The value of post-contrast delayed three-dimensional fluid-attenuated inversion recovery MRI in the diagnosis of unilateral vestibulopathy manifesting as episodic vestibular syndrome

Introduction

Unilateral vestibulopathy (UVP) is a vestibular disorder characterized by dizziness and balance disorders, representing the sixth most common cause of vertigo/dizziness. UVP is also the third most common cause of peripheral vestibular disorders, with benign paroxysmal positional vertigo ranking first, followed by Meniere’s disease (MD) (1). The annual incidence of UVP has been reported as 3.5–15.5 cases per 100,000 population (2,3), with the age of onset between 30 and 60 years (2,4). According to the International Classification of Vestibular Disorders (5), symptoms of vestibular disorders can manifest as acute vestibular syndrome, episodic vestibular syndrome (EVS), and chronic vestibular syndrome. UVP is mostly manifested as acute vestibular syndrome, called acute unilateral peripheral vestibular lesion (AUVP), which is synonymous with vestibular neuritis, and as defined by the Vestibular the Committee for the Classification of Vestibular Disorders of the Bárány Society (6), it is due to acute unilateral loss of peripheral vestibular function without evidence of acute central or acute auditory symptoms or signs. UVP can manifest as chronic vestibular syndrome, known as chronic unilateral peripheral vestibular lesion (chronic UVP), typically presenting with persistent dizziness and postural instability (7,8). EVS is a common type of vestibular syndrome, presenting with episodic vertigo, dizziness, or postural instability, lasting from several seconds to hours, and in rare cases, for several days, accompanied by signs of temporary vestibular system dysfunction (nausea, nystagmus, and sudden falls). Common vestibular diseases include benign paroxysmal positional vertigo, vestibular migraine, vestibular paroxysmia, MD, and transient ischemic attack, among others (9). With the widespread application of neurological examinations and vestibular electrophysiological tests, we have observed in clinical practice that some patients diagnosed with UVP also exhibit EVS, which is considered an atypical feature of UVP. Some studies have revealed its mechanisms, such as experiencing transient dizziness or premonitory instability before severe, prolonged vertigo, challenging the general understanding of UVP symptoms (10,11).

Currently, the diagnosis of UVP primarily relies on vestibular evaluation techniques, including the assessment of semicircular canal function by measuring the angular vestibulo-ocular reflex (aVOR) using caloric test, video head impulse test (vHIT), and rotary chair test, as well as assessment of otolith function by measuring translational vestibulo-ocular reflex using vestibular evoked myogenic potentials, subjective visual vertical, and subjective visual horizontal. These tests provide only indirect diagnostic evidence, which has limited value for inferring the etiology of the disease. In order to observe inner ear diseases more objectively, in 2007, Nakashim et al. (12) visualized the endolymph in the labyrinth by using delayed-enhanced high-resolution magnetic resonance imaging (MRI) of the inner ear with injection of gadolinium through the tympanic membrane. However, it only detects one ear and is an invasive examination. Currently, it is possible to visualize even finer lesions within the labyrinth by contrast-enhanced three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI with intravenous administration of gadolinium-based contrast media into the perilymph through the blood-labyrinth barrier (BLB) (13). A study showed that several hours after intravenous injection of gadolinium-containing contrast media, the perilymphatic space of the inner ear was enhanced on MRI (14), displaying high signal intensity on MRI images, whereas the endolymphatic space showed low signal intensity on MRI images, which can be visualized indirectly through the perilymphatic space. These MRI techniques have become useful research tools in the study of MD (15). Enhancement can also be found in the inner ear affected by mechanical trauma (13) and inflammation (14) after intravenous gadolinium administration, suggesting that disease states may increase the permeability of BLB in the inner ear to gadolinium-containing contrast media. Currently, the 3D-FLAIR MR technique has formed a standardized application scheme in the diagnosis and treatment of peripheral vertigo. Its typical imaging manifestations include endolymphatic hydrops (EH), damage to the BLB leading to increased outer lymphatic signal [perilymphatic enhancement (PE)], and lesions in the vestibular nerve pathway.

In recent years, the combined use of audiological and vestibular tests and 3D-FLAIR MRI has made great strides towards revealing the pathological mechanisms of many diseases. For patients with idiopathic sudden sensorineural hearing loss (ISSNHL), a previous study reported that among patients with four types of ISSNHL, EH was observed in ISSNHL patients with low-frequency hearing loss by 3D-FLAIR MRI, whereas the other three types of ISSNHL may be associated with blood-labyrinth dysfunction (16). High signal intensity on heavily T2-weighted 3D-FLAIR has been found to be positively correlated with the severity of cochlear damage in ISSNHL, which may provide lesion-specific prognostic information (17). Positive MRI findings have been reported to be related to poor prognostic outcomes in patients with ISSNHL accompanied by vertigo (18). For MD, Baráth proposed a three-level classification of EH based on MRI, that is, grades 0, I, and II (19). The detection and grading of EH on MRI is highly correlated with audiological test results. In 2019, based on the Baráth classification, a four-stage vestibular-cochlear EH grading system in combination with cochlear PE assessment was proposed by addition of a lower grade vestibular EH. According to the criteria, the vestibular EH can be classified as grades 0, I, II, and III; cochlear EH is also classified as grades 0, I, and II. By combining vestibular-cochlear EH and cochlear PE assessment, the sensitivity improved to 84.6% without losing specificity (92.3%). It has been shown that regardless of the absence or presence of vestibular EH, cochlear PE alone can improve the diagnosis of MD (17). For patients with vestibular dysfunction, Kim et al. (20) showed that PE observed on 4-hour delayed 3D-FLAIR images in patients with vestibular neuritis was correlated with the extent of vestibular deficits and timing of imaging acquisition. Research on the mechanism of UVP manifested as EVS is currently limited. Studies have shown that the non-persistent symptoms of UVP overlap with a broader range of other vestibular diseases, adding a layer of complexity to the differential diagnosis of new-onset EVS as UVP. Additionally, the Japanese Society for Balance Disorders proposed diagnostic criteria for MD in 1974, which were revised in 1987 and 2017 (21). In the latest criteria, MD is divided into typical MD with both cochlear and vestibular symptoms, and atypical MD with either cochlear or vestibular symptoms. The atypical vestibular symptoms of MD help to explain some of the mechanisms of UVP manifested as EVS.

Although UVP, especially UVP manifesting as EVS, is quite common in clinical practice, the exact etiology remains unclear. Few studies have investigated the use of cochleovestibular function tests combined with 3D-FLAIR MRI in patients with UVP. Therefore, in this study, we performed 3D-FLAIR MRI and cochleovestibular function tests on patients with UVP manifesting as EVS without audiological symptoms, and analyzed immunological indicators and vascular risk factors (VRFs), with the aim of investigating the relationship between 3D-FLAIR MRI findings and auditory, vestibular test results, and exploring the possible etiologies and pathogenesis of UVP manifesting as EVS. We present this article in accordance with the STROBE reporting checklist (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1515/rc).

Methods

Patients

The patients with UVP manifesting as EVS who attended the neurology department of our hospital from December 2019 to October 2024 were included. These patients had a chief complaint of dizziness or vertigo symptoms lasting from several minutes to several hours. They had a unilateral canal paresis (CP) value of >25% in the caloric test. Central nervous system disorders were excluded based on neurological signs and imaging findings.

The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Cangzhou Central Hospital (No. 2021-232-01). Written informed consent was provided by all patients.

MRI protocol

Temporal bone MRI was conducted using a 3.0 T scanner (MAGETOM Avanto) with an 8-channel head/neck coil. The specific imaging protocols included: conventional scanning sequences [T1-weighted imaging (T1WI), fast-spin-echo T2-weighted imaging (T2WI), and T2-driven equilibrium high resolution in the axial plane; post-contrast T1WI (axial and coronal); and 4-hour delayed contrast-enhanced 3D-FLAIR. The contrast agent used was gadolinium-diethylene triamine pentaacetate (Gd-DTPA), brand name: magnevist, Bayer HealthCare, Guangzhou, China]. A double dose (0.2 mmol/kg) of Gd-DTPA was injected into an antecubital vein using a high-pressure syringe (Ulrich Medical, Ulm, Germany) at a flow rate of 2.0 mL/s, followed by a 20 mL saline flush. All patients in this study completed the above magnetic resonance (MR) scans within 5 days of experiencing vertigo symptoms.

Imaging analysis

After intravenous injection of Gd-DTPA, the degree of EH in the vestibule and cochlea was assessed by visual comparison of the relative area of gadolinium-enhanced perilymph and indirectly displayed nonenhanced endolymph in the axial plane. According to the criteria previously described by Bernaerts et al. (22), the degree of vestibular EH was categorized as grades 0, I, II, and III (vestibular EH grade III was not observed in this study), the degree of cochlear EH was also categorized as grades 0, I, and II (Figure 1).

Figure 1 Grades of vestibular and cochlear EH. (A) Vestibular EH grade 0 implies that the vestibule is normal, the saccule (white solid arrow) and utricle (white dashed arrow) are distinctly separated, and their areas are <50% of the area of the vestibule; (B) vestibular EH grade I indicates that the saccule (white solid arrow) that is usually smaller than the utricle (white dashed arrow) has become equal to or larger than the utricle, but they are not yet confluent with each other; (C) vestibular hydrops grade II indicates confluence of both saccule and utricle (white solid arrow), rim enhancement of the perilymphatic space is still visible; (D) cochlear EH grade 0 implies normal cochlea, the scala tympani and scala vestibuli are recognizable (the white solid arrow indicates the cochlear structures); (E) cochlear EH grade I indicates that the scala media becomes indirect visible as a dark area of low signal intensity (the white solid arrow indicates the cochlear region); (F) cochlear EH grade II indicates that the scala vestibuli is fully obliterated by the enlarged scala media (the white solid arrow indicates the cochlea). EH, endolymphatic hydrops.

The degree of PE in the bilateral vestibule and cochlea was also visually assessed, which was divided into vestibular PE and cochlear PE according to the imaging site (Figure 2). The bilateral ear structures of all patients were systematically evaluated and the lesions were classified anatomically according to their MRI features.

Figure 2 Postcontrast delayed 3D-FLAIR MRI reveals high signal intensity in the perilymph of the right vestibule (white dashed arrows), cochlea (white solid arrows), and semicircular canals (white solid arrowheads). 3D-FLAIR MRI, three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging.

MRI images were qualitatively analyzed twice by radiologists with 10 and 25 years of experience in radiology and a neurologist with 20 years of experience in neuroimaging. They were blinded to the clinical data and the affected side of symptoms. The time interval between the two readings was 2 months.

vHIT

The vHIT was performed using the EyeSeeCam system (Interacoustics, Middelfart, Denmark). Patients were seated upright with their heads flexed 30°. A right-handed examiner delivered head impulses by rotating the patient’s head to the left and right while patients were asked to stare at a fixation target on a wall at a distance of 1 m. Head impulses were applied with a peak velocity range of 200°–250°/s, rotation amplitude of 15–20°, and duration of 150–200 ms. A minimum of 20 horizontal head pulses was delivered randomly to each right and left. Vestibulo-ocular reflex gain values were calculated automatically by the software. A pathological vHIT was defined as a mean vestibulo-ocular reflex gain of ≤0.8, the presence of overt and/or covert correcting saccades, and a saccade velocity greater than −110°/s (23).

Caloric test

The caloric test was performed using video-nystagmography (Interacoustics) in a semi-darkened room. Patients were placed in a supine position and wore an eye mask with the head elevated 30°. The right and left external auditory canals were irrigated with warm air at 50 ℃ and cold air at 24 ℃, respectively, for 1 minute. The caloric-induced nystagmus was recorded using nystagmography in the dark, with the eyes open. CP values were calculated using Jongkees’ formula (24). A CP value >25% was defined as unilateral horizontal semicircular canal dysfunction.

Determination of VRFs and immunological indicators

The VRFs, including diabetes mellitus and hyperlipidemia, as well as immunological tests, including routine blood tests, the serum levels of anti-thyroglobulin antibodies, anti-thyroperoxidase antibodies, rheumatoid factor, antinuclear antibodies, and antiphospholipid antibodies, were collected from all patients.

Statistical analysis

Statistical analysis was performed using R software (version 4.1.2; R Foundation for Statistical Computing, Vienna, Austria). Normally distributed continuous variables were expressed as mean ± standard deviation (SD). Comparisons between groups were performed using analysis of variance (ANOVA). Multiple comparisons were conducted using the Bonferroni method if differences between groups were statistically significant. Non-normally distributed continuous variables were analyzed using Kruskal-Wallis rank sum test, followed by multiple comparisons if there was a statistically significant difference between groups. Categorical variables were described by frequencies and percentages, and were compared using the chi-square test. Multiple comparisons were conducted using the Bonferroni method if differences between groups were statistically significant. All statistical analyses were two-sided, and P<0.05 was considered statistically significant.

Results

Baseline and clinical characteristics of patients with UVP manifesting as EVS

Totally, 134 patients with UVP manifesting as EVS were included in this study, including 64 patients with right-sided UVP and 70 patients with left-sided UVP. The baseline and clinical characteristics of patients are shown in Table 1. There were 55 males and 79 females. The average age was 52.16±14.28 years (range, 12–75 years), with a female-to-male ratio of 1:1.4.

The CP values ranged from 0.25 to 1 (median, 0.48). The vHIT gain values ranged from 0.3 to 1.41 (median, 1.01). Some 34.33% (46/134) of the patients had abnormal vHIT results. The pure-tone average (PTA) ranged from 10 to 100 dB (median 20 dB) at 0.25 kHz, from 10 to 110 dB (median 20 dB) at 0.5 and 2 kHz, and from 10 to 110 dB (median 17.5 dB) at 1 kHz. Of the 134 patients included, spontaneous nystagmus (SN) was found in 51.49% (69/134) of patients, VRFs were found in 35.82% (48/134) of patients, and immunological indicators were positive in 23.71% (23/97) of patients. The underlying diseases included MD (10.45%, 14/134), ISSNHL (20.9%, 28/134), and otitis media (4.48%, 6/134 cases).

MRI-positive (+) findings were defined as the presence of vestibular EH, vestibular PE, vestibular EH + vestibular PE, cochlear EH, and cochlear PE on one side. MRI-negative (−) findings were defined as the absence of EH and PE in the vestibule and cochlea. Among the 134 patients included, 65 patients showed MRI+ findings and 69 patients showed MRI− findings. The positive rate for post-contrast delayed 3D-FLAIR MRI was 48.51%.

According to the MRI findings, patients were divided into the MRI−, EH (the presence of vestibular EH, cochlear EH, vestibular + cochlear EH), PE (the present of vestibular, cochlear, and vestibular-cochlear PE), and EH + PE (the presence of vestibular EH + vestibular PE, vestibular EH + vestibular-cochlear PE, and vestibular EH + vcochlear PE) groups. There were 29 (21.64%) patients in the EH group, 23 (17.16%) patients in the PE group, and 13 (9.70%) patients in the EH + PE group (Figure 3).

Figure 3 The prevalence of EH, PE, and EH + PE in patients with UVP manifesting as EVS. (A) The prevalence of EH, n=29; (B) the prevalence of PE, n=23; (C) The prevalence of EH + PE, n=13. EH, endolymphatic hydrops; EVS, episodic vestibular syndrome; PE, perilymphatic enhancement; UVP, unilateral vestibulopathy.

According to the grading of vestibular and cochlear EH, vestibular EH grades I and II were found in 21 (51.22%) and 20 (48.78%) patients, respectively, whereas severe vestibular EH (grade III) was not noted. Cochlear EH grade I was found in 11 (91.67%) patients, and cochlear EH grade II was found in 1 (8.33%) patient (Table 1).

Pure-tone audiometry results

Statistically significant differences were found among the MRI−, EH, PE, and EH + PE groups (P<0.05). Pairwise comparison showed that the PTA at each frequency was significantly higher in the EH group than the MRI− group (P<0.05, Figure 4). The PTA at each frequency was lower in the PE group than the EH and EH + PE groups, but the differences were not statistically significant. The PTA at 0.25, 0.5, and 1 kHz was significantly higher in the EH + PE group than it was in the MRI− group (P<0.05, Figure 4).

Figure 4 Comparison of PTA at four frequencies (0.25, 0.5, 1, 2, 4 kHz) between the MRI−, EH, PE, and EH + PE groups. *, P<0.05; **, P<0.01. EH, endolymphatic hydrops; MRI−, magnetic resonance imaging-negative; PE, perilymphatic enhancement; PTA, pure-tone average.

For patients in the EH subgroup, there is no statistically significant difference in PTA between vestibular EH and vestibular EH + cochlear EH.

For patients in the EH + PE group, the PTA differed significantly among patients with vestibular EH + vestibular PE, vestibular EH + vestibular PE + cochlear PE, and vestibular EH + cochlear PE (P<0.05). Patients with vestibular EH + vestibular PE + cochlear PE had the highest PTA, followed by patients with vestibular EH + cochlear PE, and vestibular EH + vestibular PE (Table 2).

Further analysis of patients with different degrees of vestibular EH revealed statistically significant differences in PTA between patients with vestibular EH grades 0, I, and II (P<0.001). The PTA was significantly lower in patients with vestibular EH grades 0 and I than it was in those with vestibular EH grade II (P<0.001, P<0.05, respectively, Figure 5).

Figure 5 Comparison of PTA at four frequencies (0.25, 0.5, 1, 2, 4 kHz) between patients with different degrees of vestibular EH. *, P<0.05; ***, P<0.001; ****, P<0.0001. EH, endolymphatic hydrops; PTA, pure-tone average.

There was a positive correlation between the severity of vestibular EH and the PTA at four frequencies (PTA 0.25 kHz: r=0.38, P<0.001; PTA 0.5 kHz: r=0.37, and P<0.001; PTA 1 kHz: r=0.38, P<0.001; PTA 2 kHz: r=0.31, P<0.01, PTA 4 kHz: r=0.35, P<0.01, Figure 6).

Figure 6 Correlation between different degrees of vestibular EH (x-axis) and PTA (y-axis) in patients with UVP manifesting as EVS. A positive correlation was found between the degree of vestibular EH and PTA at four frequencies (PTA 0.25 kHz: r=0.38, P<0.001; PTA 0.5 kHz: r=0.37, and P<0.001; PTA 1 kHz: r=0.38, P<0.001; PTA 2 kHz: r=0.31, P<0.01; PTA 4 kHz: r=0.35, P<0.01). EH, endolymphatic hydrops; EVS, episodic vestibular syndrome; PTA, pure-tone average; UVP, unilateral vestibulopathy.

Further analysis of patients with different degrees of cochlear EH revealed statistically significant differences in PTA between patients with cochlear EH grades 0, I, and II (P<0.05). The degree of cochlear EH was positively correlated with the PTA at four frequencies (PTA 0.25 kHz: r=0.32, P<0.01; PTA 0.5 kHz: r=0.34, P<0.01; PTA 1 kHz: r=0.28, P<0.05; PTA 2 kHz: r=0.25, P<0.05, PTA 4 kHz: r=0.27, P<0.05, Figures 7,8).

Figure 7 Comparison of PTA at four frequencies (0.25, 0.5, 1, 2 kHz) between patients with different degrees of cochlear EH. *, P<0.05; **, P<0.01. EH, endolymphatic hydrops; PTA, pure-tone average.

Figure 8 Correlation between different degrees of cochlear EH (x-axis) and PTA (y-axis) in patients with UVP manifesting as EVS. A positive correlation was found between the degree of cochlear EH and PTA at four frequencies. (PTA 0.25 kHz: r=0.32, P<0.01; PTA 0.5 kHz: r=0.34, P<0.01; PTA 1 kHz: r=0.28, P<0.05; PTA 2 kHz: r=0.25, P<0.05; PTA 4 kHz: r=0.27, P<0.01). *, P<0.05; **, P<0.01; ***, P<0.001. EH, endolymphatic hydrops; EVS, episodic vestibular syndrome; MRI, magnetic resonance imaging; PTA, pure-tone average; UVP, unilateral vestibulopathy.

Caloric test results

There were statistically significant differences in the CP values between the MRI−, EH, PE, and EH + PE groups (P<0.05). Pairwise comparison showed that the PE group had significantly higher CP value compared with the MRI− (P<0.001), EH (P=0.003), and EH + PE groups (P<0.05, Figure 9).

Figure 9 Comparison of the CP values between the MRI−, EH, PE, and EH + PE groups. *, P<0.05; ***, P<0.001; ****, P<0.0001. CP, canal paresis; EH, endolymphatic hydrops; MRI−, magnetic resonance imaging-negative; PE, perilymphatic enhancement.

vHIT results

There were statistically significant differences in horizontal vHIT gains between the MRI−, EH, PE, and EH + PE groups (P<0.05). The vHIT gain value was significantly lower in the PE group than that in the MRI− group (P=0.001), the EH group (P=0.001), and the EH + PE group (P<0.05). The proportion of patients with positive vHIT differed significantly between the four groups (P<0.001). The PE group showed a significantly higher proportion of patients with abnormal vHIT results than that in the MRI− (P=0.001), EH (P<0.001), and EH + PE groups (P<0.05, Figure 10A). The proportion of patients with abnormal vHIT was also significantly higher in the EH + PE group compared with the EH group (P<0.05, Figure 10B).

Figure 10 vHIT test results. (A) Comparison of the vHIT gains between the MRI−, EH, PE, and EH + PE groups. (B) Comparison of the proportion of patients with positive vHIT between the MRI−, EH, PE, and EH + PE groups. *, P<0.05; ***, P<0.001. EH, endolymphatic hydrops; MRI−, magnetic resonance imaging-negative; PE, perilymphatic enhancement; vHIT, video head impulse test.

According to vHIT test results, patients were further divided into a negative vHIT (−) group and a positive vHIT (+) group. The proportion of patients with SN was significantly higher in the vHIT+ group than that in the vHIT− group (P<0.001, Figure 11). The vHIT− group had significantly lower CP value when compared with the vHIT+ group [median (interquartile range): 0.42 (0.3–0.6) vs. 0.7 (0.5–0.9), P<0.001; Figure 12A]. And the CP value had high sensitivity and specificity in determining whether patients had positive vHIT [area under the curve (AUC) =0.755, cut off =0.66, P<0.0001, Figure 12B].

Figure 11 Comparison of the incidence of SN between patients with negative vHIT and positive vHIT. ***, P<0.001. SN, spontaneous nystagmus; vHIT, video head impulse test.

Figure 12 Diagnostic value of the CP value in positive vHIT results. (A) Comparison of the CP values between patients with negative vHIT and positive vHIT. ****, P<0.0001. (B) Receiver operating characteristic curve of CP values for the determination of positive vHIT test results. AUC, area under the curve; CP, canal paresis; vHIT, video head impulse test.

VRFs and immunological indicators

VRFs were observed in 24.64% (17/69) of the patients in the MRI– group, 41.38% (12/17) of the patients in the EH group, 52.17% (12/23) of the patients in the PE group, and 53.85% (7/13) of the patients in the EH + PE group, and the differences between the four groups was statistically significant (P=0.034, Figure 13). Pairwise comparison showed that the prevalence of VRFs was significantly higher in the PE group than it was in the MRI− group (P<0.05, Figure 13).

Figure 13 The prevalence of vascular risk factors in patients with positive and negative MRI findings. (A) Comparison of vascular risk factors between the MRI+ and MRI− groups. (B) Comparison of vascular risk factors between the MRI−, EH, PE, and EH + PE groups. *, P<0.05; ***, P<0.001. EH, endolymphatic hydrops; MRI, magnetic resonance imaging; MRI+, MRI-positive; MRI−, MRI-negative; N-VRF, absence of VRF; PE, perilymphatic enhancement; VRF, vascular risks factors.

Immune abnormalities were observed in 21.15% (11/52) of the patients in the MRI− group, 31.82% (7/22) of the patients in the EH group, 26.67% (4/15) of the patients in the PE group, and 12.25% (1/8) of the patients in the EH + PE group. The proportion of patients with immune abnormalities was slightly higher in the EH group than that in the other three groups, but the difference was not significant (P=0.656).

Other possible etiologies

Among 134 patients included, 14 patients had a history of MD, 28 patients had a history of ISSNHL, and 6 patients had a history of otitis media. Patients with a history of ISSNHL had a significantly higher EH prevalence (P<0.005, Table 3). Patients with a history of otitis media had a significantly higher PE prevalence (P<0.05, Table 3).

Grouping according to Bernaerts’ method

The participants were divided into an MRI group, Bernaerts EH Grade I group, Bernaerts EH Grade II group, and Bernaerts PE group. Specifically, those with negative cochlear PE were classified into the MRI group, Bernaerts EH Grade I group, and Bernaerts EH Grade II group (as this study lacks cases of Grade III). Those with positive cochlear PE, where the affected side’s cochlear PE is greater than the contralateral side, or where the cochlear PE on the affected side combined with the saccule is greater than or equal to the utricle, were categorized into the Bernaerts PE group. There were statistically significant differences in PTA among the MRI group, Bernaerts EH Grade I group, Bernaerts EH Grade II group, and Bernaerts PE group (P<0.05) (Table 4). Pairwise comparisons between the groups showed that the PTA at 0.25, 0.5, 1, 2, and 4 kHz in the Bernaerts PE group were significantly higher than those in the MRI group and Bernaerts EH Grade I group (P<0.05). In intergroup comparisons, the immune indicators in the Bernaerts EH Grade II group were significantly higher than those in the MRI group and Bernaerts EH Grade I group (P<0.05).

Diagnostic value of PTA for determination of positive MRI findings

The PTA at four frequencies (0.25, 0.5, 1, 2 kHz) differed significantly between the MRI− and MRI+ groups (P<0.05), which had high sensitivity and specificity in determining positive MRI findings (PTA 0.25 kHz: AUC =0.678, cut off =25 dB, P<0.001; PTA 0.5 kHz: AUC =0.671, cut off =30 dB, P=0.001; PTA 1 kHz: AUC =0.665, cut off =35 dB, P=0.001; PTA 2 kHz: AUC =0.634, cut off =30 dB, P=0.007, PTA 4 kHz: AUC =0.67, cut off =40 dB, P=0.001, Figure 14).

Figure 14 Receiver operating characteristic curve of PTA for the determination of positive findings on delayed contrast-enhanced 3D-FLAIR MRI. **, P<0.01; ***, P<0.001. 3D-FLAIR MRI, three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging; AUC, area under the curve; MRI, magnetic resonance imaging; PTA, pure-tone average.

Diagnostic value of the CP value for determination of positive MRI findings

The mean CP value of patients with UVP was 0.54±0.22. The CP value had high sensitivity and specificity in determining whether patients had positive MR findings (cut off =0.49, AUC =0.666, P<0.0001, Figure 15).

Figure 15 Diagnostic value of the CP value in positive MRI findings. (A) Comparison of the CP value between the MRI+ and MRI− groups. ****, P<0.0001. (B) Receiver operating characteristic curve of the CP value for the determination of positive findings on delayed contrast-enhanced 3D-FLAIR MRI. 3D-FLAIR MRI, three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging; AUC, area under the curve; CP, canal paresis; MRI, magnetic resonance imaging; MRI+, MRI-positive; MRI−, MRI-negative.

Construction of logistic regression model with MRI findings as dependent variable

Binary logistic regression analysis was performed using a stepwise regression method with MRI+/MRI− findings as dependent variables. The independent variables included in the model were CP value (CP cutoff for MRI+ was 0.49, a value of 1 was assigned when CP value was ≥0.49, otherwise, a value of 0 was assigned), PTA (PTA cutoff values for MRI+ were 25 dB at 0.25 kHz, 30 dB at 0.5 kHz, 35 dB at 1 kHz, 30 dB at 2 kHz, 40 dB at 4 kHz, a value of 1 was assigned when PTA was equal to or greater than these thresholds at the respective frequencies; otherwise, a value of 0 was assigned), VRFs, SN, and vHIT. All 134 patients included in the analysis had complete data for all variables. The overall validity of the model was analyzed, and a P value of less than 0.05 was obtained, indicating that the null hypothesis was rejected, namely, the independent variables incorporated into the model were valid and the construction of the model was meaningful. The logistic regression analysis results showed that the CP value, PTA, and VRFs were identified as significant and independent determinants for positive MRI findings. The following estimation formula was created: ΔMRI result = 1.145 × CP value + 1.118 × PTA + 0.920 × atherosclerotic factors − 1.439 (R²=0.263, P<0.01, Table 5). This combined diagnostic model demonstrated moderate diagnostic efficacy to determine positive MRI findings (AUC =0.759, P<0.0001), with a sensitivity of 54.4% and a specificity of 87.0%, which had good clinical applicability.

Discussion

In recent years, with the significant advances of vestibular testing techniques, the use of caloric test, rotary chair test and vHIT for the evaluation of low-, mid-, and high-frequency semicircular canal function, the use of vestibular-evoked myogenic potentials and subjective visual vertical for the evaluation of the function of the otolithic organs, and the use of auditory electrophysiological assessment tools for the evaluation of cochlear function contribute not only to localization and diagnosis of UVP, but also to the differential diagnosis of peripheral and central vestibular disorders. The caloric test was first described by Robert Barany in 1906 to assess the function of the semicircular canals at a low frequency (0.003 Hz). It is a simple and useful test for the determination of semicircular canal function and the affected side, which is still an irreplaceable test for the evaluation of the aVOR in patients with UVP. However, the caloric test uses a nonphysiologic stimulus that may produce false-positive results in patients with MD and EH (25). In 1988, Halmagyi and Curthoys introduced a novel test for assessing semicircular canal function, namely, the head impulse test (26). In 2009, MacDougall et al. (27) developed a new test for objective and quantitative assessment of aVOR, namely, vHIT. vHIT uses a physiological stimulus with a higher frequency of 2.5 Hz (27), that complements, but is less sensitive than, the caloric test. A previous study demonstrated that 3D-FLAIR MRI can identify an underlying labyrinthine condition in the inner ear in 24–57% of ISSNHL patients, contributing to the understanding of the pathophysiologic mechanisms (28). In 2019, Bernaerts (22) reported that MRI had a sensitivity of 84.6% and a specificity of 92.3% in the diagnosis of MD. The use of the delayed post-contrast 3D-FLAIR MRI technique is conducive to further understanding whether the site of damage is nerve or labyrinth, vestibular or cochlear labyrinth, whether BLB impairment or EH mechanism is present, and the possible etiologies. Therefore, in this study, we used a combination of audiovestibular function tests and 3D-FLAIR MRI to investigate the possible correlation of 3D-FLAIR MRI findings with cochleovestibular function test results in patients with UVP manifesting as EVS, and analyzed VRFs and immunologic indicators of patients to elucidate the possible etiologies.

In this study, we found that nearly half (48.5%) of the patients with UVP manifesting as EVS showed abnormal findings on 3D-FLAIR scans. The result was consistent with the findings from imaging studies on patients with diseases such as ISSNHL and MD. The results of the current study showed UVP patients with abnormal 3D-FLAIR MRI findings were more likely to have abnormal PTA and CP values. PTA cutoff values of 25 dB (0.25 kHz), 30 dB (0.5 kHz), 35 dB (1 kHz), 30 dB (2 kHz), 40 dB (24 kHz), and a CP cutoff value of >49% yielded high sensitivity and specificity in determining positive MRI findings. We found that among MRI+ patients, only 1 patient exhibited an enhancement in the vestibular nerve, and this patient also had a history of otitis media. It is speculated that the lesion site in UVP patients manifesting as EVS may be localized to the labyrinth itself rather than the vestibular nerve. The results are consistent with the findings from a previous study showing that patients with typical AUVP exhibited semicircular canal enhancement on MRI, without asymmetric enhancement being observed in the vestibular nerve, and predominantly demonstrated PE (29).

In this study, UVP patients with abnormal 3D-FLAIR MRI findings were further divided into EH, PE, and EH + PE groups. The results showed that in the EH group, isolated cochlear EH was not found, and cochlear EH found in all patients was accompanied by vestibular EH. In the PE group, only 1 patient exhibited cochlear PE, who had a history of otitis media, and cochlear PE accompanied by vestibular PE was observed in the remaining patients. In the EH + PE group, vestibular EH observed was accompanied by vestibular PE and/or cochlear PE. These results suggest that for patients with UVP presenting with EVS, the vestibule should be the main target for detection during 3D-FLAIR MRI.

According to Bernaerts’ four-stage method, this study did not identify any patients with Bernaerts group III vestibular EH. A previous study has indicated that EH presenting as EVS is associated with milder symptoms compared to AUVP) (30). The duration of the disease is positively correlated with the extent of cochlear/vestibular EH and cochlear PE (22). Additionally, the completeness of symptom manifestation in MD patients, including whether they exhibit all symptoms (incomplete includes dizziness, fluctuating hearing loss, and ear fullness), is related to the severity of EH (31). The results of this study showed that the PTA was significantly higher in the EH group than in the MRI−, PE, and EH + PE groups. Further analysis of patients with different degrees of vestibular EH revealed statistically significant differences in PTA among patients with vestibular EH grades 0, I, and II (P<0.001). The PTA was significantly lower in patients with vestibular EH grade 0 and I than in patients with vestibular EH grade II (P<0.001, P<0.05, respectively). Vestibular EH was positively correlated with PTA. Further analysis of patients with different degrees of cochlear EH showed that PTA was significantly lower in patients with cochlear EH grade 0 than in those with cochlear EH grade I (P<0.001). In the Bernaerts grouping, the PTA 0.25, 0.5, 1, 2, and 4 kHz values in the Bernaerts PE group were significantly higher than those in the MRI group and the Bernaerts EH I group (P<0.05). There was a positive correlation between the severity of cochlear EH and PTA. Furthermore, the CP value was significantly lower in the EH group than in the PE group. The proportion of patients having vHIT+ results was also significantly lower in the EH group than that in the MRI−, EH, and EH + PE groups. Previous research (32) has reported that patients with MD showed a discrepancy between the vHIT and caloric test results, which may be a consequence of the physical enlargement of the endolymphatic duct in the hydropic labyrinths. The accepted Gentine model of the mechanism of caloric stimulation could account for this dissociation: the increased diameter of the semicircular duct in the labyrinth leads to an enlargement of endolymph circulation within the duct and subsequently a reduction of thermally induced pressure across the crista ampullaris, thus leading to abnormal caloric test results, whereas vHIT uses high-frequency physiologic stimulus, the increased duct diameter will have little effect on responses to rotation, so vHIT is therefore normal. Our study suggested that patients in the EH group had mild vestibular damage, and were mostly accompanied by cochlear involvement, with the degree of EH being positively correlated with the audiological test results. The immune indicators in the Bernaerts EH II group were significantly higher than those in the MRI− and Bernaerts EH I groups (P<0.05). Immunological abnormalities were found in 21.15% (11/52) of the patients in the MRI− group, 31.82% (7/22) of the patients in the EH group, 26.67% (4/15) of the patients in the PE group, and 12.25% (1/ 8) of patients in the EH + PE group. The prevalence of immune abnormalities was slightly higher in the EH group compared with other groups, but the difference was not statistically significant (P=0.656). Immune abnormalities may be possible mechanisms leading to EH. Future studies to validate the finding by expanding the patient sample size would be necessary.

It has been shown that high signal intensity in the inner ear on precontrast 3D-FLAIR is associated with poor hearing prognosis in patients with ISSNHL (33). The Baráth classification (three-stage grading system) (19) based on MRI images classified EH into three grades: Grades 0, I, and II. Detection and grading of EH in MD using MRI according to Baráth is highly correlated with audiological test results. In 2019, a four-stage vestibular-cochlear EH grading system in combination with cochlear PE assessment was proposed based on the Baráth classification. A combination of PE and EH assessment can improve the diagnostic accuracy of MD (22). This study shows that the PTA 0.25, 0.5, 1, 2, and 4 kHz values in the Bernaerts PE group are significantly higher than those in the MRI group and the Bernaerts EH I group (P<0.05), indicating the severity of the lesions. Research indicates that EH leads to ischemia of hair cells in the cochlear organ of Corti and the stria vascularis, which is the mechanism of cochlear PE and a manifestation of the worsening of EH (34). Vestibular and cochlear EH with high signal intensity in the base turn of the cochlea are good indicators for MD activity, reflecting vestibular and cochlear symptoms and fluctuations (35). Consistent with these findings, our results observed in the EH + PE group suggest symptomatic fluctuations.

The results of the study showed that compared with the EH and the EH + PE groups, the PE group showed significantly higher proportion of patients with vHIT+, significantly higher CP value of the caloric test, and significantly lower vHIT gain. The PTA at different frequencies was lower in the PE group than that in the EH and EH+PE groups, but the difference was not statistically significant. Patients with EVS when shown to have a low incidence of SN when compared to those with acute vestibular syndrome, implying a mild static vestibular imbalance and/or fast neurological improvement after initial loss of vestibular function (36). An increase in the horizontal vHIT gain can occur within the first few weeks after onset (37). Magliulo et al. (38) showed that at 1-year follow-up period, 85.7% of patients resumed normal vHIT and there was a significant correlation between vHIT results and clinical symptoms of patients. vHIT lacks sensitivity, which is significant for evaluating acute vestibular dysfunction or moderate vestibular lesions in patients with dizziness (39). Taking the above findings together, the positive rates of SN and vHIT in patients with UVP indicate the early/acute stage and severity of the disease. In this study, we found that patients who exhibited SN accounted for 51.5% (69/134) of the patients included in the study, and patients with vHIT+ accounted for 34.3% (46/134) of the patients. In comparison with the vHIT− group, the vHIT+ group had a significantly higher proportion of patients with SN, and a significantly higher CP value. Additionally, CP cut-off value of 66% yielded a sensitivity of 37% and a specificity of 88% in determining vHIT+, which is consistent with the findings from a previous study (40). This study showed that the PE group had the highest proportion of patients with SN, the highest CP value of the caloric test, the highest proportion of patients with abnormal vHIT results, and the lowest vHIT gain values, but with slight cochlear involvement. These results suggest that patients in the PE group predominantly had vestibular damage, and were in the acute phase of UVP, so they had more severe vestibular damage but mild cochlear damage when compared to other groups. In this study, we found that patients in the MRI+ group had a significantly higher prevalence of VRFs than those in the MRI− group [47.69% (31/65) vs. 24.64% (17/69), P=0.005]. The prevalence of VRFs was 24.64% (17/69), 41.38% (12/29), 52.17% (12/23), and 53.85% (7/13), respectively, in the MRI−, EH, PE, and EH + PE groups, and the difference between the four groups was statistically significant (P=0.034). The proportion of patients having VRFs was statistically higher in the PE group than the MRI− group. Atherosclerotic VRFs are high-risk factors for UVP manifesting as EVS, especially having a greater impact on patients with the presence of PE. The BLB is crucial for maintaining the stability of the inner ear. The inner ear is supplied by the terminal artery, has a poor tolerance to ischemia, and unstable hemodynamics, which can lead to poor metabolism of the inner ear after local labyrinthine ischemia and the development of extreme sensitivity, thus resulting in episodes of vertigo and tinnitus (41). It has been shown that inflammatory activation following infection can lead to a systemic inflammatory response that reduces microvascular perfusion and infarction of the vestibular organ, leading to loss of vestibular function (42), suggesting that damage to the vascular mechanisms also occurs following infection. High postcontrast signal intensity suggests BLB disruption, which can increase the entry of contrast agents and proteins into the perilymph (43). Due to the disruption of vascular integrity in the stria vascularis and interference with ionic homeostasis in the lymph (44), BLB disruption ultimately leads to inner ear dysfunction. Given these findings, we speculate that PE may be directly related to the ischemic mechanism.

In this study, 3D-FLAIR MRI combined with audiovestibular function tests revealed that patients with UVP presenting as EVS without audiological symptoms mostly had damage to the labyrinth, whereas the vestibular nerve was rarely affected. We speculate that in similarity with ISSNHL, UVP with EVS as the main clinical manifestation without audiological symptoms may have different pathological manifestations and related mechanisms. EH has long been considered the underlying pathology of MD (45). Diagnostic and therapeutic strategies for MD proposed by the Japan Society for Equilibrium Research in 2021 (26) pointed out that different manifestations may occur depending on the site of involvement within the inner ear labyrinth, including typical MD and atypical MD. Typical MD refers to damage of both the cochlea and vestibule, typically presenting with hearing impairment accompanied by vertigo. Atypical MD consists of vestibular MD and cochlear MD. Vestibular MD refers to damage of the vestibule, which is characterized by vertigo without hearing loss. Conversely, cochlear MD refers to damage of the cochlea, which is characterized by hearing loss without vertigo. The time delay between hearing loss and vertigo can be more than 5 years (46). UVP manifesting as EVS without audiological symptoms has clinical manifestations similar to vestibular MD, with EH being its underlying pathology, the presence of fluctuating symptoms and caloric weakness during disease attack, and the mechanism may be related to immune factors. Additionally, for UVP with EH as the pathological manifestation, the symptoms fluctuated repeatedly and continue to worsen, the underlying mechanism is considered EH accompanied by ischemia, which is directly associated with a poor prognosis. UVP manifesting as EVS without audiological symptoms can also have clinical manifestations similar to labyrinthine stroke, with BLB damage as the main pathology. The mechanism may be related to labyrinthine ischemia. The disease is acute in onset, with severe clinical symptoms and strong CN being observed, and the CP value of the caloric test is difficult to recover.

Our results suggest that post-contrast delayed 3D FLAIR MRI has a high diagnostic value for UVP manifesting as EVS and contributes to the speculation about the related mechanisms. In this study, we constructed a regression model with MRI findings as the dependent variable, and demonstrated significant regression correlations between positive MRI findings and CP values of the caloric test, audiological test results, and atherosclerosis VRFs, indicating that MRI can better reflect the degree of damage to the inner ear labyrinth. The results suggest that when patients with UVP showed high CP value (greater than 49%), audiological impairment (hearing threshold greater than 30 dB), and the presence of atherosclerotic VRFs, MRI should be performed to provide objective evidence for patients and speculate on mechanisms, thus providing a basis for future diagnosis and treatment.

Limitations

The study has some limitations. First, the study did not include healthy controls, because in a retrospective study it is almost impossible to form such a matched control group, and the application of gadolinium-based contrast agents in normal healthy volunteers is unacceptable and unethical. For patients with UVP, only one ear is affected, so in this study, the healthy ear served as the control group; the grouping was similar to those described in the previous studies of Baráth and Bernaerts. Second, in this study, we found that positive MRI findings were mainly concentrated in the vestibule, and imaging of the cochlear using MRI is faced with several limitations and technical issues, so the assessment of the cochlea is considered a secondary point in this study.

Conclusions

Our findings suggest that nearly half of the patients with UVP manifesting as EVS had abnormal findings on 3D-FLAIR MRI, primarily showing the presence of EH and PE in the vestibule. Vestibular PE occurred more frequently in the acute phase of UVP, and was often accompanied by more severe vestibular function impairment, which may be associated with ischemic and inflammatory mechanisms. The degree of vestibular EH was positively correlated with the severity of hearing impairment. A CP value >49%, PTA >30 dB, and atherosclerotic VRFs may help to predict abnormal MRI findings in UVP manifesting as EVS.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1515/rc

Data Sharing Statement: Available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1515/dss

Funding: The study was supported by the Cangzhou Science and Technology Research and Development Guidance Plan Project (No. 213106096).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-2025-1515/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the Ethics Committee of Cangzhou Central Hospital (No. 2021-232-01). Written informed consent was obtained from all patients.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

References

1. Brandt T, Dieterich M. The dizzy patient: don't forget disorders of the central vestibular system. Nat Rev Neurol 2017;13:352-62. [Crossref] [PubMed]
2. Adamec I, Krbot Skorić M, Handžić J, Habek M. Incidence, seasonality and comorbidity in vestibular neuritis. Neurol Sci 2015;36:91-5. [Crossref] [PubMed]
3. Sekitani T, Imate Y, Noguchi T, Inokuma T. Vestibular neuronitis: epidemiological survey by questionnaire in Japan. Acta Otolaryngol Suppl 1993;503:9-12. [Crossref] [PubMed]
4. Depondt M. La neuronite vestibulaire. Paralysie vestibulaire à caractéres particuliers Vestibular neuronitis. Vestibular paralysis with special characteristics. Acta Otorhinolaryngol Belg 1973;27:323-59.
5. Bisdorff AR, Staab JP, Newman-Toker DE. Overview of the International Classification of Vestibular Disorders. Neurol Clin 2015;33:541-50. vii. [Crossref] [PubMed]
6. Strupp M, Bisdorff A, Furman J, Hornibrook J, Jahn K, Maire R, Newman-Toker D, Magnusson M. Acute unilateral vestibulopathy/vestibular neuritis: Diagnostic criteria. J Vestib Res 2022;32:389-406. [Crossref] [PubMed]
7. Sadeghi NG, Sabetazad B, Rassaian N, Sadeghi SG. Rebalancing the Vestibular System by Unidirectional Rotations in Patients With Chronic Vestibular Dysfunction. Front Neurol 2018;9:1196. [Crossref] [PubMed]
8. Panichi R, Faralli M, Bruni R, Kiriakarely A, Occhigrossi C, Ferraresi A, Bronstein AM, Pettorossi VE. Asymmetric vestibular stimulation reveals persistent disruption of motion perception in unilateral vestibular lesions. J Neurophysiol 2017;118:2819-32. [Crossref] [PubMed]
9. Grønlund C, Lembeck MA, Devantier L, Lindelof M, Djurhuus BD. Ugeskr Laeger 2021;183:V10200757. [Episodic vestibular syndrome].
10. Silvoniemi P. Vestibular neuronitis. An otoneurological evaluation. Acta Otolaryngol Suppl 1988;453:1-72. [Crossref] [PubMed]
11. Lee H, Kim BK, Park HJ, Koo JW, Kim JS. Prodromal dizziness in vestibular neuritis: frequency and clinical implication. J Neurol Neurosurg Psychiatry 2009;80:355-6. [Crossref] [PubMed]
12. Nakashima T, Naganawa S, Sugiura M, Teranishi M, Sone M, Hayashi H, Nakata S, Katayama N, Ishida IM. Visualization of endolymphatic hydrops in patients with Meniere's disease. Laryngoscope 2007;117:415-20. [Crossref] [PubMed]
13. Naganawa S, Yamazaki M, Kawai H, Bokura K, Sone M, Nakashima T. Visualization of endolymphatic hydrops in Ménière's disease with single-dose intravenous gadolinium-based contrast media using heavily T(2)-weighted 3D-FLAIR. Magn Reson Med Sci 2010;9:237-42. [Crossref] [PubMed]
14. Carfrae MJ, Holtzman A, Eames F, Parnes SM, Lupinetti A. 3 Tesla delayed contrast magnetic resonance imaging evaluation of Ménière's disease. Laryngoscope 2008;118:501-5. [Crossref] [PubMed]
15. Rauch SD, Merchant SN, Thedinger BA. Meniere's syndrome and endolymphatic hydrops. Double-blind temporal bone study. Ann Otol Rhinol Laryngol 1989;98:873-83. [Crossref] [PubMed]
16. Qin H, He B, Wu H, Li Y, Chen J, Wang W, Zhang F, Duan M, Yang J. Visualization of Endolymphatic Hydrops in Patients With Unilateral Idiopathic Sudden Sensorineural Hearing Loss With Four Types According to Chinese Criterion. Front Surg 2021;8:682245. [Crossref] [PubMed]
17. Yang CJ, Yoshida T, Sugimoto S, Teranishi M, Kobayashi M, Nishio N, Naganawa S, Sone M. Lesion-specific prognosis by magnetic resonance imaging in sudden sensorineural hearing loss. Acta Otolaryngol 2021;141:5-9. [Crossref] [PubMed]
18. Conte G, Di Berardino F, Zanetti D, Iofrida EF, Scola E, Sbaraini S, Filipponi E, Cinnante C, Gaini LM, Ambrosetti U, Triulzi F, Pignataro L, Capaccio P. Early Magnetic Resonance Imaging for Patients With Idiopathic Sudden Sensorineural Hearing Loss in an Emergency Setting. Otol Neurotol 2019;40:1139-47. [Crossref] [PubMed]
19. Baráth K, Schuknecht B, Naldi AM, Schrepfer T, Bockisch CJ, Hegemann SC. Detection and grading of endolymphatic hydrops in Menière disease using MR imaging. AJNR Am J Neuroradiol 2014;35:1387-92. [Crossref] [PubMed]
20. Kim KT, Park S, Lee SU, Park E, Kim B, Kim BJ, Kim JS. Four-hour-delayed 3D-FLAIR MRIs in patients with acute unilateral peripheral vestibulopathy. Ann Clin Transl Neurol 2024;11:2030-9. [Crossref] [PubMed]
21. Iwasaki S, Shojaku H, Murofushi T, Seo T, Kitahara T, Origasa H, Watanabe Y, Suzuki M, Takeda NCommittee for Clinical Practice Guidelines of Japan Society for Equilibrium Research. Diagnostic and therapeutic strategies for Meniere's disease of the Japan Society for Equilibrium Research. Auris Nasus Larynx 2021;48:15-22. [Crossref] [PubMed]
22. Bernaerts A, Vanspauwen R, Blaivie C, van Dinther J, Zarowski A, Wuyts FL, Vanden Bossche S, Offeciers E, Casselman JW, De Foer B. The value of four stage vestibular hydrops grading and asymmetric perilymphatic enhancement in the diagnosis of Menière's disease on MRI. Neuroradiology 2019;61:421-9. [Crossref] [PubMed]
23. Matiño-Soler E, Esteller-More E, Martin-Sanchez JC, Martinez-Sanchez JM, Perez-Fernandez N. Normative data on angular vestibulo-ocular responses in the yaw axis measured using the video head impulse test. Otol Neurotol 2015;36:466-71. [Crossref] [PubMed]
24. Jongkees LB, Maas JP, Philipszoon AJ. Clinical nystagmography. A detailed study of electro-nystagmography in 341 patients with vertigo. Pract Otorhinolaryngol (Basel) 1962;24:65-93.
25. Hannigan IP, Welgampola MS, Watson SRD. Dissociation of caloric and head impulse tests: a marker of Meniere's disease. J Neurol 2021;268:431-9. [Crossref] [PubMed]
26. Halmagyi GM, Curthoys IS. A clinical sign of canal paresis. Arch Neurol 1988;45:737-9. [Crossref] [PubMed]
27. MacDougall HG, Weber KP, McGarvie LA, Halmagyi GM, Curthoys IS. The video head impulse test: diagnostic accuracy in peripheral vestibulopathy. Neurology 2009;73:1134-41. [Crossref] [PubMed]
28. Yoon RG, Choi Y, Park HJ. Clinical usefulness of labyrinthine three-dimensional fluid-attenuated inversion recovery magnetic resonance images in idiopathic sudden sensorineural hearing loss. Curr Opin Otolaryngol Head Neck Surg 2021;29:349-56. [Crossref] [PubMed]
29. Eliezer M, Maquet C, Horion J, Gillibert A, Toupet M, Bolognini B, Magne N, Kahn L, Hautefort C, Attyé A. Detection of intralabyrinthine abnormalities using post-contrast delayed 3D-FLAIR MRI sequences in patients with acute vestibular syndrome. Eur Radiol 2019;29:2760-9. [Crossref] [PubMed]
30. Tang L, Jiang W, Wang X. New onset episodic vertigo as a presentation of vestibular neuritis. Front Neurol 2022;13:984865. [Crossref] [PubMed]
31. Lorente-Piera J, Suárez-Vega V, Blanco-Pareja M, Liaño G, Garaycochea O, Dominguez P, Manrique-Huarte R, Pérez-Fernández N. Early and certain Ménière's disease characterization of predictors of endolymphatic hydrops. Front Neurol 2025;16:1566438. [Crossref] [PubMed]
32. McGarvie LA, Curthoys IS, MacDougall HG, Halmagyi GM. What does the dissociation between the results of video head impulse versus caloric testing reveal about the vestibular dysfunction in Ménière's disease? Acta Otolaryngol 2015;135:859-65. [Crossref] [PubMed]
33. Yoshida T, Sugiura M, Naganawa S, Teranishi M, Nakata S, Nakashima T. Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging findings and prognosis in sudden sensorineural hearing loss. Laryngoscope 2008;118:1433-7. [Crossref] [PubMed]
34. Álvarez De Linera-Alperi M, Dominguez P, Blanco-Pareja M, Menéndez Fernández-Miranda P, Manrique-Huarte R, Liaño G, Pérez-Fernández N, Suárez-Vega V. Is endolymphatic hydrops, as detected in MRI, a truly cochleocentric finding? Front Neurol 2024;15:1477282. [Crossref] [PubMed]
35. Kobayashi M, Yoshida T, Fukunaga Y, Hara D, Naganawa S, Sone M. Perilymphatic enhancement and endolymphatic hydrops: MRI findings and clinical associations. Laryngoscope Investig Otolaryngol 2024;9:e1312. [Crossref] [PubMed]
36. Choi KD, Oh SY, Kim HJ, Koo JW, Cho BM, Kim JS. Recovery of vestibular imbalances after vestibular neuritis. Laryngoscope 2007;117:1307-12. [Crossref] [PubMed]
37. Palla A, Straumann D. Recovery of the high-acceleration vestibulo-ocular reflex after vestibular neuritis. J Assoc Res Otolaryngol 2004;5:427-35. [Crossref] [PubMed]
38. Magliulo G, Iannella G, Gagliardi S, Re M. A 1-year follow-up study with C-VEMPs, O-VEMPs and video head impulse testing in vestibular neuritis. Eur Arch Otorhinolaryngol 2015;272:3277-81. [Crossref] [PubMed]
39. Bartolomeo M, Biboulet R, Pierre G, Mondain M, Uziel A, Venail F. Value of the video head impulse test in assessing vestibular deficits following vestibular neuritis. Eur Arch Otorhinolaryngol 2014;271:681-8. [Crossref] [PubMed]
40. Perez N, Rama-Lopez J. Head-impulse and caloric tests in patients with dizziness. Otol Neurotol 2003;24:913-7. [Crossref] [PubMed]
41. Foster CA, Breeze RE. The Meniere attack: an ischemia/reperfusion disorder of inner ear sensory tissues. Med Hypotheses 2013;81:1108-15. [Crossref] [PubMed]
42. Kassner SS, Schöttler S, Bonaterra GA, Stern-Straeter J, Hormann K, Kinscherf R, Gössler UR. Proinflammatory activation of peripheral blood mononuclear cells in patients with vestibular neuritis. Audiol Neurootol 2011;16:242-7. [Crossref] [PubMed]
43. Song CI, Pogson JM, Andresen NS, Ward BK. MRI With Gadolinium as a Measure of Blood-Labyrinth Barrier Integrity in Patients With Inner Ear Symptoms: A Scoping Review. Front Neurol 2021;12:662264. [Crossref] [PubMed]
44. Shi X. Pathophysiology of the cochlear intrastrial fluid-blood barrier Hear Res 2016;338:52-63. (review). [Crossref] [PubMed]
45. Foster CA, Breeze RE. Endolymphatic hydrops in Ménière's disease: cause, consequence, or epiphenomenon? Otol Neurotol 2013;34:1210-4. [Crossref] [PubMed]
46. Pyykkö I, Nakashima T, Yoshida T, Zou J, Naganawa S. Meniere's disease: a reappraisal supported by a variable latency of symptoms and the MRI visualisation of endolymphatic hydrops. BMJ Open 2013;3:e001555. [Crossref] [PubMed]