Quantitative Eye Movement Measurements in Patients with Acute Vestibular Syndrome

NCT06668857 | Not Yet Recruiting

• 1 other identifier: Okulomotorikstudie_KSB_2024
• Study Type: interventional
• Target: 75
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Acute Vestibular Syndrome; Vertigo; Stroke Acute; Acute Unilateral Vestibulopathy (AUV)

Keywords

vertigo; dizziness; acute vestibular syndrome; stroke; vestibular neuritis; diagnostic accuracy

Outcome Measures

Primary Outcomes (1)

• 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.

  Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset

Secondary Outcomes (5)

• Diagnostic accuracy for HINTS+ vs. brain MRI-DWI for detecting central AVS cases

  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

  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)

  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+

  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

  Two sessions will be recorded 3 months apart. For patients, session 1 will be obtained within 5 days after symptom onset

Study Arms (1)

Oculomotor and pupillomotor quantitative measurements

EXPERIMENTAL

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

Interventions

video-oculography DIAGNOSTIC_TEST

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.

Oculomotor and pupillomotor quantitative measurements

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient groups
• patients presenting with an AVS (peripheral or central), with symptom duration of 5 days or less
• being able to receive brain MRI
• All groups:
• Being able to give informed consent as documented by signature
• Age 18 years or above

You may not qualify if:

• Aged less than 18 years.
• Pregnant or lactating women
• Inability or contraindications to undergo the investigated intervention (including brain MRI in the patient groups),
• Clinically significant concomitant diseases such neurodegenerative disorders (e.g. Alzheimer's disease, Parkinson's disease)
• Pre-existing peripheral-vestibular / central-vestibular deficits
• History of brainstem / cerebellar stroke
• Pre-existing or acute severe visual loss
• Pre-existing severe hearing loss.
• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, aphasia.

Sponsors & Collaborators

• Alexander Tarnutzer: lead

Related Publications (17)

• Cnyrim CD, Newman-Toker D, Karch C, Brandt T, Strupp M. Bedside differentiation of vestibular neuritis from central "vestibular pseudoneuritis". J Neurol Neurosurg Psychiatry. 2008 Apr;79(4):458-60. doi: 10.1136/jnnp.2007.123596.

  PMID: 18344397 BACKGROUND

• Carmona S, Martinez C, Zalazar G, Moro M, Batuecas-Caletrio A, Luis L, Gordon C. The Diagnostic Accuracy of Truncal Ataxia and HINTS as Cardinal Signs for Acute Vestibular Syndrome. Front Neurol. 2016 Aug 8;7:125. doi: 10.3389/fneur.2016.00125. eCollection 2016.

  PMID: 27551274 BACKGROUND

• Bogousslavsky J, Meienberg O. Eye-movement disorders in brain-stem and cerebellar stroke. Arch Neurol. 1987 Feb;44(2):141-8. doi: 10.1001/archneur.1987.00520140013011.

  PMID: 3545158 BACKGROUND

• Vanni S, Nazerian P, Casati C, Moroni F, Risso M, Ottaviani M, Pecci R, Pepe G, Vannucchi P, Grifoni S. Can emergency physicians accurately and reliably assess acute vertigo in the emergency department? Emerg Med Australas. 2015 Apr;27(2):126-31. doi: 10.1111/1742-6723.12372. Epub 2015 Mar 10.

  PMID: 25756710 BACKGROUND

• Tarnutzer AA, Gold D, Wang Z, Robinson KA, Kattah JC, Mantokoudis G, Saber Tehrani AS, Zee DS, Edlow JA, Newman-Toker DE. Impact of Clinician Training Background and Stroke Location on Bedside Diagnostic Test Accuracy in the Acute Vestibular Syndrome - A Meta-Analysis. Ann Neurol. 2023 Aug;94(2):295-308. doi: 10.1002/ana.26661. Epub 2023 Apr 27.

  PMID: 37038843 BACKGROUND

• Tarnutzer AA, Berkowitz AL, Robinson KA, Hsieh YH, Newman-Toker DE. Does my dizzy patient have a stroke? A systematic review of bedside diagnosis in acute vestibular syndrome. CMAJ. 2011 Jun 14;183(9):E571-92. doi: 10.1503/cmaj.100174. Epub 2011 May 16. No abstract available.

  PMID: 21576300 BACKGROUND

• Shah VP, Oliveira J E Silva L, Farah W, Seisa M, Kara Balla A, Christensen A, Farah M, Hasan B, Bellolio F, Murad MH. Diagnostic accuracy of neuroimaging in emergency department patients with acute vertigo or dizziness: A systematic review and meta-analysis for the guidelines for reasonable and appropriate care in the emergency department. Acad Emerg Med. 2023 May;30(5):517-530. doi: 10.1111/acem.14561. Epub 2022 Aug 17.

  PMID: 35876220 BACKGROUND

• Newman-Toker DE, Kerber KA, Hsieh YH, Pula JH, Omron R, Saber Tehrani AS, Mantokoudis G, Hanley DF, Zee DS, Kattah JC. HINTS outperforms ABCD2 to screen for stroke in acute continuous vertigo and dizziness. Acad Emerg Med. 2013 Oct;20(10):986-96. doi: 10.1111/acem.12223.

  PMID: 24127701 BACKGROUND

• Newman-Toker DE, Edlow JA. TiTrATE: A Novel, Evidence-Based Approach to Diagnosing Acute Dizziness and Vertigo. Neurol Clin. 2015 Aug;33(3):577-99, viii. doi: 10.1016/j.ncl.2015.04.011.

  PMID: 26231273 BACKGROUND

• Kattah JC, Talkad AV, Wang DZ, Hsieh YH, Newman-Toker DE. HINTS to diagnose stroke in the acute vestibular syndrome: three-step bedside oculomotor examination more sensitive than early MRI diffusion-weighted imaging. Stroke. 2009 Nov;40(11):3504-10. doi: 10.1161/STROKEAHA.109.551234. Epub 2009 Sep 17.

  PMID: 19762709 BACKGROUND

• Saber Tehrani AS, Coughlan D, Hsieh YH, Mantokoudis G, Korley FK, Kerber KA, Frick KD, Newman-Toker DE. Rising annual costs of dizziness presentations to U.S. emergency departments. Acad Emerg Med. 2013 Jul;20(7):689-96. doi: 10.1111/acem.12168.

  PMID: 23859582 BACKGROUND

• Newman-Toker DE, McDonald KM, Meltzer DO. How much diagnostic safety can we afford, and how should we decide? A health economics perspective. BMJ Qual Saf. 2013 Oct;22 Suppl 2(Suppl 2):ii11-ii20. doi: 10.1136/bmjqs-2012-001616. No abstract available.

  PMID: 24048914 BACKGROUND

• Newman-Toker DE, Hsieh YH, Camargo CA Jr, Pelletier AJ, Butchy GT, Edlow JA. Spectrum of dizziness visits to US emergency departments: cross-sectional analysis from a nationally representative sample. Mayo Clin Proc. 2008 Jul;83(7):765-75. doi: 10.4065/83.7.765.

  PMID: 18613993 BACKGROUND

• Goeldlin M, Gaschen J, Kammer C, Comolli L, Bernasconi CA, Spiegel R, Bassetti CL, Exadaktylos AK, Lehmann B, Mantokoudis G, Kalla R, Fischer U. Frequency, aetiology, and impact of vestibular symptoms in the emergency department: a neglected red flag. J Neurol. 2019 Dec;266(12):3076-3086. doi: 10.1007/s00415-019-09525-4. Epub 2019 Sep 17.

  PMID: 31531764 BACKGROUND

• Ljunggren M, Persson J, Salzer J. Dizziness and the Acute Vestibular Syndrome at the Emergency Department: A Population-Based Descriptive Study. Eur Neurol. 2018;79(1-2):5-12. doi: 10.1159/000481982. Epub 2017 Nov 13.

  PMID: 29131011 BACKGROUND

• Kerber KA, Meurer WJ, West BT, Fendrick AM. Dizziness presentations in U.S. emergency departments, 1995-2004. Acad Emerg Med. 2008 Aug;15(8):744-50. doi: 10.1111/j.1553-2712.2008.00189.x. Epub 2008 Jul 14.

  PMID: 18638027 BACKGROUND

• Kerber KA, Brown DL, Lisabeth LD, Smith MA, Morgenstern LB. Stroke among patients with dizziness, vertigo, and imbalance in the emergency department: a population-based study. Stroke. 2006 Oct;37(10):2484-7. doi: 10.1161/01.STR.0000240329.48263.0d. Epub 2006 Aug 31.

  PMID: 16946161 BACKGROUND

MeSH Terms

Conditions

Vertigo; Stroke; Dizziness; Vestibular Neuronitis

Condition Hierarchy (Ancestors)

Vestibular Diseases; Labyrinth Diseases; Ear Diseases; Otorhinolaryngologic Diseases; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Sensation Disorders; Vestibulocochlear Nerve Diseases; Retrocochlear Diseases; Cranial Nerve Diseases

Study Officials

• Alexander A Tarnutzer, MD

  Neurology, Cantonal Hospital of Baden, Baden, Switzerland

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Alexander A Tarnutzer, MD

CONTACT

+41564861610; alexander.tarnutzer@ksb.ch

Maritta Spiegelberg, MD

CONTACT

+41564861615; maritta.spiegelberg@ksb.ch

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Senior leading physician

Study Record Dates

• First Submitted: October 28, 2024
• First Posted: October 31, 2024
• Study Start: July 1, 2025
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: October 31, 2024

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will share