Primary or secondary chronic functional dizziness: does it make a difference?

In 2017, the term \textquotedblpersistent postural-perceptual dizziness\textquotedbl (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

Intravenous Delayed Gadolinium-Enhanced MR Imaging of the Endolymphatic Space: A Methodological Comparative Study

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, mm2] and volume [3D, mm3] 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

Ventral and dorsal streams processing visual motion perception (FDG-PET study)

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

Functional Plasticity after Unilateral Vestibular Midbrain Infarction in Human Positron Emission Tomography

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

Direct comparison of activation maps during galvanic vestibular stimulation: A hybrid H-2[(15) O] PET-BOLD MRI activation study

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 (H2O)-O-15-PET and BOLD MRI responses. List mode PET acquisition started with the injection of 750 MBq (H2O)-O-15 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 (H2O)-O-15-PET and additional non-CBF effects, and the activation-deactivation pattern of the BOLD-block appears to be more similar to the (H2O)-O-15-PET than the BOLD-onset

Structural reorganization of the cerebral cortex after vestibulo-cerebellar stroke

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

Global multisensory reorganization after vestibular brain stem stroke

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