An interventional study of video-oculography in Acute Vestibular Syndrome, Vertigo and Stroke Acute, sponsored by Alexander Tarnutzer. Not yet recruiting. Open to participants aged 18 Years and older, including healthy volunteers. Per ClinicalTrials.gov, last updated 2024-10-31.
Sponsored by Alexander Tarnutzer · Not applicable, Interventional, and Diagnostic
BACKGROUND: A chief complaint of acute vertigo/dizziness is related to about 2.1-7.1% of all emergency department (ED) visits. About 25% of all patients with acute prolonged vertigo meeting diagnostic criteria of AVS (acute vestibular syndrome) suffer from a vertebrobasilar stroke and about 35% of these patients are initially missed. Differentiating dangerous central from more benign peripheral causes of AVS is essential. Subtle oculomotor paradigms such as HINTS (Head-Impulse, Nystagmus, Test-of-Skew) have been shown to detect central causes with high diagnostic accuracy, however, require sufficient training. Thus, identifying other bedside tests that can be reliably performed by frontline providers is essential to reduce misdiagnosis.
WORKING HYPOTHESIS: By using additional oculomotor (saccades, pursuit) and pupillomotor parameters at the bedside or quantitatively, the diagnostic accuracy for distinguishing peripheral from central AVS causes can be further improved, especially in the setting when expertise for applying more sophisticated algorithms (HINTS(+), STANDING) is lacking.
AIM 1: Detecting changes in oculomotor and pupillomotor responses in acutely dizzy patients and characterizing the spectrum of abnormalities in peripheral and central AVS.
AIM 2: Comparing different composite oculomotor-/pupillomotor scores to identify those scores with the highest diagnostic accuracy at the bedside and quantitatively.
AIM 3: Comparing the diagnostic accuracy of bedside and quantitative oculomotor and pupillomotor testing in AVS- identifying potential limitations of bedside testing.
METHODS: To assess oculomotor and pupillomotor responses in patients with peripheral or central AVS and healthy controls (25 participants each) at the bedside and quantitatively by use of a Pioneer research eye tracker (PRET) system and to compare the diagnostic accuracy of individual and composite responses.
EXPECTED VALUE OF THE PROJECT: The proposed project will shed more light on the value of different examination techniques in AVS for distinguishing peripheral from central causes. This is achieved by investigating oculomotor and pupillomotor parameters obtained at the bedside and quantitatively in the acute stage and at follow-up. The insights gained will likely have a direct impact on diagnostic accuracy and thus on future strategies how to evaluate acutely dizzy patients in the ED. Eventually, this may reduce the rate of misdiagnosis and may improve patients' outcome.
A chief complaint of acute vertigo or dizziness is related to about 2.1 to 7.1% of all emergency department (ED) visits, translating to about 4.3 million ED visits in the USA per year. With the differential diagnosis of patients presenting with acute or episodic vertigo / dizziness being very broad and cutting across all specialties, frontline providers and specialists may be overwhelmed by the approach to this symptom. In patients presenting to the ED with vestibular symptoms, life-threatening conditions have been identified in a single study in 23.8% of visits, with 12.5% of all visits related to cerebrovascular events. This emphasizes the need to distinguish between dangerous central and benign, self-limited peripheral vestibular disorders to avoid misdiagnosis. Patients with an acute vestibular syndrome (AVS) have acute-onset, continuous vertigo, dizziness, or unsteadiness lasting days to weeks, usually associated with vomiting, nystagmus, severe postural instability and head movement intolerance . Both patients with stroke and vestibular neuritis can present with an AVS. Approximately 25%±15% of AVS patients will be diagnosed with a stroke, usually in the posterior circulation. Established diagnostic workup in the ED include neurologic assessment, followed usually by CT-based imaging of the brain. Often neurology consultations will be ordered.
For posterior circulation strokes presenting with dizziness frontline misdiagnosis appears common, occurring in roughly 35% of cases. The desire to avoid missing a stroke often triggers brain imaging (computed tomography [CT] and magnetic resonance imaging including diffusion-weighted imaging [MRI-DWI]), laboratory workup and/or electrocardiography. Unfortunately, a recent meta-analysis found that the sensitivity of CT for central causes of dizziness was only 28.5%. Even MRI-DWI in AVS has limited sensitivity, missing about 1 out of 5 vertebrobasilar strokes presenting as an AVS when obtained within the first 24-48 hours after symptom onset. If stroke, the most common central cause of the AVS is missed or delayed, the underlying stroke mechanism goes untreated sometimes resulting in extension of the original infarct or development of a new, larger one.
The evidence base for effective bedside differentiation of inner ear diseases from stroke in patients with acute dizziness and vertigo has grown substantially over time, as emphasized recently. Although useful if present, obvious focal neurologic signs only have a sensitivity of 44% for detecting a central cause of AVS, i.e., more than 50% of strokes will be missed if one were to rely on these findings. Thus, different clinical strategies that emphasize the combined use of targeted neuro-otologic bedside examination techniques, such as the HINTS (Head Impulse, Nystagmus, Test of Skew), HINTS+ (which adds a bedside test of hearing), STANDING or gait/truncal instability (GTI) assessment have been proposed.
Both the HINTS(+) exam and the STANDING algorithm are very good exclusion tests in the hands of trained emergency physicians, non-sub-specialists and neuro-otology / neuro-ophthalmology subspecialists. Ideally, HINTS+ are combined with a graded GTI rating or the STANDING algorithm is used instead. However, absent or inadequate training in performing and interpreting subtle oculomotor findings constitute important limitations, especially in frontline providers. Most ED physicians are not yet familiar with a structured approach to the dizzy patient as e.g. outlined in the TiTrATE approach and HINTS(+) or similar bedside algorithms. While the introduction of quantitative (video oculography - VOG) HINTS to the ED seems promising, increasing the diagnostic accuracy beyond that of neuro-otology experts, this concept is far from being implemented broadly in routine emergency medicine practice.
This emphasizes the need to further improve the approach to the acutely dizzy patient now, focusing on bedside testing that can be reliably applied by untrained frontline providers including emergency physicians or neurology residents also. Brainstem and cerebellar loss of function have been demonstrated to result in dysmetric saccades and saccadic pursuit eye movements. In a previous study, vertical pursuit was saccadic significantly more often in central AVS patients than in peripheral AVS patients (88% vs. 20%, p\<0.01). In patients with (dorso)lateral medullary lesions or carotid artery dissection, pupillary abnormalities (Horner syndrome) may be noticed and in midbrain lesions an unilaterally dilated pupil (as part of a third nerve palsy) may be observed, whereas for other acute brainstem or for cerebellar lesions little is known about pupillomotor changes. Testing for both saccadic eye movements (SEM), pursuit eye movements (PEM) and pupillary responses is straight-forward and readily applicable by frontline providers.
In this proposal the investigators will address the question whether by using additional oculomotor (SEM, PEM) and pupillomotor (pupillary constriction to light) parameters at the bedside or quantitatively, the diagnostic accuracy for distinguishing peripheral from central causes in AVS can be further improved or not. This will be especially important in any setting where expertise for applying more sophisticated algorithms such as HINTS(+) or STANDING is lacking.
The risk for this study protocol is minimal (Risk Category A) due to the non-invasive nature of the measurements obtained (video-oculography, audiometry), side-effects anticipated are expected to be mild and transient only (discomfort by wearing the video-oculography device, vertigo or dizziness being more intense during the measurements, mild nausea).
The investigators do not anticipate an impact of "sex and gender" on the parameters measured, but they will assess the presence/absence of gender impact by statistical analysis.
The overriding hypothesis of this proposal is, that by using additional oculomotor (SEM, PEM) and pupillomotor (pupillary constriction to light) parameters at the bedside or quantitatively, the diagnostic accuracy for distinguishing peripheral from central causes in AVS can be further improved, especially in the setting when expertise for applying more sophisticated algorithms such as HINTS(+) or STANDING is lacking. To address this, the investigators will first collect oculomotor, pupillomotor and vestibular responses in AVS patients within the first 5 days after symptom onset, characterizing the spectrum of changes in peripheral and central causes of AVS (Aim 1). The gold standard will be brain MRI including diffusion-weighted imaging (DWI), obtained between 48 hours and 14 days after symptom onset. The investigators will compare different composite oculomotor-/pupillomotor scores to identify those scores with the highest diagnostic accuracy (Aim 2). Furthermore, comparing results retrieved when testing clinically at the bedside and quantitatively will allow the investigators to better understand if changes in SEM, PEM and pupillary responses as measured quantitatively will also be perceived by the examiner at the bedside (Aim 3). This will be critical to judge the value and thus the priority for testing these parameters at the bedside.
187 studies on the registry are indexed under Vertigo; 27 are open to participants now.
This study's planned enrollment of 75 is close to the median of 73 across 138 interventional studies indexed under Vertigo.
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The investigators will assess oculomotor and pupillomotor function at the bedside and quantitatively both in the acute stage (i.e., within the first 5 days after symptom onset on the ward) and again after 3 months at follow-up (in the outpatient center). They will measure visually-triggered saccadic eye movements and pursuit eye movements in the horizontal and vertical plane and assess pupillary responses to light. For comparison with established paradigms, they will also assess spontaneous nystagmus at primary gaze (with/without fixation), vertical ocular alignment on alternating cover test (looking for vertical deviations, termed skew deviation), gaze-evoked nystagmus on lateral gaze (GEN), and the horizontal head-impulse test (hHIT). The investigators will also test hearing. Bedside and quantitative testing will be performed at the same time.
Diagnostic Test: video-oculography
All participants will receive quantitative oculomotor and pupillomotor measurements using two different video-oculography devices. Thereby both pursuit eye movements, saccades and pupillary responses to light will be assessed. In addition, there will be a quantitative assessment of the angular vestibulo-ocular reflex (aVOR) by use of video-head-impulse testing and a hearing test.
Accuracy in visually-guided saccades in patients with AVS
As the primary end point of our interventional study, the investigators selected the diagnostic accuracy of horizontal and vertical visually-guided saccades (calculated gain, looking for hypermetria and hypometria) in patients with either central or peripheral AVS (time points: acutely, at 3-month follow-up) and in comparison to healthy controls. Differences in quantitative saccade responses in the distinct study groups will support their future use in the acute evaluation of such patients in the ED and will help guide the ED physician in the selection of tests and their interpretation. In the secondary end points (see below), the investigators will also address to which extent the combination of quantitative oculomotor parameters may improve diagnostic accuracy.
Time frame: Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset
Diagnostic accuracy for HINTS+ vs. brain MRI-DWI for detecting central AVS cases
Here the investigators will compare the diagnostic accuracy (sensitivity, specificity, NLR, PLR) of the HINTS+ score vs. brain MRI-DWI for detecting central (mostly ischemic) AVS causes. This comparison is thus between a bedside clinical score and imaging.
Time frame: One measurement in all AVS patients within 5 days of symptom-onset
Diagnostic accuracy in pursuit eye movements in AVS patients for predicting a central origin
For this secondary aim, quantitative pursuit eye movement measurements (both in the horizontal and vertical) plane obtained within 5 days after symptom onset in the AVS patients are obtained and their diagnostic value for distinguishing between peripheral and central AVS cases is evaluated. For comparison, the same measurements will also be obtained in healthy controls.
Time frame: Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset
Pupillary constriction to light (gain)
Pupillary constriction to bright light is assessed by use of the PRET video-oculography device, comparing findings in AVS patients and healthy controls. Diagnostic accuracy for detecting central AVS cases will be determined based on the pupillary response.
Time frame: Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset
Diagnostic accuracy of a combined oculomotor-pupillomotor score vs. HINTS+
Here a combined oculomotor-pupillomotor score (gain of saccades, gain of pursuit and pupillary gain) is compared agains an established bedside evaluation (HINTS+). Specifically, the diagnostic accuracy of both scores for detecting an underlying central cause of the patient's AVS is calculated.
Time frame: Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset
aVOR gain of both horizontal and vertical semicircular canals
Here the gain of the angular vestibulo-ocular reflex (aVOR) responses for all six semicircular canals (as assessed by use of video-head-impulse testing) are compared for both peripheral and central AVS patients and healthy controls. Reduced aVOR gains are anticipated for all patients with peripheral AVS and in about 20% of patients with central AVS.
Time frame: Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset
No study locations are listed for this record.
Plan to share: Yes — all IPD that underlie results in a publication
Start is estimated for Jul 2025; primary completion for Oct 2027, 27 months later.
Of 60 non-industry interventional studies with no phase under Vertigo, half reached primary completion within 21 months of starting (the median), counting those still running; a quarter within 5 and three quarters within 30. This study's planned 27 months is above that.
Counting every sponsor, half of 64 studies reached it within 19 months; a quarter within 6 and three quarters within 28.
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