Normal Vestibular Function Research Articles

Sensorineural Hearing Loss Negatively Impacts Cognition in Older Subjects with Normal Lateral Semi-Circular Canal Function

Plain Language SummaryWithin the current study, the authors aimed to explore the effect of hearing loss on cognitive functioning in older adults, considering the effects of vestibular function, anxiety and depression on cognitive performance. There is increasing evidence that hearing loss is a modifiable risk factor for cognitive decline but also vestibular dysfunction, depression and anxiety symptoms may play a role in this association. Cognitive functioning was evaluated in a group with moderate-to-severe hearing loss and a matched control group based on sex, age, education level, vestibular function, anxiety and depression rates. The patients with a hearing impairment performed significantly worse on cognitive testing and the differences were most pronounced for the cognitive subdomains of Attention and Visuospatial/Constructional memory. Results from this study confirm that hearing loss negatively impacts cognitive functioning, even in older adults with normal vestibular function.

Histaminergic System and Vestibular Function in Normal and Pathological Conditions.

Most neurotransmitter systems are represented in the central and peripheral vestibular system and are thereby involved both in normal vestibular signal processing and the pathophysiology of vestibular disorders. However, there is a special relationship between the vestibular system and the histaminergic system. The purpose of this review is to document how the histaminergic system interferes with normal and pathological vestibular function. In particular, we will discuss neurobiological mechanisms such as neuroinflammation that involve histamine to modulate and allow restoration of balance function in the situation of a vestibular insult. These adaptive mechanisms represent targets of histaminergic pharmacological compounds capable of restoring vestibular function in pathological situations. The clinical use of drugs targeting the histaminergic system in various vestibular disorders is critically discussed.

Vestibular Impairment and Postural Development in Children With Bilateral Profound Hearing Loss

Children with profound hearing loss (HL) and vestibular impairment have worse cochlear implant outcomes compared with those without vestibular impairment. However, the decision for cochlear implantation is rarely based on vestibular function assessment as a complement to audiologic testing. To identify the prevalence of vestibular impairment according to HL origin and to assess the association between vestibular impairment and delayed posturomotor development in children with profound HL. This cohort study was conducted in a pediatric referral center for cochlear implantation in Paris, France, using medical records data on HL origin, vestibular assessment, and ages of developmental milestone achievement. The cohort included children with profound HL (loss >90 dB HL) who completed vestibular assessment prior to cochlear implantation between January 1, 2009, and December 31, 2019. Data analyses were conducted between January and June 2023. The primary outcome was prevalence of vestibular impairment according to HL origin. Children were classified into 3 groups according to their responses to vestibular testing: normal vestibular function (NVF), partially impaired vestibular function (PVF), and complete bilateral vestibular loss (CBVL). Generalized logit models were performed to evaluate the association between vestibular impairment and causes of HL as well as posturomotor development delay. A total of 592 children were included (308 males [52.0%]; mean [SD] age, 38 [34] months). In children with documented HL origin (n = 266), 45.1% (120) had HL with genetic origin, 50.0% of which were syndromic (mainly Usher and Waardenburg syndromes) and 50.0% were nonsyndromic (mainly associated with connexin 26). Among patients with infectious HL origin (n = 74), 70.3% (52) had cytomegalovirus (CMV) infection. Vestibular impairment was found in 44.4% (263 of 592) of the children; it was mostly symmetrical in 88.9% (526) and was CBVL in 5.7% (34) of the cases. Vestibular impairment was present in 78.3% (47) of children with genetic syndromic HL (56.7% [34] with PVF; 21.7% [13] with CBVL) and in 69.2% (36) of children with CMV infection (57.7% [30] with PVF; 11.5% [6] with CBVL). Genetic syndromic HL origin was found to be more often associated with both PVF and CBVL than other HL causes. The odds of having delays in 4 developmental milestones (head holding, sitting, standing with support, and independent walking) were higher in both PVF and CBVL (eg, head-holding odds ratios: 2.55 and 4.79) compared with NVF, and the age of achieving these milestones was higher in CBVL than PVF (eg, head holding: 7.33 vs 4.03 years; P < .001). All 4 developmental milestones were associated with the degree of vestibular impairment. This cohort study found that among children with profound HL, vestibular impairment was prevalent, varied according to HL origin, and associated with posturomotor development; while all developmental milestones were associated with vestibular impairment severity, not all HL causes were associated with vestibular impairment severity. Children with profound HL may benefit from complete vestibular assessment before cochlear implantation, which would support early and adapted management, such as physical therapy for CBVL and cochlear implantation strategy.

Postural motion perception during vestibular stimulation depends on the motion perception threshold in persistent postural-perceptual dizziness

Patients with persistent postural-perceptual dizziness (PPPD) perceive postural instability larger than the observed sway. It is unknown whether the concept of postural misperception prevails during vestibular stimulation and whether it may account for the unsteadiness patients complain during body movements. We tested the hypothesis of an abnormal sensory-perceptual scaling mechanism in PPPD by recording objective, perceived, and the reproduced postural sway under various standing conditions, modulating visual and proprioceptive input, by binaural galvanic vestibular stimulation (GVS). We related postural sway speed to individual vestibular motion perceptional thresholds and disease-related PPPD questionnaires in 32 patients and 28 age-matched healthy control subjects (HC). All participants showed normal vestibular function tests on quantitative testing at the time of enrollment. The perception threshold of GVS was lower in patients. Compared to HC, patients showed and perceived larger sway on the firm platform. With GVS, posturo-perceptual ratios did not show group differences. The ratio of reproduced to real postural sway showed no group differences indicating normal postural sway perception during vestibular stimulation. Noticeably, only in patients, reproduced postural instability became larger with lower individual thresholds of vestibular motion detection. We conclude that posturo-perceptual (metacognitive) scaling of postural control seems to be largely preserved in PPPD during GVS. Vestibular stimulation does not destabilize patients more than HC, even in challenging postural conditions. Low individual thresholds of vestibular motion perception seem to facilitate instability and postural misperception on solid grounds. This conclusion is important for an effective physical therapy with vestibular exercises in PPPD.

The role of cochlear and vestibular afferents in long-latency cervical vestibular evoked myogenic potentials

Objective To examine the origin of cervical vestibular evoked myogenic potential (cVEMP) late waves (n34-p44) elicited with air-conducted click stimuli. Design Using a retrospective design, cVEMPs from normal volunteers were compared to those obtained from patients with vestibular and auditory pathologies. Study sample (1) Normal volunteers (n = 56); (2) severe-to-profound sensorineural hearing loss (SNHL) with normal vestibular function (n = 21); (3) peripheral vestibular impairment with preserved hearing (n = 16); (4) total vestibulocochlear deficit (n = 23). Results All normal volunteers had ipsilateral-dominant early p13-n23 peaks. Late peaks were present bilaterally in 78%. The p13-n23 response was present in all patients with SNHL but normal vestibular function, and 43% had late waves. Statistical comparison of these patients to a subset of age-matched controls showed no significant difference in the frequencies, amplitudes or latencies of their ipsilateral early and late peaks. cVEMPs were absent in all patients with vestibular impairment. Conclusion The presence of long-latency cVEMP waves was not dependent on the integrity of sensorineural hearing pathways, but instead correlated with intact vestibular function. This finding conflicts with the view that these late waves are cochlear in origin, and suggests that vestibular afferents may assume a more prominent role in their generation.

Analysis of postural stability using foam posturography in patients with persistent postural-perceptual dizziness.

Persistent postural-perceptual dizziness (PPPD) is worsened in a standing posture, or by body movement, or visual stimulation. We aimed to evaluate postural stability in PPPD patients using foam posturography and to investigate the dependence on visual and somatosensory input in the standing posture. Foam posturography was performed on 53 PPPD patients, and data from the PPPD patients were compared with the data from an age- and sex-matched healthy controls. The PPPD patients were divided into four groups based on the findings of vestibular function tests and the effect of vestibular function on posturographic data was examined. Romberg's ratios were significantly higher in PPPD patients than in controls. The median Romberg's ratios in PPPD patients with normal vestibular function were also higher than those in controls. However, foam ratio was significantly lower in PPPD patients than in controls. The median foam ratios in PPPD patients with vestibular dysfunction were also lower than those in controls. In a standing posture, PPPD patients may be more dependent on visual input and less dependent on somatosensory input than healthy subjects. Higher dependence on visual and lower dependence on somatosensory input in PPPD may be a feature unaffected by vestibular function.

Vestibular Dysfunction Among Children with Otitis Media and Effusion in a Multiracial Setting.

Otitis media with effusion (OME) is a common presentation to the Otorhinolaryngology clinic. Besides hearing impairment, recent evidence shows that approximately 30% of these children have some degree of vestibular and balance impairment. To assess the presence of vestibular dysfunction among children with OME. Children between 4 and 17, with and without OME, underwent vestibular assessment using video head impulse test (VHIT), subjective visual subjective (SVV), and single leg raising test (SLS). Data were recorded and analysed. 24 OME children were included with male predominance. No statistical significance was found between the VOR gain (p > 0.05), SVV (p = 0.056) and SLS (p = 0.06). Simple linear regression analysis showed that age and gender are potential factors for VOR gain. Our study found that children with OME have normal vestibular function.

Suppression head impulse test in children-experiences in a tertiary paediatric vestibular centre.

The suppression head impulse paradigm (SHIMP) involves suppression of the vestibulo-ocular reflex (VOR) and anticompensatory saccades generated thereof. SHIMP is gaining importance to understand vestibular compensation with its different parameters (VOR gain/peak saccadic velocity PSV/latency of saccades). SHIMP studies are emerging in adults, but pediatric studies have hardly been performed. This study is a retrospective case note audit over a period of 2 months in a tertiary pediatric vestibular center in the United Kingdom to investigate whether SHIMP is safe/robust to be used in children conforming to existing standards/norms in normal children and whether it yields any meaningful inferences in pediatric vestibular hypofunction. This is the largest pediatric SHIMP study to date. A total of 44 referred children (6-18 years, female children>male children) with a range of complaints from dizziness, imbalance, motor incoordination, postural instability, and hearing loss were included, and their SHIMP parameters were measured. All children underwent comprehensive functional/objective audiovestibular assessments. Two groups were defined-Group A with normal vestibular function and Group B with abnormal vestibular function. The normal population showed an average SHIMP VOR gain of 0.98+/-0.08 and latency of overt saccades at 215.68+/-46.16 milliseconds agreeing with published evidence. The PSV of overt saccades was 315.39+/-56.30/s, and there was a gain asymmetry of 7.42+/-4.68 between the sides. Statistically significant differences with moderate/large effect sizes were observed between the groups in terms of VOR gain and PSV but not in saccade latencies. Covert saccades were rare in SHIMP, while overt saccades were observed in 100% of children. VOR gain difference between the head impulse paradigm (HIMP) and the SHIMP was significant as well. We observed statistically significant differences in side asymmetry of VOR gain between the groups. Furthermore, we identified a group of children with cerebellar lesions where overt saccades in SHIMP were rather low in number. Further research is recommended to investigate pediatric PSV, asymmetry, and inability to generate overt saccades that may suggest useful means to assess compensation and central function. We conclude that SHIMP yields valuable information and is a safe, easy to perform, and a reliable test that should be used in children to supplement HIMP.

Visual and vestibular motion perception in persistent postural-perceptual dizziness (PPPD)

Persistent postural-perceptual dizziness (PPPD) is a chronic disorder of perceived unsteadiness. Symptoms can be exacerbated in visually complex stationary or moving environment. Visual dependence and increased motion sensitivity are predictors for PPPD but its pathophysiology remains unknown. We hypothesized an abnormal sensory–perceptual scaling mechanism in PPPD and tested visual- and vestibular perceptional thresholds in 32 patients and 28 age-matched healthy control subjects (HC). All participants showed normal vestibular function tests on quantitative testing. Visual motion coherence thresholds were assessed by random dot kinetomatograms. Vestibular perceptional thresholds of egomotion were assessed by binaural galvanic vestibular stimulation (GVS) and passive chair rotation around an earth-vertical axis. Chair rotation trials were contrasted with no-motion (sham) stimulus trials. Mean thresholds of visual motion perception were higher in patients compared to HC. The perception threshold of GVS was lower in patients but the threshold of correctly perceived egomotion during chair rotation did not differ. Interestingly, the number of trials with correct perception in the no-motion condition increased with the threshold of correct responses for rotatory egomotion in patients. Unlike expected, PPPD patients required more coherently moving random dots than HC to perceive visual motion. A poorer complex visual motion recognition, e.g., traffic visual stimuli, may increase anxiety and levels of uncertainty as visuomotor reactions might occur delayed. The vestibular rotatory perception threshold predicted the probability of making false assignments in the sham condition in PPPD, i.e., patients who readily recognize the correct egomotion direction are prone to perceive egomotion in the no-motion condition. As this relation was not found in healthy subjects, it may reflect an abnormal sensory–perceptual scaling feature of PPPD.

A clinical 3D pointing test differentiates spatial memory deficits in dementia and bilateral vestibular failure

BackgroundDeficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants.MethodsThe 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition (n = 32), (2) cognitive impairment with normal vestibular function (n = 28), and (3) combined BVP and cognitive impairment (n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits (n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman’s rho.ResultsPatients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit.ConclusionThe 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.

Vestibular function and hearing preservation in children following a minimally invasive cochlear implantation

PurposeThis retrospective cohort study aimed to investigate the effect of minimally invasive cochlear implantation (CI) on the vestibular function (VF) and residual hearing (RH) as well as their relationship in pediatric recipients before and after surgery.MethodsTwenty-four pediatric patients with preoperative low frequency residual hearing (LFRH) (250 or 500 Hz ≤ 80 dB HL) who underwent minimally invasive CI were enrolled. Pure-tone thresholds, the cervical/ocular vestibular-evoked myogenic potential (cVEMP/oVEMP), and video head impulse test (vHIT) were all evaluated in the 24 pediatric patients with preoperative normal VF before and at 1 and 12 months after surgery. The relationship between changes in hearing and VF was analyzed preoperatively and at 1 and 12 months postoperatively.ResultsThere were no significant differences on VF preservation and hearing preservation (HP) at both 1 and 12 months post-CI (p > 0.05). At 1 month post-CI, the correlations of the variations in vestibulo-ocular reflex (VOR) gains of horizontal semicircular canal (HSC) and posterior semicircular canal (PSC) and the shift in 250 Hz threshold were negatively correlated (r = − 0.41, p = 0.04 and r = − 0.43, p = 0.04, respectively). At 12 months post-CI, the shift in 250 Hz threshold negatively correlated to the variations in VOR gain of superior semicircular canal (SSC) (r = − 0.43, p = 0.04); the HP positively correlated to the variation in oVEMP-amplitude ratio (AR) (r = 0.41, p = 0.04).ConclusionOur study confirmed that there were partial correlations between VF preservation and HP both in the short- and long-terms after atraumatic CI surgery, especially with the 250 Hz threshold. Regarding the variation of PSC function, the correlation with hearing status was variable with time after atraumatic CI surgery. Minimally invasive techniques for HP are successful and effective for the preservation of VF in pediatric patients both in the short- and long-terms.

Genetic and phenotypic presentation of Usher syndrome - a case report

Usher syndrome is a genetic, clinically heterogeneous condition characterized by sensorineural hearing loss, progressive retinal degeneration, and vestibular dysfunction. There are three phenotypically recognizable types of Usher syndrome. Individuals with Usher syndrome type 1 have no vestibular function and profound sensorineural hearing loss. Individuals with Usher syndrome type 2 have normal vestibular function and mild-to-severe hearing loss with visual impairment that is presented later in life. People with Usher syndrome type III experience hearing and vision loss beginning later in life. In this case report, we are reporting a 7-year-old boy consulted for progressive hearing loss and bilateral vision impairment, and fundus exam revealed mild bilateral retinal vessel attenuation and bone spicule deposits in both eyes. A molecular genetic test done by next-generation sequencing identified a homozygous pathogenic variant in the CDH23 gene (NM_022124.5:c.2255del variant coordinate with amino acid change of p.(Gly752Valfs*13)), confirming the diagnosis of autosomal recessive Usher syndrome type ID (USH1D). The patient had a remarkable improvement with visual and optical aids. Genetic counseling, including reproductive counseling, was provided to the parents. Clinical evaluation, visual hearing tests, and genetic workup confirmed Usher syndrome, which is a rare but dangerous cause of hearing loss and visual impairment that needs to be thoroughly evaluated by a multi-disciplinary team approach.

Measurement of Ocular Vestibular Evoked Myogenic Potentials: Nasion Reference Montage as an Alternative to the Clinical Standard Montage.

To compare two novel electrode montages for ocular, vestibular evoked myogenic potential using single-nasion reference electrodes with the clinical standard montage. Randomized crossover experiment. Tertiary referral center. Sixty healthy participants. Normal hearing and vestibular function were confirmed with an extensive test-battery. All ocular, vestibular evoked myogenic potential settings were measured with air-conducted tone bursts at 100-dB normal hearing level and a frequency of 500 Hz. Three electrode montages were measured in randomized order: the clinical standard montage ("S"), the nasion reference montage ("N"), and the nasion reference montage with a more lateral active electrode ("L"). Upgaze was standardized to 35 degrees. Detection rate, latency of N1 and P1, peak-to-peak amplitude of N1 and P1, signal-to-noise ratio (SNR), asymmetry ratio (AR), concordance of expert assessment, and reliability. All electrode montages showed detection rates greater than 90%. Latencies for "L" were shorter than for "S" and "N." Amplitudes and SNR for "S" and "N" were higher than for "L," whereas the values for "S" and "N" did not differ significantly. For AR, no significant differences between the montages were assessed. Concordance of experts ranged from 78% for "L" and 89.8% for "N." All montages provided excellent day-to-day reliability (intraclass correlation coefficient ≥0.9) for amplitudes and SNR. Montage N could be a useful alternative to the clinical standard montage: although results are roughly equivalent, montage N requires one less electrode to do so.

Relation Between Horizontal Saccade Test and Anti-Compensatory Saccade in the Suppression Head Impulse Test Paradigm

Background and Objectives There is limited study reported on the relationship between horizontal saccades and anti-compensatory saccades (ACS) in the suppression head impulse paradigm (SHIMP). We investigated the relationship between horizontal saccades and ACS in SHIMP in individuals with normal vestibular function and determined the correlation between the associated factors.Subjects and Method Medical records of 79 patients with normal vestibular function and brain magnetic resonance images were retrospectively reviewed.Results ACS and horizontal saccades results were strongly correlated with velocity (R= 0.345, &lt;i&gt;p&lt;/i&gt;&lt;0.001) and latency (R=0.547, &lt;i&gt;p&lt;/i&gt;&lt;0.001). The latency of ACS was significantly shorter (&lt;i&gt;p&lt;/i&gt;&lt;0.001) than that of horizontal saccades. The velocity of ACS was negatively correlated with the latencies of ACS (R=-0.318, &lt;i&gt;p&lt;/i&gt;&lt;0.001) and horizontal saccades (R=-0.322, &lt;i&gt;p&lt;/i&gt;&lt;0.001). Bilateral ACS latency (R=0.384 and 0.471 in right and left, &lt;i&gt;p&lt;/i&gt;&lt;0.001 in both side) and left side ACS velocity (R=-0.263, &lt;i&gt;p&lt;/i&gt;=0.019) were significantly affected by age.Conclusion ACS in the SHIMP was strongly correlated with horizontal saccades. However, the latency of ACS was shorter than that of horizontal saccades. Therefore, patient age and results of the horizontal saccades tests should be considered while interpreting the ACS velocity, which reflects vestibulo-ocular reflex function in patients with vestibulopathy.

Effect of Sound Source Location and Spatial Hearing on the Vestibulo-Ocular Reflex.

There have been conflicting results on the effect of auditory stimulation on the vestibulo-ocular reflex (VOR) with some studies indicating suppression, enhancement, or no effect. No studies to date have assessed the effect of sound source location on VOR gain or the relationship between spatial hearing ability and VOR gain. The purpose of the present study was to determine if VOR gain was affected by moving the location of the sound source within participants and to determine if these effects were related to spatial hearing ability. A between subjects repeated measures experimental design was utilized. Two groups of participants (adult and child) with normal otologic, vestibular, and neurologic function. 22 adults (20 female and 2 male; average age = 23 years) and 16 children (9 female and 7 male; average age = 7.5 years) were included in data analysis. VOR gain was measured using rotational chair stimulation in the following auditory conditions: silent, insert earphones, external loudspeaker at 0° azimuth rotating with participant, and external stationary speaker. Localization ability was measured using root mean square (RMS) error. Results indicated a significant effect for sound source location on VOR gain and VOR difference gain in both groups. RMS error was positively correlated for the moving and fixed sound source locations for both adults and children. VOR gain was significantly affected by location of the sound source. Findings suggest the presence and location of an auditory stimulus during rotational testing can alter results during the assessment.

Short-term learning of the vestibulo-ocular reflex induced by a custom interactive computer game.

Retinal image slip during head rotation drives motor learning in the rotational vestibulo-ocular reflex (VOR) and forms the basis of gaze-stability exercises that treat vestibular dysfunction. Clinical exercises, however, are unengaging, cannot easily be titrated to the level of impairment, and provide neither direct feedback nor tracking of the patient's adherence, performance, and progress. To address this, we have developed a custom application for VOR training based on an interactive computer game. In this study, we tested the ability of this game to induce VOR learning in individuals with normal vestibular function, and we compared the efficacy of single-step and incremental learning protocols. Eighteen participants played the game twice on different days. All participants tolerated the game and were able to complete both sessions. The game scenario incorporated a series of brief head rotations, similar to active head impulses, that were paired with a dynamic acuity task and with a visual-vestibular mismatch (VVM) intended to increase VOR gain (single-step: 300 successful trials at ×1.5 viewing; incremental: 100 trials each of ×1.13, ×1.33, and ×1.5 viewing). Overall, VOR gain increased by 15 ± 4.7% (mean ± 95% CI, P < 0.001). Gains increased similarly for active and passive head rotations, and, contrary to our hypothesis, there was little effect of the learning strategy. This study shows that an interactive computer game provides robust VOR training and has the potential to deliver effective, engaging, and trackable gaze-stability exercises to patients with a range of vestibular dysfunctions.NEW & NOTEWORTHY This study demonstrates the feasibility and efficacy of a customized computer game to induce motor learning in the high-frequency rotational vestibulo-ocular reflex. It provides a physiological basis for the deployment of this technology to clinical vestibular rehabilitation.

RIPOR2: A new gene of non-syndromic cochleovestibular dysfunction, discrepancy between human pathology and animal models.

Cochleovestibular dysfunctions are rare conditions misrecognized. A homozygous pathogenic variation c.1561C > T (p.Arg521*) in RIPOR2 (RHO family interacting cell polarization regulator 2) has been identified by WES in Tunisian siblings suffering from congenital bilateral profound hearing and vestibular dysfunctions. In contrast to the vestibular areflexia observed in our patients, deaf Ripor2 KO mouse model and our zebrafish model have normal vestibular function.

The effects of vestibular dysfunction on balance and self-concept in children with cochlear implants.

Children with cochlear implants (CCI) have an increased rate of vestibular dysfunction. Vestibular dysfunction is associated with decreased balance and dynamic visual acuity ability. Hearing loss alone is associated with reduced speech perception and vocabulary in children. In adults, vestibular dysfunction is associated with reduced quality of life; however, similar relationships have not been studied in children with vestibular dysfunction. Therefore, the objective of the present study was to evaluate the effect of hearing loss and vestibular dysfunction on self-concept in CCI (n=33) compared to children with normal hearing (CNH, n=38). It was hypothesized that children with vestibular dysfunction would have reduced self-concept beyond that from hearing loss, secondary to the presence of balance and visual acuity deficits. The Piers-Harris Children's Self-Concept Scale - 2, speech perception, vocabulary, video head impulse test (vHIT), rotary chair, balance using the Bruininks-Oseretsky Test of Motor Proficiency (BOT-2), and dynamic visual acuity (DVA) testing were completed on all participants. In the 34 CCI, 24 had normal vestibular function, 6 had unilateral vestibular dysfunction, and 4 had bilateral vestibular dysfunction. There were no significant mean differences in the Piers-Harris Children's Self-Concept Scale - 2 between groups. A Principal Component Analysis (PCA) was conducted on the predictor variables (average horizontal canal vHIT gain, BOT-2 score, DVA, speech perception, and vocabulary) resulting in two factors; factor 1 represented "vestibular" components (vHIT, BOT-2, and DVA) and factor 2 represented "auditory-language" components (speech perception and vocabulary). In addition to age and gender, the 2 PCA factors were analyzed using multivariate regression with stepwise selection to determine which factors best predicted self-concept. The PCA auditory-language factor was the only significant predictor of self-concept. Auditory-language, not vestibular related factors, contribute to the self-concept of CCI. While adults with vestibular dysfunction have reduced quality of life, it could be that children with vestibular dysfunction have some psychosocial resilience.

Vestibular Follow-up Program for Congenital Cytomegalovirus Based on 6 Years of Longitudinal Data Collection.

Congenital cytomegalovirus (cCMV), the leading nongenetic cause of pediatric sensorineural hearing loss, can also affect vestibular function. Literature findings suggest clinical presentation of vestibular loss in cCMV to be as variable as the hearing loss. Still, probably due to the considerable additional burden it entails for both patients and diagnostic centers, longitudinal vestibular follow-up in cCMV is not well-established in clinical practice. Therefore, this study aims to propose an evidence-based vestibular follow-up program with proper balance between its feasibility and sensitivity. In this longitudinal cohort study, 185 cCMV-patients (mean age 3.2 years, SD 1.6 years, range 0.5-6.7 years) were included. Vestibular follow-up data were obtained through lateral video head impulse test (vHIT) and cervical vestibular evoked myogenic potential (cVEMP) evaluations around the ages of 6 months, 1 year, and 2 years. Around 3 and 4.5 years of age, data from vertical vHIT and ocular vestibular evoked myogenic potentials (oVEMP) were also collected. At birth, 55.1% (102/185) of patients were asymptomatic and 44.9% (83/185) were symptomatic. The mean duration of follow-up for all patients was 20.8 (SD 16.3) months (mean number of follow-up assessments: 3.2, SD 1.5). Vestibular loss occurred at some point during follow-up in 16.8% (31/185) of all patients. Six percent (10/164) of patients with normal vestibular function at first assessment developed delayed-onset vestibular loss; 80.0% (8/10) of these within the first 2 years of life. Vestibular deterioration was reported both in patients who had been treated with postnatal antiviral therapy and untreated patients. At final evaluation, both the semicircular and the otolith system were impaired in the majority of vestibular-impaired ears (29/36, 80.6%). Dysfunctions limited to the semicircular system or the otolith system were reported in 4 (4/36, 11.1%) and 3 (3/36, 8.3%) ears, respectively. The occurrence of vestibular loss was highest in patients with first trimester seroconversion (16/59, 27.1%) or with an unknown timing of seroconversion (13/71, 18.3%), patients with sensorineural hearing loss (16/31, 51.6%), and patients with periventricular cysts on magnetic resonance imaging (MRI) (7/11, 63.6%). Longitudinal vestibular follow-up, most intensively during the first 2 years of life, is recommended in cCMV-patients with vestibular risk factors (first trimester or unknown timing of seroconversion; sensorineural hearing loss; periventricular cysts on MRI). If those risk factors can be ruled out, a single evaluation early in life (around 6 months of age) might be sufficient. Both semicircular and otolith system evaluation should be part of the follow-up program, as partial losses were reported.

A Novel Biallelic Variant in CDH23 Gene in a Family with Atypical USH1D Manifestation: A Literature Review and Investigation of Genotype-Phenotype Correlation

Introduction: Usher syndrome (USH) is an autosomal recessive disorder that predominantly affects hearing, vision, and, in some cases, vestibular function. USH, according to the onset age, severity, and progression of symptoms, is categorized into four main types. In addition, there are a significant number of reports that patients’ manifestations deviate from canonical phenotypic criteria of main types of USH, which are named atypical USH. CDH23 is the second most common USH gene in which its defects result in USH1D, non-syndromic autosomal recessive deafness-12 (DFNB12), and in a few cases, atypical USH1D. While some studies have suggested that missense and truncating damaging variants in the CDH23 gene cause DFNB12 and USH1D, respectively, no genotype-phenotype correlation for atypical USH1D has been established. Methods: Using whole-exome sequencing, we studied an Iranian family with two affected siblings who manifested congenital bilateral hearing loss, late-onset nyctalopia, retinitis pigmentosa, and normal vestibular function, indicating that their clinical symptoms are consistent with USH2. Results: Whole-exome data analysis revealed a novel bi-allelic nonsense variant (c.6562G>T; p.Glu2188Ter) in the CDH23 gene, which was confirmed by Sanger sequencing. Surprisingly, CDH23 is a member of the USH1 genes; therefore, our patients suffered from atypical USH1D. Also, by conducting a literature review, we provided a clinical and mutational profile of all reported patients with atypical manifestations or those who refuted the claimed genotype-phenotype correlation. Conclusion: By reporting a novel damaging variant, we expand the mutational spectrum of the CDH23 gene that leads to atypical USH1D. Also, reviewing the literature shows that, contrary to previous claims, different genotypes occur in the CDH23 gene allelic disorders, and there is no clear-cut genotype-phenotype correlation.