Insights from the First International Conference on Hyperacusis: causes, evaluation, diagnosis and treatment.

The First International Conference on Hyperacusis gathered over 100 scientists and health care professionals in London, UK. Key conclusions from the conference included: (1) Hyperacusis is characterized by reduced tolerance of sound that has perceptual, psychological and social dimensions; (2) there is a growing awareness that children as well as adults experience symptoms of hyperacusis or misophonia; (3) the exact mechanisms that give rise to hyperacusis are not clear, but the available evidence suggests that functional changes within the central nervous system are important and in particular, hyperacusis may be related to increased gain in the central auditory pathways and to increased anxiety or emotional response to sound; (4) various counseling and sound therapy approaches seem beneficial in the management of hyperacusis, but the evidence base for these remains poor.

The neurophysiological approach to misophonia: Theory and treatment.

Clinical observations of hundreds of patients who exhibited decreased tolerance to sound showed that many of them could not be diagnosed as having hyperacusis when negative reactions to a sound depend only on its physical characteristics. In the majority of these patients, the physical characteristics of bothersome sounds were secondary, and patients were able to tolerate other sounds with levels higher than sounds bothersome for them. The dominant feature determining the presence and strength of negative reactions are specific to a given patient's patterns and meaning of bothersome sounds. Moreover, negative reactions frequently depend on the situation in which the offensive sound is presented or by whom it is produced. Importantly, physiological and emotional reactions to bothersome sounds are very similar (even identical) for both hyperacusis and misophonia, so reactions cannot be used to diagnose and differentiate them. To label this non-reported phenomenon, we coined the term misophonia in 2001. Incorporating clinical observations into the framework of knowledge of brain functions allowed us to propose a neurophysiological model for misophonia. The observation that the physical characterization of misophonic trigger was secondary and frequently irrelevant suggested that the auditory pathways are working in identical manner in people with as in without misophonia. Descriptions of negative reactions indicated that the limbic and sympathetic parts of the autonomic nervous systems are involved but without manifestations of general malfunction of these systems. Patients with misophonia could not control internal emotional reactions (even when fully realizing that these reactions are disproportionate to benign sounds evoking them) suggesting that subconscious, conditioned reflexes linking the auditory system with other systems in the brain are the core mechanisms of misophonia. Consequently, the strength of functional connections between various systems in the brain plays a dominant role in misophonia, and the functional properties of the individual systems may be perfectly within the norms. Based on the postulated model, we proposed a treatment for misophonia, focused on the extinction of conditioned reflexes linking the auditory system with other systems in the brain. Treatment consists of specific counseling and sound therapy. It has been used for over 20 years with a published success rate of 83%.

A data-driven approach to clinical decision support in tinnitus retraining therapy.

Background: Tinnitus, known as "ringing in the ears", is a widespread and frequently disabling hearing disorder. No pharmacological treatment exists, but clinical management techniques, such as tinnitus retraining therapy (TRT), prove effective in helping patients. Although effective, TRT is not widely offered, due to scarcity of expertise and complexity because of a high level of personalization. Within this study, a data-driven clinical decision support tool is proposed to guide clinicians in the delivery of TRT. Methods: This research proposes the formulation of data analytics models, based on supervised machine learning (ML) techniques, such as classification models and decision rules for diagnosis, and action rules for treatment to support the delivery of TRT. A knowledge-based framework for clinical decision support system (CDSS) is proposed as a UI-based Java application with embedded WEKA predictive models and Java Expert System Shell (JESS) rule engine with a pattern-matching algorithm for inference (Rete). The knowledge base is evaluated by the accuracy, coverage, and explainability of diagnostics predictions and treatment recommendations. Results: The ML methods were applied to a clinical dataset of tinnitus patients from the Tinnitus and Hyperacusis Center at Emory University School of Medicine, which describes 555 patients and 3,000 visits. The validated ML classification models for diagnosis and rules: association and actionable treatment patterns were embedded into the knowledge base of CDSS. The CDSS prototype was tested for accuracy and explainability of the decision support, with preliminary testing resulting in an average of 80% accuracy, satisfactory coverage, and explainability. Conclusions: The outcome is a validated prototype CDS system that is expected to facilitate the TRT practice.

Consensus Definition of Misophonia: A Delphi Study.

Misophonia is a disorder of decreased tolerance to specific sounds or their associated stimuli that has been characterized using different language and methodologies. The absence of a common understanding or foundational definition of misophonia hinders progress in research to understand the disorder and develop effective treatments for individuals suffering from misophonia. From June 2020 through January 2021, the authors conducted a study to determine whether a committee of experts with diverse expertise related to misophonia could develop a consensus definition of misophonia. An expert committee used a modified Delphi method to evaluate candidate definitional statements that were identified through a systematic review of the published literature. Over four rounds of iterative voting, revision, and exclusion, the committee made decisions to include, exclude, or revise these statements in the definition based on the currently available scientific and clinical evidence. A definitional statement was included in the final definition only after reaching consensus at 80% or more of the committee agreeing with its premise and phrasing. The results of this rigorous consensus-building process were compiled into a final definition of misophonia that is presented here. This definition will serve as an important step to bring cohesion to the growing field of researchers and clinicians who seek to better understand and support individuals experiencing misophonia.

A randomized, double-blind, placebo-controlled clinical trial to evaluate the efficacy and safety of neramexane in patients with moderate to severe subjective tinnitus.

BACKGROUND: Neramexane is a new substance that exhibits antagonistic properties at α9α10 cholinergic nicotinic receptors and N-methyl-D-aspartate receptors, suggesting potential efficacy in the treatment of tinnitus. METHODS: A total of 431 outpatients with moderate to severe subjective tinnitus (onset 3-18 months before screening) were assigned randomly to receive either placebo or neramexane mesylate (25 mg/day, 50 mg/day and 75 mg/day) for 16 weeks, with assessment at 4-week intervals. The primary (intention-to-treat) efficacy analysis was based on the change from baseline in Week 16 in the total score of the adapted German short version of the validated Tinnitus Handicap Inventory questionnaire (THI-12). RESULTS: Compared with placebo, the largest improvement was achieved in the 50 mg/d neramexane group, followed by the 75 mg/d neramexane group. This treatment difference did not reach statistical significance at the pre-defined endpoint in Week 16 (p = 0.098 for 50 mg/d; p = 0.289 for 75 mg/d neramexane), but consistent numerical superiority of both neramexane groups compared with placebo was observed. Four weeks after the end of treatment, THI-12 scores in the 50 mg/d group were significantly better than those of the controls. Secondary efficacy variables supported this trend, with p values of < 0.05 for the 50 mg/d neramexane group associated with the functional-communicational subscores of the THI-12 and the assessments of tinnitus annoyance and tinnitus impact on life as measured on an 11-point Likert-like scale. No relevant changes were observed for puretone threshold, for tinnitus pitch and loudness match, or for minimum masking levels. The 25 mg/d neramexane group did not differ from placebo. Neramexane was generally well tolerated and had no relevant influence on laboratory values, electrocardiography and vital signs. Dizziness was the most common adverse event and showed a clear dose-dependence. CONCLUSIONS: This study demonstrated the safety and tolerability of neramexane treatment in patients with moderate to severe tinnitus. The primary efficacy variable showed a trend towards improvement of tinnitus suffering in the medium- and high-dose neramexane groups. This finding is in line with consistent beneficial effects observed in secondary assessment variables. These results allow appropriate dose selection for further studies. TRIAL REGISTRATION: ClinicalTrials.gov NCT00405886.

Assessment of tinnitus-related impairments and disabilities using the German THI-12: sensitivity and stability of the scale over time.

OBJECTIVE: To evaluate the reliability, dimensionality, predictive validity, construct validity, and sensitivity to change of the THI-12 total and sub-scales as diagnostic aids to describe and quantify tinnitus-evoked reactions and evaluate treatment efficacy. DESIGN: Explorative analysis of the German tinnitus handicap inventory (THI-12) to assess potential sensitivity to tinnitus therapy in placebo-controlled randomized studies. Correlation analysis, including Cronbach's coefficient α and explorative common factor analysis (EFA), was conducted within and between assessments to demonstrate the construct validity, dimensionality, and factorial structure of the THI-12. STUDY SAMPLE: N = 618 patients suffering from subjective tinnitus who were to be screened to participate in a randomized, placebo-controlled, 16-week, longitudinal study. RESULTS: The THI-12 can reliably diagnose tinnitus-related impairments and disabilities and assess changes over time. The test-retest coefficient for neighboured visits was r > 0.69, the internal consistency of the THI-12 total score was α ≤ 0.79 and α ≤ 0.89 at subsequent visits. Predictability of THI-12 total score and overall variance increased with successive measurements. The three-factorial structure allowed for evaluation of factors that affect aspects of patients' health-related quality of life. CONCLUSIONS: The THI-12, with its three-factorial structure, is a simple, reliable, and valid instrument for the diagnosis and assessment of tinnitus and associated impairment over time.

Outcomes of clinical trial: tinnitus masking versus tinnitus retraining therapy.

A controlled clinical study was conducted to evaluate prospectively the clinical efficacy of tinnitus masking (TM) and tinnitus retraining therapy (TRT) in military veterans having clinically significant tinnitus. Qualifying patients were placed into the two groups in an alternating manner (to avoid selection bias), and treatment was administered at 0, 3, 6, 12, and 18 months. Outcomes of treatment were evaluated using three self-administered tinnitus questionnaires (Tinnitus Handicap Inventory, Tinnitus Handicap Questionnaire, Tinnitus Severity Index) and the verbally administered TRT interview forms. Findings are presented from the three written questionnaires, and from two of the interview questions (percentage time aware of, and annoyed by, tinnitus). Outcomes were analyzed on an intent-to-treat basis, using a multilevel modeling approach. Of the 123 patients enrolled, 118 were included in the analysis. Both groups showed significant declines (improvements) on these measures, with the TRT decline being significantly greater than for TM. The greater declines in TRT compared to TM occurred most strongly in patients who began treatment with a "very big" tinnitus problem. When patients began treatment with a "moderate" tinnitus problem, the benefits of TRT compared to TM were more modest.

Decreased sound tolerance: hyperacusis, misophonia, diplacousis, and polyacousis.

Definitions, potential mechanisms, and treatments for decreased sound tolerance, hyperacusis, misophonia, and diplacousis are presented with an emphasis on the associated physiologic and neurophysiological processes and principles. A distinction is made between subjects who experience these conditions versus patients who suffer from them. The role of the limbic and autonomic nervous systems and other brain systems involved in cases of bothersome decreased sound tolerance is stressed. The neurophysiological model of tinnitus is outlined with respect to how it may contribute to our understanding of these phenomena and their treatment.

Tinnitus retraining therapy for patients with tinnitus and decreased sound tolerance.

Our experience has revealed the following: (1) TRT is applicable for all types of tinnitus, as well as for decreased sound tolerance, with significant improvement of tinnitus occurring in over 80% of the cases, and at least equal success rate for decreased sound tolerance. (2) TRT can provide cure for decreased sound tolerance. (3) TRT does not require frequent clinic visits and has no side effects; however, (4) Special training of health providers involved in this treatment is required for this treatment to be effective.

Guide to conducting tinnitus retraining therapy initial and follow-up interviews.

Tinnitus Retraining Therapy (TRT) is a structured method of tinnitus treatment that has been performed since 1990. The TRT Initial Interview form was developed to guide clinicians in obtaining essential information from patients that would specify treatment needs. The TRT Follow-up Interview form is similar to the initial interview form and is designed to evaluate outcomes of treatment. The clinician administers these forms verbally. The forms have been used in a highly abbreviated format with the potential for inconsistent interview administration between examiners. This project was to expand the forms to provide specific wording for each question. The expanded forms are presented in this article, and the intent of each question is explained. Standardized administration of these interview forms will facilitate greater uniformity in the initial evaluation and outcomes analyses of patients treated with TRT.

Assessment of patients for treatment with tinnitus retraining therapy.

Clinical management for patients complaining of severe tinnitus has improved dramatically in the last 25 years. During that period of time, various methods of treatment have been introduced and are being used with varying degrees of success. One method that has received considerable attention is tinnitus retraining therapy (TRT). This method is being practiced by hundreds of clinicians worldwide, and retrospective clinical data indicate that TRT has been effective for the majority of patients. This article provides a guide for clinicians to evaluate their patients for treatment with TRT. Included in this guide is the expanded version of the TRT initial interview and specific instructions for the clinician administering the interview.

Tinnitus retraining therapy: a different view on tinnitus.

Tinnitus retraining therapy (TRT) is a method for treating tinnitus and decreased sound tolerance, based on the neurophysiological model of tinnitus. This model postulates involvement of the limbic and autonomic nervous systems in all cases of clinically significant tinnitus and points out the importance of both conscious and subconscious connections, which are governed by principles of conditioned reflexes. The treatments for tinnitus and misophonia are based on the concept of extinction of these reflexes, labeled as habituation. TRT aims at inducing changes in the mechanisms responsible for transferring signal (i.e., tinnitus, or external sound in the case of misophonia) from the auditory system to the limbic and autonomic nervous systems, and through this, remove signal-induced reactions without attempting to directly attenuate the tinnitus source or tinnitus/misophonia-evoked reactions. As such, TRT is effective for any type of tinnitus regardless of its etiology. TRT consists of: (1) counseling based on the neurophysiological model of tinnitus, and (2) sound therapy (with or without instrumentation). The main role of counseling is to reclassify tinnitus into the category of neutral stimuli. The role of sound therapy is to decrease the strength of the tinnitus signal. It is crucial to assess and treat tinnitus, decreased sound tolerance, and hearing loss simultaneously. Results from various groups have shown that TRT can be an effective method of treatment.