Abstract
Purpose
To explore the relationship between vestibular endolymphatic hydrops (EH) and prognosis in acute low-tone sensorineural hearing loss (ALHL) and to analyze the mediating role of cervical vestibular-evoked myogenic potentials (cVEMP).
Methods
A total of 53 ALHL patients were retrospectively enrolled and divided into good (n = 38) and poor (n = 15) prognosis groups based on clinical outcomes. Vestibular function (cVEMP), imaging findings (vestibular EH via MRI), and electrophysiological indicators were compared. Multivariate logistic regression identified prognostic factors, and ROC curves assessed predictive performance. A mediation model was established using regression analysis and the Bootstrap method.
Results
No significant differences were observed in baseline characteristics between the two groups (all P>0.05). The incidence of abnormal cVEMP was significantly higher in the poor prognosis group than in the good prognosis group (73.3% vs 31.6%, P=0.006), and the severity of vestibular EH was also markedly greater (P=0.004). Multivariate analysis demonstrated that the severity of vestibular EH (OR=0.251,P=0.009), cVEMP amplitude (OR=0.995,P=0.034), and abnormal cVEMP (OR=0.056, P=0.005) were independent risk factors for poor prognosis. ROC analysis revealed that vestibular EH had high predictive value (AUC=0.768). Mediation effect analysis showed that abnormal cVEMP exerted a mediating effect between vestibular EH and prognosis (indirect effect ab=-0.133, 95%CI: -0.318~-0.025, P=0.044), with a mediating proportion of 38.6%.
Conclusion
Vestibular EH is closely associated with ALHL prognosis, and this effect may be partially associated with cVEMP dysfunction. As a potential indicator linking structural abnormalities to functional outcomes, cVEMP holds potential clinical value for prognostic assessment in ALHL.
Keywords: Acute low-tone sensorineural hearing loss, Endolymphatic hydrops, MRI, Cervical vestibular-evoked myogenic potentials, Prognosis, Mediation analysis
Introduction
Acute low-tone sensorineural hearing loss (ALHL) is a specific subtype of sudden sensorineural hearing loss, mainly characterized by low-frequency hearing loss, and generally has a relatively favorable prognosis. However, some patients still experience incomplete hearing recovery, recurrent episodes, or even progression to Ménière’s disease, suggesting a close association with inner ear fluid dynamics disorders [1–3]. Endolymphatic hydrops (EH) is regarded as an important pathological basis for various inner ear diseases, characterized by abnormal accumulation of endolymph in the membranous labyrinth [4]. With the development of inner ear magnetic resonance imaging (MRI) using intravenous gadolinium contrast agents, EH can be visualized in vivo, providing an objective imaging basis for the study of inner ear diseases [5–7]. Recent studies have found that some ALHL patients present with cochlear or vestibular EH, which may represent an early manifestation of EH spectrum disorders [8–10].
Nevertheless, the clinical significance of EH in ALHL remains controversial. On the one hand, some studies have indicated that the presence and severity of EH are closely related to hearing prognosis [11–13]; on the other hand, other studies have failed to identify a consistent correlation [14]. An important reason for such heterogeneity is that MRI mainly reflects structural changes in the inner ear but provides limited evaluation of functional status. Therefore, relying solely on imaging indicators may be insufficient to fully elucidate the disease mechanism. Cervical vestibular-evoked myogenic potentials (cVEMP) is a non-invasive electrophysiological examination that can be used to evaluate saccular function and the integrity of the inferior vestibular nerve pathway [15]. Previous studies have shown that prolonged cVEMP latency, reduced amplitude, or absent response is closely associated with impaired vestibular function and exhibits certain sensitivity in EH-related diseases [16–18]. Notably, abnormal cVEMP can be detected even in patients without obvious vertigo symptoms, indicating that vestibular dysfunction may exist in the early stage of the disease [19].
Current studies on the relationship among EH, vestibular dysfunction, and clinical outcomes are mostly correlational analyses, lacking in-depth exploration of the underlying mechanistic pathways. At the cellular level, evidence from animal models suggests that EH may disrupt calcium homeostasis in vestibular hair cells, as demonstrated by Zhang et al., who found that Ca2+-ATPase activity was significantly reduced in the vestibular end organs of guinea pigs with experimental EH [20]. EH may not affect prognosis directly, but indirectly influences disease outcome by impairing vestibular function. However, this hypothesis has not been systematically verified. Therefore, based on multimodal data combined with inner ear MRI and cVEMP examination, this study systematically evaluates the relationship among vestibular EH, vestibular dysfunction, and clinical prognosis, and further explores the mediating mechanism of abnormal cVEMP between vestibular EH and prognosis.
Methods
Study design and subjects
This was a single-center retrospective observational study. Patients with unilateral ALHL who visited the Department of Otorhinolaryngology at Foshan Hospital of Traditional Chinese Medicine from April 2024 to December 2025 were enrolled.
Inclusion criteria: (1) Meeting the diagnostic criteria for ALHL: low-frequency hearing loss at 125, 250, and 500 Hz with relatively normal high-frequency hearing (≥ 2 kHz); (2) Onset duration ≤ 14 days; (3) Completion of pure tone audiometry, inner ear MRI, and cVEMP examination; (4) Complete clinical data available.
Exclusion criteria: (1) Previous history of vertigo; (2) Comorbidity with other neurological diseases that may affect hearing or vestibular function; (3) History of gadolinium contrast allergy or renal insufficiency; (4) Missing or unqualified MRI or electrophysiological data.
Pure tone audiometry
All patients underwent pure tone audiometry at initial diagnosis and 2 weeks after treatment (Grason-Stadler, Denmark; model: GSI Audiostar pro).Testing frequencies included 125, 250, 500, 1000, 2000, 4000, and 8000 Hz. Hearing thresholds at each frequency were recorded, and the low-frequency average hearing threshold (250, 500 Hz) and high-frequency average hearing threshold (2000, 4000 Hz) of the affected ear were calculated.Hearing recovery was defined as an improvement in low-frequency average hearing threshold of ≥ 10 dB or restoration to ≤ 20 dB HL after treatment. Tympanometry was performed using an immittance meter with a probe frequency of 226 Hz. Only tympanogram types were recorded to rule out middle ear diseases.
Inner ear magnetic resonance imaging
All patients underwent intravenous gadolinium-enhanced inner ear MRI within 2 weeks after onset (GE Discovery MR 750 W 3.0T; United Imaging uMR890 3.0T). Gadolinium contrast agent was intravenously administered at a dose of 0.2 mL/kg and a rate of 1.0 mL/s. Three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) scanning was performed 4 h after injection.Scanning parameters: repetition time 8000 ms, echo time 140 ms, inversion time 2250 ms, slice thickness 0.6 mm, matrix 320 × 320.
Two experienced radiologists independently reviewed images in a blinded manner to grade vestibular endolymphatic hydrops (EH). Discrepancies were resolved by consensus.Grading was performed according to the Nakashima classification:
Grade 0: no hydrops
Grade 1: saccular enlargement with normal utricle
Grade 2: saccular enlargement with mild utricular enlargement
Grade 3: marked enlargement of both saccule and utricle
Cervical vestibular-evoked myogenic potentials
All patients underwent cVEMP examination within 2 weeks after onset using an auditory evoked potential system (GN Otmetrics A/S, Denmark; model: ICS Chartr EP200). Stimulation parameters: 500 Hz tone burst, intensity 95 dB nHL, rate 5.1 times per second, 128 averages, band-pass filter 30–1500 Hz. Stimuli were delivered via insert earphones with 1.5-cycle rise/fall time, no plateau, and alternating polarity. Patients were placed in the supine position with the head elevated approximately 30° and turned to the contralateral side to maintain contraction of the sternocleidomastoid muscle. Surface electrodes were placed at the midpoint of the ipsilateral sternocleidomastoid muscle (active electrode), suprasternal fossa (reference electrode), and midforehead (ground electrode).Two runs of 128 trials were recorded per ear. The system automatically provided the average waveform of the two runs, and P1-N1 amplitude (µV) was calculated. A reliable cVEMP response was defined as reproducible P1-N1 waveforms in both runs.cVEMP abnormality was defined as absent waveform, P1 latency > 15 ms, N1 latency > 25 ms, or amplitude below the normal reference value (< 20 µV).Patients were classified into normal and abnormal groups according to the above criteria. In this study, cVEMP abnormality was mainly used as a functional indicator reflecting saccular dysfunction.
Treatment and prognosis evaluation
All enrolled patients received standardized treatment, including glucocorticoids, neurotrophic agents, and microcirculation-improving drugs. Glucocorticoid: Methylprednisolone injection 80 mg intravenously once daily for 4 days, then reduced to 40 mg intravenously once daily for a total course of 7 days. Neurotrophic drug: mecobalamin tablets 0.5 mg orally three times daily. Microcirculation-improving drugs: betahistine injection (20 mg intravenous infusion once daily) and ginkgo biloba extract injection (35 mg intravenous infusion once daily). Treatment decisions were made jointly by two otologists based on patients’ clinical characteristics and examination findings. No second-line treatments such as diuretics, intratympanic dexamethasone injection, antiviral agents, prostaglandins, vitamins, or hyperbaric oxygen were used.
Prognostic criteria [21]
Cure: hearing at the affected frequencies recovered to normal hearing level, the contralateral ear level, or the pre-onset hearing level; Marked improvement: low-frequency average hearing threshold improved by ≥ 30 dB; Effective improvement: low-frequency average hearing threshold improved by ≥ 15 dB but < 30 dB; Ineffective: low-frequency average hearing threshold improved by < 15 dB or deteriorated further. For statistical analysis, prognosis was dichotomized: Good prognosis (cure + marked improvement + effective improvement) and Poor prognosis (ineffective).
Statistical analysis
Statistical analyses were performed using R 4.3.0 and SPSS 29.0 software. For quantitative data, normality was tested using the Shapiro-Wilk test. Normally distributed data were expressed as mean ± standard deviation (x ± s) and compared between groups using independent-samples t-test. Non-normally distributed data were expressed as median (interquartile range) [M (Q1, Q3)] and compared using the Mann-Whitney U test.Categorical data were presented as number (percentage) and compared using the chi-square test or Fisher’s exact test. Multivariate logistic regression analysis was used to evaluate the independent predictive value of vestibular hydrops grade, cVEMP parameters, and cVEMP abnormality for prognosis. Variables were entered using the forward stepwise method based on the Akaike Information Criterion.Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration curves, and the Hosmer-Lemeshow test. The mediating effect of cVEMP abnormality between vestibular hydrops grade and prognosis was analyzed using the three-step regression method and Bootstrap mediation test (PROCESS macro Model 4). This mediation analysis was exploratory and intended to evaluate statistical associations rather than establish causal relationships. Mediation significance was determined if the 95% confidence interval of the indirect effect did not include 0.Mediation proportion was calculated as: (Indirect effect/Total effect) × 100%. All statistical tests were two-sided, and P < 0.05 was considered statistically significant.
Ethical statement
This study was approved by the Hospital Ethics Committee (Approval No. KY[2022]177). All patients provided written informed consent. The study was conducted in accordance with the principles of the Declaration of Helsinki.
Results
Demographic and clinical characteristics
A total of 53 patients with ALHL were enrolled in this study and divided into a good prognosis group (n = 38) and a poor prognosis group (n = 15) according to clinical efficacy. There were no statistically significant differences between the two groups in age, gender, chief complaints, past medical history, and other baseline characteristics (all P > 0.05), as shown in Table 1.
Table 1.
Demographic and clinical characteristics
| Variable | ALL (n = 53) | Poor prognosis (n = 15) | Good prognosis (n = 38) | Statistic | P |
|---|---|---|---|---|---|
| Sex | 0.956 | 0.328 | |||
| Male | 16 (30.2) | 6 (40.0) | 10 (26.3) | ||
| Female | 37 (69.8) | 9 (60.0) | 28 (73.7) | ||
| Age (years) | 38.34 ± 11.02 | 42.07 ± 11.20 | 36.87 ± 10.59 | 1.554 | 0.126 |
| Chief complaints | |||||
| Vertigo | 2.285 | 0.131 | |||
| No | 34 (64.2) | 12 (80.0) | 22 (57.9) | ||
| Yes | 19 (35.8) | 3 (20.00) | 16 (42.1) | ||
| Hearing loss | — | 1.000 | |||
| No | 2 (3.8) | 0 (0.00) | 2 (5.3) | ||
| Yes | 51 (96.2) | 15 (100.0) | 36 (94.7) | ||
| Tinnitus | 0.123 | 0.726 | |||
| No | 16 (30.2) | 4 (26.7) | 12 (31.6) | ||
| Yes | 37 (69.8) | 11 (73.3) | 26 (68.4) | ||
| Aural fullness | 0.015 | 0.902 | |||
| No | 17 (32.1) | 5 (33.3) | 12 (31.6) | ||
| Yes | 36 (67.9) | 10 (66.7) | 26 (68.4) | ||
| Nausea/vomiting | 0.051 | 0.822 | |||
| No | 45 (84.9) | 13 (86.7) | 32 (84.2) | ||
| Yes | 8 (15.1) | 2 (13.3) | 6 (15.8) | ||
| Past medical history | — | 0.519 | |||
| None | 45 (84.9) | 12 (80.0) | 33 (86.8) | ||
| Left sudden deafness | 1 (1.9) | 0 (0.0) | 1 (2.6) | ||
| Right sensorineural hearing loss | 1 (1.9) | 0 (0.0) | 1 (2.6) | ||
| Mixed hearing loss | 1 (1.9) | 1 (6.7) | 0 (0.0) | ||
| Other complications | 5 (9.4) | 2 (13.3) | 3 (7.9) |
Other complications: hypertension, hyperlipidemia, hyperthyroidism, bronchial asthma, sleep disorder
Comparison of vestibular function and electrophysiological parameters
The incidence of abnormal cVEMP was significantly higher in the poor prognosis group than in the good prognosis group (73.3% vs 31.6%, P = 0.006).The distribution of vestibular EH grade differed significantly between the two groups (P = 0.004), with a markedly higher proportion of moderate-to-severe hydrops (Grades 2–3) in the poor prognosis group (46.7% vs 10.5%). Regarding cVEMP parameters, both P1 latency and N1 latency were significantly prolonged in the poor prognosis group (P1: 18.59 ms vs 14.67 ms, P = 0.039; N1: 27.43 ms vs 23.84 ms, P = 0.007), whereas no significant difference was observed in N1-P1 amplitude (P = 0.084) (Tables 2, 3, 4, 5 and 6).
Table 2.
Comparison of vestibular function and electrophysiological parameters
| Variable | ALL (n = 53) | Poor prognosis (n = 15) | Good prognosis (n = 38) | Statistic | P |
|---|---|---|---|---|---|
| cVEMP response | 7.633 | 0.006 | |||
| Normal | 30 (56.6) | 4 (26.7) | 26 (68.4) | ||
| Abormal | 23 (43.4) | 11 (73.3) | 12 (31.6) | ||
| Vestibular hydrops grade | — | 0.004 | |||
| Grade 0 | 31 (58.5) | 4 (26.7) | 27 (71.1) | ||
| Grade 1 | 11 (20.8) | 4 (26.7) | 7 (18.4) | ||
| Grade 2 | 9 (17.0) | 5 (33.3) | 4 (10.6) | ||
| Grade 3 | 2 (3.8) | 2 (13.3) | 0 (0.0) | ||
| cVEMP parameters | |||||
| P1 (ms) | 14.83 (14.17, 18.62) | 18.59 (14.50, 21.83) | 14.67 (13.98, 17.17) | 2.073 | 0.039 |
| N1 (ms) | 24.50 (23.17, 26.47) | 27.43 (24.67, 31.00) | 23.84 (22.54, 24.94) | 2.715 | 0.007 |
| N1-P1 (uV) | 23.45 (14.11, 34.15) | 31.71 (18.04, 55.00) | 22.50 (9.88, 31.40) | 1.738 | 0.084 |
| SP latency (ms) | 0.90 (0.82, 1.03) | 0.90 (0.87, 1.05) | 0.90 (0.80, 1.00) | 0.632 | 0.533 |
| AP latency (ms) | 1.57 (1.50, 1.85) | 1.650 (1.52, 1.85) | 1.55 (1.50, 1.78) | 0.513 | 0.614 |
| SP/AP amplitude ratio | 0.49 ± 0.18 | 0.50 ± 0.24 | 0.48 ± 0.14 | 0.418 | 0.678 |
Table 3.
Multivariate logistic regression analysis of factors associated with favorable prognosis
| Predictor | β | SE | OR | 95% CI | P |
|---|---|---|---|---|---|
| P1 (ms) | 0.053 | 0.187 | 1.070 | 0.745–1.570 | 0.713 |
| N1 (ms) | −0.155 | 0.181 | 0.772 | 0.498–1.414 | 0.205 |
| N1-P1 (uV) | −0.049 | 0.021 | 0.995 | 0.910–0.994 | 0.034 |
| Vestibular hydrops grade | −1.438 | 0.506 | 0.251 | 0.075–0.646 | 0.009 |
| cVEMP response status | −2.784 | 1.028 | 0.056 | 0.005–0.364 | 0.005 |
Table 4.
ROC curve analysis of each index for poor prognosis
| Characteristic | AUC | Sensitivity (95% CI) | Specificity (95% CI) | Optimal cutoff |
|---|---|---|---|---|
| Vestibular hydrops grade | 0.768 | 0.73 (0.43–0.93) | 0.71 (0.55–0.95) | 1.00 |
| N1-P1 (uV) | 0.654 | 0.47 (0.25–1.00) | 0.92 (0.29–1.00) | 43.26 |
| Normal/abnormal vestibular potential | 0.678 | 0.87 (0.74–0.96) | 0.47 (0.21–0.76) | 1.00 |
Table 5.
Regression analysis results of mediating effect paths
| Variable | Model 1 | Model 2 | Model 3 | ||||||
|---|---|---|---|---|---|---|---|---|---|
| β | t | P | β | t | P | β | t | P | |
| Vestibular hydrops grade | −0.358 | −2.76 | 0.008 | 0.377 | 2.91 | 0.005 | −0.212 | −1.801 | 0.079 |
| Normal/abnormal vestibular potential | — | — | — | — | — | — | −0.382 | −2.86 | 0.007 |
| R2 | 0.128 | 0.142 | 0.265 | ||||||
| F | 7.620 | 8.47 | 9.19 | ||||||
Table 6.
Mediation effect analysis of vestibular EH grade, abnormal cVEMP, and prognosis
| Path | β | SE | 95% CI | P |
|---|---|---|---|---|
| a | 0.677 | 0.233 | 0.210–1.144 | 0.005 |
| b | −0.241 | 0.062 | −0.366 - −0.116 | < 0.001 |
| c | −0.345 | 0.118 | −0.581 - −0.109 | 0.005 |
| c’ | −0.212 | 0.118 | −0.450–0.026 | 0.079 |
| ab | −0.133 | 0.072 | −0.318 - −0.025 | 0.044 |
Path a: vestibular hydrops grade → abnormal cVEMP (β = 0.677, P = 0.005); Path b: abnormal cVEMP → prognosis (β = −0.241, P < 0.001); Path c: vestibular hydrops grade → prognosis (total effect, β = −0.345, P = 0.005); c’: direct effect; ab: indirect effect; mediating proportion = 38.6%
Multivariate logistic regression analysis
In logistic regression analysis, favorable prognosis was coded as 1 and poor prognosis as 0. Multivariate logistic regression analysis showed that vestibular EH grade, cVEMP amplitude, and cVEMP response status were independent influencing factors for favorable prognosis.Vestibular hydrops grade was significantly negatively associated with favorable prognosis (OR = 0.237, 95% CI: 0.075–0.582, P = 0.009), indicating that a higher hydrops grade predicted a greater risk of poor prognosis. N1-P1 amplitude was negatively correlated with favorable prognosis (OR = 0.952, P = 0.034), while abnormal cVEMP significantly increased the risk of favorable prognosis (OR = 0.062, P = 0.005) (Figs. 1, 2 and 3).
Fig. 1.
Forest plot of multivariate logistic regression. Note: Results of multivariate Logistic regression analysis of vestibular hydrops grade, cVEMP amplitude, and abnormal cVEMP for prognosis. OR values are represented by dots, and 95% confidence intervals by horizontal lines
Fig. 2.
ROC curves. Note: ROC curve analysis was performed to assess the predictive value of vestibular hydrops grade, N1-P1 amplitude, and vestibular potential status for poor prognosis. As shown in Fig. 2, vestibular hydrops grade demonstrated the highest AUC, indicating good discriminative ability. The optimal cutoff values for continuous variables were determined using the Youden index. Detailed AUC values, sensitivity, specificity, and cutoff points are summarized in Table 4
Fig. 3.
Mediation path diagram of vestibular EH grade affecting prognosis through abnormal cVEMP. Note: The diagram illustrates the mediating role of abnormal cVEMP in the relationship between vestibular hydrops grade and prognosis. Values shown are standardized regression coefficients (β). The path coefficient from vestibular hydrops grade to abnormal cVEMP is 0.677, and the direct effect coefficient from abnormal cVEMP to prognosis is −0.345. The indirect (mediated) effect was calculated using the bootstrap method. The model examines whether vestibular hydrops grade influences prognosis indirectly via its effect on cVEMP abnormality
ROC curve analysis
ROC curve analysis showed that vestibular EH grade had high predictive performance (AUC = 0.768), with better discriminative ability than cVEMP amplitude (AUC = 0.654) and cVEMP response status (AUC = 0.678). At the optimal cutoff value, vestibular hydrops grade had a sensitivity of 0.73 and specificity of 0.71, suggesting good discriminatory power for prognosis.
Pre-mediation path regression analysis
To further explore the mediating effect, regression analyses were performed on relevant variables.Vestibular EH grade was significantly associated with prognosis (β = -0.358, P = 0.008) and with abnormal cVEMP (β = 0.377, P = 0.005).After including both variables in the model, abnormal cVEMP remained significantly associated with prognosis (β = -0.382, P = 0.007), whereas the effect of vestibular hydrops grade was attenuated and no longer statistically significant (β = -0.212, P = 0.079).
Mediation effect analysis
Mediation effect analysis showed that abnormal cVEMP exerted a significant mediating effect between vestibular EH grade and prognosis. The total effect of vestibular hydrops grade on prognosis was significant (β = -0.345, P = 0.005). Path analysis revealed that vestibular hydrops grade significantly affected cVEMP response (β = 0.677, P = 0.005), and abnormal cVEMP further significantly influenced prognosis (β = -0.241, P < 0.001). After including the mediating variable, the direct effect of vestibular hydrops grade on prognosis was weakened and no longer significant (β = -0.212, P = 0.079), indicating a mediating effect. Bootstrap testing confirmed a significant indirect effect (ab = -0.133, P = 0.044), with the mediating effect accounting for 38.6% of the total effect.
Discussion
EH is considered a major potential pathological substrate of acute low-tone sensorineural hearing loss and Ménière’s disease, and the saccular structure is often involved in severe cases [22, 23]. In the present study, we observed a significant correlation between vestibular EH grade and abnormal cVEMP, both of which were independent influencing factors for disease prognosis. Further mediation effect analysis revealed that abnormal cVEMP may partially be involved in mediating the association between vestibular EH and prognosis, with a mediating proportion of 38.6%. This finding suggests that vestibular EH may be associated with poor prognosis partly through potential relationship with impaired saccular function.
In the prognostic analysis, the good prognosis group accounted for 73.6% and the poor prognosis group 26.4% in this study. Multivariate Logistic regression analysis showed that vestibular EH grade, cVEMP amplitude, and abnormal cVEMP status were all independent predictors of prognosis. ROC curve analysis further demonstrated that combined detection of the above three indicators may improve the accuracy of disease stratification, with an AUC as high as 0.933, and the predictive efficacy was significantly superior to single-index detection, suggesting the potential value multimodal assessment in risk stratification [4, 10]. Further analysis found that the incidence of abnormal cVEMP was significantly higher in the poor prognosis group, and its predictive efficacy was better than prolonged latency or reduced amplitude. This result suggests that, compared with functional decline, functional abnormality may better reflect the overall impaired status of saccular function, thus potentially providing higher discriminative power in prognostic evaluation [15]. This phenomenon indicates that the effect of saccular dysfunction on prognosis may follow a threshold-like pattern. Although a significant correlation was found between vestibular EH grade and abnormal cVEMP in this study, the correlation strength was moderate, suggesting that vestibular dysfunction may not be fully explained by EH alone. Previous studies have noted that EH exhibits dynamic changes, and its severity may fluctuate over time, leading to inconsistency between structure and function [13, 16]. Therefore, single-dimensional imaging or electrophysiological assessment may not fully capture the disease status. To clarify the underlying mechanism by which vestibular EH affects prognosis, this study integrated imaging structural indicators and vestibular functional indicators in patients with acute low-tone sensorineural hearing loss and explored the potential association pathway through mediation analysis, which is relatively rare in existing research. The results showed that the total effect of vestibular EH on prognosis was significant (β = −0.345, P = 0.005), but after including abnormal cVEMP, its direct effect was no longer statistically significant (β = −0.212, P = 0.079), whereas the indirect effect remained significant (β = −0.133, P = 0.044), with a mediating proportion of 38.6%. This result indicates that vestibular EH may not be directly associated with prognosis, but its relationship with disease outcome may be partly related to saccular dysfunction, which may represent an potential functional link between inner ear structural injury and clinical prognosis. From an anatomical and physiological perspective, the saccule is highly sensitive to changes in endolymphatic pressure. When hydrops occurs, elevated pressure in the vestibular cistern first acts on the saccular wall, which may lead to altered stiffness of stereociliary bundles in hair cells and reduced mechano-electrical transduction efficiency [22–24]. As hydrops persists, saccular hair cells may undergo further functional impairment accompanied by changes in electrophysiological properties and abnormal synaptic transmission [5]. Notably, saccular dysfunction may affect cochlear nucleus excitability through the vestibulo-cochlear inhibitory pathway, thereby interfering with auditory signal processing, which provides a neuroanatomical explanation for the influence of saccular function on hearing prognosis [25, 26]. In this study, absent cVEMP showed stronger prognostic predictive value than prolonged latency or reduced amplitude, suggesting a threshold effect of saccular dysfunction on prognosis: when function is completely lost, inner ear compensatory mechanisms may become insufficient and prognosis may consequently worsen. The 38.6% mediating proportion suggests that saccular dysfunction may be one of the potential pathways associated with the relationship between vestibular hydrops and prognosis, and also provides a theoretical basis for using cVEMP as an objective marker of poor prognosis related to vestibular hydrops [15, 16].
Several previous studies have investigated poor prognostic factors of ALHL, some of which yielded findings inconsistent with the present study. For example, higher SP/AP ratio on electrocochleography, presence of nystagmus or vertigo, time to initiation of treatment, and amplitude ratio of acoustically/electrically evoked cVEMP were all associated with worse prognosis [27–30]. However, due to the retrospective design of this study, detailed evaluation of time to treatment and specific characteristics of vertigo was not performed. Im et al. [31] found that although electrocochleography values were significantly elevated in patients with acute low-tone sensorineural hearing loss and correlated with the degree of low-frequency hearing loss, no statistically significant association was observed between its parameters and hearing recovery. These findings suggest that electrocochleography may reflect EH severity but does not necessarily determine prognosis directly.
This study has several limitations. First, the relatively small sample size may have increased the risk of overfitting in the multivariable regression and mediation analyses, potentially affecting model stability and generalizability. Therefore, the present findings should be further validated in larger prospective cohorts. In addition, the relatively small sample size limited the statistical power to detect differences, resulting in wide confidence intervals in multivariate regression analysis. Second, cVEMP testing and pure tone audiometry were not performed on the same day, and temporal differences might affect the comparability of results. Third, the cutoff values used to define abnormal cVEMP were derived from routine departmental standards, and their generalizability across different populations remains to be verified. Fourth, treatment decisions were made individually by clinicians without a standardized protocol, which might introduce treatment heterogeneity. Finally, the retrospective design restricted detailed evaluation of clinical parameters such as timing of treatment and vertigo characteristics, and ALHL may represent a clinically heterogeneous entity with underlying phenotypic variability, with different patients potentially corresponding to distinct pathophysiological subtypes. Moreover, vestibular endolymphatic hydrops assessment based on MRI and cVEMP testing are indirect measures and may be subject to diagnostic and measurement uncertainty, which could introduce variability in case classification and result interpretation. Future multicenter prospective studies are warranted to validate the prognostic value of cVEMP and to improve standardization of vestibular assessment in acute low-tone sensorineural hearing loss.
Conclusion
Based on multimodal assessment using inner ear MRI and cVEMP, this study systematically analyzed the relationship among vestibular EH, vestibular dysfunction, and prognosis of acute low-tone sensorineural hearing loss. The results demonstrated that vestibular EH grade, cVEMP amplitude, and abnormal cVEMP were all independent predictors of prognosis, highlighting the value of multimodal assessment in risk stratification. Further mediation analysis showed that abnormal cVEMP may partially mediate the association between vestibular EH and prognosis, indicating that vestibular EH influences clinical outcomes may be related to saccular function.
Acknowledgements
We are grateful to the dialysis nurses participating in the study.
Author contributions
Shu Chen: conception and design of the study; analysis and interpretation of data; drafting the manuscript; final approval of the version to be submitted.
Xiaojian Cai: conception and design of the study; project administration; analysis and interpretation of data; drafting the manuscript; final approval of the version to be submitted.
Qiqi Fan: recruitment of participants and collection of data; final approval of the version to be submitted.
Junxi Chen: recruitment of participants and collection of data; final approval of the version to be submitted.
Donghui Huang: recruitment of participants; final approval of the version to be submitted.
Jiaqi Wang: collection of data; final approval of the version to be submitted.
Funding
This research is funded by the 2022 Self-Funded Science and Technology Innovation Project of Foshan (No. 2220001004596).
Data Availability
The data supporting the findings of this study are available from the corresponding author upon reasonable request.
Declarations
Ethical statement
This study was approved by the Hospital Ethics Committee (Approval No. KY[2022]177). All patients provided written informed consent. The study was conducted in accordance with the principles of the Declaration of Helsinki.
Competing interests
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The data supporting the findings of this study are available from the corresponding author upon reasonable request.