1

Introduction

The otolith organs are sensitive to changes in linear acceleration and head tilt and are thought to play a role in postural stability. The otoliths also have sound sensitivity, and their activation in response to acoustic stimulation is the basis for the vestibular evoked myogenic potential (VEMP). The cervical VEMP (cVEMP) represents the sound-evoked attenuation of the tonically activated sternocleidomastoid muscle (SCM) following a high-intensity acoustic stimulus. The response is thought to originate from the saccule , and it assesses the vestibulocollic reflex (VCR), which coordinates neck muscle contraction for head stabilization in response to movement. Ocular VEMP (oVEMP) testing is another method of using myogenic potentials to assess the vestibular system. The oVEMP represents the sound-induced activation of extraocular muscles and is best recorded from beneath the contralateral eye (i.e. contralateral to the stimulated ear). This response assesses the integrity of the vestibulo-ocular reflex (VOR), which is mediated by the medial longitudinal fasciculus.

VEMPs have an evolving role in the diagnosis of several vestibular disorders. Decreased or unilaterally absent cVEMP responses may be seen in Ménière’s disease, vestibular neuritis, and vestibular schwannomas, while unilateral increased amplitudes and abnormally reduced response thresholds may be seen in superior semicircular canal dehiscence syndrome . oVEMPs can also be altered in various peripheral vestibular disorders , although these responses are frequently dissociated from cVEMP abnormalities in patients with peripheral vestibular dysfunction . Both cVEMP and oVEMP responses may be reduced or eliminated by advanced age .

The origin of the oVEMP has been a topic of considerable discussion. The most recent evidence suggests that the oVEMP in response to air-conducted sound and recorded with strategically placed infraorbital electrodes is generated from the utricle and superior vestibular nerve . Several anatomic studies have demonstrated that air conduction stimuli can activate utricular afferents , and the utricle has been shown to possess stronger projections to the extraocular muscles than the saccule . Additionally, abnormalities in the static subjective visual horizontal, a psychophysical test believed to assess utricular function, have been found to correlate with oVEMP abnormalities .

Since caloric testing evaluates the function of the lateral semicircular canal and superior vestibular nerve, while oVEMP tests the status of the utricle and superior nerve, the presence of a unilateral oVEMP abnormality and normal caloric responses suggests dysfunction of the utricle alone. Isolated oVEMP abnormalities with otherwise normal balance function test results have not yet been well-characterized, and their clinical significance remains unclear.

We wish to further characterize the clinical presentation of patients who are found to have isolated unilateral oVEMP abnormalities on vestibular function testing. Other reports have examined isolated unilateral utricle dysfunction as tested by abnormalities in the SVV during eccentric rotation , but to date no large series have specifically reported on clinical symptoms in patients with isolated unilateral oVEMP abnormalities. Our hypothesis was that because of compensation from the contralateral utricle and central mechanisms, vestibular symptoms and self-report measures would not suggest a greater severity of impairment that other dizzy patients with normal balance function test (BFT) results.

2

Methods

After institutional review board (IRB) approval, a retrospective chart review was performed evaluating all patients who were diagnosed with isolated oVEMP abnormalities on vestibular function evaluation at a tertiary academic referral center (2006–2011). These patients were compared to a group of 30 subjects having dizziness symptoms but demonstrating normal BFT results. All patients underwent a complete vestibular testing battery, including electronystagmography (ENG), rotational chair evaluation, and testing for cVEMP/oVEMP responses. Additionally, gender, co-morbidities, nature of vestibular complaints, associated otologic symptoms (e.g. pain, hearing loss, tinnitus), clinical diagnoses, imaging results, and scores on self-report questionnaires (see below) were also collected. Patients with anatomic imaging abnormalities that could potentially account for vestibular complaints were excluded. Because air-conducted stimuli alone were used to elicit the cVEMP/oVEMP responses, patients with audiometric evidence of conductive hearing loss were also excluded.

Electronystagmography (ENG) or videonystagmography (VNG) assessments included ocular motility testing (e.g. tests of gaze, pursuit, saccade and optokinetic system function), positional and positioning tests, and either the monothermal warm or alternate binaural, bithermal (ABBT) caloric test using techniques previously described . A significant interaural asymmetry in monothermal testing was defined as ≥ 10% between ears, and a significant ABBT interaural asymmetry was ≥ 22% .

Rotational chair testing was similarly performed using previously described techniques . Patients were seated in a commercially available, sinusoidal harmonic acceleration chair (Micromedical Technologies System 2000). The chair was in a light-proof room, and infrared VNG or ENG techniques were used to record eye position. Rotational chair testing was conducted at frequencies of 0.01 Hz, 0.08 Hz, and 0.32 Hz, with a maximum angular velocity of 50 degrees per second. Vestibulo-ocular reflex (VOR) gain, phase, and symmetry were measured.

Both oVEMP and cVEMP testing was performed using a clinical evoked potentials system (GN Otometrics ICS Charter) and recording techniques similar to those previously described . For cVEMP recordings, active electrodes were applied to the ipsilateral middle sternocleidomastoid (SCM) muscle, a reference electrode was placed on the chin , and a ground electrode was placed at the mid-frontal site. The patient was positioned in a semi-recumbent position with the head elevated and turned away from the stimulated ear; 500 Hz tone bursts presented monaurally at 95 dB HL and at a rate of 5/sec were routed through an Etymotic ER-3A insert earphone to elicit the response from each ear. Electromyogenic (EMG) recordings were amplified (× 5000), bandpass filtered (i.e. between 10 and 1500 Hz), and signal averaged (i.e. 100 msec averaging window). A minimum of 80 samples were averaged for each waveform, and each tracing was replicated at least one time. The amplitude of the P13-N23 response was then measured, and an amplitude asymmetry greater than 47% between ears was considered to be abnormal . Background EMG activity of the SCM muscle was not recorded, although an optimal positioning technique for eliciting consistent cVEMP responses was used .

oVEMP testing was performed with active electrodes placed in the infraorbital region 1 cm below each eye. Reference electrodes were placed approximately 3 cm beneath the active electrode, and a ground electrode was placed on the forehead. The patients were tested in a semi-recumbent position. During signal averaging patients were asked to stare at a target on the ceiling that forced them to elevate their gaze ~ 30 degrees, and to maintain this gaze for 20–30 seconds. The same acoustic stimulus used to record the cVEMP was also employed for oVEMP testing. The resulting myoelectrical activity was amplified by 100,000, bandpass filtered between 10 and 1500 Hz, and signal-averaged over 100 milliseconds. Each oVEMP tracing represented the average of ~ 150 individual samples. A significant oVEMP N10-P15 amplitude asymmetry was defined as > 34% .

The Dizziness Handicap Inventory (DHI) was completed by all patients using a paper-pencil administration format to assess self-reported disability/handicap. The DHI asks a patient to answer “yes” (4 points),” “sometimes” (2 points), or “no” (0 points) to a list of 25 questions relating how dizziness symptoms affect their daily lives . Also performed was the Hospital Anxiety and Depression Scale (HADS), a questionnaire with seven items assessing the extent of depression and seven which relate to anxiety. Each item on the questionnaire is scored 0–3, with a score between 11 and 21 indicating significant levels of anxiety or depression .

Data analysis was performed using STATA software (StataCorp LP, College Station, TX). Frequency and proportion calculations were made for categorical variables, while continuous variables were reported as mean and standard deviation (SD). The chi-square test of independence (p < 0.05) was used to compare proportions between patient and control groups, and the Student t test (p < 0.05) was used to compare continuous variables.

2

Methods

After institutional review board (IRB) approval, a retrospective chart review was performed evaluating all patients who were diagnosed with isolated oVEMP abnormalities on vestibular function evaluation at a tertiary academic referral center (2006–2011). These patients were compared to a group of 30 subjects having dizziness symptoms but demonstrating normal BFT results. All patients underwent a complete vestibular testing battery, including electronystagmography (ENG), rotational chair evaluation, and testing for cVEMP/oVEMP responses. Additionally, gender, co-morbidities, nature of vestibular complaints, associated otologic symptoms (e.g. pain, hearing loss, tinnitus), clinical diagnoses, imaging results, and scores on self-report questionnaires (see below) were also collected. Patients with anatomic imaging abnormalities that could potentially account for vestibular complaints were excluded. Because air-conducted stimuli alone were used to elicit the cVEMP/oVEMP responses, patients with audiometric evidence of conductive hearing loss were also excluded.

Electronystagmography (ENG) or videonystagmography (VNG) assessments included ocular motility testing (e.g. tests of gaze, pursuit, saccade and optokinetic system function), positional and positioning tests, and either the monothermal warm or alternate binaural, bithermal (ABBT) caloric test using techniques previously described . A significant interaural asymmetry in monothermal testing was defined as ≥ 10% between ears, and a significant ABBT interaural asymmetry was ≥ 22% .

Rotational chair testing was similarly performed using previously described techniques . Patients were seated in a commercially available, sinusoidal harmonic acceleration chair (Micromedical Technologies System 2000). The chair was in a light-proof room, and infrared VNG or ENG techniques were used to record eye position. Rotational chair testing was conducted at frequencies of 0.01 Hz, 0.08 Hz, and 0.32 Hz, with a maximum angular velocity of 50 degrees per second. Vestibulo-ocular reflex (VOR) gain, phase, and symmetry were measured.

Both oVEMP and cVEMP testing was performed using a clinical evoked potentials system (GN Otometrics ICS Charter) and recording techniques similar to those previously described . For cVEMP recordings, active electrodes were applied to the ipsilateral middle sternocleidomastoid (SCM) muscle, a reference electrode was placed on the chin , and a ground electrode was placed at the mid-frontal site. The patient was positioned in a semi-recumbent position with the head elevated and turned away from the stimulated ear; 500 Hz tone bursts presented monaurally at 95 dB HL and at a rate of 5/sec were routed through an Etymotic ER-3A insert earphone to elicit the response from each ear. Electromyogenic (EMG) recordings were amplified (× 5000), bandpass filtered (i.e. between 10 and 1500 Hz), and signal averaged (i.e. 100 msec averaging window). A minimum of 80 samples were averaged for each waveform, and each tracing was replicated at least one time. The amplitude of the P13-N23 response was then measured, and an amplitude asymmetry greater than 47% between ears was considered to be abnormal . Background EMG activity of the SCM muscle was not recorded, although an optimal positioning technique for eliciting consistent cVEMP responses was used .

oVEMP testing was performed with active electrodes placed in the infraorbital region 1 cm below each eye. Reference electrodes were placed approximately 3 cm beneath the active electrode, and a ground electrode was placed on the forehead. The patients were tested in a semi-recumbent position. During signal averaging patients were asked to stare at a target on the ceiling that forced them to elevate their gaze ~ 30 degrees, and to maintain this gaze for 20–30 seconds. The same acoustic stimulus used to record the cVEMP was also employed for oVEMP testing. The resulting myoelectrical activity was amplified by 100,000, bandpass filtered between 10 and 1500 Hz, and signal-averaged over 100 milliseconds. Each oVEMP tracing represented the average of ~ 150 individual samples. A significant oVEMP N10-P15 amplitude asymmetry was defined as > 34% .

The Dizziness Handicap Inventory (DHI) was completed by all patients using a paper-pencil administration format to assess self-reported disability/handicap. The DHI asks a patient to answer “yes” (4 points),” “sometimes” (2 points), or “no” (0 points) to a list of 25 questions relating how dizziness symptoms affect their daily lives . Also performed was the Hospital Anxiety and Depression Scale (HADS), a questionnaire with seven items assessing the extent of depression and seven which relate to anxiety. Each item on the questionnaire is scored 0–3, with a score between 11 and 21 indicating significant levels of anxiety or depression .

Data analysis was performed using STATA software (StataCorp LP, College Station, TX). Frequency and proportion calculations were made for categorical variables, while continuous variables were reported as mean and standard deviation (SD). The chi-square test of independence (p < 0.05) was used to compare proportions between patient and control groups, and the Student t test (p < 0.05) was used to compare continuous variables.