Hypothesis: We hypothesized that CPI-17 expression and NF2 mutations are correlated with merlin phosphorylation in the etiology of sporadic vestibular schwannoma (VS). Background: NF2 gene mutations have been identified in the majority of sporadic and NF2-associated schwannomas and NF2 gene mutations have been shown to result in merlin protein phosphorylation. CPI-17 can drive Ras activity and promote tumorigenic transformation by inhibiting the tumor suppressor merlin. The aim of this study was to determine the correlation between CPI-17 overexpression and the NF2 mutation spectrum in sporadic VS. Methods: In this study, we measured CPI-17 expression and identified NF2 gene alterations in a series of sporadic VS samples. Freshly frozen tumor and matched peripheral blood leukocytes from 44 individuals with sporadic VS were analyzed using next-generation sequencing and Sanger sequencing. Western blotting was used to determine the level of merlin phosphorylation, and immunohistochemistry and Western blotting were used to measure CPI-17 expression in the sporadic VS samples. CCK-8 and wound-healing assays were used to determine the influence of CPI-17 overexpression on cell proliferation. Results: NF2 mutations were identified in 79.5% of sporadic vestibular schwannomas, with all mutations being exclusively somatic. IHC and WB showed the expression of CPI-17 is upregulated in the sporadic VS. NF2 mutation and CPI-17 are positively correlated with merlin phosphorylation. CPI-17 overexpression induces the proliferation of HEI193 cells. Conclusion: NF2 mutations and CPI-17 expression together induce merlin phosphorylation, which is correlated with the tumorigenesis of sporadic VSs.
Objectives: 1) To provide information on the treatment of pulsatile tinnitus (PT) with transtemporal extralurninal sigmoid sinus angioplasty (ESSA); and 2) to discuss the current clinical management of PT. Study Design: This was a retrospective study. Settings: Multi-institutional tertiary university medical centers. Patients: Fifty-four PT patients with transverse sigmoid sinus enlargement and prominent transverse sigmoid junction with or without sigmoid sinus wall anomalies or transverse sinus anomalies. Intervention: All patients underwent ESSA under local anesthesia. Main Outcome Measures: Intraoperative discoveries and surgical resolution of PT, morphology; and computational fluid dynamics. Results: Fifty-three of the 54 (98%) patients experienced a significant reduction in, or complete resolution of, PT after ESSA. No major surgical complications occurred, except for one case where we observed a full collapse of the sinus wall. On average, this surgery reduced the cross-sectional area at the transverse sigmoid junction by 61.5%. Our intraoperative discoveries suggest that sigmoid sinus wall anomalies may not be a definitive cause of PT. The transverse sigmoid sinus system was significantly larger (in term of both cross-sectional area and volume) on the ipsilesional side compared with the contralesional side. Following ESSA, the vascular wall pressure and vortex flow at the transverse sigmoid junction decreased considerably, and the flow velocity and wall shear stress increased significantly. Conclusion: ESSA is a highly effective surgical technique for PT patients with transverse sigmoid sinus enlargement and prominent transverse sigmoid junction, regardless of whether they also have sigmoid sinus wall or transverse sinus anomalies. A large transverse sigmoid system with prominent transverse sigmoid junction is a predisposing factor for PT, and only by improving patients' intrasinus hemodynamics could PT be resolved efficiently. In cases without complete obstruction of venous return, ESSA is safe. No postoperative complications related to neurological disorders were observed.
Objective: Intravestibular schwannomas (IVS) are uncommon tumors in Neurofibromatosis type 2 (NF2) and are mainly associated with multiple internal auditory meatus (IAM) and cerebellopontine angle (CPA) tumors. They usually induce profound hearing loss which can be rehabilitated by cochlear implantation (CI). The aim of this study was to analyze the long-term outcomes of CI during the unpredictable evolution of NF2 disease. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Three adults with neurofibromatosis type 2 and intravestibular schwannomas, and who were cochlear implant recipients. Interventions: Periodic radiologic follow-up, tumor resection, and hearing rehabilitation. Main Outcome Measures: Audiological evolution, tumor evolution, surgical outcome, cochlear implant outcome. Results: Three NF2 patients (mean age at diagnosis, 26.3 +/- 3.2 yr) were identified with IVS in the period between 2000 and 2017. IVS were first observed by serial MRI and profound hearing loss occurred in this ear after 4 +/- 1.5 years of follow-up. IVS were removed via a translabyrinthine approach, and ipsilateral cochlear implantations were simultaneously performed. In two patients, large contralateral CPA tumors had previously been removed without hearing preservation, whereas in the third patient, a small, growing contralateral VS was excised via a retrosigmoid approach 6 months after IVS removal/cochlear implantation with serviceable hearing preservation. In all cases, CI provided good hearing outcomes. In two cases, hearing outcomes were even better for more than 5 years when ipsilateral intracanalicular vestibular schwannomas were removed in either the same or subsequent procedures. Conclusions: Rehabilitation of hearing with CI provides a favorable long-term outcome in patients with NF2-related IVS which could be altered by the occurrence of other intracanalicular and/or CPA NF2-related tumors.
Objective:This study is to investigate the hemodynamic changes of pulsatile tinnitus (PT) patients induced by sigmoid sinus wall anomalies (SSWA).Study Design:Prospective study.Setting:Tertiary referral university hospital.Patients:Fifteen unilateral PT patients with SSWA identified on computed tomography images and surgery and 15 age-, sex-, and body mass index-matched healthy volunteers underwent velocity-encoded, cine magnetic resonance imaging.Intervention:Hemodynamic data in sigmoid sinus were obtained from velocity-encoded, cine magnetic resonance imaging, and compared between PT patients and controls.Main Outcome Measures:Heart rate was recorded. Cross-sectional area (CSA), peak positive velocity (PPV), average positive flow volume per beat (APFV/beat), average flow volume per beat (AFV/beat), peak negative velocity (PNV), and average negative flow volume per beat (ANFV/beat) were measured. Average flow volume per minute (AFV/min), average positive flow volume per minute (APFV/min), average negative flow volume per minute (ANFV/min), average positive velocity (APV), average negative velocity (ANV), and regurgitation fraction (RF) were calculated.Results:APV at PT side of patients was 13.43.3cm/s, which was significantly slower than that at corresponding side of controls (15.8 +/- 2.6cm/s). PNV and RF at PT side of patients were 21.0 +/- 15.4cm/s and 2.4% respectively, which were significantly higher than those values at corresponding side of controls (both of them were 0). HR, CSA, PPV, APFV/beat, APFV/min, AFV/beat, AFV/min, ANV, ANFV/beat, and ANFV/min were 69.8 +/- 9.4beat/min, 48.4 +/- 17mm(2), 31.4 +/- 5.9cm/s, 5.4 +/- 1.8ml/beat, 373.9 +/- 117.7ml/min, 5.1 +/- 2.0ml/beat, 352.0 +/- 134.6ml/min, 2 (0-4.9) cm/s, 1 (0-2.7) ml/beat, and 4.1 (0-141.3) ml/min at PT side of patients, and 67.4 +/- 7.8beat/min, 38.2 +/- 18mm(2), 29.9 +/- 3.9cm/s, 5.3 +/- 2.0ml/beat, 350.3 +/- 125.3ml/min, 5.1 +/- 1.9ml/beat, 340.5 +/- 117.9ml/min, 0 (0-2.1) cm/s, 0 (0-0.8) ml/beat, and 0 (0-55.4) ml/min at corresponding side of controls. These hemodynamics were not significantly different between groups.Conclusion:APV, PNV, and RF changes take place in SSWA patients, which may be associated with the occurrence of PT and have the potential value to improve accurate etiological diagnosis and predict treatment success.
Objective: The aim of this study was to evaluate the feasibility and safety of transcanal underwater endoscopic bone resection (TUEBR) of the external auditory canal (EAC) for the management of cholesteatoma involving the antrum and mastoid. Study Design: Retrospective case review. Setting: Tertiary referral center. Patients: Pediatric and adult patients with primary cholesteatoma extending to the antrum and mastoid who underwent transcanal endoscopic ear surgery (TEES) with TUEBR between March 2016 and June 2017. Intervention: A rigid 2.7 mm diameter, 18 cm length Hopkins-rod telescope with an endoscopic sheath was inserted in the EAC and continuously perfused with saline during the dissection. TUEBR was performed to expose extensive cholesteatoma by using a high speed drill with curved burrs and a protected shaft. Next, removal of visible disease, reconstruction of the resected EAC, ossiculoplasty, and tympanoplasty were accomplished with TEES. Results: There were no intra- or postoperative severe complications such as facial palsy and inner ear injury except one patient suffering from secondary labyrinthitis. There was a negative linear relationship (r = -0.909) between the procedure time and procedure number of TUEBR. There was a weak relationship (r = 0.224) between the procedure time of TUEBR and the degree of the extension of cholesteatoma into the antrum and mastoid. There were two cases with residual cholesteatoma at 12 and 22 months follow-up postoperatively. Conclusion: TUEBR is a safe and efficient technique for the resection of EAC bone and transcanal exposure of extensive cholesteatoma that would otherwise require mastoid dissection.
Objective: To evaluate the auditory and speech benefit of bimodal stimulation for prelingual deafened cochlear implantation recipients. Study Design: Retrospective and comparative study. Setting: Tertiary referral center. Patients: Fifty-six children with bilateral prelingual profound sensorineural hearing loss were enrolled, including 28 consecutive children with unilateral cochlear implantation (CI group), and 28 consecutive children with bimodal stimulation (BI group) who used an additional hearing aid (HA) in the contralateral ear. Main Outcome Measures: Hearing assessments included the Infant-Toddler Meaningful Auditory Integration Scale (IT-MAIS) and Categories of Auditory Performance (CAP). Speech evaluations included the Meaningful Use of Speech Scale (MUSS), and Speech Intelligibility Rating (SIR). These measurements were evaluated at the first mapping of cochlear implants and 0.5, 1, 3, 6, 12, 18, 24 months after. Data were analyzed by repeated measures analysis. Results: The mean ages of BI and CI groups were similar (17.6 +/- 6.87 vs 19.0 +/- 8.10 months, p = 0.497). The initial scores for hearing and speech assessments showed no differences between the two groups, apart from IT-MAIS (2.46 +/- 0.631 in BI group vs 0.50 +/- 0.279 in CI group, p = 0.004). The auditory and speech development over time were different in the two groups as seen in IT-MAIS (p < 0.001), CAP (p = 0.029), MUSS (p < 0.001), and SIR (p < 0.001). A continuing but stable difference was observed in CAP, MUSS, and SIR at 3, 18, and 12 months after the first mapping, respectively. In addition, the BI group had better IT-MAIS scores at 3 and 6 months compared with the CI group; however, the difference was not significant after 12 months. Conclusion: Bimodal stimulation is beneficial for prelingually deafened CI recipients who have minimal contralateral residual hearing when bilateral CIs are not available. Hearing aid use in the contralateral ear might be recommended for children after unilateral cochlear implantation to facilitate the development of auditory and speech skills.
Background: During skull base tumor surgery, temporomandibular joint (TMJ) dissection is commonly performed. The impact of this procedure on patients' postoperative diet and TMJ function is a matter of concern to surgeons. Methods: We reviewed the Craniomandibular Index (CMI) for 32 patients (15 men and 17 women) who underwent TMJ dissection during surgery for skull base tumors between August 2015 and May 2018. Results: Fifteen patients underwent removal of the mandibular condyle, and 17 had the condyle preserved. Twenty-one patients mainly underwent infratemporal fossa approach, and 11 underwent extended temporal bone resection. No significant difference between pre- and postoperative diet was observed in any group. Significant differences in CMI index were seen in all groups. The highest score was 0.115 of Dysfunction Index, observed postoperatively in the group that underwent condyle removal. Conclusions: For skull base tumor surgery, TMJ dissection has no significant impact on postoperative diet. Patients who underwent removal of the mandibular condyle have significantly worse postoperative TMJ function.
Background: Waardenburg syndrome (WS) is a rare disorder characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. Dystopia canthorum is a hallmark of WS type 1. There are two genes linked to WS type 1, including PAX3 and EDNRB. Objective: This study aimed to investigate the genetic etiology of WS type 1 in a pair of twins from China with profound hearing loss, blond hair and eyebrows, dystopia canthorum, and brown irides. Methods: The target capture sequencing and Whole-exome sequencing were performed to detect mutations in WS-related genes. Results: A novel de novo frameshift mutation, p.L341Rfs*18 in MITF was identified in the twins. Hearing thresholds showed substantial improvements following cochlear implantation with a pure-tone average of 30 dB in free-field conditions. Conclusions: The study showed the new genotype-phenotype correlations of MITF to WS type 1. Further molecular analysis is necessary to reappraise the current classification on WS.
Objective: To address variance in clinical care surrounding sporadic vestibular schwannoma, a modified Delphi study was performed to establish a general framework to approach vestibular schwannoma care. A multidisciplinary panel of experts was established with deliberate representation from key stakeholder societies. External validity of the final statements was assessed through an online survey of registered attendees of the 8th Quadrennial International Conference on Vestibular Schwannoma. Study Design: Modified Delphi method. Methods: The panel consisted of 16 vestibular schwannoma experts (8 neurotology and 8 neurosurgery) and included delegates representing the AAOHNSF, AANS/CNS tumor section, ISRS, and NASBS. The modified Delphi method encompassed a four-step process, comprised of one prevoting round to establish a list of focus areas and three subsequent voting rounds to successively refine individual statements and establish levels of consensus. Thresholds for achieving moderate consensus, at >= 67% agreement, and strong consensus, at >= 80% agreement, were determined a priori. All voting was performed anonymously via the Qualtrics online survey tool and full participation from all panel members was required before procession to the next voting round. Results: Through the Delphi process, 103 items were developed encompassing hearing preservation (N = 49), tumor control and imaging surveillance (N = 20), preferred treatment (N = 24), operative considerations (N = 4), and complications (N = 6). As a result of item refinement, moderate (4%) or strong (96%) consensus was achieved in all 103 final statements. Seventy-nine conference registrants participated in the online survey to assess external validity. Among these survey respondents, moderate (N = 21, 20%) or strong (N = 73, 71%) consensus was achieved in 94 of 103 (91%) statements, and no consensus was reached in 9 (9%). Of the four items with moderate consensus by the expert panel, one had moderate consensus by the conference participants and three had no consensus. Conclusion: This modified Delphi study on sporadic vestibular schwannoma codifies 100% consensus within a multidisciplinary expert panel and is further supported by 91% consensus among an external group of clinicians who regularly provide care for patients with vestibular schwannoma. These final 103 statements address clinically pragmatic items that have direct application to everyday patient care. This document is not intended to define standard of care or drive insurance reimbursement, but rather to provide a general framework to approach vestibular schwannoma care for providers and patients.
Objective:To assess the influence of congenital and permanent unilateral hearing loss (UHL) on early prelingual auditory development (EPLAD) of infants and toddlers.Study Design:A cross-sectional and case-controlled design.Setting:Tertiary referral center.Patients:Sixty-five young children (median with interquartile ranges: 4.4 [3.3, 7.7] mo) with UHL, 70 children (6.0 [3.8, 9.0] mo) with bilateral normal hearing (BNH) and 32 children (5.8 [3.9, 12.1] mo) with bilateral mild hearing loss (BMHL) were enrolled and grouped. Children with UHL were further grouped according to the severity of impairment and the ear that was impaired.Interventions:Children involved were assessed by the 9-item Infant-toddler Meaningful Auditory Integration Scale (ITMAIS).Main Outcome Measures:1) EPLAD assessed by ITMAIS, 2) functions of sound detection, sound discrimination and identification and preverbal vocalization assessed by dividing ITMAIS into three sections, 3) trajectories of EPLAD estimated by ITMAIS.Results:Compared with BNH, children with UHL lagged behind in the function of sound discrimination and identification, preverbal vocalization, as well as trajectory of EPLAD. Children with severe to profound UHL exhibited more severe EPLAD handicaps than children with mild to moderate losses. The auditory functions and EPLAD trajectory of children with UHL were similar to those with BMHL.Conclusions:Children with congenital and permanent UHL demonstrate delays in EPLAD, which are evident soon after birth before initial development of speech and language. The ITMAIS is an appropriate tool to identify these delays both in children with unilateral and bilateral hearing impairment.
Objective:To determine the vestibulo-ocular reflex (VOR) performance during the attacks of Meniere's disease (MD) using video head-impulse tests (video-HITs) according to each ictal phase.Study Design:Retrospective case series review.Methods:We analyzed the results of video-HITs in 24 patients with unilateral definite MD during and between the attacks.Results:The head impulse gain of the VOR was usually normal (81%, 39 of the 48 semicircular canals [SCCs] in 16 patients) in the affected ear during the irritative or recovery phase, and did not differ from that for each SCC between the attacks (horizontal [HCs], p=0.412; anterior [ACs], p=0.920; posterior canals [PCs], p=0.477). During the paretic phase, however, the head impulse gains of the VOR were equally normal (22/42, 52%) or decreased (20/42, 48%) for the affected ear (42 SCCs in 14 patients). The gains for the HCs were lower during the paretic phase than those between the attacks in the affected ear, while those for the ACs and PCs did not differ (HCs, p=0.001; ACs, p=0.158, PCs, p=0.401). Covert saccades were more frequently observed even in the presence of normal VOR gains during the paretic phase as well.Conclusion:During the attacks of MD, HITs are usually normal during the irritative/recovery phases, but become positive in more than a half of the patients during the paretic phase. This evolution in the ictal findings of HITs may reflect characteristic ictal vestibular discharges in MD and should be considered in evaluating patients with MD according to each ictal phase during the attacks.
Objective:A/J mice are a mouse model of age-related hearing loss (AHL) with progressive degeneration of outer hair cells (OHCs), spiral ganglion neurons (SGNs), and stria vascularis. This study was carried out to observe the otoprotective effects of alpha -lipoic acid on A/J mice.Methods:A/J mouse pups at postnatal day 7 were randomly distributed into the untreated group, the dimethyl sulfoxide (DMSO) group, and the alpha -lipoic acid+DMSO group. alpha -lipoic acid was given to the mice intraperitoneally at a dosage of 50 mu g/g body weight every other day. Time course auditory-evoked brainstem response (ABR) thresholds were tested. OHC loss was counted and the densities of SGNs and the width of stria vascularis were measured at 4 and 8 weeks of age.Results:Measurement of the ABR thresholds revealed that hearing loss in A/J mice was attenuated by alpha -lipoic acid at age from 3 to 8 weeks. Moreover, preservation effects of OHCs, SGNs, and stria vascularis by alpha -lipoic acid were observed in the cochleae of A/J mice at 4 and 8 weeks of age.Conclusion:Hearing loss in A/J mice can be attenuated by alpha -lipoic acid. The otoprotective effects of alpha -lipoic acid on A/J mice may be obtained by preserving OHCs, SGNs, and stria vascularis in the cochleae. The oxidative damage related to gene mutations may be a potential target for AHL prevention and therapy.
Objective:To investigate the effectiveness of basic fibroblast growth factor (bFGF) versus placebo or no intervention in the treatment of tympanic membrane (TM) perforations from randomized controlled trials (RCTs), prospective and retrospective studies.Data Sources:PubMed, EMBASE, and Cochrane databases were screened from their inceptions to June 2019.Study Selection:Inclusion criteria: 1) English language; 2) observational (retrospective or prospective) or treatment (RCT) studies; 3) reported the outcomes on the application of bFGF in adult or pediatric population. Exclusion criteria: 1) studies without a control group; 2) animal studies, in vitro studies, review studies, and case reports.Data Extraction:Number of patients, cause of TM perforation, perforation size, treatment, mean age, follow-up time, sex, closure rate, healing time, mean air-bone gap improvement.Data Synthesis:A total of 14 studies were included, including seven RCTs and seven non-RCTs with a total of 1,072 participants. The odds ratio for closure rate of bFGF treatment was 7.33 (95% confidence interval [CI], 4.65 to 11.53; p<0.01; I-2=44%) and the standardized mean difference (SMD) for healing time was -5.89 (95% CI: -7.85 to -3.93, p<0.01, I-2=98%), suggesting bFGF application has a significant effect on closure of TM perforations. However, no significant change in hearing (SMD: 0.08, 95% CI: -0.11 to 0.27, p=0.39, I-2=0%) was seen as a result of bFGF treatment.Conclusions:Our meta-analysis has revealed that the application of bFGF can significantly enhance the closure rate as well as shorten the healing time for TM perforations. In terms of hearing, there is as yet no evidence that bFGF has a significant effect. Given its ease, availability, and safety, bFGF can be used effectively for TM repair.
Objectives: Sudden sensorineural hearing loss (SSNHL) may occur in post-irradiated nasopharyngeal carcinoma (NPC) survivors with a rare rate. This study was conducted to evaluate the clinical characteristics and prognosis of this population. Study Design: Retrospective cohort study. Setting: Tertiary otology referral center. Patients: Five hundred ninety nine SSNHL patients were recruited between January 2010 and January 2019. Patients were divided into two groups: NPC group (n = 24) and non-NPC group (n = 575). Interventions: All SSNHL patients were diagnosed by pure tone audiometry and treated with steroids, blood flow promoting agents, and hyperbaric oxygen therapy. Main Outcome Measures: We evaluated the clinical characteristics and prognosis of post-irradiated SSNHL and identified prognostic factors by logistic regression analysis. Results: In the NPC group, the initial hearing threshold, contralateral hearing threshold, rate of vertigo, rate of profound hearing loss were all higher than in the non-NPC group (p < 0.05). Hearing gains and the rate of good recovery (both complete recovery and partial recovery) were lower in the NPC group than in the non-NPC group (p < 0.05). Logistic regression analysis revealed that NPC was significantly associated with poor hearing recovery (OR = 3.499, p = 0.040), and that a higher initial hearing threshold and longer treatment delay time were related to a poor prognosis (p < 0.05). Conclusions: SSNHL occurred in post-irradiated NPC survivors often suffered a severe hearing loss with a high rate of accompanying vertigo. NPC may have an adverse impact on the prognosis of SSNHL, and higher initial hearing threshold and longer treatment delay time were indicators of poor hearing recovery.
Objective: To test the feasibility of image-guided Baha Attract implant surgery with mixed reality (MR) in the form of the HoloLens to visualize critical structures and facilitate precise Baha implant placement. Methods: A cadaveric case study of bilateral Baha Attract implant approaches was conducted using Star Atlas MR three-dimensional (3D) medical interaction system guidance at the Otolaryngology Department of PUMCH, Beijing, China. The accuracy of visual surface registration was determined by the target registration error (TRE) between the predefined points on the preoperative 3D holographic Baha Attract implant model and the postoperatively reconstructed 3D model. Results: Bilateral Baha Attract implantation was completed successfully for all four cadaveric heads using the Star Atlas MR 3D medical interaction system with the HoloLens. The preoperative 3D digital model characteristics (including bone quality and thickness and avoidance of cranial vessels, air cells, and cranial sutures) corresponded well with the 3D model of the actual implantation reconstructed postoperatively. The median TRE of our system was 2.97 mm (ranging from 1.98 to 4.58 mm) in terms of distance and 2.76 degrees (ranging from 0.59 to 6.4 degrees) in terms of angle. Conclusions: Applying MR technology in the form of the HoloLens in Baha Attract implant surgery is feasible and could improve the accuracy of the surgery. The described MR system for Baha Attract implantation has the potential to improve the surgeon's confidence, as well as the surgical safety, efficiency, and precision.