The DizzyQuest Combined with Accelerometry: Daily Physical Activities and Limitations among Patients with Bilateral Vestibulopathy Due to DFNA9.

BACKGROUND: DFNA9 is a genetic disease of the inner ear, causing progressive bilateral sensorineural deafness and bilateral vestibulopathy (BV). In this study, DizzyQuest, a mobile vestibular diary, and the MOX accelerometer were combined to assess the daily life functional limitations and physical activity of patients with DFNA9 suffering from BV. These parameters might be appropriate as potential candidacy criteria and outcome measures for new therapeutic interventions for BV. METHODS: Fifteen DFNA9 patients with BV and twelve age-matched healthy controls were included. The DizzyQuest was applied for six consecutive days, which assessed the participants' extent of functional limitations, tiredness, types of activities performed during the day, and type of activity during which the participant felt most limited. The MOX accelerometer was worn during the same six days of DizzyQuest use, measuring the participants intensity and type of physical activity. Mixed-effects linear and logistic regression analyses were performed to compare the DFNA9 patients and control group. RESULTS: DFNA9 patients with BV felt significantly more limited in activities during the day compared to the age-matched controls, especially in social participation (p < 0.005). However, these reported limitations did not cause adjustment in the types of activities and did not reduce the intensity or type of physical activity measured with accelerometry. In addition, no relationships were found between self-reported functional limitations and physical activity. CONCLUSIONS: This study demonstrated that self-reported functional limitations are significantly higher among DFNA9 patients with BV. As a result, these limitations might be considered as part of the candidacy criteria or outcome measures for therapeutic interventions. In addition, the intensity or type of physical activity performed during the day need to be addressed more specifically in future research.

Interaural and sex differences in the natural evolution of hearing levels in pre-symptomatic and symptomatic carriers of the p.Pro51Ser variant in the COCH gene.

Hearing impairment constitutes a significant health problem in developed countries. If hearing loss is slowly progressive, the first signs may not be noticed in time, or remain untreated until the moment the auditory dysfunction becomes more apparent. The present study will focus on DFNA9, an autosomal dominant disorder caused by pathogenic variants in the COCH gene. Although several cross-sectional studies on this topic have been conducted, a crucial need for longitudinal research has been reported by many authors. Longitudinal trajectories of individual hearing thresholds were established as function of age and superimposed lowess curves were generated for 101 female and male carriers of the p.Pro51Ser variant. The average number of times patients have been tested was 2.49 years with a minimum of 1 year and a maximum of 4 years. In addition, interaural and sex differences were studied, as they could modify the natural evolution of the hearing function. The current study demonstrates that, both in female carriers and male carriers, the first signs of hearing decline, i.e. hearing thresholds of 20 dB HL, become apparent as early as the 3rd decade in the highest frequencies. In addition, a rapid progression of SNHL occurs between 40 and 50 years of age. Differences between male and female carriers in the progression of hearing loss are most obvious between the age of 50 and 65 years. Furthermore, interaural discrepancies also manifest from the age of 50 years onwards. High-quality prospective data on the long-term natural evolution of hearing levels offer the opportunity to identify different disease stages in each cochlea and different types of evolution. This will provide more insights in the window of opportunity for future therapeutic intervention trials.

Compensatory strategies after an acute unilateral vestibulopathy: a prospective observational study.

PURPOSE: In case of an acute unilateral vestibulopathy (UVP), compensatory strategies such as restoration and adaptation will lead to a decrease in intensity of the symptoms. Although measurements of compensatory strategies are available, currently, an overview taking the different strategies into account is lacking. The objectives of this study are to explore compensatory strategies and to investigate the association between compensatory strategies and patient characteristics. METHODS: Restoration was objectified by the vestibulo-ocular reflex (VOR) gain on the video head impulse test, and adaptation-consisting of visual, multisensory, and behavioral substitution-was objectified by the Visual Vertigo Analog Scale (VVAS), Antwerp Vestibular Compensation Index (AVeCI), and Perez and Rey score (PR score), respectively. Adequate restoration and adaptation levels were interpreted as follows: VOR gain > 0.80, VVAS ≤ 40%, AVeCI > 0 and PR score ≤ 55. RESULTS: Sixty-two UVP patients, 34 men and 28 women, were included with an average age of 52.1 ± 17.3 years. At 10.5 ± 1.4 weeks after onset, 41.9% of the UVP patients reached adequate restoration levels and 58.1-86.9% reached adequate adaptation levels. Furthermore, significant associations were found between (1) restoration status and UVP etiology [Odds Ratio (OR) with 95% CI: 4.167 {1.353;12.828}] and balance performance (OR: 4.400 {1.258;15.386}), (2) visual sensory substitution status and perceived handicap (OR: 8.144 {1.644;40.395}), anxiety (OR: 10.000 {1.579;63.316}) and depression (OR: 16.667 {2.726;101.896}), and (3) behavioral substitution status and balance performance (OR: 4.143 {1.341;12.798}). CONCLUSION: UVP patients with adequate compensatory strategies presented with better balance performance, lower perceived handicap, and lower anxiety and depression scores.

Radiologic Features in Cochlear Implant Candidates: A Prospective Study Comparing Candidates Carrying the p.Pro51Ser Mutation in Coagulation Factor C Homology With Noncarriers.

BACKGROUND: DFNA9 is a form of autosomal progressive sensorineural hearing loss, caused by more than 30 variants in the COCH gene. p.Pro51Ser (p.P51S) variant is characterized by late-onset functional deterioration toward bilateral severe hearing loss and vestibulopathy. Focal sclerosis on computed tomography (CT) and T2-weighted magnetic resonance imaging (MRI) signal loss of semicircular canals are presumably radiologic biomarkers of advanced otovestibular deterioration. OBJECTIVES: The aim of this study was to investigate whether these biomarkers are more frequent in cochlear implant candidates carrying the p.P51S mutation versus noncarriers. Second, the correlation between the hearing and vestibular function and carrier status was studied. Finally, the relationship between the presence of these radiologic features and the degree of hearing and vestibular deterioration was investigated. METHODS: A prospective cohort study was performed on 38 candidates for cochlear implantation in a tertiary referral center. Patients underwent pure tone audiometry, videonystagmography, video head impulse tests and vestibular-evoked myogenic potentials. In addition, three dizziness questionnaires were used. All subjects were administered CT, MRI, and molecular genetic analysis. RESULTS: Sixteen of 38 patients were carriers of the p.P51S COCH mutation. Radiologic lesions were almost exclusively observed in carriers. MRI was more sensitive in showing lesions than CT. Furthermore, p.P51S carriers showed significantly lower function on most vestibular tests, including questionnaires, than noncarriers. Patients with imaging abnormalities showed more pronounced vestibulopathy. CONCLUSION: The present study supplements previous data that endorse the hypothesis that focal sclerosis of semicircular canals are biomarkers of advanced vestibular deterioration, especially in DFNA9.

Does Vestibulo-Ocular Reflex (VOR) Gain Correlate With Radiological Findings in the Semi-Circular Canals in Patients Carrying the p.Pro51Ser (P51S) COCH Variant Causing DFNA9? Relationship Between the Three-Dimensional Video Head Impulse Test (vHIT) and MR/CT Imaging.

OBJECTIVE: The primary aim was to determine whether 3D video-head-impulse-test vestibulo-ocular reflex (vHIT VOR)-gains correlate with computed tomography (CT) and magnetic resonance (MR) lesions in a series of carriers of the p.(Pro51Ser)-variant (P51S) in the COCH-gene (DFNA9). Secondary aim was to compare routine imaging with second peer review radiologic lecture. STUDY DESIGN: Analytical cross-sectional study. SETTING: Secondary referral center. PATIENTS: Twenty-four p.P51S carriers with MR and CT images. Eighteen carriers were selected of whom both 3D-vHIT and imaging data were available within a time interval of 24 months. INTERVENTIONS: All imaging data were reassessed by two independent neuroradiologists. vHIT VOR-gains were correlated with semi-circular canal (SCC) lesions. MAIN OUTCOME MEASURES: Correlation between vHIT VOR-gains and SCC lesions, and additional lesions detected during scientific lecture of imaging data. RESULTS: The average gain of the ipsilateral labyrinth was significantly lower when positive CT (0.3215; p = 0.0122) and MR results (0.3215; p = 0.0134).92% of ears presented MR lesions on at least one SCC, whereas this was 75% on CT. The posterior SCC is the most frequently affected on MR and CT. Second lecture led to nine additional MR and 16 CT lesions. CONCLUSIONS: Significant correlation was observed between radiological lesions at any SCC and lower average gain of the three ipsilateral SCC. The substantially larger number of lesions during scientific assessment stresses the need to fully inform radiologists concerning differential diagnosis to facilitate accurate diagnosis when planning imaging. Focal sclerosis and narrowing of SCC in DFNA9 represent a possible biomarker of advanced stages of otovestibular deterioration.

Driving ability in patients with dizziness: a systematic review.

PURPOSE: The aim of this systematic review was to identify and evaluate studies dealing with driving performance of dizzy patients or patients with a vestibular disorder. METHODS: A systematic review was performed according to the preferred reporting items for systematic reviews and meta-analysis guidelines. (1) PubMed, Embase, and Cochrane library. (2) Study selection: articles about driving ability and reported driving difficulties in patients with dizziness, or a diagnosed vestibular disorder, were included. (3) Data extraction was performed by two independent authors using predefined data fields: patient's characteristics, diagnostic criteria, sample size, and type of evaluation of driving ability and outcome of the study. RESULTS: Eight out of 705 articles matched the inclusion criteria but varied widely regarding the study population, study design, and outcome measures. The majority of studies reported a negative impact of dizziness and/or vestibular disorders on self-reported driving ability and car accidents. Yet several studies could not identify any impairment of driving ability. CONCLUSIONS: Driving ability was negatively affected by dizziness or a vestibular disorder in the majority of included studies with low risk of bias. This systematic review revealed a significant heterogeneity in studies reporting driving performance and contradictory results. We were, therefore, unable to identify a causal relationship between dizziness and driving ability. There is a need for prospective studies in populations with different vestibular disorders using subjective and objective outcome measures that have been validated to evaluate driving performance.

Attitudes of Potential Participants Towards Potential Gene Therapy Trials in Autosomal Dominant Progressive Sensorineural Hearing Loss.

BACKGROUND: Advances in gene therapeutic approaches to treat sensorineural hearing loss (SNHL) confront us with future challenges of translating these animal studies into clinical trials. Little is known on patient attitudes towards future innovative therapies. OBJECTIVE: We aimed to better understand the willingness of patients with progressive SNHL and vestibular function loss of autosomal dominant (AD) inheritance to participate in potential gene therapy trials to prevent, stabilize, or slow down hearing loss. METHODS: A survey was performed in carriers of the P51S and G88E pathogenic variant in the COCH gene (DFNA9). Various hypothetical scenarios were presented while using a Likert scale. RESULTS: Fifty three participants were included, incl. 49 symptomatic patients, one presymptomatic patient, and three participants at risk. Their attitude towards potential trials studying innovative therapies was overall affirmative, even if the treatment would only slow down the decline of hearing and vestibular function, rather than cure the disease. Among the different potential scenarios, the less invasive and less frequent treatments increased the likelihood to enroll. Daily oral medication and annual intravenous infusion were awarded the highest scores. The more invasive, more frequent, and more at-risk treatments were still likely to be accepted but decreased the willingness to participate. The presence of a placebo arm was met with the lowest scores of willingness to participate. CONCLUSIONS: Overall, most symptomatic DFNA9 patients would likely consider participation in future innovative inner ear therapy trials, even if it would only slow down the decline of hearing and vestibular function.

Vestibular Infant Screening (VIS)-Flanders: results after 1.5 years of vestibular screening in hearing-impaired children.

Due to the close anatomical relationship between the auditory and vestibular end organs, hearing-impaired children have a higher risk for vestibular dysfunction, which can affect their (motor) development. Unfortunately, vestibular dysfunction often goes unnoticed, as vestibular assessment in these children is not standard of care nowadays. To timely detect vestibular dysfunction, the Vestibular Infant Screening-Flanders (VIS-Flanders) project has implemented a basic vestibular screening test for hearing-impaired infants in Flanders (Belgium) with a participation rate of 86.7% during the first year and a half. The cervical Vestibular Evoked Myogenic Potentials (cVEMP) test was applied as vestibular screening tool to map the occurrence of vestibular (mainly saccular) dysfunction in this population. At the age of 6 months, 184 infants were screened. No refers on vestibular screening were observed in infants with permanent conductive hearing loss. In infants with permanent sensorineural hearing loss, a cVEMP refer rate of 9.5% was observed. Failure was significantly more common in infants with severe-profound compared to those with mild-moderate sensorineural hearing loss (risk ratio = 9.8). Since this is the first regional study with a large sample size and successful participation rate, the VIS-Flanders project aims to set an example for other regions worldwide.

Cochlear implant telemedicine: Remote fitting based on psychoacoustic self-tests and artificial intelligence.

Objective: This study aims to assess the feasibility of autonomous cochlear implant (CI) fitting by adult CI recipients based on psychoacoustic self-testing and artificial intelligence (AI). Design: A feasibility study was performed on six adult CI recipients implanted with a Nucleus device. Two weeks after processor activation in the clinic, a 'self-fitting' session was organized in a supervised simulated home environment. The CI recipient performed pure tone audiometry and spectral discrimination tests as self-tests. The AI application FOX analysed the results and recommended a new map. The participants filled out a questionnaire and were tested again after 2 months of take-home experience. Results: Four out of six patients performed the self-tests without any help from the audiologist and four were fitted by FOX without any manual intervention. All patients were comfortable with the concept of self-testing and automated fitting. Patients acknowledged that at this stage the remote supervision of an audiologist remains essential. Conclusions: The study showed that audiological self-assessment and remote CI fitting with AI under the supervision of an audiologist is feasible, at least in a number of CI recipients. Currently, there are still some technical and regulatory challenges to be addressed before this can become routine practice.

Correlations Between Vestibular Function and Imaging of the Semicircular Canals in DFNA9 Patients.

Background and Purpose: Radiologic abnormalities on computed tomography (CT), including narrowing or sclerosis of the semicircular canals (SCCs), and T2-weighted magnetic resonance imaging (MRI), including signal loss in the SCC, have been reported as potential biomarkers in patients with P51S mutations in the COCH gene (i.e., DFNA9). The aim of our study was to correlate caloric responses through electronystagmography (ENG) data with imaging results in DFNA9 patients. Materials and Methods: A retrospective study was performed in 45 patients; therefore, 90 ears with P51S mutations in the COCH gene were tested. Caloric responses and CT and MRI data were analyzed from June 2003 until May 2014. More than half of patients (54%) were candidates for cochlear implantation. Results: In our population, 91% of tested ears had sclerotic lesions and/or narrowing in one or more SCCs on CT scan. All tested ears had narrowing or signal loss in at least one SCC on T2-weighted MRI. The lateral SCC was affected in 87% on CT scan and 92% on MRI. However, in 83% of tested ears, all three SCCs were affected on MRI. Furthermore, in 77% of tested ears, caloric responses were reduced bilaterally, while 11.5% showed unilateral hypofunction and the other 11.5% had normal caloric responses. CT abnormalities correlated with hypofunction of caloric responses. This statistically significant difference was present if abnormalities were observed in at least one of the SCCs as well as in ipsilateral lateral SCC function loss. MRI abnormalities in at least one of the SCCs correlated with ENG hypofunction, but there was no direct correlation between lateral SCC abnormalities on MRI and caloric responses of the investigated lateral canal. Conclusion: Our retrospective analysis confirms the presence of CT and MRI abnormalities in DFNA9 patients with the P51S mutation in the COCH gene. A correlation between these radiologic features and vestibular function (tested by means of caloric response) was found in this population.