Search

Objectives: California has the most surfers in the United States and a high prevalence of external auditory canal exostoses (EACEs) among them. We aimed to characterize their EACE knowledge, use of earplugs, and barriers toward earplug use., Methods: A RedCap survey was distributed to online surfing forums and surfers at California beaches. Descriptive statistics and regression analyses were used to characterize responses., Results: Our cohort included 334 primarily male (n = 269, 81.52%), college-educated (n = 237, 71.17%) surfers who were on average 30.79 years old (SD = 11.07). Two hundred and ninety-seven (90.00%) heard of EACE and 317 (96.06%) believed earplugs prevent EACE. However, 214 (64.85%) had never used earplugs. Multivariable logistic regression found increased age (OR = 1.04, 95% CI = [1.00-1.08], p = 0.03), higher EACE knowledge quiz scores (OR = 1.47, 95% CI = [1.19-1.80], p < 0.001), and primarily surfing in Southern California (OR = 2.19, 95% CI = [1.15-4.16], p = 0.02) increased the likelihood of earplug use. Common reasons against earplug use included reduced hearing, discomfort, and social hindrance. Two hundred and eighty-seven (86.45%) would wear earplugs following more EACE knowledge. They preferred learning from surf community members, doctors, and surf events., Conclusion: Low earplug use despite awareness of EACE preventability suggests a need for EACE education among California surfers and more accessible, user-friendly earplugs. Younger, less-skilled surfers who were more commonly unaware of EACE may represent a key intervention group. Education could be promoted through partnerships between health professionals and renowned surf organizations, as most participants indicated a willingness to use earplugs post-education., Level of Evidence: N/A Laryngoscope, 2024., (© 2024 The Author(s). The Laryngoscope published by Wiley Periodicals LLC on behalf of The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: Excessive noise levels in music venues can negatively impact long-term hearing health. We investigated the prevalence, characteristics, and factors associated with hearing protection use among music event attendees., Study Design: Cross-sectional cohort., Methods: Adult participants (2,352) from online music forums completed a questionnaire assessing attendance at music events, hearing protection (HP) usage, type, and frequency, along with history of hearing-related symptoms and medical history. Primary outcome was defined as HP use at music venues. Data were characterized using descriptive statistics, paired t tests, and Pearson's chi-squared tests. Multivariable regression analysis elicited factors associated with any and regular HP use., Results: Our 2,352 respondents were primarily male (61.3%) and on average 28.7 years old (SD = 7.0). Of the respondents, 60.6% reported using HP, and 33.2% reported regular use; high-fidelity earplugs were the most used HP type (57.5%). HP use was associated with significantly fewer reports of negative hearing-related symptoms. In a multivariable regression model, factors associated with less likelihood of HP use included being female (vs male, OR = 0.74, CI = [0.55-0.98]), less concern about effects on hearing (OR = 0.53, CI = [0.45-0.61]), and pop music event attendance (vs EDM, OR = 0.40, CI = [0.22-0.72]). Increased attendance frequency in the past year was associated with higher likelihood of regular HP use (OR = 1.07, CI = [1.04-1.09]). Decreased attendance duration was associated with decreased likelihood (OR = 0.09, CI = [0.03-0.33])., Conclusion: HP use prevalence was high, while frequent use remained low. HP use was significantly associated with reduced hearing-related symptoms. Demographic factors, otologic symp-tomology, and attendance-related characteristics were associated with HP use. These findings may guide interventions to increase adoption at music venues., Level of Evidence: 4., Competing Interests: Conflicts of Interest and Source of Funding: The authors of this study have no conflict of interest to declare at the time of submission. Dr. Choi reported grants from the Lions Hearing Foundation and American Neurotology Society outside the submitted work., (Copyright © 2024, Otology & Neurotology, Inc.)

Objective: This study compared the utilization and outcomes of face-to-face (F2F) vestibular support groups and online support communities (OSC) for individuals with vestibular disorders., Methods: We distributed a 31-question anonymous electronic survey through the Vestibular Disorders Association (VeDA) to F2F participants, categorizing user involvement in F2F, OSCs, or both and assessed impact on medical decision-making, psychosocial benefits, and goals achieved., Results: The F2F cohort consisted of 97 individuals comprising primarily of non-Hispanic White women (mean age = 57 years, SD ± 14 years) with diagnoses including persistent postural-perceptual dizziness (19%), Meniere's disease (15%), and vestibular neuritis (13%). Most participants were diagnosed by an otolaryngologist (65%) and attended F2F meetings monthly or less frequently (78%). The OSC group comprised of 551 individuals, primarily of non-Hispanic White women, but was younger in age (mean age = 50 years, SD ± 13 years). OSC participants notably engaged more, with 36% participating on a daily basis and 32% multiple times a week. F2F participants were older (mean age 57 years vs 50 years, P  < .001) and more commonly referred by medical professionals (22% F2F vs 6% OSC, P  < .001). Both groups had similar achieved goals, including hearing from others with the same diagnosis (84% vs 89%, P  > .05) and similar impact on medical decision-making (75% vs 78%, P  > .05). More F2F participants reported increased development of coping skills (79% F2F vs 69% OSC, P  = .037). OSC participants typically found the group via an online search (75%), compared to 51% for F2F. OSC participants had higher daily engagement (36%) compared to F2F (1%)., Conclusion: F2F users are older and more commonly referred by medical professionals. Despite less frequent engagement, F2F participants reported similar influences on achieved goals, medical decision-making, and impact on psychosocial benefits. These findings highlight the importance of both F2F and OSC support groups for individuals with vestibular disorders., Competing Interests: Author’s NoteRyan S. Ziltzer, MD is also affiliated to Department of Head and Neck Surgery, West Virginia University, West Virginia, USA. Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Treatment of vestibular schwannoma (VS) has been extensively studied, but a gap in knowledge exists demonstrating how racial and socioeconomic status influence VS presentation. Our institution has a unique setting with a public safety net hospital (PSNH) and tertiary academic medical center (TAMC) in the same zip code, which we study to evaluate initial VS presentation disparities in patient populations presenting to these hospital settings., Methods: Retrospective chart review was performed of all adult patients (n = 531) presenting 2010 to 2020 for initial VS evaluation at TAMC (n = 462) and PSNH (n = 69). Ethnicity, insurance, maximum tumor size, audiometry, initial treatment recommendation, treatment received, and follow up were recorded and statistical analysis performed to determine differences., Results: Average age at diagnosis (51.7 ± 13.6 TAMC vs 52.3 ± 12.4 PSNH) and gender (58.4% TAMC vs 52.2% PSNH female) were similar. Patients' insurance (TAMC 75.9% privately insured vs PSNH 82% Medicaid) and racial/ethnic profiles (TAMC 67.7% White and 10.0% Hispanic/Latinx, vs PSNH 4.8% White but 59.7% Hispanic/Latinx) were significantly different. Tumor size was larger at PSNH (20.2 ± 13.3 mm) than TAMC (16.6 ± 10.0 mm). Hearing was more impaired at PSNH than TAMC (mean pure tone average 58.3 dB vs 43.9 dB, word recognition scores 52.3% vs 68.2%, respectively). Initial treatment recommendations and treatment received may include more than 1 modality. TAMC patients were offered 66.7% surgery, 31.2% observation, and 5.2% radiation, while PSNH patients offered 50.7% observation, 49.3% surgery, and 8.7% radiation. TAMC patients received 62.9% surgery, 32.5% observation, and 5.3% radiation, while PSNH patients received 36.2% surgery, 59.4% observation, and 14.5% radiation. Follow up and treatment at the same facility was not significantly different between hospitals., Conclusions: Hearing was worse and tumor size larger in patients presenting to PSNH. Despite worse hearing status and larger tumor size, the majority of PSNH patients were initially offered observation, compared to TAMC where most patients were initially offered surgery., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: NF2-related schwannomatosis (NF2) is characterized by bilateral vestibular schwannomas (VS) often causing hearing and neurologic deficits, with currently no FDA-approved drug treatment. Pre-clinical studies highlighted the potential of mTORC1 inhibition in delaying schwannoma progression. We conducted a prospective open-label, phase II study of everolimus for progressive VS in NF2 patients and investigated imaging as a potential biomarker predicting effects on growth trajectory., Methods: The trial enrolled 12 NF2 patients with progressive VS. Participants received oral everolimus daily for 52 weeks. Brain imaging was obtained quarterly. As primary endpoint, radiographic response (RR) was defined as ≥ 20% decrease in target VS volume. Secondary endpoints included other tumors RR, hearing outcomes, drug safety and quality of life (QOL)., Results: Eight participants completed the trial and four discontinued the drug early due to significant volumetric VS progression. After 52 weeks of treatment, the median annual VS growth rate decreased from 77.2% at baseline to 29.4%. There was no VS RR and 3 of 8 (37.5%) participants had stable disease. Decreased or unchanged VS volume after 3 months of treatment was predictive of stabilization at 12 months. Seven of eight participants had stable hearing during treatment except one with a decline in word recognition score. Ten of twelve participants reported only minimal changes to their QOL scores., Conclusions: Volumetric imaging at 3 months can serve as an early biomarker to predict long-term sensitivity to everolimus treatment. Everolimus may represent a safe treatment option to decrease the growth of NF2-related VS in patients who have stable hearing and neurological condition. TRN: NCT01345136 (April 29, 2011)., (© 2024. The Author(s).)

Objective: Assess the association between cannabis use and tinnitus in a nationally representative sample of US adults., Study Design: Cross-sectional., Setting: Population-based., Patients: Adults aged 20 to 59 years who participated in 2011 to 2012 and 2015 to 2016 National Health and Nutrition Examination Survey (NHANES) with available data on tinnitus, audiometry, and substance use., Intervention: None., Main Outcome Measure: Tinnitus, demographic information, and medical history were obtained from NHANES questionnaires. Tinnitus was defined as bothersome tinnitus in the past year. Cannabis use was categorized as never use, low-volume use (1-2 pipes/joints per day), and high-volume use (3+ pipes/joints per day). Multivariable regression models with interaction and mediation analyses were conducted. Sampling weights were incorporated to yield results generalizable to the US population., Results: Tinnitus prevalence was significantly higher among high-volume cannabis users (odds ratio [OR], 20.5%; 95% confidence interval [CI], 16.0-26.0%]) and low-volume users (OR, 17.0%; 95% CI, 14.3-20.0%) than nonusers (OR, 12.0%; 95% CI, 10.4-13.9%). High-volume cannabis use was significantly associated with tinnitus relative to nonusers in multivariable models adjusting for demographics, cardiovascular factors, hearing loss, noise exposure, and depression (OR, 2.05; 95% CI, 1.1-3.9). Tinnitus severity was comparable among high volume, low volume, and noncannabis users. There was no significant mediation or interaction of depression affecting the association between cannabis use and tinnitus., Conclusions: Bothersome tinnitus prevalence was significantly higher among cannabis users relative to nonusers. High-volume cannabis use was independently associated with tinnitus in a multivariable model accounting for relevant factors including depression. Future study is warranted to elucidate the impact of various levels of cannabis use on tinnitus., Competing Interests: Conflict of Interests: The authors disclose no conflicts of interest., (Copyright © 2023, Otology & Neurotology, Inc.)

Objectives/hypothesis: To formally document online support community (OSC) use among patients with vestibular symptoms and gain an appreciation for the perceived influence of participation on psychosocial outcomes and the impact on medical decision-making., Study Design: Self reported internet-based questionnaire., Methods: The Facebook search function was paired with a comprehensive list of vestibular diagnoses to systematically collect publicly available information on vestibular OSCs. Next, a survey was designed to gather clinicodemographic information, OSC characteristics, participation measures, perceived outcomes, and influence on medical decision-making. The anonymous instrument was posted to two OSCs that provide support for patients with general vestibular symptoms., Results: Seventy-three OSCs were identified with >250,000 cumulative members and >10,000 posts per month. The survey was completed by 549 participants, a cohort of primarily educated middle-aged (median = 50, interquartile range 40-60), non-Hispanic white (84%), and female (89%) participants. The participants' most cited initial motivation and achieved goal of participants was to hear from others with the same diagnosis (89% and 88%, respectively). Daily users and those who reported seeing ≥5 providers before receiving a diagnosis indicated that OSC utilization significantly influenced their requested medical treatments (72% daily vs. 61% nondaily, P = .012; 61% <5 providers vs. 71% ≥5 providers P = .019, respectively). Most participants agreed that OSC engagement provides emotional support (74%) and helps to develop coping strategies (68%). Membership of ≥1 year was associated with a higher rate of learned coping skills (61% membership <1-year vs. 71% ≥1-year P = .016)., Conclusions: The use of OSCs is widespread among vestibular diagnoses. A survey of two OSCs suggests these groups provide a significant source of peer support and can influence users' ability to interface with the medical system., Level of Evidence: NA Laryngoscope, 132:1835-1842, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Side-locked headaches are a common symptom having a wide-ranging differential. Unchanging in laterality, these headaches can represent neuralgias, trigeminal autonomic cephalgias, ophthalmologic disorders, otolaryngologic and craniofacial disorders, vascular disorders, and malignancy. In rarer situations, they have presented secondary to neurosurgical or dermatologic considerations. Loss of cranial nerves and visual changes warrant additional evaluation., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Headache is a common symptom in pregnancy. The differential diagnosis for headache in pregnancy is broad and includes conditions that range in acuity and severity. Most headaches in pregnancy are migraine or tension-type headaches. However, pregnant women are at an increased risk of vascular causes of headache due to hormone changes and increased hypercoagulability in pregnancy. A careful history, physical examination, and possible diagnostic workup should be performed. Treatment of headache in pregnancy varies according to the etiology, but care should be taken when performing diagnostic studies and considering pharmacologic treatments, given the possible risk to the mother and fetus., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Temporomandibular disorders (TMDs) are a prominent reason for visits to medical providers. The presentation of headaches within this population remains a challenging diagnosis, given the prevalence and overlap of symptomatology of both conditions. The literature demonstrates an undeniable association between headaches and TMD. Regardless of causality and etiology, the literature supports that prompt diagnosis and treatment results in improvement or resolution of symptoms, including headaches. Treatment of TMD headaches should begin with conservative measures, including medical management with NSAIDs, heat therapy, and muscle-stretching exercises., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Idiopathic intracranial hypertension (IIH) is a triad of headaches, visual changes, and papilledema in the absence of a secondary cause for elevated intracranial pressure. There is an association with obesity, and the incidence is rising in parallel with the obesity epidemic. Sometimes these patients present to an otolaryngologist with complaints like tinnitus, dizziness, hearing loss, and otorrhea or rhinorrhea from cerebrospinal fluid leak. IIH diagnosis in conjunction with neurology and ophthalmology, including neuroimaging and lumbar puncture with opening pressure, is key to managing of this condition. Otolaryngologists should recognize IIH as a possible diagnosis and initiate appropriate referrals and treatment., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: Determine hearing protection use in relation to occupational noise exposure, tinnitus, and audiometry-measured hearing loss in the United States from 1999 to 2016., Study Design: Cross-sectional study utilizing US National Health and Nutritional Examination Survey (NHANES) 1999 to 2016 with occupation, reported occupational noise exposure, hearing protection use, tinnitus, and audiometry-measured hearing loss data. Subgroup analysis divided data into two cohorts early 2000s and 2010s., Setting: Population-based study using NHANES database capturing representative sample of US population., Participants: Individuals with complete data 1999 to 2004 (n = 10,347) and 2011 to 2012 with 2015 to 2016 (n = 9,383)., Interventions: Participants self-reported occupational noise exposure lasting more than 4 h/d for more than 3 months. Self-reported hearing protective device uses and tinnitus frequency. Audiometric hearing loss objectively measured., Main Outcome Measures: Hearing protection use. Secondary measures included self-reported bothersome tinnitus and audiometrically measured hearing loss., Results: Across occupations, reported occupational noise exposure was higher in 2010s [32%, 95% CI: 29.6-34.6%] than 2000s [12.5%, 95% CI: 11.2-13.9%], while hearing protection use remained low in 2000s [41.3%, 95% CI: 37.8-44.8%] and 2010s [32.8%, 95% CI: 29.8-35.8%]. Less hearing protection use was associated with absence of bothersome tinnitus. Factors associated with increased hearing protection use were younger age, male sex, college education or higher, and white race in a multivariate model., Conclusions: Reported occupational noise exposure appeared to increase from 2000s to 2010s yet hearing protection use remained stable at low use rate. As noise exposure is a major risk factor for hearing loss, significant education and reinforcement of appropriate hearing protection use for workplace noise exposures is necessary to preserve workers' hearing., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Objectives: A previous study demonstrated low rates of high-frequency hearing loss and noise exposure among Asian Americans (AAs). This study examined the prevalence of tinnitus and associated factors among AAs using the first nationally representative sample of AAs., Study Design: Cross-sectional analysis of a national health survey., Methods: We analyzed data from the 2011 to 2012 National Health and Nutritional Examination Survey, during which 3,669 participants aged 20 to 69 years completed questionnaires on tinnitus (AA participants, n = 530). Tinnitus was defined as bothersome ringing lasting 5 minutes or more in the past 12 months. Prevalence of any tinnitus in the past 12 months was calculated incorporating sampling weights. Logistic regression was used to examine the associations with relevant factors., Results: The prevalence of any tinnitus was 6.6% (95% confidence interval [CI]: 4.5-8.6) among AAs, significantly lower than the prevalence among the overall population at 16.5% (95% CI: 14.3-18.8]. After adjusting for audiometric hearing loss and demographics, AAs were less likely to report any tinnitus than whites (odds ratio [OR] = 0.43 [95% CI: 0.24-0.75]), blacks (OR = 0.60 [95% CI: 0.37-0.95]), and Hispanics (OR = 0.60 [95% CI: 0.45-0.78]). Rates of tinnitus were not different from whites or blacks once comorbidities, noise exposure, and depression were taken into account. Among AAs, reporting exposure to work-related noise (OR = 2.92 [95% CI: 1.15-7.41]) and having a major depressive disorder (OR = 6.45 [95% CI: 1.15-36.12]) were significant factors associated with tinnitus in a multivariate model., Conclusions: The prevalence of tinnitus is significantly lower among AAs in comparison to other racial groups. Noise exposure and depression were significant factors associated with tinnitus among AAs., Level of Evidence: 2b Laryngoscope, 2020., (© 2020 The American Laryngological, Rhinological and Otological Society, Inc.)

Contemporary techniques have greatly enhanced the contributions of human temporal bone (HTB) histopathology to our understanding of the mechanisms of human otologic disease and disease treatment. Herein, we review some of the most salient contributions of this research to disease management. The field of HTB histopathology is challenged by limited resources as applies to trained investigators, infrastructure, and well-equipped laboratories. This research provides insights into clinical otology that cannot be obtained by any other means. Measures should be taken to preserve and extend the contributions of HTB research.

The microscopic examination of fifty-five serially sectioned implanted temporal bones has provided insight into what is being stimulated; and the changes that are the result of the insertion and presence of the implant. The ganglion cell bodies (neurons) are structures being stimulated (two laboratories have reported an inverse relationship of the number of neurons and performance). Insertion through the round window, verses a cochleostomy, produces the least fibrosis and new bone. Fibrosis and new bone do not affect the implant function unless they form in the scala vestibuli in the region of the ductus reuniens, and, block it; and produce cochlear hydrops resulting in a delayed low tone loss of hearing in hybrid implants. Animal models cannot be applied to humans because of the difference in size and myelination of the neurons.

Hypothesis: Investigation of differential protein expression will provide clues to pathophysiology in otosclerosis., Background: Otosclerosis is a bone remodeling disorder limited to the endochondral layer of the otic capsule within the temporal bone. Some authors have suggested an inflammatory etiology for otosclerosis resulting from persistent measles virus infection involving the otic capsule. Despite numerous genetic studies, implication of candidate genes in the otosclerotic process remains elusive. We employed liquid chromatography-mass spectrometry (LC-MS) analysis on formalin-fixed celloidin-embedded temporal bone tissues for postmortem investigation of otosclerosis., Methods: Proteomic analysis was performed using human temporal bones from a patient with severe otosclerosis and a control temporal bone. Sections were dissected under microscopy to remove otosclerotic lesions and normal otic capsule for proteomic analysis. Tandem 2D chromatography mass spectrometry was employed. Data analysis and peptide matching to FASTA human databases was done using SEQUEST and proteome discoverer software., Results: TGFβ1 was identified in otosclerosis but not in the normal control temporal bone specimen. Aside from TGFβ1, many proteins and predicted cDNA-encoded proteins were observed, with implications in cell death and/or proliferation pathways, suggesting a possible role in otosclerotic bone remodeling. Immunostaining using TGFβ1 monoclonal revealed marked staining of the spongiotic otosclerotic lesions., Conclusions: Mechanisms involved in cochlear extension of otosclerosis are still unclear, but the implication of TGFβ1 is supported by the present proteomic data and immunostaining results. The established role of TGFβ1 in the chondrogenesis process supports the theory of a reaction targeting the globulae interossei within the otic capsule.

Exostoses and osteomas are benign bony lesions of the auditory canal. Although common in the external auditory canal, they are rare and difficult to distinguish in the internal auditory canal (IAC). In this literature review and case presentation, we define radiologic and histologic criteria to differentiate exostoses from osteomas of the IAC. Two patients with exostoses and 1 patient with an osteoma of the IAC are described here. Patient 1 presented with disabling vertigo and was found to have bilateral exostoses with nerve impingement on the right. After removal of the right-sided exostoses via retrosigmoid craniotomy, the patient had complete resolution of her symptoms over 1 year. Patient 2 presented with bilateral pulsatile tinnitus and vertigo and was found to have bilateral IAC exostoses. Patient 3 presented with hearing loss and tinnitus, and a unilateral IAC osteoma was ultimately discovered. Because of the mild nature of their symptoms, patients 2 and 3 were managed without surgery. We show that IAC osteomas can be differentiated from exostoses by radiographic evidence of bone marrow in high-resolution computed tomography scans, or by the presence of fibrovascular channels on histologic analysis. Management of these rare entities is customized on the basis of patient symptoms.

Objectives: Vestibular schwannomas (VSs) are slow-growing benign tumors but, on rare occasion, can invade adjacent cranial nerves, causing significant morbidity, especially in association with neurofibromatosis 2 (NF2). We aimed to determine the role of the growth factors EGF, bFGF, and the hormone, Epo, in promoting such invasive behavior in VS, as well as their mechanisms of action., Methods: Immunohistochemical staining showed expression of EGFR, bFGF, Epo, EpoR in archived VS tissue. Western blots and immunofluorescence showed expression of EGFR, EpoR and FGF in HEI-193, an immortalized cell line derived from human NF2-related VS. Matrigel invasion assays were used to study the effect of Epo, FGF and bFGF on invasive behavior in HEI-193. Western blotting showed levels of phospho-Akt and phospho-Erk in HEI-193 upon addition of growth factors plus PI3K or MEK inhibitors. Quantitative RT-PCR was performed to determine the expression of MMP2 and MMP9 after treatment with growth factors., Results: EGFR, bFGF, Epo and EpoR were expressed in VS tissue and HEI193. Addition of EGF and bFGF increased cellular invasion by 10 and 3.5-fold, respectively. Epo had minimal effect on invasion. Results indicated that Erk is involved in bFGF but not EGF-induced invasion, while Akt is involved in both pathways. EGF treatment moderately induced MMP9, but is unlikely to account for the observed invasion., Conclusion: Activation of EGFR and FGFR may promote invasive behavior in VS through ERK and Akt signaling pathways. Further investigation will be necessary to elucidate their potential as useful targets in the treatment of VS.

Hypothesis: To determine the expression of the tyrosine kinases platelet-derived growth factor receptor (PDGFR) and c-Kit in vestibular schwannoma (VS) and to determine the potential role of imatinib mesylate (Gleevec) in regulating the growth and cell death of this tumor., Background: Protein tyrosine kinases are transmembrane tyrosine kinase receptors that transduce signals from inside and outside the cell and function as relay points for signaling pathways. They have a key role in numerous processes that affect cell proliferation, tumorigenesis, cancer invasion, metastasis, and modulation of apoptosis. A few of these kinases have been demonstrated to be overexpressed and dysregulated in many carcinomas, sarcomas, and benign tumors., Methods: Immunohistochemical staining was used to investigate the expression of PDGFR and c-Kit in archived acoustic neuroma tissue. Clinical data including size of tumors, age, sex, and symptoms were correlated with kinase expression, whereas Western blot analysis and immunofluorescence were performed to demonstrate the expression and localization of PDGFR and c-Kit in HEI193, an immortalized VS cell line. Clonogenic survival assays were performed to assess proliferation inhibition by Gleevec. Gleevec's effect on the cell cycle profile also was investigated via flow cytometry analysis., Results: Expression of PDGFR in the formalin-fixed VS tumor tissue was observed in 23 (67.5%) of the 34 samples. C-kit was expressed in 18 (52.9%) of the 34 samples. Western blot analysis demonstrates positive expression of c-Kit and PDGFR-Q in HEI193 and a primary VS culture. Western blot analysis showed downregulation of phospho-c-kit and phospho-PDGFR-Q with 5 and 10 uM Gleevec. Immunofluorescent staining of this cell line also reveals that PDGFR-β is localized primarily in the cytoplasm, whereas c-Kit is both nuclear and cytoplasmic. Cell cycle analysis of HEI193 96 hours after incubation with Gleevec indicates a dose-dependent increase in G1 from 61.6% to 70.7% and 74% at 5 and 10 uM of Gleevec, respectively. Colony formation assays demonstrate dose-dependent growth inhibition by Gleevec, in the HEI193 cell line as well as in a VS cell culture derived from a fresh tumor., Conclusion: The expression of PDGFR-Q and c-Kit in VS tissue may indicate novel molecular targets involved in the development of this tumor. Direct inhibition of these molecules by Gleevec may have relevant therapeutic applications.

Hypothesis: To investigate the early events in molecular progression toward schwannoma tumorigenesis, we developed an in vitro model of human Schwann cell tumorigenesis by merlin knockdown., Background: Neurofibromatosis 2 (NF2)-related and sporadic vestibular schwannoma (VS) exhibit loss of functional merlin (schwannomin). After loss of merlin expression in the Schwann cell, the initial steps toward VS tumorigenesis are unknown. Merlin, a putative tumor suppressor protein, interacts with many cellular proteins, regulating their function. Among these are receptor tyrosine kinases, including the epidermal growth factor receptor family B (ErbB) family receptors epidermal growth factor receptor and ErbB2. Functional merlin interacts with and internalizes these growth factor receptors, silencing their proliferation and survival signaling. Deregulation of CD44, the cell adhesion/signaling molecule and cancer stem cell marker, has also been implicated in VS tumorigenesis., Methods: Merlin knockdown was performed using small interfering RNA transfection into human Schwann cell primary cultures. Knockdown was confirmed by real-time quantitative PCR, immunofluorescence, and Western analysis. Expression profiles of ErbB, merlin, and the stem cell markers nestin and CD44 were examined in knockdowns. Proliferation rate was assessed with bromodeoxyuridine incorporation, and radiation sensitivity was assessed using the Annexin assay in knockdowns versus controls., Results: Merlin knockdowns demonstrated increased proliferation rate, upregulation of epidermal growth factor receptor, ErbB2, and ErbB3, CD44, and nestin. Short-term merlin depletion had no effect on gamma irradiation sensitivity compared with controls., Conclusion: Merlin depletion results in deregulation of ErbB receptor signaling, promotes a dedifferentiated state, and increases Schwann cell proliferation, suggesting critical steps toward schwannoma tumorigenesis.

Gene therapy has considerable potential for the treatment of disorders of the inner ear. Many forms of inherited hearing loss have now been linked to specific locations in the genome, and for many of these the genes and specific mutations involved have been identified. This information provides the basis for therapy based on genetic approaches. However, a major obstacle to gene therapy is the targeting of therapy to the cells and the times that are required. The inner ear is a very complex organ, involving dozens of cell types that must function in a coordinated manner to result in the formation of the ear, and in hearing. Mutations that result in hearing loss can affect virtually any of these cells. Moreover, the genes involved are active during particular times, some for only brief periods of time. In order to be effective, gene therapy must be delivered to the appropriate cells, and at the appropriate times. In many cases, it must also be restricted to these cells and times. This requires methods with which to target gene therapy in space and time. Cell-specific gene promoters offer the opportunity to direct gene therapy to a desired cell type. Moreover, conditional promoters allow gene expression to be turned off and on at desired times. Theoretically, these technologies offer a mechanism by which to deliver gene therapy to any cell, at any given time. This chapter will examine the potential for such targeting to deliver gene therapy to the inner ear in a precisely controlled manner., (Copyright (c) 2009 S. Karger AG, Basel.)

Objectives/hypothesis: Determine the role of estrogen receptor (ER) and progesterone receptor (PR) expression in sporadic and neurofibromatosis 2 (NF2)-related vestibular schwannomas (VS). Growth and proliferation signaling in human VS tumorigenesis may play a key role in molecular therapeutic targeting. VS carry mutations of the NF2 gene encoding the tumor suppressor, merlin, which interacts with ErbB2 in Schwann cells, implicating ErbB receptors in VS tumorigenesis. ErbB receptor family members are overexpressed or constitutively activated in many human tumors, and are effective therapeutic targets in some human cancers. VS occur more frequently in women and are larger, more vascular, and demonstrate increased growth rates during pregnancy. ER and PR may play a role in ErbB pathway activation and VS progression., Study Design: Quantitative real-time polymerase chain reaction (qRT-PCR) for ER and PR messenger RNA was performed using greater auricular and vestibular nerve controls (n = 8), sporadic VS (n = 23), and NF2-related VS (n = 16) tissues., Methods: The qRT-PCR data were normalized with standardization to a single constitutively expressed control gene, human cyclophylin., Results: Reverse transcription of messenger RNA from control and tumor specimens followed by RT Q-PCR demonstrated differences in ER and PR gene expression between sporadic and NF2-related VS., Conclusions: ER and PR expression in VS might have implications for development of a VS-specific drug delivery system using antihormone and ErbB pathway small molecule inhibitors, due to crosstalk between these receptors. These signals may be critical for re-establishing ErbB-mediated cell density dependent growth inhibition.

Background: Obesity and metabolic syndrome are significant problems for patients taking antipsychotic drugs. Evidence is emerging of genetic risk factors., Aims: To investigate the influence of two candidate genes, smoking and drug treatment on obesity and metabolic syndrome in patients with schizophrenia., Method: Patients (n=134) were assessed for measures of obesity, other factors contributing to metabolic syndrome, and two genetic polymorphisms (5-HT(2C) receptor -759C/T and leptin -2548A/G)., Results: Neither genotype nor smoking was significantly associated with measures of obesity. However, both leptin genotype and smoking were significantly associated with metabolic syndrome. Significant interaction occurred between the genetic polymorphisms for effects on obesity, whereby a genotype combination increased risk. Drug treatment showed significant effects on measures of obesity and triglyceride concentrations; risperidone was associated with lower values than olanzapine or clozapine., Conclusions: The findings suggest interacting genetic risk factors and smoking influence development of metabolic syndrome in patients on antipsychotic drugs.

Objective: To describe the prevalence and location of cranial nerve schwannomas, other than bilateral vestibular schwannoma, in patients with neurofibromatosis 2 (NF2). The NF2 Natural History Consortium prospectively gathered cranial magnetic resonance imaging for 83 patients across 3 annual evaluations. The time between the first and last evaluation was approximately 3 years., Results: Forty-two patients (51%) had nonvestibular cranial nerve schwannomas (NVSs). Of these, 25 (60%) also had cranial meningiomas. Twenty-one of those without NVS (25% of 83) had at least 1 meningioma. The average size of the NVS was 0.4 cubic centimeters. Overall, there was no significant change in NVS size from Year 1 to Year 3 or from Year 1 to Year 2. The most common locations of the NVS were occulomotor and trigeminal. A family history of NF2 did not predict NVS location or growth., Conclusion: Nonvestibular cranial nerve schwannoma usually affect cranial nerves III and V, as was the case in our NF2 sample. Fortunately, neuropathies associated with these tumors are rare. In contrast, lower cranial nerve schwannomas, although also rare, are associated with swallowing difficulty, aspiration, and other sequelae.

Objective: Describe neurotologic findings associated with idiopathic intracranial hypertension (IIH)., Study Design: Retrospective., Setting: Tertiary referral center., Patients: Case of IIH (>250 mm water) presenting with unilateral facial palsy and enlargement of the fallopian canal on computed tomography and magnetic resonance imaging., Intervention(s): Oral acetazolamide, corticosteroids, and cerebrospinal fluid drainage., Main Outcome Measure(s): Intracranial pressure measurement, cranial nerve examination, audiometry, and symptom assessment., Results: Audiometry revealed asymmetric sensorineural hearing loss. Enlargement of the fallopian canal with cerebrospinal fluid was evident on imaging studies. Partial resolution of IIH symptoms was achieved., Conclusion: IIH is an enigmatic disease entity. Increased intracranial pressure usually presents with headache and pulsatile tinnitus and is occasionally associated with cranial neuropathies. Abducens palsy is most common, producing diplopia. Cranial nerve involvement is often asymmetric, producing false localizing signs. Facial paralysis is an uncommon sequela of IIH. Treatment of IIH consists of reducing intracranial pressure. Corticosteroids are recommended for treatment of facial paralysis.

Objective: Melanoma rarely invades the cerebellopontine angle (CPA) and can evade accurate diagnosis, which may alter management decisions. Diagnosis may be facilitated via careful history, magnetic resonance imaging (MRI) findings, and cerebrospinal fluid (CSF) analysis., Study Design: Retrospective case review., Setting: Tertiary referral center., Patients: Thirteen internal auditory canal/CPA lesions in eight patients who presented with CPA syndrome and who had a pathological diagnosis consistent with malignant melanoma. There were four bilateral and four unilateral lesions. Six of eight patients had a history of melanoma. One was apparently primary CPA lesion, whereas all others were metastatic., Intervention(s): T1- and T2-weighted precontrast and postcontrast gadolinium-enhanced MRI were obtained, including fat suppression and fluid-attenuated inversion recovery sequence images in two patients; lumbar puncture with CSF centrifugation and cytological analysis confirmed the diagnosis in two patients. Translabyrinthine craniotomy was performed for tumor extirpation in five patients., Main Outcome Measure(s): Symptoms at presentation, MRI findings, presence of malignant cells in CSF, tumor progression, intraoperative findings, response to treatment, time interval from initial diagnosis of melanoma elsewhere, and survival., Results: Seven of eight patients had history and/or MRI findings suggestive of malignancy in the internal auditory canal and/or CPA, and diagnosis was confirmed via CSF analysis in two patients. In one patient, diagnosis was made at surgery., Conclusion: Internal auditory canal melanoma portends a grim prognosis, can occur up to 17 years after initial melanoma diagnosis/treatment, and can be detected with appropriate MRI sequences, especially enhanced fluid-attenuated inversion recovery images. In disseminated cases, diagnosis can be confirmed with lumbar puncture demonstrating malignant cells. Management includes tumor resection when melanoma seems to be solitary and malignant cells are not present in CSF. Intrathecal chemotherapy and radiation are recommended for dissemination, although the survival rate is still poor.

Patients with an endolymphatic sac tumor (ELST) typically present with palsy of cranial nerves VII and/or VIII; other presenting symptoms include hearing loss, otalgia, occipital headaches, cranial nerve palsies, vertigo, gait ataxia, tinnitus, and otorrhea. ELSTs are extremely vascular, and they can invade and destroy temporal bone. Because of these characteristics, they are often mistaken for glomus tumors of the skull base. We describe the clinical presentation, evaluation, and management of ELSTs based on our review of the limited literature and our experience with 3 adults who presented to our tertiary care referral center with large ELSTs. Although these patients presented late in the course of their disease, their symptoms were relatively minor. Preoperative tumor embolization was performed, anda near-complete resection was achieved via an extended transotic approach in all 3 patients. The facial nerve was preserved without transposition in the first patient, the second patient underwent a primary nerve anastomosis, and the third required a cable graft of the facial nerve. Postoperative radiation therapy was administered to 2 of these patients. Follow-up by MRI detected no evidence of recurrence in any of the 3 patients.

Objective: Determine the prevalence and time interval for conversion from unilateral to bilateral involvement in Meniere's disease and cochlear hydrops., Study Design and Setting: Retrospective chart review in a tertiary otologic referral center., Patients: 232 patients diagnosed with Meniere's Disease (n=186) or cochlear hydrops (n=46) between 1959 and 2001, who visited the clinic over a five-year period between 1997-2001 and have at least 2 audiograms more than 12 months apart., Main Outcome Measures: Prevalence of cochlear hydrops relative to Meniere's Disease, rate of progression from unilateral to bilateral involvement; interval between unilateral onset of symptoms and bilateral involvement; and rate of progression from cochlear hydrops to Meniere's disease., Results: Initial diagnosis was Meniere's disease in 71% and cochlear hydrops in 29% of all 950 hydropic patients presenting between 1997 and 2001. In the study sample, Meniere's disease was bilateral at presentation in 11%; an additional 12% (14% of unilaterals) became bilateral during the follow-up period. At presentation, 6.5% of cochlear hydrops patients were bilateral, with another 26% becoming bilateral. Conversion from cochlear hydrops to Meniere's disease occurred in 33% and some of these are included among the bilateral. The average time interval for conversion from unilateral to bilateral Meniere's was 7.6 years (SD=7.0 years)., Conclusion: Most otologists are aware of the potential for contralateral ear involvement and conversion from cochlear hydrops to Meniere's disease after diagnosis. These changes are significant, require long-term follow-up for detection, and may necessitate further treatment. Patients should be counseled regarding this potential when interventions are considered, especially with respect to ablative treatments.

Proteus syndrome (PS) is a rare hamartomatous disorder characterized by mosaic overgrowth of multiple tissues that manifests early in life and is progressive. The presence of unilateral external auditory canal exostoses in a patient who is not a swimmer or surfer is suggestive of PS. However, hearing loss is not a typical feature. Here, we describe exostoses and ossicular discontinuity with conductive hearing loss in a patient with PS. The treatment consisted of canalplasty and ossicular chain reconstruction. A postoperative reduction was demonstrated in the patient's air-bone gap, from 21 dB to 13 dB for the pure tone average (four frequencies) and from 41 dB to 15 dB in the high-frequency range (6,000 to 8,000 Hz). Causes of ossicular discontinuity are discussed. Routine annual audiometric and otolaryngological evaluation should be considered in all patients with temporal bone involvement of PS.

Objective: To investigate the effect of changes within the spiral ligament and stria vascularis on hearing in cochlear otosclerosis, we examined spiral ligament hyalinization, stria vascularis atrophy, and sensory hearing loss in cochlear otosclerosis and described changes in ion transport molecule expression., Study Design: Retrospective., Setting: Tertiary referral center., Patients: Thirty-two cochleae from 24 temporal bone donors with histologic evidence of cochlear otosclerosis, including spiral ligament hyalinization., Intervention: Audiography., Main Outcome Measures: Measurements of spiral ligament width, stria vascularis, and bone-conduction thresholds were compared by the amount of hyalinization. Expression of the ion transport molecules Na,K-ATPase, connexin 26, and carbonic anhydrase II were assessed by immunohistochemical techniques., Results: Hyalinization most often involved the posterior basal turn (88%) and the posterior middle turn (27%). Spiral ligament hyalinization correlated significantly with stria vascularis atrophy in the posterior middle turn of the cochlea (rho = -0.63, p < 0.01). There was a trend toward a significant association in the posterior basal turn (rho = -0.31, p < 0.08). Bone-conduction thresholds at 2,000 and 4,000 Hz were significantly associated with the amount of stria vascularis atrophy (rho = -0.44, -0.40, p < 0.05). In addition, we observed decreased immunostaining for both carbonic anhydrase II with Type I fibrocytes and Na,K-ATPase with stria vascularis and Type II and Type IV fibrocytes of the spiral ligament in cochlear otosclerosis sections compared with normal cochlea. Na,K-ATPase staining within the stria vascularis was further decreased in the presence of spiral ligament hyalinization. No significant differences were seen with connexin 26 immunostaining. However, immunostaining results were somewhat inconsistent., Conclusion: These data suggest that spiral ligament structure and function are essential for stria vascularis survival. In addition, dampened expression of ion transport molecules within the spiral ligament and stria vascularis may disrupt potassium ion recycling, resulting in loss of endocochlear potential and sensory hearing loss.

The patulous eustachian tube (pET) presents a challenging management problem. Patients with the pET disorder are disturbed to the point of mental illness by their symptoms of aural fullness and autophony, especially the echo of their own voice. Thus far, described treatment methods are often temporary or ineffective. Here, we describe a minimally invasive method for the treatment of pET that involves cauterization with autologous fat graft plugging of the ET at its nasopharyngeal orifice, in conjunction with myringotomy and ventilation tube placement. This procedure has been successful for the treatment of refractory pET in 2 patients at the House Ear Clinic with at least 1-year follow-up and we propose that it may accomplish relief of symptoms by permanent stenosis of the ET.