L-Thyroxine Improves Vestibular Compensation in a Rat Model of Acute Peripheral Vestibulopathy: Cellular and Behavioral Aspects.

Unilateral vestibular lesions induce a vestibular syndrome, which recovers over time due to vestibular compensation. The therapeutic effect of L-Thyroxine (L-T4) on vestibular compensation was investigated by behavioral testing and immunohistochemical analysis in a rat model of unilateral vestibular neurectomy (UVN). We demonstrated that a short-term L-T4 treatment reduced the vestibular syndrome and significantly promoted vestibular compensation. Thyroid hormone receptors (TRα and TRß) and type II iodothyronine deiodinase (DIO2) were present in the vestibular nuclei (VN), supporting a local action of L-T4. We confirmed the T4-induced metabolic effects by demonstrating an increase in the number of cytochrome oxidase-labeled neurons in the VN three days after the lesion. L-T4 treatment modulated glial reaction by decreasing both microglia and oligodendrocytes in the deafferented VN three days after UVN and increased cell proliferation. Survival of newly generated cells in the deafferented vestibular nuclei was not affected, but microglial rather than neuronal differentiation was favored by L-T4 treatment.

Proinflammatory activation of peripheral blood mononuclear cells in patients with vestibular neuritis.

Vestibular neuritis (VN) is characterized by acute vertigo with spontaneous nystagmus and is often accompanied by vegetative symptoms. While the pathogenetic process leading to this disease is widely unknown, increasing evidence exists that a proinflammatory environment is responsible for the induction and progression of VN. Twelve patients with acute VN and 12 healthy, age-matched individuals were included in this study. In addition to routine blood parameters, plasma levels of soluble CD40 receptor/ligand (sCD40/sCD40L) were determined by ELISA. Moreover, peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll density gradient. Afterwards, in CD14 (monocytes), CD68 (macrophages), CD3 (T lymphocytes) or CD19 (B lymphocytes) subpopulations, proinflammatory [CD40, tumor necrosis factor-α (TNF-α), and COX-2], proapoptotic [caspase-3, and poly(adenosine diphosphate ribose) polymerase] and proadhesive (CD38) proteins were measured by 2-color fluorescence-activated cell sorter analyses. In comparison to healthy individuals, patients with acute VN revealed significantly elevated plasma levels of C-reactive protein, whereas plasma levels of sCD40 and sCD40L, as well as cholesterol/triglyceride status were similar. However, we found a significant elevation of the percentage of proinflammatory CD40+, TNF-α+, COX-2+ or CD38+ PBMCs. Elevation of proinflammatory and proadhesive proteins in PBMCs of patients with acute VN in parallel with an acute phase response may contribute to disease induction and progression and, thus, may be suggested as a novel therapeutic target.

Mean platelet volume, neutrophil- and platelet to lymphocyte ratios are elevated in vestibular neuritis.

AIM: To evaluate the alterations in inflammatory markers, NLR and PLR, as well as mean platelet volume (MPV) and the other parameters of complete blood counts (CBC) in adult patients with vestibular neuritis (VN). METHOD: Designed as a case control study. The records of the patients, who were hospitalized due to an acute onset vertigo, and diagnosed as VN, were analysed retrospectively. The complete blood count (CBC) measures of the patients were statistically compared with the measures of healthy subjects. The correlations between the length of hospitalization and the neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) were also analysed. RESULTS: One hundred four patients with VN and 138 healthy controls were included. MPV, white blood cell and neutrophil counts, NLR and PLR were significantly higher; while lymphocyte count was significantly lower in the VN group (p < 0.001). There were no correlations between the length of hospitalization and NLR or PLR. CONCLUSION: The elevations of NLR and PLR support the role of inflammation in VN. The high level of MPV indicates the possible role of the vascular thrombosis in the etiology of VN.

The differential effects of acute right- vs. left-sided vestibular failure on brain metabolism.

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.

Disrupted functional connectivity of the default mode network due to acute vestibular deficit.

Vestibular neuritis is defined as a sudden unilateral partial failure of the vestibular nerve that impairs the forwarding of vestibular information from the labyrinth. The patient suffers from vertigo, horizontal nystagmus and postural instability with a tendency toward ipsilesional falls. Although vestibular neuritis is a common disease, the central mechanisms to compensate for the loss of precise vestibular information remain poorly understood. It was hypothesized that symptoms following acute vestibular neuritis originate from difficulties in the processing of diverging sensory information between the responsible brain networks. Accordingly an altered resting activity was shown in multiple brain areas of the task-positive network. Because of the known balance between the task-positive and task-negative networks (default mode network; DMN) we hypothesize that also the DMN is involved. Here, we employ functional magnetic resonance imaging (fMRI) in the resting state to investigate changes in the functional connectivity between the DMN and task-positive networks, in a longitudinal design combined with measurements of caloric function. We demonstrate an initially disturbed connectedness of the DMN after vestibular neuritis. We hypothesize that the disturbed connectivity between the default mode network and particular parts of the task-positive network might be related to a sustained utilization of processing capacity by diverging sensory information. The current results provide some insights into mechanisms of central compensation following an acute vestibular deficit and the importance of the DMN in this disease.

Early and phasic cortical metabolic changes in vestibular neuritis onset.

Functional brain activation studies described the presence of separate cortical areas responsible for central processing of peripheral vestibular information and reported their activation and interactions with other sensory modalities and the changes of this network associated to strategic peripheral or central vestibular lesions. It is already known that cortical changes induced by acute unilateral vestibular failure (UVF) are various and undergo variations over time, revealing different cortical involved areas at the onset and recovery from symptoms. The present study aimed at reporting the earliest change in cortical metabolic activity during a paradigmatic form of UVF such as vestibular neuritis (VN), that is, a purely peripheral lesion of the vestibular system, that offers the opportunity to study the cortical response to altered vestibular processing. This research reports [(18)F]fluorodeoxyglucose positron emission tomography brain scan data concerning the early cortical metabolic activity associated to symptoms onset in a group of eight patients suffering from VN. VN patients' cortical metabolic activity during the first two days from symptoms onset was compared to that recorded one month later and to a control healthy group. Beside the known cortical response in the sensorimotor network associated to vestibular deafferentation, we show for the first time the involvement of Entorhinal (BAs 28, 34) and Temporal (BA 38) cortices in early phases of symptomatology onset. We interpret these findings as the cortical counterparts of the attempt to reorient oneself in space counteracting the vertigo symptom (Bas 28, 34) and of the emotional response to the new pathologic condition (BA 38) respectively. These interpretations were further supported by changes in patients' subjective ratings in balance, anxiety, and depersonalization/derealization scores when tested at illness onset and one month later. The present findings contribute in expanding knowledge about early, fast-changing, and complex cortical responses to pathological vestibular unbalanced processing.

Metabolic changes in vestibular and visual cortices in acute vestibular neuritis.

Five right-handed patients with a right-sided vestibular neuritis were examined twice with fluorodeoxyglucose positron emission tomography while lying supine with eyes closed: once during the acute stage (mean, 6.6 days) and then 3 months later when central vestibular compensation had occurred. Regional cerebral glucose metabolism (rCGM) was significantly increased (p <0.001 uncorrected) during the acute stage in multisensory vestibular cortical and subcortical areas (parietoinsular vestibular cortex in the posterior insula, posterolateral thalamus, anterior cingulate gyrus [Brodmann area 32/24], pontomesencephalic brainstem, hippocampus). Simultaneously, there was a significant rCGM decrease in the visual (Brodmann area 17 to 19) and somatosensory cortex areas in the postcentral gyrus as well as in parts of the auditory cortex (transverse temporal gyrus). Fluorodeoxyglucose positron emission tomography thus allows imaging of the cortical activation pattern that is induced by unilateral peripheral vestibular loss. It was possible to demonstrate that the central vestibular system including the vestibular cortex exhibits a visual-vestibular activation-deactivation pattern during the acute stage of vestibular neuritis similar to that in healthy volunteers during unilateral labyrinthine stimulation. Contrary to experimental vestibular stimulation, the activation of the vestibular cortex was not bilateral but was unilateral and contralateral to the right-sided labyrinthine failure.