Verification EVestG recordings are vestibuloacoustic signals.

Introduction: Neural dysfunction is associated with aberrant nerve firing; thus, electrodiagnosis has the potential for objective diagnosis and quantification of neural dysfunction. Electrical stimulation alters nerve firing and may also have treatment potential. This article outlines some findings related to electrodiagnosis and electrical stimulation of the ear. The quasi-synchronous firing of many vestibuloacoustic nerve fibers can produce an extracellular potential defined as a field potential (FP). Electrovestibulography (EVestG) is a method to record vestibuloacoustic signals and detect the associated FPs. A clear picture of the muscle-, EEG-, saccade-related, or other artefactual origins, and the physiologic basis of FPs recorded with EVestG, is evolving. EVestG was applied to demonstrate the effect of electrical stimulation on spontaneous FPs in the ear canal. Methods: Bilateral EVestG recordings were conducted on 14 guinea pigs before and after stimulation with 3-0.5 mA ipsilateral anodal electrical pulses before and after ablation via unilateral Scarpa's ganglionectomy to elucidate the origin of the EVestG recorded spontaneous FPs. Results: Anodal electrical stimulation suppresses the recorded activity. There was a significant reduction of the level of recorded signal observed following anodal stimulation on the ablated but not the intact side. Conclusion: Electrical stimulation of the external auditory canal reduces spontaneous electrical activity in the ear canal, some of which is due to central nervous system activity. The EVestG recorded FPs have a major vestibuloacoustic component.

Does N-acetylcysteine Improve Established Hearing Loss in Guinea Pigs?

Objective: To assess whether multiple injections of a powerful antioxidant can improve established sensorineural hearing loss in guinea pigs. Study Design: Animal study. Setting: Animal science laboratory, University of Manitoba. Methods: A total of 16 guinea pigs were used in our study: 8 underwent unilateral intracochlear neomycin injection, and 8 underwent unilateral saline to serve as controls. After a period of 3 weeks for hearing loss to stabilize, 4 guinea pigs from each group received weekly intraperitoneal injections of N-acetylcysteine (NAC) for 4 weeks. Click auditory brainstem response (ABR) testing was conducted at baseline, weekly after the start of NAC injections, and after the last injection. Pure tone ABR tests were conducted prior to intracochlear injections and at completion of the study. Results: Click ABR thresholds were significantly worse in ears treated with neomycin (P < .001), as expected, but not significantly different when treated with NAC (P = .664). Thresholds for pure tone ABR were also not statistically different in neomycin-treated ears with or without NAC (P > .99). Conclusions: The aggressive antioxidant therapy performed in this study was not successful in improving established hearing loss via an antioxidant regimen that is known to change the oxidation-reduction potential in the cochlea.

Comparing Vestibular Responses to Linear and Angular Whole-Body Accelerations in Real and Immersive Environments.

The vestibular end organs differ in terms of anatomical and physiological characteristics. Sensory modalities' stimuli including visual stimuli and vestibular sensation can influence these organs differently. This paper explores differences between vestibular responses to axial tilts in physical and virtual environments. Four passive whole-body movements (linear: up-down, and angular: yaw, pitch, and roll) were applied to twenty-seven healthy participants once using a hydraulic chair (physical) and once visually using a head-mounted display (virtual). Electrovestibulography (EVestG) was used as the outcome measure to investigate the magnitude of vestibular-response-change in both ears for physical and virtual stimuli. Three features including average action potential (AP) area, AP amplitude, and mean detected firing rate change were used as indices of response. The results show that for both physical and virtual stimuli (1) generally the pitch and roll tilts produce the largest EVestG changes compared to other tilts (2) roll and pitch tilt responses are not significantly different from each other and (3) right side and left side roll tilts' responses are not significantly different. The findings indicate although visually- and physically-induced vestibular responses are different in terms of afferent activity, visual stimuli can still result in distinct responses when exposed to different axial tilts.

Physiological separation of Alzheimer's disease and Alzheimer's disease with significant levels of cerebrovascular symptomology and healthy controls.

Most dementia patients with a mixed dementia (MxD) diagnosis have a mix of Alzheimer's disease (AD) and vascular dementia. Electrovestibulography (EVestG) records vestibuloacoustic afferent activity. We hypothesize EVestG recordings of AD and MxD patients are different. All patients were assessed with the Montreal cognitive assessment (MoCA) and Hachinski ischemic scale (HIS) (> 4 HIS score < 7 is representative of MxD cerebrovascular symptomology). EVestG recordings were made from 26 AD, 21 MxD and 44 healthy (control) participants. Features were derived from the EVestG recordings of the average field potential and field potential interval histogram to classify the AD, MxD and control groups. Multivariate analysis was used to test the features' significance. Using a leave-one-out cross-validated linear discriminant analysis with 3 EVestG features yielded accuracies > 80% for separating pairs of AD/MxD/control. Using the MoCA assessment and 2 EVestG features, a best accuracy of 81 to 91% depending on the classifier was obtained for the 3-way identification of AD, MxD and controls. EVestG measures provide a physiological basis for identifying AD from MxD. EVestG measures are hypothesized to be partly related to channelopathies and changes in the descending input to the vestibular periphery. Four of the five AD or MxD versus control features used had significant correlations with the MoCA. This supports assertions that the pathologic changes associated with AD impact the vestibular system and further are suggestive that the postulated physiological changes behind these features have an association with cognitive decline severity.

Reliability of caloric testing.

OBJECTIVE: To assess the long-term stability of caloric testing in patients. METHODS: In this retrospective study, Cronbach's alpha was used to determine whether caloric testing results are stable over time (up to 7 years) in patients who have not undergone interventions. After excluding invalid records, two hundred patients who underwent repeated caloric testing in the same lab over varying periods of time were included. RESULTS: Cronbach's alpha scores were 0.512 for unilateral weakness and 0.051 for the sum of caloric tests indicating that the stability of caloric tests is poor over long terms. CONCLUSION: The stability of caloric testing with repeated testing over long terms is not reliable.

Brain-derived nerve growth factor in the cochlea - a reproducibility study.

OBJECTIVE: Brain-derived nerve growth factor (BDNF) plays an important role in cochlear development so it is plausible that it could restore hearing loss if delivered directly into the cochlea. We wished to confirm our previous report that a single intracochlear injection of brain-derived nerve growth factor (BDNF) was beneficial for hearing in guinea pigs. We wished to assess the reproducibility of our results and assess possible improved methods with a view to developing a clinical treatment for sensorineural hearing loss. METHODS: CDDP was used to create partial hearing loss in 25 guinea pigs. After 30 days the animals underwent ABR testing and unilateral BDNF injection through the round window in one ear and saline injection into the other ear. After allowing possible effects to stabilize, thirty days later, ABR threshold testing was repeated to assess change in threshold. RESULTS: Final ABR thresholds were 60-70 dB and were about 11 dB better in the ears treated with BDNF. CONCLUSION: Our original finding that Intracochlear BDNF can improve hearing in guinea pigs was confirmed, but the improvement demonstrated by the methods in this paper is too small for clinical application.

Differences Between Physical vs. Virtual Evoked Vestibular Responses.

Electrovestibulography (EVestG), a technology purported to measure vestibular activity at the vestibular periphery, was used to compare the vestibular responses to two sensory inputs: (1) back-forward physical tilt (with eyes-open and eyes-closed) and (2) virtual reality replica of the back-forward tilt (eyes-open, physically static). Twenty-seven healthy participants (10 females) were tested. From each of the EVestG recordings, two feature curves: (1) average field potential (FP), and (2) distribution of time intervals between the detected FPs were extracted. For the eyes-closed physical tilt, except for the background segment, the FP response curve was generally wider compared to that evoked during the virtual replica tilt (p < 0.05). Moreover, the eyes-closed physical tilt produced longer time intervals between FP's compared to the virtual stimulus. For this measure, for the background segment, the eyes closed and open physical tilt responses were significantly different (p < 0.05) in both ears (repeated measure experimental design). The results support: (1) both vestibular and visual inputs evoking a measurably different EVestG response, (2) the differences between physical and virtual vestibular responses are dependent on the eyes being either open or closed, and (3) for the stimuli used, the modulation of vestibular afferent activity was measurably smaller for virtual than physical stimulation.

The Role for Imaging in the Investigation of Isolated Objective Vestibular Weakness.

OBJECTIVE: Unilateral vestibular weakness has considerable potential etiologies. One source is a vestibular schwannoma. This article evaluates, in the absence of other symptoms and signs, if unilateral vestibular weakness is an analogue to asymmetric sensorineural hearing loss and serves as an indication for lateral skull base imaging. STUDY DESIGN: Retrospective chart review. SETTING: Academic tertiary center. SUBJECTS AND METHODS: All patients undergoing caloric assessment between January 1, 2012, and June 30, 2018, were investigated. Patients with unilateral vestibular weakness (a left-right difference >25% on electronystagmography) were included in the study. A provincial encompassing image library was surveyed for potential adequate imaging (computed tomography internal auditory canal infused, magnetic resonance imaging [MRI] brain, MRI internal auditory canal) of the target population within the preceding 5 years. Presence/absence of vestibular schwannoma on imaging was determined. RESULTS: Of the 3531 electronystagmography reports reviewed during the period, 864 patients were identified with unilateral vestibular weakness. Of these, 542 had sufficient imaging, and 14 vestibular schwannomas were identified. Only 1 individual had a vestibular weakness in isolation, while the remaining 13 patients also suffered from documented sensorineural hearing loss that would have mandated MRI scanning. CONCLUSION: The results of our study suggest that, in isolation, vestibular weakness is an insufficient indicator for lateral skull base imaging.

Impact of maternal iron deficiency on the auditory functions in the young and adult guinea pig.

OBJECTIVES: The aim of this study was to evaluate the hearing function in the guinea pig offspring at post-natal day (PNd) 24 and PNd84 born from dams suffering from iron deficiency during pregnancy and lactation by using the auditory brainstem response (ABR). METHOD: Female guinea pigs (n = 24 per dietary group) were fed an iron sufficient (IS) diet (114 mg/kg) or an iron deficient (ID) diet (11.7 mg/kg) during the gestation and lactation periods. Pups in both groups were weaned at PNd9 and given the IS diet. The hematocrit level was measured at every trimester of pregnancy and at the day of sacrifice in dams and at PNd24 and PNd84 in pups. The animal body weight was measured on every second day until the day of sacrifice. The ABR was used in pups to measure the hearing threshold using a broad range of stimulus intensities and latency at 100 and 80 dB in response to 2, 4, 8, 16, and 32 kHz tone pips at PNd24 and 84. RESULTS AND DISCUSSION: No significant difference between dietary groups was measured in hearing threshold and absolute latencies in pups at PNd24 and PNd84. Although the ID offspring (n = 16) did not differ in brainstem transmission times (BTTs) at 80 dB compare to the IS siblings (n = 25) at PNd24, they showed significant delayed inter-peak latency (IPL) I-IV at 100 dB suggesting a delayed BTT. At PNd84, the latency of all peaks including IPL I-IV at 80 and 100 dB significantly decreased and was also similar in pups from both dietary groups suggesting a better brain maturation. This is the first study investigating the long-term impact of maternal iron deficiency on the auditory functions in the guinea pig offspring during early development to adulthood.

Hemorrhagic stroke after Epley maneuver: a case report.

BACKGROUND: This is the first case to our knowledge of a serious adverse event following the Epley maneuver, which is the treatment of choice for benign paroxysmal positional vertigo (BPPV), the most common vestibular disorder in adults. CASE PRESENTATION: A 77 year old female presented for outpatient evaluation of vertigo at a tertiary otolaryngology clinic. She was found to have BPPV clinically, and elected to have a particle repositioning maneuver (Epley maneuver) performed in clinic. Immediately following Epley maneuver, she had severe nausea and vomiting, with evolving visual changes. A CT angiogram of the brain was performed urgently through the emergency department and demonstrated an acute intraparenchymal hemorrhage in the occipital lobe. After medical stabilization and rehabilitation, the patient continues to have a permanent visual field deficit. CONCLUSION: The Epley maneuver is safe and effective, and there are no prior reports of serious adverse events associated with its use. This case, in which a patient experienced a hemorrhagic stroke after undergoing the Epley maneuver, is the first and sole case in the medical literature of an Epley-associated serious adverse event. The indirect causation and extreme rarity of this event do not warrant any change to patterns of practice.

Systematic review of ototoxic pre-surgical antiseptic preparations - what is the evidence?

OBJECTIVE: There is uncertainty regarding the safety of surgical antiseptic preparations in the ear. A systematic review of the literature was conducted to assess the evidence regarding ototoxicity of surgical antiseptic preparations. METHODS: A literature search was conducted using the PRISMA methods. Key words included "ototoxicity" "hearing loss", "antiseptic", "surgical preparation", "tympanoplasty", "vestibular dysfunction", "chlorhexidine", "iodine", "povidone", "ethanol", and "hydrogen peroxide" using Medline, Embase, Cochrane Library, Scopus and Web of Science. We included peer-reviewed papers that 1) objectively measured ototoxicity in humans or animals through hearing, vestibular function or histologic examination, 2) studied topically applied surgical antiseptic preparations, 3) were either in English or had an English abstract. We excluded papers that were 1) in vitro studies, 2) ear trauma studies, 3) studies of ototoxic ear drops intended for therapy, or 4) case reports. Studies included in the final review were screened using the PRISMA method. Current systematic review registration number pending: 83,675. RESULTS: Fifty-six papers were identified as using PRISMA criteria. After applying our exclusion criteria, 13 papers met overall study criteria. Of these, six papers reported ototoxicity of iodine based solutions, five papers reported ototoxicity of chlorhexidine and ethanol and two papers assessed hydrogen peroxide. All papers reviewed were animal studies. Iodine based solutions show least harm overall, while chlorhexidine and high concentrations of alcohol based solutions showed most harm. The evidence on hydrogen based solutions was inconclusive. CONCLUSIONS: The overall evidence for anyone antiseptic solution is weak. There is some evidence that iodine, chlorhexidine, hydrogen peroxide and alcohol based antiseptics have ototoxicity. Conclusive evidence for human ototoxicity from any solution is not strong.

Clinical predictors of chronic rhinosinusitis: do the Canadian clinical practice guidelines for acute and chronic rhinosinusitis predict CT-confirmation of disease?

BACKGROUND: The diagnosis of chronic rhinosinusitis (CRS) based on clinical presentation alone remains challenging. To improve the accuracy of clinical diagnosis, the Canadian Rhinosinusitis Guidelines recommend the use of specific symptom and endoscopic criteria. Our study objective was to determine whether symptom and endoscopic criteria, as defined by the Canadian Rhinosinusitis Guidelines, accurately predict CT-confirmed CRS diagnosis. METHODS: A retrospective cohort study of 126 patients who underwent CT sinuses based on clinical suspicion of possible CRS. The presence of symptom and endoscopic criteria, as defined by the Canadian Rhinosinusitis Guidelines, were compared between patients with and without a CT-confirmed CRS diagnosis using two-tailed Fisher's exact tests. Positive predictive values and likelihood ratios were determined for each symptom and endoscopic finding. RESULTS: Overall, 56.3% of patients had a CT-confirmed diagnosis of CRS. With the exception of nasal polyps, none of the symptom or endoscopic criteria had a statistically significant correlation with positive CT sinuses. For symptom criteria, positive predictive values ranged from 52.4% to 63.4%; likelihood ratios ranged from 0.85 to 1.34. For endoscopic criteria, positive predictive values and likelihood ratios were 71.4% and 1.94 (edema); 63.0% and 1.32 (discharge); and 92.9% and 10.1 (nasal polyps). 35.2% of patients with CT-confirmed CRS had normal endoscopic exams. CONCLUSION: The Canadian Rhinosinusitis Guidelines' symptom and endoscopic criteria for CRS, with the exception of nasal polyps on endoscopy, do not accurately predict CT-confirmed disease. In addition, a normal endoscopic exam does not rule out CRS.

Mannitol and the blood-labyrinth barrier.

BACKGROUND: Characterization of the blood labyrinth barrier (BLB) is extremely important to determine whether the BLB can be manipulated pharmacologically. However, experiments to investigate the BLB are technically difficult to perform. In this report, we demonstrated a unique method of controlling the BLB, and established the pharmacokinetics of gentamicin in perilymph, cerebrospinal fluid (CSF) and blood with and without mannitol. STUDY DESIGN: Controlled animal research project. METHODS: Permeability of the BLB and the blood brain barrier (BBB) to gentamicin with and without mannitol was studied by collecting 175 samples from 44 guinea pigs using concentrations relevant to human clinical situations. Samples were taken from two groups of 22 animals, with each animal undergoing sampling at a different time after administration of either 10 mg/ml gentamicin (4 mg/kg) (Gardena, CA) alone or gentamicin with 20% mannitol (250 mg/kg) (Mallinckrodt Inc., KY). The sample times varied from 0.5 to 17.5 h post-infusion. Samples were also taken from 4 animals as negative controls after administration of normal saline. Our goal was to simultaneously assess the pharmacokinetics of gentamicin in each of three different fluid samples in the same animal. Thus at the pre-determined post-infusion sampling time, each animal was sampled once for perilymph, CSF, and blood before being euthanized. Each animal contributed to a single time point on the subsequent pharmacokinetic curves with more than one animal per time point. RESULTS: Mannitol increased the rate of entry and egress of gentamicin through BLB significantly (p = 0.0044) but the effects on the BBB did not reach statistical significance (p = 0.581). Mannitol did not alter renal clearance of gentamicin from the blood (p = 0.433). The concentration of gentamicin in perilymph and CSF was always significantly lower than in blood. CONCLUSIONS: Mannitol administration transiently increases the permeability of the BLB. Potential clinical benefits may accrue from selected timing of administration of osmotic agents such as mannitol augmenting the rate of entry and egress of compounds such as gentamicin into and out of perilymph.

Statistical Considerations in Otolaryngology Journals.

Statistics can be intimidating for clinicians and reviewers. Statistics are often important and useful but can mislead. Elaborate statistics can support conclusions that contradict clinical experience. This article explores some statistically related insights. Statistical reasons for rejecting papers were collated, and the frequency and complexity of statistical tests in accepted, published papers in otolaryngology journals were then studied. Most statistical errors in papers are logical misinterpretations of information rather than lack of understanding of statistics. Otolaryngology papers tend to employ relatively straightforward statistics that should be useful for clinicians. Although evidence-based medicine has changed medical publishing, clinical knowledge is more important that statistical knowledge for clinical applications of statistics.

Mutations in HYAL2, Encoding Hyaluronidase 2, Cause a Syndrome of Orofacial Clefting and Cor Triatriatum Sinister in Humans and Mice.

Orofacial clefting is amongst the most common of birth defects, with both genetic and environmental components. Although numerous studies have been undertaken to investigate the complexities of the genetic etiology of this heterogeneous condition, this factor remains incompletely understood. Here, we describe mutations in the HYAL2 gene as a cause of syndromic orofacial clefting. HYAL2, encoding hyaluronidase 2, degrades extracellular hyaluronan, a critical component of the developing heart and palatal shelf matrix. Transfection assays demonstrated that the gene mutations destabilize the molecule, dramatically reducing HYAL2 protein levels. Consistent with the clinical presentation in affected individuals, investigations of Hyal2-/- mice revealed craniofacial abnormalities, including submucosal cleft palate. In addition, cor triatriatum sinister and hearing loss, identified in a proportion of Hyal2-/- mice, were also found as incompletely penetrant features in affected humans. Taken together our findings identify a new genetic cause of orofacial clefting in humans and mice, and define the first molecular cause of human cor triatriatum sinister, illustrating the fundamental importance of HYAL2 and hyaluronan turnover for normal human and mouse development.

Tinnitus Treatment Trends.

OBJECTIVE: The American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) recently published guidelines on the treatment of tinnitus. This paper examines the possible impact of those guidelines on otologic practice. DESIGN: A survey was sent to the members of the American Neurotology Society before and after the publication of Clinical practice guideline: tinnitus. The goals of this study were to see if the guidelines changed attitudes of otologists, confirm what treatments and explanations are being used in the field before and after the guidelines were published. MAIN OUTCOMES: Five hundred fifty-eight surveys were sent out and there were 216 responses. Otologists generally seemed to practice in accordance with the recommendations of the guidelines even before these were published. Drugs and sound therapies were not commonly used for primary tinnitus either before or after publication of the guidelines. One treatment that otologists seemed to have confidence in that was omitted from the guidelines was surgical treatment of hearing loss. CONCLUSION: Opinions regarding the treatment of tinnitus vary considerably. The AAO-HNS clinical practice guideline: tinnitus has not significantly altered the practices of otologists, but the guidelines provide meaningful, important information for other clinicians who deal infrequently with tinnitus.

Methods considerations for nystagmography.

OBJECTIVES: 1. To assess the reproducibility of eye movement velocity measurement using two methods: traditional electro-oculography (EOG) and infrared video-oculography (VOG) and, 2. Determine whether the normal values for unilateral weakness and bilateral reduction of caloric responses vary according to method employed. BACKGROUND: Vestibular testing frequently involves measurement of eye movements. EOG has been the standard method for decades, but VOG and other methods have recently become popular. The assumption has been that all methods measure eye movements equally and accurately but this assumption has not been validated. In this paper we examine this assumption. METHODS: Eye movements were recorded simultaneously with commercially available EOG and VOG methods to evaluate differences in results for nineteen normal subjects undergoing caloric tests with warm and cold water. Examination of the records permitted identification and simultaneous measurement of 840 nystagmus beats. RESULTS: EOG and VOG measurements were correlated but the correlation was not strong (Spearman rho = 0.529, p < 0.01). Eye velocities recorded by the VOG system were greater than that for the EOG system. The mean VOG/EOG ratio was 1.71. Normal values used at our centre were adjusted to accommodate the use of video technology to account for the differences in sensitivity between EOG and VOG methods. CONCLUSION: The traditional EOG-based normal value for bilateral reduction of caloric response, 30 degree per second (d/s) based on traditional EOG measurements should be revised to 50 d/s for modern VOG testing in our lab. Normal values for vestibular testing may need to be re-evaluated when new technology is introduced. Each lab should verify normal values for their own methods and equipment.

A new diagnostic vestibular evoked response.

OBJECTIVE: To describe the development of a new clinically applicable method for assessing vestibular function in humans with particular application in Meniere's disease. STUDY DESIGN: Sophisticated signal-processing techniques were applied to data from human subject undergoing tilts stimulating the otolith organs and semicircular canals. The most sensitive representatives of vestibular function were extracted as "features". METHODS: After careful consideration of expected response features, Electrovestibulography, a modified electrocochleography, recordings were performed on fourteen Meniere's patients and sixteen healthy controls undergoing controlled tilts. The data were subjected to multiple signal processing techniques to determine which "features" were most predictive of vestibular responses. RESULTS: Linear discriminant analysis and fractal dimension may allow data from a single tilt to be used to adequately characterize the vestibular system. CONCLUSION: Objective, physiologic assessment of vestibular function may become realistic with application of modern signal processing techniques.

Elevated auditory brainstem response thresholds in mice with Connexin36 gene ablation.

CONCLUSION: Expression of connexin36 (Cx36) and electrical synapses formed by Cx36-containing gap junctions contribute to normal auditory brainstem response thresholds in mice. OBJECTIVES: Electrical synaptic transmission mediated by gap junctions has not been intensively studied in the auditory system. This study used transgenic mice with knockout of the gene coding for the major protein that forms neuronal gap junctions in mammalian brain (Cx36) to evaluate the role of Cx36 in murine hearing. METHODS: Auditory brainstem response (ABR) thresholds and distortion product otoacoustic emissions (DPOAEs) were measured in 26 wild-type and 26 Cx36 knockout mice. ABR thresholds were used to assess auditory brainstem function at four frequencies. DPOAEs were delivered for seven frequency pairs to assess cochlear function. RESULTS: The magnitudes of the 2f1-f2 distortion products were not different between Cx36 knockout and wild-type mice, suggesting similar cochlear function in the two groups. ABR thresholds were significantly elevated in the Cx36 knockout compared with the wild-type groups, suggesting impaired function in the auditory brainstem. The results suggest that electrical synapses formed by Cx36-containing gap junctions contribute to auditory sound processing and function at the level of the brainstem, not the cochlea. These findings may be important for understanding human auditory pathology.