Identification of target proteins involved in cochlear otosclerosis.

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: TGFß1 was identified in otosclerosis but not in the normal control temporal bone specimen. Aside from TGFß1, 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 TGFß1 monoclonal revealed marked staining of the spongiotic otosclerotic lesions. CONCLUSIONS: Mechanisms involved in cochlear extension of otosclerosis are still unclear, but the implication of TGFß1 is supported by the present proteomic data and immunostaining results. The established role of TGFß1 in the chondrogenesis process supports the theory of a reaction targeting the globulae interossei within the otic capsule.

Conservative management of vestibular schwannoma: expectations based on the length of the observation period.

OBJECTIVE: Evaluate long-term prevalence of tumor growth and need for further treatment in patients with a vestibular schwannoma treated with conservative management. STUDY DESIGN: Retrospective chart review. SETTING: Private neurotologic tertiary referral center. PATIENTS: Vestibular schwannoma patients undergoing conservative management and previously studied (N = 114). Mean time to last magnetic resonance imaging was 4.8 years and to last follow-up was 6.4 years (maximum, 18.5 yr). INTERVENTION: Serial gadolinium-enhanced magnetic resonance imaging with size measurement. MAIN OUTCOME MEASURES: Change in maximum tumor dimension of 2 mm or higher (growth), further treatment, audiologic measures-pure-tone average, word recognition, AAO-HNS (American Academy of Otolaryngology-Head and Neck Surgery) hearing class. RESULTS: Thirty-eight percent of tumors demonstrated growth; an average of 6.5 mm (SD, 3.8) at a mean rate of 3.1 mm per year. Of patients with no growth at 1 year or less, 20% grew by last follow-up. Overall, 31% had further treatment after a mean of 3.8 years (SD, 3.5; maximum, 18.5 yr). Of those followed for 5 to 10 years, 18% eventually had further treatment. Only 56% of growing tumors had further treatment by last follow-up; 14.8% with nongrowing tumors also had further treatment. Pure-tone average declined more in tumors that grew (mean Δ = 28.8 dB) than those that did not (mean Δ = 16.5 dB) (p ≤ 0.025), but there was no correlation between the amount of change in hearing and in the size of the tumor. Of patients with an initial AAO-HNS hearing Class A, 85.7% retained serviceable hearing. CONCLUSION: For patients electing an observation approach to treatment of vestibular schwannoma, about 31% may eventually undergo further treatment. Of those followed for 5 to 10 years, 18% eventually had further treatment. However, some patients are followed with radiologic evaluations for many years without necessity for further treatment.

Total ossiculoplasty: short- and long-term results using a titanium prosthesis with footplate shoe.

OBJECTIVES: Review experience using a titanium TORP with a footplate shoe; compare early and long-term hearing results and complications with those obtained using a TORP alone. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary referral neurotologic private practice. PATIENTS: Patients undergoing total ossicular replacement with a titanium prosthesis (total ossicular reconstruction prosthesis [TORP]); 74 with a TORP + footplate shoe and 62 with TORP alone. INTERVENTION: Ossicular chain reconstruction with a titanium TORP. MAIN OUTCOME MEASURES: Short- and long-term air-bone gap (ABG), change in ABG from preoperative to postoperative and from postoperative to last recorded follow-up, sensorineural hearing loss. RESULTS: The shoe group had a smaller mean postoperative ABG (17.7 dB versus 21.6 dB, p ≤ 0.048) and a greater average amount of closure in ABG (21.9 dB versus 13.2 dB, p ≤ 0.004), but there was no significant difference in percentage of patients achieving a postoperative ABG of 20 dB or lesser (57.4% versus 61.6%). There were no differences between groups at long-term follow-up or in amount of change in ABG from postoperative to last audiogram or in amount of change in sensorineural hearing from preoperative to postoperative. Although surgical factors (number of previous surgeries, and presence of a cavity) impacted outcomes, there were no interactions with prosthesis group and no differences in complications between groups. CONCLUSION: Ossicular reconstruction still presents challenges. A titanium prosthesis with a "shoe" for stabilization may offer advantages. Results in this study consistently favored the TORP + shoe group,although not all differences achieved statistical significance. A larger study might better define possible advantages of the shoe prosthesis for specific subgroups of patients.

Round window versus cochleostomy technique in cochlear implantation: histologic findings.

HYPOTHESIS: Cochleostomy or round window enlargement techniques for cochlear implant electrode insertion result in more abnormal tissue formation in the basal cochlea and are more apt to produce endolymphatic hydrops than round window electrode insertion. METHODS: Twelve temporal bones from implanted patients were examined under light microscopy and reconstructed with 3-dimensional reconstruction software to determine cochlear damage and volume of neo-ossification and fibrosis after electrode insertion. Amount of new tissue was compared between 3 groups of bones: insertion through the round window (RW), after enlarging the RW (RWE) and cochleostomy (Cochl). The probable role of the electrode was evaluated in each case with hydrops. RESULTS: More initial damage occurred in the Cochl and RWE groups than in the RW group, and the difference was significant between RWE and RW in cochlear segment I (p < 0.026). The volume of new bone in Segment I differed significantly between groups (p < 0.012) and was greater in the RWE group than in either the Cochl or RW groups (post hoc p's < 0.035 and 0.019, respectively). Hydrops was seen in 5 cases, all in the Cochl and RWE groups. Blockage of the duct was because of new tissue formation in 4 of the 5 hydrops cases. CONCLUSION: With the electrodes in this series, implantation through the RW minimized initial intracochlear trauma and subsequent new tissue formation, whereas the RW extension technique used at the time of these implantations produced the greatest damage. Future studies may clarify whether today's techniques and electrodes will produce these same patterns of damage.

Hearing preservation with the middle cranial fossa approach for neurofibromatosis type 2.

OBJECTIVES: To examine hearing preservation rates, facial nerve outcomes, and tumor recurrence rates in patients with neurofibromatosis Type 2 undergoing a primary middle cranial fossa approach for vestibular schwannoma removal. STUDY DESIGN: Retrospective chart review. SETTING: Private practice tertiary neurotology referral center. PATIENTS: All patients with neurofibromatosis Type 2 undergoing attempted hearing preservation via a middle cranial fossa approach for removal of vestibular schwannoma from January 1, 2000, to June 1, 2010. INTERVENTION: Primary middle cranial fossa approach for removal of vestibular schwannoma. MAIN OUTCOME MEASURES: Preoperative, postoperative, and change in hearing thresholds, word recognition scores, and American Academy of Otolaryngology-Head and Neck Surgery hearing class, House-Brackmann facial nerve grade, and tumor recurrence. RESULTS: Class A or B hearing according to the American Academy of Otolaryngology-Head and Neck Surgery was maintained in 50% of cases, whereas 63.6% had Class A, B, or C hearing, with an average word recognition score of 93.8% at an average follow-up period of 32.5 months. Facial nerve outcomes were excellent; 75% of cases maintained House-Brackmann Grade 1, whereas 94.3% had Grade 1 or 2 at an average of 25 months after surgery. Tumor growth within the surgical field was observed radiographically in 59% of cases. CONCLUSION: In patients with neurofibromatosis Type 2, proactive treatment of smaller tumors provides a chance to maintain serviceable hearing and obtain tumor control for extended periods. When examining hearing outcomes, it is important to use word recognition scores, in addition to American Academy of Otolaryngology-Head and Neck Surgery hearing class, to better assess functionality. Although facial nerve outcomes tend to be favorable, the growth of new tumors, including facial schwannomas, may occur within the surgical field. Continued surveillance with serial magnetic resonance scans after surgery is mandatory.

Evolution in the management of facial nerve schwannoma.

OBJECTIVE: To design a treatment algorithm based on experience with facial nerve schwannomas (FNS) over a 30-year period. STUDY DESIGN: Retrospective chart review. METHOD: Seventy-nine patients with facial nerve schwannomas seen from 1979 through 2009 at a tertiary referral private otologic practice were categorized by treatment modality. Interventions included surgical resection with grafting, bony decompression, observation, or stereotactic radiation. Outcome measures included House-Brackmann facial nerve grade before and after intervention as well as change in facial nerve grade, tumor size, involved segments of nerve, time to intervention. RESULTS: Thirty-seven patients (46.8%) ultimately underwent surgical excision with grafting or primary anastomosis, 21 (26.6%) underwent bony decompression alone, 15 (19.0%) were managed with observation only, and 6 (7.6%) had stereotactic radiation. Through 1995, 85% of cases had surgical resection and none had observation only. Of the 52 patients seen after 1995, 27% had surgical resection and grafting, 33% had bony decompression, 29% were managed with observation alone, and 11% had radiotherapy. Facial nerve grade was maintained or improved over the follow-up period (mean time = 3.9 years) in 78.9% of the decompression group and 100% of the observation and radiation groups compared to 54.8% of the resection group (P ≤ .012). CONCLUSIONS: Surgical resection and grafting, once widely accepted and practiced, has in many cases given way to observation, bony decompression, or stereotactic radiation. A wide armamentarium of options is available to the neurotologist treating facial nerve schwannomas with the ability to preserve facial function for a longer period of time.

Vestibular neuritis.

The epidemiology, diagnostic features, differential diagnosis, and treatment of vestibular neuritis are reviewed. The authors present considerations for physical examination, imaging, and management in both the acute and chronic phases of this disease. The authors also present a dizziness questionnaire in the Appendix of this publication.

Extralabyrinthine manifestations of DFNA9.

DFNA9 is an autosomal dominant cause of non-syndromic adult-onset sensorineural hearing loss with associated variable vestibular dysfunction caused by mutations in the COCH gene. DFNA9 has previously been characterized by the presence of unique histopathologic features limited to the cochlear and vestibular labyrinth. This report describes newly discovered extralabyrinthine findings within the middle ear in DFNA9 and discusses their implications. The histopathologic anatomy of extralabyrinthine structures was reviewed in 12 temporal bones from seven individuals with DFNA9 and compared with age-matched controls. All temporal bones with DFNA9 had abnormal deposits within the tympanic membrane, incudomalleal joint, and incudostapedial joint. Hematoxylin and eosin stain and Movat's pentachrome stain both revealed different staining patterns of the extralabyrinthine deposits compared with the intralabyrinthine deposits suggesting that the composition of the deposits varies with location. The deposits within the tympanic membrane resembled cartilage morphologically and stained positively for aggrecan, an extracellular matrix protein found in cartilage. However, the cellular component of the tympanic membrane deposits did not stain with immunomarkers for chondrocytes (s100 and connective tissue growth factor). These novel findings in DFNA9 have implications for the phenotypic expression of the disorder and the clinical workup of adult-onset sensorineural hearing loss.

Endolymphatic pseudohydrops of the cochlear apex.

OBJECTIVE: To demonstrate that what appears to be endolymphatic hydrops of the apical scala media is normal anatomy. STUDY DESIGN: Computer-generated three-dimensional reconstruction of the cochlear apex and tabulation of the number of cases with arched Reissner's membranes (pseudohydrops) versus flat membranes. SETTING: Temporal bone laboratory consisting of 809 documented pairs of temporal bones. SUBJECTS AND METHODS: Archival temporal bone sections from 107 bones (65 patients) were used to determine the percentage of arched (pseudohydrops) versus flat Reissner's membranes. Two bones, one of each membrane shape, were randomly selected for computer-generated three-dimensional reconstructions showing the cochlear apical anatomy. RESULTS: An arched Reissner's membrane was found in 48.6 percent of bones. In the cochlear apex, Reissner's membrane appears to be distended, simulating hydrops, due to its transition from a conical structure to a triangle bounded by the basilar membrane with the organ of Corti, the stria vascularis, and Reissner's membrane. Membrane findings were similar in both ears in 73.8 percent of the bilateral cases studied. There were no significant relationships between membrane type and clinical characteristics. CONCLUSION: What appears to be endolymphatic hydrops of the cochlear apex is the transition area of the cochlear duct from a conical shape at the extreme apex to the triangular shape found in the rest of the cochlea. The appearance of distension is dependent upon the cochlear length and the level of the microscopic section.

Cavitating otosclerosis: clinical, radiologic, and histopathologic correlations.

BACKGROUND: Despite the high prevalence of otosclerosis and its having long been a subject of scrutiny, cavitary changes in otosclerosis are rare and not well known. Here, we describe and introduce into the literature the unusual histologic and radiologic findings of cavitation and its possible clinical relevance in patients with advanced cochlear otosclerosis. METHODS: Cases with clinical otosclerosis and presence of cavitation were selected from our temporal bone collection and correlated with premortem imaging and clinical manifestations. RESULTS: Two cases of cochlear otosclerosis presented with a clinical syndrome possibly attributed to the existence of a cavity within the otosclerotic foci. CONCLUSION: Cavitating otosclerosis is a not well-known occurrence in patients with advanced cochlear otosclerosis, and it is a possible cause of a "third window" syndrome and surgical complications.

Jugular foramen tumors: clinical characteristics and treatment outcomes.

OBJECTIVE: To describe the diagnosis, management, and treatment outcome of jugular foramen (JF) tumors. STUDY DESIGN: Retrospective chart review. METHODS: Charts of the 83 patients diagnosed with JF tumors between January 1997 and May 2008 were reviewed. Presenting symptoms, otologic and neurotologic examination, audiologic thresholds, treatment procedure, surgical technique, tumor size and classification, and postoperative complications were recorded. Facial nerve function was graded using the House-Brackmann scale. Extent of tumor removal was determined at time of surgery, followed by routine radiographic follow-up. RESULTS: The mean age of patients with JF tumors was 48.5 years (standard deviation, 16.3 yr), and women (79.5%) outnumbered men (20.5%). Most had glomus jugulare (GJ) tumors (n = 67, 80.7%); 9 patients had lower cranial nerve schwannomas (10.8%), and 7 patients had meningiomas (8.4%). The most frequent initial symptoms included pulsatile tinnitus (84.3%), conductive hearing loss (75.9%), and hoarseness (34.9%). Sixty-one patients (73.5%) underwent surgery, 18.1% had radiotherapy, and 8.4% were observed. Total tumor removal was achieved in 81% of surgery cases. New lower cranial nerve (CN) deficits occurred after surgery in 18.9% of GJ, 22.2% of schwannoma, and 50% of the 4 meningiomas. At last follow-up, 88.1% of surgical patients had normal or near-normal (House-Brackmann I or II) facial function. CONCLUSION: Total resection of GJ tumors, meningiomas, and lower CN schwannomas can be a curative treatment. However, subtotal removal may be required to preserve CN function, vital vascular structures, and the brainstem. Postoperative radiotherapy is used to control residual tumor. When postoperative complications develop in patients, early rehabilitation is important to decrease mortality and morbidity. Therefore, patients should be closely followed.

Hearing results using the SMart piston prosthesis.

OBJECTIVE: SMart, a newly introduced piston prosthesis for stapedotomy, is a nitinol-based, heat-activated, self-crimping prosthesis. We review our hearing results and postoperative complications using this self-crimped piston prosthesis and compare them with those obtained using stainless steel or platinum piston prostheses. HYPOTHESIS: Audiometric results using the SMart piston are identical to those obtained using a conventional piston prosthesis. STUDY DESIGN: Retrospective chart review. SETTING: Private neurotologic tertiary referral center. PATIENTS: The 416 ears reviewed included 306 with a SMart prosthesis and 110 conventional prostheses. 61% were women. Mean follow-up time was 5.6 (standard deviation [SD], 6.3 mo) and 6.9 months (SD, 7.0 mo) for the 2 groups, respectively. INTERVENTION: Stapedotomy using the SMart or a conventional (non-SMart) prosthesis. MAIN OUTCOME MEASURES: Audiometric hearing results, including pure-tone average (PTA) and air-bone gap (ABG), and prevalence of postoperative complications. RESULTS: Mean postoperative PTA was 32.6 (SD, 16.8) dB for the SMart group and 29.4 (SD, 13.5) dB for the non-SMart group, with ABGs of 7.6 (SD, 8.9) and 6.0 (SD, 5.2) dB, respectively. Mean change (decrease) in ABG was 18.7 (SD, 13.1) dB for the SMart group and 19.9 (SD, 10.3) dB for the non-SMart group. High-frequency bone PTAs showed overclosure of 2.0 (SD, 7.9) dB for the SMart group and 3.6 (SD, 8.6) dB for the non-SMart group. Postoperative vertigo and tinnitus were infrequent. No significant differences in these audiometric outcomes or complication rates were noted between groups. There was no significant difference in rate of gap closure to within 10 dB (78.3 versus 84.2%, SMart and non-SMart, respectively) or 20 dB (94.2 and 98.0%). CONCLUSION: Compared with conventional stapes prostheses, the nitinol-based SMart is a safe and reliable stapes prosthesis that eliminates manual crimping without significantly altering the audiometric outcome. Complications are rare, but longer follow-up is needed before establishing long-term stability.

The medial wall of the jugular foramen: a temporal bone anatomic study.

OBJECTIVE: To better understand the variable and complex anatomy of the jugular foramen (JF) and the relationship between the neurovascular structures in the medial wall of the jugular bulb (JB). STUDY DESIGN: A temporal bone anatomic study. SETTING: A temporal bone laboratory within a hearing research facility. SUBJECTS AND METHODS: Twenty-two temporal bones were dissected under the operating microscope. The JF anatomy was exposed by using the modified infratemporal fossa approach (no rerouting of the facial nerve). Pictures were taken at various intervals during the dissection. Distances between important structures were measured with two-point calipers and transferred to a millimetric scale. RESULTS: The right JF was found to be larger than the left side in 72.7 percent of the dissected temporal bones. A fibrous septum separated the glossopharyngeal (CN IX) from the vagus (CN X) and accessory (CN XI) nerves in 19 specimens (86.4%), and a complete bony septum was present in three specimens (13.6%). The CNs IX, X, and XI traveled anteromedially to the JB within the JF. The inferior petrosal sinus (IPS) drained into the medial wall of the JB at various locations by two or more channels. In most of the specimens (86.4%), the IPS separated CNs IX and X. CONCLUSION: The lower cranial nerves have an intimate relationship to the medial wall of the JB. Within the JF, the neurovascular structures vary in size, shape, and location. To minimize surgical morbidity, the surgeon should be familiar with the complex anatomy of the JB and its variations.