Immunohistochemical staining with CD117 and PGP9.5 of excised vestibular tissue from patients with neuroproliferative vestibulodynia.

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.

A 3-hour time interval may not be sufficient for delayed enhancement magnetic resonance imaging with intravenous gadoteridol injection based on 3d-real IR sequence of the inner ear in Meniere's disease patient.

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.

Volume ratio and distribution rate in patients with orthostatic vertigo/dizziness using MR imaging: a comparison with vertiginous diseases.

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.

Differential Volume Increase of Endolymphatic Compartments in Ménière's Disease Is Inversely Associated With Membrane Thickness.

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.

Improving diagnostic accuracy for probable and definite Ménière's disease using magnetic resonance imaging.

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 (χ2 = 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.

The vestibular calyceal junction is dismantled following subchronic streptomycin in rats and sensory epithelium stress in humans.

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.

Presence of endolymphatic hydrops on listening difficulties in patients with normal hearing level.

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.

Resection of Intracochlear Schwannomas With Immediate Cochlear Implantation.

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.

Progression of endolymphatic hydrops and vertigo during treatment in Meniere's disease.

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.

Sindrome Vestibular Agudo posterior a la infección por SARS-COV2 / Acute Vestibular Syndrome after SARS-COV2 infection

Introducción: El Sars-CoV 2 puede afectar al nervio vestibulococlear debido a su neurotropismo. Este trabajo tiene como objetivo reportar el caso de un paciente con vértigo agudo posterior a la infección por COVID-19. Materiales y Métodos: Paciente masculino de 64 años que consultó por un ataque de vértigo agudo, de predominio en el lado izquierdo, quince días después de su convalecencia por una infección por COVID-19. Se realizaron estudios neurootológicos y de resonancia magnética. Resultados: La resonancia magnética descartó la presencia de lesiones que pudieran explicar las manifestaciones clínicas. A altas frecuencias, la audiometría tonal reveló una pérdida auditiva neurosensorial en ambos lados. vHIT (video Head Impulse Test) y VEMP cervical (potenciales miogénicos evocados vestibulares) mostraron afectación del lado izquierdo. Los VEMP oculares mostraron afectación bilateral. El paciente mejoró con rehabilitación vestibular, pero las manifestaciones de vHIT persistieron a los 6 y 12 meses. Discusión: El vértigo agudo en este paciente podría haber sido el resultado de una neuronitis vestibular, secundaria a la infección previa por Sars-CoV2. Sin embargo, no se deben descartar diferentes mecanismos virales directos

: Sars-CoV 2 may affect the vestibulocochlear nerve due to its neurotropism. This work aims to report the case of a patient with acute vertigo following COVID-19 infection. Materials and Methods: A 64-year-old male patient consulted for an acute vertigo attack, predominantly to the left side, fifteen days after his convalescence due to a COVID-19 infection. Neuro-otological and MRI studies were carried out. Results: MRI ruled out the presence of lesions that could explain clinical manifestations. At high frequencies, tonal audiometry revealed a sensorineural hearing loss on both sides. vHIT (video Head Impulse Test) and cervical VEMP (Vestibular Evoked Myogenic Potentials) showed left side involvement. Ocular VEMP showed bilateral involvement. The patient improved with vestibular rehabilitation, but vHIT manifestations persisted at 6 and 12 months. Discussion: Acute vertigo in this patient might have been the result of vestibular neuronitis, secondary to the previous Sars-CoV2 infection. However, different direct viral mechanisms should not be ruled out

Sox10 Gene Is Required for the Survival of Saccular and Utricular Hair Cells in a Porcine Model.

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.

The Impact of Vascular Loops in the Cerebellopontine Angle on Audio-Vestibular Symptoms: A Systematic Review.

It has been suggested that vascular loops in the cerebellopontine angle and internal auditory canal are involved in the etiology of audio-vestibular symptoms. Several studies have focused on the compression of the eighth cranial nerve by vascular loops but have yielded contradictory results regarding their clinical significance. The aim of this study was to investigate whether vascular loops in this region correlate with audio-vestibular symptoms and which loop features - if any - can potentially lead to symptom manifestation. This systematic review was conducted according to the PRISMA guidelines. We performed on PubMed a literature search from November 2005 to October 2020. The search strategy included the following keywords ("vascular loops" OR "AICA loops" OR "vascular compression syndrome") AND ("hearing loss" OR "tinnitus" OR "vertigo"). Fifteen studies were eligible and included in the analysis. Overall, the studies encompassed a total of 11,788 patients included in this review. The significantly larger group of patients (70%), in which no correlation of symptoms with vascular loops was found, suggests that vascular loops are probably anatomic variations in a substantial majority of cases with an uncommon subset causing some audio-vestibular symptoms. Even within the papers claiming a correlation, there is a multitude of symptoms that did not correlate with vascular loops. It has been suggested by most authors that magnetic resonance imaging should be performed to exclude the role of a vascular loop in the etiology of audio-vestibular symptoms only when vascular compression syndrome is suspected based on clinical indications and not routinely. Further studies would be useful in order to detail the relationship between the vascular structures and the nervous system.

Endolymphatic Hydrops Magnetic Resonance Imaging in Menire's Disease Patients on a Vertigo Attack.

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.

Bidirectional Transport of IgE by CD23 in the Inner Ear of Patients with Meniere's Disease.

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.

Anatomical variation of inner ear may be a predisposing factor for unilateral Ménière's disease rather than for ipsilateral delayed endolymphatic hydrops.

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 (χ2 = 0.742, p = 0.389) and ipsilateral DEH (χ2 = 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.

Three-Dimensional High-Resolution Temporal Bone Histopathology Identifies Areas of Vascular Vulnerability in the Inner Ear.

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.

Nutraceuticals for Peripheral Vestibular Pathology: Properties, Usefulness, Future Perspectives and Medico-Legal Aspects.

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.

The Value of Subjective Visual Vertical in Diagnosis of Vestibular Migraine.

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.

Repercussions of the Degrees of Hearing Loss and Vestibular Dysfunction on the Static Balance of Children With Sensorineural Hearing Loss.

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.

3D-reconstructions of Bast's Valve and Membranous Labyrinth: Insights for Vestibular Implantation and Meniere's Disease.

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.