Cochlear homeostasis and its role in genetic deafness

AbstractEach component of the human ear performs a specific function in hearing. The actual process of sound transduction takes place in the auditory portion of the inner ear, the fluid-filled cochlea. In the cochlea, the sensitivity and efficiency of sensory apparatus to convert mechanical energy into neural activity, largely depends on the fluidic and ionic environment. In the lateral wall of cochlea, the secretory epithelium stria vascularis plays an important role in the maintenance of fluidic and ionic homeostasis. A variety of gene mutations disturbs the cochlear homeostasis and subsequently leads to hearing impairment. The review covers several aspects of cochlear homeostasis, from cochlear fluid and the functional role of stria vascularis, cochlear K+recycling and its molecular substrates to genetic deafness with abnormal cochlear homeostasis

Relationship between headaches and tinnitus in a Swedish study

The heterogeneity of tinnitus is likely accounting for the lack of effective treatment approaches. Headaches have been related to tinnitus, yet little is known on how headaches impact tinnitus. We use cross-sectional data from the Swedish Tinnitus Outreach Project to i) evaluate the association between headaches and tinnitus (n = 1,984 cases and 1,661 controls) and ii) investigate the phenotypic characteristics of tinnitus subjects with tinnitus (n = 660) or without (n = 1,879) headaches. In a multivariable logistic regression model, headache was significantly associated with any tinnitus (odds ratio, OR = 2.61) and more so with tinnitus as a big problem (as measured by the tinnitus functional index, TFI ≥ 48; OR = 5.63) or severe tinnitus (using the tinnitus handicap inventory, THI ≥ 58; OR = 4.99). When focusing on subjects with tinnitus, the prevalence of headaches was 26% and reached 40% in subjects with severe tinnitus. A large number of socioeconomic, phenotypic and psychological characteristics differed between headache and non-headache subjects with any tinnitus. With increasing tinnitus severity, fewer differences were found, the major ones being vertigo, neck pain and other pain syndromes, as well as stress and anxiety. Our study suggests that headaches could contribute to tinnitus distress and potentially its severity.publishedVersio

Association between Hyperacusis and Tinnitus

The following are available online at http://www.mdpi.com/2077-0383/9/8/2412/ s1We gratefully acknowledge the support and generosity of Nancy Pedersen, head of LifeGene.Many individuals with tinnitus report experiencing hyperacusis (enhanced sensitivity to sounds). However, estimates of the association between hyperacusis and tinnitus is lacking. Here, we investigate this relationship in a Swedish study. A total of 3645 participants (1984 with tinnitus and 1661 without tinnitus) were enrolled via LifeGene, a study from the general Swedish population, aged 18–90 years, and provided information on socio-demographic characteristics, as well as presence of hyperacusis and its severity. Tinnitus presence and severity were self-reported or assessed using the Tinnitus Handicap Inventory (THI). Phenotypes of tinnitus with (n = 1388) or without (n = 1044) hyperacusis were also compared. Of 1661 participants without tinnitus, 1098 (66.1%) were women and 563 were men (33.9%), and the mean (SD) age was 45.1 (12.9). Of 1984 participants with tinnitus, 1034 (52.1%) were women and 950 (47.9%) were men, and the mean (SD) age was 47.7 (14.0) years. Hyperacusis was associated with any tinnitus [Odds ratio (OR) 3.51, 95% confidence interval (CI) 2.99–4.13], self-reported severe tinnitus (OR 7.43, 95% CI 5.06–10.9), and THI ≥ 58 (OR 12.1, 95% CI 7.06–20.6). The association with THI ≥ 58 was greater with increasing severity of hyperacusis, the ORs being 8.15 (95% CI 4.68–14.2) for moderate and 77.4 (95% CI 35.0–171.3) for severe hyperacusis. No difference between sexes was observed in the association between hyperacusis and tinnitus. The occurrence of hyperacusis in severe tinnitus is as high as 80%, showing a very tight relationship. Discriminating the pathophysiological mechanisms between the two conditions in cases of severe tinnitus will be challenging, and optimized study designs are necessary to better understand the mechanisms behind the strong relationship between hyperacusis and tinnitus.GENDER-NET Co-Plus Fund GNP-182Decibel Therapeutics, Inc.Svenska Lakaresallskapet SLS-779681Tysta SkolanHorselforskningsfonden 503European Union (EU) 72204655 848261NIHR Nottingham Biomedical Research CentreSwedish Medical Research Council (SMRC) K2014-99X-22478-01-3Karolinska InstitutetNational Institute for Health Research (NIHR

Availability of data for cost-effectiveness comparison of child vision and hearing screening programmes

Objective For cost-effectiveness comparison of child vision and hearing screening programmes, methods and data should be available. We assessed the current state of data collection and its availability in Europe. Methods The EUSCREEN Questionnaire, conducted in 2017–2018, assessed paediatric vision and hearing screening programmes in 45 countries in Europe. For the current study, its items on data collection, monitoring and evaluation, and six of eleven items essential for cost-effectiveness analysis: prevalence, sensitivity, specificity, coverage, attendance and loss to follow-up, were reappraised with an additional questionnaire. Results The practice of data collection in vision screening was reported in 36% (N = 42) of countries and in hearing screening in 81% (N = 43); collected data were published in 12% and 35%, respectively. Procedures for quality assurance in vision screening were reported in 19% and in hearing screening in 26%, research of screening effectiveness in 43% and 47%, whereas cost-effectiveness analysis was performed in 12% for both. Data on prevalence of amblyopia were reported in 40% and of hearing loss in 77%, on sensitivity of screening tests in 17% and 14%, on their specificity in 19% and 21%, on coverage of screening in 40% and 84%, on attendance in 21% and 37%, and on loss to follow-up in 12% and 40%, respectively. Conclusions Data collection is insufficient in hearing screening and even more so in vision screening: data essential for cost-effectiveness comparison could not be reported from most countries. When collection takes place, this is mostly at a local level for quality assurance or accountability, and data are often not accessible. The resulting inability to compare cost-effectiveness among screening programmes perpetuates their diversity and inefficiency

Auditory event-related potentials and mismatch negativity in children with hearing loss using hearing aids or cochlear implants - A three-year follow-up study

Objectives: The primary aim was to examine how event-related potentials (ERPs) and mismatch negativity (MMN) change and develop over time among children with hearing loss (HL) using hearing aids (HAs) or cochlear implants (CIs). Children with normal hearing (NH) were tested as a reference group. Methods: This three-year follow-up study included 13 children with sensorineural HL (SNHL); 7 children using bilateral HAs and 6 children using CIs; and 10 children with NH as a reference group. ERPs were recorded at baseline and after three years. At time for the original study the children were approximately 5-8 years old and at the follow-up study 8-11 years old. ERP recordings and data processing were identical in both sessions. A standard stimulus alternated with five different deviants (gap, intensity, pitch, location and duration), presented in a pseudorandom sequence, thus following the multi-feature paradigm, Optimum-1. MMN was calculated from the average ERP of each deviant minus the standard stimuli. Repeated measures ANOVA was used for the statistical analyses and the results were based on samples within a specific time interval; 80-224 ms. Results: There was a statistically significant difference in the obligatory responses between the NH and HA groups at baseline, but this difference disappeared after three years in our follow-up study. The children with HA also showed a significant difference in mean ERP at baseline compared to follow-up, and significant differences between the deviants at follow-up but not at baseline. This suggests an improvement over time among the children with HAs. On the other hand, the children with CIs did not differ from the NH children at baseline, but after three years their mean ERP was significantly lower compared to both the children with HA and NH, indicating a reduced development of the central auditory system in this age span among the children with CIs. Regarding MMN, there was an interaction between the duration deviant and time for the children with HA, also indicating a possible improvement over time among the HA children. Conclusions: This three-year follow-up study shows neurophysiological differences between children with HL and children with NH. The results suggest a delay in the central auditory processing among the HA children compared to children with NH, but a possible catch-up, over time, and this potential may be worth to be utilized. Regarding the CI children, similar improvement in this age span is missing, meaning there are differences between the subgroups of children with HL, i.e. the children with HAs vs. CIs. The results highlight the importance of distinguishing between subgroups of children with HL in further research.Funding Agencies|Swedish Research Council for Working Life and Social Sciences (Forskningsradet for Arbetsliv och Social Vetenskap)</p

Development of a TOOLKIT comprising of a cost-effectiveness modelling framework and strategy plan for implementation

We developed a TOOLKIT, consisting of a web-based microsimulation model as a generic tool for policymakers, and a manual for implementation or modification of child vision and hearing screening programmes. The document describes the model which can be accessed at https://miscan.euscreen.org

Development of cognitive and reading skills in deaf children with CIs

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Manual for implementation or modification of child vision and hearing screening programmes

The EUSCREEN study aimed to compare vision and hearing screening programmes for children in all EU states by using a cost-effectiveness model. The cost-effectiveness model predicts the most cost-effective and affordable way to screen children in each country, given the local circumstances. Representatives of countries in Europe were asked to provide detailed data on the following domains: demography, the general background of screening systems, existing screening systems, coverage/attendance, tests used, follow-up/diagnosis, treatment, benefits and adverse effects. Paediatric ophthalmologists, paediatric otolaryngologists, audiologists and professionals who organise and perform screening in each country were invited to participate in the study and report on the state of screening in their country. An extensive, detailed questionnaire was developed for that purpose. Screening programmes have been tested in the county of Cluj in Romania for vision, and in three counties in Albania for hearing screening. This manual for implementation or modification of child vision and hearing screening programmes was developed by detailed tracking, and from identified requisites, facilitators and barriers. The cost-effectiveness model and this manual for implementation will assist healthcare providers and policy makers worldwide in their decisions to introduce or modify vision and hearing screening programmes, and increase effectiveness, efficiency and equity of child healthcare. This manual is an interactive, web-based document, but it can also be downloaded as a single pdf file (1.62 MB)

Sex-Dependent Aggregation of Tinnitus in Swedish Families

Twin and adoption studies point towards a genetic contribution to tinnitus; however, how the genetic risk applies to different forms of tinnitus is poorly understood. Here, we perform a familial aggregation study and determine the relative recurrence risk for tinnitus in siblings (lambda s). Four different Swedish studies (N = 186,598) were used to estimate the prevalence of self-reported bilateral, unilateral, constant, and severe tinnitus in the general population and we defined whether these 4 different forms of tinnitus segregate in families from the Swedish Tinnitus Outreach Project (STOP, N = 2305). We implemented a percentile bootstrap approach to provide accurate estimates and confidence intervals for lambda s. We reveal a significant lambda s for all types of tinnitus, the highest found being 7.27 (95% CI (5.56-9.07)) for severe tinnitus, with a higher susceptibility in women (10.25; 95% CI (7.14-13.61)) than in men (5.03; 95% CI (3.22-7.01)), suggesting that severity may be the most genetically influenced trait in tinnitus in a sex-dependent manner. Our findings strongly support the notion that genetic factors impact on the development of tinnitus, more so for severe tinnitus. These findings highlight the importance of considering tinnitus severity and sex in the design of large genetic studies to optimize diagnostic approaches and ultimately improve therapeutic interventions

Sexual dimorphism in the familial aggregation of tinnitus

Twin and adoption studies point towards a genetic contribution to tinnitus; however, how the genetic risk applies to different forms of tinnitus is poorly understood. Here, we perform a familial aggregation study and determine the relative recurrence risk for tinnitus in siblings (λs). Four different Swedish studies (N = 186,598) were used to estimate the prevalence of self-reported bilateral, unilateral, constant, and severe tinnitus in the general population and we defined whether these 4 different forms of tinnitus segregate in families from the Swedish Tinnitus Outreach Project (STOP, N = 2305). We implemented a percentile bootstrap approach to provide accurate estimates and confidence intervals for λs. We reveal a significant λs for all types of tinnitus, the highest found being 7.27 (95% CI (5.56–9.07)) for severe tinnitus, with a higher susceptibility in women (10.25; 95% CI (7.14–13.61)) than in men (5.03; 95% CI (3.22–7.01)), suggesting that severity may be the most genetically influenced trait in tinnitus in a sex-dependent manner. Our findings strongly support the notion that genetic factors impact on the development of tinnitus, more so for severe tinnitus. These findings highlight the importance of considering tinnitus severity and sex in the design of large genetic studies to optimize diagnostic approaches and ultimately improve therapeutic interventions