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1.
Eur Arch Otorhinolaryngol ; 278(1): 41-48, 2021 Jan.
Article in English | MEDLINE | ID: mdl-32449024

ABSTRACT

PURPOSE: Binge drinking is associated with several adverse effects in multiple organs. This study aimed at evaluating the effects of a binge-like-drinking on the vestibulo-oculomotor reflex (VOR) using the video Head Impulse Test (vHIT) and the functional Head Impulse Test (fHIT). METHODS: Eleven healthy men (age range 32-35 years) with moderate drinking habits and no history of vestibular dysfunction were enrolled. A preliminary assessment of breath alcohol concentration (BrAC) to check for zero alcohol value and a pre-intake evaluation of VOR using the vHIT and the fHIT were carried on. Then, the subjects were asked to take drinks with different alcohol content (8-40% ethanol by volume) according to their choice, consuming at least 5 standard drinks. Volunteers stopped drinking after 3 h. After a further 30 min, post-intake BrAC measurements and VOR analysis were repeated. RESULTS: After alcohol intake, vHIT recorded an overall significant reduction of VOR gain (0.82 ± 0.07 on both sides) although the outcomes were below the normal range only in the four subjects with the highest blood alcohol levels. The post-intake fHIT outcomes were substandard in 9 participants, with a significant deterioration in performance (% of exact answers = 84.54 ± 11.05% on the left, 83.18 ± 14.53 on the right). CONCLUSIONS: Binge drinking severely affects VOR; fHIT seems more sensitive than vHIT in the assessment of VOR function for complex vestibular lesions, such as those determined by ethanol, suggesting that fHIT could support vHIT in vestibular dysfunction assessment.


Subject(s)
Alcohol Drinking/adverse effects , Binge Drinking , Head Impulse Test/methods , Reflex, Vestibulo-Ocular/drug effects , Vestibular Diseases/diagnosis , Adult , Ethanol , Humans , Male , Reflex, Vestibulo-Ocular/physiology , Vestibular Diseases/physiopathology , Vestibule, Labyrinth , Video Recording
2.
Am J Otolaryngol ; 41(5): 102579, 2020.
Article in English | MEDLINE | ID: mdl-32531621

ABSTRACT

AIM: The aim of the present study was to evaluate the effect of isotretinoin (ISO) on peripheral vestibular system using vHIT. MATERIAL AND METHOD: This is a prospective study in which 30 patients administered ISO treatment with the diagnosis of acne vulgaris was evaluated. Following ear nose and throat, examination, audiological and vestibular evaluations were carried out. vHIT tests were conducted before and three months after the use of ISO (0.5-0.75 mg/kg/day). In addition, all participants underwent perceptual vertigo and dizziness tests before and three months after the use of ISO. RESULTS: In vHIT evaluation of all patients, no overt saccade, covert saccade and spontaneous nystagmus finding was observed. Gain and asymmetry were compared before and after the use of ISO: No significant difference was found between lateral semicircular canal, anterior, and posterior semi-circular and symmetry measurements made before ISO use and those made three months after it (p = 1.00; p = 0.99; p = 0.66). Similarly, there was no significant difference in asymmetry values of vertical semicircular canals measured before ISO and three months after it (p = 0.90; p = 0.76). No statistically significant difference was found in vertigo, nausea and dizziness in terms of responses before and 3 months after ISO use (p = 0.063; p = 0.031; p = 0.063). CONCLUSION: Although the studies demonstrating the effect of ISO on cochlea and symptoms occurring during treatment such as nausea, vomiting and vertigo suggest that it may exert effects on peripheral vestibular system, the present study indicates that it has no short terms effects on structures in peripheral vestibular system and vestibuloocular reflex pathways.


Subject(s)
Acne Vulgaris/drug therapy , Diagnostic Techniques, Otological , Isotretinoin/adverse effects , Adolescent , Adult , Female , Humans , Isotretinoin/therapeutic use , Male , Nausea/chemically induced , Prospective Studies , Reflex, Vestibulo-Ocular/drug effects , Semicircular Canals/drug effects , Semicircular Canals/pathology , Vertigo/chemically induced , Vestibule, Labyrinth/drug effects , Vomiting/chemically induced , Young Adult
3.
Acta Otolaryngol ; 140(4): 314-318, 2020 Apr.
Article in English | MEDLINE | ID: mdl-31909683

ABSTRACT

Background: Intratympanic gentamicin injection (ITG) is a well-accepted means to treat intractable Meniere's disease (MD).Aims/Objectives: To investigate change of vestibule-ocular reflex (VOR) gain and pure-tone threshold after low-dose ITG for MD.Methods: Sixteen patients with definite MD who were treated by low-dose ITG were retrospectively reviewed. We defined VOR gain difference as an amount of decreased gain in video head impulse test one month after ITG. Patients were classified into two groups: single injection vs. multiple injections. Multiple injections group was composed of patients with poor vertigo control after initial ITG who required second or third ITG later in follow up period.Results: VOR gain differences of both horizontal and posterior canal plane were higher than those of anterior canal plane. Between two groups, mean VOR gain difference of horizontal canal plane in multiple injections group was lower than that in single injection group. Only two patients showed increased pure-tone threshold more than 10 dB.Conclusion and significance: Our results suggest that ITG appears to cause a differential loss of function across three semicircular canals. Furthermore, if VOR gain difference of horizontal canal is relatively low after initial ITG, patient might have poor vertigo control and be required another ITG.


Subject(s)
Anti-Bacterial Agents/therapeutic use , Gentamicins/therapeutic use , Meniere Disease/drug therapy , Reflex, Vestibulo-Ocular/drug effects , Vertigo/drug therapy , Adult , Aged , Aged, 80 and over , Anti-Bacterial Agents/pharmacology , Audiometry, Pure-Tone , Auditory Threshold , Gentamicins/pharmacology , Head Impulse Test , Humans , Injection, Intratympanic , Middle Aged , Retrospective Studies , Semicircular Canals/drug effects
4.
Acta Otolaryngol ; 139(9): 759-768, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31311369

ABSTRACT

Objectives: To determine the incidence of gentamicin vestibulotoxicity with current dosing regimens, and to evaluate the feasibility of routine video-oculography on all patients given gentamicin. Materials and methods: In this prospective incidence study serial horizontal vestibulo-ocular reflex (HVOR) gain measurements were recorded using video-oculography on adult inpatients receiving intravenous gentamicin. The primary outcome was the proportion of patients developing impairment of their HVOR gain. Results: After exclusions, 42 patients were included in the analysis. Three patients (7.1%) developed asymptomatic vestibulotoxicity, exact 95% confidence interval 1.5-19.5%. In two of these patients the deficit resolved within several hours. No patients developed symptomatic vestibulotoxicity. There was no evidence for a generalised reduction in group HVOR gain with time. HVOR gain was not associated with total gentamicin dose, dynamic visual acuity or subjective imbalance. Conclusions and significance: Gentamicin may cause reversible, asymptomatic vestibulotoxicity. Video-oculography may be useful to monitor for vestibulotoxicity in patients treated with gentamcin; however, testing all patients routinely may be challenging.


Subject(s)
Gentamicins/adverse effects , Ototoxicity/etiology , Reflex, Vestibulo-Ocular/drug effects , Vestibule, Labyrinth/drug effects , Video Recording , Adult , Cohort Studies , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Gentamicins/therapeutic use , Humans , Linear Models , Male , Middle Aged , New Zealand , Ototoxicity/diagnosis , Prospective Studies , Risk Assessment , Tertiary Care Centers , Vestibular Diseases/chemically induced
5.
J Neurol ; 266(Suppl 1): 93-100, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31270663

ABSTRACT

Vestibulo-ocular reflexes (VOR) are mediated by frequency-tuned pathways that separately transform the different dynamic and static aspects of head motion/position-related sensory signals into extraocular motor commands. Voltage-dependent potassium conductances such as those formed by Kv1.1 are important for the ability of VOR circuit elements to encode highly transient motion components. Here we describe the impact of the Kv1.1 channel blocker 4-aminopyridine (4-AP) on spontaneous and motion-evoked discharge of superior oblique motoneurons. Spike activity was recorded from the motor nerve in isolated preparations of Xenopus laevis tadpoles. Under static conditions, bath application of 1-10 µM 4-AP increased the spontaneous firing rate and provoked repetitive bursts of spikes. During motion stimulation 4-AP also augmented and delayed the peak firing rate suggesting that this drug affects the magnitude and timing of vestibular-evoked eye movements. The exclusive Kv1.1 expression in thick vestibular afferent fibers in larval Xenopus at this developmental stage suggests that the altered extraocular motor output in the presence of 4-AP mainly derives from a firing rate increase of irregular firing vestibular afferents that propagates along the VOR circuitry. Clinically and pharmacologically, the observed 4-AP-mediated increase of peripheral vestibular input under resting and dynamic conditions can contribute to the observed therapeutic effects of 4-AP in downbeat and upbeat nystagmus as well as episodic ataxia type 2, by an indirect increase of cerebellar Purkinje cell discharge.


Subject(s)
4-Aminopyridine/administration & dosage , Eye Movements/drug effects , Potassium Channel Blockers/administration & dosage , Reflex, Vestibulo-Ocular/drug effects , Vestibule, Labyrinth/drug effects , Animals , Eye Movements/physiology , Female , Male , Reflex, Vestibulo-Ocular/physiology , Vestibule, Labyrinth/physiology , Xenopus laevis
6.
J Neurol ; 265(Suppl 1): 18-25, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29556714

ABSTRACT

Vestibulo-ocular reflexes (VOR) are mediated by three-neuronal brainstem pathways that transform semicircular canal and otolith sensory signals into motor commands for the contraction of spatially specific sets of eye muscles. The vestibular excitation and inhibition of extraocular motoneurons underlying this reflex is reciprocally organized and allows coordinated activation of particular eye muscles and concurrent relaxation of their antagonistic counterparts. Here, we demonstrate in isolated preparations of Xenopus laevis tadpoles that the discharge modulation of superior oblique motoneurons during cyclic head motion derives from an alternating excitation and inhibition. The latter component is mediated exclusively by GABA, at variance with the glycinergic inhibitory component in lateral rectus motoneurons. The different pharmacological profile of the inhibition correlates with rhombomere-specific origins of vestibulo-ocular projection neurons and the complementary segmental abundance of GABAergic and glycinergic vestibular neurons. The evolutionary conserved rhombomeric topography of vestibulo-ocular projections makes it likely that a similar pharmacological organization of inhibitory VOR neurons as reported here for anurans is also implemented in mammalian species including humans.


Subject(s)
Motor Neurons/drug effects , Neural Inhibition/drug effects , Neurotransmitter Agents/pharmacology , Oculomotor Muscles/innervation , Reflex, Vestibulo-Ocular/drug effects , Action Potentials/drug effects , Action Potentials/physiology , Animals , Glycine/metabolism , Head Movements/drug effects , Head Movements/physiology , Larva , Motion Perception/drug effects , Motion Perception/physiology , Motor Neurons/physiology , Neural Inhibition/physiology , Pyridazines/pharmacology , Reflex, Vestibulo-Ocular/physiology , Semicircular Canals/drug effects , Semicircular Canals/physiology , Strychnine/pharmacology , Tegmentum Mesencephali/drug effects , Tegmentum Mesencephali/physiology , Xenopus laevis , gamma-Aminobutyric Acid/metabolism
7.
Auris Nasus Larynx ; 45(1): 39-44, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28292626

ABSTRACT

OBJECTIVE: In this retrospective study the aim of the authors was to examine the effect of gentamicin on the individual semicircular canals after low dose, single injection intratympanal gentamicin therapy in Meniere's disease. METHODS: Data of 32 patients treated between 2011 and 2015 were collected. The high frequency, high acceleration vestibuloocular reflex (VOR) gain was measured in the individual semicircular canals using video head impulse test immediately before the first intratympanal gentamicin instillation and approximately two months later. RESULTS: In all cases 'AAO-HNS Class A' vertigo control could be attained at least for several months. In 13 cases only one instillation was necessary. In the other 19 cases the attacks returned after a few months. In 11 cases the injection had to be repeated a second time, in 4 cases 3 injections, in 2 cases 4, in 1 case 5 injections and in another 6 injections were necessary. The initial VOR gain was normal in all cases and two months after one injection it decreased in average by 40% in a highly significant manner. However, there were cases in which, although the patients became free of attacks, the gain values remained normal. CONCLUSION: It was possible to demonstrate a significant correlation between the gain decrease of the individual canals. There was no prognostic correlation between the initial gain decrease after the first injection and the necessity of further injections. Gain values also decreased slightly but significantly in the lateral and posteriors canals on the contralateral, untreated side, possibly because of the missing disfacilitation from the treated side.


Subject(s)
Gentamicins/pharmacology , Meniere Disease/drug therapy , Protein Synthesis Inhibitors/pharmacology , Reflex, Vestibulo-Ocular/drug effects , Semicircular Canals/drug effects , Adult , Female , Gentamicins/administration & dosage , Head Impulse Test , Humans , Injection, Intratympanic , Male , Meniere Disease/physiopathology , Protein Synthesis Inhibitors/administration & dosage , Retrospective Studies , Vertigo/drug therapy
8.
Brain Struct Funct ; 223(2): 837-850, 2018 Mar.
Article in English | MEDLINE | ID: mdl-28942480

ABSTRACT

The vestibulo-ocular reflex (VOR) adaptation is an ideal model for investigating how the neurosteroid 17 beta-estradiol (E2) contributes to the modification of behavior by regulating synaptic activities. We hypothesized that E2 impacts VOR adaptation by affecting cerebellar synaptic plasticity at the parallel fiber-Purkinje cell (PF) synapse. To verify this hypothesis, we investigated the acute effect of blocking E2 synthesis on gain increases and decreases in adaptation of the VOR in male rats using an oral dose (2.5 mg/kg) of the aromatase inhibitor letrozole. We also assessed the effect of letrozole on synaptic plasticity at the PF synapse in vitro, using cerebellar slices from male rats. We found that letrozole acutely impaired both gain increases and decreases adaptation of the VOR without altering basal ocular-motor performance. Moreover, letrozole prevented long-term potentiation at the PF synapse (PF-LTP) without affecting long-term depression (PF-LTD). Thus, in male rats neurosteroid E2 has a relevant impact on VOR adaptation and affects exclusively PF-LTP. These findings suggest that E2 might regulate changes in VOR adaptation by acting locally on cerebellar and extra-cerebellar synaptic plasticity sites.


Subject(s)
Adaptation, Physiological/physiology , Cerebellum/physiology , Estradiol/metabolism , Long-Term Potentiation/physiology , Reflex, Vestibulo-Ocular/physiology , Adaptation, Physiological/drug effects , Animals , Aromatase Inhibitors/pharmacology , Cerebellum/drug effects , Conditioning, Classical/drug effects , Conditioning, Classical/physiology , Estradiol/pharmacology , Estrogens/pharmacology , Eye Movements/drug effects , Eye Movements/physiology , In Vitro Techniques , Letrozole/pharmacology , Long-Term Potentiation/drug effects , Male , Patch-Clamp Techniques , Photic Stimulation/adverse effects , Rats , Rats, Wistar , Reflex, Vestibulo-Ocular/drug effects
9.
Clin Neurophysiol ; 128(11): 2211-2216, 2017 11.
Article in English | MEDLINE | ID: mdl-28985517

ABSTRACT

OBJECTIVE: It has long been suggested that antivertiginous medications exert their symptomatic effect through inhibition of the vestibulo-ocular reflex (VOR). We tested this hypothesis by directly measuring the VOR after administration of three agents from different substance classes: an antihistamine, a benzodiazepine and a calcium channel antagonist. METHODS: The gain and the variability of the high velocity VOR was assessed using video head impulses (vHIT) under the following conditions: baseline, after dimenhydrinate, after diazepam and after cinnarizine. RESULTS: We found that all three medications did not change any VOR gain or variability parameter: At 60ms, the gain was 0.95 at baseline, 0.99 under dimenhydrinate, 0.99 under diazepam and 0.96 under cinnarizine. The gain variability across repetitive head impulses remained also uninfluenced. CONCLUSIONS: The human high frequency VOR remains robust to pharmacological perturbations at common clinical doses and the assumption that symptomatic vertigo relief is achieved merely through impairment of the VOR requires re-examination. SIGNIFICANCE: Alternative mechanisms of pharmacological action might be operant, such as the modulation of vestibulo-cortical pathways, a differential effect on the low frequency VOR and an altered sensitivity to drugs in acute unilateral vestibulopathy.


Subject(s)
Cinnarizine/pharmacology , Diazepam/pharmacology , Dimenhydrinate/pharmacology , Histamine H1 Antagonists/pharmacology , Reflex, Vestibulo-Ocular/drug effects , Adult , Cinnarizine/therapeutic use , Diazepam/therapeutic use , Dimenhydrinate/therapeutic use , Eye Movements/drug effects , Female , Humans , Male , Vertigo/drug therapy , Young Adult
10.
BMC Anesthesiol ; 16(1): 90, 2016 10 10.
Article in English | MEDLINE | ID: mdl-27724859

ABSTRACT

BACKGROUND: The opioid remifentanil induces a decrease of vestibulo-ocular reflex function, which has been associated with nausea and vomiting when the subjects are moved. The study investigates in healthy female volunteers if immobility after remifentanil administration protects from nausea and vomiting. METHODS: In volunteers, a standardized movement intervention (a manually applied head-trunk movement forward, backward and sideward) was started 5 min (session A), 35 min (session B) or 60 min (session C) after cessation of a remifentanil infusion (0.15 µg · kg-1 · min-1). In a cross-over design, 16 participants were randomized to the early (sessions A and B) or the late intervention group (sessions A and C). Nausea was assessed using a 11-point numerical rating scale before and after each movement intervention. Differences within and between groups were assessed with non-parametric tests for paired and unpaired data. RESULTS: Comparing sessions A, B and C, intensity of nausea was time-dependent after cessation of remifentanil administration (p = 0.015). In the early intervention group, nausea decreased from median 5.0 [IQR 1.5;6.0] in session A to 2.0 [1.0;3.0] in session B (p = 0.094); in the late intervention group nausea decreased from 3.5 [2.0;5.0] in session A to 0.5 [0.0;2.0] in session C (p = 0.031). CONCLUSIONS: In summary, in young healthy women, immobility after remifentanil administration protects from nausea and vomiting in a time-dependent manner. In analogy to motion sickness, opioid-induced nausea and vomiting in female volunteers can be triggered by movement. TRIAL REGISTRATION: German Clinical Trials Register DRKS00010667 . The trial was registered retrospectively on June, 20th 2016.


Subject(s)
Analgesics, Opioid/administration & dosage , Immobilization/methods , Piperidines/administration & dosage , Postoperative Nausea and Vomiting/prevention & control , Adult , Analgesics, Opioid/adverse effects , Cross-Over Studies , Female , Head Movements , Humans , Piperidines/adverse effects , Reflex, Vestibulo-Ocular/drug effects , Remifentanil , Time Factors , Young Adult
11.
Neuroscience ; 335: 122-33, 2016 Oct 29.
Article in English | MEDLINE | ID: mdl-27579770

ABSTRACT

Limb somatosensory signals modify the discharge of vestibular neurons and elicit postural reflexes, which stabilize the body position. The aim of this study was to investigate the contribution of the γ-amino-butyric-acid (GABA) to the responsiveness of vestibular neurons to somatosensory inputs. The activity of 128 vestibular units was recorded in anesthetized rats in resting conditions and during sinusoidal foreleg rotation around the elbow or shoulder joints (0.026-0.625Hz, 45° peak amplitude). None of the recorded units was influenced by elbow rotation, while 40% of them responded to shoulder rotation. The selective GABAA antagonist receptor, bicuculline methiodine (BIC), was applied by microiontophoresis on single vestibular neurons and the changes in their activity at rest and during somatosensory stimulation was studied. In about half of cells the resting activity increased after the BIC application: 75% of these neurons showed also an increased response to somatosensory inputs whereas 17% exhibited a decrease. Changes in responsiveness in both directions were detected also in the units whose resting activity was not influenced by BIC. These data suggest that the responses of vestibular neurons to somatosensory inputs are modulated by GABA through a tonic release, which modifies the membrane response to the synaptic current. It is also possible that a phasic release of GABA occurs during foreleg rotation, shaping the stimulus-elicited current passing through the membrane. If this is the case, the changes in the relative position of body segments would modify the GABA release inducing changes in the vestibular reflexes and in learning processes that modify their spatio-temporal development.


Subject(s)
Bicuculline/pharmacology , Neurons/drug effects , Synaptic Transmission/drug effects , Vestibule, Labyrinth/drug effects , Action Potentials/drug effects , Action Potentials/physiology , Animals , GABA-A Receptor Antagonists/pharmacology , Male , Neurons/physiology , Rats, Sprague-Dawley , Receptors, GABA-A/metabolism , Reflex, Vestibulo-Ocular/drug effects , Rotation , Synaptic Transmission/physiology , Vestibule, Labyrinth/physiology
12.
J Neurosci ; 36(35): 9097-110, 2016 08 31.
Article in English | MEDLINE | ID: mdl-27581452

ABSTRACT

UNLABELLED: Galvanic vestibular stimulation (GVS) uses modulated currents to evoke neuronal activity in vestibular endorgans in the absence of head motion. GVS is typically used for a characterization of vestibular pathologies; for studies on the vestibular influence of gaze, posture, and locomotion; and for deciphering the sensory-motor transformation underlying these behaviors. At variance with the widespread use of this method, basic aspects such as the activated cellular substrate at the sensory periphery or the comparability to motion-induced neuronal activity patterns are still disputed. Using semi-intact preparations of Xenopus laevis tadpoles, we determined the cellular substrate and the spatiotemporal specificity of GVS-evoked responses and compared sinusoidal GVS-induced activity patterns with motion-induced responses in all neuronal elements along the vestibulo-ocular pathway. As main result, we found that, despite the pharmacological block of glutamatergic hair cell transmission by combined bath-application of NMDA (7-chloro-kynurenic acid) and AMPA (CNQX) receptor blockers, GVS-induced afferent spike activity persisted. However, the amplitude modulation was reduced by ∼30%, suggesting that both hair cells and vestibular afferent fibers are normally recruited by GVS. Systematic alterations of electrode placement with respect to bilateral semicircular canal pairs or alterations of the bipolar stimulus phase timing yielded unique activity patterns in extraocular motor nerves, compatible with a spatially and temporally specific activation of vestibulo-ocular reflexes in distinct planes. Despite the different GVS electrode placement in semi-intact X. laevis preparations and humans and the more global activation of vestibular endorgans by the latter approach, this method is suitable to imitate head/body motion in both circumstances. SIGNIFICANCE STATEMENT: Galvanic vestibular stimulation is used frequently in clinical practice to test the functionality of the sense of balance. The outcome of the test that relies on the activation of eye movements by electrical stimulation of vestibular organs in the inner ear helps to dissociate vestibular impairments that cause vertigo and imbalance in patients. This study uses an amphibian model to investigate at the cellular level the underlying mechanism on which this method depends. The outcome of this translational research unequivocally revealed the cellular substrate at the vestibular sensory periphery that is activated by electrical currents, as well as the spatiotemporal specificity of the evoked eye movements, thus facilitating the interpretation of clinical test results.


Subject(s)
Action Potentials/physiology , Electric Stimulation , Motor Neurons/physiology , Reflex, Vestibulo-Ocular/physiology , Vestibular Nerve/physiology , 6-Cyano-7-nitroquinoxaline-2,3-dione/pharmacology , Animals , Calcium/metabolism , Excitatory Amino Acid Antagonists/pharmacology , Eye Movements/physiology , In Vitro Techniques , Kynurenic Acid/pharmacology , Reflex, Vestibulo-Ocular/drug effects , Xenopus laevis
13.
Toxicol Lett ; 262: 49-54, 2016 Nov 16.
Article in English | MEDLINE | ID: mdl-27659732

ABSTRACT

Cisplatin is a chemotherapeutic agent commonly used for the treatment of solid tumors, and its side-effects include vestibulotoxicity. Previous studies have reported cisplatin-induced vestibulotoxicity in various animal models, but no study has investigated in vivo mouse vestibular dysfunction after cisplatin. The aim of this study was to investigate cisplatin-induced vestibulotoxicity in C57BL/6J mice. Vestibular function was assessed by recording the vestibulo-ocular reflex (VOR). This was done during sinusoidal rotations in the horizontal plane at three frequencies (0.5, 1.0 and 2.5Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16mg/kg, but not 8mg/kg, decreased the VOR gain at 2.5Hz compared with the vehicle control. Following 16mg/kg cisplatin treatment, the animals showed no change in the optokinetic nystagmus response, suggesting that no major changes in visual or oculomotor functions had occurred. This mouse model may be useful for studying cisplatin-induced vestibulotoxicity and its treatment.


Subject(s)
Antineoplastic Agents/toxicity , Cisplatin/toxicity , Reflex, Vestibulo-Ocular/drug effects , Animals , Body Weight/drug effects , Eye Movements/drug effects , Male , Mice , Mice, Inbred C57BL , Motor Activity/drug effects , Nystagmus, Optokinetic/drug effects , Rotation , Vestibular Function Tests
16.
Otol Neurotol ; 37(4): 380-4, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26945312

ABSTRACT

OBJECTIVES: To analyze and compare, in two groups of patients affected by definite Ménière's disease (MD) but treated differently, the Video Head Impulse Test findings especially by putting them in relationship with canal paresis, hearing loss, and duration of the disease. STUDY DESIGN: Retrospective chart review. PATIENTS: Seventy patients affected by unilateral definite MD (16 in Group 1 and 54 in Group 2) observed between March 2014 and May 2015 in a tertiary referral center were retrospectively studied and then divided into two groups: Group 1 was previously treated with intratympanic gentamicin, whereas Group 2 underwent only a conservative therapy. Instrumental tests included audiometry, caloric test, and Video Head Impulse Test. All the findings were statistically analyzed; significance was set at p = 0.005. INTERVENTION: Diagnostic. MAIN OUTCOMES MEASURES: If MD is treated conservatively the high-frequency vestibulo-oculomotor reflex gain determined with Video Head Impulse Test is normal; it is pathological if MD is treated with gentamicin. RESULTS: High-frequency vestibulo-oculomotor reflex gain showed a statistically significant reduction in Group 1; at the same time, it showed no correlation in both groups with hearing loss, duration of disease or canal paresis. CONCLUSION: High-frequency vestibulo-oculomotor reflex is naturally preserved even in late stage MD if the patient has been treated conservatively; the dissociation between Caloric Test and Video Head Impulse Test findings could be considered an instrumental hallmark of MD. Gentamicin significantly reduces high-frequency vestibulo-oculomotor reflex gain: this reduction can be taken into account when determining the effectiveness of an ablative treatment.


Subject(s)
Gentamicins/adverse effects , Head Impulse Test , Meniere Disease/therapy , Protein Synthesis Inhibitors/adverse effects , Reflex, Vestibulo-Ocular/drug effects , Adult , Aged , Caloric Tests , Female , Gentamicins/administration & dosage , Humans , Injection, Intratympanic , Male , Meniere Disease/diagnosis , Meniere Disease/physiopathology , Middle Aged , Protein Synthesis Inhibitors/administration & dosage , Retrospective Studies
17.
Behav Brain Res ; 302: 152-9, 2016 Apr 01.
Article in English | MEDLINE | ID: mdl-26778789

ABSTRACT

Systemic administration of a gamma-amino butyric acid type B (GABAB) receptor agonist, baclofen, affects various physiological and psychological processes. To date, the effects on oculomotor system have been well characterized in primates, however those in mice have not been explored. In this study, we investigated the effects of baclofen focusing on vestibular-related eye movements. Two rotational paradigms, i.e. sinusoidal rotation and counter rotation were employed to stimulate semicircular canals and otolith organs in the inner ear. Experimental conditions (dosage, routes and onset of recording) were determined based on the prior studies exploring the behavioral effects of baclofen in mice. With an increase in dosage, both canal and otolith induced ocular responses were gradually affected. There was a clear distinction in the drug sensitivity showing that eye movements derived from direct vestibulo-ocular reflex pathways were relatively unaltered, while the responses through higher-order neural networks in the vestibular system were substantially decreased. These findings were consistent with those observed in primates suggesting a well-conserved role of GABAB receptors in the oculomotor system across frontal-eyed and lateral-eyed animals. We showed here a previously unrecognized effect of baclofen on the vestibular oculomotor function in mice. When interpreting general animal performance under the drug, the potential contribution of altered balance system should be taken into consideration.


Subject(s)
Eye Movements/drug effects , Receptors, GABA-A/metabolism , Reflex, Vestibulo-Ocular/drug effects , Analysis of Variance , Animals , Baclofen/pharmacology , Dose-Response Relationship, Drug , GABA-B Receptor Agonists/pharmacology , Male , Mice , Mice, Inbred C57BL , Nystagmus, Physiologic/drug effects , Otolithic Membrane/drug effects , Psychophysics , Rotation
18.
PLoS One ; 10(8): e0135263, 2015.
Article in English | MEDLINE | ID: mdl-26313751

ABSTRACT

BACKGROUND AND AIMS: Opioids are indispensable for pain treatment but may cause serious nausea and vomiting. The mechanism leading to these complications is not clear. We investigated whether an opioid effect on the vestibular system resulting in corrupt head motion sensation is causative and, consequently, whether head-rest prevents nausea. METHODS: Thirty-six healthy men (26.6 ± 4.3 years) received an opioid remifentanil infusion (45 min, 0.15 µg/kg/min). Outcome measures were the vestibulo-ocular reflex (VOR) gain determined by video-head-impulse-testing, and nausea. The first experiment (n = 10) assessed outcome measures at rest and after a series of five 1-Hz forward and backward head-trunk movements during one-time remifentanil administration. The second experiment (n = 10) determined outcome measures on two days in a controlled crossover design: (1) without movement and (2) with a series of five 1-Hz forward and backward head-trunk bends 30 min after remifentanil start. Nausea was psychophysically quantified (scale from 0 to 10). The third controlled crossover experiment (n = 16) assessed nausea (1) without movement and (2) with head movement; isolated head movements consisting of the three axes of rotation (pitch, roll, yaw) were imposed 20 times at a frequency of 1 Hz in a random, unpredictable order of each of the three axes. All movements were applied manually, passively with amplitudes of about ± 45 degrees. RESULTS: The VOR gain decreased during remifentanil administration (p<0.001), averaging 0.92 ± 0.05 (mean ± standard deviation) before, 0.60 ± 0.12 with, and 0.91 ± 0.05 after infusion. The average half-life of VOR recovery was 5.3 ± 2.4 min. 32/36 subjects had no nausea at rest (nausea scale 0.00/0.00 median/interquartile range). Head-trunk and isolated head movement triggered nausea in 64% (p<0.01) with no difference between head-trunk and isolated head movements (nausea scale 4.00/7.25 and 1.00/4.5, respectively). CONCLUSIONS: Remifentanil reversibly decreases VOR gain at a half-life reflecting the drug's pharmacokinetics. We suggest that the decrease in VOR gain leads to a perceptual mismatch of multisensory input with the applied head movement, which results in nausea, and that, consequently, vigorous head movements should be avoided to prevent opioid-induced nausea.


Subject(s)
Analgesics, Opioid/adverse effects , Nausea/chemically induced , Piperidines/adverse effects , Reflex, Vestibulo-Ocular/drug effects , Adult , Head Movements/physiology , Humans , Male , Nausea/prevention & control , Remifentanil
19.
J Appl Physiol (1985) ; 119(3): 213-8, 2015 Aug 01.
Article in English | MEDLINE | ID: mdl-25953832

ABSTRACT

Space motion sickness (SMS), a condition caused by an intravestibular conflict, remains an important obstacle that astronauts encounter during the first days in space. Promethazine is currently the standard treatment of SMS, but scopolamine is used by some astronauts to prevent SMS. However, the oral and transdermal routes of administration of scopolamine are known to have substantial drawbacks. Intranasal administration of scopolamine ensures a fast absorption and rapid onset of therapeutic effect, which might prove to be suitable for use during spaceflights. The aim of this study was to evaluate the effects of intranasally administered scopolamine (0.4 mg) on the semicircular canals (SCCs) and the otoliths. This double-blind, placebo-controlled study was performed on 19 healthy male subjects. The function of the horizontal SCC and the vestibulo-ocular reflex, as well as the saccular function and utricular function, were evaluated. Scopolamine turned out to affect mainly the SCCs centrally and peripherally but also the utricles to a lesser extent. Centrally, the most probable site of action is the medial vestibular nucleus, where the highest density of muscarinic receptors has been demonstrated and afferent fibers from the SCCs and utricles synapse. Furthermore, our results suggest the presence of muscarinic receptors in the peripheral vestibular system on which scopolamine has a suppressive effect. Given the depressant actions on the SCCs, it is suggested that the pharmacodynamic effect of scopolamine may be attributed to the obliteration of intravestibular conflict that arises during (S)MS.


Subject(s)
Postural Balance/physiology , Reflex, Vestibulo-Ocular/physiology , Saccule and Utricle/physiology , Scopolamine/administration & dosage , Semicircular Canals/physiology , Administration, Inhalation , Administration, Intranasal , Adult , Double-Blind Method , Humans , Male , Muscarinic Antagonists/administration & dosage , Nasal Sprays , Placebo Effect , Postural Balance/drug effects , Reflex, Vestibulo-Ocular/drug effects , Saccule and Utricle/drug effects , Semicircular Canals/drug effects , Treatment Outcome
20.
PLoS One ; 9(10): e110322, 2014.
Article in English | MEDLINE | ID: mdl-25329150

ABSTRACT

Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and experience disturbing oscillopsia. To compensate for the deficient vestibulo-ocular reflex (VOR), they have to rely on re-fixation saccades. Some can trigger "covert" saccades while the head still moves; others only initiate saccades afterwards. Due to their shorter latency, it has been hypothesized that covert saccades are particularly beneficial to improve dynamic visual acuity, reducing oscillopsia. Here, we investigate the combined effect of covert saccades and the VOR on clear vision, using the Head Impulse Testing Device-Functional Test (HITD-FT), which quantifies reading ability during passive high-acceleration head movements. To reversibly decrease VOR function, fourteen healthy men (median age 26 years, range 21-31) were continuously administrated the opioid remifentanil intravenously (0.15 µg/kg/min). VOR gain was assessed with the video head-impulse test, functional performance (i.e. reading) with the HITD-FT. Before opioid application, VOR and dynamic reading were intact (head-impulse gain: 0.87±0.08, mean±SD; HITD-FT rate of correct answers: 90±9%). Remifentanil induced impairment in dynamic reading (HITD-FT 26±15%) in 12/14 subjects, with transient bilateral vestibular dysfunction (head-impulse gain 0.63±0.19). HITD-FT score correlated with head-impulse gain (R = 0.63, p = 0.03) and with gain difference (before/with remifentanil, R = -0.64, p = 0.02). One subject had a non-pathological head-impulse gain (0.82±0.03) and a high HITD-FT score (92%). One subject triggered covert saccades in 60% of the head movements and could read during passive head movements (HITD-FT 93%) despite a pathological head-impulse gain (0.59±0.03) whereas none of the 12 subjects without covert saccades reached such high performance. In summary, early catch-up saccades may improve dynamic visual function. HITD-FT is an appropriate method to assess the combined gaze stabilization effect of both VOR and covert saccades (overall dynamic vision), e.g., to document performance and progress during vestibular rehabilitation.


Subject(s)
Analgesics, Opioid/pharmacology , Reflex, Vestibulo-Ocular/drug effects , Reflex, Vestibulo-Ocular/physiology , Saccades/drug effects , Vestibular Nuclei/drug effects , Vestibular Nuclei/physiopathology , Vision, Ocular/physiology , Adult , Head/physiology , Humans , Male , Movement/drug effects , Piperidines/pharmacology , Remifentanil , Vision, Ocular/drug effects , Young Adult
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