Influence of Visual and Vestibular Hypersensitivity on Derealization and Depersonalization in Chronic Dizziness

Objective: The aim of this study was to investigate the relation between visual and vestibular hypersensitivity, and Depersonalization/Derealization symptoms in patients with chronic dizziness.Materials and Methods: 319 adult patients with chronic dizziness for more than 3 months (214 females and 105 males, mean age: 58 years, range: 13–90) were included in this prospective cross-sectional study. Patients underwent a complete audio-vestibular workup and 3 auto questionnaires: Hospital Anxiety and Depression (HAD), Depersonalization/Derealization Inventory (DDI), and an in-house questionnaire (Dizziness in Daily Activity, DDA) assessing 9 activities with a score ranging from 0 (no difficulty) to 10 (maximal discomfort) and 11 (avoidance) to detect patients with visual and vestibular hypersensitivity (VVH, a score > 41 corresponding to mean + 1 standard deviation).Results: DDI scores were higher in case of VVH (6.9 ± 6.79, n = 55 vs. 4.2 ± 4.81, n = 256 without VVH, p < 0.001, unpaired t-test), migraine (6.1 ± 6.40, n = 110 vs. 4.0 ± 4.42, n = 208no migraine, p < 0.001, unpaired t-test), and motion sickness (6.8 ± 5.93, n = 41 vs. 4.4 ± 5.11, n = 277 no motion sickness, p < 0.01, unpaired t-test). Women scored DDI higher than men (5.1 ± 5.42, n = 213 vs. 3.9 ± 4.91, n = 105, respectively, p < 0.05, unpaired t-test). DDI scores were also related to depression and anxiety. DDI score was also higher during spells than during the basal state.Conclusion: During chronic dizziness, Depersonalization/Derealization symptoms seem to be related to anxiety and depression. Moreover, they were prominent in women, in those with visual and vestibular hypersensitivity, migraine, and motion sickness

Effect of Rotating Auditory Scene on Postural Control in Normal Subjects, Patients With Bilateral Vestibulopathy, Unilateral, or Bilateral Cochlear Implants

Objective: The aim of this study was to investigate the impact of a rotating sound stimulation on the postural performances in normal subjects, patients with bilateral vestibulopathy (BVP), unilateral (UCI), and bilateral (BCI) cochlear implantees.Materials and Methods: Sixty-nine adults were included (32 women and 37 men) in a multicenter prospective study. The group included 37 healthy subjects, 10 BVP, 15 UCI, and 7 BCI patients. The average of age was 47 ± 2.0 (range: 23–82). In addition to a complete audiovestibular work up, a dynamic posturography (Multitest Framiral, Grasse) was conducted in silence and with a rotating cocktail party sound delivered by headphone. The center of pressure excursion surface (COPS), sensory preferences, as well as fractal, diffusion, and wavelet analysis of stabilometry were collected.Results: The rotating sound seemed to influenced balance in all subgroups except in controls. COPS increased with sound in the BVP and BCI groups in closed eyes and sway-referenced condition indicating a destabilizing effect while it decreased in UCI in the same condition suggesting stabilization (p < 0.05, linear mixed model corrected for age, n = 69). BVP had higher proprioceptive preferences, BCI had higher vestibular and visual preferences, and UCI had only higher vestibular preferences than controls. Sensory preferences were not altered by rotating sound.Conclusions: The rotating sound destabilized BVP and BCI patients with binaural hearing while it stabilized UCI patients with monaural hearing and no sound rotation effect. This difference suggests that binaural auditory cues are exploited in BCI patients for their balance

Visual Input Is the Main Trigger and Parametric Determinant for Catch-Up Saccades During Video Head Impulse Test in Bilateral Vestibular Loss

Patients with vestibular deficit use slow eye movements or catch-up saccades (CUS) to compensate for impaired vestibulo-ocular reflex (VOR). The purpose of CUS is to bring the eyes back to the visual target. Covert CUS occur during high-velocity head rotation and overt CUS are generated after head rotation has stopped. Dynamic visual acuity is improved with an increased rate and gain of CUS. Nevertheless, the trigger and the parametric determinants of CUS are still under debate. To clarify the underlying mechanism, especially the visual contribution, we analyzed the number, amplitude and latencies of the CUS in relation with the extent of VOR deficiency. The head and eye movements were recorded in 17 patients with bilateral vestibular loss (BVL) and in 33 subjects with normal VOR gain using the Video Head Impulse Test (vHIT) in two conditions: with visible target and in darkness with an imaginary target. Our study shows that in darkness without visible target the number of CUS is significantly reduced and the relationship between the amplitude of CUS and gaze position error is lost. Results showed that there is a correlation between the number of CUS and the drop in VOR gain. CUS occurring during the head movement and when the head remained still were not always sufficiently accurate. Up to four consecutive CUS could be required to bring eyes back to the visible target. A positive correlation was found between the amplitude of overt saccades with visible target and the gaze position error, namely the remaining eye movement to reach the target. These results suggest that the visual inputs are the main trigger and parametric determinant of the CUS or at least the presence of a visual target is necessary in most cases for a CUS to occur

Effective Gene Therapy in a Mouse Model of Prion Diseases

Classical drug therapies against prion diseases have encountered serious difficulties. It has become urgent to develop radically different therapeutic strategies. Previously, we showed that VSV-G pseudotyped FIV derived vectors carrying dominant negative mutants of the PrP gene are efficient to inhibit prion replication in chronically prion-infected cells. Besides, they can transduce neurons and cells of the lymphoreticular system, highlighting their potential use in gene therapy approaches. Here, we used lentiviral gene transfer to deliver PrPQ167R virions possessing anti-prion properties to analyse their efficiency in vivo. Since treatment for prion diseases is initiated belatedly in human patients, we focused on the development of a curative therapeutic protocol targeting the late stage of the disease, either at 35 or 105 days post-infection (d.p.i.) with prions. We observed a prolongation in the lifespan of the treated mice that prompted us to develop a system of cannula implantation into the brain of prion-infected mice. Chronic injections of PrPQ167R virions were done at 80 and 95 d.p.i. After only two injections, survival of the treated mice was extended by 30 days (20%), accompanied by substantial improvement in behaviour. This delay was correlated with: (i) a strong reduction of spongiosis in the ipsilateral side of the brain by comparison with the contralateral side; and (ii) a remarkable decrease in astrocytic gliosis in the whole brain. These results suggest that chronic injections of dominant negative lentiviral vectors into the brain, may be a promising approach for a curative treatment of prion diseases

Vertiges en urgence

One person out of two has experienced (or will experience) dizziness at least once, and one out of seven acute vertigo. 5% of the patients seen by a GP have vertigo and/or disequilibrium. In 37% of the cases, patients are referred to a specialist. In 2%, a serious disorder is diagnosed: an embolic transient ischemic attack due to vertebral artery dissection, or basilar trunk dissection, affecting the posterior fossa. During diving, aero-embolic accidents affect more electively the inner ear, but sometimes severe medullary lesions may be associated. In fact, most of vertiginous patients coming to emergency departments present with benign positional paroxysmal vertigo (35%), first manifestations of a Ménière's disease (6%), or vestibular neuritis (6%); more rarely temporal bone fracture, or infectious complications such as the rare and severe infectious labyrinthitis. Knowing how to diagnose a transient ischemic attack of the posterior fossa, and being aware of adequate therapeutic strategies for each of the main causes of vertigo, are essential for the emergency doctor. © 2004 Elsevier SAS. Tous droits réservés.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

How eye movements stabilize posture in patients with bilateral vestibular hypofunction

Chronic patients with bilateral vestibular hypofunction (BVH) complain of oscillopsia and great instability particularly when vision is excluded and on irregular surfaces. The real nature of the visual input substituting to the missing vestibular afferents and improving posture control remains however under debate. Is retinal slip involved? Do eye movements play a substantial role? The present study tends to answer this question in BVH patients by investigating their posture stability during quiet standing in four different visual conditions: total darkness, fixation of a stable space-fixed target, and pursuit of a visual target under goggles delivering visual input rate at flicker frequency inducing either slow eye movements (4.5 Hz) or saccades (1.2 Hz). Twenty one chronic BVH patients attested by both the caloric and head impulse test were examined by means of static posturography, and compared to a control group made of 21 sex-and age-matched healthy participants. The posturography data were analyzed using non-linear computation of the center of foot pressure (CoP) by means of the wavelet transform (Power Spectral Density in the visual frequency part, Postural Instability Index) and the fractional Brownian-motion analysis (stabilogram-diffusion analysis, Hausdorff fractal dimension). Results showed that posture stability was significantly deteriorated in darkness in the BVH patients compared to the healthy controls. Strong improvement of BVH patients' posture stability was observed during fixation of a visual target, pursuit with slow eye movements, and saccades, whereas the postural performance of the control group was less affected by the different visual conditions. It is concluded that BVH patients improve their posture stability by (1) using extraocular signals from eye movements (efference copy, muscle re-afferences) much more than the healthy participants, and (2) shifting more systematically than the controls to a more automatic mode of posture control when they are in dual-task conditions associating the postural task and a concomitant visuo-motor task.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Stratégies thérapeutiques des maladies à prions

Les maladies à prions sont des maladies neurodégénératives qui touchent l'homme et l'animal, et dont l'issue est fatale. Ces maladies sont provoquées par l'accumulation dans le cerveau de la PrPSc, l'isoforme mal repliée de la protéine prion cellulaire. L'apparition de nouveaux risques de transmission de ces maladies et l'absence de traitement efficace, nous ont incité à explorer de nouvelles stratégies et cibles thérapeutiques. Nous avons développé deux approches thérapeutiques innovantes. La première à consister à rechercher des molécules capables de piéger les formes préamyloïdes de la PrPSc (dimères et trimères), décrites comme éléments essentiels du cycle de réplication des prions. Une technique de criblage de drogues in silico et in cellulo nous a permis de mettre en évidence des composés thiényl pyrimidiques et thiényl azines capables d'oligomériser spécifiquement la PrPSc. Ces oligomères de PrPSc réduisent l'infectiosité des prions in vivo, soulignant le potentiel thérapeutique de ces composés. Notre deuxième stratégie est une stratégie de thérapie génique utilisant les propriétés dominantes négatives de certains polymorphismes de la protéine prion, comme les mutants Q218K et Q167R. Notre objectif a été d'évaluer le potentiel thérapeutique de vecteurs lentiviraux portant les mutants PrPQ218K et PrPQ167R, chez des souris au stade tardif de la maladie. Nous avons réussi à prolonger significativement la durée de vie des souris de 20% grâce à 2 injections chroniques de vecteurs lentiviraux portant le mutant PrPQ167R. Nos résultats ouvre la voie sur de nouvelles perspespectives thérapeutiques pour les maladies à prions et autres maladies neurodégénérativesPrion diseases are fatal neurodegenerative disorders that affect both humans and animals. These diseases are induced by the accumulation in the brain of the misfolded isoform of the normal cellular prion protein: PrPSc. The emergence of new risks of transmission for these diseases and the lack of efficient treatments, prompt us to search for new therapeutic strategies and targets. We developed two innovative therapeutic approaches. The first one consisted in searching for molecules able to trap preamyloid forms of PrPSc (dimers and trimers), known as key elements in the replication cycle of prions. A drugs screening approach, in silico and in cellulo, allowed us to discover thienyl pyrimidine and thienyl azine compounds able to specifically oligomerize PrPSc molecules. These PrPSc oligomers decrease prions infectivity in vivo, highlighting the therapeutic potential of these compounds. Our second strategie is a gene therapy approach using the dominant negative properties of certain polymorphisms of the prion protein, such as the Q218K and Q167R mutants. Our objective was to evaluate the therapeutic potential of lentiviral vectors carrying the PrPQ218K and PrPQ167R mutants, in mice, at the terminal stage of the disease. We succeeded in significantly prolonging the survival time of mice of 20%, with two intracerebrally chronic injections of lentiviral vectors carrying the PrPQ167R mutant. All our results not only open the way for new therapeutic strategies against prion diseases but also will benefit for therapies of other neurodegenerative disordersMONTPELLIER-BU Sciences (341722106) / SudocSudocFranceF

Effect of Repositioning Maneuver Type and Postmaneuver Restrictions on Vertigo and Dizziness in Benign Positional Paroxysmal Vertigo

Introduction. To compare the efficiency of Epley (Ep) and Sémont-Toupet (ST) repositioning maneuvers and to evaluate postmaneuver restriction effect on short-term vertigo and dizziness after repositioning maneuvers by an analog visual scale (VAS) in benign positional paroxysmal vertigo (BPPV). Material and Methods. 226 consecutive adult patients with posterior canal BPPV were included. Patients were randomized into 2 different maneuver sequence groups (n=113): 2 ST then 1 Ep or 2 Ep then 1 ST. Each group of sequence was randomized into 2 subgroups: with or without postmaneuver restrictions. Vertigo and dizziness were assessed from days 0 to 5 by VAS. Results. There was no difference between vertigo scores between Ep and ST groups. Dizziness scores were higher in Ep group during the first 3 days but became similar to those of ST group at days 4 and 5. ST maneuvers induced liberatory signs more frequently than Ep (58% versus 42% resp., P<0.01, Fisher's test). After repositioning maneuvers, VAS scores decreased similarly in patients with and without liberatory signs. Postmaneuver restrictions did not influence VAS scores. Conclusion. Even if ST showed a higher rate of liberatory signs than Ep in this series, VAS scores were not influenced by these signs

Maturation of Subjective Visual Vertical in Children

International audienceObjective: The attraction of the subjective visual vertical (SVV) to the side of initial rod presentation has already been described in adults. The aim of this study was to evaluate this phenomenon in children and to analyze the effect of sex and maturation in this population., Study Design: Retrospective cross-sectional study., Setting: Tertiary referral center., Patients: Six hundred and one individuals aged between 4 and 19 years., Intervention: All subjects underwent a complete balance workup. SVV was measured by presenting a laser line 12 times in total darkness with a 45 degrees deviation from the vertical alternatively on the left and the right. The patient was seated and asked to replace the bar vertically with a remote control., Results: On average, SVV was tilted to the side of the rod presentation at each iteration. The cumulative tilt to the side of presentation after 12 measures was higher in the 4 to 7 years age group and decreased progressively with age (25 +/- 2.2 degrees in 4-7 years, n = 109 versus 5 +/- 1.4 in 15-19 years, n = 204, p < 0.001, analysis of variance [ANOVA]). The cumulative tilt was higher in girls than in boys in the 15 to 19 years group (8 +/- 2.5 degrees, n = 104 versus 2 +/- 1.2, n = 100, respectively, p < 0.001, ANOVA). This phenomenon appeared independent from the type of vestibular disorder., Conclusion: Young children are highly attracted to the side of rod presentation during SVV measurements. This phenomenon gradually disappears with maturation, faster in boys than in girls., Copyright (C) 2016 by Otology & Neurotology, Inc. Image copyright (C) 2010 Wolters Kluwer Health/Anatomical Chart Compan