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1.  Lipid Profiles and Obesity as Potential Risk Factors of Sudden Sensorineural Hearing Loss 
PLoS ONE  2015;10(4):e0122496.
Objectives
The objective of our study was to establish whether increased lipid profiles and obesity affect the prevalence and prognosis of sudden sensorineural hearing loss (SSNHL).
Methods
This 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.
Results
Mean 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).
Conclusions
The 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.
doi:10.1371/journal.pone.0122496
PMCID: PMC4393091  PMID: 25860024
2.  Endothelial dysfunction in patients with sudden sensorineural hearing loss 
Background:
Endothelial dysfunction probably has a role in the etiology of sudden sensorineural hearing loss (SSNHL). The aim of this study was determining of the relationship between endothelial dysfunction and SSNHL.
Materials and Methods:
In a case–control study, 30 patients with SSNHL and 30 otherwise healthy age and sex-matched controls were studied. Demographic data gathered included age, gender, family history of SSNHL, and history of smoking, cardiovascular disease, hypertension, diabetes, and dyslipidemia. Laboratory data included measurement of hemoglobin, fasting blood sugar (FBS) and lipid profile. Endothelial function was assessed by measuring flow-mediated dilation (FMD).
Results:
The two groups were the same in age (47.9 ± 9.3 and 48.1 ± 9.6 years, P = 0.946) with female/male ratio of 1:1 in both groups. Diabetes and dyslipidemia were more frequent in patients than controls (20% vs. 0%, P = 0.024). Brachial artery diameter was greater in patients than controls before (4.24 ± 0.39 vs. 3.84 ± 0.23 mm, P < 0.001) and after ischemia (4.51 ± 0.43 vs. 4.28 ± 0.27 mm, P = 0.020), but FMD was lower in patients than controls (6.21 ± 3.0 vs. 11.52 ± 2.30%, P < 0.001). Binary logistic regression analysis showed that FMD was associated with SSNHL independent from FBS and lipid profile (odds ratio [95% confidence interval] =0.439 [0.260–0.740], P = 0.002).
Conclusion:
Endothelial dysfunction, among other cardiovascular risk factors, is associated with SSNHL. This association is independent from other cardiovascular risk factors including diabetes and dyslipidemia.
doi:10.4103/2277-9175.174978
PMCID: PMC4763564  PMID: 26955626
Brachial artery diameter; endothelial dysfunction; sudden sensorineural hearing loss
3.  Increased risk of sudden sensorineural hearing loss in patients with hepatitis virus infection 
PLoS ONE  2017;12(4):e0175266.
The etiology of sudden sensorineural hearing loss (SSNHL) remains unclear. Possible causes of SSNHL include vascular diseases, viral infection, and autoimmune disorders. Therefore, we investigated whether hepatitis virus infection is correlated with the risk of SSNHL. Using data from the Taiwan Longitudinal Health Insurance Database, we conducted a retrospective matched-cohort study to compare patients diagnosed with hepatitis B or C virus (HBV/HCV) infections from January 1, 2000, to December 31, 2010, (N = 170,942) with frequency-matched controls (N = 512,826) at a ratio of 1:3 by sex, age, and index year. We followed each patient until the end of 2010 and evaluated the incidence of SSNHL. At the end of the follow-up period, 647 (0.38%, 647/170,942) patients developed SSNHL in the HBV/HCV group compared with 978 (0.19%, 978/512,826) in the control groups, with a statistical significance of P < 0.001 (using the log-rank test). The incidence rate ratio of SSNHL was 5.743-fold higher in the HBV/HCV group than in the control group (283.17 vs. 49.31 per 100,000 person-years, P < 0.001). The risk of SSNHL increased with HBV/HCV infection, and an adjusted hazard ratio of 5.103 (95% CI, 4.585–5.678) was determined using Cox proportional hazards regression. This study contributes to the awareness of the increased risk of SSNHL in HBV/HCV-infected populations. Our findings suggest that an underlying viral infection contributes to the development of SSNHL.
doi:10.1371/journal.pone.0175266
PMCID: PMC5383281  PMID: 28384326
4.  Polymorphisms in Genes Involved in Oxidative Stress Response in Patients with Sudden Sensorineural Hearing Loss and Ménière's Disease in a Japanese Population 
DNA and Cell Biology  2012;31(10):1555-1562.
The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that oxidative stress is related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the associations between genetic polymorphisms located in oxidative stress response genes and susceptibility to SSNHL and Ménière's disease. We compared 84 patients affected by SSNHL, 82 patients affected by Ménière's disease, and 2107 adults (1056 men and 1051 women; mean age, 59.2 years; range, 40–79 years) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios for SSNHL and Ménière's disease in individuals with polymorphisms in the genes glutathione peroxidase 1 (GPX1) (Pro198Leu, rs1050450), paraoxonase 1 (PON1) (Gln192Arg, rs662; and Met55Leu, rs854560), PON2 (Ser311Cys, rs7493), and superoxide dismutase 2 (SOD2) (Val16Ala, rs4880), with adjustment for age and gender. No significant differences in the distribution of the genotypes at these polymorphisms were observed among individuals with SSNHL and Ménière's disease and controls. No significant risk for SSNHL and Ménière's disease was observed in the additive genetic model, regardless of moderating variables. The C allele of SOD2 (rs4880) was more frequent in Ménière's disease cases with a hearing level over 50 dB compared with cases with a hearing level below 50 dB, suggesting that this polymorphism is associated with progression of a hearing loss in Ménière's disease. In conclusion, no significant associations between the polymorphisms of GPX1, PON1, PON2, and SOD2 and risk of SSNHL and Ménière's disease were observed in this Japanese case–control study.
Oxidative stress is centrally involved in neurodegeneration in many syndromes. In this study of Japanese patients with sudden hearing loss, polymorphisms of glutathione peroxidase 1, paraoxonase 1, and superoxide dismutase were studied, but there was no significant association of genetic polymorphisms between patients and controls.
doi:10.1089/dna.2012.1631
PMCID: PMC3458618  PMID: 22877234
5.  The Expression of AGO2 and DGCR8 in Idiopathic Sudden Sensorineural Hearing Loss 
Objectives
The microRNAs have been implicated in the development and function of the inner ear, especially in contribution to hearing. However, the impact of idiopathic sudden sensorineural hearing loss (SSNHL) on expression of miRNA biogenesis-related components has not been established. To investigate the regulations of microRNA (miRNA) biogenesis-related components, argonaute 2 (AGO2) and DiGeorge syndrome critical region gene 8 (DGCR8) mRNA expression in SSNHL and to evaluate the value of clinical parameters on their expression.
Methods
Thirty-seven patients diagnosed with SSNHL and fifty-one healthy volunteers were included in this study. We measured mRNA expression levels of AGO2 and DGCR8 in whole blood cells but erythrocytes of patients with SSNHL and controls, using reverse transcription and real-time polymerase chain reaction analysis.
Results
The mRNA expression level of AGO2 is upregulated in SSNHL. The expression level of AGO2 was significantly correlated with that of DGCR8 in both patients with SSNHL and controls. Expression level of AGO2 in SSNHL was correlated with white blood cell counts.
Conclusion
This study demonstrated for the first time that the AGO2 mRNA expression level was upregulated in SSNHL, suggesting its important role in pathobiology of SSNHL development.
doi:10.3342/ceo.2014.7.4.269
PMCID: PMC4240483  PMID: 25436045
MicroRNA biogenesis; Sudden hearing loss; DiGeorge syndrome critical region gene 8; Argonaute 2
6.  The Relationship between Serum Lipids and Sudden Sensorineural Hearing Loss: A Systematic Review and Meta-Analysis 
PLoS ONE  2015;10(4):e0121025.
Background
Sudden sensorineural hearing loss (SSNHL) is a relatively common condition that is usually of unknown etiology. A number of individual studies have investigated the association between various serum lipids and SSNHL; however, the findings have been inconsistent. In an attempt to obtain more definitive information on the relationship between serum lipids and SSNHL, we carried out a systematic review and meta-analysis.
Methods
Medline, the Cochrane Library, and EMBASE were searched using the following key words: lipid, cholesterol, triglyceride, fat, serum, blood, sudden hearing loss, hearing loss, hearing disorders. Randomized controlled trials, prospective cohort studies, and retrospective case-control studies involving patients with SSNHL and healthy controls that examined the relationship (reported as odds ratios [OR]) between lipid profiles and SSNHL were included. Primary outcomes were total cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations. Secondary outcomes were triglyceride, high-density lipoprotein cholesterol, and lipoprotein(a) concentrations.
Results
A total of 6 case-control studies were included in this systematic review/meta-analysis. The total number of participants ranged from 30 to 250 in the case group and from 43 to 271 in the control group. Meta-analysis revealed no significant difference in total cholesterol levels between the case and control groups (pooled OR = 1.79, 95% confidence interval [CI] = 0.98 to 3.26, P = 0.057). Likewise, meta-analysis revealed no significant difference in LDL-C concentrations between the case and control groups (pooled OR = 1.15, 95% CI = 0.64 to 2.07, P = 0.639). Since there were an insufficient number of studies reporting data for the secondary outcomes, meta-analysis was not possible.
Conclusions
Our results do not provide evidence for serum lipids being associated with SSNHL, nor do they definitively rule out such an association. Additional studies are needed to ascertain the relationship, or lack thereof, between serum lipids and SSNHL.
doi:10.1371/journal.pone.0121025
PMCID: PMC4395088  PMID: 25866869
7.  Prognostic Factors in Sudden Sensorineural Hearing Loss 
Balkan Medical Journal  2016;33(1):87-93.
Background:
Sudden sensorineural hearing loss (SSNHL) is still a complex and challenging process which requires clinical evidence regarding its etiology, treatment and prognostic factors. Therefore, determination of prognostic factors might aid in the selection of proper treatment modality.
Aims:
The aim of this study is to analyze whether there is correlation between SSNHL outcomes and (1) systemic steroid therapy, (2) time gap between onset of symptoms and initiation of therapy and (3) audiological pattern of hearing loss.
Study Design:
Retrospective chart review.
Methods:
Patients diagnosed at our clinic with SSNHL between May 2005 and December 2011 were reviewed. A detailed history of demographic features, side of hearing loss, previous SSNHL and/or ear surgery, recent upper respiratory tract infection, season of admission, duration of symptoms before admission and the presence of co-morbid diseases was obtained. Radiological and audiological evaluations were recorded and treatment protocol was assessed to determine whether systemic steroids were administered or not. Treatment started ≤5 days was regarded as “early” and >5 days as “delayed”. Initial audiological configurations were grouped as “upward sloping”, “downward sloping”, “flat” and “profound” hearing loss. Significant recovery was defined as thresholds improved to the same level with the unaffected ear or improved ≥30 dB on average. Slight recovery was hearing improvement between 10–30dB on average. Hearing recovery less than 10 dB was accepted as unchanged.
Results:
Among the 181 patients who met the inclusion criteria, systemic steroid was administered to 122 patients (67.4%), whereas 59 (32.6%) patients did not have steroids. It was found that steroid administration did not have any statistically significant effect in either recovered or unchanged hearing groups. Early treatment was achieved in 105 patients (58%) and 76 patients (42%) had delayed treatment. Recovery rates were no different in these two groups; however, when unchanged hearing rates were compared, it was statistically significantly lower in the early treatment group (p<0.05). When hearing outcomes were compared according to initial audiological pattern, significant recovery and unchanged hearing rates did not differ between groups; however, slight recovery rate was highest in the “flat” type audiological configuration (p<0.05).
Conclusion:
According to this patient series, oral steroid therapy does not have any influence on the outcomes of SSNHL. However, mid-frequency hearing loss of flat type and initiation of treatment earlier than 5 days from the onset of symptoms, seem to have positive prognostic effects. Further randomized controlled subject groups might contribute to determine prognostic factors of SSNHL.
doi:10.5152/balkanmedj.2015.15216
PMCID: PMC4767317  PMID: 26966623
Audiological configuration; delayed treatment; prognostic factors; sudden sensorineural hearing loss; systemic steroids
8.  Association of the 4 g/5 g polymorphism of plasminogen activator inhibitor-1 gene with sudden sensorineural hearing loss. A case control study 
Background
The 5 G/5 G genotype of PAI-1 polymorphism is linked to decreased plasminogen activator inhibitor-1 (PAI-1) levels and it has been suggested that lower PAI-1 levels may provide protective effects on inflammation, local microcirculatory disturbance, and fibrotic changes, which are likely associated with development of sudden sensorineural hearing loss (SSNHL).
Methods
The association of the 4 G/5 G PAI-1 polymorphism with the development and clinical outcome of SSNHL is evaluated via a case control study. 103 patients with SSNHL and 113 age and sex-matched controls were enrolled at University of Ferrara, Italy and hearing loss outcome was measured at least 3 months after the onset of hearing loss. DNA was isolated from peripheral blood using the QIAamp kit and the 4 G/5 G polymorphism in the −675 promoter region was genotyped with an allele-specific PCR. Genotype distribution was tested in patients and compared to controls by chi-square and odd-ratio analysis. The codominant and recessive models were used for the multiple logistic regression analyses of the PAI-1 gene allele.
Results
In this population, 5 G/5 G genotype had a two-time lower frequency in SSNHL patients compared to healthy controls (15.5% vs 30.1%) and was associated with decreased odds compared to 4 G/5 G genotype (OR 0.37, 95% CI 0.19-0.75, p = 0.005). In addition, the patients with 5 G/5 G genotype showed a trend of more than 2 times higher ratio of hearing recovery (> 20 dB) after systemic corticosteroid treatment compared to 4 G/5 G genotype (OR 2.3, 95% CI 0.32 - 16.83, p = 0.39), suggesting a better clinical outcome.
Conclusions
The 5 G/5 G genotype of PAI-1 may be associated with a reduced risk of SSNHL in the Italian population.
doi:10.1186/1472-6815-12-5
PMCID: PMC3431267  PMID: 22672326
Sudden hearing loss; Plasminogen activator inhibitor-1; 4 G/5 G polymorphism
9.  Risk of sudden sensorineural hearing loss in stroke patients 
Medicine  2016;95(36):e4841.
Abstract
Poststroke sudden sensorineural hearing loss (SSNHL) can hinder communication between patients and healthcare professionals, thereby restricting participation in rehabilitation programs and limiting improvements in physical performance. However, the relationship between stroke and SSNHL remains unclear. This study employed a nationwide population-based dataset to investigate the relationship between stroke and SSNHL.
The Taiwan Longitudinal Health Insurance Database was used to compile data from 11,115 stroke patients and a comparison cohort of 33,345 matched nonstroke enrollees. Each patient was followed for 5 years to identify new-onset SSNHL. Stratified Cox proportional-hazard regression analysis was used to examine the association of stroke with subsequent SSNHL.
Among the 44,460 patients, 66 patients (55,378 person-years) from the stroke cohort and 105 patients (166,586 person-years) from the comparison cohort were diagnosed with SSNHL. The incidence of SSNHL was approximately twice as high among stroke patients than among nonstroke patients (1.19 and 0.63/1000 person-years, respectively). Stroke patients had a 71% increased risk of SSNHL, compared with nonstroke patients (adjusted hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.24–2.36). We also observed a remarkable increase in risk of SSNHL in stroke patients within 1-year of follow-up (adjusted HR 5.65, 95% CI 3.07–10.41) or under steroid therapy during hospitalization (adjusted HR 5.14, 95% CI 2.08–12.75).
Patients with stroke had a higher risk of subsequent SSNHL compared with patients without stroke. In particular, stroke patients within 1-year follow-up and those undergoing steroid therapy during hospitalization should be treated with the utmost caution, considering that the risk of SSNHL increases by more than 5-fold.
doi:10.1097/MD.0000000000004841
PMCID: PMC5023925  PMID: 27603402
hearing loss; population; steroid therapy; stroke; sudden; Taiwan
10.  Intratympanic Steroids in Severe to Profound Sudden Sensorineural Hearing Loss as Salvage Treatment 
Objectives
Intratympanic steroids are being increasingly used in the treatment of sudden sensorineural hearing loss (SSNHL) after the failure of systemic therapy. This study evaluated the efficacy of administering intratympanic dexamethasone (ITD) as a salvage treatment for severe to profound SSNHL.
Methods
We reviewed the medical records of patients who presented with severe to profound SSNHL between January 2007 and December 2009. ITD was given about 14 days after the initial systemic treatment. Successful recovery was defined as complete or partial recovery using Sigel's criteria. We compared the results of treatment between the severe SSNHL (S-SSNHL) and profound SSNHL (P-SSNHL) groups.
Results
All the patients in the S-SSNHL group showed significant improvement, as compared to the P-SSNHL group (P=0.017). The recovery rate after the initial systemic treatment was 36% (9/25) in the S-SSNHL group and 18.1% (4/22) in the P-SSNHL group (P=0.207). In comparison, the recovery rate of ITD as a salvage treatment was 37.5% (6/16) in the S-SSNHL group and 5.5% (1/18) in the P-SSNHL group (P=0.03).
Conclusion
Our comparative study dose not support the efficacy of ITD as salvage treatment for patients with P-SSNHL as compared with that for S-SSNHL. We recommend that patients with P-SSNHL be informed about the low efficacy of ITD as a salvage treatment.
doi:10.3342/ceo.2010.3.3.122
PMCID: PMC2958501  PMID: 20978628
Sudden sensorineural hearing loss; Intratympanic; Steroid
11.  A clinical study of serum lipid disturbance in Chinese patients with sudden deafness 
Background
Pathological levels of blood lipids could be one of the causes of sudden sensorineural hearing loss (SSNHL). The objective of this manuscript is therefore to evaluate the relationship between blood lipid content and sudden sensorineural hearing loss (SSNHL).
Methods
The correlation between serum lipid parameters, including total cholesterol (TC), triglycerides, high-density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), apolipoprotein AI (apo AI), apolipoprotein B (apo B), and lipoprotein A (Lp(a)), and the onset of SSNHL was analyzed from a data set of 250 patients and an age, gender and weight matched control group of 250 subjects.
Results
The result of single factor logistic regression shows that TC (p<0.01), LDL-C (p<0.01), and apo B (p=0.03) of SSNHL group were significantly higher than those of the control group. The odds ratio of TC, LDL, and apo B are higher than 1, while the confidence intervals of the odds rations do not include 1. No significant difference was found with the prevalence of hypertension (P=0.818), diabetes (P=0.869) and smoking habits (P=0.653) between SSNHL group and control group.
Conclusion
Total cholesterol, low density lipoprotein cholesterol and apolipoprotein B concentrations may be important factors in the pathogenesis of sudden sensorineural hearing loss, and should be assessed during the investigation of patients with this condition.
doi:10.1186/1476-511X-12-95
PMCID: PMC3716951  PMID: 23819577
Sudden Hearing Loss; Cholesterol; Low Density Lipoprotein Cholesterol; Triglycerides
12.  Role of Platelet Parameters on Sudden Sensorineural Hearing Loss: A Case-Control Study in Iran 
PLoS ONE  2016;11(2):e0148149.
Sudden sensorineural hearing loss (SSNHL) is a common otological disorder characterized by a hearing loss greater than 30 dB over three consecutive frequencies, in less than 72 hours. It has been established that platelet parameters, such as mean platelet volume, are associated with ischemic heart events, whose clinical manifestations are similar to those of SSNHL. Hence, we aimed to determine if the platelet count, mean platelet volume and platelet distribution width are related to the occurrence and severity of sudden sensorineural hearing loss. A case-control prospective study was conducted in a teaching hospital in Iran. One hundred-eight patients with SSNHL and an equal number of healthy, age- and sex-matched controls were enrolled in the study. Peripheral venous blood samples were collected from the subjects, and the platelet count, mean platelet volume and platelet distribution width were measured with an automated blood cell counter. Analysis of the audiometry and hematological test results using SPSS22 software showed no statistical correlation between the platelet parameters and the occurrence of SSNHL, but correlation coefficients showed a significant correlation between PDW and hearing loss severity in patients group. However, further investigation is required to unequivocally establish the absence of correlation between the platelet parameters and occurrence of SSNHL.
doi:10.1371/journal.pone.0148149
PMCID: PMC4734775  PMID: 26829393
13.  Sleep Disturbance and Altered Expression of Circadian Clock Genes in Patients With Sudden Sensorineural Hearing Loss 
Medicine  2015;94(26):e978.
Abstract
The cause of sudden sensorineural hearing loss (SSNHL) remains unclear and therefore it is often considered as idiopathic. Sleep disturbance has been linked to SSNHL and circadian rhythm disruption, but the link between circadian rhythm disruption and SSNHL has never been investigated.
In this study, we surveyed the sleep quality of 38 patients with SSNHL using a simple insomnia sleep questionnaire. The expression of circadian clock genes in peripheral blood (PB) leukocytes from 38 patients with SSNHL and 71 healthy subjects was accessed using real-time quantitative reverse transcriptase-polymerase chain reaction and validated using immunocytochemical staining.
We found that 61.8% of patients with SSNHL suffered from insomnia before the insult of hearing loss. Besides, significantly decreased expression of PER1, CRY1, CRY2, CLOCK, BMAL1, and CKlε was found in PB leukocytes of patients with SSNHL when compared with healthy subjects. SSNHL patients with vertigo had significantly lower expression of CRY1 and CKlε than patients without vertigo symptoms. Our results imply the association of sleep disturbance and disrupted circadian rhythm in SSNHL.
doi:10.1097/MD.0000000000000978
PMCID: PMC4504592  PMID: 26131842
14.  Sleep Disturbance and Altered Expression of Circadian Clock Genes in Patients With Sudden Sensorineural Hearing Loss 
Medicine  2015;94(26):e978.
Abstract
The cause of sudden sensorineural hearing loss (SSNHL) remains unclear and therefore it is often considered as idiopathic. Sleep disturbance has been linked to SSNHL and circadian rhythm disruption, but the link between circadian rhythm disruption and SSNHL has never been investigated.
In this study, we surveyed the sleep quality of 38 patients with SSNHL using a simple insomnia sleep questionnaire. The expression of circadian clock genes in peripheral blood (PB) leukocytes from 38 patients with SSNHL and 71 healthy subjects was accessed using real-time quantitative reverse transcriptase-polymerase chain reaction and validated using immunocytochemical staining.
We found that 61.8% of patients with SSNHL suffered from insomnia before the insult of hearing loss. Besides, significantly decreased expression of PER1, CRY1, CRY2, CLOCK, BMAL1, and CKlε was found in PB leukocytes of patients with SSNHL when compared with healthy subjects. SSNHL patients with vertigo had significantly lower expression of CRY1 and CKlε than patients without vertigo symptoms. Our results imply the association of sleep disturbance and disrupted circadian rhythm in SSNHL.
doi:10.1097/MD.0000000000000978
PMCID: PMC4504592  PMID: 26131842
15.  Altered Contralateral Auditory Cortical Morphology in Unilateral Sudden Sensorineural Hearing Loss 
Otology & Neurotology  2015;36(10):1622-1627.
Objective:
To investigate the cerebral gray matter volume alterations in unilateral sudden sensorineural hearing loss patients within the acute period by the voxel-based morphometry method, and to determine if hearing impairment is associated with regional gray matter alterations in unilateral sudden sensorineural hearing loss patients.
Study Design:
Prospective case study.
Setting:
Tertiary class A teaching hospital.
Patients:
Thirty-nine patients with left-side unilateral sudden sensorineural hearing loss and 47 patients with right-side unilateral sudden sensorineural hearing loss.
Intervention:
Diagnostic.
Main Outcome Measure:
To compare the regional gray matter of unilateral sudden sensorineural hearing loss patients and healthy control participants.
Results:
Compared with control groups, patients with left side unilateral sudden sensorineural hearing loss had significant gray matter reductions in the right middle temporal gyrus and right superior temporal gyrus, whereas patients with right side unilateral sudden sensorineural hearing loss showed gray matter decreases in the left superior temporal gyrus and left middle temporal gyrus. A significant negative correlation with the duration of the sudden sensorineural hearing loss (R = −0.427, p = 0.012 for left-side unilateral SSNHL and R = −0.412, p = 0.013 for right-side unilateral SSNHL) was also found in these brain areas. There was no region with increased gray matter found in both groups of unilateral sudden sensorineural hearing loss patients.
Conclusions:
This study confirms that detectable decreased contralateral auditory cortical morphological changes have occurred in unilateral SSNHL patients within the acute period by voxel-based morphometry methods. The gray matter volumes of these brain areas also perform a negative correlation with the duration of the disease, which suggests a gradual brain structural impairment after the progression of the disease.
doi:10.1097/MAO.0000000000000892
PMCID: PMC4658668  PMID: 26595717
Contralateral auditory cortex; Unilateral sudden sensorineural hearing loss; Voxel-basedmorphometry
16.  Is Intratympanic Dexamathasone Injection Effective for the Treatment of Idiopathic Sudden Sensorineural Hearing Loss? 
Journal of Audiology & Otology  2015;19(3):154-158.
Background and Objectives
The purpose of this study is to identify the effectiveness of intratympanic (IT) steroids when used as an initial therapy in sudden sensorineural hearing loss (SSNHL), and when it is used as a salvage therapy in a refractory SSNHL.
Subjects and Methods
This retrospective study included 122 patients with SSNHL. First, patients were divided into three groups according to the initial treatment; IT steroid, systemic steroid and combined (systemic and IT steroid) groups. Second, patients were divided into two groups according to the salvage treatment in a refractory SSNHL; IT steroid and the control (non IT group). Fifty eight patients who did not respond to initial therapy were included in the second analysis. Hearing was assessed immediately before the treatment and 2 weeks, 4 weeks and 3 months after the treatments. Hearing recovery was defined as an improvement of >15 dB and the final hearing of 25-45 dB in the audiogram.
Results
When we analyzed the hearing recovery in initial treatment, the comparison of audiogram among three groups did not result in significantly different outcomes. There were no differences in the recovery rate in 2 and 4 weeks throughout all the frequencies. Also, the analysis of the salvage treatment demonstrated that neither IT steroid group nor control group was significantly effective in treating the refractory SSNHL.
Conclusions
The results suggest that initial treatment of SSNHL with IT steroid alone is as effective as systemic steroid alone or a combination therapy. Also, salvage IT steroids for refractory SSNHL did not have any additional beneficial effects.
doi:10.7874/jao.2015.19.3.154
PMCID: PMC4704555  PMID: 26771014
Sensorineural hearing loss; Intratympanic steroids; Hearing outcome
17.  Dicer Is Down-regulated and Correlated with Drosha in Idiopathic Sudden Sensorineural Hearing Loss 
Journal of Korean Medical Science  2015;30(8):1183-1188.
Previously, we reported the expression levels of specific microRNA machinery components, DGCR8 and AGO2, and their clinical association in patients with idiopathic sudden hearing loss (SSNHL). In the present study, we investigated the other important components of microRNA machinery and their association with clinical parameters in SSNHL patients. Fifty-seven patients diagnosed with SSNHL and fifty healthy volunteers were included in this study. We evaluated mRNA expression levels of Dicer and Drosha in whole blood of patients with SSNHL and the control group, using RT & real-time PCR analysis. The Dicer mRNA expression level was down-regulated in patients with SSNHL. However, the Drosha mRNA expression level was not significantly altered in patients with SSNHL. Neither the Dicer nor Drosha mRNA expression level was not associated with any clinical parameters, including age, sex, duration of initial treatment from onset (days), initial Pure tone average, Siegel's criteria, WBC, and Erythrocyte sedimentation rate. However, mRNA expression levels of Dicer and Drosha were positively correlated to each other in patients with SSNHL. In this study, we demonstrated for the first time that the Dicer mRNA expression level was down-regulated in patients with SSNHL, suggesting its important role in pathobiology of SSNHL development.
Graphical Abstract
doi:10.3346/jkms.2015.30.8.1183
PMCID: PMC4520951  PMID: 26240498
MicroRNA Biogenesis; Idiopathic Sudden Sensorineural Hearing Loss; Dicer; Drosha
18.  Current Efavirenz (EFV) or Ritonavir-Boosted Lopinavir (LPV/r) Use Correlates with Elevate Markers of Atherosclerosis in HIV-Infected Subjects in Addis Ababa, Ethiopia 
PLoS ONE  2015;10(4):e0117125.
Background
HIV patients on antiretroviral therapy have shown elevated incidence of dyslipidemia, lipodystrophy, and cardiovascular disease (CVD). Most studies, however, focus on cohorts from developed countries, with less data available for these co-morbidities in Ethiopia and sub-Saharan Africa.
Methods
Adult HIV-negative (n = 36), treatment naïve (n = 51), efavirenz (EFV)-treated (n = 91), nevirapine (NVP)-treated (n = 95), or ritonavir-boosted lopinavir (LPV/r)-treated (n=44) subjects were recruited from Black Lion Hospital in Addis Ababa, Ethiopia. Aortic pressure, augmentation pressure, and pulse wave velocity (PWV) were measured via applanation tonometry and carotid intima-media thickness (cIMT) and carotid arterial stiffness, and brachial artery flow-mediated dilation (FMD) were measured via non-invasive ultrasound. Body mass index, waist-to-hip circumference ratio (WHR), skinfold thickness, and self-reported fat redistribution were used to quantify lipodystrophy. CD4+ cell count, plasma HIV RNA levels, fasting glucose, total-, HDL-, and LDL-cholesterol, triglycerides, hsCRP, sVCAM-1, sICAM-1, leptin and complete blood count were measured.
Results
PWV and normalized cIMT were elevate and FMD impaired in EFV- and LPV/r-treated subjects compared to NVP-treated subjects; normalized cIMT was also elevated and FMD impaired in the EFV- and LPV/r-treated subjects compared to treatment-naïve subjects. cIMT was not statistically different across groups. Treated subjects exhibited elevated markers of dyslipidemia, inflammation, and lipodystrophy. PWV was associated with age, current EFV and LPV/r used, heart rate, blood pressure, triglycerides, LDL, and hsCRP, FMD with age, HIV duration, WHR, and glucose, and cIMT with age, current EFV use, skinfold thickness, and blood pressure.
Conclusions
Current EFV- or LPV/r-treatment, but not NVP-treatment, correlated with elevated markers of atherosclerosis, which may involve mechanisms distinct from traditional risk factors.
doi:10.1371/journal.pone.0117125
PMCID: PMC4411122  PMID: 25915208
19.  Idiopathic sudden sensorineural hearing loss in Japan 
Acta Oto-Laryngologica  2014;134(11):1158-1163.
Conclusion
An epidemiological survey of hospitals and private clinics in Japan regarding idiopathic sudden sensorineural hearing loss (SSNHL) revealed that the incidence of SSNHL was 60.9 per 100 000 population. There were more females than males in the younger generation.
Objective
The incidence of SSNHL varies largely by country. Because the Japanese criteria for diagnosing SSNHL have changed in accordance with those widely used in other parts of the world, a clinicoepidemiological study was undertaken using the new criteria.
Methods
Ehime, Aichi, and Iwate Prefectures were selected from the western, central, and northeastern regions of Japan, respectively. The subjects for this study were patients who suffered SSNHL between April 1, 2012 and March 31, 2013. Questionnaires were mailed to all hospitals and private clinics in which ENT doctors were working. Initial and final audiograms were requested for 10% of the patients.
Results
In all, 78 of 90 hospitals (87%) and 303 of 407 private clinics (74%) responded. It was reported that 1663 patients visited hospitals and 3090 patients visited only private clinics. It was estimated that 6205 SSNHL patients visited hospitals or private clinics in 1 year from a population of 10 145 000. Also, 23% of patients suffered acute low-tone SNHL (female to male ratio; 3:1 in definite cases).
doi:10.3109/00016489.2014.919406
PMCID: PMC4266072  PMID: 25315915
Sudden deafness; incidence; season; ENT doctors; epidemiology; acute low-tone sensorineural hearing loss; hospitals; private clinics; earthquake; population
20.  Sudden sensorineural hearing loss associated with inner ear lesions detected by magnetic resonance imaging 
PLoS ONE  2017;12(10):e0186038.
Although recent advances in magnetic resonance imaging (MRI) techniques have contributed to the detection of tiny lesions in the internal auditory canal (IAC) that may be responsible for sudden sensorineural hearing loss (SSNHL), there have been relatively few studies on the clinical characteristics of intra-labyrinthine hemorrhage (ILH) and labyrinthitis versus those regarding IAC tumors. Our purpose was to investigate the frequency of those IAC lesions on MRI and their clinical characteristics. Initial MRIs of 200 patients with SSNHL (93 men, 107 women; mean age = 48.61 years, range: 18–84 years), as well as detailed clinical histories, audiological examinations, and thyroid function, lipid battery, and serological tests (for viral agents and autoimmune disease), were performed. All patients were hospitalized at the time of diagnosis of SSNHL and were administered the same treatment protocol. Patients were divided into idiopathic and secondary groups according to their MRI results. After discharge, they underwent follow-up audiometry and clinical examination at predetermined intervals (2 weeks, 1, 2, 4, and 6 months, and 1 and 2 years). Propensity score-matching and receiver operating characteristics curves of the initial parameters were used for estimating clinical characteristics. Of the 200 patients, 25 (12.55%) who had abnormal findings suggesting inner ear lesions on MRI were assigned to the secondary SSNHL group; within this group, 10 patients (10/200, 5%) had a tumor invading the IAC, 7 (7/200, 3.5%) had ILH, 6 (6/200, 3%) had labyrinthitis, and 2 (1%) had a structural deformity of the IAC. The secondary group showed significantly poor recovery of hearing function compared with that in the idiopathic group. Patients with ILH or labyrinthitis showed prognoses that were equally poor as those of patients with tumors in the secondary group. Additionally, patients with such lesions showed significant canal paresis on the lesion side at an early stage and a high prevalence of benign paroxysmal positional vertigo (BPPV). In conclusion, the prevalence of non-tumorous lesions on MRI represents common findings and showed a poorer treatment response than that of vestibular Schwannoma in patients with SSNHL. Abnormal canal paresis (cut-off value of 35% on the lesioned side, sensitivity 65.2% and specificity 67%), spontaneous nystagmus directed to the contralesional side, and positional vertigo would be the clinical presentation of SSNHL with IAC lesions, in which the presence of acute prolonged vertigo or positional vertigo compatible with BPPV suggests the possibility of a non-tumorous lesion, such as ILH or a labyrinthitis rather than an IAC tumor.
doi:10.1371/journal.pone.0186038
PMCID: PMC5627945  PMID: 28977031
21.  Is BPPV a Prognostic Factor in Idiopathic Sudden Sensory Hearing Loss? 
Objectives
The prognostic significance of vertigo in patients with idiopathic sudden sensorineural hearing loss (SSNHL) remains a matter of debate because vertigo is associated with many different vestibular disorders. The purpose of this study is to determine the role of benign paroxysmal positional vertigo (BPPV) as a prognostic factor in patients with SSNHL.
Methods
We conducted a retrospective study of 298 patients with SSNHL. Hearing outcomes were evaluated by assessments of pre-treatment hearing and hearing gain. Comparative multivariate analyses between prognostic factors and hearing outcome were conducted.
Results
Thirty-eight (12.7%) SSNHL patients were found to also have BPPV. BPPV showed significant negative prognostic factors in hearing outcome on multivariate analysis (odds ratio, 0.15). In comparison to average pure tone audiometry (PTA), patients diagnosed with SSNHL with BPPV exhibited poorer hearing in pre- and post-treatment PTA compared to SSNHL without BPPV. Old age (>60 years), pre-treatment hearing, and canal paresis were significant outcome predictors.
Conclusion
BPPV in SSNHL patients, representing definitive vestibular damage, was closely related to poor prognosis.
doi:10.3342/ceo.2010.3.4.199
PMCID: PMC3010538  PMID: 21217960
Sudden hearing loss; Vertigo
22.  Vestibular Schwannoma in Patients with Sudden Sensorineural Hearing Loss 
Skull Base  2011;21(2):75-78.
Sudden sensorineural hearing loss (SSNHL) has several etiologies. It may be a presenting symptom of vestibular schwannoma (VS). This study aimed to establish the incidence of VS in patients with SSNHL, and we report several unusual cases among these patients. We reviewed retrospectively the charts and magnetic resonance imaging (MRI) findings of all adult patients who presented with SSNHL between 2002 and 2008. We utilized three-dimensional fast imaging with steady-state acquisition temporal MRI as a screening method. Of the 295 patients with SSNHL, VS was found in 12 (4%). All patients had intrameatal or small to medium-sized tumors. There were three cases with SSNHL in one ear and an incidental finding of intracanalicular VS in the contralateral ear. There were four cases of VS that showed good recovery from SSNHL with corticosteroid treatment. There were two cases that mimicked labyrinthitis with hearing loss and vertigo. A greater number of cases than expected of VS were detected in patients with SSNHL, as a result of increasing widespread use of MRI. Various unusual findings in these patients were identified. MRI would seem to be mandatory in all cases of SSNHL.
doi:10.1055/s-0030-1261257
PMCID: PMC3312594  PMID: 22451804
Sudden hearing loss; vestibular schwannoma; magnetic resonance imaging; steroid; vertigo
23.  Prognostic impact of standard laboratory values on outcome in patients with sudden sensorineural hearing loss 
Background
Aim of the present study was to evaluate prognostic factors, in particular standard laboratory parameters, for better outcome after idiopathic sudden sensorineural hearing loss (SSNHL).
Methods
Using a retrospective review, 173 patients were included presenting between 2006 and 2009 with unilateral SSNHL, ≥30 dB bone conduction in three succeeding frequencies between 0.125 to 8 kHz in pure tone audiometry (PTA), and a time interval between first symptoms and diagnostics ≤ 4 weeks. Hearing gain of <10 dB versus ≥10 dB in the affected ear in 6PTA values was the primary outcome criterion. Univariate and multivariate statistical tests were used to analyze predictors for better outcome.
Results
The initial hearing loss was 50.6 ± 27.2 dB. The absolute hearing gain was 15.6 ± 20.1 dB. Eighty-one patients (47%) had a final hearing gain of ≥10 dB. Low-frequency hearing loss (p <0.0001); start of inpatient treatment <4 days after onset (p = 0.018); first SSNHL (versus recurrent SSNHL, p = 0.001); initial hearing loss ≥ 60 dB (p < 0.0001); an initial quick value lower than the reference values (p = 0.040); and a pretherapeutic hyperfibrinogenemia (p = 0.007) were significantly correlated to better outcome (≥10 dB absolute hearing gain). Multivariate analysis revealed that first SSNHL (p = 0.004), start of treatment <4 days after onset (p = 0.015), initial hearing loss ≥ 60 dB (p = 0.001), and hyperfibrinogenemia (p = 0.032) were independent prognostic factors for better hearing recovery.
Conclusion
Better hearing gain in patients with hyperfibrinogenemia might be explained by the rheological properties of the applied therapy and supports the hypothesis that SSNHL is caused in part by vascular factors.
doi:10.1186/1472-6815-14-6
PMCID: PMC4099099  PMID: 25028570
Serology; Blood value; Outcome; Prognostic marker; Hearing loss
24.  Patent Foramen Ovale as Possible Cause of Sudden Sensorineural Hearing Loss: A Case Report 
Medical Principles and Practice  2017;26(5):491-494.
Objective
To present a case of sudden sensorineural hearing loss (SSNHL) and the related diagnostic workup.
Clinical Presentation and Intervention
A 54-year-old man presented with a unilateral SSNHL episode and vertigo. A severe patent foramen ovale (PFO) that included a complete ear nose and throat, audiological, and neurological examination was discovered during the diagnostic workup. Audiometry, blood, and serological tests were performed. Magnetic resonance imaging and color Doppler echography of the supra-aortic trunks and lower limbs were carried out. Finally, transthoracic followed by transesophageal echocardiography and transcranial Doppler were performed in order to confirm the diagnosis of PFO. Medical therapy with systemic steroid and antiplatelet drugs was administered.
Conclusions
This case showed a small PFO associated with an aneurysmatic interatrial septum. The PFO and paradoxical thromboembolism could be involved in the pathogenesis of SSNHL.
doi:10.1159/000484247
PMCID: PMC5757538  PMID: 29035892
Sudden sensorineural hearing loss; Patent foramen ovale; Etiology
25.  Sudden Sensorineural Hearing Loss 
Trends in Amplification  2011;15(3):91-105.
Sudden sensorineural hearing loss (SSNHL) is commonly encountered in audiologic and otolaryngologic practice. SSNHL is most commonly defined as sensorineural hearing loss of 30dB or greater over at least three contiguous audiometric frequencies occurring within a 72-hr period. Although the differential for SSNHL is vast, for the majority of patients an etiologic factor is not identified. Treatment for SSNHL of known etiology is directed toward that agent, with poor hearing outcomes characteristic for discoverable etiologies that cause inner ear hair cell loss. Steroid therapy is the current mainstay of treatment of idiopathic SSNHL in the United States. The prognosis for hearing recovery for idiopathic SSNHL is dependent on a number of factors including the severity of hearing loss, age, presence of vertigo, and shape of the audiogram.
doi:10.1177/1084713811408349
PMCID: PMC4040829  PMID: 21606048
hearing loss; sudden sensorineural hearing loss; idiopathic sudden sensorineural hearing loss; evaluation; treatment

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