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JAMA Otolaryngology-- Head & Neck... Nov 2021The use of intratympanically applied steroids is of increasing interest. Consequently, research has focused on finding an ideal drug that diffuses through the round... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of Levels of Triamcinolone Acetonide in Human Perilymph and Plasma After Intratympanic Application in Patients Receiving Cochlear Implants: A Randomized Clinical Trial.
IMPORTANCE
The use of intratympanically applied steroids is of increasing interest. Consequently, research has focused on finding an ideal drug that diffuses through the round window membrane and can be retained in the perilymph.
OBJECTIVE
To compare levels of triamcinolone acetonide (TAC) in perilymph and plasma after intratympanic injection.
DESIGN, SETTING, AND PARTICIPANTS
This randomized clinical trial included 40 patients receiving cochlear implants at a single tertiary care center in Vienna, Austria. Patients were randomized to 1 of 4 treatment groups receiving 1 of 2 intratympanic doses of TAC (10 mg/mL or 40 mg/mL) at 1 of 2 approximate time points (24 hours or 1 hour) before sampling the perilymph. Inclusion was carried out between November 2017 and January 2020, and data were analyzed in December 2020.
INTERVENTIONS
All patients underwent intratympanic injection of TAC. During cochlear implantation, perilymph and plasma were sampled for further analysis.
MAIN OUTCOMES AND MEASURES
Levels of TAC measured in perilymph and plasma.
RESULTS
Among the 37 patients (median [range] age, 57 [26-88] years; 18 [49%] men) included in the analysis, TAC was present at a median (range) level of 796.0 (46.4-7706.7) ng/mL. In the majority of patients (n = 29; 78%), no drug was detectable in the plasma after intratympanic injection. Levels above the limit of detection were less than 2.5 ng/mL. The 1-factorial analysis of variance model showed lower TAC levels in the group that received TAC, 10 mg/mL, 24 hours before surgery (median, 271 ng/mL) compared with the group that received TAC, 10 mg/mL, 1 hour before surgery (median, 2877 ng/mL), as well as in comparison with the groups receiving TAC, 40 mg/mL, 24 hours before surgery (median, 2150 ng/mL) and 1 hour before surgery (median, 939 ng/mL). The 2-factorial analysis of variance model showed lower TAC levels in the group receiving TAC, 10 mg/mL, 24 hours before surgery than the group receiving TAC, 10 mg/mL, 1 hour before surgery, and higher TAC levels in the group receiving TAC, 40 mg/mL, 24 hours before surgery compared with the group receiving TAC, 10 mg/mL, 24 hours before surgery. Patients with thickening of the middle ear had statistically significantly higher plasma levels (median, 1.4 ng/mL vs 0 ng/mL) and lower perilymph levels (median, 213.1 ng/mL vs 904 ng/mL) than individuals with unremarkable middle ear mucosa.
CONCLUSIONS AND RELEVANCE
In this randomized clinical trial, TAC was shown to be a promising drug for intratympanic therapies, with similar levels in perilymph 1 hour and 24 hours after injection (distinctly in the groups receiving the 40 mg/mL dose). There was also minimal dissemination to the plasma, especially in patients with unremarkable middle ear mucosa.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier: NCT03248856.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents; Cochlear Implantation; Drug Administration Schedule; Female; Humans; Injection, Intratympanic; Male; Middle Aged; Perilymph; Preoperative Care; Triamcinolone Acetonide; Young Adult
PubMed: 34591079
DOI: 10.1001/jamaoto.2021.2492 -
Frontiers in Molecular Neuroscience 2021Cochlin is the most abundant protein in the inner ear. To study its function in response to noise trauma, we exposed adolescent wild-type ( ) and cochlin knock-out ( )...
Cochlin is the most abundant protein in the inner ear. To study its function in response to noise trauma, we exposed adolescent wild-type ( ) and cochlin knock-out ( ) mice to noise (8-16 kHz, 103 dB SPL, 2 h) that causes a permanent threshold shift and hair cell loss. Two weeks after noise exposure, mice had substantially less elevation in noise-induced auditory thresholds and hair cell loss than mice, consistent with cochlin deficiency providing protection from noise trauma. Comparison of pre-noise exposure thresholds of auditory brain stem responses (ABRs) and distortion product otoacoustic emissions (DPOAEs) in mice and littermates revealed a small and significant elevation in thresholds of mice, overall consistent with a small conductive hearing loss in mice. We show quantitatively that the pro-inflammatory component of cochlin, LCCL, is upregulated after noise exposure in perilymph of wild-type mice compared to unexposed mice, as is the enzyme catalyzing LCCL release, aggrecanase1, encoded by . We further show that upregulation of pro-inflammatory cytokines in perilymph and cochlear soft-tissue after noise exposure is lower in cochlin knock-out than wild-type mice. Taken together, our data demonstrate for the first time that cochlin deficiency results in conductive hearing loss that protects against physiologic and molecular effects of noise trauma.
PubMed: 34108864
DOI: 10.3389/fnmol.2021.670013 -
Tidsskrift For Den Norske Laegeforening... Jan 2001Perilymphatic fistula is leakage of perilymph from the inner ear to the middle ear. The perilymph surrounds the endolymphatic system in the inner ear (cochlea and the...
BACKGROUND
Perilymphatic fistula is leakage of perilymph from the inner ear to the middle ear. The perilymph surrounds the endolymphatic system in the inner ear (cochlea and the vestibular apparatus) and is most likely a cerebrospinal fluid filtrate. Leakage can occur through the fenestra vestibuli (the oval window), the fenestra cochleae (the round window), or pathological openings in the otic capsule. The cause of perilymphatic fistula can be trauma (barotrauma, head trauma, whiplash injury, iatrogenic trauma during ear surgery or ear syringing), chronic otitis media with cholesteatoma, congenital malformations or idiopathic.
MATERIAL AND METHODS
We present 15 patients operated at Haukeland University Hospital from 1980 to 1997.
RESULTS
Symptoms and signs are not very consistent, but dizziness and hearing loss are usual. The fistula test has low sensitivity and specificity, and otomicroscopy is not diagnostic. Imaging techniques with CT and MRI are seldom helpful unless in cases of inner ear abnormalities. Surgical exploration of the middle ear can be diagnostic, but even then it may in some cases be difficult to determine if a perilymphatic fistula is present.
INTERPRETATION
The treatment of suspected perilymphatic fistula is primarily bed rest with elevated head, and avoidance of straining to facilitate spontaneous closure of a possible fistula. If the symptoms continue, or get worse, surgical exploration is indicated. The results are good regarding dizziness, but more uncertain as far as hearing improvement is concerned. Hearing improvement seems to be negatively correlated with the length of the delay before the fistula is closed.
Topics: Adult; Aged; Barotrauma; Child; Cholesteatoma; Cochlear Diseases; Craniocerebral Trauma; Female; Fistula; Humans; Male; Middle Aged; Myringoplasty; Norway; Otitis Media; Perilymph; Stapes Surgery; Vestibular Diseases
PubMed: 11475190
DOI: No ID Found -
Laryngoscope Investigative... Dec 2022To evaluate tympanostomy tube placement in patients with pressure-sensitive vertigo.
OBJECTIVE
To evaluate tympanostomy tube placement in patients with pressure-sensitive vertigo.
METHODS
Retrospective case series.
RESULTS
Six patients with pressure-sensitive vertigo reported resolution of their vertigo and other vestibular symptoms after placement of the tympanostomy tubes. All recurrences of symptoms were due to either extrusion or plugging of the tubes. All patients fulfilled the criteria for vestibular migraine. None of the patients had superior canal dehiscence on imaging or precedent event that triggered the problem, and all had a negative fistula test.
CONCLUSION
Tympanostomy tube placement should be considered in selected patients with vertigo exacerbated by seemingly small changes in atmospheric pressure (e.g., just prior to thunderstorms, air travel, or travel to the mountains). By eliminating the capability of the tympanic membrane to sense changes in pressure with a tube, patients with pressure-induced vertigo (in the absence of perilymph fistula or superior canal dehiscence) may have relief of their symptoms.
PubMed: 36544944
DOI: 10.1002/lio2.860 -
Pflugers Archiv : European Journal of... Oct 2016The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K(+)] of 150 mM. This unusual extracellular... (Review)
Review
The cochlea of the mammalian inner ear contains an endolymph that exhibits an endocochlear potential (EP) of +80 mV with a [K(+)] of 150 mM. This unusual extracellular solution is maintained by the cochlear lateral wall, a double-layered epithelial-like tissue. Acoustic stimuli allow endolymphatic K(+) to enter sensory hair cells and excite them. The positive EP accelerates this K(+) influx, thereby sensitizing hearing. K(+) exits from hair cells and circulates back to the lateral wall, which unidirectionally transports K(+) to the endolymph. In vivo electrophysiological assays demonstrated that the EP stems primarily from two K(+) diffusion potentials yielded by [K(+)] gradients between intracellular and extracellular compartments in the lateral wall. Such gradients seem to be controlled by ion channels and transporters expressed in particular membrane domains of the two layers. Analyses of human deafness genes and genetically modified mice suggested the contribution of these channels and transporters to EP and hearing. A computational model, which reconstitutes unidirectional K(+) transport by incorporating channels and transporters in the lateral wall and connects this transport to hair cell transcellular K(+) fluxes, simulates the circulation current flowing between the endolymph and the perilymph. In this model, modulation of the circulation current profile accounts for the processes leading to EP loss under pathological conditions. This article not only summarizes the unique physiological and molecular mechanisms underlying homeostasis of the EP and their pathological relevance but also describes the interplay between EP and circulation current.
Topics: Action Potentials; Animals; Cochlea; Deafness; Extracellular Fluid; Homeostasis; Humans; Potassium
PubMed: 27568193
DOI: 10.1007/s00424-016-1871-0 -
Hearing Research Oct 2017Middle ear (ME) pressure-regulation (MEPR) is a homeostatic mechanism that maintains the ME-environment pressure-gradient (MEEPG) within a range optimized for "normal"...
INTRODUCTION
Middle ear (ME) pressure-regulation (MEPR) is a homeostatic mechanism that maintains the ME-environment pressure-gradient (MEEPG) within a range optimized for "normal" hearing.
OBJECTIVE
Describe MEPR using equations applicable to passive, inter-compartmental gas-exchange and determine if the predictions of that description include the increasing ME pressure observed under certain conditions and interpreted by some as evidencing gas-production by the ME mucosa.
METHODS
MEPR was modeled as the combined effect of passive gas-exchanges between the ME and: perilymph via the round window membrane, the ambient environment via the tympanic membrane, and the local blood via the ME mucosa and of gas flow between the ME and nasopharynx during Eustachian tube openings. The first 3 of these exchanges are described at the species level using the Fick's diffusion equation and the last as a bulk gas transfer governed by Poiseuille's equation. The model structure is a time-iteration of the equation: P = ∑(P+(1/(βV)∑(Қ(P-P)). There, P and P are the ME total and species-pressures at the indexed times, P is the species-pressure for each exchange-compartment, βV is the product of the ME species-capacitance and volume, Қ is the pathway species-conductance, and ∑ and ∑ are operators for summing the expression over all species or exchange pathways.
RESULTS
When calibrated to known values, the model predicts the empirically measured ME species-pressures and the observed time-trajectories for total ME pressure and the MEEPG under a wide variety of physiologic, pathologic and non-physiologic conditions.
CONCLUSIONS
Passive inter-compartmental gas exchange is sole and sufficient to describe MEPR.
Topics: Computer Simulation; Diffusion; Ear, Middle; Gases; Hearing; Homeostasis; Humans; Models, Theoretical; Pressure; Time Factors
PubMed: 28917121
DOI: 10.1016/j.heares.2017.08.005 -
PloS One 2022Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea...
Modern proteomic analysis and reliable surgical access to gain liquid inner ear biopsies have enabled in depth molecular characterization of the cochlea microenvironment. In order to clarify whether the protein composition of the perilymph can provide new insights into individual hearing performance after cochlear implantation (CI), computational analysis in correlation to clinical performance after CI were performed based on the proteome profile derived from perilymph samples (liquid biopsies). Perilymph samples from cochlear implant recipients have been analyzed by mass spectrometry (MS). The proteins were identified using the shot-gun proteomics method and quantified and analyzed using Max Quant, Perseus and IPA software. A total of 75 perilymph samples from 68 (adults and children) patients were included in the analysis. Speech perception data one year after implantation were available for 45 patients and these were used for subsequent analysis. According to their hearing performance, patients with excellent (n = 22) and poor (n = 14) performance one year after CI were identified and used for further analysis. The protein composition and statistically significant differences in the two groups were detected by relative quantification of the perilymph proteins. With this procedure, a selection of 287 proteins were identified in at least eight samples in both groups. In the perilymph of the patients with excellent and poor performance, five and six significantly elevated proteins were identified respectively. These proteins seem to be involved in different immunological processes in excellent and poor performer. Further analysis on the role of specific proteins as predictors for poor or excellent performance among CI recipients are mandatory. Combinatory analysis of molecular inner ear profiles and clinical performance data using bioinformatics analysis may open up new possibilities for patient stratification. The impact of such prediction algorithms on diagnosis and treatment needs to be established in further studies.
Topics: Proteome
PubMed: 35239655
DOI: 10.1371/journal.pone.0263765 -
Evolution of Endolymph Secretion and Endolymphatic Potential Generation in the Vertebrate Inner Ear.Brain, Behavior and Evolution 2018The ear of extant vertebrates reflects multiple independent evolutionary trajectories. Examples include the middle ear or the unique specializations of the mammalian... (Review)
Review
The ear of extant vertebrates reflects multiple independent evolutionary trajectories. Examples include the middle ear or the unique specializations of the mammalian cochlea. Another striking difference between vertebrate inner ears concerns the differences in the magnitude of the endolymphatic potential. This differs both between the vestibular and auditory part of the inner ear as well as between the auditory periphery in different vertebrates. Here we provide a comparison of the cellular and molecular mechanisms in different endorgans across vertebrates. We begin with the lateral line and vestibular systems, as they likely represent plesiomorphic conditions, then review the situation in different vertebrate auditory endorgans. All three systems harbor hair cells bathed in a high (K+) environment. Superficial lateral line neuromasts are bathed in an electrogenically maintained high (K+) microenvironment provided by the complex gelatinous cupula. This is associated with a positive endocupular potential. Whether this is a special or a universal feature of lateral line and possibly vestibular cupulae remains to be discovered. The vestibular system represents a closed system with an endolymph that is characterized by an enhanced (K+) relative to the perilymph. Yet only in land vertebrates does (K+) exceed (Na+). The endolymphatic potential ranges from +1 to +11 mV, albeit we note intriguing reports of substantially higher potentials of up to +70 mV in the cupula of ampullae of the semicircular canals. Similarly, in the auditory system, a high (K+) is observed. However, in contrast to the vestibular system, the positive endolymphatic potential varies more substantially between vertebrates, ranging from near zero mV to approximately +100 mV. The tissues generating endolymph in the inner ear show considerable differences in cell types and location. So-called dark cells and the possibly homologous ionocytes in fish appear to be the common elements, but there is always at least one additional cell type present. To inspire research in this field, we propose a classification for these cell types and discuss potential evolutionary relationships. Their molecular repertoire is largely unknown and provides further fertile ground for future investigation. Finally, we propose that the ultimate selective pressure for an increased endolymphatic potential, as observed in mammals and to a lesser extent in birds, is specifically to maintain the AC component of the hair-cell receptor potential at high frequencies. In summary, we identify intriguing questions for future directions of research into the molecular and cellular basis of the endolymph in the different compartments of the inner ear. The answers will provide important insights into evolutionary and developmental processes in a sensory organ essential to many species, including humans.
Topics: Animals; Ear, Inner; Electrophysiological Phenomena; Endolymph; Vertebrates
PubMed: 30415265
DOI: 10.1159/000494050 -
BMC Medical Imaging Sep 2021Non-contrast FLAIR revealed increased signal within the inner ear in patients with vestibular schwannoma, which is generally assumed to occur in the perilymph; however,...
BACKGROUND
Non-contrast FLAIR revealed increased signal within the inner ear in patients with vestibular schwannoma, which is generally assumed to occur in the perilymph; however, the majority of previous studies did not differentiate between the endolymph and perilymph. Therefore, endolymph signal changes have not yet been investigated in detail. The purpose of the present study was three-fold: (1) to assess perilymph signal changes in patients with vestibular schwannoma on heavily T2-weighted (T2W) 3D FLAIR, also termed positive perilymphatic images (PPI), (2) to evaluate signal and morphological changes in the endolymph on PPI, and (3) to establish whether vertigo correlates with the signal intensity ratios (SIR) of the vestibular perilymph or vestibular endolymphatic hydrops.
METHODS
Forty-two patients with unilateral vestibular schwannoma were retrospectively recruited. We semi-quantitatively and qualitatively evaluated the perilymph signal intensity on the affected and unaffected sides. We also quantitatively examined the signal intensity of the vestibular perilymph and assessed the relationship between vertigo and the SIR of the vestibular perilymph on the affected side. We semi-quantitatively or qualitatively evaluated the endolymph, and investigated whether vestibular hydrops correlated with vertigo.
RESULTS
The perilymph on the affected side showed abnormal signal more frequently (signal intensity grade: overall mean 1.45 vs. 0.02; comparison of signal intensity: overall mean 36 vs. 0 cases) and in more parts (the entire inner ear vs. the basal turn of the cochlea and vestibule) than that on the unaffected side. No significant difference was observed in the SIR of the vestibular perilymph with and without vertigo (5.54 vs. 5.51, p = 0.18). The endolymph of the vestibule and semicircular canals showed the following characteristic features: no visualization (n = 4), signal change (n = 1), or vestibular hydrops (n = 10). A correlation was not observed between vestibular hydrops and vertigo (p = 1.000).
CONCLUSIONS
PPI may provide useful information on signal and morphological changes in the endolymph of patients with vestibular schwannoma. Further research is warranted to clarify the relationship between vertigo and the MR features of the inner ear.
Topics: Adult; Aged; Aged, 80 and over; Endolymph; Endolymphatic Hydrops; Female; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neuroma, Acoustic; Perilymph; Retrospective Studies; Vertigo
PubMed: 34563164
DOI: 10.1186/s12880-021-00670-9 -
Indian Journal of Otolaryngology and... Mar 1997In this study 26 cases of blast injury to ear were studied. Both ears were affected in 9 cases and therefore the number of ears studied being 35. The audiological...
In this study 26 cases of blast injury to ear were studied. Both ears were affected in 9 cases and therefore the number of ears studied being 35. The audiological findings along with the treatment and a followup of 2 years is presented.We found that mixed deafness was commonest and the sensorineural element of the hearing loss started recovering before conductive element, but recovery slowed down later on and was incomplete in most cases. Approximation of torn fragments of tympanic membrane improved its healing. Vertigo lasting for 1-7 days was present in 46.15% of cases. Only one patient had perilymph fistula which was repaired.
PubMed: 23119358
DOI: 10.1007/BF03021328