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After unilateral peripheral vestibular lesions, the neural activity of neurons in the ipsi-lesional medial vestibular nucleus (ipsi-MVe) are markedly decreased, resulting in static and dynamic asymmetries of the vestibulo-ocular and vestibulo-spinal reflexes. Consequently, static vestibular symptoms such as spontaneous nystagmus and postural deviation and dynamic vestibular symptoms such as oscillopsia and swaying gait are induced. However, these behavioral asymmetries gradually recover after the lesion. Progressive balance restoration is termed vestibular compensation, which is divided into two phases: static and dynamic. Static vestibular compensation is further divided into initial and late processes. In the initial process of static vestibular compensation after unilateral labyrinthectomy (UL) in rats, plastic changes in the cerebello-vestibular and vestibular commissural inhibitory pathways suppress neurons in the contra-lesional MVe (contra-MVe), resulting in the restoration of symmetrical resting activity of MVe neurons on both sides at low levels. The declining frequency of spontaneous nystagmus after UL is an index of the initial process, and short-term administration of diazepam, a GABA A receptor agonist, has been shown to accelerate the initial process in rats. Accordingly, short-term administration of diazepam is recommended for the treatment of acute vertigo in patients with unilateral vestibular dysfunction. In the late process of static vestibular compensation after UL in rats, the resting activity of ipsi-MVe neurons gradually recovers due to changes in cell membrane properties, resulting in the reinforcement of balanced intervestibular nuclear activities to nearly normal levels without the suppression of contra-MVe neurons. The declining number of MK801-induced Fos-positive neurons in contra-MVe after UL is an index of the late process, and long-term administration of betahistine, a histamine H 3 receptor antagonist, has been shown to accelerate the late process in rats. Accordingly, long-term administration of betahistine is recommended for the treatment of subacute vertigo in patients who were not compensated for unilateral vestibular dysfunction. In the process of dynamic vestibular compensation after UL, the sensitivity of ipsi-MVe neurons to head velocity and acceleration is restored due to synaptic changes such as long-term potentiation and sprouting of commissures, resulting in the restoration of the dynamic vestibulo-ocular and vestibulo-spinal reflexes. To facilitate dynamic vestibular compensation, early ambulation and subsequent vestibular rehabilitation exercise are recommended for the treatment of chronic vertigo in patients with uncompensated unilateral vestibular dysfunction. Although vestibular compensation after bilateral vestibular loss is not expected, vestibular rehabilitation with a sensory-substitution strategy can improve imbalance in patients with bilateral vestibular lesions. [ABSTRACT FROM AUTHOR]

Hearing impairment has frequently been described in β-thalassemia patients with a significant impact on the patients' quality of life. Most studies provided evidence of deferoxamine (DFO) dose-related ototoxicity, however, the data is scarce regarding deferasirox (DFX) as a sole iron chelator. We aimed to assess the prevalence and risk factors of sensorineural hearing loss (SNHL) and vestibular dysfunction in regularly transfused β-thalassemia patients who had been treated with DFX film coated tablets. We conducted a case control study on 57 transfusion dependent β-thalassemia patients with a mean age of 15.3 years who received DFX FCT as monotherapy for at least one consecutive year, and 57 healthy age and sex-matching controls. Comprehensive audiological evaluations using pure tone audiometry (PTA) and transient evoked otoacoustic emission (TEOAE) as well as vestibular evaluation using Video-nystagmography (VNG) were done. SNHL was identified in 12 patients (21.1 %) using PTA and a statistically significant difference was detected between controls and patients at 6 KHz and 12 KHz frequencies. A higher incidence of SNHL was detected using TEOAE, 22 patients (43.1 %) failed to pass TEOAE, with a statistically significant decrease in the signal at frequencies 1, 4 KHz bilaterally and at frequencies 1.5, 2 KHz in the right ear compared to controls. Canal paresis was detected in 21 (36.8 %) of thalassemic children using bithermal caloric test with significantly more unilateral weakness than control children (P = 0.008). We found no significant correlation between audio-vestibular dysfunction and age, sex, serum ferritin, frequency of blood transfusion and dose of DFX FCT in thalassemic children. We conclude that the incidence of SNHL and vestibular dysfunction was high among transfusion dependent β-thalassemia patients. Therefore, we recommend performing pre-treatment baseline audio-vestibular assessment and yearly audio-vestibular monitoring to early detect high risk patients and initiate timely management to prevent permanent damage. [ABSTRACT FROM AUTHOR]

Physiological methods that can be similarly recorded in humans and animals have a major role in sensory toxicology, as they provide a bridge between human sensory perception data and the molecular and cellular data obtained in animal studies. Vestibular toxicity research lags well behind other sensory systems in many aspects, including the availability of methods for functional assessment in animals that could be robustly translated to human significance. Here we review the methods available for the assessment of vestibular function in both humans and laboratory animals, with an emphasis on their similarity or divergence, to highlight their potential utility for the predictive assessment of vestibular toxicity. [ABSTRACT FROM AUTHOR]

Background Eye movements evoked by electrical vestibular stimulation (EVS) offer potential for diagnosing vestibular dysfunction. However, ocular recording techniques are often too invasive or impractical for routine clinical use. Furthermore, the kinematic nature of the EVS signal is not fully understood in terms of movement sensations. New method We apply sinusoidal EVS stimuli varying from 0.05 to 20 Hz, and record the eye in darkness using an infrared camera. Eye movement was measured offline using commercially available software to track iris striations. Response gain and phase were calculated separately for eye position, velocity and acceleration across all frequencies, to determine how the brain interprets the EVS signal. Results Ocular torsion responses were observed at the same frequency as the stimulus, for all frequencies, while lateral/vertical responses were minimal or absent. Response gain and phase resembled previously reported responses to natural rotation, but only when analysing eye velocity, not position or acceleration. Comparison with existing method(s) Our method offers a simple, affordable, reliable and non-invasive method for tracking the ocular response to EVS. It is more convenient than scleral coil recordings, or marking the sclera to aid video tracking. It also allows us to assess the torsional VOR at frequencies not possible with natural stimuli. Conclusions Ocular torsion responses to EVS can be readily assessed using sinusoidal stimuli combined with an infrared camera. Gain and phase analysis suggests that the central nervous system interprets the stimulus as head roll velocity. Future work will assess the diagnostic potential for patients with vestibular disorders. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the lateralization value of video head-impulse test (vHIT) for the diagnosis of vestibulopathy and to analyze cases showing dissociated results with caloric test.Methods: In total, 19 healthy volunteers and 92 dizzy patients who underwent both a caloric test and a vHIT were enrolled. Patients were divided into two groups depending on their fluctuating pattern of vertigo. The vestibulo-ocular reflex (VOR) gain and gain asymmetry (GA) of a vHIT as well as unilateral weakness (UW) and the sum of the slow-phase velocities (SPVs) of warm and cold irrigation of the same side were compared. A cutoff value of VOR gain of a vHIT was also calculated using a receiver-operating characteristic curve.Results: A VOR gain in an affected ear and GA of a vHIT showed a statistically significant correlation with UW in a caloric test. The cutoff value of a vHIT was determined to be 0.875, derived under the assumption that UW of a caloric test ≤25% is normal. However, the parameters of the two tests were dissociated in 18%.Conclusion: A VOR gain of vHIT is a valuable objective parameter with a lateralization value determining vestibular hypofunction. However, considering substantial dissociation between a vHIT and a caloric test, these tests can be complementary tools for the lateralization of vestibular impairment for the comprehensive evaluation of patients' VOR. [ABSTRACT FROM AUTHOR]

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 2.5 Hz). A high-resolution, high-frequency digital infra-red camera was used with eye-tracking algorithms. Cisplatin at 16 mg/kg, but not 8 mg/kg, decreased the VOR gain at 2.5 Hz compared with the vehicle control. Following 16 mg/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. [ABSTRACT FROM AUTHOR]

The video head impulse test (vHIT) assesses the vestibulo-ocular reflex (VOR) during a rapid high-velocity low amplitude (10°–20°) head rotation. Patients with peripheral vestibulopathy have a reduced VOR gain with corrective catch-up saccades during the head turn. There are several pitfalls, mainly technical, which may interfere with interpretation of vHIT data. In addition, intrusive eye movement disorders such as spontaneous nystagmus that affect normal eye position and tracking can affect the vHIT results. To date there has been little study of neurological saccadic eye movements that may interfere with the interpretation of vHIT data. Here, in ten patients with a range of central neurological disorders, we describe oculomotor abnormalities on vHIT in the presence of normal range VOR gain values, recorded at a tertiary vestibular neurology service. • Certain apparent catch-up saccades visible on the vHIT data may be due to the gaze-evoked nystagmus, induced by the head turn and transient eccentric positioning of the eyes. • Saccadic oscillations may affect the vHIT by appearing immediately after the head impulse and may be indistinguishable from an overt saccade if seen without clinical correlation. • Our cases highlight that oculomotor abnormalities can interfere with quantitative recording of the head impulse VOR responses and may impact the clinical diagnosis. [ABSTRACT FROM AUTHOR]

[Display omitted] • In utero exposure to VPA results in an increased risk of ASD in humans. • VPA exposure resulted in fewer neurons in vestibular nuclei and fewer CB puncta. • VPA exposure resulted in impaired performance on motor tasks. • VPA exposure resulted in delayed VEMPs and horizontal nystagmus. Autism spectrum disorder (ASD) is a neurodevelopmental disorder that includes several key neuropathological changes and behavioral impairments. In utero exposure to the anti-epileptic valproic acid (VPA) increases risk of an ASD diagnosis in human subjects and timed in utero exposure to VPA is a clinically relevant animal model of ASD. Many human subjects with ASD have cerebellar hypoplasia, fewer Purkinje cells, difficulties with balance, ophthalmic dysfunction and abnormal responses to vestibular stimulation and such vestibular difficulties are likely under reported in ASD. We have recently shown that animals exposed to VPA in utero have fewer neurons in their auditory brainstem, reduced axonal projections to the auditory midbrain and thalamus, reduced expression of the calcium binding protein calbindin (CB) in the brainstem and cerebellum, smaller and occasionally ectopic cerebellar Purkinje cells and ataxia on several motor tasks. Based on these findings, we hypothesized that in utero VPA exposure similarly impacts structure and function of the vestibular brainstem. We investigated this hypothesis using quantitative morphometric analyses, immunohistochemistry for CB, a battery of vestibular challenges, recording of vestibular-evoked myogenic potentials and spontaneous eye movements. Our results indicate that VPA exposure results in fewer neurons in the vestibular nuclei, fewer CB-positive puncta, difficulty on certain motor tasks, longer latency VEMPs and significantly more horizontal eye movements. These findings indicate that the vestibular nuclei are impacted by in utero VPA exposure and provide a basis for further study of vestibular circuits in human cases of ASD. [ABSTRACT FROM AUTHOR]

Objective: Spatial orientation and navigation depends on information from the vestibular system. Previous work suggested impaired spatial navigation in patients with bilateral vestibular failure (BVF). The aim of this study was to investigate event-related brain activity by functional magnetic resonance imaging (fMRI) during spatial navigation and visual memory tasks in BVF patients. Methods: Twenty-three BVF patients and healthy age- and gender matched control subjects performed learning sessions of spatial navigation by watching short films taking them through various streets from a driver’s perspective along a route to the Cathedral of Cologne using virtual reality videos (adopted and modified from Google Earth®). In the scanner, participants were asked to respond to questions testing for visual memory or spatial navigation while they viewed short video clips. From a similar but not identical perspective depicted video frames of routes were displayed which they had previously seen or which were completely novel to them. Results: Compared with controls, posterior cerebellar activity in BVF patients was higher during spatial navigation than during visual memory tasks, in the absence of performance differences. This cerebellar activity correlated with disease duration. Conclusions: Cerebellar activity during spatial navigation in BVF patients may reflect increased non-vestibular efforts to counteract the development of spatial navigation deficits in BVF. Conceivably, cerebellar activity indicates a change in navigational strategy of BVF patients, i.e. from a more allocentric, landmark or place-based strategy (hippocampus) to a more sequence-based strategy. This interpretation would be in accord with recent evidence for a cerebellar role in sequence-based navigation. [ABSTRACT FROM AUTHOR]

Vestibular Migraine in children can mimic other disorders, especially at presentation. Outcome is hard to predict and management may be challenging due to the fact that many of the patients are too young to describe their symptoms and these are not always accompanied by headache. To assess vestibulo-ocular reflex (VOR) in pediatric patients who meet criteria for defined Vestibular Migraine and to compare results to healthy controls. Twenty-one patients aged 11–16 years were included in this prospective multicentric study. VOR was assessed using the video Head Impulse Test by EyeSeeCam®(Interacoustics, Denmark). Patients with Vestibular Migraine (VM) have higher values of gain compared to asymptomatic patients. Video Head Impulse Test (vHIT) is a useful and relatively fast-to-perform examination in children compared to other vestibular tests. Patients with VM seem to have higher values of gain at vHIT. • Gain values in video Head Impulse Test are higher in pediatric patients with VestibularMigraine. [ABSTRACT FROM AUTHOR]

Acute vestibular syndrome is most often caused by vestibular neuritis or stroke, although demyelinating diseases may be responsible for 4% of all AVS episodes. The authors present the case of a previously healthy 17-year-old female patient complaining of spontaneous vertigo and right-sided hearing loss. Otoneurological examination suggested a peripheral vestibular cause and video head impulse test revealed a reduced vestibulo-ocular reflex gain. The presence of sensorineural hearing loss raised the suspicion of a central cause and prompted imaging evaluation. A brain MRI evidenced demyelinating lesions in the right middle cerebellar peduncle and the patient was ultimately diagnosed with Multiple Sclerosis. [ABSTRACT FROM AUTHOR]

Introduction Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and therefore experience oscillopsia, making everyday activities, such as walking or driving harder to undertake. Their dynamic vision during passive head movements depends on their residual vestibulo-ocular reflex (VOR) function and on re-fixation saccades. The Head Impulse Testing Device – Functional Test (HITD-FT) is a recently proposed and innovative technique for assessing dynamic vision during passive high-acceleration head rotations, mimicking natural everyday movements. Goals To validate the HITD-FT as a tool to assess the performance of the vestibulo-ocular reflex (VOR) and the effect of re-fixation saccades on the overall dynamic visual function in opioid-induced bilateral vestibular dysfunction. Materials and methods The opioid remifentanil was continuously administrated in 14 healthy men (median age 26 years, range 21–31) in order to reversibly induce a bilateral vestibular impairment. Each subject was tested with the HITD-FT before and during opioid administration. In each test, passive, unpredictable, high-acceleration (2000–7000°/s 2 ) and small amplitude (10–20°) the ects-FT score mirrorice comched 300°/srdmic visual function matters. Unctionality, i.e. disturbing oscillopsia lity to com head rotations where applied while subjects fixated a visual stimulus. The visual stimulus consisted of a standard Landolt ring and appeared on a screen 80 ± 2 ms after head acceleration reached 300°/s 2 . Subjects were asked to identify the orientation of the ring and the provided answers were analyzed together with eye and head movements recorded with EyeSeeCam system. Results Before opioid application, VOR and dynamic reading performances were intact (head-impulse gain: 0.87 ± 0.08, mean ± SD; HITD-FT rate of correct answers: 90 ± 9%). The opioid administration induced impairment in the VOR function (head-impulse gain 0.63 ± 0.19) and in dynamic reading (HITD-FT 26 ± 15%) in 12/14 subjects. HITD-FT scores correlated with head-impulse gain impairment ( R = 0.63, p = 0.03) and with gain difference (before/during opioid R = −0.64, p = 0.02). One subject had non-pathological head-impulse gain (0.82 ± 0.03) and high HITD-FT score (92%). One subject could read (93%) despite a low head-impulse gain (0.59 ± 0.03) performing re-fixation saccades. Summary Our study suggests that the recently proposed HITD-FT is an appropriate method to document the combined effect of VOR performance and re-fixation saccades in vestibular dysfunction. Testing dynamic vision with head movement characteristics closely related to subjects’ daily activities makes the HITD-FT a suitable tool for assessing overall dynamic visual performance, e.g., to monitor progress during vestibular rehabilitation. [ABSTRACT FROM AUTHOR]