-
Neuroradiology May 2022Heavily T2-weighted 3D FLAIR (hTw-3D-FLAIR) sequence with constant flip angle (CFA) has been reported as being more sensitive to low concentrations of gadolinium (Gd)...
PURPOSE
Heavily T2-weighted 3D FLAIR (hTw-3D-FLAIR) sequence with constant flip angle (CFA) has been reported as being more sensitive to low concentrations of gadolinium (Gd) enabling endolymphatic hydrops (EH) visualization. The purpose of this study was to compare signal-to-noise (SNR) ratio, detection rate of EH, and increased perilymphatic enhancement (PE) as well as diagnostic accuracy in diagnosing definite Menière's disease (MD), using 3D-SPACE FLAIR versus conventional 3D-TSE FLAIR.
METHODS
This retrospective study included 29 definite MD patients who underwent a 4-h delayed intravenous (IV) Gd-enhanced 3D-TSE FLAIR and 3D-SPACE FLAIR MRI between February 2019 and February 2020. MR images were qualitatively and quantitatively analyzed twice by 2 experienced head and neck radiologists. Qualitative assessment included grading of cochlear and vestibular EH and visual comparison of PE. Quantitative assessment of PE was performed by placing a region of interest (ROI) and ratio calculation in the basal turn of the cochlea and the brainstem.
RESULTS
The intra- and inter-reader reliability for grading of EH and PE was excellent (0.7 < kappa < 0.9) for 3D-SPACE FLAIR and exceeded the values for 3D-TSE FLAIR (0.5 < kappa < 0.9) The combination of EH and visual assessment of PE has the highest diagnostic accuracy in diagnosing definite MD on 3D-SPACE FLAIR with a sensitivity of 0.91 and a specificity of 0.98 resulting in a sensitivity raise of 6% compared to 3D-TSE FLAIR.
CONCLUSION
Four-hour delayed IV Gd-enhanced 3D-SPACE FLAIR sequence has a higher sensitivity and reproducibility than 3D-TSE FLAIR for the visualization of EH and increased PE in definite MD patients.
Topics: Contrast Media; Endolymphatic Hydrops; Gadolinium; Humans; Imaging, Three-Dimensional; Magnetic Resonance Imaging; Meniere Disease; Reproducibility of Results; Retrospective Studies
PubMed: 35149883
DOI: 10.1007/s00234-022-02913-0 -
Frontiers in Surgery 2021Endolymphatic sac surgery is effective in treating intractable Meniere's disease (MD), but the underlying mechanism is still unknown. Our study investigated the...
Endolymphatic sac surgery is effective in treating intractable Meniere's disease (MD), but the underlying mechanism is still unknown. Our study investigated the mechanism by which endolymphatic sac-mastoid shunt (EMS) surgery is effective in treating MD by means of imaging. The experiment included 19 patients with intractable MD who underwent 3D-fluid-attenuated inversion recovery (FLAIR) MRI with a 3-Tesla unit 6 h after intravenous administration of gadolinium, before EMS, and 2 years after the surgery. The enhanced perilymphatic space in the bilateral cochlea, vestibule, and canals was visualized and compared with that in the endolymphatic space by quantitatively scoring the scala vestibuli of the cochlea and by measuring the developing area of the vestibules quantitatively. Gadolinium was present in the perilymph of the inner ear in the cochlea, vestibules, and canals of all patients. At the 2-year follow-up, 14 (73.68%) patients had vertigo control. Both before and 2 years after surgery, significant differences were observed in the scala vestibuli scores and the area of vestibular perilymph between the affected and healthy sides. The scala vestibuli scores and the area of vestibular perilymph, however, did not differ when comparing them before and after surgery. According to our results, endolymphatic hydrops was not significantly reduced by surgery. The mechanism by which EMS controls vertigo might be unrelated to the improvement in hydrops.
PubMed: 35096954
DOI: 10.3389/fsurg.2021.673323 -
Frontiers in Neurology 2021Dizziness is a frequent complaint after head trauma. Among patients who suffer a concussion (mild traumatic brain injury or mTBI), dizziness is second only to headache... (Review)
Review
Dizziness is a frequent complaint after head trauma. Among patients who suffer a concussion (mild traumatic brain injury or mTBI), dizziness is second only to headache in symptom frequency. The differential diagnosis of post-concussive dizziness (PCD) can be divided into non-vestibular, central vestibular and peripheral vestibular causes with growing recognition that patients frequently exhibit both central and peripheral findings on vestibular testing. Symptoms that traditionally have been ascribed to central vestibular dysfunction may be due to peripheral dysfunction. Further, our ability to test peripheral vestibular function has improved and has allowed us to identify peripheral disorders that in the past would have remained unnoticed. The importance of the identification of the peripheral component in PCD lies in our ability to remedy the peripheral vestibular component to a much greater extent than the central component. Unfortunately, many patients are not adequately evaluated for vestibular disorders until long after the onset of their symptoms. Among the diagnoses seen as causes for PCD are (1) Central vestibular disorders, (2) Benign Paroxysmal Positional Vertigo (BPPV), (3) Labyrinthine dehiscence/perilymph fistula syndrome, (4) labyrinthine concussion, (5) secondary endolymphatic hydrops, (6) Temporal bone fracture, and (7) Malingering (particularly when litigation is pending). These diagnoses are not mutually exclusive and PCD patients frequently exhibit a combination of these disorders. A review of the literature and a general approach to the patient with post-concussive dizziness will be detailed as well as a review of the above-mentioned diagnostic categories.
PubMed: 35058868
DOI: 10.3389/fneur.2021.718318 -
Journal of Clinical Medicine Jan 2022In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate... (Review)
Review
In the clinical setting, the pathophysiology of sensorineural hearing loss is poorly defined and there are currently no diagnostic tests available to differentiate between subtypes. This often leaves patients with generalized treatment options such as steroids, hearing aids, or cochlear implantation. The gold standard for localizing disease is direct biopsy or imaging of the affected tissue; however, the inaccessibility and fragility of the cochlea make these techniques difficult. Thus, the establishment of an indirect biopsy, a sampling of inner fluids, is needed to advance inner ear diagnostics and allow for the development of novel therapeutics for inner ear disease. A promising source is perilymph, an inner ear liquid that bathes multiple structures critical to sound transduction. Intraoperative perilymph sampling via the round window membrane of the cochlea has been successfully used to profile the proteome, metabolome, and transcriptome of the inner ear and is a potential source of biomarker discovery. Despite its potential to provide insight into inner ear pathologies, human perilymph sampling continues to be controversial and is currently performed only in conjunction with a planned procedure where the inner ear is opened. Here, we review the safety of procedures in which the inner ear is opened, highlight studies where perilymph analysis has advanced our knowledge of inner ear diseases, and finally propose that perilymph sampling could be done as a stand-alone procedure, thereby advancing our ability to accurately classify sensorineural hearing loss.
PubMed: 35054010
DOI: 10.3390/jcm11020316 -
Drug Delivery Dec 2022Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its...
Dexamethasone sodium phosphate (Dex-SP) is the most commonly used drug administered via intratympanic injection for the treatment of acute hearing loss, but its penetration efficiency into the inner ear is very low. To address this problem, we evaluated the possibility of administering dexamethasone nanosuspensions via intratympanic injection because hydrophobic drugs might be more effective in penetrating the inner ear. Three types of dexamethasone nanosuspensions were prepared; the dexamethasone nanoparticles in the three nanosuspensions were between approximately 250 and 350 nm in size. To compare the efficiency of Dex-SP and dexamethasone nanosuspension in delivering dexamethasone to the inner ear, the concentrations of dexamethasone in perilymph and cochlear tissues were compared by liquid chromatography-mass spectrometry. The dexamethasone nanosuspensions resulted in significantly higher drug concentrations in perilymph and cochlear tissues than Dex-SP at 6 h; interestingly, animals treated with nanosuspensions showed a 26-fold higher dexamethasone concentrations in their cochlear tissues than animals treated with Dex-SP. In addition, dexamethasone nanosuspension caused better glucocorticoid receptor phosphorylation than Dex-SP both and , and in the ototoxic animal model, the nanosuspension showed a significantly better hearing-protective effect against ototoxic drugs than Dex-SP. In the safety evaluation, the nanosuspension showed no toxicity at concentrations up to 20 mg/mL. In conclusion, a nanosuspension of dexamethasone was able to deliver dexamethasone to the cochlea very safely and efficiently and showed potential as a formula for intratympanic injection.
Topics: Animals; Anti-Inflammatory Agents; Cell Line; Chemistry, Pharmaceutical; Dexamethasone; Drug Carriers; Drug Liberation; Hearing Loss; Injection, Intratympanic; Male; Mice; Mice, Inbred BALB C; Nanoparticle Drug Delivery System; Particle Size; Solubility; Surface Properties; Suspensions
PubMed: 34967280
DOI: 10.1080/10717544.2021.2021320 -
Frontiers in Cellular Neuroscience 2021Mesenchymal stromal cells (MSCs) are an adult derived stem cell-like population that has been shown to mediate repair in a wide range of degenerative disorders. The...
Mesenchymal stromal cells (MSCs) are an adult derived stem cell-like population that has been shown to mediate repair in a wide range of degenerative disorders. The protective effects of MSCs are mainly mediated by the release of growth factors and cytokines thereby modulating the diseased environment and the immune system. Within the inner ear, MSCs have been shown protective against tissue damage induced by sound and a variety of ototoxins. To better understand the mechanism of action of MSCs in the inner ear, mice were exposed to narrow band noise. After exposure, MSCs derived from human umbilical cord Wharton's jelly were injected into the perilymph. Controls consisted of mice exposed to sound trauma only. Forty-eight hours post-cell delivery, total RNA was extracted from the cochlea and RNAseq performed to evaluate the gene expression induced by the cell therapy. Changes in gene expression were grouped together based on gene ontology classification. A separate cohort of animals was treated in a similar fashion and allowed to survive for 2 weeks post-cell therapy and hearing outcomes determined. Treatment with MSCs after severe sound trauma induced a moderate hearing protective effect. MSC treatment resulted in an up-regulation of genes related to immune modulation, hypoxia response, mitochondrial function and regulation of apoptosis. There was a down-regulation of genes related to synaptic remodeling, calcium homeostasis and the extracellular matrix. Application of MSCs may provide a novel approach to treating sound trauma induced hearing loss and may aid in the identification of novel strategies to protect hearing.
PubMed: 34887728
DOI: 10.3389/fncel.2021.656930 -
European Journal of Pharmaceutics and... Jan 2022Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to...
Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to deliver gene therapy agents, or biologics to the inner ear. Further diversion from the middle ear and perilymph to blood circulation and cerebrospinal fluid via the cochlear aqueduct are one of the limiting factors and so far not understood well enough. In this study, intratympanically applied triamcinolone acetonide was determined in cerebrospinal fluid. Additionally, perilymph was sampled through the round window membrane as well as at the lateral semicircular canal to determine drug levels. Of the twenty-one included patients, triamcinolone acetonide was quantifiable in cerebrospinal fluid in 43% at very low levels (range 0 ng/ml-6.2 ng/ml) which did not correlate with perilymph levels. Drug levels at the two different perilymph sampling sites were within a range of 13.5 ng/ml to 1180.0 ng/ml. Results suggest an equal distribution of triamcinolone acetonide to semicircular canals, which might support the use of triamcinolone acetonide as a treatment option for vestibular pathologies such as Menièrés disease. On the other hand, the distribution to cerebrospinal fluid might be limiting current approaches in gene therapy where a central distribution is unwanted.
Topics: Cerebrospinal Fluid; Female; Glucocorticoids; Humans; Injection, Intratympanic; Male; Middle Aged; Neuroma, Acoustic; Perilymph; Triamcinolone Acetonide
PubMed: 34864199
DOI: 10.1016/j.ejpb.2021.11.009 -
Frontiers in Surgery 2021Loudness recruitment is commonly experienced by patients with putative endolymphatic hydrops. Loudness recruitment is abnormal loudness growth with high-level sounds...
Loudness recruitment is commonly experienced by patients with putative endolymphatic hydrops. Loudness recruitment is abnormal loudness growth with high-level sounds being perceived as having normal loudness even though hearing thresholds are elevated. The traditional interpretation of recruitment is that cochlear amplification has been reduced. Since the cochlear amplifier acts primarily at low sound levels, an ear with elevated thresholds from reduced cochlear amplification can have normal processing at high sound levels. In humans, recruitment can be studied using perceptual loudness but in animals physiological measurements are used. Recruitment in animal responses has never been unequivocally demonstrated because the animals used had damage to sensory and neural cells, not solely a reduction of cochlear amplification. Investigators have thus looked for, and found, evidence of recruitment in the auditory central nervous system (CNS). While studies on CNS recruitment are informative, they cannot rule out the traditional interpretation of recruitment originating in the cochlea. We used techniques that could assess hearing function throughout entire frequency- and dynamic-range of hearing. Measurements were made from two animal models: guinea-pig ears with endolymphatic-sac-ablation surgery to produce endolymphatic hydrops, and naïve guinea-pig ears with cochlear perfusions of 13 mM 2-Hydroxypropyl-Beta-Cyclodextrin (HPBCD) in artificial perilymph. Endolymphatic sac ablation caused low-frequency loss. Animals treated with HPBCD had hearing loss at all frequencies. None of these animals had loss of hair cells or synapses on auditory nerve fibers. In ears with endolymphatic hydrops and those perfused with HPBCD, auditory-nerve based measurements at low frequencies showed recruitment compared to controls. Recruitment was not found at high frequencies (> 4 kHz) where hearing thresholds were normal in ears with endolymphatic hydrops and elevated in ears treated with HPBCD. We found compelling evidence of recruitment in auditory-nerve data. Such clear evidence has never been shown before. Our findings suggest that, in patients suspected of having endolymphatic hydrops, loudness recruitment may be a good indication that the associated low-frequency hearing loss originates from a reduction of cochlear amplification, and that measurements of recruitment could be used in differential diagnosis and treatment monitoring of Ménière's disease.
PubMed: 34676239
DOI: 10.3389/fsurg.2021.687490 -
Neuroscience Letters Nov 2021Evaluation of hearing loss patients using clinical audiometry has been unable to give a definitive cellular or molecular diagnosis, hampering the development of... (Observational Study)
Observational Study
Evaluation of hearing loss patients using clinical audiometry has been unable to give a definitive cellular or molecular diagnosis, hampering the development of treatments of sensorineural hearing loss. However, biopsy of inner ear tissue without losing residual hearing function for pathologic diagnosis is extremely challenging. In a clinical setting, perilymph can be accessed, potentially allowing the development of fluid based diagnostic tests. Recent approaches to improving inner ear diagnostics have been focusing on the evaluation of the proteomic or miRNA profiles of perilymph. Inspired by recent characterization and classification of many neurodegenerative diseases using exosomes which not only are produced in locally in diseased tissue but are transported beyond the blood brain barrier, we demonstrate the isolation of human inner ear specific exosomes using a novel ultrasensitive immunomagnetic nano pom-poms capture-release approach. Using perilymph samples harvested from surgical procedures, we were able to isolate exosomes from sensorineural hearing loss patients in only 2-5 μL of perilymph. By isolating sensory hair cell derived exosomes through their expression level of myosin VIIa, we for the first-time sample material from hair cells in the living human inner ear. This work sets up the first demonstration of immunomagnetic capture-release nano pom-pom isolated exosomes for liquid biopsy diagnosis of sensorineural hearing loss. With the ability to isolate exosomes derived from different cell types for molecular characterization, this method also can be developed for analyzing exosomal biomarkers from more accessible patient tissue fluids such as plasma.
Topics: Adult; Audiometry; Cell Fractionation; Exosomes; Feasibility Studies; Female; Hair Cells, Auditory; Hearing Loss, Sensorineural; Humans; Immunomagnetic Separation; Liquid Biopsy; Male; Middle Aged; Perilymph
PubMed: 34619343
DOI: 10.1016/j.neulet.2021.136282 -
The Journal of International Advanced... Sep 2021To evaluate the relationship between the third window abnormalities and congenital inner ear malformations in pediatric patients with different types of hearing loss. If...
OBJECTIVE
To evaluate the relationship between the third window abnormalities and congenital inner ear malformations in pediatric patients with different types of hearing loss. If such a relationship should exist, it would be important to take it into account, in order to diagnose and treat pediatric hearing loss cases more accurately.
METHODS
Two hundred twenty-one children with hearing loss who had temporal bone computed tomography (CT) examination and were identified from 2013 to 2018 were retrospectively evaluated. The types of hearing loss were grouped as sensorineural hearing loss (SNHL), conductive hearing loss (CHL), and mixed hearing loss (MHL). Third window abnormalities included superior semicircular canal (SC) dehiscence, posterior SC dehiscence, enlarged vestibular aqueduct (EVA), X-linked stapes gusher, perilymph fistula, and bone dyscrasias. Congenital inner ear malformations included cochleovestibular, SC, and internal acoustic canal malformations. The relationships were analyzed with chi-square and Fisher's exact tests.
RESULTS
In the study, 40 patients had unilateral hearing loss and 181 had bilateral hearing loss. In 402 ears, the rates of SNHL, CHL, and MHL were 88.5%, 6.9%, and 4.4%, respectively. EVA was the most common third window abnormality (41/402; 9.7%), and SC malformations were the most common inner ear malformations (53/402; 13.2%). In the SNHL group, superior and posterior SC dehiscence were associated with cochleovestibular malformations (P = .035 and.020, respectively). In the CHL group, there was a relationship between EVA and SC malformations (P = .041). No relationships were found in the MHL group.
CONCLUSION
Third window abnormalities and congenital inner ear malformations may be encountered simultaneously in children with SNHL and CHL.
Topics: Child; Hearing Loss, Conductive; Hearing Loss, Sensorineural; Humans; Retrospective Studies; Temporal Bone; Vestibular Aqueduct
PubMed: 34617887
DOI: 10.5152/iao.2021.9482