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      The Effect of Vestibulo-Ocular Reflex Deficits and Covert Saccades on Dynamic Vision in Opioid-Induced Vestibular Dysfunction

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          Abstract

          Patients with bilateral vestibular dysfunction cannot fully compensate passive head rotations with eye movements, and experience disturbing oscillopsia. To compensate for the deficient vestibulo-ocular reflex (VOR), they have to rely on re-fixation saccades. Some can trigger “covert” saccades while the head still moves; others only initiate saccades afterwards. Due to their shorter latency, it has been hypothesized that covert saccades are particularly beneficial to improve dynamic visual acuity, reducing oscillopsia. Here, we investigate the combined effect of covert saccades and the VOR on clear vision, using the Head Impulse Testing Device – Functional Test (HITD-FT), which quantifies reading ability during passive high-acceleration head movements. To reversibly decrease VOR function, fourteen healthy men (median age 26 years, range 21–31) were continuously administrated the opioid remifentanil intravenously (0.15 µg/kg/min). VOR gain was assessed with the video head-impulse test, functional performance (i.e. reading) with the HITD-FT. Before opioid application, VOR and dynamic reading were intact (head-impulse gain: 0.87±0.08, mean±SD; HITD-FT rate of correct answers: 90±9%). Remifentanil induced impairment in dynamic reading (HITD-FT 26±15%) in 12/14 subjects, with transient bilateral vestibular dysfunction (head-impulse gain 0.63±0.19). HITD-FT score correlated with head-impulse gain (R = 0.63, p = 0.03) and with gain difference (before/with remifentanil, R = −0.64, p = 0.02). One subject had a non-pathological head-impulse gain (0.82±0.03) and a high HITD-FT score (92%). One subject triggered covert saccades in 60% of the head movements and could read during passive head movements (HITD-FT 93%) despite a pathological head-impulse gain (0.59±0.03) whereas none of the 12 subjects without covert saccades reached such high performance. In summary, early catch-up saccades may improve dynamic visual function. HITD-FT is an appropriate method to assess the combined gaze stabilization effect of both VOR and covert saccades (overall dynamic vision), e.g., to document performance and progress during vestibular rehabilitation.

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          Most cited references17

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          A clinical sign of canal paresis.

          Unilateral loss of horizontal semicircular canal function, termed canal paresis, is an important finding in dizzy patients. To our knowledge, apart from head-shaking nystagmus, no clinical sign of canal paresis has yet been described and the term derives from the characteristic finding on caloric tests: little or no nystagmus evoked by either hot or cold irrigation of the affected ear. We describe a simple and reliable clinical sign of total unilateral loss of horizontal semicircular canal function: one large or several small oppositely directed, compensatory, refixation saccades elicited by rapid horizontal head rotation toward the lesioned side. Using magnetic search coils to measure head and eye movement, we have validated this sign in 12 patients who had undergone unilateral vestibular neurectomy.
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            The video head impulse test: diagnostic accuracy in peripheral vestibulopathy.

            The head impulse test (HIT) is a useful bedside test to identify peripheral vestibular deficits. However, such a deficit of the vestibulo-ocular reflex (VOR) may not be diagnosed because corrective saccades cannot always be detected by simple observation. The scleral search coil technique is the gold standard for HIT measurements, but it is not practical for routine testing or for acute patients, because they are required to wear an uncomfortable contact lens. To develop an easy-to-use video HIT system (vHIT) as a clinical tool for identifying peripheral vestibular deficits. To validate the diagnostic accuracy of vHIT by simultaneous measures with video and search coil recordings across healthy subjects and patients with a wide range of previously identified peripheral vestibular deficits. Horizontal HIT was recorded simultaneously with vHIT (250 Hz) and search coils (1,000 Hz) in 8 normal subjects, 6 patients with vestibular neuritis, 1 patient after unilateral intratympanic gentamicin, and 1 patient with bilateral gentamicin vestibulotoxicity. Simultaneous video and search coil recordings of eye movements were closely comparable (average concordance correlation coefficient r(c) = 0.930). Mean VOR gains measured with search coils and video were not significantly different in normal (p = 0.107) and patients (p = 0.073). With these groups, the sensitivity and specificity of both the reference and index test were 1.0 (95% confidence interval 0.69-1.0). vHIT measures detected both overt and covert saccades as accurately as coils. The video head impulse test is equivalent to search coils in identifying peripheral vestibular deficits but easier to use in clinics, even in patients with acute vestibular neuritis.
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              Head impulse test in unilateral vestibular loss: vestibulo-ocular reflex and catch-up saccades.

              Quantitative head impulse test (HIT) measures the gain of the angular vestibulo-ocular reflex (VOR) during head rotation as the ratio of eye to head acceleration. Bedside HIT identifies subsequent catch-up saccades after the head rotation as indirect signs of VOR deficit. To determine the VOR deficit and catch-up saccade characteristics in unilateral vestibular disease in response to HIT of varying accelerations. Eye and head rotations were measured with search coils during manually applied horizontal HITs of varying accelerations in patients after vestibular neuritis (VN, n = 13) and unilateral vestibular deafferentation (UVD, n = 15) compared to normal subjects (n = 12). Normal VOR gain was close to unity and symmetric over the entire head-acceleration range. Patients with VN and UVD showed VOR gain asymmetry, with larger ipsilesional than contralesional deficits. As accelerations increased from 750 to 6,000 degrees /sec(2), ipsilesional gains decreased from 0.59 to 0.29 in VN and from 0.47 to 0.13 in UVD producing increasing asymmetry. Initial catch-up saccades can occur during or after head rotation. Covert saccades during head rotation are most likely imperceptible, while overt saccades after head rotation are detectable by clinicians. With increasing acceleration, the amplitude of overt saccades in patients became larger; however, initial covert saccades also became increasingly common, occurring in up to about 70% of trials. Head impulse test (HIT) with high acceleration reveals vestibulo-ocular reflex deficits better and elicits larger overt catch-up saccades in unilateral vestibular patients. Covert saccades during head rotation, however, occur more frequently with higher acceleration and may be missed by clinicians. To avoid false-negative results, bedside HIT should be repeated to improve chances of detection.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                20 October 2014
                : 9
                : 10
                : e110322
                Affiliations
                [1 ]German Center for Vertigo and Balance Disorders, Munich University Hospital, Munich, Germany
                [2 ]Department of Electrical, Computer and Biomedical Engineering, University of Pavia, Pavia, Italy
                [3 ]Department of Anesthesiology, Klinikum rechts der Isar, TU Munich, Munich, Germany
                [4 ]Clinical Neurosciences, Munich University Hospital, Munich, Germany
                [5 ]Brandenburg University of Technology, Cottbus-Senftenberg, Germany
                [6 ]Department of Neurology, Munich University Hospital, Munich, Germany
                UMR8194, France
                Author notes

                Competing Interests: ES is the managing director and a shareholder of EyeSeeTec GmbH. NL received speaker honoraria and compensation for travel expenses from Interacoustics, Autronic Reglersysteme GmbH, and Meytec GmbH Medizinsysteme, and research support from the German Federal Ministry of Education and Research (BMBF), the Faculty of Medicine of the University of Munich, and the Friedrich-Baur Foundation. She is a shareholder and paid consultant of EyeSeeTec GmbH. SR has the European patent on head impulse testing device for assessing the functionality of the semicircular canals and for the rehabilitation of vestibular loss (ep 2398377, Stefano Ramat, Marco Mandalà, 2011/12/28). CR, PC, MS, FH have no competing interests to report. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: CR FH NL. Performed the experiments: CR FH. Analyzed the data: CR MS SR NL. Contributed reagents/materials/analysis tools: CR PC MS SR ES. Contributed to the writing of the manuscript: CR MS NL SR ES.

                Article
                PONE-D-14-14554
                10.1371/journal.pone.0110322
                4203781
                25329150
                e4a4d72c-7d93-4ba9-9fe6-46efa1d7fde0
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 April 2014
                : 21 September 2014
                Page count
                Pages: 5
                Funding
                This work was supported by the German Federal Ministry of Education and Research (Grant 01 EO 0901). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Neuroscience
                Sensory Perception
                Vision
                Visual Acuity
                Medicine and Health Sciences
                Neurology
                Otorhinolaryngology
                Otology
                Vertigo
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper.

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