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Vestibular Evoked Potentials: Properties and Clinical Applications of Extraocular Reflexes

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Vestibular Evoked Potentials: Properties and Clinical Applications of Extraocular Reflexes Vestibular evoked potentials: Properties and clinical applications of extraocular reflexes. Sally Marie Rosengren A thesis submitted in fulfilment of the requirements for the degree of Doctor of Philosophy Faculty of Medicine, University of New South Wales, Australia © August 2008 i Originality statement ‘I hereby declare that this submission is my own work and to the best of my knowledge it contains no materials previously published or written by another person, or substantial proportions of material which have been accepted for the award of any other degree or diploma at UNSW or any other educational institution, except where due acknowledgement is made in the thesis. Any contribution made to the research by others, with whom I have worked at UNSW or elsewhere, is explicitly acknowledged in the thesis. I also declare that the intellectual content of this thesis is the product of my own work, except to the extent that assistance from others in the project's design and conception or in style, presentation and linguistic expression is acknowledged.’ Signed …………………………………………….......... Date …………………………………………….............. ii Copyright statement ‘I hereby grant the University of New South Wales or its agents the right to archive and to make available my thesis or dissertation in whole or part in the University libraries in all forms of media, now or here after known, subject to the provisions of the Copyright Act 1968. I retain all proprietary rights, such as patent rights. I also retain the right to use in future works (such as articles or books) all or part of this thesis or dissertation. I also authorise University Microfilms to use the 350 word abstract of my thesis in Dissertation Abstract International (this is applicable to doctoral theses only). I have either used no substantial portions of copyright material in my thesis or I have obtained permission to use copyright material; where permission has not been granted I have applied/will apply for a partial restriction of the digital copy of my thesis or dissertation.' Signed …………………………………………….......... Date …………………………………………….............. Authenticity statement ‘I certify that the Library deposit digital copy is a direct equivalent of the final officially approved version of my thesis. No emendation of content has occurred and if there are any minor variations in formatting, they are the result of the conversion to digital format.’ Signed …………………………………………….......... Date …………………………………………….............. iii Abstract Vestibular-dependent surface potentials can be recorded from over the scalp following stimulation with intense air- (AC) and bone-conducted (BC) sound. However, sound-evoked responses may be confounded by parallel stimulation of the auditory system. To demonstrate the pure vestibular origin of the cortical potentials, patients with severe to profound bilateral hearing loss were stimulated with AC and BC sound. The responses had the same amplitude as those recorded in normal subjects, and were only present in patients with preserved vestibular function, confirming their vestibular origin. One negative surface potential, the N15, was largest when measured over the forehead, and detailed mapping of this potential localised it to the eyes. This extraocular response had the same polarity on each side of the eye and was altered by changing gaze direction, suggesting an extraocular muscle origin (i.e. an ocular vestibular evoked myogenic potential, or OVEMP). Galvanic vestibular stimulation (GVS) produces large eye movements with horizontal and torsional components directed away from the cathode. A modified electrode montage was used to characterise the OVEMPs produced by GVS. OVEMPs recorded from beneath the eyes had the appropriate polarity to produce the torsional eye movement and likely originated in the inferior oblique muscles. Sound-evoked OVEMPs were investigated in patients with superior canal dehiscence (SCD), as they have vestibular hypersensitivity to sound. The SCD patients had large sound-evoked OVEMPs with low threshold, similar to the VEMP. OVEMP amplitude was much larger in the patients than controls and could be an additional diagnostic marker for this condition. iv Although SCD patients have large VEMPs and eye movements evoked by AC sound, little is known about other vestibular reflexes. It was shown that patients also have large sound-evoked vestibulo-spinal reflexes, similar to those evoked by GVS. However, despite these large reflexes, there was little consistent whole body sway. Finally, a case is reported in which the combination of VEMP and OVEMP results indicated the location and nature of a central nervous system lesion. The patient had delayed potentials when stimulated on the left side, indicating a demyelinating lesion in the root entry zone of the left vestibulocochlear nerve. v Acknowledgements This thesis was produced over many years with the help and support of many people. Above all, I wish to thank my supervisor, Professor Jim Colebatch, who provided much knowledge and guidance throughout my candidature, and taught me the qualities that make a good scientist. I am also indebted to Dr Miriam Welgampola, who spent many hours during her own PhD teaching the new research assistant about vestibular function and assessment, and much more. Tony Yakoubi and Philip Balnave provided technical support and fixed my broken leads when necessary (!), for which I am grateful and, as secretary to Professor Colebatch, Jill Booth was always there with a shoulder to lean on when things didn’t work out. My fellow students and office mates, Dr Stacey Jankelowitz, Dr Ann Bacsi, and Mr Sudipto Pal, could always be counted on for support and, when necessary, comedic relief, which helped the years pass very quickly. Thanks also to Professor Michael Halmagyi and colleagues at RPAH for providing inspiration, as well as my co-authors on the publications resulting from the thesis. I would also like to thank the National Health and Medical Research Council of Australia, the University of New South Wales and the Garnett Passe and Rodney Williams Memorial Foundation for providing the funding that supported my salary. I would like to thank my parents, Mary and Paul, for always believing in me, and my brother Michael (even though he refuses to call me Doctor!). Thankyou also to Bruce, who taught me how to stay motivated. Finishing a thesis part-time is not easy, and I would not have been able to do it without the help of my partner, Ihor, so thankyou for all the love and support. This thesis is dedicated to my grandmother, Enid Rosengren, who inspired me in so many ways and would have loved to see me finish this thesis. vi Contributions of collaborators In addition to Professor J. Colebatch, who as PhD supervisor contributed significantly to each experimental chapter of the thesis, several other researchers provided input to some chapters. In Chapter 6, eye movement recordings were kindly provided by Dr ST Aw. Apart from this, all data was collected and analysed by the candidate. Professor GM Halmagyi, Dr NPM Todd, Dr ST Aw and Dr P Jombik contributed to the experimental design and/or interpretation of data in some of the chapters. Dr JH Nogajski and Dr PD Cremer provided detailed clinical information for the case reported in Chapter 8. vii List of abbreviations ABR auditory brainstem response AC air-conducted AN acoustic neuroma AP anteroposterior ASC anterior semicircular canal BC bone-conducted CLAR cathode left/anode right CoM centre of mass CoP centre of pressure CRAL cathode right/anode left DVN descending vestibular nucleus EEG electroencephalography EMG electromyography EOG electro-oculography FL force level GVS galvanic vestibular stimulation HL hearing level HSC horizontal semicircular canal IO inferior oblique IR inferior rectus LAT mediolateral LR lateral rectus LVN lateral vestibular nucleus LVST lateral vestibulo-spinal tract viii MD Meniere’s disease ML medium-latency MLF medial longitudinal fasciculus MLR mid-latency response MR medial rectus MS multiple sclerosis MVN medial vestibular nucleus MVST medial vestibulo-spinal tract NHL normal hearing level OVEMP ocular vestibular evoked myogenic potential PAR post-auricular response PIVC parieto-insular vestibular cortex PSC posterior semicircular canal SCD superior canal dehiscence syndrome SCM sternocleidomastoid SL short-latency SO superior oblique SPL sound pressure level SR superior rectus SSC superior semicircular canal SVN superior vestibular nucleus TA tibialis anterior uVL unilateral vestibular loss VEMP vestibular evoked myogenic potential VN vestibular nucleus ix VOR vestibulo-ocular reflex Vpp volts peak-to-peak VsEP vestibular evoked potential VT VEMP threshold x Introduction This thesis consists of a series of experiments investigating vestibular evoked potentials. In Chapter 1 (Literature review) a summary is provided of the background material to the experiments described in the thesis. The literature review covers the structure and function of the vestibular system, methods of activating the vestibular system in clinical and experimental settings, and responses evoked by vestibular stimulation. It also includes a section on the peripheral vestibular disorder superior canal dehiscence (SCD), as several chapters report data on patients with this condition. Chapter 2 (General methods) describes the methods common to the experimental chapters of the thesis. In Chapters 3 to 8 the results of the main experiments are reported. The first two experimental chapters were designed to investigate
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