Introduction: The etiology of idiopathic sudden sensorineural hearing loss (ISSNHL) remains elusive, with vascular compromise as a proposed cause. This study aimed to explore the correlation between the vertebrobasilar vascular system laterality (VBVSL) and ISSNHL laterality. Methods: We conducted a retrospective analysis of consecutive patients diagnosed with ISSNHL from 2015 to 2020. The VBVSL pattern was established via magnetic resonance imaging scans by a neuroradiologist. ISSNHL occurring contralaterally to the basilar artery (BA) curvature or ipsilaterally to the dominant vertebral artery (VA) was designated as a “positive match,” with all other scenarios classified as a “negative match.” Results: Our study included 191 ISSNHL patients (median age 57 years, 89 males, 93 right ears). The majority of patients did not exhibit a positive match between ISSNHL laterality and the sides of BA curvature or dominant VA (28.8% and 36.6% for BA and VA, respectively). Notably, VA-positive match patients were significantly older than VA-negative match patients (59 vs. 53 years, p = 0.043), with a similar trend observed in BA-positive match compared to BA-negative match (59 vs. 54.5 years, p = 0.057). However, there was no significant difference in any other clinical, audiometric, or outcome factors between the positive and negative match groups. Conclusion: The findings suggest no association between VBVSL and ISSNHL laterality. Furthermore, patients in the positive match group did not exhibit distinct clinical or audiometric features compared to those without a match.

Sudden sensorineural hearing loss (SSNHL) is defined as a rapid-onset hearing impairment, almost invariably unilateral, and occurs within a 72-h window. Over 90% of SSNHL instances are classified as idiopathic (ISSNHL), with the pathogenesis that remains largely unknown and highly controversial [Chandrasekhar et al., 2019]. This definition was adopted by the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF). Various causes have been proposed, including viral infection, intracochlear membrane rupture, perilymphatic fistula, immune-mediated disorder, and vascular compromise [Hughes et al., 1996; Eisenman and Arts, 2000; Kim et al., 2016; Chandrasekhar et al., 2019]. Particularly, the vascular compromise theory is supported by the fact that the cochlea, being an “end organ” with no vascular collaterals, is vulnerable to ischemia. It is supplied solely by one or two cochlear arteries, which stem from branches of the internal auditory artery, a branch of the anterior inferior cerebellar artery (AICA) [Kim et al., 1999; Mosnier et al., 2011]. Furthermore, the acute and unilateral manifestations of ISSNHL are analogous to those of other vascular diseases, such as myocardial infarction, cerebral stroke, and amaurosis fugax [Ballesteros et al., 2009]. Additionally, acute unilateral HL can serve as the initial manifestation of an AICA infarction [Lee and Baloh, 2005; Lee et al., 2002, 2004].

Therefore, changes in the hemodynamics of the vertebrobasilar (VB) vascular system, which includes the AICA, could potentially play a role in the pathogenesis of ISSNHL. Unilateral vertebral artery (VA) dominance is common and usually favors the left side, with the diameters of the VAs being symmetrical in only 6–26% of individuals [Jeng and Yip, 2004]. It is thought that the asymmetrical flow mechanics in the VB junction leads to the development of basilar artery (BA) curvature over time in the direction opposite to the dominant VA (Fig. 1) [Tronc et al., 2000; Hong et al., 2009]. This, in turn, results in slow blood flow and reduced shear stress on the side contralateral to the curvature [Hong et al., 2009], promotes the development of branch atheromas [Hong et al., 2008], and leads to the elongation and luminal narrowing of branching vessels, such as the AICA [Kim et al., 2012]. All these factors may contribute to vascular compromise and ischemia of organs on the contralateral side of the BA curvature. In fact, an asymmetrical VB vascular anatomy has been identified as a significant contributor to peri-VB junctional infarcts, which occur more often on the side opposite the BA curvature [Hong et al., 2009]. These findings have led to the hypothesis that a similar pathogenesis may underlie ISSNHL that occurs on the side contralateral to the BA curvature and ipsilateral to the dominant VA [Kim et al., 2012, 2016]. However, the current body of evidence supporting this hypothesis remains limited [Kim et al., 2016; Maruyama et al., 2020; Sunwoo, 2022; Frosolini et al., 2023].

Fig. 1.

VB vascular system demonstrated by angiography. VB system with (a) a central (noncurved) BA and (b) a left-sided BA curvature. AICA, anterior inferior cerebellar artery; BA, basilar artery; LT VA, left vertebral artery; RT VA, right vertebral artery.

Fig. 1.

VB vascular system demonstrated by angiography. VB system with (a) a central (noncurved) BA and (b) a left-sided BA curvature. AICA, anterior inferior cerebellar artery; BA, basilar artery; LT VA, left vertebral artery; RT VA, right vertebral artery.

Close modal

Given this background and the potential link between the VB system asymmetrical hemodynamics and vascular compromise to end organs such as the cochlea, our study aims to explore the association between the VB vascular system laterality (VBVSL) and ISSNHL laterality, under the hypothesis that ISSNHL is more likely to occur on the side contralateral to the BA curvature and/or ipsilateral to the dominant VA. Furthermore, we aim to investigate whether patients with a positive match of ISSNHL laterality and the side of BA curvature and/or VA dominance display distinct clinical or audiometric profiles compared to those with a negative match.

Ethical Consideration

This study protocol was reviewed and approved by the Tel Aviv Sourasky Medical Center Research Ethics Committee (approval number TLV-0203-19). Informed consent was waived.

Study Population and Data Collection

This is a retrospective chart review study of consecutive medical records of all adult patients (>18 years of age) who were diagnosed with unilateral ISSNHL of any severity and treated at the Department of Otolaryngology, Head and Neck Surgery of our medical center between 2015 and 2020. SSNHL was diagnosed based upon history, physical examination, and formal audiogram at the initial encounter. In accordance with the recently published clinical guidelines from the AAO-HNSF, SSNHL is typically defined as an audiometric loss of at least 30 dB in three consecutive frequencies occurring within a 3-day period. However, these guidelines also accommodate a more encompassing perspective, permitting the inclusion of cases demonstrating less than 30 dB of hearing loss [Chandrasekhar et al., 2019]. The audiometric inclusion criteria in our study were consistent with these guidelines' expanded definitions. All audiograms were obtained by a qualified clinical audiologist (AC-40 Clinical Audiometer, Interacoustics; Denmark), who was blind to the magnetic resonance imaging (MRI) scan. Air and bone conduction (BC) (masked when necessary) were evaluated using the latest (2005) American Speech-Language-Hearing Association (ASHA) Guidelines for Manual Pure-Tone Threshold Audiometry (American Speech-Language-Hearing Association, 2005). Shortly, pure-tone hearing thresholds were evaluated using 1–2 s duration stimuli, starting on 5 dB SPL, and an increase in 5 dB SPL steps, until the response is documented. Threshold was defined as the lowest decibel hearing level at which responses occur in at least one half of a series of ascending trials.

Patients with known previous asymmetrical HL, middle ear disease, retrocochlear pathology, degenerative central nervous system disorders, previous intracranial surgery or radiotherapy, craniofacial abnormalities, or inner ear disease other than the index idiopathic SSNHL were excluded. Patients suspected of having SSNHL secondary to an autoimmune disease, as indicated by their medical history or the course of their hearing loss, were referred to a rheumatologist for further workup. Only patients whose hearing loss was determined to be idiopathic were included in the study.

The collected data included age, sex, side of HL, presence of associated symptoms (including tinnitus and vertigo), medical history, audiometry at presentation, and extent of improvement after steroidal treatment (complete, partial, or none). The extracted audiometric data included pure-tone BC thresholds at six major frequencies (250 Hz, 500 Hz, 1 kHz, 2 kHz, 4 kHz, and 8 kHz), pure-tone average, speech reception thresholds, and speech discrimination scores for both the affected and unaffected ears. The audiometric configuration was defined as flat, rising, sloping, cookie bite, tent, and no response. Severity was defined as either mild-to-moderate (highest BC threshold ≤70 dB) or severe-to-profound (highest BC threshold >70 dB). A low-tone HL was defined when all affected frequencies were confined between 250 Hz and 1 kHz, and a high-tone HL when all affected frequencies were between 2 kHz and 8 kHz. Low and high HL was defined when both ranges of frequencies were affected. Thresholds that were not measurable because they were beyond the limits of the audiometer were “dummy coded” with the highest test level of the audiometer (100 dB) [Chen et al., 2003]. Additionally, whenever the 8 kHz BC threshold could not be measured due to the limitations of the audiometer, the air conduction threshold was taken as the BC threshold for the purposes of analysis.

Radiological Methods

All of the included patients underwent a contrast-enhanced targeted brain MRI study in our institute (1.5T or 3T SIEMENS MRI scanners). Most of the scans included high-resolution steady-state free precession (SSFP) T2 sequences (axial contiguous slices of 0.5–1 mm in thickness, and an SI of 0.4–0.5 mm, depending upon the MRI specifications) directed to the internal auditory canal and cerebellopontine angle. Each high-resolution three-dimensional (SSFP) T2 series was reconstructed on the coronal plane. We used a 3DMPRAGE T1 post-gadolinium sequence for the few cases in which the exam did not include the SSFP T2 series.

After ruling out any inner ear or intracranial pathology, all MRI scans were independently reviewed by a single neuroradiologist, who was blind to the clinical data and the HL side. The anatomy of the VB vascular system was analyzed by determining the BA curvature and visually classifying it using axial plane and coronal reconstructions. BA lateralization in relation to the pons and medulla was classified into four categories of curvature: center (noncurved) – midline, located in the basilar groove; mild – lateral to midline; moderate – opposite the anterior right or left part of the pons or medulla, anterior to the pyramidal tract; and severe – opposite the lateral right or left part of the pons or medulla, situated in the cerebellopontine angle (Fig. 2).

Fig. 2.

High-resolution axial SSFP T2 (CISS (a, c, and d)/Zoomit (b)) of internal auditory canal directed MRI scans (SW = 0.5 mm) demonstrates four categories of severity for BA curvature (right sided). a Center (noncurved). b Mild. c Moderate. d Severe.

Fig. 2.

High-resolution axial SSFP T2 (CISS (a, c, and d)/Zoomit (b)) of internal auditory canal directed MRI scans (SW = 0.5 mm) demonstrates four categories of severity for BA curvature (right sided). a Center (noncurved). b Mild. c Moderate. d Severe.

Close modal

VA dominancy was determined by measuring the diameters of each VA at the distal segment and comparing them. The dominant VA was defined as the one with the larger diameter. VA dominancy was classified as left, right, or none (i.e., symmetric with a <0.3 mm difference in diameter) (Fig. 3).

Fig. 3.

High-resolution axial SSFP T2 (CISS (a)/Zoomit (b)) of internal auditory canal directed MRI scans (SW = 0.5 mm) demonstrates a pair of vertebral arteries in 2 different patients. a Left vertebral artery dominancy. b Right vertebral artery dominancy.

Fig. 3.

High-resolution axial SSFP T2 (CISS (a)/Zoomit (b)) of internal auditory canal directed MRI scans (SW = 0.5 mm) demonstrates a pair of vertebral arteries in 2 different patients. a Left vertebral artery dominancy. b Right vertebral artery dominancy.

Close modal

Cohort Stratification

Participants were classified based on whether the HL side and vasculature laterality corresponded, drawing on the hypothesis that ISSNHL is vascular-related and more likely to occur contralateral to the BA curvature and ipsilateral to the dominant VA [Kim et al., 2012, 2016]. Therefore, the “BA-positive match” group comprised patients with a BA curvature contralateral to the HL side, while the “BA-negative match” group included patients with a central BA or a BA curvature ipsilateral to the HL side. Similarly, the “VA-positive match” group consisted of patients with a dominant VA ipsilateral to the HL side, and the “VA-negative match” group included patients with symmetrical VAs or a dominant VA contralateral to the HL side. Our initial analysis aimed to assess the validity of this hypothesis in our study group, specifically whether the positive match group outnumbered the negative match group. Subsequently, we compared the positively and negatively matched groups to identify clinical and audiometric factors that characterized the positive match patients and set them apart from those with a negative match.

Statistical Analysis

For power calculation, we employed a single-group design with a one-sample exact test, setting an α of 0.05, to see if the proportion (positive match) significantly deviates from a hypothetical value of 50%. To identify a 20% difference with 80% power, a sample of 47 subjects was needed. The calculation was conducted using PASS 2022, version 22.0.5. Categorical variables were presented as frequencies and percentages, while continuous variables were assessed for normality using histograms. As only age displayed a near-normal distribution, a Kolmogorov-Smirnov test was applied. All variables, showing nonnormal distribution, were presented as median with interquartile range. We used a one-sample binomial test for analyzing the association between HL side and VBVSL, and χ2, Fisher, and Mann-Whitney tests for comparisons between the positively and negatively matched groups. Two-sided statistical tests were employed with a significance set at p < 0.05. Analyses were conducted using SPSS software (version 25, IBM, 2017).

Of the 191 patients with ISSNHL included in this study, the average age at the time of the first audiometric evaluation was 57 years (interquartile range, 39–70 years). The cohort comprised 89 males (46.6%) and 102 females (53.4%). Demographics and clinical presentation are outlined in Table 1. The HL manifested in the right ear for 93 patients (48.7%) and in the left ear for 98 patients (51.3%). Audiometric data are detailed in Table 2.

Table 1.

Patient characteristics: demographic and clinical factors

Characteristicsn = 191
Hearing loss side, n (%) 
 Right 93 (48.7) 
 Left 98 (51.3) 
Median age, years (IQR) 57 (39–70) 
Sex, male, n (%) 89 (46.6) 
Tinnitus, n (%) 150 (78.5) 
Vertigo/dizziness, n (%) 69 (36.1) 
Smoking history, n (%) 37 (19.4) 
Autoimmune disease, n (%) 12 (6.3) 
Preceding infectious disease, n (%) 31 (16.2) 
CV risk factors, n (%) 85 (44.5) 
 HTN, n (%) 60 (31.4) 
 DM, n (%) 30 (15.7) 
 IHD, n (%) 22 (11.5) 
 CVA/TIA, n (%) 7 (3.7) 
 PVD, n (%) 4 (2.1) 
Number of CV risk factors, n (%) 
 1 52 (27.2) 
 2 26 (13.6) 
 ≥3 6 (3.1) 
Characteristicsn = 191
Hearing loss side, n (%) 
 Right 93 (48.7) 
 Left 98 (51.3) 
Median age, years (IQR) 57 (39–70) 
Sex, male, n (%) 89 (46.6) 
Tinnitus, n (%) 150 (78.5) 
Vertigo/dizziness, n (%) 69 (36.1) 
Smoking history, n (%) 37 (19.4) 
Autoimmune disease, n (%) 12 (6.3) 
Preceding infectious disease, n (%) 31 (16.2) 
CV risk factors, n (%) 85 (44.5) 
 HTN, n (%) 60 (31.4) 
 DM, n (%) 30 (15.7) 
 IHD, n (%) 22 (11.5) 
 CVA/TIA, n (%) 7 (3.7) 
 PVD, n (%) 4 (2.1) 
Number of CV risk factors, n (%) 
 1 52 (27.2) 
 2 26 (13.6) 
 ≥3 6 (3.1) 

IQR, interquartile range; SHL, sudden hearing loss; CV, cardiovascular; HTN, hypertension; DM, diabetes mellitus; IHD, ischemic heart disease; CVA/TIA, cerebrovascular accident/transient ischemic attack; PVD, peripheral vascular disease.

Table 2.

Patient characteristics: audiometric data

Characteristicsn = 191
Median BC thresholds (IQR), affected ear 
 250 Hz 40 dB (30–45) 
 500 Hz 45 dB (30–60) 
 1,000 Hz 42.5 dB (25–70) 
 2,000 Hz 45 dB (25–70) 
 4,000 Hz 52.5 dB (25–70) 
 8,000 Hz 65 dB (35–90) 
Median SRT (IQR) 
 Affected ear 45 dB (25–70) 
 Nonaffected ear 15 dB (10–20) 
Median WRS, % (IQR) 
 Affected ear 88 (16–96) 
 Nonaffected ear 100 (96–100) 
PTA (IQR)  
 Affected ear 45 dB (25–70) 
 Nonaffected ear 15 dB (10–20) 
Audiogram configuration, n (%) 
 Flat 27 (14.1) 
 Rising 23 (12.8) 
 Sloping 69 (36.1) 
 Cookie bite 19 (9.9) 
 Tent 18 (9.4) 
 No response 24 (12.6) 
Characteristicsn = 191
Median BC thresholds (IQR), affected ear 
 250 Hz 40 dB (30–45) 
 500 Hz 45 dB (30–60) 
 1,000 Hz 42.5 dB (25–70) 
 2,000 Hz 45 dB (25–70) 
 4,000 Hz 52.5 dB (25–70) 
 8,000 Hz 65 dB (35–90) 
Median SRT (IQR) 
 Affected ear 45 dB (25–70) 
 Nonaffected ear 15 dB (10–20) 
Median WRS, % (IQR) 
 Affected ear 88 (16–96) 
 Nonaffected ear 100 (96–100) 
PTA (IQR)  
 Affected ear 45 dB (25–70) 
 Nonaffected ear 15 dB (10–20) 
Audiogram configuration, n (%) 
 Flat 27 (14.1) 
 Rising 23 (12.8) 
 Sloping 69 (36.1) 
 Cookie bite 19 (9.9) 
 Tent 18 (9.4) 
 No response 24 (12.6) 

IQR, interquartile range; BC, bone conduction; dB, decibels; SRT, speech reception threshold; WRS, word recognition score; PTA, pure-tone average.

VB vascular system configurations and the laterality of ISSNHL are summarized in Table 3. The BA curved to the right in 74 patients (38.7%), to the left in 53 patients (27.8%), and was central in 64 patients (33.5%). Left VA dominance was observed in 84 patients (44%), right VA dominance in 48 patients (25.1%), and symmetrical VAs in 59 patients (30.9%). The BA-positive match group, marked by a BA curvature contralateral to the affected ear, included 55 patients (28.8%). Conversely, the BA-negative match group was larger, encompassing 136 patients (71.2%) with either a central BA (n = 64, 33.5%) or a BA curvature ipsilateral to the affected ear (n = 72, 37.7%). In the VA-positive match group, 70 patients (36.6%) had a dominant VA ipsilateral to the affected ear. Meanwhile, the VA-negative match group, with either symmetrical VAs (n = 59, 30.9%) or a dominant VA contralateral to the affected ear (n = 62, 32.5%), included 121 patients (63.4%). Counter to the initial hypothesis, the percentage of patients with a negative match for both BA curvature and VA dominance was significantly higher than those with a positive match (p < 0.001).

Table 3.

Configurations of the VB system and the laterality of SSNHL

BA curvatureVA dominancy
RightCentralLeftRightSymmetricLeft
SevereModerateMildMildModerateSevere
HL side Left  33  34  31  23 30 45 
(2) (8) (23)  (21) (10) (0) 
Right  41  30  22  25 29 39 
(2) (9) (30)  (8) (10) (4) 
BA curvatureVA dominancy
RightCentralLeftRightSymmetricLeft
SevereModerateMildMildModerateSevere
HL side Left  33  34  31  23 30 45 
(2) (8) (23)  (21) (10) (0) 
Right  41  30  22  25 29 39 
(2) (9) (30)  (8) (10) (4) 

BA, basilar artery; VA, vertebral artery; HL, hearing loss.

Note: Shadowed cells represent a positive match between the hearing loss side and BA curvature/VA dominancy, according to the hypothesis.

Subsequently, we compared the positive match group to the negative match group for both BA curvature and VA dominance. The clinical and audiometric factors of the two groups are summarized in Tables 4 and 5, respectively. VA-positive match patients were significantly older than VA-negative match patients (59 vs. 53 years, p = 0.043). A trend toward older age was observed in the BA-positive match group compared to the BA-negative match group (59 vs. 54.5 years, p = 0.057). However, no significant difference was found in other clinical parameters, such as sex, symptoms at presentation, and medical history, which includes cardiovascular risk factors and diseases. Likewise, all audiometric parameters – BC thresholds, pure-tone averages, speech reception thresholds, speech discrimination scores, HL severity, range of affected frequencies, audiometric configuration, and degree of improvement (data were available for 181/191 patients) after steroidal treatment – showed no significant difference.

Table 4.

Comparison of clinical parameters for the positive- and negative-match groups

BA curvature – hearing lossVA dominancy – hearing loss
positive match (n = 55)negative match (n = 136)p valuepositive match (n = 70)negative match (n = 121)p value
Median age, years (IQR) 59 (43–71) 54.5 (38–67.5) 0.057 59 (44–70) 53 (38–69) 0.043 
Sex, male, n (%) 30 (54.5) 59 (43.4) 0.161 34 (48.6) 55 (45.5) 0.677 
Tinnitus, n (%) 42 (76.4) 108 (79.4) 0.642 54 (77.1) 96 (79.3) 0.722 
Vertigo/dizziness, n (%) 18 (32.7) 51 (37.5) 0.729 19 (27.1) 50 (41.3) 0.082 
Smoking, n (%) 11 (24.4) 26 (22.8) 0.826 17 (30.9) 20 (19.2) 0.097 
Autoimmune disease, n (%) 3 (5.5) 9 (6.6) >0.999 5 (7.1) 7 (5.8) 0.761 
Preceding infectious disease, n (%) 7 (12.7) 24 (17.6) 0.404 11 (15.7) 20 (16.5) 0.883 
CV risk factors, n (%) 27 (49.1) 58 (42.6) 0.417 32 (45.7) 53 (43.8) 0.798 
 HTN, n (%) 17 (30.9) 43 (31.6) 0.924 23 (32.9) 37 (30.6) 0.744 
 DM, n (%) 10 (18.2) 21 (14.7) 0.55 13 (18.6) 17 (14) 0.408 
 IHD, n (%) 8 (14.5) 14 (10.3) 0.405 6 (8.6) 16 (13.2) 0.332 
 CVA/TIA, n (%) 1 (1.8) 6 (4.4) 0.675 1 (1.4) 6 (5) 0.426 
 PVD, n (%) 3 (5.5) 1 (0.7) 0.074 3 (4.3) 1 (0.8) 0.142 
CV risk factors, n (%)   0.336   0.716 
 1 19 (34.5) 33 (24.3)  23 (32.9) 29 (24)  
 2 7 (12.7) 19 (14)  7 (10) 19 (15.7)  
 ≥3 2 (3.6) 4 (2.9)  3 (4.3) 3 (2.5)  
BA curvature – hearing lossVA dominancy – hearing loss
positive match (n = 55)negative match (n = 136)p valuepositive match (n = 70)negative match (n = 121)p value
Median age, years (IQR) 59 (43–71) 54.5 (38–67.5) 0.057 59 (44–70) 53 (38–69) 0.043 
Sex, male, n (%) 30 (54.5) 59 (43.4) 0.161 34 (48.6) 55 (45.5) 0.677 
Tinnitus, n (%) 42 (76.4) 108 (79.4) 0.642 54 (77.1) 96 (79.3) 0.722 
Vertigo/dizziness, n (%) 18 (32.7) 51 (37.5) 0.729 19 (27.1) 50 (41.3) 0.082 
Smoking, n (%) 11 (24.4) 26 (22.8) 0.826 17 (30.9) 20 (19.2) 0.097 
Autoimmune disease, n (%) 3 (5.5) 9 (6.6) >0.999 5 (7.1) 7 (5.8) 0.761 
Preceding infectious disease, n (%) 7 (12.7) 24 (17.6) 0.404 11 (15.7) 20 (16.5) 0.883 
CV risk factors, n (%) 27 (49.1) 58 (42.6) 0.417 32 (45.7) 53 (43.8) 0.798 
 HTN, n (%) 17 (30.9) 43 (31.6) 0.924 23 (32.9) 37 (30.6) 0.744 
 DM, n (%) 10 (18.2) 21 (14.7) 0.55 13 (18.6) 17 (14) 0.408 
 IHD, n (%) 8 (14.5) 14 (10.3) 0.405 6 (8.6) 16 (13.2) 0.332 
 CVA/TIA, n (%) 1 (1.8) 6 (4.4) 0.675 1 (1.4) 6 (5) 0.426 
 PVD, n (%) 3 (5.5) 1 (0.7) 0.074 3 (4.3) 1 (0.8) 0.142 
CV risk factors, n (%)   0.336   0.716 
 1 19 (34.5) 33 (24.3)  23 (32.9) 29 (24)  
 2 7 (12.7) 19 (14)  7 (10) 19 (15.7)  
 ≥3 2 (3.6) 4 (2.9)  3 (4.3) 3 (2.5)  

BA, basilar artery; VA, vertebral artery; IQR, interquartile range; CV, cardiovascular; HTN, hypertension; DM, diabetes mellitus; IHD, ischemic heart disease; CVA/TIA, cerebrovascular accident/transient ischemic attack; PVD, peripheral vascular disease.

Table 5.

Comparison of audiometric parameters and outcomes for the positive- and negative-match groups

BA curvature – hearing lossVA dominancy – hearing loss
Positive match (n = 55)Negative match (n = 136)p valuePositive match (n = 70)Negative match (n = 121)p value
Median BC thresholds (IQR), affected ear       
 250 Hz 40 dB (30–45) 40 dB (25–50) 0.545 40 dB (25–45) 40 dB (30–50) 0.439 
 500 Hz 45 dB (35–60) 45 dB (25–60) 0.729 45 dB (35–60) 45 dB (30–60) 0.856 
 1,000 Hz 50 dB (35–65) 40 dB (20–70) 0.431 40 dB (30–70) 50 dB (20–70) 0.942 
 2,000 Hz 50 dB (30–65) 45 dB (20–72) 0.607 45 dB (25–65) 50 dB (25–73) 0.674 
 4,000 Hz 55 dB (30–65) 50 dB (25–70) 0.788 50 dB (25–65) 55 dB (25–70) 0.958 
 8,000 Hz 70 dB (50–85) 60 dB (30–90) 0.149 65 dB (35–90) 65 dB (35–90) 0.757 
Median SRT (IQR)       
 Affected ear 45 dB (34–65) 40 dB (24–75) 0.331 45 dB (25–65) 45 dB (25–71) 0.672 
 Nonaffected ear 15 dB (10–25) 15 dB (5–20) 0.319 15 dB (10–25) 15 dB (10–20) 0.434 
Median WRS, % (IQR) 
 Affected ear 84 (66–96) 88 (2–96) 0.808 88 (55–96) 88 (0–96) 0.719 
 Nonaffected ear 100 (94–100) 100 (96–100) 0.426 100 (92–100) 100 (96–100) 0.441 
PTA (IQR) 
 Affected ear 45 dB (36–64) 41 dB (26–71) 0.548 41 dB (28–65) 46 dB (28–69) 0.85 
 Nonaffected ear 16 dB (9–28) 13 dB (8–28) 0.218 15 dB (9–30) 14 dB (9–27) 0.695 
Severity, n (%)   0.511   0.086 
 Mild to moderate 25 (50) 71 (55.5)  40 (62.5) 56 (49.1)  
 Severe to no response 25 (50) 57 (44.5)  24 (37.5) 58 (50.9)  
Affected frequencies, n (%)   0.684   0.276 
 Low 17 (34.7) 53 (41.1)  24 (37.5) 46 (40.4)  
 High 22 (44.9) 55 (42.6)  25 (39.1) 52 (45.6)  
 Low and high 10 (20.4) 21 (16.3)  15 (23.4) 16 (14)  
Audiometric configuration, n (%) 
 Flat 9 (18.4) 18 (13.7) 0.439 11 (17.2) 16 (13.8) 0.542 
 Rising 3 (6.1) 19 (14.5) 0.126 8 (12.5) 14 (12.1) 0.933 
 Sloping 21 (42.9) 48 (36.6) 0.445 27 (42.2) 42 (36.2) 0.43 
 Cookie bite 4 (8.2) 15 (11.5) 0.523 6 (9.4) 13 (11.2) 0.702 
 Tent 6 (12.2) 12 (9.2) 0.58 5 (7.8) 13 (11.2) 0.467 
 No response 5 (10.2) 19 (14.5) 0.45 6 (9.4) 18 (15.5) 0.246 
Improvement, n (%)   0.76   0.207 
 None 14 (26.4) 31 (24.2)  22 (31.9) 23 (20.5)  
 Partial 32 (60.4) 84 (65.6)  41 (59.4) 75 (67)  
 Complete 7 (13.2) 13 (10.2)  6 (8.7) 14 (12.5)  
BA curvature – hearing lossVA dominancy – hearing loss
Positive match (n = 55)Negative match (n = 136)p valuePositive match (n = 70)Negative match (n = 121)p value
Median BC thresholds (IQR), affected ear       
 250 Hz 40 dB (30–45) 40 dB (25–50) 0.545 40 dB (25–45) 40 dB (30–50) 0.439 
 500 Hz 45 dB (35–60) 45 dB (25–60) 0.729 45 dB (35–60) 45 dB (30–60) 0.856 
 1,000 Hz 50 dB (35–65) 40 dB (20–70) 0.431 40 dB (30–70) 50 dB (20–70) 0.942 
 2,000 Hz 50 dB (30–65) 45 dB (20–72) 0.607 45 dB (25–65) 50 dB (25–73) 0.674 
 4,000 Hz 55 dB (30–65) 50 dB (25–70) 0.788 50 dB (25–65) 55 dB (25–70) 0.958 
 8,000 Hz 70 dB (50–85) 60 dB (30–90) 0.149 65 dB (35–90) 65 dB (35–90) 0.757 
Median SRT (IQR)       
 Affected ear 45 dB (34–65) 40 dB (24–75) 0.331 45 dB (25–65) 45 dB (25–71) 0.672 
 Nonaffected ear 15 dB (10–25) 15 dB (5–20) 0.319 15 dB (10–25) 15 dB (10–20) 0.434 
Median WRS, % (IQR) 
 Affected ear 84 (66–96) 88 (2–96) 0.808 88 (55–96) 88 (0–96) 0.719 
 Nonaffected ear 100 (94–100) 100 (96–100) 0.426 100 (92–100) 100 (96–100) 0.441 
PTA (IQR) 
 Affected ear 45 dB (36–64) 41 dB (26–71) 0.548 41 dB (28–65) 46 dB (28–69) 0.85 
 Nonaffected ear 16 dB (9–28) 13 dB (8–28) 0.218 15 dB (9–30) 14 dB (9–27) 0.695 
Severity, n (%)   0.511   0.086 
 Mild to moderate 25 (50) 71 (55.5)  40 (62.5) 56 (49.1)  
 Severe to no response 25 (50) 57 (44.5)  24 (37.5) 58 (50.9)  
Affected frequencies, n (%)   0.684   0.276 
 Low 17 (34.7) 53 (41.1)  24 (37.5) 46 (40.4)  
 High 22 (44.9) 55 (42.6)  25 (39.1) 52 (45.6)  
 Low and high 10 (20.4) 21 (16.3)  15 (23.4) 16 (14)  
Audiometric configuration, n (%) 
 Flat 9 (18.4) 18 (13.7) 0.439 11 (17.2) 16 (13.8) 0.542 
 Rising 3 (6.1) 19 (14.5) 0.126 8 (12.5) 14 (12.1) 0.933 
 Sloping 21 (42.9) 48 (36.6) 0.445 27 (42.2) 42 (36.2) 0.43 
 Cookie bite 4 (8.2) 15 (11.5) 0.523 6 (9.4) 13 (11.2) 0.702 
 Tent 6 (12.2) 12 (9.2) 0.58 5 (7.8) 13 (11.2) 0.467 
 No response 5 (10.2) 19 (14.5) 0.45 6 (9.4) 18 (15.5) 0.246 
Improvement, n (%)   0.76   0.207 
 None 14 (26.4) 31 (24.2)  22 (31.9) 23 (20.5)  
 Partial 32 (60.4) 84 (65.6)  41 (59.4) 75 (67)  
 Complete 7 (13.2) 13 (10.2)  6 (8.7) 14 (12.5)  

BA, basilar artery; VA, vertebral artery; IQR, interquartile range; dB, decibels; SRT, speech reception threshold; WRS, word recognition score; PTA, pure-tone average.

The statistical analysis was repeated excluding cases with central BA (noncurved BA) initially included in the negative match group. Even when accounting only for patients with a curved BA, the negative match group remained larger than the positive match group (72 [57.1%] versus 54 [42.9%], p = 0.13). An additional analysis excluding mild BA curvatures and including only moderate and severe ones also indicated that the negative BA match group was significantly larger than the positive match group (p < 0.001), with 136 (85%) and 24 (15%) patients, respectively. No significant differences were found in demographic, clinical, or audiometric factors between the positive and negative match groups under either of these two stratifications.

The underlying pathophysiology of ISSNHL continues to be a subject of debate despite the numerous studies undertaken over the past decades. Among the proposed etiologies is cochlear ischemia. This hypothesis draws on several past studies, which have identified associations between atherosclerotic vascular risk factors such as hypertension, hyperglycemia, and hypercholesterolemia, and the development of, or recovery from, ISSNHL [Duck et al., 1997; Chang et al., 2014; Ryu et al., 2014; Saba et al., 2023]. Similarly, prothrombotic hematological markers such as elevated blood viscosity and plasma fibrinogen levels have been associated with an increased risk of ISSNHL [Ohinata et al., 1994; Suckfüll and Hearing Loss Study Group, 2002; Lin et al., 2012; Xie et al., 2023]. The association between ISSNHL and vascular risk factors is further supported by evidence that patients with ISSNHL demonstrate an increased risk of experiencing subsequent vascular events, such as stroke and myocardial infarction [Lin et al., 2008, 2013; Kim et al., 2018; Khosravipour and Rajati, 2021].

Various mechanisms can potentially lead to cochlear ischemia, one of which is the vascular configuration of VB system. In this mechanism, the asymmetric blood flow pattern in the VB system resulting from asymmetric VAs could trigger vascular remodeling. This would cause the BA to curve toward the nondominant VA side, leading to several hemodynamic changes [Hong et al., 2009; Zhang et al., 2014]. The alterations include slow blood flow and reduced wall shear stress on the curvature's inner surface, which may create an atherothrombogenic environment [Cunningham and Gotlieb, 2005]. In addition, BA curvature and displacement could result in the stretching and thinning of the AICA on the side contralateral to the curvature [Kim et al., 2016]. These morphological changes, combined with the cochlea’s lack of vascular collaterals, may contribute to inner ear ischemia and the development of ISSNHL on the contralateral side of the BA curvature and the ipsilateral side of the dominant VA.

This vascular pathogenesis hypothesis is supported by previous studies, showing a correlation between VBVSL and the side of infarcts in the posterior circulation [Hong et al., 2009]. However, clinical evidence for the link between ISSNHL laterality and VBVSL remains limited. Kim et al. [2012] first suggested this association in 2012 [Kim et al., 2012] and further investigated it in 2016 in a study involving 121 ISSNHL patients. They reported an inverse relationship between ISSNHL laterality and the BA curvature direction [Kim et al., 2016]. Subsequent studies, however, have yielded conflicting results. For instance, Murayama et al. [2020] found that neither the BA curvature direction nor the dominant VA side was associated with ISSNHL laterality [Maruyama et al., 2020].

In contrast to the existing hypothesis, our results indicated a lack of correlation between ISSNHL laterality and VBVSL. We observed a “negative match” in the majority of patients, a term we used to denote a lack of alignment between the side of hearing loss and the side of either the BA curvature or the VA dominance, as postulated by the hypothesis. It is noteworthy that this negative match group was predominantly larger due to the inclusion of cases with a central BA or symmetric VAs. This absence of support for the initial hypothesis persisted even when we excluded patients with a central BA from our analysis. Despite their smaller number, we considered that positive match patients could potentially represent a distinct ISSNHL subgroup with a unique, possibly vascular, pathogenesis. Consequently, we undertook a comparison of the “positive” and “negative match” groups in an attempt to identify any distinguishing factors. We found that patients with a positive VA match were significantly older than those with a negative VA match (59 vs. 53 years, respectively, p = 0.043). Additionally, there was a trend toward older age in the BA-positive match group compared to the BA-negative match group (59 vs. 54.5 years, p = 0.057). The clinical implications of these findings, however, remain unclear. While one might interpret this to suggest that the positive match group represents a subset of older SSNHL patients more susceptible to ischemic events, this conjecture seems improbable given the lack of significant differences in all other parameters between the two groups, including medical history and cardiovascular risk factors. Furthermore, we found no significant difference in any of the audiometric parameters, including HL severity and the extent of audiometric improvement following treatment. In a further analysis, we accounted for the possibility that greater degrees of vascular asymmetry in the VB system might have a stronger correlation with vascular compromise and ischemia and, therefore, would be more likely to match the side of the HL. To examine this, we conducted an analysis that included only cases with moderate-to-severe BA curvatures, excluding those with mild BA curvature. However, our findings remained consistent: no significant difference was observed between the positive and negative match groups. In summary, our results suggest that a positive match does not appear to define a distinct subset within the ISSNHL patient population with distinctive characteristics.

While the findings of our research do not support an ischemic mechanism rooted in the VB vascular configuration as a potential cause of ISSNHL, the observed VB system configuration among our study participants was consistent with earlier studies on vessel laterality. Like the existing literature on VBVSL, a left dominant VA (44%) was more prevalent than a right dominant VA (25.1%) [Jeng and Yip, 2004; Perren et al., 2007; Hong et al., 2009; Zhu et al., 2016]. Accordingly, more patients had a right-sided BA curvature (38.7%) rather than a left-sided one (27.8%). We noted a slightly higher occurrence of symmetric VAs (30.9%) compared to the reported rates in other studies (6–26%) [Jeng and Yip, 2004]. This discrepancy could be attributed to divergences in the cutoff values employed to classify the dominant VA and the tools used for measurement – prior rates were derived from angiographic and postmortem studies, whereas we used brain MRI with gadolinium for our measurements.

Though vascular disturbances are considered a plausible etiology for ISSNHL, they have yet to translate into successful therapeutic strategies. Indications of vascular involvement in ISSNHL have been suggested since the early 2000s [Stokroos and Albers, 1996; Haberkamp and Tanyeri, 1999; Kim et al., 2016]. However, the majority of the proposed hemodilution and vasoactive therapies, including pentoxifylline, heparin, dextran, Ginkgo biloba, carbogen inhalation, prostaglandin E1, and nifedipine, have not demonstrated any substantial benefit [Conlin and Parnes, 2007; Klemm et al., 2007; Agarwal and Pothier, 2009]. Consequently, these approaches have largely been abandoned, with the focus shifting toward anti-inflammatory treatments. Despite this, the recent introduction of hyperbaric oxygen therapy for ISSNHL [Chandrasekhar et al., 2019; Joshua et al., 2022] suggests that strategies targeting vascular compromise may still hold potential in the management of ISSNHL.

There are several inherent limitations in our study that bear mention, including its retrospective design and the lack of a control group with normal hearing. However, comparing the VBVSL in ISSNHL patients to a healthy population was not an objective of this study. Rather, we aimed to investigate the association of the ISSNHL laterality with the vascular laterality; thus, the negative match group served as a control group to the positive match group. Another limitation of our study is the reliance on measurements of blood vessel diameter and geometry to represent the hemodynamic asymmetry in the VB system. While these MRI measurements are well-established methods for evaluating the vascular anatomy of the VB system [Samim et al., 2016], they do not provide real-time flow metrics and only offer a rough estimation of chronic flow patterns.

Our findings suggest that the anatomical characteristics of the VB vascular system may not directly correlate with the side of hearing loss in ISSNHL patients. Notably, there were no distinctive clinical or audiometric factors found in patients with a positive match, implying that they do not represent a unique ISSNHL subgroup. These observations challenge the hypothesis that ISSNHL laterality is linked to the vasculature of the VB system. Nevertheless, the pathogenesis of ISSNHL is likely multifactorial, and vascular factors could interact with other physiological, pathological, and environmental factors. Further research is needed to corroborate these findings and to fully understand the complex etiology of ISSNHL.

Esther Eshkol, the institutional medical and scientific copyeditor, is thanked for editorial assistance.

This study protocol was reviewed and approved by the Tel Aviv Sourasky Medical Center Research Ethics Committee (approval number TLV-0203-19). The need for informed consent was waived by the Tel Aviv Sourasky Medical Center Research Ethics Committee.

The authors have no conflicts of interest to disclose.

The authors have no funding or financial relationships to disclose.

Shahaf Shilo, MD: data collection and manuscript writing. Dor Gilboa, BSc: data collection and statistical analysis. Yahav Oron, MD: study design and critical revision. Ophir Handzel, MD, and Rani Abu Eta, MD: critical revision. Nidal Muhanna, MD, PhD: study design. Adi Brenner‐Ullman, MD: radiological measurements. Omer Jacob Ungar, MD: manuscript writing and critical revision.

Additional Information

Shahaf Shilo, Dor Gilboa, and Adi Brenner‐Ullman contributed equally to this work.

All data generated or analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.

1.
American Speech-Language-Hearing Association. Guidelines for manual pure-tone threshold audiometry [Guidelines]. 2005. Available from: www.asha.org/policy.
2.
Agarwal L, Pothier DD. Vasodilators and vasoactive substances for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev. 2009;2009(4):CD003422.
3.
Ballesteros F, Alobid I, Tassies D, Reverter JC, Scharf RE, Guilemany JM, et al. Is there an overlap between sudden neurosensorial hearing loss and cardiovascular risk factors?Audiol Neurootol. 2009;14(3):139–45.
4.
Chandrasekhar SS, Tsai Do BS, Schwartz SR, Bontempo LJ, Faucett EA, Finestone SA, et al. Clinical practice guideline: sudden hearing loss (update). Otolaryngol Head Neck Surg. 2019;161(1_Suppl):S1–45.
5.
Chang SL, Hsieh CC, Tseng KS, Weng SF, Lin YS. Hypercholesterolemia is correlated with an increased risk of idiopathic sudden sensorineural hearing loss: a historical prospective cohort study. Ear Hear. 2014;35(2):256–61.
6.
Chen CY, Halpin C, Rauch SD. Oral steroid treatment of sudden sensorineural hearing loss: a ten year retrospective analysis. Otol Neurotol. 2003;24(5):728–33.
7.
Conlin AE, Parnes LS. Treatment of sudden sensorineural hearing loss: I. A systematic review. Arch Otolaryngol Head Neck Surg. 2007;133(6):573–81.
8.
Cunningham KS, Gotlieb AI. The role of shear stress in the pathogenesis of atherosclerosis. Lab Invest. 2005;85(1):9–23.
9.
Duck SW, Prazma J, Bennett PS, Pillsbury HC. Interaction between hypertension and diabetes mellitus in the pathogenesis of sensorineural hearing loss. Laryngoscope. 1997;107(12 Pt 1):1596–605.
10.
Eisenman D, Arts HA. Effectiveness of treatment for sudden sensorineural hearing loss. Arch Otolaryngol Head Neck Surg. 2000;126(9):1161–4.
11.
Frosolini A, Fantin F, Caragli V, Franz L, Fermo S, Inches I, et al. Vertebrobasilar and basilar dolichoectasia causing audio-vestibular manifestations: a case series with a brief literature review. Diagnostics. 2023;13(10):1750.
12.
Haberkamp TJ, Tanyeri HM. Management of idiopathic sudden sensorineural hearing loss. Am J Otol. 1999;20(5):587–92; discussion 593-5.
13.
Hong JM, Bang OY, Chung CS, Joo IS, Huh K. Frequency and clinical significance of acute bilateral cerebellar infarcts. Cerebrovasc Dis. 2008;26(5):541–8.
14.
Hong JM, Chung CS, Bang OY, Yong SW, Joo IS, Huh K. Vertebral artery dominance contributes to basilar artery curvature and peri-vertebrobasilar junctional infarcts. J Neurol Neurosurg Psychiatry. 2009;80(10):1087–92.
15.
Hughes GB, Freedman MA, Haberkamp TJ, Guay ME. Sudden sensorineural hearing loss. Otolaryngol Clin North Am. 1996;29(3):393–405.
16.
Jeng JS, Yip PK. Evaluation of vertebral artery hypoplasia and asymmetry by color-coded duplex ultrasonography. Ultrasound Med Biol. 2004;30(5):605–9.
17.
Joshua TG, Ayub A, Wijesinghe P, Nunez DA. Hyperbaric oxygen therapy for patients with sudden sensorineural hearing loss: a systematic review and meta-analysis. JAMA Otolaryngol Head Neck Surg. 2022;148(1):5–11.
18.
Khosravipour M, Rajati F. Sensorineural hearing loss and risk of stroke: a systematic review and meta-analysis. Sci Rep. 2021;11(1):11021.
19.
Kim JS, Lopez I, DiPatre PL, Liu F, Ishiyama A, Baloh RW. Internal auditory artery infarction: clinicopathologic correlation. Neurology. 1999;52(1):40–4.
20.
Kim C, Sohn JH, Choi HC. Vertebrobasilar angulation and its association with sudden sensorineural hearing loss. Med Hypotheses. 2012;79(2):202–3.
21.
Kim C, Sohn JH, Jang MU, Hong SK, Lee JS, Kim HJ, et al. Ischemia as a potential etiologic factor in idiopathic unilateral sudden sensorineural hearing loss: analysis of posterior circulation arteries. Hear Res. 2016;331:144–51.
22.
Kim SY, Lim JS, Sim S, Choi HG. Sudden sensorineural hearing loss predicts ischemic stroke: a longitudinal follow-up study. Otol Neurotol. 2018;39(8):964–9.
23.
Klemm E, Bepperling F, Burschka MA, Mösges R; Study Group. Hemodilution therapy with hydroxyethyl starch solution (130/0.4) in unilateral idiopathic sudden sensorineural hearing loss: a dose-finding, double-blind, placebo-controlled, international multicenter trial with 210 patients. Otol Neurotol. 2007;28(2):157–70.
24.
Lee H, Sohn SI, Jung DK, Cho YW, Lim JG, Yi SD, et al. Sudden deafness and anterior inferior cerebellar artery infarction. Stroke. 2002;33(12):2807–12.
25.
Lee H, Ahn BH, Baloh RW. Sudden deafness with vertigo as a sole manifestation of anterior inferior cerebellar artery infarction. J Neurol Sci. 2004;222(1-2):105–7.
26.
Lee H, Baloh RW. Sudden deafness in vertebrobasilar ischemia: clinical features, vascular topographical patterns and long-term outcome. J Neurol Sci. 2005;228(1):99–104.
27.
Lin C, Lin SW, Lin YS, Weng SF, Lee TM. Sudden sensorineural hearing loss is correlated with an increased risk of acute myocardial infarction: a population-based cohort study. Laryngoscope. 2013;123(9):2254–8.
28.
Lin HC, Chao PZ, Lee HC. Sudden sensorineural hearing loss increases the risk of stroke: a 5-year follow-up study. Stroke. 2008;39(10):2744–8.
29.
Lin RJ, Krall R, Westerberg BD, Chadha NK, Chau JK. Systematic review and meta-analysis of the risk factors for sudden sensorineural hearing loss in adults. Laryngoscope. 2012;122(3):624–35.
30.
Maruyama A, Kawashima Y, Fujikawa T, Makabe A, Ito T, Takeda T, et al. Potential confounding factors may influence the association between configurations of the vertebrobasilar system and the incidence of idiopathic sudden sensorineural hearing loss and canal paresis. Otol Neurotol. 2020;41(5):e548–55.
31.
Mosnier I, Stepanian A, Baron G, Bodenez C, Robier A, Meyer B, et al. Cardiovascular and thromboembolic risk factors in idiopathic sudden sensorineural hearing loss: a case-control study. Audiol Neurootol. 2011;16(1):55–66.
32.
Ohinata Y, Makimoto K, Kawakami M, Haginomori SI, Araki M, Takahashi H. Blood viscosity and plasma viscosity in patients with sudden deafness. Acta Otolaryngol. 1994;114(6):601–7.
33.
Perren F, Poglia D, Landis T, Sztajzel R. Vertebral artery hypoplasia: a predisposing factor for posterior circulation stroke?Neurology. 2007;68(1):65–7.
34.
Ryu OH, Choi MG, Park CH, Kim DK, Lee JS, Lee JH. Hyperglycemia as a potential prognostic factor of idiopathic sudden sensorineural hearing loss. Otolaryngol Head Neck Surg. 2014;150(5):853–8.
35.
Saba ES, Swisher AR, Ansari GN, Rivero A. Cardiovascular risk factors in patients with sudden sensorineural hearing loss: a systematic review and meta-analysis. Otolaryngol Head Neck Surg. 2023;168(5):907–21.
36.
Samim M, Goldstein A, Schindler J, Johnson MH. Multimodality imaging of vertebrobasilar dolichoectasia: clinical presentations and imaging spectrum. Radiographics. 2016;36(4):1129–46.
37.
Stokroos RJ, Albers FW. Therapy of idiopathic sudden sensorineural hearing loss. A review of the literature. Acta Otorhinolaryngol Belg. 1996;50(1):77–84.
38.
Suckfüll M; Hearing Loss Study Group. Fibrinogen and LDL apheresis in treatment of sudden hearing loss: a randomised multicentre trial. Lancet. 2002;360(9348):1811–7.
39.
Sunwoo W. Basilar artery tortuosity as a predictive factor for the efficacy of heparin adjuvant therapy in unilateral idiopathic sudden sensorineural hearing loss. Braz J Otorhinolaryngol. 2022;88(3):381–9.
40.
Tronc F, Mallat Z, Lehoux S, Wassef M, Esposito B, Tedgui A. Role of matrix metalloproteinases in blood flow–induced arterial enlargement: interaction with NO. Arterioscler Thromb Vasc Biol. 2000;20(12):e120–6.
41.
Xie W, Karpeta N, Tong B, Liu J, Peng H, Li C, et al. Etiological analysis of patients with sudden sensorineural hearing loss: a prospective case–control study. Sci Rep. 2023;13(1):5221.
42.
Zhang DP, Zhang SL, Zhang JW, Zhang HT, Fu SQ, Yu M, et al. Basilar artery bending length, vascular risk factors, and pontine infarction. J Neurol Sci. 2014;338(1-2):142–7.
43.
Zhu W, Wang YF, Dong XF, Feng HX, Zhao HQ, Liu CF. Study on the correlation of vertebral artery dominance, basilar artery curvature and posterior circulation infarction. Acta Neurol Belg. 2016;116(3):287–93.