Management of transmodiolar and transmacular cochleovestibular schwannomas with and without cochlear implantation.

INTRODUCTION: Hearing rehabilitation with cochlear implants has attracted increasing interest also for patients with cochleovestibular schwannoma. The authors report their experience with the surgical management of tumors with rare transmodiolar or transmacular extension and outcomes after cochlear implantation (CI). METHODS: This retrospective case series included nine patients with either primary intralabyrinthine tumors or secondary invasion of the inner ear from the internal auditory canal. The primary endpoint with CI, performed in six patients, was word recognition score at 65 dB SPL (sound pressure level). Secondary endpoints were intra- and postoperative electrophysiological parameters, impedance measures, the presence of a wave V in the electrically evoked (via the CI) auditory brainstem responses, the specifics of postoperative CI programming, and adverse events. RESULTS: Hearing rehabilitation with CI in cases of transmodiolar tumor growth could be achieved only with incomplete tumor removal, whereas tumors with transmacular growth could be completely removed. All six patients with CI had good word recognition scores for numbers in quiet conditions (80-100% at 65 dB SPL, not later than 6 to 12 months post CI activation). Four of these six patients achieved good to very good results for monosyllabic words within 1-36 months (65-85% at 65 dB SPL). The two other patients, however, had low scores for monosyllables at 6 months (25 and 15% at 65 dB SPL, respectively) with worsening of results thereafter. CONCLUSIONS: Cochleovestibular schwannomas with transmodiolar and transmacular extension represent a rare entity with specific management requirements. Hearing rehabilitation with CI is a principal option in these patients.

[Management of transmodiolar and transmacular cochleovestibular schwannomas with and without cochlear implantation. German version]. / Management transmodiolärer und transmakulärer Vestibularis- und Cochlearisschwannome mit und ohne Cochleaimplantation.

INTRODUCTION: Hearing rehabilitation with cochlear implants has attracted increasing interest also for patients with cochleovestibular schwannoma. The authors report their experience with the surgical management of tumors with rare transmodiolar or transmacular extension and outcomes after cochlear implantation (CI). METHODS: This retrospective case series included nine patients with either primary intralabyrinthine tumors or secondary invasion of the inner ear from the internal auditory canal. The primary endpoint with CI, performed in six patients, was word recognition score at 65 dB SPL (sound pressure level). Secondary endpoints were intra- and postoperative electrophysiological parameters, impedance measures, the presence of a wave V in the electrically evoked (via the CI) auditory brainstem responses, the specifics of postoperative CI programming, and adverse events. RESULTS: Hearing rehabilitation with CI in cases of transmodiolar tumor growth could be achieved only with incomplete tumor removal, whereas tumors with transmacular growth could be completely removed. All six patients with CI had good word recognition scores for numbers in quiet conditions (80-100% at 65 dB SPL, not later than 6 to 12 months post CI activation). Four of these six patients achieved good to very good results for monosyllabic words within 1-36 months (65-85% at 65 dB SPL). The two other patients, however, had low scores for monosyllables at 6 months (25 and 15% at 65 dB SPL, respectively) with worsening of results thereafter. CONCLUSIONS: Cochleovestibular schwannomas with transmodiolar and transmacular extension represent a rare entity with specific management requirements. Hearing rehabilitation with CI is a principal option in these patients.

Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation with cochlear implants.

Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebellopontine angle (CPA), 1a transotic including the CPA, and 1 a multilocular location. The tumors were removed surgically in 9 patients, whereas 3 patients decided for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3 underwent labyrinthectomy and cochlear implant (CI) surgery in a single-stage procedure; 1 patient had extended cochleostomy with CI surgery; 3 underwent partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI surgery (n = 1) or implantation of electrode dummies for possible later CI after repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the internal auditory canal and cerebellopontine angle exhibiting transmodiolar or transmacular growth were removed by combined translabyrinthine-transotic resection. For the intracochlear tumors, vestibular function could mostly be preserved after surgery. In all cases with CI surgery, hearing rehabilitation was successful, although speech discrimination was limited for the case with subtotal cochleoectomy. Surgical removal of intracochlear schwannomas via partial or subtotal cochleoectomy is, in principle, possible with preservation of vestibular function. In the authors' opinion, radiotherapy of ILS is only indicated in isolated cases. Cochlear implantation during or after tumor resection (i. e., as synchronous or staged surgeries) is an option for hearing rehabilitation in cartain cases and represents a therapeutic approach in contrast to a "wait-and-test-and-scan" strategy.

[Intralabyrinthine schwannomas : Surgical management and hearing rehabilitation with cochlear implants. German version]. / Intralabyrinthäre Schwannome : Chirurgisches Management und Hörrehabilitation mit Cochleaimplantaten.

Intralabyrinthine schwannomas (ILS) are a rare differential diagnosis of sudden hearing loss and vertigo. In an own case series of 12 patients, 6 tumors showed an intracochlear, 3 an intravestibular, 1 a transmodiolar including the cerebello-pontine angle (CPA), 1 a transotic including the CPA and 1 a multilocular location. The tumors were removed surgically in 9 patients, whereas 3 patients opted for a "wait-and-test-and-scan" strategy. Of the surgical patients, 3 underwent labyrinthectomy and cochlear implant (CI) surgery in a single stage procedure; 1 patient received extended cochleostomy with CI surgery; 3 underwent partial or subtotal cochleoectomy, with partial cochlear reconstruction and CI surgery (n = 1) or implantation of electrode dummies for possible later CI following repeated MRI follow-up (n = 2); and in 2 patients, the tumors of the internal auditory canal and cerebellopontile angle exhibiting transmodiolar or transmacular growth were removed by combined translabyrinthine-transotic resection. For the intracochlear tumors, vestibular function could mostly be preserved after surgery. In all cases with CI surgery, hearing rehabilitation was successful, although speech discrimination was limited for the case with subtotal cochleoectomy. Surgical removal of intracochlear schwannomas via partial or subtotal cochleoectomy is, in principle, possible with preservation of vestibular function. In the authors' opinion, radiotherapy of ILS is only indicated in isolated cases. Provided performed early enough, cochlear implantation after surgical removal of ILS is an option for auditory rehabilitation, thus representing-in contrast to the "wait-and-test-and-scan" strategy-a therapeutic approach.

Expression of histamine receptors in the human endolymphatic sac: the molecular rationale for betahistine use in Menieres disease.

The human endolymphatic sac (ES) is situated in a duplicature of the dura in the posterior cranial fossa and constitutes a part of the inner ear. The sac possesses immunological capacities and is responsible for a major part of the trans-epithelial ion transport occurring within the inner ear, via molecular mechanisms similar to that of the kidney collecting duct epithelia. Dysfunction of the trans-epithelial ion transport has been hypothesized as the reason for the endolymphatic hydrops occurring in Menieres diseases. Thus, candidate drug selection for medical treatment of Menieres disease has been based on a potential capability of improving trans-epithelial ion transport. However, recent human studies seems to rule out diuretic therapy and The Committee for Medicinal Products for Human Use redrew the recommendation for trimetazidine (Vastarel) treatment in the management of Meniere disease in 2012. This leaves betahistine (Betaserc) as the only drug for potential prevention of the incapacitating attacks of dizziness, tinnitus and hearing loss. However, the histamine receptors targeted by betahistine have never been demonstrated in the human ES. Accordingly, this study aims to investigate the expression of histamine receptors of the human ES epithelium and sub-epithelial stroma. Following sampling of human endolymphatic sac tissue during translabyrinthine surgery, the expression of histamine receptor genes was determined by cDNA microarray analysis. Results were subsequently verified by immuno-histochemistry. The combined results of microarrays and immuno-histochemistry showed expression of the histamine receptor HRH1 in the epithelial lining of the ES, whereas HRH3 was expressed exclusively in the sub-epithelial capillary network. Receptors HRH2 and -4 were not expressed. The present data provide the first direct evidence of a molecular rationale for betahistine treatment in Menieres disease. A potential betahistine effect in Menieres disease may primarily be through the H3-receptor antagonism, leading to inhibition of vestibular neuro-transmission and central vaso-dilation. The H1-receptor localization in the ES epithelium suggests an immuno-regulatory effect.

Peak and ceiling effects in final-product analysis of mastoidectomy performance.

BACKGROUND: Virtual reality surgical simulation of mastoidectomy is a promising training tool for novices. Final-product analysis for assessing novice mastoidectomy performance could be limited by a peak or ceiling effect. These may be countered by simulator-integrated tutoring. METHODS: Twenty-two participants completed a single session of self-directed practice of the mastoidectomy procedure in a virtual reality simulator. Participants were randomised for additional simulator-integrated tutoring. Performances were assessed at 10-minute intervals using final-product analysis. RESULTS: In all, 45.5 per cent of participants peaked before the 60-minute time limit. None of the participants achieved the maximum score, suggesting a ceiling effect. The tutored group performed better than the non-tutored group but tutoring did not eliminate the peak or ceiling effects. CONCLUSION: Timing and adequate instruction is important when using final-product analysis to assess novice mastoidectomy performance. Improved real-time feedback and tutoring could address the limitations of final product based assessment.

Spontaneous tumour shrinkage in 1261 observed patients with sporadic vestibular schwannoma.

OBJECTIVE: To determine the rate of spontaneous tumour shrinkage in a group of patients with sporadic vestibular schwannoma managed with a 'wait and scan' approach. PATIENTS: All patients with a unilateral cerebello-pontine angle tumour resembling a vestibular schwannoma were registered prospectively in a national database in Denmark. Patients registered with tumour shrinkage were identified and all computed tomography and magnetic resonance imaging scans retrieved, re-evaluated and related to the clinical data. RESULTS: Of 1261 observed patients, 48 displayed spontaneous shrinkage (3.81 per cent). Mean absolute shrinkage was 6.25 mm, equivalent to 52.1 per cent. Absolute shrinkage correlated with tumour size and followup period, whereas relative shrinkage was significantly greater for tumours which were purely intrameatal at diagnosis. There was no correlation between age and the degree of shrinkage. CONCLUSION: Four per cent of sporadic vestibular schwannomas shrink spontaneously. These findings substantiate the 'wait and scan' strategy for tumours with a largest extrameatal diameter of up to 20 mm.

Residual tumour after vestibular schwannoma surgery.

OBJECTIVE: To evaluate residual tumour occurrence after vestibular schwannoma surgery, based on intra-operative registration and magnetic resonance imaging one year post-operatively. METHODS: Patients undergoing translabyrinthine surgery for vestibular schwannoma in Denmark between 1976 and 2008 were registered in a national database covering 5.5 million inhabitants. RESULTS: Translabyrinthine surgery was undertaken on 1143 patients. Of these, 978 had total, 140 near-total and 25 subtotal tumour excision, as assessed intra-operatively by the surgeon. One year after surgery, 65 per cent of small tumour remnants and 11 per cent of large tumour remnants were not visible on magnetic resonance imaging. The mean pre-operative size was significantly smaller for totally excised tumours, compared with near-totally and subtotally excised tumours. Revision surgery was performed for 14 patients (1.2 per cent), of whom 2 had received total, 5 near-total and 6 subtotal excisions initially. CONCLUSION: Most residual tumours disappear spontaneously, probably due to devascularisation. Few patients with a small residual vestibular schwannoma will require revision surgery or secondary radiotherapy.

Allergic rhinitis is associated with otitis media with effusion: a birth cohort study.

BACKGROUND: Childhood otitis media with effusion is a common disease and a link to allergic diseases has been suggested. OBJECTIVE: To investigate the association between atopic disease and otitis media with effusion diagnosed according to strict objective case definitions by age 6 years. METHODS: We evaluated 291 children in the 6th year of life from the Copenhagen Prospective Studies on Asthma in Childhood (COPSAC) 2000 birth cohort. Otitis media with effusion was diagnosed based on tympanometric and objective evaluation. Asthma, eczema, allergic- and non-allergic rhinitis was diagnosed prospectively by pre-defined algorithms. Nasal mucosal swelling was assessed using acoustic rhinometry and nasal eosinophilia from scrapings. Analyses were performed using logistic regression and adjusted for dog, cat and smoking exposure, paternal atopy, household income, older siblings, gender and number of acute otitis media episodes. RESULTS: Otitis media with effusion was diagnosed in 39% of the cohort and was associated with allergic rhinitis (aOR = 3.36, CI = 1.26-8.96, P = 0.02), but not with nasal mucosal swelling, nasal oeosinophilia, non-allergic rhinitis, asthma or eczema. CONCLUSION: Otitis media with effusion is closely associated with allergic rhinitis presumably caused by allergic inflammation, but not mechanical nasal mucosal swelling. These findings warrant an increased awareness of otitis media with effusion in children with allergic rhinitis.

Bacterial adherence in otitis media: determination of N-acetylgalactosamine (GalNAc) residues in the submucosal glands and surface epithelium of the normal and diseased Eustachian tube.

BACKGROUND: Acute otitis media (AOM) is the most common childhood infection caused by bacteria. The pathogenesis of AOM implicates initial adherence of a pathogen to the nasopharyngeal epithelium, which is followed by bacterial colonization of the middle ear cavity through the Eustachian tube. N-acetylgalactosamine (GalNAc) is an important constituent of mucins and GalNAc containing sugar residues seem to be essential for initial adherence of respiratory bacteria to the surface of epithelial cells. OBJECTIVE: To explore the localization of GalNAc residues, we incubated Eustachian tube sections from Streptococcus pneumoniae infected and normal control rats with seven biotinylated, GalNAc recognizing lectins: Bauhinia purpurea lectin (BPA), Psophocarpus tetragonolobus lectin (PTA), Helix aspersa lectin (HAA), Helix pomatia lectin (HPA), Phaseolus lunatus lectin (PLA), Sophora japonica lectin (SJA) and Vicia Villosa isolectin B4 (VVA-B4). RESULTS: The mucin producing epithelium and submucosal glands of the normal Eustachian tube contained GalNAc residues, as evidenced by binding of several of the lectins. Lectin binding specificity and intensity changed following acute middle ear infection. BPA was the only lectin that exclusively stained the surface epithelium and the serous acini of the submucosal glands in the infected animals, whereas no binding was detected in the normal controls. HPA, HAA, PTA and VVA-B4 binding to surface epithelial cells increased after infection, indicating an active secretion of GalNAc containing glycans. Quantitative analysis of submucosal gland staining intensity showed significantly more GalNAc residues in the normal Eustachian tube, compared to infected animals. CONCLUSION: We conclude that the mucous producing elements of the normal rat Eustachian tube contain GalNAc residues essential for respiratory pathogen adherence. In addition, the GalNAc residue specificity and reacting intensity change in relation to acute infection, which may be important in relation to subsequent development of secretory otitis media or formation of a bacterial biofilm in the middle ear. The results show that GalNAc residues increased in both the submucosal serous glands and in the surface epithelium of the Eustachian tube after middle ear infection with S. pneumoniae.

Hearing outcomes of vestibular schwannoma patients managed with 'wait and scan': predictive value of hearing level at diagnosis.

AIMS: This study aimed to evaluate the predictive value of both hearing level (at various frequencies) and speech discrimination for forecasting hearing outcome after a period of observation, in patients with vestibular schwannoma. SUBJECTS: Over a 33-year period, 1144 patients with vestibular schwannoma were allocated to 'wait and scan' management, with annual magnetic resonance imaging and audiological examination. Two complete pure tone and speech discrimination audiograms were available for 932 patients. RESULTS: The predictive value of initial hearing level better than 10 dB for forecasting hearing outcome after observation increased from 59 per cent at 250 Hz to 94 percent at 4000 Hz. At diagnosis, hearing level of 10 dB or better at 4000 Hz was found in only 18 of the 932 VS ears, while good speech discrimination was found in 159 patients (17 per cent). Of the latter patients, 138 maintained good hearing after observation. CONCLUSION: In vestibular schwannoma patients, good high frequency hearing and good speech discrimination at diagnosis are useful tools in predicting good hearing after observation.

Change in hearing during 'wait and scan' management of patients with vestibular schwannoma.

AIM: To evaluate hearing changes during 'wait and scan' management of patients with vestibular schwannoma. SUBJECTS: Over a 10-year period, 636 patients have prospectively been allocated to 'wait and scan' management, with annual magnetic resonance scanning and audiological examination. RESULTS: At the time of diagnosis, 334 patients (53 per cent) had good hearing and speech discrimination of better than 70 per cent; at the end of the 10-year observation period, this latter percentage was 31 per cent. In 17 per cent of the patients, speech discrimination at diagnosis was 100 per cent; of these, 88 per cent still had good hearing at the end of the observation period. However, in patients with even a small initial speech discrimination loss, only 55 per cent maintained good hearing at the end of the observation period. CONCLUSION: After comparing the hearing results of hearing preservation surgery and of radiation therapy with those of 'wait and scan' management, it appears that, in vestibular schwannoma patients with a small tumour and normal speech discrimination, the main indication for active treatment should be established tumour growth.

Hearing loss and cochlear damage in experimental pneumococcal meningitis, with special reference to the role of neutrophil granulocytes.

Hearing loss is a well-known sequelae from meningitis, affecting up to 25% of survivors. However, the principal components of the infectious and inflammatory reaction responsible for the sensorineural hearing loss remain to be identified. The present study aimed to investigate the impact of an augmented neutrophil response on the development of hearing loss and cochlear damage in a model of experimental pneumococcal meningitis in rats. Hearing loss and cochlear damage were assessed by distortion product oto-acoustic emissions (DPOAE), auditory brainstem response (ABR) and histopathology in rats treated with ceftriaxone 28 h after infection. Rats were treated with Granulocyte Colony Stimulating Factor (G-CSF) initiated prior to infection, 28 h after infection or with ceftriaxone only. Rats were followed for 7 days, and assessment of hearing was performed before infection and 24 h and day 8 after infection. Pretreatment with G-CSF increased hearing loss 24 h after infection and on day 8 compared to untreated rats (Mann-Whitney, P = 0.012 and P = 0.013 respectively). The increased sensorineural hearing loss at day 8 was associated with significantly decreased spiral ganglion cell counts (P = 0.0006), increased damage to the organ of Corti (P = 0.007), increased areas of inflammatory infiltrates (P = 0.02) and increased white blood cell (WBC) counts in cerebrospinal fluid on day 8 after infection (P = 0.0084). Initiation of G-CSF 28 h after infection did not significantly affect hearing loss or cochlear pathology compared to controls. In conclusion, the inflammatory host reaction contributes significantly to the development of hearing loss in experimental meningitis.

Cartilage palisade tympanoplasty in sinus and tensa retraction cholesteatoma.

OBJECTIVE: The aim of this study was to investigate whether reconstruction of the eardrum with palisade cartilage technique could prevent retraction of the new eardrum after surgery for sinus and tensa retraction cholesteatoma in children and to investigate the postoperative hearing. STUDY DESIGN: In 32 children aged 5 to 15 years, operated on from June 1995 to October 2000 for cholesteatoma (21 with sinus cholesteatoma and 11 with tensa retraction cholesteatoma) the eardrum was reconstructed with the palisade cartilage technique. Postoperatively, the children were seen as outpatients and were recently reevaluated with otomicroscopy, tympanometry, and audiometry. All patients (100%) were reevaluated on an average of 37 months (range 3-63 months). MAIN OUTCOME MEASURES: Postoperative retractions, perforations, cholesteatoma recurrence, and hearing. RESULTS: At the final examination, posterosuperior retraction was observed in two patients, both operated on for sinus cholesteatoma with reconstruction of the ossicular chain. In those cases, the palisades were not placed in the posterosuperior drilling defect behind the interpositioned incus. All the patients had an intact tympanic membrane at the final follow-up visit. One small perforation was surgically closed during the observation period. No patients developed cholesteatoma during the follow-up period. The postoperative hearing was good, and the hearing did not deteriorate with increasing observation time. CONCLUSIONS: The palisade technique effectively prevented postoperative retraction of the eardrum. The postoperative hearing was good.

Goblet cell density in acute otitis media caused by Moraxella catarrhalis.

HYPOTHESIS AND BACKGROUND: Secretory otitis media is associated with a highly increased goblet cell density, confirming the secretory pathogenesis of this disease. Previous studies have shown that the middle ear goblet cell density, and thus the secretory capacity, are massively increased during experimental acute otitis media and at least 6 months thereafter, conceivably predisposing to the subsequent development of secretory otitis media. These studies used middle ear inoculation of either Streptococcus pneumoniae, nontypeable Haemophilus influenzae, or H. influenzae type b. The present study aimed at determining the goblet cell density during and after acute otitis media caused by Moraxella catarrhalis to clarify whether this bacterium induces an equivalently enhanced secretory capacity. METHODS: Twenty-five 25 rat middle ears were inoculated with M. catarrhalis. Five rats were killed on days 4, 8, 16, 60, and 180 after inoculation, followed by staining, dissection, and whole-mount embedding of the middle ear mucosae. The goblet cell density was determined by counting in 24 fields, covering the entire middle ear. RESULTS: In comparison with 25 normal middle ears, the goblet cell density was significantly increased in almost all counting localities, from day 4 and < or = 2 months after inoculation. The goblet cell density peaked on day 16, subsided thereafter, and in some areas reached a normal level 6 months after the acute incident. Mucosal areas containing goblet cells were consistently enlarged, thus leaving the middle ear with an increased secretory capacity during and 6 months after inoculation. CONCLUSION: The goblet cell density of the middle ear mucosa is increased during acute otitis media caused by M. catarrhalis and up to several months thereafter. This may predispose to the subsequent development of secretory otitis media. However, in comparison with acute otitis media caused by other bacteria, M. catarrhalis induced only modest changes in goblet cell density.

Middle ear secretory capacity after acute otitis media caused by Streptococcus pneumoniae, Moraxella catarrhalis, non-typeable or type B Haemophilus influenzae. A comparative analysis based on goblet cell density.

To investigate whether the type of bacteria is correlated with an increase in goblet cell density during and after acute otitis media, we inoculated the middle ear of 25 rats with either Streptococcus pneumoniae, Moraxella catarrhalis, non-typeable or type b Haemophilus influenzae. Mucosal goblet cell density was determined by a whole-mount method on days 4, 8, 16, 60 and 180 post-inoculation. The goblet cell density was increased on all days of sacrifice, employing either bacteria, except M. catarrhalis 6 months after the acute incident. Type b H. influenzae induced the highest increase, followed by non-typeable H. influenzae, S. pneumoniae and M. catarrhalis. The mucosal area containing goblet cells was enlarged on all examination days, employing either bacteria. We conclude, that mucosal secretory capacity is highly increased during and up to 6 months after acute middle ear infection caused by either bacteria, conceivably predisposing a subsequent development of secretory otitis media. The results indicate that type b H. influenzae seems to be the bacteria most likely to induce a subsequent secretory condition.