Etiologies and hearing status in bilateral vestibulopathy: a retrospective study of 315 patients.

Importance: The development of a vestibular implant has reached milestones and seems to be a promising therapeutic tool for bilateral vestibulopathy (BV). Given the former lack of therapeutic options for BV, the disease has received scant attention in the previous research literature. It is therefore of major importance to gain more insight into the underlying pathology of BV. Furthermore, as some research groups specifically use a combined vestibulo-cochlear implant, the size of the group of BV patients with associated hearing loss is of special interest. Objectives: The study aimed to determine the definite and probable etiology in bilateral vestibulopathy (BV) patients and to report on their hearing status. Design: This study involves multicenter retrospective study design. Setting: The research setting is at tertiary referral centers. Participants: Consecutive BV patients diagnosed at the Antwerp University Hospital between 2004 and 2018 at the Maastricht University Medical Center between 2002 and 2015 and at the Geneva University Hospital between 2013 and 2018, who met the BV diagnostic criteria of the Bárány Society. Main outcome measures: Primary interests were the etiology and hearing status of BV patients. Moreover, the data of vestibular tests were examined (caloric irrigation, rotatory chair tests, and video-head impulse test). Results: The authors identified 315 BV patients, of whom 56% were male patients. Mean age at diagnosis was 58.6 ± 15.1 (range 7-91) years. The definite cause was determined in 37% of the patients and the probable cause in 26% of the patients. No cause was identified in 37% of BV patients. The largest subgroup included patients with genetic etiology (31%), most frequently COCH mutation. Only 21% of patients (n = 61) had bilateral normal hearing. Almost half of the patients (45%, n = 134) had profound hearing loss in at least one ear. Conclusion: BV is a heterogeneous condition, with over a third of cases remaining idiopathic, and nearly three-quarters affected by hearing loss. COCH mutation is the most common non-idiopathic cause of BV in our population. Only 21% of our BV patients presented with bilateral normal hearing.

Suppression Head Impulse Test (SHIMP) versus Head Impulse Test (HIMP) When Diagnosing Bilateral Vestibulopathy.

The Suppression Head Impulse (SHIMP) test was introduced as an alternative to the Head Impulse Paradigm (HIMP) to overcome challenges in VOR gain calculation due to the interference of covert saccades. The objectives of this study were (1) to determine if SHIMP, compared to HIMP, reduces covert saccades in BV patients and (2) to define the agreement on diagnosing BV between SHIMP and HIMP. First, the number of covert saccades was compared between SHIMP and HIMP. Secondly, VOR gain was compared between SHIMP and HIMP. Lastly, the agreement between SHIMP and HIMP on identifying BV (horizontal VOR gain <0.6) was evaluated. A total of 98 BV patients were included. To our knowledge, this is the largest study population on SHIMP testing in BV patients. Covert saccades were significantly reduced, and a lower VOR gain was found during SHIMP compared to HIMP (p < 0.001). However, the clinical relevance of these statistically significant differences is small. In 93% of the patients, an agreement was found between the two paradigms regarding the diagnosis of BV, and both paradigms detect BV in the vast majority of patients.

Patterns of Vestibular Impairment in Bilateral Vestibulopathy and Its Relation to Etiology.

Objective: This study aimed to investigate (1) the patterns of vestibular impairment in bilateral vestibulopathy (BVP) and subsequently, the implications regarding patient eligibility for vestibular implantation, and (2) whether this pattern and severity of vestibular impairment is etiology dependent. Methods: A total of one hundred and seventy-three subjects from three tertiary referral centers in Europe were diagnosed with BVP according to the Bárány Society diagnostic criteria. The subjects underwent vestibular testing such as the caloric test, torsion swing test, video Head Impulse Test (vHIT) in horizontal and vertical planes, and cervical and/or ocular vestibular evoked myogenic potentials (c- and oVEMPs). The etiologies were split into idiopathic, genetic, ototoxicity, infectious, Menière's Disease, (head)trauma, auto-immune, neurodegenerative, congenital, and mixed etiology. Results: The caloric test and horizontal vHIT more often indicated horizontal semicircular canal impairment than the torsion swing test. The vHIT results showed significantly higher gains for both anterior canals compared with the horizontal and posterior canals (p < 0.001). The rates of bilaterally absent oVEMP responses were higher compared to the bilaterally absent cVEMP responses (p = 0.010). A total of fifty-four percent of the patients diagnosed with BVP without missing data met all three Bárány Society diagnostic test criteria, whereas 76% of the patients were eligible for implantation according to the vestibular implantation criteria. Regarding etiology, only horizontal vHIT results were significantly lower for trauma, neurodegenerative, and genetic disorders, whereas the horizontal vHIT results were significantly higher for Menière's Disease, infectious and idiopathic BVP. The exploration with hierarchical cluster analysis showed no significant association between etiology and patterns of vestibular impairment. Conclusion: This study showed that caloric testing and vHIT seem to be more sensitive for measuring vestibular impairment, whereas the torsion swing test is more suited for measuring residual vestibular function. In addition, no striking patterns of vestibular impairment in relation to etiology were found. Nevertheless, it was demonstrated that although the implantation criteria are stricter compared with the Bárány Society diagnostic criteria, still, 76% of patients with BVP were eligible for implantation based on the vestibular test criteria. It is advised to carefully examine every patient for their overall pattern of vestibular impairment in order to make well-informed and personalized therapeutic decisions.

Bilateral vestibulopathy decreases self-motion perception.

OBJECTIVE: Current diagnostic criteria for bilateral vestibulopathy (BV) primarily involve measurements of vestibular reflexes. Perceptual self-motion thresholds however, are not routinely measured and their clinical value in this specific population is not yet fully determined. Objectives of this study were (1) to compare perceptual self-motion thresholds between BV patients and control subjects, and (2) to explore patterns of self-motion perception performance and vestibular function in BV patients. METHODS: Thirty-seven BV patients and 34 control subjects were included in this study. Perceptual self-motion thresholds were measured in both groups using a CAREN platform (Motek Medical BV, Amsterdam, The Netherlands). Vestibular function was evaluated (only in BV patients) by the caloric test, torsion swing test, video head impulse test of all semicircular canals, and cervical- and ocular vestibular-evoked myogenic potentials. Differences in thresholds between both groups were analyzed. Hierarchical cluster analysis was performed to visualize patterns between self-motion perception and vestibular function within the group of BV patients. RESULTS: Perceptual self-motion thresholds were significantly higher in BV patients compared to control subjects, regarding nearly all rotations and translations (depending on the age group) (p ≤ 0.001). Cluster analysis showed that within the group of BV patients, higher perceptual self-motion thresholds were generally associated with lower vestibular test results (significant for yaw rotation, caloric test, torsion swing test, and video head impulse test (p ≤ 0.001)). CONCLUSION: Self-motion perception is significantly decreased in BV patients compared to control subjects regarding nearly all rotations and translations. Furthermore, decreased self-motion perception is generally associated with lower residual vestibular function in BV patients. TRIAL REGISTRATION: Trial registration number NL52768.068.15/METC.

Bilateral vestibulopathy patients' perspectives on vestibular implant treatment: a qualitative study.

OBJECTIVES: The aim of this study was to explore expectations of patients with bilateral vestibulopathy regarding vestibular implant treatment. This could advance the definition of recommendations for future core outcome sets of vestibular implantation and help to determine on which characteristics of bilateral vestibulopathy future vestibular implant research should focus. METHODS: Semi-structured interviews were conducted with 50 patients diagnosed with bilateral vestibulopathy at Maastricht UMC + . Interviews followed a semi-structured interview guide and were recorded and transcribed. Transcripts were analyzed thematically by two independent researchers. A consensus meeting took place to produce a joint interpretation for greater dimensionality and to confirm key themes. RESULTS: Overall, patient expectations centralized around three key themes: (physical) symptom reduction, functions and activities, and quality of life. These themes appeared to be interrelated. Patient expectations focused on the activity walking (in a straight line), reducing the symptom oscillopsia and being able to live the life they had before bilateral vestibulopathy developed. In general, patients indicated to be satisfied with small improvements. CONCLUSION: This study demonstrated that patient expectations regarding a vestibular implant focus on three key themes: symptom reduction, functions and activities, and quality of life. These themes closely match the functional improvements shown in recent vestibular implantation research. The results of this study provide a clear guideline from the patient perspective on which characteristics of bilateral vestibulopathy, future vestibular implant research should focus. TRIAL REGISTRATION: NL52768.068.15/METC.

Prospective cohort study on the predictors of fall risk in 119 patients with bilateral vestibulopathy.

OBJECTIVES: To identify predictive factors for falls in patients with bilateral vestibulopathy (BV). Specific variables contributing to the general work-up of a vestibular patient were compared between BV patients experiencing falls and those who did not. DESIGN: Prospective multi-centric cohort study. SETTING: Department of Otorhinolaryngology & Head and Neck Surgery at two tertiary referral centers: Antwerp University Hospital and Maastricht University Medical Center. PARTICIPANTS: In total, 119 BV patients were included. BV diagnosis was defined in accordance with the diagnostic BV criteria, established by the Bárány Society in 2017. MAIN OUTCOME MEASURES: Patients were divided into fallers and non-fallers, depending on the experience of one or more falls in the preceding 12 months. Residual vestibular function on caloric testing, rotatory chair testing, video head impulse test (vHIT) and cervical vestibular evoked myogenic potentials (cVEMP) was evaluated as a predictive factor for falls. Furthermore, hearing function (speech perception in noise (SPIN)), sound localization performance, etiology, disease duration, sport practice, scores on the Dizziness Handicap Inventory (DHI) and the Oscillopsia Severity Questionnaire (OSQ) were compared between fallers and non-fallers. RESULTS: Forty-five (39%) patients reported falls. In a sub-analysis in the patients recruited at UZA (n = 69), 20% experienced three or more falls and three patients (4%) suffered from severe fall-related injuries. The DHI score and the OSQ score were significantly higher in fallers. Residual vestibular function, SPIN, sound localization performance, etiology, disease duration, age and sport practice did not differ between fallers and non-fallers. CONCLUSIONS: Falls and (severe) fall-related injuries are frequent among BV patients. A DHI score > 47 and an OSQ score > 27.5 might be indicative for BV patients at risk for falls, with a sensitivity of 70% and specificity of 60%. Residual vestibular function captured by single vestibular tests (vHIT, calorics, rotatory chair, cVEMP) or by overall vestibular function defined as the number of impaired vestibular sensors are not suitable to distinguish fallers and non-fallers in a BV population.

Restoring the High-Frequency Dynamic Visual Acuity with a Vestibular Implant Prototype in Humans.

INTRODUCTION: The vestibular implant could become a clinically useful device in the near future. This study investigated the feasibility of restoring the high-frequency dynamic visual acuity (DVA) with a vestibular implant, using the functional Head Impulse Test (fHIT). METHODS: A 72-year-old female, with bilateral vestibulopathy and fitted with a modified cochlear implant incorporating three vestibular electrodes (MED-EL, Innsbruck, Austria), was available for this study. Electrical stimulation was delivered with the electrode close to the lateral ampullary nerve in the left ear. The high-frequency DVA in the horizontal plane was tested with the fHIT. After training, the patient underwent six trials of fHIT, each with a different setting of the vestibular implant: (1) System OFF before stimulation; (2) System ON, baseline stimulation; (3) System ON, reversed stimulation; (4) System ON, positive stimulation; (5) System OFF, without delay after stimulation offset; and (6) System OFF, 25 min delay after stimulation offset. The percentage of correct fHIT scores for right and left head impulses were compared between trials. RESULTS: Vestibular implant stimulation improved the high-frequency DVA compared to no stimulation. This improvement was significant for "System ON, baseline stimulation" (p = 0.02) and "System ON, positive stimulation" (p < 0.001). fHIT scores changed from 19 to 44% (no stimulation) to maximum 75-94% (System ON, positive stimulation). CONCLUSION: The vestibular implant seems capable of improving the high-frequency DVA. This functional benefit of the vestibular implant illustrates again the feasibility of this device for clinical use in the near future.

The walking speed-dependency of gait variability in bilateral vestibulopathy and its association with clinical tests of vestibular function.

Understanding balance and gait deficits in vestibulopathy may help improve clinical care and our knowledge of the vestibular contributions to balance. Here, we examined walking speed effects on gait variability in healthy adults and in adults with bilateral vestibulopathy (BVP). Forty-four people with BVP, 12 healthy young adults and 12 healthy older adults walked at 0.4 m/s to 1.6 m/s in 0.2 m/s increments on a dual belt, instrumented treadmill. Using motion capture and kinematic data, the means and coefficients of variation for step length, time, width and double support time were calculated. The BVP group also completed a video head impulse test and examinations of ocular and cervical vestibular evoked myogenic potentials and dynamic visual acuity. Walking speed significantly affected all gait parameters. Step length variability at slower speeds and step width variability at faster speeds were the most distinguishing parameters between the healthy participants and people with BVP, and among people with BVP with different locomotor capacities. Step width variability, specifically, indicated an apparent persistent importance of vestibular function at increasing speeds. Gait variability was not associated with the clinical vestibular tests. Our results indicate that gait variability at multiple walking speeds has potential as an assessment tool for vestibular interventions.

A New and Faster Test to Assess Vestibular Perception.

Objective: Clinical vestibular testing mainly consists of testing reflexes, but does not routinely include testing for perceptual symptoms. The objective of this study was to investigate a new and faster test for vestibular perception, and to compare its results with previous studies. Methods: Fifty-five healthy subjects with no prior vestibular complaints were included and divided into three age groups. Vestibular perceptual thresholds were measured using a hydraulic platform in the dark. The platform delivered 12 different movements: six translations (forward, backward, right, left, up, and down) and six rotations/tilt (yaw left, yaw right, pitch forward, pitch backward, roll left, and roll right). The subject had to report the correct type and direction of movements. Thresholds were determined by a double confirmation of the lowest threshold. General trends in thresholds like relative interrelationship and the influence of age were analyzed and compared with values reported previously. Results: Mean thresholds of age groups ranged between 0.092 and 0.221 m/s2 for translations, and between 0.188 and 2.255°/s2 for rotations. The absolute values differed from previous reports, but the relative interrelationship of thresholds between type and direction of motion remained. An association between age and vestibular thresholds was found, similar to previous reports. Conclusion: This new and faster test for vestibular perception showed comparable patterns in perceptual thresholds when compared to more research oriented, lengthy tests. This might pave the way for establishing vestibular perception testing protocols useful for the clinic.

Full Spectrum of Reported Symptoms of Bilateral Vestibulopathy Needs Further Investigation-A Systematic Review.

OBJECTIVE: To systematically review the symptoms reported by patients with bilateral vestibulopathy (BV) in clinical studies and case reports. This would serve as the first step in establishing a validated patient-reported outcome measures (PROM) for BV. METHODS: A search on symptoms reported by patients with BV was performed in PubMed, and all publications covering these symptoms were included. Exclusion criteria comprised reviews and insufficient details about the frequency of occurrence of symptoms. RESULTS: 1,442 articles were retrieved. 88 studies were included (41 clinical studies, 47 case reports). In consensus, 68 descriptions of symptoms were classified into 6 common and generic symptoms. Frequency of symptoms in clinical studies and case reports were reviewed, respectively; imbalance (91 and 86%), chronic dizziness (58 and 62%), oscillopsia (50 and 70%), and recurrent vertigo (33 and 67%). BV could be accompanied by hearing loss (33 and 43%) and tinnitus (15 and 36%). 15 clinical studies and 10 case reports reported symptoms beyond vestibular and hearing deficits such as limited social activities, depression, concentration, and memory impairment and reduced quality of life in general. CONCLUSION: The literature on BV symptomatology mainly focuses on classic symptoms such as imbalance and oscillopsia, while only few report additional symptoms such as cognitive memory impairment and performing dual tasks. In fact, none of the reviewed clinical studies and case reports provided a comprehensive overview of BV symptoms. To develop a validated PROM, qualitative research using semi-structured and unstructured interviews is needed to explore the full spectrum of BV symptoms.

The Vestibular Implant: Hearing Preservation during Intralabyrinthine Electrode Insertion-A Case Report.

OBJECTIVE: The vestibular implant seems feasible as a clinically useful device in the near future. However, hearing preservation during intralabyrinthine implantation remains a challenge. It should be preserved to be able to treat patients with bilateral vestibulopathy and (partially) intact hearing. This case study investigated the feasibility of hearing preservation during the acute phase after electrode insertion in the semicircular canals. METHODS: A 40-year-old woman with normal hearing underwent a translabyrinthine approach for a vestibular schwannoma Koos Grade IV. Hearing was monitored using auditory brainstem response audiometry (ABR). ABR signals were recorded synchronously to video recordings of the surgery. Following the principles of soft surgery, a conventional dummy electrode was inserted in the lateral semicircular canal for several minutes and subsequently removed. The same procedure was then applied for the posterior canal. Finally, the labyrinthectomy was completed, and the schwannoma was removed. RESULTS: Surgery was performed without complications. No leakage of endolymph and no significant reduction of ABR response were observed during insertion and after removal of the electrodes from the semicircular canals, indicting no damage to the peripheral auditory function. The ABR response significantly changed when the semicircular canals were completely opened during the labyrinthectomy. This was indicated by a change in the morphology and latency of peak V of the ABR signal. CONCLUSION: Electrode insertion in the semicircular canals is possible without acutely damaging the peripheral auditory function measured with ABR, as shown in this proof-of-principle clinical investigation.

The Vestibular Implant Input Interacts with Residual Natural Function.

OBJECTIVE: Patients with bilateral vestibulopathy (BV) can still have residual "natural" function. This might interact with "artificial" vestibular implant input (VI-input). When fluctuating, it could lead to vertigo attacks. Main objective was to investigate how "artificial" VI-input is integrated with residual "natural" input by the central vestibular system. This, to explore (1) whether misalignment in the response of "artificial" VI-input is sufficiently counteracted by well-aligned residual "natural" input and (2) whether "artificial" VI-input is able to influence and counteract the response to residual "natural" input, to show feasibility of a "vestibular pacemaker." MATERIALS AND METHODS: Five vestibular electrodes in four BV patients implanted with a VI were available. This involved electrodes with a predominantly horizontal response and electrodes with a predominantly vertical response. Responses to predominantly horizontal residual "natural" input and predominantly horizontal and vertical "artificial" VI-input were separately measured first. Then, inputs were combined in conditions where both would hypothetically collaborate or counteract. In each condition, subjects were subjected to 60 cycles of sinusoidal stimulation presented at 1 Hz. Gain, asymmetry, phase and angle of eye responses were calculated. Signal averaging was performed. RESULTS: Combining residual "natural" input and "artificial" VI-input resulted in an interaction in which characteristics of the resulting eye movement responses could significantly differ from those observed when responses were measured for each input separately (p < 0.0013). In the total eye response, inputs with a stronger vector magnitude seemed to have stronger weights than inputs with a lower vector magnitude, in a non-linear combination. Misalignment in the response of "artificial" VI-input was not sufficiently counteracted by well-aligned residual "natural" input. "Artificial" VI-input was able to significantly influence and counteract the response to residual "natural" input. CONCLUSION: In the acute phase of VI-activation, residual "natural" input and "artificial" VI-input interact to generate eye movement responses in a non-linear fashion. This implies that different stimulation paradigms and more complex signal processing strategies will be required unless the brain is able to optimally combine both sources of information after adaptation during chronic use. Next to this, these findings could pave the way for using the VI as "vestibular pacemaker."