Cochlear Implants in Subjects Over Age 65: Quality of Life and Audiological Outcomes.

BACKGROUND Cochlear implants (CIs) have been recognized as a safe and effective means for profound hearing loss rehabilitation in children and adults and recently their use has been extended to subjects over 65 years of age. The aim of this paper was to assess indices related to changes in the quality of life (QoL) in elderly CI recipients. MATERIAL AND METHODS A case-control paradigm was used to assess the effects of CIs on the QoL. Forty-two subjects were assigned to the Case group and 15 subjects to the Control group. All 57 subjects were affected by profound hearing loss and had received a CI. Audiological data were collected from both groups at: (i) 1 month pre-implantation [T1]; (ii) 1 day pre- implantation [T2]; (iii) 30 days post-implantation, with CI used in free field [T3]; and (iv) 12 months post-implantation, with CI used in a free field [T4]. The QoL was assessed via a Glasgow Benefit Inventory (GBI) questionnaire, adapted to otolaryngology. To compare subjects across different ages with varying degrees of speech development, a perception parameter was used from the Speech Perception Categories test developed by Geers and Moog. RESULTS Hearing performance was considerably improved after CI. In relation to the hearing performance at time T1, statistically significant threshold gains were observed in both groups in the T3 and T4 observation windows. At time T4, a threshold gain of 70 dB HL in the Case group and a gain of 84 dB HL in the Control group were observed. With speech therapy rehabilitation, a perception level of 6 was reached by 80.0% of patients in the Case group and by 100% of patients in the Control group. In terms of QoL, both groups showed improved post-CI scores. Statistical differences were observed between the 2 groups, with the Control group outperforming the Case group in all but the social section. CONCLUSIONS Despite age-related changes in auditory system and prolonged hearing deprivation, CIs offer audiological and QoL benefits in the elderly.

The relationship between distortion product otoacoustic emissions and extended high-frequency audiometry in tinnitus patients. Part 1: normally hearing patients with unilateral tinnitus.

BACKGROUND: The aim of this study was to evaluate distortion product otoacoustic emissions (DPOAEs) and extended high-frequency (EHF) thresholds in a control group and in patients with normal hearing sensitivity in the conventional frequency range and reporting unilateral tinnitus. MATERIAL/METHODS: Seventy patients were enrolled in the study: 47 patients with tinnitus in the left ear (Group 1) and 23 patients with tinnitus in the right ear (Group 2). The control group included 60 otologically normal subjects with no history of pathological tinnitus. Pure-tone thresholds were measured at all standard frequencies from 0.25 to 8 kHz, and at 10, 12.5, 14, and 16 kHz. The DPOAEs were measured in the frequency range from approximately 0.5 to 9 kHz using the primary tones presented at 65/55 dB SPL. RESULTS: The left ears of patients in Group 1 had higher median hearing thresholds than those in the control subjects at all 4 EHFs, and lower mean DPOAE levels than those in the controls for almost all primary frequencies, but significantly lower only in the 2-kHz region. Median hearing thresholds in the right ears of patients in Group 2 were higher than those in the right ears of the control subjects in the EHF range at 12.5, 14, and 16 kHz. The mean DPOAE levels in the right ears were lower in patients from Group 2 than those in the controls for the majority of primary frequencies, but only reached statistical significance in the 8-kHz region. CONCLUSIONS: Hearing thresholds in tinnitus ears with normal hearing sensitivity in the conventional range were higher in the EHF region than those in non-tinnitus control subjects, implying that cochlear damage in the basal region may result in the perception of tinnitus. In general, DPOAE levels in tinnitus ears were lower than those in ears of non-tinnitus subjects, suggesting that subclinical cochlear impairment in limited areas, which can be revealed by DPOAEs but not by conventional audiometry, may exist in tinnitus ears. For patients with tinnitus, DPOAE measures combined with behavioral EHF hearing thresholds may provide additional clinical information about the status of the peripheral hearing.

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait.

Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.

Rehabilitation of Severe to Profound Sensorineural Hearing Loss in Adults: Audiological Outcomes.

The aim of this article is to describe the audiological patterns of 71 adult patients presenting severe to profound sensorineural hearing loss, who were rehabilitated by cochlear implants (CIs) and hearing aids. This is a retrospective study in a university setting, where the clinical records of 71 adult patients were reviewed and processed. Speech intelligibility was evaluated at one aided ear (CI) or at both aided ears (double CI or a combination of CI and hearing aid [HA]). Patients with a bilateral CI or with a bimodal hearing setup (CI and HA) performed better than those with a single CI; data from the phonetic matrices test showed that there was a statistically significant difference among patients aided by a single CI versus binaural setup (double CI or CI + HA). In particular, patients aided by a bilateral CI, or by a CI and HA, showed an improvement in the functional results of the speech tests, compared to patients using a single CI. Binaural hearing (either with a bilateral CI or bimodal) allows an improvement in the functional results at the speech tests, compared to the use of a CI only.

The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment.

Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.

Genetic variants in the RELN gene are associated with otosclerosis in multiple European populations.

Otosclerosis is a common form of hearing loss characterized by abnormal bone remodeling in the otic capsule. It is considered a complex disease caused by both genetic and environmental factors. In a previous study, we identified a region on chr7q22.1 located in the RELN gene that is associated with otosclerosis in Belgian-Dutch and French populations. Evidence for allelic heterogeneity was found in this chromosomal region in the form of two independent signals. To confirm this finding, we have completed a replication study that includes four additional populations from Europe (1,141 total samples). Several SNPs in this region replicated in these populations separately. While the power to detect significant association in each population is small, when all four populations are combined, six of seven SNPs replicate and show an effect in the same direction as in the previous populations. We also confirmed the presence of allelic heterogeneity in this region. These data further implicate RELN in the pathogenesis of otosclerosis. Functional research is warranted to determine the pathways through which RELN acts in the pathogenesis of otosclerosis.

High Human Papillomavirus DNA loads in Inflammatory Middle Ear Diseases.

Background. Previous studies reported human papillomaviruses (HPVs) in middle ear tumors, whereas these viruses have been poorly investigated in chronic inflammatory middle ear diseases. We investigated HPVs in non-tumor middle ear diseases, including chronic otitis media (COM). Methods. COM specimens (n = 52), including chronic suppurative otitis media (CSOM) (n =38) and cholesteatoma (COMC) (n = 14), as well as normal middle ear (NME) specimens (n = 56) were analyzed. HPV sequences and DNA loads were analyzed by quantitative-PCR. HPV genotyping was performed by direct sequencing. Results. HPV DNA was detected in 23% (12/52) of COM and in 30.4% (17/56) of NME (p > 0.05). Specifically, HPV DNA sequences were found in 26.3% (10/38) of CSOM and in 14.3% (2/14) of COMC (p > 0.05). Interestingly, the HPV DNA load was higher in COMC (mean 7.47 copy/cell) than in CSOM (mean 1.02 copy/cell) and NME (mean 1.18 copy/cell) (P = 0.03 and P = 0.017 versus CSOM and NME, respectively). HPV16 and HPV18 were the main genotypes detected in COMC, CSOM and NME. Conclusions. These data suggest that HPV may infect the middle ear mucosa, whereas HPV-positive COMCs are associated with higher viral DNA loads as compared to NME.

Occupational noise, smoking, and a high body mass index are risk factors for age-related hearing impairment and moderate alcohol consumption is protective: a European population-based multicenter study.

A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.

Cerebral Inflow and Outflow Discrepancies in Severe Sudden Sensorineural Hearing Loss.

The aim of this study is to evaluate whether cerebral inflow and outflow abnormalities, assessed by the means of a validated ultrasound model, could be associated with Sudden Sensorineural Hearing Loss (SSNHL). According to Clark, a total of 42 patients affected by severe SSNHL and 19 healthy volunteers matched by gender without any history of sudden hearing impairment have been included in this study. Patients and controls underwent EchocolorDoppler assessment of brain hemodynamics. All subjects affected by SSNHL were also assessed with Auditory Brainstem Responses (ABR) and Magnetic Resonance Imaging (MRI) in order to exclude retrocochlear pathology. The head inflow through the common carotid artery was practically equivalent between groups, but at the level of the carotid bifurcation, the external carotid artery showed a highly significant flow rate in SSNHL 5.4±2 vs 3.9±1.1 ml/s in controls (p=0.01). The brain inflow was similar between patients and controls, but interestingly the flow rate of the vertebral artery was significantly reduced in SSNHL 1.6±0.8 vs 2.8±0.9 ml/s (p=0.01). The brain outflow was found significantly restricted at the level of the jugular outlet 6.6±6 vs 9.9±6 ml/s (p=0.002); consequently, the collateral flow index was significantly increased in SSNHL (p=0.001). The present study shows a discrepant distribution of the brain inflow which seems to penalize the posterior segments of the Willis polygon in patients affected by severe SSNHL. In addition, our study confirms the presence of chronic cerebrospinal venous insufficiency in SSNHL with significant activation of venous collateral circulation.

The contribution of GJB2 (Connexin 26) 35delG to age-related hearing impairment and noise-induced hearing loss.

HYPOTHESIS: The common GJB2 (Connexin 26) 35delG mutation might contribute to the development of age-related hearing impairment (ARHI) and noise-induced hearing loss (NIHL). BACKGROUND: GJB2, a gene encoding a gap junction protein expressed in the inner ear, has been suggested to be involved in the potassium recycling pathway in the cochlea. GJB2 mutations account for a large number of individuals with nonsyndromic recessive hearing loss, with 35delG being the most frequent mutation in populations of European origin. Other genes involved in potassium homeostasis have been suggested to be associated with ARHI and NIHL, and distortion product otoacoustic emission distortions indicative of hearing loss alterations have been found in 35delG carriers. METHOD: We genotyped 35delG in two distinct sample sets: an ARHI sample set, composed of 2,311 Caucasian samples from nine different centers originating from seven different countries with an age range between 53 and 67 years, and an NIHL sample set consisting of 702 samples from the two extremes of a noise-exposed Polish sample. RESULTS: After statistical analysis, we were unable to detect an association between 35delG and ARHI, nor between 35delG and NIHL. CONCLUSION: Our findings indicate that there is no increased susceptibility in 35delG carriers for the development of ARHI or NIHL.

High Resolution M-mode Evaluation of Jugular Vein Valves in Patients with Neurological and Neurosensory Disorders.

BACKGROUND: High prevalence of valve absence was found in the internal jugular vein (IJV) of healthy volunteers by means of M-mode high-resolution Echo Colour Doppler (ECD). However, the prevalence of valve in neurovascular disorders linked to Chronic Cerebrospinal Venous Insufficiency (CCSVI) is still unknown. METHODS: A cohort of 83 Healthy Controls (HC), 71 Multiple Sclerosis (MS), 99 Inner Ear Disorders (IED) underwent ECD investigation of the IJV valve, including M-mode evaluation and related hemodynamics. The primary outcome measure was characterization of valve presence, morphology and motility, whereas the secondary outcome was the rate of flow alteration. RESULTS: Bilateral valve presence was found in 38% of HC, 58% of MS and 25% of IED, whereas, bilateral valve absence was recorded in 16% of HC, 10% of MS and 31% of IED (p<0.003). Bicuspid morphology was more prevalent in HC 56%, while monocusp was more prevalent in patients: 75% MS and 57% IED (p<0.0001). The main finding was the presence of mobile valve leaflets in 98% of HC, contrarily fixed valve leaflets were recorded in 82% of MS and in 41% of IED, p< 0.0001. Finally, by stratifying the entire cohort according to the presence of mobile and not mobile valve leaflets, normal monodirectional and phasic flow were commonly found in the mobile leaflets subgroup, p<0.0001. CONCLUSION: In patients with miscellaneous neurological disorders, a significant higher rate of defective valves was found with respect to HC. The latter condition is strongly associated to brain outflow abnormalities described in CCSVI condition.

Familial aggregation of pure tone hearing thresholds in an aging European population.

OBJECTIVE: To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated. STUDY DESIGN: Multicenter survey in 8 European centers. SUBJECTS: One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study. RESULTS: We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies. DISCUSSION: Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.

Clinical evaluation of cochlear implant sound coding taking into account conjectural masking functions, MP3000™.

Efficacy of the SPEAK and ACE coding strategies was compared with that of a new strategy, MP3000™, by 37 European implant centers including 221 subjects. The SPEAK and ACE strategies are based on selection of 8-10 spectral components with the highest levels, while MP3000 is based on the selection of only 4-6 components, with the highest levels relative to an estimate of the spread of masking. The pulse rate per component was fixed. No significant difference was found for the speech scores and for coding preference between the SPEAK/ACE and MP3000 strategies. Battery life was 24% longer for the MP3000 strategy. With MP3000 the best results were found for a selection of six components. In addition, the best results were found for a masking function with a low-frequency slope of 50 dB/Bark and a high-frequency slope of 37 dB/Bark (50/37) as compared to the other combinations examined of 40/30 and 20/15 dB/Bark. The best results found for the steepest slopes do not seem to agree with current estimates of the spread of masking in electrical stimulation. Future research might reveal if performance with respect to SPEAK/ACE can be enhanced by increasing the number of channels in MP3000 beyond 4-6 and it should shed more light on the optimum steepness of the slopes of the masking functions applied in MP3000.