WBN infants (average age 48 h) and 350 low-birth-weight NICU infants, all randomly selected. RESULTS: Statistical analyses comparing the signal-to-noise ratios (S/N), at the predefined f(2) frequencies, indicated that the P1 and P2 DPOAE protocols generated similar responses. Significant S/N differences were observed in the P3 to P2 dataset comparisons. DPOAE scoring criteria were estimated from the P3 dataset using a one-sided, distribution-free confidence intervals. The scoring criteria for a 'pass' were estimated as a minimum S/N of 6.0, 7.0 and 6.0 dB at 2.0, 3.0 and 4.0 kHz, respectively. In terms of feasibility, the P3 protocol generated responses in 98% of the WBN and 94.8% of the NICU infants. CONCLUSIONS: All three DPOAE protocols demonstrated shorter time-recording requirements than the standard TEOAE test. The false-positive and false-negative rates for the NICU infants were estimated as 0.0028 and 0.003%, respectively.

Neonatal newborn hearing screening: four years' experience at Ferrara University Hospital (CHEAP project): part 1.

The Child Hearing Early Assessment Programme (CHEAP) regional project, was a combined departmental approach (Audiology, Neonatology) of the University Hospital of Ferrara, aimed at identifying neonatal hearing impairment and defining early intervention strategies. Aims of this project have been: (i) construction of a neonatal screening programme using evoked otoacoustic emission and auditory brainstem responses; (ii) the calculation of a precise estimate of cost-benefits for every child tested; (iii) the development of an information flow instrument (database) for the storage of data and the statistical analysis of the results. The present report refers only to the results of the project related to the otoacoustic emission data from well-babies and intensive care unit residents. In the period January 2000-December 2004, 4269 full-term newborns and 654 Neonatal Intensive Care Unit babies were tested at the Neonatology Department. The cost of the Universal Neonatal Hearing Screening was estimated at Euro 9.20 per child, considering the use of the ILO-292 apparatus, and Euro 8.28 per child in the case of an automatic screener. In this screening model, the initial hardware costs can be re-iterated into budget in a period of two years, if 1000 children per year are tested.

Noise-induced hearing loss: a study on the pharmacological protection in the Sprague Dawley rat with N-acetyl-cysteine.

Noise-induced hearing loss is one of the most common causes of deafness and, at present, there is no treatment for the recovery of the normal hearing threshold after prolonged exposure to loud acoustic stimuli and the generation of acoustic trauma. Prolonged exposure to noise can cause oxidative stress in the cochlea which results in the loss (via apoptotic pathways) of the outer hair cells of the organ of Corti. It has been demonstrated that some antioxidant molecules, for example L-N-acetyl-cysteine, can prevent oxidative stress in the inner ear. Aim of the study was to evaluate whether L-N-acetyl-cysteine, given at various dosages, can preserve the fine structures of the cochlea from the insult of continuous noise. A series of 18 Sprague Dawley male albino rats were exposed to continuous noise (8 kHz octave band noise, 105 dB SPL, 4 hours), and cochlear functionality was evaluated by recordings of transient evoked otoacoustic emissions and distortion products otoacoustic emissions). The group which showed the best protection was that which received a total dosage of 1500 mg/kg of L-N-acetyl-cysteine. These data suggest that while L-Nacetyl-cysteine can partially protect the cochlea from continuous noise, the protection effect is strongly dose-dependent: lower dosages do not fully protect the cochlea and higher dosages can damage the rat systemically (e.g. pulmonary toxicity).

Protection against cisplatin ototoxicity in a Sprague-Dawley rat animal model.

Cisplatin (CDDP) is an anti-neoplastic drug extensively used in cases of head and neck cancer. Cisplatin induces numerous untoward side-effects including ototoxicity. In this study, cisplatin ototoxicity in Sprague-Dawley rat animal model has been evaluated and the oto-protection provided by the systemic administration of the antioxidant drug D-methionine has been tested. A total of 12 Sprague-Dawley rats were used: 8 were treated intra-peritoneally with D-methionine (300 mg/kg) and cisplatin (16 mg/kg, slow 30 min-infusion), 4 only with cisplatin. The hearing threshold of the animals was evaluated by electrophysiological procedures as Otoacoustic Emissions and Auditory Brainstem Responses. The effects of protection were evaluated after 72 hours. The data from the Otoacoustic Emissions (in the 4.0-12 kHz band) and Auditory Brainstem Responses recordings suggested that D-methionine can partially protect from Cisplatin ototoxicity.

TEOAE recording protocols revised: data from adult subjects.

The objective of this study was the experimental re-evaluation of the current clinical transiently evoked otoacoustic emission (TEOAE) protocols, based on linear and non-linear protocol paradigms from a population of 42 adult subjects serving as a normative database. The linear and non-linear TEOAE responses were elicited by clicks with average intensities of 72 and 84 dB p.e. SPL respectively. An initial comparison between non-processed non-linear and linear recordings, at early recording segments from 3.2 to 5.2 ms, showed that the responses had highly similar contours and no statistically significant mean differences. The stimulus-induced artefact in the linear TEOAE responses was suppressed by post-processing the data with a window function (3.8-13.8 ms) and by a high-pass filter at 830 Hz. A repeated-measures model was used to evaluate the differences between post-processed linear and non-linear responses across clinical variables of interest (such as TEOAE response, noise, correlation, and signal-to-noise ratios (SNRs) at 1.0-5.0 kHz). The data indicated that the linear recordings demonstrate significantly lower levels of noise (and thus superior SNRs) and higher values of reproducibility. Normative adult scoring criteria were calculated from free distribution tolerance intervals for the TEOAE correlation and the SNRs at 2.0 and 3.0 kHz.

[Cisplatin and carboplatin-induced ototoxicity in children: clinical aspects and perspectives for prevention]. / Ototossicità da cisplatino e carboplatino in età pediatrica: aspetti clinici e prospettive di prevenzione.

In 70% of the cases of malignant neoplasms in pediatric patients antiblast therapy is used. The administration of platinum compounds, Cisplatin (CDDP) or Carboplatin (CBDCA), often at high cumulative doses, necessarily implies a certain degree of toxicity which normally takes on secondary significance in the healing of the child. Among the side effects, early and delayed ototoxicity is well known and, in the child, take on particular aspects. While not abandoning the treatment of the base pathology, the therapeutic findings, increasingly comforting in terms of long-term survival, require more accurate evaluation and overall control of the quality of life of these young patients. Since initial cochlear damage can be reversible, auditory function must be carefully monitored in order to prevent the lesions from becoming permanent, in particular prior to the onset of speech. For this reason a retrospective study was made of a group of 26 children affected by malignant neoplasms all of whom had undergone a polychemotherapy protocol with the administration of CDDP in 14 cases and CBDCA in 12 cases. All these young patients were monitored with conventional audiometry. The presence of different variables (antiblastic drug administration schedule, course of the disease, general conditions) only permitted evaluation of a single correlation: between auditory function at the end of the treatment (or after a few cycles of therapy) and the overall dose of CDDP or CBDCA administered. In 16 cases (62%) typical bilateral perceptive deafness was detected progressively involving the hyperacute and acute frequencies. The finding of hearing loss was significantly greater in the patients treated with CDDP (86%) vs. those treated with CBDCA (33%). Moreover, analysis of the results showed that, within certain limits, ototoxicity can depend more on individual sensitivity to the drug than to the total dose administered. The results confirm the well-known ototoxicity of platinum compounds, in particular CDDP. As ever improved therapeutic results are achieved in the treatment of malignant neoplasms in pediatric patients, greater attention can be paid to the quality of life of these young patients after the disease has been healed. Careful monitoring of auditory function can be extremely important in the pursuit this objective; indeed, this makes it possible to adjust antiblast drug administration, particularly in the later stages of treatment, customizing the treatment schedule to individual patient sensitivity.

Hearing loss evaluation of Sjögren's syndrome using distortion product otoacoustic emissions.

Sjögren's syndrome (SS) is a cell-mediated immune disorder primarily affecting the exocrine glands and hearing loss may be the first otological manifestation of this autoimmune disease. In order to assess the degree of sensorineural hearing loss in SS, 22 female patients were examined by means of standard audiometric tests (pure-tone audiometry, acoustic reflexes and impedance testing) and using distortion product otoacoustic emissions (DPOAEs). The results indicated that only 36.3% of the patients had mild sensorineural hearing loss. Hearing level and distortion product threshold estimates were found to be significantly correlated. No relationship was found between the duration of the disease and the DPOAE and hearing threshold variables. The data suggest that SS may not directly cause sensorineural hearing loss.

Cisplatin ototoxicity in the Sprague Dawley rat evaluated by distortion product otoacoustic emissions.

The present study has evaluated the use of distortion product otoacoustic emission (DPOAE) responses in the detection of cisplatin-induced ototoxicity in a Sprague Dawley rat animal model. The cisplatin was administered as a 16 mg/kg, dose introduced by a slow 30-min intraperitoneal infusion. Data from three DP-gram protocols, DPOAE input-output responses at 8 kHz, and auditory brainstem responses (ABRs) at 8, 12 and 16 kHz were collected before and 72 h after treatment. The post-treatment ABRs at 16 kHz showed the greatest mean threshold shift of 33.6 dB. The post-treatment DP-gram data showed significant reduction of the signal to noise ratios in the majority of the frequencies tested, across all tested protocols. The data suggest that the most sensitive DPOAE procedure for the early detection of the cisplatin-induced ototoxic damage is the DPOAE I/O protocol. Morphological analyses indicated that the inner hair cells remained intact, while several types of alterations were observed in the arrangement of the stereocilia in the outer hair cells.

Efficient otoacoustic emission protocols employed in a hospital-based neonatal screening program.

Within the context of a hospital-based newborn hearing screening program, we have studied the application of two OAE protocols (TEOAE and DPOAE) on a group of 250 well babies. The main goal of this study was to evaluate the performance of DPOAE protocol in a relatively large population sample. using a preset number of five tested frequencies, in comparison with a default TEOAE screening protocol. The data were collected on the second day of life and during spontaneous sleep. The TEOAE recordings were acquired with linear protocols using click stimuli of 70-75 dB SPL and were used as indicators of normal cochlear function. The cubic distortion product DPOAE responses were evoked by an asymmetrical 75-65 dB SPL protocol, with a frequency ratio of 1.22. Five frequencies (referring to F2) were tested at 1.5, 2.0, 3.0, 4.0 and 5.0 kHz. The data from the DPOAE responses show a similar pass rate (similarity = 0.98) to the linear TEOAE protocol. The data presented suggest that a DPOAE cochlear evaluation, at 5 pre-selected frequencies, has clinical potential.

Correlations between risk factors for hearing impairment and TEOAE screening test outcome in neonates at risk for hearing loss.

The aim of the study was to find the correlation between specific risk factors for hearing impairment as well as between risk factors and TEOAE screening results in neonates at risk for hearing impairment. Seventy-one newborns at risk for hearing impairment have been included in the study. Strong correlations between specific risk factors were found. Investigation of the relationship between specific risk factors and TEOAE signal-to-noise ratio (SNR) showed that in children with genetic risk factors, TORCH (toxoplasmosis, rubella, CMV, herpes virus, others) infections and in those treated with ototoxic drugs, the values of SNRs were significantly lower than in children at risk who did not present those factors. In case of hyperbilirubinaemic children the values of SNR were significantly higher than in the controls. In our opinion these relationships may be partially explained by the positive predictive values of these risk factors, but other intrinsic factors may also be involved.

Comparison of neonatal transient evoked otoacoustic emission responses recorded with linear and QuickScreen protocols.

Linear and QuickScreen (non-linear) transient evoked otoacoustic emission (TEOAE) protocols were compared in terms of standardized clinical parameters in order to define the protocol producing recordings with the highest signal quality. Neonatal responses (520) were obtained from three different screening sites. The linear recordings were evoked by 69 and 75-dB p.e. SPL clicks. All responses were post-windowed by a 3.5- to 12.5-ms window, chosen by time-frequency analysis as the segment representing 97.35 per cent (linear) and 95.6 per cent (quick) of the total cumulative spectral energy. Evidence from hearing loss cases and the high similarity between the profile contours of the QuickScreen and the linear normal recordings have strongly suggested that a linear response evoked by a 75-dB p.e. SPL stimulus and post-processed by a 3.5 to 12.5 window is free of stimulus artefacts. The data indicate that the 75-dB linear protocol produces higher signal to noise ratios at 2.0, 3.0, and 4.0 kHz, higher wave reproducibility, and lower TEOAE noise values than the QuickScreen protocol.

Time-frequency analyses of TEOAE recordings from normals and SNHL patients.

This study evaluated the characteristics of transient evoked otoacoustic emission (TEOAE) time-frequency (TF) representations from normal and hearing-impaired ears. Linear and non-linear TEOAE recordings from normally-hearing subjects (40) and non-linear recordings from patients with sensorineural hearing loss (SNHL) (40) were analysed using the short-time-Fourier-transform spectrogram, the Gabor spectrogram, and the adaptive spectrogram. The TF representations of the TEOAE recordings indicated a considerable dispersion of energy across frequencies and TEOAE time segments >4.0 ms. The linear and non-linear recordings from the normal subjects showed common frequency peaks. The TF representations from the patients with SNHL indicated that the significantly reduced energy in the mid-to-high TEOAE frequencies did not correlate closely with the threshold elevation. As in the recordings from the normal subjects, a high percentage of the TEOAE cumulative energy was found within a short TEOAE segment (4-14 ms).

Optimization of TEOAE recording protocols: a linear protocol derived from parameters of a time-frequency analysis: a pilot study on neonatal subjects.

Linear and non-linear TEOAE protocols were compared in terms of nine parameters in order to define the protocol producing recordings with the highest signal quality (lowest noise and highest signal-to-noise ratio). The pilot project acquired data using ILO-92 apparatus from 220 neonates (397 ears) at the second/third day after birth in three European laboratories. A Gabor spectrogram time-frequency representation of the recordings showed considerable frequency dispersion in TEOAE latencies >4.0 ms. The data, analysed with a Wilcoxon test, indicated that a linear TEOAE protocol: (i) generates recordings of a lower noise and a higher signal-to-noise (S/N) ratio in the 2.0, 3.0, 4.0 kHz TEOAE bands; (ii) the increase in the S/N ratio can result in a decrement of the required number of TEOAE sweeps; (iii) the higher values of S/N can be used in the estimation of more robust pass-fail criteria, minimizing the percentage of false positives and negatives.

[Distortion product otoacoustic emission (DPOAEs) and newborn hearing screening: a feasibility and performance study]. / Otoemissioni Acustiche dei Prodotti di Distorsione (DPOAEs) e screening audiologico neonatale: studio di applicabilità e performance.

In view of the great psychological effect deafness has on one's social life, the scientific community has long sought the best way to define the hearing function. The development of new technologies in this field has set "early intervention" as the primary target for screening. For this reason, within the contest of a program of audiological newborn hearing screening, the Authors have used data from a selected group of 1250 newborns to (a) compare the clinical feasibility and performance of three different DPOAE protocols and (b) establish the scoring criteria defining "pass" or "fail" responses. All subjects participating in this study were randomly selected and their normal hearing was verified by linear TEOAE recordings. The test was carried out, using an Otodynamics ILO92 Analyser version 5.60, on the second day of life or later (in case of extended recovery), during natural sleep and after feeding. The DPOAE recordings were elicited using asymmetric stimuli with L1 > L2 and a frequency-ratio of 1.22 following three different SPL protocols: 60-50 dB (PR1), 65-55 dB (PR2) and 75-65 dB (PR3). Five frequencies of the cubic distortion product (referring to f2) were tested with an ILO macro at 1.5 KHz, 2.0 KHz, 3.0 KHz, 4.0 KHz and 5.0 KHz. The statistical evaluation of differences in the signal-to-noise ratio (S/N) between the PR1 and PR2 protocols showed no significant differences. On the other hand significant differences were found between the PR3 and the PR2 S/N ratios, the former providing the best performance (higher values). The scoring criteria were defined by minimum free distribution tolerance intervals of the S/N ratios at the five tested frequencies. In conclusion this study confirms the feasibility of DPOAE recordings in a un iversal newborn hearing screening program and shows the appropriate pass-fail parameters to be used for this purpose. It should be noted that this approach enables acquisition of frequency-specific information which might further improve audiological diagnosis.