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Background: Spatial 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., Methods: A 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., Results: Self-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., Conclusion: In 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Gerb, Oertle, Becker-Bense, Brandt and Dieterich.)

Objective: The vestibular system is closely connected to emotion-processing neuronal circuits. Patients with bilateral vestibulopathy (BVP), a chronic loss of vestibular function, show remarkably lower rates of psychiatric comorbidities and vertigo-related anxiety (VRA) than those with episodic vertigo/dizziness (v/d). This study aimed to evaluate whether patients with BVP differ from those with episodic v/d in terms of VRA, general anxiety, and cognitions about body and health., Methods: This cross-sectional study involved a subsample of 202 patients with episodic v/d (i.e., vestibular migraine, vestibular paroxysmia, or Menière's disease) and 43 patients with BVP. All patients underwent standardised neurological/neurotological examinations, structured clinical interviews (SCID-I), and self-report questionnaires, such as the Vertigo Handicap Questionnaire (VHQ), Beck Anxiety Inventory (BAI), Trait Anxiety from the State-Trait-Anxiety Inventory (STAI-T), and Cognitions About Body and Health questionnaire (CABAH). Non-parametric tests were used for analysis. Due to multiple testing, the significance level was set at p ≤ .008., Results: Patients with episodic v/d exhibited higher VRA levels than those with BVP. However, this difference was not statistically significant (p = .04; r = 0.15, small effect). Additionally, patients with BVP reported more catastrophizing cognitions (p < .001; r = 0.25, small effect) and bodily weakness (p = .003; r = 0.22, small effect) compared to those with episodic v/d. There were no differences in general anxiety levels (BAI and STAI-T) between patients with v/d and those with BVP., Conclusion: Patients with episodic v/d and BVP differed in their appraisal (cognition). The difference in VRA (subjective feeling) was not statistically significant. These preliminary results are discussed using a component approach to emotions., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any personal, commercial, or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Inc.)

Background: Vestibular 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 ( i MRI) also revealed an EH in VM. The major questions were the frequency and distribution characteristics of EH in VM for diagnostic use., Methods: In 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 of i MRI of the endolymphatic space included volumetric quantification, stepwise regression, correlation with neurotological parameters and support vector machine classification., Results: EH 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., Conclusion: Three features of the i MRI 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., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The current diagnostic workup for chronic dizziness in elderly patients often neglects neuropsychological assessment, thus missing a relevant proportion of patients, who perceive dizziness as a subjective chief complaint of a concomitant cognitive impairment. This study aimed to establish risk prediction models for cognitive impairment in chronic dizzy patients based on data sources routinely collected in a dizziness center., Methods: One hundred patients (age: 74.7 ± 7.1 years, 41.0% women) with chronic dizziness were prospectively characterized by (1) neuro-otological testing, (2) quantitative gait assessment, (3) graduation of focal brain atrophy and white matter lesion load, and (4) cognitive screening (MoCA). A linear regression model was trained to predict patients' total MoCA score based on 16 clinical features derived from demographics, vestibular testing, gait analysis, and imaging scales. Additionally, we trained a binary logistic regression model on the same data sources to identify those patients with a cognitive impairment (i.e., MoCA < 25)., Results: The linear regression model explained almost half of the variance of patients' total MoCA score (R 2  = 0.49; mean absolute error: 1.7). The most important risk-predictors of cognitive impairment were age (β = - 0.75), pathological Romberg's sign (β = - 1.05), normal caloric test results (β = - 0.8), slower timed-up-and-go test (β = - 0.67), frontal (β = - 0.6) and temporal (β = - 0.54) brain atrophy. The binary classification yielded an area under the curve of 0.84 (95% CI 0.70-0.98) in distinguishing between cognitively normal and impaired patients., Conclusions: The need for cognitive testing in patients with chronic dizziness can be efficiently approximated by available data sources from routine diagnostic workup in a dizziness center., (© 2024. The Author(s).)

Background: There is increasing evidence for close interrelations between vestibular and emotional brain networks. A study in patients with bilateral peripheral vestibulopathy (BVP) showed relatively low vertigo-related anxiety (VRA), despite high physical impairment. The current working hypothesis proposes the integrity of the peripheral vestibular system as a prerequisite for development of VRA. Here we contribute by evaluating VRA and vestibular-related handicap in central vestibular disorders., Methods: Of 6396 patients presenting in a tertiary vertigo centre, 306 were identified with four clear central vestibular disorders: pure cerebellar ocular motor disorder (COD; 61), cerebellar ataxia (CA; 63), atypical parkinsonian syndromes (APS; 28), vestibular migraine (VM; 154). Their results of the Vertigo Handicap Questionnaire (VHQ), with its subscales for anxiety and handicapped activity, were compared to those of 65 BVP patients. Postural instability was measured on a force-plate. Multivariate linear regression was used to adjust for patient demographics., Results: Patients with chronic central vestibular disorders (COD, CA, APS) had relatively low VRA levels comparable to those in BVP, independent of increased handicapped activity or postural instability. Only VM patients showed significantly higher VRA, although their activity impairment and postural instability were lowest. No significant differences within chronic central vestibular disorders were found for VRA and subjective activity impairment., Conclusions: Subjective and objective vestibular-related impairment are not necessarily correlated with vestibular-related anxiety in central vestibular disorders. Our findings rather support the hypothesis that, in addition to an intact peripheral, an intact central vestibular system could also serve as a prerequisite to develop specific VRA., (© 2023. The Author(s).)

Objective: The aim of the study was to deepen our insights into central compensatory processes of brain networks in patients with cerebellar ataxia (CA) before and with treatment with acetyl-DL-leucine (AL) by means of resting-state [ 18 F]-FDG-PET brain imaging., Methods: Retrospective analyses of [ 18 F]-FDG-PET data in 22 patients with CA (with vestibular and ocular motor disturbances) of different etiologies who were scanned before (PET A) and on AL treatment (PET B). Group subtraction analyses, e.g., for responders and non-responders, comparisons with healthy controls and correlation analyses of regional cerebral glucose metabolism (rCGM) with symptom duration, ataxia (SARA) and quality of life (QoL) scores were calculated., Results: Prior to treatment rCGM was consistently downregulated at the cerebellar level and increased in multisensory cortical areas, e.g., somatosensory, primary and secondary visual (including V5, precuneus), secondary vestibular (temporal gyrus, anterior insula), and premotor/supplementary motor areas. With AL (PET B vs. A) cerebellar hypometabolism was deepened and sensorimotor hypermetabolism increased only in responders with clinical benefit, but not for the non-responders and the whole CA group. A positive correlation of ataxia improvement with rCGM was found in visual and vestibular cortices, a negative correlation in cerebellar and brainstem areas. QoL showed a positive correlation with rCGM in the cerebellum and symptom duration in premotor and somatosensory areas., Conclusions: Central compensatory processes in CA mainly involve multisensory visual, vestibular, and somatosensory networks as well as premotor/primary motor areas at the cortical level. The enhanced divergence of cortical sensorimotor up- and cerebellar downregulation with AL in responders could reflect amplification of inhibitory cerebellar mechanisms., (© 2022. The Author(s).)

Background and Purpose: Dizziness and vertigo are common symptoms after COVID-19-vaccination. We aimed to prospectively evaluate objective central or peripheral vestibular function in patients with dizziness, vertigo, and postural symptoms that started or worsened after COVID-19-vaccination., Methods: Of 4137 patients who presented between January 2021 and April 2022 at the German Center for Vertigo and Balance Disorders, Ludwig Maximilian University of Munich, we identified 72 patients (mean age = 47 years) with enduring vestibular symptoms following COVID-19 vaccination. All underwent medical history-taking, and neurological and neuro-otological workup with bithermal caloric test, video head-impulse test, orthoptics, and audiometry. Diagnoses were based on international criteria. The distribution of diagnoses was compared to a cohort of 39,964 patients seen before the COVID-19 pandemic., Results: Symptom onset was within the first 4 weeks postvaccination. The most prevalent diagnoses were somatoform vestibular disorders (34.7%), vestibular migraine (19.4%), and overlap syndromes of both (18.1%). These disorders were significantly overrepresented compared to the prepandemic control cohort. Thirty-six percent of patients with somatoform complaints reported a positive history of depressive or anxiety disorders. Nine patients presented with benign paroxysmal positional vertigo, three with acute unilateral vestibulopathy, and seven with different entities (vestibular paroxysmia, Ménière disease, polyneuropathy, ocular muscular paresis). Causally related central vestibular deficits were lacking. Novel peripheral vestibular deficits were found in four patients., Conclusions: Newly induced persistent vestibular deficits following COVID-19 vaccination were rare. The predominant causes of prolonged vestibular complaints were somatoform vestibular disorders and vestibular migraine, possibly triggered or aggravated by stress-related circumstances due to the COVID-19 pandemic or vaccination. An increase of other central or peripheral vestibular syndromes after COVID-19 vaccination was not observed., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

In 2016, the Bárány Society defined new diagnostic criteria for the neurovascular compression syndrome of the eighth nerve, called "vestibular paroxysmia" (VP), differentiating between definite (dVP) and probable (pVP) forms. The aim of this study was (1) to describe clinical symptoms and laboratory findings in a well-diagnosed large patient cohort according to those criteria, and (2) to evaluate the long-term course over years in dVP. We identified 146 patients (73 dVP, 73 pVP) from our tertiary dizziness center registry. Data of structured history-taking, clinical neurological, neuro-ophthalmological/-otological examinations as well as MRI imaging were extracted for analyses. Overall, attack frequency ranged between 5 and 30 attacks per day; spinning vertigo was the most frequent type. In two-thirds of patients, attacks occurred spontaneously; in one-quarter, they were triggered by head movements. The majority (approximately 70%) reported no accompanying symptoms; in those with symptoms, mild unilateral cochlear symptoms prevailed. One-third of patients initially showed hyperventilation-induced nystagmus without specific direction, and a deviation of the subjective visual vertical between 3° and 6°. Complete loss of peripheral vestibular function was never evident. dVP and pVP significantly differed concerning the vertigo type, e.g., spinning vertigo was more frequent in dVP. Fortunately, three-quarters of dVP patients remained attack-free during follow-up (mean 4.8 years, standardized questionnaire), more than half of them even without any medication. Patients with ongoing attacks showed significantly higher attack frequency at baseline, but reported persistent frequency reduction. Overall, the long-term prognosis of VP appears favorable, not necessarily requiring ongoing treatment., (© 2022. The Author(s).)

Background and Purpose: Recently, the Classification Committee of the Bárány Society defined the new syndrome of "presbyvestibulopathy" for elderly patients with chronic vestibular symptoms due to a mild bilateral peripheral vestibular hypofunction. However, control of stance and gait requires multiple functioning systems, for example, the somatosensory, visual, auditory, musculoskeletal, and cardio- and cerebrovascular systems. The aim of this cross-sectional database-driven study was to evaluate the frequency and characteristics of presbyvestibulopathy and additional gait-relevant comorbidities., Methods: In total, 707 patients aged ≥60 years with chronic vertigo/dizziness were admitted to our tertiary hospital and received detailed neurological, neuro-orthoptic, and laboratory audiovestibular examination. Medical history, comorbidities, functional impairment, and quality of life (Dizziness Handicap Inventory [DHI], European Quality of Life Scale, Vestibular Activities and Participation) were compared between presbyvestibulopathy and bilateral vestibulopathy in a matched-paired study., Results: In 95.5% of patients, complaints were better accounted for by another vestibular, neurological, cardiac, or psychiatric disease, and 32 patients (4.5%) met the diagnostic criteria for presbyvestibulopathy. Of these 32 patients, the majority showed further relevant comorbidities in other sensorimotor systems. Only one patient of 707 had "isolated" presbyvestibulopathy (0.14%). The mean total DHI scores indicated lower moderate impairment in presbyvestibulopathy than in bilateral vestibulopathy (40.6 vs. 49.0), which was confirmed by significant differences in the matched-paired analysis (p < 0.001)., Conclusions: Isolated presbyvestibulopathy is a very rare entity. It is regularly accompanied by other multisensory dysfunctions. These results indicate a potential role of mild vestibular hypofunction as a cofactor in multifactorial impairment. Thus, patients should be treated in an interdisciplinary setting with an awareness of diverse comorbidities., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: We aimed to delineate common principles of reorganization after infarcts of the subcortical vestibular circuitry related to the clinical symptomatology. Our hypothesis was that the recovery of specific symptoms is associated with changes in distinct regions within the core vestibular, somatosensory, and visual cortical and subcortical networks., Methods: We used voxel- and surface-based morphometry to investigate structural reorganization of subcortical and cortical brain areas in 42 patients with a unilateral, subcortical infarct with vestibular and ocular motor deficits in the acute phase. The patients received structural neuroimaging and clinical monitoring twice (acute phase and after 6 months) to detect within-subject changes over time., Results: In patients with vestibular signs such as tilts of the subjective visual vertical (SVV) and ocular torsion in the acute phase, significant volumetric increases in the superficial white matter around the parieto-opercular (retro-)insular vestibular cortex (PIVC) were found at follow-up. In patients with SVV tilts, spontaneous nystagmus, and rotatory vertigo in the acute phase, gray matter volume decreases were located in the cerebellum and the visual cortex bilaterally at follow-up. Patients with saccade pathology demonstrated volumetric decreases in cerebellar, thalamic, and cortical centers for ocular motor control., Conclusions: The findings support the role of the PIVC as the key hub for vestibular processing and reorganization. The volumetric decreases represent the reciprocal interaction of the vestibular, visual, and ocular motor systems during self-location and egomotion detection. A modulation in vestibular and ocular motor as well as visual networks was induced independently of the vestibular lesion site., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Objective: The integration of somatosensory, ocular motor and vestibular signals is necessary for self-location in space and goal-directed action. We aimed to detect remote changes in the cerebral cortex after thalamic infarcts to reveal the thalamo-cortical connections necessary for multisensory processing and ocular motor control., Methods: Thirteen patients with unilateral ischemic thalamic infarcts presenting with vestibular, somatosensory, and ocular motor symptoms were examined longitudinally in the acute phase and after six months. Voxel- and surface-based morphometry were used to detect changes in vestibular and multisensory cortical areas and known hubs of central ocular motor processing. The results were compared with functional connectivity data in 50 healthy volunteers., Results: Patients with paramedian infarcts showed impaired saccades and vestibular perception, i.e., tilts of the subjective visual vertical (SVV). The most common complaint in these patients was double vision or vertigo / dizziness. Posterolateral thalamic infarcts led to tilts of the SVV and somatosensory deficits without vertigo. Tilts of the SVV were higher in paramedian compared to posterolateral infarcts (median 11.2° vs 3.8°). Vestibular and ocular motor symptoms recovered within six months. Somatosensory deficits persisted. Structural longitudinal imaging showed significant volume reduction in subcortical structures connected to the infarcted thalamic nuclei (vestibular nuclei region, dentate nucleus region, trigeminal root entry zone, medial lemniscus, superior colliculi). Volume loss was evident in connections to the frontal, parietal and cingulate lobes. Changes were larger in the ipsilesional hemisphere but were also detected in homotopical regions contralesionally. The white matter volume reduction led to deformation of the cortical projection zones of the infarcted nuclei., Conclusions: White matter volume loss after thalamic infarcts reflects sensory input from the brainstem as well the cortical projections of the main affected nuclei for sensory and ocular motor processing. Changes in the cortical geometry seem not to reflect gray matter atrophy but rather reshaping of the cortical surface due to the underlying white matter atrophy., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

Competing Interests: Die Autorinnen erklären, dass kein Interessenkonflikt besteht.

In-vivo non-invasive verification of endolymphatic hydrops (ELH) by means of intravenous delayed gadolinium (Gd) enhanced magnetic resonance imaging of the inner ear (iMRI) is rapidly developing into a standard clinical tool to investigate peripheral vestibulo-cochlear syndromes. In this context, methodological comparative studies providing standardization and comparability between labs seem even more important, but so far very few are available. One hundred eight participants [75 patients with Meniere's disease (MD; 55.2 ± 14.9 years) and 33 vestibular healthy controls (HC; 46.4 ± 15.6 years)] were examined. The aim was to understand (i) how variations in acquisition protocols influence endolymphatic space (ELS) MR-signals; (ii) how ELS quantification methods correlate to each other or clinical data; and finally, (iii) how ELS extent influences MR-signals. Diagnostics included neuro-otological assessment, video-oculography during caloric stimulation, head-impulse test, audiometry, and iMRI. Data analysis provided semi-quantitative (SQ) visual grading and automatic algorithmic quantitative segmentation of ELS area [2D, mm 2 ] and volume [3D, mm 3 ] using deep learning-based segmentation and volumetric local thresholding. Within the range of 0.1-0.2 mmol/kg Gd dosage and a 4 h ± 30 min time delay, SQ grading and 2D- or 3D-quantifications were independent of signal intensity (SI) and signal-to-noise ratio (SNR; FWE corrected, p < 0.05). The ELS quantification methods used were highly reproducible across raters or thresholds and correlated strongly (0.3-0.8). However, 3D-quantifications showed the least variability. Asymmetry indices and normalized ELH proved the most useful for predicting quantitative clinical data. ELH size influenced SI (cochlear basal turn p < 0.001), but not SNR. SI could not predict the presence of ELH. In conclusion, (1) Gd dosage of 0.1-0.2 mmol/kg after 4 h ± 30 min time delay suffices for ELS quantification. (2) A consensus is needed on a clinical SQ grading classification including a standardized level of evaluation reconstructed to anatomical fixpoints. (3) 3D-quantification methods of the ELS are best suited for correlations with clinical variables and should include both ears and ELS values reported relative or normalized to size. (4) The presence of ELH increases signal intensity in the basal cochlear turn weakly, but cannot predict the presence of ELH., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Boegle, Gerb, Kierig, Becker-Bense, Ertl-Wagner, Dieterich and Kirsch.)

Objective: Structural reorganization following cerebellar infarcts is not yet known. This study aimed to demonstrate structural volumetric changes over time in the cortical vestibular and multisensory areas (i.e., brain plasticity) after acute cerebellar infarcts with vestibular and ocular motor symptoms. Additionally, we evaluated whether structural reorganization in the patients topographically correlates with cerebello-cortical connectivity that can be observed in healthy participants., Methods: We obtained high-resolution structural imaging in seven patients with midline cerebellar infarcts at two time points. These data were compared to structural imaging of a group of healthy age-matched controls using voxel-based morphometry (2×2 ANOVA approach). The maximum overlap of the infarcts was used as a seed region for a separate resting-state functional connectivity analysis in healthy volunteers., Results: Volumetric changes were detected in the multisensory cortical vestibular areas around the parieto-opercular and (retro-) insular cortex. Furthermore, structural reorganization was evident in parts of the frontal, temporal, parietal, limbic, and occipital lobes and reflected functional connections between the main infarct regions in the cerebellum and the cerebral cortex in healthy individuals., Conclusions: This study demonstrates structural reorganization in the parieto-opercular insular vestibular cortex after acute vestibulo-cerebellar infarcts. Additionally, the widely distributed structural reorganization after midline cerebellar infarcts provides additional in vivo evidence for the multifaceted contribution of cerebellar processing to cortical functions that extend beyond vestibular or ocular motor function., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

In 2017, the term "persistent postural-perceptual dizziness" (PPPD) was coined by the Bárány Society, which provided explicit criteria for diagnosis of functional vertigo and dizziness disorders. PPPD can originate secondarily after an organic disorder (s-PPPD) or primarily on its own, in the absence of somatic triggers (p-PPPD). The aim of this database-driven study in 356 patients from a tertiary vertigo center was to describe typical demographic and clinical features in p-PPPD and s-PPPD patients. Patients underwent detailed vestibular testing with neurological and neuro-orthoptic examinations, video-oculography during water caloric stimulation, video head-impulse test, assessment of the subjective visual vertical, and static posturography. All patients answered standardized questionnaires (Dizziness Handicap Inventory, DHI; Vestibular Activities and Participation, VAP; and Euro-Qol-5D-3L). One hundred and ninety-five patients (55%) were categorized as p-PPPD and 162 (45%) as s-PPPD, with female gender slightly predominating (♀:♂ = 56%:44%), particularly in the s-PPPD subgroup (64%). The most common somatic triggers for s-PPPD were benign paroxysmal positional vertigo (27%), and vestibular migraine (24%). Overall, p-PPPD patients were younger than s-PPPD patients (44 vs. 48 years) and showed a bimodal age distribution with an additional early peak in young adults (about 30 years of age) beside a common peak at the age of 50-55. The most sensitive diagnostic tool was posturography, revealing a phobic sway pattern in 50% of cases. s-PPPD patients showed higher handicap and functional impairment in DHI (47 vs. 42) and VAP (9.7 vs. 8.9). There was no difference between both groups in EQ-5D-3L. In p-PPPD, anxiety (20% vs. 10%) and depressive disorders (25% vs. 9%) were more frequent. This retrospective study in a large cohort showed relevant differences between p- and s-PPPD patients in terms of demographic and clinical features, thereby underlining the need for careful syndrome subdivision for further prospective studies.

Objective: Patients with acute central vestibular syndrome suffer from vertigo, spontaneous nystagmus, postural instability with lateral falls, and tilts of visual vertical. Usually, these symptoms compensate within months. The mechanisms of compensation in vestibular infarcts are yet unclear. This study focused on structural changes in gray and white matter volume that accompany clinical compensation., Methods: We studied patients with acute unilateral brain stem infarcts prospectively over 6 months. Structural changes were compared between the acute phase and follow-up with a group of healthy controls using voxel-based morphometry., Results: Restitution of vestibular function following brain stem infarcts was accompanied by downstream structural changes in multisensory cortical areas. The changes depended on the location of the infarct along the vestibular pathways in patients with pathological tilts of the SVV and on the quality of the vestibular percept (rotatory vs graviceptive) in patients with pontomedullary infarcts. Patients with pontomedullary infarcts with vertigo or spontaneous nystagmus showed volumetric increases in vestibular parietal opercular multisensory and (retro-) insular areas with right-sided preference. Compensation of graviceptive deficits was accompanied by adaptive changes in multiple multisensory vestibular areas in both hemispheres in lower brain stem infarcts and by additional changes in the motor system in upper brain stem infarcts., Interpretation: This study demonstrates multisensory neuroplasticity in both hemispheres along with the clinical compensation of vestibular deficits following unilateral brain stem infarcts. The data further solidify the concept of a right-hemispheric specialization for core vestibular processing. The identification of cortical structures involved in central compensation could serve as a platform to launch novel rehabilitative treatments such as transcranial stimulations., (© 2020 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.)

Background and Purpose: Acute vestibular symptoms have a profound impact on patients' well-being. In this study, health-related quality of life (HRQoL) and functional impairment were investigated prospectively in patients with different peripheral and central vestibular disorders during the acute symptomatic stage to decipher the most relevant underlying factors., Methods: In all, 175 patients with acute vestibular disorders were categorized as central vestibular (CV, n = 40), peripheral vestibular (PV, n = 68) and episodic vestibular disorders (EV, n = 67). All patients completed scores to quantify generic HRQoL (European Quality of Life Score Five Dimensions Five Levels, EQ-5D-5L) and disease-specific HRQoL (Dizziness Handicap Inventory, DHI). Vestibular-ocular motor signs were assessed by video-oculography, vestibular-spinal control by posturography and verticality perception by measurement of subjective visual vertical., Results: Patients with PV had a poorer HRQoL compared to patients with CV and EV (EQ-5D-5L/DHI: PV, 0.53 ± 0.31/56.1 ± 19.7; CV, 0.66 ± 0.28/43.3 ± 24.0; EV, 0.75 ± 0.24/46.7 ± 21.4). After adjusting for age, gender, cardiovascular risk factors and non-vestibular brainstem/cerebellar dysfunction patients with PV persisted to have poorer generic and disease-specific HRQoL (EQ-5D-5L -0.17, DHI +11.2) than patients with CV. Horizontal spontaneous nystagmus was a highly relevant factor for subgroup differences in EQ-5D-5L and DHI, whilst vertical spontaneous nystagmus, subjective visual vertical and sway path were not. EQ-5D-5L decreased significantly with more intense horizontal subjective visual vertical in CV (rho = -0.57) and PV (rho = -0.5) but not EV (rho = -0.13)., Conclusions: Patients with PV have the highest functional impairment of all patients with acute vestibular disorders. Vestibular-ocular motor disturbance in the yaw plane has more impact than vestibular-spinal or vestibular-perceptive asymmetry in the roll and pitch plane, suggesting that horizontal visual stability is the most critical for HRQoL., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Previous unimodal PET and fMRI studies in humans revealed a reproducible vestibular brain activation pattern, but with variations in its weighting and expansiveness. Hybrid studies minimizing methodological variations at baseline conditions are rare and still lacking for task-based designs. Thus, we applied for the first time hybrid 3T PET-MRI scanning (Siemens mMR) in healthy volunteers using galvanic vestibular stimulation (GVS) in healthy volunteers in order to directly compare H215O-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq H215O simultaneously to MRI EPI sequences. Group-level statistical parametric maps were generated for GVS vs. rest contrasts of PET, MR-onset (event-related), and MR-block. All contrasts showed a similar bilateral vestibular activation pattern with remarkable proximity of activation foci. Both BOLD contrasts gave more bilateral wide-spread activation clusters than PET; no area showed contradictory signal responses. PET still confirmed the right-hemispheric lateralization of the vestibular system, whereas BOLD-onset revealed only a tendency. The reciprocal inhibitory visual-vestibular interaction concept was confirmed by PET signal decreases in primary and secondary visual cortices, and BOLD-block decreases in secondary visual areas. In conclusion, MRI activation maps contained a mixture of CBF measured using H215O-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the H215O-PET than the BOLD-onset., Competing Interests: The authors have declared that no competing interests exist.

Epidemiological studies have shown an increased risk of cardiovascular events in migraineurs. The pathophysiological mechanisms of this observation remain largely unknown. Recent genetic and epidemiologic studies suggest, that atherosclerosis might be the overlapping pathophysiological mechanism in migraine and coronary heart disease. The aim of the present study was to evaluate if the increased cardiovascular risk in migraineurs is attributed to an increased coronary artery calcification. For this the coronary artery calcium score was assessed by computed tomography of the heart in 1.437 patients of which 337 were migraineurs. All patients had a similar cardiovascular risk profile, so that the risk for coronary calcifications could be considered similar between migraineurs and non-migraineurs. The results showed no significant differences in the amount of coronary calcifications in patients with or without migraine. This suggests that a more pronounced coronary artery calcification, as a surrogate marker of coronary atherosclerosis, does not underlie the increased cardiovascular risk in migraineurs. A distinct common pathophysiological mechanism in migraine and coronary heart disease such as endothelial dysfunction or vasospasm should be discussed instead. However, it has to be considered, that the coronary artery calcification score does not indicate the total risk of atherosclerotic changes in the coronary arteries.

Background: Mental health comorbidities are frequent in patients with vertigo and dizziness. The current study was conducted in a specialized interdisciplinary university center for vertigo and dizziness. Clinical routines consist of a structured work-up in which neuro-otological and neurological tests are performed to first detect possible organic vestibular deficits. In addition, psychiatric disorders and comorbidities are considered. The study aimed to evaluate neurologists' awareness of psychiatric next to somatic disorders within patients' first examination in terms of diagnostic congruence between neurologists' diagnoses and structured clinical assessment of mental disorders. Methods: The study involved 392 patients. Diagnostic evaluation included (a) structured history-taking (including psychosocial anamnesis), neurological, and neuro-otological diagnostics conducted by neurologists and (b) a structured clinical interview for mental disorders (SCID-I) conducted by psychologists and final-year medical or psychology students. Cohen's Kappa was calculated to determine agreement rates regarding depression and anxiety disorders; additionally, sensitivity and specificity were evaluated. Results: Neurologists' assessments led to at least one psychiatric diagnosis among the main diagnoses in 40 (10.2 %) patients, whereas the structured clinical interview led to at least one DSM-IV psychiatric diagnosis in 174 (44.4%) of the patients. Agreement was low (κ < 0.2); sensitivity was low (15%) but specificity was high (98%). Conclusions: Agreement between the diagnosis of neurologists and structured clinical interviews for psychiatric disorders is low. Since psychiatric disorders are frequent in vertigo and dizziness and tend to take a chronic course, improving early recognition and implementing appropriate care concepts is vital.

Purpose: Comprehensive phenotypical data across countries is needed to understand the determinants, prognosis and consequences of vestibular disease. The registry is a data repository for the members of the European DizzyNet. We report results from a pilot study using data from Turkey and Germany., Methods: The pilot study included a convenience sample of patients aged 18 or above referred to Ege University Medical School Hospital, Dokuz Eylül University Hospital, Izmir, Turkey, and the German Center for German Center for Vertigo and Balance Disorders, University on Munich, Germany, with symptoms of vertigo or dizziness. Health-related quality of life was assessed with the EQ5-D and the Dizziness Handicap Inventory (DHI). To obtain comparable groups we matched data from the two countries for age, sex and diagnosis by propensity score., Results: We included 80 adult patients, 40 from each country (60% female, mean age 54.1, SD 12.4). Matching was successful. Vestibular migraine (34%) was the most frequent diagnosis, followed by benign paroxysmal positional vertigo (29%) and Menière's disease (12%). Clinical signs and symptoms were comparable in both countries. Patients from Turkey were more likely to report headaches (65 vs. 32%) and to show gait unsteadiness (51 vs. 5%). Patients from Germany reported significantly higher quality of life and lower values of the DHI score., Conclusions: Sharing data facilitates research, enhances translation from basic science into clinical applications, and increases transparency. The DizzyNet registry is a first step to data sharing in vestibular research across Europe.

Vertigo and dizziness are frequent chief complaints in clinical practice. Symptoms may originate from otological, neurological, medical and psychiatric etiologies, which poses an interdisciplinary challenge. Systematic analysis of case history and clinical examination generally allow classification into peripheral-, central- or non-vestibular disorders. The most important criteria for differentiation are the timeline, quality of symptoms, modulating factors and accompanying symptoms. As concerns the clinical examination, the following tests are relevant: head impulse test, test for spontaneous nystagmus, positional nystagmus, central ocular motor signs and the Romberg test. However, neuro-otological disorders with combined peripheral and central vestibular pathology do exist. Occlusion of the anterior inferior cerebellar artery results in ischemia of the labyrinth and cerebellum and therefore causes acute vestibular syndrome and unilateral hearing loss. Repetitive attacks of vertigo or dizziness which are accompanied by ear symptoms and headaches may be due to an overlap syndrome of Menière's disease and vestibular migraine. In this case patients often have to be treated with a dual prophylactic medication to control symptoms. In case of chronic dizziness and instability of gait a subsample of patients may suffer from CANVAS, which is a combination of bilateral vestibulopathy, a cerebellar syndrome and polyneuropathy. Chronic dizziness with signs of peripheral and central vestibular dysfunction can also originate from tumors of the cerebellopontine angle with compression of central structures. In conclusion, the diagnostic algorithm in the workup of patients with vertigo and dizziness should always include tests for peripheral and central vestibular and ocular motor function.

The functional relevance of reactive gliosis for recovery from acute unilateral vestibulopathy is unknown. In the present study, glial activation was visualized in vivo by [ 18 F]GE180-PET in a rat model of unilateral labyrinthectomy (UL) and compared to behavioral vestibular compensation (VC) overtime. 14 Sprague-Dawley rats underwent a UL by transtympanic injection of bupivacaine/arsenilate, 14 rats a SHAM UL (injection of normal saline). Glial activation was depicted with [ 18 F]GE180-PET and ex vivo autoradiography at baseline and 7, 15, 30 days after UL/SHAM UL. Postural asymmetry and nystagmus were registered at 1, 2, 3, 7, 15, 30 days after UL/SHAM UL. Signs of vestibular imbalance were found only after UL, which significantly decreased until days 15 and 30. In parallel, [ 18 F]GE180-PET and ex vivo autoradiography depicted glial activation in the ipsilesional vestibular nerve and nucleus on days 7 and 15 after UL. Correlation analysis revealed a strong negative association of [ 18 F]GE180 uptake in the ipsilesional vestibular nucleus on day 7 with the rate of postural recovery ( R  = -0.90, p  < 0.001), suggesting that glial activation accelerates VC. In conclusion, glial activation takes place in the ipsilesional vestibular nerve and nucleus within the first 30 days after UL in the rat and can be visualized in vivo by [ 18 F]GE180-PET.

Background: Somatic symptom disorder (SSD) is a diagnosis that was newly included in DSM-5. Currently, data on the course of SSD are largely lacking. The present study aimed to evaluate the natural course of SSD in a one-year follow-up study in patients with vertigo and dizziness (VD) symptoms., Methods: We investigated n=239 outpatients presenting in a tertiary care neurological setting over a one-year period. Patients had a medical examination at baseline and completed self-report questionnaires, which were re-assessed after 12months. DSM-5 SSD was assigned retrospectively. We evaluated the prevalence of SSD at baseline and 12-month follow-up and investigated predictors of the persistence of SSD during the study period., Results: The prevalence rate of SSD was 36% at baseline and 62% at 12-months follow-up. The persistence rate of SSD was 82% and the incidence rate was high, leading to a markedly increased prevalence rate at follow-up. Risk factors for persistent SSD were a self-concept of bodily weakness (OR: 1.52, 95% CI: 1.30-1.78) and an increase of depression during the study period (OR: 1.11, 95% CI: 1.02-1.22). Further, the diagnosis of an anxiety disorder (OR: 7.52, 95% CI: 1.17-48.23) or both anxiety and depressive disorder (OR: 23.14, 95% CI: 2.14-249.91) at baseline were significant predictors., Conclusions: Our findings point out that SSD is highly prevalent in patients with VD symptoms, the incidence of the disorder widely outweighs its remission. Potential predictors of a persistence of SSD are discussed and can be chosen as a focus in therapy., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of the study was to uncover mechanisms of central compensation of vestibular function at brainstem, cerebellar, and cortical levels in patients with acute unilateral midbrain infarctions presenting with an acute vestibular tone imbalance. Eight out of 17 patients with unilateral midbrain infarctions were selected on the basis of signs of a vestibular tone imbalance, e.g., graviceptive (tilts of perceived verticality) and oculomotor dysfunction (skew deviation, ocular torsion) in F18-fluordeoxyglucose (FDG)-PET at two time points: A) in the acute stage, and B) after recovery 6 months later. Lesion-behavior mapping analyses with MRI verified the exact structural lesion sites. Group subtraction analyses and comparisons with healthy controls were performed with Statistic Parametric Mapping for the PET data. A comparison of PET A of acute-stage patients with that of healthy controls showed increases in glucose metabolism in the cerebellum, motion-sensitive visual cortex areas, and inferior temporal lobe, but none in vestibular cortex areas. At the supratentorial level bilateral signal decreases dominated in the thalamus, frontal eye fields, and anterior cingulum. These decreases persisted after clinical recovery in contrast to the increases. The transient activations can be attributed to ocular motor and postural recovery (cerebellum) and sensory substitution of vestibular function for motion perception (visual cortex). The persisting deactivation in the thalamic nuclei and frontal eye fields allows alternative functional interpretations of the thalamic nuclei: either a disconnection of ascending sensory input occurs or there is a functional mismatch between expected and actual vestibular activity. Our data support the view that both thalami operate separately for each hemisphere but receive vestibular input from ipsilateral and contralateral midbrain integration centers. Normally they have gatekeeper functions for multisensory input to the cortex and automatic motor output to subserve balance and locomotion, as well as sensorimotor integration., Competing Interests: The authors have declared that no competing interests exist.

About 30 % of patients presenting to general practitioners complain of episodic or chronic vertigo or dizziness symptoms mostly with substantial impact on their daily living and activities. 30 to 50 % of the dizziness disorders are organically not sufficiently explained and are caused by mental or psychosomatic diseases. Somatoform dizziness syndromes can occur without a preceding vestibular disorder (e. g., primary somatoform dizziness) or they can develop in consequence of an organic vestibular disorder (secondary somatoform dizziness). However, it often takes months or even years until the correct diagnosis is made and an appropriate psychosomatic therapy can be initiated. Therefore, it is essential for the course of the disease that at an early stage not only careful interdisciplinary organic but also psychosomatic diagnostics are applied., (© Georg Thieme Verlag KG Stuttgart · New York.)

The human vestibular system is represented in the brain bilaterally, but it has functional asymmetries, i.e., a dominance of ipsilateral pathways and of the right hemisphere in right-handers. To determine if acute right- or left-sided unilateral vestibular neuritis (VN) is associated with differential patterns of brain metabolism in areas representing the vestibular network and the visual-vestibular interaction, patients with acute VN (right n = 9; left n = 13) underwent resting state (18)F-FDG PET once in the acute phase and once 3 months later after central vestibular compensation. The contrast acute vs. chronic phase showed signal differences in contralateral vestibular areas and the inverse contrast in visual cortex areas, both more pronounced in VN right. In VN left additional regions were found in the cerebellar hemispheres and vermis bilaterally, accentuated in severe cases. In general, signal changes appeared more pronounced in patients with more severe vestibular deficits. Acute phase PET data of patients compared to that of age-matched healthy controls disclosed similarities to these patterns, thus permitting the interpretation that the signal changes in vestibular temporo-parietal areas reflect signal increases, and in visual areas, signal decreases. These data imply that brain activity in the acute phase of right- and left-sided VN exhibits different compensatory patterns, i.e., the dominant ascending input is shifted from the ipsilateral to the contralateral pathways, presumably due to the missing ipsilateral vestibular input. The visual-vestibular interaction patterns were preserved, but were of different prominence in each hemisphere and more pronounced in patients with right-sided failure and more severe vestibular deficits.

Background: Absence of peripheral vestibular input in bilateral vestibular failure (BVF) has been suggested to induce plastic reorganization in various brain regions. Among several neurotransmitters, dopamine is known to play a key role in cortico-striatal-sensorimotor processing. However, the role of dopamine in vestibular plasticity is scantly documented., Objective: Assessment of D 2/3 formula-receptors in patients with BVF., Methods: D 2/3 formula-receptor-PET using [18F]fallypride and MRI examinations were performed in 12 BVF-patients and 13 healthy controls., Results: BVF-patients showed reduced D 2/3 formula-receptor availability (approximately 40%) in the temporo-parieto-occipital cortex bilaterally, including the multisensory vestibular cortex and visual motion-sensitive areas (MT/MST), as well as in the striatum and the right thalamus. Longer illness duration was associated with bilaterally lower D 2/3 formula-receptor availability in the middle/superior temporal gyrus (GTm/s). D 2/3 formula-receptor availability in the right GTm/s and bilateral insula decreased with severity of symptoms. BVF-patients with oscillopsia showed reduced D 2/3 formula-receptor availability in the right MT/MST and midbrain tectum., Conclusions: Reduced D 2/3 formula-receptor availability in multisensory vestibular cortical network areas and basal ganglia may indicate a receptor down-regulation due to the lack of peripheral vestibular input. The more pronounced decline in D 2/3 formula-receptor availability in the multisensory vestibular cortex in patients with prolonged illness suggests the occurrence of progressive changes in dopamine transmission.

The present study aimed to reveal the effects of age on the temporal profile of the positive blood-oxygen-level-dependent response (PBR) during low-velocity optokinetic nystagmus (OKN) in healthy subjects. We were specifically interested in comparing these effects with the effects of age on the PBR elicited by pure visual and motor tasks. Therefore, we conducted 2 additional control experiments: a checkerboard experiment (visual stimulation) and a finger-tapping (motor task) experiment. Whereas the oculomotor performance of the subjects remained unaltered, the temporal profile of the PBR changed significantly with increasing age in visual and oculomotor areas. None of the control experiments revealed significant age-related PBR changes. Thus, this study demonstrates that the PBR changes during OKN occur before any changes in the oculomotor performance can be detected. These effects of age are specific for the OKN task and probably reflect both changes in the neurovascular coupling and changes in the neural processing during OKN., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Objective: The aim of this fluorodeoxyglucose (FDG)-PET study was to determine whether the activation pattern in patients with an acute unilateral central vestibular lesion (e.g., lesion of the vestibular nucleus) differs from that known in patients with an acute peripheral vestibular deficit., Methods: Twelve patients with circumscribed unilateral medullary brainstem infarctions (6 right, 6 left) causing acute vestibular imbalance underwent resting-state (18)F-FDG-PET. Regional cerebral glucose metabolism was measured twice without any stimulation and with eyes closed: in the acute phase after infarct onset on mean day 8 (range 4-12), and again 6 months later in 7 patients after recovery. Group subtraction analyses and comparisons with a dataset of 12 age-matched controls were done with Statistic Parametric Mapping., Results: In the acute stage, the pattern of signal increases differed from that in peripheral vestibular lesions: whereas signals in the infratentorial areas in the contralateral medulla and cerebellum (peduncle, vermis, hemispheres) were increased, areas at the cortical level were largely spared. Signal decreases were found in similar sites in the visual cortex bilaterally., Conclusions: The current data provide evidence that the lesion site significantly modifies the glucose metabolism pattern in an acute vestibular lesion. Different compensation strategies seem to be apparent: after vestibular nucleus lesions, compensation occurs preferably in brainstem-cerebellar loops; after peripheral lesions, it occurs at the cortical level.

Background: Earlier functional imaging studies on visually induced self-motion perception (vection) disclosed a bilateral network of activations within primary and secondary visual cortex areas which was combined with signal decreases, i.e., deactivations, in multisensory vestibular cortex areas. This finding led to the concept of a reciprocal inhibitory interaction between the visual and vestibular systems. In order to define areas involved in special aspects of self-motion perception such as intensity and duration of the perceived circular vection (CV) or the amount of head tilt, correlation analyses of the regional cerebral glucose metabolism, rCGM (measured by fluorodeoxyglucose positron-emission tomography, FDG-PET) and these perceptual covariates were performed in 14 healthy volunteers. For analyses of the visual-vestibular interaction, the CV data were compared to a random dot motion stimulation condition (not inducing vection) and a control group at rest (no stimulation at all)., Results: Group subtraction analyses showed that the visual-vestibular interaction was modified during CV, i.e., the activations within the cerebellar vermis and parieto-occipital areas were enhanced. The correlation analysis between the rCGM and the intensity of visually induced vection, experienced as body tilt, showed a relationship for areas of the multisensory vestibular cortical network (inferior parietal lobule bilaterally, anterior cingulate gyrus), the medial parieto-occipital cortex, the frontal eye fields and the cerebellar vermis. The "earlier" multisensory vestibular areas like the parieto-insular vestibular cortex and the superior temporal gyrus did not appear in the latter analysis. The duration of perceived vection after stimulus stop was positively correlated with rCGM in medial temporal lobe areas bilaterally, which included the (para-)hippocampus, known to be involved in various aspects of memory processing. The amount of head tilt was found to be positively correlated with the rCGM of bilateral basal ganglia regions responsible for the control of motor function of the head., Conclusions: Our data gave further insights into subfunctions within the complex cortical network involved in the processing of visual-vestibular interaction during CV. Specific areas of this cortical network could be attributed to the ventral stream ("what" pathway) responsible for the duration after stimulus stop and to the dorsal stream ("where/how" pathway) responsible for intensity aspects.