BackgroundVestibular migraine (VM), the most frequent episodic vertigo, is difficult to distinguish from Ménière’s disease (MD) because reliable biomarkers are missing. The classical proof of MD was an endolymphatic hydrops (EH). However, a few intravenous gadolinium-enhanced MRI studies of the inner ear (iMRI) also revealed an EH in VM. The major questions were the frequency and distribution characteristics of EH in VM for diagnostic use.MethodsIn a prospective case-control study of 200 participants, 75 patients with VM (49 females; mean age 46 years) and 75 with MD (36 females; mean age 55 years), according to the Bárány and International Headache Society, and 50 age-matched participants with normal vestibulocochlear testing (HP), were enrolled. Analyses ofiMRI of the endolymphatic space included volumetric quantification, stepwise regression, correlation with neurotological parameters and support vector machine classification.ResultsEH was maximal in MD (80%), less in VM (32%) and minimal in HP (22%). EH was milder in VM (mean grade 0.3) compared with MD (mean grade 1.3). The intralabyrinthine distribution was preferably found in the vestibulum in VM, but mainly in the cochlea in MD. There was no interaural lateralisation of EH in VM but in the affected ear in MD. The grade of EH in the vestibulum was correlated in both conditions with the frequency and duration of the attacks.ConclusionThree features of theiMRI evaluation were most supportive for the diagnosis of VM at group and individual levels: (1) the bilateral manifestation, (2) the low-grade EH and (3) the intraaural distribution.

Abstract Spatial normalization of multisubject inner ear imaging data is challenging, due to both substantial intraindividual differences and the small size of the organ compared to other intracranial structures. Automatic whole brain co-registration to standard space can only roughly co-align the peripheral vestibular endorgan, and complemental manual registration is highly time-consuming. Here, we compared the accuracy of four geometry-maintaining co-registration methods (one semi-manual method and three automatic methods). High-resolution structural T2-MRI of 153 inner ears from patients and healthy participants were co-registered to an inner-ear atlas. The semi-manual method used a three-point landmark-based approach (3P), two automatic methods were based on unassisted standard algorithms (Advanced Normalization Tools (ANTs), Elastix (EL)), while the fourth automatic method utilized a volumetrically dilated, atlas-based mask (thick inner ear, TIE) for probabilistic inner ear masking. Registration accuracy was evaluated by neurotologists blinded to the respective registration paradigm, and the resulting median volumes were quantified using colocalization analyses. The mask-aided automatic approach showed the best ratings, followed by the semi-manual three-point landmark-based registration (mean ratings (lower: better) TIE 2.21 ± 1.15; 3P 2.58 ± 0.61; EL 3.42 ± 1.06; ANTs 3.49 ± 1.26). The semi-manual method had the lowest rate of insufficient registrations, followed by TIE (3P: 3.70%; TIE: 8.28%; EL: 22.66%; ANTs: 27.02%). TIE showed the highest colocalization metrics with the atlas. Only TIE and 3P allowed for sufficient semicircular canal visualization in method-wise average volumes. Overall, geometry-preserving spatial normalization of multisubject inner ear imaging data is possible and could allow groupwise examinations of the bony labyrinth or temporal bone morphology in the future.

BackgroundPersistent Postural-Perceptual Dizziness (PPPD) is a frequent chronic functional disorder that manifests with dizziness, unsteadiness, or non-spinning vertigo present for at least 3 months. Characteristic provocation factors are moving or complex visual stimuli and exclusion of organic diseases. To assess the severity and impact of PPPD, Japanese researchers developed the Niigata PPPD Questionnaire (NPQ). The study's aim was to evaluate the concurrent construct validity and reliability [including test-retest reliability, internal consistency, standard error of measurement (SEM), and minimal detectable change (MDC)] of the German version of the NPQ (12 items) and its revised version, NPQ-R, which contains 19 items addressing additional symptoms and symptom behavior.MethodsThe Swiss Reha Rheinfelden and the German Center for Vertigo and Balance Disorders included 265 PPPD patients (mean age 50.2 ± 16.8 years, disease duration 46.3 ± 76.6 months). Patients completed the NPQ and the NPQ-R (twice), the DHI and potentially related constructs: anxiety (ABC-Scale, VSS), depression (HADS), and general health (SF-36) once. To assess the questionnaires' reliability and validity, several statistical measures were calculated, including Spearman's rank correlation coefficients, Intraclass Correlation Coefficients (ICC2, 1), Cronbach's alpha, SEM, and MDC.ResultsOn average, patients scored 29.9 ± 13.2 for NPQ and 52.3 ± 19.6 for NPQ-R. Correlations between NPQ/NPQ-R and (1) disease-specific questionnaires were rs= 0.712 and rs= 0.752 (DHI), rs=0.426 and rs= 0.0.462 (VSS-V), rs= -0.500 and rs= -0.545 (ABC-Scale), (2) anxiety-specific subscales rs = 0.394 and rs = 0.430 (VSS-A) and rs= 0.354 and rs= 0.430 (HADS-A), (3) depression-related subscales rs=0.438 and rs= 0.487 (HADS-D), and (4) general health rs ranged between rs= -0.216 and −0.578 (all SF-36 subscales). Internal consistency, test-retest reliability, SEM and MDC calculated for NPQ/NPQ-R were α = 0.88/α = 0.91, ICC=0.83 (CI 0.77 to 0.0.87), SEM 5.55/8.37, and MDC 15/23 points.ConclusionThe German versions of NPQ and NPQ-R are valid and reliable patient-reported outcome measures for assessing PPPD, demonstrating satisfactory psychometric measurement properties including convergent construct validity and reliability parameters: internal consistency, test-retest reliability, SEM, and MDC as an evaluative measure. The NPQ-R, with its additional subscales addressing associated symptoms and symptom behavior, represents both the patient and clinician perspective on PPPD-specific problems. Therefore, we recommend utilizing the NPQ-R for a comprehensive assessment of PPPD.

AbstractBackgroundUni‐ or bilateral peripheralvestibular impairment causes objective spatial orientation deficits, which can be measured using pen‐and‐paper‐tests or sensorimotor tasks (navigation or pointing). For patients’ subjective orientation abilities, questionnaires are commonly used (e.g., Santa Barbara sense of direction scale [SBSODS]). However, the relationship between subjective assessment of spatial skills and objective vestibular function has only been scarcely investigated.MethodsA total of 177 patients (mean age 57.86 ± 17.53 years, 90 females) who presented in our tertiary Center for Vertigo and Balance Disorders underwent neuro‐otological examinations, including bithermal water calorics, video head impulse test (vHIT), and testing of the subjective visual vertical (SVV), and filled out the SBSODS (German version). Correlation analyses and linear multiple regression model analyses were performed between vestibular test results and self‐assessment scores. Additionally, groupwise vestibular function for patients with low, average, and high self‐report scores was analyzed.ResultsForty‐two patients fulfilled the diagnostic criteria for bilateral vestibulopathy, 93 for chronic unilateral vestibulopathy (68 unilateral caloric hypofunction and 25 isolated horizontal vestibulo‐ocular reflex deficits), and 42 patients had normal vestibular test results. SBSODS scores showed clear sex differences with higher subjective skill levels in males (mean score males: 4.94 ± 0.99, females 4.40 ± 0.94; Student's t‐test: t‐3.78, p < .001***). No stable correlation between objective vestibular function and subjective sense of spatial orientation was found. A multiple linear regression model could not reliably explain the self‐reported variance. The three patient groups with low, average, and high self‐assessment‐scores showed no significant differences of vestibular function.ConclusionSelf‐reported assessment of spatial orientation does not robustly correlate with objective peripheral vestibular function. Therefore, other methods of measuring spatial skills in real‐world and virtual environments are required to disclose orientation deficits due to vestibular hypofunction.

An earlier observational study described selected patients with acute neck pain syndrome, who experienced short bursts of cervical vertigo elicited by rapid head movements. The current study on a larger cohort of 20 patients with chronic or frequently recurring neck pain syndrome and age-matched controls focused on two major questions: (1) Can head movements in subjects with exacerbations of neck pain and restrictions of neck mobility also elicit bursts of vertigo? (2) What is the impact on postural balance measured by analysis of body sway and locomotion? A detailed questionnaire was applied, posture and gait were evaluated by use of instrumented posturography—and gait analysis with and without slow or rapid horizontal head rotations in the yaw plane with and without sight/visual input. All patients reported some or frequent episodes of dizziness in the range of seconds only elicited by rapid, not by slow head movements. Postural sway in patients was unremarkable in undisturbed conditions without head movements, but specifically increased by rapid but not slow head turns. The latter is best explained by the lack of continuous control of velocity and amplitude of saccadic head movements. Gait analysis revealed a slowed and cautious gait pattern already at undisturbed condition that was even exaggerated during rapid head turns. These observations demonstrate that chronic or recurrent neck pain is associated with episodic experiences of dizziness and above results in both chronic and episodic alterations of stance and gait that resemble those described for patients with phobic postural vertigo/persistent postural perceptual dizziness, a functional gait disorder.

Background Deficits in spatial memory, orientation, and navigation are often neglected early signs of cognitive impairment or loss of vestibular function. Real-world navigation tests require complex setups. In contrast, simple pointing at targets in a three-dimensional environment is a basic sensorimotor ability which provides an alternative measure of spatial orientation and memory at bedside. The aim of this study was to test the reliability of a previously established 3D-Real-World Pointing Test (3D-RWPT) in patients with cognitive impairment due to different neurodegenerative disorders, bilateral vestibulopathy, or a combination of both compared to healthy participants. Methods The 3D-RWPT was performed using a static array of targets in front of the seated participant before and, as a transformation task, after a 90-degree body rotation around the yaw-axis. Three groups of patients were enrolled: (1) chronic bilateral vestibulopathy (BVP) with normal cognition ( n = 32), (2) cognitive impairment with normal vestibular function ( n = 28), and (3) combined BVP and cognitive impairment ( n = 9). The control group consisted of age-matched participants (HP) without cognitive and vestibular deficits ( n = 67). Analyses focused on paradigm-specific mean angular deviation of pointing in the azimuth (horizontal) and polar (vertical) spatial planes, of the preferred pointing strategy (egocentric or allocentric), and the resulting shape configuration of the pointing array relative to the stimulus array. Statistical analysis was performed using age-corrected ANCOVA-testing with Bonferroni correction and correlation analysis using Spearman’s rho. Results Patients with cognitive impairment employed more egocentric pointing strategies while patients with BVP but normal cognition and HP used more world-based solutions (pBonf 5.78 × 10-3**). Differences in pointing accuracy were only found in the azimuth plane, unveiling unique patterns where patients with cognitive impairment showed decreased accuracy in the transformation tasks of the 3D-RWPT (pBonf < 0.001***) while patients with BVP struggled in the post-rotation tasks (pBonf < 0.001***). Overall azimuth pointing performance was still adequate in some patients with BVP but significantly decreased when combined with a cognitive deficit. Conclusion The 3D-RWPT provides a simple and fast measure of spatial orientation and memory. Cognitive impairment often led to a shift from world-based allocentric pointing strategy to an egocentric performance with less azimuth accuracy compared to age-matched controls. This supports the view that cognitive deficits hinder the mental buildup of the stimulus pattern represented as a geometrical form. Vestibular hypofunction negatively affected spatial memory and pointing performance in the azimuth plane. The most severe spatial impairments (angular deviation, figure frame configuration) were found in patients with combined cognitive and vestibular deficits.

BackgroundSpatial memory and orientation deficits often precede cognitive impairment in incipient dementia, e.g., Alzheimer’s disease. Therefore, early diagnosis of spatial impairment may be crucial to the initiation of an adequate therapeutic intervention. Subjective tests, such as spatial anxiety and spatial discomfort questionnaires, and objective tests in the form of quantitative measures of orientation, are available. In these tests, vestibular hypofunction has often been neglected as a potential confounder. The major research question in this study was how self-assessed questionnaires correlate with the data from objective measures in participants with proven normal vestibular function.MethodsA heterogeneous group of 135 participants (72 females, 63 males, mean age 62.75 ± 14.46 years) from a tertiary center for vertigo and balance disorders consisting of two cohorts, with (n = 49) and without (n = 86) cognitive deficits in a screening test (MoCA), was examined (a) with a newly introduced inventory for subjective spatial discomfort (Extended Inventory for Spatial Orientation Discomfort, EISOD), (b) a well-established questionnaire for subjective spatial skills (Santa Barbara Sense of Direction Scale, SBSODS), and (c) the objective three-dimensional real-world pointing task (3D-RWPT) before and after horizontal body rotations. In all patients, acute central or peripheral vestibular deficits were ruled out by neuro-orthoptics, bithermal water calorics and video head impulse testing.ResultsSelf-assessed spatial orientation discomfort (EISOD) correlated with the amount of spatial impairment in the 3D-RWPT for both cohorts. The cognitively impaired patients showed significantly higher levels of spatial discomfort (i.e., lower scores; Welch’s t-test t-2.58, p < 0.01, Cohen’s d − 0.46), and higher angular deviations in the (cognitively demanding) transformation paradigm of the 3D-RWPT (t 2.37, p 0.02, Cohen’s d 0.44). They preferred retinotopic/egocentric spatial encoding strategies in the pointing task (Welch’s t-test t-2.61, p < 0.01, Cohen’s d − 0.47). In contrast, the self-report of spatial abilities (SBSODS) yielded no significant group differences (t − 1.66, p 0.10) and was not reliably associated with objective accuracy in the pointing task.ConclusionIn patients without vestibular deficits, subjective spatial discomfort (EISOD) correlated with the accuracy in an objective 3D-pointing task for both cohorts, and higher discomfort was associated with more severe cognitive impairment. EISOD-scores showed higher correlation indices than a self-report of spatial skills using the SBSODS. When investigating spatial abilities in patients with suspected cognitive impairment, it appears reasonable that both subjective spatial discomfort, subjective spatial abilities, and objective spatial measures should be combined. Future research in patients with vestibular dysfunction is needed to understand the role of vestibular deficits for the development of spatial orientation discomfort.

Abstract Background Deficits in spatial memory are often early signs of neurological disorders. Here, we analyzed the geometrical configuration of 2D-projections of pointing performances to a memorized array of spatially distributed targets with respect to gender differences in healthy participants and patients with cognitive impairment. Methods 56 right-handed healthy participants (28 female, mean age 48.89 ± 19.35 years) and 22 right-handed patients with cognitive impairment (12 female, mean age 71.73 ± 7.41 years) underwent a previously validated 3D-real-world pointing test (3D-RWPT). Participants were shown a 9-dot target matrix and afterwards asked to point towards each target with closed eyes in different body positions relative to the matrix. Two-dimensional projections of these pointing vectors were then quantified using morphological analyses. Results Shape configurations in healthy volunteers largely reflected the real-world target pattern with gender-dependent differences (ANCOVA area difference male/female = 38350.43, pbonf=3.69x10− 3**). Patients with cognitive impairment showed impaired rectangularity and made more large-scale errors, resulting in decreased overall average diameters and solidity (ANCOVA diameter difference normal cognition/cognitive impairment = 31.22, pbonf=3.19x10− 3**; solidity difference = 0.07, pbonf=6.76x10− 3**). Conclusion Shape configuration analysis of the 3D-RWPT target set by morphological properties appears to be a suitable holistic measure of spatial performance, differentiating sex effects and cognitive impairment when analyzed by group- and paradigm-wise averages.

Objective: To compare the efficacy of the new SemontPLUS maneuver (SM+) with the Epley maneuver (EM) in patients with posterior canal benign paroxysmal positional vertigo (pc-BPPV canalithiasis). Background: In a previous study we demonstrated that the SM+ is superior to the regular SM. Since other studies showed that the regular SM and the Epley maneuver (EM) are equally effective, we hypothezised that the SM+ is more effective than the EM for the treatment of the posterior canal BPPV canalithiasis. Design/Methods: In a prospective multinational (Germany, Italy, Belgium) randomized treatment trial, patients with proven posterior canal BPPV canalithiasis – according to the diagnostic criteria of the International Classification of Vestibular Disorders – were randomly assigned (1:1) to "SM+" or EM. The SM+ is characterized by an overextension of the head/body by at least 60° below earth horizontal line during step 2 of the maneuver. The first three maneuvers were performed by the physician. The patients were then instructed on how to do the self-maneuvers which they perform three times in the morning, three times at noon and three times at night. Each morning after the first maneuver of each day the patient documented in a standardized evaluation sheet whether vertigo occurred. The primary endpoint was: "How long (in days) does it take until no attacks can be induced "in the morning" by the maneuvers?" Results: 195 patients were finally analyzed. For the EM it took a mean of 3.34 days (SD 3.6) and a median 1 day for recovery. F or the SM+ it took a mean of 1.96 days (SD 1.6) and a median 1 day for recovery. Statistical analysis with the two-sided Mann-Whitney-u-test revealed a P value of 0.012. Conclusions: This prospective tri-national randomized trial shows that the SM+ maneuver is superior to the EM in terms of the time it takes until recovery. Disclosure: Dr. Strupp has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for IntraBio. Dr. Strupp has received personal compensation in the range of $0-$499 for serving as a Consultant for AurisMedical. Dr. Strupp has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer. Dr. Strupp has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers. Dr. Strupp has stock in IntraBio. Dr. Vinck has nothing to disclose. Otmar Bayer has nothing to disclose. Dr. Goldschagg has received personal compensation in the range of $500-$4,999 for serving as a Consultant for IntraBio. Mr. Gerb has nothing to disclose. Mr. Mavrodiev has nothing to disclose. Marco Mandala has nothing to disclose.

Original texts and expert translations from various ancient cultures covering a time span from the 2nd millennium BC to the ninth century AD were searched for historical observations of involuntary eye movements. Abnormal, spontaneous eye movements are an easily recognisable neuro-ophthalmological symptom that can be both congenital and acquired. Ocular oscillations termed 'hippos' by Hippocrates (460-370BC) and Galenos (129-216AD) are synonymous with nystagmus, a term first introduced in the eighteenth century. The original description of hippos suggests an innate onset, which retrospectively can be related to either congenital (infantile) nystagmus or continuous involuntary eye movements of the blind. Other descriptions of abnormal involuntary eye movements with different beating directions, possibly associated with vertigo, seizures or ear symptoms and their impact on patients' quality of life (e.g. oscillopsia, blurred vision) are preserved in many fragmentary ancient documents including papyrus scrolls and stone tablets from Egypt, Mesopotamia, India, China, Greece, Rome and the Middle East. Although the sparse original descriptions of the direction and type of eye movements may inspire daring medical interpretations, caution is required when attempting to assign them to distinct nystagmus forms according to our current clinical classification of ocular motor disorders.

In a retrospective study, the data of direction-dependent deviations in dynamic subjective visual vertical (SVV) testing were analysed in 1811 dizzy patients (174 benign paroxysmal positional vertigo, 99 unilateral vestibulopathy, 67 bilateral vestibulopathy, 151 Menière’s disease, 375 vestibular migraine, 82 cerebellar disorder, 522 functional dizziness, 341 unclear diagnosis) and in 59 healthy controls. Major findings were (i) a significant gender difference with higher directional deviations in females over the entire range of age, (ii) a significant increase of directional deviations with increasing age for both genders and in all disease subgroups as well as in healthy controls, and (iii) a lack of significant difference of directional deviations between all tested diseases. Thus, the data allow no recommendation for performing additional angular deviation analysis in dynamic SVV testing as part of routine clinical management of dizzy patients. However, as shown in earlier longitudinal studies, it still appears reasonable that dynamic SVV in acute rather than chronic vestibular disorders may provide a useful instrument for the monitoring of acute unilateral vestibular tonus imbalances in the course of the disease.

Importance:Questions remain concerning treatment efficacy for the common condition of benign paroxysmal positional vertigo (BPPV). Objective:To compare the effectiveness of the Semont-plus maneuver (SM-plus) and the Epley maneuver (EM) for treatment of posterior canal benign paroxysmal positional vertigo (pcBPPV) canalolithiasis. Design, Setting, and Participants:This prospective randomized clinical trial was performed at 3 national referral centers (in Munich, Germany; Siena, Italy; and Bruges, Belgium) over 2 years, with a follow-up to 4 weeks after the initial examination. Recruitment took place from June 1, 2020, until March 10, 2022. Patients were selected randomly during routine outpatient care after being referred to 1 of the 3 centers. Two hundred fifty-three patients were assessed for eligibility. After consideration of the exclusion criteria as well as informed consent, 56 patients were excluded and 2 declined to participate, with 195 participants included in the final analysis. The analysis was prespecified and per-protocol. Interventions:After being randomized to the SM-plus or the EM group, patients received 1 initial maneuver from a physician, then subsequently performed self-maneuvers at home 3 times in the morning, 3 times at noon, and 3 times in the evening. Main Outcome and Measures:Patients had to document whether they could provoke positional vertigo every morning. The primary end point was the number of days until no positional vertigo could be induced on 3 consecutive mornings. The secondary end point was the effect of the single maneuver performed by the physician. Results:Of the 195 participants included in the analysis, the mean (SD) age was 62.6 (13.9) years, and 125 (64.1%) were women. The mean (SD) time until no positional vertigo attacks could be induced in the SM-plus group was 2.0 (1.6) days (median, 1 [range, 1-8] day; 95% CI, 1.64-2.28 days); in the EM group, 3.3 (3.6) days (median, 2 [range, 1-20] days; 95% CI, 2.62-4.06 days) (P = .01; α = .05, 2-tailed Mann-Whitney test). For the secondary end point (effect of a single maneuver), no significant difference was detected (67 of 98 [68.4%] vs 61 of 97 [62.9%]; P = .42; α = .05). No serious adverse event was detected with both maneuvers. Nineteen patients (19.6%) in the EM group and 24 (24.5%) in the SM-plus group experienced relevant nausea. Conclusions and Relevance:The SM-plus self-maneuver is superior to the EM self-maneuver in terms of the number of days until recovery in pcBPPV. Trial Registration:ClinicalTrials.gov Identifier: NCT05853328.

Deficits in spatial memory are often early signs of neurological disorders. Here, we analyzed the geometrical shape configuration of 2D-projections of pointing performances to a memorized array of spatially distributed targets in order to assess the feasibility of this new holistic analysis method. The influence of gender differences and cognitive impairment was taken into account in this methodological study. 56 right-handed healthy participants (28 female, mean age 48.89 ± 19.35 years) and 22 right-handed patients with heterogeneous cognitive impairment (12 female, mean age 71.73 ± 7.41 years) underwent a previously validated 3D-real-world pointing test (3D-RWPT). Participants were shown a 9-dot target matrix and afterwards asked to point towards each target in randomized order with closed eyes in different body positions relative to the matrix. Two-dimensional projections of these pointing vectors (i.e., the shapes resulting from the individual dots) were then quantified using morphological analyses. Shape configurations in healthy volunteers largely reflected the real-world target pattern with gender-dependent differences (ANCOVA area males vs. females F(1,73) = 9.00, p 3.69 × 10 −3 , partial η 2 = 0.10, post-hoc difference = 38,350.43, p bonf= 3.69 × 10 −3 **, Cohen’s d 0.76, t 3.00). Patients with cognitive impairment showed distorted rectangularity with more large-scale errors, resulting in decreased overall average diameters and solidity (ANCOVA diameter normal cognition/cognitive impairment F(1,71) = 9.30, p 3.22 × 10 −3 , partial η 2 = 0.09, post-hoc difference = 31.22, p bonf= 3.19 × 10 −3 **, Cohen’s d 0.92, t 3.05; solidity normal cognition/cognitive impairment F(1,71) = 7.79, p 6.75 × 10 −3 , partial η 2 = 0.08, post-hoc difference = 0.07, p bonf= 6.76 × 10 −3 ** Cohen’s d 0.84, t 2.79). Shape configuration analysis of the 3D-RWPT target array appears to be a suitable holistic measure of spatial performance in a pointing task. The results of this methodological investigation support further testing in a clinical study for differential diagnosis of disorders with spatial memory deficits.

Spatial orientation is based on a complex cortical network with input from multiple sensory systems. It is affected by training, sex and age as well as cultural and psychological factors, resulting in different individual skill levels in healthy subjects. Various neurological disorders can lead to different patterns or specific deficits of spatial orientation and navigation. Accordingly, numerous tests have been proposed to assess these abilities. Here, we compare the results of (1) a validated questionnaire-based self-estimate of orientation/navigation ability (Santa Barbara Sense of Direction Scale, SBSODS) and (2) a validated pen-and-paper two-dimensional perspective test (Perspective Taking Spatial Orientation Test, SOT) with (3) a newly developed test of finger-arm pointing performance in a 3D real-world (3D-RWPT) paradigm using a recently established pointing device. A heterogeneous group of 121 participants (mean age 56.5 ± 17.7 years, 52 females), including 16 healthy volunteers and 105 patients with different vestibular, ocular motor and degenerative brain disorders, was included in this study. A high correlation was found between 2D perspective task and 3D pointing along the horizontal (azimuth) but not along the vertical (polar) plane. Self-estimated navigation ability (SBSODS) could not reliably predict actual performance in either 2D- or 3D-tests. Clinical assessment of spatial orientation and memory should therefore include measurements of actual performance, based on a 2D pen-and-paper test or a 3D pointing task, rather than memory-based questionnaires, since solely relying on the patient’s history of self-estimated navigation ability results in misjudgments. The 3D finger-arm pointing test (3D-RWPT) reveals additional information on vertical (polar) spatial performance which goes undetected in conventional 2D pen-and-paper tests. Diseases or age-specific changes of spatial orientation in the vertical plane should not be clinically neglected. The major aim of this pilot study was to compare the practicability and capability of the three tests but not yet to prove their use for differential diagnosis. The next step will be to establish a suitable clinical bedside test for spatial memory and orientation.

Introduction: Delayed intravenous Gadolinium (Gd) enhanced, high-resolution magnetic resonance imaging of the inner ear (iMRI) confirmed that both patients with Menière's disease (MD) and vestibular migraine (VM) can present with endolymphatic hydrops (EH) [1]. VOLT is a recently proposed semi-automatic open-source image analysis pipeline using volumetric local thresholding for iMRI [2]. This study examined the EH characteristics in patients with VM, MD, or VM with concurrent MD (VM-MD) and searched for pathology-specific EH interrelations to neurotologic testing. Methods: We included 62 patients (45 females, aged 25-81y, mean: 56.6y). 25 patients suffered from VM (19 definite VM, 6 probable VM), 29 suffered from MD (17 definite MD, 12 probable MD), while 8 patients presented with VM and concurrent MD (VM-MD). The diagnostic workup included neurotologic assessments (videooculography (VOG) during caloric stimulation & head-impulse-test, ocular & cervical vestibular evoked myogenic potentials, as well as pure tone audiometry) and an iMRI using the HYDROPSMi2-protocol [for details see: 3]. In addition, the EH was assessed using a conventional radiological visual 2D-grading system [4] as well as after 3D quantification using a probabilistic atlas-based [5] segmentation of the bony labyrinth and the VOLT [2] pipeline. Results: EH in VM was observed twice (8%, Fig. 1), while 13 of 25 (52.0%) VM patients reported varying auditory symptoms without EH (cp. Fig. 1A). EH in MD was frequent (23/29, 79.3%, cp. Fig. 1B). Location and laterality of EH and neurophysiological testing classifications were highly associated (Fisher exact test, p < 0.005). In MD, visual semi-quantitative grading and volumetric quantification correlated highly to each other (rS = 0.8, p < 0.005, two-sided) and to side differences in VOG during caloric irrigation (vestibular EH ipsilateral: rS = 0.6, p < 0.05, two-sided). In VM, correlations were less pronounced. VM-MD assumed an intermediate position between VM and MD regarding EH frequency (2/8, 25%, cp. Fig. 1C) and correlation to VOG side differences. Conclusion: (i) The semi -automatic analysis VOLT [2] can be easily applied to HYDROPSMi2 [3] with the assistance of probabilistic atlas [5]. (ii) Cochlear and vestibular hydrops can occur in MD and VM patients with auditory symptoms. EH grades often correlate with auditory symptoms like hearing impairment or tinnitus. Further research is required to uncover whether migraine is one causative factor of EH or whether EH in VM patients with auditory symptoms suggests an additional pathology due to MD [1]. References: [1] Brandt & Dieterich, Nat Rev Neurol 2017 [2] Gerb et al., J Neurol 2020 [3] Naganawa et al., Magn Res Med Sci 2017 [4] Nakashima al., Acta Oto-Laryngol 2009 [5] Kirsch et al., J Neurol 2019.

Deficits in spatial memory, orientation, and navigation are often early or neglected signs of degenerative and vestibular neurological disorders. A simple and reliable bedside test of these functions would be extremely relevant for diagnostic routine. Pointing at targets in the 3D environment is a basic well-trained common sensorimotor ability that provides a suitable measure. We here describe a smartphone-based pointing device using the built-in inertial sensors for analysis of pointing performance in azimuth and polar spatial coordinates. Interpretation of the vectors measured in this way is not trivial, since the individuals tested may use at least two different strategies: first, they may perform the task in an egocentric eye-based reference system by aligning the fingertip with the target retinotopically or second, by aligning the stretched arm and the index finger with the visual line of sight in allocentric world-based coordinates similar to using a rifle. The two strategies result in considerable differences of target coordinates. A pilot test with a further developed design of the device and an app for a standardized bedside utilization in five healthy volunteers revealed an overall mean deviation of less than 5° between the measured and the true coordinates. Future investigations of neurological patients comparing their performance before and after changes in body position (chair rotation) may allow differentiation of distinct orientational deficits in peripheral (vestibulopathy) or central (hippocampal or cortical) disorders.

Combining magnetic resonance imaging (MRI) sequences that permit the determination of vestibular nerve angulation (NA = change of nerve caliber or direction), structural nerve integrity via diffusion tensor imaging (DTI), and exclusion of endolymphatic hydrops (ELH) via delayed gadolinium-enhanced MRI of the inner ear (iMRI) could increase the diagnostic accuracy in patients with vestibular paroxysmia (VP). Thirty-six participants were examined, 18 with VP (52.6 ± 18.1 years) and 18 age-matched with normal vestibulocochlear testing (NP 50.3 ± 16.5 years). This study investigated whether (i) NA, (ii) DTI changes, or (iii) ELH occur in VP, and (iv) to what extent said parameters relate. Methods included vestibulocochlear testing and MRI data analyses for neurovascular compression (NVC) and NA verification, DTI and ELS quantification. As a result, (i) NA increased NVC specificity. (ii) DTI structural integrity was reduced on the side affected by VP (p < 0.05). (iii) 61.1% VP showed mild ELH and higher asymmetry indices than NP (p > 0.05). (iv) “Disease duration” and “total number of attacks” correlated with the decreased structural integrity of the affected nerve in DTI (p < 0.001). NVC distance within the nerve’s root-entry zone correlated with nerve function (Roh = 0.72, p < 0.001), nerve integrity loss (Roh = − 0.638, p < 0.001), and ELS volume (Roh = − 0.604, p < 0.001) in VP. In conclusion, this study is the first to link eighth cranial nerve function, microstructure, and ELS changes in VP to clinical features and increased vulnerability of NVC in the root-entry zone. Combined MRI with NVC or NA verification, DTI and ELS quantification increased the diagnostic accuracy at group-level but did not suffice to diagnose VP on a single-subject level due to individual variability and lack of diagnostic specificity.