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Pathology repositories worldwide store millions of celloidin-processed human brain and temporal bone (TB) sections vital for studying central nervous system diseases and sensory organs. However, accessing these sections for modern molecular-pathological research, like immunohistochemistry, is hindered by the challenge of removing celloidin without damaging tissue. In this study, we explored the use of polyethylene glycols (PEGs), a class of non-hazardous, ethylene glycol oligomers, combined with an improved section mounting technique, to gently and effectively dissolve celloidin from sections archived for up to 40 years. Optimizing our protocol involved exploring celloidin dissolution kinetics in PEGs of varying molecular weights and terminations, as well as different temperatures. Low molecular weight PEGs, particularly PEG 200, were the most efficient celloidin solvent. Nuclear magnetic resonance (NMR) spectroscopy of celloidin-PEG 200 dissolution products revealed no chemical alterations, suggesting pure solvation without chemical modification. Because the solvation of celloidin in PEG was inhibited by proteins, we further developed a protein-free mounting protocol allowing complete celloidin removal in 30 to 60 minutes by immersing in PEG 200. In summary, our approach overcomes major methodological hurdles, rendering decades-old archival celloidin sections viable for immunohistochemical and other molecular biological techniques, while enhancing safety and workflow efficiency. [ABSTRACT FROM AUTHOR]

In this study, the presence of rare missense variants and frame shift deletions in the I TECTA i gene in six unrelated families with MD suggests a role of this gene in the pathophysiology of the disease. Three rare missense variants (colored in blue) and two short deletions (colored in red) were found in four multicase MD families (arrow shaped) and two additional families with one MD patient and relatives with partial syndromes (diamond shaped). Dear Editor Although there have been considerable advances in recent years, the contribution of genetic factors to Meniere's disease (MD) is not yet fully understood. [Extracted from the article]

We describe the use of calcium sulfate beads as antibiotic carrier in a patient, who suffered from chronic mastoiditis with consecutive otogenic meningitis due to Burkholderia cenocepacia. Our findings suggest a possible role of calcium sulfate matrix as a local antibiotic carrier in the mastoid in complicated mastoiditis cases. [ABSTRACT FROM AUTHOR]

BACKGROUND: Surgical treatment of vestibular schwannoma (VS) leads to acute ipsilateral vestibular loss if there is residual vestibular function before surgery. To overcome the sequelae of acute ipsilateral vestibular loss and to decrease postoperative recovery time, the concept of preemptive vestibular ablation with gentamicin and vestibular prehabilitation before surgery has been developed ("vestibular prehab"). OBJECTIVE: Studying postural stability during walking and handicap of dizziness over a 1-year follow-up period in VS patients undergoing vestibular prehab before surgical treatment of VS. METHODS: A retrospective review of consecutive patients with a diagnosis of a VS undergoing surgical therapy from June 2012 to March 2018 was performed. All patients were included with documentation of the length of hospital duration and the Dizziness Handicap Inventory (DHI) and the Functional Gait Assessment (FGA) assessed preoperatively as well as 6 weeks and 1 year postoperatively. RESULTS: A total 68 VS patients were included, of which 29 patients received preoperative vestibular ablation by intratympanic injection of gentamicin. Mean VS diameter was 20.2 mm (SD 9.4 mm) and mean age at surgery was 49.6 years (SD 11.5 years). Vestibular prehab had no effect on DHI and FGA at any time point studied. CONCLUSIONS: We found no effect of vestibular prehab on postural stability during walking and on the handicap of dizziness. These findings add to the body of knowledge consisting of conflicting results of vestibular prehab. Therefore, vestibular prehab should be applied only in selected cases in an experimental setting. [ABSTRACT FROM AUTHOR]

Objective: Meniere's disease (MD) progresses from unilateral to bilateral disease in up to 50% of patients, often chronically and severely impairing balance and hearing functions. According to previous studies, 91% of bilateral MD patients demonstrate bilateral hypoplasia of the endolymphatic sac (ES) upon histological and radiological examination of their inner ears. Here, we seek to validate a radiological marker for ES hypoplasia that predicts the risk for future progression to bilateral MD in individual patients. Methods: Patients with unilateral MD and radiological evidence for ES hypoplasia in either the clinically affected inner ear (cohort MDuni-hpuni) or both inner ears (cohort MDuni-hpbi) were included. Given our hypothesis that ES hypoplasia critically predisposes the inner ear to MD, we expected progression to bilateral MD only in the MDuni-hpbi cohort. To investigate eventual progression to bilateral MD, clinical, audiometric, and imaging data were retrospectively collected over follow-up periods of up to 31 years. Results: A total of 44 patients were included in the MD-hpuni (n = 15) and MDuni-hpbi (n = 29) cohorts. In line with our radiology-based predictions, none (0/15) of the MD-hpuni patients exhibited progression to bilateral MD, whereas 20/29 (69%) MD-hpbi patients have already progressed to bilateral MD. Using the Kaplan–Meier estimator, bilateral disease progression would be observed in 100% of MD-hpbi patients 31 years after the initial diagnosis with an estimated median time to bilateral progression of 12 years. The nine MD-hpbi patients who, so far, remained with unilateral disease demonstrated a median time since initial (unilateral) MD diagnosis of only 6 years and are thus still expected to progress to bilateral disease. Conclusion: Progression to bilateral MD adheres to predictions based on the radiological presence or absence of ES hypoplasia. This prognostic tool, if validated by prospective long-term studies, will provide clinically relevant information about a patient's future disease burden and will help to select more personalized treatment regimens. [ABSTRACT FROM AUTHOR]

Signal transducer and activator of transcription 1 (STAT1) is known to be an important player in inflammatory responses. STAT1 as a transcription factor regulates the expression of multiple proinflammatory genes. Inflammatory response is one of the common effects of ototoxicity. Our group reported that hair cells of STAT1 knockout (STAT1-KO) mice are less sensitive to ototoxic agents in-vitro. The effect of inflammatory responses in STAT1-KO mice has primarily been studied challenging them with several pathogens and analyzing different organs of those mice. However, the effect of STAT1 ablation in the mouse inner ear has not been reported. Therefore, we evaluated the cochlear function of wild type and STAT1-KO mice via auditory brain stem response (ABR) and performed histopathologic analysis of their temporal bones. We found ABR responses were affected in STAT1-KO mice with cases of bilateral and unilateral hearing impairment. Histopathologic examination of the middle and inner ears showed bilateral and unilateral otitis media. Otitis media was characterized by effusion of middle and inner ear that varied between the mice in volume and inflammatory cell content. In addition, the thickness of the middle ear mucosae in STAT1-KO mice were more pronounced than those in wild type mice. The degree of middle and inner ear inflammation correlated with ABR threshold elevation in STAT1-KO mice. It appears that a number of mice with inflammation underwent spontaneous resolution. The ABR thresholds were variable and showed a tendency to increase in homozygous and heterozygous STAT1-KO mice. These findings suggest that STAT1 ablation confers an increased susceptibility to otitis media leading to hearing impairment. Thus, the study supports the new role of STAT1 as otitis media predisposition gene. [ABSTRACT FROM AUTHOR]

Aminoglycoside ototoxicity is common in clinical practice but reliable protective agents currently do not exist. Aminoglycoside regimens causing ototoxicity in different laboratory animals are under investigation. The assessment method used most commonly to determine auditory effects is the auditory brainstem response (ABR). Distortion product otoacoustic emissions (DPOAE) have been used less frequently. A precise recommendation on the specific method to assess peripheral auditory function before and after aminoglycoside toxicity in mice does not exist. In order to evaluate various mouse models for ototoxic injury caused by various aminoglycoside regimens, there is a need for performing preliminary tests in small cohorts before large experiments. The aim of our study was to investigate different aminoglycoside regimens that cause substantial ototoxic damage in vivo. Aminoglycosides are safe and produce a detectable hearing threshold shift in a small cohort of mice that can be used as a model for preliminary tests. Different ototoxic regimens were assessed by ABR and DPOAE measurements pre- and post-treatment. Further, the sensory cell loss was quantified by counting hair cells in the cochlea. It was revealed that an ototoxic regimen with kanamycin twice daily for 15 consecutive days is safe, well tolerated and produces an early significant hearing threshold shift detected by DPOAE in a small cohort of mice. The study compared ABR and DPOAE in mentioned regimens for the first time and illustrated that DPOAE is well suited for detecting hearing threshold shifts in high frequencies before ABR threshold shifts occur in accordance with predominating outer hair cell damage mainly in the basal turn of the cochlea. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the quality of perceived sound after stapedotomy over a 1-year follow-up period focussing on incidence of dysacusis, particularly distorted sound perception (DSP). DSP was assessed by (i) determination of the frequencies and hearing level that such perceptions are elicited by pure tones (pure-tone-evoked distorted sound perception, PTE-DSP), a novel psychoacoustic measurement introduced in this paper, and (ii) assessment of patient-reported occurrence of DSP using the Amsterdam Post Operative Sound Evaluation (APOSE) questionnaire (APOSE-DSP). Design: Prospective study. Study sample: Patients (n = 23) with otosclerosis undergoing stapedotomy. Results: An air-bone gap of <20 dB was achieved in 100% of the patients. Three weeks postoperatively, 48% of the patients reported measured PTE-DSP and 39% of the patients experienced APOSE-DSP. The PTE-DSP significantly decreased during the 1-year follow-up period (p = 0.03). Postoperatively, APOSE-DSP was associated with a smaller benefit (improvement in air conduction; p = 0.03), yet, a lower bone conduction pure-tone average was associated with PTE-DSP (p = 0.006). Conclusions: DSP after stapedotomy is associated with a smaller benefit 3 months after stapedotomy. DSP commonly occur after stapedotomy, but decrease over time. This is important information to be included in patient counselling before stapedotomy. [ABSTRACT FROM AUTHOR]

Posttraumatic Meniere's syndrome is a rare clinical entity. The pathomechanism by which temporal bone trauma leads to fluctuating audiovestibular symptoms, in some cases with a delay of onset many years after trauma, remains elusive. Here, a clinical case and the respective temporal bone imaging data were reviewed to investigate the underlying inner ear pathology. A 44-year-old patient presented with left-sided Meniere's syndrome 34 years after he suffered an ipsilateral temporal bone fracture caused by a car accident. Clinical imaging showed left cochleovestibular hydrops (gadolinium-enhanced MRI) and bony obliteration of the left VA (CT imaging), resulting in discontinuity of the ES. Our findings suggest that a temporal bone fracture with a "retrolabyrinthine" course, traversing the VA, caused intraaqueductal callus bone formation and progressive blockage of the VA. As a result, the extraosseous (distal) endolymphatic sac (eES) became separated from the cochleovestibular labyrinth, an event that presumably underlies endolymphatic hydrops formation and that precipitates the onset of clinical Meniere's symptoms in this case. [ABSTRACT FROM AUTHOR]

Two histopathological subtypes of Meniere's disease (MD) were recently described in a human post-mortem pathology study. The first subtype demonstrated a degenerating distal endolymphatic sac (ES) in the affected inner ear (subtype MD-dg); the second subtype (MD-hp) demonstrated an ES that was developmentally hypoplastic. The two subtypes were associated with different clinical disease features (phenotypes), suggesting that distinct endotype-phenotype patterns exist among MD patients. Therefore, clinical endotyping based on ES pathology may reveal clinically meaningful MD patient subgroups. Here, we retrospectively determined the ES pathologies of clinical MD patients (n = 72) who underwent intravenous delayed gadolinium-enhanced inner ear magnetic resonance imaging using previously established indirect radiographic markers for both ES pathologies. Phenotypic subgroup differences were evidenced; for example, the MD-dg group presented a higher average of vertigo attacks (ratio of vertigo patterns daily/weekly/other vs. monthly, MD-dg: 6.87: 1; MD-hp: 1.43: 1; p = 0.048) and more severely reduced vestibular function upon caloric testing (average caloric asymmetry ratio, MD-dg: 30.2% ± 30.4%; MD-hp: 13.5% ± 15.2%; p = 0.009), while the MD-hp group presented a predominantly male sex ratio (MD-hp: 0.06:1 [f/m]; MD-dg: 1.2:1 [f/m]; p = 0.0004), higher frequencies of bilateral clinical affection (MD-hp: 29.4%; MD-dg: 5.5%; p = 0.015), a positive family history for hearing loss/vertigo/MD (MD-hp: 41.2%; MD-dg: 15.7%; p = 0.028), and radiographic signs of concomitant temporal bone abnormalities, i.e., semicircular canal dehiscence (MD-hp: 29.4%; MD-dg: 3.6%; p = 0.007). In conclusion, this new endotyping approach may potentially improve the diagnosis, prognosis and clinical decision-making for individual MD patients. [ABSTRACT FROM AUTHOR]

Objective: In the assessment of chronic otitis media (COM) and its treatment, patient-reported outcomes are becoming increasingly important. The aim of the present study was to translate and validate the Zurich chronic middle ear inventory (ZCMEI-21) in Japanese in order to provide the first Japanese-language instrument for measuring health-related quality of life (HRQoL) in COM.Methods: The ZCMEI-21 was translated into Japanese according to published guidelines. In order to assess validity, the ZCMEI-21-Jap total score was compared to a question directly addressing HRQoL as well as the five-level version of the EQ-5D questionnaire, a generic measure of HRQoL.Results: Demographic data and validity were assessed in a total of 91 COM patients. The ZCMEI-21-Jap total and subscale scores were well comparable to those of the original validation study. Cronbach's α of the ZCMEI-21-Jap was 0.85, indicating an excellent internal consistency. The ZCMEI-21-Jap total score showed a strong correlation (r=0.68, p<0.0001) to the question directly addressing HRQoL and, as expected, only a moderate correlation to the EQ-5D scores (r=0.49, p<0.0001 for descriptive system score and r=0.44, p<0.0001 for VAS score).Conclusion: We successfully translated the ZCMEI-21 into Japanese and were able to obtain sufficient information during the validation process for the use of the ZCMEI-21-Jap to quantify HRQoL in patients with COM. With the current study, we aim to take a step forward towards an international standardization of reporting HRQoL in COM. [ABSTRACT FROM AUTHOR]