Computed tomography in the diagnosis of exudative otitis media

Temporal bone computed tomography (CT) was used to examine 37 patients aged 2 to 55 years who had exudative otitis media; in 27 patients of them, a pathological process was bilateral. An analysis of 58 temporal bone CT scans identified the CT signs of chronic exudative otitis media. These included a partial or complete block of the osseous foramen of the auditory tube; impaired pneumatization of the tympanic cavity, mastoid process fenestrae, and antrum; pathological drawing-in of the tympanic membrane. The preservation of the auditory ossicles and the absence of destructive changes in the walls of the cavities of the middle ear were observed in most cases. Repeated temporal bone CT study was performed in 10 patients (14 temporal bones) in different periods (from 2 months to 3 years) after surgery. The results of tympanostomy were visually assessed. These included recovered pneumatization of middle ear cavities (7 temporal bones), a cicatricial process in the tympanic cavity (5 temporal bones), recurrence of the CT manifestations of exudative otitis media (2 temporal bones).     

Potentialities of temporal bone computed tomography in the identification of causes of hypoacusis of postinflammatory genesis

Temporal bone computed tomography (CT) was used to examine 64 patients with impaired hearing due to inflammatory diseases of the middle year. In 21 patients, the pathological process was bilateral. A total of 85 series of temporal bone CT scans were analyzed. The patients' age ranged from 2 to 66 years. CT verified adhesive otitis media in 62 cases, otosclerosis in 7, local malformation of the auditory ossicles and/or the labyrinthine fenestrae in 11. No CT changes were revealed in 5 cases. The CT symptoms of adhesive otitis media were identified. These included soft tissue bands and/or soft tissue-density portions that fix the auditory ossicles or block the niches of the labyrinthine fenestrae (31 temporal bones); sclerosis or ossification of the ligaments and tendons of the middle ear (7 temporal bones); calcification foci in the tympanic cavity (9 cases); osteosclerotic changes in the epitympanus (2 cases); cicatricial changes in the tympanic membrane (24 cases); destructive changes in the auditory ossicles (19 temporal bones). There has been evidence that CT may be used for the differential diagnosis of adhesive otitis media from otosclerosis and congenital malformations of the structures of the middle ear.     

Potentialities of temporal bone CT in the diagnosis of chronic purulent otitis media and its complications

Temporal bone CT was used to examine a group of 87 patients with chronic purulent otitis media (103 temporal bones). The patients' age ranged from 2 to 74 years. A scheme was developed and proposed to evaluate the temporal bone by CT. The CT signs of chronic purulent otitis media uncomplicated by cholesteatoma and those of cholesteatomic purulent otitis were identified. The CT symptomatology of chronic purulent otitis includes: sclerotic changes in the bone tissue of the mastoid process, impaired pneumatization of the cavities of the middle ear, including the tympanic cavity, destructive changes in auditory ossicles, carious changes in the walls of the cavities of the middle ear. The CT semiotics of cholesteatoma depends on its site and spread into the temporal bone and includes as follows: deformation of the epitympanum due to soft tissue mass-induced destruction of the lateral wall; the dilated entrance into the antrum; the presence of a cavity with the sclerosed walls in the antromastoid area; carious changes in the auditory ossicles; the displacement of a chain of ossicles medially or laterally in relation to the initial site of cholesteatoma. CT reflects carious changes in the walls of the cavities of the middle ear, including the roof and labyrinthine wall of the tympanum, which allows labyrinthine fistula and intracranial cholesteatomic complications. The study of the temporal bone by the proposed scheme may reveal anomalies and the specific features of its structure: the presentation of the sigmoid sinus, the high elevation of the bulb of the jugular vein, diverticulum of the latter, the low standing of the bottom of the ACH.     

Auditory rehabilitation

Auditory rehabilitation depends of the cause and the severity of the hearing loss (or deafness). Hearing losses dues to middle ear pathologies can beneficiate of medical or surgical treatments, by ossicular prostheses, if it is necessary to restore the function of the ossicles chain. In the sensorineural hearing losses, with inner ear pathology, the use of auditory aid is immediately considered. In the cases for which they are insufficient because of severity of the hearing loss or not suitable because of local non-tolerance, it is possible to use middle ear implant or cochlear implant. The indications of the auditory brainstern implants remain at this day limited to the total bilateral hearing losses due to a complete destruction of cochleae and auditory nerves. These therapeutic orientations are selected after a multidisciplinary evaluation of the deaf person, evaluation that allows the characterization of the hearing loss and its repercussion. In all the cases, the restoration of a bilateral hearing has to be done if possible, making an improvement of the speech comprehension, mainly in the noisy situations, as well as the localization of the sound sources.     

Structure and development of cochlear afferent innervation in mammals

In mammals, sensorineural deafness results from damage to the auditory receptors of the inner ear, the nerve pathways to the brain or the cortical area that receives sound information. In this review, we first focused on the cellular and molecular events taking part to spiral ganglion axon growth, extension to the organ of Corti, and refinement. In the second half, we considered the functional maturation of synaptic contacts between sensory hair cells and their afferent projections. A better understanding of all these processes could open insights into novel therapeutic strategies aimed to re-establish primary connections from sound transducers to the ascending auditory nerve pathways.     

The protective effects of systemic dexamethasone on sensory epithelial damage and hearing loss in targeted Cx26-null mice

Mutations in the GJB2 gene (encoding Connexin26(Cx26)) are the most common cause of hereditary deafness, accounting for about a quarter of all cases. Sensory epithelial damage is considered to be one of the main causes of deafness caused by GJB2 gene mutation. Dexamethasone (DEX) is widely used in the treatment of a variety of inner ear diseases including sudden sensorineural hearing loss (SSNHL), noise-induced hearing loss (NIHL), and deafness caused by ototoxic drugs. Whether DEX has a direct therapeutic effect on hereditary deafness, especially GJB2-related deafness, remains unclear. In this study, we revealed that DEX can effectively prevent hair cell death caused by oxidative stress in cochlear explants. Additionally, two distinct Cx26-null mouse models were established to investigate whether systemic administration of DEX alleviate the cochlear sensory epithelial injury or deafness in these models. In a specific longitudinally Cx26-null model that does not cause deafness, systemic administration of DEX prevents the degeneration of outer hair cells (OHCs) induced by Cx26 knockout. Similarly, in a targeted-Deiter’s cells (DCs) Cx26-null mouse model that causes deafness, treatment with DEX can almost completely prevent OHCs loss and alleviates auditory threshold shifts at some frequencies. Additionally, we observed that DEX inhibited the recruitment of CD45-positive cells in the targeted-DCs Cx26-null mice. Taken together, our results suggest that the protective effect of dexamethasone on cochlear sensory epithelial damage and partially rescue auditory function may be related to the regulation of inner ear immune response in Cx26 deficiency mouse models.Subject terms: Neurological disorders, Cell death     

Atrophic thyroid follicles and inner ear defects reminiscent of cochlear hypothyroidism in Slc26a4-related deafness

Thyroid hormone is essential for inner ear development and is required for auditory system maturation. Human mutations in SLC26A4 lead to a syndromic form of deafness with enlargement of the thyroid gland (Pendred syndrome) and non-syndromic deafness (DFNB4). We describe mice with an Slc26a4 mutation, Slc26a4 ^loop/loop , which are profoundly deaf but show a normal sized thyroid gland, mimicking non-syndromic clinical signs. Histological analysis of the thyroid gland revealed defective morphology, with a majority of atrophic microfollicles, while measurable thyroid hormone in blood serum was within the normal range. Characterization of the inner ear showed a spectrum of morphological and molecular defects consistent with inner ear pathology, as seen in hypothyroidism or disrupted thyroid hormone action. The pathological inner ear hallmarks included thicker tectorial membrane with reduced β-tectorin protein expression, the absence of BK channel expression of inner hair cells, and reduced inner ear bone calcification. Our study demonstrates that deafness in Slc26a4 ^loop/loop mice correlates with thyroid pathology, postulating that sub-clinical thyroid morphological defects may be present in some DFNB4 individuals with a normal sized thyroid gland. We propose that insufficient availability of thyroid hormone during inner ear development plays an important role in the mechanism underlying deafness as a result of SLC26A4 mutations.     

A family with X-linked deafness showing linkage to the proximal Xq region of the X chromosome

Linkage analysis has been carried out in a family with severe congenital sensorineural deafness with a structural abnormality of the inner ear. Recombinations show the gene responsible for deafness in this family to lie between the loci DXS255 (Xp11.22) and DXS94 (Xq22). Close linkage was found to locus DXS159 (cpX289) in Xq12, with a LOD score of 3.155 and 0 recombination. This location is consistent with other linkage studies of X-linked deafness.     

Diffusion Tensor Imaging of the Auditory Neural Pathway for Clinical Outcome of Cochlear Implantation in Pediatric Congenital Sensorineural Hearing Loss Patients

Although conventional structural MRI provides vital information in the evaluation of congenital sensorineural hearing loss (SNHL), it is relatively insensitive to white matter microstructure. Our objective was to evaluate possible changes in microstructure of the auditory pathway in children with congenital sensorineural hearing loss (SNHL), and the possible distinction between good and poor outcome of cochlear implantation (CI) patients by using diffusion tensor imaging (DTI). Twenty-four patients with congenital SNHL and 20 healthy controls underwent conventional MRI and DTI examination using a 1.5T MR scanner. The DTI metrics of fractional anisotropy (FA) and mean diffusivity (MD) of six regions of interest (ROIs) positioned along the auditory pathway—the trapezoid body, superior olivary nucleus, inferior colliculus, medial geniculate body, auditory radiation and white matter of Heschl''s gyrus—was measured in all subjects. Among the 24 patients, 8 patients with a categorie of auditory performance (CAP) score over 6 were classified into the good outcome group, and 16 patients with a CAP score below 6 were classified into the poor outcome group. A significant decrease was observed in FA values while MD values remained unchanged at the six ROIs of SNHL patients compared with healthy controls. Compared to good outcome subjects, poor outcome subjects displayed decreased FA values at all of the ROIs. No changes were observed in MD values. Correlation analyses only revealed strong correlations between FA values and CAP scores, and strong correlations between CAP scores and age at implant were also found. No correlations of FA values with age at implant were observed. Our results show that preoperative DTI can be used to evaluate microstructural alterations in the auditory pathway that are not detectable by conventional MR imaging, and may play an important role in evaluating the outcome of CI. Early cochlear implantation might be more effectively to restore hearing in SNHL patients.     

Phosphatidylinositol 4-kinase β mutations cause nonsyndromic sensorineural deafness and inner ear malformation

Congenital hearing loss is a common disorder worldwide. Heterogeneous gene variation accounts for approximately 20–25% of such patients. We investigated a five-generation Chinese family with autosomal-dominant nonsyndromic sensorineural hearing loss (SNHL). No wave was detected in the pure-tone audiometry, and the auditory brainstem response was absent in all patients. Computed tomography of the patients, as well as of two sporadic SNHL cases, showed bilateral inner ear anomaly, cochlear maldevelopment, absence of the osseous spiral lamina, and an enlarged vestibular aqueduct. Such findings were absent in nonaffected persons. We used linkage analysis and exome sequencing and uncovered a heterozygous missense mutation in the PI4KB gene (p.Gln121Arg) encoding phosphatidylinositol 4-kinase β (PI4KB) from the patients in this family. In addition, 3 missense PI4KB (p.Val434Gly, p.Glu667Lys, and p.Met739Arg) mutations were identified in five patients with nonsyndromic SNHL from 57 sporadic cases. No such mutations were present within 600 Chinese controls, the 1000 genome project, gnomAD, or similar databases. Depleting pi4kb mRNA expression in zebrafish caused inner ear abnormalities and audiosensory impairment, mimicking the patient phenotypes. Moreover, overexpression of 4 human missense PI4KB mutant mRNAs in zebrafish embryos resulted in impaired hearing function, suggesting dominant-negative effects. Taken together, our results reveal that PI4KB mutations can cause SNHL and inner ear malformation. PI4KB should be included in neonatal deafness screening.     

The effects of cetrimide and potassium bromate on the potassium ion concentration in the inner ear fluid of the guinea-pig

The mammalian inner ear is located deep within the temporal bone. The organ of Corti, the delicate sensory system for sound, is surrounded by two fluid systems; the potassium-rich endolymph and the sodium-rich perilymph. The pathogenesis of inner ear deafness is thought to be largely due to an imbalance of potassium and sodium ions in the inner ear fluids. Dynamic changes in K+ in the endolymph and perilymph were studied in the guinea-pig following cetrimide (cetrimonium bromide, a powerful cationic detergent which shows ototoxicity) applications on the round window membrane, intramuscular injection of potassium bromate (bread whitener, known to cause renal damage and permanent deafness in animals and man). Maximum fall in K+ concentration in the endolymoh (mM/min) and maximum K+ conductance (mM/min/mV) were 3.54 +/- 1.65 and 0.036 +/- 0.02 in cetrimide, and 1.85 +/- 0.35 and 0.021 +/- 0.009 in potassium bromate, respectively. In view of these findings, the influence of the active transport mechanism to K+ concentrations are discussed in comparison with dynamic changes in endolymph K+ induced by asphyxia and ethacrynic acid.     

A compendium of mouse knockouts with inner ear defects

Genetically engineered strains of mice, modified by gene targeting (knockouts), are increasingly being employed as alternative effective research tools in elucidating the genetic basis of human deafness. An impressive array of auditory and vestibular mouse knockouts is already available as a valuable resource for studying the ontogenesis, morphogenesis and function of the mammalian inner ear. This article provides a current catalog of mouse knockouts with inner ear morphogenetic malformations and hearing or balance deficits resulting from ablation of genes that are regionally expressed in the inner ear and/or within surrounding tissues, such as the hindbrain, neural crest and mesenchyme.     

Targeted ablation of connexin26 in the inner ear epithelial gap junction network causes hearing impairment and cell death

Mutations in the gene encoding the gap junction protein connexin26 (Cx26) are responsible for the autosomal recessive isolated deafness, DFNB1, which accounts for half of the cases of prelingual profound hereditary deafness in Caucasian populations. To date, in vivo approaches to decipher the role of Cx26 in the inner ear have been hampered by the embryonic lethality of the Cx26 knockout mice. To overcome this difficulty, we performed targeted ablation of Cx26 specifically in one of the two cellular networks that it underlies in the inner ear, namely, the epithelial network. We show that homozygous mutant mice, Cx26(OtogCre), have hearing impairment, but no vestibular dysfunction. The inner ear developed normally. However, on postnatal day 14 (P14), i.e., soon after the onset of hearing, cell death appeared and eventually extended to the cochlear epithelial network and sensory hair cells. Cell death initially affected only the supporting cells of the genuine sensory cell (inner hair cell, IHC), thus suggesting that it could be triggered by the IHC response to sound stimulation. Altogether, our results demonstrate that the Cx26-containing epithelial gap junction network is essential for cochlear function and cell survival. We conclude that prevention of cell death in the sensory epithelium is essential for any attempt to restore the auditory function in DFNB1 patients.     

The ESF meeting on "The proteomics, epigenetics and pharmacogenetics of pendrin"

Human pendrin (SCL26A4, PDS) is a 780 amino acid integral membrane protein with transport function. It acts as an electroneutral, sodium-independent anion exchanger for a wide range of anions, such as iodide, chloride, formate, bicarbonate, hydroxide and thiocyanate. Pendrin expression was originally described in the thyroid gland, kidney and inner ear. Accordingly, pendrin mutations with reduction or loss of transport function result in thyroid and inner ear abnormalities, manifested as syndromic (Pendred syndrome) and non-syndromic hearing loss with an enlarged vestibular aqueduct (ns-EVA). Pendred syndrome, the most common form of syndromic deafness, is an autosomal recessive disease characterized by sensorineural deafness due to inner ear malformations and a partial iodide organification defect that may lead to thyroid goiter. Later, it became evident that not only pendrin loss of function, but also up-regulation could participate in the pathogenesis of human diseases. Indeed, despite the absence of kidney dysfunction in Pendred syndrome patients, evidence exists that pendrin also plays a crucial role in this organ, with a potential involvement in the pathogenesis of hypertension. In addition, recent data underscore the role of pendrin in exacerbations of respiratory distresses including bronchial asthma and chronic obstructive pulmonary disease (COPD). Pendrin expression in other organs such as mammary gland, testis, placenta, endometrium and liver point to new, underscored pendrin functions that deserve to be further investigated.     

Conditional deletion of calcium-modulating cyclophilin ligand causes deafness in mice

Calcium-modulating cyclophilin ligand (Caml) is a ubiquitously expressed cytoplasmic protein that is involved in multiple signaling and developmental pathways. An observation in our laboratory of a protein-protein interaction between Caml and the cytoplasmic region of Cadherin23 led us to speculate that Caml might be important in the inner ear and play a role in the development and/or function of hair cells. To address this question, we generated a mouse line in which Caml expression was eliminated in Atoh1-expressing cells of the inner ear upon administration of tamoxifen. Tamoxifen was administered immediately after birth to neonates to assess the effect of loss of Caml in the inner ear during postnatal development. Hearing in treated animals was tested by auditory brain stem response (ABR) analysis and cochlear pathology was evaluated by light microscopy. Lack of Caml expression in the inner ear leads to severe loss of cochlear hair cells and complete deafness. Elucidating the role of Caml in the inner ear will aid our understanding of the molecular pathways important for auditory development and function.     

The effect of the mtDNA4834 deletion on hearing

Mutations in mitochondrial DNA (mtDNA) are associated with diverse pathological states in humans, notably sensorineural deafness. In humans, mtDNA4977 deletion, known as common deletion, is thought to play a critical role in presbyacusis. A similar mtDNA deletion occurs in the naturally aging rats is mtDNA4834 deletion. Today, it is still obscure about the effect of common mtDNA deletion on the presbyacusis and hearing loss. We establish a model of rat associated with mtDNA4834 deletion in inner ear by d-galactose. It was found that the malondialdehyde (MDA) increased with superoxide dismutase (SOD) decreasing in the inner ear of the rat treated with d-galactose than of the control. However, there was no significant difference in elevation of ABR threshold between the rat with mtDNA4834 deletion induced by d-galactose and control. After aminoglycoside antibiotic injected, the hearing threshold of the rats carrying mtDNA4834 deletion increased significantly compared with the rats without mtDNA4834 deletion. The results show that resembled accelerated aging in the inner ear of the rat could be induced by injecting d-galactose. Moreover, those suggest that mtDNA4834 deletion can not directly induce the hearing loss, but acting as a predisposing factor which can greatly enhance the sensitivity of the inner ear to the aminoglycoside antibiotic.     

Missing mitochondrial Mpv17 gene function induces tissue-specific cell-death pathway in the degenerating inner ear

The Mpv17 gene encodes a mitochondrial inner-membrane protein that has been implicated in the metabolism of reactive oxygen species. The loss of function in Mpv17-/- mice leads to early sensorineural deafness associated with severe inner ear degeneration and late onset of kidney failure. The present study demonstrates that the onset of the degeneration of the cochlear neuroepithelia is related to the onset of auditory function and appears to be first restricted to the outer hair cells (OHC), which subsequently undergo rapid degeneration. At the age of 18 days, the OHC lateral membrane degenerates and extensive vacuolization of the cytoplasm is followed by lysis of the OHCs. Such degenerative processes have been seen for the first time in relation to auditory dysfunction. The structural degeneration pattern of the OHC appears to be similar to the described paraptotic processes (an alternative form of programmed cell death) discussed in the literature as a cause of cytoplasmic neurodegeneration. In contrast, the melanocyte-like intermediate cells that are of neural crest origin and that are located in the stria vascularis, undergo apoptosis, as documented ultrastructurally. A lack of Mpv17 protein function in mitochondria thus seems to initiate tissue-specific cell-death pathways resulting in the pathology seen during the degeneration process.