Low-frequency Hearing Loss Research Articles

Clinical characteristics with long-term follow-up of four Okinawan families with moderate hearing loss caused by an OTOG variant

We describe the clinical features of four Japanese families with moderate sensorineural hearing loss due to the OTOG gene variant. We analyzed 98 hearing loss-related genes in patients with hearing loss originally from the Okinawa Islands using next-generation sequencing. We identified a homozygous variant of the gene encoding otogelin NM_001277269(OTOG): c.330C>G, p.Tyr110* in four families. All patients had moderate hearing loss with a slightly downsloping audiogram, including low frequency hearing loss without equilibrium dysfunction. Progressive hearing loss was not observed over the long-term in any patient. Among the three patients who underwent newborn hearing screening, two patients passed the test. OTOG-associated hearing loss was considered to progress early after birth, leading to moderate hearing loss and the later stable phase of hearing loss. Therefore, there are patients whose hearing loss cannot be detected by NHS, making genetic diagnosis of OTOG variants highly useful for complementing NHS in the clinical setting. Based on the allele frequency results, hearing loss caused by the p.Tyr110* variant in OTOG might be more common than we identified. The p.Tyr110* variant was reported in South Korea, suggesting that this variant is a common cause of moderate hearing loss in Japanese and Korean populations.

The natural progression of low-frequency hearing loss in patients who meet hybrid implant system candidacy criteria.

To investigate the natural progression of hearing loss in patients with high-frequency hearing loss whose audiograms met the criteria for a hybrid cochlear implant (CI). Retrospective database review. We retrospectively identified patients who met the criteria for a hybrid CI from our audiometric database. We also recorded the etiology of hearing loss in each patient and excluded patients with retrocochlear etiologies, those age <6 years, duration of observation <1 year, or those with a mixed or conductive hearing loss. We calculated the pre-CI progression of residual low-frequency (LF) hearing level in decibels per year and investigated the risk factor of the progression of hearing loss. A total of 1,083 ears of 944 patients were included in this study. The average rate of hearing loss progression for all etiologies was 1.70 ± 0.10 dB/yr at an average of 250 Hz, 500 Hz, and 1 kHz in the affected ear(s). The progression of hearing loss was 5.0 ± 0.93 dB/yr in patients with Meniere's disease and 3.5 ± 0.76 dB/yr in those with autoimmune disease, both of which were significantly faster than progression rates in other etiologies. In patients with idiopathic, genetic/hereditary, and congenital hearing loss, the progression of hearing loss was 1.46 ± 0.10 dB/yr. Patients with steeply sloping hearing loss experienced significantly faster progression in the ipsilateral ear compared to patients with another audiometric type. It is suggested that Meniere's disease, autoimmune-mediated inner ear disease, and steeply sloping hearing loss in the ipsilateral ear are risk factors for faster progression of residual LF hearing level. 4 Laryngoscope, 130:1299-1303, 2020.

Incidence of Developing Contralateral Ménière's Disease in Patients Undergoing Transmastoid Labyrinthectomy for Unilateral Ménière's Disease.

To analyze the incidence of developing contralateral Ménière's disease (MD) in patients who undergo labyrinthectomy for vestibular dysfunction in unilateral MD. Retrospective chart review. Adult patients with a diagnosis of MD who underwent surgical labyrinthectomy with minimum follow-up of 12 months were included. Patients who experienced chemical labyrinthectomy, surgical labyrinthectomy for a diagnosis other than MD, contralateral ear surgery, or bilateral MD before the labyrinthectomy were excluded. The key outcome measure is whether symptoms of MD developed in the contralateral ear post-labyrinthectomy. Statistical analysis was performed using χ2 (Fisher exact) test for discrete variables and the Student t test for continuous variables. A P value < .05 was considered significant. Of the140 patients who underwent labyrinthectomy for intractable vertigo due to unilateral MD, 84 had at least 1 year follow-up appointments. Twelve percent (10/84) of these patients developed contralateral MD, which was diagnosed by a neuro-otologist based on symptoms consistent with MD, including low-frequency sensorineural hearing loss. Average age in years is 63.12 (10.83; mean [SD]) at time of surgery. Average follow-up was 35.57 (15.89) months (range: 12-69 months). The incidence of contralateral MD development in patients who underwent labyrinthectomy for unilateral MD is 12%. The current literature states that MD has a 30% bilateral involvement rate. Our incidence is significantly lower when compared to the current literature.

Stem Cell Based Drug Delivery for Protection of Auditory Neurons in a Guinea Pig Model of Cochlear Implantation.

Background: The success of a cochlear implant (CI), which is the standard therapy for patients suffering from severe to profound sensorineural hearing loss, depends on the number and excitability of spiral ganglion neurons (SGNs). Brain-derived neurotrophic factor (BDNF) has a protective effect on SGNs but should be applied chronically to guarantee their lifelong survival. Long-term administration of BDNF could be achieved using genetically modified mesenchymal stem cells (MSCs), but these cells should be protected – by ultra-high viscous (UHV-) alginate (‘alginate-MSCs’) – from the recipient immune system and from uncontrolled migration.Methods: Brain-derived neurotrophic factor-producing MSCs were encapsulated in UHV-alginate. Four experimental groups were investigated using guinea pigs as an animal model. Three of them were systemically deafened and (unilaterally) received one of the following: (I) a CI; (II) an alginate-MSC-coated CI; (III) an injection of alginate-embedded MSCs into the scala tympani followed by CI insertion and alginate polymerization. Group IV was normal hearing, with CI insertion in both ears and a unilateral injection of alginate-MSCs. Using acoustically evoked auditory brainstem response measurements, hearing thresholds were determined before implantation and before sacrificing the animals. Electrode impedance was measured weekly. Four weeks after implantation, the animals were sacrificed and the SGN density and degree of fibrosis were evaluated.Results: The MSCs survived being implanted for 4 weeks in vivo. Neither the alginate-MSC injection nor the coating affected electrode impedance or fibrosis. CI insertion with and without previous alginate injection in normal-hearing animals resulted in increased hearing thresholds within the high-frequency range. Low-frequency hearing loss was additionally observed in the alginate-injected and implanted cochleae, but not in those treated only with a CI. In deafened animals, the alginate-MSC coating of the CI significantly prevented SGN from degeneration, but the injection of alginate-MSCs did not.Conclusion: Brain-derived neurotrophic factor-producing MSCs encapsulated in UHV-alginate prevent SGNs from degeneration in the form of coating on the CI surface, but not in the form of an injection. No increase in fibrosis or impedance was detected. Further research and development aimed at verifying long-term mechanical and biological properties of coated electrodes in vitro and in vivo, in combination with chronic electrical stimulation, is needed before the current concept can be tested in clinical trials.

The Effect of Hearing Aid Bandwidth and Configuration of Hearing Loss on Bimodal Speech Recognition in Cochlear Implant Users.

(1) To determine the effect of hearing aid (HA) bandwidth on bimodal speech perception in a group of unilateral cochlear implant (CI) patients with diverse degrees and configurations of hearing loss in the nonimplanted ear, (2) to determine whether there are demographic and audiometric characteristics that would help to determine the appropriate HA bandwidth for a bimodal patient. Participants were 33 experienced bimodal device users with postlingual hearing loss. Twenty three of them had better speech perception with the CI than the HA (CI>HA group) and 10 had better speech perception with the HA than the CI (HA>CI group). Word recognition in sentences (AzBio sentences at +10 dB signal to noise ratio presented at 0° azimuth) and in isolation [CNC (consonant-nucleus-consonant) words] was measured in unimodal conditions [CI alone or HAWB, which indicates HA alone in the wideband (WB) condition] and in bimodal conditions (BMWB, BM2k, BM1k, and BM500) as the bandwidth of an actual HA was reduced from WB to 2 kHz, 1 kHz, and 500 Hz. Linear mixed-effect modeling was used to quantify the relationship between speech recognition and listening condition and to assess how audiometric or demographic covariates might influence this relationship in each group. For the CI>HA group, AzBio scores were significantly higher (on average) in all bimodal conditions than in the best unimodal condition (CI alone) and were highest at the BMWB condition. For CNC scores, on the other hand, there was no significant improvement over the CI-alone condition in any of the bimodal conditions. The opposite pattern was observed in the HA>CI group. CNC word scores were significantly higher in the BM2k and BMWB conditions than in the best unimodal condition (HAWB), but none of the bimodal conditions were significantly better than the best unimodal condition for AzBio sentences (and some of the restricted bandwidth conditions were actually worse). Demographic covariates did not interact significantly with bimodal outcomes, but some of the audiometric variables did. For CI>HA participants with a flatter audiometric configuration and better mid-frequency hearing, bimodal AzBio scores were significantly higher than the CI-alone score with the WB setting (BMWB) but not with other bandwidths. In contrast, CI>HA participants with more steeply sloping hearing loss and poorer mid-frequency thresholds (≥82.5 dB) had significantly higher bimodal AzBio scores in all bimodal conditions, and the BMWB did not differ significantly from the restricted bandwidth conditions. HA>CI participants with mild low-frequency hearing loss showed the highest levels of bimodal improvement over the best unimodal condition on CNC words. They were also less affected by HA bandwidth reduction compared with HA>CI participants with poorer low-frequency thresholds. The pattern of bimodal performance as a function of the HA bandwidth was found to be consistent with the degree and configuration of hearing loss for both patients with CI>HA performance and for those with HA>CI performance. Our results support fitting the HA for all bimodal patients with the widest bandwidth consistent with effective audibility.

Caloric test and hearing characteristics in patients with vestibular migraine and Meniere's disease

Objective:This study was designed to distinguish vestibular migraine(VM) from Meniere's disease(MD) by comparing age, sex, family history, audiological and vestibular test results in patients with VM or MD. Method:Forty-six patients with suspected VM, 60 patients with confirmed VM, and 60 patients with confirmed MD were studied. All patients were asked for detailed medical history, and then underwent bithermal caloric test and audiological test. The hearing function and vestibular function were analyzed. Result:①General conditions: the sex ratio with suspected VM, confirmed VM and confirmed MD was 1∶4.75, 1∶5.67 and 1∶1. Family history in these three groups was 80.43%（37/46）,66.67%（40/60）,6.67%（4/60）, respectively. ②In the three groups, the abnormal rates of caloric test were 50.00% (23/46), 31.67% (19/60) and 78.33%(47/60), respectively.③The rate of pure tone audiometry abnormality in the three groups was 60.87% (28/46), 63.33% (38/60) and 100.00% (60/60), respectively. Of 46 suspected VM patients, 18 (39.13%) had high frequency hearing loss, 7 (15.22%) had full frequency hearing loss, and 3 (6.52%) had low frequency hearing loss. Among 60 confirmed VM patients, 18 (30.00%) had high frequency hearing loss, 15 (25.00%) had full frequency hearing loss, 4 (6.67%) had low frequency hearing loss, and 1 case (1.67%) with low frequency and high frequency hearing loss. Among 60 confirmed MD patients, 56 (93.33%) had full frequency hearing loss, and 4 (6.67%) had low frequency hearing loss. ④The difference of audiological test between patients with confirmed VM and patients with suspected VM was not statistically significant（P>0.05）. The difference of bithermal caloric test between patients with confirmed VM and patients with suspected VM was not statistically significant（P>0.05）.Compared with MD patients, the incidence of hearing loss and the incidence of abnormal bithermal caloric test in VM patients is lower（P<0.05）. Conclusion:The abnormality rate of caloric test and the incidence of hearing loss in MD patients were higher than VM. The confirmed and suspected VM patients can be accompanied by hearing loss mainly with high hearing frequency decline. There was no difference in clinical characteristics between confirmed and suspected VM patients.

Sequential versus Combination Treatment Using Steroids and Diuretics for Acute Low-Frequency Sensorineural Hearing Loss: A Noninferiority Trial.

Acute low-frequency hearing loss (ALHL) is typically treated with combination therapy, including steroids and diuretics. To avoid unnecessary use of steroids we proposed a method of sequential administration using these two drugs, and compared the efficacy of our protocol with that of existing combination treatments. A prospective, randomized, open-label, single-blind, noninferiority clinical trial was conducted to investigate whether the effectiveness of sequential treatment is noninferior to that of combination treatment for ALHL. Ninety-two patients with ALHL received either steroids and diuretics simultaneously for 2 weeks (combination group), or diuretics for 2 weeks followed by steroids for another 2 weeks if they did not respond to diuretic treatment (sequential group). The primary outcome measure was a change in mean hearing threshold at three frequencies (125, 250, and 500 Hz) at 4 weeks after treatment. The mean hearing threshold of the low frequencies improved 20.0 and 17.2 dB in the combination and the sequential group, respectively. The 95% lower confidence interval was -8.0 dB and noninferiority was established at p < 0.05. At 4 weeks after treatment, the complete recovery rate was 80.5 and 82.9% in the combination and sequential groups, respectively. This is the first study on ALHL treatment following the establishment of Consolidated Standards of Reporting Trials (CONSORT). The sequential treatment is not inferior to combination treatment for ALHL, and therefore may be a better treatment guideline for ALHL considering that patients receive less steroid exposure and smaller restrictions in diuretic use compared with steroids.

The effects of age and sex on rates of hearing loss for pure tones varying in duration

Mice are frequently used to study and model presbycusis due to similarities in the human and mouse cochleae and in genetic makeup. Most of the previous research on presbycusis used electrophysiological measures of hearing in mice, leading to an underrepresentation of behavioral experiments in the literature on mouse aging. The goal of the current research was to fill this gap by behaviorally measuring audiograms and temporal summation functions in aging mice. Adult mice were trained and tested using an accelerated longitudinal design. Mice were trained on a detection task using operant conditioning procedures with positive reinforcement. Audiograms were constructed using thresholds for 8, 16, 24, 42, and 64 kHz pure tones. Temporal summation functions were constructed for 16 and 64 kHz pure tones ranging from 20 to 800 ms in duration. The results revealed that mice retain pure tone hearing late into their lifespan, with high-frequency hearing loss preceding low-frequency hearing loss. Mice also benefit from increases in the duration of pure tones; however. this benefit decreases with age. Generally, male mice lose hearing at a faster rate than females. These results highlight the importance of measuring hearing in awake, trained, behaving subjects when comparing presbycusis across species.

Impact of TBI, PTSD, and Hearing Loss on Tinnitus Progression in a US Marine Cohort.

Mild TBI (TBI) is associated with up to a 75.7% incidence of tinnitus, and 33.0% of tinnitus patients at the US Veterans Administration carry a diagnosis of post-traumatic stress syndrome (PTSD). Yet factors contributing to new onset or exacerbation of tinnitus remain unclear. Here we measure intermittent and constant tinnitus at two time points to ascertain whether pre-existing or co-occurring traumatic brain injury (TBI), hearing loss, or post-traumatic stress disorder (PTSD) predicts new onset, lack of recovery and/or worsening of tinnitus in 2,600 United States Marines who were assessed before and after a combat deployment. Ordinal regression revealed that constant tinnitus before deployment was likely to continue after deployment (odds ratio [OR] = 28.62, 95% confidence interval [CI]: 9.84,83.26). Prior intermittent tinnitus increased risk of post-deployment constant tinnitus (OR = 4.95, CI: 2.97,8.27). Likelihood of tinnitus progression increased with partial PTSD (OR = 2.39, CI: 1.50,3.80) and TBI (OR = 1.59, CI: 1.13,2.23), particularly for blast TBI (OR = 2.01, CI: 1.27,3.12) and moderate to severe TBI (OR = 2.57, CI: 1.46,4.51). Tinnitus progression also increased with low frequency hearing loss (OR = 1.94, CI: 1.05,3.59), high frequency loss (OR = 3.01, CI: 1.91,4.76) and loss across both low and high frequency ranges (OR = 5.73, CI: 2.67,12.30). Screening for pre-existing or individual symptoms of PTSD, TBI, and hearing loss may allow for more focused treatment programs of comorbid disorders. Identification of those personnel vulnerable to tinnitus or its progression may direct increased acoustic protection for those at risk.

Relating tinnitus features and audiometric characteristics in a cohort of 34 tinnitus subjects

Although tinnitus, the conscious perception of a sound without a sound source external or internal to the body, is highly correlated with hearing loss, the precise nature of such correlation remains still unknown. People with high pitch tinnitus are used to suffer from high frequency hearing losses, and vice versa, low pitch tinnitus is mostly associated with low frequency hearing losses. However, many subjects with low or high frequency losses do no develop tinnitus. Thus, studies trying to relate audiometric characteristics and tinnitus features are still relevant. This article presents a correlational study of audiometric and tinnitus variables in a sample of 34 subjects, paying special attention to the heterogeneous subtypes of both audiometry shape and tinnitus etiology. Our results, which concur with others previously published, demonstrate that the tinnitus pitch, the main frequency of the tinnitus spectrum, in subjects with high-steep high-frequency and continuously steep hearing losses, are highly correlated with the frequency at which hearing loss reaches 50 dB HL.

Occlusal analysis and management of a patient with low-frequency hearing loss and ear fullness: A case report

Occlusal analysis and management of a patient with low-frequency hearing loss and ear fullness: A case report

Noise-induced hearing loss as a suspected cause of low-frequency hearing loss

Noise-induced hearing loss as a suspected cause of low-frequency hearing loss

Clinical Features and Endolymphatic Hydrops in Patients With MRI Evidence of Hydrops.

The purpose of this study was to investigate the correlation between grades of endolymphatic hydrops (ELH) and clinical characteristics and determine the detailed clinical characteristics of Ménière's disease (MD) patients with evidence of hydrops based on magnetic resonance imaging (MRI). One hundred ninety-eight MD patients (396 ears) with MRI evidence of hydrops were included. ELH grades were evaluated using the Nakashima grading standard. Correlations between the extent of ELH and clinical features were evaluated. Detailed clinical characteristics were analyzed to assess the clinical diagnostic criteria. Of 198 patients, ELH was observed in 100% of cases on the clinically affected side and 8.6% of cases on the asymptomatic side. In addition, 98.5% of ELH was classified as moderate or significant grade. Low-frequency hearing loss was significantly correlated with the extent of both vestibular and cochlear hydrops, whereas the vertigo attack frequency showed no significant correlation with ELH grades. The disease duration of MD with bilateral ELH was longer than that with unilateral ELH. The clinical characteristics were variant and did not completely fit the proposed diagnostic criteria. MRI findings have relevance to the clinical severity, to a certain extent, but not vestibular symptoms. The proposed diagnostic criteria based on clinical characteristics may be partially effective; analysis of the detailed clinical characteristics of MD was meaningful. Diagnosis of MD based on both MRI and clinical symptoms could facilitate an early diagnosis.

Significance of 1 kHz Pure-tone Threshold in Acute Low-frequency Sensorineural Hearing Loss.

To analyze risk factors for acute low-frequency hearing loss (ALFHL), and compare treatment outcomes in the presence or absence of such risk factors. A case series featuring retrospective chart review. An academic university hospital. We included 170 ALFHL patients without vertigo. All of the patients received one of four treatments: low-dose steroid (LD-steroid), high-dose steroid (HD-steroid), LD-steroid and diuretics (LD-combination therapy), and ITDI (intratympanic dexamethasone injection) and diuretics (ITDI-combination therapy). To identify risk factors, we reviewed the clinical features of patients such as age, sex, chief complaint, accompanying symptoms, diabetes, hypertension, time from disease onset, the extent of hearing loss, treatment methods, and 1 kHz involvement. ALFHL was diagnosed based on the average hearing loss >30 dB at 250 and 500 Hz. The overall rates of hearing recovery were 70-80% in the four treatment groups. In terms of the prognosis of ALFHL patients, we found that a longer time from disease onset and 1 kHz involvement were independent risk factors for poor prognosis. In addition, we compared treatment outcomes of four treatment methods in the presence or absence of risk factors. In ALFHL patients with risk factors, we found statistically significant differences (p = 0.042) among treatment methods; effectiveness ranged in the order if ITDI-combination therapy, LD-combination therapy, HD-steroid, and LD-steroid. Risk factors for poor hearing recovery in ALFHL included longer symptom duration and 1 kHz involvement. In ALFHL with such risk factors, combination therapy was more effective than oral steroid therapy.

Contribution of the GSTP1 c.313A>G variant to hearing loss risk in patients exposed to platin chemotherapy during childhood.

Ototoxicity is a potential adverse effect of chemotherapy with platin drugs, such as cisplatin and carboplatin, in children. Hearing loss (HL) affecting frequencies below 4kHz can compromise speech perception. The aim of this study was to investigate whether genetic variants previously implicated in ototoxicity are associated with HL overall and HL below 4kHz in pediatric oncology patients treated with cisplatin or carboplatin. Patients given cisplatin or carboplatin for a pediatric cancer at least 5years prior to the start of the study were enrolled. The patients underwent comprehensive audiological evaluations and genotyping to detect the presence of the GJB2 c.35delG, GSTP1 c.313A>G, and MT-RNR1m.1555A>G polymorphisms. HL was identified in 31/61 patients (50.8%), including 28/42 treated with cisplatin (66.6%) and 3/19 treated with carboplatin (15.8%). HL was associated with higher mean doses of cisplatin (p = .002) and carboplatin (p = .010). The c.313A>G variant of GSTP1 (heterozygous or homozygous) was detected in 31/61 patients (50.8%). An association between this variant allele and HL involving frequencies ≤ 4kHz was identified (p = .020; 10-fold vs. non-carriers). No associations with HL were observed for GJB2 or MT-RNR1 gene variants. The GSTP1 c.313A>G variant may increase the risk of low-frequency HL in pediatric oncology patients treated with cisplatin or carboplatin chemotherapy.

Hearing Preservation With Standard Length Electrodes in Pediatric Cochlear Implantation.

Preserving low frequencies following cochlear implantation improves outcomes and allows patients to use a combination of electrical and acoustic stimulation. This importance has been reflected in advances in electrode design and refined surgical techniques. Full insertion of standard length electrodes may be advantageous over shortened electrodes because more electrodes can be activated over time if low frequency hearing loss progresses. Surgeons must counsel patients over this choice but data is lacking regarding the degree and likelihood of hearing preservation achievable with standard length electrodes in children. We report our experience using standard length cochlear implant arrays for hearing preservation in children. Retrospective case series. preoperative hearing ≤85 dB HL at 250 Hz and aged ≤18 years. Hearing preservation percentages are calculated using the HEARRING group formula. (Equation is included in full-text article.)Preservation of > 75% was considered complete, 25 to 75% partial, and 1 to 25% minimal. Patients were implanted with either MED-EL FLEX28 or Cochlear Nucleus CI522. Standardized operative technique with facial recess approach, posterior tympanotomy and minimally traumatic round window insertion. Fifty-two implantations in 27 pediatric patients met inclusion criteria. Mean age at implantation: 9.8 years. Average latest audiogram: 8 months. Mean total pre- and postoperative pure-tone averages were 82.8 and 92.6 dB. Seventeen (33%) ears demonstrated complete hearing preservation, 22 (42%) ears partial hearing preservation, 7 (13%) minimal hearing preservation, and 6 (12%) exhibited no acoustic hearing postoperatively. Mean hearing preservation was 55.5%. Hearing preservation is achievable to varying degrees in pediatric cochlear implantation using standard length electrodes though it is difficult to predict preoperatively which children may benefit. This study is among the largest additions to the knowledge base for this patient group.

Prognosis of Sudden Low Frequency Hearing Loss during Long-term Follow-up

Objectives The prognosis of sudden low frequency hearing loss (SLFHL) is relatively good, but recurrences of hearing loss and possible progression to Meniere’s disease is still a clinically important concern. This study was conducted to confirm the rate at which SLFHL proceeds to Meniere’s disease. Methods We retrospectively analyzed the medical records of 160 SLFHL patients who were followed up for more than 6 months from September 2005 to August 2013. Progression, initial hearing level, recovery and recurrence of hearing loss were reviewed. Results 106 patients (66.25%) had complete hearing recovery, 32 (20%) had recurrent hearing loss. Of the 32 recurrent group, 15 (9.38%) had progressed to Meniere’s disease after average of 1.7±1.4 years. The mean age of nonrecurrent group was higher than recurrent group (55.3±14.6 and 48.0±13.4, respectively, p=0.011). The threshold of 250Hz was significantly higher in the nonrecurrent group compared with recurrent group (p=0.047). Conclusions In patients with SLFHL, recurrence at relatively young age should be considered with the possibility of progression to Meniere’s disease. Keywords: Sudden hearing loss; Sensorineural hearing loss; Prognosis; Meniere disease 중심 단어: 돌발성 난청, ê°ê°ì‹ ê²½ì„± 난청, 예후, 메니에르 병

Correction: Genetic and clinical aspects of Wolfram syndrome 1, a severe neurodegenerative disease.

The original version of this Article erroneously cropped part of the abstract. The abstract has now been corrected to read 'Wolfram syndrome 1 (WS1) is a rare autosomal recessive neurodegenerative disease characterized by diabetes insipidus, diabetes mellitus, optic atrophy, deafness, and other abnormalities. WS1 usually results in death before the age of 50 years. The pathogenesis of WS1 is ascribed to mutations of human WFS1 gene on chromosome 4p encoding a transmembrane protein called wolframin, which has physiological functions in membrane trafficking, secretion, processing, and/or regulation of ER calcium homeostasis. Different types of WFS1 mutations have been identified, and some of these have been associated with a dominant, severe type of WS. Mutations of CISD2 gene cause autosomal recessive Wolfram syndrome 2 (WS2) characterized by the absence of diabetes insipidus and psychiatric disorders, and by bleeding upper intestinal ulcer and defective platelet aggregation. Other WFS1-related disorders such as DFNA6/14/38 nonsyndromic low-frequency sensorineural hearing loss and Wolfram syndrome-like disease with autosomal dominant transmission have been described. WS1 is a devastating disease for the patients and their families. Thus, early diagnosis is imperative to enable proper prognostication, prevent complications, and reduce the transmission to further progeny. Although there is currently no effective therapy, potential new drugs have been introduced, attempting to improve the progression of this fatal disease." in both the PDF and HTML versions of the Article.

Intermittent Low Frequency Hearing Loss after Repeated Use of Moxifloxacin Eye Drops

Intermittent Low Frequency Hearing Loss after Repeated Use of Moxifloxacin Eye Drops

Hearing preservation at low frequencies by insulin-like growth factor 1 in a guinea pig model of cochlear implantation

The hybrid or electric-acoustic stimulation cochlear implant is indicated in patients with a residual hearing at low frequencies. It provides electric and acoustic stimulation for compensating for high- and low-frequency sounds, respectively. However, the implantation procedure damages the cochlea, resulting in loss of the residual-hearing and diminished effects of the acoustic-hearing in several patients. To prevent hearing loss after implantation, corticosteroids have been used clinically although their effects are limited. As an alternative to corticosteroids, insulin-like growth factor 1 (IGF1) has shown potent effects in various types of cochlear injury. In this study, the effects of IGF1 on hearing preservation were examined after cochlear implantation to a normal-hearing guinea pig model. The electrode was inserted in an atraumatic way through the round window membrane of guinea pigs with the application of a gelatin-sponge soaked with IGF1 or saline. The auditory brainstem response (ABR) was recorded pre-operatively, immediately after cochlear implantation, and 7, 14, 28, and 56 days after electrode insertion. In comparison to the control group, the IGF1-treated group showed better hearing preservation at low frequencies, 7 days after surgery. IGF1 application was effective at low frequencies (2 and 4 kHz) throughout the period of examination. Histological studies revealed that outer hair cell numbers, in the IGF1-treated group, were maintained in the cochlear region responsible for low-frequency hearing (upper midbasal turn) and that there was less fibrous tissue formation around the electrode. Both the outer hair cell counts and the extent of fibrosis significantly correlated with the ABR threshold shifts at low frequencies. These results indicate that IGF1 might attenuate loss of low-frequency hearing after cochlear implantation, suggesting its possible clinical use in soft surgeries involving cochlear implants with electric-acoustic stimulation for hearing preservation.