Pathogenesis Of Sudden Sensorineural Hearing Loss Research Articles

Serum fat-soluble vitamin levels may be related to sudden sensorineural hearing loss

Background Few related studies reported yet the association between vitamins and the onset of sudden sensorineural hearing loss (SSNHL). Objective To explore the relationship between the serum levels of fat-soluble vitamins A, D, and E and the risk of SSNHL. Methods This retrospective analysis included 310 SSNHL patients and 154 people without risk of hearing loss. The demographic information of all participants like age, gender, body mass index, occupation, cigarette smoking or drinking status, etc. were recorded. The serum levels of vitamins A, D, and E were determined using the electrochemical method. Results The results indicated that serum vitamin D levels in SSNHL patients were significantly lower. Vitamin D deficiency was only observed in SSNHL group. Similarly, serum vitamin A levels in female SSNHL patients were significantly lower than the control group. Meanwhile, serum vitamin E levels in male SSNHL patients were significantly lower than the control group. Conclusion and significance Our results revealed that the serum levels of fat-soluble vitamins A, D, and E in SSNHL patients were lower than those in the control group with normal hearing, indicating that the decrease of serum fat-soluble vitamins may be related to SSNHL pathogenesis.

Differentially expressed miRNA profiles of serum-derived exosomes in patients with sudden sensorineural hearing loss.

This study aimed to compare the expressed microRNA (miRNA) profiles of serum-derived exosomes of patients with sudden sensorineural hearing loss (SSNHL) and normal hearing controls to identify exosomal miRNAs that may be associated with SSNHL or serve as biomarkers for SSNHL. Peripheral venous blood of patients with SSNHL and healthy controls was collected to isolate exosomes. Nanoparticle tracking analysis, transmission electron microscopy, and Western blotting were used to identify the isolated exosomes, after which total RNA was extracted and used for miRNA transcriptome sequencing. Differentially expressed miRNAs (DE-miRNAs) were identified based on the thresholds of P < 0.05 and |log2fold change| > 1 and subjected to functional analyses. Finally, four exosomal DE-miRNAs, including PC-5p-38556_39, PC-5p-29163_54, PC-5p-31742_49, and hsa-miR-93-3p_R+1, were chosen for validation using quantitative real-time polymerase chain reaction (RT-qPCR). Exosomes were isolated from serum and identified based on particle size, morphological examination, and expression of exosome-marker proteins. A total of 18 exosomal DE-miRNAs, including three upregulated and 15 downregulated miRNAs, were found in SSNHL cases. Gene ontology (GO) functional annotation analysis revealed that target genes in the top 20 terms were mainly related to "protein binding," "metal ion binding," "ATP binding," and "intracellular signal transduction." Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis revealed that these target genes were functionally enriched in the "Ras," "Hippo," "cGMP-PKG," and "AMPK signaling pathways." The expression levels of PC-5p-38556_39 and PC-5p-29163_54 were significantly downregulated and that of miR-93-3p_R+1 was highly upregulated in SSNHL. Consequently, the consistency rate between sequencing and RT-qPCR was 75% and sequencing results were highly reliable. This study identified 18 exosomal DE-miRNAs, including PC-5p-38556_39, PC-5p-29163_54, and miR-93-3p, which may be closely related to SSNHL pathogenesis or serve as biomarkers for SSNHL.

Cardiovascular Risk Factors and Sudden Sensorineural Hearing Loss: A Case-Control Study.

To investigate the role of cardiovascular risk factors (specifically hypertension [HTN], hyperlipidemia/dyslipidemia, diabetes mellitus I and II, and body mass index (BMI) on the development of sudden sensorineural hearing loss (SSNHL). Case-control retrospective chart review. A tertiary referral center. Patients aged 18 to 85 years who presented to the clinic over a 1-year span (September 17, 2020 to September 17, 2021) for evaluation of sudden sensorineural hearing loss. Comparing the prevalence of the different cardiovascular risk factors (CVRFs) in patients with sudden sensorineural hearing loss compared with when compared with non-SSNHL patients at a neurotology clinic. Two hundred twenty-three patients with SSNHL were compared with age- and gender-matched comparison group to investigate the prevalence of cardiovascular risk factors within each group. There are no statistically significant differences (p > 0.05) in the prevalence of HTN, hyperlipidemia/dyslipidemia, diabetes mellitus I and II, and BMI in patients with sudden sensorineural hearing loss when compared with non-SSNHL patients at a neurotology clinic. Despite correlation between CVRF and SSNHL found in some other studies, we did not find a significant correlation between CVRF (diabetes, HTN, dyslipidemia, and high BMI) and SSNHL in our retrospective case control study of patients presenting to a nonacademic tertiary neurotology clinic. Although there may be other factors contributing to the pathogenesis of SSNHL, we have not yet identified these factors.

Comparison of the incidence of sudden sensorineural hearing loss in Northern Taiwan and Southern Taiwan (2000–2015)

Background: The aim of the study is to compare the incidence of sudden sensorineural hearing loss (SSNHL) in Northern and Southern Taiwan, areas with different levels of air pollution. Methods: This was a retrospective, cross-sectional, 15-year nationwide study of SSNHL diagnoses between 2000 and 2015 in Taiwan National Health Insurance Research Database. Results: In total, 12,497 patients were included, 5584 in Northern Taiwan and 2532 in Southern Taiwan. In Northern and Southern Taiwan, the mean patients' age was 50.94 ± 16.62 and 50.70 ± 15.86 years, respectively; males (53.56% vs. 53.48%) were more frequently diagnosed than females (46.44% vs. 46.52%). The crude incidence was 41.13/100,000 and 49.45/100,000 in Northern and Southern Taiwan. The increasing trend was significantly higher in Southern than in Northern Taiwan. The maximal difference between Northern and Southern Taiwan, 44.31 versus 77.01/100,000 people/year, occurred in 2012. Mean particulate matter (PM2.5) annual concentration steadily decreased from 25.5 μg/m3 in 2010 to 19.20 μg/m3 in 2015 in Northern Taiwan, 37.10 μg/m3 in 2010 to 26.50 μg/m3 in 2015 in Southern Taiwan, Tainan City area, and 38.20 μg/m3 in 2010 to 25.10 μg/m3 in 2015 in Southern Taiwan, Kaohsiung City area. Cumulative PM2.5 exposure (PM2.5-year) from 2000 to 2015 was 441.1 μg/m3 × year in Northern Taiwan, 563.3 μg/m3 × year in Southern Taiwan – Tainan City area, and 684.3 μg/m3 × year in Southern Taiwan – Kaohsiung City area. Conclusion: SSNHL incidence increased from 2000 to 2015 and was higher in Southern than in Northern Taiwan. Cumulative PM2.5 exposure was higher in Southern than in Northern Taiwan. The relationship between cumulative PM2.5 exposure and SSNHL pathogenesis needs further investigation.

Differential Levels of Endoplasmic Reticulum Stress in Peripheral Blood Mononuclear Cells from Patients with Sudden Sensorineural Hearing Loss.

BackgroundSudden sensorineural hearing loss (SSNHL) is currently treated with a combination of drugs, predominantly with glucocorticoids (GCs). However, the mechanisms of action of GCs in SSNHL are unknown. This study aimed to analyze the role of endoplasmic reticulum stress (ERS) in SSNHL pathogenesis and prognosis.Material/MethodsIn this study, we evaluated the expression and activation status of the protein kinase RNA-like endoplasmic reticulum kinase (PERK)-C/EBP homologous protein (CHOP) pathway in peripheral blood mononuclear cells (PBMCs) from patients with SSNHL and compared them with those in healthy controls. We also compared differences in expression of activating transcription factor 4 (ATF4) and CHOP before and after glucocorticoid treatment in patients with improved and unimproved SSNHL.ResultsTreatment with GCs significantly improved hearing in 55% of patients with SSNHL. Levels of phosphorylated PERK (p-PERK) and phosphorylated eukaryotic initiation factor 2α were increased in PBMCs from patients with SSNHL compared with healthy controls. ATF4 and CHOP expression were also significantly elevated. After treatment, the amount of ATF4 and CHOP proteins in PBMCs in the patients whose SSNHL improved was significantly reduced compared with the levels measured before treatment in all patients with SSNHL. The expression of the ATF4 and CHOP proteins in PBMCs in the unimproved group, however, was not significantly changed relative to pretreatment levels.ConclusionsERS may play a significant role in the pathogenesis of SSNHL, and the responsiveness of the condition to GC-mediated mitigation of ERS may be one of the key factors that affect patient prognosis.

Coagulation States in Patients With Sudden Sensorineural Hearing Loss Evaluated by Thromboelastography.

The state of coagulation is controversial in patients with sudden sensorineural hearing loss (SSNHL). We used thromboelastography (TEG) to explore the relationships between blood coagulation parameters and SSNHL pathogenesis and recovery. Prospective study. Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. A total of 104 newly diagnosed patients with SSNHL and 29 matched healthy controls were recruited. Hearing assessments, TEG, and conventional coagulation tests (CCTs) were performed, followed by standard treatments and follow-up. The TEG parameters of patients with SSNHL were in the normal range, but the group exhibited a significantly prolonged kinetic time (K; P = .004) and a smaller angle (P = .003) as compared with the controls. After grouping the patients with SSNHL according to audiograms and comparing them in pairs, we found that the differences were significant only when controls were compared with patients with low-frequency SSNHL (K, P = .023; angle, P = .04) and flat-type SSNHL (K, P = .017; angle, P = .014). Logistic regression analysis showed that neither TEG nor CCT parameters significantly affected hearing improvement after SSNHL treatment. Although the K value and angle were significantly increased and significantly reduced, respectively, in the test group as compared with the control group, the state of coagulation in patients with SSNHL was still within the normal range. No CCT or TEG coagulation parameters (except the angle) differed significantly among patients in each group according to hearing recovery status, which suggested that the coagulation status does not determine the prognosis of patients with SSNHL.

Evaluation of Oxidative-Stress Pathway and Recovery of Sudden Sensorineural Hearing Loss.

Introduction Although the pathogenesis of sudden sensorineural hearing loss (SSNHL) has been discussed in the literature, many unclear points remain. Several authors have hypothesized that oxidative stress plays a role in the pathogenesis of noise-related hearing loss, as well as in drug- and aging-related hearing loss. Reactive oxygen species (ROS) may contribute to the pathogenesis of SSNHL in a similar way as in cases of ototoxicity, noise-induced hearing loss and presbyacusis. Objective The aim of the present study was to find potential peripheral biomarkers to show the levels of oxidative stress in samples of peripheral blood collected from SSNHL patients with and withouth metabolic disease. Methods In total, 80 consecutive patients with SSNHL were evaluated in the otolaryngology emergency room and outpatient clinic of a tertiary hospital between May 2017 and May 2019. All patients underwent detailed anamnesis, physical examination, audiometry, magnetic resonance imaging (MRI) of the inner ears, and blood tests for serum lipids and plasma activity of thiobarbituric acid reactive species (TBARS). Results No significant effect of malondialdehyde (MDA) activity was observed regarding the hearing recovery of patients who developed SSNHL. Conclusion We did not observe a significant correlation between the concentration of TBARs in the peripheral blood or the presence of arterial hypertension and the severity of the initial hearing loss or the prognosis of hearing recovery in patients with SSNHL. The concentration of TBARs in the peripheral blood may not adequately represent the abnormalities that occur in the intracoclear environment.

Genetic Polymorphisms in Sudden Sensorineural Hearing Loss: An Update.

To investigate the association between genetic polymorphisms and sudden sensorineural hearing loss (SSNHL). Most of the SSNHL cases still remain idiopathic, and several etiopathogenetic hypotheses, including a genetic predisposition, have been proposed. A literature review was conducted using different databases: Medline/PubMed, EMBASE, and CINAHL, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All databases have been searched from May 2016 to April 2020. Genetic susceptibility could represent a key element in the pathogenesis of SSNHL. A number of genetic polymorphisms related to (1) inner ear microvascular disease and endothelial dysfunction and (2) to inner ear oxidative stress and inflammation have been addressed in the current literature. The potential identification of a genetic profile related to SSNHL could provide a more accurate prognostic evidence of idiopathic SSNHL (ISSNHL), offering to the patients not only early-prevention strategies but eventually information on various inheritance modalities.

Metabolic syndrome components and sudden sensorineural hearing loss: a case-control study.

Cardiovascular risk factors, including metabolic syndrome (MetS) components, were reported as possible risk factors of sudden sensorineural hearing loss (SSNHL). The objective of this study was to evaluate the relationship between MetS (and its components) and SSNHL. Eighty-one SSNHL patients and 243 sex-, aged-matched controls participated from January 2018 to July 2019. The participants included 176 (54.3%) men and 148 (45.7%) women. The correlation between Mets components, total cholesterol, low-density lipoprotein-cholesterol, and the onset of SSNHL was analyzed using used multivariate conditional logistic regression analysis. A total 12 patients (14.8%) with SSNHL and 27 subjects (11.1%) in control group had MetS (p>0.05). The rate of low levels of high-density lipoprotein-cholesterol (HDL-C), hypertriglyceridemia, and hypertension was significantly higher in the SSNHL group than those in the control group (p<0.05). A trend of odds SSNHL was observed with increasing the number of MetS components (p<0.001). The multivariable analysis revealed that the rate of hypertriglyceridemia and low HDL-C concentration was significantly higher in the SSNHL groups compared to the controls. Hypertriglyceridemia and low levels of HDL-C may be important factors in the pathogenesis of SSNHL, and should be assessed during the investigation of patients with this condition.

Plasma levels of endothelial cell-specific molecule-1 and pentraxin-3 in idiopathic sudden sensorineural hearing loss.

To evaluate the plasma levels of endothelial cell-specific molecule-1 (ESM-1) and pentraxin-3 (PTX-3) in patients with idiopathic sudden sensorineural hearing loss, and to compare the pre- and post-treatment levels in patients responsive and non-responsive to therapy. The study included 108 subjects: 51 with idiopathic sudden sensorineural hearing loss and 57 controls. For ESM-1 and PTX-3 analyses, blood samples were collected before and three months after treatment initiation in the idiopathic sudden sensorineural hearing loss group and once for the control group. Treatment response was evaluated three months after therapy initiation with pure tone audiometry, and the patients were divided into two groups: responsive and non-responsive to treatment. Serum ESM-1 levels were significantly higher in the idiopathic sudden sensorineural hearing loss group than the control group, whereas the difference was not significant for PTX-3. In the responsive and non-responsive groups, ESM-1 and PTX-3 levels were not statistically different before and after treatment. To our knowledge, this is the first study investigating plasma ESM-1 and PTX-3 levels in idiopathic sudden sensorineural hearing loss. Increased plasma ESM-1 levels may confirm endothelial dysfunction involvement in idiopathic sudden sensorineural hearing loss pathogenesis, which could be associated with vascular impairment.

Coexistence of IL-6 -572C/G and ICAM-1 K469E Polymorphisms among Patients with Sudden Sensorineural Hearing Loss.

Sudden sensorineural hearing loss (SSNHL) is a multifactorial disease, and its etiology remains elusive. SSNHL is possibly caused by both the environmental factors and genetic alterations. Recently, several studies suggested that inflammation may be involved in the pathogenesis of SSNHL, and certain gene polymorphisms may have correlations with SSNHL. Interleukin 6 (IL-6) functions both as a pro-inflammatory cytokine and an anti-inflammatory factor. Intercellular adhesion molecule-1 (ICAM-1) is a member of the immunoglobulin family that is also involved in inflammation response. Importantly, the IL-6 gene promoter contains a single nucleotide polymorphism (SNP), -572C/G, and ICAM-1 gene contains a SNP (A/G) in the protein-coding region, Lys (AAG)/Glu (GAG) at codon 469, known as K469E polymorphism. However, there is no study about the ICAM-1 gene polymorphism among SSNHL patients. In this study, we explored the relationship between SSNHL with IL-6 -572C/G and ICAM-1 K469E polymorphisms. We conducted a case-control study including 75 SSNHL patients and 165 healthy controls and analyzed the distribution and odds ratios of IL-6 and ICAM-1 genotypes. The frequency of the G allele at IL-6 -572C/G polymorphism was significantly higher among SSNHL patients than that among healthy individuals. In multivariate analysis, the coexistence of IL-6 -572G allele (GG/CG) and E allele (EE/KE) of ICAM-1 K469E polymorphism was significantly associated with an increased SSNHL risk (P < 0.001). In conclusion, we propose that the combination of IL-6 -572C/G and ICAM-1 K469E polymorphisms have a synergistic effect on the onset of SSNHL.

RNA sequencing uncovers the key microRNAs potentially contributing to sudden sensorineural hearing loss.

This study aimed to identify miRNAs that may contribute to the pathogenesis of sudden sensorineural hearing loss (SSNHL) by RNA-seq (RNA-sequencing).RNA was extracted from SSNHL patients and healthy volunteers, respectively. Sequencing was performed on HiSeq4000 platform. After filtering, clean reads were mapped to the human reference genome hg19. Differential expression analysis of miRNAs between the SSNHL samples and the normal samples was performed using DEseq to identify differentially expressed microRNAs (DEMs). The target genes of the DEMs were predicted using the online tool miRWalk, which were then mapped to DAVID (https://david.ncifcrf.gov/) for functional annotation based on GO database and for pathway enrichment analysis based on KEGG. Finally, a miRNA-target-protein-protein interaction (PPIs) network was constructed using the DEMs and their target genes with interaction.Differential expression analysis reveals 24 DEMs between the SSNHL group and control group. A total of 1083 target genes were predicted. GO functional annotation analysis reveals that the target genes in the top 10 terms are mainly related to the development of salivary glands, neurotransmission, dendritic development, and other processes. KEGG pathway enrichment analysis reveals that the target genes were functionally enriched in pathways arachidonic acid metabolism, complement and coagulation cascades, linoleic acid metabolism, and MAPK signaling pathway. In the miRNA-target-PPI network, hsa-miR-34a/548n/15a/143/23a/210/1255a/18b/ /1180/99b had the most target genes; genes YWHAG, GSK3B, CDC42, NR3C1, LCK, UNC119, SIN3A, and NFKB2, interact with most other genes among all the predicted target genes.Hsa-miR-34a/15a/23a/210/18b/548n/143 is likely to have a role in the pathogenesis of SSNHL.

Erythrocyte Membrane Fluidity Alterations in Sudden Sensorineural Hearing Loss Patients: The Role of Oxidative Stress.

Introduction Sudden sensorineural hearing loss (SSNHL) involves an acute unexplained hearing loss, nearly always unilateral, that occurs over less than a 72-hour period. SSNHL pathogenesis is not yet fully understood. Cochlear vascular occlusion has been proposed as a potential mechanism of hearing damage and cochlear ischaemia has been related to alterations of cochlear microvessels. In addition, some researchers have focused their attention on the rheological alterations and blood hyperviscosity. Erythrocyte deformability plays a key role in determining blood viscosity, and it is critical to cochlear perfusion. It has been shown that oxidative stress-induced erythrocyte membrane fluidity alterations are linked to the progression of cardiovascular diseases. Methods To determine whether erythrocytes from SSNHL patients show signs of oxidative stress, and whether this condition can modify the haemorheologic profile in these patients, we analysed haemorheologic profile and erythrocyte oxidative stress in 35 SSNHL patients and 35 healthy subjects, matched for age and sex. Fluorescence anisotropy was used to evaluate the fluidity of erythrocyte membranes. Results Our results show a significant structural and functional involvement of erythrocyte membrane alterations in SSNHL, as well as elevated levels of membrane lipid peroxidation and intracellular reactive oxygen species (ROS) production. In addition, erythrocyte-derived ROS and erythrocyte lipid peroxidation positively correlated with whole blood viscosity and erythrocyte deformability. Moreover, in vitro experiments demonstrated that ROS display a key role in erythrocyte membrane fluidity. Conclusion These findings indicate that erythrocyte oxidative stress plays a key role in the pathogenesis of SSNHL and pave the way to new therapeutic interventions.

Lipid profiles and obesity as potential risk factors of sudden sensorineural hearing loss.

ObjectivesThe objective of our study was to establish whether increased lipid profiles and obesity affect the prevalence and prognosis of sudden sensorineural hearing loss (SSNHL).MethodsThis was a case-controlled study with a longitudinal design. According to our criteria, 324 patients with SSNHL were included in this study. To manage potential covariates, 972 subjects with normal hearing from the Korean National Health and Nutrition Examination Survey were matched as control group according to their propensity scores. Age, level of total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and body mass index (BMI) were obtained from the clinical data. Multivariate logistic regression analysis was used to investigate the association between SSNHL and lipid profiles or obesity in the 1296 subjects. Multivariate Cox regression analysis was used to determine whether lipid profiles and obesity are prognostic factors in patients with SSNHL.ResultsMean body weight, BMI, TC, and TG were significantly higher in patients with SSNHL compared with control subjects (p<0.05). However, LDL-C values did not differ significantly between the two groups. Subjects with elevated TC and TG levels had a 2.20- (95% CI 1.50–3.24) and 1.50-fold (95% CI 1.08–2.08) increased odds, respectively, of SSNHL compared with subjects with normal TC and TG levels. Subjects with grade III BMI had a 1.59-fold (95% CI 1.17–2.16) increased odds of SSNHL. Multivariate Cox regression analyses revealed that BMI was an independent risk factor of treatment outcome, as patients with BMI ≥27.5 were less likely to achieve complete recovery than those with BMI <27.5 (p<0.05).ConclusionsThe results of this study revealed that elevated TC and TG levels and increased BMI are significantly associated with the prevalence of SSNHL and its prognosis, indicating that vascular compromise may play an important role in the pathogenesis of SSNHL.

Relation between Stress-Related Hormone and Sudden Sensorineural Hearing Loss

Received September 27, 2013 Revised February 10, 2014 Accepted February 12, 2014 Address for correspondence Byung don Lee, MD, PhD Department of OtolaryngologyHead and Neck Surgery, Soonchunhyang University College of Medicine, 59 Daesagwan-ro, Yongsan-gu, Seoul 140-743, Korea Tel +82-2-709-9363 Fax +82-2-709-9134 E-mail bdlee12@schmc.ac.kr Background and ObjectivesZZThe plasma stress-related hormonal [cortisol, growth hormone, prolactin, antidiuretic hormone (ADH), adrenocorticotropic hormone (ACTH)] levels have been reported to be elevated in sudden sensorineural hearing loss (SSNHL) patients. However, little is known regarding the mechanisms related with the elevation of stress-related hormonal levels in SSNHL. Therefore, we measured the level of plasma stress-related hormones in SSNHL patients and in normal persons to demonstrate the association between the stress-related hormones and SSNHL. Subjects and MethodZZStress-related hormonal levels were measured from 68 patients who were diagnosed with SSNHL. These values were compared with the stress-related hormonal levels of 24 healthy control subjects. ResultsZZThe plasma ADH levels was significantly higher in SSNHL group compared with that in their normal control group, as shown by their respective values, 4.46 [95% confidence interval (CI): 3.80-5.24 pg/mL] and 3.05 (95% CI: 2.34-3.98 pg/mL). The values for plasma cortisol, growth hormone, and ACTH levels whose values were 2.07 (95% CI: 1.65-2.61 μg/L), 0.20 (95% CI: 0.14-0.29 μg/L), and 12.79 (95% CI: 11.16-14.66 pg/mL), respectively, were significantly lower in the SSNHL group than those in the normal control group whose values were 7.86 (95% CI: 5.33-5.24 μg/L), 0.61 (95% CI: 0.36-1.04 μg/L), 18.48 (95% CI: 14.9922.78 pg/mL), respectively. But there was no significant difference in prolactin between the two groups. ConclusionZZThis study demonstrates a possible role of stress-related hormones in the pathogenesis of SSNHL. However, only ADH level was higher than the control group. Furthermore, ACTH, growth hormone and cortisol levels were lower than the control groups. This means ADH, growth hormone, cortisol, ACTH levels are related with SSNHL. However, the impact of this hormone on the inner ear and endolymph homeostasis is still unknown. Further investigation is necessary to identify the action mechanism of these hormones in the inner ear. Korean J Otorhinolaryngol-Head Neck Surg 2014;57(6):373-8

No increased risk of sudden sensorineural hearing loss following recent herpes zoster: a nationwide population-based study

Conclusion: There is no increased risk for sudden sensorineural hearing loss (SSNHL) among people who have experienced a recent herpes zoster attack, compared with a matching population. Objective: The pathogenesis of SSNHL remains unknown, but viral infection is considered to be one of the main causes. The objective of this case-cohort study was to investigate the frequency and risk for SSNHL following a recent herpes zoster attack in the general population. Methods: We extracted 313 612 patients with herpes zoster from a nationwide health registry in Taiwan, and also randomly selected 313 612 matched control subjects. Each participant was individually tracked for 2 months from their index ambulatory care visit to identify those who developed SSNHL. Stratified Cox proportional hazard regressions were conducted to analyze the risk of SSNHL for the sampled patients. Results: Of the sample of 627 224 patients, 121 (0.02%) had SSNHL during the 2-month follow-up period, 59 from the study group (0.02% of the herpes zoster patients) and 62 from the comparison group (0.02% of patients without herpes zoster). Regression analysis revealed no increased adjusted hazard of SSNHL during the 2-month follow-up period for patients with herpes zoster as compared to those without (hazard ratio = 0.89, 95% confidence interval (CI) = 0.63–1.28, p = 0.540).

Contribution of 1425G/A Polymorphism in Protein Kinase C-Eta (PRKCH) Gene and Brain White Matter Lesions to the Risk of Sudden Sensorineural Hearing Loss in a Japanese Nested Case-Control Study

: Protein kinase C-eta (PRKCH) gene has been recently identified as a susceptible risk locus for cerebral infarction and hemorrhage in the Asian populations. The inner ear artery, a usual branch of anterior inferior cerebellar artery, is an end artery with minimal collaterals, therefore, the inner ear is particularly vulnerable to ischemia. The potential association between the development of stroke and sudden sensorineural hearing loss (SSNHL) has been implied. The authors hypothesized that the PRKCH polymorphism predisposing to stroke is associated with SSNHL risk, in view of brain magnetic resonance imaging (MRI) findings. The authors compared 33 cases of prevalent SSNHL with other cases among 2188 adults aged 40 to 79 years who participated in the Study of Aging, to assess the impact of PRKCH 1425G/A polymorphism in consideration of brain MRI findings. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL, with adjustment for other possibly influential factors under additive model of minor allele. The per-allele OR for SSNHL risk was 1.770 (95% confidence interval: 1.024–3.060) after adjustments. The effect of the 1425A-allele varied by white matter lesion (WML) status. A significant impact of the A-allele on SSNHL risk increment was observed in higher-WML group, but not in no- or mild-WML group. The 1425A-allele of PRKCH has probably contributed to the susceptibility to SSNHL, despite the etiological heterogeneity of SSNHL, and the impact of the PRKCH 1425A variation observed in this study may imply underlying vascular pathogenesis of SSNHL.

Sudden Sensorineural Hearing Loss: Subclinical Viral and Toxoplasmosis Infections as Aetiology and How They Alter the Clinical Course

Aim: To explore in a prospective study the evidence of certain viral and toxoplasmosis infections in sudden sensorineural hearing loss (SSHL). Methods: 84 consecutive patients with SSHL meeting certain criteria. All patients were assessed for specific IgM antibodies against cytomegalovirus, herpes simplex virus, toxoplasma and Epstein-Barr virus. All were treated with intravenous steroids and assigned to two groups: 76 IgM negative (NV group) and 8 IgM positive (no history of acute infection – V group). Results: The mean hearing level at presentation was 86.5 dB HL (median, 100) in the V group and 60.7 dB HL (median, 61) in the NV group. The difference was statistically significant (p = 0.003). The mean hearing level following treatment was 81.8 dB HL (median, 88) in the V group and 48.7 dB HL (median, 39) in the NV group. The difference was statistically significant (p = 0.004). There was a considerable improvement in hearing after treatment only in the NV group (p < 0.000001). Conclusions: Recent subclinical viral or toxoplasmosis infections may be involved in the pathogenesis of SSHL (in approx. 10% of cases), suggesting that SSHL is not a single disease. When certain viruses or toxoplasmoses are involved, the hearing is much worse in comparison to patients with no such indication of infection. An alteration in treatment dosage or method of steroid administration may be needed in such cases.

The Role of Soluble Adhesion Molecules and Cytokines in Sudden Sensorineural Hearing Loss

The underlying pathology of sudden sensorineural hearing loss (SSNHL) is still not completely understood. Inflammatory and vascular factors are part of the present discussion. The aim of this study was to learn more about the possible role of adhesion molecules and cytokines in patients with SSNHL. These molecules are thought to contribute to endothelial dysfunction. Case-control study with planned data collection. Tertiary referral center. Blood samples of 35 patients presenting with SSNHL of more than 30 dB in at least 3 contiguous frequencies were compared to a gender- and age-matched control group of normal-hearing subjects. Levels of the soluble adhesion molecules intercellular adhesion molecule (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), endothelial selectin (E-selectin), and concentration of interleukin 6 (IL-6), interleukin 8 (IL-8), and monocyte chemoattractant protein 1 (MCP-1) were measured using established enzyme-linked immunosorbent assays. These parameters as well as fibrinogen and lipid values were statistically analyzed. Levels of soluble ICAM-1, VCAM-1, E-selectin, IL-6, IL-8, and MCP-1 were not significantly elevated in patients with SSNHL. The clinical chemistry and hematologic determinations showed no significant differences between patients and control subjects. This study revealed no association concerning SSNHL and typical vascular risk factors such as lipids and fibrinogen. Soluble adhesion molecules were not elevated in the SSNHL group. The role of endothelial dysfunction represented by increased levels of soluble adhesion molecules in the pathogenesis of SSNHL remains unclear. Further studies are necessary to elucidate the vascular etiology of SSNHL.

A preliminary study on the role of inherited prothrombotic risk factors in Taiwanese patients with sudden sensorineural hearing loss

Sudden sensorineural hearing loss (SSHL) is a disease with unknown etiology. Recently, several studies revealed that some inherited prothrombotic risk factors are associated with SSHL in western populations. The objective of this study was to investigate the roles of the two most common genetic prothrombotic factors, the factor V Leiden G1691A and prothrombin G20210A in Taiwanese patients with SSHL. Twenty-four patients diagnosed with SSHL of more than 30 dB on average pure tone audiometry (PTA) and thirty-six healthy subjects without a history of hearing loss were enrolled in this study. Genomic DNA was isolated from peripheral blood leukocytes and the single nucleotide polymorphisms (SNPs) genotyping of factor V Leiden G1691A and prothrombin G20210A were analyzed using the TaqMan genotyping assays. Neither factor V Leiden G1691A nor prothrombin G20210A was detected in SSHL patients or in the control subjects. Both the patient group and the control group exhibited wild-type V Leiden 1691GG and wild-type prothrombin 20210GG. In conclusion, the factors V Leiden G1691A and prothrombin G20210A do not seem to play any role in Taiwanese patients with SSHL. Further studies with a large series of patients are needed to identify other possible candidate genes in order to elucidate the pathogenesis of SSHL.