Vestibular Deafferentation Research Articles

The D 2 dopamine receptor and locomotor hyperactivity following bilateral vestibular deafferentation in the rat

Rats and mice with bilateral vestibular loss exhibit dramatic locomotor hyperactivity and circling behaviours, which to date cannot be explained. Dysfunction of the striatal dopaminergic system is responsible for a number of known movement disorders and the D 2 dopamine receptor is known to be implicated. Therefore, it is possible that changes in striatal function are responsible for locomotor hyperactivity and circling following bilateral vestibular lesions. The aim of this study was to investigate the effects of the D 2 receptor antagonist, eticlopride (0.02, 0.04 and 0.06 mg/kg; s.c.), on locomotor behaviour in rats at 5 months following bilateral vestibular deafferentation (BVD), using an open field maze. The levels of the D 2 receptor protein in the striatum were measured at 1 and 6 months post-BVD using western blotting. BVD rats exhibited locomotor hyperactivity and circling, which eticlopride did not eliminate. However, BVD rats did exhibit a decreased response to the inhibitory effect of eticlopride compared to sham controls at the 0.02 mg/kg dose. There were no changes in the amount of the D 2 receptor in the striatum at 1 or 6 months post-BVD; however, D 2 receptor levels were significantly higher on the right side than the left in both sham and BVD animals. These results suggest that locomotor hyperactivity and circling behaviours following BVD are not due simply to changes in D 2 receptor protein expression in the striatum and that other neurophysiological changes in the brain account for these behaviours following BVD.

The effects of the D2 dopamine receptor antagonist, eticlopride, on attention following bilateral vestibular deafferentation in the rat

Loss of vestibular function has been associated with cognitive impairment, including attentional problems. The aim of this study was to investigate the effects of the D2 dopamine receptor antagonist, eticlopride (0.02, 0.04 and 0.06mg/kg; s.c.), on attention and impulsivity in rats at 2 months following bilateral vestibular deafferentation (BVD), using a 5 choice serial reaction time task (5CSRTT). The levels of the D2 receptor protein in the frontal cortex were measured at 1 and 6 months post-BVD using western blotting. Eticlopride caused a dose-dependent decrease in response in the 5CSRTT, which was greater for sham than for BVD rats in terms of the percentage of correct responses and the number of perseverative responses. There were no changes in the amount of the D2 receptor in the frontal cortex at 1 or 6 months post-BVD; however, D2 receptor levels were significantly higher on the right side than the left in both sham and BVD animals. These results suggest that BVD causes an increase in perseverative behaviour that D2 receptor blockade does not eliminate, but that D2 receptors in the frontal cortex are unchanged.

Neurogenic Potential of the Vestibular Nuclei and Behavioural Recovery Time Course in the Adult Cat Are Governed by the Nature of the Vestibular Damage

Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferentation has an incidence on the neurogenic potential of the vestibular nuclei, and on the time course of behavioural recovery. Three animal models that mimic different vestibular pathologies were used: unilateral and permanent suppression of vestibular input by unilateral vestibular neurectomy (UVN), or by unilateral labyrinthectomy (UL, the mechanical destruction of peripheral vestibular receptors), or unilateral and reversible blockade of vestibular nerve input using tetrodotoxin (TTX). Neurogenesis and astrogenesis were revealed in the vestibular nuclei using bromodeoxyuridine (BrdU) as a newborn cell marker, while glial fibrillary acidic protein (GFAP) and glutamate decarboxylase 67 (GAD67) were used to identify astrocytes and GABAergic neurons, respectively. Spontaneous nystagmus and posturo-locomotor tests (static and dynamic balance performance) were carried out to quantify the behavioural recovery process. Results showed that the nature of vestibular loss determined the cellular plastic events occurring in the vestibular nuclei and affected the time course of behavioural recovery. Interestingly, the deafferented vestibular nuclei express neurogenic potential after acute and total vestibular loss only (UVN), while non-structural plastic processes are involved when the vestibular deafferentation is less drastic (UL, TTX). This is the first experimental evidence that the vestibular complex in the brainstem can become neurogenic under specific injury. These new data are of interest for understanding the factors favouring the expression of functional neurogenesis in adult mammals in a brain repair perspective, and are of clinical relevance in vestibular pathology.

Septal elicitation of hippocampal theta rhythm did not repair cognitive and emotional deficits resulting from vestibular lesions

Bilateral vestibular lesions cause atrophy of the hippocampus in humans and subsequent deficits in spatial memory and the processing of emotional stimuli in both rats and humans. Vestibular lesions also impair hippocampal theta rhythm in rats. The aim of the present study was to investigate whether restoring theta rhythm to the hippocampus of a rat, via stimulation of the medial septum, would repair the deficits caused by vestibular lesions. It was hypothesized that the restoration of theta would repair the deficits and the vestibular rats would exhibit behavior and EEG similar to that of the sham rats. Rats were given either sham surgery or bilateral vestibular deafferentation (BVD) followed in a later operation by electrode implants. Half of the lesioned rats received stimulation. Subjects were tested in open field, elevated T-maze and spatial nonmatching to sample tests. BVD caused a deficit in hippocampal theta rhythm. Stimulation restored theta power at a higher frequency in the vestibular-lesioned rats, however, the stimulation did not repair the cognitive and emotional deficits caused by the lesions. It was concluded that stimulation, at least in the form used here, would not be a viable treatment option for vestibular damaged humans.

Surgical indication in Menière’s disease therapy: clinical and epidemiological aspects

The aim of this study was to evaluate the frequency of surgical approach in a population of patients affected by definite Menière's disease (MD). In the majority of patients, relief from vertigo attacks can be achieved by means of medical therapy (MT). In cases in which MT fails surgery may offer relief to vertigo. The most applied surgical procedures are intratympanic gentamicin (ITG) and vestibular neurectomy (VN), based on vestibular deafferentation. Until now, the real incidence of the different therapeutic approaches for MD has not been evaluated. The study design was a retrospective study. The study was performed in 177 patients affected by definite MD. Subjects referred directly for surgery by other centers were excluded from the study. All the patients were medically treated with salt restriction and diuretics. In case of MT failure, surgical therapy, ITG or retrosigmoid VN were proposed. In the 75% of cases, the only therapeutic approach was MT, while in 20% of cases we carried out ITG and in 5% VN. In 33% of VN group, this operation was carried out after ITG failure and in 67% as the first surgical approach. The VN group was characterized by younger age and higher disability degree. The primary therapy in definite MD seems to be MT. Ablative therapy represents the second choice: ITG was carried out in 80% of cases, while VN was performed in 20%.

Pre-operative vestibular pattern and balance compensation after vestibular schwannoma surgery

This longitudinal study aimed to assess the sensorimotor balance strategies before and after vestibular schwannoma (VS) surgery according to the degree of pre-operative vestibular lesion. Thirty-eight VS patients were split in three groups according to caloric vestibular test results before surgery; nine had a symmetrical vestibular response (vestibular normoreflexy), 19 with a decreased response of more than 20% of the affected side (vestibular hyporeflexy) and 10 with an absent caloric response on the side of the affected labyrinth (vestibular areflexy). They underwent pendular rotary vestibular testing (RVT), allowing to evaluate gain and directional preponderance of the vestibulo-ocular reflex, and a sensory organisation test (SOT), evaluating balance control in six conditions (C1 to C6). These tests were performed shortly before, and 8 and 90 days after surgery. Directional preponderance performances of patients with vestibular normoreflexy or hyporeflexy followed a classical time-course with a huge asymmetry just after surgery and a recovery to pre-operative performances at 90 days; patients with vestibular areflexy were relatively stable in time. Variation in SOT performances of patients with vestibular normoreflexy, especially in the more complex C4 to C6, followed a classical time-course with an important postural degradation just after surgery and a recovery to pre-operative performances at 90 days. Patients with vestibular areflexy showed no balance degradation just after surgery and a marked increase in performances at 90 days after surgery, especially in C5 and C6. Performances of patients with vestibular hyporeflexy were intermediate, close to performances of patients with vestibular normoreflexy before surgery and close to performances of patients with vestibular areflexy at 8 and 90 days after surgery. Pre-operative vestibular function alteration triggers an adaptive process, characterized by a restoration of the symmetry of the vestibular nuclei activity and by sensory substitution and new behavioural strategies, allowing the anticipation of unilateral vestibular deafferentation effects.

Cannabinoid CB1 receptor expression and affinity in the rat hippocampus following bilateral vestibular deafferentation

Numerous studies have shown that bilateral vestibular deafferentation (BVD) results in spatial memory deficits and hippocampal dysfunction in rats and humans. Since cannabinoid CB1 receptors are well known to regulate synaptic plasticity in the hippocampus, we investigated whether BVD resulted in changes in CB1 receptor expression and affinity in the rat hippocampus at 1, 3 and 7 days post-surgery, using a combination of Western blotting and radioligand binding. Using Western blotting, we found that CB1 receptor expression was significantly lower in BVD animals compared to sham controls only in the CA3 area across the 3 time points (P=0.03). CB1 receptor expression decreased significantly over time for both the BVD and sham animals (P=0.000). The radioligand binding assays showed no significant change in the IC50 of the CB1 receptor for the cannabinoid CB1/CB2 receptor agonist, WIN55,212-2. These results suggest that the CB1 receptor down-regulates in the CA3 region of the hippocampus following BVD, but with no changes in the affinity of the CB1 receptor for WIN55,212-2.

Evidence that spatial memory deficits following bilateral vestibular deafferentation in rats are probably permanent

Previous studies of rats with bilateral vestibular deafferentation (BVD) have demonstrated spatial memory deficits, suggesting adverse effects on the hippocampus. However, the longest post-operative time interval that has been studied was approx. 5–7months post-surgery. In this study, we investigated whether rats exhibited spatial memory deficits at 14months following BVD and whether these deficits could be exacerbated by administration of cannabinoid (CB) drugs. Twenty-eight adult rats were divided into four groups: (1) sham surgery+vehicle; (2) sham surgery+the CB1/CB2 receptor agonist WIN55,212-2 (‘WIN’); (3) BVD+vehicle; and (4) BVD+WIN. WIN (1.0 or 2.0mg/kg/day) or vehicle, was administered (s.c.) on days 1–10 and 11–20 (respectively), 30min before the rats performed in a foraging task. On day 21, the CB receptor inverse agonist, AM251 (3.0mg/kg, s.c.), was administered before WIN or vehicle. To our surprise, BVD animals were impaired in using the visual cues during the probe test in light. In the dark trials, when visual cues were unavailable, BVD animals were unable to use self-movement cues in homing. However, WIN at 2mg/kg, significantly improved BVD animals’ homing time and number of errors in the dark through strategies other than the improvement in using self-movement cues. Furthermore, AM251 significantly improved heading angle in vehicle-treated animals and the first home choice in WIN-treated animals. These results suggest that at 14months post-BVD, the animals are not only impaired in path integration, but also piloting and that the spatial memory deficits may be permanent. The involvement of the cannabinoid system is more complicated than expected.

Presynaptic and postsynaptic ion channel expression in vestibular nuclei neurons after unilateral vestibular deafferentation

Vestibular compensation refers to the recovery of function occurring after unilateral vestibular deafferentation, but some patients remain uncompensated. Similarly, more than half of the operated chickens compensate three days after unilateral vestibular ganglionectomy (UVG), but the rest remain uncompensated. This review focuses on the studies performed on the principal cells of the chick tangential nucleus after UVG. The tangential nucleus is a major avian vestibular nucleus whose principal cells are all second-order, vestibular reflex projection neurons participating in the vestibuloocular and vestibulocollic reflexes controlling posture, balance, and eye movements. Using whole-cell patch-clamp approach in brain slice preparations, spontaneous spike firing, ionic conductances, and spontaneous excitatory postsynaptic currents (sEPSCs) are recorded in principal cells from controls and operated chickens three days after UVG. In compensated chickens, the proportion of spontaneous spike firing principal cells and their spike discharge rate are symmetric on the lesion and intact sides, with the rates increased over controls. However, in the uncompensated chickens, the spike discharge rate increases on the lesion side, but not on the intact side, where only silent principal cells are recorded. In all the experimental groups, including controls, silent principal cells are distinguished from spontaneous spiking cells by smaller persistent sodium conductances and higher activation thresholds for the fast sodium channel. In addition, silent principal cells on the intact side of uncompensated chickens have larger dendrotoxin-sensitive potassium conductances, with a higher ratio of immunolabeling for surface/cytoplasmic expression of a dendrotoxin-sensitive, potassium channel subunit, Kv1.1. Finally, in compensated chickens, sEPSC frequency is symmetric bilaterally, but in uncompensated chickens sEPSC frequency increased only on the lesion side, where the expression of Kv1.2 decreased in synaptotagmin-labeled terminal profiles on the principal cell bodies. Altogether, the specific sodium and potassium channels important for the development of spike firing pattern and/or presynaptic glutamate release on vestibular reflex projection neurons may be critically involved in changing postsynaptic neuron excitability after vestibular deafferentation.

Rebalancing the commissural system: Mechanisms of vestibular compensation

Vestibular compensation after unilateral vestibular loss is a complex, multi-factored process involving synaptic and neuronal plasticity in many areas of the brain, and it is a challenge to identify the key sites of plasticity that determine the rate and extent of behavioural recovery. Experimental evidence strongly implicates the vestibular commissural inhibitory system which links the brainstem vestibular nuclei of the two sides, both in causing the initial severe oculomotor and postural symptoms of vestibular deafferentation, and in the subsequent recovery that takes place in the early stages of compensation. Of particular interest are changes in GABAergic neurotransmission within the commissural system, and the possibility that histaminergic drugs as well as stress steroids and neurosteroids that can modulate compensation, may do so at least in part by their effects on commissural inhibition. A fuller understanding of the role of the commissural system in compensation and the effects of GABAergic neuromodulators is likely to reveal the mechanisms of action of histamine in the vestibular system and the interactions between stress, anxiety and vestibular dysfunction.

Changes in TNFα, NFκB and MnSOD protein in the vestibular nuclei after unilateral vestibular deafferentation

BackgroundUnilateral vestibular deafferentation results in strong microglial and astroglial activation in the vestibular nuclei (VN) that could be due to an inflammatory response. This study was aimed at determining if markers of inflammation are upregulated in the VN after chemical unilateral labyrinthectomy (UL) in the rat, and if the inflammatory response, if any, induces the expression of neuroprotective factors that could promote the plasticity mechanisms involved in the vestibular compensation process. The expressions of inflammatory and neuroprotective factors after chemical or mechanical UL were also compared to verify that the inflammatory response was not due to the toxicity of sodium arsanilate.MethodsImmunohistological investigations combined the labeling of tumor necrosis factor α (TNFα), as a marker of the VN inflammatory response, and of nuclear transcription factor κB (NFκB) and manganese superoxide dismutase (MnSOD), as markers of neuroprotection that could be expressed in the VN because of inflammation. Immunoreactivity (Ir) of the VN cells was quantified in the VN complex of rats. Behavioral investigations were performed to assess the functional recovery process, including both static (support surface) and dynamic (air-righting and landing reflexes) postural tests.ResultsChemical UL (arsanilate transtympanic injection) induced a significant increase in the number of TNFα-Ir cells in the medial and inferior VN on both sides. These changes were detectable as early as 4 h after vestibular lesion, persisted at 1 day, and regained nearly normal values at 3 days. The early increase in TNFα expression was followed by a slightly delayed upregulation of NFκB 8 h after chemical UL, peaking at 1 day, and regaining control values 3 days later. By contrast, upregulation of MnSOD was more strongly delayed (1 day), with a peak at 3 days, and a return to control values at 15 days. Similar changes of TNFα, NFκB, and MnSOD expression were found in rats submitted to mechanical UL. Behavioral observations showed strong posturo-locomotor deficits early after chemical UL (1 day) and a complete functional recovery 6 weeks later.ConclusionsOur results suggest that the upregulation of inflammatory and neuroprotective factors after vestibular deafferentation in the VN may constitute a favorable neuronal environment for the vestibular compensation process.

Cell proliferation and survival in the vestibular nucleus following bilateral vestibular deafferentation in the adult rat

Cell proliferation and neurogenesis in the brainstem vestibular nucleus complex (VNC) has previously been reported following unilateral vestibular neurectomy in the cat. In this study, we examined the rate of cell proliferation and survival in the adult rat VNC following bilateral vestibular deafferentation (BVD), using injections of bromodeoxyuridine (BrdU) and stereological cell counting. We measured cell proliferation at 24, 48, 72 h and 1 week following BVD and found that it was significantly greater than in sham controls ( P = 0.002) and that it varied significantly over time ( P = 0.01), peaking at 48 h in the BVD group. Of note was that sham surgery was also associated with an increase in cell proliferation, which changed over time. When we compared the survival of new cells at 1 month after BrdU injection, there was no significant difference in survival between the sham and BVD groups. These results raise questions about the potential functional significance of cell proliferation in the VNC following vestibular lesions.

Vestibular function outcomes after vestibular neurectomy in Meniere disease: Can vestibular neurectomy provide complete vestibular deafferentation?

Vestibular neurectomy is considered the reference treatment of incapacitating vertigo accompanying Meniere disease, with an efficiency rate of 85-95% in most literature reports. The aim of this study is to evaluate if vestibular neurectomy can provide a complete vestibular deafferentation by investigating complete vestibular function after surgery. Prospective study. Twenty-four patients suffering from incapacitated Meniere vertigo crisis beneficiated from a vestibular neurectomy by retrosigmoid approach. The average time between surgery and vestibular evaluation was 1 year. We performed (i) kinetic test, (ii) caloric test and (iii) vibration-induced nystagmus (VIN) at 30, 60 and 100Hz under videonystagmography recording, (iv) vestibular evoked myogenic potentials (VEMP), (v) video head impulsed test (VHIT) for each semicircular canals and (vi) an evaluation of visual vertical and horizontal subjective (VVS and HVS). On clinical evaluation, all the patients except one had never experienced any recurrence of vertigo crisis after surgery. The 24 patients would definitely undergo the surgery again. On vestibular evaluation, on the operated side, all patients showed a total areflexia at caloric test; 23 patients had no VEMP response; 23 patients had abolished canals response to VHIT. All the patients had VVS and HVS deviated towards the operated side; 23 patients had a high velocity VIN from 30 to 60Hz. This study proves that vestibular neurectomy can provide a complete vestibular deafferentation. We discuss this vestibular evaluation protocol and the main difficulties encounter during surgery, which could lead to partial nerve section and partial relief, and explain residual vestibular function after vestibular neurectomy.

Vestibular PREHAB and gentamicin before schwannoma surgery may improve long-term postural function

Background:Unilateral vestibular deafferentation (uVD), as performed in vestibular schwannoma surgery, results in a chronic vestibular deficit, though most of the insufficiency can be compensated by other sensory input. By vestibular...

Hippocampal synaptic transmission and LTP in vivo are intact following bilateral vestibular deafferentation in the rat

Numerous studies in animals and humans have shown that damage to the vestibular system in the inner ear results in spatial memory deficits, presumably because areas of the brain such as the hippocampus require vestibular input to accurately represent the spatial environment. Consistent with this hypothesis, studies in animals have demonstrated that complete bilateral vestibular deafferentation (BVD) causes a disruption of place cell firing as well as theta activity. The aim of this study was to investigate whether BVD in rats affects baseline field potentials (field excitatory postsynaptic potentials and population spikes) and long-term potentiation (LTP) in CA1 and the dentate gyrus (DG) of awake freely moving rats up to 43 days post-BVD and of anesthetized rats at 7 months post-BVD. Compared to sham controls, BVD had no significant effect on either baseline field potentials or LTP in either condition. These results suggest that although BVD interferes with the encoding, consolidation, and/or retrieval of spatial memories and the function of place cells, these changes are not related to detectable in vivo decrements in basal synaptic transmission or LTP, at least in the investigated pathways.

Bilateral vestibular deafferentation causes deficits in a 5-choice serial reaction time task in rats

Peripheral lesions of the vestibular system have been associated with spatial memory deficits in animals and humans; however, no study to date has investigated the effects of such lesions on attention. In this study, we used a 5-choice serial reaction time task (5-CSRTT) to determine whether rats with bilateral vestibular deafferentation (BVD) had attention deficits at 5 months post-op. compared to sham controls. We found that BVD rats took longer than sham animals to reach the designated criterion of >70% correct responses (P=0.006), they made significantly fewer correct responses (P=0.005), and significantly more incorrect responses (P=0.000), while showing no difference in omissions and premature responses and a significant decrease in perseverative responses (P=0.03). BVD rats also responded with a significantly shorter response latency, whether their response was correct (P=0.001) or incorrect (P=0.002), and obtained their reward for a correct response more quickly (P=0.000). These results suggest that rats with bilateral vestibular loss exhibit deficits on a 5-CSRTT that cannot be explained by an inability to respond and that their speed of response is altered.

Anxiety‐Related Behavior and Biogenic Amine Pathways in the Rat following Bilateral Vestibular Lesions

Many clinical studies have reported that patients with vestibular disorders have a high rate of anxiety disorders and depression. By contrast, there have been few studies of affective behavior in animals following vestibular lesions. Recent studies using the vestibular impaired ci2/ci2 mutant rat strain have shown that rather than preferring the closed arm of the elevated plus maze, as rats would normally, they make more open-arm entries and spend more time on the open arms compared to wild-type controls. In the open-field maze, rather than preferring to explore the outer zone near the walls ("thigmotaxis"), ci2/ci2 rats prefer the inner region of the maze. In rats with bilateral vestibular deafferentation (BVD), similar results were obtained. Compared to sham controls, at 3 and 5 months post-op, BVD rats spent more time on the open arms of the elevated plus maze, more time in the inner zone of the open-field maze, and failed to learn inhibitory avoidance in the elevated T maze. They did not display increased hyponeophagia; however, they did exhibit a decrease in social interaction. Blood corticosterone levels were not significantly different from sham controls. At 6 months post-op, BVD rats demonstrated circumscribed changes in the expression of tyrosine hydroxylase, the serotonin transporter, and tryptophan hydroxylase, in various regions of the medial temporal and frontal lobes, suggesting changes in biogenic amine pathways.

Tell Me Your Vestibular Deficit, and I’ll Tell You How You’ll Compensate

Most patients with unilateral vestibular loss exhibit a similar static and dynamic vestibular syndrome consisting of vestibulo-ocular, posturolocomotor, and perceptive deficits. This vestibular syndrome recovers more or less completely and more or less rapidly over time. One open question is whether recovery mechanisms differ according to vestibular pathology and/or patients. It is reported here (1) data from three different cat models of unilateral vestibular loss reproducing vestibular pathology with sudden (unilateral vestibular neurectomy [UVN] model), gradual (unilateral labyrinthectomy [UL] model), or reversible (tetrodotoxine [TTX]) model) loss of vestibular function, and (2) clinical observations in a population of unilateral vestibular loss patients suffering the same pathology (Menière's disease). Animal models show that time courses and mechanisms of recovery depend on the type of vestibular deafferentation, and clinical findings show that Menière's patients compensate their postural and perceptive deficits using different vicarious processes. Taken together, results point to a more complex picture of compensation after unilateral vestibular loss, which cannot be reduced either to a common recovery mechanism or to a single process identical for all individuals. These findings should guide physiotherapists in treatment and rehabilitation for vestibular deficits.

Gray‐Matter Atrophy after Chronic Complete Unilateral Vestibular Deafferentation

It has been shown in blind patients that the abolition of sensory input can lead to changes in white- and cortical gray-matter volumes. Here the white- and gray-matter changes found with whole brain voxel-based morphometry in 16 patients with complete chronic unilateral vestibular deafferentation (UVD) due to vestibular schwannoma removal several years prior are reported on. Subtle deficits in spatial memory and navigation were previously shown in patients with right UVD. Images of the brains of right-UVD patients were flipped, standard preprocessing steps were performed, and the data were modulated. Patients showed a gray-matter volume reduction in the cerebellum due to schwannoma removal, in the supramarginal gyrus ipsilateral to the lesion, as well as in the postcentral and superior temporal gyrus, areas involved in the vestibular cortical network, and in the motion-sensitive area MT/V5. There was no correlation with behavioral navigational abilities. No gray-matter atrophy was found in the insular cortical vestibular region or the hippocampus, both of which receive bilateral vestibular projections. The thalamus and tegmentum of the mesencephalon showed gray-matter reduction on the opposite side; this was possibly due to reduced auditory input, which is known to cross at this level. In comparison to healthy controls, no regional increases in gray-matter volume were seen. No white-matter changes were detected at the selected threshold.

Horizontal head impulse test detects gentamicin vestibulotoxicity

Parenteral antibiotic therapy with gentamicin, even in accepted therapeutic doses, can occasionally cause bilateral vestibular loss (BVL) due to hair cell toxicity. To quantify in patients with gentamicin vestibulotoxicity (GVT) the extent of acceleration gain deficit of the horizontal vestibulo-ocular reflex at different accelerations with a graded head impulse test (HIT) in comparison with standard caloric and rotational testing. To characterize the corresponding HIT catch-up saccade pattern to provide the basis for its salience to clinicians. Horizontal HIT of graded acceleration (750 degrees-6,000 degrees/sec2) was measured with binocular dual search coils in 14 patients with GVT and compared with 14 normal subjects and a control subject with total surgical BVL. Patients showed mostly symmetric HIT gain deficits with a continuous spectrum from almost normal to complete BVL. Gain deficits were present even at the lowest head accelerations. HIT gain correlated better with caloric (Spearman rho = 0.85, p = 0.0001) than rotational testing (rho = 0.55, p = 0.046). Cumulative amplitude of overt saccades after head impulses was 5.6 times larger in patients than in normal subjects. Compared with previously published patients after unilateral vestibular deafferentation, GVT patients with BVL generated only approximately half the percentage of covert saccades during head rotation (23% at 750 degrees/sec2 to 46% at 6,000 degrees/sec2). Head impulse testing is useful for early bedside detection of gentamicin vestibulotoxicity because most patients, even those with partial bilateral vestibular loss (BVL), have large overt saccades. Covert saccades, which can conceal the extent of BVL, are only approximately half as frequent as in unilateral patients, but may be present even in total BVL.