Controlled exploration of the effects of conductive hearing loss on wideband acoustic immittance in human cadaveric preparations.

Current clinical practice cannot distinguish, with any degree of certainty, the multiple pathologies that produce conductive hearing loss in patients with an intact tympanic membrane and a well-aerated middle ear without exploratory surgery. The lack of an effective non-surgical diagnostic procedure leads to unnecessary surgery and limits the accuracy of information available during pre-surgical consultations with the patient. A non-invasive measurement to determine the pathology responsible for a conductive hearing loss prior to surgery would be of great value.

Cochlear neuropathy in human presbycusis: Confocal analysis of hidden hearing loss in post-mortem tissue.

Recent animal work has suggested that cochlear synapses are more vulnerable than hair cells in both noise-induced and age-related hearing loss. This synaptopathy is invisible in conventional histopathological analysis, because cochlear nerve cell bodies in the spiral ganglion survive for years, and synaptic analysis requires special immunostaining or serial-section electron microscopy. Here, we show that the same quadruple-immunostaining protocols that allow synaptic counts, hair cell counts, neuronal counts and differentiation of afferent and efferent fibers in mouse can be applied to human temporal bones, when harvested within 9 h post-mortem and prepared as dissected whole mounts of the sensory epithelium and osseous spiral lamina.

Power reflectance as a screening tool for the diagnosis of superior semicircular canal dehiscence.

Hypothesis: Power reflectance (PR) measurements in ears with superior canal dehiscence (SCD) have a characteristic pattern, the detection of which can assist in diagnosis.

Background: The aim of this study was to determine whether PR coupled with a novel detection algorithm can perform well as a fast, noninvasive, and easy screening test for SCD. The screening test aimed to determine whether patients with various vestibular and/or auditory symptom(s) should be further considered for more expensive and invasive tests that better define the diagnosis of SCD (and other third-window lesions).

Familial superior canal dehiscence syndrome.

Importance: The etiology of superior canal dehiscence (SCD) involving the arcuate eminence is not completely understood, but genetic factors may play a role. One hypothesis is that patients are born with a defect of the superior canal, and an acute event (such as head trauma) or progressive loss of bone (eg, due to dural pulsations) may result in the onset of SCD symptoms. Familial SCD has only been briefly mentioned in the literature to date.

Auditory analysis of xeroderma pigmentosum 1971-2012: hearing function, sun sensitivity and DNA repair predict neurological degeneration.

To assess the role of DNA repair in maintenance of hearing function and neurological integrity, we examined hearing status, neurological function, DNA repair complementation group and history of acute burning on minimal sun exposure in all patients with xeroderma pigmentosum, who had at least one complete audiogram, examined at the National Institutes of Health from 1971 to 2012. Seventy-nine patients, aged 1-61 years, were diagnosed with xeroderma pigmentosum (n = 77) or xeroderma pigmentosum/Cockayne syndrome (n = 2). A total of 178 audiograms were included.

Wave motion on the surface of the human tympanic membrane: holographic measurement and modeling analysis.

Sound-induced motions of the surface of the tympanic membrane (TM) were measured using stroboscopic holography in cadaveric human temporal bones at frequencies between 0.2 and 18 kHz. The results are consistent with the combination of standing-wave-like modal motions and traveling-wave-like motions on the TM surface.

Correlation of computed tomography with histopathology in otosclerosis.

Objective: Until now, the use of computed tomography (CT) in the diagnosis and evaluation of otosclerosis has been based on correlation of radiologic findings to patient histories, intraoperative examinations, and audiologic data. The purpose of this study was to compare CT findings in otosclerosis to histopathology.

Study Design: Prospective blinded.

Otopathology in Osteogenesis Imperfecta.

Background: Osteogenesis Imperfecta (OI) is a genetic disorder of connective tissue matrix. OI is caused by mutations that affect type I collagen. The hearing loss in OI is characterized by onset in early adulthood and can be conductive, sensorineural, or mixed.

Third-generation bisphosphonates for treatment of sensorineural hearing loss in otosclerosis.

Objective: To evaluate hearing outcomes in patients treated with third generation bisphosphonates for otosclerosis-related sensorineural hearing loss (SNHL).

Hypothesis: Otosclerosis is a disease of abnormal bone remodeling in the otic capsule. In recent years, third generation bisphosphonates, with more powerful anti-resorptive properties and increased bone affinity, have demonstrated effectiveness in the treatment of osteoporosis and other metabolic bone diseases.

The effect of superior semicircular canal dehiscence on intracochlear sound pressures.

Semicircular canal dehiscence (SCD) is a pathological opening in the bony wall of the inner ear that can result in conductive hearing loss. The hearing loss is variable across patients, and the precise mechanism and source of variability are not fully understood. Simultaneous measurements of basal intracochlear sound pressures in scala vestibuli (SV) and scala tympani (ST) enable quantification of the differential pressure across the cochlear partition, the stimulus that excites the cochlear partition.

Large jugular bulb abnormalities involving the middle ear.

Objective: Jugular bulb abnormalities (JBA), such as jugular bulb diverticula (JBD) or large jugular bulbs, rarely present in the middle ear. We review a large series of temporal bone histopathologic specimens to determine their prevalence and present a series of cases of JB abnormalities involving the middle ear (JBME) that shed light on the probable mechanism for their development.

Patients: 1,579 unique temporal bone specimens and individuals with radiographically-diagnosed JBME.

Prevalence of jugular bulb abnormalities and resultant inner ear dehiscence: a histopathologic and radiologic study.

Objective: Jugular bulb abnormalities (JBA), including high-riding jugular bulb (HRJB) and jugular bulb diverticulum (JBD), can erode into the inner ear. In this study, the authors investigate the prevalence and consequences of JBA and their erosion into inner ear structures using temporal bone histopathology and computed tomography (CT).

Study Design: Cross-sectional study of temporal bone histopathology and radiology.

Clinical follow-up and histopathology of the temporal bones in Nathalie syndrome.

The Nathalie syndrome (OMIM 255990) comprises a combination of features that do not resemble any other known syndrome and is as such an independent, rare entity. It is characterized by sensorineural hearing impairment, juvenile cataract, spinal muscular atrophy, skeletal abnormalities, retardation of growth, underdeveloped secondary gender characteristics and cardiomyopathy. Worldwide, only one family with this syndrome is known.

Dysfunction of the cochlea contributing to hearing loss in acoustic neuromas: an underappreciated entity.

Objective: Hearing loss is a common symptom in patients with cochleovestibular schwannoma. Clinical and histologic observations have suggested that the hearing loss may be caused by both retrocochlear and cochlear mechanisms. Our goal was to perform a detailed assessment of cochlear pathology in patients with vestibular schwannoma (VS).

Histopathology of the temporal bone in a case of superior canal dehiscence syndrome.

Objectives: We describe the histopathologic findings in the temporal bones of a patient who had, during life, received a diagnosis of superior canal dehiscence (SCD) syndrome.

Methods: The patient was found to have SCD syndrome at 59 years of age. She became a temporal bone donor, and died of unrelated causes at 62 years of age.

A clinical and histopathologic study of jugular bulb abnormalities.

Objective: To further define the spectrum of clinical presentation and explore the histologic sequelae of jugular bulb abnormalities (JBAs).

Design: Retrospective review.

Setting: Academic medical center.

What is the site of origin of cochleovestibular schwannomas?

The belief that cochleovestibular schwannomas arise from the glial-Schwann cell junction has repeatedly been quoted in the literature, although there is no published evidence that supports this statement. A systematic evaluation of the nerve of origin and the precise location of cochleovestibular schwannomas using our respective archival temporal bone collections was conducted. Forty tumors were within the internal auditory canal (IAC), while 10 were intralabyrinthine neoplasms.

New data on the motion of the normal and reconstructed tympanic membrane.

Hypothesis: The sound-induced motion of the tympanic membrane has features that are most consistent with modal responses to a uniform stimulus.

Background: Conceptual models of the coupling of tympanic membrane motion to the ossicular chain can be classified as either modal responses to a uniform stimulation of the entire membrane or traveling wave models in which sound energy is captured at the membrane's rim and travels along the surface to the umbo. The stroboscopic holography technique we use can separate strongly modal or traveling wave-dominated motions of the tympanic membrane surface.

Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS): a review of the clinical features and video-oculographic diagnosis.

The association of bilateral vestibulopathy with cerebellar ataxia was first reported in 1991 and delineated as a distinct syndrome with a characteristic and measurable clinical sign--an absent visually enhanced vestibulo-ocular reflex--in 2004. We reviewed 27 patients with this syndrome and show that a non-length-dependent sensory deficit with absent sensory nerve action potentials is an integral component of this syndrome, which we now call "cerebellar ataxia with neuropathy and bilateral vestibular areflexia syndrome" (CANVAS). All patients had brain MRI and 22/27 had evidence of cerebellar atrophy involving anterior and dorsal vermis, as well as the hemispheric crus I.

Superior canal dehiscence syndrome associated with the superior petrosal sinus in pediatric and adult patients.

Objective: To determine whether pediatric and adult patients with superior canal dehiscence (SCD) at the superior petrosal sinus (SPS) develop superior canal dehiscence syndrome (SCDS).

Study Design: Retrospective review.

Setting: Tertiary care academic medical center.

Temporal bone findings in a case of Susac's syndrome.

Objective: To describe the histopathologic findings in the temporal bones of a patient with Susac's syndrome (SS).

Background: The key clinical features of SS consist of symptoms of encephalopathy, visual defects due to occlusion of branches of the retinal artery, and sensorineural hearing loss. The otopathology in SS has not been described.

Ear-canal reflectance, umbo velocity, and tympanometry in normal-hearing adults.

Objective: This study compares measurements of ear-canal reflectance (ECR) to other objective measurements of middle ear function including audiometry, umbo velocity (VU), and tympanometry in a population of strictly defined normal-hearing ears.

Design: Data were prospectively gathered from 58 ears of 29 normal-hearing subjects, 16 females and 13 males, aged 22 to 64 yr. Subjects met all of the following criteria to be considered as having normal hearing: (1) no history of significant middle ear disease; (2) no history of otologic surgery; (3) normal tympanic membrane on otoscopy; (4) pure-tone audiometric thresholds of 20 dB HL or better for 0.

Comparison of ear-canal reflectance and umbo velocity in patients with conductive hearing loss: a preliminary study.

Objective: The goal of the present study was to investigate the clinical utility of measurements of ear-canal reflectance (ECR) in a population of patients with conductive hearing loss in the presence of an intact, healthy tympanic membrane and an aerated middle ear. We also sought to compare the diagnostic accuracy of umbo velocity (VU) measurements and measurements of ECR in the same group of patients.

Design: This prospective study comprised 31 adult patients with conductive hearing loss, of which 14 had surgically confirmed stapes fixation due to otosclerosis, 6 had surgically confirmed ossicular discontinuity, and 11 had computed tomography and vestibular evoked myogenic potential confirmed superior semicircular canal dehiscence (SCD).

Age-related primary cochlear neuronal degeneration in human temporal bones.

In cases of acquired sensorineural hearing loss, death of cochlear neurons is thought to arise largely as a result of sensory-cell loss. However, recent studies of acoustic overexposure report massive degeneration of the cochlear nerve despite complete hair cell survival (Kujawa and Liberman, J Neurosci 29:14077-14085, 2009). To assess the primary loss of spiral ganglion cells (SGCs) in human ears, neuronal counts were performed in 100 temporal bones from 100 individuals, aged newborn to 100 years, selected to include only cases with a normal population of inner and outer hair cells.

Proteome of human perilymph.

Current diagnostic tools limit a clinician's ability to discriminate between many possible causes of sensorineural hearing loss. This constraint leads to the frequent diagnosis of the idiopathic condition, leaving patients without a clear prognosis and only general treatment options. As a first step toward developing new diagnostic tools and improving patient care, we report the first use of liquid chromatography-tandem mass-spectrometry (LC-MS/MS) to map the proteome of human perilymph.