Inner Ear Research Papers - Academia.edu (original) (raw)

Dear Editor, Cochlear implantation in congenital and acquired deafness is an approved auditory rehabilitation treatment. Malformations are of special interest nowadays, as the indication for cochlear implant surgery is expanding.... more

Dear Editor, Cochlear implantation in congenital and acquired deafness is an approved auditory rehabilitation treatment. Malformations are of special interest nowadays, as the indication for cochlear implant surgery is expanding. Inner-ear malformations constitute about 20% of congenital sensorineural hearing loss. 1 In a retrospective evaluation, we found 12% malformations in children and 3% malformations in adults. 2 In 1987, Jackler 1 presented a classification of inner-ear malformations, based on the embryological genesis. Sennaroglu and Saatci 3 suggested an extension, based on the initial classification. The basic classification distinguishes malformations of the cochlea and vestibular labyrinth, and additionally abnormalities of the internal auditory canal (IAC). This classification provides an excellent basis for detecting malformations of the inner ear. Nevertheless, it must be expanded to include malformations due to syndromes, which, in their complexity, are not simple to classify, for example innerear malformations in Mondini dysplasia, CHARGE-syndrome and X-linked deafness syndrome. We used these classifications in 29 patients as a basis for a newly developed flow chart which enabled us to preoperatively calculate adaptation of the surgical procedure according to the extent of the malformations. The description of our flow chart is based on two patients with complex malformations of the labyrinth.

The bony labyrinth provides a proxy for the morphology of the inner ear, a primary cognitive organ involved in hearing, body perception in space, and balance in vertebrates. Bony labyrinth shape variations often are attributed to... more

The bony labyrinth provides a proxy for the morphology of the inner ear, a primary cognitive organ involved in hearing, body perception in space, and balance in vertebrates. Bony labyrinth shape variations often are attributed to phylogenetic and ecological factors. Here we use three-dimensional (3D) geometric morphometrics to examine the phylogenetic and ecological patterns of variation in the bony labyrinth morphology of the most species-rich and ecologically diversified traditionally recognized superfamily of Carnivora, the Musteloidea (e.g. weasels, otters, badgers, red panda, skunks, raccoons, coatis). We scanned the basicrania of specimens belonging to 31 species using high-resolution X-ray computed micro-tomography (lCT) to virtually reconstruct 3D models of the bony labyrinths. Labyrinth morphology is captured by a set of six fixed landmarks on the vestibular and cochlear systems, and 120 sliding semilandmarks, slid at the center of the semicircular canals and the cochlea. We found that the morphology of this sensory structure is not significantly influenced by bony labyrinth size, in comparisons across all musteloids or in any of the individual traditionally recognized families (Mephitidae, Procyonidae, Mustelidae). PCA (principal components analysis) of shape data revealed that bony labyrinth morphology is clearly distinguishable between musteloid families, and permutation tests of the Kmult statistic confirmed that the bony labyrinth shows a phylogenetic signal in musteloids and in most mustelids. Both the vestibular and cochlear regions display morphological differences among the musteloids sampled, associated with the size and curvature of the semicircular canals, angles between canals, presence or absence of a secondary common crus, degree of lateral compression of the vestibule, orientation of the cochlea relative to the semicircular canals, proportions of the cochlea, and degree of curvature of its turns. We detected a significant ecological signal in the bony labyrinth shape of musteloids, differentiating semi-aquatic taxa from non-aquatic ones (the taxa assigned to terrestrial, arboreal, semiarboreal, and semi-fossorial categories), and a significant signal for mustelids, differentiating the bony labyrinths of terrestrial, semi-arboreal, arboreal, semi-fossorial and semi-aquatic species from each other. Otters and minks are distinguished from non-aquatic musteloids by an oval rather than circular anterior canal, sinuous rather than straight lateral canal, and acute rather than straight angle between the posterior and lateral semicircular canalseach of these morphological characters has been related previously to animal sensitivity for detecting head motion in space.

The vertebrate inner ear has been extensively studied as a model system of morphogenesis and differentiation. The interactions between epithelium and surrounding mesenchyme have not previously been studied directly, because an appropriate... more

The vertebrate inner ear has been extensively studied as a model system of morphogenesis and differentiation. The interactions between epithelium and surrounding mesenchyme have not previously been studied directly, because an appropriate experimental system had not been established. Here we describe a mesenchyme-free culture system of E11.5 mouse otic vesicle which retains the ability for (1) formation of the cochlear loop, (2) emigration of ganglion cells from the epithelium and (3) invagination of semicircular canal epithelium. E10.5 otic vesicle was maintained using the same method, but morphogenesis was less successful. Culture of the E11.5 cochlear region alone resulted in regeneration of a structure with semicircular canal character from the cut end, indicating that region-specific cell fate within the otic vesicle is not irreversibly determined at this stage. Co-culturing otic vesicle with cochleovestibular ganglion (CVG) resulted in enhanced looping or ectopic diverticulum formation of the cochlear region, suggesting that the CVG provides a morphogenetic signal for cochlear looping. Cochlear looping was specifically blocked by inhibiting actin polymerization by cytochalasin D, while morphogenesis of the semicircular canal region remained intact. Hyaluronidase treatment inhibited semicircular canal morphogenesis, resulting in a cystic form of the otic vesicle. These data validate this culture system as a tool for elucidating the mechanism of morphogenesis of the otic vesicle.

We describe the treatment of two patients with peripheral vestibular dysfunction using a novel, staged exercise program. Response to treatment was documented. The first patient, a 62-year-old woman with unilateral vestibular dysfunction... more

We describe the treatment of two patients with peripheral vestibular dysfunction using a novel, staged exercise program. Response to treatment was documented. The first patient, a 62-year-old woman with unilateral vestibular dysfunction (UVD) and a 6-month history of disequilibrium following herpes zoster oticus resulting in damage to the right inner ear, was treated with an 8-week course of vestibular physical therapy. During the 8 weeks, the patient attended weekly physical therapy sessions and was trained to perform vestibular adaptation exercises on a daily basis at home. The second patient, a 53-year-old woman with progressive disequilibrium secondary to profound bilateral vestibular hypofunction (BVH), was treated with a 16-week course of vestibular physical therapy. During the first 8 weeks, the patient attended weekly physical therapy sessions and was trained to perform vestibular adaptation and substitution exercises on a daily basis at home. During the second 8 weeks, the ...

Animal experiments in this laboratory have led to the suggestion that a major pathway in bone conduction stimulation to the inner ear is via the skull contents (brain and CSF). This hypothesis was now tested in humans. Auditory nerve... more

Animal experiments in this laboratory have led to the suggestion that a major pathway in bone conduction stimulation to the inner ear is via the skull contents (brain and CSF). This hypothesis was now tested in humans. Auditory nerve brainstem evoked responses could be recorded in neonates to bone conduction stimulation over the fontanelle and audiometric responses were obtained in neurosurgical patients with the bone vibrator on the skin over a craniotomy. There were no differences in threshold between these responses and those obtained to bone conduction stimulation over skull bone in the same subjects. Audiometric thresholds in response to bone vibrator stimulation of the eye (a`natural craniotomy') were no different from those to bone stimulation delivered to several sites on the head. Thus there is no need to vibrate bone in order to obtain`bone conduction' responses. Bone vibrator thresholds to stimulation at the head region with thinnest bone (temporal) were better than those to stimulation at the forehead region which has much thicker bone, implying that the vibrations penetrate the skull at the site of the vibrator. In addition, the magnitude of vibration (acceleration) measured at various sites around the head in response to bone vibrator stimulation at a fixed point on the forehead generally decreased with distance from the point of vibration. Therefore it seems that the vibrations produced by a bone vibrator at a point on the head are also able to penetrate the skull, setting up audio-frequency pressures in the CSF which spread by fluid communications to the inner ear fluids, exciting the ear. ß

Barotrauma is pressure-induced injury. The application of direct pressure to the body may cause trauma, including positive pressure from artificial ventilation. Trauma may also be caused by the effects of pressure changes on... more

Barotrauma is pressure-induced injury. The application of direct pressure to the body may cause trauma, including positive pressure from artificial ventilation. Trauma may also be caused by the effects of pressure changes on gas-containing body spaces, not in communication with the environment. This can include the external ear, the middle ear (and, indirectly, the inner ear), the para-nasal sinuses, the lungs, the gut, and abscess cavities (for example, in the teeth). Gas may penetrate tissues adjoining the affected space (such as the anterior cranial fossa, via the ethmoid sinus), or may embolise via the blood stream. The most severe expression of this is cerebral arterial gas embolism, which may present as a stroke. The management of these problems includes prevention, the use of pressure-equalizing techniques, vasoconstrictor drugs, surgery, and hyperbaric oxygen therapy.

In vertebrates (including humans) altered gravitational environments such as weightlessness can induce malfunction of the inner ears due to a mismatch between canal and statolith afferents. This leads to an illusionary tilt because the... more

In vertebrates (including humans) altered gravitational environments such as weightlessness can induce malfunction of the inner ears due to a mismatch between canal and statolith afferents. This leads to an illusionary tilt because the inputs from the inner ear are not confirmed by the other sensory organs, which then results in intersensory conflict. Vertebrates in orbit therefore face severe orientation problems. In humans the intersensory conflict may additionally lead to a malaise commonly referred to as space motion sickness (SMS). After the initial days of weightlessness the orientation problems (and SMS) disappear as the brain develops a new interpretation of the available sensory data. The present contribution reviews the neurobiological responses, particularly those of fish, observed under altered gravitational states concerning behavior and neuroplastic reactivities. Investigations employing microgravity (spaceflight, parabolic aircraft flights, clinostat) and hypergravity (laboratory centrifuges as ground-based research tools) provide insights for understanding the basic phenomena, many of which remain only incompletely explained

Hearing loss (HL) occurs in approximately 2 out of every 1,000 births and is genetic in origin in approximately 50% of cases. This high incidence coupled with the increasing number of genes implicated in HL and the trend toward universal... more

Hearing loss (HL) occurs in approximately 2 out of every 1,000 births and is genetic in origin in approximately 50% of cases. This high incidence coupled with the increasing number of genes implicated in HL and the trend toward universal newborn screening led to the establishment of the Genetics of Hearing Loss Clinic at The Children's Hospital of Philadelphia to manage the diagnosis, genetic screening, and counseling of families with an affected child. To date 500 individuals have been evaluated from 1999 to 2004. To determine the cause of their HL and screen for syndromic forms of HL, individuals were offered a panel of tests. Depending on the type and severity of the HL, recommendations included GJB2 mutation analysis, renal and thyroid function studies, a CT scan of the temporal bones, an ophthalmology evaluation, an EKG, and, at times, additional genetic tests. Of the 500 patients evaluated 70 (14%) had a syndromic etiology for their HL. Twenty-eight different syndromic etiologies were identified. Enlarged vestibular aqueducts (EVAs) and/or Mondini malformations were seen in 18% of individuals with HL who had a CT or MRI of the temporal bones. Genetic testing of the GJB2 gene was completed for 310 of the 377 patients with bilateral sensorineural HL (82.2%). Nineteen different variants were identified in the GJB2 gene. Through GJB2 mutational analysis, clinical examination, and laboratory testing, a definitive etiologic diagnosis was established in 110/500 (22%) of patients. ß 2006 Wiley-Liss, Inc.

Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often overlooked due to the absence of a speciWc diagnostic test. Furthermore, in several systemic autoimmune diseases... more

Autoimmune inner ear disease probably accounts for less than 1% of all cases of balance disorders, but its incidence is often overlooked due to the absence of a speciWc diagnostic test. Furthermore, in several systemic autoimmune diseases the vestibulo-cochlear system may be aVected. Clinical features comprise generalized imbalance, ataxia, motion intolerance, episodic vertigo and positional vertigo. An autoimmune mechanism seems to be responsible for 6% of unilateral and 16% of bilateral forms of Ménière's disease. Oscillopsia and disequilibrium secondary to a bilateral vestibular paresis are probably caused by an autoimmune response in 5% of cases. Balance disorders of central origin may be due to other immuno-mediated disorders such as multiple sclerosis, brainstem encephalitis and vasculitidis. Aim of this paper is to assess the clinical features of autoimmune vertigo disorders through a systematic literature review.

Usher syndrome type IIa (USH2A) combines moderate to severe congenital hearing impairment and retinitis pigmentosa. It is the most common genetic form of USH. USH2A encodes usherin, which was previously defined as a basement membrane... more

Usher syndrome type IIa (USH2A) combines moderate to severe congenital hearing impairment and retinitis pigmentosa. It is the most common genetic form of USH. USH2A encodes usherin, which was previously defined as a basement membrane protein. A much larger USH2A transcript predicted to encode a transmembrane (TM) isoform was recently reported. Here, we address the role of TM usherin in the inner ear. Analysis of the usherin alternative transcripts in the murine inner ear revealed the existence of several predicted TM usherin isoforms with modular ectodomains of different lengths. In addition, we identified in the usherin cytoplasmic region a predicted 24 amino acid peptide, derived from a newly defined exon that is predominantly expressed in the inner ear but not in the retina. In mouse and rat inner ears, we show that TM usherin is present at the base of the differentiating stereocilia, which make up the mechanosensitive hair bundles receptive to sound. The usherin immunolabeling is transient in the hair bundles of cochlear hair cells (HCs), but persists in mature hair bundles of vestibular HCs. Several lines of evidence support the involvement of TM usherin in the composition of the ankle links, a subset of filamentous lateral links connecting stereocilia at the base. By co-immunoprecipitation and in vitro binding assays, we establish that the usherin cytodomain can bind to whirlin and harmonin, two PDZ domain-containing proteins that are defective in genetic forms of isolated deafness and USH type I, respectively. These PDZ proteins are suitable to provide the anchoring of interstereocilia lateral links to the F-actin core of stereocilia. Our results strongly suggest that congenital deafness in USH type I and type II shares similar pathogenic mechanisms, i.e. the disruption of hair bundle links-mediated adhesion forces that are essential for the proper organization of growing hair bundles.

Background: Up to 53% of individuals suffering from traumatic brain injuries develop tinnitus. Objective: To review the current literature on trauma-associated tinnitus in order to provide orientation for the clinical management of... more

Background: Up to 53% of individuals suffering from traumatic brain injuries develop tinnitus. Objective: To review the current literature on trauma-associated tinnitus in order to provide orientation for the clinical management of patients with trauma-associated tinnitus. Materials: A systematic literature search has been conducted in PubMed database applying the search terms posttraumatic tinnitus and trauma-associated tinnitus. Results have been complemented by related studies, book chapters, and the authors' clinical experience. Results: Not only mechanical, pressure-related, or noise-related head traumata but also neck injuries and emotional trauma can cause tinnitus. Exact diagnosis is essential. Disorders such as ossicular chain disruption, traumatic eardrum perforation, or perilymphatic fistula can be surgically treated. It should also be considered that pulsatile tinnitus can be a sign of life-threatening disorders such as carotid cavernous fistulas, arteriovenous malformations, and carotid dissections. Also, posttraumatic stress disorder should be taken into consideration as a potential contributing factor. Conclusions: There is an evident mismatch between the high incidence of trauma-associated tinnitus and scarce literature on the topic. A consistent and-at best-standardized assessment of tinnitus-and hearing-related sequelae of trauma is recommended both for the improvement of clinical care and for a deeper understanding of the various pathophysiological mechanisms of trauma-associated tinnitus.

Those suffering from a severe to profound sensorineural hearing loss can obtain substantial benefit from a cochlear implant prosthesis. An electrode array implanted in the inner ear stimulates auditory nerve fibers by direct injection of... more

Those suffering from a severe to profound sensorineural hearing loss can obtain substantial benefit from a cochlear implant prosthesis. An electrode array implanted in the inner ear stimulates auditory nerve fibers by direct injection of electrical current. A major limitation of today's technology is the imprecise control of intracochlear current flow, particularly the relatively wide spread of neural excitation. A better understanding of the intracochlear electrical fields is, therefore, required. This paper analyzes the structure of intracochlear potential measurements in relation to both the subject's anatomy and to the properties of the electrode array. An electrically equivalent network is proposed, composed of small lumped circuits for the interface impedance and for the cochlear tissues. The numerical methods required to estimate the model parameters from high-quality electrical potential recordings are developed. Finally, some models are presented for subjects wearing a Clarion CII device with a HiFocus electrode and discussed in terms of model reliability.

Complications of cholesteatoma can be of a different nature from those of other otitis media. This review aims to undertake an analysis of current literature regarding management of the complications of cholesteatoma. Despite a... more

Complications of cholesteatoma can be of a different nature from those of other otitis media. This review aims to undertake an analysis of current literature regarding management of the complications of cholesteatoma. Despite a significant decline in the incidence of complications secondary to cholesteatoma in developed countries it is still a considerable problem in the developing countries. Among intratemporal complications, facial nerve paralysis and labrynthine fistula and among intracranial complications, meningitis, brain abscess and lateral sinus thrombosis are most common. In cases of facial nerve paralysis, decompression with complete disease eradication is considered to be the mainstay of treatment and usefulness of an epineural incision and the range of the decompression are still debatable. Labyrinthine fistula is commonly managed by a single staged matrix removal, followed by closure of the fistula. Partial labrynthectomy in difficult cases is gaining favor among surgeo...

Enfermedad de Ménière: desde las ciencias básicas hacia la medicina clínica. Ponencia Oficial del LX Congreso Nacional de la Sociedad Española de Otorrinolaringología Enfermedad de Ménière: desde las ciencias básicas hacia la medicina... more

Enfermedad de Ménière: desde las ciencias básicas hacia la medicina clínica. Ponencia Oficial del LX Congreso Nacional de la Sociedad Española de Otorrinolaringología Enfermedad de Ménière: desde las ciencias básicas hacia la medicina clínica

La surdité brusque est idiopathique. Elle s'installe en moins de 24 heures et régresse spontanément dans deux tiers des cas en 15 jours. L'imagerie participe à l'élimination des autres causes de surdité d'apparition brutale (schwannome... more

La surdité brusque est idiopathique. Elle s'installe en moins de 24 heures et régresse spontanément dans deux tiers des cas en 15 jours. L'imagerie participe à l'élimination des autres causes de surdité d'apparition brutale (schwannome vestibulaire, dissection des artères vertébrales, accident vasculaire cérébral [AVC]) et permet également de faire une analyse morphologique de l'oreille interne. Des études portant sur cet aspect de l'imagerie ont fourni un substrat anatomique à un nouveau concept : « l'oreille fragile ». Les anomalies morphologiques les plus souvent rencontrées touchaient, par ordre décroissant de fréquence : le canal semi-circulaire externe (hypoplasie ou dilatation), le canal semi-circulaire supérieur, le canal semi-circulaire postérieur, le vestibule et la cochlée. Notons par ailleurs qu'une dilatation de l'aqueduc du vestibule est également fréquemment rencontrée.

Among cochlear implant candidates there are patients who have abnormal middle and/or inner-ear conditions that make them unsuitable for implantation. Insertion of a foreign body may also be contraindicated in the setting of an existing or... more

Among cochlear implant candidates there are patients who have abnormal middle and/or inner-ear conditions that make them unsuitable for implantation. Insertion of a foreign body may also be contraindicated in the setting of an existing or potential intracranial communication, or when the ear is prone to infection. Five patients presented with such unfavorable conditions. These included a Mondini dysplasia with persistent cerebrospinal fluid leak, an atretic mastoid with meningocele, chronic otitis media, a transverse petrous bone fracture, and a temporal bone adenoma. All patients underwent subtotal petrosectomies and cochlear implantations. In four cases implantation was performed concomitantly with subtotal petrosectomy, while the remaining case required a twostage procedure. No complications occurred. The technique is described in detail, and the cases and the indications for surgery are discussed. By obliterating and isolating the tympanomastoid cleft from the outer environment and utilizing the technique of subtotal petrosectomy, a broader spectrum of patients can now be implanted safely.

The vertebrate otic placode is a transient embryonic structure that gives rise to the inner ear. This structure is composed of around 1000 cells where several genes are expressed in different domains. These early expression patterns... more

The vertebrate otic placode is a transient embryonic structure that gives rise to the inner ear. This structure is composed of around 1000 cells where several genes are expressed in different domains. These early expression patterns position the structures that, later on, will differentiate into diverse cell types or sensory organs necessary for hearing and balance. Experimentalists have shown that the Notch genetic network is crucial for the separation of different territories (boundary formation [1, 2]), as well as for the generation of different cell ...

Currently in physical anthropology there is a need for reliable methods of sex estimation for immature individuals and highly fragmented remains. This study develops a sex estimation technique from discriminant function analysis of the... more

Currently in physical anthropology there is a need for reliable methods of sex estimation for immature individuals and highly fragmented remains. This study develops a sex estimation technique from discriminant function analysis of the bony labyrinth as it matures before puberty and can survive taphonomic conditions that would destroy most other skeletal material. The bony labyrinth contains the organs of hearing and balance. For this reason biologists and paleoanthropologists have undertaken research in this area to understand evolutionary changes in locomotion. Prior studies have found clear differences between species, but within-species variation has not been satisfactorily investigated. 3D segmentations of the left and right labyrinths of 94 individuals from a Cretan collection were generated and measured. Mean measurements of height, width, size, and shape indices were analyzed for sexual dimorphism, bilateral asymmetry, and measurement error. Significant sexual dimorphism was detected for several measurements. For sex estimation, the single best variable was the radius of curvature of the posterior semicircular canal, which achieved 76% accuracy. Two multivariate functions increased accuracy to 84%. Although these equations are less accurate than equations for complete long bones and crania, they appear to be as accurate as or better than other techniques for sexing immature individuals and temporal bones. Am J Phys Anthropol 151:290-301, 2013.

Acoustic communication is widespread in animals. According to the sensory drive hypothesis [Endler JA (1993) Philos Trans R Soc Lond B Biol Sci 340(1292):215-225], communication signals and perceptual systems have coevolved. A clear... more

Acoustic communication is widespread in animals. According to the sensory drive hypothesis [Endler JA (1993) Philos Trans R Soc Lond B Biol Sci 340(1292):215-225], communication signals and perceptual systems have coevolved. A clear illustration of this is the evolution of the tetrapod middle ear, adapted to life on land.

Background: Paediatric cochlear implantation (PCI) requires complex case evaluation and counselling, surgical intervention, and habilitation. Outcomes vary and many cases have sub-optimal outcomes as a result of a broad spectrum of... more

Background: Paediatric cochlear implantation (PCI) requires complex case evaluation and counselling, surgical intervention, and habilitation. Outcomes vary and many cases have sub-optimal outcomes as a result of a broad spectrum of adverse influences. Objective: To systematically review the literature to identify research papers that indicate a demonstrated outcome or prognostic factor in paediatric CI, the overall aim being to develop a prognostic index for clinical use. Methods: Six main literature domains were assessed: medical/surgical; audiology; psychology; speech/language; education; and family. Search strategies were applied to appropriate databases and journals. A strict inclusion criterion was utilized. A critical appraisal tool was administered to evaluate the final eligible citations. Results: The review identified 92 citations, of which 38 were eligible. Heterogeneity in study design prevented a quantitative meta-analysis of the data. Discussion: While there are a large range of factors that impact PCI outcomes, well-constructed case control studies are limited in number and scope and relatively few demonstrated significant prognostic factors. Only four factors were identified as consistently influencing PCI outcomes: age at implantation, Connexin 26, inner ear malformations, and meningitis. Conclusion: Evaluation of relevant adverse prognostic factors in paediatric CI remains a largely unreported field. Better identification of these factors is required for improving vital pre-operative counselling and resultant surgical expectations and outcomes.

Hearing loss is the most common sensory impairment in humans and currently disables 466 million people across the world. Congenital deafness affects at least 1 in 500 newborns, and over 50% are hereditary in nature. To date, existing... more

Hearing loss is the most common sensory impairment in humans and currently disables 466 million people across the world. Congenital deafness affects at least 1 in 500 newborns, and over 50% are hereditary in nature. To date, existing pharmacologic therapies for genetic and acquired etiologies of deafness are severely limited. With the advent of modern sequencing technologies, there is a vast compendium of growing genetic alterations that underlie human hearing loss, which can be targeted by therapeutics such as gene therapy. Recently, there has been tremendous progress in the development of gene therapy vectors to treat sensorineural hearing loss (SNHL) in animal models in vivo. Nevertheless, significant hurdles remain before such technologies can be translated toward clinical use. These include addressing the blood-labyrinth barrier, engineering more specific and effective delivery vehicles, improving surgical access, and validating novel targets. In this review, we both highlight recent progress and outline challenges associated with in vivo gene therapy for human SNHL.

Objectives/Hypothesis: The objectives were to report the authors' experience with the long-term follow-up of patients with diving-related inner ear decompression sickness and inner ear barotrauma and to discuss residual cochlear and... more

Objectives/Hypothesis: The objectives were to report the authors' experience with the long-term follow-up of patients with diving-related inner ear decompression sickness and inner ear barotrauma and to discuss residual cochlear and vestibular damage in relation to the question of fitness to dive. Study Design: Retrospective consecutive case series. Methods: Eleven recreational divers with inner ear decompression sickness and nine with inner ear barotrauma (IEB) were followed. A complete otoneurological physical examination and laboratory evaluation were carried out. The latter included audiometry, electronystagmography, a rotatory chair test using the sinusoidal harmonic acceleration protocol, and computerized dynamic posturography. Results: Residual cochleovestibular deficits were found in 10 (91%) of the patients with inner ear decompression sickness and 3 (33%) of those with IEB (P < .02, Fisher's Exact test; odds ratio, 20). A significantly shorter follow-up period was required for the inner ear barotrauma group (P < .05, simple t test) because three patients (33%) recovered completely within 1 month of the diving accident. Eight patients had residual vestibular deficits on follow-up, but only one (12.5%) was symptomatic. However, five (56%) of the nine patients who had a cochlear insult, as documented by follow-up audiometry, complained of significant hearing loss and tinnitus. Conclusion: Inner ear decompression sickness carries a high risk for residual inner ear damage despite hyperbaric oxygen recompression therapy. A favorable prognosis might be anticipated for inner ear barotrauma. The finding that most patients with residual vestibular deficits were asymptomatic at the time of follow-up emphasizes the need for a complete vestibular evaluation, including specific bedside testing and laboratory examinations, before a return to diving activity may be considered.

Introduction The facial nerve follows a complex course through the skull base. Understanding its anatomy is crucial during standard skull base approaches and resection of certain skull base tumors closely related to the nerve, especially,... more

Introduction The facial nerve follows a complex course through the skull base. Understanding its anatomy is crucial during standard skull base approaches and resection of certain skull base tumors closely related to the nerve, especially, tumors at the cerebellopontine angle. Methods Herein, we review the fallopian canal and its implications in surgical approaches to the skull base. Furthermore, we suggest a new classification. Conclusions Based on the anatomy and literature, we propose that the meatal segment of the facial nerve be included as a component of the fallopian canal. A comprehensive knowledge of the course of the facial nerve is important to those who treat patients with pathology of or near this cranial nerve.

Background: The purpose of this study was to call attention to the subtemporal approach directed through the petrous apex to the IAM. We studied the microsurgical anatomy of the middle floor to delineate a reliable angle between the GSPN... more

Background: The purpose of this study was to call attention to the subtemporal approach directed through the petrous apex to the IAM. We studied the microsurgical anatomy of the middle floor to delineate a reliable angle between the GSPN and the IAM to precisely localize and expose the IAM from above. A new technique for the elevation of middle fossa floor in an anterior-to-posterior direction has also been examined in cadaveric dissections and performed in surgery. Methods: The microsurgical anatomy of the middle fossa floor was studied in 10 adult cadaveric heads (20 sides) after meatal drilling on the middle fossa. Five latex-injected specimens were dissected in a stepwise manner to further define the microsurgical anatomy of the middle fossa approach. The middle fossa approach is illustrated in a patient for the decompression of the facial nerve to demonstrate the surgical technique and limitations of bone removal. Results: Elevation of middle fossa dura in an anterior-to-posterior direction leads to early identification of the GSPN, where the nerve passes under V3. The most reliable and easily appreciated angle to be used in localizing the IAM is between the IAM and the long axis of the GSPN, which is approximately 61°. Beginning drilling the meatus medially at the petrous ridge is safer than beginning laterally, where the facial and vestibulocochlear nerves become more superficial. The cochlea anteromedially, vestibule posterolaterally, and superior semicircular canal posteriorly significantly limit the bone removal at the lateral part of the IAM. Conclusions: The surgical technique for the middle fossa approach which includes an anterior-toposterior elevation of middle fossa dura starting from the foramen ovale and uses the angle between the IAM and the long axis of the GSPN to localize the meatus from above may be an alternative to previously proposed surgical methods.

Conclusions Transient vestibular symptoms and middle ear barotraumas are common in diving. This study found no evidence of long-term vestibular effects. Vestibular disorders in divers are probably related to singular events, like inner... more

Conclusions Transient vestibular symptoms and middle ear barotraumas are common in diving. This study found no evidence of long-term vestibular effects. Vestibular disorders in divers are probably related to singular events, like inner ear barotraumas or inner ear DCI, rather than frequent diving per se.

Homing pigeons could detect extremely low frequency sounds (infrasounds) as low as 0.05 Hz in a sound isolation chamber. Classically conditioned heart rate changes were used as a behavioral measure of sensitivity. An audiogram of... more

Homing pigeons could detect extremely low frequency sounds (infrasounds) as low as 0.05 Hz in a sound isolation chamber. Classically conditioned heart rate changes were used as a behavioral measure of sensitivity. An audiogram of thresholds was determined for 13 frequencies between 0.05 Hz and 200 Hz. Below 10 Hz, the pigeons are at least 50 dB more sensitive than humans. Surgical removal of middle ear or inner ear structures reduced or eliminated the infrasound responses. Natural infrasounds come from many sources including weather patterns, topographic features, and ocean wave activity. Infrasounds propagate long distances and can be detected hundreds or even thousands of km away from their sources. These laboratory experiments are part of a series designed to find out if homing pigeons can use outdoor infrasounds as cues for orientation and navigation.

Cholesteatoma invasion into the internal auditory canal (IAC) is rare and usually results in irreversible, complete hearing loss and facial paralysis on the aVected side. This retrospective study examines the clinical characteristics of... more

Cholesteatoma invasion into the internal auditory canal (IAC) is rare and usually results in irreversible, complete hearing loss and facial paralysis on the aVected side. This retrospective study examines the clinical characteristics of seven patients with cholesteatoma invading the IAC, analyzes possible routes of the cholesteatoma's extension and describes the surgical approaches used and patient outcome. Extension to the IAC was via the supralabyrinthine route in most patients. A subtotal petrosectomy, a translabyrinthine approach or a middle cranial fossa approach combined with radical mastoidectomy were required for the complete removal of the cholesteatoma. All seven patients presented with some preoperative facial nerve palsy. The facial nerve was decompressed in four patients and facial nerve repair was performed in three others, two by hypoglossal-facial anastomosis and one by a greater auricular nerve interposition grafting. All patients ended up with total deafness in the operate ear. At 1 year following surgery, the facial nerve function was House-Brackmann grade III in six cases and grade II in one. In conclusion, cholesteatoma invading the IAC is a separate entity with characteristic clinical presentations, require a unique surgical approach, and result in signiWcant morbidity, such as total deafness in the operated ear and impaired facial movement.

Slitrks are type I transmembrane proteins that share conserved leucine-rich repeat domains similar to those in the secreted axonal guidance molecule Slit. They also show similarities to Ntrk neurotrophin receptors in their... more

Slitrks are type I transmembrane proteins that share conserved leucine-rich repeat domains similar to those in the secreted axonal guidance molecule Slit. They also show similarities to Ntrk neurotrophin receptors in their carboxy-termini, sharing a conserved tyrosine residue. Among 6 Slitrk family genes in mammals, Slitrk6 has a unique expression pattern, with strong expression in the sensory epithelia of the inner ear. We generated Slitrk6-knockout mice and investigated the development of their auditory and vestibular sensory organs. Slitrk6-deficient mice showed pronounced reduction in the cochlear innervation. In the vestibule, the innervation to the posterior crista was often lost, reduced, or sometimes misguided. These defects were accompanied by the loss of neurons in the spiral and vestibular ganglia. Cochlear sensory epithelia from Slitrk6-knockout mice have reduced ability in promoting neurite outgrowth of spiral ganglion neurons. Indeed the Slitrk6deficient inner ear showed a mild but significant decrease in the expression of Bdnf and Ntf3, both of which are essential for the innervation and survival of sensory neurons. In addition, the expression of Ntrk receptors, including their phosphorylated forms was decreased in Slitrk6-knockout cochlea. These results suggest that Slitrk6 promotes innervation and survival of inner ear sensory neurons by regulating the expression of trophic and/or tropic factors including neurotrophins from sensory epithelia.

Objectives: Identification and evaluation of prognostic factors that are associated with paediatric cochlear implantation (PCI) outcomes was the aim of this study. Methods: A retrospective review of 174 charts was performed at the Royal... more

Objectives: Identification and evaluation of prognostic factors that are associated with paediatric cochlear implantation (PCI) outcomes was the aim of this study. Methods: A retrospective review of 174 charts was performed at the Royal Children's Hospital and the Hear and Say Centre, Brisbane. This examined the possible influence of a number of variables (including age at implant, family, additional disabilities, surgical complications, gender, GJB2 mutations, meningitis, inner ear malformations, and prematurity) on outcome measures: receptive, expressive, and total language, receptive and expressive vocabulary, speech articulation and categories of auditory performance at 18-24 months post-implant. Multiple regression analysis was used to identify variables related to language and vocabulary outcomes. Results: The findings suggest that inner ear malformations and family concern are negatively associated with receptive and expressive language and receptive vocabulary scores. There was marginal evidence to suggest that increasing age at implantation was associated with lower receptive and expressive language scores. Discussion: Prognostic factors that have been adequately validated statistically include inner ear malformations, the influence of family and late age at implantation. However, this study identified a need to define better the impact of the various degrees of inner ear malformations, to particularly emphasize the role of family as a strong predictor of PCI outcomes, and to confine the study of 'age at implantation' to pre-lingually deafened children. Conclusion: Evaluation of prognostic factors is a key element in PCI. This study confirmed several factors that are strongly associated with outcomes. For better research, there is a need for universal standardized outcome measures and development of a standardized framework for recording patient data.

Some knowledge of the hearing abilities of right whales is important for understanding their acoustic communication system and possible impacts of anthropogenic noise. Traditional behavioral or physiological techniques to test hearing are... more

Some knowledge of the hearing abilities of right whales is important for understanding their acoustic communication system and possible impacts of anthropogenic noise. Traditional behavioral or physiological techniques to test hearing are not feasible with right whales. Previous research on the hearing of marine mammals has shown that functional models are reliable estimators of hearing sensitivity in marine species. Fundamental to these models is a comprehensive analysis of inner ear anatomy. Morphometric analyses of 18 inner ears from 13 stranded North Atlantic right whales (Eubalaena glacialis) were used for development of a preliminary model of the frequency range of hearing. Computerized tomography was used to create two-dimensional (2D) and 3D images of the cochlea. Four ears were decalcified and sectioned for histologic measurements of the basilar membrane. Basilar membrane length averaged 55.7 mm (range, 50.5 mm-61.7 mm). The ganglion cell density/mm averaged 1,842 ganglion cells/mm. The thickness/width measurements of the basilar membrane from slides resulted in an estimated hearing range of 10 Hz-22 kHz based on established marine mammal models. Additional measurements from more specimens will be necessary to develop a more robust model of the right whale hearing range. Anat Rec, 290:734-744, 2007Rec, 290:734-744, . 2007 Wiley-Liss, Inc.

Objectives/Hypothesis: Middle and external ear anomalies are well recognized in Down syndrome (DS, trisomy 21). Inner ear anomalies are much less frequently described. This study reviews inner ear morphology on imaging to determine the... more

Objectives/Hypothesis: Middle and external ear anomalies are well recognized in Down syndrome (DS, trisomy 21). Inner ear anomalies are much less frequently described. This study reviews inner ear morphology on imaging to determine the prevalence of cochlear and vestibular anomalies in children with DS. Study Design: The authors conducted a retrospective review of imaging features of (DS) inner ear structures. Methods: Fifty-nine sequential patients with DS with imaging of the inner ear were identified by a radiology report text search program. Quantitative biometric assessment of the inner ear was performed on patients with high-resolution computed tomography or magnetic resonance images of the petrous bone. Petrous imaging was performed for evaluation of inflammatory disease or hearing loss. Spinal imaging, which included petrous views, was performed in most cases to exclude C1 to 2 dislocation, a potential complication of DS. Measurements were compared with normative data. Results: Inner ear dysplasia is much more common in DS than previously reported. Inner ear structures are universally hypoplastic. Vestibular malformations are particularly common and a small bony island of the lateral semicircular canal (<3 mm in diameter) appears highly typical. Additional findings in some patients were persistent lateral semicircular anlage with fusion of the lateral semicircular canal and vestibule into a single cavity, vestibular aqueduct and endolymphatic sac fossa enlargement, cochlear nerve canal hypoplasia, and stenosis or duplication of the internal auditory canal. Stenosis of the external meatus, poor mastoid pneumatization, middle ear and mastoid opacification, and cholesteatoma were common, as expected. Key Words: Down syndrome, trisomy 21, inner ear dysplasia, temporal bone CT.

Purpose: To investigate the incidence of radiation-induced ototoxicity according to the total dose delivered to specific parts of the auditory system, fractionation, and chemotherapy. Methods and Materials: Records of 325 patients treated... more

Purpose: To investigate the incidence of radiation-induced ototoxicity according to the total dose delivered to specific parts of the auditory system, fractionation, and chemotherapy. Methods and Materials: Records of 325 patients treated for primary extracranial head and neck tumors with curative intent who received radiotherapy between 1964 and 2000 (median follow-up, 5.4 years) were retrospectively reviewed. Reconstructions of the treatment plans were generated to estimate the doses received by components of the auditory system. Results: Radiotherapy-induced morbidity developed in 41.8% of patients (external ear, 33.2%; middle ear, 28.6%; and inner ear, 26.8%). Univariate/multivariate analyses indicate that total dose received by parts of the auditory system seem to be significant, though fractionation and chemoradiation may contribute to the incidence of ototoxicities. Sensorineural hearing loss (SNHL) was observed in 49 patients (15.1%). Univariate and multivariate analyses indicated that age (p ‫؍‬ 0.0177 and p ‫؍‬ 0.005) and dose to cochlea (p < 0.0001 and p < 0.0001) were significant, and chemoradiation (p ‫؍‬ 0.0281 and p ‫؍‬ 0.006) may increase the incidence of SNHL.

Acute vestibular syndrome is characterized by a rapid unilateral injury to either peripheral or central vestibular structures. It consists of severe vertigo, nausea and vomiting, spontaneous nystagmus, and postural instability. In many... more

Acute vestibular syndrome is characterized by a rapid unilateral injury to either peripheral or central vestibular structures. It consists of severe vertigo, nausea and vomiting, spontaneous nystagmus, and postural instability. In many cases, a peripheral etiology is considered although it may be due to an underlying serious central pathology. The present study was designed to investigate the feasibility of differentiating the cause of acute vestibular syndrome in such patients using clinical, audiovestibular and radiologic tools. We performed a case series study of patients complaining of acute vertigo at a university referring center for hearing and balance disorders. Thirty patients with history of acute vertigo within 3 days onset with no history of previous otological or neurological disorders. Eighteen patients were due to acute peripheral vestibular lesion, 1 due to psychiatric illness under antidepressant drugs and 11 were of central vestibular lesion. The most important step in the diagnosis of acute vertigo is a thorough and detailed history. The common error of carrying out investigations in place of a detailed history is to be avoided. The clinical evaluation has the highest sensitivity and specificity in differentiating central from peripheral vestibular lesions.

The development and evolution of mechanosensory cells and the vertebrate ear is reviewed with an emphasis on delineating the cellular, molecular and developmental basis of these changes. Outgroup comparisons suggests that mechanosensory... more

The development and evolution of mechanosensory cells and the vertebrate ear is reviewed with an emphasis on delineating the cellular, molecular and developmental basis of these changes. Outgroup comparisons suggests that mechanosensory cells are ancient features of multicellular organisms. Molecular evidence suggests that key genes involved in mechanosensory cell function and development are also conserved among metazoans.

The objective of this retrospective study is to evaluate the efficiency of hyperosmolar therapy for cerebrum spinal fluid (CSF) leakage in cochlear implant (CI) surgery in children with inner ear malformations. Between 1991 and 2006, 490... more

The objective of this retrospective study is to evaluate the efficiency of hyperosmolar therapy for cerebrum spinal fluid (CSF) leakage in cochlear implant (CI) surgery in children with inner ear malformations. Between 1991 and 2006, 490 cochlear implantations were performed in Armand Trousseau Children's Hospital. Thirty-seven patients (7.5%) had inner ear malformation. They were classified as isolated enlargement of the vestibular aqueduct (EVA) (18 cases), incomplete partition (IP) (11 cases), common cavity (CC) (1 case) and variable canal and vestibular malformations (VSCC) (7 cases). A hyperosmolar protocol was applied during surgery to 13 patients after 2003 (Gp) to be compared to the 24 patients without treatment previously to this date (G0). Mean age at implant CI was 8.1 years (1-20 years), mean follow up was 3.9 years (1 month-15 years). Per operative observations were collected for all patients with an empiric method of evaluation of the leakage. A grading using five steps ranged from Grade 0 (no leak) to Grade 4 (gusher). Grading, complications and perceptive results in closed and open set word (Lafon lists) at respectively preoperatively, at 3 and 24 months were gathered and compared between the two groups. Important per operative leak was observed (Grade 4) in 24.3% cases (9/37) of Grade 4, 88.8% of them in G0 (8/9). In 66.6% cases there was a severe dysplasia (CC or IP) (6/9), to be compared to the 21.4% of cases of severe dysplasia with Grade < 3 (6/28) ( p = 0.02). Grade 4 was seen in 45% cases of IP (5/11); it represented 33.3% of the IP in Gp (1/3), and 50% of the IP in G0 (4/8) ( p > 0.05). Grade 4 was seen in 16.6% cases of EVA (3/18); there were no Grade 4 observed in Gp (0/10), and 37.5% cases of EVA in G0 (3/8) ( p = 0.04). Grade 4 was observed in 100% case in CC in the G0 (1/1). Severe complications were misplacement of the electrode in one case (G0), persistent leakage in one case (G0) and meningitis in one case (Gp). Vertigo was observed in 29.7% of cases (11/37) in this population, 72.7% of them in G0 * Corresponding author at: Service d'Oto-rhino-laryngologie et de chirurgie cervico-faciale, Hôpital d'enfants Armand-Trousseau,

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that... more

The human Usher syndrome (USH) is the most frequent cause of combined hereditary deaf-blindness. USH is genetically heterogeneous with at least 11 chromosomal loci assigned to 3 clinical types, USH1-3. We have previously demonstrated that all USH1 and 2 proteins in the eye and the inner ear are organized into protein networks by scaffold proteins. This has contributed essentially to our current understanding of the function of USH proteins and explains why defects in proteins of different families cause very similar phenotypes. We have previously shown that the USH1G protein SANS (scaffold protein containing ankyrin repeats and SAM domain) contributes to the periciliary protein network in retinal photoreceptor cells. This study aimed to further elucidate the role of SANS by identifying novel interaction partners. In yeast two-hybrid screens of retinal cDNA libraries we identified 30 novel putative interacting proteins binding to the central domain of SANS (CENT). We confirmed the direct binding of the phosphodiesterase 4D interacting protein (PDE4DIP), a Golgi associated protein synonymously named myomegalin, to the CENT domain of SANS by independent assays. Correlative immunohistochemical and electron microscopic analyses showed a co-localization of SANS and myomegalin in mammalian photoreceptor cells in close association with microtubules. Based on the present results we propose a role of the SANS-myomegalin complex in microtubule-dependent inner segment cargo transport towards the ciliary base of photoreceptor cells. j o u r n a l h o m e p a g e : w w w. e l s ev i e r. c o m / l o c a t e / b b a m c r

The positional cues for formation of individual inner ear components are dependent on pre-established axial information conferred by inductive signals from tissues surrounding the developing inner ear. This review summarizes some of the... more

The positional cues for formation of individual inner ear components are dependent on pre-established axial information conferred by inductive signals from tissues surrounding the developing inner ear. This review summarizes some of the known molecular pathways involved in establishing the three axes of the inner ear, anterior-posterior (AP), dorsal-ventral (DV) and medial-lateral (ML). Signals required to establish the AP axis of the inner ear are not known, but they do not appear to be derived from the hindbrain. In contrast, the hindbrain is essential for establishing the DV axis of the inner ear by providing inductive signals such as Wnts and Sonic hedgehog. Signaling from the hindbrain is also required for the formation of the ML axis, whereas formation of the lateral wall of the otocyst may be a result of first establishing both the AP and DV axes. In addition, this review addresses how genes induced within the otic epithelium as a result of axial specification continue to mediate inner ear morphogenesis.

In this case report we describe a patient with agenesis of the corpus callosum and asymmetric bilateral sensorineural hearing loss, who was found to have a bilateral inner ear dysplasia. Both of these anomalies have been associated with... more

In this case report we describe a patient with agenesis of the corpus callosum and asymmetric bilateral sensorineural hearing loss, who was found to have a bilateral inner ear dysplasia. Both of these anomalies have been associated with different members of the Pax gene family. However, to our knowledge this is the first report demonstrating the coexistence of these two unusual entities. By uncovering the inner ear malformation, we are able to better counsel this patient with regard to avoidance of high-risk activities such as contact sports and recommend prophylactic vaccination for meningitis prevention.

Magnetic fields have the potential to noninvasively direct and focus therapy to disease targets. External magnets can apply forces on drug-coated magnetic nanoparticles, or on living cells that contain particles, and can be used to... more

Magnetic fields have the potential to noninvasively direct and focus therapy to disease targets. External magnets can apply forces on drug-coated magnetic nanoparticles, or on living cells that contain particles, and can be used to manipulate them in vivo. Significant progress has been made in developing and testing safe and therapeutic magnetic constructs that can be manipulated by magnetic fields. However, we do not yet have the magnet systems that can then direct those constructs to the right places, in vivo, over human patient distances. We do not yet know where to put the external magnets, how to shape them, or when to turn them on and off to direct particles or magnetized cells-in blood, through tissue, and across barriers-to disease locations. In this article, we consider ear and eye disease targets. Ear and eye targets are too deep and complex to be targeted by a single external magnet, but they are shallow enough that a combination of magnets may be able to direct therapy t...

Anxiety states and disorders amplify the symptoms and impairment associated with vestibular dysfunction. Five patients with inner ear vestibular dysfunction and anxiety were prospectively treated with fluoxetine, 20-60 mg/day, and... more

Anxiety states and disorders amplify the symptoms and impairment associated with vestibular dysfunction. Five patients with inner ear vestibular dysfunction and anxiety were prospectively treated with fluoxetine, 20-60 mg/day, and received an extensive battery of assessments at baseline and after 12 weeks of treatment. Fluoxetine led to significant or near significant reductions in anxiety measures and in impairment due to dizziness; improvements in clinical balance function and vestibular function were less clear. The data add to the literature suggesting a role for selective serotonin reuptake inhibitors in the treatment of dizziness and anxiety.

Thus, these two neurotrophins and their associated receptors have been shown to be absolutely necessary for the normal development of afferent innervation of the inner ear. Current research efforts are testing the therapeutic potential... more

Thus, these two neurotrophins and their associated receptors have been shown to be absolutely necessary for the normal development of afferent innervation of the inner ear. Current research efforts are testing the therapeutic potential for neurotrophins to treat hearing loss.

Two bilaterally deaf and three unilaterally deaf pups were identified from a litter of 10 Dogo Argentino pups presented for hearing evaluation by electrophysiological investigation. One pup, a bilaterally deaf female aged 43 days, was... more

Two bilaterally deaf and three unilaterally deaf pups were identified from a litter of 10 Dogo Argentino pups presented for hearing evaluation by electrophysiological investigation. One pup, a bilaterally deaf female aged 43 days, was available for histopathology. Examination of both inner ears revealed bilateral cochlear degeneration with atrophy of the stria vascularis, collapse of the cochlear duct, degeneration of the organ of Corti, and abnormal tectorial membrane. The left vestibule, including the sacculus, was normal. The spiral and vestibular ganglia were essentially normal. This is the first histopathological description of lesions associated with deafness in a Dogo Argentino, but abnormalities were similar to those previously described in deaf Dalmatian pups and in other white hair-coated breeds. The defect was classified as a cochleosaccular degeneration. It was probably congenital and genetic causes were suspected.