Tinnitus emerging in the context of a COVID-19 infection seems not to differ in its characteristics from tinnitus unrelated to COVID-19.

Background and aim: COVID-19 is a respiratory disease caused by the new coronavirus SARS-CoV-2, for which the first cases were reported in China, by December 2019. The spectrum of clinical presentations is wide, ranging from asymptomatic cases to a severe acute respiratory syndrome, sometimes with multiple systems involvement. Viral infections, including those related to respiratory virus, may cause hearing loss and, by extent, considering its pathophysiology, tinnitus. A systematic review on inner ear related symptoms in patients with COVID-19 reported 4.5% occurrence rate of tinnitus, with high variance of prevalence between the studies. Our aim is to further explore the relationship between COVID-19 and tinnitus. For this purpose we analyzed a sample of people who had suffered from a COVID-19 infection in the city of Volta Redonda, Brazil. In detail, we compared those with new onset tinnitus during or after the COVID-19 infection with those without tinnitus and those with tinnitus onset before the COVID-19 infection. Methods: Fifty-seven patients over 18 years old and previously diagnosed with COVID-19 confirmed by a RT-PCR test were included. Patients were subdivided in three groups: no tinnitus (NT), tinnitus that already existed before COVID-19 (chronic tinnitus, CT) and tinnitus that arose during or after COVID-19 (post-COVID-19 tinnitus, PCT). Data concerning COVID-19 symptoms, drugs prescribed for COVID-19, tinnitus characteristics, comorbidities and other otological symptoms were collected. For all the patients, tonal audiometry and otoacoustic emissions were performed. Tinnitus patients fulfilled the Tinnitus Handicap Inventory (THI) and visual-analog scales (VAS) for loudness and distress. Patients with CT answered a simple question about the worsening of their tinnitus after COVID-19. Results: PCT was reported by 19.3% of the patients, while 22.8% reported CT. No statistical difference was found between CT and PCT concerning hearing function, tinnitus characteristics and tinnitus distress. There was also no statistically significant difference between PCT and NT with respect to COVID-19 symptoms and pharmacological COVID-19 treatment. Patients with CT reported worsening of their tinnitus after COVID-19. Conclusion: As with other viral infections, inner ear symptoms may be associated with COVID-19. In our sample patients with tinnitus onset before COVID-19 and those with tinnitus onset during or after COVID-19 did not differ significantly in their clinical characteristics and their hearing function, suggesting that tinnitus occurring in the context of a COVID-19 infection is not related to a unique pathophysiological mechanism. The comparison of COVID-19 patients, who developed tinnitus with those who did not develop tinnitus did not reveal any differences in COVID-19 symptoms or COVID-19 treatment. Thus, there was no hint, that a specific expression of COVID-19 is closely related to post COVID-19 tinnitus onset. Although some drugs used to treat tinnitus are known to damage the inner ear cells (especially hydroxychloroquine), we did not see any relationship between the intake of these drugs and tinnitus onset, eventually due to the short prescription time and low doses. Among those patients who had tinnitus before COVID-19 30,8% reported worsening after COVID-19. Overall, tinnitus emerging in the context of a COVID-19 infection seems not to differ from tinnitus unrelated to COVID-19. For further exploring the relationship of tinnitus and COVID-19, large population based studies are warranted.

Tinnitus Treatment with Oxytocin: A Pilot Study.

INTRODUCTION: Tinnitus is the perception of sound in the absence of an external stimulus. It is a frequent condition for which there is as yet no pharmacological treatment approved. Auditory and non-auditory pathways are involved in tinnitus' pathophysiology. Oxytocin is a neurohormone and eventual neurotransmitter that plays a complex role in social cognition and behavior. OBJECTIVE: To evaluate the potential of oxytocin as a tinnitus treatment. STUDY DESIGN: Two studies were performed. Study 1 was a long-term open pilot study, while study 2 investigated short-term effects with a double-blinded placebo-controlled cross-over study. SETTING: Ambulatory ENT care. SUBJECTS AND METHOD: In study 1, 15 patients were investigated over a 10-week period in an open pilot study. In study 2, 16 patients were included in a placebo-controlled crossover trial to investigate short-term effects following a single dose. RESULTS: For the long-term study (study 1), analysis of variance revealed a significant decrease in tinnitus sensation, both for the Tinnitus Handicap Inventory and Clinical Global Impression (CGI). Also, the short-term effects in study 2 revealed a significant reduction of tinnitus because of the oxytocin nasal spray as measured with the Visual Analog Scale and the CGI Scale. CONCLUSION: These preliminary studies demonstrated that oxytocin may represent a helpful tool for treating tinnitus and further larger controlled studies are warranted.

Tinnitus assessment by means of standardized self-report questionnaires: psychometric properties of the Tinnitus Questionnaire (TQ), the Tinnitus Handicap Inventory (THI), and their short versions in an international and multi-lingual sample.

BACKGROUND: Tinnitus research in an international context requires standardized and validated questionnaires in different languages. The aim of the present set of analyses was the reassessment of basic psychometric properties according to classical test theory of self-report instruments that are being used within the multicentre Tinnitus Research Initiative (TRI) database project. METHODS: 1318 patients of the TRI Database were eligible for the analyses. The basic psychometric properties reliability, validity, and sensitivity of Tinnitus Handicap Inventory (THI), Tinnitus Questionnaire (TQ) and Tinnitus Beeinträchtigungs Fragebogen (i.e., Tinnitus Impairment Questionnaire, TBF-12) were assessed by the use of Cronbach's alpha, corrected item-total correlations, correlation coefficients and standardized response means. RESULTS: Throughout the languages, all questionnaires showed high internal consistencies (Cronbach's alpha > 0.79) and solid item-total correlations, as well as high correlations among themselves (around 0.8) and in combination with the self-reported tinnitus severity. However, some paradoxical correlations between individual items of the TBF-12, constructed as a shortform of the THI, and the corresponding THI-items were seen. Standardized Response Means (SRM) were low if tinnitus did not change, and between 0.3 and 1.09 for improved or worsened tinnitus complaints, indicating the sensitivity of the measures. CONCLUSIONS: All investigated instruments have high internal consistency, high convergence and discriminant validity and good change sensitivity in an unselected large multinational clinical sample and thus appear appropriate to evaluate the effects of tinnitus treatments in a cross-cultural context.

Tinnitus: network pathophysiology-network pharmacology.

Tinnitus, the phantom perception of sound, is a prevalent disorder. One in 10 adults has clinically significant subjective tinnitus, and for one in 100, tinnitus severely affects their quality of life. Despite the significant unmet clinical need for a safe and effective drug targeting tinnitus relief, there is currently not a single Food and Drug Administration (FDA)-approved drug on the market. The search for drugs that target tinnitus is hampered by the lack of a deep knowledge of the underlying neural substrates of this pathology. Recent studies are increasingly demonstrating that, as described for other central nervous system (CNS) disorders, tinnitus is a pathology of brain networks. The application of graph theoretical analysis to brain networks has recently provided new information concerning their topology, their robustness and their vulnerability to attacks. Moreover, the philosophy behind drug design and pharmacotherapy in CNS pathologies is changing from that of "magic bullets" that target individual chemoreceptors or "disease-causing genes" into that of "magic shotguns," "promiscuous" or "dirty drugs" that target "disease-causing networks," also known as network pharmacology. In the present work we provide some insight into how this knowledge could be applied to tinnitus pathophysiology and pharmacotherapy.

Pharmacological approaches to the treatment of tinnitus.

Tinnitus is the conscious perception of a phantom sound in the absence of an external source. For 1 in 100 of the general population, the condition severely affects quality of life. In spite of the fact that the market for a drug indicated for tinnitus relief is huge, there are still no FDA-approved drugs, and the quest for a tinnitus-targeted compound faces important challenges. A wide variety of drugs have been used off-label to treat tinnitus sufferers, with limited but significant effects in subsets of patients. If the compounds being developed at present by the pharmaceutical industry finally reach the market, they will establish a turning point in the treatment of this pathology.

Tinnitus treatment with piribedil guided by electrocochleography and acoustic otoemissions.

INTRODUCTION: Tinnitus is a frequent disorder and very difficult to treat. Both animal studies and clinical observations suggest that dopaminergic substances might have potential for the treatment of tinnitus. Here, we investigated the dopamine agonist piribedil for the treatment of chronic tinnitus. In all participants, we performed audiometry, electrocochleography (ECoG), and otoacoustic emissions before treatment began. OBJECTIVE: To assess the efficacy and safety of the dopaminergic drug piribedil for the treatment of tinnitus and to evaluate whether ECoG and acoustic otoemissions might be useful for predicting treatment response. STUDY DESIGN: Prospective randomized double-blind crossover study. SUBJECTS AND METHOD: One hundred patients with tinnitus were randomized into a double-blind, placebo-controlled, prospective crossover study. All patients underwent distortion product acoustic otoemissions with and without contralateral suppression and ECoG. Patients received 50 mg piribedil and placebo for 90 days each, separated by a 30-day washout period. Treatment effects were assessed by using the Tinnitus Handicap Inventory and a visual analog scale. Fifty-six patients completed the trial. RESULTS: There was no significant improvement of Tinnitus Handicap Inventory and visual analog scale score after piribedil treatment as compared with placebo. However, results were characterized by high interindividual variability. Post hoc analysis of piribedil effects revealed that piribedil treatment responders differed from nonresponders by the occurrence of a double peak in the ECoG. In addition, normal distortion product acoustic otoemission suppression patterns indicated better treatment response with piribedil. The incidence of side effects during piribedil treatment was 23.3%, leading to interruption of treatment in all cases. CONCLUSION: Piribedil is not superior to placebo in the treatment of tinnitus. Piribedil treatment responders differed from nonresponders by specific findings in the ECoG and in the distortion product acoustic otoacoustic emissions, suggesting a beneficial effect of piribedil in an electrophysiologically characterized tinnitus subgroup.