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Basilar artery tortuosity as a predictive factor for the efficacy of heparin adjuvant therapy in unilateral idiopathic sudden sensorineural hearing loss

Abstract

Introduction

Cochlear ischemia is hypothesized as one of the major etiologies of idiopathic sudden sensorineural hearing loss. Therefore, anticoagulant therapies are designed to be beneficial in certain patients with this condition.

Objective

This study aimed to determine which patients with idiopathic sudden sensorineural hearing loss would benefit from heparin treatment as adjuvant therapy.

Methods

In total, 134 patients who underwent magnetic resonance imaging for unilateral idiopathic sudden sensorineural hearing loss at a tertiary referral hospital between January 2014 and December 2018 were included in this retrospective study. All patients received Intratympanic steroid injections or heparin therapy plus oral corticosteroids. Radiological parameters of the vertebrobasilar system and clinical data from pre- and post-treatment assessments were analyzed.

Results

Most patients (71.6%) had a tortuous basilar artery The 65 patients with severe-to-profound idiopathic sudden sensorineural hearing loss showed a significant relationship between idiopathic sudden sensorineural hearing loss laterality and basilar artery displacement to the opposite side (p= 0.036), while the 69 patients with mild-to-moderate idiopathic sudden sensorineural hearing loss did not (p= 0.950). Additionally, the degree of basilar artery tortuosity was significantly associated with the degree of hearing impairment in the severe-to-profound idiopathic sudden sensorineural hearing loss group (p= 0.015). When idiopathic sudden sensorineural hearing loss occurred on the opposite side to basilar artery displacement, the improvement of hearing was significantly greater in patients treated with heparin than in those treated with intratympanic steroids (p= 0.041).

Conclusion

In a subset of patients with severe-to-profound idiopathic sudden sensorineural hearing loss, basilar artery tortuosity had a significant directional relationship with idiopathic sudden sensorineural hearing loss laterality. In these selected patients, a significant effect of heparin therapy on improving hearing was observed.

Keywords
Hearing loss, unilateral; Magnetic resonance imaging; Basilar artery; Ischemia; Heparin

Resumo

Introdução

A isquemia coclear é considerada uma das principais etiologias da perda auditiva neurossensorial súbita idiopática. Portanto, espera-se que as terapias anticoagulantes sejam benéficas em certos pacientes com esse diagnóstico.

Objetivo

Determinar quais pacientes com perda auditiva neurossensorial súbita idiopática se beneficiariam do tratamento com heparina como terapia adjuvante.

Método

Foram incluídos neste estudo retrospectivo 134 pacientes submetidos à ressonância magnética por perda auditiva neurossensorial súbita idiopática unilateral em um hospital de referência terciário entre janeiro de 2014 e dezembro de 2018. Todos os pacientes receberam injeções intratimpânicas de corticosteroides ou terapia com heparina juntamente com corticosteroides orais. Os parâmetros radiológicos do sistema vertebro-basilar e os dados clínicos das avaliações pré e pós-tratamento foram analisados.

Resultados

A maioria dos pacientes (71,6%) apresentava uma artéria basilar tortuosa. Os 65 pacientes com perda auditiva neurossensorial súbita idiopática grave a profunda mostraram uma relação significativa entre a lateralidade da perda auditiva e o deslocamento da artéria basilar para o lado oposto (p = 0,036), enquanto os 69 pacientes com perda auditiva neurossensorial súbita idiopática leve a moderada não apresentaram esse deslocamento (p = 0,950). Além disso, o grau de tortuosidade da artéria basilar foi significativamente associado ao grau de deficiência auditiva no grupo com perda auditiva neurossensorial súbita idiopática grave a profunda (p = 0,015). Quando a perda auditiva neurossensorial súbita idiopática ocorreu no lado oposto ao deslocamento da artéria basilar, a melhoria da audição foi significativamente maior nos pacientes tratados com heparina do que naqueles tratados com injeções intratimpânicas de corticosteroide (p = 0,041).

Conclusão

Em um subgrupo de pacientes com perda auditiva neurossensorial súbita idiopática grave a profunda, a tortuosidade da artéria basilar mostrou uma relação direcional significativa com a lateralidade da perda auditiva. Nesses pacientes selecionados, foi observado um efeito significante da terapia com heparina na melhoria da audição.

Palavras-chave
Perda auditiva unilateral; Imagem de ressonância magnética; Artéria basilar; Isquemia; Heparina

Introduction

Cochlear ischemia caused by atherothrombotic events is hypothesized to be one of the major etiologies of Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL).11 Nakashima T, Naganawa S, Sone M, Tominaga M, Hayashi H, Yamamoto H, et al. Disorders of cochlear blood flow. Brain Res Brain Res Rev. 2003;43:17-28. Although many studies have reported a positive association between the risk factors for ischemic vascular disease and ISSNHL,22 Capaccio P, Ottaviani F, Cuccarini V, Bottero A, Schindler A, Cesana BM, et al. Genetic and acquired prothrombotic risk factors and sudden hearing loss. Laryngoscope. 2007;117:547-51.,33 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;22:624-35. the effect of these thromboembolic risk factors on the likelihood of developing ISSNHL is still controversial.44 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;16:55-66. Discrepancies in the results of previous studies suggest that several different mechanisms of pathogenesis, including viral infection and autoimmunity, can cause ISSNHL. Therefore, ISSNHL of vascular origin needs to be differentiated from other causes to enable the selection of appropriate treatments such as anticoagulant therapies.

Blood to the cochlea is supplied by the internal auditory artery, which usually arises from a branch of the Basilar Artery (BA). Because the BA is formed by the union of two Vertebral Arteries (VA) that are commonly asymmetric in size, tortuosity of the BA is frequently observed. Morphologic and hemodynamic changes in the tortuous BA can contribute to the development of atherothrombosis on the side contralateral to its angulation.55 Kim C, Sohn JH, Choi HC. Vertebrobasilar angulation and its association with sudden sensorineural hearing loss. Med Hypotheses. 2012;79:202-3. Thus, BA tortuosity on the opposite side to that of hearing loss could support the inference of vascular involvement in ISSNHL.66 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. In addition, Magnetic Resonance Imaging (MRI), which is increasingly being used as a non-invasive imaging method for the examination of the vertebrobasilar system, has improved our ability to assess the vasculature when evaluating ISSNHL.77 Samim M, Goldstein A, Schindler J, Johnson MH. Multimodality Imaging of Vertebrobasilar Dolichoectasia: Clinical Presentations and Imaging Spectrum. Radiographics. 2016;36:1129-46.

Oral corticosteroids are currently widely used as the standard treatment for ISSNHL. Although there are many observational studies that suggest a treatment benefit of corticosteroid treatment, additional therapies are often required due to the lack of effectiveness of steroids based on randomized controlled trials.88 Wei BP, Stathopoulos D, O’Leary S. Steroids for idiopathic sudden sensorineural hearing loss. Cochrane Database Syst Rev. 2013;7:CD003998. Since different types of treatment entail different risks, the guideline update group of the American Academy of Otolaryngology-Head and Neck Surgery Foundation made strong negative recommendation for the routine use of additional pharmacologic agents to avoid adverse events of unnecessary treatment.99 Chandrasekhar SS, Do BS Tsai, 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. Theoretically, anticoagulant therapy in patients with vascular ISSNHL may be valuable to aid the recovery of hearing. Multiple studies have shown a benefit of heparin usage in some patients with ISSNHL.1010 Lumio JS, Aho J. Sudden deafness with special reference to anticoagulant treatment. Acta Otolaryngol. 1966;224, 203-0.

11 Donaldson JA. Heparin therapy for sudden sensorineural hearing loss. Arch Otolaryngol. 1979;105:351-4.

12 Clark SK, Tremann JA, Sennewald FR, Donaldson JA. Priapism: an unusual complication of heparin therapy for sudden deafness. Am J Otolaryngol. 1981;2:69-72.

13 Yue WL, Li P, Qi PY, Li HJ, Zhou H. Role of low-molecularweight heparins in the treatment of sudden hearing loss. Am J Otolaryngol. 2003;24:328-33.

14 Park KH, Lee CK, Lee JD, Park MK, Lee BD. Combination therapy with systemic steroids, an antiviral agent, anticoagulants, and stellate ganglion block for treatment of sudden sensorineural hearing loss. Korean J Audiol. 2012;16:71-4.
-1515 Kim J, Jeong J, Ha R, Sunwoo W. Heparin therapy as adjuvant treatment for profound idiopathic sudden sensorineural hearing loss. Laryngoscope. 2020;130:1310-5. The aim of this study was therefore to determine which patients would benefit from heparin treatment as adjuvant therapy for ISSNHL, and to discourage clinicians from routinely using unnecessary treatment.

Methods

Ethical consideration

The study protocol and a waiver of consent for retrospective chart review were approved by the Institutional Review Board of the Clinical Research Institute (GBIRB2019-419). The study was carried out in accordance with the Declaration of Helsinki.

Subjects

This was a retrospective cohort study performed in a tertiary referral center. Electronic medical records were reviewed for the period between January 2014 and December 2018, and adult patients (> 18 years old) who were diagnosed with unilateral ISSNHL and underwent temporal bone MRI were considered for inclusion. Patients who had any identifiable cause of hearing loss were excluded. A total of 134 patients were finally included in this study.

Interventions

All of the patients were admitted and started on treatment with a standard oral steroid protocol (a course of 48 mg methylprednisolone tapered over 11 days) less than 7 days after the onset of hearing loss. In addition to systemic steroid therapy, patients received either heparin (10,000 IU of unfractionated heparin, intravenously, daily for 5 − 10 days) or intratympanic steroid injection (ITS, five doses over 10 days of 5 mg/mL dexamethasone) as adjuvant therapy. Patients who had hypertension, diabetes, or cardiovascular disease were also given specific treatment for these conditions along with the oral steroid and adjuvant therapy.

Audiological assessment

Hearing was evaluated using pure tone audiometry at the initial visit and at the three-month followup. The Pure Tone Average (PTA) was calculated as the arithmetic mean of the hearing thresholds (dB) at 0.5, 1, 2, and 4 kHz in the affected ear.1616 Rauch SD, Halpin CF, Antonelli PJ, Babu S, Carey JP, Gantz BJ, et al. Oral vs Intratympanic Corticosteroid Therapy for Idiopathic Sudden Sensorineural Hearing Loss: A Randomized Trial. JAMA. 2011;305:2071-9. The degree of hearing loss was classified into one of two groups using a cut-off value of 70 dB: mild-to-moderate (PTA < 70 dB) and severe-to-profound hearing loss (PTA ≥ 70 dB). The final PTA values at the three-month followup audiogram were used to assess the outcome of therapy. Based on Siegel’s criteria, the hearing recovery outcomes were classified into 4 groups: complete recovery (final PTA < 25 dB), partial recovery (> 15 dB gain and final PTA 25 − 45 dB), slight improvement (> 15 dB gain and final PTA > 45 dB), and no improvement (<15 dB gain or final PTA > 75 dB).1717 Siegel LG. The treatment of idiopathic sudden sensori-neural hearing loss. Otolaryngol Clin North Am. 1975;8:467-73.

MRI analysis

Temporal bone MRI was performed using a 3.0 T scanner (Skyra, Siemens Medical System, Erlangen, Germany). Morphologic characteristics of the vertebrobasilar system were analyzed blinded to the clinical information. Images were analyzed to determine the tortuosity (side and degree) and the diameter of the BA, and the presence of a dominant VA. The transverse diameter of the BA at the midpontine level was measured on axial T2-weighted images.1818 Smoker WR, Price MJ, Keyes WD, Corbett JJ, Gentry LR. High-resolution computed tomography of the basilar artery: 1. Normal size and position. Am J Neuroradiol. 1986;7:55-60. BA tortuosity was determined from coronal T2-weighted images (Fig. 1). The degree of BA laterality was graded from 0 to 3 on the basis of severity (0, midline; 1, questionably off midline; 2, definite displacement; 3, reaching the cerebellopontine angle).77 Samim M, Goldstein A, Schindler J, Johnson MH. Multimodality Imaging of Vertebrobasilar Dolichoectasia: Clinical Presentations and Imaging Spectrum. Radiographics. 2016;36:1129-46.

Figure 1
Assessment of the tortuosity of the basilar artery on coronal T2-weighted images. A, Tortuous basilar artery with marked displacement to the right. B, Straight basilar artery in the midline.

Statistical analysis

All statistical analyses were performed using SPSS software (version 19.0, IBM Corp., Armonk, NY, USA). Descriptive data are reported as counts (proportion, %) or mean ± Standard Deviation (SD), as appropriate. The chi square test and Fisher’s exact test were used to compare categorical variables, as appropriate for the data. For continuous variables with a normal distribution, Student's t-tests were used. For skewed variables, groups were compared using the Mann-Whitney U test. The relationship between the side affected by hearing loss and the radiological characteristics of the vertebrobasilar system was assessed using the linear-by-linear association test; p-values of < 0.05 were considered statistically significant.

Results

Demographics and clinical characteristics

We included a total of 134 patients (aged 52.2 ± 11.9 years) divided in two groups: those with mild-to-moderate hearing loss (n = 69) and those with severe-to-profound hearing loss (n = 65). The mean initial PTA in the affected ears was 52.2 ± 12.8 dB for the mild-to-moderate group and 92.9 ± 16.3 dB for the severe-to-profound group. Table 1 shows a comparison of the demographic and clinical characteristics of the two groups. There were no significant differences between the two groups with respect to age, sex, vascular risk factors, the affected side, and the time between onset and the initiation of treatment. However, there was a statistically significant difference between the groups in the presence of vertigo and the final PTA after treatment (p= 0.010 and < 0.001, respectively). The rates of vertigo at presentation and the follow-up PTA were higher in patients with severe-to-profound hearing loss.

Table 1
Demographics and clinical characteristics of the patients.

Radiological characteristics of the vertebrobasilar system

The overall radiological assessment demonstrated that 71.6% (96/134) of the patients had a tortuous BA and 67.1% (90/134) had an asymmetric VA (Table 2). The mean diameter of the BA was 3.36 ± 0.54 mm. Only five patients showed an ectatic BA with a diameter larger than 4.5 mm.1212 Clark SK, Tremann JA, Sennewald FR, Donaldson JA. Priapism: an unusual complication of heparin therapy for sudden deafness. Am J Otolaryngol. 1981;2:69-72. A dominant VA on the left side and BA displacement to the right side were more frequent. When the study populations were divided into two groups according to the degree of hearing impairment, there was no statistically significant difference between the groups in terms of BA diameter, BA tortuosity (side and degree), and VA asymmetry (Table 2).

Table 2
Radiological characteristics of the vertebrobasilar system.

Relationships between radiological and audiological findings

In this study, right-sided hearing loss (identified in 57.5% of patients) and right-sided BA displacement (identified in 41.0%) were more frequently seen than left-sided hearing loss and displacement. However, there was no significant directional relationship between the sides of hearing loss and BA displacement (p= 0.152, linear-by-linear association). We further analyzed the directional relationship within each hearing level group (PTA < 70 dB, and PTA ≥ 70 dB). Fig. 2 shows the significant difference in the trends between the two groups. Hearing loss laterality in the mild-to-moderate hearing loss group was not associated with the side of BA displacement (p = 0.950). On the other hand, in the severe-to-profound hearing loss group, 48 (73.8%) patients had lateral displacement of the BA (≥ Grade 1), and a significant directional relationship was detected, with hearing loss more likely to be on the opposite side to BA displacement (p= 0.036). Additionally, the degree of hearing impairment in the severe-to-profound hearing loss subgroup of patients with a tortuous BA was associated with the degree of BA tortuosity (Fig. 3). Our subgroup analysis showed that the initial PTA was significantly higher in patents with a Grade 3 BA displacement than patients with a Grade 1 BA displacement (p= 0.015).

Figure 2
The relationship between the side of hearing loss and the side of basilar artery displacement for two groups classified according to the degree of hearing loss. A, Mild-to-moderate hearing loss group (initial pure tone average < 70 dB). B, Severe-to-profound hearing loss group (initial pure tone average ≥ 70 dB).

Figure 3
The degree of hearing impairment at the initial visit in the severe-to-profound hearing loss group. Subgroup analysis according to the degree of basilar artery laterality.

Hearing recovery

The above results indicate that our hypothesis on vascular etiology was valid only in the severe-to-profound hearing loss group. Thus, further analyses of the efficacy of adjuvant therapies were performed in patients with initial PTA ≥ 70 dB, all of whom received adjuvant therapy. The frequency of vertigo was 36.2% in patients treated with ITS (ITS group, n = 47) vs. 16.7% in patients treated with heparin (heparin group, n = 18) (p = 0.108). With regard to the initial PTA, the ITS group had poorer hearing than the heparin group (p = 0.015) (Table 3). However, final hearing outcomes, absolute hearing gains, and hearing recovery did not significantly differ between the two groups (Table 3). Among 16 patients with no improvements, 9 patients (8.0% of the ITS group vs. 4.3% of the heparin group, p= 0.108) showed worsening of hearing from initial hearing level, which was between 1.25-12.5 dB worse. To select cases that were more likely to experience a hearing improvement following heparin therapy, we hypothesized that anticoagulant therapy may be more efficient in the subgroup of patients who had ISSNHL of vascular origin. Among the 65 patients in the severe-to-profound hearing loss group, 35 patients had hearing loss on the contralateral side of BA displacement. Our analysis of this subgroup showed that these patients achieved greater benefit from heparin than ITS as an adjuvant therapy (Fig. 4). In the heparin group, the follow-up PTA at three months improved to 35.8 ± 22.2 dB compared with 59.1 ± 30.7 dB in the ITS group (p= 0.041).

Figure 4
Assessment of hearing level at the initial visit and at the three-month follow-up in selected patients with idiopathic sudden sensorineural hearing loss: 1) those with an initial pure tone average ≥ 70 dB, and 2) those with displacement of the basilar artery to the contralateral side. Comparison of the therapeutic effects of heparin and intratympanic steroid injection as adjuvant treatments for these patients.

Table 3
Comparison of hearing measures in patients with severe-to-profound hearing loss.

There were no significant complications during or after heparin therapy, including hemorrhage, hypersensitivity, thrombocytopenia, or priapism. In addition, no patient experienced serious adverse events related to ITS, including tympanic membrane perforation, otitis media, and vertigo.

Discussion

Interruption of the vascular supply and resultant cochlear ischemia is thought to contribute to ISSNHL in some cases. In the context of this vascular etiology, heparin adjuvant therapy to improve cochlear blood flow has been implemented for the treatment of some ISSNHL cases in our department. Since treatment decisions were generally based on the clinician’s preference rather than on findings that implied an underlying etiology, this intervention improved hearing in some patients but not others. Therefore, this study was designed to identify possible vascular causes for ISSNHL using MRI of the vertebrobasilar system and to help determine which patients will benefit from heparin adjuvant therapy. It is of particular clinical importance to note that both a severe-to-profound degree of initial hearing impairment (PTA ≥ 70 dB) and the presence of hearing loss on the opposite side to that of BA displacement were associated with an increased chance of success of heparin therapy.

The present study is the first to use MRI to evaluate the benefit profile of anticoagulant adjuvant therapy in patients with unilateral ISSNHL. The current analyses provide evidence that anticoagulant therapy was associated with a better hearing outcome in the subset of patients for whom a vascular etiology was inferred from MRI findings regarding the vertebrobasilar system. A strength of this study is that routine evaluation for retrocochlear pathology was performed using temporal bone MRI for cases of sudden sensorineural hearing loss. Considering the significant prevalence (4.4%−13.75%) of pathogenic MRI abnormalities, including vestibular schwannoma and pontine infarction, in patients with sudden sensorineural hearing loss,99 Chandrasekhar SS, Do BS Tsai, 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. exclusion of these abnormalities through MRI supports an idiopathic diagnosis and reduces the risk of bias from diagnostic heterogeneity. In addition, the temporal bone MRI protocol in our department routinely included high resolution T2-weighted three-dimensional sequences. The cisternographic effect of these sequences enables the reliable identification of vascular structures within the cerebrospinal fluid such as the vertebral artery, the basilar artery, and even the Anterior Inferior Cerebellar Artery (AICA) without the risks of using contrast medium (Fig. 1B).

Some previous studies have reviewed the relationship between ISSNHL and the vertebrobasilar system. In 2016, Kim et al. conducted a study of 121 patients to analyze the characteristics of the vertebrobasilar system in relation to ISSNHL laterality.66 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. In accordance with the present study, they found that an opposite direction of BA displacement was significantly associated with ISSNHL laterality. In contrast to our findings, left-sided hearing loss (57.9%) was predominant in their study, and they did not report the opposite directional relationship for right-sided hearing loss. Other studies reviewed the relationship between ISSNHL and the characteristics of the AICA, which is a branch of the BA.1919 Gorrie A, Warren FM 3rd, de la Garza AN, Shelton C, Wiggins RH 3rd. Is there a correlation between vascular loops in the cerebellopontine angle and unexplained unilateral hearing loss? Otol Neurotol. 2010;31:48-52.,2020 Kim SH, Ju YR, Choi JE, Jung JY, Kim SHY, Lee MY. Anatomical location of AICA loop in CPA as a prognostic factor for ISSNHL. PeerJ. 2019;7:e6582. However, these authors found no significant correlations between ISSNHL and the anatomical shape and location of the AICA.

Currently, it is impossible to directly detect cochlear ischemia using a noninvasive method. Thus, it is difficult to precisely determine a vascular etiology of ISSNHL without pathological confirmation. On the other hand, the acute onset of sensorineural hearing loss in patients with vertebrobasilar ischemic stroke is commonly expected to result from a vascular cause, and this diagnosis is easily made using MRI.2121 Lee H, Kim JS, Chung EJ, Yi HA, Chung IS, Lee SR, et al. Infarction in the territory of anterior inferior cerebellar artery: spectrum of audiovestibular loss. Stroke. 2009;40:3745-51. A recent study examining a consecutive case series of unilateral pontine infarction in the AICA territory showed a similar directional association with BA displacement as in the current study. Hong et al. reported that pontine infarcts on the opposite side to the direction of BA displacement occurred in 72.3% (34/47) of patients.2222 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;80:1087-92. Given these findings, our results could substantiate the previous hypothesis that atherothrombotic events may occur more frequently on the opposite side to that of BA displacement, and these can eventually lead to ISSNHL of a vascular etiology.55 Kim C, Sohn JH, Choi HC. Vertebrobasilar angulation and its association with sudden sensorineural hearing loss. Med Hypotheses. 2012;79:202-3.

Interestingly, the initial degree of hearing impairment had a significant influence on the directional relationship between hearing loss laterality and the direction of BA displacement. The group of patients who had mild-to-moderate hearing loss (PTA < 70 dB) at initial presentation did not show a relationship between the laterality of hearing loss and the side of BA displacement (Fig. 2A). Common variations in anastomoses between the AICA and collateral arteries could explain this finding.2323 Nishijima Y. Anatomical analysis of the basilar artery and its branches with special reference to the arterial anastomosis, and its course and distribution on the pontine ventral surface. Nihon Ika Daigaku Zasshi. 1994;61:529-47. Experiments in guinea pig models have shown that the Posterior Inferior Cerebellar Artery (PICA) plays an important role in cochlear blood supply when the AICA or other branches of the BA are occluded.2424 Makino K, Morimitsu T. Effects of arterial occlusion on endocochlear DC potential and cochlear blood flow in guinea pigs. Auris Nasus Larynx. 1994;21:75-83. A cadaveric study has reported that anastomosis between the AICA and the PICA was observed in 27% of temporal bones.2525 Ishii T. Arteries from basal brain to inner ear Observation of 20 Japanese. Nihon Jibiinkoka Gakkai Kaiho. 1964;67:1387-99. This suggests that if atherothrombotic events occur in the BA or its branches, severe hearing impairment can easily follow as a result of cochlear ischemia in cases without collateral cochlear arteries. On the contrary, in cases with collateral arteries to the cochlea, hemodynamic changes that occur in the displaced BA may not be enough to affect cochlear circulation and cause severe hearing loss. Unfortunately, none of our patients underwent conventional angiography, and confirming the existence of anastomosing vessels from the PICA is beyond the resolution of MRI.

The contribution of BA tortuosity to cochlear ischemia can be explained by the effect of traction of BA branches, as well as a procoagulant state associated with slow blood flow and reduced shear stress on the concave side of the vessel.55 Kim C, Sohn JH, Choi HC. Vertebrobasilar angulation and its association with sudden sensorineural hearing loss. Med Hypotheses. 2012;79:202-3. Therefore, when patients with BA tortuosity develop ISSNHL in the contralateral ear, anticoagulant therapy is deemed to be a reasonable adjuvant treatment. However, in rare cases, labyrinthine hemorrhage may also be the vascular etiology of ISSNHL.2626 Salomone R, Abu TAA, Chaves AG, Bocalini MCC, de Oliveira Vicente A, Riskalla PE. Sudden hearing loss caused by labyrinthine hemorrhage. Braz J Otorhinolaryngol. 2008;74:776-9. Since it is known that systemic anticoagulation itself can increase the risk of labyrinthine hemorrhage, the use of heparin could constitute a potential harm to some patients with ISSNHL.2727 Kothari M, Knopp E, Jonas S, Levine D. Presumed vestibular hemorrhage secondary to warfarin. Neuroradiology. 1995;37:324-5. Labyrinthine hemorrhage can be suspected by hyperintense signal in the T1-weighted sequence.2828 Berrettini S, Seccia V, Fortunato S, Forli F, Bruschini L, Piaggi P, et al. Analysis of the 3-dimensional fluid-attenuated inversion-recovery (3D-FLAIR) sequence in idiopathic sudden sensorineural hearing loss. JAMA Otolaryngol Head Neck Surg. 2013;139:456-64. In this study, only 1 of 134 (0.75%) patients had a hyperintense cochlear signal in T1. That patient was treated with ITS, resulting in improvement of hearing (27.5 dB). Moreover, the dose of heparin in our protocol is even lower than that in standard low-dose heparin regimens for thromboembolism prophylaxis.2929 Owings JT, Blaisdell FW. Low-Dose Heparin Thromboembolism Prophylaxis. Arch Surg. 1996;131:1069-73. Based on our results, we believe that heparin adjuvant therapy has a role in selected patients with ISSNHL of obstructive vascular etiology. We have identified a combination of two independent factors that can be used to predict the likelihood of benefit from heparin adjuvant therapy, namely the presence of severe-to-profound hearing loss pretreatment (PTA ≥ 70 dB) and BA displacement to the contralateral side from the affected ear. However, heparin therapy for ISSNHL, in addition to being unproven in efficacy, is currently not recommended by any treatment guidelines and this study does not aim to validate its use in the clinical practice. Nevertheless, we anticipate that these two factors may predict the efficacy of other consensus recommendations targeting cochlear ischemia, such as hyperbaric oxygen therapy, in patients with ISSNHL.3030 Mathieu D, Marroni A, Kot J. Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb Med. 2017;47:24-32.

This study has some limitations. The main limitation are lack of randomization and sample size because of its retrospective nature. The analysis of the effectiveness of adjuvant therapy for treating patients with ISSNHL was inferior to that of high quality randomized clinical trials. However, it is believed that significant bias may be reduced by the selection of adjuvant therapy without knowing the disease status. Patients were allocated randomly to one of four physicians in our clinic, and every physician used only one protocol consistently during study period. Second, this study only relied on clinical characteristics, audiological measures, and MRI findings of the vertebrobasilar system to diagnose cochlear ischemia. Therefore, the suggested explanations for the contribution of BA tortuosity to ISSNHL remains speculative. To overcome these limitations, randomized controlled prospective study of clinical cases is needed to confirm the results of this study.

Conclusion

In a subset of patients with severe-to-profound ISSNHL, BA tortuosity had a significant directional relationship with ISSNHL laterality. In these selected patients who meet specific conditions, a significantly positive therapeutic effect of heparin on improving the recovery of hearing was observed.

Acknowledgement

We would like to thank Editage (www.editage.co.kr) for English language editing.

  • Funding
    This work was supported by the Gachon University Gil Medical Center (Grant number: FRD2019-01).
  • Peer Review under the responsibility of Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial.

References

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    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;22:624-35.
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    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;16:55-66.
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Publication Dates

  • Publication in this collection
    27 June 2022
  • Date of issue
    May-Jun 2022

History

  • Received
    15 Apr 2020
  • Accepted
    25 June 2020
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