Active middle ear implant coupled bilaterally to the round window despite bilateral implanted stapes prostheses.

After stapes surgery, patients with mixed or moderate hearing loss have limited possibilities for hearing improvement. We are reporting on a patient who underwent stapedotomy bilaterally 20 years ago and had sensorineural and mixed hearing loss. Recurrent otitis externa prevented the use of hearing aids. This patient was treated bilaterally with the Vibrant Soundbridge (Med-El, Innsbruck, Austria) successively. The Schuknecht piston stapes prostheses remained in situ. The Floating Mass Transducer (FMT; Med-El) was coupled to the round window (RW) and provided good acoustic reinforcement bilaterally. In conclusion, for patients with otosclerosis and stapes surgery, the FMT-RW coupling (Bess AG, Berlin, DE) is a safe procedure with good acoustic amplification. Laryngoscope, 2016 127:500-503, 2017.

Medial and mediolateral orbital decompression in intractable Graves' Orbitopathy.

OBJECTIVE: Graves' Orbitopathy (GO) has well established treatment guidelines; however, its management is still controversial. The aim was to evaluate the results of medial and mediolateral orbital decompression (OD) in intractable GO. METHODS: Retrospective chart review of all patients with advanced stages of GO, who underwent medial (1-wall) or mediolateral (2-wall) OD between May 2012 and November 2014 in our institution. Ophthalmologic examinations included visual acuity, Hertel exophthalmometry (proptosis), intraocular pressure (IOP), visual field (30:2) and diplopia. Follow-up was performed 1 week, 3 months and 1 year postoperatively. Additionally, a questionnaire was used to investigate subjective benefits. RESULTS: The study included 34 eyes of 20 patients. In our study, GO patients who underwent mediolateral OD had significantly higher IOP preoperatively (p<0.05) and lower visual acuity, proptosis and visual field compared with patients who underwent medial OD. After 1- and 2-wall OD, visual acuity, proptosis, visual field and IOP in upgaze improved significantly. Using a questionnaire, the patients reported significant improvements in impaired vision, eye pain and pressure, vitality and social life. 94% of all patients reported they would repeat the operation. After 2-wall OD, the surgical scar had little effect. CONCLUSION: With GO patients in advanced stages, both medial (1-wall) and mediolateral (2-wall) OD procedures are convincing therapeutic options. In more advanced GO stages with high IOP, 2-wall OD should be prioritized, as mediolateral OD had superior long-term functional outcomes.

Gender-specific risk factors in post-tonsillectomy hemorrhage.

There are gender-specific differences in the frequency and course of different diseases. Specifically, some studies have shown an increased risk of post-tonsillectomy hemorrhage (PTH). The aim of the study was to investigate gender-specific risk factors for hemorrhage after tonsillectomy (TE)/abscess-TE. We anonymously reviewed and recorded the relevant data of all patients (≥14 years) who underwent a TE/abscess-TE between 2011 and 2013 in the ENT Clinic of the Charité Universitätsmedizin Berlin, Campus Benjamin Franklin. A patient survey was used to complete missing data. We analyzed gender-specific risk factors for PTH. During the study period, 460 operations were performed and the data of 250 patients were analyzed (213 TE and 37 abscess-TE). The median patient age was 27 years (ranging from 14 to 83 years). The rate of primary PTH (<24 h after TE/abscess-TE) was 3 %, and the rate of secondary PTH (>24 h) was 23 %. A significantly higher PTH rate was associated with males (p = 0.037), which was still apparent in ages 21-30 after sub-classification. Multivariate analysis calculated diagnosis, regular alcohol consumption and administration of glucocorticoids to be independent risk factors associated with gender. In conclusion, the PTH rate is gender-specific, and male patients are at higher risk, especially in young adulthood. Therefore, doctors should advise male patients of the increased risk of bleeding and stress the importance of compliance. Also, close postoperative follow-up is desirable.

Incidence and long-term survival of patients with de novo head and neck carcinoma after liver transplantation.

BACKGROUND: Liver transplant recipients have an increased risk of developing de novo malignancies. METHODS: We conducted a prospective evaluation of clinicopathological data and predictors for overall survival (OS) in patients with head and neck squamous cell carcinoma (HNSCC) after liver transplantation (1988 to 2010). RESULTS: Thirty-three of 2040 patients who underwent liver transplantation (1.6%) developed de novo HNSCC. The incidence of HNSCC in liver transplant recipients with end-stage alcoholic liver disease (26) was 5%. After a median follow-up of 9 years, 1-year, 3-year, and 5-year OS rates were 74%, 47%, and 34%, respectively. Tumor size, cervical lymph node metastases, tumor site, and therapy (surgery only vs surgery and adjuvant radiotherapy [RT]/chemoradiotherapy [CRT] vs RT/CRT only; p < .0001) were significantly associated with OS in univariate analysis. However, surgery only predicted OS independently in multivariate analysis. CONCLUSION: Early diagnosis and surgical treatment of de novo HNSCC are crucial to the outcome. HNSCC risk should be taken into close consideration during posttransplantation follow-up examinations, especially among patients with a positive history of smoking and alcohol consumption.

Meta-analysis of survival in patients with HNSCC discriminates risk depending on combined HPV and p16 status.

Data indicate a better prognosis for human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC). HPV and p16 detection are established markers for HPV-related HNSCC. Both are accepted as survival-independent predictors. Previous studies investigating the survival in HNSCC patients depending on HPV(+/-) and p16(+/-) status consistently found discordant results with p16(-)/HPV(+) and p16(+)/HPV(-). However, no meta-analysis regarding the survival according to combined HPV/p16 status has been performed yet. The objective of this study was to discriminate the impact of combined HPV(+/-) and p16(+/-) status on survival. Data sources were identification and review of publications assessing survival of the distinct subgroups with both p16 and HPV investigated in HNSCC until February, 2015. A meta-analysis was performed to classify survival and clinical outcomes. 18 out of 397 articles (4424 patients) were eligible for the meta-analysis. The percent proportion of the subgroups was 25 % for HPV(+)/p16(+), 61.2 % for HPV(-)/p16(-), 7.1 % for HPV(-)/p16(+) and 6.8 % for HPV(+)/P16(-). The meta-analysis showed a significantly improved 5-year overall survival (OS), 5-year disease-free survival and their corresponding hazard ratio for HPV(+)/p16(+) HNSCC in comparison to HPV(-)/p16(-), HPV(+)/p16(-) and HPV(-)/p16(+). The 5-year OS of the HPV(-)/p16(+) subgroup was intermediate while HPV(+)/p16(-) and HPV(-)/p16(-) HNSCC had the shortest survival. With current therapeutic strategies, survival of patients with HNSCC is better if associated with HPV(+)/p16(+) or HPV(-)/p16(+). Clinical trials are needed to confirm the distinct survival pattern and to investigate possible differences in survival for HPV(+)/p16(-) and HPV(-)/p16(+) HNSCC. To further differentiate p16(+) HNSCC, HPV testing may be advisable.

Positron Emission Tomography Imaging Reveals Auditory and Frontal Cortical Regions Involved with Speech Perception and Loudness Adaptation.

Considerable progress has been made in the treatment of hearing loss with auditory implants. However, there are still many implanted patients that experience hearing deficiencies, such as limited speech understanding or vanishing perception with continuous stimulation (i.e., abnormal loudness adaptation). The present study aims to identify specific patterns of cerebral cortex activity involved with such deficiencies. We performed O-15-water positron emission tomography (PET) in patients implanted with electrodes within the cochlea, brainstem, or midbrain to investigate the pattern of cortical activation in response to speech or continuous multi-tone stimuli directly inputted into the implant processor that then delivered electrical patterns through those electrodes. Statistical parametric mapping was performed on a single subject basis. Better speech understanding was correlated with a larger extent of bilateral auditory cortex activation. In contrast to speech, the continuous multi-tone stimulus elicited mainly unilateral auditory cortical activity in which greater loudness adaptation corresponded to weaker activation and even deactivation. Interestingly, greater loudness adaptation was correlated with stronger activity within the ventral prefrontal cortex, which could be up-regulated to suppress the irrelevant or aberrant signals into the auditory cortex. The ability to detect these specific cortical patterns and differences across patients and stimuli demonstrates the potential for using PET to diagnose auditory function or dysfunction in implant patients, which in turn could guide the development of appropriate stimulation strategies for improving hearing rehabilitation. Beyond hearing restoration, our study also reveals a potential role of the frontal cortex in suppressing irrelevant or aberrant activity within the auditory cortex, and thus may be relevant for understanding and treating tinnitus.

Biology and immunology of cancer stem(-like) cells in head and neck cancer.

Immunological approaches against tumors including head and neck squamous cell carcinoma (HNSCC) have been investigated for about 50 years. Such immunotherapeutic treatments are still not sufficiently effective for therapy of HNSCC. Despite the existence of immunosurveillance tumor cells may escape from the host immune system by a variety of mechanisms. Recent findings have indicated that cancer stem(-like) cells (CSCs) in HNSCC have the ability to reconstitute the heterogeneity of the bulk tumor and contribute to immunosuppression and resistance to current therapies. With regard to the CSC model, future immunotherapy possibly in combination with other modes of treatment should target this subpopulation specifically to reduce local recurrence and metastasis. In this review, we will summarize recent research findings on immunological features of CSCs and the potential of immune targeting of CSCs.

Inhibition of pan-class I phosphatidyl-inositol-3-kinase by NVP-BKM120 effectively blocks proliferation and induces cell death in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is the most frequent aggressive lymphoma, with a great demand for novel treatments for relapsing and refractory disease. Constitutive activation of the phosphatidyl-inositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway is often detected in this lymphoma. Inhibition of this signaling cascade with the pan-class I PI3K inhibitor NVP-BKM120 decreased cell proliferation and increased apoptotic cell death. DLBCL proliferation was further decreased if NVP-BKM120-induced autophagy was blocked. Treatment with NVP-BKM120 was associated with an increase of the pro-apoptotic BH3-only proteins Puma and Bim and down-regulation of the anti-apoptotic Bcl-xL and Mcl-1. Translation of Bcl-xL and Mcl-1 is facilitated by cap-dependent mRNA translation, a process that was partially inhibited by NVP-BKM120. Overall, we demonstrated here the potential of NVP-BKM120 for the treatment of DLBCL.

Safety and efficacy of Nasya/Prevalin in reducing symptoms of allergic rhinitis.

BACKGROUND: Nasya/Prevalin is a natural, drug-free nasal spray for treatment and prevention of allergic rhinitis. Because of its thixotropic property, it forms a barrier on the nasal mucosa, preventing allergen contact. This study assesses the clinical efficacy and safety of Nasya/Prevalin in a nasal provocation test with house dust mite allergens. METHODOLOGY/PRINCIPAL: In this randomised, double-blind, placebo-controlled trial, 20 subjects suffering from allergic rhinitis because of house dust mite allergens received a single dose of Nasya/Prevalin or saline spray before allergen challenge. Total nasal symptom score and total ocular symptom score were assessed 15, 30, 60, 75, 90, 120 and 240 min after challenge. Further, the appearance of the mucosa was examined by rhinoscopy. RESULTS: A single treatment with Nasya/Prevalin led to a significant reduction of TNSS at 60, 75 and 90 min after dust mite allergen challenge as compared with placebo (pVCAS = 0.021, pVCAS = 0.035, pVCAS = 0.036, respectively). Mucosa changes assessed by the rhinoscopic score (on swelling, secretion and colour) were significantly worse in the placebo group compared with the Nasya/Prevalin group (P = 0.033). Nasya/Prevalin was well tolerated, and the safety was comparable with placebo. CONCLUSIONS: Treatment with Nasya/Prevalin was effective in preventing allergic reactions induced by dust mite allergen challenge.

Neural representation in the auditory midbrain of the envelope of vocalizations based on a peripheral ear model.

The auditory midbrain implant (AMI) consists of a single shank array (20 sites) for stimulation along the tonotopic axis of the central nucleus of the inferior colliculus (ICC) and has been safely implanted in deaf patients who cannot benefit from a cochlear implant (CI). The AMI improves lip-reading abilities and environmental awareness in the implanted patients. However, the AMI cannot achieve the high levels of speech perception possible with the CI. It appears the AMI can transmit sufficient spectral cues but with limited temporal cues required for speech understanding. Currently, the AMI uses a CI-based strategy, which was originally designed to stimulate each frequency region along the cochlea with amplitude-modulated pulse trains matching the envelope of the bandpass-filtered sound components. However, it is unclear if this type of stimulation with only a single site within each frequency lamina of the ICC can elicit sufficient temporal cues for speech perception. At least speech understanding in quiet is still possible with envelope cues as low as 50 Hz. Therefore, we investigated how ICC neurons follow the bandpass-filtered envelope structure of natural stimuli in ketamine-anesthetized guinea pigs. We identified a subset of ICC neurons that could closely follow the envelope structure (up to ~100 Hz) of a diverse set of species-specific calls, which was revealed by using a peripheral ear model to estimate the true bandpass-filtered envelopes observed by the brain. Although previous studies have suggested a complex neural transformation from the auditory nerve to the ICC, our data suggest that the brain maintains a robust temporal code in a subset of ICC neurons matching the envelope structure of natural stimuli. Clinically, these findings suggest that a CI-based strategy may still be effective for the AMI if the appropriate neurons are entrained to the envelope of the acoustic stimulus and can transmit sufficient temporal cues to higher centers.

RORγt⁺ innate lymphoid cells acquire a proinflammatory program upon engagement of the activating receptor NKp44.

RORγt⁺ innate lymphoid cells (ILCs) are crucial players of innate immune responses and represent a major source of interleukin-22 (IL-22), which has an important role in mucosal homeostasis. The signals required by RORγt⁺ ILCs to express IL-22 and other cytokines have been elucidated only partially. Here we showed that RORγt⁺ ILCs can directly sense the environment by the engagement of the activating receptor NKp44. NKp44 triggering in RORγt⁺ ILCs selectively activated a coordinated proinflammatory program, including tumor necrosis factor (TNF), whereas cytokine stimulation preferentially induced IL-22 expression. However, combined engagement of NKp44 and cytokine receptors resulted in a strong synergistic effect. These data support the concept that NKp44⁺ RORγt⁺ ILCs can be activated without cytokines and are able to switch between IL-22 or TNF production, depending on the triggering stimulus.

Frequency representation within the human brain: stability versus plasticity.

A topographical representation for frequency has been identified throughout the auditory brain in animals but with limited evidence in humans. Using a midbrain implant, we identified an ordering of pitch percepts for electrical stimulation of sites across the human inferior colliculus (IC) that was consistent with the IC tonotopy shown in animals. Low pitches were perceived by the subject for stimulation of superficial IC sites while higher pitches were perceived for stimulation of deeper sites. Interestingly, this pitch ordering was not initially observed for stimulation across the IC, possibly due to central changes caused by prior hearing loss. Daily implant stimulation for about 4 months altered the pitch percepts from being predominantly low to exhibiting the expected ordering across the stimulated IC. A presumably normal tonotopic representation may have been maintained within the IC or accessible through IC stimulation that helped form this pitch ordering perceived in higher centers.

Alterations in early auditory evoked potentials and brainstem transmission time associated with tinnitus residual inhibition induced by auditory electrical stimulation.

INTRODUCTION: Residual inhibition (RI) is the temporary inhibition of tinnitus by use of masking stimuli when the device is turned off. OBJECTIVE: The main aim of this study was to evaluate the effects of RI induced by auditory electrical stimulation (AES) in the primary auditory pathways using early auditory-evoked potentials (AEPs) in subjective idiopathic tinnitus (SIT) subjects. MATERIALS AND METHODS: A randomized placebo-controlled study was conducted on forty-four tinnitus subjects. All enrolled subjects based on the responses to AES, were divided into two groups of RI and Non-RI (NRI). The results of the electrocochleography (ECochG), auditory brain stem response (ABR) and brain stem transmission time (BTT) were determined and compared pre- and post-AES in the studied groups. RESULTS: The mean differences in the compound action potential (CAP) amplitudes and III/V and I/V amplitude ratios were significantly different between the RI, NRI and PES controls. BTT was significantly decreased associated with RI. CONCLUSION: The observed changes in AEP associated with RI suggested some peripheral and central auditory alterations. Synchronized discharges of the auditory nerve fibers and inhibition of the abnormal activity of the cochlear nerve by AES may play important roles associated with RI. Further comprehensive studies are required to determine the mechanisms of RI more precisely.

Coactivation of different neurons within an isofrequency lamina of the inferior colliculus elicits enhanced auditory cortical activation.

The phenomenal success of the cochlear implant (CI) is attributed to its ability to provide sufficient temporal and spectral cues for speech understanding. Unfortunately, the CI is ineffective for those without a functional auditory nerve or an implantable cochlea required for CI implementation. As an alternative, our group developed and implanted in deaf patients a new auditory midbrain implant (AMI) to stimulate the central nucleus of the inferior colliculus (ICC). Although the AMI can provide frequency cues, it appears to insufficiently transmit temporal cues for speech understanding. The three-dimensional ICC consists of two-dimensional isofrequency laminae. The single-shank AMI only stimulates one site in any given ICC lamina and does not exhibit enhanced activity (i.e., louder percepts or lower thresholds) for repeated pulses on the same site with intervals <2-5 ms, as occurs for CI pulse or acoustic click stimulation. This enhanced activation, related to short-term temporal integration, is important for tracking the rapid temporal fluctuations of a speech signal. Therefore, we investigated the effects of coactivation of different regions within an ICC lamina on primary auditory cortex activity in ketamine-anesthetized guinea pigs. Interestingly, our findings reveal an enhancement mechanism for integrating converging inputs from an ICC lamina on a fast scale (<6-ms window) that is compromised when stimulating just a single ICC location. Coactivation of two ICC regions also reduces the strong and long-term (>100 ms) suppressive effects induced by repeated stimulation of just a single location. Improving AMI performance may require at least two shanks implanted along the tonotopic gradient of the ICC that enables coactivation of multiple regions along an ICC lamina with the appropriate interstimulus delays.

Cochlear implant performance in geriatric patients.

OBJECTIVES/HYPOTHESIS: To evaluate the hearing performance with cochlear implants (CIs) in patients who were 70 years or older at the time of implantation (geriatric patients) and compare it with the performance in younger adults. STUDY DESIGN: Individual, retrospective, cohort study. METHODS: A cohort of 1,005 postlingually deafened adults was selected for this study. According to their age at the time of cochlear implantation, patients were divided into four age groups: group 1, 18 to 39 years; group 2, 40 to 59 years; group 3, 60 to 69 years; and group 4, 70 years and older). The test battery was composed of four standard German speech tests: Freiburger Monosyllabic Test, Speech Tracking Test, and Hochmair-Schulz-Moser (HSM) Sentence Test in quiet and in 10 dB noise. RESULTS: Geriatric patients showed a similar learning curve as the younger adults in the first 2 years after implantation. The direct comparison of speech perception in the Freiburger Monosyllabic Test, Speech Tracking Test, and HSM Test in quiet revealed no differences between the average performance of the geriatric patients and younger adults. However, in the HSM Test in noise, the performance of the geriatric group was significantly lower than the younger adults. CONCLUSIONS: Geriatric CI patients have a similar learning curve to younger adults, and in speech tests in quiet they show a comparable performance. However, their performance is significantly lower in noisy surroundings. This may be due to the central presbycusis in patients older than 70 years and should be taken into account in postoperative fitting of these patients. Further prospective studies are required to evaluate the role of special rehabilitation methods and cognitive training to improve the speech perception in noise in geriatric CI patients.

Effect of gender on the hearing performance of adult cochlear implant patients.

OBJECTIVES/HYPOTHESIS: To evaluate the role of gender on the hearing performance of postlingually deafened adult patients with cochlear implants. STUDY DESIGN: Individual retrospective cohort study. METHODS: There were 638 postlingually deafened adults (280 men and 358 women) selected for a retrospective evaluation of their hearing performance with cochlear implants. Both genders underwent the same surgical and rehabilitative procedures and benefited from the latest technological advances available. There was no significant difference in the age, duration of deafness, and preoperative hearing performance between the genders. The test battery was composed of the Freiburger Monosyllabic Test, Speech Tracking, and the Hochmair-Schulz-Moser (HSM) sentence test in quiet and in 10-dB noise. The results of 5 years of follow-up are presented here. RESULTS: Genders showed a similar performance in Freiburger Monosyllabic Test and Speech Tracking Test. However, in the HSM test in noise, men performed slightly better than women in all of the follow-up sessions, which was statistically significant at 2 and 4 years after implantation. CONCLUSIONS: Although normal-hearing women use more predictive cognitive strategies in speech comprehension and are supposed to have a more efficient declarative memory system, this may not necessarily lead to a better adaptation to the altered auditory information delivered by a cochlear implant. Our study showed that in more complex listening situations such as speech tests in noise, men tend to perform slightly better than women. Gender may have an influence on the hearing performance of postlingually deafened adults with cochlear implants.

Long-term performance of cochlear implants in postlingually deafened adults.

OBJECTIVE: To evaluate the stability of long-term hearing performance after cochlear implantation (CI) in postlingually deafened adults and to explore the boundaries and limitations of the present test batteries for adult CI patients. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral center. SUBJECTS AND METHODS: A cohort of 1005 postlingually deafened adult cochlear implantees, who received their implants after age 18 years, was unilaterally implanted and had no inner ear malformations or cochlear ossification. Hearing performance with cochlear implant was evaluated with the help of 5 standard German speech tests. RESULTS: The average performance improved significantly during the first 6 months in all tests (learning phase) and afterward entered a plateau phase in which no statistically significant improvements or deteriorations were observed for more than 20 years of follow-up. For each test, the average performance of the cohort, the ceiling effect, and the average results for high and low performers are presented. CONCLUSIONS: In this study, postlingually deafened adults required about 6 months to learn how to process the artificial signals delivered by the cochlear implant. After this learning phase, the hearing performance entered a stable plateau phase for more than 20 years. This stability reveals the long-term reliability of the technology and the biological stability of the electrode-nerve interface over years. In this study, the authors also evaluated the "ceiling effect" with 5 standard German speech tests, used for evaluation of postlingually deafened adult CI patients.

Effect of technological advances on cochlear implant performance in adults.

OBJECTIVES/HYPOTHESIS: To evaluate the effect of technological advances in the past 20 years on the hearing performance of a large cohort of adult cochlear implant (CI) patients. STUDY DESIGN: Individual, retrospective, cohort study. METHODS: According to technological developments in electrode design and speech-processing strategies, we defined five virtual intervals on the time scale between 1984 and 2008. A cohort of 1,005 postlingually deafened adults was selected for this study, and their hearing performance with a CI was evaluated retrospectively according to these five technological intervals. The test battery was composed of four standard German speech tests: Freiburger monosyllabic test, speech tracking test, Hochmair-Schulz-Moser (HSM) sentence test in quiet, and HSM sentence test in 10 dB noise. RESULTS: The direct comparison of the speech perception in postlingually deafened adults, who were implanted during different technological periods, reveals an obvious improvement in the speech perception in patients who benefited from the recent electrode designs and speech-processing strategies. The major influence of technological advances on CI performance seems to be on speech perception in noise. CONCLUSIONS: Better speech perception in noisy surroundings is strong proof for demonstrating the success rate of new electrode designs and speech-processing strategies. Standard (internationally comparable) speech tests in noise should become an obligatory part of the postoperative test battery for adult CI patients.

Preoperative prediction of vestibular schwannoma's nerve of origin with posturography and electronystagmography.

CONCLUSION: Chances of hearing preservation are better in patients with vestibular schwannoma (VS) from the superior vestibular nerve (SVN) than from the inferior vestibular nerve (IVN). Pathologic posturography and electronystagmography (ENG) findings are more common in schwannomas from the SVN compared with tumors from the IVN. In this way, computerized dynamic platform posturography (CDPP) and ENG contribute to predict the nerve of origin of VS and can be used indirectly as a prognostic factor for hearing preservation. OBJECTIVES: To test whether preoperative CDPP or ENG results contribute to predict the nerve of origin in VS and also to evaluate the influence of the nerve of origin on hearing preservation. METHODS: Eighty-nine patients with VS originating from the IVN and 22 patients with VS from the SVN were included. Hearing loss due to surgery was calculated on postoperative and preoperative audiograms. Caloric response was measured by ENG and condition 5 and 6 score were recorded by CDPP before surgery. RESULTS: Hearing loss due to surgery was significantly lower in patients with tumors from the SVN than from the IVN (p = 0.011). Pathologic results in preoperative ENG (p < 0.0001) and CDPP (p = 0.025) were significantly more frequent in subjects with SVN than with IVN schwannomas.