-
Scientific Reports Jun 2024This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and...
This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.
Topics: Humans; Neuroma, Acoustic; Female; Male; Middle Aged; Proteome; Perilymph; Hearing Loss; Adult; Aged; Cerebrospinal Fluid; Audiometry, Pure-Tone
PubMed: 38898156
DOI: 10.1038/s41598-024-64352-6 -
Frontiers in Pharmacology 2024The inner ear is the organ responsible for hearing and balance. Inner ear dysfunction can be the result of infection, trauma, ototoxic drugs, genetic mutation or... (Review)
Review
The inner ear is the organ responsible for hearing and balance. Inner ear dysfunction can be the result of infection, trauma, ototoxic drugs, genetic mutation or predisposition. Often, like for Ménière disease, the cause is unknown. Due to the complex access to the inner ear as a fluid-filled cavity within the temporal bone of the skull, effective diagnosis of inner ear pathologies and targeted drug delivery pose significant challenges. Samples of inner ear fluids can only be collected during surgery because the available procedures damage the tiny and fragile structures of the inner ear. Concerning drug administration, the final dose, kinetics, and targets cannot be controlled. Overcoming these limitations is crucial for successful inner ear precision medicine. Recently, notable advancements in microneedle technologies offer the potential for safe sampling of inner ear fluids and local treatment. Ultrasharp microneedles can reach the inner ear fluids with minimal damage to the organ, collect μl amounts of perilymph, and deliver therapeutic agents . This review highlights the potential of ultrasharp microneedles, combined with nano vectors and gene therapy, to effectively treat inner ear diseases of different etiology on an individual basis. Though further research is necessary to translate these innovative approaches into clinical practice, these technologies may represent a true breakthrough in the clinical approach to inner ear diseases, ushering in a new era of personalized medicine.
PubMed: 38327988
DOI: 10.3389/fphar.2024.1328460 -
Magnetic Resonance in Medical Sciences... Apr 2024The endolymph of the inner ear, vital for balance and hearing, has long been considered impermeable to intravenously administered gadolinium-based contrast agents...
PURPOSE
The endolymph of the inner ear, vital for balance and hearing, has long been considered impermeable to intravenously administered gadolinium-based contrast agents (GBCAs) due to the tight blood-endolymph barrier. However, anecdotal observations suggested potential GBCA entry in delayed heavily T2-weighted 3D-real inversion recovery (IR) MRI scans. This study systematically investigated GBCA distribution in the endolymph using this 3D-real IR sequence.
METHODS
Forty-one patients suspected of endolymphatic hydrops (EHs) underwent pre-contrast, 4-h, and 24-h post-contrast 3D-real IR imaging. Signal intensity in cerebrospinal fluid (CSF), perilymph, and endolymph was measured and analyzed for temporal dynamics of GBCA uptake, correlations between compartments, and the influence of age and presence of EH.
RESULTS
Endolymph showed a delayed peak GBCA uptake at 24h, contrasting with peaks in perilymph and CSF at 4h. Weak to moderate positive correlations between endolymph and CSF contrast effect were observed at both 4 (r = 0.483) and 24h (r = 0.585), suggesting possible inter-compartmental interactions. Neither the presence of EH nor age significantly influenced endolymph enhancement. However, both perilymph and CSF contrast effects significantly correlated with age at both time points.
CONCLUSION
This study provides the first in vivo systematic confirmation of GBCA entering the endolymph following intravenous administration. Notably, endolymph uptake peaked at 24h, significantly later than perilymph and CSF. The lack of a link between endolymph contrast and both perilymph and age suggests distinct uptake mechanisms. These findings shed light on inner ear fluid dynamics and their potential implications in Ménière's disease and other inner ear disorders.
PubMed: 38569839
DOI: 10.2463/mrms.mp.2024-0011 -
Frontiers in Neurology 2023Vestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive...
BACKGROUND
Vestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive function, and processing speed among others. Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems; however, individuals also experience measurable deficits in basic decision-making, short-term memory, concentration, spatial cognition, and depression. These suggest central mechanisms of impairment are associated with vestibular disorders; therefore, we directly tested this hypothesis using both an auditory and visual decision-making task of varying difficulty levels in our model of SSCD.
METHODS
Adult Mongolian gerbils ( = 33) were trained on one of four versions of a Go-NoGo stimulus presentation rate discrimination task that included standard ("easy") or more difficult ("hard") auditory and visual stimuli. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Animals with persistent circling or head tilt were excluded to minimize effects from acute vestibular injury. Testing recommenced at postoperative day 5 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out.
RESULTS
Behavioral data (d-primes) were compared between preoperative performance (training day 8-10) and postoperative days 6-8 and 13-15. Behavioral performance was measured during the peak of SSCD induced ABR and c + VEMP impairment and the return towards baseline as the dehiscence began to resurface by osteoneogenesis. There were significant differences in behavioral performance (d-prime) and its behavioral components (Hits, Misses, False Alarms, and Correct Rejections). These changes were highly correlated with persistent deficits in c + VEMPs at the end of training (postoperative day 15). The controls demonstrated additional learning post procedure that was absent in the SSCD group.
CONCLUSION
These results suggest that aberrant asymmetric vestibular output results in decision-making impairments in these discrimination tasks and could be associated with the other cognitive impairments resulting from vestibular dysfunction.
PubMed: 37905188
DOI: 10.3389/fneur.2023.1259030