Influence of Cochlear Dead Regions on Hearing Outcome in Sudden Sensorineural Hearing Loss.

OBJECTIVE: The aims of this multicenter study were to prospectively evaluate the prevalence of dead regions (DRs) in sudden sensorineural hearing loss (SSNHL) and compare the clinical characteristics and hearing outcomes of SSNHL according to the presence of DRs. STUDY DESIGN: Prospective study. SETTING: Multicenter study. PATIENTS AND METHODS: The threshold-equalizing noise (TEN) test was prospectively performed on a total of 130 patients diagnosed with SSNHL. All patients received systemic steroid therapy and/or intratympanic steroid injection within 1 month after onset. Pure-tone audiograms and the TEN test were conducted before and after steroid treatment. Age, sex, side of affected ear, recurrence, onset of symptoms, presence of dizziness, and comorbid diseases were also collected. The prevalence of DRs in SSNHL and clinical factors related to the DRs were assessed. Hearing outcomes for SSNHL according to DRs were evaluated in 68 patients who followed a pure-tone audiogram. RESULTS: The overall prevalence of one or more DRs in SSNHL evaluated using the TEN test was 20.8% (27/130 subjects) and the overall frequency-specific prevalence of DR was 6.7% (61/910 DRs). Although the DRs (+)and DR (-) groups had similar initial pure-tone thresholds, the DRs (+) group had significantly worse initial WRS compared to the DRs (-) group (p = 0.015). The presence of DRs was not associated with hearing recovery in a multivariate logistic regression model, but it was significantly associated with the degree of hearing gain in a multivariate linear regression model (p = 0.018). CONCLUSIONS: The presence of DRs can be considered one of the poor prognostic factors for SSNHL and the TEN test may contribute to assess the prognosis of SSNHL in clinical settings.

Dysphagia Induced by Nasal Septal Chondroma: A Case Report.

Chondromas rarely occur in the nasal area and are usually found in the metaphyseal area of the phalanges and metacarpals of the hands, as well as the pelvis, sternum and scapula. The authors present an unusual case of dysphagia induced by histologically confirmed chondroma arising from the nasal septum. Treatment is to completely remove the mass with adequate margins of normal tissues to prevent recurrence and malignancy. Intranasal endoscopic removal of tumor with an adequate margin of normal tissue. After one year of treatment, there was no evidence of recurrence. We present a case of nasal septal chondroma in 18-year-old male. Keywords: chondroma; dysphagia; septum.

First recognized n-butanol concentration may be simple and useful index for assessing olfactory dysfunction in geriatric patients.

The KVSSII is widely used to evaluate olfactory function in the Korean population. We evaluated the usefulness of the first recognized n-butanol concentration, which is obtained at the beginning part of KVSS II, in predicting olfactory dysfunction. Three hundred seventy two subjects were enrolled in our study. The results of KVSS II and the demographic characteristics were statistically analyzed. The first recognized n-butanol concentration was positively correlated with the result of KVSS II. The mean value of first recognized n-butanol concentration was 5.59 ± 1.42 in normosmia, 4.10 ± 1.40 in hyposmia, and 0.84 ± 1.68 in the anosmia group. By ROC curve, cut-off value of 2.5 showed sensitivity of 85.9% and specificity of 90.6% for anosmia, and cut-off value of 4.5 showed sensitivity of 77.6% and specificity of 69.8% for hyposmia. Consequently, we suggest that it may be useful in assessing olfactory function, in geriatric patients who are not able to tolerate conventional KVSS II.

Losartan Prevents Maladaptive Auditory-Somatosensory Plasticity After Hearing Loss via Transforming Growth Factor-ß Signaling Suppression.

OBJECTIVES: Hearing loss disrupts the balance of auditory-somatosensory inputs in the cochlear nucleus (CN) of the brainstem, which has been suggested to be a mechanism of tinnitus. This disruption results from maladaptive auditory-somatosensory plasticity, which is a form of axonal sprouting. Axonal sprouting is promoted by transforming growth factor (TGF)-ß signaling, which can be inhibited by losartan. We investigated whether losartan prevents maladaptive auditory-somatosensory plasticity after hearing loss. METHODS: The study consisted of two stages: determining the time course of auditory-somatosensory plasticity following hearing loss and preventing auditory-somatosensory plasticity using losartan. In the first stage, rats were randomly divided into two groups: a control group that underwent a sham operation and a deaf group that underwent cochlea ablation on the left side. CNs were harvested 1 and 2 weeks after surgery. In the second stage, rats were randomly divided into either a saline group that underwent cochlear ablation on the left side and received normal saline or a losartan group that underwent cochlear ablation on the left side and received losartan. CNs were harvested 2 weeks after surgery. Hearing was estimated with auditory brainstem responses (ABRs). Western blotting was performed for vesicular glutamate transporter 1 (VGLUT1), reflecting auditory input; vesicular glutamate transporter 2 (VGLUT2), reflecting somatosensory input; growth-associated protein 43 (GAP-43), reflecting axonal sprouting; and p-Smad2/3. RESULTS: Baseline ABR thresholds before surgery ranged from 20 to 35 dB sound pressure level. After cochlear ablation, ABR thresholds were higher than 80 dB. In the first experiment, VGLUT2/VGLUT1 ratios did not differ significantly between the control and deaf groups 1 week after surgery. At 2 weeks after surgery, the deaf group had a significantly higher VGLUT2/VGLUT1 ratio compared to the control group. In the second experiment, the losartan group had a significantly lower VGLUT2/VGLUT1 ratio along with significantly lower p-Smad3 and GAP-43 levels compared to the saline group. CONCLUSION: Losartan might prevent axonal sprouting after hearing loss by blocking TGF-ß signaling thereby preventing maladaptive auditory-somatosensory plasticity.

Clinical utility of cervical vestibular-evoked myogenic potentials in predicting residual dizziness after benign paroxysmal positional vertigo.

OBJECTIVES: In the present study, the value of cervical vestibular-evoked myogenic potential (cVEMP) as a predictive factor for residual dizziness after recovery of benign paroxysmal positional vertigo (BPPV) was evaluated. METHODS: The present study included 65 patients who had BPPV and underwent cVEMP testing. Patients were divided into two groups depending on the presence or absence of residual dizziness after recovery of BPPV. Univariate and multivariate analyses were performed to determine the factors associated with residual dizziness using age, gender, affected semicircular canal, affected side, BPPV duration, and cVEMP parameters. RESULTS: In univariate analysis, cVEMP-modified interaural amplitude difference (IAD) ratio and p13 latency showed a relatively significant association (p < 0.20) with residual dizziness. Based on multivariate analysis, increased cVEMP-modified interaural amplitude difference (IAD) ratio at the affected side (≥25%; p = 0.018, OR 6.623) remained as an associated factor. CONCLUSIONS: Increased cVEMP-modified IAD ratio at the affected side is associated with residual dizziness. BPPV patients with increased cVEMP-modified IAD ratio at the affected side are more likely to have residual dizziness after recovery of BPPV. SIGNIFICANCE: cVEMP testing could be used for the prediction of residual dizziness. An increased cVEMP-modified IAD ratio at the affected side may be used as a predictor of residual dizziness.

Characterization of Detailed Audiological Features of Cytomegalovirus Infection: A Composite Cohort Study from Groups with Distinct Demographics.

Congenital cytomegalovirus (cCMV) infection is a common congenital infection that causes sensorineural hearing loss (SNHL). Despite its substantial impact on public health and cost burden, epidemiology and clinical features of CMV-related SNHL have never been reported in the Korean populations. This study investigated the detailed audiologic phenotypes of cCMV infection to see if a specific SNHL pattern is associated with a particular clinical setting. A total of 38 patients with cCMV infection were studied retrospectively. Patients were classified into three groups with distinct demographics: clinically driven diagnosis (n=17), routine newborn CMV screening according to the NICU protocols (n=10), or referral to ENT for cochlear implant (CI) (n=11). The incidence of cCMV infection was 3.6%, showing 33.3% of SNHL among cCMV patients, 38% of asymmetric hearing loss, 29% of late-onset hearing loss, and diverse severity spectrum in patients with CMV-related SNHL. CI recipients with CMV-related SNHL showed a significantly improved speech perception. Surprisingly, in 36.4 % of CI implantees, initial audiological manifestation was significant asymmetry of hearing thresholds between both ears, with better ear retaining significant residual hearing up to 50dB. CMV turns out to be a significant etiology of SNHL, first to date reported in the Korean pediatric population. Analysis of audiologic phenotypes showed a very wide spectrum of SNHL and favorable CI outcomes in case of profound deafness. Especially for the patients with asymmetric hearing loss, close surveillance of hearing should be warranted and CI could be considered on the worse side first, based on the observation of rapid progression to profound deafness of better side.

Surgical Labyrinthectomy of the Rat to Study the Vestibular System.

To study the vestibular system or the vestibular compensation process, a number of methods have been developed to cause vestibular damage, including surgical or chemical labyrinthectomy and vestibular neurectomy. Surgical labyrinthectomy is a relatively simple, reliable, and rapid method. Here, we describe the surgical technique for rat labyrinthectomy. A postauricular incision is made under general anesthesia to expose the external auditory canal and the tympanic membrane, after which the tympanic membrane and the ossicles are removed without the stapes. The stapes artery, which is located between the stapes and the oval window, is a vulnerable structure and must be preserved to obtain a clear surgical field. A hole to fenestrate the vestibule is made with a 2.1-mm drill bur superior to the stapes. Then, 100% ethanol is injected through this hole and aspirated several times. Meticulous dissection under a microscope and careful bleeding control are essential to obtain reliable results. Symptoms of vestibular loss, such as nystagmus, head tilting, and a rolling motion, are seen immediately after surgery. The rotarod or rotation chair test can be used to objectively and quantitatively evaluate the vestibular function.

One-step noninvasive prenatal testing (NIPT) for autosomal recessive homozygous point mutations using digital PCR.

Previously, we introduced a noninvasive prenatal testing (NIPT) protocol for diagnosing compound heterozygous autosomal recessive point mutations via maternal plasma DNA and simulated control genomic DNA sampling based on fetal DNA fraction. In our present study, we have improved our NIPT protocol to make it possible to diagnose homozygous autosomal recessive point mutations without the need to acquire fetal DNA fraction. Moreover, chi-squared test and empirical statistical range based on the proportion of mutant allele reads among the total reads served as the gatekeeping method. If this method yielded inconclusive results, then the Bayesian method was performed; final conclusion was drawn from the results of both methods. This protocol was applied to three families co-segregating congenital sensorineural hearing loss with monogenic homozygous mutations in prevalent deafness genes. This protocol successfully predicted the fetal genotypes from all families without the information about fetal DNA fraction using one-step dPCR reactions at least for these three families. Furthermore, we suspect that confirmatory diagnosis under this protocol is possible, not only by using picodroplet dPCR, but also by using the more readily available chip-based dPCR, making our NIPT protocol more useful in the diagnosis of autosomal recessive point mutations in the future.

Expansion of phenotypic spectrum of MYO15A pathogenic variants to include postlingual onset of progressive partial deafness.

BACKGROUND: MYO15A variants, except those in the N-terminal domain, have been shown to be associated with congenital or pre-lingual severe-to-profound hearing loss (DFNB3), which ultimately requires cochlear implantation in early childhood. Recently, such variants have also been shown to possibly cause moderate-to-severe hearing loss. Herein, we also demonstrate that some MYO15A mutant alleles can cause postlingual onset of progressive partial deafness. METHODS: Two multiplex Korean families (SB246 and SB224), manifesting postlingual, progressive, partial deafness in an autosomal recessive fashion, were recruited. Molecular genetics testing was performed in two different pipelines, in a parallel fashion, for the SB246 family: targeted exome sequencing (TES) of 129 known deafness genes from the proband and whole exome sequencing (WES) of all affected subjects. Only the former pipeline was performed for the SB224 family. Rigorous bioinformatics analyses encompassing structural variations were executed to investigate any causative variants. RESULTS: In the SB246 family, two different molecular diagnostic pipelines provided exactly the same candidate variants: c.5504G > A (p.R1835H) in the motor domain and c.10245_10247delCTC (p.S3417del) in the FERM domain of MYO15A. In the SB224 family, c.9790C > T (p.Q3264X) and c.10263C > G (p.I3421M) in the FERM domain were detected as candidate variants. CONCLUSIONS: Some recessive MYO15A variants can cause postlingual onset of progressive partial deafness. The phenotypic spectrum of DFNB3 should be extended to include such partial deafness. The mechanism for a milder phenotype could be due to the milder pathogenic potential from hypomorphic alleles of MYO15A or the presence of modifier genes. This merits further investigation.

The Protective Effect of Egb 761 Against 3-Nitropropionic Acid-Induced Hearing Loss: The Role of Sirtuin 1.

OBJECTIVES: Local administration of 3-nitropropionic acid (3-NP) to the inner ear induces sensorineural hearing loss. Several studies have shown the otoprotective effects of ginkgo biloba extract EGb 761. Moreover, EGb 761 has been reported to activate Sirtuin 1 (SIRT1). The present study was designed to investigate whether EGb 761 prevents 3-NP-induced sensorineural hearing loss and determine its effects on the expression of SIRT1. METHODS: Sprague Dawley rats were divided into four experimental groups: control group receiving vehicle of 3-NP, EGb group receiving EGb 761, 3-NP group receiving 3-NP, and EGb+3-NP group receiving EGb 761 and 3-NP. EGb 761 was given orally for 5 days. The 3-NP solution was injected into the tympanum 3 days after the start of EGb 761 administration. The auditory brainstem response was recorded before and after the injection. At 4 weeks after the administration of 3-NP or vehicle of 3-NP, cochleae were harvested, and hematoxylin and eosin staining and immunohistochemistry for SIRT1 antibody were performed. RESULTS: EGb+3-NP group showed significantly lower threshold shifts than 3-NP group. There was a significant preservation of type II fibrocytes and spiral ganglion cells in EGb+3-NP group than in 3-NP group. In EGb+3-NP group, there was a significantly greater number of SIRT1 immunopositive type II fibrocytes and spiral ganglion cells than in 3-NP group. Calculating the percentage of SIRT1 immunoreactive type II fibrocytes and spiral ganglion cells in viable type II fibrocytes and spiral ganglion cells, respectively, EGb+3-NP group showed significantly higher SIRT1 immunoreactive cells than 3-NP group. CONCLUSION: These results suggest that EGb 761 may prevent hearing loss induced by 3-NP in an acute ototoxic animal model, which appears to be related with SIRT1 expression.

Using temporal bone computed tomography to predict sensorineural hearing loss in otic capsule-sparing temporal bone fracture.

OBJECTIVES: The purpose of this study was to investigate the efficacy of otic capsule-sparing (OCS) length for the prediction of sensorineural hearing loss (SNHL) in patients with OCS temporal bone fracture. METHODS: Thirty-four patients with OCS temporal bone fracture were enrolled, and their temporal bone computed tomography (TBCT), audiogram, and medical records were reviewed. The TBCT measured the shortest length between the otic capsule and fracture line. This length was referred to as the OCS length and was used to predict SNHL. Ossicular dislocation and fracture were also evaluated. Patients were divided into two groups according to the presence of SNHL. Univariate and multivariate analyses were performed for age, gender, brain hemorrhage, mean bone conduction threshold on the contralesional side, OCS length, and ossicular dislocation and fracture on TBCT. A receiver operating characteristic (ROC) curve was produced to evaluate the efficacy of OCS length for the prediction of SNHL. To determine an association between degree of SNHL and OCS length, regression analysis was conducted in the SNHL group. RESULTS: The mean OCS lengths of the SNHL and non-SNHL groups were 4.42±1.67mm and 8.00±5.71mm, respectively. In the univariate analysis, a relatively significant association (P <0.20) was found between SNHL and age, brain hemorrhage, mean bone conduction threshold on the contralesional side, OCS length, and incus dislocation. Multivariate analysis was performed using these factors. On multivariate analysis, OCS length (P=0.030, odds ratio=0.598; 95% confidence interval 0.375-0.952) was the only independent factor associated with SNHL. The area under the curve (AUC) was 0.747. When the cut-off value of OCS length was 5.27mm, the sensitivity and specificity for the prediction of SNHL were 71.4% and 69.2%, respectively. In the regression analysis, OCS length showed a significant association with degree of SNHL in the SNHL group (P=0.025, ß=-12.822, SE=5.282). CONCLUSIONS: The major finding of our study was that OCS length was significantly associated with SNHL in patients with OCS temporal bone fracture. Such patients with a short OCS length had a higher likelihood of SNHL.

MicroRNAs 218a-5p, 219a-5p, and 221-3p regulate vestibular compensation.

Unilateral vestibular deafferentation (UVD) interrupts afferent signals from one side, resulting in an imbalance of the resting activity between bilateral vestibular nuclei. Vestibular compensation is the process of balancing the resting activity to reestablish homeostasis. Here, we investigated microRNAs (miRNAs) that regulate vestibular compensation using the Sprague-Dawley rat. After determining the progression of vestibular compensation following UVD, microarray analysis was performed and nine miRNAs were selected as candidates. Following validation by quantitative reverse transcription-PCR, three miRNAs remained. We assessed the effect of these miRNAs on vestibular compensation using miRNA oligomers. We compared the results of the rotarod test and 5-bromo-2'-deoxyuridine immunohistochemistry following UVD between the control group and the groups in which the candidate miRNA oligomers were administered. Administration of miR-218a-5p, 219a-5p, and 221-3p oligomers significantly affected vestibular compensation. Target pathway analysis of these miRNAs supported our results. Our findings suggest that the miRNAs 218a-5p, 219a-5p, and 221-3p regulate vestibular compensation.

Comparison of Free-Beam- and Fiber-Type CO2 Laser Delivery Systems in Stapes Surgery.

BACKGROUND AND OBJECTIVES: A free-beam-type CO2 laser, which use a micromanipulator mounted on a microscope as the delivery system, has the merit of not being affected by hand tremor at the time of shooting. However, this delivery system has several disadvantages, including a restricted operation range and a risk of incorrect focusing. A fiber-type CO2 laser uses a hand-held delivery system and has the opposite merits and demerits. We compared the results of stapes surgery with free-beam and fiber type delivery systems. SUBJECTS AND METHODS: The study enrolled 36 patients who underwent stapedotomy with free-beam- (n=26) or fiber- (n=10) type CO2 lasers. The air-bone (AB) gap closure, bone conduction (BC) change, and operating time were evaluated. The AB gap closure was calculated by subtracting the preoperative BC thresholds from the postoperative air conduction thresholds. The BC change was calculated by subtracting the postoperative BC thresholds from the preoperative BC thresholds. RESULTS: The mean operating time was significantly (p=0.035) shorter in the fiber-type group (72.5±8.2 min) than in the free-beam-type group (80.5±11.4 min). The mean AB gap closure did not differ significantly (p=0.297) between the free-beamand fiber-type groups (5.8±10.1 and 1.4±6.8 dB, respectively). The mean BC change did not differ significantly (p=0.873) between the free-beam- and fiber-type groups (2.4±6.9 and 2.8±5.3 dB, respectively). The hearing outcomes did not differ significantly between the two groups. CONCLUSIONS: Operating times were significantly shorter using the fiber-type CO2 laser, while hearing outcomes did not differ significantly between the two groups.

The Effect of Systemic Steroid on Hearing Preservation After Cochlear Implantation via Round Window Approach: A Guinea Pig Model.

HYPOTHESIS: When administered perioperatively, systemic dexamethasone will reduce the hearing loss associated with cochlear implantation (CI) performed via the round window approach. BACKGROUND: The benefits of electroacoustic stimulation have led to interest in pharmacological interventions to preserve hearing after CI. METHODS: Thirty guinea pigs were randomly divided into three experimental groups: a control group; a 3-day infusion group; and a 7-day infusion group. Dexamethasone was delivered via a mini-osmotic pump for either 3 or 7 days after CI via the round window. Pure tone-evoked auditory brainstem response (ABR) thresholds were monitored for a period of 12 weeks after CI. The cochleae were then collected for histology. RESULTS: At 4 and 12 weeks after CI, ABR threshold shifts were significantly reduced in both 7-day and 3-day infusion groups compared with the control group. Furthermore, the 7-day infusion group has significantly reduced ABR threshold shifts compared with the 3-day infusion group. The total tissue response, including fibrosis and ossification, was significantly reduced in the 7-day infusion group compared with the control group. On multiple regression the extent of fibrosis predicted hearing loss across most frequencies, while hair cell counts predicted ABR thresholds at 32 kHz. CONCLUSION: Hearing protection after systemic administration of steroids is more effective when continued for at least a week after CI. Similarly, this treatment approach was more effective in reducing the fibrosis that encapsulates the CI electrode. Reduced fibrosis seemed to be the most likely explanation for the hearing protection.

The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model.

The present study aimed to evaluate the effects of systemic lipoic acid on hearing preservation after cochlear implantation. Twelve Dunkin-Hartley guinea pigs were randomly divided into two groups: the control group and the lipoic acid group. Animals in the lipoic acid group received lipoic acid intraperitoneally for 4 weeks. A sterilised silicone electrode-dummy was inserted through the round window to a depth of approximately 5 mm. The hearing level was measured using auditory brainstem responses (ABRs) prior to electrode-dummy insertion, and at 4 days and 1, 2, 3 and 4 weeks after electrode-dummy insertion. The threshold shift was defined as the difference between the pre-operative threshold and each of the post-operative thresholds. The cochleae were examined histologically 4 weeks after electrode-dummy insertion. Threshold shifts changed with frequency but not time. At 2kHz, ABR threshold shifts were statistically significantly lower in the lipoic acid group than the control group. At 8, 16 and 32kHz, there was no significant difference in the ABR threshold shift between the two groups. Histologic review revealed less intracochlear fibrosis along the electrode-dummy insertion site in the lipoic acid group than in the control group. The spiral ganglion cell densities of the basal, middle and apical turns were significantly higher in the lipoic acid group compared with the control group. Therefore, systemic lipoic acid administration appears to effectively preserve hearing at low frequencies in patients undergoing cochlear implantation. These effects may be attributed to the protection of spiral ganglion cells and prevention of intracochlear fibrosis.

Clinical implication of cervical vestibular evoked myogenic potentials in benign paroxysmal positional vertigo.

OBJECTIVES: To evaluate the value of cervical vestibular evoked myogenic potential (cVEMP) as a prognostic factor for benign paroxysmal positional vertigo (BPPV). METHODS: We reviewed 65 patients with BPPV who underwent cVEMP. Patients were divided into two groups according to resistance to the repositioning maneuver. Univariable and multivariable analyses were performed with age, gender, affected semicircular canal, affected side and cVEMP parameters to find the associated factors for resistance to the repositioning maneuver. RESULTS: From univariable analysis, cVEMP interaural amplitude difference (IAD) ratio, the affected semicircular canal and the affected side showed a better association (p<0.10) with resistance to the repositioning maneuver. With multivariable analysis, decreased cVEMP IAD ratio at the affected side (⩽-25%) (p=0.043, OR=4.934) and the posterior semicircular canal (p=0.049, OR=3.780) remained as associated factors. CONCLUSIONS: Decreased cVEMP IAD ratio at the affected side is associated with resistance to the repositioning maneuver. BPPV patients with decreased cVEMP IAD ratio at the affected side have a higher likelihood of their BPPV persisting after a single repositioning maneuver. SIGNIFICANCE: cVEMP test may provide a prognosis of BPPV. A decreased cVEMP IAD ratio at the affected side may be prognostic of BPPV not resolving after a single repositioning maneuver.

Comparison of Treatment Outcomes Following Either Prefrontal Cortical-only or Dual-site Repetitive Transcranial Magnetic Stimulation in Chronic Tinnitus Patients: A Double-blind Randomized Study.

OBJECTIVES: We evaluated treatment outcomes following single-site repetitive transcranial magnetic stimulation (rTMS) in the dorsolateral prefrontal cortex (DLPFC) and dual-site rTMS in the auditory cortex (AC) and DLPFC (AC + FC). STUDY DESIGN AND PATIENTS: This prospective randomized double-blind trial initially included 19 patients with chronic tinnitus and 17 of these patients received rTMS on the left AC and left DLPFC or only the left DLPFC. The subjects were randomly allocated to either the dual-site rTMS (AC + FC) protocol (Group 1, n = 9) or the singlesite rTMS (DLPFC) protocol (Group 2, n = 8). Group 1 received daily treatments with 2,000 pulses applied to the AC and 1,000 pulses applied to the DLPFC for 4 days (total of 12,000 pulses) and Group 2 received daily treatments with 3,000 pulses applied the DLPFC for 4 days (total of 12,000 pulses). MAIN OUTCOME MEASURES: The severity of tinnitus was assessed before rTMS treatment using the Tinnitus Handicap Inventory (THI) and the self-rated Visual Analog Scale. These measures were used to determine the awareness, loudness, annoyance, and effects of tinnitus on daily life at 1, 2, 4, and 12 weeks after treatment. RESULTS: The improvement in THI score was significantly better in Group 1 than in Group 2, even after controlling for the between-group differences in pretreatment THI score. In terms of psychological factors, Group 1 exhibited significant improvements in scores on the State-Trait Anxiety Inventory (STAI) for both state anxiety (STAI-X1) and trait anxiety (STAI-X2) at 12 weeks posttreatment and scores on the Pittsburgh Sleep Quality Index at 4 weeks posttreatment. Group 2 showed an improvement in only the STAI-X2 score at 12 weeks posttreatment. CONCLUSIONS: The rTMS protocol effectively suppressed tinnitus in the dual-site rTMS (AC+FC) group but not in the single-site rTMS (DLPFC) group. Although recent evidence has shown that non-auditory cortices in the tinnitus network play an important role in the generation of tinnitus, our findings indicate that rTMS on non-auditory cortical sites alone may not be sufficient for treatment. Thus, dual-site rTMS in the AC and DLPFC may be preferable for controlling this condition.

Tinnitus therapy using tailor-made notched music delivered via a smartphone application and Ginko combined treatment: A pilot study.

OBJECTIVE: Notched music therapy has been suggested to be effective for relieving tinnitus. We have developed a smartphone application using tailor-made notched music for tinnitus patients. This study aimed to evaluate the effect of this smartphone application on reducing tinnitus. In addition, we investigated the predictive factors for tinnitus treatment outcome using this smartphone application. METHODS: A total of 26 patients who were chronically distressed by tinnitus with a ≥18 Tinnitus Handicap Inventory (THI) score were recruited from March 2013 to March 2015 (National Clinical Trial (NCT) Identifier Number 01663467). Patients were instructed to listen to tailor-made notched music through our smartphone application for 30-60min per day and were prescribed Ginkgo biloba for 3 months. Treatment outcome was evaluated using the THI, a visual analogue scale that measures the effects of tinnitus in terms of loudness, noticeable time, annoyance, and disruption of daily life. Demographic data, including age, sex, duration of tinnitus, and pre-treatment scores on questionnaires such as the Beck Depression Inventory (BDI), State Trait Anxiety Inventory (TAI), and Pittsburgh Sleep Quality Index (PSQI) scores were compared between the effective and non-effective groups according to the differences between their pre- and post-treatment THI scores. RESULTS: Smartphone application-delivered notched music therapy and Ginko combined treatment improved the THI score from 33.9±18.9 to 23.1±15.2; the effect was particularly marked for the emotional score of the THI. Improvement in the THI score was positively correlated with the initial THI score (P=0.001, adjusted estimated value=0.49, 95% confidence interval=0.25-0.73). CONCLUSION: Chronic tinnitus patients who underwent smartphone application-delivered notched music therapy and Ginko combined treatment showed improved THI scores, particularly the emotional score of the THI. A smartphone application-delivered therapy and Ginko combined treatment may be more effective in tinnitus patients who have had a higher initial THI.

Impact of control of blood glucose level during treatment of sudden deafness in diabetics: relationship with prognosis.

The objective of this study is to investigate the impact of control of blood glucose level during treatment of sudden deafness. A retrospective study was performed involving 197 patients from January, 2011 to September, 2015. All patients were administrated prednisolone (Pharmaprednisolone tab®, 5 mg/T; KoreaPharma) p.o under the following regimen: 60 mg/day for 4 days, 40 mg/day for 2 days, 30 mg/day for 1 day, 20 mg/day for 1 day, and 10 mg/day for 2 days. During treatment, pure tone audiometry and blood glucose level were investigated for each patient and the results were statistically analyzed. Mean hearing improvement was 19.2 dB for the non-diabetes group and 24.8 dB for the diabetes group. The greater improvement for diabetics was not statistically significant (p = 0.146). Hearing improvement was 25.1 dB for subjects with mean blood glucose <200 mg/dl and 24.6 dB for subjects with mean blood glucose >200 mg/dl; the difference was not statistically significant (p = 0.267). Mean blood glucose level was 200.8 mg/dl for subjects with hearing improvement >20 dB and 181.8 mg/dl for subjects with hearing improvement <20 dB; the difference was not statistically significant (p = 0.286). Control of blood glucose level during treatment of sudden deafness does not have a direct effect on prognosis.

Development of novel noninvasive prenatal testing protocol for whole autosomal recessive disease using picodroplet digital PCR.

We developed a protocol of noninvasive prenatal testing (NIPT), employing a higher-resolution picodroplet digital PCR, to detect genetic imbalance in maternal plasma DNA (mpDNA) caused by cell-free fetal DNA (cffDNA). In the present study, this approach was applied to four families with autosomal recessive (AR) congenital sensorineural hearing loss. First, a fraction of the fetal DNA in mpDNA was calculated. Then, we made artificial DNA mixtures (positive and negative controls) to simulate mpDNA containing the fraction of cffDNA with or without mutations. Next, a fraction of mutant cluster signals over the total signals was measured from mpDNA, positive controls, and negative controls. We determined whether fetal DNA carried any paternal or maternal mutations by calculating and comparing the sum of the log-likelihood of the study samples. Of the four families, we made a successful prediction of the complete fetal genotype in two cases where a distinct cluster was identified for each genotype and the fraction of cffDNA in mpDNA was at least 6.4%. Genotyping of only paternal mutation was possible in one of the other two families. This is the first NIPT protocol potentially applicable to any AR monogenic disease with various genotypes, including point mutations.