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International Journal of Molecular... Dec 2022As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic...
Prevention of Noise-Induced Hearing Loss In Vivo: Continuous Application of Insulin-like Growth Factor 1 and Its Effect on Inner Ear Synapses, Auditory Function and Perilymph Proteins.
As noise-induced hearing loss (NIHL) is a leading cause of occupational diseases, there is an urgent need for the development of preventive and therapeutic interventions. To avoid user-compliance-based problems occurring with conventional protection devices, the pharmacological prevention is currently in the focus of hearing research. Noise exposure leads to an increase in reactive oxygen species (ROS) in the cochlea. This way antioxidant agents are a promising option for pharmacological interventions. Previous animal studies reported preventive as well as therapeutic effects of Insulin-like growth factor 1 (IGF-1) in the context of NIHL. Unfortunately, in patients the time point of the noise trauma cannot always be predicted, and additive effects may occur. Therefore, continuous prevention seems to be beneficial. The present study aimed to investigate the preventive potential of continuous administration of low concentrations of IGF-1 to the inner ear in an animal model of NIHL. Guinea pigs were unilaterally implanted with an osmotic minipump. One week after surgery they received noise trauma, inducing a temporary threshold shift. Continuous IGF-1 delivery lasted for seven more days. It did not lead to significantly improved hearing thresholds compared to control animals. Quite the contrary, there is a hint for a higher noise susceptibility. Nevertheless, changes in the perilymph proteome indicate a reduced damage and better repair mechanisms through the IGF-1 treatment. Thus, future studies should investigate delivery methods enabling continuous prevention but reducing the risk of an overdosage.
Topics: Animals; Guinea Pigs; Auditory Threshold; Cochlea; Hearing; Hearing Loss, Noise-Induced; Insulin-Like Growth Factor I; Perilymph; Synapses
PubMed: 36613734
DOI: 10.3390/ijms24010291 -
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 -
International Journal of Pharmaceutics:... Dec 2022The aim of this study was to better understand the long term behavior of silicone-based cochlear implants loaded with dexamethasone: in vitro as well as in vivo...
The aim of this study was to better understand the long term behavior of silicone-based cochlear implants loaded with dexamethasone: in vitro as well as in vivo (gerbils). This type of local controlled drug delivery systems offers an interesting potential for the treatment of hearing loss. Because very long release periods are targeted (several years/decades), product optimization is highly challenging. Up to now, only little is known on the behavior of these systems, including their drug release patterns as well as potential swelling or shrinking upon exposure to aqueous media or living tissue. Different types of cylindrical, cochlear implants were prepared by injection molding, varying their dimensions (being suitable for use in humans or gerbils) and initial drug loading (0, 1 or 10%). Dexamethasone release was monitored in vitro upon exposure to artificial perilymph at 37 °C for >3 years. Optical microscopy, X-ray diffraction and Raman imaging were used to characterize the implants before and after exposure to the release medium in vitro, as well as after 2 years implantation in gerbils. Importantly, in all cases dexamethasone release was reliably controlled during the observation periods. Diffusional mass transport and limited drug solubility effects the silicone matrices seem to play a major role. Initially, the dexamethasone is homogeneously distributed throughout the polymeric matrices in the form of tiny crystals. Upon exposure to aqueous media or living tissue, limited amounts of water penetrate into the implant, dissolve the drug, which subsequently diffuses out. Surface-near regions are depleted first, resulting in an increase in the apparent drug diffusivity with time. No evidence for noteworthy implant swelling or shrinkage was observed in vitro, nor in vivo. A simplified mathematical model can be used to facilitate drug product optimization, allowing the prediction of the resulting drug release rates during decades as a function of the implant's design.
PubMed: 36465275
DOI: 10.1016/j.ijpx.2022.100141 -
Frontiers in Neurology 2022To present a case of intralabyrinthine schwannoma (ILS) presenting as Ménière's disease diagnosed 4-h delayed gadolinium-enhanced three-dimensional fluid-attenuated...
Case report: Concurrent intravestibular schwannoma mimicking Ménière's disease and cochlear hydrops detected delayed three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging.
OBJECTIVE
To present a case of intralabyrinthine schwannoma (ILS) presenting as Ménière's disease diagnosed 4-h delayed gadolinium-enhanced three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (3D-FLAIR MRI) and treated successfully using the translabyrinthine approach.
PATIENT
A patient who was diagnosed with intravestibular ILS.
INTERVENTIONS
The patient underwent comprehensive preoperative neurological examinations and MRI. The tumor was resected using the translabyrinthine approach and was pathologically confirmed as schwannoma based on the surgical specimen.
MAIN OUTCOME MEASURES
Preoperative audiogram and vestibular test findings and MRI images.
RESULTS
Preoperatively, pure-tone audiogram showed progressive sensorineural hearing loss only on the affected side. The video head impulse test and vestibular evoked myogenic potential test showed vestibular dysfunction on the affected ear. Immediate gadolinium-enhanced T1-weighted MRI revealed an enhanced region in the vestibule. Meanwhile, magnetic resonance cisternography showed a filling defect. Delayed 3D-FLAIR MRI revealed a signal void in the scala media of the cochlea indicative of cochlear hydrops, and a strong signal in the perilymph at the basal cochlea suggestive of impaired blood-labyrinthine barrier.
CONCLUSION
Delayed 3D-FLAIR MRI is useful in diagnosing concurrent ILSs and endolymphatic hydrops.
PubMed: 36438944
DOI: 10.3389/fneur.2022.1043452 -
Frontiers in Neurology 2022We evaluated the inner ear distribution of O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic...
We evaluated the inner ear distribution of O-labeled saline administered to the human tympanic cavity. Magnetic resonance imaging was performed after intratympanic administration in five healthy volunteers and one patient with cochlear endolymphatic hydrops. In all volunteers, O-labeled water permeated the cochlear basal turn and vestibule at 30 min and disappeared gradually within 2-4 h. All participants experienced positional vertigo lasting a few hours to a few days. Visualization of O-labeled water distribution in the endolymphatic space of the posterior ampulla showed indistinct separation of endolymph and perilymph in the cochlea and most of the vestibule in all participants. Intralabyrinthine distribution of O-labeled water differed from that in previous reports of intratympanically administered gadolinium-based contrast agent. O-labeled water in the endolymphatic space may cause heavier endolymph and positional vertigo. These results of this study may add new insights for investigating the distribution and the effects of molecules in the inner ear after the intratympanic administration in living humans.
PubMed: 36408495
DOI: 10.3389/fneur.2022.1016577 -
Lin Chuang Er Bi Yan Hou Tou Jing Wai... Nov 2022To investigate the relationship between imaging characteristics and intraoperative perilymph gusher in patients with Mondini inner ear malformation in cochlear...
To investigate the relationship between imaging characteristics and intraoperative perilymph gusher in patients with Mondini inner ear malformation in cochlear implantation, in order to provide basis and clinical guidance for predicting of intraoperative perilymph gusher before cochlear implantation. According to Sennaroglu's classification method, children with severe sensorineural hearing loss screened from January 2020 to December 2021 were divided into Mondini group, simple enlarged vestibular aqueduct group and normal inner ear group according to inclusion criteria strictly. The images of temporal bone HRCT and inner ear MRI were post-processed, some relative indicators were measured, including cochlear height and width of vestibular aqueduct, etc., and the gusher situation during cochlear implantation was recorded. The mean value of each indicator among the three groups were compared respectively, and the differences of each indicator between the gusher group and the non-gusher group were analyzed. There were statistically significant differences in cochlear height, length of cochlear bottom turn, width of cochlear aperture, vestibular length and vestibular width among the Mondini group(24 cases), simple EVA group(15 cases) and normal inner ear group(28 cases). The incidence of gusher of Mondini group in cochlear implantation was 30.77%(8/26). The outer diameter of the VA([3.10±0.74]mm) and the middle width of the VA([1.90±0.68] mm) in the gusher group were wider than those in the non-gusher group, and the difference was statistically significant. The incidence of intraoperative gusher in patients with EVA was 20.00%(3/15), and there was statistically significant difference in the length of endolymph sac between gusher group and non-gusher group(<0.05). The causes of intraoperative perilymph gusher in patients with Mondini inner ear malformation are complex. The enlarged vestibular aqueduct may be one of the anatomical basis. Whether it can be used to guide the preoperative assessment of the risk of intraoperative perilymph gusher need to be further confirmed by a large sample of clinical research from multiple centers in the future.
Topics: Child; Humans; Perilymph; Hearing Loss, Sensorineural; Vestibular Aqueduct; Cochlear Implantation; Vestibule, Labyrinth; Retrospective Studies
PubMed: 36347576
DOI: 10.13201/j.issn.2096-7993.2022.11.006 -
Hearing Research Dec 2022The emergence of therapeutics targeted at hearing loss holds great promise in the development of novel treatments for this heterogenous condition. Whilst such... (Review)
Review
The emergence of therapeutics targeted at hearing loss holds great promise in the development of novel treatments for this heterogenous condition. Whilst such therapeutics are largely designed to be efficacious in and of themselves, the possibility of combination with devices, namely cochlear implants, could result in much more effective treatment options. Here, we review the otoprotective molecules currently in clinical development, as well as generic steroids, discussing mechanisms of action and mode of delivery to the perilymph of the cochlea. Presenting both preclinical and clinical data, we explore the challenges these molecules face in reaching the inner ear. Furthermore, we consider the role of the cochlear implant as a drug delivery platform along with the ability of these drugs to preserve residual hearing and improve outcomes in implant recipients.
Topics: Humans; Cochlear Implantation; Cochlear Implants; Cochlea; Hearing; Deafness
PubMed: 36306608
DOI: 10.1016/j.heares.2022.108637 -
Scientific Reports Oct 2022A mouse model with cisplatin-induced ototoxicity was used in addition to human samples from the ITMAT Biobank at the University of Pennsylvania. Mouse auditory brainstem...
A mouse model with cisplatin-induced ototoxicity was used in addition to human samples from the ITMAT Biobank at the University of Pennsylvania. Mouse auditory brainstem responses (ABR), inner ear histology, perilymph cisplatin sampling, and measurement of serum prestin via ELISA were performed. Human serum prestin level was measured via ELISA in patients with otological issues after cisplatin treatment and compared to matched controls. Serum prestin was significantly elevated before ABR threshold shifts in mice exposed to cisplatin compared to control mice. Prestin concentration also correlated with the severity of hearing threshold shifts in mice. After an extended rest post-cisplatin treatment, prestin returned to baseline levels in mice and humans. Prestin was significantly elevated in the serum before the onset of objective hearing loss and correlated with the severity of hearing damage indicating that prestin may function as an effective biomarker of cisplatin-induced ototoxicity. Human serum prestin levels responded similarly to mice > 3 weeks from ototoxic exposure with decreased levels of prestin in the serum.
Topics: Humans; Mice; Animals; Cisplatin; Ototoxicity; Evoked Potentials, Auditory, Brain Stem; Hearing Loss; Biomarkers; Antineoplastic Agents
PubMed: 36302835
DOI: 10.1038/s41598-022-23034-x -
Biomolecules Oct 2022Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with...
Noise-induced hearing loss (NIHL) is one of the leading causes of sensorineural hearing loss with global importance. The current treatment of choice for patients with hearing problems is a hearing aid or a cochlear implant. However, there is currently no treatment to restore physiological hearing. The development of preventive drugs is currently the focus of hearing research. In order to test the efficacy of a drug, the active ingredient has to be applied at reliable concentrations over a period of time. Osmotic minipumps can provide local drug delivery into the perilymph. Combined with a cochlear implant or a tube, the implantation of the pumps may lead to increased hearing thresholds. Such surgery-related threshold shifts complicate the examination of other factors, such as noise. The aim of the present study was to develop an animal model for the examination of substances that potentially prevent NIHL. For this purpose, six male guinea pigs were unilaterally implanted with a silicon catheter with a hook-shaped microcannula at its tip, attached to an artificial perilymph containing osmotic minipump. One week after surgery, the animals were exposed to four hours of a musical piece, presented at 120 dB SPL, to induce a threshold shift. The implantation of the hook-delivery device caused a moderate threshold shift that allows to detect an additional noise-induced temporary threshold shift. This method enables to investigate drug effects delivered prior to the noise insult in order to establish a preventive strategy against noise-induced temporary threshold shifts. The established drug delivery approach allows the release of drugs into the inner ear in a known concentration and for a known duration. This provides a scientific tool for basic research on drug effects in normal hearing animals.
Topics: Guinea Pigs; Male; Animals; Hearing Loss, Noise-Induced; Cochlea; Silicon; Hearing; Ear, Inner; Disease Models, Animal
PubMed: 36291636
DOI: 10.3390/biom12101427 -
Ear, Nose, & Throat Journal Oct 2022On a perilymphatic fistula, there is an extravasation of the perilymph fluid into the middle ear cavity. Cross-sectional imaging techniques have very important role in...
On a perilymphatic fistula, there is an extravasation of the perilymph fluid into the middle ear cavity. Cross-sectional imaging techniques have very important role in evaluation of inner and middle ear structures and temporal bone. While thin section CT scans can show successfully pneumolabyrinth and temporal bone fracture, high-resolution 3D volumetric MRI sequences can help to demonstrate posttraumatic ear effusion and cerebrospinal fluid fistula into inner ear or middle ear.
PubMed: 36193877
DOI: 10.1177/01455613221131302