Catherine de Waele

Vestibular evoked myogenic potentials in patients suffering from an unilateral acoustic neuroma: a study of 170 patients

OBJECTIVEnTo determine the value of investigating the vestibular evoked myogenic potentials (VEMPs) induced by clicks and 500 Hz short tone burst (STB) for the diagnosis of acoustic neuromas.nnnMETHODSnWe studied the average responses to 100dB clicks and 500 Hz STB in the ipsilateral sternomastoid muscle. Ninety-five healthy subjects and 170 patients suffering from a unilateral acoustic neuroma were included in that study. Caloric and audiometric tests results were also analyzed.nnnRESULTSnThirty-six/170 patients (21.2%) exhibited normal responses to clicks and to STB whereas 134/170 (78.8%) gave abnormally low or no responses. 78/170 (45.9%) showed no responses to both clicks and STB. In 56/170 patients (32.9%), VEMPs induced by high level clicks and STB were discordant: STB VEMPs were either normal (n=32) or low (n=24) in patients with an abnormal response to clicks (no response n=40 or low response n=16). In contrast, STB-induced VEMPs were always normal in cases of normal responses to clicks. No strong, systematic correlation could be found between saccular nerve dysfunction and either the degree of 4-8 kHz hearing loss or the extent of horizontal canalar impairment.nnnCONCLUSIONSnThese data indicate that high level clicks and STB provide complementary information about the functionality of the saccular nerve. Clicks are useful to detect a minor saccular nerve dysfunction. In cases in which there is no response to clicks, STB gives valuable information about a potential residual function of the saccular nerve.

Saccular stimulation of the human cortex: A functional magnetic resonance imaging study

Recent imaging studies have reported the projection of semicircular canal signals onto wide regions of the cerebral cortex but little is known about otolith projections onto the cerebral cortex. We used functional magnetic resonance imaging (fMRI) to investigate the activation of the cortex by loud clicks that selectively stimulate the sacculus. Twelve normal volunteers were presented with auditory stimuli via an earphone containing a piezo electric element. High-intensity [maximum volume of 120 dB (SPL)] or low-intensity [maximum volume of 110 dB (SPL)] clicks were delivered at a frequency of 1 Hz and lasted 1 ms. We first checked that the high-intensity, but not low-intensity, clicks stimulated the sacculus by determining the vestibular evoked myogenic potentials. We then analyzed two task conditions (high- and low-intensity clicks) in a boxcar paradigm. We obtained gradient echo echo-planar images by using a 1.5 T MRI system. We analyzed the fMRI time series data with SPM2. High-intensity clicks activated wide areas of the cortex, namely, the frontal lobe (prefrontal cortex, premotor cortex, and frontal eye fields), parietal lobe (the region around the intraparietal sulcus, temporo-parietal junction, and paracentral lobule), and cingulate cortex. These areas are similar to those reported in previous imaging studies that analyzed the cortical responses to the activation of the semicircular canals. Thus, semicircular canal and otolith/saccular signals may be processed in similar regions of the human cortex.

Excitatory amino acid receptors in normal and abnormal vestibular function.

Although excitatory amino acid (FAA) receptors have been investigated extensively in the limbic system and neocortex, less is known of the function of EAA receptors in the brainstem. A number of biochemical and electrophysiological studies suggest that the synapse between the ipsilateral vestibular (VIIIth) nerve and the brainstem vestibular nucleus (VN) is mediated by an EAA acting predominantly on kainate or α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors. In addition, there is electrophysiological evidence that input from the contralateral vestibular nerve via the contralateral VN is partially mediated byN-methyl-d-aspartate (NMDA) receptors. Input to the VN from the spinal cord may also be partially mediated by NMDA receptors. All of the electrophysiological studies conducted so far have used in vitro preparations, and it is possible that denervation of the VN during the preparation of an explant or slice causes changes in EAA receptor function. Nonetheless, these results suggest that EAA receptors may be important in many different parts of the vestibular reflex pathways. Studies of the peripheral vestibular system have also shown that EAAs are involved in transmission between the receptor hair cells and the vestibular nerve fibers. A number of recent studies in the area of vestibular plasticity have reported that antagonists for the NMDA receptor subtype disrupt the behavioral recovery that occurs following unilateral deafferentation of the vestibular nerve fibers (vestibular compensation). It has been suggested that vestibular compensation may be owing to an upregulation or increased affinity of NMDA receptors in the VN ipsilateral to the peripheral deafferentation; however; at present, there is no clear evidence to support this hypothesis.

Effect of post-training unilateral labyrinthectomy in a spatial orientation task by guinea pigs.

The effects of unilateral labyrinthectomy in guinea pigs have been studied on an angular orientation task consisting, in an open field, of running to a hidden goal oriented at 45 degrees with respect to the cephalocaudal axis of the animal placed in a starting-box. The task was conducted in light but in an homogeneous environment, i.e. without visual, auditory or olfactory cues indicating the location of the goal. A second group of animals was submitted to a similar task running to a hidden goal but the place of the goal was indicated by a colored card. All the animals were trained before the lesion and tested in their respective task for 1 month after the lesion. In the task conducted without conspicuous cues, animals were dramatically disturbed. In contrast, animals pretrained in the visually guided task were not impaired after the lesion. These results point out the important role of vestibular information in performing spatial tasks based on angular estimation, since, even if proprioceptive and visuokinesthetic information remain available, subjects seemed not able to maintain a correct angular trajectory. The trajectories being not disturbed in the visually guided task, one can exclude the hypothesis that such deficit was due to a purely motor disturbance.

Lack of growth-associated protein-43 reemergence or of growth-associated protein-43 mRNA modulation in deafferented vestibular nuclei during the first 6 weeks after unilateral inner ear lesion

Abstract. We investigated whether a unilateral inner ear lesion that destroyed the labyrinthine receptors, the cochlear receptors, and the spiral ganglion induced collateral sprouting in rat vestibular and auditory brainstem nuclei, using growth-associated protein-43 (GAP-43) as an indicator of synaptic remodeling. Both immunocytochemistry and in situ hybridization were performed to detect a potential modulation of GAP-43 and of its messenger RNA (mRNA) at different times after surgery. We failed to observe a reemergence of GAP-43 or a modulation of its mRNA in the deafferented vestibular nuclei at all survival times tested. In contrast, a substantial increase in the expression of GAP-43 was observed in the neuropil of the ipsilateral deafferented cochlear nuclei and in cell bodies of the ipsilateral superior olive. This increase was associated with an up- and downregulation of the mRNA coding for GAP-43 in the ipsilateral ventral cochlear nucleus and in the ipsilateral superior olive, respectively. These data indicate that synaptic remodeling, as assessed by GAP-43 expression, does not seem to occur in the deafferented vestibular complex during the first 6xa0weeks after labyrinthectomy, whereas it occurs within the first deafferented auditory relays at times as early as 4xa0days following spiral ganglion and cochlear receptors removal. We conclude that recovery of a normal resting discharge of the deafferented central vestibular neurons and consequently recovery of a normal resting posture and eye position may not depend on collateral sprouting of the remaining vestibular afferents. In contrast, we confirmed that a reactive synaptogenesis occurs in the brainstem auditory nuclei following cochlea and spiral ganglion removal. Its functional significance remains an open question.

Modulation of glycine receptor subunits and gephyrin expression in the rat facial nucleus after axotomy

In the last decade, numerous studies have investigated molecular changes in excitatory glutamatergic receptors in axotomized motoneurons, but few data are available concerning the modulation of inhibitory amino acid receptors. We report here the effect of axotomy on the expression of glycine receptors, gephyrin, vesicular inhibitory amino acid transporter (VIAAT) and synapsinu2003I in rat facial motor neurons as demonstrated by in situ hybridization and immunohistochemistry. The facial nerve trunk was sectioned unilaterally and rats were killed 1, 3, 8, 30 or 60u2003days after surgery. We investigated the mechanisms underlying the changes in production of these proteins following axotomy by perfusing the facial nerve with colchicine or tetrodotoxin, and injecting cardiotoxin or botulinum toxin independently and unilaterally into the whisker pads of normal rats. Animals were killed 8u2003days later and processed for immunohistochemistry. The abundance of GlyR subunits and gephyrin fell sharply in the axotomized facial nucleus. This decrease began 1u2003day after axotomy and was lowest at 8u2003days, with protein levels returning to normal by dayu200360. Abnormal synapsin immunolabelling was also observed between daysu20038 and 60 after axotomy but we detected no change in VIAAT immunoreactivity. The effect of colchicine was similar to, but weaker than, that of axotomy. In contrast, tetrodotoxin, cardiotoxin and botulinum toxin had no significant effect. Thus, axotomy‐induced changes probably resulted from a loss of trophic factor transported from the periphery or a positive injury signal, or both. They did not seem to depend on the disruption of activity.

Saccular projections in the human cerebral cortex.

Abstract: The cerebral cortical areas processing saccular information were investigated in human subjects using the fMRI method and loud clicks, which selectively activate the saccule. The results were compared with previous vestibular evoked potential (VEP) studies in anesthetized patients following vestibular nerve stimulation. Nine normal subjects participated in fMRI studies. By comparing the cortical areas activated by a click at 85 dB (auditory activation) with those activated by 102 dB (auditory plus saccular activation), the following cortical areas were selectively activated by saccular stimulation: intraparietal sulcus, frontal eye fields, prefrontal cortex, and postcentral gyrus, in addition to insula, supplementary motor area, and anterior and posterior cingulate cortex. Previous VEP studies also revealed similar activation areas by vestibular nerve stimulation with latencies at 6 ms, suggesting that the shortest pathways for activation of cerebral cortical neurons from the labyrinth are trisynaptic, with a relay in the thalamus. The activated areas are also consistent with results in previous studies using caloric stimulation, which primarily activates horizontal semicircular canals. These results suggest that canal and otolith information is processed largely by similar cortical areas in humans. Multiple cortical areas activated by these studies suggest that these areas are involved in different aspects of processing vestibular information. The saccular projections to the prefrontal and frontal cortex suggest that these areas are involved in planning motor synergies to counteract loss of equilibrium.

Neck muscle activity after unilateral labyrinthectomy in the alert guinea pig

Abstractu2002In the guinea pig, lateral deviation of the head is a cardinal symptom of the vestibular syndrome caused by unilateral labyrinthectomy. In the course of recovery from this syndrome (vestibular compensation), lateral deviation of the head disappears completely in 2–3 days. Because this symptom is known to be due to the lesion of the horizontal semicircular canal system, and since obliquus capitis inferior (OCI) muscle is activated predominantly by yaw rotation (horizontal vestibulocollic reflex), we hypothesized that changes in the activity of this muscle could be at least in part responsible for the lateral head deviation caused by unilateral labyrinthectomy. In order to test this hypothesis, electromyographic (EMG) activities of the right and left OCI muscles, as well as eye movements, were recorded in 12 head-fixed alert guinea pigs at various times after left surgical labyrinthectomy (performed with the animals under halothane anesthesia). After the operation, a decrease in tonic EMG activity was observed in the right (contralateral to the lesion) OCI muscle while an increase in tonic EMG activity was detected in the left (ipsilateral) OCI muscle. In addition, phasic changes in EMG activity associated with ocular nystagmic beats occurred in the OCI muscles. These phasic changes were in the opposite direction to those of the tonic changes. There were bursts of activity in the right OCI and pauses in the left OCI. From measurements of rectified averaged EMG activities which took into account both parts (tonic and phasic) of the phenomenon, it was concluded that the labyrinthectomy-induced asymmetry between the activities of the left and right OCI muscles was high enough and lasted long enough to be an important mechanism in the lateral deviation of the head caused by unilateral labyrinthectomy.

Reappearance of activity in the vestibular neurones of labyrinthectomized guinea‐pigs is not delayed by cycloheximide

1 In mammals, unilateral labyrinthectomy induces an immediate depression of the resting discharges in the neurones of the ipsilateral vestibular nuclei. Later on, a spontaneous restoration of this activity occurs. The aim of the present study was to test the possibility that protein synthesis could be involved in the start of this process in the guinea‐pig. 2 Cycloheximide (CHX), a protein synthesis inhibitor, was injected intramuscularly 1 h before (30 mg kg−1) and 5 h after (15 mg kg−1) labyrinthectomy. 3 In a first group of animals, CHX was found to induce an inhibition of protein synthesis at levels ranging from 71 to 93 % for 9 h after labyrinthectomy. 4 In a second group of alert animals, we studied single unit activity of second‐order vestibular neurones. It was found that, in the 12–16 h post‐labyrinthectomy period, at a time when restoration began in guinea‐pigs not treated with CHX, the discharges in the labyrinthectomized group treated with CHX were not different from those observed in a previous study in labyrinthectomized animals not treated with CHX. 5 We conclude that protein synthesis is not required for the start of restoration of activity in the vestibular neurones deprived of their ipsilateral labyrinthine input.