@misc{DonaldTanChakrapanietal., author = {Donald, Aimee and Tan, Chong Y. and Chakrapani, Anupam and Hughes, Derralyn A. and Sharma, Reena and Cole, Duncan and Bardins, Stanislav and Gorges, Martin and Jones, Simon A. and Schneider, Erich}, title = {Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease}, series = {Orphanet journal of rare diseases : OJRD}, volume = {15}, journal = {Orphanet journal of rare diseases : OJRD}, issn = {1750-1172}, doi = {10.1186/s13023-020-01637-9}, pages = {12}, abstract = {Background: Neurological forms of Gaucher disease, the inherited disorder of β-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.}, language = {en} } @misc{BelyakovaBodinaRatanovSchneideretal., author = {Belyakova-Bodina, Alexandra and Ratanov, Mikhail and Schneider, Erich and Seliverstov, Yury and Nuzhnyi, Evgenii and Klyushnikov, Sergey and Broutian, Amayak}, title = {Uncovering bilateral vestibulopathy in patients with SANDO syndrome caused by mutations in POLG gene: a case series}, series = {Journal of Neurology}, volume = {268}, journal = {Journal of Neurology}, number = {10}, issn = {1432-1459}, doi = {10.1007/s00415-021-10650-2}, pages = {3909 -- 3912}, abstract = {The triad of sensory ataxic neuropathy, dysarthria, and ophthalmoparesis (SANDO) comprise a distinct phenotype of rare mitochondrial disease. It is caused mainly by mitochondrial DNA depletion and deletions due to mutations in the nuclear genes, with POLG being one of the most common ones [1]. In SANDO syndrome, balance and gait disturbances have traditionally been attributed to sensory ataxic neuropathy and, in some patients, to cerebellar ataxia and/or limb weakness [2, 3]. However, there has been a report of bilateral vestibulopathy (BV) in a patient with SANDO caused by mutations in the POLG gene [4]. We present five patients with SANDO due to POLG gene mutations, whose vestibular and oculomotor function were assessed with video-oculography (VOG)}, language = {en} } @misc{MorrisonKerkeniKordaetal., author = {Morrison, Miranda and Kerkeni, Hassen and Korda, Athanasia and R{\"a}ss, Simone and Caversaccio, Marco Domenico and Abegg, Mathias and Schneider, Erich and Mantokoudis, Georgios}, title = {Automated alternate cover test for 'HINTS' assessment: a validation study}, series = {European archives of oto-rhino-laryngology and head \& neck}, journal = {European archives of oto-rhino-laryngology and head \& neck}, issn = {1434-4726}, doi = {10.1007/s00405-021-06998-w}, pages = {2873 -- 2879}, abstract = {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.}, language = {en} } @misc{KordaZamaroWagneretal., author = {Korda, Athanasia and Zamaro, Ewa and Wagner, Franca and Morrison, Miranda and Schneider, Erich and Caversaccio, Marco Domenico and Sauter, Thomas C. and Mantokoudis, Georgios}, title = {Acute vestibular syndrome: is skew deviation a central sign?}, series = {Journal of Neurology}, volume = {269}, journal = {Journal of Neurology}, number = {3}, issn = {1432-1459}, doi = {10.1007/s00415-021-10692-6}, pages = {1396 -- 1403}, abstract = {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.}, language = {en} } @misc{SpiegelClaassenTeufeletal., author = {Spiegel, Rainer and Claassen, Jens and Teufel, Julian and Bardins, Stanislav and Schneider, Erich and Lehrer, Nicole and Jahn, Klaus and Anciaes da Silva, F{\´a}bio and Hahn, Ales and Farahmand, Parvis and Brandt, Thomas and Strupp, Michael and Kalla, Roger}, title = {Resting in darkness improves downbeat nystagmus: evidence from an observational study}, series = {Annals of the New York Academy of Sciences}, volume = {1375}, journal = {Annals of the New York Academy of Sciences}, number = {1}, issn = {1749-6632}, doi = {10.1111/nyas.13172}, pages = {66 -- 73}, abstract = {Resting in an upright position during daytime decreases downbeat nystagmus (DBN). When measured in brightness only, that is, without intermitting exposure to darkness, it does not make a significant difference whether patients have previously rested in brightness or in darkness. In real-world scenarios, people are often exposed to brightness and darkness intermittently. The aim of this study was to analyze whether resting in brightness or resting in darkness was associated with a lower post-resting DBN after intermitting exposures to brightness and darkness. Eight patients were recorded with three-dimensional video-oculography in brightness and darkness conditions, each following two 2-h resting intervals under either brightness or darkness resting conditions. The dependent variable was DBN intensity, measured in mean slow phase velocity. A repeated measures ANOVA with the factors measurement condition (brightness vs. darkness), resting condition (brightness vs. darkness), and time (after first vs. second resting interval) showed a significant effect for the factor resting condition, where previous resting in darkness was associated with a significantly lower DBN relative to previous resting in brightness (P < 0.01). The clinical relevance is to advise patients with DBN to rest in darkness.}, language = {en} } @misc{StriteskaChovanecSteinmetzeretal., author = {Striteska, Maja and Chovanec, Martin and Steinmetzer, Tobias and Chrobok, Viktor and Profant, Oliver and Schneider, Erich and Kremlacek, Jan and Valis, Martin}, title = {Binocular video head impulse test: Normative data study}, series = {Frontiers in Neurology}, volume = {14}, journal = {Frontiers in Neurology}, issn = {1664-2295}, doi = {10.3389/fneur.2023.1153102}, abstract = {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.}, language = {en} } @misc{FriedrichSchneiderBuerkleinetal., author = {Friedrich, Maximilian U. and Schneider, Erich and Buerklein, Miriam and Taeger, Johannes and Hartig, Johannes and Volkmann, Jens and Peach, Robert and Zeller, Daniel}, title = {Smartphone video nystagmography using convolutional neural networks: ConVNG}, series = {Journal of Neurology}, volume = {270}, journal = {Journal of Neurology}, issn = {1432-1459}, doi = {10.1007/s00415-022-11493-1}, pages = {2518 -- 2530}, abstract = {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.}, language = {en} } @misc{RamaioliSteinmetzerBrietzkeetal., author = {Ramaioli, Cecilia and Steinmetzer, Tobias and Brietzke, Adrian and Meyer, Paul and Pham Xuan, Rebecca and Schneider, Erich and Gorges, Martin}, title = {Assessment of vestibulo-ocular reflex and its adaptation during stop-and-go car rides in motion sickness susceptible passengers}, series = {Experimental Brain Research}, volume = {241}, journal = {Experimental Brain Research}, number = {6}, issn = {1432-1106}, doi = {10.1007/s00221-023-06619-4}, pages = {1523 -- 1531}, abstract = {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.}, language = {en} } @misc{DongHanSchneiderSangYeonetal., author = {Dong-Han, Lee and Schneider, Erich and Sang-Yeon, Lee and Kim, Ji-Soo and Koo, Ja-Won}, title = {Objective measurement of HINTS (Head Impulse, Nystagmus, Test of Skew) in peripheral vestibulopathy}, series = {Auris Nasus Larynx}, volume = {49}, journal = {Auris Nasus Larynx}, number = {6}, issn = {1879-1476}, doi = {10.1016/j.anl.2022.03.003}, pages = {938 -- 949}, abstract = {ABSTRACT 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.}, language = {en} } @misc{AubeleGrillEggertetal., author = {Aubele, Maria and Grill, Eva and Eggert, Thomas and Schneider, Erich and Strobl, Ralf and Jahn, Klaus and M{\"u}ller, Martin and Holle, Rolf and Linkohr, Birgit and Heier, Margit and Ladwig, Karl-Heinz and Lehnen, Nadine}, title = {Symptoms in unilatral vestibular hypofunction are associated with number of catch-up saccades and retinal errors: results from the population-based KORA FF4study}, series = {Frontiers in Neurology}, volume = {2023}, journal = {Frontiers in Neurology}, number = {14}, issn = {1664-2295}, pages = {8}, abstract = {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.}, language = {en} }