Multi-frequency VEMPs improve detection of present otolith responses in bilateral vestibulopathy.

Objective: To investigate whether multi-frequency Vestibular Evoked Myogenic Potential (VEMP) testing at 500, 750, 1,000, and 2,000 Hz, would improve the detection of present dynamic otolith responses in patients with bilateral vestibulopathy (BV). Methods: Prospective study in a tertiary referral center. BV patients underwent multi-frequency VEMP testing. Cervical VEMPs and ocular VEMPs were recorded with the Neuro-Audio system (v2010, Neurosoft, Ivanovo, Russia). The stimuli included air-conducted tone bursts of 500, 750, 1,000, and 2,000 Hz, at a stimulation rate of 13 Hz. Outcome measures included the percentage of present and absent VEMP responses, and VEMP thresholds. Outcomes were compared between frequencies and type of VEMPs (cVEMPs, oVEMPs). VEMP outcomes obtained with the 500 Hz stimulus, were also compared to normative values obtained in healthy subjects. Results: Forty-nine BV patients completed VEMP testing: 47 patients completed cVEMP testing and 48 patients completed oVEMP testing. Six to 15 % more present VEMP responses were obtained with multifrequency testing, compared to only testing at 500 Hz. The 2,000 Hz stimulus elicited significantly fewer present cVEMP responses (right and left ears) and oVEMP responses (right ears) compared to the other frequencies (p ≤ 0.044). Using multi-frequency testing, 78% of BV patients demonstrated at least one present VEMP response in at least one ear. In 46% a present VEMP response was found bilaterally. BV patients demonstrated a significantly higher percentage of absent VEMP responses and significantly higher VEMP thresholds than healthy subjects, when corrected for age (p ≤ 0.002). Based on these results, a pragmatic VEMP testing paradigm is proposed, taking into account multi-frequency VEMP testing. Conclusion: Multi-frequency VEMP testing improves the detection rate of present otolith responses in BV patients. Therefore, multi-frequency VEMPs should be considered when evaluation of (residual) otolith function is indicated.

Reported thresholds of self-motion perception are influenced by testing paradigm.

BACKGROUND/OBJECTIVE: Different testing paradigms have been proposed to investigate perceptual self-motion thresholds. They can differ regarding the amount of possible motions that patients have to choose from. Objective of this study was to compare the two-option paradigm and twelve-option paradigm, to investigate whether reducing the choice options significantly influences the reported thresholds of self-motion perception of healthy subjects. METHODS: Thirty-three volunteers with no prior vestibular complaints were included and sequentially tested with both paradigms at a random sequence. Perceptual self-motion thresholds were measured using a hydraulic motion platform in the absence of external visual and auditory cues. The platform delivered twelve different movements: six translations and six rotations. Each subject had to report the correct type and direction of movements. Thresholds were determined by a double confirmation of the lowest threshold, in combination with a double rejection of the one-step lower stimulus. Perceptual self-motion thresholds of both paradigms were compared using the mixed model analysis. RESULTS: The twelve-option paradigm showed significantly higher reported thresholds for yaw rotations and translations left, right and down (p < 0.001), compared to the two-option paradigm. No statistical difference was found for rolls and translations up. No significant gender effect, learning effect and carry-over effect were present in any of the applied motion directions. CONCLUSION: Reported thresholds of self-motion perception of healthy subjects are influenced by the testing paradigm. The twelve-option paradigm showed significantly higher thresholds than the two-option paradigm. Results obtained with each testing paradigm should, therefore, be compared to paradigm-specific normative data.

Fitting the determined impedance in the guinea pig inner ear to Randles circuit using square error minimization in the range of 100 Hz to 50 kHz.

Objective. Several lumped and distributed parameter models of the inner ear have been proposed to improve vestibular implant stimulation. The models should account for all significant physical phenomena that influence the current propagation, such as the electrical double layer (EDL) and medium polarization. The electrical properties of the medium are reflected in the electrical impedance; therefore, the study aimed to measure the impedance in the guinea pig inner ear and construct its equivalent circuit.Approach. The electrical impedance was measured from 100 Hz to 50 kHz between a pair of platinum electrodes immersed in 0.9% NaCl saline solution using sinusoidal voltage signals. The Randles circuit was fitted to the measured impedance in the saline solution in order to estimate the EDL parameters (C,W,andRct) of the electrode interface in saline. Then, the electrical impedance was measured between all combinations of the electrodes located in the semicircular canal ampullae and the vestibular nerve in the guinea pigin vitro. The extended Randles circuit considering the medium polarization (Ri,Re,Cm) together with EDL parameters (C,Rct) obtained from the saline solution was fitted to the measured impedance of the guinea pig inner ear. The Warburg element was assumed negligible and was not considered in the guinea pig model.Main results. For the set-up used, the obtained EDL parameters were:C=27.09*10-8F,Rct=18.75kΩ.The average values of intra-, extracellular resistances, and membrane capacitance wereRi=4.74kΩ,Re=45.05kΩ,Cm=9.69*10-8F,respectively.Significance. The obtained values of the model parameters can serve as a good estimation of the EDL for modelling work. The EDL, together with medium polarization, plays a significant role in the electrical impedance of the guinea pig inner ear, therefore, they should be considered in electrical conductivity models to increase the credibility of the simulations.

The DizzyQuest: relation between self-reported hearing loss, tinnitus and objective hearing thresholds in patients with Meniere's disease.

BACKGROUND: Combining a mobile application-based vestibular diary called the DizzyQuest and an iPad-based hearing test enables evaluation of the relationship between experienced neuro-otological symptoms and hearing thresholds in daily life setting. The aim was to investigate the relationship between self-reported hearing symptoms and hearing thresholds in patients with Meniere's disease (MD), using the DizzyQuest and the iPad-based hearing test simultaneously. METHODS: The DizzyQuest was administered for 3 weeks in 21 patients. Using the experience-sampling-method (ESM), it assessed hearing loss and tinnitus severity for both ears separately. Each day after the DizzyQuest, an iPad-based hearing test was used to measure hearing thresholds. A mixed model regression analysis was performed to investigate relationships between hearing thresholds and self-reported hearing loss and tinnitus severity. RESULTS: Fifteen patients were included. Overall, pure-tone averages (PTAs) were not correlated with self-reported hearing loss severity and tinnitus. Individual differences in PTA results between both ears did not significantly influence the difference in self-reported hearing loss severity between both ears. Self-reported hearing loss and tinnitus scores were significantly higher in ears that corresponded with audiometric criteria of MD (p < 0.001). Self-reported tinnitus severity significantly increased with self-reported hearing loss severity in affected (p = 0.011) and unaffected ears (p < 0.001). CONCLUSION: Combining the DizzyQuest and iPad-based hearing test, facilitated assessment of self-reported hearing loss and tinnitus severity and their relationship with hearing thresholds, in a daily life setting. This study illustrated the importance of investigating neuro-otological symptoms at an individual level, using multiple measurements. ESM strategies like the DizzyQuest should therefore be considered in neuro-otological research.

Curriculum for Vestibular Medicine (VestMed) proposed by the Bárány Society.

This document presents the initiative of the Bárány Society to improve diagnosis and care of patients presenting with vestibular symptoms worldwide.The Vestibular Medicine (VestMed) concept embraces a wide approach to the potential causes of vestibular symptoms, acknowledging that vertigo, dizziness, and unsteadiness are non-specific symptoms that may arise from a broad spectrum of disorders, spanning from the inner ear to the brainstem, cerebellum and supratentorial cerebral networks, to many disorders beyond these structures.The Bárány Society Vestibular Medicine Curriculum (BS-VestMed-Cur) is based on the concept that VestMed is practiced by different physician specialties and non-physician allied health professionals. Each profession has its characteristic disciplinary role and profile, but all work in overlapping areas. Each discipline requires good awareness of the variety of disorders that can present with vestibular symptoms, their underlying mechanisms and etiologies, diagnostic criteria and treatment options. Similarly, all disciplines require an understanding of their own limitations, the contribution to patient care from other professionals and when to involve other members of the VestMed community. Therefore, the BS-VestMed-Cur is the same for all health professionals involved, the overlaps and differences of the various relevant professions being defined by different levels of detail and depth of knowledge and skills.The BS-VestMed-Cur defines a Basic and an Expert Level Curriculum. The Basic Level Curriculum covers the VestMed topics in less detail and depth, yet still conveys the concept of the wide net approach. It is designed for health professionals as an introduction to, and first step toward, VestMed expertise. The Expert Level Curriculum defines a Focused and Broad Expert. It covers the VestMed spectrum in high detail and requires a high level of understanding. In the Basic and Expert Level Curricula, the range of topics is the same and runs from anatomy, physiology and physics of the vestibular system, to vestibular symptoms, history taking, bedside examination, ancillary testing, the various vestibular disorders, their treatment and professional attitudes. Additionally, research topics relevant to clinical practice are included in the Expert Level Curriculum. For Focused Expert proficiency, the Basic Level Curriculum is required to ensure a broad overview and additionally requires an expansion of knowledge and skills in one or a few specific topics related to the focused expertise, e.g. inner ear surgery. Broad Expert proficiency targets professionals who deal with all sorts of patients presenting with vestibular symptoms (e.g. otorhinolaryngologists, neurologists, audiovestibular physicians, physical therapists), requiring a high level of VestMed expertise across the whole spectrum. For the Broad Expert, the Expert Level Curriculum is required in which the minimum attainment targets for all the topics go beyond the Basic Level Curriculum. The minimum requirements regarding knowledge and skills vary between Broad Experts, since they are tuned to the activity profile and underlying specialty of the expert. The BS-VestMed-Cur aims to provide a basis for current and future teaching and training programs for physicians and non-physicians. The Basic Level Curriculum could also serve as a resource for inspiration for teaching VestMed to students, postgraduate generalists such as primary care physicians and undergraduate health professionals, or anybody wishing to enter VestMed. VestMed is considered a set of competences related to an area of practice of established physician specialties and non-physician health professions rather than a separate clinical specialty. This curriculum does not aim to define a new single clinical specialty. The BS-VestMed-Cur should also integrate with, facilitate and encourage translational research in the vestibular field.

Bilateral vestibulopathy: beyond imbalance and oscillopsia.

OBJECTIVE: To optimize the current diagnostic and treatment procedures for patients with bilateral vestibulopathy (BV), this study aimed to determine the complete spectrum of symptoms associated with BV. METHOD: A prospective mixed-method study design was used. Qualitative data were collected by performing semi-structured interviews about symptoms, context, and behavior. The interviews were recorded and transcribed until no new information was obtained. Transcriptions were analyzed in consensus by two independent researchers. In comparison to the qualitative results, quantitative data were collected using the Dizziness Handicap Inventory (DHI), Hospital Anxiety and Depression Scale (HADS) and a health-related quality of life questionnaire (EQ-5D-5L). RESULTS: Eighteen interviews were transcribed. Reported symptoms were divided into fourteen physical symptoms, four cognitive symptoms, and six emotions. Symptoms increased in many situations, such as darkness (100%), uneven ground (61%), cycling (94%) or driving a car (56%). These symptoms associated with BV often resulted in behavioral changes: activities were performed more slowly, with greater attention, or were avoided. The DHI showed a mean score of severe handicap (54.67). The HADS questionnaire showed on average normal results (anxiety = 7.67, depression = 6.22). The EQ-5D-5L demonstrated a mean index value of 0.680, which is lower compared to the Dutch age-adjusted reference 0.839 (60-70 years). CONCLUSION: BV frequently leads to physical, cognitive, and emotional complaints, which often results in a diminished quality of life. Importantly, this wide range of symptoms is currently underrated in literature and should be taken into consideration during the development of candidacy criteria and/or outcome measures for therapeutic interventions such as the vestibular implant.

Bilateral vestibulopathy and age: experimental considerations for testing dynamic visual acuity on a treadmill.

INTRODUCTION: Bilateral vestibulopathy (BVP) can affect visual acuity in dynamic conditions, like walking. This can be assessed by testing Dynamic Visual Acuity (DVA) on a treadmill at different walking speeds. Apart from BVP, age itself might influence DVA and the ability to complete the test. The objective of this study was to investigate whether DVA tested while walking, and the drop-out rate (the inability to complete all walking speeds of the test) are significantly influenced by age in BVP-patients and healthy subjects. METHODS: Forty-four BVP-patients (20 male, mean age 59 years) and 63 healthy subjects (27 male, mean age 46 years) performed the DVA test on a treadmill at 0 (static condition), 2, 4 and 6 km/h (dynamic conditions). The dynamic visual acuity loss was calculated as the difference between visual acuity in the static condition and visual acuity in each walking condition. The dependency of the drop-out rate and dynamic visual acuity loss on BVP and age was investigated at all walking speeds, as well as the dependency of dynamic visual acuity loss on speed. RESULTS: Age and BVP significantly increased the drop-out rate (p ≤ 0.038). A significantly higher dynamic visual acuity loss was found at all speeds in BVP-patients compared to healthy subjects (p < 0.001). Age showed no effect on dynamic visual acuity loss in both groups. In BVP-patients, increasing walking speeds resulted in higher dynamic visual acuity loss (p ≤ 0.036). CONCLUSION: DVA tested while walking on a treadmill, is one of the few "close to reality" functional outcome measures of vestibular function in the vertical plane. It is able to demonstrate significant loss of DVA in bilateral vestibulopathy patients. However, since bilateral vestibulopathy and age significantly increase the drop-out rate at faster walking speeds, it is recommended to use age-matched controls. Furthermore, it could be considered to use an individual "preferred" walking speed and to limit maximum walking speed in older subjects when testing DVA on a treadmill.

Introducing the DizzyQuest: an app-based diary for vestibular disorders.

BACKGROUND: Most questionnaires currently used for assessing symptomatology of vestibular disorders are retrospective, inducing recall bias and lowering ecological validity. An app-based diary, administered multiple times in daily life, could increase the accuracy and ecological validity of symptom measurement. The objective of this study was to introduce a new experience sampling method (ESM) based vestibular diary app (DizzyQuest), evaluate response rates, and to provide examples of DizzyQuest outcome measures which can be used in future research. METHODS: Sixty-three patients diagnosed with a vestibular disorder were included. The DizzyQuest consisted of four questionnaires. The morning- and evening-questionnaires were administered once each day, the within-day-questionnaire 10 times a day using a semi-random time schedule, and the attack questionnaire could be completed after the occurrence of a vertigo or dizziness attack. Data were collected for 4 weeks. Response rates and loss-to-follow-up were determined. Reported symptoms in the within-day-questionnaire were compared within and between patients and subgroups of patients with different vestibular disorders. RESULTS: Fifty-one patients completed the study period. Average response rates were significantly higher than the desired response rate of > 50% (p < 0.001). The attack-questionnaire was used 159 times. A variety of neuro-otological symptoms and different disease profiles were demonstrated between patients and subgroups of patients with different vestibular disorders. CONCLUSION: The DizzyQuest is able to capture vestibular symptoms within their psychosocial context in daily life, with little recall bias and high ecological validity. The DizzyQuest reached the desired response rates and showed different disease profiles between subgroups of patients with different vestibular disorders. This is the first time ESM was used to assess daily symptoms and quality of life in vestibular disorders, showing that it might be a useful tool in this population.

Comparison of three video head impulse test systems for the diagnosis of bilateral vestibulopathy.

INTRODUCTION: A horizontal vestibulo-ocular reflex gain (VOR gain) of < 0.6, measured by the video head impulse test (VHIT), is one of the diagnostic criteria for bilateral vestibulopathy (BV) according to the Báràny Society. Several VHIT systems are commercially available, each with different techniques of tracking head and eye movements and different methods of gain calculation. This study compared three different VHIT systems in patients diagnosed with BV. METHODS: This study comprised 46 BV patients (diagnosed according to the Báràny criteria), tested with three commercial VHIT systems (Interacoustics, Otometrics and Synapsys) in random order. Main outcome parameter was VOR gain as calculated by the system, and the agreement on BV diagnosis (VOR gain < 0.6) between the VHIT systems. Peak head velocities, the order effect and covert saccades were analysed separately, to determine whether these parameters could have influenced differences in outcome between VHIT systems. RESULTS: VOR gain in the Synapsys system differed significantly from VOR gain in the other two systems [F(1.256, 33.916) = 35.681, p < 0.000]. The VHIT systems agreed in 83% of the patients on the BV diagnosis. Peak head velocities, the order effect and covert saccades were not likely to have influenced the above mentioned results. CONCLUSION: To conclude, using different VHIT systems in the same BV patient can lead to clinically significant differences in VOR gain, when using a cut-off value of 0.6. This might hinder proper diagnosis of BV patients. It would, therefore, be preferred that VHIT systems are standardised regarding eye and head tracking methods, and VOR gain calculation algorithms. Until then, it is advised to not only take the VOR gain in consideration when assessing a VHIT trial, but also look at the raw traces and the compensatory saccades.

The DizzyQuest: to have or not to have a vertigo attack?

BACKGROUND: The DizzyQuest, an app-based vestibular diary, provides the opportunity to capture the number and nature of vertigo attacks in daily life. To accomplish this, the DizzyQuest provides different strategies: event sampling using an attack questionnaire, and time sampling using an evening questionnaire. Objective of this study was to investigate whether the number and nature of reported vertigo attacks was comparable between the two questionnaires. METHODS: Fifty-seven patients, who reported vertigo attacks, used the DizzyQuest for on average 24 days. The number and nature (including symptoms, triggers and duration) of vertigo attacks were compared between the attack and the evening questionnaire. RESULTS: The attack questionnaire was used 192 times. In contrast, at least 749 new vertigo attacks were reported in 446 evening questionnaires. A vertigo attack was not always reported in both questionnaires during the same day. Vertigo attacks that were most likely captured by both questionnaires were not always reported the same in both questionnaires regarding triggers and duration. CONCLUSION: Event sampling using an attack questionnaire has low recall bias and, therefore, reliably captures the nature of the attack, but induces a risk of under-sampling. Time sampling using an evening questionnaire suffers from recall bias, but seems more likely to capture less discrete vertigo attacks and it facilitates registration of the absence of vertigo attacks. Depending on the clinical or research question, the right strategy should be applied and participants should be clearly instructed about the definition of a vertigo attack.

The Functional Head Impulse Test to Assess Oscillopsia in Bilateral Vestibulopathy.

Introduction: Bilateral vestibulopathy (BV) is a chronic condition in which vestibular function is severely impaired or absent on both ears. Oscillopsia is one of the main symptoms of BV. Oscillopsia can be quantified objectively by functional vestibular tests, and subjectively by questionnaires. Recently, a new technique for testing functionally effective gaze stabilization was developed: the functional Head Impulse Test (fHIT). This study compared the fHIT with the Dynamic Visual Acuity assessed on a treadmill (DVAtreadmill) and Oscillopsia Severity Questionnaire (OSQ) in the context of objectifying the experience of oscillopsia in patients with BV. Methods: Inclusion criteria comprised: (1) summated slow phase velocity of nystagmus of <20°/s during bithermal caloric tests, (2) torsion swing tests gain of <30% and/or phase <168°, and (3) complaints of oscillopsia and/or imbalance. During the fHIT (Beon Solutions srl, Italy) patients were seated in front of a computer screen. During a passive horizontal head impulse a Landolt C optotype was shortly displayed. Patients reported the seen optotype by pressing the corresponding button on a keyboard. The percentage correct answers was registered for leftwards and rightwards head impulses separately. During DVAtreadmill patients were positioned on a treadmill in front of a computer screen that showed Sloan optotypes. Patients were tested in static condition and in dynamic conditions (while walking on the treadmill at 2, 4, and 6 km/h). The decline in LogMAR between static and dynamic conditions was registered for each speed. Every patient completed the Oscillopsia Severity Questionnaire (OSQ). Results: In total 23 patients were included. This study showed a moderate correlation between OSQ outcomes and the fHIT [rightwards head rotations (r s = -0.559; p = 0.006) leftwards head rotations (r s = -0.396; p = 0.061)]. No correlation was found between OSQ outcomes and DVAtreadmill, or between DVAtreadmill and fHIT. All patients completed the fHIT, 52% of the patients completed the DVAtreadmill on all speeds. Conclusion: The fHIT seems to be a feasible test to quantify oscillopsia in BV since, unlike DVAtreadmill, it correlates with the experienced oscillopsia measured by the OSQ, and more BV patients are able to complete the fHIT than DVAtreadmill.

The Video Head Impulse Test and the Influence of Daily Use of Spectacles to Correct a Refractive Error.

OBJECTIVE: To determine the influence of daily use of spectacles to correct a refractive error, on the vestibulo-ocular reflex (VOR) gain measured with the video head impulse test (vHIT). STUDY DESIGN: This prospective study enrolled subjects between 18 and 80 years old with and without a refractive error. Subjects were classified into three groups: (1) contact lenses, (2) spectacles, and (3) control group without visual impairment. Exclusion criteria comprised ophthalmic pathology, history of vestibular disorders, and alternated use of spectacles and contact lenses in daily life. Corrective spectacles were removed seconds before testing. One examiner performed all vHIT's under standardized circumstances using the EyeSeeCam system. This system calculated the horizontal VOR gain for rightward and leftward head rotations separately. RESULTS: No statistically significant difference was found in VOR gain between the control group (n = 16), spectacles group (n = 48), and contact lenses group (n = 15) (p = 0.111). Both the spectacles group and contact lenses group showed no statistically significant correlation between VOR gain and amount of refractive error, for rightwards (p = 0.071) and leftwards (p = 0.716) head rotations. There was no statistical significant difference in VOR gain between testing monocularly or binocularly (p = 0.132) and between testing with or without wearing contact lenses (p = 0.800). CONCLUSION: In this study, VOR gain was not influenced by wearing corrective spectacles or contact lenses on a daily basis. Based on this study, no corrective measures are necessary when performing the vHIT on subjects with a refractive error, regardless of the way of correction.

An Exploratory Study to Detect Ménière's Disease in Conventional MRI Scans Using Radiomics.

OBJECTIVE: The purpose of this exploratory study was to investigate whether a quantitative image analysis of the labyrinth in conventional magnetic resonance imaging (MRI) scans using a radiomics approach showed differences between patients with Ménière's disease (MD) and the control group. MATERIALS AND METHODS: In this retrospective study, MRI scans of the affected labyrinths of 24 patients with MD were compared to the MRI scans of labyrinths of 29 patients with an idiopathic asymmetrical sensorineural hearing loss. The 1.5- and 3-T MRI scans had been previously made in a clinical setting between 2008 and 2015. 3D Slicer 4.4 was used to extract several substructures of the labyrinth. A quantitative analysis of the normalized radiomic image features was performed in Mathematica 10. The image features of the two groups were statistically compared. RESULTS: For numerous image features, there was a statistically significant difference (p-value <0.05) between the MD group and the control group. The statistically significant differences in image features were localized in all the substructures of the labyrinth: 43 in the anterior semicircular canal, 10 in the vestibule, 22 in the cochlea, 12 in the posterior semicircular canal, 24 in the horizontal semicircular canal, 11 in the common crus, and 44 in the volume containing the reuniting duct. Furthermore, some figures contain vertical or horizontal bands (three or more statistically significant image features in the same image feature). Several bands were seen: 9 bands in the anterior semicircular canal, 1 band in the vestibule, 3 bands in the cochlea, 0 bands in the posterior semicircular canal, 5 bands in the horizontal semicircular canal, 3 bands in the common crus, and 10 bands in the volume containing the reuniting duct. CONCLUSION: In this exploratory study, several differences were found in image features between the MD group and the control group by using a quantitative radiomics approach on high resolution T2-weighted MRI scans of the labyrinth. Further research should be aimed at validating these results and translating them in a potential clinical diagnostic method to detect MD in MRI scans.

Anatomy, physiology, and physics of the peripheral vestibular system.

Many medical doctors consider vertigo and dizziness as the major, almost obligatory complaints in patients with vestibular disorders. In this chapter, we will explain that vestibular disorders result in much more diverse and complex complaints. Many of these other complaints are unfortunately often misinterpreted and incorrectly classified as psychogenic. When we really understand the function of the vestibular system, it becomes quite obvious why patients with vestibular disorders complain about a loss of visual acuity, imbalance, fear of falling, cognitive and attentional problems, fatigue that persists even when the vertigo attacks and dizziness decreases or even disappears. Another interesting new aspect in this chapter is that we explain why the function of the otolith system is so important, and that it is a mistake to focus on the function of the semicircular canals only, especially when we want to understand why some patients seem to suffer more than others from the loss of canal function as objectified by reduced caloric responses.

Characterization of pulse amplitude and pulse rate modulation for a human vestibular implant during acute electrical stimulation.

OBJECTIVE: The vestibular system provides essential information about balance and spatial orientation via the brain to other sensory and motor systems. Bilateral vestibular loss significantly reduces quality of life, but vestibular implants (VIs) have demonstrated potential to restore lost function. However, optimal electrical stimulation strategies have not yet been identified in patients. In this study, we compared the two most common strategies, pulse amplitude modulation (PAM) and pulse rate modulation (PRM), in patients. APPROACH: Four subjects with a modified cochlear implant including electrodes targeting the peripheral vestibular nerve branches were tested. Charge-equivalent PAM and PRM were applied after adaptation to baseline stimulation. Vestibulo-ocular reflex eye movement responses were recorded to evaluate stimulation efficacy during acute clinical testing sessions. MAIN RESULTS: PAM evoked larger amplitude eye movement responses than PRM. Eye movement response axes for lateral canal stimulation were marginally better aligned with PRM than with PAM. A neural network model was developed for the tested stimulation strategies to provide insights on possible neural mechanisms. This model suggested that PAM would consistently cause a larger ensemble firing rate of neurons and thus larger responses than PRM. SIGNIFICANCE: Due to the larger magnitude of eye movement responses, our findings strongly suggest PAM as the preferred strategy for initial VI modulation.

Vestibular assistance systems: promises and challenges.

The handicap resulting from a bilateral vestibular deficit is often underestimated. In most cases the deficit settles gradually. Patients do not understand what is happening to them and have many difficulties to describe their symptoms. They have to consult several doctors with different medical specialties before diagnosis. Once the diagnosis is made there is no biological way to "repair" the deficient vestibular apparatus and vestibular exercises are mildly effective. Attempts have been made to help patients using substitution devices replacing the defective vestibular information by tactile or acoustic cues. Currently, efforts are being made towards the development of a vestibular implant, conceptually similar to the cochlear implant for the rehabilitation of deaf patients. In recent years, several experiments on animal models have demonstrated the feasibility of this project. This paper reports the steps accomplished in human experiments and the main results obtained in our laboratory.

Vestibular implants: Hope for improving the quality of life of patients with bilateral vestibular loss.

The vestibular system plays an essential role in crucial tasks such as postural control, gaze stabilization, and spatial orientation. Currently, there is no effective treatment for a bilateral loss of the vestibular function (BVL). The quality of life of affected patients is significantly impaired. During the last decade, our group has explored the potential of using electrical stimulation to artificially restore the vestibular function. Our vestibular implant prototype consists of a custom modified cochlear implant featuring one to three vestibular electrodes implanted in the proximity of the ampullary branches of the vestibular nerve; in addition to the main cochlear array. Special surgical techniques for safe implantation of these devices have been developed. In addition, we have developed stimulation strategies to generate bidirectional eye movements as well as the necessary interfaces to capture the signal from a motion sensor (e.g., gyroscope) and use it to modulate the stimulation signals delivered to the vestibular nerves. To date, 24 vestibular electrodes have been implanted in 11 BVL patients. Using a virtual motion profile to modulate the "baseline" electrical stimulation, vestibular responses could be evoked with 21 electrodes. Eye movements with mean peak eye velocities of 32°/s and predominantly in the plane of the stimulated canal were successfully generated. These are within the range of normal compensatory eye movements during walking and were large enough to have a significant effect on the patients' visual acuity. These results indicate that electrical stimulation of the vestibular nerve has a significant functional impact; eye movements generated this way could be sufficient to restore gaze stabilization during essential everyday tasks such as walking. The innovative concept of the vestibular implant has the potential to restore the vestibular function and have a central role in improving the quality of life of BVL patients in the near future.

[The effect of elevated ozone levels in the ambient air on lung function of children engaged in sports]. / De invloed van verhoogde ozonconcentraties in de buitenlucht op de longfunctie van sportende kinderen.

In the summer of 1989, ozone levels in the ambient air were regularly found to be increased in The Netherlands. The question was studied whether this affected pulmonary function of children aged 7 to 12 years practising sports in the open air. Before and after sessions of training in the open air, the peak expiratory flow rate was determined using peak flow meters (mini-Wright). This was done on 37 different days with varying ozone concentrations. Measurements were carried out on four or more days in a total of 65 children. No correlation between ozone concentration during training and differences between pre- and post-training peak flows was found. No correlation was found either between the maximal ozone concentration on a given day and the peak flow at the end of training on that day. However, a negative correlation was found between the maximal ozone concentration on the day preceding the pulmonary function tests and the peak flow after the training.

The urinary excretion of prostaglandins and thromboxane B2 in healthy volunteers: a study in males and females, and on the influence of seminal fluid contamination.

Radioimmunoassay measurements of prostaglandins (PGs) E2, F2 alpha, 6-keto-PGF1 alpha and thromboxane (Tx) B2 in 24 h urine specimens from a male and a female healthy volunteer on several consecutive days revealed a dramatic increase of PGE2, PGF2 alpha, 6-keto-PGF1 alpha on days, upon which they had sexual intercourse; only TxB2 remained stable. Furthermore, the PGE2/PGF2 alpha ratio rose to values greater than 0.5 on days with sexual intercourse. This was found to be due to contamination of the urine samples by seminal fluid. Two 24 h urine samples from each of 26 healthy male and female volunteers (HV) revealed higher (p less than 0.01) mean PGE2 and PGF2 alpha values in males than in females. The results show that the interpretation of the urinary PG excretion as a measure of renal PG synthesis should be considered carefully, and that a PGE2/PGF2 alpha ratio greater than 0.5 indicates probable seminal contamination of urine.