Unilateral Vestibular Dysfunction Research Articles

Assessment of Postural Stability Using Foam Posturography at the Chronic Stage After Acute Unilateral Peripheral Vestibular Dysfunction

To investigate the utility of foam posturography for assessing equilibrium at the chronic stage after acute unilateral peripheral vestibulopathy. Thirty-four consecutive patients (16 patients at the chronic stage) with acute unilateral peripheral vestibulopathy and absent caloric responses unilaterally were recruited, along with 66 healthy control subjects. Two-legged stance tasks were performed in 4 conditions: with eyes open or closed, with or without using foam rubber. We adopted 6 parameters: the movement velocity of the center of pressure, the envelopment area traced by the movement of the center of pressure with eyes closed/foam rubber, Romberg's ratios of velocity and area with foam rubber, and the foam ratios (the ratio of a parameter measured with and without foam rubber) of velocity and area with eyes closed. All 6 parameters were significantly higher in the patients in the acute/subacute stage (<3 mo) than in the control subjects (p < 0.0001). Five parameters, excluding the foam ratio of the area with eyes closed, were still significantly higher in the patients at the chronic stage (>3 mo) than in the control subjects (p < 0.01). Foam posturography is useful for assessing equilibrium even at the chronic stage after acute unilateral peripheral vestibulopathy.

Postural responses without versus with acute external cervical spine fixation: a comparative study in healthy subjects and patients with acute unilateral vestibular loss

Using a diagnostic prospective cohort single center study design, the influence of a cervical collar on standing balance during dynamic postural perturbations in healthy adults and patients with acute unilateral vestibular dysfunction was measured in 31 healthy subjects and 27 patients with acute unilateral vestibular loss. The main outcome measures were completed standard protocols on the Sensory Organization Test (SOT) and Motor Control Test (MCT) of the NeuroCom Equitest(®) computerized posturography platform measured without and with acute cervical fixation, respectively. Paired t test showed no significant difference during the six conditions of neither the SOT scores nor analyzing the SOT strategies or during the MCT between the non-fixed and fixed neck in healthy subjects and in the patients (all p > 0.05). Older healthy subjects showed decreased SOT scores but equal MCT results. The age effect was more dominant in the patients when wearing the collar. Gender had no influence whether in healthy individuals nor in patients. In almost all conditions of the SOT but only in some MCT subtests patients had significantly lower scores than healthy subjects without collar and with collar (all p < 0.05). In conclusion, the SOT but only some subtest of the MCT could clearly distinguish between healthy adults and patient with acute unilateral vestibular loss. Equilibrium scores did not change significantly when the cervical spine was fixed with a collar. Acute fixation of the neck with a collar seems not to affect standing balance, even not when vestibular, visual and/or somatosensory input are also reduced.

Platform Tilt Perturbation as an Intervention for People With Chronic Vestibular Dysfunction

Training to improve responses to perturbations may be beneficial for individuals with unilateral vestibular dysfunction. We evaluated the effects of an incrementally increasing surface tilt perturbation intervention for individuals with chronic vestibular pathology on gait, activities of daily living, and dizziness. Participants (n = 29) were randomly assigned to 1 of 3 groups. The first group received random surface tilt perturbations of increasing angles and speed, half of the trials with vision-occluding goggles, 3 times weekly for 3 weeks (P group). The second group received tilt perturbation intervention (as above) plus a home program of vestibular rehabilitation exercises (P+EX group). The third group performed only the vestibular rehabilitation exercises (EX group). Outcome measures included temporospatial gait measures, Dynamic Gait Index (DGI), Dizziness Handicap Inventory (DHI), Patient Specific Functional Scale (PSFS), and a Perceived Outcomes Scale (POS). The P and P+EX groups showed greater improvement on the PSFS and the POS compared to the EX group. DGI scores indicated decreased fall risk in 8 of 9 individuals who participated in P or P+EX training and who initially scored below the 19-point cutoff score. Both the P and P+EX groups showed significant within-group changes on some gait characteristics, DGI, DHI, PSFS, and POS measures. The EX group showed within-group change only on the DHI. Surface tilt perturbation training appears to be more effective for improving abilities at the activities and participation levels than vestibular exercises alone. In addition, tilt perturbation training reduced fall risk as measured by the DGI.

Ocular vestibular evoked myogenic potentials produced by impulsive lateral acceleration in unilateral vestibular dysfunction

Objective To deduce the connectivity underlying ocular vestibular evoked myogenic potentials (OVEMPs) recorded from two sites and produced by lateral transmastoid stimulation in patients with unilateral vestibular dysfunction. Methods OVEMPs were recorded using lateral impulsive stimuli delivered by a hand-held minishaker placed at the mastoid. Twelve patients were tested using the typical OVEMP recording montage placed inferior to the eyes. In a subset of 6 patients, recordings were also made using a lateral electrode montage. The majority of patients were tested following surgery for inner ear disease. Patient responses were compared to those in normal subjects under similar recording conditions. Results For the inferior montage, regardless of which mastoid was stimulated, deficits were observed only from the eye opposite the affected ear. In contrast, OVEMPs recorded using the lateral electrode montage showed changes on both sides. Conclusions OVEMPs produced using lateral transmastoid stimulation and recorded from beneath the eyes are generated by a crossed vestibulo-ocular pathway while the projections underlying the lateral responses are likely to be bilateral. Significance The vestibular-ocular connectivity underlying the OVEMPs recorded from inferior and lateral recording sites differs. For clinical use, the inferior recording site is the simplest to interpret.

A positive review supporting vestibular rehabilitation for unilateral vestibular dysfunction

A positive review supporting vestibular rehabilitation for unilateral vestibular dysfunction

Gait initiation characteristics in elderly patients with unilateral vestibular impairment

The study tested the hypothesis that vestibular patients (n=14) with chronic unsteadiness caused by a documented peripheral unilateral vestibular dysfunction would display differences in muscular activation and movement pattern during gait initiation compared to age-, gender- and body-size-matched healthy Controls (n=14). The displacements of the whole body Center of Pressure (CoP) during the preparatory phase before the swing leg is lifted, were markedly different in vestibular patients. The backward shift during this phase was significantly smaller than in Controls, coupled with a larger secondary corrective forward shift of the CoP. Conversely, the CoP-shift in the M-L direction towards the stance leg was larger in the vestibular patients. Most vestibular patients lacked the anticipatory tibialis anterior (TA) burst, which normally is a prerequisite for the backward displacement of the CoP that precedes the forward movement. The vestibular patients displayed more pronounced TA-Gastrocnemius coactivation in the stance leg when the swing leg was lifted. The duration of the preparatory phase was significantly longer in vestibular patients than in Controls, with no time differences in the later gait initiation events. The vestibular patients started from a more symmetrical stance and with less M-L variation than the Controls. It is concluded that chronically impaired vestibular function leads to a different strategy to create forward momentum to the body. In addition, there is evidence that vestibular patients have diminished postural stability, or alternatively a more cautious behaviour, when initiating the second step.

Ocular and cervical VEMPs: A study of 74 patients suffering from peripheral vestibular disorders

Objective This study compared the results of ocular and cervical vestibular evoked myogenic potentials (VEMPs) tests for healthy subjects with those for patients suffering from vestibular diseases to try to determine the clinical usefulness of combined ocular and cervical STB VEMP testing. Methods Thirty-two healthy volunteers and 74 patients with unilateral vestibular dysfunction underwent tests for ocular and cervical VEMPs induced by AC 100 dB nHL 500 Hz STB combined with caloric and audiometric tests. Results In healthy subjects, the mean P13–N23 peak-to-peak amplitude of cervical VEMPs was much larger than the mean n1–p1 peak-to-peak amplitude of ocular VEMPs. In patients, cervical and ocular VEMPs may be dissociated. The peak-to-peak amplitude of both cervical and ocular tests was abnormally in most of patients suffering from vestibular lesions. No correlations were found between VEMPs, the degree of hearing loss and/or of horizontal canalar paresis. Conclusions Ocular and cervical VEMPs provide complementary information about saccular and utricular otolithic function. Significance Testing of ocular and cervical VEMPs allows the crossed vestibulo-ocular reflex and ipsilateral sacculo-collic reflex to be determined. These tests can help describe vestibular lesions and assess the effects of treatment and should therefore be used clinically.

Effects of neck muscle vibration on subjective visual vertical: comparative analysis with effects on nystagmus

In patients with unilateral vestibular dysfunction, vibratory stimulation to the neck muscles not only induces shift of the subjective visual vertical (SVV), but also enhances the generation of nystagmus. In the present study, the effects of neck vibration on the SVV were compared with those on nystagmus in patients with unilateral vestibular schwannoma (14 patients; 6 males and 8 females, mean age 54.2 years). The results indicated that the presence of nystagmus and magnitude of the SVV were generally correlated, neck vibration significantly increased the abnormal shift of the SVV and the presence of nystagmus, and the effects of vibration to the ipsilateral dorsal neck were significantly larger than those to the contralateral dorsal neck on the SVV, whereas no significant difference was observed in slow phase velocity of nystagmus. The present study suggests that both SVV and nystagmus induced by vibration have many similar clinical features and may be important in assessing the unilateral vestibular dysfunction.

Vestibular and taste disorders after bilateral cochlear implantation

The objective of this study was to investigate the occurrence of vestibular receptor deficiency and taste disorders after bilateral cochlear implantation in postlingually deafened patients and to find out whether the risk for these complications is higher for the second implantation. In a retrospective cohort study, we examined 20 patients (11-58 years, mean age 41.5 years), implanted sequentially between 2000 and 2007 (mean period between cochlear implantation 32.9 ± 25 months). Pre- and postoperative vestibular testing was performed by subjective rating [Dizziness Handicap Inventory (DHI)], caloric irrigation [vestibuloocular reflex (VOR)] and by vestibular-evoked myogenic potential (VEMP) recordings for saccular function. The sense of taste was evaluated pre- and postoperatively by a questionnaire and testing (sour/sweet/bitter/salty bilaterally on the tongue). DHI evaluation showed a moderate not significant mean increase by 2.7 ± 7.7 SD points after the first and a significant increase by 9.4 ± 16.6 SD points after the second implantation. Ipsilateral VEMP responses disappeared in three ears (27.3%) after the first and in two ears (18.2%) after the second operation. VOR disappeared only once (5.9%) after the first implantation. One (5%) patient complained of a persisting disturbance of taste in the questionnaire after unilateral and 3 (15%) after bilateral implantation. Specific testing showed in one case (5%) a unilateral taste disorder after ipsilateral cochlear implantation. Our data show that there is a higher risk for subjective vertigo after the second implantation. The occurrence of unilateral and/or bilateral vestibular dysfunction and the potential risk of taste disorder should be included in the risk counseling before bilateral cochlear implantation to increase patients' and medicolegal safety in the decision-making process.

Short-Term Effects of Vestibular Rehabilitation in Patients With Chronic Unilateral Vestibular Dysfunction: A Randomized Controlled Study

Giray M, Kirazli Y, Karapolat H, Celebisoy N, Bilgen C, Kirazli T. Short-term effects of vestibular rehabilitation in patients with chronic unilateral vestibular dysfunction: a randomized controlled study. Objective To evaluate the short-term effects of vestibular rehabilitation on symptom, disability, balance, and postural stability in patients with chronic unilateral vestibular dysfunction. Design Randomized controlled trial. Setting Department of Physical Medicine and Rehabilitation, University Hospital. Participants Patients (N=42) with chronic vestibular dysfunction were divided into either a rehabilitation group (group 1) or a control group (group 2). Interventions Patients in group 1 were treated with a customized exercise program for 4 weeks, while the patients in the control group did not receive any treatment. Main Outcome Measures Subjects were assessed before and after the rehabilitation program with respect to symptoms (visual analog scale [VAS]), disability (Dizziness Handicap Inventory [DHI]), balance (Berg Balance Scale [BBS]), and postural stability (modified Clinical Test for Sensory Interaction on Balance [mCTSIB]). Results Significant improvements in all parameters (VAS, DHI, BBS, mCTSIB) were observed in group 1 ( P<.05). When the 2 groups were compared, there were significant improvements in postexercise VAS, DHI (emotional, functional, physical, total), BBS, and mCTSIB (standing on a firm surface with eyes open, standing on a foam surface with eyes open, standing on a foam surface with eyes closed, mCTSIB mean) in favor of group 1 ( P<.05). No significant improvements were seen in any parameters in the control group ( P>.05). Conclusions Significant improvements were seen in symptom, disability, balance, and postural stability in chronic unilateral vestibular dysfunction after an exercise program. Customized exercise programs are beneficial in treatment of chronic unilateral vestibular dysfunction.

On‐Road Assessment of Driving Performance in Bilateral Vestibular‐Deficient Patients

This study measured on-road driving behavior in subjects with bilateral vestibular loss (BVL). Data included point-of-regard (what the driver is looking at and attending to), gaze stability (the performance of the vestibulo-ocular reflex), and head movement, during complex maneuvers such as changing lanes, cornering, pulling into traffic, and parking. Subjective and objective measures showed few differences between BVL subjects and age-matched controls, and that it is possible to drive well with little or no peripheral vestibular function. This has important implications for driver licensing, road-safety policy, and for the potential successful rehabilitation of vestibular patients. Patients with unilateral vestibular dysfunction may have more difficulty driving than their bilateral counterparts.

一側迷路障害例の重心動揺における最大リアプノフ指数の検討

In the present study, we investigated the body sway in patients with unilateral vestibular dysfunction by the largest Lyapunov exponents using a chaotic time series analysis. The largest Lyapunov exponent is regarded as a parameter indexing an orbital instability. Subjects consisted of 55 normal healthy subjects, 11 patients diagnosed as having vestibular neuritis (VN), 6 patients diagnosed as having sudden deafness (SD) with vertigo, 23 patients diagnosed as having Meniere disease (MD), 11 patients diagnosed as having benign paroxysmal positional vertigo (BPPV) and 14 patients diagnosed as having other vestibular disorders. Using a stabilometer, the sway of the body center of gravity in an upright standing position was recorded with eyes open and closed for 60 seconds under each condition. From the time series data obtained, the largest Lyapunov exponents were calculated using a chaos analysis program. In normal healthy subjects and patients with unilateral vestibular dysfunction, the largest Lyapunov exponents on right-left sway were larger than those on forward-backward sway with eyes open and closed. The largest Lyapunov exponents in patients with unilateral vestibular dysfunction on forward-backward sway with eyes closed were significantly larger than those in normal healthy subjects. A few patients with the instability of standing posture judged from conventional analysis (area of sway, locus length per time) showed higher values of the LLE. We investigated the variation of the values of the largest Lyapunov exponents in patients with unilateral vestibular dysfunction at each stage during recovery from their vestibular damage. The largest Lyapunov exponents at the early stage with stable standing posture were significantly higher than those at the late stable stage with stable standing posture. Some patients at the very early stage had lower values of the largest Lyapunov exponents. We speculate that the orbital instability indicated by the values of the largest Lyapunov exponents has a different significance from instability of standing posture indicated by a conventional analysis. We propose that the largest Lyapunov exponents may be an useful subsidiary measure to evaluate postural stability and its change due to vestibular dysfunction.

Susceptibility genes for gentamicin-induced vestibular dysfunction

Background: Approximately 5% of patients administered gentamicin (GM), an aminoglycoside antibiotic, experience vestibular ototoxicity resulting in balance dysfunction. In the present study, we sought to identify susceptibility genes associated with GM-induced vestibular dysfunction using a case/control design. Methods: White cases (n = 137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n = 126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Candidate genes were identified primarily for their roles in oxidative stress based on predicted mechanisms of gentamicin-induced ototoxicity. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes. Results: Both single gene and MDR analyses revealed the NOS3 (ENOS) p.Glu298Asp polymorphism as significantly associated with GM-induced vestibular dysfunction (both p ⩽ 0.03). MDR analysis revealed a three-gene combination, consisting of NOS3 (p.Glu298Asp), GSTZ1 (p.Lys32Glu), and GSTP1 (p.Ile105Val), that provided the highest predictive model for GM-induced vestibular dysfunction (64% accuracy; p = 0.009). Conclusions: The results indicate that carriers of risk alleles at three oxidative stress-related genes have increased susceptibility to GM-induced vestibular dysfunction.

Subjective Visual Vertical and Horizontal

(1) To study the subjective visual vertical (SVV) and subjective visual horizontal (SVH) in patients with long-standing unilateral peripheral vestibular dysfunction (PVD) and unilateral Ménière's disease (MD) compared with controls. (2) To study the relationship between the direction of deviation of the linear marker (preset angle) and measures of SVV and SVH values. Prospective case-control study. Outpatient clinic in a tertiary neuro-otology department. Seventeen healthy volunteers (mean age, 35.5 years), 9 patients with PVD (mean age, 43.1 years), and 10 patients with MD (mean age, 50.7 years) were included in the analysis. All subjects had a detailed neuro-otological evaluation. Twelve replicate readings of SVV and SVH were taken for each subject, with random preset angles, 6 in the clockwise and 6 in the counterclockwise direction. The SVV and SVH values were correlated with clinical features and the direction of the preset angle. The 2 subjects with PVD who had abnormal mean SVV and SVH values had symptoms of dysequilibrium and otolithic involvement. The 5 patients in the MD group who had abnormal mean SVV and SVH values had either recent acute vertiginous attacks or total canal paresis on the affected side. A previously unreported finding, to our knowledge, is that the SVV value depends on the direction of the preset angle in all subject groups, more so in the PVD and MD groups compared with controls. The SVV is inclined toward the direction of the preset angle. A weaker relation is seen between the SVH and preset angle. The preset angle should be considered when comparing SVV and SVH values.

Extracts from The Cochrane Library: Vestibular rehabilitation for unilateral peripheral vestibular dysfunction (review)

The "Cochrane Corner" is a quarterly section in the Journal that highlights systematic reviews relevant to otolaryngology--head and neck surgery, with invited commentary to highlight implications for clinical decision making. This installment features a Cochrane Review entitled "Vestibular rehabilitation for unilateral peripheral vestibular dysfunction," which concludes that there is moderate to strong evidence from high-quality randomized trials supporting the safety and efficacy of this intervention.

Improved postural control after computerized optokinetic therapy based on stochastic visual stimulation in patients with vestibular dysfunction

Balance is accomplished by the congruent integration of visual, vestibular and somatosensory input and the execution of adequate control movements. With increasing age, nonlinear dynamics of central control systems become more regular. In unilateral vestibular dysfunction, sensory input to central systems is similarly less complex, because of one sided reduction of information influx. This study aimed to increase postural stability in patients with vestibular asymmetry and resulting disequilibrium by implementing a computerized visual training method relying on the principles of stochastic resonance. 24 subjects (average age 64a, 31-78a, 15 women, 9 men), with minimum 3 months of persisting disequilibrium due to vestibular dysfunction, were either treated with computerized optokinetic therapy (COKT), or solely observed. Treated patients were requested to read texts, stochastically moving in a previously defined matrix, during 10 sessions over three weeks. The Sensory Organization Test (SOT) was used for comparative posturographic measurements. COKT patients showed significant improvement in conditions 4, 6 and composite score. A significant post-therapeutic difference was seen between therapy and control groups in conditions 1, 6 and composite score. The results show a clinical benefit and we conclude COKT to be an effective rehabilitation method in patients with chronic disequilibrium.

加齢と前庭神経炎後遺症

Central vestibular compensation after vestibular neuronitis consists of the following stages: inhibition of the contralesional medial vestibular nucleus (contra-MVe) activity in the acute stage after unilateral vestibular dysfunction (UVD) and recovery and maintenance of the spontaneous activity of the ipsilesional MVe (ipsi-MVe) in the chronic stage after UVD. Once vestibular compensation has been accomplished, patients no longer have persistent positional nystagmus or dizziness. In clinical practice, however, some elderly patients are seen to suffer from UVD-induced persistent canal paresis and subsequent motion-evoked dizziness, i.e., delayed vestibular compensation. To elucidate the relationships between aging and the activities of daily living in patients with UVD caused by vestibular neuronitis, we conducted caloric tests and administered dizziness questionnaires to patients with vestibular neuronitis treated at our hospital between 1997 and 2006. We found that elderly patients (age y.o.≥50) with UVD (canal paresis (CP) %≥25) (age y.o.≥50) had significantly more severe handicaps in daily life due to dizziness induced by head and body movements than younger patients (age y.o.<50). It is suggested that attempts must be made to improve the peripheral vestibular function in the acute stage and/or investigate the breakthrough [?] in the central vestibular rehabilitation in the chronic stage.

Nystagmus induced by high frequency vibrations of the skull in total unilateral peripheral vestibular lesions

Conclusion. The skull vibration-induced nystagmus test (SVINT) is a useful complementary test to the caloric test, which evaluates very low frequencies, and the head shaking test (HST), which explores medium range frequencies. These three tests are fully correlated in total unilateral vestibular lesions (tUVL) with a sensitivity of 98% and a specificity of 94% for the SVINT. The results of the interference of the SVINT with the cold caloric test on the intact ear suggest that different vestibular sensory cells are involved in these two tests. The stimulus location optimization suggests that vibrations directly stimulate the inner ear on the intact side. Objectives. The aim of this study was to establish the effectiveness of a rapid, non-invasive test used to detect vestibular asymmetry at 30, 60 and 100 Hz stimulation in tUVL. Patients and methods. The high frequency vibration test applied to the skull using the SVINT was compared to the results of HST and caloric test in 134 patients and 95 normal subjects: 131 patients had a total unilateral vestibular dysfunction and 3 had a bilateral total lesion (tBVL). The effects of stimulus frequency, topography and head position were studied using a video-nystagmograph. Results. In tUVL, the SVINT always revealed a lesional nystagmus beating toward the healthy side at all frequencies. The mastoid site was more efficient than the cervical and vertex sites (p<0.005). The mean skull vibratory nystagmus (SVN) slow phase velocity (SPV) is 10.7°/s (SD =7.5; n=20). Mastoid stimulation efficiency was not correlated with the side of stimulation. SVN SPV was correlated with the total caloric efficiency on the healthy ear (p=0.03). The interference of the SVINT during the cold caloric test on the intact ear demonstrated a reversal of the caloric nystagmus at each application of the vibrator. In tBVL, SVINT revealed no nystagmus.

Clinical Use of Subjective Visual Horizontal and Vertical in Patients of Unilateral Vestibular Neuritis

Subjective visual horizontal (SVH) and subjective visual vertical (SVV) used to assess otolith dysfunction and ipsilesional deviation of SVV and SVH in unilateral vestibular dysfunction is well known. The goal of this study was to investigate the clinical use of SVH/SVV and a dizziness scale in the clinical setting of acute unilateral vestibular neuritis. Thirty-five patients with unilateral vestibular neuritis were investigated. Every patient was diagnosed by physical examination and electronystagmography. Subjective visual horizontal and SVV were assessed during the acute or subacute period; the Dizziness Handicap Inventory (DHI) and Vestibular Disorder Activities of Daily Living Scale (VADL) were used for a self-dizziness scale at the same time. All patients underwent rehabilitation therapy. Subjective visual horizontal/SVV and DHI/VADL were assessed again approximately 4 weeks later. Postrehabilitation SVH/SVV and DHI/VADL data were compared with initial data. Dizziness Handicap Inventory and VADL were improved after 4 weeks of rehabilitation, and the deviation toward ipsilesional side SVH and SVV was also improved. These results demonstrate that SVH and SVV correlated with clinical dizziness symptoms in patients with acute unilateral vestibular neuritis. Therefore, SVH and SVV would be useful tools for the evaluation of clinical manifestations of unilateral vestibular neuritis.

Susceptibility genes for gentamicin‐induced vestibular dysfunction

Background: Approximately 5% of patients administered gentamicin (GM), an aminoglycoside antibiotic, experience vestibular ototoxicity resulting in balance dysfunction. In the present study, we sought to identify susceptibility genes associated with GM-induced vestibular dysfunction using a case/control design. Methods: White cases (n = 137; 55 men, 82 women) were recruited based on physician-confirmed unilateral or bilateral vestibular dysfunction attributed to GM administration. Controls (n = 126; 54 men, 72 women) were healthy, age-matched individuals without vestibular dysfunction or balance impairment. Buccal cell samples were obtained from all subjects and DNA was genotyped for 15 polymorphisms in 9 genes. Candidate genes were identified primarily for their roles in oxidative stress based on predicted mechanisms of gentamicin-induced ototoxicity. Statistical analyses included the multi-dimensionality reduction (MDR) method for identifying gene x gene interactions across multiple candidate genes. Results: Both single gene and MDR analyses revealed the NOS3 (ENOS) p.Glu298Asp polymorphism as significantly associated with GM-induced vestibular dysfunction (both p 0.03). MDR analysis revealed a three-gene combination, consisting of NOS3 (p.Glu298Asp), GSTZ1 (p.Lys32Glu), and GSTP1 (p.Ile105Val), that provided the highest predictive model for GM-induced vestibular dysfunction (64% accuracy; p = 0.009). Conclusions: The results indicate that carriers of risk alleles at three oxidative stress-related genes have increased susceptibility to GM-induced vestibular dysfunction.