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The objective of this systematic review is to compare the diagnostic value of endolymphatic hydrops (EH) magnetic resonance imaging (MRI) with audiovestibular function tests, including electro cochleography (ECochG), cervical vestibular evoked myogenic potential (cVEMP) and caloric tests for the diagnosis of definite Meniere's disease (DMD). An electronic search was performed in the PubMed, Embase and Cochrane databases in August 2022. Original studies which reported the efficacy of gadolinium MRI for diagnosis of DMD were compared with ECochG, cVEMP and caloric tests from 2007 to 2022 published in English. Two reviewers extracted the methodology and results of MRI and functional tests, assessing them independently. A modified version of the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) was used for the assessment of the quality and the risk of bias of each study. The proportion of DMD cases diagnosed by MRI hydrops vs corresponding functional tests were calculated and the relationship between MRI and functional tests were evaluated using the Cohen's Kappa test. Concerning the MRI, the proportion diagnostic of DMD was 0.67 by cochlear EH and 0.80-0.82 by vestibular EH. Regarding the functional test, the propotiojn diagnostic of DMD was 0.48 by ECochG, 0.76 by cVEMP and 0.65 by caloric test. The findings of this systematic review were that the vestibular EH on imaging most effectively assisted in diagnosing DMD. Among the functional tests, cVEMP was the second most effective test. The agreement between imaging and cVEMP was moderate (0.44), indicating a gap between the patients identified by the imaging and functional tests based on the relatively small number of patients.
The purpose of this study was to prove the hypothesis that caloric response in Ménière's disease (MD) is reduced by hydropic expansion of the vestibular labyrinth, not by vestibular hypofunction, by evaluating the correlation morphologically using an intravenous Gadolinium (IV-Gd) inner ear MRI. In study I, the prevalence of abnormal video Head Impulse Test (vHIT) results among the patients with definite unilateral MD (n = 24) and vestibular neuritis (VN) (n = 22) were investigated. All patients showed abnormal canal paresis (CP) (> 26%) on caloric tests. The prevalence of abnormal vHIT in patients with abnormal CP was significantly lower in MD patients (12.5%) than that in VN patients (81.8%) (p < 0.001). In study II, morphological correlation between caloric tests and vestibular hydrops level was evaluated in unilateral MD patients (n = 16) who had normal vHIT results. Eleven patients (61%) had abnormal CP. After taking the images of IV-Gd inner ear MRI, the vestibular hydrops ratio (endolymph volume/total lymph volume = %VH) was measured. In addition, the relative vestibular hydrops ratio (%RVH = (%VHaffected ear-%VHunaffected ear) / (%VHaffected ear + %VHunaffected ear)) was calculated. Each ratio (%VH and %RVH) was compared with average peak slow phase velocity (PSPV) and CP, respectively. In the MD patients, %VH of the affected ear correlated significantly with mean PSPV on the same side (rs = -0.569, p = 0.024), while %RVH correlated significantly with CP (rs = 0.602, p = 0.014). In most MD patients (87.5%) compared to VN patients, vHIT results were normal even though the caloric function was reduced. In addition, the reduced caloric function with normal vHIT was related to the severity of the vestibular hydrops measured by the IV-Gd inner ear MRI. These findings concluded that the abnormal caloric tests with normal vHIT in MD indicated severe endolymphatic hydrops rather than vestibular hypofunction.
Vestibular disorders have been reported following cochlear implant (CI) surgery, but the literature shows a wide discrepancy in the reported clinical impact. The aim of this meta-analysis is to quantify the effect of CI before and after surgery on the outcomes of vestibular tests, postural stability, and subjective perception of dizziness.
Schistosomal myeloradiculopathy (SMR), the most severe and disabling ectopic form of Schistosoma mansoni infection, is caused by embolized ova eliciting local inflammation in the spinal cord and nerve roots. The treatment involves the use of praziquantel and long-term corticotherapy. The assessment of therapeutic response relies on neurological examination. Supplementary electrophysiological exams may improve prediction and monitoring of functional outcome. Vestibular evoked myogenic potential (VEMP) triggered by galvanic vestibular stimulation (GVS) is a simple, safe, low-cost and noninvasive electrophysiological technique that has been used to test the vestibulospinal tract in motor myelopathies. This paper reports the results of VEMP with GVS in patients with SMR.
Introduction: The inner ear vestibular system is essential to balance function. Although hearing loss is well-described and quite common following meningitis, the literature evaluating vestibular function following meningitis is very limited. In particular, information on results of contemporary vestibular function tests, e.g., the video head impulse test (VHIT), is scarce. Using contemporary vestibular function tests, this study examines the vestibular function of patients with profound hearing loss (HL) after meningitis. Methods: Review of the literature and retrospective controlled study. Patients: Twenty-one consecutive patients with profound HL after meningitis (cochlear implant candidates) matched with 20 patients with profound HL of unknown etiology and examined during the period 2013-2018. Outcome Measure: Vestibular function loss, as evaluated with VHIT vestibulo-ocular reflex (VOR) gain, eye movement saccades, and cervical vestibular-evoked myogenic potentials (cVEMPs). The results of these tests were correlated to inner ear imaging findings (MRI/CT) and the level of hearing loss. Results: Mean VHIT gain was 0.48 in the meningitis group compared to 0.86 in the control group (p < 0.01). Saccades were present in 21 ears (62%) in the meningitis group compared to six ears (15%) among the controls (p < 0.01). cVEMP responses were present on five ears (18%) in the meningitis group and 25 ears (66%) in the control group (p < 0.01). Discussion: Postmeningitic hearing loss is associated with poor vestibular function, as evaluated by VHIT, saccades, and cVEMP. Loss of vestibular function correlates with the degree of hearing loss and inner ear imaging findings, although not in all cases. Vestibular function should be examined in patients surviving meningitis with hearing loss in order to individualize rehabilitation and improve balance outcome.
Background: Cochlear implantation (CI) helps patients with severe or profound sensorineural hearing loss (SNHL) restore hearing and speech abilities. However, some patients exhibit abnormal vestibular functions with symptoms such as dizziness or balance disorders, after CI. Whether age at CI and CI approach (unilateral or sequential bilateral) affect vestibular functions in users with cochlear implants remains unclear. Objectives: To investigate the vestibular functions in children and adults before and after unilateral or sequential bilateral CI. Materials and Methods: Thirty-seven patients with severe or profound SNHL who were candidates for a first- or second-side CI were divided into three groups: first-side CI-implanted adults (≥18 years), first-side CI-implanted children (6-17 years), and second-side CI-implanted children (6-17 years). All cases were implanted with the round window approach to minimize damage to the intra-cochlear structures. The caloric test, vestibular evoked myogenic potential (VEMP) test, video head impulse test (vHIT), Dizziness Handicap Inventory (DHI), Pediatric Vestibular Symptom Questionnaire (PVSQ), and audiometric tests were performed before and 1 month after CI. Results: The abnormal rates of caloric test and VEMP test after CI in the first-side CI-implanted adults and children significantly increased compared with those before CI. The pre-implantation VEMP test showed significantly higher abnormal rates between first- and second-side CI-implanted children. No other significant differences of abnormal rates between first- and second-side CI-implanted children or between first-side CI-implanted adults and children were found. In second-side CI-implanted children, PVSQ scores significantly increased at day 3 post-implantation but decreased at day 30. Conclusion: CI has a negative effect on the results of caloric and VEMP tests, but not on vHIT, indicating that the otolith and low-frequency semicircular canal (SCC) are more vulnerable to damage from CI. The alterations of vestibular functions resulting from CI surgery may be independent of age at CI and CI approach (unilateral or sequential bilateral). Long-term impacts on the vestibular function from CI surgery, as well as the chronic electrical stimulation to the cochlea, are still to be investigated.
Convergent clinical and neuroimaging evidence suggests that higher vestibular function is subserved by a distributed network including visuospatial, cognitive-affective, proprioceptive, and integrative brain regions. Clinical vestibular syndromes may perturb this network, resulting in deficits across a variety of functional domains. Here, we leverage structural and functional neuroimaging to characterize this extended network in healthy control participants and patients with post-concussive vestibular dysfunction (PCVD). Then, 27 healthy control subjects (15 females) and 18 patients with subacute PCVD (12 female) were selected for participation. Eighty-two regions of interest (network nodes) were identified based on previous publications, group-wise differences in BOLD signal amplitude and connectivity, and multivariate pattern analysis on affective tests. Group-specific "core" networks, as well as a "consensus" network comprised of connections common to all participants, were then generated based on probabilistic tractography and functional connectivity between the 82 nodes and subjected to analyses of node centrality and community structure. Whereas the consensus network was comprised of affective, integrative, and vestibular nodes, PCVD participants exhibited diminished integration and centrality among vestibular and affective nodes and increased centrality of visual, supplementary motor, and frontal and cingulate eye field nodes. Clinical outcomes, derived from dynamic posturography, were associated with approximately 62% of all connections but best predicted by amygdalar, prefrontal, and cingulate connectivity. No group-wise differences in diffusion metrics or tractography were noted. These findings indicate that cognitive, affective, and proprioceptive substrates contribute to vestibular processing and performance and highlight the need to consider these domains during clinical diagnosis and treatment planning.
Self-motion perception was studied in patients with unilateral vestibular lesions (UVL) due to acute vestibular neuritis at 1 wk and 4, 8, and 12 mo after the acute episode. We assessed vestibularly mediated self-motion perception by measuring the error in reproducing the position of a remembered visual target at the end of four cycles of asymmetric whole-body rotation. The oscillatory stimulus consists of a slow (0.09 Hz) and a fast (0.38 Hz) half cycle. A large error was present in UVL patients when the slow half cycle was delivered toward the lesion side, but minimal toward the healthy side. This asymmetry diminished over time, but it remained abnormally large at 12 mo. In contrast, vestibulo-ocular reflex responses showed a large direction-dependent error only initially, then they normalized. Normalization also occurred for conventional reflex vestibular measures (caloric tests, subjective visual vertical, and head shaking nystagmus) and for perceptual function during symmetric rotation. Vestibular-related handicap, measured with the Dizziness Handicap Inventory (DHI) at 12 mo correlated with self-motion perception asymmetry but not with abnormalities in vestibulo-ocular function. We conclude that 1) a persistent self-motion perceptual bias is revealed by asymmetric rotation in UVLs despite vestibulo-ocular function becoming symmetric over time, 2) this dissociation is caused by differential perceptual-reflex adaptation to high- and low-frequency rotations when these are combined as with our asymmetric stimulus, 3) the findings imply differential central compensation for vestibuloperceptual and vestibulo-ocular reflex functions, and 4) self-motion perception disruption may mediate long-term vestibular-related handicap in UVL patients.NEW & NOTEWORTHY A novel vestibular stimulus, combining asymmetric slow and fast sinusoidal half cycles, revealed persistent vestibuloperceptual dysfunction in unilateral vestibular lesion (UVL) patients. The compensation of motion perception after UVL was slower than that of vestibulo-ocular reflex. Perceptual but not vestibulo-ocular reflex deficits correlated with dizziness-related handicap.
Usher syndrome is the most common cause of deafness-blindness in the world. Usher syndrome type 1B (USH1B) is associated with mutations in MYO7A. Patients with USH1B experience deafness, blindness, and vestibular dysfunction. In this study, we applied adeno-associated virus (AAV)-mediated gene therapy to the shaker-1 (Myo7a4626SB/4626SB) mouse, a model of USH1B. The shaker-1 mouse has a nonsense mutation in Myo7a, is profoundly deaf throughout life, and has significant vestibular dysfunction. Because of the ∼6.7-kb size of the MYO7A cDNA, a dual-AAV approach was used for gene delivery, which involves splitting human MYO7A cDNA into 5' and 3' halves and cloning them into two separate AAV8(Y733F) vectors. When MYO7A cDNA was delivered to shaker-1 inner ears using the dual-AAV approach, cochlear hair cell survival was improved. However, stereocilium organization and auditory function were not improved. In contrast, in the vestibular system, dual-AAV-mediated MYO7A delivery significantly rescued hair cell stereocilium morphology and improved vestibular function, as reflected in a reduction of circling behavior and improved vestibular sensory-evoked potential (VsEP) thresholds. Our data indicate that dual-AAV-mediated MYO7A expression improves vestibular function in shaker-1 mice and supports further development of this approach for the treatment of disabling dizziness from vestibular dysfunction in USH1B patients.
We investigated fibroblast growth factor 12 (FGF12) as a transcript enriched in the inner ear by searching published cDNA library databases. FGF12 is a fibroblast growth factor homologous factor, a subset of the FGF superfamily. To date, its localisation and function in the inner ear have not been determined. Here, we show that FGF12 mRNA is localised in spiral ganglion neurons (SGNs) and the vestibular ganglion. We also show that FGF12 protein is localised in SGNs, the vestibular ganglion, and nerve fibres extending beneath hair cells. Moreover, we investigated FGF12 function in auditory and vestibular systems using Fgf12-knockout (FGF12-KO) mice generated with CRISPR/Cas9 technology. Our results show that the inner ear morphology of FGF12-KO mice is not significantly different compared with wild-type mice. However, FGF12-KO mice exhibited an increased hearing threshold, as measured by the auditory brainstem response, as well as deficits in rotarod and balance beam performance tests. These results suggest that FGF12 is necessary for normal auditory and equilibrium function.
Electrical Vestibular Stimulation (EVS) is a non-invasive technique for activating the vestibular-ocular reflex, evoking mainly a torsional eye movement response. We have previously demonstrated that this response can be used to detect vestibular asymmetry in patients with vestibular schwannoma (VS). Here we perform a direct comparison of EVS with caloric irrigation in this patient group. We studied 30 patients with unilateral VS, alongside an equal number of aged-matched healthy control subjects. EVS current was delivered to the mastoid process in a monaural configuration using a sinusoidal stimulus (2 Hz; ± 2 mA; 10 s), with an electrode placed over the spinous C7 process. Evoked eye movements were recorded from the right eye in darkness using an infra-red sensitive camera while the subject sat relaxed with their head on a chinrest. Ocular torsion was subsequently tracked off-line using iris striations. Each subject separately underwent water caloric irrigation, in accordance with the British Society of Audiology guidelines. For the caloric test, eye movement was recorded in the yaw axis using electro-oculography. For both EVS and calorics, inter-aural response asymmetry was calculated to determine the extent of canal paresis. Both tests revealed impaired vestibular function in the ipsilesional ear of VS patients, with a mean asymmetry ratio of 15 ± 17% and 18 ± 16% for EVS and calorics, respectively. Overall, the caloric test results discriminated controls from patients slightly more effectively than EVS (Cohen's D effect size = 1.44 vs. 1.19). Importantly, there was a significant moderate correlation between the AR values produced by EVS and calorics (r = 0.53, p < 0.01), and no significant difference between mean AR estimates. When questioned, ≥85% of participants subjectively preferred the EVS experience, in terms of comfort. Moreover, it took ~15 min to complete, vs. ~1 h for caloric. These results confirm that the results of the EVS test broadly agree with those of caloric irrigation, in terms of detecting vestibular asymmetry. Furthermore, they suggest a higher degree of convenience and patient comfort.
The DFNB31 gene plays an indispensable role in the cochlea and retina. Mutations in this gene disrupt its various isoforms and lead to non-syndromic deafness, blindness and deaf-blindness. However, the known expression of Dfnb31, the mouse ortholog of DFNB31, in vestibular organs and the potential vestibular-deficient phenotype observed in one Dfnb31 mutant mouse (Dfnb31(wi/wi)) suggest that DFNB31 may also be important for vestibular function. In this study, we find that full-length (FL-) and C-terminal (C-) whirlin isoforms are expressed in the vestibular organs, where their stereociliary localizations are similar to those of developing cochlear inner hair cells. No whirlin is detected in Dfnb31(wi/wi) vestibular organs, while only C-whirlin is expressed in Dfnb31(neo/neo) vestibular organs. Both FL- and C-whirlin isoforms are required for normal vestibular stereociliary growth, although they may play slightly different roles in the central and peripheral zones of the crista ampullaris. Vestibular sensory-evoked potentials demonstrate severe to profound vestibular deficits in Dfnb31(neo/neo) and Dfnb31(wi/wi) mice. Swimming and rotarod tests demonstrate that the two Dfnb31 mutants have balance problems, with Dfnb31(wi/wi) mice being more affected than Dfnb31(neo/neo) mice. Because Dfnb31(wi/wi) and Dfnb31(neo/neo) mice faithfully recapitulate hearing and vision symptoms in patients, our findings of vestibular dysfunction in these Dfnb31 mutants raise the question of whether DFNB31-deficient patients may acquire vestibular as well as hearing and vision loss.
Anxiety disorders are among the most common mental disorders, and are comorbid with balance disorders in a significant proportion of these individuals. Presently, it is unclear whether anxiety and balance disorders are causally related, and what direction this causality may take. We argue that balance disorders may predispose an individual to anxiety and that demonstration of such causality may be informative to the development of preferred treatment for such individuals. To demonstrate that balance disorders may predispose to anxiety, we studied headbanger (Hdb) mutant mice in which the balance disorder is due to progressive vestibular impairment and wildtype (Wt) mice. Balance was assessed by swim and tail-hang tests that demonstrated clear behavioral balance deficits in the Hdb mice. Anxiety was assessed by open-field and elevated plus-maze tests, which confirmed elevated anxiety in the Hdb mice. These findings demonstrate that congenital vestibular genotype predisposes the animal to elevated levels of anxiety in space-related tests. Similar causality in clinics may redirect treatment strategies in afflicted patients.
Lateral semicircular canal (LSCC) dysplasia is the most common inner ear malformation. The severity of dysplasia can appear in various spectrums, from a short and broad LSCC with normal or small-sized central bony island (CBI) to a single fluid-filled cavity confluent with the vestibule without CBI. However, reports on the association between LSCC dysplasia and the loss of vestibular function are still lacking. In this study, the results of vestibular function tests [caloric test and video-head impulse test (vHIT)] in patients with LSCC dysplasia were analyzed and compared between groups with and without CBI.
Connexins are components of gap junctions which facilitate transfer of small molecules between cells. One member of the connexin family, Connexin 26 (Cx26), is prevalent in gap junctions in sensory epithelia of the inner ear. Mutations of GJB2, the gene encoding Cx26, cause significant hearing loss in humans. The vestibular system, however, does not usually show significant functional deficits in humans with this mutation. Mouse models for loss of Cx26 function demonstrate hearing loss and cochlear pathology but the extent of vestibular dysfunction and organ pathology are less well characterized. To understand the vestibular effects of Cx26 mutations, we evaluated vestibular function and histology of the vestibular sensory epithelia in a conditional knockout (CKO) mouse with Cx26 loss of function. Transgenic C57BL/6 mice, in which cre-Sox10 drives excision of the Cx26 gene from non-sensory cells flanking the sensory epithelium of the inner ear (Gjb2-CKO), were compared to age-matched wild types. Animals were sacrificed at ages between 4 and 40 weeks and their cochlear and vestibular sensory organs harvested for histological examination. Cx26 immunoreactivity was prominent in the peripheral vestibular system and the cochlea of wild type mice, but absent in the Gjb2-CKO specimens. The hair cell population in the cochleae of the Gjb2-CKO mice was severely depleted but in the vestibular organs it was intact, despite absence of Cx26 expression. The vestibular organs appeared normal at the latest time point examined, 40 weeks. To determine whether compensation by another connexin explains survival of the normal vestibular sensory epithelium, we evaluated the presence of Cx30 in the Gjb2-CKO mouse. We found that Cx30 labeling was normal in the cochlea, but it was decreased or absent in the vestibular system. The vestibular phenotype of the mutants was not different from wild-types as determined by time on the rotarod, head stability tests and physiological responses to vestibular stimulation. Thus presence of Cx30 in the cochlea does not compensate for Cx26 loss, and the absence of both connexins from vestibular sensory epithelia is no more injurious than the absence of one of them. Further studies to uncover the physiological foundation for this difference between the cochlea and the vestibular organs may help in designing treatments for GJB2 mutations.
The vestibulo-ocular reflex maintains gaze stabilization during angular or linear head accelerations, allowing adequate dynamic visual acuity. In case of bilateral vestibular hypofunction, patients use saccades to compensate for the reduced vestibulo-ocular reflex function, with covert saccades occurring even during the head displacement. In this study, we questioned whether covert saccades help maintain dynamic visual acuity, and evaluated which characteristic of these saccades are the most relevant to improve visual function. We prospectively included 18 patients with chronic bilateral vestibular hypofunction. Subjects underwent evaluation of dynamic visual acuity in the horizontal plane as well as video recording of their head and eye positions during horizontal head impulse tests in both directions (36 ears tested). Frequency, latency, consistency of covert saccade initiation, and gain of covert saccades as well as residual vestibulo-ocular reflex gain were calculated. We found no correlation between residual vestibulo-ocular reflex gain and dynamic visual acuity. Dynamic visual acuity performance was however positively correlated with the frequency and gain of covert saccades and negatively correlated with covert saccade latency. There was no correlation between consistency of covert saccade initiation and dynamic visual acuity. Even though gaze stabilization in space during covert saccades might be of very short duration, these refixation saccades seem to improve vision in patients with bilateral vestibular hypofunction during angular head impulses. These findings emphasize the need for specific rehabilitation technics that favor the triggering of covert saccades. The physiological origin of covert saccades is discussed.
Bilateral vestibulopathy (BV) is a chronic vestibular disorder, characterized by bilaterally absent or significantly impaired vestibular function. Symptoms typically include, but are not limited to, unsteadiness and movement-induced blurred vision (oscillopsia). This prospective case-control study aimed to elucidate the impact of BV on cognitive and motor performance and on cognitive-motor interference. Cognitive and motor performance, as well as cognitive-motor interference were measured in persons with BV and normal hearing using the 2BALANCE dual-task protocol. The experimental group was matched to a healthy control group based on age, sex, and educational level. The 2BALANCE protocol comprises cognitive tests assessing visuospatial memory, mental rotation, visual and auditory response inhibition, visual and auditory working memory, and processing speed. The cognitive tests were performed in single-task condition (while seated), and in dual-task condition (during a static and a dynamic motor task). The static motor task consisted of balancing on a force platform with foam pad. The dynamic motor task consisted of walking at a self-selected speed. These motor tasks were also performed in single-task condition. A generalized estimating equations model was used to investigate group differences for all cognitive and motor outcome measures. The estimated marginal means, as well as the odds ratios (OR), and their 95% confidence intervals (CI) were calculated. For the backward digit recall test, a baseline measurement was performed and analyzed using a student-t test. A total of 22 patients with BV and normal hearing and 22 healthy control subjects were assessed [mean age (SD), BV = 53.66 (13.35) and HC = 53.21 (13.35), 68% male]. The BV group had poorer mental rotation skills in single-task condition, compared to the control group [odds ratio (OR) = 2.30, confidence interval (CI) = 1.12-4.73, P = 0.024]. Similarly, auditory and visual working memory were also poorer in the BV group in single-task condition (P = 0.028 and P = 0.003, respectively). The BV group also performed poorer on the mental rotation task and the visual response inhibition task in dual-task condition (OR = 2.96, CI = 1.57-5.59, P < 0.001 and OR = 1.08, CI = 1.01-1.16, P = 0.032, respectively). Additionally, an interaction effect, indicating increased cognitive-motor interference in the BV group, was observed for mental rotation, response inhibition, and auditory working memory (P = 0.003 to 0.028). All static motor outcome parameters indicated more postural sway in the BV group compared to the control group for all test conditions (P < 0.001 to 0.026). No group differences were noted for the dynamic motor task. These findings suggest a link between vestibular function and cognitive performance, as well as a greater interference between cognitive and motor performance in BV, compared to healthy controls.
Vestibular-evoked myogenic potential triggered by galvanic vestibular stimulation (galvanic-VEMP) evaluates the motor spinal cord and identifies subclinical myelopathies. We used galvanic-VEMP to compare spinal cord function in individuals infected with human T-cell lymphotropic virus type 1 (HTLV-1) from asymptomatic status to HTLV-1-associated myelopathy (HAM).
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