414 research outputs found
Progress in neuro-otology research in the last year
Herein, we summarize articles in the field of neuro-otology published in the Journal of Neurology over the last year. Topics included acute and chronic vertigo as well as auditory and ocular motor disorders. Characteristic lesion locations in Pusher syndrome are reported and the usefulness of bedside ocular motor tests in vertebrobasilar stroke is revisited. Probing the vestibular system and its value in predicting the outcome in vegetative state is discussed. Several articles address new diagnostic and therapeutic approaches in different disorders associated with chronic vestibular, auditory or gait deficits. In a series of case reports, we focus on different eye movement disorders in the vertical plane, which are often difficult to asses
Asymmetric short-term adaptation of the vertical vestibulo-ocular reflex in humans
Anatomical and electrophysiological studies have demonstrated up-down asymmetries in vertical ocular motor pathways. We investigated whether these asymmetries extend to the capacity for short-term adaptation of the vertical vestibulo-ocular reflex (VVOR) in humans. Specifically, we asked whether smooth pursuit signals are sufficient to asymmetrically adapt the VVOR. Healthy human subjects (N=8), positioned 90° left-ear-down and fixating with their eyes upon a small laser dot (diameter: 0.1°) projected on a sphere (distance: 1.4m) were trained toward low VVOR gain for 30min with symmetric and asymmetric visual VVOR cancellation paradigms, while being oscillated (0.2Hz, ±20°) on a motorized turntable about the interaural earth-vertical axis. During asymmetric VVOR cancellation, the target was head-fixed in either the pitch-up or pitch-down half-cycles of oscillation (=trained direction) and space-fixed during the other half-cycles (=untrained direction). During symmetric VVOR cancellation, the target was head-fixed throughout the oscillations. Before and after adaptation, the pitch-up and pitch-down VOR gains were assessed during turntable oscillation in complete darkness. Before adaptation, average gains of pitch-up (0.75±0.15 SD) and pitch-down (0.79±0.19 SD) VOR were not significantly different (paired t test: P>0.05). On an average, relative gain reductions induced by selective pitch-up (pitch-up VOR: 32%; pitch-down VOR: 21%) and pitch-down (pitch-up VOR: 18%; pitch-down VOR: 30%) VOR cancellation were significantly (P<0.05) larger in the trained than in the untrained direction. Symmetric visual VVOR cancellation led to a significantly (P<0.01) larger relative gain reduction of the pitch-down (41%) than the pitch-up (33%) VOR. None of the paradigms led to significant changes of phase or offset. We conclude that, in human subjects, the smooth pursuit system is capable to asymmetrically decrease the gain of the VVOR equally well in both the upward and downward direction. The unexpected asymmetric decrease of the VVOR gain after symmetric visual cancellation may be related to the directional preferences of vertical gaze-velocity sensitive Purkinje cells in the flocculus for the downward directio
Human 3-D aVOR with and without otolith stimulation
We describe in detail the frequency response of the human three-dimensional angular vestibulo-ocular response (3-D aVOR) over a frequency range of 0.05-1Hz. Gain and phase of the human aVOR were determined for passive head rotations in the dark, with the rotation axis either aligned with or perpendicular to the direction of gravity (earth-vertical or earth-horizontal). In the latter case, the oscillations dynamically stimulated both the otolith organs and the semi-circular canals. We conducted experiments in pitch and yaw, and compared the results with previously-published roll data. Regardless of the axis of rotation and the orientation of the subject, the gain in aVOR increased with frequency to about 0.3Hz, and was approximately constant from 0.3 to 1Hz. The aVOR gain during pitch and yaw rotations was larger than during roll rotations. Otolith and canal cues combined differently depending upon the axis of rotation: for torsional and pitch rotations, aVOR gain was higher with otolith input; for yaw rotations the aVOR was not affected by otolith stimulation. There was a phase lead in all three dimensions for frequencies below 0.3Hz when only the canals were stimulated. For roll and pitch rotations this phase lead vanished with dynamic otolith stimulation. In contrast, the horizontal phase showed no improvement with additional otolith input during yaw rotations. The lack of a significant otolith contribution to the yaw aVOR was observed when subjects were supine, prone or lying on their sides. Our results confirm studies with less-natural stimuli (off-vertical axis rotation) that the otoliths contribute a head-rotation signal to the aVOR. However, the magnitude of the contribution depends on the axis of rotation, with the gain in otolith-canal cross-coupling being smallest for yaw axis rotations. This could be because, in humans, typical yaw head movements will stimulate the otoliths to a much lesser extent then typical pitch and roll head movement
Head roll dependent variability of subjective visual vertical and ocular counterroll
We compared the variability of the subjective visual vertical (SVV) and static ocular counterroll (OCR), and hypothesized a correlation between the measurements because of their shared macular input. SVV and OCR were measured simultaneously in various whole-body roll positions [upright, 45° right-ear down (RED), and 75° RED] in six subjects. Gains of OCR were −0.18 (45° RED) and −0.12 (75° RED), whereas gains of compensation for body roll in the SVV task were −1.11 (45° RED) and −0.96 (75° RED). Normalized SVV and OCR variabilities were not significantly different (P>0.05), i.e., both increased with increasing roll. Moreover, a significant correlation (R 2=0.80, slope=0.29) between SVV and OCR variabilities was found. Whereas the gain of OCR is different from the gain of SVV, trial-to-trial variability of OCR follows the same roll-dependent modulation observed in SVV variability. We propose that the similarities in variability reflect a common otolith input, which, however, is subject to distinct central processing for determining the gain of SVV and OC
Head-Shaking Nystagmus Depends on Gravity
In acute unilateral peripheral vestibular deficit, horizontal spontaneous nystagmus (SN) increases when patients lie on their affected ear. This phenomenon indicates an ipsilesional reduction of otolith function that normally suppresses asymmetric semicircular canal signals. We asked whether head-shaking nystagmus (HSN) in patients with chronic unilateral vestibular deficit following vestibular neuritis is influenced by gravity in the same way as SN in acute patients. Using a three-dimensional (3-D) turntable, patients (N = 7) were placed in different whole-body positions along the roll plane and oscillated (1Hz, ±10°) about their head-fixed vertical axis. Eye movements were recorded with 3-D magnetic search coils. HSN was modulated by gravity: When patients lay on their affected ear, slow-phase eye velocity significantly increased upon head shaking and consisted of a horizontal drift toward the affected ear (average: 1.2°/s ±0.5 SD), which was added to the gravity-independent and directionally nonspecific SN. In conclusion, HSN in patients with chronic unilateral peripheral vestibular deficit is best elicited when they are lying on their affected ear. This suggests a gravity-dependent mechanism similar to the one observed for SN in acute patients, i.e., an asymmetric suppression of vestibular nystagmus by the unilaterally impaired otolith organ
A model-based theory on the origin of downbeat nystagmus
The pathomechanism of downbeat nystagmus (DBN), an ocular motor sign typical for vestibulo-cerebellar lesions, remains unclear. Previous hypotheses conjectured various deficits such as an imbalance of central vertical vestibular or smooth pursuit pathways to be causative for the generation of spontaneous upward drift. However, none of the previous theories explains the full range of ocular motor deficits associated with DBN, i.e., impaired vertical smooth pursuit (SP), gaze evoked nystagmus, and gravity dependence of the upward drift. We propose a new hypothesis, which explains the ocular motor signs of DBN by damage of the inhibitory vertical gaze-velocity sensitive Purkinje cells (PCs) in the cerebellar flocculus (FL). These PCs show spontaneous activity and a physiological asymmetry in that most of them exhibit downward on-directions. Accordingly, a loss of vertical floccular PCs will lead to disinhibition of their brainstem target neurons and, consequently, to spontaneous upward drift, i.e., DBN. Since the FL is involved in generation and control of SP and gaze holding, a single lesion, e.g., damage to vertical floccular PCs, may also explain the associated ocular motor deficits. To test our hypothesis, we developed a computational model of vertical eye movements based on known ocular motor anatomy and physiology, which illustrates how cortical, cerebellar, and brainstem regions interact to generate the range of vertical eye movements seen in healthy subjects. Model simulation of the effect of extensive loss of floccular PCs resulted in ocular motor features typically associated with cerebellar DBN: (1) spontaneous upward drift due to decreased spontaneous PC activity, (2) gaze evoked nystagmus corresponding to failure of the cerebellar loop supporting neural integrator function, (3) asymmetric vertical SP deficit due to low gain and asymmetric attenuation of PC firing, and (4) gravity-dependence of DBN caused by an interaction of otolith-ocular pathways with impaired neural integrator functio
Eye position dependency of nystagmus during constant vestibular stimulation
Alexander's law, the eye position dependency of nystagmus due to peripheral vestibular lesions, has been hypothesized to occur due to adaptive changes in the brainstem velocity-to-position neural integrator in response to non-reciprocal vestibular stimulation. We investigated whether it develops during passive head rotations that produce constant nystagmus for>35s. The yaw rotation stimulus consisted of a 1-s acceleration (100°/s2), followed by a lower acceleration ramp (starting at 7.3°/s2 and increasing at 0.04°/s2/s) until 400°/s was reached after 38s. This stimulus was designed to offset the~15 s vestibular ocular reflex time constant (and the 150 s adaptation time constant) and produce constant velocity slow phases. In contrast to peripheral lesions, this vestibular stimulation is the result of real head turns and has the push-pull characteristics of natural movements. The procedure was successful, as the average velocity of 31°/s was unchanged over the final 35s of the acceleration period. In all 10 healthy human subjects, we found a large and stable Alexander's law, with an average velocity-versus-position slope of −0.366 in the first half that was not significantly different in the second half, −0.347. These slopes correspond to integrator time constants of<3s, are much less than normal time constants (~25s), and are similar to those observed in patients with peripheral vestibular lesions. Alexander's law also developed, on average, in 10s. We conclude that Alexander's law is not simply a consequence of non-reciprocal vestibular stimulatio
A non-invasive biomechanical model of mild TBI in larval zebrafish
A mild traumatic brain injury is a neurological dysfunction caused by biomechanical forces transmitted to the brain in physical impacts. The current understanding of the neuropathological cascade resulting in the manifested clinical signs and symptoms is limited due to the absence of sensitive brain imaging methods. Zebrafish are established models for the reproduction and study of neurobiological pathologies. However, all available models mostly recreate moderate-to-severe focal injuries in adult zebrafish. The present work has induced a mild brain trauma in larval zebrafish through a non-invasive biomechanical approach. A custom-made apparatus with a commercially available motor was employed to expose larvae to rapidly decelerating linear movements. The neurophysiological changes following concussion were assessed through behavioural quantifications of startle reflex locomotor distance and habituation metrics. Here we show that the injury was followed, within five minutes, by a transient anxiety state and CNS dysfunction manifested by increased startle responsivity with impaired startle habituation, putatively mirroring the human clinical sign of hypersensitivity to noise. Within a day after the injury, chronic effects arose, as evidenced by an overall reduced responsivity to sensory stimulation (lower amplitude and distance travelled along successive stimuli), reflecting the human post-concussive symptomatology. This study represents a step forward towards the establishment of a parsimonious (simple, less ethically concerning, yet sensitive) animal model of mild TBI. Our behavioural findings mimic aspects of acute and chronic effects of human concussion, which warrant further study at molecular, cellular and circuit levels. While our model opens wide avenues for studying the underlying cellular and molecular pathomechanisms, it also enables high-throughput testing of therapeutic interventions to accelerate post-concussive recovery
Neuro-ophthalmology update
This review summarizes the most relevant articles from the field of neuro-ophthalmology published in the Journal of Neurology from January 2012 to July 2013. With the advent of video-oculography, several articles describe new applications for eye movement recordings as a diagnostic tool for a wide range of disorders. In myasthenia gravis, anti-Kv1.4 and anti-Lrp4 have been characterized as promising novel autoantibodies for the diagnosis of hitherto ‘seronegative' myasthenia gravis. Several articles address new diagnostic and therapeutic approaches to neuromyelitis optica, which further sharpen its profile as a distinct entity. Additionally, 4-aminopyridine has become a standard therapeutic for patients with cerebellar downbeat nystagmus. Finally, revised diagnostic criteria have been proposed for chronic relapsing inflammatory optic neuropathy based on a careful literature review over the last decade
Dizziness and benign paroxysmal positional vertigo among retirement home residents: a cross-sectional descriptive and interventional study
BACKGROUND
The prevalence of dizziness increases with age. We aimed to determine the point prevalence of dizziness and, in particular, of benign paroxysmal positional vertigo (BPPV) among retirement home residents. Furthermore, we aimed to evaluate the efficacy of a 2-axis turntable based BPPV treatment.
METHODS
We contacted all large retirement homes in or around the city of Zurich (Switzerland). 10 retirement homes (with a total of 536 residents) agreed to participate in this study. 83 rejected inquiries by residents led to a potential study population of 453 residents. After a structured interview evaluating the presence and characteristics of dizziness, all willing patients were tested for positional vertigo and nystagmus on a portable and manually operated 2-axis turntable that was transported to the retirement home. Testing consisted of the Dix-Hallpike and supine roll maneuvers to both sides. Participants were immediately treated with the appropriate liberation maneuver whenever BPPV was diagnosed. Otherwise, taking the resident's medical history, a neuro-otological bedside examination, and a review of the available medical documentation was used to identify other causes of dizziness.
RESULTS
Out of the 453 residents, 75 (16.6%; average age: 87.0 years; 68% female) were suffering from dizziness presently or in the recent past and gave their consent to participate in this study. Among the participants tested on the turntable (n = 71), BPPV was present in 11.3% (point prevalence). Time-related properties, triggering factors and qualitative attributes of vertigo or dizziness were not significantly different between the dizzy participants with and those without BPPV. In all BPPV patients, appropriate liberation maneuvers were successful.
CONCLUSIONS
BPPV could be demonstrated in about one tenth of retirement home residents with dizziness or recent dizziness. Such point prevalence of BPPV translates to a much higher yearly prevalence if one assumes that BPPV is not present on every day. Our finding suggests that retirement home residents suffering from dizziness should be regularly tested for BPPV and treated with appropriate liberation maneuvers, ideally on turntable to reduce strain.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT03643354
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