Imaging as an early biomarker to predict sensitivity to everolimus for progressive NF2-related vestibular schwannoma.

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).

Comparing Light-Driven Contact Hearing Aids with Acoustic Hearing Aids: Data and Clinical Tips.

INTRODUCTION: Contact hearing aids (CHA) offer potential advantages over conventional acoustic hearing aids (AHA) in terms of sound quality, reduced occlusion, and increased high-frequency gain. This study evaluates objective and subjective outcome data for CHA compared to AHA. METHODS: Clinical outcome data were retrospectively reviewed for patients wearing CHA. Individual and group data were analyzed and then compared to unaided and AHA data. Adverse effects, device complaints, and clinical utility were documented throughout the device fitting and follow-up process. RESULTS: CHA outcomes were better than unaided hearing and AHA for all patients completing the 3-month CHA trial period (45%). However, CHA return rate was high (55%), most often due to device repair and fit issues. Two patients returned the devices due to poor hearing benefit, though both were off-label audiometric candidates. Significantly more clinical time was required from both audiologists and otolaryngologists to successfully fit and maintain maximum device benefit. CONCLUSIONS: For proper audiometric and otologic candidates, this light-driven CHA can offer significant improvements in high-frequency sound fidelity, word recognition, and sound quality compared to AHA technology. Administering questionnaires was helpful in illuminating real-world improvements. Device fit, alignment, and quality control issues are improving, though still contributing to high device return rates at this time. Operational factors should be considered when incorporating CHA into a hearing health care practice.

Novel age-dependent targets in vestibular schwannomas.

BACKGROUND: Schwannomas are the most common neurofibromatosis type 2 (NF2)-associated tumors with significant phenotypic heterogeneity in patients. The most severe subtype has an early and rapid progression and the mild type has a later onset and a less aggressive course. The aim of this study was to elucidate the underlying molecular differences between these groups. We compared the gene expression pattern between patients with early to late age of onset. RESULTS: A gene signature of 21 genes was constructed to differentiate between early-onset and late-onset patients. We confirmed these results by real-time PCR for SNF1LK2, NGFRAP1L1 (BEX 5), GMNN, and EPHA2. CONCLUSION: Genes identified here may be additional aberrations in merlin-depleted cells that govern the disease onset. A significant number of these genes have been suggested as having a role in carcinogenesis and are used as biomarkers for prognosis in several other cancers. The role of these genes in NF2 carcinogenesis and their potential as biomarkers or drug target are worthwhile exploring.

Schwannomas exhibit distinct size-dependent gene-expression patterns.

AIM: Neurofibromatosis type 2 (NF2)-associated vestibular schwannomas have variable size at presentation which presents a unique challenge in NF2 patient management. Therefore, we investigated the molecular signature characteristic of the differences in size for improved individualized precise therapy. MATERIALS & METHODS: RNA expression analysis was performed on 15 small and 27 large NF2-associated vestibular schwannoma tumors using a microarray analyzing over 47,000 transcripts. RESULTS: A signature of 11 genes was found to be correlated with NF2 tumor size. CONCLUSION: We have identified the genetic hallmark that differentiates large NF2-associated tumors from smaller tumors. This is the first time that these genes have been shown to be the hallmark for NF2 tumor size.

New Paradigm of Music Listening: Hearing Protection Perceptions and Treatment Decision-Making Among Music Venue Attendees.

OBJECTIVE: Investigate the prevalence of hearing protection (HP) use and behavioral motivations and barriers among adults attending music venues. STUDY DESIGN: Cross-sectional online survey study. SETTING: Noise exposure levels at popular social music venues often exceed national guidelines. METHODS: Surveys were distributed on online music communities. Respondents (n = 2352) were asked about demographics, HP use at music venues, knowledge about noise exposure impact, and perceptions of HP use. Data were characterized through descriptive statistics. Multivariable regression analysis explored differences in knowledge and perception between HP users and nonusers. RESULTS: In this cohort (mean age 29 ± 7 years, 61% male), HP users were significantly more aware of the impact of music venues on hearing (P < .01), believed their hearing ability had decreased after attending music venues (P < 0.01), and believed HP could protect from hearing loss (P < .01) than non-HP users. HP nonusers most frequently cited never considering HP (14.45%) and apathy about it affecting music quality (12.71%). Common sources of HP information were recommended by a friend/peer. Multivariable regression analysis accounting for demographics, medical history, and attendance characteristics found belief that HP use at music venues could protect from hearing loss (ß = 0.64, 95% confidence interval [CI] = [0.49-0.78]) and HP use (ß = 1.73, 95% CI = [1.47-1.98]) were significantly associated with increased subjective enjoyment while wearing HP. CONCLUSION: HP users and nonusers have significantly different perceptions of HP use and its impact. Our findings have implications for understanding motivations and barriers related to HP use and developing strategies to promote HP use at music venues.

Music to Define a Generation: Factors Associated With Hearing Protection Use at Music Venues.

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.

Disparities in Sporadic Vestibular Schwannoma Initial Presentation Between a Public Safety Net Hospital and Tertiary Academic Medical Center at the Same Zip Code 2010 to 2020.

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.

Utilization of Face-to-Face Vestibular Support Groups: A Comparison to Online Group Participation.

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.

Association between Cannabis Use and Tinnitus in US Adults.

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.

Nummular and Side-locked Headaches for the Otolaryngologist.

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.

Idiopathic Intracranial Hypertension: Implications for the Otolaryngologist.

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.

Headache in Pregnancy.

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.

Temporomandibular Joint Syndrome from an Ear Versus Dental-Related Standpoint.

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.

Comprehensive Management of Headache for the Otolaryngologist: A Summary.

Otolaryngologists will frequently encounter patients with head and facial pain. The headache may be a primary disorder or a symptom of a secondary pathology. Understanding diagnostic criteria and the autonomic and otologic manifestations of primary headaches is imperative for accurate diagnosis and treatment. This article summarizes key points in the issue "Comprehensive Management of Headache for the Otolaryngologist" and can be used as a cursory reference.

Trends in Hearing Protection Use With Occupational Noise Exposure in the United States 1999 to 2016.

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.

An Exploration of Online Support Community Participation Among Patients With Vestibular Disorders.

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.

Comparative case series of exostoses and osteomas of the internal auditory canal.

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.

Prevalence of Tinnitus and Associated Factors Among Asian Americans: Results From a National Sample.

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.

Contributions of Contemporary Human Temporal Bone Histopathology to Clinical Otology.

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.

ErbB and Nrg: potential molecular targets for vestibular schwannoma pharmacotherapy.

OBJECTIVE: Identify molecular targets for development of tumor-specific pharmacotherapeutics aimed at treating vestibular schwannomas (VSs). Activated epidermal growth factor receptor B (ErbB) 2 and ErbB3 are abundantly expressed in VS. ErbB2 signaling is essential for Schwann cell differentiation, survival, and proliferation. VS arise after loss of functional merlin, a putative tumor suppressor. Merlin internalizes ErbB2 receptors in rodent Schwann cells. Unregulated ErbB signaling may contribute to VS tumorigenesis. STUDY DESIGN: Molecular analyses, retrospective clinical correlation. SETTING: Tertiary referral center. PATIENTS: Thirty-eight specimens from patients operated for sporadic (n=21) and neurofibromatosis (NF) 2-related (n=17) VS. INTERVENTION(S): VS analyses via real-time polymerase chain reaction, immunohistochemistry, and correlation with patient clinical data. MAIN OUTCOME MEASURE(S): ErbB signaling molecule expression, tumor size, age, and NF2 status. RESULTS: VS upregulated epidermal growth factor (EGF) receptor in 68% (62% sporadic and 75% NF2-associated VS) and ErbB2 in 84% (76% sporadic and 94% NF2-related VS). ErbB3 was upregulated in 34%, and ErbB4 is downregulated in NF2-related VS. Of EGF receptor (EGFR) ligands, EGF was upregulated in all NF2-related VS, but none of the sporadic VS (p<0.01), and transforming growth factor alpha and beta-cellulin showed upregulation in 67% of NF2-related VS but not sporadic VS (p=0.02 and p=0.01, respectively). Neuregulin (Nrg) was upregulated in 86% of sporadic VS versus 19% of NF2-related VS (p<0.01). EGFR expression levels correlated directly with VS tumor size and inversely with patient age, whereas Nrg expression correlated directly with age (p=0.0005). EGF expression predicts NF2 status, whereas Nrg predicts non-NF2 status (p<0.01). CONCLUSION: These findings implicate the ErbB pathway in VS growth and as potential molecular targets for VS pharmacotherapy.