Auditory profiling and hearing-aid satisfaction in hearing-aid candidates.

INTRODUCTION: Hearing-impaired (HI) listeners often complain about difficulties communicating in the presence of background noise, although audibility may be restored by a hearing-aid (HA). The audiogram typically forms the basis for HA fitting, i.e. people with similar audiograms are given the same prescription by default. This study aimed at identifying clinically relevant tests that may serve as an informative addition to the audiogram and which may relate more directly to HA satisfaction than the audiogram does. METHODS: A total of 29 HI and 26 normal-hearing listeners performed tests of spectral and temporal resolution, binaural hearing, speech intelligibility in stationary and fluctuating noise and a working-memory test. Six weeks after HA fitting, the HI listeners answered a questionnaire evaluating HA treatment. RESULTS: No other measures than masking release between fluctuating and stationary noise correlated significantly with audibility. The HI listeners who obtained the least advantage from fluctuations in background noise in terms of speech intelligibility experienced greater HA satisfaction. CONCLUSION: HI listeners have difficulties in different hearing domains that are not predictable from their audiogram. Measures of temporal resolution or speech perception in both stationary and fluctuating noise could be relevant measures to consider in an extended auditory profile. FUNDING: The study was supported by Grosserer L.F. Foghts Fond. TRIAL REGISTRATION: The protocol was approved by the Science Ethics Committee of the Capital Region of Denmark (reference H-3-2013-004).

The middle ear immune defense changes with age.

Otitis media is a common disease in childhood. In adults, the disease is relatively rare, but more frequently associated with complications. Possible reasons for this discrepancy are age-related differences in pathogen exposure, anatomy of the Eustachian tube and immune system. The objective of this study was to analyze the relationship between age and the mucosal immune system in the middle ear. It is hypothesized that genes involved in the middle ear immune system will change with age. A comprehensive assessment of these genetic differences using the techniques of complementary DNA has not been performed. Complementary DNA microarray technology was used to identify immune-related genes differentially expressed between the normal middle ear mucosa of young (10 days old) and adult rats (80 days old). Data were analyzed using tools of bioinformatics. A total of 260 age-related genes were identified, of which 51 genes were involved in the middle ear mucosal immune system. Genes related to the innate immune system, including alpha-defensin, calcium-binding proteins S100A9 and S100A8, were upregulated in young rats, whereas genes related to the adaptive immune system, including CD3 molecules, zeta-chain T-cell receptor-associated protein kinase and linker of activated T-cells, were upregulated in the adult. This study concludes that the normal middle ear immune system changes with age. Genes related to the innate immune system are upregulated in young rats, whereas genes related to the adaptive immune system are upregulated in adults.

[Vestibular migraine]. / Vestibulær migræne.

Dizziness caused by migraine, vestibular migraine (VM), has been highly debated over the last three decades. The co-morbidity of migraine and dizziness is higher than a random concurrence. One third of the patients with migraine and dizziness have VM. Recently, The International Headache Society approved VM as a diagnostic entity and the diagnostic criteria for VM appear in the appendix for The International Classification of Headache Disorders. VM is common but often underdiagnosed. Treatment follows migraine management guidelines although evidence is sparse.

Auto-inflammatory challenge of the endolymphatic sac--Cochlear damage measured by distortion product oto-acoustic emissions.

CONCLUSION: Twenty-five rats were challenged by an immunologic attack of the endolymphatic sac. After 6 months, distortion product oto-acoustic emissions (DPOAE) revealed a dysfunction of the outer hair cells and immunological active cells were observed in the endolymphatic sac. This information could contribute to the understanding of Ménière's disease. OBJECTIVES: This study investigated if an autoimmune challenge of the endolymphatic sac could affect DPOAE output measurements in rats. Also, a potential autoimmune cell infiltration of the endolymphatic sac was investigated. METHODS: Eighteen Lewis rats were immunized with a crude endolymphatic sac extract in complete Freund's adjuvant. Seven control animals were injected with Freund's adjuvant in saline. Cochlear damage was estimated by DPOAE dynamics 3 weeks and 6 months after the immunization. Infiltrative cells in the endolymphatic sac were investigated with transmission electron microscopy. RESULTS: The hearing assessment 6 months after immunization revealed a reduction of the DPOAE, on the full range of frequencies (2-63 kHz) in an average of the mean, of 2 dB ± 1.1 in the immunized group compared to the controls (p < 0.05). The same test showed a 2.5 dB decrease from 2 to 5 kHz (p < 0.01). Immunological active cells were observed in the endolymphatic sac in most of the immunized rats.

Labyrinthitis Ossificans: On the Mechanism of Perilabyrinthine Bone Remodeling.

INTRODUCTION: It has been suggested that remodeling of the otic capsule is highly suppressed by the action of anti-resorptive signals emanating from structures of the inner ear space. Labyrinthitis ossificans (LO) is a severe complication to bacterial meningitis and is characterized by destruction of inner ear structures by the formation of new bone. The aim of this study was to explore the impact of LO on bone remodeling of the otic capsule. MATERIAL AND METHODS: In 11 human temporal bones with extensive LO and 10 control specimens, the degree of bone remodeling was explored indirectly by estimating the viability of osteocytes in perilabyrinthine bone and the mastoid. RESULTS: The viability of osteocytes was significantly lower in the perilabyrinthine bone compared to the mastoid in both groups. However, the loss of perilabyrinthine osteocytes was the same in the 2 groups, and the presence of cartilage remnants appeared to be the same. CONCLUSION: This study indicates that the factors affecting bone remodeling of the otic capsule and the degeneration of osteocytes are not altered by wholesale destruction of inner ear soft tissue and its replacement by bone. Therefore, alternative mechanisms may be implicated in the suppression of capsular bone remodeling.

Differential gene expression in the otic capsule and the middle ear--an annotation of bone-related signaling genes.

HYPOTHESIS: A number of bone-related genes may be responsible for the unique suppression of perilabyrinthine bone remodeling. BACKGROUND: Bone remodeling is highly inhibited around the inner ear space most likely because of osteoprotegerin (OPG), which is a well-known potent inhibitor of osteoclast formation and function. However, other signaling molecules may also be responsible for the inhibition of bone remodeling within the otic capsule. METHODS: Microarray technology was used to determine bone-related genes differentially expressed between the lining tissues of the otic capsule (spiral ligament and stria vascularis) and the lining tissues from the middle ear of the rat. Data was analyzed with statistical bioinformatics tools. Gene expression levels of selected genes were validated using quantitative polymerase chain reaction. RESULTS: A total of 413 genes were identified when young inner bulla (growing) were compared with young otic capsule and 358 genes were identified when adult inner bulla (quiescent) were compared with adult otic capsule. Fourteen genes were involved in bone metabolism of which four genes have been previously discussed in the literature of perilabyrinthine bone biology. CONCLUSION: The gene expression of the otic capsule was significantly different from that of the middle ear. This study identified a number of differentially expressed bone-related mRNAs of potential significance and confirmed the OPG/receptor activator of nuclear factor kappa-B (RANK)/RANK ligand (RANKL) pathway as the key signaling system for the unique behavior of bone cells within the otic capsule. No differentially expressed up- or downstream messengers in the OPG/RANK/RANKL pathway were found.

Bone signaling in middle ear development: a genome-wide differential expression analysis.

Common middle ear diseases may affect bone behavior in the middle ear air cell system. To understand this pathologic pneumatization, the normal development of bone in the middle ear should be investigated. The objective of this study was to analyze gene expression of bone-related signaling factors and gene sets in the developing middle ear. Microarray technology was used to identify bone-related genes and gene sets, which were differentially expressed between the lining tissue of adult (quiescent) bulla and young (resorbing/forming) bulla. Data were analyzed using tools of bioinformatics and expression levels of selected genes were validated using quantitative polymerase chain reaction. The candidate gene products were compared with previously published data on middle ear bone metabolism. No differentially expressed genes were found on the outer surface of bulla. On the inner lining a total of 260 genes were identified of which 22 genes were involved in bone metabolism. Gene set analysis revealed five enriched bone-related gene sets. The identified differentially expressed bone-related mRNAs and gene sets are of potential significance in the normally developing bulla. These factors and gene sets may also play important roles during pathologic pneumatization of the middle ear air cell system in common middle ear diseases. In addition, this study suggests that the control of growth rate and wall thickness from resorptive as well as formative signals all originate from the inner lining cells of the bulla wall.

Experimental hyperactivity of the endolymphatic sac.

Injury to the endolymphatic sac may play an important role in the pathogenesis of Ménière's disease, an inner ear disorder characterized by hearing loss, tinnitus and attacks of vertigo. Isoimmunization of 16 inbred Lewis rats with a crude endolymphatic sac extract and complete Freund's adjuvant induced hyperactivity of the endolymphatic sac. One group of rats was immunized by a single dose whereas a second group was immunized twice. Control animals were injected with Freund's adjuvant in saline only. Serum was collected from all rats by the end of the study and harvested autoantibodies were tested by immunohistochemistry. The endolymphatic sacs were investigated by transmission electron microscopy. Endolymphatic sac stimulation was observed in all immunized rats. Based on detailed ultrastructural observations, the degree of reactivity seemed proportional to the number of injections and the extent of immunization. Moreover, the ribosome-rich cells seemed hyperactive with an extravagant content of intracellular components: numerous rough endoplasmic reticulum and free ribosomes, morphological signs of extensive endo- and exocytosis, vesicles of material with a density similar to the homogeneous substance of which many were observed to fuse with primary lysozymes. Basolateral foldings were numerous and in the subepithelial capillaries formation of multiple and apposing fenestrations were observed. No endolymphatic sac stimulation was observed in the control animals. Specific ribosome-rich cell alterations identical to those present in the endolymphatic sac of Ménière's disease were observed 21 days after the first immunization. The observations suggest that either an autoantigen or a trophic factor, capable of inducing a hyperactivity of the ribosome-rich cells and an imbalance of the homogeneous substance metabolism, exists in the endolymphatic sac of the rat.

Gene expression of the endolymphatic sac.

CONCLUSION: The endolymphatic sac is part of the membranous inner ear and is thought to play a role in the fluid homeostasis and immune defense of the inner ear; however, the exact function of the endolymphatic sac is not fully known. Many of the detected mRNAs in this study suggest that the endolymphatic sac has multiple and diverse functions in the inner ear. OBJECTIVES: The objective of this study was to provide a comprehensive review of the genes expressed in the endolymphatic sac in the rat and perform a functional characterization based on measured mRNA abundance. METHODS: Microarray technology was used to investigate the gene expression of the endolymphatic sac with the surrounding dura. Characteristic and novel endolymphatic sac genes were determined by comparing with expressions in pure dura. RESULTS: In all, 463 genes were identified specific for the endolymphatic sac. Functional annotation clustering revealed 29 functional clusters.

Objective measurement of the human endolymphatic sac dimensions in Ménière's disease.

HYPOTHESIS: To identify structural differences between the endolymphatic sac of temporal bones with and without Ménière's disease by applying design-based stereology. BACKGROUND: The dimension of the human endolymphatic sac has previously been studied by extrapolating 2-dimensional irregularities on the sectional level into 3-dimensional quantities via unfolding algorithms. These computer renderings require certain geometrical assumptions of the object studied. The term design-based used in the present study signifies that the methods and sampling schemes are defined a priori, in such a manner that consideration of the size, shape, spatial orientation, and distribution of the investigated structures are eliminated. MATERIALS AND METHODS: Archival materials of 15 human temporal bones with Ménière's disease and 15 control specimens were investigated by design-based stereology. RESULTS: The total surface area of the endolymphatic sac was significantly lower in the Ménière's disease group (24.8 mm) compared with the control group (47.0 mm), p = 0.006. The volume fraction of the homogenous substance was significantly higher in the Ménière's disease group (17.5%) compared with the control group (5.7%), p = 0.031. No significant differences were found between the volumes of the homogenous substance, the volumes of the endolymphatic sac, and the surface-to-volume ratio in the 2 groups. The study revealed a large biological variation. CONCLUSION: Design-based stereology is a robust, unbiased and efficient tool to quantify 3-dimensional structures derived from 2-dimensional histologic sections. A 2-fold reduction in the surface area of the endolymphatic sac and a 3-fold increase in the volume fraction of homogenous substance in temporal bones with Ménière's disease may, at least in part, be involved in the dysfunction of endolymph fluid homeostasis and the development of endolymphatic hydrops.

Vestibular tributaries to the vein of the vestibular aqueduct.

CONCLUSION: The vein of the vestibular aqueduct drains blood from areas extensively lined by vestibular dark cells (VDCs). A possible involvement in the pathogenesis of an impaired endolymphatic homeostasis can be envisioned at the level of the dark cells area. OBJECTIVES: The aim of this study was to investigate the vascular relationship between the vein of the vestibular aqueduct and the vestibular apparatus, with focus on the VDCs. METHODS: Sixteen male Wistar rats were divided into groups of 6 and 10. In the first group, 2 µm thick sections including the vein of the vestibular aqueduct, utricle, and crista ampullaris of the lateral ampulla were examined by light microscopy and computer-generated three-dimensional imaging. In the second group, ultrathin sections including venules and VDCs were examined by transmission electron microscopy. RESULTS: A microvascular network was observed in close relation to the VDCs in the utricle and the crista ampullaris of the lateral semicircular canal in the vestibular apparatus. One major vein emanated from these networks, which emptied into the vein of the vestibular aqueduct. Veins draining the saccule and the common crus of the superior and posterior semicircular canals were likewise observed to merge with the vein of the vestibular aqueduct.

[Ménière's-like symptoms following meningioma]. / Menière-lignende symptomer efter meningeom.

A 36-year-old woman who presented with a right sided hearing loss, tinnitus and attacks of dizziness was initially diagnosed with Ménière's disease. A meningioma was found along the posterior surface of the petrosal bone, centred partly on the external aperture of the vestibular aqueduct with no relation to the meatal canal. Removal of the meningial tumour improved the hearing but Ménière's-like symptoms recurred after 18 months despite surgery. Ménière's-like symptoms could hypothetically be caused by changes of the endolymphatic duct or the vein of the vestibular aqueduct.

Functional blood flow patterns of the endolymphatic sac in the rat.

CONCLUSION: Visualization of the endolymphatic sac vascular network under video fluorescence microscopy showed a typical microvascular organization. The microvascular arrangement and the microcirculation may reflect a functional state of the endolymphatic sac. Damage or change of the blood circulation following endolymphatic sac surgery is discussed. OBJECTIVES: To visualize and study the dynamic microcirculation of the endolymphatic sac in live rats. METHOD: An experimental animal study using in vivo video fluorescence microscopy. RESULTS: Visualization of the endolymphatic sac vascular network showed a typical microvascular organization. The endolymphatic sac appeared hypervascular and independent from other vascular systems. The microcirculation of the endolymphatic sac was supplied by ramification of a single artery, while venous trunks perpendicular to the length of the endolymphatic sac served as return paths for the microcirculation. The blood flow pattern was highly variable between rats.

The vein of the vestibular aqueduct with potential pathologic perspectives.

HYPOTHESIS: Pathologic changes around the vein of the vestibular aqueduct (VVA) may cause obstruction to the flow of blood toward the sigmoid sinus. Furthermore, a distal obstruction of this vessel may be responsible for a development of a retrograde flow of blood with concomitant drainage of endolymphatic sac (ES) substances to the inner ear. BACKGROUND: The VVA is responsible for the venous drainage of the vestibular apparatus and endolymphatic duct and ES. Previous studies have linked the VVA to Ménière's disease. The aim of the present article was a 3-dimensional perspective study of the VVA with its adjacent anatomic structures. METHODS: In 14 rats, the VVA was examined by 3-dimensional reconstruction of 2-microm serial sections, corrosion cast technique, and scanning electron microscopy. RESULTS: From the external aperture of the vestibular aqueduct, the VVA is interposed between the ES and the operculum. Three to 4 collecting venules from the ES drain into the VVA. The VVA merges at an oblique angle with the sigmoid sinus. CONCLUSION: The VVA courses near the ES, operculum, and sigmoid sinus and is potentially vulnerable to expanding structures in the cranial posterior fossa. The possible role of the VVA for the function of the ES under normal and pathologic conditions is discussed.

A potential portal flow in the inner ear.

OBJECTIVES/HYPOTHESIS: The aim of the present study was to visualize the flow direction of blood in the extraosseous part of the vein of the vestibular aqueduct (VVA) and to explore the effect of an induced obstruction in the distal part of the VVA before it merges with the sigmoid sinus. The endolymphatic sac has been implicated as a potential endocrine gland, which venules drain to the VVA. A reversal of the direction of flow in the VVA toward the inner ear could, through vestibular arteriovenous anastomosis, cause portal circulation in the inner ear. STUDY DESIGN: The authors conducted an experimental animal study using in vivo fluorescence microscopy. RESULTS: Obstructing the distal part of the VVA just before it empties into the sigmoid sinus immediately reverses the flow of blood in the VVA toward the inner ear. CONCLUSIONS: After an obstruction of the VVA, the drained venous blood from the endolymphatic sac may enter a portal circulation in the inner ear, which could cause disturbances in the endolymph homeostasis and potentially symptoms as seen in Meniere disease.