Onset Of Tinnitus Research Articles

Animal Behavioral Models of Tinnitus

The pathophysiology of tinnitus is poorly understood and treatments are often unsuccessful. A number of animal models have been developed in order to gain a better understanding of tinnitus. A great deal has been learned from these models regarding the electrophysiological and neuroanatomical correlates of tinnitus following exposure to noise or ototoxic drugs. Reliable behavioral data is important for determining whether such electrophysiological or neuroanatomical changes are indeed related to tinnitus. Of the many documented tinnitus animal behavioral paradigms, the acoustic startle reflex had been proposed as a simple method to identify the presence or absence of tinnitus. Several behavioral models based on conditioned response suppression paradigms have also been developed. In addition to determining the presence or absence of tinnitus, some of the behavioral paradigms have provided signs of the onset, frequency, and intensity of tinnitus in animals. Although none of these behavioral models have been proved to be a perfect model, these studies provide useful information on understanding the neural mechanisms underlying tinnitus.

Therapeutic effect of sildenafil on blast-induced tinnitus and auditory impairment

Blast-induced tinnitus, along with associated auditory impairment and traumatic brain injury, is a primary concern facing military service members. To search for treatment, we investigated the therapeutic effects of sildenafil, a phosphodiesterase-5 inhibitor, given its vasodilatory effects and evidence suggesting its beneficial effects on noise-induced hearing loss. Rats were subjected to three consecutive blast exposures at 22psi and were monitored for tinnitus using a gap-detection acoustic startle reflex paradigm. Hearing thresholds and detection were tested using auditory brainstem responses and prepulse inhibition, respectively. Blasted rats were either treated with sildenafil or tap water following blast exposure, while age-matched sham control rats were treated with sildenafil and no blast exposure. Our results showed that sildenafil did not effectively prevent acute tinnitus onset and hearing impairment. Instead, sildenafil significantly suppressed high-frequency tinnitus from 3 to 6weeks after blast exposure and reduced hearing impairment during the first week after blast exposure. Complex results were observed in the startle force data, where sildenafil-treated rats displayed significantly reduced startle force compared to the untreated blasted group, suggesting possible mitigation of traumatic brain injury and suppression of hyperacusis-like percepts. Taken together, sildenafil showed a therapeutic effect on blast-induced tinnitus and audiological impairment in a time-dependent manner. Other regimens such as higher dosage prior to blast exposure and combination with other treatments deserve further investigation to optimize the therapeutic effects.

Erratum to: Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus

Recent findings regarding differences in tinnitus-related neural activity according to onset age have raised a question on possible onset age-related differences in neural substrates of distress. Hence we collected quantitative electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29 early-onset tinnitus (EOT) (mean onset age 52.3 and 29.0 years, respectively) participants. According to the tinnitus questionnaire (TQ) score grade, LOTs were then subdivided into 13 high distress (HD; TQ grade 3 or 4) and 15 low distress (LD; TQ grade 1 or 2), while EOTs into 14 HD and 15 LD. Compared to the EOT group, the LOT group demonstrated increased qEEG source-localized activity and functional connectivity primarily in the anterior cingulate cortex (ACC) and parahippocampus. In subgroup comparisons, the ACC was activated more in HD-LOT participants than in LD-LOT participants for the beta 1, beta 2 and gamma frequency bands, while the left orbitofrontal cortex and left dorsolateral prefrontal cortex were activated more in HD-EOT than in LD-EOT for the delta/beta and gamma frequency bands, respectively. Even with the same amount of tinnitus-related distress level, responsible neural substrates are different according to the onset age. These differences may be important for exploring different target areas of treatment according to tinnitus onset age, as well as for conducting similar studies on other pathologies, such as depression or pain.

Tinnitus among Serbian secondary school students in relation to their behavior and habits.

Although tinnitus is a very common symptom, risk factors related to behavior and habits have not been sufficiently investigated. As no investigation on this problem has been performed in Serbia, the aim of our study was to establish the prevalence of tinnitus among Serbian adolescents and to investigate the relationship between their behavior and habits and tinnitus. This investigation was designed as a cross-sectional interview study among secondary school students in Belgrade, Serbia (277 boys and 494 girls). An anonymous questionnaire was self-administered at classes. The investigated variables were: The presence of tinnitus, sources of noise, night outs at noisy places, use of personal music players, smoking, second hand smoke (SHS), substance abuse, coffee and alcohol consumption. Spearman's rank-order correlations and multiple logistic regressions were performed with variables related to behavior and habits as independent ones and tinnitus as a dichotomized dependent variable. Tinnitus was reported by 99 students (12.8%), more frequently among girls compared with boys (P = 0.009). Multivariate logistic regression analysis in boys revealed a significant independent effect of a regular drug abuse on the onset of tinnitus. The chances of tinnitus were 13 times higher among drug addicts compared with non-drug users (odds ratio [OR] and 95% confidence interval [CI] for tinnitus = 13.072; 1.335-127.946). In girls, the significant independent effect on tinnitus was found for daily duration of exposure to SHS (OR and 95% CI for tinnitus = 1.328; 1.073-1.644 /per 2 hours of exposure/).

Effects of Tinnitus Duration and Concomitant Hearing Loss on the Cognitive-Behavioral Treatment Outcomes

Background and ObjectivesZZSeveral reports indicated that tinnitus treatment was influ enced by several factors including age of patients, concomitant hearing loss, onset and duration of tinnitus, etc. The purpose of this study was to investigate the effects of the duration of tinnitus and the degree of hearing loss on the treatment outcomes. Subjects and MethodZZSeventy-two subjects with tinnitus were divided into several groups according to the duration of tinnitus and the degree of hearing loss. All subjects were treated by cognitive-behavioral treatment program in tinnitus clinic. Treatment effects were studied by Tinnitus Handicap Inventory (THI) and Visual Analogue Scale (VAS), which were used to measure the loudness, awareness, and annoyance of tinnitus. ResultsZZTHI and VAS scores were decreased significantly after the treatment. Tinnitus of 12 months or shorter duration showed greater improvement than those cases of longer than 12 months. The lower degree of hearing loss also showed greater improvement when compared with the greater degree of hearing loss. ConclusionZZTinnitus of shorter duration and milder hearing loss showed better prognosis: the results of this study may help in treatment counseling for tinnitus patients.

PReS-FINAL-2312: Cogan's syndrome: a diagnostic challenge. Report and review of the literature

Cogan's syndrome is a rare disorder of unknown origin characterized by inflammatory eye disease and vestibuloauditory symptoms. Usually syndrome affects young adults but cases in children have been reported. Typically, patients suffer from interstitial keratitis and sudden onset of tinnitus and hearing loss.

Onset-related differences in neural substrates of tinnitus-related distress: the anterior cingulate cortex in late-onset tinnitus, and the frontal cortex in early-onset tinnitus

Recent findings regarding differences in tinnitus-related neural activity according to onset age have raised a question on possible onset age-related differences in neural substrates of distress. Hence we collected quantitative electroencephalography (qEEG) findings of 28 late-onset tinnitus (LOT) and 29 early-onset tinnitus (EOT) (mean onset age 52.3 and 29.0 years, respectively) participants. According to the tinnitus questionnaire (TQ) score grade, LOTs were then subdivided into 13 high distress (HD; TQ grade 3 or 4) and 15 low distress (LD; TQ grade 1 or 2), while EOTs into 14 HD and 15 LD. Compared to the EOT group, the LOT group demonstrated increased qEEG source-localized activity and functional connectivity primarily in the anterior cingulate cortex (ACC) and parahippocampus. In subgroup comparisons, the ACC was activated more in HD-LOT participants than in LD-LOT participants for the beta 1, beta 2 and gamma frequency bands, while the left orbitofrontal cortex and left dorsolateral prefrontal cortex were activated more in HD-EOT than in LD-EOT for the delta/beta and gamma frequency bands, respectively. Even with the same amount of tinnitus-related distress level, responsible neural substrates are different according to the onset age. These differences may be important for exploring different target areas of treatment according to tinnitus onset age, as well as for conducting similar studies on other pathologies, such as depression or pain.

Correlation of Tinnitus Loudness and Onset Duration with Audiological Profile Indicating Variation in Prognosis

Purpose. Subjective tinnitus has different forms and degrees of severity. Many studies in the literature have assessed psychoacoustic characteristics of tinnitus but hardly any of them had focused on the association of audiological profile with onset duration and loudness perception. The aim of this study was to evaluate existence of any association between tinnitus loudness/onset duration and audiological profile to explain differences in prognosis. Method. Study design was prospective. The sample consisted of 26 subjects having tinnitus, which was divided into tinnitus and nontinnitus ears. Audiological profile included pure-tone audiometry, speech audiometry, tympanometry, acoustic reflex test, and auditory evoked potentials (early and middle latency). Unpaired t-test was applied to compare two subgroups. Correlation and association between tinnitus onset duration/loudness perception and audiological profile were also assessed by calculating Spearman's coefficient and Fischer exact value. Results. The two subgroups had significant differences for pure-tone and speech audiometry hearing thresholds. A significant association was observed between the high frequency/extended high frequency and tinnitus loudness/onset duration. Conclusion. The changes in hearing thresholds and auditory pathway are associated with an increase in tinnitus loudness and its onset duration. This knowledge would be helpful to differentiate between severity and chronicity of the patients for planning therapeutic management and predicting prognosis.

Clinical Efficacy and Safety of AM‐101 in the Treatment of Acute Tinntius

Objectives: Glutamate excitotoxicity following cochlear trauma can trigger aberrant excitation of the auditory neurons, resulting in tinnitus. AM-101, a small molecule NMDA receptor antagonist, has shown evidence of preventing onset of tinnitus in animal models of cochlear trauma after intratympanic delivery. We present the results of the European and U.S. phase II clinical trials. Methods: Three hundred and twenty subjects with persistent tinnitus were enrolled in a double blind placebo controlled trial of AM-101. Efficacy endpoints included change in subjective tinnitus loudness, annoyance, sleep difficulties, the THI-12 questionnaire, and minimum masking level and loudness match. A patient global impression of change assessed the change in tinnitus severity over the study duration. Results: A dose dependent and statistically significant improvement of tinnitus loudness, annoyance, sleep difficulties, and the THI-12 over placebo could be demonstrated in subjects with tinnitus following acute noise trauma or otitis media. The improvement was most pronounced in the AM-101 810 µg/mL treatment group and continued to increase to Day 90 of the study. In contrast, the subgroup of sudden hearing loss related tinnitus did not show an improvement in tinnitus. The study drug was well tolerated. Conclusions: The study established human proof of concept for application of AM-101 in the treatment of tinnitus arising from cochlear glutamate excitotoxicity. Local delivery of AM-101 in a defined patient population in the acute stage of injury allows for a substantial and persisting attenuation of tinnitus with minimal systemic exposure and side effects.

How Much Additional Information Is Provided by High‐Frequency‐Audiometry in Tinnitus Patients with Normal Standard Audiogram?

Objectives: The majority of tinnitus patients suffer from hearing loss. However, a significant proportion of tinnitus patients show normal hearing thresholds in the standard pure tone audiogram (PTA, 125Hz – 8kHz). It has been argued that PTA is not sensitive for all forms of hearing impairment and the additional measurement of high frequencies (9 – 16 kHz) should complete the diagnostic set-up. Here we aimed to investigate whether the results of high frequency audiometry (HFA) provide relevant additional information in tinnitus patients with normal standard PTA. Methods: From the database of the Tinnitus Clinic of the University of Regensburg we identified 75 patients with normal hearing thresholds in the standard PTA. We then contrasted patients with normal and pathological HFA and compared these two groups with respect to tinnitus severity, laterality, duration, tinnitus pitch, the presentation of selected somatic symptoms, and triggers of tinnitus onset. Results: Patients with pathological HFA were significantly older and had higher scores on the Tinnitus Questionnaire and the Tinnitus Handicap Inventory in comparison to patients with normal HFA. Furthermore, there was an association of high frequency audiograms and the laterality of tinnitus: patients with left and bilateral tinnitus had more pronounced high frequency hearing loss in the left ear. Conclusions: In summary, our data indicate that in patients with normal hearing in standard PTA, some additional information is provided by HFA. The association between tinnitus laterality and asymmetry of HFA suggests a potential causal role for the high frequency hearing loss in tinnitus etiopathogenesis.

“Distressed aging”: the differences in brain activity between early- and late-onset tinnitus

Recent findings regarding different characteristics according to the age of tinnitus onset prompted us to conduct a study on the differences in tinnitus-related neural correlates between late-onset tinnitus (LOT; mean onset age, 60.4 years) and early-onset tinnitus (EOT; mean onset age, 29.7 years) groups. Hence, we collected quantitative electroencephalography findings of 29 participants with LOT and 30 with EOT, and from 59 controls. We then compared the results between the 2 groups and between the tinnitus groups and age- and sex-matched control groups using resting state electroencephalography source-localized activity and connectivity analyses. Compared with the EOT and older control groups, the LOT group demonstrated increased localized activity and functional connectivity in components of previously described tinnitus distress networks, and the default mode and intrinsic alertness networks, such as the prefrontal cortices, dorsal anterior cingulate cortex, and insula. The current findings of intrinsic differences in tinnitus-related neural activity between the LOT and EOT groups might be applicable for planning individualized treatment modalities according to age of onset. Moreover, differences with regard to the age of tinnitus onset might be a milestone for future studies on onset-related differences in other similar pathologies, such as pain or depression.

Pulsatile Tinnitus with a Dural Arterio-Venous Fistula Diagnosed by Computed Tomography-Angiography

A 43 year-old female patient suffered the sudden onset of pulsatile tinnitus in the left ear 2 months ago. The tinnitus did not subside spontaneously and remained unchanged. The patient had no history of head trauma or surgery of the head and neck. The character of the tinnitus was pulsatile, and it was synchronous with the heart beat. Audiologic examinations were performed and all of the results were normal. Computed tomography with angiography was performed and evidence of an arterio-venous fistula (AVF) was found. 4-vessel angiography was performed to confirm the dural AVF between the external carotid artery and sigmoid sinus. Embolization of the feeder-vessels was done under a fluoroscope and 70% of the fistula flow was controlled after embolization and the tinnitus totally subsided during the embolization.

Ménière's disease: a reappraisal supported by a variable latency of symptoms and the MRI visualisation of endolymphatic hydrops

ObjectivesTo evaluate the onset of vertigo, hearing loss and tinnitus in Ménière's disease and the associated endolymphatic hydrops (EH) of the inner ear.DesignMulticentre evaluation of three patient groups.SettingsDisease-specific symptoms were...

Benign paroxysmal positional vertigo and tinnitus.

In our clinical experience, some of the patients affected by benign paroxysmal positional vertigo (BPPV) reported the onset of tinnitus shortly before or in association with the positional vertigo. The aim of this study was to describe the prevalence and the clinical patterns of tinnitus episodes which occurred in association with BPPV and to suggest possible interpretative hypotheses. 171 normal hearing patients affected by BPPV (50 males and 122 females; age range: 25-77 years; mean age 60.3 years ± 14.9) underwent pure tone audiometry, immittance test and a clinical vestibular evaluation before and after repositioning manoeuvers. Those suffering from tinnitus were also assessed using visual analogue scales and tinnitus handicap inventory. 19.3% of the patients reported the appearance of tinnitus concurrently with the onset of the positional vertigo. It was mostly unilateral, localized on the same ear as the BPPV, slight in intensity and intermittent. Tinnitus disappeared or decreased in all patients except two, either spontaneously, before performing the therapeutic manoeuvers, or shortly after. A possible vestibular origin of tinnitus determined by the detachment of macular debris into the ductus reuniens and cochlear duct is discussed.

An Unusual cause of Vertigo, Tinnitus, and Hyperacusis: Vogt-Koyanagi-Harada Syndrome

We describe the case of a 36-year-old woman with a history of vitiligo who presented with an insidious onset of neurologic, vestibular, ocular, and auditory symptoms. She had recently noted the onset of vertigo, tinnitus, and hypersensitivity to sound. Findings on audiometry were within normal limits, although the patient reported some auditory discomfort during the testing. The patient had a history of bilateral uveitis and peripheral neurologic symptoms. She was diagnosed with Vogt-Koyanagi-Harada (VKH) syndrome and started on corticosteroid therapy. Her neurologic, vestibular, ocular, and auditory symptoms resolved. VKH syndrome is an uncommon cause of vertigo and hearing loss, but it should be considered in the differential diagnosis of patients with autoimmunity-related inner ear symptoms.

Trauma-Associated Tinnitus: Audiological, Demographic and Clinical Characteristics

BackgroundTinnitus can result from different etiologies. Frequently, patients report the development of tinnitus after traumatic injuries. However, to which extent this specific etiologic factor plays a role for the phenomenology of tinnitus is still incompletely understood. Additionally, it remains a matter of debate whether the etiology of tinnitus constitutes a relevant criterion for defining tinnitus subtypes.ObjectiveBy investigating a worldwide sample of tinnitus patients derived from the Tinnitus Research Initiative (TRI) Database, we aimed to identify differences in demographic, clinical and audiological characteristics between tinnitus patients with and without preceding trauma.MaterialsA total of 1,604 patients were investigated. Assessment included demographic data, tinnitus related clinical data, audiological data, the Tinnitus Handicap Inventory, the Tinnitus Questionnaire, the Beck Depression Inventory, various numeric tinnitus rating scales, and the World Health Organisation Quality of Life Scale (WHOQoL).ResultsOur data clearly indicate differences between tinnitus patients with and without trauma at tinnitus onset. Patients suffering from trauma-associated tinnitus suffer from a higher mental burden than tinnitus patients presenting with phantom perceptions based on other or unknown etiologic factors. This is especially the case for patients with whiplash and head trauma. Patients with posttraumatic noise-related tinnitus experience more frequently hyperacousis, were younger, had longer tinnitus duration, and were more frequently of male gender.ConclusionsTrauma before tinnitus onset seems to represent a relevant criterion for subtypization of tinnitus. Patients with posttraumatic tinnitus may require specific diagnostic and therapeutic management. A more systematic and – at best - standardized assessment for hearing related sequelae of trauma is needed for a better understanding of the underlying pathophysiology and for developing more tailored treatment approaches as well.

Temporomandibular Joint Disorder Complaints in Tinnitus: Further Hints for a Putative Tinnitus Subtype

ObjectiveTinnitus is considered to be highly heterogeneous with respect to its etiology, its comorbidities and the response to specific interventions. Subtyping is recommended, but it remains to be determined which criteria are useful, since it has not yet been clearly demonstrated whether and to which extent etiologic factors, comorbid states and interventional response are related to each other and are thus applicable for subtyping tinnitus. Analyzing the Tinnitus Research Initiative Database we differentiated patients according to presence or absence of comorbid temporomandibular joint (TMJ) disorder complaints and compared the two groups with respect to etiologic factors.Methods1204 Tinnitus patients from the Tinnitus Research Initiative (TRI) Database with and without subjective TMJ complaints were compared with respect to demographic, tinnitus and audiological characteristics, questionnaires, and numeric ratings. Data were analysed according to a predefined statistical analysis plan.ResultsTinnitus patients with TMJ complaints (22% of the whole group) were significantly younger, had a lower age at tinnitus onset, and were more frequently female. They could modulate or mask their tinnitus more frequently by somatic maneuvers and by music or sound stimulation. Groups did not significantly differ for tinnitus duration, type of onset (gradual/abrupt), onset related events (whiplash etc.), character (pulsatile or not), hyperacusis, hearing impairment, tinnitus distress, depression, quality of life and subjective ratings (loudness etc.).ConclusionReplicating previous work in tinnitus patients with TMJ complaints, classical risk factors for tinnitus like older age and male gender are less relevant in tinnitus patients with TMJ complaints. By demonstrating group differences for modulation of tinnitus by movements and sounds our data further support the notion that tinnitus with TMJ complaints represents a subgroup of tinnitus with clinical features that are highly relevant for specific therapeutic management.

Delayed Onset of Papilledema in Cerebral Venous Sinus Thrombosis (CVST) (P07.257)

Objective: To present 2 cases of delayed onset papilledema and visual disturbance in CVST patients presenting initially with only headaches. Background The clinical presentations of CVST are variable, but the most common are headache (70-97%) and isolated intracranial hypertension (18-40%). Although 28-41% of patients have papilledema at presentation, it9s unusual to have delayed intracranial hypertension with papilledema after there9s sinus recanalization. Design/Methods: We report 2 CVST cases of worsening intracranial hypertension with visual symptoms and signs, despite improvement of thromboses on imaging. Results: 33-year-old male body builder with 2 months of worsening headaches had normal neurological exam. Contrast MR venogram showed superior sagittal sinus thrombosis. Investigations revealed myeloproliferative disorder with JAK-2 mutation, and antiphospholipid syndrome. Treated with heparin bridging to warfarin (INR2-3). Two months later, CT venogram showed no thrombus, but he developed visual obscurations, tinnitus, and new onset papilledema, peripheral field defects with normal visual acuity. Ten weeks later, he had worsening constrictive field deficits, with recurrence of thromboses in multiple sinuses. Visual field loss progressed on acetazolamide, so he had ventriculoperitoneal shunting, then aspirin and warfarin (INR3-3.5). Papilledema resolved and visual fields improved at 4months. 14-year-old girl had sudden onset headache, photophobia and vomiting after sneezing, and normal neurological exam. Contrast MR venogram showed right transverse sinus thrombosis. On contraceptive pill (estrogen & progestin), with MTHFR heterozygosity and elevated factor VIII. Received heparin then warfarin. Three weeks later, partial sinus recanalization, but she developed tinnitus, blurred vision and diplopia, with new onset severe papilledema, constrictive field deficits, partial left abducens nerve palsy, but normal visual acuity. Acetazolamide has stabilized papilledema and visual field defects at 10weeks. Conclusions: Clinicians need to remain vigilant in assessing for delayed onset papilledema and visual loss in CVST, even after anticoagulation and sinus recanalization. Follow up with serial quantitative perimetry rather than visual acuity is necessary. Disclosure: Dr. Wang has nothing to disclose. Dr. Matar has nothing to disclose. Dr. Allport has nothing to disclose.

A Case Report of Onset of Tinnitus Following Discontinuation of Antidepressant and a Review of the Literature

This case report describes a 46-year-old woman with long-standing episodic severe depression (ICD-10 code F33) who discontinued venlafaxine over a 4-week taper after taking the antidepressant for 8 years. Severe discontinuation syndrome was experienced. Panic and relapse of depression occurred 2 months after achieving discontinuation, and the development of tinnitus took place concurrently to the discontinuation. The experience of the tinnitus as a side effect of discontinuation is different from cases reported in the literature in which the tinnitus was experienced when the antidepressant was started and ceased when the antidepressant was stopped. Here, the patient experienced the tinnitus as a discontinuation symptom, and it persisted even after the antidepressant was reintroduced. A review of the literature on antidepressant discontinuation syndrome is also provided.

Internal-Carotid-Artery Dissection and Cranial-Nerve Palsies

A 45-year-old woman presented to the emergency department 3 days after the acute onset of severe dysphagia, breathy dysphonia, and earache and pulsatile tinnitus in the left ear. Her medical history was unremarkable. Physical examination revealed leftward deviation of the protruded tongue that was consistent with a lesion in cranial nerve XII, hypernasal speech and rightward deviation of the soft palate on phonation that was consistent with lesions in cranial nerves IX and X, and a paralyzed left vocal cord detected on laryngoscopic examination that was consistent with a lesion in cranial nerve X (see video). Axial magnetic resonance images . . .