Hearing sensitivity differs between zebrafish lines used in auditory research

Publication date: Available online 16 September 2016
Source:Hearing Research
Author(s): J. David Monroe, Dustin P. Manning, Phillip M. Uribe, Ashwin Bhandiwad, Joseph A. Sisneros, Michael E. Smith, Allison B. Coffin
Zebrafish are increasingly used in auditory studies, in part due to the development of several transgenic lines that express hair cell-specific fluorescent proteins. However, it is largely unknown how transgene expression influences auditory phenotype. We previously observed reduced auditory sensitivity in adult Brn3c:mGFP transgenic zebrafish, which express membrane-bound green fluorescent protein (GFP) in sensory hair cells. Here, we examine the auditory sensitivity of zebrafish from multiple transgenic and background strains. We recorded auditory evoked potentials in adult animals and observed significantly higher auditory thresholds in three lines that express hair cell-specific GFP. There was no obvious correlation between hair cell density and auditory thresholds, suggesting that reduced sensitivity was not due to a reduction in hair cell density. FM1-43 uptake was reduced in Brn3c:mGFP fish but not in other lines, suggesting that a mechanotransduction defect may be responsible for the auditory phenotype in Brn3c animals, but that alternate mechanisms underlie the increased AEP thresholds in other lines. We found reduced prepulse inhibition (a measure of auditory-evoked behavior) in larval Brn3c animals, suggesting that auditory defects develop early in this line. We also found significant differences in auditory sensitivity between adults of different background strains, akin to strain differences observed in mouse models of auditory function. Our results suggest that researchers should exercise caution when selecting an appropriate zebrafish transgenic or background strain for auditory studies.



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Hearing sensitivity differs between zebrafish lines used in auditory research

Publication date: Available online 16 September 2016
Source:Hearing Research
Author(s): J. David Monroe, Dustin P. Manning, Phillip M. Uribe, Ashwin Bhandiwad, Joseph A. Sisneros, Michael E. Smith, Allison B. Coffin
Zebrafish are increasingly used in auditory studies, in part due to the development of several transgenic lines that express hair cell-specific fluorescent proteins. However, it is largely unknown how transgene expression influences auditory phenotype. We previously observed reduced auditory sensitivity in adult Brn3c:mGFP transgenic zebrafish, which express membrane-bound green fluorescent protein (GFP) in sensory hair cells. Here, we examine the auditory sensitivity of zebrafish from multiple transgenic and background strains. We recorded auditory evoked potentials in adult animals and observed significantly higher auditory thresholds in three lines that express hair cell-specific GFP. There was no obvious correlation between hair cell density and auditory thresholds, suggesting that reduced sensitivity was not due to a reduction in hair cell density. FM1-43 uptake was reduced in Brn3c:mGFP fish but not in other lines, suggesting that a mechanotransduction defect may be responsible for the auditory phenotype in Brn3c animals, but that alternate mechanisms underlie the increased AEP thresholds in other lines. We found reduced prepulse inhibition (a measure of auditory-evoked behavior) in larval Brn3c animals, suggesting that auditory defects develop early in this line. We also found significant differences in auditory sensitivity between adults of different background strains, akin to strain differences observed in mouse models of auditory function. Our results suggest that researchers should exercise caution when selecting an appropriate zebrafish transgenic or background strain for auditory studies.



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Hearing sensitivity differs between zebrafish lines used in auditory research

Publication date: Available online 16 September 2016
Source:Hearing Research
Author(s): J. David Monroe, Dustin P. Manning, Phillip M. Uribe, Ashwin Bhandiwad, Joseph A. Sisneros, Michael E. Smith, Allison B. Coffin
Zebrafish are increasingly used in auditory studies, in part due to the development of several transgenic lines that express hair cell-specific fluorescent proteins. However, it is largely unknown how transgene expression influences auditory phenotype. We previously observed reduced auditory sensitivity in adult Brn3c:mGFP transgenic zebrafish, which express membrane-bound green fluorescent protein (GFP) in sensory hair cells. Here, we examine the auditory sensitivity of zebrafish from multiple transgenic and background strains. We recorded auditory evoked potentials in adult animals and observed significantly higher auditory thresholds in three lines that express hair cell-specific GFP. There was no obvious correlation between hair cell density and auditory thresholds, suggesting that reduced sensitivity was not due to a reduction in hair cell density. FM1-43 uptake was reduced in Brn3c:mGFP fish but not in other lines, suggesting that a mechanotransduction defect may be responsible for the auditory phenotype in Brn3c animals, but that alternate mechanisms underlie the increased AEP thresholds in other lines. We found reduced prepulse inhibition (a measure of auditory-evoked behavior) in larval Brn3c animals, suggesting that auditory defects develop early in this line. We also found significant differences in auditory sensitivity between adults of different background strains, akin to strain differences observed in mouse models of auditory function. Our results suggest that researchers should exercise caution when selecting an appropriate zebrafish transgenic or background strain for auditory studies.



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Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family.

Screening of DFNB3 in Iranian families with autosomal recessive non-syndromic hearing loss reveals a novel pathogenic mutation in the MyTh4 domain of the MYO15A gene in a linked family.

Iran J Basic Med Sci. 2016 Jul;19(7):772-8

Authors: Reiisi S, Tabatabaiefar MA, Sanati MH, Chaleshtori MH

Abstract
OBJECTIVES: Non-syndromic sensorineural hearing loss (NSHL) is a common disorder affecting approximately 1 in 500 newborns. This type of hearing loss is extremely heterogeneous and includes over 100 loci. Mutations in the GJB2 gene have been implicated in about half of autosomal recessive non-syndromic hearing loss (ARNSHL) cases, making this the most common cause of ARNSHL. For the latter form of deafness, most frequent genes proposed include GJB2, SLC26A4, MYO15A, OTOF, and CDH23 worldwide.
MATERIALS AND METHODS: The aim of the present study was to define the role and frequency of MYO15A gene mutation in Iranian families. In this study 30 Iranian families were enrolled with over three deaf children and negative for GJB2. Then linkage analysis was performed by six DFNB3 short tandem repeat markers. Following that, mutation detection accomplished using DNA sequencing.
RESULTS: One family (3.33%) showed linkage to DFNB3 and a novel mutation was identified in the MYO15A gene (c.6442T>A): as the disease-causing mutation. Mutation co-segregated with hearing loss in the family but was not present in the 100 ethnicity-matched controls.
CONCLUSION: Our results confirmed that the hearing loss of the linked Iranian family was caused by a novel missense mutation in the MYO15A gene. This mutation is the first to be reported in the world and affects the first MyTH4 domain of the protein.

PMID: 27635202 [PubMed]

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An Overlapping Case of Alport Syndrome and Thin Basement Membrane Disease.

An Overlapping Case of Alport Syndrome and Thin Basement Membrane Disease.

J Clin Med Res. 2016 Oct;8(10):764-7

Authors: Alganabi M, Eter A

Abstract
We report a case of a 48-year-old male who presented with hematuria of at least 10 years, and has a daughter with hematuria as well. The patient has a history of degenerative hearing loss, decreased vision and cataract formation, but no diabetes, hypertension or proteinuria. A full serology and urology workup was negative for any abnormality. A kidney biopsy for the patient revealed a diagnosis of Alport syndrome but was unable to rule out thin basement membrane disease. The biopsy was inconclusive in making the diagnosis but the patient's clinical presentation led to the diagnosis of Alport syndrome. The patient's 10-year-old daughter also has hematuria with no clear etiology but now can subsequently be anticipatorily managed for Alport syndrome progression. Due to the rarity of the disease, diagnosis is often missed or delayed by primary care providers especially when no associated proteinuria has yet developed. This can lead to confusion and misdiagnosis with thin basement membrane disease, a generally benign hematuria without kidney failure progression. Additionally, biopsy can be inconclusive in these patients, relying on the physician's history and physical examination findings to diagnose. It is important to appropriately diagnose Alport syndrome not only to manage the patient's rate of kidney failure progression but also allow for a higher degree of suspicion, screening and intervention in the patient's family members. Both the inconclusive nature of kidney biopsies and the usefulness of diagnosis for family member screening are often overlooked in medical literature but are explored in this case.

PMID: 27635185 [PubMed]

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Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

Severe early onset retinitis pigmentosa in a Moroccan patient with Heimler syndrome due to novel homozygous mutation of PEX1 gene.

Eur J Med Genet. 2016 Sep 12;

Authors: Ratbi I, Jaouad IC, Elorch H, Al-Sheqaih N, Elalloussi M, Lyahyai J, Berraho A, Newman WG, Sefiani A

Abstract
Heimler syndrome (HS) is a rare recessive disorder characterized by sensorineural hearing loss (SNHL), amelogenesis imperfecta, nail abnormalities, and occasional or late-onset retinal pigmentation. It is the mildest form known to date of peroxisome biogenesis disorder caused by hypomorphic mutations of PEX1 and PEX6 genes. We report on a second Moroccan family with Heimler syndrome with early onset, severe visual impairment and important phenotypic overlap with Usher syndrome. The patient carried a novel homozygous missense variant c.3140T > C (p.Leu1047Pro) of PEX1 gene. As standard biochemical screening of blood for evidence of a peroxisomal disorder did not provide a diagnosis in the individuals with HS, patients with SNHL and retinal pigmentation should have mutation analysis of PEX1 and PEX6 genes.

PMID: 27633571 [PubMed - as supplied by publisher]

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Mental practice in postgraduate training: a randomized controlled trial in mastoidectomy skills.

Mental practice in postgraduate training: a randomized controlled trial in mastoidectomy skills.

J Otolaryngol Head Neck Surg. 2016;45(1):46

Authors: Conlin A, Lea J, Bance M, Chadha N, Kilty S, Kozak F, Savage J, Sidhu R, Chen J, Westerberg BD

Abstract
BACKGROUND: Mental practice, the cognitive rehearsal of a task in the absence of overt physical movement, has been successfully used in teaching complex psychomotor tasks including sports and music, and recently, surgical skills. The objectives of this study were, 1) To develop and evaluate a mental practice protocol for mastoidectomy 2) To assess the immediate impact of mental practice on a mastoidectomy surgical task among senior Otolaryngology─Head & Neck Surgery (OHNS) residents.
METHOD: Three expert surgeons were interviewed using verbal protocol analysis to develop a mastoidectomy mental practice script. Twelve senior Residents from Canadian training programs were randomized into two groups. All Residents were video-recorded performing a baseline mastoidectomy in a temporal bone lab. The intervention group received mental practice training, while the control group undertook self-directed textbook study. All subjects were then video-recorded performing a second mastoidectomy. Changes in pre- and post-test scores using validated expert ratings, the Task Specific Evaluation of Mastoidectomy and the Global Evaluation of Mastoidectomy, were statistically analyzed.
RESULTS: A mental practice script was successfully developed based on interviews of three expert surgeon-educators. Task Specific Evaluation and Global Evaluation scores increased in both the mental practice and textbook study groups; there was no significant difference between the two groups in the change in scores post-intervention. There was a high and statistically signficant correlation between evaluators on the outcome measures.
CONCLUSIONS: We were not able to demonstrate a significant difference for the benefits of mental practice in mastoidectomy, possibly due to the sample size. However, mental practice is a surgical education tool which is portable, accessible, inexpensive and safe.

PMID: 27634316 [PubMed - in process]

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The applicability of conventional cytotoxicity assays to predict safety/toxicity of mesoporous silica nanoparticles, silver and gold nanoparticles and multi-walled carbon nanotubes.

The applicability of conventional cytotoxicity assays to predict safety/toxicity of mesoporous silica nanoparticles, silver and gold nanoparticles and multi-walled carbon nanotubes.

Toxicol In Vitro. 2016 Sep 12;

Authors: Mannerström M, Zou J, Toimela T, Pyykkö I, Heinonen T

Abstract
Developing new, validated methods for screening of the effects of nanomaterials is a huge and expensive task. It is therefore necessary to try to employ already existing and validated methods, developed for chemicals. In the present study cytotoxicity of gold (Au) and silver (Ag) nanoparticles (NP), two different mesoporous silica nanoparticles (MSNP), and multi-walled carbon nanotubes (MWCNT) were investigated in BALB/c 3T3 fibroblasts, NR8383 macrophages, and U937 monocytes using standard assays, namely WST-1 and NRU. In addition, preliminary attempts were made to investigate ENM-mediated effects on cell motility as a potential end point for NP toxicity. AgNPs were most toxic to BALB/c 3T3 fibroblasts while other ENMs were insignificantly toxic. NR8383 macrophages were most sensitive cells, as in addition to AgNPs, also MWCNTs were toxic to NR8383 cells. AgNP was toxic also to U937 cells, other ENMs had minor effect. Different media resulted in different-sized aggregates of the same ENMs. AgNP inhibited BALB/c motility most, whereas NR8383 motility was inhibited most by MWCNTs. In conclusion, conventional cytotoxicity assays are better suited to rank the order of toxicity of different nanoparticles instead of producing accurate IC50 data. Moreover, using immune cells, especially macrophages together with fibroblasts, would bring more relevant predictions of ENM cytotoxicity as immune cells may discover cytotoxicity that is not captured by BALB/c 3T3 cells alone.

PMID: 27633900 [PubMed - as supplied by publisher]

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Mental practice in postgraduate training: a randomized controlled trial in mastoidectomy skills.

Mental practice in postgraduate training: a randomized controlled trial in mastoidectomy skills.

J Otolaryngol Head Neck Surg. 2016;45(1):46

Authors: Conlin A, Lea J, Bance M, Chadha N, Kilty S, Kozak F, Savage J, Sidhu R, Chen J, Westerberg BD

Abstract
BACKGROUND: Mental practice, the cognitive rehearsal of a task in the absence of overt physical movement, has been successfully used in teaching complex psychomotor tasks including sports and music, and recently, surgical skills. The objectives of this study were, 1) To develop and evaluate a mental practice protocol for mastoidectomy 2) To assess the immediate impact of mental practice on a mastoidectomy surgical task among senior Otolaryngology─Head & Neck Surgery (OHNS) residents.
METHOD: Three expert surgeons were interviewed using verbal protocol analysis to develop a mastoidectomy mental practice script. Twelve senior Residents from Canadian training programs were randomized into two groups. All Residents were video-recorded performing a baseline mastoidectomy in a temporal bone lab. The intervention group received mental practice training, while the control group undertook self-directed textbook study. All subjects were then video-recorded performing a second mastoidectomy. Changes in pre- and post-test scores using validated expert ratings, the Task Specific Evaluation of Mastoidectomy and the Global Evaluation of Mastoidectomy, were statistically analyzed.
RESULTS: A mental practice script was successfully developed based on interviews of three expert surgeon-educators. Task Specific Evaluation and Global Evaluation scores increased in both the mental practice and textbook study groups; there was no significant difference between the two groups in the change in scores post-intervention. There was a high and statistically signficant correlation between evaluators on the outcome measures.
CONCLUSIONS: We were not able to demonstrate a significant difference for the benefits of mental practice in mastoidectomy, possibly due to the sample size. However, mental practice is a surgical education tool which is portable, accessible, inexpensive and safe.

PMID: 27634316 [PubMed - in process]

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The applicability of conventional cytotoxicity assays to predict safety/toxicity of mesoporous silica nanoparticles, silver and gold nanoparticles and multi-walled carbon nanotubes.

The applicability of conventional cytotoxicity assays to predict safety/toxicity of mesoporous silica nanoparticles, silver and gold nanoparticles and multi-walled carbon nanotubes.

Toxicol In Vitro. 2016 Sep 12;

Authors: Mannerström M, Zou J, Toimela T, Pyykkö I, Heinonen T

Abstract
Developing new, validated methods for screening of the effects of nanomaterials is a huge and expensive task. It is therefore necessary to try to employ already existing and validated methods, developed for chemicals. In the present study cytotoxicity of gold (Au) and silver (Ag) nanoparticles (NP), two different mesoporous silica nanoparticles (MSNP), and multi-walled carbon nanotubes (MWCNT) were investigated in BALB/c 3T3 fibroblasts, NR8383 macrophages, and U937 monocytes using standard assays, namely WST-1 and NRU. In addition, preliminary attempts were made to investigate ENM-mediated effects on cell motility as a potential end point for NP toxicity. AgNPs were most toxic to BALB/c 3T3 fibroblasts while other ENMs were insignificantly toxic. NR8383 macrophages were most sensitive cells, as in addition to AgNPs, also MWCNTs were toxic to NR8383 cells. AgNP was toxic also to U937 cells, other ENMs had minor effect. Different media resulted in different-sized aggregates of the same ENMs. AgNP inhibited BALB/c motility most, whereas NR8383 motility was inhibited most by MWCNTs. In conclusion, conventional cytotoxicity assays are better suited to rank the order of toxicity of different nanoparticles instead of producing accurate IC50 data. Moreover, using immune cells, especially macrophages together with fibroblasts, would bring more relevant predictions of ENM cytotoxicity as immune cells may discover cytotoxicity that is not captured by BALB/c 3T3 cells alone.

PMID: 27633900 [PubMed - as supplied by publisher]

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Adaptation and Compensation of Vestibular Responses Following Superior Canal Dehiscence Surgery

Objective: To describe vestibulo-ocular function and compensatory mechanisms in the immediate postoperative period after superior canal dehiscence surgery. Study Design: Prospective longitudinal study. Setting: Tertiary medical center. Patients: Five patients who underwent plugging of superior semicircular canal via middle cranial fossa approach. Interventions: Bedside quantitative video head impulse testing (vHIT). Main Outcome Measures: Dynamic measures of vestibulo-ocular reflex (VOR) function including VOR gain and compensatory saccades during vHIT. Results: Mean VOR gain of the ipsilateral superior semicircular canal (SC) decreased from 0.71 ± 0.1 preoperatively to 0.28 ± 0.07 on postoperative day (POD) 2–4 (p = 0.0031), consistent with plugging. There was also a significant immediate postoperative decrease of VOR gain for the other ipsilateral canals (posterior canal (PC) from gain 0.91 ± 0.33 down to 0.55 ± 0.14, p = 0.040; horizontal canal (HC) from 0.81 ± 0.08 down to 0.54 ± 0.19, p = 0.038). On PODs 1–2, compensatory saccades after testing the plugged SC occurred exclusively after the head stopped moving (overt) with latency of 186.2 ms ± 19.9 ms. By POD 7 saccade latency decreased to 141.0 ± 17.5 ms (p = 0.032), and saccades were occurring during the vertical head rotation (covert saccades). Follow-up >40 days was consistent with previous findings in that mean SC gain remained low. HC gain recovered fully, but some cases did not have full recovery of PC gain. Conclusion: When the SC is plugged surgically, early quantitative vHIT demonstrates significantly reduced VOR gain for all of the ipsilateral canals. Possible mechanisms include labyrinthine inflammation and loss of perilymph at the time of surgery. Full recovery is typical for the horizontal canal but not always for the PC. Evidence of central compensation occurred by the elicitation of compensatory saccades and by reducing their latencies within the first week after surgery.

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Letter From the New Editor-in-Chief

No abstract available

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What Could Posturography Tell Us About Balance Problems in Parkinson's Disease?

Objective: Impaired balance in patients with Parkinson's disease (PD) leads to loss of balance and frequent falls. Computerized dynamic posturography allows the assessment of stance tasks whereas mobile posturography analyzes the balance in free-field conditions, where falls among PD patients commonly occur (e.g. sitting down or standing up). The aim of the present study is to assess postural stability in PD patients with both techniques. Study Design: Prospective study. Setting: University Hospitals, ambulatory care (outpatient clinic). Patients: Thirty-three patients diagnosed with idiopathic PD. Intervention: Balance assessment. Main Outcome Measures: Dizziness handicap inventory (DHI), activities-specific balance confidence scale (ABC), composite score of sensory organization test (SOT), results of free-field body sway analysis (standard balance deficit test (SBDT)), or geriatric SBDT. Results: PD patients showed a significantly higher sway in the roll direction in almost all of the SBDT conditions. Also, pathological sway compared with normative values was more prominent in complex tasks. There is a significant correlation between the different objective variables of the postural study (SOT and SBDT) and the ABC, but not with the DHI. Finally, the percentage of PD patients with a pathological score in SOT-composite score was 54.5% whereas in SBDT-composite score it was significantly higher (93.9%). Conclusion: Mobile posturography is more accurate in depicting the reality of balance impairment in PD patients than platform posturography. Also, ABC relates better than DHI to the significant psychological consequences of balance impairments. An increased lateral trunk sway seems to be a key factor of postural instability in PD patients.

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The Chronic Ear: John L. Dornhoffer and Michael B. Gluth, eds.; New York: Thieme, 2016.

No abstract available

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Role of STAT1 and Oxidative Stress in Gentamicin-Induced Hair Cell Death in Organ of Corti

Rationale: Oxidative stress plays a critical role in gentamicin-induced hair cell death. Previous work has implicated the cytoplasmic transcription factor signal transducer and activator of transcription 1 (STAT1) as a potential mediator of drug-induced ototoxicity, but role in aminoglycosides is largely unknown. This study investigated aminoglycosides-induced cell death, exploring contributions of reactive oxygen species and STAT1 pathway in injury and protection. Methods: Neonatal murine organ of Corti explants from 2 to 3 day postnatal pups (n = 96) were treated with gentamicin at (4 μM, 50 μM) for 4 to 72 hours, with/without protectants. Effects on STAT1 pathway and gentamicin-induced hair cell death were measured with 50 μM Epigallocatechin gallate (EGCG, a STAT1 inhibitor) and all-trans retinoic acid (atRA, a STAT1 activator). Hair cell morphology was evaluated and hair cell loss was quantified with cytocochleograms. Mitochondrial membrane potential was assayed and superoxide generation and suppression was measured with dihydroethidium (DHE) staining. Results: Co-administration of 50 μM EGCG conferred protection from 4 μM gentamicin toxicity (p 

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Music-induced Hearing Loss in Children, Adolescents, and Young Adults: A Systematic Review and Meta-analysis

Objective: Exposure to loud music has increased significantly because of the current development of personal music players and mobile phones. The aim of this study was to provide an overview of music-induced hearing loss and its symptoms in children. Data Sources: The search was performed in the databases Embase, Medline (OvidSP), Web-of-science, Scopus, Cinahl, Cochrane, PubMed publisher, and Google Scholar. Only articles written in English were included. Study Selection: Articles describing hearing levels and music exposure in children were used, published from 1990 until April 2015. Data Extraction: The quality of the studies was assessed on reporting, validity, power, and the quality of audiometric testing. Data Synthesis: Data of each publication was extracted into spreadsheet software and analyzed using best evidence synthesis. Conclusion: The prevalence of increased hearing levels (>15 dB HL) was 9.6%, and high-frequency hearing loss was found in 9.3%. The average hearing thresholds were 4.79 dB HL at low frequencies (0.5, 1, and 2 kHz) and 9.54 dB HL at high frequencies (3, 4, and 6 kHz). Most studies reported no significant association between pure-tone air thresholds and exposure to loud music. However, significant changes in hearing thresholds and otoacoustic emissions, and a high tinnitus prevalence suggest an association between music exposure and hearing loss in children.

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Intracranial Pressure and Promontory Vibration With Soft Tissue Stimulation in Cadaveric Human Whole Heads

Hypothesis: Intracranial pressure and skull vibrations are correlated and depend on the stimulation position and frequency. Background: A hearing sensation can be elicited by vibratory stimulation on the skin covered skull, or by stimulation on soft tissue such as the neck. It is not fully understood whether different stimulation sites induce the skull vibrations responsible for the perception or whether other transmission pathways are dominant. The aim of this study was to assess the correlation between intracranial pressure and skull vibration measured on the promontory for stimulation to different sites on the head. Methods: Measurements were performed on four human cadaver heads. A bone conduction hearing aid was held in place with a 5-Newton steel headband at four locations (mastoid, forehead, eye, and neck). While stimulating in the frequency range of 0.3 to 10 kHz, acceleration of the cochlear promontory was measured with a Laser Doppler Vibrometer, and intracranial pressure at the center of the head with a hydrophone. Results: Promontory acceleration and intracranial pressure was measurable for all stimulation sites. The ratios were comparable between all stimulation sites for frequencies below 2 kHz. Conclusion: These findings indicate that both promontory acceleration and intracranial pressure are involved for stimulation on the sites investigated. The transmission pathway of sound energy is comparable for the four stimulation sites.

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Outer Hair Cell Molecular Protein, Prestin, as a Serum Biomarker for Hearing Loss: Proof of Concept

Hypothesis: At present there are no serum biomarkers available to monitor cochlear health in those at risk of hearing loss. Outer hair cells (OHCs) play an important role in cochlear function and are one of the cellular elements most vulnerable to damage, such as acoustic trauma. We hypothesized that an OHC-specific protein can serve as a biomarker for OHC damage in circulation. Methods: After assessing auditory function, rats were exposed to intense octave band noise for 2 to 3 hours. Auditory function was assessed 14 days after trauma. Blood samples were collected and prestin concentration was measured using enzyme-linked immunosorbent assay. Results: Circulating prestin was detectable in all control and noise-exposed animals. At 14 days after trauma, however, noise-exposed rats demonstrated statistically significant decrease in prestin concentrations compared with control animals. Conclusion: This work, for the first time, provides proof of concept that an otologic serum biomarker level can change after acoustic trauma and hearing loss. Our approach represents an entirely novel strategy in hearing diagnostics and has both research and clinical potential. Further work is needed to map out the temporal course of change in serum prestin concentrations after inner ear trauma, better define the relationship of serological and functional changes, and explore application to other etiologies of hearing loss (e.g., ototoxins).

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Postoperative Complications and Readmission Rates Following Surgery for Cerebellopontine Angle Schwannomas

Objective: To investigate the 30-day postoperative complication, readmission, and reoperation rates following surgery for cerebellopontine angle (CPA) schwannomas. Study Design: Cross-sectional analysis. Setting: National surgical quality improvement program dataset (NSQIP) 2009 through 2013. Patients: All surgical cases with an International Classification of Diseases, 9th edition, Clinical Modification (ICD-9-CM) diagnosis code of 225.1, benign neoplasms of cranial nerves, and one of the following current procedural terminology (CPT) codes, were included: 61616, 61526, 61530, and 61520. Intervention(s): Surgical resection as indicated by the CPT codes above. Main Outcome Measure(s): Demographics, comorbidities, 30-day postoperative complications, readmission rate, and reoperation rate. Results: Overall, 404 cases were identified, of which 42.6% were men. The average age was 51 years. Comorbidities were present in 45.3%. NSQIP-tracked complications occurred in 9.7% of patients. Most common complications were wound infections including surgical-site infection and wound dehiscence (11 patients, 2.7%), sepsis (10 patients, 2.5%), blood loss (nine patients, 2.2%), and deep vein thrombosis (DVT; seven patients, 1.7%). Mortality occurred in four patients (1.0%). The complication rate was statistically higher in patients with comorbidities versus those without (10.2% versus 4.1%, p = 0.04). Patients with complications were more likely to undergo reoperation (2.5% with versus 4.1% without, p = 0.001). Unplanned readmissions occurred in 41 cases (10.1%) and reoperations occurred in 23 patients (5.7%). Conclusions: Most common NSQIP-tracked complications in excision of CPA neoplasms are infections, sepsis, blood loss, and deep vein thrombosis (DVT). Further, investigation of patients with unplanned readmission and reoperation are warranted. Neurotologists need to take an active role in the data to be gathered in the NSQIP database as it relates to vestibular schwannomas.

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Applying Neurotrophins to the Round Window Rescues Auditory Function and Reduces Inner Hair Cell Synaptopathy After Noise-induced Hearing Loss

Hypothesis: Applying neurotrophins to the round window immediately after a single noise exposure will prevent noise-induced hidden hearing loss. Background: Loud noise can eliminate neural connections between inner hair cells and their afferent neurons (thereby diminishing sound perception) without causing a detectable change on audiogram. This phenomenon is termed hidden hearing loss. Methods: Guinea pigs were exposed for 2 hours to 4 to 8 kHz noise at either 95 or 105 dB SPL. Immediately afterward a 4 μl bolus of neurotrophins (brain-derived neurotrophic factor 1 μg/μl, and neurotrophin-3 1 μg/μl) was delivered to the round window of one ear, and saline to the other. Auditory brainstem responses to pure-tone pips were acquired preoperatively, and at 1 and 2 weeks’ postexposure. Cochleae were removed and whole mounted for immunohistochemical analysis, with presynaptic ribbons of inner hair cells and associated postsynaptic glutamatergic AMPA receptors identified using CtBP2 and GluA2 antibodies respectively. Results: After exposure to 105 dB noise, threshold did not change, but the amplitude growth of the auditory brainstem response was significantly reduced in control ears in response to 16 and 32 kHz tones. The amplitude growth was also reduced neurotrophin ears, but to a lesser degree and the reduction was not significant. Similar results were obtained from control ears exposed to 95 dB, but amplitude growth recovered in neurotrophin-treated ears, this reaching statistical significance in response to 16 kHz tones. There were significantly more presynaptic ribbons, postsynaptic glutamate receptors, and colocalized ribbons after neurotrophin treatment. Conclusion: A single dose of neurotrophins delivered to the round window reduced synaptopathy and recovered high-frequency hearing in ears exposed to 95 dB noise. These findings suggest that hidden hearing loss may be reduced by providing trophic support to the cochlea after injury.

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Hyperostotic En Plaque Meningioma Mimicking Fibrous Dysplasia of the Temporal Bone

No abstract available

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The Underlying Mechanism of Preventing Facial Nerve Stimulation by Triphasic Pulse Stimulation in Cochlear Implant Users Assessed With Objective Measure

Hypothesis: Triphasic pulse stimulation prevents from facial nerve stimulation (FNS) because of a different electromyographic input–output function compared with biphasic pulse stimulation. Background: FNS is sometimes observed in cochlear implant users as an unwanted side effect of electrical stimulation of the auditory nerve. The common stimulation applied in current cochlear implant consists of biphasic pulse patterns. Two common clinical remedies to prevent unpleasant FNS caused by activation of certain electrodes are to expand their pulse phase duration or simply deactivate them. Unfortunately, in some patients these methods do not provide sufficient FNS prevention. In these patients triphasic pulse can prevent from FNS. The underlying mechanism is yet unclear. Methods: Electromyographic (EMG) recordings of muscles innervated by the facial nerve (musculi orbicularis ori and oculi) were applied to quantitatively assess the effects on FNS. Triphasic and biphasic fitting maps were compared in four subjects with severe FNS. Based on the recordings, a model is presented which intends to explain the beneficial effects of triphasic pulse application. Results: Triphasic stimulation provided by fitting of an OPUS 2 speech processor device. For three patients, EMG was successfully recorded depending on stimulation level up to uncomfortable and intolerable FNS stimulation as upper boarder. The obtained EMG recordings demonstrated high individual variability. However, a difference between the input–output function for biphasic and triphasic pulse stimulation was visually observable. Compared with standard biphasic stimulation, triphasic pulses require higher stimulation levels to elicit an equal amount of FNS, as reflected by EMG amplitudes. In addition, we assume a steeper slope of the input–output function for biphasic pulse stimulation compared with triphasic pulse stimulation. Conclusion: Triphasic pulse stimulation prevents from FNS because of a smaller gradient of EMG input–output function compared with biphasic pulse stimulation. The underlying mechanism can be modeled by differences in spatiotemporal spread of the electrical field.

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Long-term Hearing Preservation Outcomes After Cochlear Implantation for Electric-Acoustic Stimulation

Objective: This study reviewed outcomes of hearing preservation (HP) surgery in a cochlear implant patient population, with clinical follow-up results up to 11 years after implantation. Study Design: Retrospective case review. Setting: Tertiary referral university hospital. Patients: Ninety six patients (103 ears) with partial deafness who underwent HP surgery at the University Hospital Frankfurt since 1999 were included. Electrode carriers were Cochlear Slim Straight, MED-EL Standard, Medium, Flex20, and Flex24. Intervention: Cochlear implantation using the HP surgery technique with either the cochleostomy or round window approach. Main Outcome Measures: Pure-tone averages for low frequencies (125 Hz, 250 Hz, 500 Hz, PTAlow) and speech perception scores of the Freiburg monosyllable and number tests in quiet. PTAlow shifts were used to evaluate HP as complete for ≤10 dB, partial between 10 and 30 dB, and minimal for ≥30 dB. Time intervals were: preoperative, postoperative, after 12 months, and long-term (>24 months, mean 51.4 months, range 2–11 years). Impacts of electrode design and surgical approach were analyzed. Results: Postoperatively (n = 103), HP was complete in 32 (31.1%), partial in 49 (47.6%), minimal in 14 (13.6%), and loss of hearing occurred in 8 cases (7.8%). After 12 months (n = 81), HP was complete in 22 (27.2%), partial in 33 (40.7%), minimal in 11 (13.6%), and loss of hearing occurred in 7 additional cases. For long-term outcomes (n = 62) HP was complete in 7 (11.3%), partial in 24 (38.7%), minimal in 9 (14.5%), and loss of hearing occurred in 7 additional cases (total 22/103, 21.4%). Cases with residual hearing who could utilize acoustic amplification (i.e., PTAlow 

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Cochlear Implants in Adults: Effects of Age and Duration of Deafness on Speech Recognition

Objective: Unexplained outcome variability exists among adults with cochlear implants (CIs). Two significant predictors are age and duration of deafness, with older patients and those with longer durations of deafness generally demonstrating poorer speech recognition. However, these factors are often highly correlated. Thus, it is unclear whether poorer outcomes should be attributed primarily to age-related declines or to the experience of auditory deprivation. Our aim was to examine the effects of aging and duration of hearing loss on outcomes for postlingually deaf adults with CIs. Study Design: Retrospective review of adults who received CIs from 1983 to 2014. Setting: Tertiary adult CI program. Patients: Sixty-four adult patients with postlingual hearing loss beginning after age 12 years, full electrode insertion, normal cochlear anatomy, and availability of postoperative outcome measures. Intervention: Cochlear implantation with 12 months or greater of device use. Main Outcome Measures: Postoperative pure-tone averages (0.5, 1, 2, and 3 kHz) and recognition of words in sentences (Hearing in Noise Test and AzBio). Results: Age at postoperative testing had a negative partial correlation with AzBio scores, when controlling for duration of deafness, whereas duration of deafness had a positive partial correlation with AzBio scores, when controlling for age. No other effects were identified. Conclusion: Older age at testing was associated with poorer recognition of words in difficult sentences, suggesting that cognitive aging may negatively impact CI outcomes. Further studies are needed to examine how a long duration of auditory deprivation affects CI outcomes.

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Calcium Homeostasis During Attack and Remission in Patients With Idiopathic Benign Paroxysmal Positional Vertigo

Objective: To evaluate changes in calcium metabolism in patients with idiopathic benign paroxysmal positional vertigo (BPPV) on initial presentation and at the follow-up visit. Subjects and Methods: The study comprised a total of 31 patients aged greater than 18 years who presented at the otorhinolaryngology outpatient clinic of our hospital, newly diagnosed as idiopathic BPPV based on the history compatible with BPPV and positive provocative maneuver (either Dix-Hallpike or Roll test). The first blood sample was obtained on the day of initial presentation when the patient was found to have active unilateral BPPV. After 6 months, a blood sample was again drawn in accordance with the procedure. Blood samples were analyzed for data on 25-hydroxyvitamin D (25(OH)-D), total calcium, parathormone and ionized calcium on initial presentation, and at the follow-up visit. Results: The patients comprised 20 (64.5%) women and 11 (35.5%) men with a mean age of 49.78 years (range, 23–75 years). During an attack a higher prevalence of decreased serum Vitamin D is less than 20 ng/ml, was determined (93.5% versus 38.7%). There were statistical differences between the Vitamin D values, parathormone, and corrected by pH ionized calcium in both periods (p 

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Cone Beam CT Versus Multislice CT: Radiologic Diagnostic Agreement in the Postoperative Assessment of Cochlear Implantation

Objective: To evaluate the diagnostic concordance between multislice computed tomography (MSCT) and cone beam computed tomography (CBCT) in the early postoperative assessment of patients after cochlear implantation. Study Design: Prospective, randomized, single-center, interventional, pilot study on the diagnostic performance of a medical device. Setting: Tertiary referral center. Patients: Patients aged over 18 years requiring a computed tomographic (CT) scan after cochlear implant surgery. Interventions: Nine patients were implanted with electrode arrays from three different manufacturers, including one bilateral. High-resolution MSCT and CBCT were then performed, and two experienced radiologists blinded to the imaging modality evaluated the randomized images, twice. Main Outcome Measures: Concordance between MSCT and CBCT for assessing the scalar position (tympani or vestibuli) of the electrodes. Secondary outcome measures were also studied: length of the intracochlear electrode array, percentage of implanted cochlea, number of intracochlear electrodes, and radiation doses. Results: There was a good agreement between both CT scanners in determining the scalar position and estimating the number of implanted electrodes and percentage of implanted cochlea. CBCT had a lower radiation exposure. Conclusions: The CBCT appears to be a useful tool for postoperative assessment of cochlear implanted adult patients and is comparable to the conventional scanner in determining the scalar position, with lower radiation exposure.

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Real Incidence of Vestibular Schwannoma? Estimations From a National Registry

Objective: To identify incidence of vestibular schwannoma (VS) in The Netherlands. Determining incidence of VS poses considerable challenges given the lack of complete epidemiologic data. Study Design: Retrospective patient review. Setting: Tertiary referral center. Patients: Patients with VS in The Netherlands. Data on patients with VS during 2001 to 2012 were obtained from The Netherlands Cancer Registry (NCR). Notification to the NCR is primarily pathology-based, but additional sources are used, including databases from hospital registrations and radiology departments. In addition, VS incidence estimations for the Leiden region were made; since these data are considered most complete, it was anticipated that estimates calculated from this region approximated the true incidence of VS in The Netherlands. Intervention(s): Magnetic resonance imaging (MRI). Main Outcome Measure(s): Incidence of VS. Results: From 2001 to 2012, a total of 3,663 patients of VS were registered. One thousand forty patients (28.4%) were pathologically confirmed, the majority only had a clinical diagnosis (n = 2623, 71.6%). Incidence increased from 10.3 per one million inhabitants (European Standardized Rate, ESR) to 15.5. Considerable variation in incidence rates was observed across regions, ranging from 12.0 to 24.9 per million over the total period. In the Leiden region, incidence was estimated at 25.5 per million during 2005 to 2007, and 33.2 per million during 2009 to 2012. In this region, the ratio of clinical versus histopathological diagnoses rose from 1.4 to 6.7. Conclusions: Completeness of the registration of VS varies across regions in The Netherlands. Incidence estimates obtained from regions with the highest rates are higher than those reported by previous studies.

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Air-Bone Gaps Contribute to Functional Hearing Preservation in Cochlear Implantation

Objective: To examine the incidence and effect of postoperative air-bone gaps in subjects who received cochlear implants for the purpose of hearing preservation. Study Design: Prospective, multicenter, nonrandomized, repeated measures within subject design. Setting: Ten tertiary care institutions. Patients: Fifty adults participating in a multicenter clinical trial of the Cochlear Nucleus Hybrid implant system. Intervention(s): Cochlear implantation with Hybrid L24 electrode. Audiometric testing including air and bone conductive thresholds and tympanometry preoperatively and at multiple time points postoperatively for 1 year. Main Outcome Measure(s): Average air-bone gaps (ABG) and percentage of patients with ABGs (≥15 dB HL) measured for each time point for 1 year postoperatively at 250, 500, and 1000 Hz. Correlation of tympanograms and ABGs. Results: The mean ABGs at 250, 500, and 1000 Hz increased postoperatively (p 60% of patients at 250 Hz, in >38% at 500 Hz, and in >50% at 1000 Hz in those with residual hearing. No significant relationships were found between abnormal tympanograms and ABG. Conclusion: The incidence of ABGs postoperatively is higher than previously expected and does not correlate to abnormalities on tympanometry. ABGs can adversely affect the fitting of postoperative residual hearing and associated functional benefit. Additionally, intraoperative strategies should be used to potentially reduce ABGs, and bone conduction thresholds should be measured postoperatively.

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The Clinical Behavior of Asymptomatic Incidental Vestibular Schwannomas Is Similar to That of Symptomatic Tumors

Background: The clinical behavior of asymptomatic incidentally diagnosed vestibular schwannoma (VS) remains undefined. Specifically, it is unknown whether these tumors represent a more indolent biological variant. Such information would be beneficial toward patient counseling regarding treatment strategy and surveillance intervals during observation. Study Design: Case series with matched cohort. Setting: Single tertiary academic referral center. Patients: All patients with asymptomatic incidentally diagnosed VS who were evaluated between January 2000 and December 2015 were analyzed. Only cases where imaging was obtained for unrelated indications in patients with symmetrical or normal hearing and lack of any attributable symptoms were included. A separate VS reference cohort composed of patients with typical symptomatology, matched according to tumor size, age and sex, was used for comparison. Main Outcome Measures: Growth, symptom progression, treatment. Results: A total of 38 incidental VS were evaluated, representing approximately 1.6% of all VS evaluated during this time. There was a statistically significant increase in the rate of incidental tumor diagnosis over time. Estimated survival free of tumor growth or treatment (95% CI; number still at risk) at 1, 3, and 5 years after diagnosis was 89% (77–100; 22), 74% (57–95; 13), and 54% (35–84; 4), respectively. The median growth rate for the 11 patients with tumor growth was 1.3 mm/year. Time to growth or treatment (p = 0.18), growth rate (p = 0.60), and rate of audiometric decline was not statistically significantly different between incidentally discovered and symptomatic reference groups. Conclusion: The frequency of asymptomatic, incidentally diagnosed VS is rising. These data demonstrate that the clinical behavior of asymptomatic incidental VS is not different than that of age-, sex-, and size-matched symptomatic VS. Thus, if initial observation is undertaken, patients with asymptomatic incidental tumors still require long-term magnetic resonance imaging surveillance performed at regular time intervals.

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Massive Tension Pneumocephalus Following Cochlear Implant Surgery

Objective: To report clinical presentation, management and outcomes of a rare complication of cochlear implant surgery. Patient: A 68-year-old man, affected by profound bilateral deafness because of superficial cerebral hemosiderosis, presented to Authors’ Department 8 days after cochlear implant surgery with vomiting, fever, and mental confusion. Brain computed tomographic (CT) scan showed a massive collection of intracranial air from an osteodural defect in the right tegmen mastoideum because of repeated nose blowing in the postoperative period. Intervention: A multilayer reconstruction of the tegmen with obliteration of the mastoid cavity using abdominal subcutaneous adipose tissue was performed, preserving the cochlear implant in place. Main Outcome and Results: Following surgery the patient showed rapid neurological improvement and CT scan performed 2 days later showed complete resolution of the intracranial air collection. He is currently using the cochlear implant with open set performances. Conclusion: Pneumocephalus is a rare complication of cochlear implant surgery. In patients with severe neurological signs following cochlear implantation (CI), pneumocephalus should be suspected. Drilling of mastoid air cells may expose dura mater and positive high pressure events may break meningeal layers and force air into the cranial cavity.

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