Search

The issuing of International Classification of Vestibular Disorders（ICVD） by Brny society（2015） greatly facilitates the progress of vestibular medicine. The syndromic classification of vestibular disorders by ICVD enable the physician to narrow the spectrum of differential diagnosis for the vestibular disorder in clinical practice. However, the division of vestibular pathway, especially the central vestibular system, has not be classified yet in the ICVD（2015）. Central vertigo, being a group of heterogeneous disorders, may present diverse clinical spectrums. The misdiagnosis of central vestibular as well as peripheral vestibular disorders have been reported in the clinic practice. Therefore, the author by review study proposes a structural classification of vestibular disorders combined the Vestibular System Functional Anatomy Division with Syndromes（VeSFADS）. The VeSFADS classification of vestibular disorders could help the physician in clinical practice to narrow the spectrum of vestibular disorders, in addition to the syndromic classification, by the clinical feature of vestibular disorders from different division of vestibular system. And the VeSFADS classification of vestibular disorders may facilitate to clarify the clinical features of vestibular disorders at different Division of vestibular pathway., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

KCNQ4 is a voltage-gated K + channel was reported to distribute over the basolateral surface of type 1 vestibular hair cell and/or inner surface of calyx and heminode of the vestibular nerve connected to the type 1 vestibular hair cells of the inner ear. However, the precise localization of KCNQ4 is still controversial and little is known about the vestibular phenotypes caused by KCNQ4 dysfunction or the specific role of KCNQ4 in the vestibular organs. To investigate the role of KCNQ4 in the vestibular organ, 6-g hypergravity stimulation for 24 h, which represents excessive mechanical stimulation of the sensory epithelium, was applied to p.W277S Kcnq4 transgenic mice. KCNQ4 was detected on the inner surface of calyx of the vestibular afferent in transmission electron microscope images with immunogold labelling. Vestibular function decrease was more severe in the Kcnq4 p.W277S/p.W277S mice than in the Kcnq4 +/+ and Kcnq4 +/p.W277S mice after the stimulation. The vestibular function loss was resulted from the loss of type 1 vestibular hair cells, which was possibly caused by increased depolarization duration. Retigabine, a KCNQ activator, prevented hypergravity-induced vestibular dysfunction and hair cell loss. Patients with KCNQ4 mutations also showed abnormal clinical vestibular function tests. These findings suggest that KCNQ4 plays an essential role in calyx and afferent of type 1 vestibular hair cell preserving vestibular function against excessive mechanical stimulation., (© 2024. The Author(s).)

Background: Neuroproliferative vestibulodynia (NPV), a provoked genital pain characterized by severe allodynia and hyperalgesia, is confirmed in excised vestibular tissue by immunohistochemical staining (>8 CD117-positive immunostained cells/100× microscopic field) rather than by hematoxylin and eosin staining., Aim: In this study we sought to assess immunostaining of tissue samples obtained during vestibulectomy surgery and to correlate results with patient outcomes., Methods: Patients (n = 65) meeting criteria for NPV who underwent vestibulectomy during the period from June 2019 through December 2022 formed the study cohort. We performed assessment of pathology of vestibular tissues by use of immunohistochemical staining, including quantitation of mast cells by CD117 (mast cell marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments., Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement., Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the marker) and nerve fibers by protein gene product (PGP) 9.5 (neuronal marker). We analyzed 725 photomicrographs of immunostained tissue sections (100× and 200×) by manual counting and computer-assisted histometry and correlated these data to clinical assessments., Outcomes: Outcomes included density of CD117 and PGP9.5 immunostaining in the 1:00-11:00 o'clock and 12:00 o'clock vestibular regions, and patient-reported outcomes assessing sexual function, pain, distress, and symptom improvement., Results: All 65 NPV patients (median age 26 years), 45 with lifelong and 20 with acquired NPV, had severe pain documented by PROs and vulvoscopy and had >8 CD117-immunopositive cells/100× microscopic field. Median cell count values were similar in the 1:00-11:00 o'clock and 12:00 vestibular regions (28.5 and 29.5/100× field, respectively). Likewise, the median area of CD117 immunostaining was similar in both regions (0.69% and 0.73%). The median area of PGP9.5 immunostaining was 0.47% and 0.31% in these same regions. Pain scores determined with cotton-tipped swab testing were nominally higher in lifelong vs acquired NPV patients, reaching statistical significance in the 1:00-11:00 o'clock region (P < .001). The median score for the McGill Pain Questionnaire affective subscale dimension was also significantly higher in lifelong vs acquired NPV patients (P = .011). No correlations were observed between hematoxylin and eosin results and density of mast cells or neuronal markers. Of note, 63% of the patient cohort reported having additional conditions associated with aberrant mast cell activity., Clinical Implications: The pathology of NPV is primarily localized to the vestibular epithelial basement membrane and subepithelial stroma with no visible vulvoscopic findings, making clinical diagnosis challenging., Strengths and Limitations: Strengths of this study include the large number of tissues examined with what is to our knowledge the first-ever assessment of the 12:00 vestibule. Major limitations are specimens from a single timepoint within the disease state and lack of control tissues., Conclusions: Performing immunohistochemical staining of excised vestibular tissue with CD117 and PGP9.5 led to histometric confirmation of NPV, indications that NPV is a field disease involving all vestibular regions, validation for patients whose pain had been ignored and who had experienced negative psychosocial impact, and appreciation that such staining can advance knowledge., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: Magnetic resonance imaging (MRI) can be applied to visualize endolymphatic hydrops (EH)., Aims/objectives: To explore whether a 3-h time interval was feasible for clinical practice., Materials and Methods: We prospectively enrolled 15 patients with unilateral Meniere's disease, each of whom underwent delayed enhancement MRI scan of the inner ear after intravenous gadoteridol injection at a 3-h interval. The ears of these patients were divided into two groups (group A: the affected ears; group B: the unaffected ears). Among the two groups, the signal intensity in perilymphatic area of the basal turn of cochlea, the results of visual evaluations in the vestibule, cochlea and semicircular canal and the detection results of EH were compared., Results: Regarding the signal intensity, a difference was found between group A and group B ( p  = .016). Besides, no difference was found between the visual evaluations in the vestibule, cochlea and semicircular canal of the two groups. Regarding the detection results of EH, group A (6 vestibules were undiagnosable; 8 cochleae were undiagnosable); group B (9 vestibules were undiagnosable; 10 cochleae were undiagnosable)., Conclusions and Significance: In the clinical application of gadoteridol for the inner ear, 3-h delayed MR imaging may not be sufficient.

Objectives: Our aim in this study was to characterize the morphology of the endolymphatic compartment on histopathology in individuals with Ménière's disease (MD) and to determine why hydrops of the saccule is more pronounced than that of other compartments of the inner ear in MD., Methods: Temporal bones from 9 patients with idiopathic MD and from 10 individuals without MD/endolymphatic hydrops were examined. The inner ear fluid compartments in normal ears, and ears with MD were three-dimensionally reconstructed and their volume was calculated. The thickness of the membranes of the labyrinth was measured, and both ruptures of the membranes and patency of the utriculoendolymphatic (UEV; Bast's) valve were assessed., Results: In ears with MD, the saccule and the cochlear duct were most frequently hydropic; the utricle was involved approximately half as frequently. In ears without MD, the Reissner's membrane and the membranous wall of the saccule were thinner than that of the utricle and of the lateral semicircular canal ( p < 0.01). The lateral semicircular canal did not show signs of hydrops. In all ears with MD in which the utricle exceeded the average volume of normals (6 of 12), the UEV was open or there was a rupture in the utricle., Conclusion: Increases in endolymphatic pressure may cause a primary swelling of the apical cochlear duct and saccule, both of which have relatively thin membranes. Hydrops in the utricle may occur less frequently because of a thicker wall, because of a functioning UEV, and when the saccule has already occupied most of the vestibular perilymphatic space., Competing Interests: The authors disclose no conflicts of interest. B.K.W. is supported by grants from the National Institutes of Health (K23DC018302), the Hearing Health Foundation, and the Katie and Robert Niehaus Foundation and has a patent US10646723 that is unrelated to the current work. B.B. receives royalties from Oxford University Press., (Copyright © 2023, Otology & Neurotology, Inc.)

Purpose: To determine whether magnetic resonance imaging (MRI) can improve diagnostic accuracy for definite and probable Ménière's disease (MD) based on perilymphatic enhancement (PE) and endolymphatic hydrops (EH)., Methods: 363 patients with unilateral MD (probable MD, n = 75 and definite MD, n = 288) were recruited. A three-dimensional zoomed imaging technique with parallel transmission SPACE real inversion recovery was performed 6 h after intravenous gadolinium injection to investigate the presence of PE and to evaluate the grading and location of EH. PE and EH characteristics were analyzed and compared between the probable and definite MD groups., Results: The cochlear and vestibular EH grading on the affected side was more severe in the definite MD group than that in the probable MD group (P < 0.001). The EH locations within the inner ear on the affected side also differed between the two groups (χ 2  = 81.15, P < 0.001). The signal intensity ratio (SIR) on the affected side was significantly higher in the definite MD group than in the probable MD group (t = 2.18, P < 0.05). The assessment of the combination of PE and EH parameters within the inner ear revealed a higher area under the curve (AUC) in the definite MD group (0.82) compared with the AUCs of the parameters assessed alone., Conclusion: The assessment of a combination of PE and EH parameters improved the diagnostic accuracy for probable and definite MD, suggesting that MRI findings may be clinically useful in the diagnosis of MD., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Orthostatic dizziness/vertigo (ODV) is characterized by lightheadedness owing to postural changes., Aims/objectives: To measure the endolymphatic space (ELS)/total fluid space (TFS) volume ratio and the distribution rate of endolymphatic fluid (ELF) of patients with ODV and compare them with those of control subjects (CS)., Materials and Methods: This study included 22 patients (44 ears) with ODV and 52 controls (104 ears, CS). The ELS/TFS volume ratio (%) and distribution rate (%) of the inner ear components were measured using 3-dimensional magnetic resonance imaging., Results: In the ODV group, the mean ELS/TFS volume ratios of the cochlea, vestibule, and semi-circular canals (SCCs) were 12.1%, 18.6%, and 18.1%, respectively; the mean ELS distribution rates for the cochlea, vestibule, and SCCs were 27.3%, 26.2%, and 46.6%, respectively. The ELS distribution rate of the vestibule was significantly lower ( p  < .01) and the ELS distribution rate of the SCCs was significantly higher in the ODV than in the CS group ( p  < .01)., Conclusions and Significance: The ELS distribution rate in the vestibule + SCCs among patients with ODV did not differ from that in the CS; ELF in the vestibule moved to the SCCs, and a large amount of ELF was distributed only in the SCCs.

Hair cell (HC) loss by epithelial extrusion has been described to occur in the rodent vestibular system during chronic 3,3'-iminodipropionitrile (IDPN) ototoxicity. This is preceded by dismantlement of the calyceal junction in the contact between type I HC (HCI) and calyx afferent terminals. Here, we evaluated whether these phenomena have wider significance. First, we studied rats receiving seven different doses of streptomycin, ranging from 100 to 800 mg/kg/day, for 3-8 weeks. Streptomycin caused loss of vestibular function associated with partial loss of HCI and decreased expression of contactin-associated protein (CASPR1), denoting calyceal junction dismantlement, in the calyces encasing the surviving HCI. Additional molecular and ultrastructural data supported the conclusion that HC-calyx detachment precede HCI loss by extrusion. Animals allowed to survive after the treatment showed functional recuperation and rebuilding of the calyceal junction. Second, we evaluated human sensory epithelia obtained during therapeutic labyrinthectomies and trans-labyrinthine tumour excisions. Some samples showed abnormal CASPR1 label strongly suggestive of calyceal junction dismantlement. Therefore, reversible dismantlement of the vestibular calyceal junction may be a common response triggered by chronic stress, including ototoxic stress, before HCI loss. This may partly explain clinical observations of reversion in function loss after aminoglycoside exposure., (© 2023. The Author(s).)

Introduction: Intralabyrinthine schwannomas, including the intracochlear variety, are rare benign tumors. They can cause a number of symptoms and have the potential to grow to involve other critical structures of the inner ear and skull base. While surgical resection is feasible, there is typically permanent hearing dysfunction as a result of resection and subsequent fibrosis. Here, we present 2 cases of intracochlear schwannomas (ICS) that were successfully resected with simultaneous cochlear implant placement., Methods: Patient 1 presented with an intravestibulocochlear schwannoma. This patient underwent a translabyrinthine approach. Endoscopic assistance was used to dissect the tumor from the vestibule and basal turn of the cochlea, through an enlarged round window approach. A cochlear implant was placed via a round window cochleostomy. Patient 2 presented with an intracochlear schwannoma involving the basal and middle turns of the cochlea. The patient underwent a trans-otic approach for resection. A large portion of the cochlear promontory required unroofing for complete exposure of the tumor. A cochlear implant was then placed via a round window cochleostomy., Results: Upon cochlear implant activation, Patient 1's sound field thresholds using the implant were near the normal range of hearing, ranging from 25 to 50 dB HL from 250 to 6000 Hz. Patient 2's 6-month post-operative cochlear implant sound field testing ranged from 20 to 30 dB HL from 250 to 6000 Hz and speech recognition testing revealed 59% on AZ Bio sentences compared to 0% pre-operatively., Conclusion: Simultaneous cochlear implantation after resection of intracochlear schwannomas is safe and successful in restoring hearing. Attention to adequate exposure and endoscopic assistance, when required, allow for gross total resection while minimizing trauma to cochlear structures. In such cases, immediate cochlear implantation allows for hearing rehabilitation before likely cochlear fibrosis can occur.

Background: Listening difficulties (LiD) present difficulties in listening and paying attention to spoken information despite normal pure tone audiometry. Endolymphatic hydrops (EH) is a common inner ear condition associated with Ménière's disease but may also be present in the asymptomatic ear., Objectives: Using magnetic resonance imaging, we investigated EH in patients with LiD and assessed whether the severity of EH was related to the results of auditory processing tests (APTs)., Materials and Methods: 111 patients with no abnormalities on pure tone audiometry, but displaying difficulties in listening, underwent evaluation through APTs and questionnaires. Upon obtaining informed consent, the inner ears of 20 consenting patients were evaluated utilizing a 3-Tesla magnetic resonance imaging., Results: A higher percentage of patients diagnosed with LiD by APTs had significant EH in the cochlea and vestibule than in previously reported control cases. The percentage of correct answers in the speech-in-noise test was significantly lower in patients with than in those without significant EH., Conclusion and Significance: In this study, significant EH of the cochlea was associated with poor listening to noise. The presence of EH affects the functioning of the auditory processing system, even in ears that test normally on standard audiometric tests.

Background: Patients with Meniere's disease (MD) receive treatment to reduce vertigo., Purpose: To explore the fluctuation of vertigo symptoms and the changes in endolymphatic hydrops (EHs) in MD patients during long-term regular medication., Materials and Methods: We enrolled MD patients who had received two magnetic resonance imaging with intravenous contrast agents., Results: Of the 42 patients in the study, 18(42.9%) had progressive EHs and 3(7.1%) had remission. The change value of the signal intensity ratio (SIR; cochlear perilymph/cerebellum) on the affected side (1.2) was larger than that on the healthy side (0.9), but there was no statistical difference. Among the 30 patients followed up, two patients had complete control of vertigo, two patients had substantial control, and three patients had worse control. The other 23 patients had insignificant control of vertigo symptoms before and after treatment. The correlation between the progression of cochlear and vestibular hydrops and the improvement of vertigo symptoms in MD patients was not significant., Conclusions and Significance: In treated patients with MD, EHs may progress or relieve over the long course of the disease. But there was no correlation between the development of EHs and changes in vertigo symptoms.

Pathological changes of the cochlea and hearing loss have been well addressed in Waardenburg syndrome (WS). However, the vestibular organ malformation in WS is still largely unknown. In this study, the differentiation and development of vestibular sensory epithelium and vestibular function caused by SOX10 mutation, a critical gene induces WS, have been studied in minature pig model. Degeneration of vestibular hair cells was found in this Sox10 mutation porcine model. Inner ear phenotype of the SOX10 +/R109W miniature pigs showed cochlear abnormalities as well as saccular hypofunction. In the mutant pigs, no prominent dissimilarity was shown in the bone structure of the semicircular canals. However, the saccular membrane was collapsed, and the infusion of stereocilia of the hair cells was observed. There were no dark cells in the utricles in the mutant pigs. The density of the utricular hair cells was also significantly lower in the mutant pigs compared to the wild type. Our study demonstrated that the SOX10 gene and melanocytes play important roles in the vestibular organ development. Sox10 mutation disrupts the KIT-DCT signaling pathway, affects the development of melanocytes, and leads to vestibule morphogenesis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: Radiological anatomical variations, measured by magnetic resonance imaging (MRI), were evaluated in patients with ipsilateral delayed endolymphatic hydrops (DEH) and unilateral Ménière's disease (MD). The role of anatomical variations in different subtypes of hydropic ear disease was investigated., Methods: Twenty-eight patients with ipsilateral DEH, 76 patients with unilateral MD, and 59 control subjects were enrolled. The radiological indices included the distance between the vertical part of the posterior semicircular canal and the posterior fossa (MRI-PP distance) and the visibility of vestibular aqueduct (MRI-VA). These variations among patients with DEH, MD, and control subjects were compared. The correlation between radiological anatomical variations and clinical features or audio-vestibular findings was also examined., Results: (1) MRI-PP distance in the affected side of unilateral MD was shorter than that in ipsilateral DEH (Z =  - 2.481, p = 0.013) and control subjects (Z =  - 2.983, p = 0.003), while the difference of MRI-PP distance between the affected side of ipsilateral DEH and control subjects was not statistically significant (Z =  - 0.859, p = 0.391). (2) There was no significant interaural difference of MRI-PP distance in patients with unilateral MD (Z =  - 0.041, p = 0.968) and ipsilateral DEH (t =  - 0.107, p = 0.915) respectively. (3) No significant interaural difference of MRI-VA visibility was observed in patients with unilateral MD (χ 2  = 0.742, p = 0.389) and ipsilateral DEH (χ 2  = 0.327, p = 0.567) respectively. (4) No correlation was found between these anatomical variables and clinical features or audio-vestibular findings in patients with unilateral MD and ipsilateral DEH respectively (p > 0.05)., Conclusions: Anatomical variations of inner ear may be a predisposing factor in the pathogenesis of unilateral MD rather than ipsilateral DEH., Key Points: • Patients with ipsilateral delayed endolymphatic hydrops showed normal distance between the vertical part of the posterior semicircular canal and the posterior fossa. • Compared to patients with ipsilateral delayed endolymphatic hydrops and control subjects, patients with unilateral Ménière's disease exhibited shorter distance between the vertical part of the posterior semicircular canal and the posterior fossa. • Anatomical variations of inner ear may be a predisposing factor in the pathogenesis of unilateral Ménière's disease rather than ipsilateral delayed endolymphatic hydrops., (© 2021. The Author(s).)

Objective: To investigate the characteristics of endolymphatic hydrops (EH) in Menire's disease (MD) patient on a vertigo attack., Study Design: Prospective study., Setting: Tertiary referral center., Patients: Thirty-six MD patients underwent the enhanced magnetic resonance imaging (MRI) examinations of the inner ear on a vertigo attack were enrolled., Main Outcome Measures: All patients met the diagnostic criteria for MD and underwent intravenous gadolinium injection 4 hours before the MRI examinations. The MRI examinations were performed in MD patients on a vertigo attack., Results: Various degrees of vestibular EH appeared in almost all affected ears (2 ears had no EH, 11 ears had mild EH, 26 ears had significant EH). The positive rate of vestibular EH was 37/39 (94.9%). Cochlear EH occurred in 29 ears among 39 affected ears (17 ears had mild EH, 12 ears had significant EH)., Conclusion: MRI with intravenous gadolinium injection can provide a better assessment of EH in MD patient on a vertigo attack. Vestibular EH seems to be closely related with the vertigo attacks in MD patients, which needs further study., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022, Otology & Neurotology, Inc.)

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD ( n = 103), acoustic neuroma ( n = 5), and healthy subjects ( n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment., (Copyright © 2022 by The American Association of Immunologists, Inc.)

Objectives: Hypothesized causes of vestibular neuritis/labyrinthitis include neuroinflammatory or vascular disorders, yet vascular disorders of the inner ear are poorly understood. Guided by known microvascular diseases of the retina, we developed 2 hypotheses: (1) there exist vascular vulnerabilities of artery channels in cases of hypothetical nerve swelling for the superior, inferior, and vestibulocochlear artery and (2) there are arteriovenous crossings that could compromise vascular flow in disease states., Methods: Two fully mounted and stained temporal bones were used to render three-dimensional reconstructions of the labyrinth blood supply. Using these maps, areas of potential vascular compression were quantified in 50 human temporal bones., Results: Although inner ear arteries and veins mostly travel within their own bony channels, they may be exposed (1) at the entrance into the otic capsule, and (2) where the superior vestibular vein crosses the inferior vestibular artery. At the entry into the otic capsule, the ratio of the soft tissue to total space for the superior vestibular artery was significantly greater than the inferior vestibular artery/cochleovestibular artery (median 44, interquartile range 34-55 vs. 14 [9-17], p < 0.0001)., Conclusions: Three-dimensional reconstruction of human temporal bone histopathology can guide vascular studies of the human inner ear. Studies of retinal microvascular disease helped identify areas of vascular vulnerability in cases of hypothetical nerve swelling at the entrance into the otic capsule and at an arteriovenous crossing near the saccular macula. These data may help explain patterns of clinical findings in peripheral vestibular lesions., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Hypothesis/background: Bast's valve is a poorly understood inner ear structure located at the junction between pars superior and inferior in the membranous labyrinth. Anatomically precise three-dimensional reconstructions (3D-reconstructions) of Bast's valve can help illuminate the morphology of the valve, and point toward its role in normal physiology and pathological states such as endolymphatic hydrops. This is of particular relevance to the development of a vestibular implant, a device intended to rehabilitate deficits in the vestibular system., Methods: Six postmortem human temporal bones from healthy donors were scanned using a micro-computed tomography (microCT) scanner. The microCT data allowed 3D-reconstructions of the membranous labyrinth, with a particular focus on Bast's valve, vestibule, and cochlear duct., Results: The microCT images of Bast's valve showed a rigid lip containing a core of soft tissue, opposing the thin membranous wall of the utricle. The maximum recorded length and width of the rigid lip were 440.4 μm and 88 μm, respectively. The 3D-reconstructions illustrated the slit-like opening of Bast's valve into the utricle, the twisting course of the basal turn of the cochlear duct, and the spatial orientation of utricle and saccule with respect to the stapes footplate., Conclusions: The present study provided a novel anatomical perspective on the microscopic structure of Bast's valve. The interplay between endolymphatic hydrops and Bast's valve is an ongoing area of research, but defining this anatomy in 3D will play a key role in furthering our understanding of the disease process. Implications for vestibular implantation are explored through the various 3D-reconstructions., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2021, Otology & Neurotology, Inc.)

Three Dimensional-magnetic resonance imaging of the inner ear endolymphatic space was performed in 100 control human subjects. Ear endolymphatic space was visualized using contrast-enhanced magnetic resonance imaging with intravenous gadolinium injection. The images were acquired on a 3-tesla magnetic resonance scanner using a 32-channel array head coil for all patients. The ear endolymphatic space and total fluid space volumes of the inner ear, cochlea, and vestibule were measured, and the ear endolymphatic space in the cochlea and vestibule was classified into four categories. The cochlea categories were: c-1, no ear endolymphatic space; c-2, ear endolymphatic space visualized only until the upper turn; c-3, ear endolymphatic space visualized from the upper turn to the second turn; and c-4, ear endolymphatic space visualized up to the basal turn. The vestibule categories were: v-1, no ear endolymphatic space; v-2, ear endolymphatic space visualized only in the utriculus; v-3, ear endolymphatic space visualized in the utriculus and sacculus separately; and v-4, ear endolymphatic space visualized in the utriculus and sacculus together. The mean TFS volumes of the inner ear, cochlea, and vestibule were 282.1 ± 33.2 µL, 112.9 ± 15.9 µL, and 69.1 ± 9.9 µL, respectively, and that of the ampulla of the posterior semicircular canal was 7.8 ± 1.7 µL. The mean ear endolymphatic space/total fluid space volume ratio in the cochlea was 10.3 ± 6.7% and that in the vestibule was 17.3 ± 12.2%. This ratio in the cochlea was between the results of categories c-1 and c-2 and that in the vestibule between those of categories v-2 and v-3. Two subjects had ear endolymphatic space extending from the vestibule to the posterior non-ampullated crus of the lateral semicircular canal. These findings can be applied as standard reference values for further research.

Vestibular disorders may generate complex signs and symptoms, which may alter patients' balance and the quality of life. Dizziness and vertigo can strongly affect daily activities and relations. Despite the presence of conventional drugs, maneuvers, and surgery, another interesting therapeutic opportunity is offered by nutraceuticals. These molecules are often used in the treatment of dizziness and vertigo, but the rationale of their application is not always solidly demonstrated by the scientific evidence. Several substances have shown a variable level of efficacy/usefulness in this field, but there is lack of important evidence for most of them. From a medico-legal point of view, specific information must be provided to the patient regarding the efficacy and possibilities that the use of these preparations can allow. Administering the right nutraceutical to the proper patient is a fundamental clinical skill. Integrating conventional drug treatment with nutraceutical administration seems to be easy, but it may be difficult considering the (in part unexplored) pharmacodynamics and pharmacokinetics of nutraceuticals. The aim of the scientific community should be to elevate nutraceuticals to the same law and technical dignity of conventional drugs.

Objective: The purpose of this study was to assess the static balance of children with sensorineural hearing loss (SNHL) according to the degrees of SNHL and the function of the vestibular system., Methods: This cross-sectional study was conducted in public schools located in Caruaru, Pernambuco state, Brazil, with 130 children (65 with normal hearing and 65 with SNHL as documented by air and bone conduction audiometry) of both sexes between 7 and 11 years old. Static balance was assessed by a stabilometric analysis using a force platform consisting of the circular area of center-of-pressure displacement of the children evaluated in 3 positions: bipedal support with feet together and parallel (PF), tandem feet (TF), and 1 foot (OF), carried out under 2 sensory conditions each, with eyes open and eyes closed. After balance assessments, the children with SNHL received examinations of auditory and vestibular functions-through audiometry and computerized vectoelectronystagmography, respectively-to compose the groups according to degrees of SNHL and vestibular function., Results: The children with severe and profound SNHL demonstrated more static balance instabilities than the children with normal hearing in 5 positions assessed with eyes open (PF, TF, and OF) and eyes closed (PF and TF). The same phenomenon occurred in children with SNHL and associated vestibular dysfunction in all of the positions assessed with eyes open and eyes closed (PF, TF, and OF)., Conclusion: The larger the degree of SNHL, the greater the balance instability of the children. The children with SNHL and associated vestibular dysfunction showed the highest balance instabilities in this study., Impact: Children with larger degrees of SNHL and associated vestibular dysfunction might require prolonged periods to rehabilitate their balance., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Physical Therapy Association. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Objective: To study the value of the subjective visual vertical (SVV) in the diagnosis of vestibular migraine (VM)., Methods: This study recruited 128 VM patients and 64 age-matched normal subjects. We detected the SVV during the interval between attacks in both groups, in sitting upright, and the head tilted at 45° to the left or right. We then examined the correlation between the SVV results with the vestibular evoked myogenic potential (VEMP) and canal paresis (CP)., Results: It was found there was a significant difference in SVV at the upright position between VM patients and normal controls (P=0.006) and no significant difference was found at the tilts of 45° to the left or right between the two groups. The SVV results at the upright position were significantly correlated with cervical VEMP (P=0.042) whereas not significantly correlated with CP and VEMP. There existed no significant difference in the conformity to the Müller effect (M effect) between the two groups. ROC analysis exhibited that the sensitivity, specificity of SVVs at the upright were 67.200% and 62.500% respectively. The diagnostic value of SVV at the upright position was significantly higher than that at tilts of 45° to the left and right (P=0.006). Nonetheless the diagnostic accuracy was relatively low., Conclusion: Abnormality in SVV possibly stems from the lasting functional disorder of cerebellar or high-level cortical centers in VM patients or is linked to the vestibular compensation. The SVV is of low diagnostic value for VM and the value of SVV in VM warrants further study., (© 2021. The Author(s).)

Aging is associated with a gradual decline in the sensory systems and noisier sensory information. Some research has found that older adults compensate for this with enhanced multisensory integration. However, less is known about how aging influences visual-vestibular integration, an ability that underlies self-motion perception. We examined how visual-vestibular integration changes in participants from across the lifespan (18-79 years old) with a simple reaction time task. Participants were instructed to respond to visual (optic flow) and vestibular (inertial motion) acceleration cues, presented either alone or at a stimulus onset asynchrony. We measured reaction times and computed the violation area relative to the race model inequality as a measure of visual-vestibular integration. Across all ages, the greatest visual-vestibular integration occurred when the vestibular cue was presented first. Age was associated with longer reaction times and a significantly lower detection rate in the vestibular-only condition, a finding that is consistent with an age-related increase in vestibular noise. Although the relationship between age and visual-vestibular integration was positive, the effect size was very small and did not reach statistical significance. Our results suggest that although age is associated with a significant increase in vestibular perceptual threshold, the relative amount of visual-vestibular integration remains largely intact., (Copyright © 2021. Published by Elsevier Inc.)

Epidemiological and experimental studies indicate that a number of aromatic solvents widely used in the industry can affect hearing and balance following chronic exposure. Animal studies demonstrated that long-term exposure to aromatic solvents directly damages the auditory receptor within the inner ear: the cochlea. However, no information is available on their effect on the vestibular receptor, which shares many structural features with the cochlea and is also localized in inner ear. The aim of this study was to use an in vitro approach to assess and compare the vestibular toxicity of different aromatic solvents (toluene, ethylbenzene, styrene and ortho-, meta-, para-xylene), all of which have well known cochleotoxic properties. We used a three-dimensional culture model of rat utricles ("cysts") with preserved functional sensory and secretory epithelia, and containing a potassium-rich (K + ) endolymph-like fluid for this study. Variations in K + concentrations in this model were considered as biomarkers of toxicity of the substances tested. After 72 h exposure, o-xylene, ethylbenzene and styrene decreased the K + concentration by 78 %, 37 % and 28 %, respectively. O- xylene and styrene both caused histopathological alterations in secretory and sensory epithelial areas after 72 h exposure, whereas no anomalies were observed in ethylbenzene-exposed samples. These in vitro results suggest that some widely used aromatic solvents might have vestibulotoxic properties (o-xylene, styrene and ethylbenzene), whereas others may not (p-xylene, m-xylene, toluene). Our results also indicate that variations in endolymphatic K + concentration may be a more sensitive marker of vestibular toxicity than histopathological events. Finally, this study suggests that cochleotoxic solvents might not be necessarily vestibulotoxic, and vice versa., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Ménière disease (MD) is an idiopathic inner ear disorder, and endolymphatic hydrops (EH) being considered to be its pathological basis. Currently, there is no gold standard for diagnosing MD. Previous study has reported visualized EH using MRI by intratympanic gadolinium-based contrast media (GBCM) administration (IT-Gd) in patients with MD, and this technique was gradually established for MD diagnosis. However, few studies reported their diagnostic sensitivity and specificity in clinical application. This prospective study aimed at investigating the clinical characteristics and magnetic resonance imaging (MRI) results of patients with MD, and analyzing the relationship between clinical results and MRI findings in MD patients. Our study shows that the diagnostic sensitivity and specificity of MRI were 79.2% and 80.7% respectively. Moreover, there was no significant correlation between hearing levels and cochlear grading scores, nor vestibular grading scores. The duration of disease was not significantly associated with cochlear or vestibular grading scores. These findings suggest that IT-Gd MRI offers reliable radiological diagnostic criteria for MD.

The aim of our study was to validate the method of head-shake static posturography (HS-posturography) in healthy individuals and to establish the value of this novel method in the diagnostics of patients with unilateral vestibular lesion (UV). The study included 202 participants divided into two groups, one consisting of 133 patients with canal paresis CP > 19% and one of 69 healthy subjects. Participant was tested according to the standard protocol of static posturography (SP), and with head movements of 0.3 Hz (HS 40), 0.6 Hz (HS 70) in random order controlled by a metronome. HS-posturography revealed a similar repeatability and internal consistency as the standard posturography. In patients with UV, 4th condition revealed higher sensitivity (74%) and specificity (71%) in HS 40 than in the standard posturography (67%, 65% respectively) and HS 70 (54%, 70% respectively). Static posturography and HS- posturography revealed a high reliability of the testing method. The head movements added to static posturography improve the sensitivity and specificity of the method in group with vestibular impairment. The most important test for that purpose seems to be the one on unstable surface with the eyes closed, with low frequency of head movements.

Age-associated loss of muscle function is exacerbated by a concomitant reduction in balance, leading to gait abnormalities and falls. Even though balance defects can be mitigated by exercise, the underlying neural mechanisms are unknown. We now have investigated components of the proprioceptive and vestibular systems in specific motor neuron pools in sedentary and trained old mice, respectively. We observed a strong age-linked deterioration in both circuits, with a mitigating effect of exercise on vestibular synapse numbers on motor neurons, closely associated with an improvement in gait and balance in old mice. Our results thus describe how the proprioceptive and vestibular systems are modulated by age and exercise, and how these changes affect their input to motor neurons. These findings not only make a strong case for exercise-based interventions in elderly individuals to improve balance, but could also lead to targeted therapeutic interventions aimed at the respective neuronal circuitry., (© 2020 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)

Hearing impairment is a reported complication of sickle cell disease, yet inner ear pathology is not fully understood. The study purpose was to examine the patterns of inner ear involvement in patients with sickle cell disease by magnetic resonance imaging (MRI) and to assess its association with auditory functions. A cross-sectional study included 22 children with sickle cell disease examined for inner ear pathology by audiogram, MRI inner ear and transcranial Doppler (TCD) with revision of their hospital records for transfusion, chelation and hydroxyurea (HU) therapy. Abnormal MRI in the form of intrinsic T1 hyperintensity within the lumen of inner ear structures and cochlear neuropathy was found in five (22.7%) patients; left middle cerebral artery (MCA) flow velocity was higher in patients with abnormal MRI (83.4 ± 5.3 cm/sec) compared to normal MRI (68.2 ± 11.1 cm/sec) ( p  = 0.015), however, none of the patients had TCD of >170 cm/sec. There was no significant difference between patients with normal and abnormal MRI as regards hearing level and speech audiometry. Sensorineural hearing loss (SNHL) was present in two (9.1%) and conductive hearing loss (CHL) in two (9.1%) patients. There was a significant negative correlation between right ear mean hearing level and right MCA flow velocity and significant negative correlation between left ear mean hearing level and basilar artery (BA) flow velocity. We concluded that inner ear pathology is not uncommon in asymptomatic patients with sickle cell anemia, yet it did not correlate with hearing impairment and may occur with normal TCD results.

Introduction: Etiology of ISSNHL includes cessation of vascular perfusion, viral infection and cochlear membrane injury. Precise location of injury should be defined for a target-oriented treatment. Vestibular complaints in ISSNHL are hypothesized as involvement of vestibule. Vestibular complaints can be either due to involvement of inner ear or neural tract at any level., Objectives: In the present study we aimed to demonstrate involvement of vestibular organs in the absence of vestibular symptoms. It was aimed to evaluate superior and inferior vestibular neural pathways., Methods: c-vemp and o-vemp were applied to patients suffering ISSNHL without vertigo. Pure tone averages, audiogram configurations, degree of hearing loss were analyzed. Latencies of P1 and N1 waves, amplitudes of P1-N1 waves were evaluated. Asymmetrical vemp wave patterns were compared between two ears regarding difference of PTA., Results: Latencies of c-vemp waves were longer and amplitudes were smaller. o-vemp parameters were similar on both sides. Positive correlation was observed between c-vemp latencies and degree hearing loss., Conclusion: Inferior vestibular nerve pathway is affected in the absence of vertigo in ISSNHL with spared superior vestibular nerve pathway. Damage in IVN pathway correlates with degree of ISSNHL.

Objective: Patients with acute central vestibular syndrome suffer from vertigo, spontaneous nystagmus, postural instability with lateral falls, and tilts of visual vertical. Usually, these symptoms compensate within months. The mechanisms of compensation in vestibular infarcts are yet unclear. This study focused on structural changes in gray and white matter volume that accompany clinical compensation., Methods: We studied patients with acute unilateral brain stem infarcts prospectively over 6 months. Structural changes were compared between the acute phase and follow-up with a group of healthy controls using voxel-based morphometry., Results: Restitution of vestibular function following brain stem infarcts was accompanied by downstream structural changes in multisensory cortical areas. The changes depended on the location of the infarct along the vestibular pathways in patients with pathological tilts of the SVV and on the quality of the vestibular percept (rotatory vs graviceptive) in patients with pontomedullary infarcts. Patients with pontomedullary infarcts with vertigo or spontaneous nystagmus showed volumetric increases in vestibular parietal opercular multisensory and (retro-) insular areas with right-sided preference. Compensation of graviceptive deficits was accompanied by adaptive changes in multiple multisensory vestibular areas in both hemispheres in lower brain stem infarcts and by additional changes in the motor system in upper brain stem infarcts., Interpretation: This study demonstrates multisensory neuroplasticity in both hemispheres along with the clinical compensation of vestibular deficits following unilateral brain stem infarcts. The data further solidify the concept of a right-hemispheric specialization for core vestibular processing. The identification of cortical structures involved in central compensation could serve as a platform to launch novel rehabilitative treatments such as transcranial stimulations., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Vestibular compensation (VC) refers to a behavioral recovery process in which firing rates of bilateral vestibular nuclei neurons are rebalanced. Our study aimed to investigate the underlying mechanism by which miR-219a-5p regulates Ca 2+ /calmodulin-dependent protein kinase II γ isoform (CaMKIIγ) and protein kinase C (PKC) in VC. A unilateral vestibular deafferentation rat model was established by unilateral labyrinthectomy (UL), after which VC was evaluated in rats with UL-induced vertigo-like behavior by measuring vestibular defect behavior and performing rotarod tests, as well as by BrdU immunohistochemistry on medial vestibular nuclei. We found that miR-219a-5p was increased while CaMKIIγ was decreased during VC in the medial vestibular nucleus of rats that had undergone UL. Next, gain- and loss-of-function assays were conducted to evaluate the effects of miR-219a-5p and CaMKIIγ on the vestibular defect behaviors and VC, the results of which suggested that in rats after UL overexpression of CaMKIIγ inhibited VC, while overexpression of miR-219a-5p facilitated VC. A dual-luciferase reporter gene assay identified that miR-219a-5p targeted CaMKIIγ. This led to additional experiments showing that miR-219a-5p aptomir expression downregulated CaMKIIγ in cortical cells with a concomitant increase in PKC expression, which were verified further in vivo. In summary, in rats with acute vertigo, miR-219a-5p overexpression inhibits CaMKIIγ and elevates PKC, thereby facilitating VC. Our study offers possible targets for further evaluation as treatment of acute vertigo in humans., (© 2020 New York Academy of Sciences.)

A flat epithelium (FE) may be found in the vestibular end organs of humans and mice with vestibular dysfunction. However, the pathogenesis of FE is unclear and inducing hair cell (HC) regeneration is challenging, as both HCs and supporting cells (SCs) in vestibular FE are damaged. To determine the cellular origin of vestibular FE and examine its response to Atoh1 overexpression, we fate-mapped vestibular epithelial cells in three transgenic mouse lines (vGlut3-iCreER T2 :Rosa26 tdTomato , GLAST-CreER T2 :Rosa26 tdTomato , and Plp-CreER T2 :Rosa26 tdTomato ) after inducing a lesion by administering a high dose of streptomycin. Atoh1 overexpression in vestibular FE was mediated by an adeno-associated virus serotype 8 (AAV8) vector. Suberoylanilide hydroxamic acid (SAHA), a histone deacetylase inhibitor, was administered with AAV8 to enhance Atoh1 overexpression. The transduction efficiency and population of myosin VIIa-positive cells were analyzed. A small number of HCs were present in vestibular FE. FE did not show broad GLAST-Cre or Plp-Cre expression, unlike the original SCs. SAHA dramatically enhanced AAV8-mediated exogenous gene overexpression, and Atoh1 overexpression plus SAHA promoted myosin VIIa expression in FE cells. Our data provide insight into FE formation and will facilitate studies of gene therapy for vestibular FE., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Following partial or total loss of peripheral vestibular inputs, a phenomenon called central vestibular compensation takes place in the hours and days following the injury. This neuroplasticity process involves a mosaic of profound rearrangements within the brain stem vestibular nuclei. Among them, the setting of a new neuronal network is maybe the most original and unexpected, as it involves an adult reactive neurogenesis in a brain area not reported as neurogenic so far. Both the survival and functionality of this newly generated neuronal network will depend on its integration to pre-existing networks in the deafferented structure. Far from being aberrant, this new structural organization allows the use of inputs from other sensory modalities (vision and proprioception) to promote the restoration of the posture and equilibrium. We choose here to detail this model, which does not belong to the traditional niches of adult neurogenesis, but it is the best example so far of the reparative role of the adult neurogenesis. Not only it represents an original neuroplasticity mechanism, interesting for basic neuroscience, but it also opens new medical perspectives for the development of therapeutic approaches to alleviate vestibular disorders., (© 2020 médecine/sciences – Inserm.)

Noisy galvanic vestibular stimulation (nGVS) delivered at imperceptible intensities can improve vestibular function in health and disease. Here we evaluated whether nGVS effects on vestibular function are only present during active stimulation or may exhibit relevant post-stimulation after-effects. Initially, nGVS amplitudes that optimally improve posture were determined in 13 healthy subjects. Subsequently, effects of optimal nGVS amplitudes on vestibular roll-tilt direction recognition thresholds (DRT) were examined during active and sham nGVS. Ten of 13 subjects exhibited reduced DRTs during active nGVS compared to sham stimulation (p < 0.001). These 10 participants were then administered to 30 mins of active nGVS treatment while being allowed to move freely. Immediately post-treatment , DRTs were increased again (p = 0.044), reverting to baseline threshold levels (i.e. were comparable to the sham nGVS thresholds), and remained stable in a follow-up assessment after 30 min. After three weeks, participants returned for a follow-up experiment to control for learning effects, in which DRTs were measured during and immediately after 30 min application of sham nGVS. DRTs during both assessments did not differ from baseline level. These findings indicate that nGVS does not induce distinct post-stimulation effects on vestibular motion perception and favor the development of a wearable technology that continuously delivers nGVS to patients in order to enhance vestibular function.

Aim: We investigated if loop characteristics correlate with audio-vestibular symptoms or hemifacial spasm in patients with a vascular loop in the root entry zone (VII and VIII) and in the internal auditory canal., Materials and Methods: A retrospective, multicenter study analyzed 2622 consecutive magnetic resonance imaging (MRI) scans of the cerebellopontine angle of patients with asymmetric audio-vestibular symptom or hemifacial spasm; patients' symptoms were confirmed by clinical tests. MRIs displaying vascular loops visible in the axial view were analyzed using multiplanar reconstruction. We evaluated (1) depth of penetration of the loop into the internal auditory canal (IAC); (2) largest diameter of the vessel; (3) nerve(s) involved in the vascular impingement, position of the loop relative to such nerve(s) and number of contacts between vessel and nerve(s); (4) length of such contact. The loop metrics described above were correlated with the patients' audio-vestibular symptoms and hemifacial spasm., Results: Three hundred ninety-nine patients displayed a loop visible in the MRI axial view and out of them only 118 displayed a direct contact between loop and nerve. The cochlear nerve was involved in a contact in 57.7%. Loops in direct nerve contact had a calibre > 0.85 mm, were located in the middle portion of the IAC, and correlated with vertigo (p = 0.002), tinnitus (p = 0.003), and hemifacial spasm (p < 0.001). Asymmetric sensorineural hearing loss (SNHL) correlated with number of contacts (p < 0.001) and length of contact (p < 0.05). The contact was asymptomatic in 41.5% of patients., Conclusion: Loop characteristics may help predict whether a vascular impingement is responsible for a symptom and guide the physician to select the best treatment., Key Points: • A vascular loop in the internal auditory canal was observed in 18-20% of the patients in this study; whether a loop can be responsible for a compressive syndrome is still unclear in particular referred to the vestibulocochlear nerve. • Compression by a loop on the facial nerve causes hemifacial spasm; compression by a loop on the cochlear or vestibular nerve may cause audio-vestibular symptoms. • In patients with a loop, the loop calibre, the loop position, and the number of loop-nerve(s) assessed via the multiplanar MRI reconstruction technique may help assess whether the patient will manifest audio-vestibular symptoms or hemifacial spasm.

Background: Histological study of vestibular end organs has been challenging due to the difficulty in preserving their structures for histological analysis and due to their complex geometry. Recently, radiology advances have allowed to deepen the study of the membranous labyrinth., Summary: A review and analysis of surgical implications related to the anatomy of the vestibular end organ is performed. Radiological advances are key in the advancement of the knowledge of the anatomy and pathology of the vestibule. Thus, application of such knowledge in the development or improvement of surgical procedures may facilitate the development of novel techniques. Key Messages: During the last few decades, the knowledge of the anatomy of the auditory system through histology and radiology had improved. Technological advances in this field may lead to a better diagnosis and therapeutic approach of most common and important diseases affecting the inner ear., (© 2020 The Author(s) Published by S. Karger AG, Basel.)

Near threshold stochastic vestibular stimulation (SVS) enhances postural control and improves other symptoms in neurodegenerative disorders like Parkinson's disease (PD). Improvement of postural control can tentatively be explained by increased responsivity of the vestibular system, but the mechanism behind other effects of near threshold SVS, like improved motor symptoms and cognitive responsiveness in PD, are not known. To better understand the effect of vestibular stimulation on brain activity in PD, c-Fos expression was used as a marker of change in functional activity following SVS in 6-hydroxydopamine (6-OHDA) hemi-lesioned and in sham-lesioned rats. The results were compared with the effect of a single levodopa injection in 6-OHDA hemi-lesioned or saline in sham-lesioned rats. SVS was found to increase c-Fos expression more than levodopa as well as saline in the parvocellular medial vestibular nucleus (MVePC) and more in 6-OHDA hemi-lesioned than in sham-lesioned animals. Furthermore, c-Fos expression increased more in the habenula nucleus (LHb) after SVS than it did after levodopa in 6-OHDA hemilesioned animals and after saline in the sham-lesioned animals. SVS and levodopa induced similar c-Fos expression in several regions, e.g. the caudate putamen (CPu), where saline had no effect. In conclusion there was overlap between SVS-activated areas and levodopa-activated areas, but activation was more pronounced following SVS in the MVePC of 6-OHDA lesioned and in the LHb in both lesioned and sham-lesioned rats., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

The tail-lift reflex and the air-righting reflex are anti-gravity reflexes in rats that depend on vestibular function. To obtain objective and quantitative measures of performance, we recorded these reflexes with slow-motion video in two experiments. In the first experiment, vestibular dysfunction was elicited by acute exposure to 0 (control), 400, 600, or 1000 mg/kg of 3,3'-iminodipropionitrile (IDPN), which causes dose-dependent hair cell degeneration. In the second, rats were exposed to sub-chronic IDPN in the drinking water for 0 (control), 4, or 8 weeks; this causes reversible or irreversible loss of vestibular function depending on exposure time. In the tail-lift test, we obtained the minimum angle defined during the lift and descent maneuver by the nose, the back of the neck, and the base of the tail. In the air-righting test, we obtained the time to right the head. We also obtained vestibular dysfunction ratings (VDRs) using a previously validated behavioral test battery. Each measure, VDR, tail-lift angle, and air-righting time demonstrated dose-dependent loss of vestibular function after acute IDPN and time-dependent loss of vestibular function after sub-chronic IDPN. All measures showed high correlations between each other, and maximal correlation coefficients were found between VDRs and tail-lift angles. In scanning electron microscopy evaluation of the vestibular sensory epithelia, the utricle and the saccule showed diverse pathological outcomes, suggesting that they have a different role in these reflexes. We conclude that these anti-gravity reflexes provide useful objective and quantitative measures of vestibular function in rats that are open to further development.

A four-year-old female French bulldog was presented for evaluation of acute, left-sided peripheral vestibular syndrome. Computed tomographic (CT) examination of the head revealed the presence of air within the left cochlea and vestibule, consistent with pneumolabyrinth. This was concurrent with ipsilateral otitis media and externa. Pneumolabyrinth is an uncommon finding in humans and is most frequently due to head trauma and temporal bone fracture. This is the first report describing pneumolabyrinth in a dog, apparently of nontraumatic origin in this case., (© 2017 American College of Veterinary Radiology.)

Hypothesis: Cochlear implantation may result in an increase in the density of macrophages in vestibular endorgans in the human., Background: Vestibular symptoms are a common complication of cochlear implantation. In a previous study, we demonstrated histological evidence of a foreign-body response caused by silicon and platinum in the human cochlea following cochlear implantation. The objective of the current study was to seek evidence of a possible immune response in vestibular endorgans after cochlear implantation., Methods: The density of macrophages immunostained with anti-Iba1 antibody in the vestibular endorgans (lateral and posterior semicircular canals, utricle and saccule) in 10 human subjects who had undergone unilateral cochlear implantation was studied by light microscopy. The densities of macrophages in the neuroepithelium, subepithelial stroma, and among dendritic processes in the mid-stromal zone in four vestibular endorgans in the implanted and the opposite unimplanted ears were compared. The distributions of macrophage morphology (amoeboid, transitional and ramified) were also compared., Results: The densities of macrophages in implanted ears in four vestibular endorgans were significantly greater than that in opposite unimplanted ears except in the subepithelial zone of the utricle and posterior semicircular canal. In contrast to the neuroepithelium, the subepithelial distribution of amoeboid macrophages in implanted ears was significantly less than in unimplanted ears., Conclusion: An increase in the density of macrophages in four vestibular endorgans after implantation was demonstrated. The transition among phenotype of macrophages suggested possible migration of amoeboid macrophages from the subepithelial stroma into the neuroepithelium.

Introduction: Sensorineural hearing loss frequently has been described in patients with leukemia, and in fact, hearing loss may be the presenting symptom of this disease. However, the pathogenesis of sensorineural hearing loss in leukemia is not well understood., Objective: To describe the temporal bone histopathology in 1 patient with leukemia and sensorineural hearing loss., Methods: The histopathology of the temporal bones of 1 patient with chronic myelomonocytic leukemia who suffered well-documented bilateral sequential profound sensorineural hearing loss 4 months before death was investigated using light microscopy., Result: There was evidence of ischemic necrosis of the neuroepithelium and intravascular fibrin micro-thrombi suggestive of intravascular coagulation in the cochlea and vestibular labyrinth., Conclusion: Intravascular coagulation may be a contributing factor in the commonly reported finding of hemorrhage in the cochlea in leukemia and may play a role in the pathogenesis of sensorineural loss in some cases of leukemia.

Third window defects have increasingly been identified as a cause of vertigo. These defects are bony dehiscences that occur in the bony labyrinth, resulting in abnormal pressure gradient in the inner ear fluids leading to sound (Tullio's phenomenon) or pressure (Hennebert's sign) induced vertigo. The superior semicircular canal dehiscence syndrome is a well-described entity in this regard, however defects of the posterior semicircular canal are rare and may have overlapping symptomatology. We describe the history, clinical profile and management of a patient who had importunate symptoms despite being on conservative management for a year and had resolution of vestibular symptoms following surgical management., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The thickness of Listing's plane accurately reflects gravitational recognition, constructed through the integration of visual, vestibular, and proprioceptive sensory input in the neural integrator of the central nervous system. Spinocerebellar degeneration (SCD) is a progressive degenerative disease mainly involving the cerebellum and brainstem that leads to destabilize the gravitational recognition, and may thicken thickening of Listing's plane. Objective: The aim of this study is to evaluate the gravitational recognition in response to positional change in patients with SCD, using the thickness of Listing's plane as a parameter. Materials and methods: In this prospective study, we evaluated the thickness of Listing's plane in 21 consecutive patients with SCD and 32 healthy subjects in the seated and supine positions, and investigated the association with other neuro-otological examinations (electronystagmography including caloric test and posturography). Results: We detected significant thickening of Listing's plane in SCD patients only when they were in the seated position. The thickness of Listing's plane correlated with neither the caloric response nor Romberg's ratio or the total center of the pressure path length. Conclusions and significance: The thickness of Listing's plane could be a useful parameter for assessing a gravity-oriented internal model in SCD patients.

Purpose: 3D-FLAIR sequences with delayed acquisition after contrast medium injection have demonstrated new insights into blood-labyrinthine barrier (BLB) abnormalities in various diseases. The aim of this study was to assess the BLB in patients referred with unilateral acute vestibular syndrome (UAVS)., Materials and Methods: In this retrospective multicenter imaging study, we performed 3D-FLAIR and steady-state free precession (SSFP) sequences 4 h after contrast medium administration in 26 healthy volunteers and in 30 patients with UAVS. Two radiologists, blinded to the clinical data, independently assessed the asymmetrical enhancement of the labyrinthine structures and the vestibular nerve on 3D-FLAIR sequences, and the signal of the labyrinthine structures on SSFP sequences. Inter-reader agreement tests were performed., Results: An asymmetrical enhancement of the semicircular canals was observed in 26 out of 30 ears (86.6%, p < 0.001) and never observed in healthy subjects. An asymmetrical enhancement of the vestibular nerve was never observed in either patients or healthy subjects. An asymmetrical enhancement of the cochlea was observed on the 3D-FLAIR sequence in 6 out of 30 ears only in the patients' group (20%, p = 0.03) and always associated with an enhancement of at least one semicircular canal. A low signal on SSFP sequences was observed only in 11 out of 30 symptomatic ears (36.7%, p < 0.001), involving the utricle in 7 ears and the superior semicircular canal in 4 ears., Conclusion: Patients with typical UAVS presented with semicircular canal enhancement on MRI, while an asymmetrical enhancement of the vestibular nerve was not displayed., Trial Registration: NCT02529475 KEY POINTS: • Patients with typical vestibular neuronitis presented with semicircular canal enhancement on MRI in 87% of cases. • An enhancement of the vestibular nerve was never displayed.

Background: Unilateral labyrinthectomy (UL) causes the disappearance of ipsilateral medial vestibular nuclear (ipsi-MVe) activity and induces spontaneous nystagmus (SN), which disappears during the initial process of vestibular compensation (VC). Ipsi-MVe-activity restores in the late process of VC., Objective: We evaluated the late process of VC after UL in rats and examined the effects of thioperamide (H3 antagonist) on VC., Materials and Methods: MK801 (NMDA antagonist)-induced Fos-like immunoreactive (-LIR) neurons in contra-MVe, which had been suppressed by NMDA-mediated cerebellar inhibition in UL rats was used as an index., Results: The number of MK801-induced Fos-LIR neurons in contra-MVe gradually decreased to the same level as that of sham-operated rats 14 days after UL. Thioperamide moved the disappearance of the MK801-induced Fos-LIR neurons 2 days earlier. The number of MK801-induced Fos-LIR neurons in thioperamide-treated rats was significantly decreased, compared with that of vehicle rats on days 7 and 12 after UL. But, thioperamide did not influence the decline of SN frequency in UL rats., Conclusion: These findings suggested that the number of MK801-induced Fos-LIR neurons in contra-MVe was decreased in concordance with the restoration of ipsi-MVe-activity during the late process of VC after UL and that thioperamide accelerated the late, but not the initial process of VC.

Noisy galvanic vestibular stimulation (nGVS) has been shown to improve dynamic walking stability, affect postural responses, enhance balance in healthy subjects, and influence motor performance in individuals with Parkinson's disease. Although the studies to fully characterize the effect of nGVS are still ongoing, stochastic resonance theory which states that the addition of noisy signal may enhance a weak sensory input signals transmission in a non-linear system may provide a possible explanation for the observed positive effects of nGVS. This study explores the effect of nGVS on fine tracking behavior in healthy subjects. Ten healthy participants performed a computer-based visuomotor task by controlling an object with a joystick to follow an amplitude-modulated signal path while simultaneously receiving a sham or pink noise nGVS. The stimulation was generated to have a zero-mean, linearly detrended 1/f-type power spectrum, Gaussian distribution within 0.1-10 Hz range, and a standard deviation (SD) set to 90% based on each participant's cutaneous threshold value. Results show that simultaneous nGVS delivery statistically improved the tracking performance with a decreased root-mean-squared error of 5.71±6.20% (mean±SD), a decreased time delay of 11.88±9.66% (mean±SD), and an increased signal-to-noise ratio of 2.93% (median, interquartile range (IQR) 3.31%). This study showed evidence that nGVS may be beneficial in improving sensorimotor performance during a fine motor tracking task requiring fine wrist movement in healthy subjects. Further research with a more comprehensive subset of tasks is required to fully characterize the effects of nGVS on fine motor skills., Competing Interests: The authors have declared that no competing interests exist.

Objective: Endolymphatic hydrops (EH) has been reported in ears with otosclerosis. The objective of this study was to investigate the clinical features of ears with otosclerosis and EH on magnetic resonance imaging (MRI) and identify predictors for the presence of EH., Study Design: Retrospective study., Setting: University hospital., Materials and Methods: Forty-six ears from 37 patients with otosclerosis were included in the present study., Interventions: The subjects were divided into three groups, those with no, mild, or significant EH, based on 3-T MRI with intravenous injection of gadolinium. Hearing levels and the extent of otosclerotic lesions graded based on the computed tomography (CT) findings were compared among the groups. Moreover, to examine the vascular activity of the disease, intraoperative measurements of blood flow were also evaluated., Main Outcome Measures: Imaging, hearing levels, and blood flow values., Results: The overall rate of EH was 58.7% (27 of 46 ears); cochlear EH (52.2%) was more frequent than vestibular EH (26.1%). Average thresholds in ears with significant EH were significantly higher at several frequencies, both on air and bone conduction, than those with no or mild EH. Significant EH was more frequently observed in ears with advanced stages on CT than in those without advanced stages. The values of blood flow in the area anterior to the oval window were higher in some ears with EH than in ears without EH., Conclusion: EH was frequently present in ears with otosclerosis, especially those with severe hearing loss or advanced disease on CT.