Evaluation of a Less Invasive Cochlear Implant Surgery in OPA1 Mutations Provoking Deafblindness.

Cochlear implantation (CI) for deafblindness may have more impact than for non-syndromic hearing loss. Deafblind patients have a double handicap in a society that is more and more empowered by fast communication. CI is a remedy for deafness, but requires revision surgery every 20 to 25 years, and thus placement should be minimally invasive. Furthermore, failed reimplantation surgery will have more impact on a deafblind person. In this context, we assessed the safety of minimally invasive robotically assisted cochlear implant surgery (RACIS) for the first time in a deafblind patient. Standard pure tone audiometry and speech audiometry were performed in a patient with deafblindness as part of this robotic-assisted CI study before and after surgery. This patient, with an optic atrophy 1 (OPA1) (OMIM#165500) mutation consented to RACIS for the second (contralateral) CI. The applicability and safety of RACIS were evaluated as well as her subjective opinion on her disability. RACIS was uneventful with successful surgical and auditory outcomes in this case of deafblindness due to the OPA1 mutation. RACIS appears to be a safe and beneficial intervention to increase communication skills in the cases of deafblindness due to an OPA1 mutation. The use of RACIS use should be widespread in deafblindness as it minimizes surgical trauma and possible failures.

Global Research on Hereditary Hearing Impairment Over the Last 40 Years: A Bibliometric Study.

BACKGROUND: Research on hereditary hearing impairment has had several boosts to identify deafness-causing genes. The number of studies regarding the diagnosis and treatment modalities of hereditary hearing impairment is enormous and increasing; however, little or no research has been conducted for evaluating the development of scientific output and trends in the field. Here, we provide a comprehensive overview of centers that focus their research on hereditary hearing impairment and their scientific output. METHODS: Bibliometric analysis of the publications related to hereditary hearing impairment published between 1980 and 2019 were used in this study, which were also indexed in Web of Science database. RESULTS: The highest number of scientific articles on hereditary hearing impairment came from the United States, and it was also the most cited country. The University of Iowa is a leading center in the domain of hereditary hearing impairment in the world over the last 40 years. Fudan University, Central South University, and Harvard Medical School are also institutions that have had a focus on hereditary hearing impairment. CONCLUSIONS: There is a progressive increase in scientific papers on hereditary hearing impairment over the last 40 years that we have found in our bibliometric study. We identified key centers in the scientific research on hereditary hearing impairment in the world and also key journals that focus on hereditary hearing impairment. This information can facilitate new researchers in this field to seek collaboration with experienced partners, better synthesize the orientation and boundaries of the subject, and find target journals. Ultimately, we provided a certain benchmark value for key centers that perhaps should have a more prominent role in constructing experimental research or even clinical guidelines.

Effects of polylactic acid film on middle ear mucosa and cochlear function in Guinea pigs.

Our aim was to assess the effects of polylactic acid (PLA) on middle ear mucosa and cochlea, to be used as a film barrier for postoperative adhesion prevention in the middle ear. Twenty-one albino Guinea pigs were included in the study. A window was opened on both tympanic bulla and on one side PLA material was placed in the middle ear and on the other side only fenestration was performed and used as a control. All Guinea pigs underwent evaluation of tympanic membranes microscopically; functional hearing was analyzed by auditory brainstem responses preoperatively, in the first and the sixth month. All Guinea pigs were killed on the sixth month for histopathologic evaluation of their temporal bones. There was no statistical difference between both groups regarding hearing thresholds, interpeak wave latencies preoperatively and on first and the sixth months postoperatively. Histopathological evaluation revealed no specific changes. There was a mild local inflammation both in the PLA implanted and control ears. PLA film barrier most likely has no toxic effects on Guinea pig middle ear and does not show any ototoxic side effects.

Preliminary results of a novel quorum sensing inhibitor against pneumococcal infection and biofilm formation with special interest to otitis media and cochlear implantation.

The purpose of the study is to assess the effect of a novel quorum sensing inhibitor (QSI), coded as 'yd 47', against otitis media and biofilm formation on Cochlear implants (CIs). Small pieces cut from cochlear implant were implanted under the skin in the retroauricular area on both sides of four guinea pigs. The implant pieces in the study and control sides were implanted in Streptococcus pneumoniae strain solution and saline, respectively. The right and left middle ears were also instilled with a solution containing pneumococci and saline, respectively. The animals were only given an intraperitoneal 'yd 47' twice daily for three months to be assessed later with electron microscopy. Clinical examination with palpation, inspection and otoscopy did not reveal any sign of implant infection or otitis media. In the study and control implant materials, soft tissues around the implant and tympanic membranes, there was no biofilm formation by pneumococci. Contamination by various cells and some rod-shaped bacteria (not diplococcic) were seen in some of the materials. In conclusion, the novel QSI seems promising in the prevention of otitis media and biofilm formation on CIs by pneumococci.

Utilizing ethnic-specific differences in minor allele frequency to recategorize reported pathogenic deafness variants.

Ethnic-specific differences in minor allele frequency impact variant categorization for genetic screening of nonsyndromic hearing loss (NSHL) and other genetic disorders. We sought to evaluate all previously reported pathogenic NSHL variants in the context of a large number of controls from ethnically distinct populations sequenced with orthogonal massively parallel sequencing methods. We used HGMD, ClinVar, and dbSNP to generate a comprehensive list of reported pathogenic NSHL variants and re-evaluated these variants in the context of 8,595 individuals from 12 populations and 6 ethnically distinct major human evolutionary phylogenetic groups from three sources (Exome Variant Server, 1000 Genomes project, and a control set of individuals created for this study, the OtoDB). Of the 2,197 reported pathogenic deafness variants, 325 (14.8%) were present in at least one of the 8,595 controls, indicating a minor allele frequency (MAF) > 0.00006. MAFs ranged as high as 0.72, a level incompatible with pathogenicity for a fully penetrant disease like NSHL. Based on these data, we established MAF thresholds of 0.005 for autosomal-recessive variants (excluding specific variants in GJB2) and 0.0005 for autosomal-dominant variants. Using these thresholds, we recategorized 93 (4.2%) of reported pathogenic variants as benign. Our data show that evaluation of reported pathogenic deafness variants using variant MAFs from multiple distinct ethnicities and sequenced by orthogonal methods provides a powerful filter for determining pathogenicity. The proposed MAF thresholds will facilitate clinical interpretation of variants identified in genetic testing for NSHL. All data are publicly available to facilitate interpretation of genetic variants causing deafness.

Methods and preliminary outcomes of pediatric auditory brainstem implantation.

OBJECTIVE: The objective was to provide information about methods used and preliminary outcomes for pediatric ABI (auditory brainstem implant). STUDY DESIGN: An analysis of outcome was performed in children who received an ABI. METHODS: Twelve children received a MED-EL ABI system. Progress in audition and language was monitored through parental reports, questionnaires, profiles, and closed-set tests. RESULTS: The median number of active electrodes was 9 of 12. Seven of 12 users consistently respond to sound, and 5 of 12 do not. Highest performers can recognize words in small sets and have begun to use some words. CONCLUSION: Auditory brainstem implants appear to be beneficial for some pediatric patients who cannot benefit from traditional cochlear implant surgery. Benefits in the short-term can be recognition of environmental sounds, recognition of some words and very commonly used phrases, and the beginning use of words. Although some of our ABI users demonstrate no response to sound, they do want to wear their sound processors all waking hours. The cause of lack of response may be related to the second intervention, which might have led to displacement of the electrode array, or presence of additional handicaps or syndromes. However, the results are less than optimal. The relatively short postoperative follow-up duration is a considered weakness of this study.

Vibrant SoundBridge application to middle ear windows versus conventional hearing aids: a comparative study based on international outcome inventory for hearing aids.

In this study, we aimed to compare the outcomes of satisfaction of the patients who used hearing aids preceding the vibrant sound bridge (VSB) application on middle ear windows (14 oval window and 5 round window). Nineteen adult patients with conductive or mixed hearing loss were included in the study. All patients used behind the ear hearing aids on the site which was selected for VSB application. The patients used hearing aids for at least 3 months before the VSB operation. The floating mass transducer (FMT) was placed on one of the middle ear windows (oval or round) in VSB operation. The patients were evaluated with International Outcome Inventory for Hearing Aids (IOI-HA) preoperatively after at least 3 months trial of conventional hearing aid and postoperatively after 3 months use of VSB. No perioperative problem was encountered. The total score of IOI-HA was significantly higher with VSB compared with conventional hearing aids (p < 0.05). No statistically significant difference was found between the daily use, residual activity limitations, satisfaction, impact on others, quality of life between middle ear implant and hearing aid (p > 0.05). The IOI-HA scores were significantly higher with the middle ear implant than the conventional hearing aid regarding benefit and residual participation restrictions (p < 0.05). Although the scores for quality of life assessment was similar between VSB and hearing aid use, there was a superiority of VSB in terms of benefit and residual participation restrictions as well as overall IOI-HA scores as the FMT was placed on one of the middle ear windows.

An analysis of petrous bone cholesteatomas treated with translabyrinthine transotic petrosectomy.

CONCLUSION: In cases of petrous apex cholesteatoma, radical removal should be prioritized over an unreasonable sparing of hearing or facial symmetry. Restoration of facial nerve function is achievable by reanimation procedures. OBJECTIVES: To analyze clinical manifestations, surgical findings, and postoperative functional results of petrous apex cholesteatoma. METHODS: From 1995 to 2012, 34 cases of petrous apex cholesteatoma underwent operations. Clinical and surgical findings and postoperative functional outcomes were analyzed retrospectively. RESULTS: Hearing loss was the most common symptom in 95% of patients, followed by otorrhea in 64% and facial palsy in 59%. Four patients had recurrent facial palsy. In eight (24%) patients petrous apex cholesteatomas were recurrent or iatrogenic in origin. The supralabyrinthine and massive type of petrous bone cholesteatoma were the most common types, followed by, infralabyrinthine-apical, infralabyrinthine, and apical. Among 18 cases with facial nerve paralysis, 8 underwent hypoglossal-facial nerve anastomosis, 4 underwent rerouting and end to end anastomosis, 3 of them did not undergo any treatment because of the duration of facial palsy (> 3 years), and another 3 patients for whom we had recommended facial-hypoglossal anastomosis did not accept the operation. There were no major complications. Recurrence was observed in two (5%) cases.

Functional outcomes of Vibrant Soundbridge applied on the middle ear windows in comparison with conventional hearing aids.

CONCLUSION: Vibrant Soundbridge (VSB) application to the middle ear windows yields better functional outcomes than conventional hearing aids. However, speech discrimination scores obtained with VSB and conventional hearing aids are similar. OBJECTIVE: To assess audiological outcomes of round and oval window applications of VSB in comparison with conventional hearing aids. METHODS: Nineteen adult patients were included in the study. The patients had mild to moderate, moderate or moderate to profound conductive or mixed hearing loss. During surgery the floating mass transducer (FMT) was placed on the round (n = 14) or oval (n = 5) window. After the surgery, audiometric evaluation and free field audiometric evaluation of both ears was carried out. RESULTS: The hearing thresholds in the low frequencies were not significantly different between the conventional hearing aids and VSB. The functional gains obtained with oval and round window approaches were similar except for 500 Hz. The hearing thresholds in the mid and high frequencies were significantly better with VSB than the conventional hearing aids. The functional gain in the low frequencies was not significantly different between VSB and conventional hearing aids. The functional gain in the other frequencies was significantly better with VSB than conventional hearing aids.

Labyrinthotomy or vestibulotomy in anatomic and congenital variations of the oval window and facial nerve.

OBJECTIVE: To present the results of our experience with labyrinthotomy or vestibulotomy in cases where the oval window is blocked by the facial nerve and in the presence of bilateral congenital agenesis of the oval window, respectively. STUDY DESIGN: Retrospective analysis of the records of the patients operated in two different centers. METHODS: Between 2007 and 2012, 5 ears of 4 patients who were operated on in two different clinics with a presumptive diagnosis of otosclerosis were included in the study. There were 3 female patients and 1 male. The ages ranged from 10 to 26 (mean 19 years). All patients had unilateral conductive hearing loss except 1 (10-year-old girl or patient 1). Pure tone averages were calculated at the frequencies 0.5, 1, 2 and 4 kHz both pre- and postoperatively according to the Committee on Hearing and Equilibrium 1995 Guidelines for the Evaluation of Results of Treatment of Conductive Hearing Loss. All patients underwent a middle ear exploration and postoperatively the initial audiological examination was performed after 6 months. RESULTS: Retrospective analysis revealed that vestibulotomy or labyrinthotomy was performed in 5 ears of 4 patients. Postoperative dizziness was encountered in 2 patients who had vestibulotomy due to oval window agenesis, which ceased spontaneously at 1 month postoperatively. The perioperative period was otherwise uneventful. None of the patients had sensorineural hearing loss or deterioration of hearing. There was a significant improvement in hearing after the operation. A 28-dB improvement in the mean air conduction pure tone thresholds was achieved. CONCLUSION: Vestibulotomy and labyrinthotomy are safe and effective procedures in terms of hearing restoration, which can be applied in cases of congenital agenesis of the oval window or obstruction of the oval window by the facial nerve.

Association of GJB2 gene mutation with cochlear implant performance in genetic non-syndromic hearing loss.

OBJECTIVE: To analyze the association of GJB2 gene mutations with cochlear implant performance in children. METHODS: Sixty-five consecutive children who underwent cochlear implantation due to congenital profound senseurineural hearing between 2006 and 2008 were included in the study. In children, GJB2 gene mutation analysis was performed. Their auditory performance was assessed using MAIS, MUSS and LittlEARS tests. RESULTS: Twenty-two of sixty-five patients GJB2 mutations, and 35delG was the most frequent mutation. No significant difference was found between the auditory performance of mutation positive and negative children after one year follow up (p>0.05). CONCLUSION: GJB2 gene mutations do not impact on the outcome of cochlear implantation.

Complications of pediatric auditory brain stem implantation via retrosigmoid approach.

OBJECTIVE: We aimed to present the complications of auditory brain stem implantations (ABI) in pediatric patients which were performed via retrosigmoid approach. METHODS: Between March 2007 and February 2010, five prelingually deaf children underwent ABI (Medel device) operation via retrosigmoid approach. All children had severe cochlear malformations. The ages ranged from 20 months to 5 years. The perioperative complications encountered in 2 patients were evaluated retrospectively. RESULTS: No intraoperative complication was observed in the patients. Cerebrospinal fluid (CSF) leakage was the most common postoperative complication that was seen in 2 patients. The CSF leak triggered a cascade of comorbidities, and elongated the hospitalization. CONCLUSION: Pediatric ABI surgery can lead to morbidity. The CSF leak is the most common complication encountered in retrosigmoid approach. The other complications usually result from long-term hospital stay during treatment period of the CSF leak. Therefore, every attempt must be made to prevent occurrence of CSF leaks in pediatric ABI operations.

Vestibular evoked myogenic potentials in patients with fibromyalgia syndrome.

OBJECTIVE: To assess vestibular evoked myogenic potentials in patients with fibromyalgia syndrome. METHODS: Twenty-four patients with fibromyalgia syndrome (two men and 22 women) and 21 female controls were included in the study. All patients underwent vestibular evoked myogenic potential testing. RESULTS: Statistical comparison of fibromyalgia patients with control subjects showed a significant difference with respect to n23 latencies and interpeak latencies (p < 0.05). There was no significant difference in p13 latencies, nor in p13 amplitudes, n23 amplitudes or interpeak amplitudes (p > 0.05). CONCLUSIONS: Although patients with fibromyalgia syndrome generally have subjective neurotological symptoms, clinical and laboratory assessments usually fail to detect any objective abnormality. However, it is possible to detect abnormalities on vestibular evoked myogenic potential testing in such patients, indicating dysfunction in the vestibulospinal pathway, possibly in the saccule. Elongation of the n23 latency and of the interpeak latency of waves p13-n23, during vestibular evoked myogenic potential testing, may be a useful, objective indicator demonstrating neurotological involvement in fibromyalgia syndrome patients. Future research investigating the mechanisms of this latency elongation may help increase understanding of the pathogenesis of fibromyalgia syndrome.

Significance of serotonin transporter gene polymorphism in tinnitus.

OBJECTIVES: To assess the role of serotonin transporter gene (SLC6A4) polymorphism in tinnitus. MATERIALS AND METHODS: Fifty-four consecutive patients experiencing subjective tinnitus and 174 healthy controls were allocated for the study. Psychoacoustic parameters of tinnitus were measured. Beck Depression Inventory was used to assess the depression level of the patients. Tinnitus Handicap Inventory was used to assess the severity of tinnitus. A visual analog scale was designed to measure the impact of tinnitus on quality of life of the patients. The 44-bp insertion-deletion in the promoter region (5-HTTLPR) and 17-bp variable number tandem repeats in the second intron of the serotonin transporter gene were assessed. RESULTS: No difference was found between the genotypes and allele frequencies of the patients and controls regarding variable number tandem repeats and 5-HTTLPR polymorphisms (p > 0.05). There was no association between the psychoacoustic parameters of tinnitus and SLC6A4 polymorphism (p > 0.05). There was a significant association between the 5-HTTLPR polymorphism and scores from the visual analog scale of the patients (p < 0.05). CONCLUSION: Generation of tinnitus signal is not associated with SLC6A4 polymorphism and possibly with serotonergic mechanisms. However, the "ll" genotype variant of the SLC6A4 polymorphic promoter region seems associated with the limbic and autonomic nervous system symptoms of the patients with tinnitus. Therefore, serotonergic mechanisms may help explain the neurophysiological model of tinnitus, and serotonin replacement or serotonin reuptake inhibitors may increase the success rate of tinnitus treatment modalities based on the neurophysiologic model of tinnitus.

Management of cerebrospinal fluid leak following retrosigmoid posterior cranial fossa surgery.

OBJECTIVE: To detail our experience in the management of cerebrospinal fluid (CSF) leak following posterior cranial fossa surgery by the retrosigmoid approach. PATIENTS AND METHODS: 412 patients who underwent posterior cranial fossa surgery by the retrosigmoid approach for a variety of diseases were included in the study. RESULTS: There were 32 CSF leaks (7.7%) in the 412 patients. Of these, 16 were leaks from the incision site (50%) and 16 (50%) were CSF rhinorrheas. The CSF leaks were documented in 22 of the vestibular schwannoma surgeries (68.7%) and 10 of the vestibular nerve sectioning surgeries (31.3%). No CSF leak was seen following microvascular decompression and auditory brain stem implantation surgeries. Ten patients could be treated conservatively. Twelve patients needed the placement of a lumbar drainage. Surgical reexploration was performed in 10 patients. CONCLUSIONS: Initially, a conservative treatment should be instituted in the case of a CSF leak. If the conservative treatment fails, the placement of a lumbar drainage should be considered. Patients that do not respond to lumbar drainage require surgical reexploration. The abovementioned algorithm represents the safest and best option in the presence of a CSF leak, as confirmed by the absence of recurrences or multiple revisions in this study.

Role of nitric oxide synthase gene intron 4 and exon 7 polymorphisms in obstructive sleep apnea syndrome.

The objective of our study was to assess the association of eNOS4 and eNOS296 polymorphisms of endothelial nitric oxide synthase (eNOS) gene with obstructive sleep apnea syndrome (OSAS). Forty-eight patients with OSAS and 181 healthy volunteers were included in the study. Genotype analyses were performed for eNOS intron 4 VNTR and exon 7, Glu298Asp (G --> T) polymorphisms. There was no significant difference between the patients and controls regarding eNOS4 polymorphism (P > 0.05). There was a significant difference between the patients and controls regarding eNOS296 polymorphism. Glu/Asp variant was more frequent whereas Glu/Glu variant was less frequent in the patients compared to controls (P < 0.001). There was no relationship between eNOS4 and eNOS296 polymorphisms and polysomnography parameters, apnea-hypopnea index, age, gender, body weight and height, body mass index, hypertension, coronary artery disease, arrhythmia, diabetes mellitus, hypercholesterolemia and smoking (P > 0.05). The eNOS4 polymorphism of NOS gene is not associated with OSAS. However, eNOS296 polymorphism of NOS gene is associated with occurrence of OSAS, but not with severity of OSAS.

GJB2 and mitochondrial A1555G gene mutations in nonsyndromic profound hearing loss and carrier frequencies in healthy individuals.

This study aimed to assess mutations in GJB2 gene (connexin 26), as well as A1555G mitochondrial mutation in both the patients with profound genetic nonsyndromic hearing loss and healthy controls. Ninety-five patients with profound hearing loss (>90 dB) and 67 healthy controls were included. All patients had genetic nonsyndromic hearing loss. Molecular analyses were performed for connexin 26 (35delG, M34T, L90P, R184P, delE120, 167delT, 235delC and IVS1+1 A-->G) mutations, and for mitochondrial A1555G mutation. Twenty-two connexin 26 mutations were found in 14.7% of the patients, which were 35delG, R184P, del120E and IVS1+1 A-->G. Mitochondrial A1555G mutation was not encountered. The most common GJB2 gene mutation was 35delG, which was followed by del120E, IVS1+1 A-->G and R184P, and 14.3% of the patients segregated with DFNB1. In consanguineous marriages, the most common mutation was 35delG. The carrier frequency for 35delG mutation was 1.4% in the controls. 35delG and del120E populations, seems the most common connexin 26 mutations that cause genetic nonsyndromic hearing loss in this country. Nonsyndromic hearing loss mostly shows DFNB1 form of segregation.

Outcomes of otologic surgeries with special interest in learning curves of residents in a tertiary referral setting.

OBJECTIVES: We evaluated outcomes of otologic surgeries with a special interest in learning curves of residents in a tertiary referral setting. METHODS: A retrospective review of the outcomes of 811 otologic operations was performed. The outcomes of faculty staff (group 1), senior residents (fifth year; group 2), and residents (fourth year) under supervision of the faculty staff (group 3) were assessed and compared. The faculty staff were available for consultation if needed and were ready to intervene at any stage for group 2. RESULTS: There were 397 female patients (48.95%) and 414 male patients (51.04%) from 17 to 71 years of age. There was no statistically significant difference between the groups regarding graft take rate or hearing outcome (p > .05). CONCLUSIONS: The otologic training of residents appears to be successful in Turkey, as the surgical outcomes of residents were comparable to those of faculty staff.