Dispersed DNA variants underlie hearing loss in South Florida's minority population.

BACKGROUND: We analyzed the genetic causes of sensorineural hearing loss in racial and ethnic minorities of South Florida by reviewing demographic, phenotypic, and genetic data on 136 patients presenting to the Hereditary Hearing Loss Clinic at the University of Miami. In our retrospective chart review, of these patients, half self-identified as Hispanic, and the self-identified racial distribution was 115 (86%) White, 15 (11%) Black, and 6 (4%) Asian. Our analysis helps to reduce the gap in understanding the prevalence, impact, and genetic factors related to hearing loss among diverse populations. RESULTS: The causative gene variant or variants were identified in 54 (40%) patients, with no significant difference in the molecular diagnostic rate between Hispanics and Non-Hispanics. However, the total solve rate based on race was 40%, 47%, and 17% in Whites, Blacks, and Asians, respectively. In Non-Hispanic Whites, 16 different variants were identified in 13 genes, with GJB2 (32%), MYO7A (11%), and SLC26A4 (11%) being the most frequently implicated genes. In White Hispanics, 34 variants were identified in 20 genes, with GJB2 (22%), MYO7A (7%), and STRC-CATSPER2 (7%) being the most common. In the Non-Hispanic Black cohort, the gene distribution was evenly dispersed, with 11 variants occurring in 7 genes, and no variant was identified in 3 Hispanic Black probands. For the Asian cohort, only one gene variant was found out of 6 patients. CONCLUSION: This study demonstrates that the diagnostic rate of genetic studies in hearing loss varies according to race in South Florida, with more heterogeneity in racial and ethnic minorities. Further studies to delineate deafness gene variants in underrepresented populations, such as African Americans/Blacks from Hispanic groups, are much needed to reduce racial and ethnic disparities in genetic diagnoses.

Genotype-phenotype associations in paragangliomas of the temporal bone in a multi-ethnic cohort.

BACKGROUND: Temporal bone paragangliomas are rare tumours with variable presentation that can be hereditary. Identification of clinical and genetic factors of aggressive tumour behaviour is important. OBJECTIVE: To determine the underlying genetic mutations and genotype/phenotype correlations in a multi-ethnic population of South Florida with sporadic temporal bone paragangliomas. METHODS: In a cohort of glomus tympanicum (GT) and glomus jugulare (GJ) cases, we assessed the frequency of pathogenic single nucleotide variants, insertions, deletions, and duplications in coding exons of genes that have been associated with paragangliomas (SDHB, SDHC, SDHD, SDHA, SDHAF2, RET, NF1, VHL, TMEM127, and MAX). RESULTS: None of the 12 GT cases had mutations. Among 13 GJ cases, we identified four mutation carriers (31%); two in SDHC, one in SDHB, and one in SDHD. All patients with pathogenic mutations were of Hispanic ethnicity, presented at a younger age (mean 27.5 versus 52.11 years), and with more advanced disease when compared to mutation-negative GJ cases.Conclusions and Significance: Mutations in the SDH genes are found in 31% of sporadic GJ. SDH-associated GJ had advanced disease and a 50% risk of metastasis. Our data supports emerging recommendations for genetic screening in all populations with GJ tumours as the genetic status informs management.

Microsurgical Management of Vestibular Schwannoma (Acoustic Neuroma): Facial Nerve Outcomes, Radiographic Analysis, Complications, and Long-Term Follow-Up in a Series of 420 Surgeries.

OBJECTIVE: The purpose of this study is to retrospectively evaluate the clinical and surgical outcomes of a large surgical series of vestibular schwannoma from North America over 20 years. METHODS: After institutional review board approval a retrospective review of the senior author's personal case logs to identify patients who had operations for vestibular schwannoma was performed. The clinical notes, operative record, preoperative and postoperative imagings, and long-term clinical follow-up notes were evaluated. RESULTS: A total of 415 patients who underwent 420 surgeries were identified from the years 1998-2021. The average length of follow-up was 3 years and 9 months. Overall, at last follow-up the rate of "good" facial nerve outcomes (House-Brackmann [HB] score I and II) was 86% and "poor" facial nerve outcomes (HB III-VI) was 14%. The amount of cerebellopontine angle extension (P = 0.023), tumor volume (P = 0.015), facial nerve consistency (P < 0.001), preoperative HB score (P < 0.001), and FN stimulation threshold at the end of the procedure (P < 0.001) were correlated to facial nerve function at the last follow-up. CONCLUSIONS: This study represents one of the largest recently reported surgical series of vestibular schwannoma in North American literature with available long term follow-up. Facial nerve outcomes correlated with cerebellopontine angle extension, tumor volume, facial nerve stimulation threshold, facial nerve consistency, preoperative facial nerve function, and history of a prior resection. Tumor recurrence remains significantly higher after subtotal resection. We believe the data supports a continuation of a strategy of general intent of gross total resection, greatly modifiable by intraoperative findings and judgment.

Safety and Facial Nerve Outcomes of Intracisternal Papaverine Irrigation for Vestibular Schwannoma Resection.

BACKGROUND: Papaverine, a vasodilator approved for use by the U.S. Food and Drug Administration, has shown efficacy in treating vasospasm in cardiology, urology, and nephrology. The vasodilatory effect of papaverine is also hoped to protect the facial nerve from ischemic damage and nerve manipulation during vestibular schwannoma surgery. Our institution uses intracisternal papaverine irrigation during vestibular schwannoma resection to protect the facial nerve in patients with neuromonitoring changes. Our objective was to investigate the safety and facial nerve outcomes of intracisternal papaverine irrigation during vestibular schwannoma resection. METHODS: We retrospectively reviewed patients who underwent resection of vestibular schwannoma at our institution between 2008 and 2021. Patients received papaverine if the intraoperative facial nerve stimulation threshold increased above 0.05 mA. Postoperative outcomes were compared with control patients who did not receive papaverine. RESULTS: A total of 283 cases were included in our analysis. Patients who received papaverine (n = 60) had lower immediate postoperative House-Brackmann (HB) grades than did control individuals (mean, 1.54 vs. 1.95; P = 0.029) and a lower likelihood of immediate postoperative HB grade >1 (odds ratio, 0.514; P = 0.039). At long-term follow-up, there was no significant difference in HB grade. Papaverine use was not associated with increased rates of perioperative complications (P = 0.24). CONCLUSIONS: The off-label use of intracisternal papaverine irrigation during vestibular schwannoma resection can certainly be used safely for select cases. It is associated with improved immediate postoperative facial nerve outcomes, similar long-term facial nerve outcomes, and no significant increase in complications.

Mesenchymal Stem Cells for Treatment of Delayed-Healing Tympanic Membrane Perforations Using Hyaluronate-based Laminas as a Delivery System: An Animal Model With Histopathologic Study.

HYPOTHESIS: Bone marrow derived-mesenchymal stem cells (BM-MSCs) improve the healing of chronic tympanic membrane perforations (cTMPs) in an animal model. BACKGROUND: cTMPs generate significant morbidity and reduced quality of life, usually requiring surgical assistance. With growing interest in alternative therapies, we sought to evaluate the effect of BM-MSC-therapy on the healing of cTMPs. METHODS: Sixty cTMPs were established in C57Bl/6 mice and randomized into four groups: hyaluronate scaffold as graft plus BM-MSCs (n = 19 ears), scaffold plus cell culture media (n = 16), scaffold plus phosphate-buffered saline (PBS, n = 12), and no intervention (n = 13). Hyaluronate scaffolds with or without BM-MSCs were applied on 8-week perforated eardrums. After a blinded assessment of perforation sizes at baseline and 2 weeks after treatment, mean perforation reduction rates (%) were compared. Histology characterization was then performed. RESULTS: Mean perforation size reduction rates were significantly higher for cTMPs that received scaffolds plus BM-MSCs (Student's t test, p = 0.0207, 12.3% [95% CI: 7.8-16.7]) and scaffolds plus cell culture media (p = 0.0477, 11.3% [95% CI: 4.4-18.2]) when compared with no intervention (4.2% [95% CI: 1.2-7.2]). This was not observed when treating eardrums with scaffolds plus PBS (7.3% [95% CI: 2.7-11.9]). On histology, BM-MSC-treated eardrums demonstrated restoration of the trilaminar configuration and reduced inflammatory changes, while other groups developed tissue architecture disorganization and hypercellular infiltrates surrounding the perforation site. CONCLUSIONS: BM-MSCs and cell culture media equivalently increased cTMP healing rates. Cell-based therapy conferred a restoration of the trilaminar configuration of the eardrum with relatively compact and organized fibrous layers.

Catchment Profile of Large Cochlear Implant Centers in the United States.

OBJECTIVE: To characterize the catchment area and patient profile of large cochlear implant (CI) centers in the United States. STUDY DESIGN: Multi-institutional retrospective case series. SETTING: Tertiary referral CI centers. METHODS: Patients who underwent CI surgery at 7 participating CI centers between 2015 and 2020 were identified. Patients' residential zip codes were used to approximate travel distances and urban vs rural residential areas. RESULTS: Over the 6-year study period (2015-2020), 6313 unique CI surgical procedures occurred (4529 adult, 1784 pediatric). Between 2015 and 2019, CI procedures increased by 43%. Patients traveled a median 52 miles (interquartile range, 21-110) each way; patients treated at rural CI centers traveled greater distances vs those treated at urban centers (72 vs 46 miles, P < .001). Rural residents represented 61% of the patient population and traveled farther than urban residents (73 vs 24 miles, P < .001). Overall, 91% of patients lived within a 200-mile radius of the institution, while 71% lived within a 100-mile radius. In adults, multiple regression analysis redemonstrated an association between greater travel distances and (1) older age at the time of CI and (2) residential rural setting (both P < .001, r2 = 0.2). CONCLUSIONS: While large CI centers serve geographically dispersed populations, most patients reside within a 200-mile radius. Strategies to expand CI utilization may leverage remote programming, telemedicine, and strategic placement of new centers and satellite clinics to ameliorate travel burden.

The Epidemiological and Financial Effects of Pneumococcal Vaccination on Otitis Media Related Admissions in the United States.

OBJECTIVE: To quantify the prevalence of hospital admissions, the financial impact, and the trends in surgical procedure rates for AOM and CAOM for all ages before and after 13-valent pneumococcal conjugate vaccine (PCV13) introduction. METHODS: Retrospective analysis of the National Inpatient Sample (NIS) from 1998 to 2013 to determine the prevalence of AOM/CAOM related admissions and weighted frequencies of AOM/CAOM related International Classification of Diseases, ninth revision (ICD-9) hospital diagnoses. Prevalence of surgical procedures to treat CAOM, cost of admission, length of stay, and cost per day of admission were tabulated. Trend analysis of this data was performed. RESULTS: A total of 46 580 patients were hospitalized with AOM in the designated time period, of which 37 366 had CAOM. The prevalence of hospital admission due to AOM had the most pronounced decrease from pre-vaccine era (1998) to post-PCV13 implementation (2013) in age group 0 to 4 (32%) followed by age group 5 to 19 (7%). Age groups 20-64 and 65+ showed slight increases in prevalence. The trend in prevalence of admissions due to CAOM mirrors that of overall admissions with an 18% and 5.8% decrease in age groups 0-4 and 5-19, respectively, and a 1% increase in ages 20+. The inflation adjusted mean cost of admission did not significantly increase between 2001 and 2013. The total cost per admission was $4428 and $7546 for those with AOM and CAOM, respectively. Mastoidectomy rates increased by 17% in hospitalized children during the post-vaccine era but decreased in the elderly population. CONCLUSION: The prevalence of AOM/CAOM hospital admissions decreased from the pre-vaccine era (1998) to post-PCV13 implementation (2013) in pediatric patients. Surgical procedure utilization and cost of hospital admission for AOM/CAOM did not increase throughout the study period.

Animal Model of Chronic Tympanic Membrane Perforation.

Chronic tympanic membrane perforations (TMP) can be a source of significant morbidity from hearing loss, recurrent middle ear infections, changes in lifestyle, and risk of cholesteatoma formation. Laboratory experiments of TMP have been fraught by the rapid and high rate of spontaneous healing observed in animal models. There is controversy on the minimal time that perforations in animal models must have in order to be considered chronic TMP and thus have clinical relevance, with authors suggesting time periods of perforation patency of 8-12 weeks. In this article, we sought to create a clinically significant experimental model that could yield a high rate of perforation patency for at least 8 weeks. Animals undergoing acute TMP were exposed to three different experimental situations to delay the healing of the perforation: fractionated radiation, topical lipopolysaccharide application, and a combined dexamethasone and mitomycin C (DXM/MC) solution. In our study, the use of DXM/MC reliably produced TMP lasting at least 8 weeks in 86.48% of the cases without the need to reopen the perforation, infolding the edges of the membrane, or using physical barriers to prevent TMP closure. Histologically, the resulting perforated tympanum showed hyaline changes of the remnant tympanum and hyperkeratosis of the squamous epithelia of the external auditory canal. We believe that this model is reproducible and has potential use in experiments of delayed healing of TMP. Anat Rec, 303:619-625, 2020. © 2019 American Association for Anatomy.

Cervical VEMP tuning changes by Meniere's disease stages.

OBJECTIVE: To determine if changes in cervical vestibular-evoked myogenic potential (cVEMP) testing reflect the different stages of cochlea-saccular hydrops in Meniere's disease (MD). METHODS: This is a case-control retrospective series. Forty-seven patients with unilateral MD by American Academy of Otolaryngology-Head and Neck Surgery diagnostic and staging criteria, and 30 with non-MD vertigo as control. Meniere patients were further classified based on symptoms at the time of testing as active or stable. Subsequently, patients underwent cVEMP testing by tone-burst stimuli at 500 and 1,000 Hz. The main outcome measure was to compare the cVEMP 1,000 and 500 Hz amplitude ratio in ears with MD and non-MD vertigo, and in active versus stable MD. RESULTS: The cVEMP 1,000/500 Hz amplitude ratio was higher in Meniere's ears (mean = 1.14 µV, SD = 0.25) than in non-Meniere's ears (mean = 0.96 µV, SD = 0.2) (Student's t test, P = .001), and higher in active (mean = 1.22 µV, SD = 0.25) than in stable MD (mean = 1.00 µV, SD = 0.18) (P = .0035). The diagnostic value of cVEMP 1,000/500 Hz amplitude ratio to differentiate MD versus non-MD vertigo was evaluated with a receiver-operating characteristics (ROC) curve and the area under the curve (AUC) was 0.716 (95% confidence interval [CI] [0.591, 0.829]). The ideal cutoff point was 0.9435 with sensitivity and specificity values of 83% and 53%, respectively. The sensitivity and specificity values for this test to differentiate active versus stable MD were 68% and 81%, respectively, with AUC 0.746 (95% CI [0.607, 0.885]) and cutoff value of 1.048. In all ears, the 1,000/500 Hz amplitude ratio increased by a decrease of the 500 Hz amplitude with increasing age. CONCLUSION: The cVEMP 1,000/500 Hz amplitude ratio is elevated in ears with MD but not in those with non-MD vertigo. After corrected by age, this ratio is higher in active but not in stable MD, probably reflecting dynamic changes in saccular membrane motion mechanics in hydrops, and may be a useful marker of disease progression and the effect of therapy. LEVEL OF EVIDENCE: IV.

The pattern of hearing outcome following surgery of the semicircular canals.

OBJECTIVE: To analyze demographic, clinical, surgical, and audiometric factors that may affect hearing outcome following surgery for the semicircular canals (SCC). METHOD: This is a retrospective case review of adults who underwent surgeries for superior SCC (SSCC), lateral SCC (LSCC), or posterior SCC (PSCC) and whose data were extracted and analyzed for factors affecting the hearing outcome in these procedures. RESULTS: Thirteen patients underwent surgery for SSCC, seven cases for the LSCC, one for the PSCC, and one case of combined PSCC/SSCC surgery. The mean age was 49.8 ± 12 years (21-66). There was no difference between the preoperative and postoperative pure tone average (PTA) thresholds at 0.5-3 kHz. Higher thresholds were noted at 4, 6, and 8 kHz postoperatively. Deterioration (>10 dB) in the bone-conduction (BC) PTA was demonstrated in 3 of 22 (13.6%) cases with no significant difference in the demographic, clinical, surgical, and preoperative audiometric parameters relative to the cases without PTA BC change. A significantly larger difference in PTA BC (pre- vs. postoperative) was seen for males. Small effect size was noted for Air conduction (AC) PTA in males, and moderate effect size for Word Recognition Score (WRS) in surgery for the LSCC compare to SSCC. CONCLUSIONS: SCC surgeries carry a relatively low risk of deterioration in PTA BC. High frequency thresholds should also be included in postoperative hearing outcome assessment. Cases of LSCC for intractable Meniere's disease and surgery in males carry higher risk of poor postoperative hearing outcomes. Level of Evidence: 4.

The Feasibility of Retrofacial Approach for Cochlear Implantation.

HYPOTHESIS: The retrofacial approach is a feasible approach to the round window niche and that the Round window-Sigmoid sinus line will help determine the feasibility of retrofacial approach for cochlear implantation unless there is a very high jugular bulb. BACKGROUND: When the round window cannot be visualized by facial recess approach during cochlear implantation, other conservative techniques can be used to improve visualization such as the retrofacial approach. METHODS: Thirteen adult dry cadaveric temporal bones were studied. Computed tomography (CT) scan was obtained on all temporal bones. An imaginary Round window-Sigmoid sinus line was drawn on the axial images. We assessed whether this line is anterior (including intersection) or posterior to the facial nerve (FN). The following closest distances were measured on CT scans: 1) posterior semicircular canal (PSC)-FN, 2) PSC-Stapedius muscle, 3) PSC-Jugular bulb, 4) lateral semicircular canal (LSC)-Jugular bulb, 5) sigmoid sinus-FN. A canal wall-up mastoidectomy, facial recess, and retrofacial approach were performed in all specimens. We have noted whether we need a standard or an extended mastoidectomy. RESULTS: The Round window-Sigmoid sinus line was posterior to the FN in all specimens. The retrofacial approach was feasible and the round window was visualized in all specimens. Extended mastoidectomy was required in seven specimens and the PSC-FN was ≤ 3 mm in five of them. CONCLUSION: Retrofacial approach is feasible in cochlear implantation when the Round window-Sigmoid sinus line is posterior to the FN and the jugular bulb is not obstructing the round window.

A new technique to find the facial nerve and recess by using the short process of the incus and the spine of Henle as landmarks: incus-spine angle.

BACKGROUND: Precise techniques to find the facial nerve (FN) and recess are lacking. OBJECTIVES: We aimed to define incus-spine and incus-FN angles which can be used to localize the FN and recess during mastoidectomy. MATERIAL AND METHODS: Thirty adult cadaveric temporal bones were studied. Canal-wall up mastoidectomy with a facial recess approach was performed. The temporal bones and microscope were positioned differently to change the visual angle. The following distances were measured: (1) Short process of the incus (SPI)-FN; (2) Body of the incus-FN. Photographs were taken. Three lines were drawn on the photographs between the SPI, FN, and the spine of Henle. The angles were created and measured. RESULTS: Three of the temporal bones were excluded due to the absence of the spine of Henle and two of them due to the displacement of the SPI. The mean of the incus-spine angle in 25 temporal bones was 90.12° and the mean of the Incus-FN angle was 135.96°. The mean distances of the SPI-FN and body of incus-FN were 4.85 and 9.26 mm, respectively. CONCLUSIONS AND SIGNIFICANCE: The incus-spine and the incus-FN angles along with the distances can help localize the FN and recess.

The effect of n-acetyl-cysteine on recovery of the facial nerve after crush injury.

OBJECTIVE: Facial nerve dysfunction can vary in severity and recovery is dependent on the character of the injury. N-acetyl-cysteine prevents oxidative stress and cellular damage, and its use in the setting of nerve dysfunction from crush injury has not yet been established. In this study, rats with facial nerve crush injury will be treated with n-acetyl-cysteine or control and functional recovery and electrophysiologic outcome will be compared. STUDY DESIGN: Prospective, randomized animal study. METHODS: Twenty-four Wistar rats underwent unilateral facial nerve crush injury. Rats were implanted with a subcutaneous osmotic pump filled with saline (n = 12) or n-acetyl-cysteine 50 mg/kg/day (n = 12). Functional and electromyographic recovery was recorded at two and four weeks postoperatively. RESULTS: When compared to untreated rats, n-acetyl-cysteine treated rats had a greater electromyography amplitude recovery at 2 weeks with regard to eye blink (p=0.006) but not vibrissae function. At four weeks, the electromyography amplitude recovery of the vibrissae function was greater in n-acetyl-cysteine treated rats (P=0.001), but the amplitude recovery difference in eye blink was only marginally significant between groups (p=0.07). The functional score was higher in n-acetyl-cysteine-treated rats than in untreated rats at all of the time points. CONCLUSION: This study demonstrated that n-acetyl-cysteine facilitated facial nerve recovery with improved functional and electromyography outcomes in the setting of crush injury. LEVEL OF EVIDENCE: NA.

Comparison of packing material in an animal model of middle ear trauma.

PURPOSE: To compare the performance of absorbable gelatin sponge (AGS) with polyurethane foam (PUF) as middle ear packing material after mucosal trauma. MATERIALS AND METHODS: Using a randomized, controlled and blinded study design fifteen guinea pigs underwent middle ear surgery with mucosal trauma performed on both ears. One ear was packed with either PUF or AGS while the contralateral ear remained untreated and used as non-packed paired controls. Auditory brainstem response (ABR) thresholds were measured pre-operatively and repeated at 1, 2, and 6weeks postoperatively. Histological analysis of middle ear mucosa was done in each group to evaluate the inflammatory reaction and wound healing. Another eighteen animals underwent middle ear wounding and packing in one ear while the contralateral ear was left undisturbed as control. Twelve guinea pigs were euthanized at 2weeks postoperatively, and six were euthanized at 3days post-operatively. Mucosal samples were collected for analysis of TGF-ß1 levels by enzyme-linked immunosorbent assay. RESULTS: ABR recordings demonstrate that threshold level changes from baseline were minor in PUF packed and control ears. Threshold levels were higher in the AGS packed ears compared with both control and PUF packed ears for low frequency stimuli. Histological analysis showed persistence of packing material at 6weeks postoperatively, inflammation, granulation tissue formation, foreign body reaction and neo-osteogenesis in both AGS and PUF groups. TGF-ß1 protein levels did not differ between groups. CONCLUSION: PUF and AGS packing cause inflammation and neo-osteogenesis in the middle ear following wounding of the mucosa and packing.

Predicting depth of electrode insertion by cochlear measurements on computed tomography scans.

OBJECTIVES/HYPOTHESIS: To evaluate the effectiveness of cochlear measures obtained by high-resolution computed tomography (HRCT) scan in predicting depth of cochlear implant insertion. STUDY DESIGN: Retrospective case review. METHODS: Patients who underwent cochlear implantation in an academic referral center between 2010 and 2013 were considered. Inclusion criteria included available preoperative HRCT scan and complete operative data. Subjects with labyrinthitis ossificans, cochlear hypoplasia, or major inner ear malformations were excluded. Subsequently, measures of cochlear height in the coronal plane and basal turn width in the axial plane were obtained using electronic calipers of the stored digital HRCT images by a blinded investigator. The insertion was considered deep when the electrode was placed at least 23 mm into the cochlea. Subjects were divided into those who had a deep insertion and those who did not. Regression analyses were done to associate cochlear measures with deep insertion. RESULTS: A deep insertion was possible in 25 patients out of 35. There was no statistically significant association between deep insertion and age at implantation, gender, and type of cochleostomy. The mean cochlear height was 6.22 mm (standard deviation [SD] = 0.32 mm) and 5.80 mm (SD = 0.3mm) in subjects with and without deep insertion, respectively (Student t test, P = .0015). Only cochlear height showed an association with deep insertion (logistic regression, P = .0007). For a cochlear height of 6.27 mm, the probability of deep insertion was 0.90. CONCLUSIONS: Linear measurements of standard CT scans of the cochlea can predict the depth of insertion and may help the selection of the appropriate electrode array preoperatively. LEVEL OF EVIDENCE: 4. Laryngoscope, 126:1656-1661, 2016.

Current concepts in the pathogenesis and treatment of chronic suppurative otitis media.

Otitis media (OM) is an inflammation of the middle ear associated with infection. Despite appropriate therapy, acute OM (AOM) can progress to chronic suppurative OM (CSOM) associated with ear drum perforation and purulent discharge. The effusion prevents the middle ear ossicles from properly relaying sound vibrations from the ear drum to the oval window of the inner ear, causing conductive hearing loss. In addition, the inflammatory mediators generated during CSOM can penetrate into the inner ear through the round window. This can cause the loss of hair cells in the cochlea, leading to sensorineural hearing loss. Pseudomonas aeruginosa and Staphylococcus aureus are the most predominant pathogens that cause CSOM. Although the pathogenesis of AOM is well studied, very limited research is available in relation to CSOM. With the emergence of antibiotic resistance as well as the ototoxicity of antibiotics and the potential risks of surgery, there is an urgent need to develop effective therapeutic strategies against CSOM. This warrants understanding the role of host immunity in CSOM and how the bacteria evade these potent immune responses. Understanding the molecular mechanisms leading to CSOM will help in designing novel treatment modalities against the disease and hence preventing the hearing loss.

Utricular paresis and semicircular canal hyperactivity: a distinct otolith syndrome.

CONCLUSIONS: Although combined utricular and canal paresis has been described previously, this is the first report of canal hyperactivity associated with utricular hypofunction. Unsteadiness and swaying were the most common symptoms, and patients with shorter duration of symptoms also had positional vertigo. We propose that this syndrome is a variant of utricular dysfunction and should be considered in the differential diagnosis of peripheral vestibular disorders. OBJECTIVE: To describe a syndrome of instability associated with utricular dysfunction and hyperactive caloric responses. METHODS: The study comprised 11 consecutive patients exhibiting abnormalities of the eccentric subjective visual vertical test (e-SVV) and high responses during the caloric test of the videonystagmography (VNG). We carried out a review of symptoms, physical examination, and vestibular tests. RESULTS: There was no gender predilection or obvious etiology. The patients' main complaint included instability with linear symptoms (i.e., tilting, rocking, and swaying), with positional vertigo as a secondary symptom. Oculomotor testing, visual fixation index, and brain MRI were normal, excluding a central nervous system disorder. VNG was essentially normal except for hyperactive responses during the caloric testing in all patients. Abnormal e-SVV was found in 10 patients unilaterally and bilaterally in 1 patient. Abnormal oVEMP was found in seven of seven patients, further supporting a utricular site of lesion.

Conservative management of vestibular schwannoma: Predictors of growth and hearing.

OBJECTIVE: To describe the clinical outcomes of patients undergoing serial observation for vestibular schwannoma (VS) and identify factors that may predict tumor growth or hearing loss. STUDY DESIGN: Retrospective review. METHODS: A retrospective review was conducted of patients seen at a tertiary care medical center between 2002 and 2013 with an International Classification of Diseases-9 diagnosis code of 225.1. Patients electing observation as initial management, with at least two documented imaging results, were included. Exclusion criteria comprised bilateral VS, diagnosis of neurofibromatosis type 2, and neoplasms other than VS. Decline in serviceable hearing, tumor growth, and changes in management strategy were recorded. Survival analysis to assess median time to outcomes and multiple logistic regression analyses were performed. RESULTS: A total of 94 patients met inclusion criteria. While undergoing observation, 22.3% of patients underwent a change in management strategy to microsurgical excision or stereotactic radiotherapy. For patients with initial serviceable hearing, 24.3% observed a decline to a nonserviceable level. No significant clinical factors were identified to predict changes in hearing. Survival analysis revealed that an estimated 69.1% of patients electing observation as initial management continued to do so at 5 years. Imbalance or disequilibrium at presentation was found to be associated with an increased adjusted odds ratio (OR) (OR 2.96; 95% confidence interval, 1.03-8.50; P = 0.04) for tumor growth. CONCLUSION: Serial observation of VS is a viable treatment strategy for selected patients, with two-thirds of patients electing to continue this management option after 5 years. Disequilibrium as a presenting symptom may be associated with subsequent tumor growth. LEVEL OF EVIDENCE: 4.

Utricular Dysfunction in Refractory Benign Paroxysmal Positional Vertigo.

OBJECTIVE: To determine the prevalence of otolith dysfunction in patients with refractory benign paroxysmal positional vertigo (BPPV). STUDY DESIGN: Unmatched case control. SETTING: Tertiary care institution. SUBJECTS AND METHODS: Patients included were diagnosed with BPPV, failed initial in-office canalith repositioning maneuvers (CRMs), and completed vestibular testing and vestibular rehabilitation (n = 40). Refractory BPPV (n = 19) was defined in patients whose symptoms did not resolve despite vestibular rehabilitation. These patients were compared with a control group of those with nonrefractory BPPV (n = 21) for results of a caloric test, cervical vestibular evoked myogenic potential (cVEMP), and subjective visual vertical (SVV). RESULTS: Forty-six of 251 patients failed initial treatment with in-office CRM. Forty patients met inclusion criteria. There was no significant difference between the cases (refractory BPPV) (n = 19) and controls (nonrefractory BPPV) (n = 21) in terms of age, duration of symptoms, laterality of BPPV, and BPPV symptoms. There was no difference in the prevalence of caloric weakness and cVEMP abnormalities (P > .05), with odds ratios (ORs [95% confidence interval (CI)]) of having abnormal results among cases vs controls of 1.1818 (0.3329-4.1954) and 4.3846 (0.7627-25.2048), for caloric and cVEMP, respectively. Abnormal eccentric SVV was more prevalent in refractory BPPV cases (58%) than in controls (14%) (P < .0072). The OR (95% CI) of having abnormal SVV was 8.25 (1.7967-37.8822) higher among patients with refractory BPPV than those with nonrefractory BPPV. CONCLUSION: Patients with refractory BPPV are more likely to have abnormal eccentric SVV and thus underlying utricular dysfunction. This finding is important to take into account when designing rehabilitation strategies for patients with BPPV who fail CRM.