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Frontiers in Neurology 2023Ménière's disease (MD) is a chronic inner ear disorder with a multifactorial etiology. Decreased visualization of the endolymphatic duct (ED) and sac (ES) is thought...
BACKGROUND
Ménière's disease (MD) is a chronic inner ear disorder with a multifactorial etiology. Decreased visualization of the endolymphatic duct (ED) and sac (ES) is thought to be associated with MD, although controversy exists about whether this finding is specific to MD. Recent literature has revealed that two distinct ES pathologies, developmental hypoplasia and epithelial degeneration, can be distinguished in MD using the angular trajectory of the vestibular aqueduct (ATVA) or ED-ES system as a radiographic surrogate marker. It has been suggested that these two subtypes are associated with distinct phenotypical features. However, the clinical differences between the ATVA subtypes require further validation.
RESEARCH OBJECTIVE
The objective of this study is to investigate whether (1) non-visualization of the ED-ES system is a discriminative radiological feature for MD in a cohort of vertigo-associated pathologies (VAPs) and whether (2) different angular trajectories of the ED-ES system in MD are associated with distinguishable clinical features.
SETTING
The study was conducted in the Vertigo Referral Center (Haga Teaching Hospital, The Hague, the Netherlands).
METHODS
We retrospectively assessed 301 patients (187 definite MD and 114 other VAPs) that underwent 4h-delayed 3D FLAIR MRI. We evaluated (1) the visibility of the ED-ES system between MD and other VAP patients and (2) measured the angular trajectory of the ED-ES system. MD patients were stratified based on the angular measurements into α ≤ 120° (MD-120), α 120°-140° (MD-intermediate), or α ≥ 140° (MD-140). Correlations between ATVA subgroups and clinical parameters were evaluated.
RESULTS
Non-visualization of the ED-ES system was more common in definite MD patients compared with other VAPs ( < 0.001). Among definite MD patients, the MD-140 subtype demonstrated a longer history of vertigo ( = 0.006), a higher prevalence of bilateral clinical disease ( = 0.005), and a trend toward a male preponderance ( = 0.053). No significant differences were found between ATVA subgroups regarding the presence or severity of auditory symptoms, or the frequency of vertigo attacks.
CONCLUSION
Non-visualization of the ED-ES system is significantly associated with MD. Among MD patients with a visible ED-ES system, we demonstrated that the MD-140 subtype is associated with a longer disease duration, a higher prevalence of bilateral MD, and a trend toward a male preponderance.
PubMed: 37719762
DOI: 10.3389/fneur.2023.1239422 -
European Archives of... Sep 2023MR imaging was used to visualize the vestibular and cochlear endolymphatic hydrops in patients with Meniere's disease (MD). The relationship between the degree of...
PURPOSE
MR imaging was used to visualize the vestibular and cochlear endolymphatic hydrops in patients with Meniere's disease (MD). The relationship between the degree of hydrops and clinical characteristics, audiovestibular function, anxiety and depression state in MD patients.
METHODS
70 patients with definitely or probably unilateral Meniere's disease received bilateral intratympanic gadolinium administration and MR scanning. The degree of bilateral vestibular and cochlea hydrops were analyzed and evaluated by three-dimensional real inversion recovery (3D-real IR) sequence, and the correlation between the grades of endolymphatic hydrops (EH) and disease course, vertigo grading assessment, the duration of vertigo, hearing loss level, caloric test, vestibular myogenic evoked potential (VEMP), electrocochleogram (EcoG), vertigo disability scale (physical, emotional, functional), anxiety and depression scale were studied.
RESULTS
It was found that the vestibule and cochlea EH of the affected and the contralateral ear had different degrees of hydrops and there was no statistical difference between the left and right vestibules. The degree of vestibule EH (V-EH) was significantly positively correlated with the degree of cochlear EH (C-EH). C-EH and hearing loss level were positively correlated with EcoG. There was positive correlation between vestibular EH and hearing loss level, VEMP, caloric test, disease course or vertigo duration. There was a negative relationship between Dizziness Handicap Inventory (Emotion) (DHI(E)) and VEMP. Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores were positive correlated with DHI(E) and DHI total scores in MD patients.
CONCLUSION
Endolymph-enhancing MRI was used as an important imaging method for the diagnosis of labyrinthine hydrops in Meniere's disease. There were certain correlation between EH and the degree of vertigo attack, hearing loss level, vestibular function, and further changes in anxiety and depression emotion.
Topics: Humans; Meniere Disease; Imaging, Three-Dimensional; Endolymphatic Hydrops; Vertigo; Magnetic Resonance Imaging; Hearing Loss; Edema
PubMed: 36849561
DOI: 10.1007/s00405-023-07899-w -
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 -
Trials Jul 2023Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however,... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tinnitus is a leading cause of disease burden globally. Several therapeutic strategies are recommended in guidelines for the reduction of tinnitus distress; however, little is known about the potentially increased effectiveness of a combination of treatments and personalized treatments for each tinnitus patient.
METHODS
Within the Unification of Treatments and Interventions for Tinnitus Patients project, a multicenter, randomized clinical trial is conducted with the aim to compare the effectiveness of single treatments and combined treatments on tinnitus distress (UNITI-RCT). Five different tinnitus centers across Europe aim to treat chronic tinnitus patients with either cognitive behavioral therapy, sound therapy, structured counseling, or hearing aids alone, or with a combination of two of these treatments, resulting in four treatment arms with single treatment and six treatment arms with combinational treatment. This statistical analysis plan describes the statistical methods to be deployed in the UNITI-RCT.
DISCUSSION
The UNITI-RCT trial will provide important evidence about whether a combination of treatments is superior to a single treatment alone in the management of chronic tinnitus patients. This pre-specified statistical analysis plan details the methodology for the analysis of the UNITI trial results.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04663828 . The trial is ongoing. Date of registration: December 11, 2020. All patients that finished their treatment before 19 December 2022 are included in the main RCT analysis.
Topics: Humans; Tinnitus; Combined Modality Therapy; Anesthetics, Local; Cognitive Behavioral Therapy; Europe
PubMed: 37488627
DOI: 10.1186/s13063-023-07303-2 -
Neurotherapeutics : the Journal of the... Jun 2024Dizziness is one of the most common chief complaints in both the ambulatory care setting and the emergency department. These symptoms may be representative of a broad... (Review)
Review
Dizziness is one of the most common chief complaints in both the ambulatory care setting and the emergency department. These symptoms may be representative of a broad range of entities. Therefore, any attempt at treatment must first start with determining the etiology. In this current perspective, we focus specifically on the diagnosis of and treatment of vestibular migraine, which is common and overlaps clinically with a variety of other diagnoses. We discuss the traditional treatments for vestibular migraine in addition to the recent explosion of novel migraine therapeutics. Because vestibular migraine can mimic, or co-exist with, a variety of other vestibular diseases, we discuss several of these disorders including persistent postural-perceptual dizziness, benign paroxysmal positional vertigo, post-concussive syndrome, Ménière's disease, and cerebrovascular etiologies. We discuss the diagnosis of each, as well as overlapping and distinguishing clinical features of which the reader should be aware. Finally, we conclude with evidence based as well as expert commentary on management, with a particular emphasis on vestibular migraine.
PubMed: 38845250
DOI: 10.1016/j.neurot.2024.e00381 -
Journal of the Association For Research... Feb 2024To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
PURPOSE
To assess the available evidence to support a genetic contribution and define the role of common and rare variants in tinnitus.
METHODS
After a systematic search and quality assessment, 31 records including 383,063 patients were selected (14 epidemiological studies and 17 genetic association studies). General information on the sample size, age, sex, tinnitus prevalence, severe tinnitus distribution, and sensorineural hearing loss was retrieved. Studies that did not include data on hearing assessment were excluded. Relative frequencies were used for qualitative variables to compare different studies and to obtain average values. Genetic variants and genes were listed and clustered according to their potential role in tinnitus development.
RESULTS
The average prevalence of tinnitus estimated from population-based studies was 26.3% for any tinnitus, and 20% of patients with tinnitus reported it as an annoying symptom. One study has reported population-specific differences in the prevalence of tinnitus, the white ancestry being the population with a higher prevalence. Genome-wide association studies have identified and replicated two common variants in the Chinese population (rs2846071; rs4149577) in the intron of TNFRSF1A, associated with noise-induced tinnitus. Moreover, gene burden analyses in sequencing data from Spanish and Swede patients with severe tinnitus have identified and replicated ANK2, AKAP9, and TSC2 genes.
CONCLUSIONS
The genetic contribution to tinnitus is starting to be revealed and it shows population-specific effects in European and Asian populations. The common allelic variants associated with tinnitus that showed replication are associated with noise-induced tinnitus. Although severe tinnitus has been associated with rare variants with large effect, their role on hearing or hyperacusis has not been established.
Topics: Humans; Tinnitus; Genome-Wide Association Study; Hearing; Hearing Loss, Sensorineural; Hyperacusis
PubMed: 38334885
DOI: 10.1007/s10162-024-00925-6 -
Journal of Neurology Feb 2024Nystagmus generated during bithermal caloric test assesses the horizontal vestibulo-ocular-reflex. Any induced symptoms are considered unwanted side effects rather than...
BACKGROUND
Nystagmus generated during bithermal caloric test assesses the horizontal vestibulo-ocular-reflex. Any induced symptoms are considered unwanted side effects rather than diagnostic information.
AIM
We hypothesized that nystagmus slow-phase-velocity (SPV) and subjective symptoms during caloric testing would be higher in vestibular migraine (VM) patients compared with peripheral disorders such as Meniere's disease (MD) and non-vestibular dizziness (NVD).
METHODS
Consecutive patients (n = 1373, 60% female) referred for caloric testing were recruited. During caloric irrigations, patients scored their subjective sensations. We assessed objective-measures, subjective vertigo (SVS), subjective nausea (SNS), and test completion status.
RESULTS
Nystagmus SPV for VM, MD (unaffected side), and NVD were 29 ± 12.8, 30 ± 15.4, and 28 ± 14.2 for warm irrigation and 24 ± 8.9, 22 ± 10.0, and 25 ± 12.8 for cold-irrigation. The mean SVS were 2.5 ± 1.1, 1.5 ± 1.33, and 1.5 ± 1.42 for warm irrigation and 2.2 ± 1.1, 1.1 ± 1.19, and 1.1 ± 1.16 for cold-irrigation. Age was significantly correlated with SVS and SNS, (p < 0.001) for both. The SVS and SNS were significantly higher in VM compared with non-VM groups (p < 0.001), and there was no difference in nystagmus SPV. VM patients SVS was significantly different to the SVS of migraineurs in the other diagnostic groups (p < 0.001). Testing was incomplete for 34.4% of VM and 3.2% of MD patients. To separate VM from MD, we computed a composite value representing the caloric data, with 83% sensitivity and 71% specificity. Application of machine learning to these metrics plus patient demographics yielded better separation (96% sensitivity and 85% specificity).
CONCLUSION
Perceptual differences between VM and non-VM patients during caloric stimulation indicate that subjective ratings during caloric testing are meaningful measures. Combining objective and subjective measures could provide optimal separation of VM from MD.
Topics: Humans; Female; Male; Vertigo; Vestibular Diseases; Meniere Disease; Migraine Disorders; Nausea; Caloric Tests; Nystagmus, Pathologic
PubMed: 37847290
DOI: 10.1007/s00415-023-12027-z -
Cureus Feb 2024This narrative review examines the role of vitamin D as a biomarker in ear disorders, including benign paroxysmal positional vertigo (BPPV), otitis media, bell's palsy,... (Review)
Review
This narrative review examines the role of vitamin D as a biomarker in ear disorders, including benign paroxysmal positional vertigo (BPPV), otitis media, bell's palsy, Meniere's disease, and hearing loss. PubMed, The Cochrane Library, and Google Scholar were utilized to conduct a comprehensive literature search, and findings were combined from studies from 2014 to 2024. As highlighted in this review, there is a consistent association between vitamin D deficiency and an increased risk and recurrence of disease especially in BPPV and otitis media. Its importance as a prognostic biomarker is emphasized in Bell's palsy, where higher levels of deficiencies in vitamin D are associated with higher grades of severity on the House Brackmann grading system. Vitamin D deficiency can also lead to sensorineural hearing loss due to its receptors present in the inner ear or its effect on calcium metabolism. Serum levels of vitamin D have also been shown to influence treatment outcome of sensorineural hearing loss. The role of vitamin D in Meniere's disease is unclear as no cause has been identified for the increase in endolymphatic fluid. The findings of this review emphasize the importance of serum vitamin D as a biomarker in ear disorders and advocate for more studies to be conducted to assess the importance of optimal dosing of vitamin D for the progression and outcome of these diseases.
PubMed: 38529449
DOI: 10.7759/cureus.54812 -
Journal of the Association For Research... Dec 2023Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVE
Tinnitus would benefit from an objective biomarker. The goal of this study is to identify plasma biomarkers of constant and chronic tinnitus among selected circulating inflammatory proteins.
METHODS
A case-control retrospective study on 548 cases with constant tinnitus and 548 matched controls from the Swedish Tinnitus Outreach Project (STOP), whose plasma samples were examined using Olink's Inflammatory panel. Replication and meta-analysis were performed using the same method on samples from the TwinsUK cohort. Participants from LifeGene, whose blood was collected in Stockholm and Umeå, were recruited to STOP for a tinnitus subtyping study. An age and sex matching was performed at the individual level. TwinsUK participants (n = 928) were selected based on self-reported tinnitus status over 2 to 10 years. Primary outcomes include normalized levels for 96 circulating proteins, which were used as an index test. No reference standard was available in this study.
RESULTS
After adjustment for age, sex, BMI, smoking, hearing loss, and laboratory site, the top proteins identified were FGF-21, MCP4, GDNF, CXCL9, and MCP-1; however, these were no longer statistically significant after correction for multiple testing. Stratification by sex did not yield any significant associations. Similarly, associations with hearing loss or other tinnitus-related comorbidities such as stress, anxiety, depression, hyperacusis, temporomandibular joint disorders, and headache did not yield any significant associations. Analysis in the TwinsUK failed in replicating the top candidates. Meta-analysis of STOP and TwinsUK did not reveal any significant association. Using elastic net regularization, models exhibited poor predictive capacity tinnitus based on inflammatory markers [sensitivity = 0.52 (95% CI 0.47-0.57), specificity = 0.53 (0.48-0.58), positive predictive value = 0.52 (0.47-0.56), negative predictive values = 0.53 (0.49-0.58), and AUC = 0.53 (0.49-0.56)].
DISCUSSION
Our results did not identify significant associations of the selected inflammatory proteins with constant tinnitus. Future studies examining longitudinal relations among those with more severe tinnitus and using more recent expanded proteomics platforms and sampling of cerebrospinal fluid could increase the likelihood of identifying relevant molecular biomarkers.
Topics: Humans; Tinnitus; Retrospective Studies; Hearing Loss; Hyperacusis; Biomarkers
PubMed: 38079022
DOI: 10.1007/s10162-023-00920-3 -
Brazilian Journal of Otorhinolaryngology 2024When air irrigation is used for caloric stimulation in patients with a perforated ear, warm irrigation may elicit a nystagmus that initially beats in the opposite...
OBJECTIVES
When air irrigation is used for caloric stimulation in patients with a perforated ear, warm irrigation may elicit a nystagmus that initially beats in the opposite direction of what is expected for warm irrigations, which is referred to as "caloric inversion". This study aimed to investigate the disease group in which caloric inversion appeared in patients who underwent caloric testing and to classify the patterns of caloric inversion.
METHODS
We conducted a retrospective review of bithermal caloric test results that were collected in our dizziness clinic between 2005 and 2022. Caloric inversion was defined when nystagmus induced by caloric stimulation appeared in the opposite direction to that expected. The incidence of caloric inversion among all patients who underwent bithermal caloric tests was calculated. To confirm the clinical diagnoses of the patients with caloric inversion, their clinical records were reviewed.
RESULTS
Out of 9923 patients who underwent bithermal caloric tests, 29 patients (0.29%) showed a caloric inversion. The most common clinical diagnosis was chronic otitis media (21 of 29, 72%). Of the 21 patients with chronic otitis media, 20 patients showed a caloric inversion by warm air irrigation and one patient showed caloric inversion by cold air stimulation. Patients with clinical diagnoses other than chronic otitis media such as sudden sensorineural hearing loss, benign paroxysmal vertigo of childhood and recurrent vestibulopathy showed caloric inversion by warm air irrigation. Caloric inversion by warm water irrigation was observed in patients with lateral semicircular canal cupulopathy and recurrent vestibulopathy. Two patients (one with Meniere's disease and one with age-related dizziness) showed caloric inversion by cold water irrigation.
CONCLUSION
Caloric inversion can be observed in various diseases other than chronic otitis media with tympanic membrane perforation. Special care should be taken in the interpretation of caloric test results.
LEVEL OF EVIDENCE
Level 4.
Topics: Humans; Vestibular Neuronitis; Dizziness; Caloric Tests; Benign Paroxysmal Positional Vertigo; Otitis Media; Chronic Disease; Water
PubMed: 38219445
DOI: 10.1016/j.bjorl.2023.101378