Audiology and Neurotology

Published by Karger
Online ISSN: 1421-9700
Print ISSN: 1420-3030
Publications
Change of VEMPs and caloric responses before and after imbibing alcohol
The aim of this study was to investigate the effect of alcohol on sacculocollic and vestibulo-ocular reflex systems, when the breath alcohol concentration (BrAC) is close to the legal limit of 0.25 mg/l. Twenty healthy male volunteers underwent vestibular evoked myogenic potential and caloric coupled with visual suppression tests. These tests were conducted prior to imbibing alcohol at a dosage of 0.5 g/kg to achieve a peak BrAC of around 0.25 mg/l. Once the peak BrAC was reached, these tests were performed again. Predosing and postdosing analytical results were compared, as were those with BrAC levels > or = 0.25 mg/l and <0.25 mg/l. After ingesting alcohol, 36 ears (90%) showed vestibular evoked myogenic potential responses, with a significantly increased latency of peak p13. The mean slow-phase velocity of caloric nystagmus in 40 ears after dosing was significantly reduced, and that with BrAC > or =0.25 mg/l was significantly less than that with BrAC <0.25 mg/l. Likewise, the visual suppression index decreased considerably after alcohol ingestion. In conclusion, from the perspective of vestibular function, the 0.25-mg/l BrAC limit gains clinical significance, because the vestibulo-ocular reflex performance deteriorates further, when the BrAC exceeds 0.25 mg/l. However, impaired performance of sacculocollic reflex and vestibulocerebellar interaction has occurred, when the BrAC was <0.25 mg/l, suggesting that a lower legal threshold is appropriate.
 
Inhibition of cochlear N-methyl-D-aspartate (NMDA) receptors with AM-101, a small molecule antagonist delivered by intratympanic injection, represents a novel approach to treat acute tinnitus triggered by glutamate excitotoxicity. An earlier double-blind, randomized, placebo-controlled phase II clinical trial (TACTT0) had demonstrated a significant and dose-dependent improvement in tinnitus triggered by acute acoustic trauma or otitis media from baseline to day 90. A second phase II trial (TACTT1) now sought to evaluate the most appropriate dose regimen for this treatment. Outcomes from the TACTT1 trial showed no significant difference in tinnitus improvement between a single-dose treatment and a dose regimen comprising three doses over 2 weeks. Taken together, three injections over 3 consecutive days showed the best results in the two phase II trials, suggesting that repeated and concentrated inhibition of cochlear NMDA receptors provides best treatment effects, while keeping the procedural impact on patients short. © 2015 S. Karger AG, Basel.
 
Effective pharmacological treatments for tinnitus have proven elusive. Emerging evidence suggests that dysregulation of cochlear N-methyl-D-aspartate (NMDA) receptors may underlie aberrant excitation of the auditory nerve, which in turn is perceived as tinnitus. The blocking of these receptors thus represents a promising therapeutic approach. In a recent phase I/II clinical trial, the safety and local tolerance of intratympanic injections of the NMDA receptor antagonist AM-101 was evaluated for the first time in humans. The results from the double-blind, randomized, placebo-controlled study show that intratympanically injected AM-101 was well tolerated by study participants, and provided the first indications of therapeutic efficacy.
 
Recessive mutations in the SLC26A4 gene are responsible for nonsyndromic enlarged vestibular aqueduct (EVA) and Pendred syndrome. However, in some affected families, only 1 or 0 mutated allele can be identified, as well as no clear correlation between SLC26A4 genotypes and clinical phenotypes, hampering the accuracy of genetic counseling. To elucidate the genetic composition of nonsyndromic EVA and Pendred syndrome, we screened related genomic fragments, including the SLC26A4 coding regions, the SLC26A4 promoter and the FOXI1 transcription factor gene, in 101 Taiwanese families, and analyzed their phenotypic and genotypic results. Mutation screening in the SLC26A4 coding regions by direct sequencing and quantitative polymerase chain reaction detected 2 mutations in 63 (62%) families, 1 mutation in 24 (24%) families and no mutation in 14 (14%) families. The radiological findings, the presence of goiters and the audiological results were not different among probands (i.e. index cases of the families) with different SLC26A4 genotypes. Specifically, probands heterozygous for SLC26A4 mutations demonstrated clinical features indistinguishable from those of probands with 2 mutated alleles, implicating that there might be undetected mutations. However, except for a variant (c.-2554G>A of SLC26A4) with possible pathological consequences, no definite mutation was detected after extensive screening in the SLC26A4 promoter and FOXI1. In other words, in most Taiwanese families nonsyndromic EVA or Pendred syndrome might not result from aberrance in the transcriptional control of SLC26A4 by FOXI1. Meanwhile, exploration of undetected mutations in the SLC26A4 noncoding regions revealed 9 divergent haplotypes among the 21 no-mutation-detected SLC26A4 alleles of the c.919-2A>G heterozygotes, indicating that there might be no common and predominant mutations in the SLC26A4 introns.
 
Pedigree of Dutch family W06- 792 with the novel TMC1 mutation (c.1763+3A→G). The pedigree has been modified for privacy reasons. Squares = males; circles = females; black symbol =clinically affected; empty symbol = clinically unaffected; slash = deceased individual; arrow = proband. The generation is indicated in the symbol legend.
TMC1 mutations described in DFNA36 and DFNB7/11 families
Partial sequence of the TMC1 gene showing the splice site mutation c.1763+3A→G in an affected family member (VI:6) and in a control individual. b Nested RT-PCR on lymphocyte RNA of an affected individual (VII:6) and an unrelated control individual, using primers located in exons 18 and 20 of TMC1. In the affected individual, a PCR product of 383 bp was present, while in the control sample, a smaller band of 336 bp was detected. c Sequence analysis of the 383-bp PCR product presented in b. Due to the mutation, a cryptic splice site was used, resulting in the addition of 47 nucleotides to exon 19 of the mutant TMC1 transcript. d Overview of previously described TMC1 mutations causing DFNA36 or DFNB7/11. Rectangles: exons of the TMC1 gene, with the protein-coding part indicated in black. The various mutations are presented below the gene. Protein-truncating and splice site mutations are depicted in black, while missense changes are presented in purple (online version only). The 2 missense changes causing DFNA36 (D572N and D572H) are depicted in green (online version only).
Longitudinal binaural mean air conduction threshold data of the 3 affected individuals (W06-792). Age (y) is shown by symbol. Some measurements have been omitted for clarity. a VII:6 male. b VII:7 male. c VII:9 female.
In a Dutch family with autosomal recessive hearing loss, genome-wide single-nucleotide polymorphism analysis mapped the genetic defect to the DFNB7/11 locus. A novel homozygous A-to-G change in the TMC1 gene was detected near the splice donor site of intron 19 (c.1763+3A→G) segregating with the hearing loss in this family. One of the 6 transmembrane domains and the actual TMC channel domain are predicted to be absent in the mutant protein. The sensorineural hearing impairment in this DFNB7/11 family has a postlingual onset. Audiometric analysis initially showed a steeply downward-sloping threshold configuration. The progressive phenotype in this family resembles the phenotype previously described for families with dominant TMC1 mutations (DFNA36) rather than that of families with recessive TMC1 mutations (DFNB7/11) which invariably cause severe-to-profound prelingual hearing impairment.
 
Medicines procured from herbs, animals or the soil have been with humanity since the dawn of civilization. Mostly, we assume, as cures for our ailments, but also to our detriment, as Socrates’ hemlock and Shakespeare’s ‘juice of cursed hebona’ attest (although we might argue that the murder of Hamlet’s father was not to the detriment but the benefit of our literary world). Were there any ‘ototoxic’ drugs among these remedies, adversely affecting hearing or balance? Undoubtedly, as we can deduce with near certainty from modern experience. Some of the most valuable drugs of our times have originated from plants, molds or bacteria, and notable among the ototoxic compounds of natural origin are quinine and salicylates (from tree bark) and the aminoglycoside antibiotics (from soil-dwelling bacteria). Even though we have reaped innumerable benefits, we are still suffering the consequences of the ototoxic potential of both natural and synthetic drugs (table 1). As diverse as the pharmacological properties of these drugs are their effects on the auditory system. These effects may vary in the location (organ of Corti or stria vascularis) and the nature of the hearing impairment (temporary or permanent threshold shift, tinnitus). However, admittedly, we knew little about toxic side effects of medications until modern times.
 
Studies using the prestin knockout mouse indicate that removal of the outer hair cell (OHC) motor protein is associated with loss of sensitivity, frequency selectivity and somatic electromotility. Here we provide data obtained from another prestin mouse model that was produced commercially. In vivo electrical recordings from the round window indicate that the phenotype is similar to that of the original knockout generated by the Zuo group at St. Jude Children's Research Hospital. Hence, compound action potential (CAP) thresholds are shifted in a frequency-dependent manner and CAP tuning curves at 12 kHz are flat for masker frequencies between 3 and 18 kHz. Although CAP input-output functions at 6 kHz show a shift in sensitivity at low levels, responses approach wild-type magnitudes at high levels where the cochlear amplifier has less influence. In order to confirm that the loss of sensitivity and frequency selectivity is due to loss of prestin, we performed immunohistochemistry using a prestin antibody. Cochlear segments from homozygous mutant mice showed no fluorescence, while wild-type mice displayed a fluorescent signal targeted to the OHC's lateral membrane. Absence of prestin protein was confirmed using LDS-PAGE/Western blot analysis. These results indicate that the loss of function phenotype is associated with loss of prestin protein. Lack of prestin protein also results in a shortening of OHC length to approximately 60% of wild-type, similar to that reported previously by Liberman's group. The linkage shown between the loss of prestin protein and abnormal cochlear function validates the original knockout and attests to the importance of OHC motor function in the auditory periphery.
 
CAO Staging System of Cholesteatoma
Demographic characteristics of the patients
Pre-and postoperative hearing results for three types of tympanoplasty
Figures
Objective: Following cholesteatoma surgery, effective long-term hearing preservation in children is difficult and is not typically expected. Hence, long-term data on hearing outcomes are lacking. The aim of this study was to analyze long-term hearing outcomes in children following cholesteatoma surgery. Methods: For this study, 49 ears in 47 children (≤16 years) with acquired cholesteatomas following atticotomy-limited mastoidectomy with cartilage reconstruction (inside-out approach) during 1986-2010 were included. Pre- and post-operative recidivism-free audiometric results were compared. Hearing success was defined as a post-operative air conduction (AC) threshold of ≤30 dB (serviceable hearing). Logistic regression analyses were used to evaluate potential prognostic factors that independently contributed to the prediction of hearing success. These factors included stapes condition, pre-operative AC threshold, ossicular chain integrity, disease severity, age, and gender. Results: The mean duration of follow-up was 14.2 years. The post-operative AC (33.55 ± 15.42 dB) and air-bone gap (17.88 ± 12.94 dB) were significantly improved compared with the pre-operative AC (42.90 ± 16.47 dB, p < 0.001) and air-bone gap (30.23 ± 13.68 dB, p < 0.001). The probability of hearing success following surgery (40.8%) was significantly higher than prior to surgery (24.5%, p = 0.008). Multivariate logistic regression analyses revealed a statistically significant correlation between hearing success and stapes integrity only (p = 0.005). Conclusions: This study provides important information on effective long-term hearing preservation over a mean follow-up of 14 years. In addition, stapes destruction is an independent negative prognostic determinant of achieving hearing success. The prediction model in this study provides otologists with useful pre-operative information to inform patients and parents on expected hearing outcomes and may be useful for post-operative observations.
 
The age at onset and the severity of hearing impairment (HI) varies widely among subjects and within families with the m.1555A>G mutation in mitochondrial DNA. We examined prospectively the hearing of 19 children in three nuclear families of a pedigree with m.1555A>G during a period of 7.8 years. The children underwent an audiological examination annually. At the end of the follow-up, the children were 2-13 years old. The parents were asked about the exposure of the children to risk factors of HI. We found that the 19 children with m.1555A>G were born with normal hearing and that 10 of them had developed HI by the end of the follow-up. High frequencies were affected first. The median age at the onset of HI was 3.7 years. Both the severity of HI and the age of onset varied within and between families. Most commonly, audiograms revealed a sensorineural, progressive HI sloping towards high frequencies. We could not identify environmental factors which could modify the development of HI. In conclusion, we were able to pinpoint the time of onset of HI and to follow the progression of HI in childhood. Our results show that there are distinct phenotypes, but at present there are no means to predict which phenotype will develop. It is important to follow up the hearing of children in families with the m.1555A>G mutation, because these children generally pass the newborn hearing screening, and the age at onset or the phenotype of HI cannot be predicted.
 
The inserts from 2400 cDNA clones isolated from a normalized Rattus norvegicus vestibular periphery cDNA library were sequenced and characterized. The Wackym-Soares vestibular 3' cDNA library was constructed from the saccular and utricular maculae, the ampullae of all three semicircular canals and Scarpa's ganglia containing the somata of the primary afferent neurons, microdissected from 104 male and female rats. The inserts from 2400 randomly selected clones were sequenced from the 5' end. Each sequence was analyzed using the BLAST algorithm compared to the Genbank nonredundant, rat genome, mouse genome and human genome databases to search for high homology alignments. Of the initial 2400 clones, 315 (13%) were found to be of poor quality and did not yield useful information, and therefore were eliminated from the analysis. Of the remaining 2085 sequences, 918 (44%) were found to represent 758 unique genes having useful annotations that were identified in databases within the public domain or in the published literature; these sequences were designated as known characterized sequences. 1141 sequences (55%) aligned with 1011 unique sequences had no useful annotations and were designated as known but uncharacterized sequences. Of the remaining 26 sequences (1%), 24 aligned with rat genomic sequences, but none matched previously described rat expressed sequence tags or mRNAs. No significant alignment to the rat or human genomic sequences could be found for the remaining 2 sequences. Of the 2085 sequences analyzed, 86% were singletons. The known, characterized sequences were analyzed with the FatiGO online data-mining tool (http://fatigo.bioinfo.cnio.es/) to identify level 5 biological process gene ontology (GO) terms for each alignment and to group alignments with similar or identical GO terms. Numerous genes were identified that have not been previously shown to be expressed in the vestibular system. Further characterization of the novel cDNA sequences may lead to the identification of genes with vestibular-specific functions. Continued analysis of the rat vestibular periphery transcriptome should provide new insights into vestibular function and generate new hypotheses. Physiological studies are necessary to further elucidate the roles of the identified genes and novel sequences in vestibular function.
 
Objective: To update a 15-year-old study of 800 postlinguistically deaf adult patients showing how duration of severe to profound hearing loss, age at cochlear implantation (CI), age at onset of severe to profound hearing loss, etiology and CI experience affected CI outcome. Study design: Retrospective multicenter study. Methods: Data from 2251 adult patients implanted since 2003 in 15 international centers were collected and speech scores in quiet were converted to percentile ranks to remove differences between centers. Results: The negative effect of long duration of severe to profound hearing loss was less important in the new data than in 1996; the effects of age at CI and age at onset of severe to profound hearing loss were delayed until older ages; etiology had a smaller effect, and the effect of CI experience was greater with a steeper learning curve. Patients with longer durations of severe to profound hearing loss were less likely to improve with CI experience than patients with shorter duration of severe to profound hearing loss. Conclusions: The factors that were relevant in 1996 were still relevant in 2011, although their relative importance had changed. Relaxed patient selection criteria, improved clinical management of hearing loss, modifications of surgical practice, and improved devices may explain the differences.
 
Mutations in the connexin 26 (Cx26) gene (GJB2) are a common cause of hereditary hearing impairment which affects approximately 1 in 2000 newborn children. We report the identification of a novel Cx26 point mutation (439 G-->A) linked to familial, autosomal recessive, sensorineural hearing loss. This missense mutation (E147K) is located in the highly conserved, putative K(+) channel lining sequence of the third transmembrane domain (TM3) of Cx26. Hearing impairment associated with this mutation was congenital, moderate to profound and showed no signs of progressive deterioration.
 
This study addressed the question of whether a hearing loss caused by mutations in the connexin 26 gene had a significant effect on language and speech perception outcomes in children using cochlear implants or hearing aids. The families of children who had participated in two previous studies of language development were invited to participate in this genetic study. From the 52 children whose families agreed to participate, 15 children with connexin 26 mutations in both chromosomes were identified. After taking into account other factors which are known to affect language development and speech perception in children with impaired hearing, no significant differences were found between the 15 children where connexin 26 was known to be the cause of deafness and the other 37 children in the study.
 
The phenotype of the HID (hystrix-like ichthyosis, deafness)/KID (keratitis, ichthyosis, deafness) syndrome is primarily characterized by skin changes. However, the connexin 26 (Cx 26) autosomal dominant mutation underlying this syndrome is of special neurotological interest. In the present paper, the clinical pattern, audiovestibular and neuroimaging findings and the detailed genetic analysis of 4 patients with identical HID/KID-associated mutation D50N of Cx 26 are reported. The audiological test results demonstrated profound sensorineural hearing loss in all of the patients. Neurotological testing revealed inconsistent abnormalities in dynamic posturography (sensory organization test), but the vestibular ocular reflex upon caloric irrigation was normal in all patients. Vestibular-evoked myogenic potential testing for otolith function (saccule) showed a regular response in 1 patient and pathologic responses in 3 patients, while subjective haptic vertical (utricular function) testing was normal in all of the patients. CCT showed an extended (in length), but very thin (in diameter) bony lining between the basal portion of the internal auditory canal and the vestibule in the 3 scanned patients. Our study provides evidence for functionally intact semicircular canals and normal utricular function in subjects with the autosomal dominant D50N mutation of Cx 26, in contrast to saccular function which was generally compromised and hearing loss which was profound.
 
It has been shown that alphaMSH and the nonmelanotropic ACTH/MSH(4-9) analog ORG 2766 can ameliorate cisplatin-induced neurotoxicity and ototoxicity. Here, we investigated whether these peptides delay the occurrence of the cisplatin-induced shift in auditory threshold, and whether they affect the subsequent recovery of cochlear potentials. Chronically implanted round window electrodes were used to obtain daily recordings of auditory nerve compound action potentials (CAP) and cochlear microphonics at frequencies ranging from 2 to 16 kHz. Cisplatin (1.5 mg/kg i.p.) plus alphaMSH, ORG 2766 (75 mug/kg s.c.), or saline were injected daily until the 40-dB CAP threshold shift at 8 kHz was reached. Endocochlear potential (EP) was measured either 1-2 days or 28 days later, followed by morphometric analysis of the cochlea. Peptide cotreatment did not consistently delay the threshold shift; however, the CAP threshold recovered faster and to a greater extent, with the potency order being alphaMSH > ORG 2766 > saline. Significant recovery at the 2 highest frequencies was seen in the alphaMSH-treated animals only. CAP amplitude at high sound pressures, which depends more on nerve function than on outer hair cell (OHC) function, decreased severely in all groups but recovered significantly in the alphaMSH- and completely in the ORG-2766-cotreated group. EP was significantly lower in the first days after the threshold shift but had completely recovered at 28 days. Morphometric analysis of the spiral ganglion also indicated involvement of ganglion cells. OHC loss was most severe in the basal turn of saline-cotreated animals. These data suggest that the cisplatin-induced acute threshold shift might be due to reversible strial failure, whereas subsequent OHC survival determines the final degree of functional recovery. Both OHC loss and neuronal function were ameliorated by peptide cotreatment.
 
Noise exposure induces the formation in the cochlea of 8-isoprostaglandin F(2alpha) (8-iso-PGF(2alpha)), a marker for reactive oxygen species [Ohinata et al., 2000a] and a potent vasoconstrictor, raising the possibility that 8-iso-PGF(2alpha) may be responsible for noise-induced reductions in cochlear blood flow (CBF). To test this hypothesis, CBF was assessed in the guinea pig in response to 'local' (via the anterior inferior cerebellar artery) and systemic (i.v.) delivery of 8-iso-PGF(2alpha) using laser Doppler flowmetry. Local 8-iso-PGF(2alpha) induced a clear reduction in CBF. With systemic infusion, vascular conductance (VC), the ratio of CBF to systemic blood pressure, decreased in a dose-dependent manner up to 30%, consistent with an 8-iso-PGF(2alpha)-induced constriction of the cochlear vasculature. Infusion of SQ29548, a specific antagonist of 8-iso-PGF(2alpha), appropriately blocked an 8-iso-PGF(2alpha)-induced CBF response. Similarly, noise-induced changes in CBF and VC were prevented by infusion of SQ29548 during noise exposure or by antioxidant treatment (glutathione monoethyl ester) prior to exposure. Prevention of isoprostane-mediated vasoconstriction may have clinical utility in the protection from noise-induced hearing loss.
 
The effects of primary tone frequency ratio (f2/f1 ratio) and relative level (L2/L1) on the amplitude of the cubic difference tone (CDT: 2f1-f2) distortion product otoacoustic emissions (DPOAEs) were investigated in adult White Leghorn chickens (Gallus domesticus). In experiment 1, 9 f2/f1 ratios ranging from 1.05 to 1.8 were investigated. Measurements were obtained from both ears of 4 chickens at 7 f1 frequencies ranging from 0.8 to 4.0 kHz. The primary tones were equal in level, and varied from 20 to 80 dB SPL. The mean CDT amplitude increased with increasing primary tone level once the measurement noise floor was exceeded. The input/ output functions assumed one of two shapes: one in which there was a systematic increase in DPOAE amplitude with increasing primary tone level, and the other in which there was a plateau in the input/output function near 65-70 dB SPL. At the highest primary tone level (80 dB SPL), there was a decrease in the CDT amplitude with increasing f2/f1 ratio. At high primary tone levels, the f2/f1 ratio which produced the largest CDT was 1.05 or 1.1, while at lower primary tone levels the largest CDT occurred at f2/f1 ratios of 1.2-1.3. In experiment 2, L2 was held constant at 70 dB SPL, and L1 varied from 50 to 80 dB SPL. For f1 frequencies of 0.8 and 3.2 kHz, there was an increase in the CDT amplitude with increasing L1, followed by an asymptote at higher levels. In contrast, for 1.6 and 2.0 kHz f1 frequencies, the amplitude increased, plateaued and then increased again at higher levels. Informal measurements suggest that spontaneous otoacoustic emissions (SOAEs) are rarely seen in chickens. However, a reliable SOAE was observed in 1 chicken, which could be suppressed by external sounds and anoxia.
 
Transient (click)-evoked oto-acoustic emissions (TEOAEs) and distortion product oto-acoustic emissions (DPOAEs) were recorded in a feasibility study in 7 healthy mixed-breed dogs using the ILO 92 OAE analyser (Otodynamics, Hartfield, UK). Five dogs were found to have normal hearing in both ears and 2 dogs in the left ear only following otoscopy, tympanometry and auditory brainstem response audiometry. Twelve sets of TEOAEs (click-evoked) to 80 dB peSPL click stimulus and 9 sets of DPOAEs (2F1-F2) to 8 different stimulus levels of the primary tones (L1/L2) were collected at 11 test frequencies (F2) in these normal-hearing dogs. TEOAEs were successfully recorded in 11 of the 12 ears using the default user setting and in all 12 ears using the quickscreen program. DPOAEs were successfully recorded in all 9 ears tested. While the TEOAEs parameters matched those for humans, the average signal-to-noise ratio of DPOAEs was considerably higher in the dogs. Stimulus levels at 55/55, 55/45 and 55/35 dB SPL were demonstrated to produce DPOAEs that seem to reflect the active dynamic status of the outer hair cell system. Postmortem DPOAEs at these stimulus levels and TEOAEs at 80 Db peSPL could not be elicited 5 min following euthanasia of dogs. However, DPOAEs could still be recorded albeit with reduced amplitude at stimulus levels where L1 > 55 dB SPL. The results suggest that TEOAEs and DPOAEs in dogs have the potential to provide valuable insights into their mechanisms of generation, and the specific role and behaviour of outer hair cells of the cochlea in certain pathological conditions, particularly in drug-induced ototoxicity, in humans.
 
Summary of GJB2 and GJB6 mutations
Relative frequencies of the degree of hearing loss in the 5 classes of genotypes. The proportions of patients in each subgroup are shown. T/T genotypes were associated with a significantly more pronounced hearing loss (p < 0.00001).
Summary of GJB2 and GJB6 genotypes
Correlation of genotypes and audiometric data in 100 patients (92 families) with biallelic and monoallelic GJB2 and GJB6 mutations
We report on 335 patients (319 families) with mild-to-profound nonsyndromic sensorineural hearing loss. We identified 178 mutated GJB2 alleles representing 29 different sequence changes (including 3 novel mutations: Q7P, N14D, H100Q), and 2 alleles with the deletion del(GJB6-D13S1830) of the GJB6 gene. Eleven GJB2 mutations (119 mutated alleles) were truncating (T), and 18 mutations (59 alleles) were nontruncating (NT). Biallelic GJB2 mutations were found in 71 patients (21.2%; 67 families; 25 different genotypes). Audiograms of 62 patients (56 families) with biallelic GJB2 mutations typically indicated a profound hearing loss with T/T mutations, moderate hearing loss with T/NT mutations, and mild hearing impairment with NT/NT mutations (p < 0.01, Student's t test). From 37 patients (34 families) with biallelic GJB2 mutations, audiograms at different ages were available and indicated progressive hearing loss (>15 dB) in 10 patients (27.0%, 10 families). Interestingly, we identified an unexpectedly large subset of patients (n = 29; 8.7%) presenting with only one GJB2 mutation (n = 14 T/wild-type; n = 15 NT/wild-type). This strongly suggests the presence of additional recessive mutations that are not detected by current GJB2 mutation and GJB6 deletion analyses.
 
Intraoperative findings of stapes surgery in 34 ears from 22 patients with genetically confirmed osteogenesis imperfecta (OI) are reported, as well as the audiometric results after the longest postoperative follow-up published to date. Twenty-nine out of 34 ears underwent primary stapes surgery and 5 ears revision surgery. Postoperative audiometric follow-up ranged from 6 months to 37 years. Stapes footplates were fixed in all ears. Additionally, footplates were thickened or fragile, stapes crura atrophic or fractured, and middle ear mucosae thickened or hypervascularized. Short-term postoperative audiometry revealed improved hearing and reduced air-bone gaps in 28/29 primary operated ears and in all revision cases. In the 22 ears with long-term postoperative follow-up (mean duration: 16 years), hearing gain was still significant at the latest audiometric evaluation. Independently of the patients being diagnosed with OI type I or IV and independently of the underlying OI genotype, beneficial results are obtained in the majority of OI patients undergoing primary or revision stapes surgery for reduction of conductive hearing loss components caused by stapes footplate fixation. Despite the progressive course of the concomitant sensorineural component, hearing gain remains beneficial over several decades.
 
Glucocorticoids effectively manage autoimmune hearing loss, although the cochlear mechanisms involved are unknown. Previous studies of steroid-responsive hearing loss in autoimmune (lupus) mice showed glucocorticoids and mineralocorticoids were equally effective, suggesting the ion homeostasis functions of glucocorticoids may be as relevant as immunosuppression for control of autoimmune-induced inner ear disease. Therefore, to better characterize the role of the glucocorticoid receptor in autoimmune hearing loss therapy, its function was blocked with the antagonist RU-486 (mifepristone) during glucocorticoid (prednisolone) treatments. Following baseline auditory brainstem response (ABR) thresholds, MRL/MpJ-Fas(lpr) autoimmune mice were implanted with pellets providing combinations of 1.25 mg/kg of RU-486, 4 mg/kg of prednisolone, or their respective placebos. After 1 month, animals were retested with ABR and blood was collected for immune complex analyses. Mice receiving no prednisolone (placebo + placebo and placebo + RU-486) showed continued declines in hearing. On the other hand, mice receiving prednisolone (prednisolone + placebo and prednisolone + RU-486) had significantly better hearing (p < 0.05) than the non-prednisolone groups. Immune complexes were significantly elevated in the placebo + RU-486 group, suggesting RU-486 effectively blocked glucocorticoid receptor-mediated immune suppression. These results showed that blockage of the glucocorticoid receptor with RU-486 did not prevent prednisolone's effects in the ear, suggesting its ion homeostasis actions via the mineralocorticoid receptor were more relevant in hearing control. The mineralocorticoid receptor-mediated actions of glucocorticoids are potentially relevant in steroid-responsive hearing disorders, implying disrupted cochlear ion transport functions may underlie the vascular problems proposed in some forms of immune-mediated hearing loss.
 
Patient characteristics of implanted ears per cochlear implant centre (years)
Scores on the BKB sentences test of 28 English-speaking patients. The poor performers (group 2) included a larger proportion of patients with relatively older-generation devices than the good performers (group 1).
To analyse the speech perception performance of 53 cochlear implant recipients with otosclerosis and to evaluate which factors influenced patient performance in this group. The factors included disease-related data such as demographics, pre-operative audiological characteristics, the results of CT scanning and device-related factors. Data were reviewed on 53 patients with otosclerosis from 4 cochlear implant centres in the United Kingdom and the Netherlands. Comparison of demographics, pre-operative CT scans and audiological data revealed that the patients from the 4 different centres could be considered as one group. Speech perception scores had been obtained with the English AB monosyllable tests and Dutch NVA monosyllable tests. Based on the speech perception scores, the patients were classified as poor or good performers. The characteristics of these subgroups were compared. There was wide variability in the speech perception results. Similar patterns were seen in the phoneme scores and BKB sentence scores between the poor and good performers. The two groups did not differ in age at onset of hearing loss, duration of hearing loss, progression, age at onset of deafness, or duration of deafness. The clinical presentation of the otosclerosis (rapid or slow progression) did not influence speech perception. Better performance was related to less severe signs of otosclerosis on CT scan, full insertion of the electrode array, little or no facial nerve stimulation and little or no need to switch off electrodes.
 
To further develop a multiple stimulus method for the rapid acquisition of auditory brainstem responses (ABRs), a 56-stimulus train was tested in mice. Stimuli in the train were tone bursts spaced at 0.5-octave intervals from 4 to 32 kHz. ABR thresholds, latency-intensity and amplitude-intensity functions were obtained using stimuli presented singly (one at a time) and using the 56-stimulus train. Responses from stimuli presented singly and those obtained using the 56-stimulus train were compared. There were no significant differences in thresholds (0.01 level) and very small differences in response latencies and amplitudes. These findings demonstrate the feasibility of multiple stimulus trains for the rapid acquisition of ABRs.
 
Results of tSNPs retrieved from HapMap and ABI TaqMan pre-designed commercial assay 
Distribution of HSP70 genotype and allele frequencies, ORs, and 95% CI of different noise susceptibility groups 
Distribution of haplotypes and odds ratios in the noise-susceptible and non-susceptible groups 
Noise-induced hearing loss (NIHL) is the major cause of adult sensorineural hearing loss. It is a complex disease caused by the interaction of environmental and genetic factors. Previous studies found that heat shock proteins (HSPs) were associated with the development of NIHL. Specifically, polymorphisms in the heat shock protein 70 (HSP70) gene family are associated with a susceptibility to NIHL. In this study, three single nucleotide polymorphisms (SNPs) of the HSP70 family (SNP1: rs2075800; SNP2: rs1043618; SNP3: rs2763979) were genotyped in 349 noise-exposed Taiwanese workers. The subjects were categorized into noise-susceptible (NS; n = 27) and general susceptibility (GS; n = 322) groups by the change of a 4K-weighted audiometric average in an interval of 5 years. The G/C genotype of SNP2 was found to be associated with NIHL susceptibility (adjusted OR = 2.634; 95% CI = 1.096-6.328). No significant association was found for SNP1 and SNP3 with NIHL susceptibility. Analysis of haplotypes composed of these three SNPs revealed a significant association between NIHL susceptibility and haplotype CCC (OR = 2.197; 95% CI = 1.110-4.370). In conclusion, the genetic polymorphisms in the HSP70 genes seem to be associated with the individual's susceptibility to NIHL in the Taiwanese population. These findings could be used as a reference in the understanding and prevention of NIHL.
 
Sudden sensorineural hearing loss (SSNHL) is frequently classified as 'idiopathic' since the causative factor responsible for its onset is not identified in most cases. In the present study, we determined whether SSNHL is clinically associated with serum anti-heat shock protein-70 (anti-HSP70) and antiphospholipids (anti-PLs) autoantibodies and whether these autoantibodies have an impact on the prognosis of SSNHL. Sera from 63 patients with SSNHL were screened prospectively for the presence of anti-HSP70 and anti-PLs autoantibodies by an enzyme-linked immunosorbent assay test. Anti-PLs antibodies in this study consisted of anticardiolipin, and anti-beta(2)-glycoprotein-1 antibodies. Serum was assayed for anti-HSP70 IgG antibodies using recombinant human HSP70. Demographic, clinical, and audiometric variables were analyzed to find the possible role of serum autoantibodies in SSNHL patients. Sixteen patients (25.4%) had demonstrable anti-HSP70 antibodies in serum. Twenty-one patients (33.3%) showed a positive result for at least one isotype (IgM or IgG) of anti-PLs. In 19% of the patients, anti-HSP70 and anti-PLs antibodies were positive in two combinations. A statistically significant association was found between anti-HSP70 antibodies and the Siegel recovery grade subgroup. SSNHL patients who were positive for anti-HSP70 antibodies showed a significantly higher rate of complete recovery and incomplete but partial recovery than SSNHL patients without anti-HSP70 antibodies (p = 0.0496). Statistically significant association was found between total anticardiolipin, total anti-beta(2)-glycoprotein-1, total anti-PLs, and anti-PLs in combination with anti-HSP70 antibodies and age (p = 0.0229). The detection of autoantibodies to HSP70 and PLs offers a pliable explanation for the immune-mediated mechanism of SSNHL. The present study confirms and supports previous studies regarding the association between anti-HSP70 and anti-PLs antibodies with SSNHL, and is the first to identify a positive association between anti-HSP70 antibodies and a positive outcome of SSNHL. Further studies are necessary in order to identify and further clarify the immunologic role of the presence of autoantibodies and their impact on the prognosis of SSNHL.
 
B aseline demographics of subjects 
D istribution of HSP70 genotype and allele frequencies, ORs, and 95% CI of SSNHL susceptibility and control groups 
Three SNPs and their relationships with SSNHL under three genetic models (dominant, additive, and recessive) 
Background: Heat shock proteins protect cells and tissues against different types of damage. Previous studies have revealed that the serum level of heat shock protein 70 (HSP70) increases in sudden sensorineural hearing loss (SSNHL) patients. We hypothesized that genetic variants of the HSP70 gene are associated with susceptibility to SSNHL. Methods: We conducted a case-control study with 160 SSNHL cases and 178 controls. Three tagging single nucleotide polymorphisms (SNPs) were selected. The genotypes were determined using TaqMan technology. Hardy-Weinberg equilibrium was tested for each SNP, and genetic effects were evaluated according to three inheritance modes. A haplotype analysis was also performed. Results: All three SNPs were in Hardy-Weinberg equilibrium. The CT genotype of rs2075800 exhibited an adjusted odds ratio of 0.59 (95% confidence interval 0.37-0.94; p = 0.027). The T allele of SNP rs2075800 was associated with SSNHL under the dominant model (p = 0.019; odds ratio 0.59). Haplotype analysis of the three SNPs demonstrated that the haplotype TGC (rs2075800/rs1043618/rs2763979) was statistically significant (p = 0.0137). Conclusions: These results suggest that HSP70 gene polymorphisms influence the susceptibility to the development of SSNHL in the Taiwanese population.
 
A new method for detecting the acoustic reflex that utilizes standard otoacoustic emissions recording techniques is introduced and discussed. Two successive identical tone bursts of 100 ms duration and 10 ms interstimulus interval are presented in the occluded ear canal at a repetition rate of one per second. If the acoustic reflex is elicited, the contraction of the stapedius muscle is delayed with respect to the onset of the first stimulus. Hence, the acoustic compliance in the ear canal decreases primarily during the second stimulus. The difference of the microphone signals produced by the two stimuli is computed and averaged across a certain number of repetitions of the sequence. The presentation level is increased until this difference is larger than -40 dB (with respect to the stimulus level) and if its signal-to-noise ratio exceeds 20 dB. For normal-hearing subjects, the acoustic reflex threshold measured with this method is on average 8 dB lower than in a standard clinical setup. In 5 out of the 10 tested hearing-impaired subjects, the new method could detect an acoustic reflex at one or more frequencies where no reflex was detected in the clinical setup.
 
The reliability and frequency specificity of the 80-Hz amplitude-modulation-following response (80-Hz AMFR) during sleep detected by phase coherence as a measure of the hearing threshold was evaluated in 169 affected ears of 125 children with hearing impairment. The 80-Hz AMFR at a carrier frequency of 1000 Hz was monitored in all 169 ears and the auditory brainstem response (ABR) elicited by 1000-Hz tone pips was evaluated in 93 ears. Both responses were examined during sleep, and the thresholds were compared with the behavioral hearing threshold, which was determined by standard pure-tone audiometry or play audiometry. In 24 ears of 22 children with various patterns of audiogram, the 80-Hz AMFR was examined at different carrier frequencies, and the threshold pattern was compared with the pure-tone audiogram to investigate the frequency specificity of 80-Hz AMFR. The mean and standard deviation of the difference between the 80-Hz AMFR at a carrier frequency of 1000 Hz and pure-tone thresholds of 1000 Hz was 3.8 and 12.9 dB, and that between the ABR and pure-tone thresholds was 6.8 and 14.1 dB, respectively. The threshold patterns of 80-Hz AMFR clearly followed the corresponding audiogram patterns in all types of hearing impairment. The measurement of 80-Hz AMFR thus appears to be accurate in hearing assessment and to have good frequency specificity in children during sleep.
 
To compare the quality of perilymphatic enhancement in the rat inner ear after intratympanic injection of two types of gadolinium with a 9.4-tesla micro-MRI. Gadolinium was injected into the middle ear in 6 Sprague-Dawley rats via the transtympanic route. The left ear was injected with Gd-DO3A-butrol first, and then the right ear was injected with Gd-DOTA. MR images of the inner ear were acquired 1.0, 1.5, 2.0, 2.5, 3.0, 3.5, and 4 h after intratympanic (IT) injection using an Agilent MRI system 9.4T/160/AS. The normalized signal intensity was quantitatively analyzed at the scala vestibuli (SV), scala media, and scala tympani (ST) using a Marosis M-view system. Then the normalized signal intensities (SIs) were compared between the two contrast agents. For Gd-DO3A-butrol, the SI was as low as 1.0-1.5 throughout 1-4 h at the SV and ST of the basal turn. The maximum SI was 1.5 ± 0.5 at the SV (2 h) and 1.3 ± 0.5 at the ST (2 h). For Gd-DOTA, the 1-hour postinjection SI at the basal turn was 2.5 ± 0.5 at the SV, 1.6 ± 0.3 at the ST, and 1.2 ± 0.3 at the scala media. In the apical turn, the maximum SI was reached after 2.5 h. The maximum SI in the apical turn was 1.8 ± 0.4 at the SV (3.5 h), 1.8 ± 0.4 at the ST (4 h), and 1.4 ± 0.3 at the scala media (4 h). We were able to clearly visualize and separate the ST and SV using IT Gd and 9.4-tesla micro-MRI. We recommend using Gd-DO3A-butrol over Gd-DOTA and to perform the MRI 2.5 h after using IT Gd in the rat inner ear. © 2015 S. Karger AG, Basel.
 
Vestibular-evoked myogenic potentials (VEMP) in response to 90-dB-nHL clicks were studied in 20 patients (22 ears) with superior canal dehiscence syndrome. Their amplitude was compared to the VEMP from the 'unaffected' ears of 113 patients using the same stimulus level. The 113 control subjects were those from a previous study on 1,000 patients who had had large VEMP amplitudes in response to 500-Hz 129-dB-SPL tone bursts, and, because of this, had been tested with 90-dB-nHL clicks (which are a much weaker sound stimulus than our routine 500-Hz tone burst). It was found that 90-dB-nHL clicks clearly distinguished patients with vestibular hypersensitivity to sounds. In patients, the VEMP amplitude was usually larger than the simultaneously recorded background electromyographic activity (i.e. 'corrected' amplitude >1), whereas this was not the case for the controls. Consequently, it is suggested that 90-dB-nHL clicks can be used to screen for vestibular hypersensitivity to sounds. This finding has clinical implications for patients with suspected Tullio phenomenon because the definitive VEMP test for this (i.e. estimation of VEMP threshold) is not only time-consuming, but there is also difficulty related to the low signal-to-noise ratio close to the threshold.
 
M ean values of ABR absolute latencies of waves I-V, and interwave latencies I-III, I-V, III-V of ipsilateral and contralateral ears before radiation (baseline recording) and at different times of radiation exposure (stimulus: click alternating, 80 dBnHL)
Example of baseline ABR recording. R = Response obtained from right ear; L = response obtained from left ear.
The objective of the present study was to investigate the possible electrophysiological time-related changes in auditory pathway during mobile phone electromagnetic field exposure. Thirty healthy rabbits were enrolled in an experimental study of exposure to GSM-900 radiation for 60 min and auditory brainstem responses (ABRs) were recorded at regular time-intervals during exposure. The study subjects were radiated via an adjustable power and frequency radio transmitter for GSM-900 mobile phone emission simulation, designed and manufactured according to the needs of the experiment. The mean absolute latency of waves III-V showed a statistically significant delay (p < 0.05) after 60, 45 and 15 min of exposure to electromagnetic radiation of 900 MHz, respectively. Interwave latency I-III was found to be prolonged after 60 min of radiation exposure in correspondence to wave III absolute latency delay. Interwave latencies I-V and III-V were found with a statistically significant delay (p < 0.05) after 30 min of radiation. No statistically significant delay was found for the same ABR parameters in recordings from the ear contralateral to the radiation source at 60 min radiation exposure compared with baseline ABR. The ABR measurements returned to baseline recordings 24 h after the exposure to electromagnetic radiation of 900 MHz. The prolongation of interval latencies I-V and III-V indicates that exposure to electromagnetic fields emitted by mobile phone can affect the normal electrophysiological activity of the auditory system, and these findings fit the pattern of general responses to a stressor.
 
D iagnosis of canal involvement with the Dix-Hallpike test
N umber of CRPs performed on admission
Background: Canalith repositioning procedure (CRP) has increasingly been utilized for the last 15 years for the treatment of benign paroxysmal positional vertigo (BPPV). We assess the short- and long-term efficacy of CRP on the treatment of patients with BPPV. Methods: Nine hundred sixty-five patients (481 men and 484 women, from 18 to 87 years of age) were enrolled in this prospective study during 1995-2010. Inclusion criteria were a patient history compatible with BPPV and a positive provocative maneuver (either Dix-Hallpike or Roll test). Reported duration of symptoms at the time of their first examination varied from 1 day to 18 months. Variants of the Epley and Barbeque maneuver were used for posterior and anterior canal involvement, and horizontal canal involvement, respectively. Short-term follow-up was obtained 48 h and 7 days after initial treatment, whereas long-term follow-up was obtained at repeated 6-month intervals. Results: Symptoms subsided immediately in 819 patients (85%) by the first CRP. Only 19 patients (2%) required CRP more than 3 times. Patients' mean follow-up was 74 months; symptom recurrence was noted in 139 patients. A statistically significantly higher recurrence rate was noted in elderly people or those with head trauma or a history of vestibular neuropathy (p<0.001). Conclusions: This study provides class IV evidence that CRP remains an efficient and long-lasting noninvasive treatment for BPPV, especially for younger patients without a history of head trauma or vestibular neuropathy. Elderly people have a significantly higher recurrence rate requiring additional education to minimize potential morbidity of their falls.
 
Statistical characteristics of participants with tinnitus in this study
Audiometric information and satisfaction score according to the type of tinnitus pitch
The aim of this longitudinal study was to explore whether a hearing aid or noise generator would be an effective audiological treatment for blast-induced chronic tinnitus. The amount of satisfaction from different hearing devices (hearing aid, noise generator, or both) during different time periods (1, 6, 12 and 24 months after fitting) was assessed. The 974 subjects enrolled in this study were Iran-Iraq war veterans, suffering from tinnitus for at least 2 years. About 84% of the subjects preferred just a hearing aid. Only 2.7% chose the noise generator, and the others preferred to use both devices. There were no significant differences between the hearing thresholds of the 3 groups. The satisfaction score for the hearing aid and combined devices increased by time but decreased for the noise generator. There was no correlation between the satisfaction score and parameters such as hearing thresholds, audiogram configuration and tinnitus pitch. We concluded that, compared with a noise generator, the most long-lasting treatment for blast-induced tinnitus is a hearing aid. The possible cause for such a performance is probably the recovery of the auditory function and neuroplasticity through the hearing aid. © 2015 S. Karger AG, Basel.
 
The adult auditory cortex is capable of a plastic reorganization of its tonotopic map after damage to restricted parts of the cochlear sensory epithelium. We examine the precise conditions of cochlear damage required to demonstrate such plasticity in the primary auditory cortex (A1) of the cat and the changes observed in neuronal responses in the A1 which has reorganized in plasticity of the tonotopic map. From these data we attempt to predict the conditions required for similar plasticity to occur in humans after cochlear damage.
 
The aim of this work is to characterize possible modifying factors in 2 large families carrying the A1555G mitochondrial mutation. The heteroplasmy of the mutation, the presence of aminoglycosides, the cosegregation with other mitochondrial mutations, the proposed linkage in chromosome 8 and the association with TRMU and MTO1 genes were studied. None of the mentioned modifying factors were related with the phenotype presentation of A1555G mutation. However, TRMU G28T single nucleotide polymorphism is present in 1 of the studied families.
 
Example traces of ABR from each genotype from 12-kHz tone presentations. The SPL is illustrated on the left-hand side of each graph, and the genotype of the animal is listed below the graph. The wave peaks are illustrated by roman numerals above the first waveform.
Eph receptors and ephrin ligands are large families of cell surface proteins which have established roles in axonal growth and guidance. These are well characterized in the visual and somatosensory systems but are less well documented in the auditory pathway. We examined the possible functional role of two ephrin genes (ephrin-A2 and ephrin-A5) in the auditory system by measuring auditory brainstem responses (ABR) to tone bursts from 6 to 30 kHz in ephrin-A2(-/-), ephrin-A5(-/-) and ephrin-A2A5(-/-) (knockout) mice. At high frequencies, the ephrin-A2A5(-/-) mice exhibited thresholds that were significantly lower than in wild-type mice by approximately 20 dB, suggesting ephrin-A2 and ephrin-A5 may have frequency-specific effects on the auditory system. There were also alterations in ABR wave peak amplitudes that were specific to each mouse strain which suggested both peripheral and central involvement of EphA-ephrin-A signalling in auditory function. © 2014 S. Karger AG, Basel.
 
Mean results for the ATT in quiet over time with the first and second implants alone and with bilateral implants. At 12 and 24 months the performance of the unilateral control group is also depicted. The bars indicate the standard error of the mean. The numbers at each measurement point refer to the number of subjects with bilateral implants that were tested. Children with normal hearing obtain an average SRT of 24 dB SPL [Crul et al., 1994].
The percentage of children who could (1) not lateralize significantly above chance level and (2) lateralize significantly above chance level with loudspeakers placed at ±90°, ±30° and ±15° azimuth. In the postoperative condition, the children were only tested with bilateral implants activated.
Data on MAAs in children with BiCIs plotted against age at receiving the CI2. MAAs are expressed for loudspeaker locations. An MAA could be measured in 83% (BiCI condition) and 41% (CI1 alone condition) of the instances.
D etails with regard to the subject characteristics
D irectional hearing tests
The advantages of sequential bilateral cochlear implantation were assessed in 29 children with a severe to profound hearing loss. The effect of age at second implantation and the effect of duration of bilateral implant use on the outcomes in speech perception and directional hearing were investigated. The children received their second cochlear implant at an age ranging from 2.8 to 8.5 years. Measurements were carried out preoperatively and postoperatively after 6, 12 and 24 months of bilateral implant use. A matched control group of 9 children with a unilateral implant were also measured over time and were compared with the study group after 12 and 24 months. Speech reception in both quiet and in noise and lateralization were measured. After 24 months, a minimum audible angle task was carried out. Bilateral advantages with regard to speech reception in quiet and in noise were already present after 6 months of bilateral implant use and improved thereafter. After 24 months, speech reception in noise had significantly improved with bilateral implants compared to that of children with a unilateral implant. The percentage of children that could accurately lateralize increased from 57% after 6 months to 83% after 24 months. With regard to the minimum audible angle task, loudspeakers were placed on average at ±42°. Age at second implantation did not have an influence on all outcomes. From the results it can be concluded that the advantages of bilateral hearing occur after sequential bilateral implantation and that age at second implantation does not influence the amount of bilateral advantage. Furthermore, it can be concluded that longer periods of bilateral implant use lead to greater bilateral advantages.
 
Schematic of Digisonic SP Binaural device. a A single receiver connects two electrode arrays. The longer contralateral electrode array is inserted under the scalp. b A Widex CROS microphone on the contralateral side is connected by a wire to the processor.
D eafness history overview of the 14 included subjects
Signal processing line and electrical stimulation performed by the Digisonic SP Binaural device. Dotted squares correspond to the physical parts of the device. Electrical pulses are represented as an example over five channels on each side (here, electrode 4 on ipsilateral side and electrode 5 on contralateral side are not stimulated because of peak extraction strategy). As in all Digisonic implants the phases of the delivered electrical pulses are asymmetric and electrically balanced (active charge and capacitive passive discharge).
In this prospective study the outcome of the Digisonic® SP Binaural cochlear implant (CI), a device enabling electric stimulation of both cochleae by a single receiver, was evaluated in 14 postlingually deafened adults after 12 months of use. Speech perception was tested using French disyllabic words in quiet and in speech-shaped noise at +10 dB signal-to-noise ratio. Horizontal sound localization in quiet was tested using pink noise coming from 5 loudspeakers, from -90 to +90° along the azimuth. Speech scores in quiet were 76% (±19.5 SD) in the bilateral condition, 62% (±24 SD) for the better ear alone and 43.5% (±27 SD) for the poorer ear alone. Speech scores in noise were 60% (±27.5 SD), 46% (±28 SD) and 28% (±25 SD), respectively, in the same conditions. Statistical analysis showed a significant advantage of the bilateral use in quiet and in noise (p < 0.05 compared to the better ear). Significant spatial perception benefits such as summation effect (p < 0.05), head shadow effect (p < 0.0001) and squelch effect (p < 0.0005) were noted. Sound localization accuracy improved significantly when using the device in the bilateral condition with an average root mean square of 35°. Compared with published outcomes of usual bilateral cochlear implantation, this device could be a valuable alternative to two CIs. Prospective controlled trials, comparing the Digisonic SP Binaural CI with a standard bilateral cochlear implantation are mandatory to evaluate their respective advantages and cost-effectiveness.
 
This research on children's speech in noise and cognitive abilities aimed to determine the age-related trends in speech in noise perception abilities and the relationship between speech in noise perception and cognitive abilities. Monosyllabic distinguishable (consonant-vowel-consonant) words was the most recognisable word category, followed by monosyllabic confusable words (consonant-vowel-consonant), disyllabic non-words (/aCa/) and monosyllabic syllables (/Ca/), demonstrating that phoneme distinctiveness and a reduction in word confusability contribute to their recognition. Older children outperformed younger children on all speech in noise tasks, indicating that there are age-related trends in speech in noise abilities. Children with higher cognitive abilities did not outperform children with lower cognitive abilities on speech in noise tasks, indicating that the ability to hear speech in noise may be an intrinsic feature of the auditory system that matures with age.
 
In osteoarthritis, the joint cartilage breaks down. Cartilage exists within the incudomalleolar and incudostapedial joints. In addition, the cartilage-covered base of the stapes footplate is bound to the cartilage-covered rim of the oval window by the annular ligament. Thus, higher prevalence of middle ear abnormalities and hearing loss can be expected in osteoarthritis due to degeneration of the cartilage and the subsequent abnormal repair response. In this study, tympanometric and audiometric data were obtained from 15 individuals diagnosed with osteoarthritis and 15 gender- and age-matched individuals without the diagnosis of arthritis. Results showed a significantly higher prevalence of middle ear abnormalities and hearing loss in ears with arthritis when compared to the control group. Interestingly, osteoarthritis and hearing loss are considered among the top chronic health concerns in older individuals although the connection between these two conditions has not been previously reported.
 
TEOAE amplitude and suppression values by ear in the SM and control groups
Two efferent feedback pathways to the auditory periphery may play a role in monitoring self-vocalization: the middle-ear acoustic reflex (MEAR) and the medial olivocochlear bundle (MOCB) reflex. Since most studies regarding the role of auditory efferent activity during self-vocalization were conducted in animals, human data are scarce. The working premise of the current study was that selective mutism (SM), a rare psychiatric disorder characterized by consistent failure to speak in specific social situations despite the ability to speak normally in other situations, may serve as a human model for studying the potential involvement of auditory efferent activity during self-vocalization. For this purpose, auditory efferent function was assessed in a group of 31 children with SM and compared to that of a group of 31 normally developing control children (mean age 8.9 and 8.8 years, respectively). All children exhibited normal hearing thresholds and type A tympanograms. MEAR and MOCB functions were evaluated by means of acoustic reflex thresholds and decay functions and the suppression of transient-evoked otoacoustic emissions, respectively. Auditory afferent function was tested by means of auditory brainstem responses (ABR). Results indicated a significantly higher proportion of children with abnormal MEAR and MOCB function in the SM group (58.6 and 38%, respectively) compared to controls (9.7 and 8%, respectively). The prevalence of abnormal MEAR and/or MOCB function was significantly higher in the SM group (71%) compared to controls (16%). Intact afferent function manifested in normal absolute and interpeak latencies of ABR components in all children. The finding of aberrant efferent auditory function in a large proportion of children with SM provides further support for the notion that MEAR and MOCB may play a significant role in the process of self-vocalization. © 2013 S. Karger AG, Basel.
 
Speech perception mean scores (percent correct) for open-set sentences (striped), open-set words (grey), and open-set words (black) and PPVT SS (dotted) for children with cochlear and/or vestibular abnormality using an oral communication mode and sign communication mode.
Demographic, audiological and outcome data for children with common cavity (n = 5)
Demographic, audiological and outcome data for children with Mondini and EVA (n = 12)
Demographic, audiological and outcome data for children with EVA (n = 18)
Demographic, audiological and outcome data for children with scans unclassified (n = 4)
CT and MRI scans for 48 children with cochlear and/or vestibular abnormality were classified in decreasing severity; common cavity, Mondini plus enlarged vestibular aqueduct, Mondini dysplasia alone and enlarged vestibular aqueduct alone. No significant relationship between degree of cochlea abnormality and surgical issues (cerebrospinal fluid gusher, depth of insertion, number of electrodes) or speech perception/language outcomes was found. A significant relationship was observed between cerebrospinal fluid gusher and partial electrode insertion, fewer active electrodes and poorer sentence understanding. Optimum language outcomes were associated with younger age at implant.
 
Recordings from the 12 subjects showing the individual binaural difference waveform, i.e. the remainder after subtracting the binaural response to 4,096 clicks from the algebraic sum of the two monaural responses to 4,096 clicks each. The β wave latencies are marked according to the results in the automatic analysis.
Relation between the ß wave amplitude (ÌV) and latency (ms) at the different ITDs
The effect of unilaterally delayed acoustic stimuli on binaural interaction was studied in 12 subjects with normal hearing. Auditory brainstem response (ABR) was obtained in the midline between the forehead and the neck, and click stimuli were unilaterally delayed at 0.2-ms intervals in the 0- to 1-ms range. Binaural interaction was evaluated by measuring the beta wave in the binaural difference waveform, i.e. the remainder after subtracting the binaurally evoked registration from the sum of the two monaural registrations. Computation of the binaural difference waveform showed the beta wave amplitude to be relatively stable throughout the 0- to 1-ms range of interaural time differences. This finding suggests stable binaural interaction within the range of interaural time differences where binaural click stimuli induce a binaurally fused intracranial image.
 
The failure of standard ABR measures to detect small (< or =1 cm) acoustic tumors has led to the use of enhanced magnetic resonance imaging (MRI) as the standard to screen for small tumors. This study investigates the suitability of the stacked ABR as a sensitive screening alternative to MRI for small acoustic tumors (SATs). The objective of the study was to determine the sensitivity and specificity of the stacked ABR technique for detecting SATs. A total of 54 patients with acoustic tumors identified by MRI that were either < or =1 cm in size or undetected by standard ABR methods, irrespective of size, were studied. A control population of 78 nontumor normal-hearing subjects was also tested. For comparison, two standard ABR measures (IT5 and I-V delay) were also analyzed. The stacked ABR demonstrated 95% sensitivity and 88% specificity; 100% sensitivity was obtained at 50% specificity. Standard ABR measures were much poorer in detecting these tumors. In conclusion, the stacked ABR can be used as a sensitive, widely-available, cost-effective, and comfortable tool for screening SATs.
 
Several mechanisms have been suggested to explain the clearance of fluids from the middle ear. These include a pumping action through the eustachian tube, mucociliary beating through the tube, outflow of water to the blood due to osmotic gradients and an active Na(+) transport driving water absorption. In order to assess these mechanisms, the middle ear cavity of paralyzed, ventilated (eustachian tube occluded) guinea pigs was filled with fluids varying in osmotic pressure (hypotonic, isotonic, hypertonic) to which a vertical tube was attached. The change in height of fluid in the tube was taken as a measure of changes in middle ear fluid volume. A greater fluid volume reduction was seen with the hypotonic (1/5 saline) solution. A small volume increase was observed with the hypertonic solution. These results provide evidence that in these experimental conditions, water absorption due to osmotic gradients can contribute to middle ear fluid clearance.
 
Benign paroxysmal positional vertigo (BPPV) due to canalithiasis can be treated with particle repositioning manoeuvres, which aim to evacuate trapped particles from the semicircular canals (SCC). The movement of particles within the SCC is affected by gravity as well as by the accelerations of the head during the manoeuvres. Moreover, as experienced by the particles, gravity is indistinguishable from an upward acceleration of the SCC in free space. We used a set of three orthogonal linear accelerometers to measure the net three-dimensional linear acceleration vector acting on the head during the Hallpike manoeuvre and Epley and Semont particle repositioning manoeuvres (which are used to treat posterior canal BPPV). The projection of the net acceleration vector onto the SCC planes showed that both the Epley and Semont manoeuvres approximated to stepwise, 360 degrees , backward rotations in the plane of the targeted posterior canal. Angular velocity measurements however showed that the rotational component during the central stages of these two manoeuvres is opposite in direction. A simple model of head rotations during particle repositioning manoeuvres was created which showed good agreement to the linear acceleration measurements. Analysis of modelled and measured data identified that speed of movement during the Semont manoeuvre should be critical to its clinical success.
 
Exposure to intense noise stress can cause a permanent noise-induced hearing loss which is thought to be due to elevation of reactive oxygen species in excess of the inherent antioxidant mechanisms of the cell. However, preconditioning to low levels of stress of one type can activate cellular mechanisms leading to the elevation of antioxidant levels so that the cell is then better able to tolerate subsequent severe stress of a different type. This has been called cross-tolerance. Here, we tested this hypothesis by acclimating rats to a moderate heat stress (30 days at 34 degrees C). The rats were exposed to 113 dB SPL noise for 3 days (12 h/day) in three different groups: heat acclimated then noise exposed; noise exposed and then heat acclimated; heat acclimated, then noise exposed and then heat acclimated again. Permanent changes in auditory function--auditory nerve brainstem evoked responses (ABR) and distortion product otoacoustic emissions (DPOAEs)--were evaluated in each of these animals and compared with those in rats exposed to noise only and in control groups of rats. Statistical evaluation of the results showed that when assessed with ABR, each of the heat-acclimated, noise-exposed groups was protected from the noise, even the group that was heat-acclimated after the noise exposure. When assessed with DPOAE, protection was statistically apparent only in the group that was heat acclimated, then exposed to noise, and not in the other groups. Thus, heat acclimation provides protection against permanent noise-induced hearing loss.
 
Localization ability – interaction between frequency and location. Hit accuracy (circles: group mean, whiskers: SD) plotted against the respective reference locations in the frontal azimuthal hemifield for all children and adolescents aged 6–18 years for LF (black circles) and HF (grey circles) signals. This interaction was significant (p = 0.002). This frequency–direction interaction indicates that absolute localization of HF signals is disproportionately more inaccurate than for frontal directions or for LF signals in general. Thus, the slope from frontal to lateral is steeper for HF signals than for LF stimuli, which holds true not only for mean values but also for interindividual variability.
M AA -descriptive statistics
Localization ability – intraindividual variability. Dispersion plotted against the respective reference locations in the frontal azimuthal hemifield for 6- to 7-year-old children (a), 8- to 12-year-old children (b), and 13- to 18-year-old adolescents (c). Median (black line), 25th and 75th percentile (boxes), and 10th and 90th percentile (whiskers) for LF (left panels) and HF (right panels) signals. Note that adolescents (13–18 years) were not tested in the 45° condition. Dispersion was measured by means of the absolute difference between the 6 pointed locations and the median pointed locations per participant and condition. Dispersion increased slightly with increasing laterality of the presented signals. However, in contrast to hit accuracy, dispersion decreased with increasing age and did not show frequency dependence.
MAA. Discrimination thresholds plotted against the respective reference locations in the frontal azimuthal hemifield for 6- to 7-year-old children (a), 8- to 12-year-old children (b), and 13- to 18-year-old adolescents (c). Median (black line), 25th and 75th percentile (boxes), and 10th and 90th percentile (whiskers) for LF (left panels) and HF (right panels) signals. MAA thresholds showed a strong dependency on reference location and on signal frequency. Threshold values decreased with increasing age.
The present study investigated the development of two parameters of spatial acoustic perception in children and adolescents with normal hearing, aged 6-18 years. Auditory localization accuracy was quantified by means of a sound source identification task and auditory spatial discrimination acuity by measuring minimum audible angles (MAA). Both low- and high-frequency noise bursts were employed in the tests, thereby separately addressing auditory processing based on interaural time and intensity differences. Setup consisted of 47 loudspeakers mounted in the frontal azimuthal hemifield, ranging from 90° left to 90° right (-90°, +90°). Target signals were presented from 8 loudspeaker positions in the left and right hemifields (±4°, ±30°, ±60° and ±90°). Localization accuracy and spatial discrimination acuity showed different developmental courses. Localization accuracy remained stable from the age of 6 onwards. In contrast, MAA thresholds and interindividual variability of spatial discrimination decreased significantly with increasing age. Across all age groups, localization was most accurate and MAA thresholds were lower for frontal than for lateral sound sources, and for low-frequency compared to high-frequency noise bursts. The study also shows better performance in spatial hearing based on interaural time differences rather than on intensity differences throughout development. These findings confirm that specific aspects of central auditory processing show continuous development during childhood up to adolescence.
 
Top-cited authors
Paul Van de Heyning
  • Universitair Ziekenhuis Antwerpen
René H Gifford
  • Vanderbilt University
Olivier Sterkers
  • Hôpital Beaujon – Hôpitaux Universitaires Paris Nord Val de Seine
Stephen O'Leary
  • University of Melbourne
Richard Charles Dowell
  • University of Melbourne