[Expert consensus on vestibular rehabilitation in vestibular disorders].

Vestibular rehabilitation therapy (VRT) is a highly effective treatment approach for addressing both peripheral and central vestibular disorders, offering the ability to significantly improve patients' coordination and control across the vestibular, visual, and proprioceptive systems, all of which are crucial factors in maintaining balance. By promoting vestibular compensation, VRT has been shown to mitigate or even eliminate symptoms of dizziness, vertigo, and instability. With the rapid development of vestibular research, VRT has evolved into a more individualized and precise treatment approach based on evidence-based medicine. Its clinical effectiveness has been increasingly validated in numerous studies. With the involvement of multidisciplinary experts, this article aims to reach a consensus on the pre-treatment evaluation, formulation/implementation of treatment plans, and evidence-based treatment recommendations for common vestibular disorders, focusing on the prospects of vestibular rehabilitation. The goal is to further standardize and update VRT protocols for different vestibular disorders, providing comprehensive and context-specific guidance primarily tailored to the Chinese healthcare landscape, with a notable emphasis on its clinical applicability. Concurrently, it aspires to present new insights and serve as a valuable reference point for forthcoming high-quality clinical research on vestibular rehabilitation in China.

[Vestibular rehabilitation for peripheral vestibular hypofunction: an interdisciplinary consensus]. / Vestibulyarnaya reabilitatsiya pri perifericheskoi vestibulyarnoi gipofunktsii: mezhdistsiplinarnyi konsensus.

The literature review presents approaches to the management of patients with vestibular disorders. The principles of organization of vestibular rehabilitation in peripheral vestibular hypofunction, indications for appointment, factors influencing its implementation, technique, methods of evaluating effectiveness are considered in detail. Attention is drawn to the fact that the selection of exercises and the duration of vestibular rehabilitation is carried out individually and depends on many factors, including the nature of vestibular deficiency and the specific characteristics of the patient. The possibilities of using additional pharmacological therapy with histamine preparations, which can accelerate the onset of vestibular compensation, are shown. It is noted that vestibular rehabilitation is a safe and effective method of treating peripheral vestibular hypofunction and should be recommended to patients of all ages with vestibular disorders leading to limited social and physical activity.

[Wideband acoustic immittance characteristics and machine learning-based diagnostic model for children with large vestibular aqueduct syndrome].

Objective:This study was to investigate the wideband acoustic immittance（WAI） characteristics of children with large vestibular aqueduct syndrome（LVAS） and to construct a diagnostic model for LVAS based on WAI and machine learning（ML） techniques. Methods:We performed a retrospective analysis of the data from 38 children（76 ears） with LVAS and 44 children（88 ears） with normal hearing. The data included conventional audiological examination, temporal bone CT scan and WAI test. We performed statistical analysis and developed multivariate diagnostic models based on different ML techniques. Results:The two groups were balanced in terms of ear, gender, and age（P>0.05）. The wideband absorbance（WBA） of the LVAS group was significantly lower than that of the control group at 1 000-2 519 Hz, while the WBA of the LVAS group was significantly higher than that of the control group at 4 000-6 349 Hz（P<0.05）. WBA at 5 039 Hz under ambient pressure had a certain diagnostic value（AUC=0.767）. The multivariate diagnostic model had a high diagnostic value（AUC>0.8）, among which the KNN model performed the best（AUC=0.961）. Conclusion:The WAI characteristics of children with LVAS are significantly different from those of normal children. The diagnostic model based on WAI and ML techniques has high accuracy and reliability, and provides new ideas and methods for intelligent diagnosis of LVAS.

Increased prevalence of peripheral vestibular disorder among patients with Fabry disease.

BACKGROUND: Although peripheral vestibular disorder is a non-fatal complication of Fabry disease, fatalities have been reported in some case reports and case series. To date, no studies have examined the relative risk of peripheral vestibular disorder in patients with Fabry disease compared to the general population without the condition. Due to the high prevalence of Fabry disease in East Asia and the potential shared pathogenic pathways between Fabry disease and vasculopathy, we conducted a study using a nationwide population-based dataset to compare the prevalence of peripheral vestibular disorder between patients with Fabry disease and matched comparison patients. METHODS: Data was sourced from Taiwan's Longitudinal Health Insurance Database 2010. this study consists of 11,668 sampled patients, 2917 study patients with Fabry disease and 8751 propensity-score-matching comparison patients. We conducted multiple logistic regression analysis to study the association between peripheral vestibular disorder and Fabry disease. RESULTS: The study identified notable differences in the prevalence of various vestibular disorders between the study and comparison groups. Specifically, there was a 7.2% increased prevalence of peripheral vestibular disorder in the study group (28.3%) compared to the comparison group (20.9%), Meniere's disease (5.4% vs. 3.7%), benign paroxysmal positional vertigo (5.1% vs. 3.3%), and other/ unspecified peripheral vestibular dizziness (15.6% vs. 11.8%) (all p < 0.001). The odds ratios for PVD, MD, BPPV, and other PVD were 1.44 (95% CI = 1.29-1.60), 1.50 (95% CI = 1.23-1.83), 1.59 (95% CI = 1.30-1.95), and 1.40 (95% CI = 1.24-1.58), respectively, among the Fabry disease group relative to the comparison group after adjusting for age, monthly income, geographic location, urbanization level, hyperlipidemia, diabetes, coronary heart disease, and hypertension. CONCLUSION: This study found that patients with Fabry disease had increased prevalence of peripheral vestibular disorder.

[Analysis of a case of Kabuki syndrome due to a novel variant of KMT2D gene].

OBJECTIVE: To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. METHODS: A child diagnosed with KS at the Fujian Children's Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis. RESULTS: The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c.6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+PS2+PM2_Supporting). CONCLUSION: The c.6285dup variant of the KMT2D gene probably underlay the KS in this child.

Audiological and Vestibular Measurements in Chronic Renal Failure Patients Receiving Hemodialysis Treatment.

BACKGROUND: The aim was to evaluate the changes in the audiovestibular system in adult patients with the diagnosis of chronic renal failure who were treated with hemodialysis. METHODS: Thirty-five patients diagnosed with chronic renal failure and receiving hemodialysis treatment 3 days a week and 35 healthy individuals were tested with pure tone audiometry, video head impulse test, and post-head shake nystagmus test. Dizziness Handicap Inventory was applied to all participants. RESULTS: The Dizziness Handicap Inventory scores of the patient groups are higher than the control groups (P=.001). In the video head impulse test, there is no statistically significant difference between the patient and control groups in terms of gain asymmetry. 17.1% of the patients had both left and right lateral saccades (P=.03). A statistically significant difference was also found after the post-head shake test (P=.025). In the patient group, an inverse relationship between the presence of left anterior right posterior saccades and blood urea nitrogen-creatinine ratio and a direct relationship between the presence of right anterior left posterior saccades and creatinine elevation were determined. The presence of saccades in the video head impulse test increased significantly as the disease duration of hemodialysis patients increased. CONCLUSION: It was determined that the overt and covert saccades in the video head impulse test increased significantly as the creatinine increased and the duration of the disease increased in the patients with chronic renal failure. The common clinical usage of video head impulse test in monitoring the vestibular side effects of creatinine elevation and disease duration in chronic renal failure patients may be possible with future studies.

Recognition of Genetic Conditions After Learning With Images Created Using Generative Artificial Intelligence.

Importance: The lack of standardized genetics training in pediatrics residencies, along with a shortage of medical geneticists, necessitates innovative educational approaches. Objective: To compare pediatric resident recognition of Kabuki syndrome (KS) and Noonan syndrome (NS) after 1 of 4 educational interventions, including generative artificial intelligence (AI) methods. Design, Setting, and Participants: This comparative effectiveness study used generative AI to create images of children with KS and NS. From October 1, 2022, to February 28, 2023, US pediatric residents were provided images through a web-based survey to assess whether these images helped them recognize genetic conditions. Interventions: Participants categorized 20 images after exposure to 1 of 4 educational interventions (text-only descriptions, real images, and 2 types of images created by generative AI). Main Outcomes and Measures: Associations between educational interventions with accuracy and self-reported confidence. Results: Of 2515 contacted pediatric residents, 106 and 102 completed the KS and NS surveys, respectively. For KS, the sensitivity of text description was 48.5% (128 of 264), which was not significantly different from random guessing (odds ratio [OR], 0.94; 95% CI, 0.69-1.29; P = .71). Sensitivity was thus compared for real images vs random guessing (60.3% [188 of 312]; OR, 1.52; 95% CI, 1.15-2.00; P = .003) and 2 types of generative AI images vs random guessing (57.0% [212 of 372]; OR, 1.32; 95% CI, 1.04-1.69; P = .02 and 59.6% [193 of 324]; OR, 1.47; 95% CI, 1.12-1.94; P = .006) (denominators differ according to survey responses). The sensitivity of the NS text-only description was 65.3% (196 of 300). Compared with text-only, the sensitivity of the real images was 74.3% (205 of 276; OR, 1.53; 95% CI, 1.08-2.18; P = .02), and the sensitivity of the 2 types of images created by generative AI was 68.0% (204 of 300; OR, 1.13; 95% CI, 0.77-1.66; P = .54) and 71.0% (247 of 328; OR, 1.30; 95% CI, 0.92-1.83; P = .14). For specificity, no intervention was statistically different from text only. After the interventions, the number of participants who reported being unsure about important diagnostic facial features decreased from 56 (52.8%) to 5 (7.6%) for KS (P < .001) and 25 (24.5%) to 4 (4.7%) for NS (P < .001). There was a significant association between confidence level and sensitivity for real and generated images. Conclusions and Relevance: In this study, real and generated images helped participants recognize KS and NS; real images appeared most helpful. Generated images were noninferior to real images and could serve an adjunctive role, particularly for rare conditions.

Vestibular Decompensation Following COVID-19 Infection in a Person With Compensated Unilateral Vestibular Loss: A Rehabilitation Case Study.

BACKGROUND AND PURPOSE: Surgical removal of a vestibular schwannoma (vestibular schwannoma resection; VSR) results in a unilateral vestibular hypofunction with complaints of dizziness and imbalance. Although the anatomic lesion is permanent, recovery of balance and diminution of dizziness occurs through central neurophysiologic compensation. Compensation of the system is maintained through daily activity. Unfortunately, interruption of stimulus, such as decreased activities due to illness, can cause decompensation. Decompensation is described as the return of symptoms consistent with that experienced during the initial insult/injury (eg, dizziness, oscillopsia, balance difficulty). This case study describes a reoccurrence of vestibular dysfunction in a person with a history of VSR following hospitalization and protracted recovery from a COVID-19 infection. It further documents her recovery that may be a result of vestibular rehabilitation. CASE DESCRIPTION: A 49-year-old woman (M.W.) with a surgical history of VSR (10 years prior) and a medical history of significant COVID-19 infection, resulting in an intensive care unit stay and prolonged use of supplemental oxygen, presented to physical therapy with persistent dizziness and imbalance. The video head impulse test confirmed unilateral vestibular hypofunction. INTERVENTION: M.W. attended biweekly vestibular rehabilitation for 6 weeks and completed daily home exercises. OUTCOMES: At discharge, M.W. demonstrated improvements in patient-reported outcomes (Dizziness Handicap Inventory), functional testing (MiniBEST, 2-Minute Walk Test), and gaze stability measures (video head impulse testing, dynamic visual acuity). DISCUSSION: Vestibular decompensation preluded by a COVID-19 infection caused a significant decrease in functional mobility. Vestibular rehabilitation targeted at gaze and postural stability effectively reduced symptoms and facilitated recovery to M.W.'s pre-COVID-19 level of function. Video Abstract available for more insights from the authors (see the Video, Supplemental Digital Content 1 available at: http://links.lww.com/JNPT/A458 ).

Sex-specific difference in phenotype of Kabuki syndrome type 2 patients: a matched case-control study.

BACKGROUND: Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki syndrome type 2 (KS2, MIM#300867), which accounts for only 5%-8% of KS. Previous studies suggested that female patients with KS2 may have a milder phenotype. METHOD: We summarized the phenotype and genotype of KS2 patients who were diagnosed in Shanghai Children's Medical Center since July 2017 and conducted a 1:3 matched case-control study according to age and sex to investigate sex-specific differences between patients with and without KS2. RESULTS: There were 12 KS2 cases in this study, and 8 of them matched with 24 controls. The intelligence quotient (IQ) score of the case group was significantly lower than that of the control group (P < 0.001). In addition, both the incidence of intellectual disability (ID) (IQ < 70) and moderate-to-severe ID (IQ < 55) were significantly higher in the case group than those in the control group. No sex-specific difference was found in the incidence of ID or moderate-to-severe ID between the female cases and female controls, whereas there was a significant difference between male cases and male controls. Furthermore, the rate of moderate-to-severe ID and congenital heart disease (CHD) was significantly higher in the male group than that in the female group. CONCLUSIONS: Our results showed that a sex-specific difference was exhibited in the clinical phenotypes of KS2 patients. The incidence of CHD was higher in male patients, and mental retardation was significantly impaired. However, the female patients' phenotype was mild.

Clinical characteristics of persistent postural-perceptual dizziness and its visual subtype in Korean patients: A multicenter cross-sectional study.

OBJECTIVES: Persistent postural-perceptual dizziness (PPPD) is a chronic functional vestibular disorder for which the Bárány Society has established diagnostic criteria. This nationwide multicenter study aims to investigate the clinical features of individuals with definite PPPD and clinical variant PPPD who do not fully meet the diagnostic criteria, with a particular focus on visual exaggeration. METHODS: Between September 2020 and September 2021, a total of 76 individuals with definite PPPD and 109 individuals with clinical variant PPPD who did not meet all three exacerbating factors outlined in Criterion B were recruited from 18 medical centers in South Korea. The study gathered information on demographic factors, clinical manifestations, balance scales, and personality assessments. RESULTS: Comparative analysis between groups with definite PPPD and clinical variant with visual exacerbation revealed no significant differences in sociodemographic characteristics, clinical course, dizziness impact, and specific precipitants. Only disease duration was significantly longer in definite PPPD compared with variant with visual exacerbation. However, the variant without visual exacerbation displayed significantly reduced rates of panic disorder, diminished space-motion discomfort, lesser impact of dizziness, and decreased prevalence of depression when compared with the definitive PPPD. CONCLUSION: This is the first comprehensive nationwide study examining clinical features of both definite PPPD patients and its clinical variants, considering visual exacerbating factors. Differences in dizziness and personality traits emerged between definite PPPD and its potential variant without visual issues. Our results highlight the possibility of a distinct clinical variant of PPPD influenced by visual dependency.

Blood biomarkers for the differentiation between central and peripheral vertigo in the emergency department: a systematic review and meta-analysis.

BACKGROUND/INTRODUCTION: In patients with acute vestibular syndrome (AVS), differentiating between stroke and nonstroke causes is challenging in the emergency department (ED). Correct diagnosis of vertigo etiology is essential for early optimum treatment and disposition. OBJECTIVES: The aim of this systematic review and meta-analysis was to summarize the published evidence on the potential of blood biomarkers in the diagnosis and differentiation of peripheral from central causes of AVS. METHODS: A literature search was conducted for studies published until January 1, 2023, in PubMed, Ovid Medline, and EMBASE databases analyzing biomarkers for the differentiation between central and peripheral AVS. The Quality Assessment of Diagnostic Accuracy Studies questionnaire 2 was used for quality assessment. Pooled standardized mean difference and 95% confidence intervals were calculated if a biomarker was reported in two or more studies. Heterogeneity among included studies was investigated using the I2 metric. RESULTS: A total of 17 studies with 859 central and 4844 peripheral causes of acute dizziness or vertigo, and analysis of 61 biomarkers were included. The general laboratory markers creatinine, blood urea nitrogen, albumin, C-reactive protein, glucose, HbA1c, leukocyte counts, and neutrophil counts and the brain-derived biomarkers copeptin, S100 calcium-binding protein ß (S100ß), and neuron-specific enolase (NSE) significantly differentiated central from peripheral causes of AVS. CONCLUSIONS: This systematic review and meta-analysis highlights the potential of generalized inflammatory markers and brain-specific blood protein markers of NSE and S100ß as diagnostic biomarkers for central from peripheral differentiation in AVS. These results, as a complement to clinical characteristics, provide guidance for future large-scale diagnostic research, in this challenging ED patient population.

The Role of Motion Sensitivity and Headaches on Vestibular Rehabilitation Outcomes in Pediatric Vestibular Migraines.

OBJECTIVE: To determine the utility of the motion sensitivity quotient (MSQ) in diagnosing pediatric vestibular migraine (VM) and to characterize the role of motion sensitivity and headache control on vestibular rehabilitation (VR) outcomes in pediatric VM. STUDY DESIGN: Retrospective cohort analysis. SETTING: Pediatric tertiary referral center. PATIENTS: Children (≤18 years old) with dizziness who completed vestibular testing from January 2016 to August 2022, diagnosed with either VM or another vestibular disorder. INTERVENTIONS: VR, which included MSQ testing. MAIN OUTCOME MEASURES: Initial MSQ, number and duration of vestibular physical therapy (PT) sessions, PT goals met, and posttreatment MSQ. RESULTS: Two hundred fifty-seven patients met study criteria. MSQ was not a reliable diagnostic marker in pediatric VM as there was no difference in initial MSQ between VM and non-VM patients (9.4 vs. 7.8 in non-VM, p = 0.014). Both VM (n = 116) and non-VM (n = 141) patients demonstrated significant improvement in MSQ after VR (p = 0.004). However, VM patients tended to be less likely to meet at least one PT goal (60 vs. 77% in non-VM, p = 0.016, d = 0.37), although not significant. VM patients with more frequent headaches had significantly higher initial MSQ (p = 0.008). VM patients with more frequent headaches or higher initial MSQ tended to require increased number and longer duration of VR (small/medium effect size although not statistically significant after Bonferroni correction). CONCLUSION: VR is an effective treatment for both VM and non-VM pediatric patients. VM patients, especially those with severe motion sensitivity or poorly controlled headaches, may be less responsive to VR and may require increased frequency and duration of VR. Our findings propose the importance of counseling pediatric patients with severe motion sensitivity or uncontrolled migraines regarding realistic expectations of their VR course.

[Dynamic visual acuity screening test results analysis of 25 patients with peripheral vertigo].

Objective:To observe the results of dynamic visual acuity screening tests in patients with peripheral vertigo and explore its clinical significance. Methods:The number of 48 healthy volunteers were enrolled as control group and 25 peripheral vertigo patients as experimental group. In the experimental group, there are 12 patients with vestibular neuritis, 1 patient with Hunt syndrome, 5 patients with sudden deafness with vertigo and 7 patients with bilateral vestibular dysfunction. Horizontal and vertical dynamic visual acuity screening tests were performed on them. The number of lost rows of horizontal and vertical dynamic visual acuity was compared between the control group and the experimental group to figure out if there is a statistical difference. The number of lost rows of horizontal and vertical dynamic visual acuity was compared within the experimental group to figure out if there is a statistical difference. The two groups of 18 cases of unilateral vestibular function decline and 7 cases of bilateral vestibular function decline in the experimental group were compared with the control group, and figure out if there is a statistical difference. Results:The median number of lost rows of horizontal dynamic visual acuity in 48 healthy volunteers was 1.5 and median number of lost rows of vertical dynamic visual acuity was 1.0 in the control group. The median number of lost rows of horizontal dynamic visual acuity of 26 healthy volunteers was 6 and median number of lost rows of vertical dynamic visual acuity was 5 in the experimental group. Compared to the experimental group, the number of lost rows both have statistical significance in horizontal and vertical dynamic visual acuity（P<0.01）. The comparison of horizontal and vertical lost rows within the test group also have statistical significance（P<0.01）. Twenty five patients with exceptional vestibular disease in the experimental group were divided into unilateral vestibular function reduction group（n=18） and bilateral vestibular function reduction group（n=7）. Compared with the control group, there was significant differences in the number of horizontal and vertical lost rows（P<0.01） within the three groups. After pairwise comparison, the number of lost rows of horizontal and vertical in the control group was significantly lower than that in the unilateral vestibular function reduction group and the bilateral vestibular function reduction group（P<0.01）. There was a highly significant correlation between the number of horizontally lost rows of DVA and the mean vHIT values of bilateral horizontal semicircular canals in 25 patients（P<0.01）; and a highly significant correlation between the number of vertically lost rows of DVA and the mean vHIT values of vertical semicircular canals in 4 groups bilaterally（P<0.01）. Conclusion:The Dynamic Visual Acuity Screening Test is a useful addition to existing tests of peripheral vestibular function, particularly the vHIT test, and provides a rapid assessment of the extent of 2 Hz VOR impairment in patients with reduced vestibular function.

Vestibular migraine and persistent postural perceptual dizziness.

Dizziness is a common symptom among patients in primary care, general neurology, and headache clinic practices. Vestibular migraine is conceptualized as a condition of recurrent attacks of vestibular symptoms attributed to migraine. It is now considered the most common cause of spontaneous episodic vertigo. Persistent postural-perceptual dizziness (PPPD) has more recently been defined based on four previous clinical entities as a syndrome of chronic daily dizziness, unsteadiness, or nonspinning vertigo that fluctuates and is exacerbated by postural, motion, or visual factors. Although PPPD is more often precipitated by other conditions causing vertigo, unsteadiness, or dizziness, it is discussed at length in this chapter because vestibular migraine is among the most common triggers for development of PPPD. Pathophysiology of each is incompletely understood, and with lack of biomarkers, the diagnosis of each rests on consensus-derived, symptom-based criteria. Areas of uncertainty exist regarding some overlapping symptoms that may create potential diagnostic confusion between the conditions. This chapter provides a comprehensive review of the current state of vestibular migraine and PPPD, including diagnostic and management guidance for when they occur separately, together, or along with other common comorbidities.

The vertical computerized rotational head impulse test.

The computerized rotational head impulse test (crHIT) uses a computer-controlled rotational chair to deliver whole-body rotational impulses to assess the semicircular canals. The crHIT has only been described for horizontal head plane rotations. The purpose of this study was to describe the crHIT for vertical head plane rotations. In this preliminary study, we assessed four patients with surgically confirmed unilateral peripheral vestibular abnormalities and two control subjects. Results indicated that the crHIT was well-tolerated for both horizontal head plane and vertical head plane stimuli. The crHIT successfully assessed each of the six semicircular canals. This study suggests that the crHIT has the potential to become a new laboratory-based vestibular test for both the horizontal and vertical semicircular canals.

Vestibular dysfunction leads to cognitive impairments: State of knowledge in the field and clinical perspectives (Review).

The vestibular system may have a critical role in the integration of sensory information and the maintenance of cognitive function. A dysfunction in the vestibular system has a significant impact on quality of life. Recent research has provided evidence of a connection between vestibular information and cognitive functions, such as spatial memory, navigation and attention. Although the exact mechanisms linking the vestibular system to cognition remain elusive, researchers have identified various pathways. Vestibular dysfunction may lead to the degeneration of cortical vestibular network regions and adversely affect synaptic plasticity and neurogenesis in the hippocampus, ultimately contributing to neuronal atrophy and cell death, resulting in memory and visuospatial deficits. Furthermore, the extent of cognitive impairment varies depending on the specific type of vestibular disease. In the present study, the current literature was reviewed, potential causal relationships between vestibular dysfunction and cognitive performance were discussed and directions for future research were proposed.

Patient-Reported Outcomes After Vestibular Implantation for Bilateral Vestibular Hypofunction.

Importance: Standard-of-care treatment proves inadequate for many patients with bilateral vestibular hypofunction (BVH). Vestibular implantation is an emerging alternative. Objective: To examine patient-reported outcomes from prosthetic vestibular stimulation. Design, Setting, and Participants: The Multichannel Vestibular Implant (MVI) Early Feasibility Study is an ongoing prospective, nonrandomized, single-group, single-center cohort study conducted at Johns Hopkins Hospital that has been active since 2016 in which participants serve as their own controls. The study includes adults with severe or profound adult-onset BVH for at least 1 year and inadequate compensation despite standard-of-care treatment. As of March 2023, 12 candidates completed the eligibility screening process. Intervention: The MVI system electrically stimulates semicircular canal branches of the vestibular nerve to convey head rotation. Main Outcomes and Measures: Patient-reported outcome instruments assessing dizziness (Dizziness Handicap Inventory [DHI]) and vestibular-related disability (Vestibular Disorders-Activities of Daily Living [VADL]). Health-related quality of life (HRQOL) assessed using the Short Form-36 Utility (SF36U) and Health Utilities Index Mark 3 (HUI3), from which quality-adjusted life-years were computed. Results: Ten individuals (5 female [50%]; mean [SD] age, 58.5 [5.0] years; range, 51-66 years) underwent unilateral implantation. A control group of 10 trial applicants (5 female [50%]; mean [SD] age, 55.1 [8.5] years; range, 42-73 years) completed 6-month follow-up surveys after the initial application. After 0.5 years of continuous MVI use, a pooled mean (95% CI) of within-participant changes showed improvements in dizziness (DHI, -36; 95% CI, -55 to -18), vestibular disability (VADL, -1.7; 95% CI, -2.6 to -0.7), and HRQOL by SF36U (0.12; 95% CI, 0.07-0.17) but not HUI3 (0.02; 95% CI, -0.22 to 0.27). Improvements exceeded minimally important differences in the direction of benefit (exceeding 18, 0.65, and 0.03, respectively, for DHI, VADL, and SF36U). The control group reported no mean change in dizziness (DHI, -4; 95% CI, -10 to 2), vestibular disability (VADL, 0.1; 95% CI, -0.9 to 1.1) or HRQOL per SF36U (0; 95% CI, -0.06 to 0.05) but an increase in HRQOL per HUI3 (0.10; 95% CI, 0.04-0.16). Lifetime HRQOL gain for MVI users was estimated to be 1.7 quality-adjusted life-years (95% CI, 0.6-2.8) using SF36U and 1.4 (95% CI, -1.2 to 4.0) using HUI3. Conclusions and Relevance: This cohort study found that vestibular implant recipients report vestibular symptom improvements not reported by a control group. These patient-reported benefits support the use of vestibular implantation as a treatment for bilateral vestibular hypofunction.

Next generation phenotyping for diagnosis and phenotype-genotype correlations in Kabuki syndrome.

The field of dysmorphology has been changed by the use Artificial Intelligence (AI) and the development of Next Generation Phenotyping (NGP). The aim of this study was to propose a new NGP model for predicting KS (Kabuki Syndrome) on 2D facial photographs and distinguish KS1 (KS type 1, KMT2D-related) from KS2 (KS type 2, KDM6A-related). We included retrospectively and prospectively, from 1998 to 2023, all frontal and lateral pictures of patients with a molecular confirmation of KS. After automatic preprocessing, we extracted geometric and textural features. After incorporation of age, gender, and ethnicity, we used XGboost (eXtreme Gradient Boosting), a supervised machine learning classifier. The model was tested on an independent validation set. Finally, we compared the performances of our model with DeepGestalt (Face2Gene). The study included 1448 frontal and lateral facial photographs from 6 centers, corresponding to 634 patients (527 controls, 107 KS); 82 (78%) of KS patients had a variation in the KMT2D gene (KS1) and 23 (22%) in the KDM6A gene (KS2). We were able to distinguish KS from controls in the independent validation group with an accuracy of 95.8% (78.9-99.9%, p < 0.001) and distinguish KS1 from KS2 with an empirical Area Under the Curve (AUC) of 0.805 (0.729-0.880, p < 0.001). We report an automatic detection model for KS with high performances (AUC 0.993 and accuracy 95.8%). We were able to distinguish patients with KS1 from KS2, with an AUC of 0.805. These results outperform the current commercial AI-based solutions and expert clinicians.

Structural investigation of pathogenic RFC1 AAGGG pentanucleotide repeats reveals a role of G-quadruplex in dysregulated gene expression in CANVAS.

An expansion of AAGGG pentanucleotide repeats in the replication factor C subunit 1 (RFC1) gene is the genetic cause of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), and it also links to several other neurodegenerative diseases including the Parkinson's disease. However, the pathogenic mechanism of RFC1 AAGGG repeat expansion remains enigmatic. Here, we report that the pathogenic RFC1 AAGGG repeats form DNA and RNA parallel G-quadruplex (G4) structures that play a role in impairing biological processes. We determine the first high-resolution nuclear magnetic resonance (NMR) structure of a bimolecular parallel G4 formed by d(AAGGG)2AA and reveal how AAGGG repeats fold into a higher-order structure composed of three G-tetrad layers, and further demonstrate the formation of intramolecular G4s in longer DNA and RNA repeats. The pathogenic AAGGG repeats, but not the nonpathogenic AAAAG repeats, form G4 structures to stall DNA replication and reduce gene expression via impairing the translation process in a repeat-length-dependent manner. Our results provide an unprecedented structural basis for understanding the pathogenic mechanism of AAGGG repeat expansion associated with CANVAS. In addition, the high-resolution structures resolved in this study will facilitate rational design of small-molecule ligands and helicases targeting G4s formed by AAGGG repeats for therapeutic interventions.