An Integrated System for Comprehensive Mouse Peripheral Vestibular Function Evaluation Based on Vestibulo-ocular Reflex.

Perioperative vestibular assessment and testing

The function of sensory hair cells of the cochlea and vestibular organs depends on an influx of K(+) through apical mechanosensitive ion channels and its subsequent removal over their basolateral membrane. The KCNQ4 (Kv7.4) K(+) channel, which is mutated in DFNA2 human hearing loss, is expressed in the basal membrane of cochlear outer hair cells where it may mediate K(+) efflux. Like the related K(+) channel KCNQ5 (Kv7.5), KCNQ4 is also found at calyx terminals ensheathing type I vestibular hair cells where it may be localized pre- or postsynaptically. Making use of Kcnq4(-/-) mice lacking KCNQ4, as well as Kcnq4(dn/dn) and Kcnq5(dn/dn) mice expressing dominant negative channel mutants, we now show unambiguously that in adult mice both channels reside in postsynaptic calyx-forming neurons, but cannot be detected in the innervated hair cells. Accordingly, whole cell currents of vestibular hair cells did not differ between genotypes. Neither Kcnq4(-/-), Kcnq5(dn/dn) nor Kcnq4(-/-)/Kcnq5(dn/dn) double mutant mice displayed circling behavior found with severe vestibular impairment. However, a milder form of vestibular dysfunction was apparent from altered vestibulo-ocular reflexes in Kcnq4(-/-)/Kcnq5(dn/dn) and Kcnq4(-/-) mice. The larger impact of KCNQ4 may result from its preferential expression in central zones of maculae and cristae, which are innervated by phasic neurons that are more sensitive than the tonic neurons present predominantly in the surrounding peripheral zones where KCNQ5 is found. The impact of postsynaptic KCNQ4 on vestibular function may be related to K(+) removal and modulation of synaptic transmission.

To evaluate the function of vestibular ocular reflex (VOR) in patients with unilateral peripheral vestibular disorder (uPVD) by the head impulse test (HIT). The HIT and caloric test were carried out in 135 cases of patients with uPVD. The results of HIT were considered as normal (negative reaction) and abnormal (positive reaction). The results of vestibular function evaluated by caloric test were divided into three kinds, including normal, decreased and deficit according to the degree of canal paresis as less than 30 percent, from 30 to 99 percent, and equal to 100 percent, respectively. The sensitivity, specificity, positive and negative predictive value of HIT in assessing the vestibular function was analyzed. For the 135 patients with uPVD, the HIT was normal in 90 (66.7%) cases and abnormal in 45 (33.3%) cases. When the caloric test was normal, the HIT was normal or abnormal in 58 cases and 6 cases, respectively. And when the canal paresis was from 30 to 99 percent, the HIT was normal or abnormal in 28 and 24 cases, respectively. When the vestibular function was deficit (CP was 100%), the HIT was normal or abnormal in 4 cases and 15 cases, respectively. When the results of caloric test were considered as the standard method to evaluate the VOR, the sensitivity, specificity, positive and negative predictive value of HIT were 54.9%, 90.6%, 86.7%, and 64.4%, respectively. When assessing the function of VOR in patients with uPVD, the HIT could not replace the caloric test, but it can be a supplementary method. The information from both the HIT and caloric test can be combined to evaluate the patients with vestibular hypofunction comprehensively.

Inhibition of central vestibular neurons from the contralateral labyrinth and its mediating pathway.

Partial or total unilateral vestibular loss is the third most common cause of peripheral vestibular dysfunction. Dysfunction of one or both of the vestibular mechanisms can manifest physically as abnormalities of posture, balance, and/or visual acuity. This case report describes physical therapy examination and individualized intervention with vestibular rehabilitation for a patient with unilateral vestibular hypofunction. The patient was an 80-year-old male with electronystamographically confirmed unilateral vestibular loss of 98.3%. He demonstrated altered balance and gaze stability classifying him as having an increased risk for falling. After 5 weeks of individualized vestibular rehabilitation, the patient significantly decreased his fall risk from 11 to 20 of 24 on the Dynamic Gait Index. His gaze stability also improved from a 4 to 1 line disparity with dynamic visual acuity testing. The patient also had a decrease in perceived disability on the Dizziness Handicap Inventory from 30/100 at evaluation to 12/100 at discharge. Individualized vestibular rehabilitation decreased fall risk and improved gaze stability for a patient with significant unilateral vestibular hypofunction.

Background Benign paroxysmal positional vertigo (BPPV) frequently recurs, posing diagnostic challenges when distinguishing recurrent BPPV (rBPPV) from other positional vertigo disorders. Objective To investigate vestibular and auditory function in rBPPV versus other recurrent positional vertigo patients, and assess the clinical utility of vestibular function tests in differential diagnosis. Methods Seventy-four patients with rBPPV or other positional vertigo underwent vestibular evoked myogenic potentials (VEMP), caloric test, video head impulse test (vHIT), and pure tone audiometry(PTA) at Beijing Tongren Hospital. Results Among 33 rBPPV patients (15 right posterior canal), 41 non-BPPV cases (30 vestibular migraine, VM) were identified. rBPPV showed lower ocular vestibular evoked myogenic potential(oVEMP) elicitation rates and reduced bilateral cervical vestibular evoked myogenic potential(cVEMP) responses. Caloric and vHIT abnormalities were more prevalent in rBPPV, with lower right posterior canal vestibulo-ocular reflex(VOR) gain on vHIT. Conclusion The reduced oVEMP elicitation rate and unilateral cVEMP elicited may be directed to rBPPV. Meanwhile, the abnormality of the caloric test and vHIT test may also be related to rBPPV. Other vertigo disorders, such as VM, may also appear position-induced and be confused with rBPPV. Abnormal otolith and semicircular canal function is a key indicator for differential diagnosis in rBPPV.

The role of the otoliths in mammals in the normal angular vestibuloocular reflex (VOR) was characterized in an accompanying study based on the Otopetrin1 (Otop1) mouse, which lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. That study showed that otoliths do not contribute to the normal horizontal (rotation about Earth-vertical axis parallel to dorso-ventral axis) and vertical (rotation about Earth-vertical axis parallel to interaural axis) angular VOR but do affect gravity context-specific VOR adaptation. By using these animals, we sought to determine whether the otoliths play a role in the angular VOR after unilateral labyrinthectomy when the total canal signal is reduced. In five Otop1 mice and five control littermates we measured horizontal and vertical left-ear-down and right-ear-down sinusoidal VOR (0.2-10 Hz, 20-100°/s) during the early (3-5 days) and plateau (28-32 days) phases of compensation after unilateral labyrinthectomy and compared these measurements with baseline preoperative responses from the accompanying study. From similar baselines, acute gain loss was ~25% less in control mice, and chronic gain recovery was ~40% more in control mice. The acute data suggest that the otoliths contribute to the angular VOR when there is a loss of canal function. The chronic data suggest that a unilateral otolith signal can significantly improve angular VOR compensation. These data have implications for vestibular rehabilitation of patients with both canal and otolith loss and the development of vestibular implants, which currently only mimic the canals on one side. NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) on the acute and chronic angular vestibuloocular reflex (VOR) after unilateral labyrinthectomy in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. This study shows that the otolith signal is used to augment the acute angular VOR and help boost VOR compensation after peripheral injury.

Summary The literature review summarizes the principles and methodology of the caloric test, a unique vestibular examination that allows for the separate evaluation of the excitatory and inhibitory functions of the vestibulo-ocular reflex (VOR) on each side of the peripheral vestibular system, specifically the lateral semicircular canals (LSCC). The article describes how the caloric test induces nystagmus based on the convection current of endolymph in the LSCC, depending on the temperature used. It explains the significance of evaluating unilateral weakness and directional preponderance as the main comparative results of the test. Furthermore, it addresses the interpretation of the absolute values of the caloric test. The caloric test, despite being time-consuming in routine clinical practice, remains an irreplaceable tool for the detailed assessment of the function of the peripheral vestibular end organ. Modern videonystagmography technology and sophisticated software for the analysis of recordings have significantly improved the accuracy and sensitivity of the test. Key words caloric test – vestibuloocular reflex – unilateral weakness – Jongkees’ formula – calorization – canal paresis – stronger ear formula – directional preponderance

Twelve patients undergoing unilateral vestibular neurectomy for the treatment of refractory vertigo were investigated. Vestibular motion perception was assessed using a self-rotational task and "vestibular remembered saccades". Cervical perception was also measured with remembered saccades. The tests were performed pre- and post-operatively to examine changes in vestibular and cervical perception following an acute vestibular lesion, and to monitor the progress of vestibular compensation. These perception tests were carried out in conjunction with a conventional evaluation of the vestibular ocular reflex (VOR), using electro-oculography. The patients' subjective symptoms at each stage of testing were also quantified with questionnaires. Generally, in the vestibular tests, for stimulation to the operated side, responses became strongly hypometric directly after the neurectomy, with a partial recovery during convalescence. In the cervical test, responses were bilaterally reduced immediately after operation. Results from both of the vestibular perception tests were significantly correlated with the VOR assessment of vestibular function. Scores for the patients' subjective symptoms of "vertigo" were only significantly correlated with the vestibular perception tests, and not with the conventional measures of vestibular function. Perceptual measurements afford useful complementary information in the assessment of vestibular patients.

Dynamic posturography by measurement of center of pressure (COP) is a widely employed technique for evaluating the vestibular system. However, the relationship of COP motion to vestibulo-ocular reflex (VOR) function and image stability on the retina has not been determined previously. To assess these relationships, we report gaze, head, and trunk stability during dynamic posturography in 11 normal volunteers, 7 subjects with unilateral vestibular lesions, and 3 subjects with bilateral vestibular lesions. Posturographic tasks consisted of standing still and standing on a platform that was sliding (0.2 Hz), tilting (0.1 Hz), or covered with a foam cushion 6 cm thick while tilting (0.1 Hz). Each perturbation was imposed in the anterior-posterior and repeated in the medial-lateral direction, in both light and darkness. Subjects viewed (or in darkness remembered) a target located 50, 100, or 500 cm distant. COP, angular eye position, and angular and linear orbit and trunk positions were measured using magnetic search coils and flux gate magnetometer sensors. With the target visible, the velocity of image motion on the retina was on average always less than 1 degree/s, well within the range consistent with high visual acuity. In darkness, gaze velocity increased for normal and vestibulopathic subjects. During tilt, vestibulopathic subjects had a significantly greater gaze velocity than controls. Gain of the angular VOR (eye velocity/head velocity) was significantly lower in darkness than in light and in vestibulopathic as compared to control subjects. Gain of the VOR was significantly correlated with gaze instability, but variation in VOR gain accounted for only 20-40% of the variance. In darkness, the velocity of the COP was significantly greater in vestibulopathic than control subjects for every condition tested. In light, this difference was small and often not significant. Although spectral analysis of the COP indicated frequencies above 1 Hz that were not observed in motion of the trunk and orbit, root mean square (RMS) velocities of the trunk and orbit in the horizontal plane were higher in darkness and in vestibulopathic subjects, mirroring COP findings. Only in vestibulopathic subjects tested in darkness was there a correlation between COP velocity and gaze velocity; COP velocity was otherwise uncorrelated with gaze. Gaze velocity was greater with near than with distant targets. Vertical VOR gain was higher with near targets. No other significant effects of target distance were found. Head movement strategy, VOR gain, and COP were all unaffected by target proximity. These data show that gaze velocity measurements during dynamic posturography in darkness are sensitive to vestibular loss. With a visible target, both COP and gaze stability of vestibulopathic subjects are difficult to distinguish from normal. During visual feedback, it is likely that image stabilization over the range of frequencies tested is achieved through better head stability and through visual tracking, allowing vestibulopathic subjects to maintain adequate visual acuity.

Commentary on: Convergence Vestibulo-ocular Reflex in Unilateral Vestibular Hypofunction: Behavioral Evidence in Support for a Novel Gaze Stability Exercise.

The squirrel monkey vestibulo-ocular reflex (VOR) was studied in darkness during Earth-horizontal rotation over a frequency range, 0.01-4 Hz, with the head positioned both centrally and displaced radially relative to the axis of rotation. With the head centered, the canal-mediated angular VOR (AVOR) was recorded in isolation. However, with the head placed eccentrically, otolith-mediated linear VOR (LVOR) components interact with the AVOR to yield a combined AVOR-LVOR response. The plane of the ocular response could be manipulated by placing the head in different orientations relative to gravity (i.e. upright or nose-up). When the head was upright and centered, the horizontal AVOR was recorded. Comparisons between eye and head angular velocity showed that gain (pk eye/pk head velocity) was nearly flat, averaging 0.83, across the frequency range. Phase (difference in degrees between eye and head velocity, shifted 180 degrees by convention) was near 0 degrees, except at frequencies below 0.1 Hz where phase leads were seen. When the head was displaced eccentrically and in the nose-out position (facing away from the axis of rotation), gain rose above that of the AVOR alone. The enhancement was progressive with increasing frequency, but only for frequencies above 0.25 Hz. When the subject was turned nose-in, gain declined relative to the AVOR alone, and in a similar frequency-dependent fashion. These results are consistent with the notion that nose-out and nose-in responses to eccentric rotation represent a combined influence of the horizontal AVOR and LVOR, the latter driven by inter-aural tangential acceleration. To further evaluate this possibility, eccentric rotation was also used to assess the LVOR in isolation. With the head in the nose-up orientation, the AVOR was shifted into the head's roll plane and generated torsional ocular responses. With the head centered over the axis of rotation, no systematic horizontal responses were observed. However, when the head was displaced eccentrically and placed in the head-out and head-in positions, horizontal ocular responses were recorded which were proportional to head eccentricity and were of appropriate polarity to presume that they represented the inter-aural LVOR activated by inter-aural tangential acceleration. Response gain rose with increasing frequency, as did tangential acceleration. The LVOR in its resting state in darkness could be characterized by an average sensitivity of 40.3 degrees/s/g (g = 9.81 m/s2).(ABSTRACT TRUNCATED AT 400 WORDS)

ABSTRACTThe purpose of this article is to review relevant literature on the effect of mild traumatic brain injury (mTBI) and blast injury on the vestibular system. Dizziness and imbalance are common sequelae associated with mTBI, and in some individuals, these symptoms may last for six months or longer. In war-related injuries, mTBI is often associated with blast exposure. The causes of dizziness or imbalance following mTBI and blast injuries have been linked to white matter abnormalities, diffuse axonal injury in the brain, and central and peripheral vestibular system damage. There is some evidence that the otolith organs may be more vulnerable to damage from blast exposure or mTBI than the horizontal semicircular canals. In addition, benign paroxysmal positional vertigo (BPPV) is a common vestibular disorder following head injury that is treated effectively with canalith repositioning therapy. Treatment for (non-BPPV) mTBI-related vestibular dysfunction has focused on the use of vestibular rehabilitation (VR) augmented with additional rehabilitation methods and medication. New treatment approaches may be necessary for effective otolith organ pathway recovery in addition to traditional VR for horizontal semicircular canal (vestibulo-ocular reflex) recovery.

Vestibulo-ocular reflex (VOR) makes images remain relatively stable on the retina. To keep appropriate performance and minimize image slip throughout life, VOR is subject to long-term adaptive regulation by visual input. It has been reported that adaptive changes in VOR gain (eye velocity/head velocity) are evoked either by fitting subjects with magnifying, miniaturizing, or reversing spectacles during normal behavior or by moving a large visual field in or out of phase relative to the subject's head movement. These feature frequency-selectivity. We studied the flexibility of adaptive gain change in VOR required by a horizontal visual-vestibular mismatch in earth vertical axis rotation (EVAR), including adaptive gain change from EVA to off-vertical axis rotation (OVAR) and other velocities. The visual-vestibular mismatch was made by oscillating subjects in EVAR for 30 minutes at 0.3 Hz with the peak velocity of 30 deg/s and 60 deg/s, synchronized with both in-phase (gain decrease: x 0 experiment) and out-of-phase (gain increase: x 2 experiment) sinusoidal rotation of white-black stripe patterns. Subjects were 19 healthy adult volunteers with no history of neurological symptoms. Horizontal and vertical eye positions were recorded by bitemporal DC-coupled electrooculography. In the x 2 adaptation experiment with 0.3 Hz at the peak velocity of 30 deg/s, the percent change in gain (post-pre/ pre) was 110% at the same stimulation and 100% at 40 deg/s in EVA. In the x 0 adaptation experiment with 0.3 Hz at the peak velocity of 30 deg/s, the percent change in gain was -50% at the same stimulation in EVA. In the x 2 adaptation experiment with 0.3 Hz at the peak velocity of 60 deg/s, the percent change in gain was 66% at the same stimulation in EVA, 30% at the same stimulation in nose-up position, and 74% at the same stimulation in nose-down position. In the x 0 adaptation experiment with 0.3 Hz at the peak velocity of 60 deg/s, the percent change in gain was -34% at the same stimulation in EVA. No change in VOR gain was observed at other peak velocities. These results suggest that VOR adaptation depends frequency and maximum angular head velocity, and this characteristic is observed in OVAR.

Background:Superior canal dehiscence syndrome (SCDS) is a condition in which an abnormal communication between the superior semicircular canal and the middle cranial fossa causes patients to hear internal noises transmitted loudly to their affected ear as well as to experience vertigo with pressure changes or loud sounds. Patients with SCDS can have an elevated ratio of summating potential (SP) to action potential (AP) as measured by electrocochleography (ECochG). Changes in this ratio have been observed during surgical intervention to correct this abnormal communication.Case Description:We present a case of SCDS along with history, physical examination, vestibular function testing, and computed tomography imaging. Due to the disabling symptoms, the patient elected to undergo surgery for plugging of the superior semicircular canal by middle cranial fossa approach. Simultaneous intraoperative ECochG and auditory brainstem response (ABR) were performed. Changes in SP/AP ratio, SP amplitude, and ABR wave I latency were observed during surgery, with a large ECochG SP amplitude generating a new wave, identifiable on the ABR and preceding the traditional wave I. The patient's symptoms resolved after surgery, and no long-term detriment to hearing was observed.Conclusions:This case demonstrates the intraoperative changes in ECochG during surgery for repair of a SCDS. The substantial intraoperative changes in the summating potential can create a novel wave on intraoperative ABR.