Patients with unilateral tinnitus: Evaluation of high-frequency audiometry and ABR results

Authors

Abstract

Aim This study aimed to investigate the pathology of tinnitus by analyzing Auditory Brainstem Response (ABR) waves and Extended High-Frequency Audiometry (EHFA) in patients with unilateral tinnitus without clinically detectable hearing loss.
Materials and Methods In a retrospective case-control study, data from 48 patients with unilateral tinnitus were divided into two groups: ears with tinnitus and ears without tinnitus. ABR test results and EHFA test results were compared. The ABR test was applied in two different protocols, and the results were compared.
Results Revealing significant differences in ABR wave latencies and amplitudes between ears with and without tinnitus. Specifically, the latency of the wave I was prolonged, and the wave III and V amplitudes were reduced in ears with tinnitus. EHFA results showed a higher number of ears exceeding the hearing threshold in tinnitus ears, although no significant difference was observed between ears with and without tinnitus. Comparison of ABR results based on stimulus repetition rates revealed significant differences in most parameters.
Discussion The study emphasizes that distal pathologies of the 8th nerve should be investigated, and changes in ABR latencies despite normal hearing thresholds should be taken into consideration in terms of possible degeneration in the future. It also recommends specifying ABR stimulus repetition rates in research and applying EHFA in patients with unilateral tinnitus complaints to comprehensively assess tinnitus pathology.

Keywords

Introduction

Tinnitus is defined as the sensation of ringing in the ear or head in the absence of an acoustic stimulus. It affects approximately 10% of the global population. Although the majority of individuals with tinnitus exhibit some degree of hearing loss, there are instances where no clinically detectable hearing loss is present [1, 2, 3]. Nevertheless, this does not provide definitive evidence that individuals with tinnitus have unimpaired cochlear function. A number of theories have been put forth to explain this phenomenon, including the “hidden hearing loss” theory. Pure tone audiometry represents the most widely employed clinical hearing test. The human auditory system is capable of detecting sounds within the frequency range of 20-20,000 Hz. However, the conventional pure tone audiometry test is limited to a frequency range of 125-8,000 Hz. In contrast, EHFA can measure the hearing threshold at 10-20 kHz, which may be indicative of the early stages of cochlear damage [4]. Consequently, EHFA facilitates the early diagnosis and treatment of hearing disorders, thereby playing an important role in clinical audiology [5].
One potential mechanism that may elucidate the underlying pathophysiology of tinnitus is the presence of abnormal neural activity within the cochlear nerve. The persistence of tinnitus despite cochlear nerve interruption indicates that retrocochlear auditory pathways and auditory cortex pathology may be involved [6, 7, 8, 9]. Auditory brainstem response (ABR) testing can be employed to objectively evaluate the neural pathway activation between the cochlear nerve and the inferior colliculus, thus allowing for the assessment of retrocochlear pathology [10].
ABR tests are acoustically evoked signals that represent synchronized neural activation along neural pathways. It should be noted that ABR recordings are dependent on a number of variables, including sex, age, head size, and skull thickness [11]. In the majority of published studies, ABR results for individuals with and without tinnitus were matched according to these parameters. The use of poorly matched controls can often result in the generation of misleading results. A review of the literature revealed considerable variability in the methodology employed in studies investigating tinnitus. There was considerable inconsistency between studies with regard to the differences in amplitude and latency observed between the tinnitus patient group and the control group. The most detailed findings across studies were a longer latency and reduced amplitude of wave I in the normal hearing tinnitus groups compared with matched controls. However, it is important to note that the precision of wave I amplitude and latency measurements in the ABR is limited due to the bony protection of this recording [12]. In order to address the impact of individual variables and reduce heterogeneity, we conducted a direct comparison of ABR results and EHFA hearing thresholds between the tinnitus ear and the non-tinnitus ear within the same population. The objective of this study was to contribute to the understanding of both central and peripheral factors in tinnitus pathology.

Materials and Methods

Study Design and Population
This retrospective study was conducted from April to June 2023, using data from patients who presented with unilateral tinnitus at the ENT outpatient clinic of Ankara City Hospital between June 2020 and March 2024. A total of 48 patients meeting the inclusion criteria were identified.
Inclusion Criteria
Participants were adults aged 18–65 years with unilateral tinnitus and no history of clinically detectable hearing loss. All patients met the following criteria:
• Pure tone audiometry thresholds <25 dB HL across all frequencies (250–8,000 Hz)
• Normal acoustic reflex thresholds (70–100 dB SPL)
• Type A tympanogram
• Transient-evoked otoacoustic emissions recorded
• No vestibular, neurological, or psychological disorders
• No use of vestibulotoxic drugs
• Normal temporal MRI findings
Audiometric measurements
Patients with pure tone averages ≥25 dB HL at frequencies below 8,000 Hz were excluded. High-frequency audiometric thresholds at 9,000 Hz, 10,000 Hz, and 11,200 Hz were recorded and categorized into normal (<25 dB HL) or impaired (≥25 dB HL).
ABR Testing
ABR tests were conducted using Neurosoft Neuro-Audio equipment under two protocols:
• Protocol 1: Click stimuli at 70 dB nHL, 27.1/s, alternating
polarity.
• Protocol 2: Click stimuli at 70 dB nHL, 66.6/s, alternating
polarity.
Absolute latencies for waves I, III, and V, as well as interpeak latencies (I–III, III–V, I–V), were recorded.
Statistical Analysis
Data normality was assessed using the Kolmogorov–Smirnov test. Categorical variables were analyzed using Pearson’s Chi- square test, while parametric and non-parametric data were evaluated using independent t-tests, Mann–Whitney U tests, and Wilcoxon Signed Ranks tests, as appropriate. Correlations were determined using Spearman’s rho, and ROC curve analysis identified potential tinnitus predictors.
Ethical Approval
This study was approved by the Ethics Committee of Ankara City Hospital (Date: 2023-02-08, No: E1/3240/2023).

Results

Demographics
The study included 48 patients (19 women, 29 men) with a mean age of 50.92 ± 9.91 years. Tinnitus was reported in the left ear by 28 participants (58.3%) and in the right ear by 20 participants (41.7%).
ABR Protocol 1
Wave I latency was significantly prolonged in tinnitus ears compared to non-tinnitus ears (p = 0.012). Wave III and V amplitudes were significantly reduced in tinnitus ears (p < 0.05). However, interpeak latencies showed no significant differences (Table 1).
ABR Protocol 2
No significant differences were observed in any parameters between tinnitus and non-tinnitus ears (Table 1).
EHFA
High-frequency hearing thresholds at 9,000 Hz, 10,000 Hz, and 11,200 Hz showed no significant differences between tinnitus and non-tinnitus ears (Table 1).
Comparative Analysis of Protocols In tinnitus ears, wave III and V latencies were significantly longer in Protocol 2 compared to Protocol 1 (p < 0.05). Amplitude reductions were observed only for wave V in Protocol 2 (p = 0.002) (Table 2).
ROC Curve Analysis
Wave I latency (L1_P1) emerged as a significant predictor of tinnitus in Protocol 1 (p = 0.015). A latency >1.60 ms may indicate tinnitus with 63% sensitivity and 56% specificity (Table 3).

Discussion

The findings suggest that prolonged wave I latency in tinnitus patients may reflect early degenerative changes in the eighth cranial nerve, potentially serving as a precursor to hearing loss. While our study did not find evidence supporting cochlear synaptopathy, variations in ABR parameters highlight the importance of standardizing testing protocols. Larger studies are required to validate these preliminary findings and refine diagnostic criteria.
The primary objective was to examine the delay and amplitude of ABR waves in patients presenting with unilateral tinnitus by comparing them with the healthy ear, to ascertain whether ABR results are influenced by the repetition rate of the stimulus, and to identify the presence of hearing loss in the ear with tinnitus in EHFA. To this end, patients presenting with unilateral tinnitus were compared between the affected ear and the non-affected ear, with the aim of controlling for other potential confounding variables.
The outcomes of patients who underwent a click stimulus ABR test with varying stimulus repetition rates, as outlined in Protocols 1 (27.1/sec) and 2 (66.6/sec), were subjected to analysis. The measurements taken with the stimulus repetition rate for Protocol 1 revealed a significantly longer wave I latency in the ear with tinnitus (p = 0.012). Nevertheless, no significant difference was observed in the latencies of waves III and V. In the study conducted by Chen et al. [13], no significant difference was found in ABR wave latencies and amplitudes. In the study conducted by Kehrle et al. [14], although the wave latencies were within the normal range, the latencies of waves I, III, and V were found to be significantly longer in the tinnitus group. The results of the comparisons revealed a significant prolongation of wave I latency in the ear with tinnitus in the present study (p = 0.012).
This leads us to hypothesize that the etiology of tinnitus may be caused by pathologies related to the eighth nerve. Despite normal hearing thresholds at speaking frequencies, the observed difference in latencies can be attributed to the fact that degenerative changes in the nerve occur over time. This suggests that changes in the eighth nerve, which may result in hearing loss in the future, may be an early symptom in patients with tinnitus complaints.
In the study conducted by Roland Schaette et al. [15], a decrease in wave I amplitudes was observed in the tinnitus group, while no significant difference was observed in wave V amplitudes. The researchers posited that these findings could be explained by central gain theory, which postulates that the excitability of the central auditory pathways increases to compensate for the reduction in input from the auditory nerve resulting from hidden hearing loss. Consequently, they proposed that there is no alteration in wave V amplitudes while wave I amplitudes decline. However, the study did not analyze the latencies of the waves. In their study, Shim HJ et al. [16], found no significant difference in amplitudes and were therefore unable to support the theory of ‘hidden hearing loss’. Additionally, the authors of the study proposed that the subjects in Schaette’s study were not homogeneous, which could have influenced the results due to the presence of various confounding variables. A comparison of sound tolerance levels was conducted to test the increased central gain theory, yet no significant difference was identified between ears with tinnitus and ears without tinnitus. A comparison with the control group without tinnitus revealed a decrease in sound tolerance levels among the tinnitus patient group. It was proposed that this could be explained by the role of lateral olivocochlear efferents [17], which have the capacity to balance the activity of the cochlear nerve between the ears. In our study, as in Shim’s study, ears with tinnitus were compared with ears without tinnitus in the same subjects. No difference was found between the wave I amplitudes. In contrast, our study revealed a statistically significant reduction in wave III and wave V amplitudes in ears with tinnitus when assessed using Protocol 1. The measurements obtained with Protocol 2 did not yield any statistically significant differences, which aligns with the findings of Shim et al. [16].
In their study, the authors employed a protocol comprising a repetition rate of 13.3/sec and an intensity of 90 dB in their ABR measurements. The stimulus repetition rate is employed in the differential diagnosis of retrocochlear pathologies in order to distinguish them from normal responses and cochlear pathologies. As the stimulus repetition rate increases, the latencies of the waves increase. In cases of retrocochlear pathologies, this increase is more pronounced. Furthermore, higher stimulus repetition rates result in reduced wave amplitudes, leading to the progressive loss of waveform detail [18].The discrepancy in results between our study and that of Shim et al. [16] may be attributed to the significant differences observed between measurements taken with different protocols in the same patient group. In his review study, Milloy et al. [12] observed heterogenity in the data on this subject and recommended that further studies be included in the literature to determine standard protocols and eliminate this heterogeneity.
In the study conducted by Liberman et al. in 2016, it was found that the tinnitus group exhibited better hearing thresholds at high frequencies [19]. In the present study, a comparison of high-frequency hearing thresholds revealed no significant difference between ears with tinnitus and ears without tinnitus. Furthermore, the study conducted by Liberman et al. in 2017 revealed a correlation between high-frequency thresholds and SP/AP ratios in electrocochleography and identified a reduced incidence of cochlear synaptopathy in the tinnitus group [20]. This can be attributed to the fact that the degeneration of nerve fibers can take years to manifest and may require a significant period of time to induce alterations in the ABR. An additional potential explanation is that ABR may lack sufficient sensitivity to indicate synaptopathy, or that synaptopathy does not directly lead to the onset of tinnitus.
In conducting ROC-curve analysis on parameters that may serve as predictors of tinnitus, the ABR values L1_P1, A3_P1, A5_P1, and the A3_P1/A1_P ratio can be employed for Protocol 1. Upon performing logistic regression analysis among these parameters, it was determined that wave I latency (L1_P1) is the most valuable parameter in ABR performed with Protocol 1 (p = 0.020). If the wave I latency is above 1.60 ms and the patient does not have hearing loss between 250 and 8000 Hz, it can be posited that the patient may have tinnitus with a sensitivity of 63% and a specificity of 56%. These findings demonstrate the potential of this objective parameter in the detection of tinnitus, which is a subjective complaint. Further research is required, given the paucity of existing studies in this field.

Limitations

The study has a limited sample size and a retrospective design. Therefore, it doesn’t have longitudinal follow-up or correlation with patient outcomes. The lack of electrocochleography findings, the gold standard for assessing cochlear health, is a limiting factor in the standardization of variables. However, the selection of patients without cochlear pathology on MRI scans was intended to limit the impact of this limitation on the variables.

Conclusion

Prolonged wave I latencies in tinnitus patients with normal hearing suggest possible degenerative changes in the eighth nerve, indicating a potential early sign of future hearing loss. However, our study found no support for cochlear synaptopathy with increased central gain in tinnitus subjects with normal audiograms. There was no statistically significant difference in high-frequency hearing thresholds, but larger studies covering higher frequency thresholds are needed. Differences in ABR comparisons highlight the sensitivity of measurements to changes in stimulus repetition rates, prompting further research in comparing ABR models and repetition rates. While elongated wave I latency in ABR Protocol 1 may predict the presence of tinnitus with 63% sensitivity, larger patient series studies are necessary to confirm this marker’s validity.

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