The value of saccade metrics and VOR gain in detecting a vestibular stroke.

OBJECTIVE: A normal video Head Impulse Test is the gold standard in the emergency department to rule-in patients with an acute vestibular syndrome and a stroke. We aimed to compare the diagnostic accuracy of vHIT metrics regarding the vestibulo-ocular reflex gain and the corrective saccades in detecting vestibular strokes. METHODS: Prospective cross-sectional study (convenience sample) of patients presenting with acute vestibular syndrome in the emergency department of a tertiary referral centre between February 2015 and May 2020. We screened 1677 patients and enrolled 76 patients fulfilling the inclusion criteria of acute vestibular syndrome. All patients underwent video head impulse test with automated and manual data analysis. A delayed MRI served as a gold standard for vestibular stroke confirmation. RESULTS: Out of 76 patients, 52 were diagnosed with acute unilateral vestibulopathy and 24 with vestibular strokes. The overall accuracy of detecting stroke with an automated vestibulo-ocular reflex gain was 86.8%, compared to 77.6% for cumulative saccade amplitude and automatic saccade mean peak velocity measured by an expert and 71% for cumulative saccade amplitude and saccade mean peak velocity measured automatically. Gain misclassified 13.1% of the patients as false positive or false negative, manual cumulative saccade amplitude and saccade mean peak velocity 22.3%, and automated cumulative saccade amplitude and saccade mean peak velocity 28.9% respectively. CONCLUSIONS: We found a better accuracy of video head impulse test for the diagnosis of vestibular strokes when using the vestibulo-ocular reflex gain than using saccade metrics. Nevertheless, saccades provide an additional and important information for video head impulse test evaluation. The automated saccade detection algorithm is not yet perfect compared to expert analysis, but it may become a valuable tool for future non-expert video head impulse test evaluations.

Symptoms in unilateral vestibular hypofunction are associated with number of catch-up saccades and retinal error: results from the population-based KORA FF4 study.

Objective: The presence and intensity of symptoms vary in patients with unilateral vestibular hypofunction. We aimed to determine which saccadic and vestibulo-ocular reflex parameters best predict the presence of symptoms in unilateral vestibular hypofunction in order to better understand vestibular compensation and its implications for rehabilitation therapy. Methods: Video head impulse test data were analyzed from a subpopulation of 23 symptomatic and 10 currently symptom-free participants with unilateral vestibular hypofunction, embedded in the KORA (Cooperative Health Research in the Region of Augsburg) FF4 study, the second follow-up of the KORA S4 population-based health survey (2,279 participants). Results: A higher number of catch-up saccades, a higher percentage of covert saccades, and a larger retinal error at 200 ms after the onset of the head impulse were associated with relevant symptoms in participants with unilateral vestibular hypofunction (p = 0.028, p = 0.046, and p = 0.038, respectively). After stepwise selection, the number of catch-up saccades and retinal error at 200 ms remained in the final logistic regression model, which was significantly better than a null model (p = 0.014). Age, gender, saccade amplitude, saccade latency, and VOR gain were not predictive of the presence of symptoms. Conclusion: The accuracy of saccadic compensation seems to be crucial for the presence of symptoms in unilateral vestibular hypofunction, highlighting the role of specific gaze stabilization exercises in rehabilitation. Early saccades, mainly triggered by the vestibular system, do not seem to compensate accurately enough, resulting in a relevant retinal error and the need for more as well as more accurate catch-up saccades, probably triggered by the visual system.

Binocular video head impulse test: Normative data study.

Introduction: The video head impulse test (vHIT) evaluates the vestibulo-ocular reflex (VOR). It's usually recorded from only one eye. Newer vHIT devices allow a binocular quantification of the VOR. Purpose Aim: To investigate the advantages of simultaneously recorded binocular vHIT (bvHIT) to detect the differences between the VOR gains of the adducting and the abducting eye, to define the most precise VOR measure, and to assess gaze dys/conjugacy. We aimed to establish normative values for bvHIT adducting/abducting eye VOR gains and to introduce the VOR dysconjugacy ratio (vorDR) between adducting and abducting eyes for bvHIT. Methods: We enrolled 44 healthy adult participants in a cross-sectional, prospective study using a repeated-measures design to assess test-retest reliability. A binocular EyeSeeCam Sci 2 device was used to simultaneously record bvHIT from both eyes during impulsive head stimulation in the horizontal plane. Results: Pooled bvHIT retest gains of the adducting eye significantly exceeded those of the abducting eye (mean (SD): 1.08 (SD = 0.06), 0.95 (SD = 0.06), respectively). Both adduction and abduction gains showed similar variability, suggesting comparable precision and therefore equal suitability for VOR asymmetry assessment. The pooled vorDR here introduced to bvHIT was 1.13 (SD = 0.05). The test-retest repeatability coefficient was 0.06. Conclusion: Our study provides normative values reflecting the conjugacy of eye movement responses to horizontal bvHIT in healthy participants. The results were similar to a previous study using the gold-standard scleral search coil, which also reported greater VOR gains in the adducting than in the abducting eye. In analogy to the analysis of saccade conjugacy, we propose the use of a novel bvHIT dysconjugacy ratio to assess dys/conjugacy of VOR-induced eye movements. In addition, to accurately assess VOR asymmetry, and to avoid directional gain preponderance between adduction and abduction VOR-induced eye movements leading to monocular vHIT bias, we recommend using a binocular ductional VOR asymmetry index that compares the VOR gains of only the abduction or only the adduction movements of both eyes.

Assessment of vestibulo-ocular reflex and its adaptation during stop-and-go car rides in motion sickness susceptible passengers.

Motion sickness is a physiological condition that negatively impacts a person's comfort and will be an emerging condition in autonomous vehicles without proper countermeasures. The vestibular system plays a key role in the origin of motion sickness. Understanding the susceptibility and (mal) adaptive mechanisms of the highly integrated vestibular system is a prerequisite for the development of countermeasures. We hypothesize a differential association between motion sickness and vestibular function in healthy individuals with and without susceptibility for motion sickness. We quantified vestibular function by measuring the high-frequency vestibulo-ocular reflex (VOR) using video head impulse testing (vHIT) in 17 healthy volunteers before and after a 11 min motion sickness-inducing naturalistic stop-and-go car ride on a test track (Dekra Test Oval, Klettwitz, Germany). The cohort was classified as motion sickness susceptible (n = 11) and non-susceptible (n = 6). Six (out of 11) susceptible participants developed nausea symptoms, while a total of nine participants were free of these symptoms. The VOR gain (1) did not differ significantly between participant groups with (n = 8) and without motion sickness symptoms (n = 9), (2) did not differ significantly in the factor time before and after the car ride, and showed no interaction between symptom groups and time, as indicated by a repeated measures ANOVA (F(1,15) = 2.19, p = 0.16. Bayesian inference confirmed that there was "anecdotal evidence" for equality of gain rather than difference across groups and time (BF10 < 0.77). Our results suggest that individual differences in VOR measures or adaptation to motion sickness provocative stimuli during naturalistic stop-and-go driving cannot predict motion sickness susceptibility or the likelihood of developing motion sickness.

Smartphone video nystagmography using convolutional neural networks: ConVNG.

BACKGROUND: Eye movement abnormalities are commonplace in neurological disorders. However, unaided eye movement assessments lack granularity. Although videooculography (VOG) improves diagnostic accuracy, resource intensiveness precludes its broad use. To bridge this care gap, we here validate a framework for smartphone video-based nystagmography capitalizing on recent computer vision advances. METHODS: A convolutional neural network was fine-tuned for pupil tracking using > 550 annotated frames: ConVNG. In a cross-sectional approach, slow-phase velocity of optokinetic nystagmus was calculated in 10 subjects using ConVNG and VOG. Equivalence of accuracy and precision was assessed using the "two one-sample t-test" (TOST) and Bayesian interval-null approaches. ConVNG was systematically compared to OpenFace and MediaPipe as computer vision (CV) benchmarks for gaze estimation. RESULTS: ConVNG tracking accuracy reached 9-15% of an average pupil diameter. In a fully independent clinical video dataset, ConVNG robustly detected pupil keypoints (median prediction confidence 0.85). SPV measurement accuracy was equivalent to VOG (TOST p < 0.017; Bayes factors (BF) > 24). ConVNG, but not MediaPipe, achieved equivalence to VOG in all SPV calculations. Median precision was 0.30°/s for ConVNG, 0.7°/s for MediaPipe and 0.12°/s for VOG. ConVNG precision was significantly higher than MediaPipe in vertical planes, but both algorithms' precision was inferior to VOG. CONCLUSIONS: ConVNG enables offline smartphone video nystagmography with an accuracy comparable to VOG and significantly higher precision than MediaPipe, a benchmark computer vision application for gaze estimation. This serves as a blueprint for highly accessible tools with potential to accelerate progress toward precise and personalized Medicine.

Objective measurement of HINTS (Head Impulse, Nystagmus, Test of Skew) in peripheral vestibulopathy.

OBJECTIVE: To evaluate how often the positive sign of HINTS (Head-Impulse, Gaze Evoked Nystagmus, Test of Skew) appears in patients with acute peripheral vestibular lesion, HINTS findings were quantitatively measured and analyzed in patients with peripheral vestibulopathy accompanying spontaneous nystagmus. METHODS: HINTS was evaluated in 14 vertigo patients with spontaneous nystagmus. Horizontal vestibulo-ocular reflex (VOR) gain was measured using the video head impulse test (vHIT). To evaluate gaze-evoked nystagmus (GEN), slow-phase velocities at different points of lateral gaze were measured and plotted, then the slope and its inverse value, the neural integrator time constant, were calculated. Skew deviation was tested using anaglyph filters to simulate the alternate cover test, and the degree and latency of vertical eyeball deviation were measured. The ABCD2 score was calculated to evaluate the risk of stroke. RESULTS: Among 13 patients of peripheral vestibulopathy, 7 showed positive signs in HINTS (normal vHIT: 5, direction-changing GEN: 0, skew deviation: 3). One patient with a cerebellopontine angle tumor presented with both a peripheral and central pattern and showed positive HINTS findings (presence of direction-changing GEN). The mean VOR gain of patients with abnormal vHIT was 0.58±0.29 and 1.10±0.11 in the affected and contralateral side, respectively, while those in patients with normal vHIT were 1.04±0.21 and 1.13±0.12, respectively. The neural integrator time constant calculated from the mean slope of horizontal slow-phase velocity according to horizontal eye position was 42.9 s. The mean vertical eyeball deviation of patients with positive skew was 2.14±1.18° while uncovering the eye on the affected side, and -1.97±1.59° while uncovering the eye on the unaffected side. The median ABCD2 score of 14 patients was 2 (range, 1-3). CONCLUSIONS: HINTS findings were objectively measured in vertigo patients with spontaneous nystagmus. Although positive findings of HINTS have been recognized as a central sign, 54% (7/13) of cases with peripheral vestibulopathy showed positive HINTS signs. HINTS results should be interpreted carefully considering that a substantial proportion of peripheral vestibulopathy shows a positive HINTS sign.

Automated alternate cover test for 'HINTS' assessment: a validation study.

OBJECTIVE: The alternate cover test (ACT) in patients with acute vestibular syndrome is part of the 'HINTS' battery test. Although quantitative, the ACT is highly dependent on the examiner's experience and could theoretically vary greatly between examiners. In this study, we sought to validate an automated video-oculography (VOG) system based on eye tracking and dedicated glasses. METHODS: We artificially induced a vertical strabismus to simulate a skew deviation on ten healthy subjects, aged from 26 to 66, using different press-on Fresnel prisms on one eye while recording eye position with VOG of the contralateral eye. We then compared the system's performance to that of a blinded trained orthoptist using conventional, semi-quantitative method of skew measurement known as the alternate prism cover test (APCT) as a gold standard. RESULTS: We found a significant correlation between the reference APCT and the Skew VOG (Pearson's R2 = 0.606, p < 0.05). There was a good agreement between the two tests (intraclass correlation coefficient 0.852, 95 CI 0.728-0.917, p < 0.001). The overall accuracy of the VOG was estimated at 80.53% with an error rate of 19.46%. There was no significant difference in VOG skew estimations compared with the gold standard except for very small skews. CONCLUSIONS: VOG offers an objective and quantitative skew measurement and proved to be accurate in measuring vertical eye misalignment compared to the ACT with prisms. Precision was moderate, which mandates a sufficient number of tests per subject.

Acute vestibular syndrome: is skew deviation a central sign?

OBJECTIVE: Skew deviation results from a dysfunction of the graviceptive pathways in patients with an acute vestibular syndrome (AVS) leading to vertical diplopia due to vertical ocular misalignment. It is considered as a central sign, however, the prevalence of skew and the accuracy of its test is not well known . METHODS: We performed a prospective study from February 2015 until September 2020 of all patients presenting at our emergency department (ED) with signs of AVS. All patients underwent clinical HINTS and video test of skew (vTS) followed by a delayed MRI, which served as a gold standard for vestibular stroke confirmation. RESULTS: We assessed 58 healthy subjects, 53 acute unilateral vestibulopathy patients (AUVP) and 24 stroke patients. Skew deviation prevalence was 24% in AUVP and 29% in strokes. For a positive clinical test of skew, the cut-off of vertical misalignment was 3 deg with a very low sensitivity of 15% and specificity of 98.2%. The sensitivity of vTS was 29.2% with a specificity of 75.5%. CONCLUSIONS: Contrary to prior knowledge, skew deviation proved to be more prevalent in patients with AVS and occurred in every forth patient with AUVP. Large skew deviations (> 3.3 deg), were pointing toward a central lesion. Clinical and video test of skew offered little additional diagnostic value compared to other diagnostic tests such as the head impulse test and nystagmus test. Video test of skew could aid to quantify skew in the ED setting in which neurotological expertise is not always readily available.

Leukocyte chemotactic receptor Fpr1 protects against aging-related posterior subcapsular cataract formation.

Cataracts are a common consequence of aging; however, pathogenesis remains poorly understood. Here, we observed that after 3 months of age mice lacking the G protein-coupled leukocyte chemotactic receptor Fpr1 (N-formyl peptide receptor 1) began to develop bilateral posterior subcapsular cataracts that progressed to lens rupture and severe degeneration, without evidence of either systemic or local ocular infection or inflammation. Consistent with this, Fpr1 was detected in both mouse and human lens in primary lens epithelial cells (LECs), the only cell type present in the lens; however, expression was confined to subcapsular LECs located along the anterior hemispheric surface. To maximize translucency, LECs at the equator proliferate and migrate posteriorly, then differentiate into lens fiber cells by nonclassical apoptotic signaling, which results in loss of nuclei and other organelles, including mitochondria which are a rich source of endogenous N-formyl peptides. In this regard, denucleation and posterior migration of LECs were abnormal in lenses from Fpr1-/- mice, and direct stimulation of LECs with the prototypic N-formyl peptide agonist fMLF promoted apoptosis. Thus, Fpr1 is repurposed beyond its immunoregulatory role in leukocytes to protect against cataract formation and lens degeneration during aging.

Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease.

BACKGROUND: Neurological forms of Gaucher disease, the inherited disorder of ß-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with enzyme replacement therapy, however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of 'type 3' Gaucher disease. METHODS: We undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video-oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups. RESULTS: We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared a GBA1 variant. CONCLUSIONS: This striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.

Apoptotic and anti-proliferative effect of guanosine and guanosine derivatives in HuT-78 T lymphoma cells.

The effects of 100 µM of 3',5'-cGMP, cAMP, cCMP, and cUMP as well as of the corresponding membrane-permeant acetoxymethyl esters on anti-CD3-antibody (OKT3)-induced IL-2 production of HuT-78 cutaneous T cell lymphoma (Sézary lymphoma) cells were analyzed. Only 3',5'-cGMP significantly reduced IL-2 production. Flow cytometric analysis of apoptotic (propidium iodide/annexin V staining) and anti-proliferative (CFSE staining) effects revealed that 3',5'-cGMP concentrations > 50 µM strongly inhibited proliferation and promoted apoptosis of HuT-78 cells (cultured in the presence of αCD3 antibody). Similar effects were observed for the positional isomer 2',3'-cGMP and for 2',-GMP, 3'-GMP, 5'-GMP, and guanosine. By contrast, guanosine and guanosine-derived nucleotides had no cytotoxic effect on peripheral blood mononuclear cells (PBMCs) or acute lymphocytic leukemia (ALL) xenograft cells. The anti-proliferative and apoptotic effects of guanosine and guanosine-derived compounds on HuT-78 cells were completely eliminated by the nucleoside transport inhibitor NBMPR (S-(4-Nitrobenzyl)-6-thioinosine). By contrast, the ecto-phosphodiesterase inhibitor DPSPX (1,3-dipropyl-8-sulfophenylxanthine) and the CD73 ecto-5'-nucleotidase inhibitor AMP-CP (adenosine 5'-(α,ß-methylene)diphosphate) were not protective. We hypothesize that HuT-78 cells metabolize guanosine-derived nucleotides to guanosine by yet unknown mechanisms. Guanosine then enters the cells by an NBMPR-sensitive nucleoside transporter and exerts cytotoxic effects. This transporter may be ENT1 because NBMPR counteracted guanosine cytotoxicity in HuT-78 cells with nanomolar efficacy (IC50 of 25-30 nM). Future studies should further clarify the mechanism of the observed effects and address the question, whether guanosine or guanosine-derived nucleotides may serve as adjuvants in the therapy of cancers that express appropriate nucleoside transporters and are sensitive to established nucleoside-derived cytostatic drugs.

Real-space navigation testing differentiates between amyloid-positive and -negative aMCI.

OBJECTIVE: To distinguish between patients with amyloid-positive (A+) and -negative (A-) amnestic mild cognitive impairment (aMCI) by simultaneously investigating navigation performance, visual exploration behavior, and brain activations during a real-space navigation paradigm. METHODS: Twenty-one patients with aMCI were grouped into A+ (n = 11) and A- cases by amyloid-PET imaging and amyloid CSF levels and compared to 15 healthy controls. Neuropsychological deficits were quantified by use of the Consortium to Establish a Registry for Alzheimer's Disease-plus cognitive battery. All participants performed a navigation task in which they had to find items in a realistic spatial environment and had to apply egocentric and allocentric route planning strategies. 18F-fluorodeoxyglucose was injected at the start to detect navigation-induced brain activations. Subjects wore a gaze-controlled, head-fixed camera that recorded their visual exploration behavior. RESULTS: A+ patients performed worse during egocentric and allocentric navigation compared to A- patients and controls (p < 0.001). Both aMCI subgroups used fewer shortcuts, moved more slowly, and stayed longer at crossings. Word-list learning, figural learning, and Trail-Making tests did not differ in the A+ and A- subgroups. A+ patients showed a reduced activation of the right hippocampus, retrosplenial, and parietal cortex during navigation compared to A- patients (p < 0.005). CONCLUSIONS: A+ patients with aMCI perform worse than A- patients with aMCI in egocentric and allocentric route planning because of a more widespread impairment of their cerebral navigation network. Navigation testing in real space is a promising approach to identify patients with aMCI with underlying Alzheimer pathology.

Gentamicin vestibulotoxicity with modern systemic dosing regimens: a prospective study using video-oculography.

Objectives: To determine the incidence of gentamicin vestibulotoxicity with current dosing regimens, and to evaluate the feasibility of routine video-oculography on all patients given gentamicin. Materials and methods: In this prospective incidence study serial horizontal vestibulo-ocular reflex (HVOR) gain measurements were recorded using video-oculography on adult inpatients receiving intravenous gentamicin. The primary outcome was the proportion of patients developing impairment of their HVOR gain. Results: After exclusions, 42 patients were included in the analysis. Three patients (7.1%) developed asymptomatic vestibulotoxicity, exact 95% confidence interval 1.5-19.5%. In two of these patients the deficit resolved within several hours. No patients developed symptomatic vestibulotoxicity. There was no evidence for a generalised reduction in group HVOR gain with time. HVOR gain was not associated with total gentamicin dose, dynamic visual acuity or subjective imbalance. Conclusions and significance: Gentamicin may cause reversible, asymptomatic vestibulotoxicity. Video-oculography may be useful to monitor for vestibulotoxicity in patients treated with gentamcin; however, testing all patients routinely may be challenging.

Hydrolysis of the non-canonical cyclic nucleotide cUMP by PDE9A: kinetics and binding mode.

The non-canonical cyclic nucleotide cUMP and the phosphodiesterase PDE9A both occur in neuronal cells. Using HPLC-coupled tandem mass spectrometry, we characterized the kinetics of PDE9A-mediated cUMP hydrolysis. PDE9A is a low-affinity and high-velocity enzyme for cUMP (Vmax = ~ 6 µmol/min/mg; Km = ~ 401 µM). The PDE9 inhibitor BAY 73-6691 inhibited PDE9A-catalyzed cUMP hydrolysis (Ki = 590 nM). Docking studies indicate two H-bonds between the cUMP uridine moiety and Gln453/Asn405 of PDE9A. By contrast, the guanosine moiety of cGMP forms three H-bonds with Gln453. cCMP is not hydrolyzed at a concentration of 3 µM, but inhibits the PDE9A-catalyzed cUMP hydrolysis at concentrations of 100 µM or more. The probable main reason is that the cytosine moiety cannot act as H-bond acceptor for Gln453. A comparison of PDE9A with PDE7A suggests that the preference of the former for cGMP and cUMP and of the latter for cAMP and cCMP is due to stabilized alternative conformations of the side chain amide of Gln453 and Gln413, respectively. This so-called glutamine switch is known to be involved in the regulation of cAMP/cGMP selectivity of some PDEs.

Prolonged allocentric navigation deficits indicate hippocampal damage in TGA.

OBJECTIVE: To investigate long-term recovery of allocentric and egocentric spatial orientation as a sensitive marker for hippocampal and extrahippocampal network function in transient global amnesia (TGA). METHODS: A group of 18 patients with TGA performed an established real-space navigation paradigm, requiring allo- and egocentric spatial orientation abilities, 3 days (postacute stage) and 3 months (follow-up) after symptom onset. Visual exploration behavior and navigation strategy were documented by a gaze-controlled, head-fixed camera. Allo- and egocentric spatial orientation performance was compared to that of 12 age-matched healthy controls. Navigation-induced brain activations were measured using [18F]-fluorodeoxyglucose-PET in a subgroup of 8 patients in the postacute stage and compared to those of the controls. RESULTS: In the postacute stage, the patients navigated worse and had higher error rates than controls in allocentric (p = 0.002), but not in egocentric, route planning (p = 0.30), despite complete recovery of verbal (p = 0.58) and figural memory (p = 0.11). Until follow-up, allocentric navigation deficits improved, but higher error rates and reduced use of shortcuts persisted (p < 0.0001). Patients still exhibited relatively more fixations of unique landmarks during follow-up (p = 0.05). PET measurements during the postacute stage showed increased navigation-induced brain activations in the right hippocampus, bilateral retrosplenial, parietal, and mesiofrontal cortices, and cerebellar dentate nucleus in patients compared to controls (p < 0.005). CONCLUSIONS: Patients with TGA show selective and prolonged deficits of allocentric spatial orientation. Activations in right hippocampal and extrahippocampal hubs of the cerebral navigation network functionally substitute for the deficit in creating and updating the internal cognitive map in TGA.

Prevalence, Determinants, and Consequences of Vestibular Hypofunction. Results From the KORA-FF4 Survey.

Objective: Uni- or bilateral vestibular hypofunction (VH) impairs balance and mobility, and may specifically lead to injury from falls and to disability. The extent of this problem in the general population is still unknown and most likely to be underestimated. Objective of this study was to determine the prevalence, determinants, and consequences of VH in the general population. Methods: Data originates from the cross-sectional second follow-up (FF4) in 2013/14 of the KORA (Cooperative Health Research in the Region of Augsburg)-S4 study (1999-2001) from Southern Germany. This was a random sample of the target population consisting of all residents of the region aged 25-74 years in 1999. We included all participants who reported moderate or severe vertigo or dizziness during the last 12 months and a random sub-sample of participants representative for the general population without vertigo or dizziness during the last 12 months were tested. VH was assessed with the Video-Head Impulse Test (vHIT). Trained examiners applied high-acceleration, small-amplitude passive head rotations ("head impulses") to the left and right in the plane of the horizontal semicircular canals while participants fixated a target straight ahead. During head impulses, head movements were measured with inertial sensors, eye movements with video-oculography (EyeSeeCam vHIT). Results: A total of 2,279 participants were included (mean age 60.8 years, 51.6% female), 570 (25.0%) with moderate or severe vertigo or dizziness during the last 12 months. Of these, 450 were assessed with vHIT where 26 (5.8%) had unilateral VH, and 16 (3.6%) had bilateral VH. Likewise, 190 asymptomatic participants were tested. Of these 5 (2.6%) had unilateral VH, and 2 (1.1%) had bilateral VH. Prevalence of uni- or bilateral VH among tested symptomatic participants was 2.4% in those < 48 years, and 32.1% in individuals aged 79 and over. Age-adjusted prevalence was 6.7% (95% CI 4.8%; 8.6%). VH was associated with worse health, falls, hearing loss, hearing impairment, and ear pressure. Conclusion: VH may affect between 53 and 95 million adults in Europe and the US. While not all affected persons will experience the full spectrum of symptoms and consequences, adequate diagnostic and therapeutic measures should become standard of care to decrease the burden of disease.

Usability of the Video Head Impulse Test: Lessons From the Population-Based Prospective KORA Study.

Objective: The video head impulse test (vHIT) has become a common examination in the work-up for dizziness and vertigo. However, recent studies suggest a number of pitfalls, which seem to reduce vHIT usability. Within the framework of a population-based prospective study with naïve examiners, we investigated the relevance of previously described technical mistakes in vHIT testing, and the effect of experience and training. Methods: Data originates from the KORA (Cooperative Health Research in the Region of Augsburg) FF4 study, the second follow-up of the KORA S4 population-based health survey. 681 participants were selected in a case-control design. Three examiners without any prior experience were trained in video head impulse testing. VHIT quality was assessed weekly by an experienced neuro-otologist. Restrictive mistakes (insufficient technical quality restricting interpretation) were noted. Based on these results, examiners received further individual training. Results: Twenty-two of the 681 vHITs (3.2%) were not interpretable due to restrictive mistakes. Restrictive mistakes could be grouped into four categories: slippage, i.e., goggle movement relative to the head (63.6%), calibration problems (18.2%), noise (13.6%), and low velocity of the head impulse (4.6%). The overall rate of restrictive mistakes decreased significantly during the study (12% / examiner within the first 25 tested participants and 2.1% during the rest of the examinations, p < 0.0001). Conclusion: Few categories suffice to explain restrictive mistakes in vHIT testing. With slippage being most important, trainers should emphasize the importance of tight goggles. Experience and training seem to be effective in improving vHIT quality, leading to high usability.

Head-Movement-Emphasized Rehabilitation in Bilateral Vestibulopathy.

Objective: Although there is evidence that vestibular rehabilitation is useful for treating chronic bilateral vestibular hypofunction (BVH), the mechanisms for improvement, and the reasons why only some patients improve are still unclear. Clinical rehabilitation results and evidence fromeye-head control in vestibular deficiency suggest that headmovement is a crucial element of vestibular rehabilitation. In this study, we assess the effects of a specifically designed head-movement-based rehabilitation program on dynamic vision, and explore underlying mechanisms. Methods: Two adult patients (patients 1 and 2) with chronic BVH underwent two 4-week interventions: (1) head-movement-emphasized rehabilitation (HME) with exercises based on active head movements, and (2) eye-movement-only rehabilitation (EMO), a control intervention with sham exercises without head movement. In a double-blind crossover design, the patients were randomized to first undergo EMO (patient 1) and-after a 4-week washout-HME, and vice-versa (patient 2). Before each intervention and after a 4-week follow-up patients' dynamic vision, vestibulo-ocular reflex (VOR) gain, as well as re-fixation saccade behavior during passive headmotion were assessed with the head impulse testing device-functional test (HITD-FT). Results: HME, not EMO, markedly improved perception with dynamic vision during passive head motion (HITD-FT score) increasing from 0 to 60% (patient 1) and 75% (patient 2). There was a combination of enhanced VOR, as well as improved saccadic compensation. Conclusion: Head movement seems to be an important element of rehabilitation for BVH. It improves dynamic vision with a combined VOR and compensatory saccade enhancement.