Unilateral Vestibular Deafferentation Research Articles

The Association Between Physical Activity and Chronic Symptoms After a Unilateral Vestibular Deafferentation: Narrative Review

The Association Between Physical Activity and Chronic Symptoms After a Unilateral Vestibular Deafferentation: Narrative Review

Effect of vestibular loss on head-on-trunk stability in individuals with vestibular schwannoma

The vestibulo-collic reflex generates neck motor commands to produce head-on-trunk movements that are essential for stabilizing the head relative to space. Here we examined the effects of vestibular loss on head-on-trunk kinematics during voluntary behavior. Head and trunk movements were measured in individuals with vestibular schwannoma before and then 6 weeks after unilateral vestibular deafferentation via surgical resection of the tumor. Movements were recorded in 6 dimensions (i.e., 3 axes of rotation and 3 axes of translation) using small light-weight inertial measurement units while participants performed balance and gait tasks. Kinematic measures differed between individuals with vestibular schwannoma (at both time points) and healthy controls for the more challenging exercises, namely those performed in tandem position or on an unstable surface without visual input. Quantitative assessment of the vestibulo-ocular reflex (VOR) revealed a reduction in VOR gain for individuals with vestibular schwannoma compared to control subjects, that was further reduced following surgery. These findings indicated that the impairment caused by either the tumor or subsequent surgical tumor resection altered head-on-trunk kinematics in a manner that is not normalized by central compensation. In contrast, we further found that head-on-trunk kinematics in individuals with vestibular schwannoma were actually comparable before and after surgery. Thus, taken together, our results indicate that vestibular loss impacts head-on-trunk kinematics during voluntary balance and gait behaviors, and suggest that the neural mechanisms mediating adaptation alter the motion strategies even before surgery in a manner that may be maladaptive for long-term compensation.

Are Vestibuloocular Reflex Gain and Dynamic Visual Acuity Responsible of Oscillopsia After Complete Unilateral Vestibular Loss?

Acute and complete unilateral vestibular deafferentation induces a significant change in ipsilateral vestibuloocular reflex gain, making the patient unable to stabilize gaze during active or passive head movements. This inability creates the illusion that the visual environment is moving, resulting in persistent visual discomfort during rapid angular or linear acceleration of the head. This is known as oscillopsia. Our objective was to understand if the spontaneous sensation of oscillopsias after complete unilateral vestibular deafferentation by vestibular neurotomy at 5 days (D5) and at 3 months (M3) is correlated with the loss of vestibuloocular reflex gain and dynamic visual acuity. Retrospective cohort study was conducted in an otolaryngology tertiary care center (2019-2022) on patients with complete unilateral vestibular loss by vestibular neurotomy. They were divided into 2 groups according to the presence (group G1) or absence (group G2) of a spontaneous complaint of oscillopsia assessed at M3. Severity of oscillopsias evaluated by Oscillopsia Severity Questionnaire. Vestibuloocular reflex gain based on video head impulse test (vHIT) and the dynamic visual acuity were measured for each group at D5 and M3. Categorical variables were compared using χ2 test and quantitative variables using the nonparametric Wilcoxon-Mann-Whitney test. All patients have a complete vestibular deafferentation at D5 and M3. At D5 (G1 = 8 patients, G2 = 5 patients), there is no significant difference for ipsilateral and contralateral vestibuloocular reflex gains and dynamic visual acuity losses. The Oscillopsia Severity Questionnaire was 2.68 ± 1.03 in G1 and 1.23 ± 1.03 in G2 (P < .05). At M3 (G1 = 9 patients, G2 = 6 patients), there is no significant difference between groups for epidemiologic and clinical data and for vestibuloocular reflex and dynamic visual acuity losses. The Oscillopsia Severity Questionnaire was 2.10 ± 0.63 in G1 and 1.24 ± 0.28 in G2 (P < .05). The spontaneous disabling sensation of oscillopsia after complete unilateral vestibular loss is well assessed by the Oscillopsia Severity Questionnaire but cannot be explained by objective vestibular tests assessing vestibuloocular reflex gain (vHIT) or dynamic visual acuity loss at D5 or M3. Further studies are needed to measure the sensation of oscillopsia under real-life conditions and to identify the factors responsible for its persistence. Retrospectively registered.

Motion Tracking in Diagnosis: Gait Disorders Classification with a Dual-Head Attentional Transformer-LSTM

Gait and motion stability analysis in gait dysfunction problems is a very interesting research area. Usually, patients who undergo vestibular deafferentation are affected by changes in their dynamic balance. Therefore, it is important both patients and physicians are able to monitor the progress of the so-called vestibular compensation to observe the rehabilitation process objectively. Currently, the quantification of their progress is highly dependent on the physician’s opinion. In this article, we designed a novel methodology to classify the gait disorders associated with unilateral vestibular deafferentation in patients undergoing vestibular schwannoma surgery (model of complete vestibular loss associated with imbalance due to vestibular nerve section and eventual labyrinthectomy). We present a dual-head attentional transformer-LSTM (DHAT-LSTM) to evaluate the problem of rehabilitation from gait dysfunction, which is observed by a Kinect. A system consisting of a key-point-RCNN detector is used to compute body landmark measures and evaluate gait dysfunction based on a DHAT-LSTM network. This structure is used to quantitatively assess gait classification by tracking skeletal features based on the temporal variation of feature sequences. The proposed deep network analyses the features of the patient’s movement. These extracted high-level representations are then fed to the final evaluation of gait dysfunction. The result analytically demonstrates its effectiveness in classification evaluation when used in conjunction with state-of-the-art pose estimation and feature extraction techniques. An accuracy greater than 81% was achieved for given sets of individuals using velocity-based, angle-based, and position features for both the whole body and the symmetric features of the body.

Compensatory saccades differ between those with vestibular hypofunction and multiple sclerosis pointing to unique roles for peripheral and central vestibular inputs.

Individuals with peripheral or central vestibular dysfunction recruit compensatory saccades (CSs) in response to high acceleration, yaw head impulses. Although CSs have been shown to be an effective strategy for reducing gaze position error (GPE) in individuals with peripheral hypofunction, for individuals with central vestibular dysfunction, the effectiveness of CS is unknown. The purpose of our study was to compare the effectiveness of CS, defined as the ability to compensate for head velocity and eye position errors, between persons with central and peripheral vestibular dysfunction. We compared oculomotor responses during video head impulse testing between individuals with unilateral peripheral vestibular deafferentation, a disorder of the peripheral vestibular afferents, and individuals with multiple sclerosis, a condition affecting the central vestibular pathways. We hypothesized that relative to individuals with peripheral lesions, individuals with central dysfunction would recruit CSs that were delayed and inappropriately scaled to head velocity and GPE. We show that CSs recruited by persons with central vestibular pathology were not uniformly deficient but instead were of a sufficient velocity to compensate for reductions in VOR gain. Compared to those with peripheral vestibular lesions, individuals with central pathology also recruited earlier covert CS with amplitudes that were better corrected for GPE. Conversely, those with central lesions showed greater variability in the amplitude of overt CS relative to GPE. These data point to a unique role for peripheral and central vestibular inputs in the recruitment of CS and suggest that covert CSs are an effective oculomotor strategy for individuals with multiple sclerosis.NEW & NOTEWORTHY Compensatory saccades (CSs) are recruited by individuals with unilateral vestibular deafferentation (UVD) to compensate for an impaired vestibulo-ocular reflex (VOR). The effectiveness of CS in multiple sclerosis (MS), a central vestibular impairment, is unknown. We show that in UVD and in MS, covert CSs compensate for reduced VOR gain and minimize gaze position error (GPE), yet in >50% of individuals with MS, overt CS worsened GPE, suggesting unique roles for peripheral and central vestibular inputs.

Unique compensatory oculomotor behavior in people living with multiple sclerosis

IntroductionGlobally, there are 3 million people living with multiple sclerosis (PLW-MS). A large proportion of PLW-MS have abnormal vestibular function tests that suggest central vestibular lesions. Yet, data regarding vestibular-ocular control in PLW-MS is limited. Thus, we aimed to further characterize compensatory saccade (CS) behavior in PLW-MS. MethodsWe analyzed video head impulse data from four groups of six age- and sex-matched adults: people living with mild MS (PLW-mild-MS, people living with moderate MS (PLW-moderate-MS), people living with unilateral vestibular deafferentation (PLW-UVD), and healthy controls (HC). ResultsPLW-moderate-MS had lower lateral canal vestibulo-ocular reflex (VOR) gain bilaterally compared to PLW-mild MS (p < 0.001), HC (p < 0.001), and PLW-UVD (p < 0.001). CS frequency was higher for impulses towards the less affected side in PLW-moderate-MS versus the more (p = 0.01) and less (p < 0.001) affected sides in PLW-mild-MS. CS latency was shorter (p < 0.001) and CS peak velocity was lower (p < 0.001) with impulses towards the more affected side versus the less affected side in PLW-moderate-MS. However, CS peak velocity with impulses towards each side was similar in PLW-mild-MS (p = 0.12). Gaze position error (GPE) was larger after impulses towards the more affected side versus the less affected side in PLW-moderate-MS (p < 0.001) and PLW-mild-MS (p < 0.001). MS-related disability was moderately associated with VOR gain (p < 0.001) and GPE (p < 0.001). Additionally, we identified micro-saccades and position correcting saccades that were uniquely employed by PLW-MS as compensatory gaze stabilizing strategies. ConclusionsIn PLW-MS, the characteristics of compensatory oculomotor behavior depend on the extent of residual VOR gain.

Subjective perception of activity level: A prognostic factor for developing chronic dizziness after vestibular schwannoma resection?

IntroductionA vestibular schwannoma (VS) resection causes an acute unilateral vestibular deafferentation resulting in acute postoperative symptoms. Despite the expected resolution of most of the symptoms, due to central vestibular compensation, more than one out of four patients develop chronic dizziness. Several predictive factors, such as age and tumor size, have been suggested. Despite its potential effect on the process of central vestibular compensation, the level of physical activity after VS resection was not yet considered. Therefore, the association between the level of physical activity and chronic dizziness after VS resection will be investigated.MethodsThis retrospective cohort study included 66 patients who underwent a retro-sigmoid VS resection between October 2001 and February 2007. Patients were assessed before surgery and at 9 weeks and 6 months postoperatively. At 9 weeks, patients were asked to report their level of physical activity (PA) during the past week by using a visual analogue scale and their balance performance was assessed by four standing balance conditions with eyes closed and the Timed Up and Go test (TUG). Based on the Dizziness Handicap Inventory (DHI) score at 6 months, patients were divided in a chronic dizziness group (DHI > 30) and non-chronic dizziness group (DHI-score ≤ 30). Age, sex, Koos classification, preoperative vestibular function, treatment group, balance performance, and level of PA were compared between both groups and used as independent variables in linear regression analyses with the DHI score at 6 months as dependent variable.ResultsThe chronic dizzy patients revealed to have significantly lower levels of PA (p < 0.001) and worse static and dynamic balance performance (p = 0.023 and p = 0.041, respectively) 9 weeks after surgery. After elimination, the multiple regression analysis resulted in a model with two variables (PA level, TUG) which significantly predicted the DHI score (F2,42 = 6.581; R2 = 0.239; p = 0.003).ConclusionThis study revealed associations between (1) the level of PA and balance performance in the subacute phase and (2) chronic dizziness after VS resection. Assessment of the level of PA and balance performance during the subacute phase, which can be performed in a non-invasive and non-time-consuming way, might therefore provide prognostic information after VS resection.

The human vestibulo-ocular reflex and compensatory saccades in schwannoma patients before and after vestibular nerve section

ObjectiveTo examine the vestibulo-ocular reflex (VOR) and compensatory-saccades before and after complete unilateral vestibular deafferentation (UVD). MethodsForty patients were studied before and after surgery for vestibular or facial schwannoma using the video head-impulse test (vHIT) and multivariable regression. ResultsPrior to UVD (median(IQR), 14(58.4) days), the average VOR-gain towards the lesioned-ear was lower than in normal for all semicircular canals (lateral, anterior, posterior: 0.69, 0.72, 0.49). One-week after UVD (5(3.0) days) VOR gains were further reduced (0.22, 0.37, 0.27), however, within one-year after UVD (171(125.0) days) the lesioned-ear VOR gains had slightly increased (+0.08, +0.11, +0.03), maximally for the anterior-canal. After UVD, the VOR gain asymmetry (gain towards minus away from intact-ear) was lower for the intact posterior-canal plane (0.56, 0.56, 0.22). For the lesioned canals, the frequency and amplitude of the first compensatory-saccade increased from 61–93% and 1.9–3.6° pre-surgery, to 98–99% and to 3.1–5.9° one-week post-surgery and remained unchanged over one-year; second saccade frequency and amplitude decreased over the same timespan. ConclusionsAfter UVD the high-acceleration VOR for the intact posterior-canal plane is more symmetrical than the other canals. First compensatory-saccades adapt within one week and subsequently change only marginally. SignificanceSaccade compensation from surgical UVD is near complete by one-week.

Different Types of Environmental Stressors Could Have Disruptive or Constructive Effects on Vestibular Compensation

Background and Aim: Stress could play either helpful or harmful roles in vestibular compensation, the process of recovery after vestibular system lesions. Herein, we examined the effect of two stressor types on vestibular compensation: chronic anxiety disorder induced by early maternal separation (MS), and caloric restriction by an intermittent fasting (IF) diet. Methods: Male Wistar rats (n=56) received maternal separation (the MS group), intermittent fasting (IF group), unilateral vestibular deafferentation (UVD group), or a mixture of these interventions (UVD+IF, UVD+MS, and UVD+IF+MS). All the groups were compared with control animals. The animals’ balance, motor coordination, anxiety, locomotor activity, and serum cortisol levels were evaluated by rotarod, open field, and enzyme-linked immunosorbent assay methods, respectively. The data were compared with those of the healthy control (HC) group. Results: The UVD animals did not show a significant change in the time on the rod, except for the IF+UVD group (p=0.04). There was no significant difference between the experimental groups on the open field indices, except for the MS+IF+UVD group which traveled a significantly less total distance (p=0.02). Serum cortisol levels were significantly higher than HCs for all the groups except for the sham saline and IF+UVD group (p&lt;0.05). Conclusion: IF seems to promote compensation after UVD, while MS may disrupt it. However, IF loses its beneficial outcomes if the animal has received another source of stress, i.e. MS.

The Differential Effects of Acute Right- vs. Left-Sided Vestibular Deafferentation on Spatial Cognition in Unilateral Labyrinthectomized Mice.

This study aimed to investigate the disparity in locomotor and spatial memory deficits caused by left- or right-sided unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL) and to examine the effects of galvanic vestibular stimulation (GVS) on the deficits over 14 days. Five experimental groups were established: the left-sided and right-sided UL (Lt.-UL and Rt.-UL) groups, left-sided and right-sided UL with bipolar GVS with the cathode on the lesion side (Lt.-GVS and Rt.-GVS) groups, and a control group with sham surgery. We assessed the locomotor and cognitive-behavioral functions using the open field (OF), Y maze, and Morris water maze (MWM) tests before (baseline) and 3, 7, and 14 days after surgical UL in each group. On postoperative day (POD) 3, locomotion and spatial working memory were more impaired in the Lt.-UL group compared with the Rt.-UL group (p < 0.01, Tamhane test). On POD 7, there was a substantial difference between the groups; the locomotion and spatial navigation of the Lt.-UL group recovered significantly more slowly compared with those of the Rt.-UL group. Although the differences in the short-term spatial cognition and motor coordination were resolved by POD 14, the long-term spatial navigation deficits assessed by the MWM were significantly worse in the Lt.-UL group compared with the Rt.-UL group. GVS intervention accelerated the vestibular compensation in both the Lt.-GVS and Rt.-GVS groups in terms of improvement of locomotion and spatial cognition. The current data imply that right- and left-sided UVD impair spatial cognition and locomotion differently and result in different compensatory patterns. Sequential bipolar GVS when the cathode (stimulating) was assigned to the lesion side accelerated recovery for UVD-induced spatial cognition, which may have implications for managing the patients with spatial cognitive impairment, especially that induced by unilateral peripheral vestibular damage on the dominant side.

Transcanal Transvestibular Endoscopic Neurectomy: First Experience.

Ménière's disease is an idiopathic inner ear disorder characterized by recurrent vertigo, fluctuating sensorineural hearing loss, and persistent tinnitus. In 10% to 30% of cases, conservative therapy fails, and Ménière's disease is defined as intractable. In these patients, ablative techniques with unilateral vestibular deafferentation are mandatory. Several approaches for vestibular neurectomy, which preserve hearing capability, are described. In patients presenting severe dizziness associated with high-grade sensorineural hearing loss, surgical labyrinthectomy, or selected vestibular neurectomy through a translabyrinthine approach are the treatments commonly considered. This study reports the first application of transcanal transvestibular endoscopic neurectomy in two patients with frequent disabling vertigo and high-grade sensorineural hypoacusia. This was a retrospective chart review including patients with intractable Ménière's disease who underwent vestibular neurectomy, performed in our ENT department between January 2017 and January 2020, selecting patients with disabling vertigo and high-grade sensorineural hypoacusia. We describe step-by-step the surgical technique of transcanal transvestibular endoscopic neurectomy. Overall, two patients underwent transcanal transvestibular endoscopic neurectomy. We performed transcanal transvestibular neurectomy in all cases. No intraoperative complications were observed. On the 2nd postoperative day, one patient presented CSF leak, leading to surgical revision. A complete resolution of vertigo attacks was observed 6 months after surgery. Even though this study presents a limited number of cases, transcanal transvestibular neurectomy is a promising, safe, and effective procedure in selected cases.

Effects of Galvanic Vestibular Stimulation on Vestibular Compensation in Unilaterally Labyrinthectomized Mice.

Objectives: To investigate the ameliorating effects of sinusoidal galvanic vestibular stimulation (GVS) on vestibular compensation from unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL).Methods: Sixteen male C57BL/6 mice were allocated into two groups that comprise UL groups with GVS (GVS group, n = 9) and without GVS intervention (non-GVS group, n = 7). In the experimental groups, we assessed vestibulo-ocular reflex (VOR) recovery before (baseline) and at 3, 7, and 14 days after surgical unilateral labyrinthectomy. In the GVS group, stimulation was applied for 30 min daily from postoperative days (PODs) 0–4 via electrodes inserted subcutaneously next to both bony labyrinths.Results: Locomotion and VOR were significantly impaired in the non-GVS group compared to baseline. The mean VOR gain of the non-GVS group was attenuated to 0.23 at POD 3 and recovered continuously to the value of 0.54 at POD 14, but did not reach the baseline values at any frequency. GVS intervention significantly accelerated recovery of locomotion, as assessed by the amount of circling and total path length in the open field tasks compared to the non-GVS groups on PODs 3 (p < 0.001 in both amount of circling and total path length) and 7 (p < 0.01 in amount of circling and p < 0.001 in total path length, Mann–Whitney U-test). GVS also significantly improved VOR gain compared to the non-GVS groups at PODs 3 (p < 0.001), 7 (p < 0.001), and 14 (p < 0.001, independent t-tests) during sinusoidal rotations. In addition, the recovery of the phase responses and asymmetry of the VOR was significantly better in the GVS group than in the non-GVS group until 2 weeks after UVD (phase, p = 0.001; symmetry, p < 0.001 at POD 14).Conclusion: Recoveries for UVD-induced locomotion and VOR deficits were accelerated by an early intervention with GVS, which implies that GVS has the potential to improve vestibular compensation in patients with acute unilateral vestibular failure.

Selective optogenetic stimulation of glutamatergic, but not GABAergic, vestibular nuclei neurons induces immediate and reversible postural imbalance in mice.

Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate that glutamatergic, but not GABAergic VN neuronal subpopulation is responsible for immediate and strong posturo-locomotor deficits, comparable to unilateral vestibular deafferentation models. During optogenetic stimulation, the support surface dramatically increased in VNVGluT2+ mice, and rapidly fell back to baseline after stimulation, whilst it remained unchanged during similar stimulation of VNGAD2+ mice. This effect persisted when vestibular tactilo kinesthesic plantar inputs were removed. Posturo-locomotor alterations evoked in VNVGluT2+ animals were still present immediately after stimulation, while they disappeared 1 h later. Overall, these results indicate a fundamental role for VNVGluT2+ neurons in balance and posturo-locomotor functions, but not for VNGAD2+ neurons, in this specific context. This new optogenetic approach will be useful to characterize the role of the different VN neuronal populations involved in vestibular physiology and pathophysiology.

Galvanic Vestibular Stimulation Improves Spatial Cognition After Unilateral Labyrinthectomy in Mice.

Objectives: To investigate the deficits of spatial memory and navigation from unilateral vestibular deafferentation (UVD) and to determine the efficacy of galvanic vestibular stimulation (GVS) for recovery from these deficits using a mouse model of unilateral labyrinthectomy (UL).Methods: Thirty-six male C57BL/6 mice were allocated into three groups that comprise a control group and two experimental groups, UVD with (GVS group) and without GVS intervention (non-GVS group). In the experimental groups, we assessed the locomotor and cognitive behavioral function before (baseline) and 3, 7, and 14 days after surgical UL, using the open field (OF), Y maze, and Morris water maze (MWM) tests. In the GVS group, the stimulations were applied for 30 min daily from postoperative day (POD) 0–4 via the electrodes inserted subcutaneously close to both bony labyrinths.Results: Locomotion and spatial cognition were significantly impaired in the mice with UVD non-GVS group compared to the control group. GVS significantly accelerated recovery of locomotion compared to the control and non-GVS groups on PODs 3 (p < 0.001) and 7 (p < 0.05, Kruskal–Wallis and Mann–Whitney U tests) in the OF and Y maze tests. The mice in the GVS group were better in spatial working memory assessed with spontaneous alternation performance and spatial reference memory assessed with place recognition during the Y maze test than those in the non-GVS group on POD 3 (p < 0.001). In addition, the recovery of long-term spatial navigation deficits during the MWM, as indicated by the escape latency and the probe trial, was significantly better in the GVS group than in the non-GVS group 2 weeks after UVD (p < 0.01).Conclusions: UVD impairs spatial memory, navigation, and motor coordination. GVS accelerated recoveries in short- and long-term spatial memory and navigation, as well as locomotor function in mice with UVD, and may be applied to the patients with acute unilateral vestibular failure.

The Instrumented Timed "Up & Go" Test Distinguishes Turning Characteristics in Vestibular Hypofunction.

Deficits in vestibular function increase the risk for falls while turning. However, the clinical assessment of turning in patients with vestibular dysfunction is lacking, and evidence is limited that identifies the effectiveness of vestibular physical therapy in improving turning performance. The purpose of this study was to quantify walking and turning performance during the instrumented Timed "Up & Go" (TUG) test using body-worn inertial measurement units (IMUs). Novel instrumented TUG parameters were investigated for ability to distinguish patients with unilateral vestibular deafferentation (UVD) from control groups and discriminate the differences in turning parameters of patients with UVD following vestibular physical therapy. Thirty-eight individuals were recruited following UVD surgery: 26 age-matched veteran controls with reports of dizziness not from a peripheral vestibular origin, and 12 age-matched healthy controls. Participants were donned with IMUs and given verbal instructions to complete the TUG test as fast as safely possible. The IMU-instrumented and automated assessment of the TUG test provided component-based TUG parameters, including the novel walk:turn ratio. Among the participants with UVD, 19 completed an additional instrumented TUG testing after vestibular physical therapy. The walk:turn time ratio showed that turning performance in patients with UVD before rehabilitation is significantly more impaired than both the individuals with nonperipheral conditions and healthy controls. Vestibular rehabilitation significantly improved turning performance and "normalized" their walk:turn time ratio compared with healthy controls. The duration of the straight walking component in individuals with UVD before vestibular physical therapy, however, was not significantly different compared with that component in people after vestibular physical therapy and in healthy controls. The IMU-instrumented TUG test can be used to distinguish individuals with vestibular deafferentation and to objectively quantify the change in their turning performance after vestibular physical therapy. The IMU-based instrumented TUG parameters have the potential to quantify the efficacy of vestibular physical therapy and be adopted in the clinic.

Spontaneous Recovery of the Vestibulo-Ocular Reflex After Vestibular Neuritis; Long-Term Monitoring With the Video Head Impulse Test in a Single Patient.

Vestibular rehabilitation of patients in whom the level of vestibular function is continuously changing requires different strategies than in those where vestibular function rapidly becomes stable: where it recovers or where it does not and compensation is by catch-up saccades. In order to determine which of these situations apply to a particular patient, it is necessary to monitor the vestibulo-ocular reflex (VOR) gains, rather than just make a single measurement at a given time. The video Head Impulse Test (vHIT) is a simple and practical way to monitor precisely the time course and final level of VOR recovery and is useful when a patient has ongoing vestibular symptoms, such as after acute vestibular neuritis. In this study, we try to show the value of ongoing monitoring of vestibular function in a patient recovering from vestibular neuritis. Acute vestibular neuritis can impair function of any single semicircular canal (SCC). The level of impairment of each SCC, initially anywhere between 0 and 100%, can be accurately measured by the vHIT. In superior vestibular neuritis the anterior and lateral SCCs are the most affected. Unlike after surgical unilateral vestibular deafferentation, SCC function as measured by the VOR can recover spontaneously after acute vestibular neuritis. Here we report monitoring the VOR from all 6 SCCs for 500 days after the second attack in a patient with bilateral sequential vestibular neuritis. Spontaneous recovery of the VOR in response to anterior and lateral SCC impulses showed an exponential recovery with a time to reach stable levels being longer than previously considered or reported. VOR gain in response to low-velocity lateral SCC impulses recovered with a time constant of around 100 days and reached a stable level at about 200 days. However, in response to high-velocity lateral SCC and anterior SCC impulses, VOR gain recovered with a time constant of about 150 days and only reached a stable level toward the end of the 500 days monitoring period.

MicroRNA-219a-5p-mediated inhibition of CaMKIIγ facilitates vestibular compensation in acute vertigo by promoting protein kinase C expression.

Vestibular compensation (VC) refers to a behavioral recovery process in which firing rates of bilateral vestibular nuclei neurons are rebalanced. Our study aimed to investigate the underlying mechanism by which miR-219a-5p regulates Ca2+ /calmodulin-dependent protein kinase II γ isoform (CaMKIIγ) and protein kinase C (PKC) in VC. A unilateral vestibular deafferentation rat model was established by unilateral labyrinthectomy (UL), after which VC was evaluated in rats with UL-induced vertigo-like behavior by measuring vestibular defect behavior and performing rotarod tests, as well as by BrdU immunohistochemistry on medial vestibular nuclei. We found that miR-219a-5p was increased while CaMKIIγ was decreased during VC in the medial vestibular nucleus of rats that had undergone UL. Next, gain- and loss-of-function assays were conducted to evaluate the effects of miR-219a-5p and CaMKIIγ on the vestibular defect behaviors and VC, the results of which suggested that in rats after UL overexpression of CaMKIIγ inhibited VC, while overexpression of miR-219a-5p facilitated VC. A dual-luciferase reporter gene assay identified that miR-219a-5p targeted CaMKIIγ. This led to additional experiments showing that miR-219a-5p aptomir expression downregulated CaMKIIγ in cortical cells with a concomitant increase in PKC expression, which were verified further in vivo. In summary, in rats with acute vertigo, miR-219a-5p overexpression inhibits CaMKIIγ and elevates PKC, thereby facilitating VC. Our study offers possible targets for further evaluation as treatment of acute vertigo in humans.

The intrinsic plasticity of medial vestibular nucleus neurons during vestibular compensation\u2014a systematic review and meta-analysis

BackgroundVestibular compensation is a homeostatic process that occurs in the central nervous system in response to peripheral vestibular dysfunction. Experimental studies in rodent models have suggested that unilateral peripheral vestibular lesions are correlated with an increase in the intrinsic excitability of central vestibular neurons. This process may be dependent on the intrinsic properties of the neurons themselves. We aimed to conduct a systematic review of the literature to survey the evidence for changes in intrinsic plasticity observed during the acute phase of vestibular compensation.MethodsWe systematically reviewed the literature regarding the electrophysiological effect of experimentally induced unilateral vestibular deafferentation (UVD) on the intrinsic membrane properties of medial vestibular nucleus neurons in animal models. We developed tools to assess the methodological quality (precision, validity and bias) of studies that met pre-determined inclusion and exclusion criteria. We extracted numerical data and performed a meta-analysis of specific quantitative data pooled from these studies.ResultsWe identified 17 studies that satisfied the inclusion criteria. There is moderate quality evidence to suggest a statistically significant increase in the intrinsic excitability of medial vestibular nucleus neurons following unilateral vestibular deafferentation. Specifically, the spontaneous discharge rate increases by 4 spikes/s on average and the sensitivity to current stimuli increases.ConclusionUsing this novel approach, we demonstrate that the methodology of systematic review and meta-analysis is a useful tool in the summation of data across experimental animal studies with similar aims.

Evidence a shared mechanism mediates ipsi- and contralesional compensatory saccades and gait after unilateral vestibular deafferentation

The study objective was to understand how the contralesional labyrinth contributes to gaze and gait stability after unilateral vestibular deafferentation (UVD). Head impulse testing (vHIT) was completed in 37 individuals [22 women (59%); age 52.13 ± 11.59 yr, mean ± SD] with UVD from vestibular schwannoma resection. Compensatory saccades (CS) and vestibulo-ocular reflex (VOR) gain were analyzed for both ipsilesional and contralesional impulses. Gait speed (10-m walk test) and endurance (2-min walk test) were collected for 35 individuals. CS were recruited during contralesional head rotation regardless of VOR gain on either the ipsilesional [ρ = 0.21 (-0.14, 0.57); Spearman rank (95% confidence interval)] or contralesional side [ρ = -0.04 (-0.42, 0.35)]. Additionally, the latency of these CS (151.19 ± 52.41 ms) was similar to that of CS generated during ipsilesional rotation (165.65 ± 21.62 ms; P = 0.159). CS recruited during ipsilesional vHIT were of a higher velocity (P < 0.001) and greater frequency (P < 0.001) compared with contralesional CS. VOR gain asymmetry was significantly correlated with gait speed [ρ = -0.37 (-0.73, -0.01)], yet individual VOR gain was not correlated [ipsilesional: ρ = 0.17 (-0.20, 0.55); contralesional: ρ = -0.18 (-0.52, 0.15)]. Our data reveal CS are recruited at similar latencies without correlation to VOR gain or direction of head rotation, and that the central integration of ipsilesional and contralesional vestibular afference correlates with gait. Together, our data suggest the brain considers vestibular afference from both sides when generating related behavioral output after UVD.NEW & NOTEWORTHY After unilateral vestibular deafferentation, compensatory saccades (CS) have similar latencies regardless of the direction of head rotation, and those CS generated during contralesional head rotation are unrelated to extent of vestibular loss. Additionally, the extent of asymmetry in residual vestibular function, not the extent of vestibular loss, correlates with gait speed. Our data suggest a common mechanism is responsible for the generation of CS and restoration of gait speed in vestibular compensation.

Improvement After Vestibular Rehabilitation Not Explained by Improved Passive VOR Gain.

Gaze stability exercises are a critical component of vestibular rehabilitation for individuals with vestibular hypofunction and many studies reveal the rehabilitation improves functional performance. However, few studies have examined the vestibular physiologic mechanisms (semicircular canal; otolith) responsible for such recovery after patients with vestibular hypofunction complete gaze and gait stability exercises. The purpose of this study was to compare behavioral outcome measures (i.e., visual acuity during head rotation) with physiological measures (i.e., gain of the vestibulo-ocular reflex) of gaze stability following a progressive vestibular rehabilitation program in patients following unilateral vestibular deafferentation surgery (UVD). We recruited n = 43 patients (n = 18 female, mean 52 ± 13 years, range 23–80 years) after unilateral deafferentation from vestibular schwannoma; n = 38 (25 female, mean 46.9 ± 15.9 years, range 22–77 years) age-matched healthy controls for dynamic visual acuity testing, and another n = 28 (14 female, age 45 ± 17, range 20–77 years) healthy controls for video head impulse testing. Data presented is from n = 19 patients (14 female, mean 48.9 ± 14.7 years) with UVD who completed a baseline assessment ~6 weeks after surgery, 5 weeks of vestibular physical therapy and a final measurement. As a group, subjective and fall risk measures improved with a meaningful clinical relevance. Dynamic visual acuity (DVA) during active head rotation improved [mean ipsilesional 38.57% ± 26.32 (n = 15/19)]; mean contralesional 39.96% ± 22.62 (n = 12/19), though not uniformly. However, as a group passive yaw VOR gain (mean ipsilesional pre 0.44 ± 0.18 vs. post 0.44 ± 0.15; mean contralesional pre 0.81 ± 0.19 vs. post 0.85 ± 0.09) did not show any change (p ≥ 0.4) after rehabilitation. The velocity of the overt compensatory saccades during ipsilesional head impulses were reduced after rehabilitation; no other metric of oculomotor function changed (p ≥ 0.4). Preserved utricular function was correlated with improved yaw DVA and preserved saccular function was correlated with improved pitch DVA. Our results suggest that 5 weeks of vestibular rehabilitation using gaze and gait stability exercises improves both subjective and behavioral performance despite absent change in VOR gain in a majority of patients, and that residual otolith function appears correlated with such change.