Otolith Function and Disorders

............................Otolith Function and Disorders

..

............................

Advances inOto-Rhino-LaryngologyVol. 58

Series Editor W. Arnold, Munich

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Otolith Function andDisorders

Volume Editors P. Tran Ba Huy, ParisM. Toupet, Paris

36 figures, 1 in color and 3 tables, 2001

............................Prof. P. Tran Ba Huy,Prof. M. ToupetHopital Lariboisiere2, rue Ambroise PareF–74574 Paris (France)

Library of Congress Cataloging-in-Publication Data

Otolith function and disorders / volume editors, P. Tran Ba Huy, M. Toupet.p.; cm. – (Advances in oto-rhino-laryngology, ISSN 0065-3071; vol. 58)

Papers from a conference held in Paris in Jan. 22, 2000.Includes bibliographical references and indexes.ISBN 3805571305 (hard cover : alk. paper)1. Otolith organs – Pathophysiology – Congresses. 2. Otolith

organs – Abnormalities – Congresses. 3. Vertigo – Congresses. I. Tran, Patrice Ba Huy. II.Toupet, M. (Michel) III. Series.

[DNLM: 1. Otolithic Membrane – physiopathology – Congresses. 2. OtolithicMembrane – abnormalities – Congresses. 3. Vertigo – Congresses. 4. VestibularDiseases – Congresses. WV 255 O88 2001]RF268 .O86 2001617.8�82–dc21

00-049737

Bibliographic Indices. This publication is listed in bibliographic services, including Current ContentsÔ andIndex Medicus.

Drug Dosage. The authors and the publisher have exerted every effort to ensure that drug selection anddosage set forth in this text are in accord with current recommendations and practice at the time of publication.However, in view of ongoing research, changes in government regulations, and the constant flow of informationrelating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug forany change in indications and dosage and for added warnings and precautions. This is particularly importantwhen the recommended agent is a new and/or infrequently employed drug.

All rights reserved. No part of this publication may be translated into other languages, reproduced orutilized in any form or by any means electronic or mechanical, including photocopying, recording, microcopying,or by any information storage and retrieval system, without permission in writing from the publisher.

Ó Copyright 2001 by S. Karger AG, P.O. Box, CH–4009 Basel (Switzerland)www.karger.comPrinted in Switzerland on acid-free paper by Reinhardt Druck, BaselISSN 0065–3071ISBN 3–8055–7130–5

............................Contents

VII Preface

1 The Mammalian Otolithic Receptors: A Complex Morphological andBiochemical OrganizationSans, A.; Dechesne, C.J.; Dememes, D. (Montpellier)

15 Pathophysiology and Clinical Testing of Otolith DysfunctionGresty, M.A. (London); Lempert, T. (Berlin)

34 Otolithic VertigoBrandt, T. (Munich)

48 Physiopathology of Otolith-Dependent Vertigo. Contribution of the CerebralCortex and Consequences of Cranio-Facial AsymmetriesBerthoz, A. (Paris); Rousie, D. (Lille)

68 Clinical and Instrumental Investigational Otolith FunctionOdkvist, L. (Linkoping)

77 The Subjective Visual VerticalVan Nechel, Ch. (Paris/Bruxelles); Toupet, M. (Paris); Bodson, I. (Paris/Liege)

88 Clinical Application of the Off Vertical Axis Rotation Test (OVAR)Wiener-Vacher, S. (Paris)

98 VEMP Induced by High Level Clicks. A New Test of Saccular Otolith Functionde Waele, C. (Paris)

110 Peripheral Disorders in the Otolith System. A Pathophysiological andClinical OverviewTran Ba Huy, P.; Toupet, M. (Paris)

129 Subject Index

............................Preface

For decades, peripheral vestibular function and its related pathologieshave been attributed to the canal system. In this view, vertigo could only giverotatory sensations. Otherwise, the disorder was automatically considered ascentral in nature. For almost a century, functional explorations were limitedto caloric and/or rotatory testing. From the responses arising from a singlepair of canals, the lateral ones, generations of otologists have founded thescience of Vestibulology.

Yet, clinicians facing dizzy patients on a daily basis were aware thatthis clinical and instrumental approach was oversimplified and reductionistic.Indeed, they knew of two small and mysterious sensory structures hiddenwithin the bony vestibule, but largely ignored their exact role in pathophysiol-ogy and lacked the techniques to investigate them.

During recent years, a considerable body of experimental and clinicalwork has demonstrated the direct involvement of the otolith organs in stabiliz-ing body and gaze and led to the development of specific functional tests.Thanks to these advances, an otolith semiology has emerged. We now knowthat drunken-like sensations and movements, lateropulsion, gait disturbance,visual symptoms, disorientation or erroneous sensations of upright posture,to quote but a few ill-defined or bizarre symptoms, must direct the cliniciantoward an otolith problem. New investigative tools are now available which candemonstrate the direct involvement of the utricle and saccule in the pathology.

On the 22th of January, 2000, an international meeting devoted to ‘OtolithFunction and Disorders’ was held in Paris with the participation of some ofthe pioneers in the field. All aspects of otolith function were covered. AlainSans, of the INSERM at Montpellier, presented the ultrastructural features

VII

of the two maculae with special emphasis on the neuromediators involvedin vestibular signal processing. Michael Gresty, from London, reviewed thephysiology of the otolith organs and underlined some fascinating and unexpec-ted roles of these structures in current clinical symptoms. Thomas Brandtdiscussed the principal otolith-related syndromes drawing upon his exceptionalclinical experience. Alain Berthoz developed his thoughts on the role of otolithsin the perception of movement. Lars Odvkist opened the session on clinicaland instrumental investigation of otolith function, and presented a criticalappraisal of the tests used in vestibulometric practice, with emphasis on hisexperience in eccentric rotatory testing. Following this, Christian Van Nechel,Sylvette Wiener-Vacher and Catherine de Waele reported their use of thesubjective visual vertical test, off-vertical axis rotation and click-evoked myo-genic potentials as tools for functional investigations of the otolith organs.

This volume gathers together the contributions of these authors in anattempt to provide an exhaustive view of a new field in vestibulology. We hopethat it will prove to be a valuable clinical tool concerning a system which hasremained the wild card of sensory pathology for too long.

Patrice Tran Ba HuyMichel Toupet

VIIIPreface

Tran Ba Huy P, Toupet M (eds): Otolith Functions and Disorders.Adv Otorhinolaryngol. Basel, Karger, 2001, vol 58, pp 1–14

............................The Mammalian Otolithic Receptors:A Complex Morphological andBiochemical Organization

Alain Sans, Claude J. Dechesne, Danielle Dememes

INSERM U 432, Montpellier, France

The vestibular sensory organs of vertebrates detect angular accelerations,by means of the ampullar receptors, and linear accelerations, by means of theotolithic receptors. The otolithic receptors consist of the utricle and the saccule,each being formed by a sensory epithelium, covered by the otoconial mem-brane, which supports calcium carbonate crystals, the otoliths or otoconia,in the form of aragonite or calcite. The utricle and saccule specifically perceivelinear accelerations induced by movements of the head in the gravity field.This sensory information is used by the central nervous system to control eyemovement and body position.

This chapter does not aim to describe the morphology of the mammalianotolithic receptors, which is already well documented, for the vestibular sensoryepithelia by Hunter-Duvar and Hinojosa [1], and for the otoconial membraneby Lim [2]. Instead, it deals with correlations between anatomy and functionby taking into account the distribution of specific proteins in the varioussensory cells and their afferent and efferent nerve fibers: (1) calcium-bindingproteins in the type I and type II sensory cells and their afferent nerve fibers,and (2) the neurotransmitters involved in afferent and efferent regulation.Work carried out in our laboratory has shown regional biochemical differencesin the organization of the otolithic organs, suggesting that there may befunctional differences between the central and peripheral parts of the macularreceptors.

Fig. 1. Surface views of the rat utricle. Both utricles are similarly oriented with themedial part, with respect to the axis of the body, on the right-hand side. a Immunocytochem-ical labeling for calretinin, observed by confocal microscopy. In the striolar area (S), indicatedby a dotted line, the calyces surrounding the type I sensory cells are labeled (see fig. 5b). In theextra-striolar zones, calretinin immunostaining is detected in type II sensory cells. b Scanningelectron microscopy identifies the hair bundles. Note that the borders of the utricle areslightly raised.

The Otolithic Receptors: An Overview of Their MorphologicalCharacteristics (schematic diagram fig. 7a)

Scanning Electron MicroscopyThe Utricle. The utricular macula is kidney-shaped, with the concave

part in the medial position and the convex part in the lateral position (fig. 1).In some mammals, such as rodents, the anterior part is tilted at an angleof 30º from the horizontal. In humans, the utricle is in the horizontal planewhen the head is held in the vertical position. The sensory surface is coveredby the sensory hair bundles. This sensory epithelium is covered by a gelatinousmembrane, the otoconial membrane, upon which rest the otoconia. Thelower surface of this membrane is attached to the supporting cells of thesensory epithelium by a filamentous network known as the subcupularmeshwork [2]. The otoconial membrane and the subcupular meshwork delimitthe alveoli, into which the hair bundles are inserted (fig. 2a). In birds andmammals, the otoconia consist of calcite crystals of various sizes, dependingon their location. Those in the lateral parts of the utricle are large whereas

2Sans/Dechesne/Dememes

a b

Fig. 2. Otoconial membrane and otoconia overlying the utricle observed by scanningelectron microscopy. a After partial removal of the otoconia (o), the otoconial membraneshows a honeycomb structure. The hair bundle stereocilia (st) are inserted into the cells ofthe honeycomb. b Regional differences in the size of the otoconia on the otoconial membrane.The otoconia in the striolar area (S) are smaller and the surface they form is lower thanthat of the otoconia in the extra-striolar zones.

those in the striolar area, a crescent-shaped depression located off-center tothe lateral side, are small (fig. 1b, 2b). The striolar area is a specific zoneof the sensory epithelium with the following characteristics: (1) inversepolarization of the hair bundles (the kinocilia face each other); (2) thestereocilia are smaller than those of the cells in the medial and peripheralextra-striolar zones; (3) there is almost no subcupular meshwork. This lackof the subcupular meshwork in the striolar area results in the formation ofa space, delimited by the otoconial membrane, in the form of a curvedtunnel.

Due to the small size of the stereocilia and the presence of a unique cavityin the striolar area, the hair bundles in this area are free and are not joinedto the otoconial membrane, unlike those of the extra-striolar zones. Thisanatomical feature undoubtedly affects the processes of the mechanic transmis-sion in this area, which accounts for about 10% of the total sensory surfacearea.

The Saccule. The saccular macula is hook-shaped and the anterior enddiffers in length and curvature between species. In humans, the saccule isin the vertical plane when the head is held erect. The general architectureof the saccule is similar to that of the utricle. However, there are severalimportant differences: the otoconia of the striolar region protrude slightlyabove the surface of the otoconial membrane. The hair bundles in the striolarregion are polarized inversely to those in the utricle (the stereocilia face eachother).

3The Mammalian Otolithic Receptors

Fig. 3. Transmission electron micrograph of a transverse section of a guinea pig utricularepithelium. The type I hair cells (1) are surrounded by afferent nerve calyces containingnumerous mitochondria. The type II hair cells (2) are contacted at their bases by afferentendings and by efferent boutons (dark arrows). The nuclei of the supporting cells (sc) linethe lower part of the epithelium and these cells have numerous intracytoplasmic secretorygranules at their apices. ST>Stereocilia.

Transmission Electron MicroscopyThe sensory epithelium of the otolithic receptors has been extensively

described. It consists of two types of sensory hair cell: type I cells, which arepear-shaped and surrounded by an afferent nerve calyx, and type II cells,which are rectangular parallelepipeds and contacted by afferent and efferentboutons (fig. 3). These cells are separated by the supporting cells, the lowerpart of which rests on the basal membrane.

There are, however, regional differences in the shape of these sensorycells and their afferentation by nerve fibers. The striolar area is a zone witha specific organization with regard to which the extra-striolar zones aredefined. Type I cells are more globular in the striolar area than in the lateralareas and are contacted exclusively by complex afferent calyx endings fromlarge-diameter nerve fibers. In contrast, the type II hair cells of the peripheralzones are mainly contacted by afferent boutons originating from thin nervefibers. The type I and II hair cells in the peristriolar zones are connectedby dimorphic nerve fibers that provide mixed innervation to both hair celltypes [3, 4]. To this general scheme should be added two types of result


Fig. 4. Microvesicles located at the apex of the afferent nerve calyx surrounding a type Ihair cell (transmission electron microscopy). a Transverse section of a type I hair cell show-ing the bundle of microtubules in the neck of the cell. The upper part of the nerve calyxcontains clear microvesicles (small dark arrows). b Transverse section in the plane indicatedby the dotted line in (a). The microtubules present in the neck of the nerve calyx appear assmall circles. The microvesicles present in the nerve calyx (c) correspond to clear vesicles(small dark arrows) and dense-cored vesicles (white arrows).

demonstrating the complex regional regulation of the vestibular sensory in-formation.

Our group has shown that, at the apex of afferent nerve calyces, there areclear microvesicles and dense-cored microvesicles [5]; (fig. 4a, b). In this partof the calyces proteins are also found which are usually associated with synaptic


vesicles in presynaptic compartments: synapsin I and synaptophysin [6], whichare associated with the membrane of the synaptic vesicle [7, 8], and rab 3A[9], a protein essential for vesicle docking and the last steps of exocytosis [8].We have also shown that there are glutamate receptors on the membrane ofthe sensory cells [10]. Although the synaptic release of neuromediators by theapex of the calyces has not yet been demonstrated experimentally, the resultsobtained consistently provide evidence for the existence of a short controlloop regulating the type I hair cell activity by their afferent calyces.

Ross [11] has demonstrated the presence of extensions of fibers or afferentcalyces, forming synaptic contacts with the adjacent type II cells, which facesubsynaptic membrane cisternae. Asymmetric synaptic contacts are also foundat the base of the calyces and of intramacular nerve fibers. These extensions,rich in small (40–60 nm in diameter) clear vesicles, form a network at the baseof the macular epithelium. Extensions from the neck of the afferent nervecalyces are also found (fig. 4b). These extensions contact their neighboringsensory cells and also contain clear microvesicles as well as large (80 nmdiameter) dense-cored vesicles. This double network, basal and apical, probablyregulates the early mechanosensory messages before their transmission to thecentral nervous system.

Differential Expression of Parvalbumin, Calretinin andCalbindin in the Utricle (schematic diagram fig. 7a)

Calcium plays a key role in the physiology of sensory cells and neurons.A large number of calcium-binding proteins have been detected by immuno-cytochemistry in the sensory hair cells and afferent nerve fibers of the vestibularsensory epithelium.

The distributions of the three main calcium-binding proteins, parvalbu-min, calretinin and calbindin, differ not only with respect to each other, butalso in the different regions of the utricle. Parvalbumin [12] is present mostlyin the type I cells of the striolar region (fig. 5a), whereas calretinin [13] ispresent in the type II cells of the periphery of the macula and in the afferentnerve calyces of the striolar region (fig. 1a, 5b). Finally, calbindin [14] isdetected in very large amounts only in the nerve calyces of the striolar area(fig. 5c).

These regional differences in the distribution of calcium-binding proteinsalmost certainly reflect differences in cellular calcium metabolism between thesensory cells located in the striolar area and those of the peristriolar zones,particularly those of the peripheral zones. In addition, in the striolar zone,only the fibers ending in calyces and multicalyces contain calretinin whereas


Fig. 5. Differences in the distribution of calcium-binding proteins in the rat utricle.Immunolabeling of parvalbumin (a), calretinin (b) and calbindin (c) observed by laser con-focal microscopy. a Most of the parvalbumin-immunoreactive hair cells are type I hair cellsin the striolar area (S, limits are indicated by two white arrowheads). A few immunoreactivecells are located outside the striolar area. The insert shows the cytosolic labeling of a type Ihair cell. b Calretinin is detected in nerve calyces in the striolar area (see also insert) and ina few type II hair cells outside the striolar area. c Calbindin is found only in the nervecalyces of the striolar area.


the calyces of the dimorphic fibers do not contain calretinin [15]. This isreflected in the vestibular ganglion in which only the large-diameter neuronsending in calyces contain calretinin [16] and present low voltage-activatedcurrents [17].

These biochemical results thus demonstrate that it is essential to considerthe electrophysiological properties of the vestibular sensory cells not only inrelation with their cell type (I or II), but also in relation with their type ofafferentation and their location in the utricular macula.

Efferent and Afferent Systems: Differential Expression of CGRP andSubstance P in the Utricle (schematic diagram fig. 7b)

Efferent SystemThe cell bodies of the efferent nerve fibers are located in the brainstem

below the 4th ventricle. These fibers contact type II cells directly, or afferentfibers and calyces, controlling and regulating the transmission of sensoryinformation. The neuromediators of the vestibular efferent system are acetyl-choline and the calcitonin gene-related peptide (CGRP) [18–21]. Both arecolocalized in the efferent boutons. Acetylcholine is thought to have an inhibi-tory role and CGRP is thought to be excitatory. Thus, the presence of thesetwo neuromodulators of antagonist effects at the same location suggests thatthere is a complex peripheral regulation of the afferent activity by the efferentsystem.

In addition, it is known that the distribution of efferent fibers differsbetween utricular regions. It has been shown by autoradiography that thereare more efferent endings in the medial and peripheral zones of the utricle thanin the striolar area [22]. This result has been confirmed by immunocytochemicallabeling of the efferent fibers and boutons with an anti-CGRP antibody(fig. 6a). It therefore seems that the control exerted by the efferent system overthe transmission of sensory information in the maculae differs between thestriolar and extra-striolar zones.

Afferent SystemThe afferent nerve fibers that contact the sensory cells transmit sensory

information to the central nervous system via the vestibular nuclei. The afferentsystem is essentially glutamatergic. Glutamate is present in all the sensorycells and ionotropic [23] and metabotropic glutamatergic receptors are foundin the vestibular afferent neurons. Immunocytochemical detection of the iono-tropic glutamate receptors AMPA and NMDA in the sensory epithelia showedno regional differences in their distribution.


Fig. 6. Differences in the distribution of neuropeptides in the efferent and afferent fibersof the rat utricle. a Surface view of the utricle immunostained with an antibody directedagainst the calcitonin-gene related peptide (CGRP). CGRP is present in the efferent fibersand endings. Immunolabeled fibers and endings are more dense in the medial (M) and lateral(L) regions than in the striolar area (indicated by a dotted line). A remnant of the otoconialmembrane shows nonspecific staining (white arrow). b Transverse section of a utricle im-munostained with an antibody directed against substance P. Substance P is detected in theafferent boutons and calyces, mostly outside the striolar area (S, limits are indicated by twowhite arrowheads).


Fig. 7. a Schematic diagram of a transverse section of a mammalian utricle showingthe different distributions of two calcium-binding proteins. The utricle is divided by a virtualline, the striola (S), with opposite polarization of the hair bundles on either side of that line.In the striolar region, all the hair bundles are located in a common cavity and are notconnected to the otoconial membrane. In the extra-striolar zones, the hair bundles are locatedin individual cavities of the otoconial membrane and the kinocilia are connected to thismembrane (red dotted line). The striolar and extra-striolar zones also differ in the distributionof calcium-binding proteins. In the striolar area, parvalbumin (blue) is present in type Isensory cells (I) and calretinin (red) is present in the calyces and multicalyces surroundingthe parvalbumin-positive type I sensory cells. In the peripheral extra-striolar zones, calretininis present in some type II sensory cells (II). The otoconia (O) are smaller in the striolar areathan elsewhere. The synaptic bodies (sb in dark blue) are indicated in the sensory cells. Theapical part of the nerve calyces contains microvesicles (yellow). The efferent fibers are shownin solid black. sc>Supporting cell. b Schematic diagram of a transverse section of a utricle


In contrast, the neuropeptides substance P and neurokinin A are presentin specific afferent nerve endings and fibers [24]. These neuropeptides aredetected exclusively in the extra-striolar areas and are absent from afferentfibers ending in calyces [24] and containing calretinin (fig. 6b). The presenceof substance P in the postsynaptic afferent endings may appear surprising,but we have already shown that there are clear microvesicles in the afferentfibers, which probably contain glutamate, and vesicles with electron-densecores, characteristic of the presence of neuropeptides.

Discussion

Lim [2] demonstrated that the hair bundles in the striolar zone are shortand not attached to the otoconial membrane, unlike those of the peristriolarand peripheral zones in which the stereocilia are longer and which partlypenetrate the otoconial membrane [25]. This led him to suggest that hair cellsin the striolar region would be more strongly stimulated than those elsewhereby fluid drag, and would be sensitive to velocity rather than displacement.The ampullar cristae of the mouse have be shown to be organized in a similarmanner, with the hair bundles in the apical and central areas having shortstereocilia and those in the basal and peripheral areas having long stereociliaincluded in the cupula [26]. Recent morphological and immunocytochemicalstudies have confirmed these observations suggesting that each vestibular re-ceptor should be considered to consist of two different parts, the central andperipheral areas.

In the central part of the macula, the striolar area, type I cells are immuno-stained for parvalbumin. These cells are enclosed in calyces or multicalycesarising from fibers with a very large diameter and containing calretinin (fig. 7a).These high-threshold fibers are controlled by rare efferent endings (fig. 7b).In this case, peripheral regulation may essentially involve feedback control(short control loop) involving the release of neurotransmitters by the microves-icles located at the apex of the calyces [5, 6, 27]. This local control is probablysupplemented by control via the neighboring vesiculated ‘efferent’ fibers from

showing the differences in distribution of neuromediators in the nerve fibers. In the striolararea (S), afferent fibers and calyces do not contain substance P; efferent fibers and endingsimmunostained for CGRP (green) are more sparse than in the other zones. In the extra-striolar areas, afferent fiber endings in boutons and calyces contain substance P (orange)and the CGRP-positive efferent fibers and endings are more numerous. Microvesicles (yellow)containing glutamate are present in the apical part of the afferent nerve calyces. Modifiedfrom Lim [2].


afferent origin, as shown by Ross [11]. This latter control may be exerted atthe apex and base of the epithelia by two parallel networks. The vestibularinformation produced by the striolar zone would thus be extensively pretreatedbefore its transmission to the vestibular nuclei and there would be minimalefferent control of central origin.

The more peripheral areas contain type II cells contacted by small sizefibers forming bouton-type units, and type I and II cells contacted by mixedunits forming calyces and boutons at the ends of medium-size fibers. Withthe exception of a few peristriolar type I cells, these cells do not containparvalbumin. Some type II cells in the most peripheral zones contain calreti-nin. These cells are contacted by afferent fibers that are strongly immunos-tained for substance P. In addition, in these extrastriolar zones, the efferentendings originating from the central nervous system are very dense andprobably exert considerable control over the transmission of sensory informa-tion.

In conclusion, the results obtained indicate that the messages producedby the utricular and saccular maculae differ greatly according to the regionsactivated. The hair cells of the striolar zones would be directly sensitive tothe displacement of endolymph, that would result in the sensory cells rapidlysending a phased message to the central nervous system, via large-caliberfibers. This message would be extensively refined and regulated by feedbackcontrols originating from the short loops involving both the type I sensorycells and their calyces, and the intraepithelial afferent networks carryingmessages between the neighboring units. The extrastriolar zones would besensitive to the relative displacement of the otoconial membrane with regardto the hair bundles. The sensory cells contacted by fibers of medium orsmall diameter would send an essentially tonic message to the central nervoussystem, mostly regulated by a long loop involving the central efferent neurons.This morphological and functional organization presents some similarity tothat of another, even more complex organ, the retina. However, in thevestibule, the respective roles of the central and peripheral zones in theorganization of the sensory message with regard to the type of stimulus areunknown.

Acknowledgments

We thank D. Orcel for the diagram drawings. Partly supported by CNES grants 793/98and 793/99.


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Alain Sans, INSERM U 432, UM 2, CC 89, Place Bataillon,F–34095 Montpellier cedex 5 (France)Tel. +33 467 14 48 10, Fax +33 467 14 36 96, E-Mail [email protected]



............................Pathophysiology and Clinical Testing ofOtolith Dysfunction

Michael A. Gresty a, Thomas Lempert b

a MRC Human Movement and Balance Unit, National Hospital for Neurology andNeurosurgery, London, UK;

b Neurologische Klinik, Charite, Campus Virchow-Klinikum, Berlin, Germany

This paper is based on a talk on the pathophysiology of the otolithorgans which was given in Paris in the early days of this third millennium.The purpose was to attempt a didactic statement about our understandingof the otolith which could be of value to physicians and surgeons dealingwith patients who present with vestibular disease. As such it would be acultural affront and an expression of historical ignorance not to commencewith a reference to the views of FH Quix who gave his lectures ‘Les Methodesd’Examen de L’Organe Vestibulaire’ in that same city more than 70 yearsago [1]. Figure 1 is reproduced from lecture notes and shows Professor Quixdemonstrating the orientations of the utricles and saccules using his handsto indicate the planes of the maculae. Figure 2 reproduces Quix’s illustrationof the changes of posture, including eye movements, which follow asymmet-rical tonus between the right and left vestibular organs. Quix’s experimentalmethod for producing tonus in normal man was by galvanic stimulationacross the mastoids. The figures show that in the case of canal asymmetrythere is principally a turn of all parts of the body in the frontal and horizontalplanes. In the case of otolithic asymmetry the major effect is the tilt of thebody towards the hypotonic side; notably involving also a tonic tilt incyclotorsion of the eyes to this side. Within these general schemata Quixalso made a distinction between the functional responses of the utricles andsuccules which, I believe, even today could provoke thought for experimenta-tion.

What we have learnt since Quix? Certainly we have learnt much aboutthe detailed physiology of these organs and their central connections, but

Fig. 1. Portraits of FH Quix illustrating the orientations of the utricules and saccules [1].

Fig. 2. Quix’s illustrations of schematic postural responses to canalicular and otolithicasymmetrical tonus taken from Quix [1].

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mainly in animals. We have also ascertained the dynamics of some of theirfunctions in man but the writers remain convinced that many clinical problemsremain little understood and without adequate investigative techniques. Beforecommencing a detailed account of otolith pathophysiology, it is appropriateto place the problem in a pointed context by asking the reader the followingquestion: ‘Conceive the possibility of a surgical intervention which could repairin some way the whole or part of the otolith organ. The procedure would bea craniotomy with the usual risks of deafness of paralysis of the facial nerveor worse. Which symptoms would you accept as definite indications of an otolithicdisorder and which tests, of which the results are indications of abnormal andlateralised otolithic disorder, you would accept?’

Relevant Basic Anatomy and Electrophysiology of theOtolith Apparatus

It is appropriate to start with a brief discussion of the anatomy andelectrophysiology of the otolith organs because their basic structure and trans-duction properties suggest the ways in which their signals may be used by thenervous system. The basic hair cell of the maculae is an initial force transducerand as such responds to linear acceleration of the head and (its Einsteinianequivalent) changes in the strength and orientation of the gravitational vector.The multitudinous orientations of the hair cells ensure transduction of theseinitial forces in all orientational directions in three-dimensional space. Thedynamics of otolithic unit responses show that they are sensitive to staticinitial forces, such as would be effected by a tilt of the head with respect togravity or prolonged acceleration down a runway in an aeroplane, up to thehigh frequency movements of the head experienced during sparring in boxingor running. A subclass of the otolith units also renders a signal which approxi-mates the rate of acceleration, suggesting that they can give a very fast trig-gering response [2].

According to the nature of otolithic signals one would presume they maycontribute to a variety of important behavioral functions [3]: viz, the senseor perception of linear acceleration and gravitational tilt; compensatory andbalancing movements of the eye head and body as well as autonomic responses,particularly the regulation of blood pressure and volume distribution whichare so critically dependent on changes in spatial orientation. Each of thesepossible functions will now be discussed in turn.

17Pathophysiology and Clinical Testing of Otolith Dysfunction

Perception of Spatial Orientation

One would presume that the otolith plays a role in the perception ofsubjective verticality, detection of thresholds and directions of linear motionand estimating trajectory. There are apparently only two systematic studieswhich have tried to establish the thresholds of perception of linear accelerationin normal subjects in comparison with patients with bilateral absence of vestib-ular function [4–6]. In Gianna’s experiment, the subject sat on a train runningon linear rails and was exposed to linear accelerations with several configura-tions including sinusoidal oscillations, ramp and parabolic onset accelerations.The threshold for perception for normal subjects was found to be about 5 cm/s/swhereas patient thresholds were only slightly raised at a mean of 7 cm/s/swhich was not statistically significantly different. One might conclude fromthis study that otolithic signals only reduce the noise around the thresholdfor detection of linear motion; no more. Incidentally, the thresholds found inGianna’s study were similar to those established by numerous laboratories forexposure to linear motion on the part of normal subjects.

There is a certain similarity between sensitivity to tilt from gravitationalupright and thresholds for linear motion, since tilt detection requires the abilityto detect a slight change in the magnitude and direction of an imposed staticlinear acceleration. One would think that the otolith apparatus, with its sensi-tive hair cells optimally orientated in the utricles for detection of tilt fromupright, would give very precise and sensitive estimates of tilt of the body fromupright. However, when other somatosensory cues are masked by immersion inwater, as with undersea divers, the ability to sense the subjective vertical isseriously degraded to the extent that divers readily become spatially disorien-tated when deprived of visual cues; a very dangerous situation which has beenextensively studied [7, 8]. Thus, it would seem that the signals from the otolithorgans, when used in isolation from contextual somatosensory cues, are neithersensitive nor accurate cues for estimating the subjective postural vertical.

This conclusion has been borne out by parallel studies which have com-pared the performance of normal subjects with patients with labyrinthinelesions [9–11]. When exposed to low-frequency passive tilting in a flight simu-lator the ability of patients with bilateral unilateral labyrinthine disorders toindicate the true direction of earth vertical is similar to that of normal subjectswhich leads to the conclusion that somatosensory signals predominate indetermining the subjective vertical. In an attempt to mask somatosensorysignals, a recent experiment used vibration of the simulator to degrade thevalue of the somatosensory input to estimates of the subjective vertical [12].Subjects sat on the simulator and with the aid of a joystick were tasked withreturning themselves to upright then the simulator tilted gently away from the

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normal upright attitude. Without vibration both normal subjects and patientswith unilateral vestibular loss could maintain an upright flight attitude withease. However, when the whole simulator vibrated, in the subjects with unilat-eral vestibular loss the simulator tilted by up to 10º to the side of their lesion.Patients’ tilts were found to be a robust effect observed in both the acute andchronic (up to 10 years) stages after vestibular loss. The authors argued thatthe otolith signal to indicate uprightness had a more significant influenceduring simulator oscillation and the asymmetry of orientation was due to thedifferences in densities of hair cells of the utricular macula oriented, respec-tively, in the rightwards and leftwards direction so that the total output gavea slightly biased tonus which could be corrected by tilting to the lesion side.The effect of vibration was thought to be either by masking somatosensoryinput alternatively by putting time pressure on the nervous system so thatappropriate cross checks between somatosensory and vestibular signals couldnot be made adequately, thereby revealing the slightly erroneous estimate fromthe otolith apparatus.

Vertigo in Otolithic Disease

One might think that canal activity, e.g. pro-rotatory stimulation, lendsa sensational perception of turning whereas otolithic activity lends a perceptionof linear movement or of tilt or perhaps of a sudden fall. Certainly, the firstof these suppositions is false. For example, when an aviator pulls out of aprolonged roll maneuver he may experience the illusion of a tilted and tortingvisual horizon with accompanying sensations of bodily tilting due to thenystagmic and perceptual consequences of post-rotatory activity in the verticalcanals [13–15]. This scenario may provoke accidents since it is the temptationon the part of the aviator to make a sudden and inappropriate attitude correc-tion of his aircraft if he believes that the craft is actually continuing to roll.The illusion does not have an otolithic component since there is no otolithstimulation of tilt or turn in the level attitude achieved immediately after theroll. Thus, a perception of tilt can be imparted by canal activity. Similarly, ifa false otolithic signal causes a perception of tilt in the body there may alsobe an associated component of tilting as the false signal develops. A tilting isalso a rotation in the vertical plane ‘the one implies the other’ and it isnot clear whether one can separate these perceptions. The question becomesphilosophical. In conclusion, it is not so apparent that symptoms of tiltingor turning of the body are strong indications for lesions for particular partof the labyrinth, vis-a-vis canal verses otolithic disorder. In case of a purelinear movement as, for example, the illusion of surging forwards in a vehicle


or moving purely linearly up and down one might think that they could havea purely otholithic origin but would presumably imply fairly symmetricalbilateral changes in otholithic functional status. This would be rare to saythe least and the authors have almost never encountered patients who havecomplained of a purely linear movement. By far the most common symptoms,the illusory motions we tend to ascribe to a possible otolithic disorder arethose of tilting as if on the deck of a ship. Turning and rotation in some wayare implicit in this illusion so it is doubtful that one can definitely ascribethem to a purely otolithic disorder.

Compensatory Eye Movement Reflexes

Linear Movement in Horizontal and Vertical Planes and Results of LesionsAs with the canals, the otoliths provide eye movement reflexes which

compensate for movement of the head [16–20] (fig. 3). These reflexes maintainthe directional view on visual targets through the linear components of move-ment, for example through vertical linear head movements encountered whensparring. From geometrical considerations (that parallel lines meet at infinity),it is apparent that one needs linear compensatory eye movements only whentargets are fairly close to the subject since when one looks into the distancethe effect of a small movement of the head on the direction on vision gaze isnegligible. Of significance which will appear below it is noteworthy that linearcompensatory eye movements are fast, commencing with a latency of about20 ms after head motion in man.

Certainly bilateral vestibular loss abolishes all compensatory eye move-ment that would normally be evoked by linear head acceleration [17, 21]. Itwould not be immediately clear, however, what happens to compensatory eyemovements after one unilateral loss of vestibular function. Since hair cellsof the surviving utriclar maculae have directional orientations in both therightwards and leftwards direction, it is possible that signals derived fromthese two orientations could be used to drive both rightwards and leftwardseye movements and thus compensate for contralateral loss of function. Byrecording the compensatory eye movements evoked by lateral accelerationfrom subjects seated on a motorised train, it has been shown that, in the acutestage of unilateral vestibular loss, there is a specific reduction in amplitude ofcompensatory eye movement generated by linear acceleration to the side ofthe lesion (fig. 3). In a period of several months this may compensation sothat bi-directional responses are regained. In the surviving utricle it is themedially situated hair cells which are stimulated by acceleration to the lesionside and laterally cited hair cells which are excited by acceleration stimuli to

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Fig. 3. Normal repertoire of compensatory eye movements attributable to the otolithiccomponents of vestibular-ocular reflexes.

the intact side. Thus for acceleration towards the intact side the lateral haircells of the intact organ generate a normal compensatory eye movement.However, for linear acceleration to the lesion side it would seem that excitatorystimulation of the medial hair cells of the intact utricle cannot generate arobust compensatory eye movement, at least in the acute phase of unilateral


vestibular loss [22–26]. Since static ocular counter-rolling is weak when thehead tilts to the side of the of the lesion (fig. 4), which depresses activity ofthe medial hair cells of the surviving utricle, and is robust when the head tiltsto the intact side which excited these medial located hair cells one would alsoconclude that the medial located hair cells of the utricle preferentially controlcompensatory ocular counter-rolling. This division of the utricle maculae intolaterally located cells responsible for horizontal compensatory eye movementsand medially located cells response for static ocular counter-rolling as deter-mined by behavioral observations in man is in accordance with the muchearlier observations of Fluur [27] employing microstimulation of differentregions of the otolith organ in the cat.

Otolithic Control of Cyclo-Version (Ocular Counter-Rolling)In contrast with the robust eye movements evoked by lateral and vertical

linear acceleration of the head, tilt of the head with respect to gravitationalvector evokes cyclotorsional compensatory eye movements which, in man,are weak in comparison with those to be observed in lateral-eyed animals[28]. It is possible to provoke static cyclo-version, which is attributed largelyto otolith function, not only by tilt but also by linear acceleration. Whenprovoked by lateral linear acceleration cyclo-torsion appears in a more ‘pureotolithic’ form uncontaminated by the more robust dynamic counter-rollingnystagmus which is largely driven by the vertical semi circular canals. Theamplitude of cyclo-torsional compensatory eye movement evoked by laterallinear acceleration is small and the latency is long, typically around 300 msin a normal subject. Such a long latency implies a low pass characteristicwhich is a consequence of brain mechanisms filtering the high-frequencycomponents of the otolithic signal [20, 28]. It is been proposed that thisfiltering mechanism for cyclo-versional eye movement which has a perceptualcounterpart in the perceptual response of tilting when it is exposed to alaterally acting acceleration (as in the centrifuge or on certain fair groundrides) is a mechanism used by the brain to distinguish between tilts withrespect to the gravitational vector and actual acceleratory motion across theearth’s surface. It is perhaps worth emphasising this latter point in greaterdetail. If, for example, a subject is suddenly accelerated laterally with aconstant level of acceleration then the first eye movement response wouldbe a horizontal plane compensatory movement at short latency. If the motionwas sustained it would then follow the development of the slow ocular cyclo-torsion as if the subject was actually tilting and eventually the perceptionof subjective tilt would develop. In the case of a subject remaining seatedupright, the new ‘inertial force vertical’ is determined by the vector sum ofgravitational acceleration and the linear acceleration of the vehicle. This is

22Gresty/Lempert

Fig. 4. Abnormal eye deviations and nystagmus following acute unilateral loss of otolithfunction. The schema are partly hypothetical and continue to be the subject of debate. Onerarely sees the full repertoire of abnormality in any one patient. In this paper we attributethe spontaneous cyclo-version observed with the head in the normal upright position tounopposed tonus of the medial portion of the surviving utricle. Previous authors haveproposed that it arises from a net tonic imbalance which results from summing hair cellactivity over the whole utricle [30–32].


tilted in the direction of vehicle motion, in which case the subject wouldexperience being tilted away from upright.

Ocular Cyclo-Torsion and the Visual Vertical in Unilateral Otolithic LesionsIt is been known for a very long time, certainly since Quix [1] (fig. 2), that

an asymmetry of the vestibula can lead to a tonic tilt of the eyes attributableto asymmetrical otolithic function. In recent times this was exploited first byFriedman [29] in the form of the visual vertical as a ‘test’ for unilateral otolithicdisorder. In simple terms, the visual vertical is determined largely by the retinalcoordinates of the eye. If the eye tilts for any reason a subject will set a visualvertical target line tilted by approximately the same amount as the eye rotationand in the direction of the eye rotation. Accordingly, if a unilateral vestibularlesion deviates the eyes in cyclo-torsional tilt to the lesion side the visualvertical is set according to the ocular tilt and thus in turns becomes an indicatorof the laterality of vestibular loss by virtue of its tilt towards the side of lesion.This effect is relatively acute and the visual vertical may become apparentlynormal or near normal within 6 months to a year [30–34].

Apparently simple, this scheme can be difficult to apply to clinical investi-gation. In the first place, any cyclo-torsional nystagmus will also influence thevisual vertical and this type of nystagmus is frequently present in patientswith acute vestibular lesions [35–42]. Secondly, a pre-existing ophthalmologicdisorder may effect the visual vertical as possibly would other sensory inputs,particularly from the neck which is so interrelated to vestibular function.Finally, the assumption that a static cyclo-torsion following vestibular injuryreflects the otolithic component to disordered function seems to stem froman implicit assumption that static eye deviations are generally otolithic inorigin whereas nystagmus events are canalicular in origin. It is not at all clearthat this is necessarily the case [41, 42]. Here one could use a similar argumentfor the one detailed above for canal versus otolith vertigo. Since we know thatotolith stimulation can produce both static eye deviations and nystagmus (inthe form of L nystagmus) why is it not also possible that canal stimulationcan produce small static bias effects on eye position as well as the more franknystagmus? If the latter case is true then it is possible that tilt of the visualvertical could have a canalicular origin; particularly in vertical canal asym-metry.

Symptoms of Disorder Linear Compensatory Eye Movement: OscillopsiaFrom the point of view of symptoms one would wonder whether patients

who have bilateral otolithic lesions suffer from oscillopsia when undergoinglinear motion with respect to nearby targets in parallel with the oscillopsiathey would experience from head rotations. Perhaps this is so but the oscillopsia

24Gresty/Lempert

provoked by canal lesions is much worse and would certainly dominate sympto-matically. However, there is experimental evidence that patients with bilateralotolithic lesions do suffer from oscillopsia when trying to reach targets duringlinear head oscillation [22]. The experience was undertaken with subjects sittingimmobilised on a train running on a straight tract. It was found that duringoscillatory motion of the train in the lateral direction normal subjects were ableto read an earth-fixed target whereas patients with bilateral loss of vestibularfunction reported oscillopsia and suffered a marked loss of visual acuity. Thus,the consequences to visual acuity of bilateral otolithic loss are quantifiablebut the technical requirements mean that it is expensive to do.

Otolith-Spinal Function

It is very difficult to ascribe any subdivision of vestibulo-spinal reflexesto a specific otolith function because the sort of body movements whichstimulate the otoliths would also stimulate well nigh every other sensorysystem in the body. Accordingly, the following discussion is concerned withvestibulo-spinal responses and effects which we believe to be largely otolithicin origin.

A rapid fall or tilt of the body which involves abrupt movement of thehead provokes a generalised response in most skeletal muscles which is thoughtto be in part a startle response [43–49]. However, the earliest part of thisstartle response is purely vestibular in origin. It is very likely that this responseis triggered by stimulation of the otolith apparatus as one could tentativelysuggest by the irregular units specifically. These early responses are abolishedin patients with bilateral loss of vestibular function.

A tilt of the floor which affects the body provokes a coordinated balancingresponse in which the various parts of the body return towards upright: thisresponse is a compensation for the tilt illustrated in figure 2 by Quix. A verysimilar coordinated postural adjustment may be seen with low levels of galvanicstimulation of the labyrinth, suggesting that small currents tend to preferen-tially stimulate the otoliths [50–52]. A further feature of galvanic stimulationis that the body tends to lean slightly in the direction of stimulation and thisleaning can be vectored by turning the head so for example one ear faces tothe front. This lean has been ascribed to a subtle shift in the frame of referenceof standing posture caused by otolithic stimulation [52] roughly similar to thetilted attitude adopted by unilateral labyrinthine defectives when flying in aflight simulator as described above [12].

Presently there is perhaps only one clinical test which is specific forvestibulo-spinal function. This depends on the effect of loud noise on the


sacculus. A brief loud click (0.1 ms, greater than 95 dB HL) to the ear evokesan inhibitory response in the ipsilateral sternocleidomastoid muscle with alatency of 8 ms [53–58]. The whole muscle response has a positive signalpeak at 13 ms with a negative peak at 23 ms and is abolished by vestibularneurectomy, although preserved in the case of profound hearing loss. Experi-ments in animals and in patients with diverse lesions of the vestibular appar-atus suggest that the origin of this response is in stimulation of the sacculus[57–64]. In the case of certain disorders of the labyrinth, such as the phenom-enon of Tullio [65], it is possible to observe an accentuation of this responsesuggesting hyperexcitability of the labyrinth. In such cases we do not knowif the response remains a function of the saccule or whether other parts ofthe labyrinth have become similarly sensitive to noise. In conclusion, althoughresponses of the neck to auditory clicks demonstrate the integrity of saccularfunction their application in investigating disorders of the labyrinth remainsexperimental.

Otolithic Control of Autonomic Function

Spatial reorientations demand adjustments of blood pressure and bloodvolume distribution. The vestibular apparatus is the only sensory organ special-ised for signalling spatial reorientations and therefore its signal should beimportant for guiding the patterning of neuro-vegetative responses to reori-entation. In addition, as they can be so fast, vestibular signals are ideallysuited to trigger patterns of autonomic response. It is perhaps Yates and hisassociates’ work in particular that has shown in the cat that there are importantfairly direct pathways by which the otolith organ regulates the mechanism ofblood pressure and respiratory muscle [66–68]. It is interesting that animalwork has also failed to show any cannalicular pathways for controlling neuro-vegetative functions of comparable significance.

In general terms there are two sorts of mechanisms proposed to explainsymptoms of malaise in patients with disorders of the vestibular apparatus.The first involves the fairly direct pathways recently described in animal experi-ments. If the otoliths provide important signals for controlling heart rate,blood pressure, and respiration during rapid spatial reorientation, then onecould easily imagine how abnormal otolithic functions either spontaneouslyor as a consequence of inadequate response to spatial reorientation lead tothe vaso-vagal symptoms (and occasional syncope) frequently encountered inpatients with vestibular disease. The second route by which vaso-vagalsymptoms could be provoked in vestibular patients is through the route ofmotion sickness mechanisms [69]. It is well established that motion sickness

26Gresty/Lempert

Fig. 5. Respective alignment and misalignment of an active, anticipating driver andpassive, unprepared passenger with respect to the inertial ‘vertical’ during acceleration in avehicle. If the driver maintains his alignment he experiences little otolithic stimulation.

is provoked when vestibular signals are in conflict or ‘mismatched’ (fig. 5)with somaesthetic or visual information. In addition the most provocativecircumstances for motion sickness involve movements which change orienta-tion of the body with respect to vertical and thereby stimulate the otoliths.Clearly, a unilateral vestibular lesion could be the source of conflict becauseof the mismatch between signals from the diseased part of the labyrinth andsignals from healthy labyrinthine receptors and other sensory inputs. In thisview, the malaise experienced by patients with vestibular disease is a form ofmotion sickness.


Several recent experiments have addressed the problem of understandingthe causes of malaise in vestibular disease in man with emphasis on theinvolvement of otolith function. Brief linear acceleration of the body has beenshown to provoke a pressor response with elevation of blood pressure andheart rate (up to 10 mm Hg systolic) which lasts approximately 10 s after aperiod of linear acceleration of 1–2 s duration [68]. This pressor response isprobably largely a function of the otolith stimulation during linear accelerationbecause it is much diminished in patients with bilateral loss of vestibularfunction. Our own unpublished observations have shown that it matters littleexactly what spatial reorientation is undertaken. If the movement is fast apressor response is provoked with the obvious function of preparing the bodyfor any counteraction that may be necessary. This is the reason perhaps thatone encounters patients with bilateral vestibular loss who feel faint whenthey move quickly or suffer vertigo, the reason being that they have lostthe vestibularly triggered pressor response required for dealing with spatialreorientation whether illusory or real.

Applications of Otolith Physiology

Finally, we would like to discuss an important possible application ofotolithic physiology which is the problem of inappropriate autonomic changesprovoked during passive motion in a vehicle. In addition to motion sicknessexperienced by normal subjects there is some evidence suggesting that ambu-lance transport can compromise even further the state of an already sickpatient. The reason for this is not clear and could be a combination of motionsickness [70, 71], inability to make rapid autonomic changes in response toaccelerations of the vehicles, and inability to deal with passive shifting of thebody fluids, particularly the blood, also due to vehicle acceleration. The ques-tion is can one protect the passenger from inappropriate stimulation by accel-eration?

Consider the motorbike driver who leans into the direction of accelera-tion when opening the throttle to accelerate his bike and thereby maintainshis head and torso in alignment with the inertial force vector which tiltsforwards as the bike accelerates forwards (fig. 5). In contrast, his unwarypassenger may be thrown backwards when the bike takes off thus tiltingmarkedly with respect to the inertial upright (fig. 5). The driver receivesvery little change in otolithic stimulation whereas the passenger receives astrong otolithic signal of tilt with respect to the upright (fig. 6). Since, inanimals at least, it is the otoliths that primarily drive vaso-vagal responsesone would presume that the driver is relatively protected against autonomic

28Gresty/Lempert

Fig. 6. Sensory systems stimulated by various tactics of alignment with the inertial‘vertical’ during vehicle acceleration. Although alignment with the inertial vector will tendto minimise otolith stimulation it provokes sensory mismatch. It is an unresolved questionas to which would be more detrimental to cardiovascular control.

changes which are inappropriate for a person sitting and being passivelytransported in a vehicle.

To determine what happens during acceleration with the body alignedwith the inertial upright and misaligned, we exposed subjects to brief linearaccelerations with a visual display which guided them to make head move-ments which aligned and compensated for the linear acceleration or alterna-tively misaligned: similar to the body movements of the motorbike driverand passenger, respectively [72]. In the aligned condition heart rate andblood pressure changes measured tonometrically on the radial artery wereminimal during accelerations whereas in the misaligned conditions a markedpressor response was evoked with a mean peak systolic blood pressurechange of 7 mm Hg. A similar experiment has also been conducted in Japan[73] on subjects who were carried within a vehicle on an actively suspendedstretcher which would similarly align or misalign their body with the inertialforce vector generated by accelerating and breaking of the vehicle. Theauthors similarly found that the subjects were protected against blood pres-sure changes when the stretcher aligned with the tilting of the inertial forcevector.

With the recent advent of active suspension systems, for example, asavailable in Citroen motorcars, it should be possible to tune the ‘ride’ of avehicle to protect passengers against inappropriate autonomic changes. It


remains to be seen whether this would help protect patients during transportin ambulances or normal subjects who are particularly susceptible to motionsickness.

Conclusions

It is difficult to ascribe any set of clinical signs or symptoms and resultsof related investigations as specific to otolithic disorder. Appropriate testingcan be expensive and yield equivocal results. In future, attention should be paidto validation and assessment of sensitivity and specificity of tests purporting toevaluate otolith dysfunction.

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41 Gall RM, Ireland DJ, Robertson DD: Subjective visual vertical in patients with benign paroxysmalpositional vertigo. J Otolaryngol 1999;28:162–169.


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43 Greenwood R, Hopkins A: Muscle responses during sudden falls in man. J Physiol 1976;254:507–518.

44 Greenwood R, Hopkins A: Landing from an unexpected fall and a voluntary step. Brain 1976;99:375–386.

45 Halmagyi GM, Gresty MA: Blink reflexes to sudden free falls: A test of otolith function. J NeurolNeurosurg Psychiatry 1983;46:844–847.

46 Ito Y, Corna S, von Brevern M: Neck muscle responses to abrupt free fall of the head: Comparisonof normal with labyrinthine-defective human subjects. J Physiol 1995;489:911–916.

47 Ito Y, Corna S, von Brevern M: The functional effectiveness of neck muscle reflexes for head-righting in response to sudden fall. Exp Brain Res 1997;117:266–272.

48 Bisdorff AR, Bronstein AM, Gresty MA: Responses in neck and facial muscles to sudden free falland a startling auditory stimulus. EEG Clin Neurophysiol 1994;93:409–416.

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Dr. Michael A. Gresty, Senior Scientist, MRC Human Movement and Balance Unit,National Hospital for Neurology and Neurosurgery,Queen Square, London WC1N 3BG (UK)Tel. +44 171 8373 611, E-Mail [email protected]



............................Otolithic Vertigo

Thomas Brandt

Department of Neurology, Ludwig-Maximilians University, Klinikum Grosshadern,Munich, Germany

There are several reasons why most vestibular syndromes involve bothsemicircular canal function and otolithic function:

(1) The different receptors for perception of angular and linear accelera-tions are housed in a common labyrinth.

(2) Their peripheral (eighth nerve) and central (e.g. medial longitudinalfascicle) pathways take the same course.

(3) Otolith and semicircular canal input converge at all central vestibularlevels, from the vestibular nuclei to the vestibular cortex.

Thus, most vestibular syndromes are mixed as regards otolithic and canalfunction. A peripheral prototype of such a mixed syndrome is vestibularneuritis. It is caused by inflammation of the superior division of the vestibularnerve that subserves the horizontal and the anterior semicircular canals andthe maculae of the utricle and the anterosuperior part of the saccule. A centralprototype is Wallenberg’s syndrome. In this disorder the medial and superiorvestibular nuclei are involved where otolith and canal input converge. Wallen-berg’s syndrome typically causes ocular and body lateropulsion and torsionalspontaneous nystagmus.

Nevertheless, with caloric irrigation of the external acoustic meatus it ispossible to selectively stimulate single canals. The prototype of a semicircularcanal disease is benign paroxysmal positioning vertigo of the posterior orhorizontal canal. Typical signs and symptoms of semicircular canal vertigoare:

(a) Rotational vertigo and deviation of perceived straight-ahead.(b) Spontaneous vestibular nystagmus with oscillopsia.(c) Postural imbalance with Romberg fall and pastpointing.(d) Nausea and vomiting if severe.

The 3-D spatial direction of nystagmus and vertigo depends on the spatialplane of the affected semicircular canal and on whether the dysfunction iscaused by ampullofugal or ampullopetal stimulation or by a unilateral lossof afferent information. Malfunction of a single or more than one semicircularcanal can be detected by 3-D analysis of spontaneous nystagmus [1–3] orperception of rotation [4]. Central vestibular syndromes may hide the semicir-cular canal or otolithic types. They are best classified according to the threemajor planes of action of the vestibular ocular reflex: yaw, roll, and pitch. Toput it simply, ‘dynamic’, rotatory vertigo and nystagmus indicate that (angular)canal function is affected, whereas ‘static’ ocular tilt reaction, body lateropul-sion, or tilts of perceived vertical point to (linear) otolith function.

The following is largely adopted from a more detailed presentation in themonograph Vertigo – Its Multisensory Syndromes [5]. This review focuses onperipheral rather than central otolithic syndromes.

Otolithic Syndromes

Although the pathophysiology of otolithic dysfunction is poorly under-stood, a disorder of otolithic function at a peripheral or central level shouldbe suspected if a patient describes symptoms of falls, sensations of linearmotion, or tilt, or else shows signs of specific derangements of ocular motorand postural orienting and balancing responses [6]. A significant number ofpatients presenting to neurologists have signs and symptoms that suggestdisorders of otolithic function. Nevertheless, diseases of the otoliths are poorlyrepresented in our diagnostic repertoire (table 1). Of these diseases, posttrau-matic otolith vertigo [7] may be the most significant. The rare otolith Tulliophenomenon may be the most thoroughly studied [8, 9]. Other examples arevestibular drop attacks (Tumarkin’s otolithic crisis) and a number of centralvestibular syndromes that indicate tone imbalance of graviceptive circuits (skewdeviation, ocular tilt reaction, lateropulsion, room-tilt illusion), some of whichmanifest without the sensation of dizziness or vertigo.

Vestibular Drop Attacks (Tumarkin’s Otolithic Crisis)

Vestibular drop attacks can occur not only in the later stages of endo-lymphatic hydrops [10, 11] but at any time during the course of Meniere’sdisease [12]. In exceptional cases it may even be the initial manifestation [13].Over a 10-year period Baloh and coworkers identified only 12 of 175 patientswith Meniere’s disease to have drop attacks. and colleagues [14] reported a

35Otolithic Vertigo

Table 1. Peripheral and central vestibular syndromes affecting otolith function [5]

Disorder Signs/symptoms Mechanism

Peripheral vestibularLabyrinth

Posttraumatic head motion intolerance, gait ataxia, dislodged otoconia cause unequal heavy loadsOtolith vertigo to-and-fro vertigo, tilt of perceived with ‘graviceptive’ tone imbalance

vertical, skew deviation, lateropulsion

Vestibular drop attacks sudden falls, sensation of being pushed to sudden changes in endolymphatic fluid pressure(Tumarkin’s otolithic crisis the ground, Meniere’s triad with inappropriate otolith stimulation causingin Meniere’s disease) reflex-like vestibulospinal loss of postural tone

Endolymphatic hydrops episodic to-and-fro vertigo, unsteadiness, ‘floating labyrinth’, deformation or pressureMeniere’s disease changes in the membranous labyrinth

Perilymph fistula to-and-fro vertigo, gait ataxia with sneezing, perilymph leakage, abnormal elasticity of the(otolith type) coughing, or physical exercise, positive bony labyrinth with irritative otolith

fistula signs (e.g. Valsalva’s maneuver) stimulation during head motion, intracranialpressure changes

Vestibular atelectasis episodic to-and-fro vertigo, gait ataxia collapse of the walls of the ampulla and utricle

Otolith Tullio phenomenon sound or pressure-induced paroxysms of inadequate mechanical stimulation of otolith byperceived tilt, oscillopsia, skew hypermobile stapes footplate (stapedius reflex)deviation, and lateropulsion caused by loud sounds

Eighth nerve/or labyrinthOcular tilt reaction triad of head tilt, skew deviation, and ocular ‘graviceptive’ tone imbalance due to unilateral

ocular torsion associated with perceived tilt loss or irritation of (utricular) otolithic function

Eighth nerveVestibular (otolithic) paroxysms of vertical and torsional diplopia, neurovascular crosscompression of theParoxysmia perceived tilt, head and body lateropulsion (utricular?) nerve with ephaptic spreading

Central vestibularCortical

Vestibular epilepsy paroxysmal perceived tilts and body falls epileptic discharges in vestibular cortexwith or without ocular motorabnormalities

Cortical lateropulsion body tilt and tilts of perceived vertical cortical ‘graviceptive’ tone imbalance withacute lesions of the parieto-insularvestibular cortex

Room-tilt illusion transient illusions of upside-down vision cortical mismatch of visual and otolithicor apparent 90º tilts of the visual scene 3-D maps of spatial orientation

ThalamusThalamic astasia lateropulsion and tilt of perceived vertical ‘graviceptive’ tone imbalance with acute lesions

of vestibular subnuclei

BrainstemOcular tilt reaction see above see aboveLateropulsion see above see aboveRoom-tilt illusion see above see aboveUpbeat/downbeat nystagmusprovoked or modulated bychanges in head position

36Brandt

similar incidence (11 of 200 patients). The drop attacks occur from a standingor sitting position without typical triggers or prodromi. The patients describethe typical features [11, 13] in the following ways: (a) they felt they were beingpushed or shoved to the ground, or (b) the surroundings suddenly moved ortilted, causing their fall.

As distinct from patients with syncopies or epileptic seizures, these patientshave no associated loss of consciousness and are able to stand up immediately.Contrary to patients with transient upside-down vision or room-tilt illusions,patients with drop attacks fall without appropriate postural reflexes. Accordingto the pathophysiological viewpoint, sudden changes in endolymphatic fluidpressure cause inappropriate end-organ stimulation that results in a reflex-likevestibulospinal loss of postural tone or an inappropriate vestibulospinal reflexthat leads to a fall.

In the series of Baloh et al. [13], the first drop attack occurred from lessthan 1 year to 29 years after onset of Meniere’s disease, and the total numberof attacks varied from 2 to 18, with only 2 of 12 patients having more thansix attacks. Drop attacks tend to occur in a flurry during a period of 1year or less and are followed by spontaneous remission [12, 13]. Therefore,conservative management is recommended, not surgical intervention as Blacket al. [14] proposed.

Drop attacks disappeared completely after gentamicin treatment (appliedintratympanally) [15]. Transtympanic aminoglycoside treatment is increasinglybeing preferred to surgery. All reported experience with this kind of treat-ment indicates that one injection per week (1–2 ml of concentrations less than30 mg/ml) on an outpatient basis is recommended in order to better monitorthe delayed ototoxic effects.

Traumatic Otolithic Vertigo

Patients often describe their posttraumatic vertigo as a nonrotatory to-and-fro vertigo that is particularly associated with head acceleration and anunsteadiness of gait similar to walking on pillows. Since these posttraumaticsymptoms resemble otolith dysfunction in many patients, one can speculatethat the otolith, a vulnerable accelerometer, is affected by trauma [7]. Thecalcareous material embedded in its gelatinous matrix may loosen, resultingin unequal loads on the macula beds and a tonus imbalance between thetwo. This has been shown in centrifuge experiments with animals [16, 17].Engineering accelerometers are just as vulnerable. Such a mechanism alsofits the finding of DeWit and Bles [18] that postural sway is increased afterheadshaking in dizzy patients who have suffered a concussion. For these

37Otolithic Vertigo

patients visual stabilization plays a greater role than in normal subjects. Theauthors erroneously believed their findings could be ascribed to the brainstemconcussion.

A considerable proportion of traumatic vertigo can be assumed to bedue to dislodged otoconia, with or without concurrent benign paroxysmalpositional vertigo, which depends on the position of the debris within themembraneous labyrinth. No clinical test is yet available to establish a diagnosisof traumatic otolithic vertigo, but our own unpublished measurements oftransient deviation of the subjective visual vertical in these patients provideevidence of the condition.

Central compensation (rearrangement) would account for the gradualrecovery within days or weeks, thus supporting the view that exercise is thebest therapy.

Benign Paroxysmal Positioning Vertigo (Otolithic Canalolithiasis)

Benign paroxysmal positioning vertigo (BPPV; also known as positionalvertigo) was initially defined by Barany [19] in 1921. The term itself was coinedby Dix and Hallpike [20]. BPPV is only labeled an otolithic vertigo in thecontext of this review, since otolithic debris in the semicircular canals arecausative. Lanska and Remler [21] describe in detail the history of BPPV,its original description, the proper eponymic designation for the provocativepositioning test, and the steps leading to our current understanding of itspathophysiology. BPPV is the most common cause of vertigo, particularly inthe elderly. By age 70, about 30% of all elderly subjects have experienced BPPVat least once. This condition is characterized by brief attacks of rotatory vertigoand concomitant positioning rotatory-linear nystagmus. These attacks areelicited by rapid changes in head position relative to gravity. BPPV is a mechan-ical disorder of the inner ear in which the precipitating positioning of thehead causes an abnormal stimulation, usually of the posterior semicircularcanal (p-BPPV) of the undermost ear, less frequently of the horizontal semicir-cular canal (h-BPPV).

Schuknecht [22] and Schuknecht and Ruby [23] hypothesized that heavydebris settle on the cupula (cupulolithiasis) of the canal, transforming it froma transducer of angular acceleration into a transducer of linear acceleration.It is now generally accepted that the debris float freely within the endolymphof the canal (‘canalolithiasis’) [24–26]. The debris – particles detached fromthe otoliths – congeal to form a free-floating clot (plug). Since the clot isheavier than the endolymph, it will always gravitate to the most dependentpart of the canal during changes in head position which alter the angle of the

38Brandt

cupular plane relative to gravity. Analogous to a plunger, the clot inducesbidirectional (push or pull) forces on the cupula, thereby triggering the BPPVattack. Canalolithiasis explains all the features of BPPV: latency, short dura-tion, fatigability (diminution with repeated positioning), changes in directionof nystagmus with changes in head position, and the efficacy of physicaltherapy [26–28] (fig. 1).

In 1980, Brandt and Daroff [29] proposed the first effective physical ther-apy (positioning exercises) for BPPV. Based on the assumption that cupulolithi-asis was the underlying mechanism, the exercises were a sequence of rapidlateral head/trunk tilts, repeated serially to promote loosening and, ultimately,dispersion of the debris toward the utricular cavity. In 1988, Semont et al.[30] introduced a single liberatory maneuver, and Epley promoted a variationin 1992, which Herdman et al. [31] later modified. If performed properly,all three forms of therapy (Brandt-Daroff exercises and Semont and Epley’sliberatory maneuvers) are effective in BPPV patients [31, 32]. The efficacy ofphysical therapy makes selective surgical destruction such as transsection ofthe posterior nerve [33] or nonampullary plugging of the posterior semicircularcanal [34] largely unnecessary.

About 5–10% of BPPV patients suffer from horizontal canalolithiasis(h-BPPV) [35]. h-BPPV is elicited when the head of the supine patient isturned from side to side, around the longitudinal z-axis. Combinations arepossible, and transitions from p-BPPV to h-BPPV occur, if the clot movesfrom one to the other semicircular canal. Transitions from canalolithiasisto cupulolithiasis in h-BPPV patients have been described [36]. Most of thecases appear to be idiopathic (degenerative?), their incidence increasing withadvancing age. Prolonged bedrest also facilitates their occurrence. Othercases arise due to trauma, vestibular neuritis, or inner ear infections. Forthe time being, the recommended treatment is prolonged bedrest with thehead turned toward the unaffected ear [37]. This should be maintained forup to 12 h. If no effect is observed after 2 days, we advise the patients toperform the exercises described by Brandt and Daroff [29]. Both physicaltherapies can be performed at home and do not require the presence of aphysical therapist.

The diagnosis of typical BPPV is simple and safe: the patient must havethe usual history and exhibit positioning nystagmus toward the causative,undermost ear. Diagnosis is less easy in rare cases, for example, in patients withhorizontal semicircular canal cupulolithiasis who exhibit positional nystagmusbeating toward the uppermost ear for several minutes. Differential diagnosisincludes different forms of central vestibular vertigo or nystagmus, vestibularparoxysmia, perilymph fistula, drug or alcohol intoxication, vertebrobasilarischemia, Meniere’s disease and psychogenic vertigo.

39Otolithic Vertigo

Fig. 1. Schematic drawing of the Semont liberatory maneuver in a patient with typicalBPPV of the left ear. Boxes from left to right: position of body and head, position of labyrinthin space, position and movement of the clot in the posterior canal and resulting cupuladeflection, and direction of the rotatory nystagmus. The clot is depicted as an open circlewithin the canal; a black circle represents the final resting position of the clot. (1) In thesitting position, the head is turned horizontally 45º to the unaffected ear. The clot, whichis heavier than endolymph, settles at the base of the left posterior semicircular canal. (2) Thepatient is tilted approximately 105º toward the left (affected) ear. The change in head position,relative to gravity, causes the clot to gravitate to the lowermost part of the canal and thecupula to deflect downward, inducing BPPV with rotatory nystagmus beating toward theundermost ear. The patient maintains this position for 1 min. (3) The patient is turnedapproximately 195º with the nose down, causing the clot to move toward the exit of thecanal. The endolymphatic flow again deflects the cupula such that the nystagmus beatstoward the left ear, now uppermost. The patient remains in this position for 1 min. (4) Thepatient is slowly moved to the sitting position; this causes the clot to enter the utricularcavity. A, P and H>Anterior, posterior, horizontal semicircular canals; Cup>cupula; UT>utricular cavity; RE>right eye; LE>left eye. From Brandt et al. [28].

40Brandt

Perilymph Fistulas

The perilymph space surrounds the endolymph-filled membranous laby-rinth, and both are encapsuled by the bony labyrinth. Perilymph fistulas (PLF)– abnormal communications between the perilymph space and the middle ear– are caused by traumatic pressure changes in either the cerebrospinal fluid(explosive force) and/or the middle ear (implosive force). PLF may lead toepisodic vertigo and sensorineural hearing loss, owing to pathological elasticityof the otic capsule or leakage of perilymph, usually at the oval and roundwindows. The fistula and a partial collapse of the membranous labyrinth(‘floating’ labyrinth) permit abnormal transfer of ambient pressure changesto maculae and cupulae receptors.

The typical history is that of an ‘otolithic ataxia’, or a semicircularcanal type of vertigo, and/or a sudden hearing loss resulting from barotrauma(flying, diving), trauma to the head, to the ear (e.g. postsurgery), or fromstrenuous activity, such as lifting of heavy weights (excessive Valsalvamaneuver). As trauma is a frequent etiology of the first manifestations ofPLF, the subsequently vulnerable patients often report on typical triggers(lifting weights, nose blowing, traveling through mountains) that set off

the clinical signs of episodic vertigo and/or sensorineural hearing loss. Insome patients PLF appear as sound-induced vestibular symptoms, whichare called the Tullio phenomenon, either of the semicircular canal or otolithtype.

The clinical picture of PLF is characterized by a wide range of symptoms:pure vestibular symptoms; pure hearing loss; combinations of both, includingtinnitus and fullness of the ear; or the absence of symptoms. Patient historyis very important, especially if the first manifestation is associated with headtrauma.

With respect to vertigo and vestibular function two types of PLF can bedistinguished:

(1) The semicircular canal type by rotational vertigo and nystagmus.(2) The otolith type by unsteadiness, gait ataxia, and oscillopsia.Both types manifest in episodes lasting from hours to days. Frequent

triggers are ambient pressure changes transferred to the inner ear, certain headpositions in space, head movements, or locomotion.

Otolith Type of PLF

Healy et al. [38, 39] were the first to stress that this condition shouldbe suspected in patients with severe gait disturbance and ataxia without

41Otolithic Vertigo

evidence of central nervous system disease, even in the absence of grosshearing defects. In our experience, these patients represent a well-definedsubgroup of fistula patients. It is justified to call this syndrome ‘otolith typeof PLF’, since the vertigo symptoms can be explained by inappropriateotolithic stimulation secondary to oval window fistulas. Most of these patientsare free from vertigo with the head stationary, but they experience a dis-tressing to-and-fro movement of both body and surroundings with headaccelerations, for example, when rising from a sitting position and particularlywhen walking. The sensation, described as ‘walking on pillows’, is similarto that described by patients in the initial phase of BPPV or in phobicpostural vertigo. The gait is broad-based and ataxic, but clinical examinationdoes not reveal cerebellar or spinal ataxia. It is striking that head movements,which preferentially stimulate the canals (horizontal oscillation in yaw), aremuch better tolerated than linear accelerations. Sometimes a linear vertigo,described as a tilt or slow falling, is precipitated in the supine position(especially with the affected ear undermost). Nausea and vomiting are rare,unlike in canal disease. Symptoms most often associated with this otolithicvertigo are fluctuating fullness of the ear, tinnitus, and sensorineural hearingloss.

The disease is more often episodic than chronic. Episodes are sometimesinduced by strenuous activities such as lifting heavy objects, jogging, or allkinds of Valsalva pressure increases (sneezing, coughing). The severity of theepisodes varies. Some patients, who are able to detect the beginning of anepisode by an audible ‘pop’ or increasing fullness of the ear, can prevent thedevelopment of more severe symptoms merely by stopping the precipitatingactivity.

Tullio Phenomenon

Sound-induced vestibular symptoms such as vertigo, nystagmus, oscillop-sia, and postural imbalance in patients with PLF are commonly known asthe Tullio phenomenon [40]. The occurrence of a distressing ‘Tullio sympto-matology’ presupposes PLF pathology; however, only rare patients with PLFsuffer from the Tullio phenomenon. It seems, nevertheless, justified to give adetailed and separate description of the Tullio phenomenon in conjunctionwith PLF, since this pathological condition has revealed new details abouthuman vestibular function in connection with ocular motor and posturalcontrol. Oculographic, posturographic, and EMG studies allow a unique anal-ysis of vestibulo-ocular and vestibulospinal otolith reflexes in humans usingsound stimulation.

42Brandt

Clinical Types of Tullio Phenomena

Two mechanisms are generally acknowledged to be involved in a Tulliophenomenon in humans: more than one mobile window or a fistula opensinto the vestibular labyrinth [41, 42] and there is a pathological contiguity ofthe tympano-ossicular chain and the membranous labyrinth, for example, ifthe stapes is in contact with the saccule because of endolymphatic hydrops[42–44].

Within the heterogeneous group of Tullio phenomena, an otolith typeand a semicircular canal (nystagmus) type, e.g., due to window rupture, canand must be differentiated. In the latter, the pathological elasticity of thebony labyrinth makes it possible for high-intensity sound to move the peri-endolymph system of the canals rather than to push the otoliths. Click-evokedvestibulocollic reflexes were studied in a patient with a unilateral Tullio phe-nomenon who showed an abnormally low threshold and larger reaction whenelicited from the symptomatic side [45, 46]. This is compatible with a patholo-gical increase in the normal vestibular sensation to sound. Most of the oldercase descriptions in the literature suffer from imprecise descriptions or thefailure to register induced eye/head movements, so that it is impossible retro-spectively to classify them as an otolith or a semicircular canal type.

Otolith Tullio Phenomenon

There is evidence based on an otoneurological examination of a typicalpatient as well as the reevaluation of cases described in the literature that anotolith Tullio phenomenon due to a hypermobile stapes footplate typicallymanifests with the pattern of sound-induced paroxysms of ocular tilt reaction(OTR) [8, 44, 47].

The patients complain of distressing attacks of vertical oblique and rota-tory oscillopsia (apparent tilt of the visual scene) as well as postural imbalance(fall toward the unaffected ear and backward). These attacks are elicited byloud sounds, particularly when the sounds are applied to the affected ear ata maximum frequency (e.g. 500 Hz). Uttering vowels or blowing the nosecauses similar symptoms of varying severity.

The clinical picture of simultaneous paroxysms of eye-head synkinesis(OTR) includes the triad of skew deviation (ipsilateral over contralateral hyper-tropia), ocular torsion, and head tilt toward the undermost eye.

Electronystagmographic recordings as well as special video analysis (timeresolution: 1,000 images/s) revealed a latency for the eye movements of 22 mswith an initial rapid and phasic rotatory-upward deviation [8], which was

43Otolithic Vertigo

followed by a smaller tonic effect as long as sound stimulation lasted. Thisshort latency agrees with the short-latency compensatory eye movements (16.4–18.5 ms) found during brief periods of free fall in the monkey [48]. Skewdeviation in the patient is caused by a disconjugate larger deviation of theipsilateral eye. Repetitive sound stimulation leads to habituation of the phasiccomponent of eye movements. Rottach et al. [49] reported a latency of 16 msfor sound stimuli-induced horizontal-torsional nystagmus in a patient withTullio phenomenon. Cohen et al. [50] described oscillopsia and vertical eyemovements with a longer latency of 2.2 s in another patient. Our patientexhibited a surprisingly short latency vestibulospinal reflex on electromyo-graphic recording [47]; there was an EMG response after 47 ms in the tibialisanterior muscle and after 52 ms in the gastrocnemius muscle during uprightstance. Using a posturography platform we measured a considerable posturalperturbation: the shortest latency was 80 ms and there was a direction-specificdiagonal body sway. Increasing intracranial pressure by Valsalva’s maneuvermay evoke slow tonic eye movements and oscillopsia opposite in direction tothose of the Tullio phenomenon.

The hypothesis that the Tullio phenomenon arises from non-physiologicalmechanical otolith stimulation is based on (1) the location of the otolithsdirectly adjacent to the stapes footplate, and (2) the typical response patternof OTR. Surgical exploration of the middle ear of our patient revealed asubluxated stapes footplate; the hypertrophic stapedius muscle caused patho-logically large amplitude movements during the stapedius reflex. OTR is aneye-head synkinesis initiated by stimulation [51] or lesion [52] of the otoliths orgraviceptive pathways. Inadvertent utricular damage following stapedectomycauses an ipsilateral transient OTR [53]. This specific role of the utricle in thegeneration of OTR has been supported by findings in animal experiments incats [54] and in guinea pigs [55] using electrical stimulation of single utricularnerves or localized electrical stimulation of spots on the utricular macula,respectively. Synaptic organization of utricular input provides a pattern ofactivation for both spinal motor neurons (head tilt, body sway) and conjugatecyclodeviation with disconjugate vertical divergence [56–59]. A 3-D mathemat-ical model based on the known peripheral and central utricular-ocular circuitrycan adequately simulate skew deviation and ocular torsion in patients withunilateral utricular loss, lesions of the vestibular nuclei, and central ‘gravicep-tive’ pathways lesions [60].

Otolith Tullio phenomena may not be as rare as originally thought. Thetwo most obviously detailed case descriptions of a Tullio phenomenon byDeecke et al. [61] and by Vogel et al. [62] include typical features of OTR,although they described the syndrome in different terms. The patient describedby Deecke et al. [61] exhibited head tilt to the left with disconjugate ocular

44Brandt

torsion to the left, both of which lasted throughout an utterance. The patientof Vogel et al. [62] showed mainly vertical eye movements, consisting of aninitial component followed by a slower resetting movement, which was oftendivided into two parts with different velocities. These authors discussed thepossibility of an otolithic mechanism without, however, providing surgicalproof of the site of the fistula. Another patient, described by Spitzer andRitter [63] in retrospect, suffered from an otolith Tullio phenomenon, whichin his case was due to fracture of the medial wall of the tympanon and involvedthe stapes footplate, causing sound-induced contraversive head and body tiltwithout nystagmus.

Conclusion

A disorder of otolithic function at a peripheral or central level should besuspected if a patient describes symptoms of falls, sensations of linear motion,or tilt, or else shows signs of specific derangements of ocular motor andpostural orienting and balancing responses. A significant number of patientspresenting to neurologists have signs and symptoms that suggest disorders ofotolithic function. Of these, posttraumatic otolith vertigo may be the mostsignificant; the rare otolith Tullio phenomenon may be the most thoroughlystudied. Other examples are otolithic types of perilymph fistulas, vestibulardrop attacks (Tumarkin’s otolithic crisis) and a number of central vestibularsyndromes that indicate tone imbalance of graviceptive circuits (skew deviation,ocular tilt reaction, lateropulsion, room-tilt illusion), some of which manifestwithout the sensation of dizziness or vertigo.

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vertigo. Otolaryngol Head Neck Surg 1992;107:399–404.26 Brandt Th, Steddin S: Current view of the mechanism of benign paroxysmal positioning vertigo:

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paroxysmal positional vertigo. J Laryngol Otol 1991;105:901–906.35 McClure JA: Horizontal canal BPPV. J Otolaryngol 1985;14:30–35.36 Steddin S, Brandt T: Horizontal canal benign paroxysmal positioning vertigo (h-BPPV): Transition

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38 Healy GB, Strong MS, Feldman RG: Ataxia secondary to labyrinthine fistula. Laryngoscope 1973;83:502–507.

39 Healy GB, Strong MS, Sampogna D: Ataxia, vertigo, and hearing loss: A result of rupture of innerear window. Arch Otolaryngol 1974;100:130–135.

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41 Cawthorne T: Chronic adhesive otitis. J Laryngol Otol 1956;70:559–564.42 Kacker SK, Hinchcliffe R: Unusual Tullio phenomena. J Laryngol Otol 1970;84:155–166.43 Cody DTR, Simonton KM, Hallberg OE: Automatic repetitive decompression of the saccule in

endolymphatic hydrops (Tack operation). Laryngoscope 1967;77:1480–1501.44 Brandt Th, Dieterich M, Fries W: Otolithic Tullio phenomenon typically presents as paroxysmal

ocular tilt reaction. Adv Oto-Rhino-Laryngol 1988;42:153–156.45 Colebatch JG, Rothwell JC; Bronstein A, Ludmann H: Click-evoked vestibular activation in the

Tullio phenomenon. J Neurol Neurosurg Psychiatry 1994;57:1538–1540.46 Bronstein AM, Faldon M, Rothwell J, GrestyMA, Colebatch J, Ludman H: Clinical and electrophysio-

logical findings in the Tullio phenomenon. Acta Otolaryngol (Stockh) 1995;(suppl 520):209–211.47 Fries W, Dieterich M, Brandt Th: Otolithic control of posture: Vestibulo-spinal reflexes in a patient

with a Tullio phenomenon. Adv Oto-Rhino-Laryngol 1988;41:162–165.48 Bush GA, Miles FA: Short-latency compensatory eye movements associated with a brief period of

free fall. Exp Brain Res 1996;108:337–340.49 RottachKG,vonMaydellRD,DiScennaAO,ZivotofskyAZ,Averbuch-HellerL,LeighRJ:Quantitative

measurements of eye movements in a patient with Tullio phenomenon. J Vestib Res 1996;6:255–259.50 Cohen H, Allen JR, Congdon SL, Jenkins HA: Oscillopsia and vertical eye movements in Tullio’s

phenomenon. Arch Otolaryngol Head Neck Surg 1995;12:459–462.51 Westheimer G, Blair SM: The ocular tilt reaction: A brainstem oculomotor routine. Invest Ophthal-

mol 1975;14:833–839.52 Brandt Th, Dieterich M: Pathological eye-head coordination in roll: Tonic ocular tilt reaction in

mesencephalic and medullary lesions. Brain 1987;110:649–666.53 Halmagyi GM, Gresty MA, Gibson WPR: Ocular tilt reaction with peripheral vestibular lesion.

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1987;58(suppl 9)A:192–197.56 Gacek RR: Anatomical demonstration of the vestibulo-ocular projections in the cat. Laryngoscope

1971;81:1559–1595.57 Reisine H, Highstein SM: The ascending tract of Deiters’ conveys a head velocity signal to medial

rectus motoneurons. Brain Res 1979;170:172–176.58 Lang W, Buttner-Ennever JA, Buttner U: Vestibular projections to the monkey thalamus: An

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nucleus and cell group ‘y’. Brain Res (Amsterdam) 1985;336:256–287.60 Glasauer S, Dieterich M, Brandt Th: Simulation of pathological ocular counter-roll and skew-

torsion by a 3-D mathematical model. NeuroReport 1999;10:1843–1848.61 Deecke L, Mergner T, Plester D: Tullio phenomenon with torsion of the eyes and subjective tilt of

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Thomas Brandt, MD, FRCP, Department of Neurology, Klinikum Grosshadern,Ludwig-Maximilians University, Marchioninistrasse 15, D–81377 Munich (Germany)Tel. +49 89 7095 2570, Fax +49 89 7095 8883, E-Mail [email protected]

47Otolithic Vertigo


............................Physiopathology of Otolith-DependentVertigoContribution of the Cerebral Cortex and Consequences ofCranio-Facial Asymmetries

A. Berthoz a, D. Rousie b

a College de France, Paris, etb Universite de Lille, France

Vertigo is a conscious perception of the disorientation between the bodyand space and of illusory movements of the body and/or the environment.Vertigo is not only due to sensory conflicts but can also be due to a conflictbetween defective or biased sensory inputs and internal representations of thebody. In particular, some forms of spatial disorientation are not due to peri-pheral deficits but to high level mechanisms involving the cerebral cortex andthe hippocampus which contribute to the construction of the coherence ofperception and the solution of perceptual ambiguities [1, 2]. It has beenproposed that a number of spatial orientation disorders involve hippocampusand the parieto-hippocampal-prefontal networks for spatial memory duringnavigation [2], ‘spatial neglect’ and the general problem of the perception ofthe subjective mid-sagittal plane of the body [3] and visuo-spatial anxiety [4].

Cognitive Contribution of Otoliths to Spatial Orientation and to thePerception of Movement

The Ambiguity of PerceptionThe otoliths organs of the vestibular system are linear acceleration sensors.

They detect the changes of head velocity in the planes of the maculae with asensitivity of a fraction of one centimeter per second squared. In additionthey detect the static tilts of the head with respect to gravity because gravity

is a kind of linear acceleration whose component on the maculae are indistin-guishable from a linear acceleration.

It has also been suggested that the otoliths do contribute to the estimationof the angular acceleration of the head in cooperation with the semicircularcanals.

The ambiguity of the otolith information (which therefore codes for linearacceleration and static tilt) requires a cooperation with the information givenby vision or proprioception in order to estimate properly the movement andorientation of the body. But visual signals themselves are ambiguous becausethey cannot distinguish between movement of the body in space. For exampleLackner [5] has shown that the same otolithic stimulation can be interpretedin several ways: For instance if one takes a subject in a prone position androtates him in total darkness around a horizontal axis (the so-called ‘barbecueexperiment’), the subject first feels that he is rotating horizontally around themain axis of his body. If then one just applies a pressure on the subject’s feethe suddenly shifts to a percept indicating that he is still rotating around themain axis of his body but this time he is upright. We have ourselves shown[6] that the rotation around an axis inclined with respect to the vertical, thatwe have been the first to introduce in France, induces a perception of a conicrotation whose characteristics can be calculated from an appropriate modelof otolith dynamics and geometry. But this percept itself can vary accordingto the context of the turn.

It is therefore not surprising that many types of spatial disorientation andvertigo can occur depending upon the various reasons for which the coherenceor sensory input is destroyed.

Perception of the Subjective Vertical Can Be Modified by ImaginationThe interpretation of otolithic information is therefore under the control

of central mechanisms of perception which vary according to the referenceframe in which movements are coded. I have insisted upon the flexibility ofthese reference frames [7] which vary depending upon the action in which asubject is involved. We now know that the brain codes movements of limbs,eyes, body, environment in several action-dependant reference frames.

Among all these frames the subjective vertical is a fundamental one: itcorresponds to the perception of the angle of the main axis of the body withrespect to the gravitational vertical. The subjective vertical is an essentialelement of the maintenance of our equilibrium and of the orientation of ourbody in space.

As demonstrated by the experiment using the off vertical axis rotationchair the otoliths play a fundamental role in the perception of the verticaltogether with proprioceptive inputs. An abundant literature deals with this

49Physiopathology of Otolith-Dependent Vertigo

Fig. 1. Perception of forward linear translation. Diagram of the experimental procedure.The subject viewed either the target I or the target II, located, respectively, at 0.8 or 2.4 maway from S (start). Target was straight ahead if the displacement of the sled was programmedalong the X-axis, and on the left side of the subject if the programmed displacement wasalong the Y-axis. Then the subject was blindfolded and was required to push a button whencrossing the previously seen target. The sled moved from S to E (outward) and then backto S (return). Expected (theoretical) responses are situated at target locations on the travelledpath from T1 to T4. From Israel et al. [21].

aspect and I will not come back to these well-known properties. Recently wehave shown, for the first time experimentally, that ‘top-down’ cognitive influ-ences may modify the percept of subjective vertical [8].

Perception and Memory of Pure Angular or Linear MotionWhen we move around in the world we remember our movements. This

‘topokinetic’ or ‘topokinesthetic’ memory is, in part, subserved by a memoryof our head movement measured by the vestibular system. We have studiedthis ‘vestibular memory’ in our laboratory. We have first shown that the braincan use angular acceleration detected by the semicircular canals for the memoryof rotations [9–11].

However, the capacity of the brain to use otolithic information duringnavigation for the memory of travelled paths is still under discussion. Ourgroup has demonstrated the fact that otolithic information interferes andcooperates with visual optic flow for the perception of translations [12–14].We were the first to demonstrate that during vestibular stimulation along alinear path the vestibular system can inhibit visual motion perception. We

50Berthoz/Rousie

Fig. 2. Simulation of subjective position. Bottom part: Sled acceleration (×1 m/s2; thickline) and otolith response (estimate of translational acceleration; thin line). Top part: Sledposition (thick line), target position (horizontal dotted lines), and estimate of subjectiveposition through double integration of the otolith response (thin line). Open squares showthe observed average responses, and filled squares are the simulated expected responses, i.e.the projection of the simulated subjective position onto sled position when the former isequal to target position. From Israel et al. [21].

have observed and measured a striking suppression of visual motion perceptionduring vestibular linear stimulation which suggested this cross-modal inhibi-tory interaction recently also found in brain imaging experiments. In addition,we have shown that otolithic stimulation improves the tracking of acoustictargets [15–17].

We also know that otolith information can contribute to the control ofgaze during passive displacements when the subject has to follow a target withboth the eyes and the head [18].

Finally, we have demonstrated that otolith information can be used forestimation and memory of displacement during passive linear translations(fig. 1) and, most importantly, that the perception of subjects can be predictedwith mathematical models of the otolith organs and the perceptual processes[19–23].

All these results, however, suggest that the precision at which a subject canevaluate his or her translations from otoliths is not as good as the estimation ofrotations from the semicircular canals. The reason for this difference is stillunknown.


Fig. 3. Mobile robot for the study of the perception of 2D motion. A Experimentalsetup: The subject sits on the robot with seat belt fastened, wearing black goggles andearphones. To replicate passive transport he or she uses a joystick. Connection with themicrocomputer is provided by wireless modems. B Procedure: A sample trial measured byodometry. B The subject can indicate, eye closed, the orientation of his body with respectto space with the use of a pointer on a tablet held on his knees (see A ). During the rotationof the robot the subject has indicated with a great accuracy the rotation. C Schematic viewof applied trajectories.

Interaction between Canals and Otoliths for the Perception of2D Displacement TrajectoriesIt is very rare that during our natural displacements we only perform

pure rotations or translations. Most of the time we experience combinationsof rotations and translations. The perception of these displacements impliestherefore both canals and otoliths. Using a mobile robot (fig. 2), we havestudied the interaction between canals and otoliths in the perception of 2Dtrajectories [24]. In these experiments, the subjects were seated on the mobilerobot in darkness. They were submitted to pure rotations (180º), or pure

52Berthoz/Rousie

Fig. 4. Semicircular motion (combination of canal and otolith stimulation). A Schematicview of the applied trajectory. The evolution of the linear acceleration vector is shown withthe arrows. B Rotation and change in magnitude of the linear acceleration vector relativeto the head (the numbers denote the time from the beginning of motion in seconds). C Meanof pointer position responses for all subjects (×1 SEM, thin lines) and actual seat orientationin space. D Superimposed drawings by the subjects of the perceived trajectory. From Ivanenkoet al. [24].

translations (4.5 m) or semicircular trajectories (radius 1.5 m, angular ac-celeration: 0.2 radians per second per second) (fig. 3, 4 and 5). The capacityof subjects to orient themselves eyes closed during their passive transportwas measured by asking them to orient a hand-held pointer towards atarget fixed in the environment. In addition, after the experiment they wereasked to draw their trajectory on a paper. Several manipulations of themovement of the body on the robot during the displacement allowed theidentification of the respective role of canals and otoliths in the perceptionof 2D motion.


In general, the subjects perceived correctly their rotations during thesemicircular trajectory. This suggests a great independence of the perceptionof rotations with respect to the perception of translation. Our hypothesis istherefore that the brain separates these two kinds of perceptions.

It could, however, be that this is dependent upon the intensity of theaccelerations. If confirmed this would have very important implications in thestudy of the pathology of vertigo.

The second interesting result of this work is that the perceived trajectory,as reproduced by drawing, reveals illusions of false trajectories in certainconditions: the trajectory perceived by the subjects is mainly explicable by thestimulation of the semicircular canals in all cases? In fact, the subjects had acorrect perception of their trajectory only when the orientation of the bodywas coherent with the general direction of their movement. The subject per-ceived linear motion when only translations were imposed, but circular trajec-tories were perceived when a 360º rotation was combined with a translation.

Neural Basis of Otolithic Contribution to Spatial Orientation andPerception of Displacement

We now know of at least two pathways for carrying vestibular informationto the cerebral cortex. One of these pathways is through an area called the‘vestibular cortex’.

Vestibular Fields in the CortexExperimental proof of the existence of the PIVC in the monkey was

reported by Grusser and colleagues [25, 26]. Recording the Macaca fascicularis,these authors showed that about two-thirds of the neurons in this area respondto angular vestibular stimulation. The others respond mostly to somatosensorystimulation of the neck and shoulders. Nearly all the vestibular respondingneurons are also activated by movements of the visual environment and bysomatosensory stimulation. The main property of the vestibular neurons inthe PIVC is their sensitivity to angular rotations in various planes, to visualmotion in the directions corresponding to the opposite of the direction ofhead motion in which they are sensitive, and to neck movements in the samedirection as the vestibular response. These properties suggest that the PIVCneurons are coding head movement in space from a combination of vestibular,visual, and somatosensory cues.

It is speculated that one of the operations accomplished in the PIVC isthe extension of the coding of head motion in planes that are more numerousthan in the vestibular nuclei. It is well known that the vestibular and the

54Berthoz/Rousie

Fig. 5. Examples of three experimental conditions for the study of canal otolith inter-action. The subjects are seated on the robot eye closed and are passively transported accordingto the indicated paradigm. A Semicircular motion. B Drawing of the perceived trajectoryafter the motion. C Semicircular motion with the head stabilized in one direction, theresultant acceleration vectors are shown. D Drawing by the subject of his perceived trajectory,note that the circular trajectory has not been perceived. E Translation with a rotation of thesubject on the robot. F Perceived trajectory. Note that the subject has not perceived thetranslational component of the trajectory. From Ivaneko et al. [24].

optokinetic coding of head motion (through the accessory optic pathways) isdone in the planes of the semicircular canals. This geometric selection isprobably useful for matching these two signals at the level of the brainstem.At the level of the cortex, however, the representation of head movements isprobably matched with visual inputs from the medio-temporal (MT) and otherareas, and with various intentions of movement. Therefore, the coding maybe more complex. It is important in the future to study the deficits in patientswith lesions in this area (see Israel et al. 1995). It was also proposed that thePIVC area 3aV, and area 7ant form an ‘inner vestibular circuit’.


Fig. 6. Cortical activation induced by a galvanic vestibular stimulation (Lobel et al.,J. Neurophysiol. 1998).

A second line of evidence [27] comes from the discovery of an influenceof head tilt (i.e. otolithic signals on the receptive field of visual neurons inareas V2 and V3). These authors demonstrated that nearly 40% of the neuronsin area V2 show modifications of their processing of contours during a statichead tilt. They concluded that otolithic signals contribute to the mechanismsof contour processing at the early stages of visual pathways.

Cortical Areas Involved in Vestibular Processing duringGalvanic StimulationAnatomic and electrophysiological studies in the monkey revealed the

existence of multiple interconnected areas in which vestibular signals convergewith visual and/or somatosensory inputs. Although recent functional imagingstudies using caloric vestibular stimulation (CVS) [28, 29] suggest that vestibu-lar signals in the human cerebral cortex may be similarly distributed, thepresent knowledge of the human cortical vestibular system is imprecise.

Galvanic vestibular stimulation (GVS) has been used for almost 200 yearsfor the exploration of the vestibular system. By contrast with CVS, whichmediates its effects mainly via the semicircular canals (SCC), GVS has beenshown to act equally on SCC and otolith afferents. Since galvanic stimuli canbe precisely controlled, GVS is ideally suited for the investigation of thevestibular cortex by means of functional imaging techniques.

We studied [30] the brain areas activated by sinusoidal GVS using func-tional magnetic resonance imaging (fMRI) (fig. 6). An adapted set-up includingLC filters tuned for resonance at the Larmor frequency protected the volunteers

56Berthoz/Rousie

against burns through radiofrequency pickup by the stimulation electrodes.Control experiments ensured that potentially harmful effects or degradationof the functional images did not occur.

Six male, right-handed volunteers participated in the study. In all of themGVS induced clear perceptions of body movement and moderate cutaneoussensations at the electrode sites. Comparison with anatomic data on the primatecortical vestibular system and with imaging studies using somatosensory stimu-lation indicated that most activation foci could be related to the vestibularcomponent of the stimulus.

Activation appeared in the region of the temporo-parietal junction, thecentral sulcus and the intraparietal sulcus. These areas may be analogous toareas PIVC, 3aV and 2v, respectively, in the monkey brain, which form the‘inner vestibular circle’, as named by Grusser, of the cortical vestibular system.Activation also occurred in premotor regions of the frontal lobe. Althoughundetected in previous imaging-studies using CVS, involvement of these areascould be predicted from anatomic data showing projections from areas 6paand 8a of the frontal lobe to the ‘inner vestibular circle’ and the vestibularnuclei.

Using a simple paradigm we showed that GVS can be safely implementedin the fMRI environment. Manipulating stimulus waveforms and thus theGVS-induced subjective vestibular sensations in future imaging studies mayyield further insights into the cortical processing of vestibular signals. Otherinvestigations of the cortical areas involved in the processing of vestibularinformation have been recently performed [28, 31, 32]. It is also interesting tocompare the areas involved in the processing of vestibular signals with thoseinvolved in the perception of the mid-sagittal plane of the body which alsoinvolve parieto-frontal areas [3].

The Head Direction Cell SystemVestibular signals may also reach the cerebral cortex and the hippocampus

through a second route. A ‘head direction’ cell system has been discovered[33, 34]. These neurones, first discovered in the post-subiculum of the rat, firewhenever the head of the animal is directed towards a particular direction inspace independently of where the animal is located in the room. These neuronesare influenced by visual cues and their direction is closely related to theorganisation of the ‘place cells’ in the hippocampus which code location ofthe animal in space. Further studies [35, 36] have revealed that this headdirection information from the vestibular nuclei, through the anterior thal-amus, the mamillary bodies and the subiculum, could reach the hippocampusafter receiving visual environmental information from the parietal cortex,and contribute to the reconstruction at this level of spatial localisation and


Fig. 7. Patient suffering from a cranio-facial asymmetry (torsion of the basio-cra-nium). Observe the asymmetrical positionsof the eyes and ears, the deviation of the noseand the head tilt (with permission).

orientation. At present, only horizontal directions (in the plane of the hori-zontal semicircular canals) have been found in these cells.

The brain has therefore at least two main pathways which seem to carryvestibular information: the PIVC route which codes angular head rotation inmany planes, and the head direction system which codes static head directionin all horizontal directions.

The important result here is that neither of these systems seems specific tocarry translational information from the otoliths. The neural system underlyingotolithic information about translations is therefore still a mystery.

Cranio-Facial Asymmetry: A New Pathology of the Vestibular SystemWe would like to report here a new set of symptoms [37] which are

probably due to a fundamental asymmetry of the anatomical dispositionof the vestibular organs following cranio-facial asymmetry (CFA) whichconcern, at different levels, all the units of the cephalic pole: the vault, thebasicranium, the maxillary and the jaw. These CFA are largely spread inthe European population but they have never been studied as malformativesyndrome because they are located between the ‘normal’ and the ‘path-ological’.

These patients have a number of symptoms (fig. 7): laterocolis (headtilt in roll), most of the time, to the right side, eye skew deviations, oculartorsion, cephalic and back pains, scoliosis, spatial disorientation and some-

58Berthoz/Rousie

Fig. 8. Asymmetry of the otoliths organs of the labyrinth. MRI measurement of theasymmetrical position of the labyrinths: The auditory meatus or the horizontal canals areused as markers to estimate the asymmetry (in position and in orientation) between the rightand left labyrinths. Observe the concomitant asymmetry of the inferior temporal lobe.1>Auditory meatus; 2>horizontal canal. From Rousie [39].

times agoraphobia, etc., which have been studied (Rousie D. 1999) on morethan 2,500 patients with the collaboration of several departments of theUniversity of Lille (Pr. Hache, Pr. Gieu, Dr. Van Tichelen, Dr. Deroubaixand Dr. Pertuzon). We shall only report here a summary of these deficitsand the results of some functional tests. Most of the tests which we haveperformed so far are static and the contribution of otolithic asymmetrycannot be separated from the consequence of semicircular canal asymmetries.In addition, we cannot exclude that, given that these patients present ahead tilt, and a pronounced spatial asymmetry of the anatomy of theorbits, proprioceptive biases do contribute to some of the postural or evenoculomotor asymmetries observed. We believe that a fundamental compo-nent of the functional perturbations of posture and of the oculo-vestibularsystem as well as some cognitive dysfunctions are due to a distortion inthe body schema induced, to distortion in the vestibular anatomy and toan uncompensated asymmetrical anatomy of the otoliths, and the orbitalasymmetry.


MethodsThese cranio-facial asymmetries are induced by asymmetries of the basi-

cranium which have been measured using MRI scanning (fig. 8) and a newreference frame. The use of this reference allows comparisons between differ-ents subjects [37, 38]. The principle of MRI exploration consists of determin-ing an intracranial reference system formed by two planes: a vertical (mediansagittal) and a horizontal plane, perpendicular to each other. These twoplanes are constructed by using points as close as possible to the embryonicepicenter of the cerebral growth [38, 39]. We have used neural tube points:middle of the hypophysis, the steepest point of the third ventricle, one ormore points of the stalk of the pituitary. This reference makes it possible toobtain reproducible measurements independent of the position of the patient’shead in the machine. Therefore, it is necessary to re-orient the subject’s headin the three axes of possible movement: along the craniocaudal axis (roll)and the transverse axis (pitch). The pitch position was determined by thedeviation from the perpendicular given in the two other planes mentionedabove. This determination is facilitated by placing the head in the Frankfortorientation before the examination. We used a high-field Philips gyroscan(1.5 Tesla) which allows double correction of angulation. Its reliability wasevaluated at 1º and 1 mm.

The topographic asymmetry of the two posterior hemibases, expressedby the respective positions of the external semicircular canals, the cochleae orthe auditory meatus taken as reference points, is easily obtained by multiplyingthe number of sections separating these structures by the distance betweensections.

Anatomical FindingsThe asymmetries in otolith anatomy had to be derived from the observa-

tion of the geometrical disposition of the semicircular canals. The analysis of62 cases of CFA allowed the classification of several types of CFA accordingto the spatial position of the external semicircular canals taken as points ofreference.

Anteroposterior Asymmetry. The horizontal semicircular canals appear onthe same horizontal section but on different coronal sections. This indicatesthat one of the canals is anterior to the other in the median sagittal plane.This induces an A-P positional asymmetry of the two posterior hemibasesconstituting the petrous bones. We have observed variations between 0 and6.6 mm. In 14 cases of such A-P asymmetry, we have observed 11 cases inwhich the left canals were anterior to the right canals (78.5%). In this typeof asymmetry, most subjects had canals strictly parallel to each other. In thisstudy, asymmetry of orientation was only encountered once.

60Berthoz/Rousie

Examination of the position of the orbital cones revealed an identicalasymmetry: the face demonstrates exactly the anomalies of the underlyingbasis. Thus, for a left canal placed more anteriorly in the coronal plane,a more anterior left orbital cone will be found. Keeping in mind the lawof correspondence of the visual axes activated during fixation (Law ofCorrespondence of Hering), we looked for an expression of this asymmetryat the level of the eyeballs and we observed a significant proportion ofesophorias or of convergent strabisms located in the more posterior eye,as though the eyes were attempting to compensate the deeper position inthe orbit. This deviation of the eyeball was accompanied by an abnormalposition of the head – in rotation (yaw) as though the patients were com-pensating for the retreat into the orbit with their head and seeking a‘mean’ position of comfort, perhaps with a desire to regulate depth per-ception to the best extent possible? In any case, the stereotypic test used(Wirt) did not reveal any extreme anomaly, no doubt because it is notprecise enough.

Asymmetry in Torsion. The canals appear on different sections, bothin the horizontal and in the coronal plane. This indicates a true torsion ofthe base of the skull. This is by far the most frequent type of asymmetry(62.9% out of 62 patients). In this population, analysis of the variationsincluded between 2.2 and 6.6 mm revealed a much larger proportion ofelevated left labyrinths in the vertical plane (71.7%) associated, in thehorizontal plane, with left labyrinths in a more anterior position (48.7%).This deformation is in agreement with the counter-clockwise cerebral de-formation (petalia) described before [40–42]. This is an expression of thepredominance of the left hemisphere. As in A-P asymmetries, the face followsthe direction of the twisting of the base. This is expressed by frequentdeviations of the nasal septum and of the spatial asymmetry of the orbitalcones.

Vertical Asymmetry. In these cases, asymmetry is only found in the verticaldirection. Frequency is 15.3% out of 62 patients. This is a variant of torsionalsymmetry described above.

Lateral Asymmetry. In these cases, it is the distance of a canal, taken asa reference point in relation to the midline, which presents a right/left asym-metry. The frequency is rare, at only 3 of 62. This type of CFA seems to haveno effect on the oculo-labyrinthine system and rather seems related to a‘fluctuating asymmetry’ as described by Lacy and Horner [43].

Asymmetries of Orientation. We have found 12 cases of asymmetries oforientation out of 62. It should be pointed out that within the framework ofthis study, no precise measurement was made of the difference in orientationbetween right and left canals.


Fig. 9. Measurement of ocular torsion; the image of the scanner ophthalmoscope isused to calculate a static torsion. O is the center of the macula. OAB gives the angular valueof the torsion. In this case torsion is 9º on the right eye and 0º on the left eye. From Rousie[39].

Visual AcuityWe shall only, in the frame of this review, describe a few examples of

the results obtained in the various functional tests which have been usedto characterise the anomalies in these patients; detailed accounts have beenpublished elsewhere [39].

Examinations of visual acuity undertaken to eliminate subjects with majorophthalmic anomalies which might bias the results have shown an increasedfrequency of astigmatism of curvature and/or of hypermetropia (70% of 50 pa-tients), probably an expression of the asymmetry of orbital cones both in theirshape and their spatial position. Standard oculomotor evaluations have shownan increased frequency of convergence insufficiency, especially in distant vision.

SLO ExaminationIn a group of 50 subjects carrying CFA, the comparison of foveal position

right eye/left eye performed with a scanner ophthalmoscope (fig. 9) revealeda more elevated frequency of exocyclotorsion in the left eye, namely 30 casesout of 50 or 60%, whereas in the right eye it was in 16 cases out of 50 or32%, for a difference of 28%. The mean value of cumulated torsions is –5.72ºfor the right eye and –8.04º for the left eye.

In order to clearly separate the CFA pathological effect from nonpatholo-gical cases, we investigated eye position on two control groups.

In a first group of 50 nonselected control subjects, we found a moreelevated frequency of cyclotorsion in the left eye (21 cases out of 50 or 42%)than in the right eye (7 cases out of 50 or 14%). This gives a difference of28%. The mean value of the cumulated torsions of the left eye is –5.70º and

62Berthoz/Rousie

Fig. 10. Test of the index. This test isperformed eye closed and the patient is askedto indicate the subjective horizontal. Thephotograph is taken when small body oscilla-tions appear indicating that the subject haslost the memory of the visual vertical. Theangle made with respect to the true hori-zontal (or the true vertical) which can bemeasured by reference to a line drawn on thewall (behind the subject) gives the measureof the deviation of the subjective nonvisualhorizontal.

for the right eye, –3.08º. Thus, on the average, the foveal positions are locatedcloser to the horizontal central pupillary axis of reference than in CFA subjects.This group is interesting because it calls attention to the frequency of thefoveal position in a control population: we found a 44% frequency of fovealsymmetry in which the difference between right and left was less than 2º. Itshould be kept in mind that because of the frequency of occurrence of CFAin the population, this group presented an epidemiological bias which justifiedstudying the second group.

A second group of subjects composed of selected control subjects pre-senting no scoliosis, no use of eye glasses, no instability, no multiple musculo-articular pain or CFA visible to the naked eye. In this group, only one caseof cyclotorsion was found, in the right eye, representing a frequency of 2%.The mean value of the cumulated foveal positions of the right eye was –2.66ºand of the left eye was –3º.

The SLO made it possible to look for a possible exocyclotorsion associatedwith identified vestibular deficit as judged by the studies of Deroubaix.

In a group of 45 CFA patients presenting some clinical signs of vestibulardisorders, we found 100% high-level exocyclotorsions, in a range from 5º to13º (with the average cumulative value for left and right of foveal positionsbeing 8.4º, and with 23 torsions in the left eye and 22 in the right). Comparisonbetween the eye with torsion and the defective labyrinth showed that in 39cases, the torsion was on the same side as the vestibular deficit; in only 6 caseswas there an inverse localization.

In a control group of 17 patients having vestibular signs but no CFA, wealso found 100% exocyclotorsion with a mean value identical to that of the


Fig. 11. Scoliotic deformation in a pa-tient with cranio-facial asymmetry. X-rayreveals a deformation of the spine with aleft lumbar curvature associated with a righthead tilt in the roll plane.

previous group. The torsion was always ipsilateral with the labyrinthine deficit.In these two groups, the comparison of the two ipsilateral signs (torsion andvestibular deficit) with the direction of the laterocolis showed an identicallateralization, in agreement with the ocular tilt reaction described by Brandtand Dieterich [44, 45].

Spinal Column and PostureThe test of Fukuda (walking in place with eye closed and measuring the

deviation of the orientation of the feet in the horizontal plane) was considerednegative for a left or right rotation less than 30º. 34% of patients presented aright deviation and 66% presented a left deviation. It should be pointed outthat these deviations are in a direction opposite to the head tilt and ipsilateralwith the lumbar convexity. The mean value of the deviation is 50º, both tothe right and to the left.

The test of the nonvisual subjective horizontal (test of the index) showed(fig. 10), out of 50 patients, that 9 did not present inclination of the index fingers.25 presented a right deviation (50%) and 16 presented a left deviation. The devi-ation of the slope of the index fingers was always ipsilateral with the head tilt.

Scoliotic deformations (fig. 11) were also found with often a left lumbarcurvature associated with right head tilt in the roll plane. This finding shows

64Berthoz/Rousie

that probably the whole body scheme in these patients is distorted and furtherwork is needed to understand the hierarchy of mechanisms between vestibularasymmetry, ocular deviation and postural asymmetries.

Blind walking test: Patients were asked to walk straight, eyes closed, fora distance of about 5 m. Horizontal path deviation was always ipsilateral withthe head tilt.

Test of VideonystagmographyA search for spontaneous nystagmus was carried out with open eyes, with

and without focusing (on the center), with eyes open in darkness, alwayscarried out at the beginning of the examination so that results can dictate thechoice of another test: In a group of 45 patients with CFA, 3 presented avertical nystagmus of cervical origin, 17 of 45 presented nystagmus with openeyes without fixation, that is, 37% of the cases.

The patients were also submitted to a number of vestibular tests forhorizontal canal function. The impulsional rotation test [46] revealed thelargest number of anomalies in the two groups. Labyrinthine performancewas measured on the Courtat graph: this test showed 100% interlabyrinthineasymmetry, with 15 cases of left-sided deficit and 30 cases of right-sided deficit.

For 16 subjects, this asymmetry disappeared under the effect of intensestimulation (head-shaking test) whereas for 29 subjects, the asymmetry per-sisted. For these 29 subjects, other tests described here were able to refine thediagnosis. For 15 subjects, the failure of the asymmetry to disappear had acentral origin, for 23 subjects, it had a central cervical origin, and for 7 subjects,a traumatic origin was found.

More work is obviously needed to elucidate the contribution of the otolithsin this pathology but we would like to propose that vestibular asymmetry maybe a common cause to symptoms which are treated separately and that thesepatients suffer from a more general distorsion of their body schema. This mayexplain some of the cognitive spatial disorders which are associated withcranio-facial asymmetry. It may also explain why wearing adequate prismsoften improves a number of the symptoms.

Acknowledgements

We thank F. Maloumian for the preparation of the figures. We also thank Dr. Deroubaix,Service ORL de Bethune, Dr. Pertuzon, Service de Neuroradiologie, CHRU Lille, and Dr. VanTichelen, rheumatologist, for their active collaboration, Prof. Hache, Service d’Explorationfonctionnelle de la vision, CHRU Lille, for his support and the use of the SLO, and Prof.Pellegrin for his support throughout this research. This work was supported by the CentreNational d’Etudes Spatiales.


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23 Israel I, Berthoz A: Contribution of the otoliths to the calculation of linear deplacement. J Neurophy-siol 1989;62:247–263.

24 Ivanenko YP, Grasso R, Israel I, Berthoz A: The contribution of otoliths and semicircular canalsto the perception of two-dimensional passive whole-body motion in humans. J Physiol (Lond) 1997;502:223–233.

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37 Rousie D, Hache JC, Pellegrin P, Deroubaix JP, Berthoz A: in Cohen B (ed): Oculomotor, posturaland perceptual asymmetries associated with a common cause: Craniofacial asymmetries and asym-metries in vestibular organs anatomy, in Cohen B ed 8. New York, Annals New York Academy ofSciences, 1999.

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primate. Ann NY Acad Sci 1976;280:349–364.43 Lacy RC, Horner BE: Effects of inbreeding of skeletal development of Rattus. J Hered 1996;87:

277–287.44 Dieterich M, Brandt T: Ocular torsion and tilt of subjective visual vertical are sensitive brainstem

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Dr. A. Berthoz, College de France, UMR CNRS 9950,11, Place Marcelin Berthelot, F–75005, Paris (France)E-Mail [email protected]



............................Clinical and Instrumental InvestigationalOtolith Function

Lars Odkvist

Department of Otolaryngology, University Hospital, Linkoping, Sweden

For balancing and oculomotor function the inner ears are of great impor-tance. Proprioception and vision converge and cooperate with the inner earafferents in the vestibular nuclei, the thalamus, the cerebellum and the cerebralcortex. The semicircular canals are transducers of the angular acceleration ofthe head and the otoliths, sacculus and utriculus, are the sensors for linearaccelerations. These linear accelerations are the gravity and the forces de-veloped when we perform motions. In health the afferents from vision, proprio-ception and inner ears result in harmonic and efficient movements, appro-priate ocular movements and also perception of movement and position. Indisease, malfunction of the otolithic organs may cause vertigo, illusion of tilt,balance disorders and oscillopsia.

Otolith Functions

Utriculus and sacculus are endolymph filled and in near proximity to thesemicircular canals. The neuroepiphelium is concentrated to a plate in eachutriculus and sacculus. This plate consists of gelatinous substance with calcium-carbonate crystals, otoconia, embedded on the free surface and with cilia ofhair cells projecting into the membrane. The specific weight of endolymph isaround 1, and the density of the crystals is 2.7. When there are linear forcesalong the plane of the macula, the gelatinous material supported by theotoconia tend to slide somewhat according to inertia or force of gravity.Although the displacement of the otolithic membrane only is about 1 lm, itis enough to cause polarization or depolarization in the hair cells. This causesan increase or decrease of the firing rate in the utricular and saccular nerves.

The plane of the macula sacculi is vertical and thus the sacculus responds tovertical movements. The plane of the utricular maculi is in the plane of thelateral semicircular canals. Thus, they respond mostly to horizontal move-ments. In the utriculus the polarisation of the hair cells is such that 75–80%of the cells respond mostly to a force directed in the lateral direction. Thismeans that the main response of a tilt towards right is coming from the rightinner ear utricle. When tilting towards left the utricle in the left inner earcontributes with approximately 75% of the response, 25% coming from theright utricle. This background has importance for understanding of the utricletesting. Some otolithic afferents show a regular firing but others have anirregular pattern. The neurones with regular firings show little adaptation tomaintained forces, but the irregular neurones have an intense reaction to thechange of stimulus but adapt rapidly [1]. Otolithic stimulation causes eyemovements [2]. Electrical stimulation causes a torsion of the eyes away fromthe stimulated side. Unilateral vestibular nerve sectioning causes a torsion ofthe eyes towards the contralateral side [3].

Ocular Counter Torsion

In clinical investigations it is easy to see that tilting the head causes atorsion of the eyes around the visual axis to compensate for the head tilt. Theamount of the torsion (counter-rolling) is approximately 10% of the head tilt.Subjects without otolith function do not have counter-rolling. Static counter-torsion depends on otolithic influence and is not a semicircular canal response.The response is mainly a function of the utricles. The size of the counter-rolling response is corresponding the shear force acting on the macula utriculi[4, 5]. Different studies are not in unison concerning the direction of counter-torsion in unilateral loss which makes it somewhat uncertain whether measure-ments of ocular counter-rolling can localize unilateral lesions with certainty[6, 7]. For recording counter-rolling, a computer-based pattern recognitionsystem is necessary.

Eccentric Rotatory Testing

When a subject is seated in a rotatory chair and angular acceleration isperformed, the semicircular canals are stimulated. In order to have the fullresponse from the lateral semicircular canals, the head should be tilted 30ºforwards during the test. As the canals react to acceleration, there is no responsefrom the semicircular canals during constant velocity rotation. However, in

69Clinical and Instrumental Investigational Otolith Function

Fig. 1. Eccentric rotatory testing in theclockwise direction. The patient is ready toadjust the LED bar in darkness.

this position and during constant velocity rotation there is a centripetal forceacting upon the utricular maculae. In this test the patient should be seatedsome distance from the rotation center facing the direction of rotation whichwill provide a constant lateral acceleration stimulus (fig. 1). The effect of theinitial angular acceleration will cease some time after the rotation has reacheda constant speed. To exclude visual cues to the true orientation of the subject,the rotation takes place in complete darkness. Despite the pressure from thechair on the body and shoulder it is obvious the subject will experience astrong sensation of lateral tilt. He may then give a subjective estimate of howan imagined horizontal surface would be oriented in front of him. This angle,relative to true horizontal, is an estimate of subjective tilt. The sensation oftilt depends on information from both otolithic organs. The side which isdirected outwards in the rotation gives the biggest contribution to the responseand the opposite side contributes only to a minor extent. This is due to theorientation of the hair cells in the macula utriculi. Thus, the response can beconsidered mainly an estimate of the function of the otolith organ in thelaterally directed ear. The equipment consists of a low torque rotatory chairwith the subject 100 cm from the vertical rotation of axis facing the directionof the constant rotation. The chair may be turned around 180º on the bar inorder to change the rotation direction. Rotation may be started with an angularacceleration of 10º/s2 until angular velocity 120º/s is reached. Using this param-

70Odkvist

Fig.2. Top: Thebiasbarwith LEDs. Bottom: In dark-ness, only the dimly lit row ofLEDs are visible.

eter the theoretical tilt angle is 24º (fig. 3). The room is in total darkness.Approximately 60 cm in front of the subject’s eyes a dimly lit light emittingdiode (LED) bar is turned on for the subject to adjust (fig. 2). This is performedvia a three-button keyboard in the patient’s hands. The patient is asked toposition the bar in the position horizontal water surface would have. Bydefinition, a perceived tilt outwards results in a positive angle due to the tiltillusion the patient has during the constant velocity rotation. A software inthe computer administrates the test via an operator and reads the set anglesof the LED bar. The subject is strongly strapped to the chair to minimizebody movements and the head is held in an adjustable frame. Eight or sixmeasurements of perceived horizontal are performed before rotation is started.The mean and standard deviation is computed. The chair is started in one


Fig. 3. Accelerations acting on a person ineccentric rotation. ah>Horizontal accelera-tion; g>gravity; R>resulting linear accel-eration; />angle of vertical illusion.

direction and after 1 min of constant rotation, another eight measurementsare done. The chair is decelerated and after 1 min of complete stop anothereight measurements are conducted. After some minutes the chair is turned inorder to conduct an identical series of measurements using the other rotationdirection, again with the patient facing the directional rotation. Before rotationthe subjects do not perceive any significant tilt from true vertical. Duringconstant rotation a tilt outwards of about 20º is perceived. After rotation aninwards tilt of only roughly 0.5º is experienced. For practical purposes obvi-ously this very small illusion of postrotatory tilt is neglected. A standarddeviation of about 6º in each direction is found in healthy subjects. In thesame healthy subjects there was no difference between the responses with theright ear outwards compared to the left ear outwards. As the test is performedin darkness, vision has no horizontal structures to relate to. We have alsoshown that the results are the same even if the test is performed only withone eye open and the other closed. The fact that the reported tilt as a meanis 20º and not 24º may be due to the influence of proprioceptive cues fromthe position of the body and head in the rotatory chair. The instruction to

72Odkvist

the patient is important so that the patient does not try to adjust the LEDbar in perpendicular line to the body axis. In clinical practice, the eccentricrotatory test is useful to monitor unilateral or bilateral loss of utricular func-tion. It is also possible to record recovery after certain types of nonpermanentvestibular lesions and also the improvement caused by central compensatorymechanisms [8–10].

Subjective Visual Horizontal Test without Rotation

If a person is sitting in a chair, in a totally dark room and ask to alignan LED bar horizontally, most persons come with an error smaller than 2º[8]. If the test is performed before and after vestibular nerve sectioning, afterhaving been normal, after surgery they set the bar tilted towards the lesion’sside between 5 and 15º. The reason is that they see the gravitationally horizontalbar tilted towards the intact side. Many months and even years after the lesionthey often have a subjective horizontal error of approximately 4º [9]. The testusing the LED bar in darkness for subject horizontal testing is very useful inclinical practice.

The Tilting Chair

The subjective visual horizontal may be measured in different tilt positions.The chair with an adjustable tilt in the lateral direction is used. The patientshould be secured in the chair with support for body and head. The headshould be tilted approximately 10º nose down compared to natural headposition. In front of the eyes at a comfortable distance there is a LED barwhich is adjustable concerning tilt with a remote control. The patient is testedin 10º, 20º and 30º tilt. The tilt makes the test more sensitive than test in zerotilt [11, 12].

Vestibular-Evoked Myogenic Potentials

Loud monaural clicks evoke myogenic potentials in the ipsilateral sterno-cleido muscle. It is obvious that these potentials are evoked by the vestibularorgan in the inner ear. They appear even if the ear is deaf. Thus, the vestibular-evoked myogenic potentials can be used as a clinical test of the vestibulocolicreflex. The origin of the reflex is the sacculus situated close to the cochlea andbeing stimulated by endolymph movement caused by the clicks. The click


should be 0.1 ms with 95 dB loudness. The electrode placed over thesternocleido muscles picks up a short latency response usually sized 60–300 mV.During the test, the patient in the prone position should be contracting thesternocleido muscles by lifting the head somewhat. The positive/negative poten-tial has peaks at 13 and 23 ms. If there is no vestibular function due to, e.g.neurectomy the responses are absent. Sensorineural hearing loss does notinhibit the reflex. The reflex is generated by synchronous discharges of musclecells. If there is a conductive hearing loss, the click does not reach the innerear fluids and there is a very low intensity of the response. In those cases abilateral myogenic potential can be stimulated by using small rubber hammertap the forehead [13].

Discussion

In some instances it is of value to know if a patient has utricular andsaccular function in the inner ear. The patient may have symptoms that leadto the suspicion that there is faulty function of the otolithic organs. Also inthe diagnostics of a possible acoustic neuroma the rotatory test investigatesboth lateral semicircular canals and the caloric test mainly is able to diagnosethe function of the lateral semicircular canal. This canal is represented in theupper part of the vestibular nerve but a test for the inferior vestibular nerveseems necessary. For testing of the sacculus, vestibular evoked myogenic poten-tials seems to be a method of choice using monaural clicks. The ipsilateralreaction in the sternocleido muscle can be detected and thus loss of functionin the inferior vestibular nerve can be diagnosed [14]. Loss of hearing in theear does not abolish the myogenic potential.

In Meniere’s disease a loss of sacculus function proven with vestibularevoked myogenic potentials is often found [15]. We have also found that in someMeniere’s patients the utriculus function is diminished or absent according tothe eccentric rotatory test. After gentamicin treatment usually the utricularfunction is lost or diminished but can be present even if the caloric responseis gone. After gentamicin treatment the vertigo attacks are usually gone butsometimes the patient complains about some attacks of vertigo but withouta sensation of rotation [13]. This might be due to a lack of vestibular rehabilita-tion and nonperfect central compensation but could also be due to otolithicreactions to variations of the endolymphatic pressure. If there is a remainingotolithic function, additional installments of gentamicin in the inner ear maysolve the problem [16].

Not infrequently do patients after vestibular neuritis develop benign par-oxysmal positioning vertigo. If there is no caloric response it may be intriguing

74Odkvist

for the physician that a nonfunctioning ear can cause the rotatory attacks.Caloric testing with the head positioned in such a way that the posteriorsemicircular canal is in the vertical plane may, however, show that there issome caloric response and furthermore a sacculus test can prove that theinferior vestibular nerve still has function. Thus, a benign paroxysmal posi-tioning vertigo can appear from a functioning posterior semicircular canal[17].

Even in cases with hypermobile stapes and dehiscent superior semicircularcanal the click-evoked myogenic potential test can be of help [18].

The myogenic potential test may even prove that in some patients therehas been an acute loss of function in the inferior vestibular nerve proven bythe evoked myogenic potential test in an ear with a normal caloric responsethus proving the inferior nerve vestibular neuronitis [19].

For practical purposes the LED bias bar test seems to be simple tointroduce and useful for utriculus testing [20]. This test using the subjectivehorizontal may be improved using the tilting chair. An even stronger stimulusis introduced with the eccentric rotatory chair. Introducing the click-evokedvestibular-evoked myogenic potential test seems possible in most laboratoriesas the statement for auditory testing usually can be applied for this procedure.

The otolithic organs are often forgotten, but the new simple test methodsoffer the clinician tools for the relatively easy diagnostics.

References

1 Goldberg, JM, Fernandez C: The vestibular system; in: Handbook of Physiology. The NervousSystem III. Washington, American Physiologic Society, 1982, pp 977–1022.

2 Suzuki J-I, Tokomasu K, Goto K: Eye movements from single utricular nerve stimulation in thecat. Acta Otolaryngol 1969;68:350.

3 Dai MJ, Curthoys IS, Halmagyi GM: Linear acceleration perception in the roll plane before andafter unilateral vestibular neurectomy. Exp Brain Res 1989;77:315–328.

4 Woellner RC, Graybiel A: Counterrolling of the eyes and its dependence on the magnitude ofgravitational or inertial force acting laterally on the body. J Appl Physiol 1959;14:632–634.

5 Colenbrander A: Eye and otoliths. Aeromed Acta 1964;9:45–91.6 Krejcova H, Highstein S, Cohen B: Labyrinthine and extra-labyrinthine effects on ocular counter-

rolling. Acta Otolaryngol 1971;72:165–171.7 Diamond SG, Markham CH, Furya N: Binocular counterrolling during sustained body tilt in

mormal humans and in a patient with unilateral vestibular nerve section. Ann Otol 1982;91:225–229.8 Curthoys IS, Dai MJ, Halmagyi GM: Human otolithic function before and after unilateral vestibular

neurectomy. J Vestib Res 1991;1:199–209.9 Halmagyi GM, Curthoys IS, Dai MJ: The effects of unilateral vestibular deafferentation on human

otolith function; in Sharpe JA, Barber HO (eds): The Vestibulo-Ocular Reflex and Vertigo. NewYork, Raven Press, 1993, pp 89–104.

10 Gripmark M, Odkvist LM, Larsby B, Ledin T: Perceived subjective horizontal during eccentricrotatory testing; in Claussen CF, Sakata E, Itoh A (eds): Vertigo, Nausea, Tinnitus and HearingLoss in Central and Peripheral Vestibular Diseases. Elsevier, Amsterdam, 1995, pp 355–359.


11 Tribukait A, Bergenius J, Brantberg K: The subjective visual horizontal for different body tilts inthe roll plane: Characterization of normal subjects. Brain Res Bull 1996;40:375–383.

12 Bergenius J, Tribukait A, Brantberg K: The subjective horizontalat different angles of roll tilt inpatients with unilateral vestibular impairment. Brain Res Bull 1996;40:385–391.

13 Colebatch JG, Rothwell JC: Vestibular-evoked EMG responses in human neck muscles. J Physiol1993;473:18P.

14 Murofushi T, Matsuzaki M, Mizuno M: Vestibular evoked myogenic potentials in patients withacoustic neuromas. Arch Otolaryngol Head Neck Surg 1998;124:509–512.

15 de Waele C, Tran Ba Huy, Dirad J-P, Freyys G, Vidal P-P: Saccular dysfunction in Meniere’s disease.Am J Otol 1999;20:223.

16 Odkvist LM, Bergenius J, Moller C: When and how to use gentamicin in the treatment of Meniere’sdisease. Acta Otolaryngol (Stockh) 1997;(suppl 526):54–57.

17 Colebatch JG, Rothwell JC, Bronstein A, Ludman H: Click-evoked vestibular activation in theTullio phenomenon. J Neurol Neurosurg Psychiatry 1994;57:1538–1540.

18 Minor LB, Solomon D, Zinreich JS, See DS: Tullio’s phenomenon due to bone dehiscence of thesuperior semicircular canal. Arch Otolaryngol Head Neck Surg 1998;124:249.

19 Fetter M, Dichgans J: Vestibular neuritis spares the inferior division of the vestibular nerve. Brain1996;119:755.

20 Odkvist LM, Ledin T, Larsby B, Gripmark M, Noaksson L, Olsson S: Otolithic tests in Meniere’sdisease; in Soren V, Morten K, Pernille M (eds): Meniere’s Disease. 16th Danavox Symposium,September 19–22, 1995, pp 247–254. Koldning, Scanticon, 1995.

Lars Odkvist, Department of Otolaryngology, University Hospital,SE–581 85 Linkoping, (Sweden)Tel. +46 13 22 20 00, Fax +46 13 22 25 04, E-Mail [email protected]

76Odkvist


............................The Subjective Visual Vertical

Ch. Van Nechel a, b, M. Toupet a, c, I. Bodson a, d

a IRON (Institut de Recherche en Oto-Neurologie), Paris, France;b Unite de Neuro-Ophtalmologie, Cliniques Universitaires de Bruxelles Erasme et

CHU Brugmann, Service de Revalidation Neurologique, Bruxelles, Belgium;c Centre d’explorations fonctionnelles otoneurologiques, Paris, France;d CHU La Citadelle, Service ORL, Liege, Belgium

The subjective visual vertical (SVV) is the angle between the physicalvertical line (gravitational axis) and the position of a visual linear markeradjusted vertically by a subject. This SVV is probably computed from thesame sensory information as the postural vertical (position of the body axiswhen the subject estimates he is vertical), but the respective contribution ofeach of these informations to the estimation of these two verticals is highlydifferent. The SVV is probably not an intermediate stage in the elaborationof the postural verticals. This explains the discrepancies between tiltings ofpostural and visual vertical. As far as the SVV is considered here as anapproach to the evaluation of the otolithic function and not as a tool tryingto explain an impaired posture, this discrepancy will not be further consideredin this paper.

The sensibility of otolithic organs to the gravity force suggests that theyplay the main role in the estimation of the physical vertical orientation. Visualinformation can, however, modify this perception [3]. Moreover, the efficientuse of these otolithic and visual informations for the postural control impliesan adjustment according to the position of the head with regard to the trunk.Cervical somatosensory but also cutaneous, muscular and articular infor-mation are able to contribute to the estimation of the physical vertical orien-tation.

The SVV is frequently impaired in labyrinthic disorders [4], in lesions ofthe vestibular nerve [9], of the vestibular pathways within the brainstem [10]or in the vestibular cortical areas [6]. Is it allowed then to consider the measureof the SVV as a tool for the evaluation of the otolithic function?

To validate this measure, it is necessary first to prove its sensitivity to theotolithic dysfunctions and then to demonstrate that the methodology usedreduces the risks of interference of the other sources of error, and is notaffected by any substitutions for otolithic deficit.

The SVV in the Otolithic Disorders

An isolated otolithic dysfunction is rare, it is chiefly based on complaintsand, so far, the specific stimulation of this function requires a heavy instru-mentation. The deficit of the otolithic function, in association with the other,more dynamic, labyrinthic components, is however warranted in surgical le-sions such as labyrinthectomies or neurectomies. The SVV being a staticmeasure, it is reasonable to think that the deficit of the dynamic componentsinterferes little with it. So, ipsilateral tilt of the SVV in acute one-sided vestibu-lar deficits resulting from labyrinthectomy and neurectomy [9, 13, 20] suggeststhe implication of otolithic organs in the estimation of the visual vertical. Itis also frequently disturbed in less complete lesions. The rate of abnormalitiesof the SVV amounts to 89% in a group of vestibular neuritis [4] and to 47%in acute labyrinthitis [20].

The lesions of the central pathways originating from vertical canals andotolithic organs also lead to an ipsi- or contralateral tilt of the SVV accordingto their location [5, 6]. If the most striking clinical signs of benign paroxysmalpositioning vertigo (BPPV) are very likely of canalar origin, the pathologicalstarting point is well otolithic. One can thus wonder about the possible effectof otoconia loss on the SVV. A first study concerning 19 cases suggested theabsence of abnormality of the SVV [4]. We studied the SVV in 1,000 consecutivecases of BPPV, of which 933 were one-side according to the clinical examina-tion. The comparison of the distributions of the values for SVV measuredbinocularly, with straight head, in these patients with an estimation of theSVV in a normal population, computed on base of a group of 81 controlsubjects, shows a spreading of the distribution (fig. 1). Values of more than2.8º, were present in less than 5% of control subjects, but were observed for16.4% of the right BPPV and in 14.2% of the left BPPV. The deviation of theSVV is more often ipsilateral to the side considered as affected by the clinicalexamination (v2 test: p>0.002). The presence of contralateral tilts neverthelesscalls for some comments. The area of the utricule macular disrupted by theloss of otoconia could be in cellular fields sensitive to ipsi- or contralateralhead tilt. Another explanation could be a bilateral otolithic disorder expressingonly by a one-sided BPPV. Finally, the structures of the visuo-vestibular in-tegration could have developed a correction by moving contralaterally the

78Van Nechel/Toupet/Bodson

Fig. 1. SVV distribution in 993 patients suffering from unilateral BPPV compared witha VVS estimation in a normal population (N), computed from a sample of 81 controlsubjects.

‘otolithic’ vertical (calibration of the zero point) to maintain a good agreementbetween vestibular and visual information.

If the deviation of the SVV is frequent in acute lesions of the vestibularsystem, it becomes rare in chronic deficits, including bilateral vestibular are-flexia [8].

So if the SVV seems rather sensitive to acute lesions disturbing the otolithicsystem, it is now necessary to consider its specificity. This leads us to look atthe other factors likely to modify the SVV.

The Stages of the SVV Measure

A model (fig. 2) resuming the various stages of the measure allows toidentify the potential, not vestibular, sources of SVV impairments, or thesubstitution strategies capable of masking a vestibular disorder. The estimationof the subjective vertical can be performed by adjusting a marker using visual,somatosensory or postural information. We shall only consider measures invisual modality and in a frontal plane.

The Visual InputThe first stage of the SVV measure is the visual perception of a linear

marker projected on the retina after a passage through the transparent struc-

79The Subjective Visual Vertical

Fig. 2. Theoretical model of the VVS measure.

tures of the eye. This first stage can already introduce a deviation of the SVV.So, an uncorrected oblique astigmatism, or an ocular torsion (rotation aroundthe optical axis of the eye) can, independently of any notion of verticality,lead to an error in the orientation perception of a visual object. These torsionsare present in oculomotor palsies but also, physiologically, when the positionof the eyes is a combination of horizontal and vertical rotations in the orbits(tertiary position). The direction of these physiological torsions can be pre-dicted by the Listing law. This defines all the positions of the eyes by theirrotation on the axis situated in an equatorial plane. The tilt of this axis isconstant for every position of the eyes, whatever way this position is reached.As a consequence, the meridian of the eye, vertical in primary position bowsfor all the tertiary positions of the gaze. Precise measures of these eye torsionsby magnetic coils confirmed the direction predicted by the Listing law [12].This led us to study, by means of a Wilcoxon’s nonparametric test for pairedobservations, the direction of the deviation of the SVV according to theposition of the eyes in the orbit [19]. Three of the four tertiary positions ofthe gaze showed highly significant modifications (p00.01) in the orientationof the SVV with regard to the measures in primary position. The directionof these deviations is in accordance with the predictions based on the Listinglaw. The discrepancy of the fourth position can result either from a badestimation of the gaze primary position with a not strictly frontal Listingplane, or from unpredictable fluctuations in the eye torsions.


The adjustment of the orientation of a linear visual marker with regardto a subjective notion of vertical implies first the elaboration of a subjectivevertical reference and later a process of comparison (fig. 2).

Subjective Vertical ReferenceThis is built from one of several sources of information liable to give us

indications on physical vertical or horizontal orientations.Visual Contribution. One of these sources is the visual system. During the

maturation of the visual system, the innate orthogonal axes, related to theorganization of the primary visual cerebral cortex [16], were reinforced by therepetitive experience of stimuli with strong horizontal and vertical dominants.There is thus a purely visual skill allowing to estimate the orientation of alinear stimulus in the space with regard to the physical vertical or horizontal.However, these orthogonal axes ‘engraved’ in the cerebral cortex and fixedlyconnected to the retinal receptors, were built according to the most frequentposition of eyes in orbits and head with regard to the physical vertical. Whenthe head and eyes are not in this most common position, the visual system,if besides it is deprived of any element usually taken as vertical or horizontal(door, building, horizon), cannot by itself estimate correctly horizontality orverticality of a neutral linear perception (having no usual orientation).

Experimental data show the effect of attraction of a tilted structuredbackground on the measure of the SVV [3]. With the increase of the tilt, thecontribution of this visual information becomes more and more variableamong subjects.

Vestibular Contribution. This is probably dominant in the healthy subject.Otolithic organs are specific receptors of the gravitational force, but othersensors, especially close to the kidneys, and the vestibular dynamic information,reflecting the required movements around the equilibrium position, couldalso contribute to this perception. It is thus difficult to isolate the otolithiccontribution to the SVV but the best approach is probably obtained by mea-sures made in submersion, which neutralize somatosensory and visual contri-butions to the SVV. In these conditions the SVV is similar to that obtainedon earth provided the body remains directed in the range of physiologicalfunctioning of the utricules [15]. Measures made in centrifuging room are lessselective because they associate disturbances of the otolithic and somatosen-sory systems.

Somatosensory Inputs. Many somatosensory data contribute to the elab-oration of a vertical reference. Besides the cutaneous receptors (especiallyplantar), to the pressure, the muscular and tendon tension receptors providedata about the static and dynamic moments of inertia of the work of antigravificmuscles. They are sources of information useful for the construction of a


referential system [18]. This information is probably more determining inthe adjustment of the postural vertical than for the SVV. The absence ofsomatosensory information does not however disturb the SVV in a patientwho had lost all deep sensibility of the trunk and the members, when he satwith the head in straight position [21].

We wanted to estimate the influence of very asymmetrical proprioceptivecervical information of the SVV by measuring it in 4 healthy subjects lyingon the left or the right side but with their head maintained vertical [19]. Itseems that under normal functioning of the vestibular system and when thehead remains straight, the cervical proprioception does not influence signifi-cantly the SVV. Nevertheless, the role of the somatosensory inputs becomeprobably of prime necessity when otolithic information is no longer availableas suggested by the measures of SVV made in immersion with important tiltsof the body [8]. These inputs very likely explain the progressive normalizationof the SVV in bilateral vestibular areflexia.

Thus, these multimodal references contribute with a variable weight, ac-cording to the circumstances and possible disorders, to build an image of avertical reference in our visual space representation. The site of this synthesiswithin the central nervous system is not known but a candidate of choicewould be the human homologue of the parieto-insular vestibular cortex ofthe monkey, a site of confluence of vestibular, visual and somatosensory in-formation.

This mental representation of the vertical will then be compared with theorientation of the linear stimulus serving as marker of the SVV.

The Comparison ProcessVisuo-spatial disorders, without known relation with the vestibular sys-

tem, can impair this comparison process and so the SVV measures. Theelementary comparison of the orientation of two linear stimuli presentedsimultaneously can be significantly impaired in cases of lesions of the associa-tive visual vortex. Benton [2] asked his subjects to identify on a protractorthe correct orientation of two lines. Results shows already a non-negligiblerate of error in control subjects, a great increase of these errors in subjectspresenting a right brain damage, and in a lesser degree in left hemisphericallesions. If the right hemisphere seems specifically qualified to estimate theorientation of the stimulus, the left hemisphere appears to play a role in thedecision-taking process and specially in the decision of the marker adjustment[22].

We use a test made up of two oblique lines, one red and one green,presented on a computer screen of which only a circular window is left visibleby a mask. The subject has to line up a line in the same direction as the other


one. The model line and the mobile line are presented, either simultaneously,or with an interval of 10 s. This test confirms that the patients presenting aleft lateropulsion resulting from a right hemispheric lesion, and very often aleft tilt of the SVV, also have difficulties to reach the parallelism of the twolines.

Thus, the mechanism of the impairment of the subjective visual verticalline in parieto-temporal cortical lesions is probably mixed, by failure of theintegration and by impairment of specifical visual tasks related to the method-ology.

Considering this multisensory character of the SVV, how can the method-ology be optimized?

Methodological Implications

The StimulusThe main methodological point in the absence, during the test, of any

visual element susceptible to supply a horizontal or vertical reference (com-puter screen, daylight under a door …).

It is also necessary to take into account an effect of the visual memoryof orientation. After transition to the darkness or after limitation of the visualfield, the subject keeps in memory the vertical orientation of the surroundingobjects. We tested this memory effect on oblique positions in 4 subjects [19].Results obtained in our control subjects (n>80) shows that 98% have an SVVless then 3.4º. The average error during our visual memory task exceeds thisvalue only 22 s after the disappearance of the model. It is so necessary towait for this delay before performing the first measure and between successivemeasures.

The initial position of the mark must be clearly oblique to prevent anyindication of vertical reference. According to the size of the marker and thepoint stared at by the subject, it will fall completely or partially in one or theother visual hemi-field. Given the different hemispherical skill in visuo-spatialtasks, it seemed interesting to check if, in the same subject, the direction ofthe initial tilt of the marker was capable to modify the results significantly.One could also fear of a hysteresis phenomenon according to this initial tilt,similar to that described during the tilting of the subject [17]. No significantdifference (n>72; paired t test: p>0.07) was observed between measuresperformed with an initial left or right tilt of the marker [19]. This probablyresults from the bi-hemispherical representation of the central part of thevisual field and from the integrity of the inter-hemispherical transfer in thetested subjects. It is possible that the same measures performed in subjects


Table 1. Means, SD and values at the cumulative frequencies (Fc) of 2.5and 97.5% of the SVV distribution of the control group (n>81)

Mean SD Fc>2.5% Fc>97.5%

Binocular v –0.08 1.43 –2.8 2.73Right eye v 0.06 1.83 –3.5 3.6Left eye v –0.64 1.98 –4.5 3.2Right eye r –1.05 3.9 –8.7 6.6Left eye r –0.15 3.8 –7.6 7.3Right eye l –0.03 3.65 –7.2 7.1Left eye l –0.51 4.11 –8.6 7.5

SVV were performed binocularly with a vertical head axis (v), monocularlywith a vertical head axis (v), with the head axis tilted to the right (r) or to theleft (l).

suffering from a parieto-occipital or callosal lesion would show a significantdifference.

The SubjectThe measures must be performed with the usual optical correction of the

subject. For instance, measures performed with and without the correction ina patient suffering from an oblique astigmatism of +3 dpt differed by 3.8º.

Is it necessary to record the SVV in monocular or binocular condition?The distribution of the normal values of our control group was sharper inbinocular than in monocular vision (table 1) and this was also observed byother authors [11]. Binocular vision involves the mechanisms of torsionalsensory fusion able to correct cyclodeviations between the two eyes. These arefrequent in the normal population and usually completely asymptomatic dueto this fusion mechanism. A monocular measure is thus susceptible to becorrupted by a cyclodeviation which is not of otolithic origin but results froman asymptomatic oculomotor imbalance. It is relevant in connection with thisthat congenital palsies of the superior oblique muscle are seldom associatedwith a tilt of the visual field despite the presence of an eye torsion. Unlikemonocular measures, no abnormality of SVV was observed with binocularvision in acquired oculomotor palsies [11]. However, the otolithic systemcontrols the torsional movements of the eye, especially by counter-torsionreflexes. Its disturbance can induce cyclotorsions which are not necessarilysymmetrical in the two eyes. This appears clearly in the ocular tilt reaction.It is significant from this point of view, that the 3 patients presenting an


impaired monocular SVV (patients 7, 28 and 35) among the 13 patientssuffering from a Wallenberg’s syndrome of the Brandt’s study [7] had a majorcyclotorsion of this eye (respectively, of 13, 14 and 16º) in the same directionas the deviation of the SVV. This was also confirmed in their 23 patientssuffering from an infarct of the middle cerebral artery [6]. Three among thesepresented a deviation of the SVV only monocularly (patients 2, 12 and 15).These 3 patients were among the 4 subjects which presented during one oftheir examinations a monocular torsion of the same direction. In our studyof 933 one-sided BPPV, monocular assessment of the SVV enabled us toidentify only one supplementary defective case as compared with the binocularevaluation, when specific standards were used for every situation.

Thus, it seems that the exclusively monocular deviations of the SVV, resultmost frequently from a cyclotorsion of the eye. This can be a sign of otolithicdisorder or of a pure oculomotor imbalance. The binocular measures of theSVV reflect probably more specifically the otolithic action but with a lessersensibility than monocular measures.

The aim of our measure being to approach most selectively the otolithiccomponent of the SVV, monocular measures of the SVV will probably bedistorted by more false positives. The attempts of eye torsion quantificationby measure of the orientation of the papillo-macular axis on fundus photosallows to reveal only important torsion. Actually, the normal range of thispapillo-macular angle is about 12º and this is rarely known in a patient beforehis first complaints.

The use of a physical constraint to keep the head in a vertical positionis an essential condition when the angle of the SVV is measured with regardto a cephalic reference, as with the use of Maddox glasses (frame with rotatingstreaked glasses). Except for this situation, this constraint seems not to bejustified. The proprioception is not relevant for the SVV when an otolithicinformation is available, as suggested by many results: our control group(table 1), the measures in immersion [15], the SVV of the patients sufferingfrom spasmodic torticollis [1], our group of patients suffering from a BPPV(table 2) and our measures in subjects side-lying with straight head. On theother hand, if this otolithic information is not available, the constraining headposition could supply an indication of an orthogonal reference able to maskan SVV deviation.

The sitting position of the patient during the SVV measures in the com-plete darkness is especially justified for safety reasons. It is possible that thesomatosensory input differences between the standing and sitting position canmodify the SVV measures in the patients lacking of vestibular informationand very dependent of their proprioception. But these patients are presentingthe greatest risk of fall in darkness.


Table 2. Frequencies of the SVV outside the confidence interval of 95%,performed with a vertical head axis (v), tilted to the right (r) or to the left (l)in patients who suffered from BPPV

Right BPPV Left BPPV

(n>551) (n>382)

n % n %

Binocular v 87 16 52 14Right eye v 63 11 40 10Left eye v 38 7 27 7Right or left eye v 87 16 53 14Right eye r 29 5 27 7Left eye r 42 8 4 1Right eye 1 31 6 29 8Left eye l 24 4 25 7

The InstrumentThe measuring can be very simple but has to be of a sufficient precision.

Metrological error is usually considered to have an amplitude equivalent tohalf the tool graduation. The narrow range of normal measures (average:–0.08º, SD: 1.4º) imposes a precision at least equivalent to one degree.This precision is rarely reached with the Maddox glasses usually used inophthalmology.

References

1 Anastasopoulos D, Bhatia K, Bronstein AM, Gresty MA, Marsden CD: Perception of spatialorientation in spasmodic torticollis. 2. The visual vertical. Mov Disord 1997;12:709–714.

2 Benton AL, Varney NR, Hamsher K: Visuo-spatial judgment: A clinical test. Arch Neurol 1978;52:364–367.

3 Bischof N: Optic-vestibular orientation to the vertical. Handb Sensoriphysiol Vestib Sys 1974;VI:155–190.

4 Bohmer A, Rickenmann J: The subjective visual verticals as a clinical parameter of vestibularfunction in peripheral vestibular disease. J Vestib Res 1995;5:35–45.

5 Brandt T, Dieterich M: Skew deviation with ocular torsion: A vestibular brainstem sign of topo-graphic diagnostic value. Ann Neurol 1993;33:528–534.

6 Brandt T, Dieterich M, Danek A: Vestibular cortex lesions affect the perception of verticality. AnnNeurol 1994;35:403–412.

7 Brandt T, Dieterich M: Cyclorotation of the eyes and subjective visual vertical in vestibular brainstem lesions. Ann NY Acad Sci 1992;22:537–549.

8 Clark B, Graybiel A: Influence of contact cues on the perception of the oculogravic illusion. ActaOtolaryngol 1968;65:373–380.


9 Curthoys IS, Halmagyi GM, Dai MJ: The acute effects of unilateral vestibular neurectomy onsensory and motor tests of human otolithic function. Acta Otolaryngol (Stockh) 1991;(suppl 481):5–10.

10 Dieterich M, Brandt T: Ocular torsion and tilt of subjective visual vertical are sensitive brainstemsigns. Ann Neurol 1993;33:192–299.

11 Dieterich M, Brandt T: Ocular torsion and perceived vertical in oculomotor, trochlear and abducensnerve palsies. Brain 1993;116:1095–1104.

12 Ferman L, Collewijn H, Van den Berg V: A direct test of Listing’s law. I. Human ocular torsionmeasured in static tertiary positions. Vision Res 1987;27:929–938.

13 Friedmann G: The influence of unilateral labyrinthectomy on orientation in space. Acta Otolaryngol1971;71:289–298.

14 Gibson E, Walk RD: The visual cliff. Contemporary psychology. Sci Am 1971:77–84.15 Graybiel A, Miller EF, Newson BD, Kennedy RS: The effect of water immersion on perception of

the oculogravic illusion in normal and labyrinthine defective subjects. Acta Otolaryngol 1968;65:599–610.

16 Hubel DH, Wiesel TN: Receptive fields, binocular interaction and functional architecture in thecat’s visual cortex. J Physiol 1962;160:106–154.

17 Lechner-Steinleitner S, Schone H: Hysteresis in orientation to the vertical (the effect of time ofpreceding tilt on the subjective vertical); in Hood JD (ed): Vestibular Mechanisms in Health andDisease. London, Academic Press, 1978, pp 326–331.

18 Stoffregen TA, Riccio GE: An ecological theory of orientation and the vestibular system. PsycholRev 1988;95:3–14.

19 Van Nechel C, Toupet M, Bodson I: Are proprioceptive and oculomotor factors relevant in theassessment of the subjective visual vertical in healthy subjects. Submitted.

20 Vibert D, Hausler R, Safran AB: Subjective visual vertical in peripheral unilateral vestibular disease.J Vestib Res 1999;9:145–152.

21 Yardley L: Contribution of somatosensory information to perception of the visual vertical withbody tilt and rotating visual field. Percept Psychophys 1990;48:113–134.

22 Ziyah M, Freda N: Dissociate contributions of the two cerebral hemispheres to judgments of theline orientation. J Intern Neuropsychol Soc 1996;2:335–339.

Dr. Ch. Van Nechel, IRON (Institut de Recherche en Oto-Neurologie),10, rue Falguiere, F–75015 Paris (France)Tel. +33 1 43 35 35 30, Fax +33 1 40 47 68 57, E-Mail [email protected]



............................Clinical Application of the Off VerticalAxis Rotation Test (OVAR)

Sylvette Wiener-Vacher

Hopital Robert-Debre Service ORL, Unite d’Explorations Oto-neuro-ophtalmologiques, Paris (France)

Off vertical axis rotation with vestibulo-ocular responses (VOR) record-ings is one of the few methods of vestibular evaluation of the otolith functioncurrently available in medical practice. It provides a global assessment of thevestibular otolith system.

Since 1991, we have applied this test to children with balance problems,deafness and delay in posturo-motor development and have demonstrated thevalue of this test for diagnosis in pediatrics practice. We have also used thistest in normal children to study the maturation of the vestibular system. Inadults we used it to study the processes of central compensation after surgicalsection of the vestibular nerve or to uncover possible otolith system disturb-ances in patients suffering from distortion of movement sensation.

What is the Off Vertical Axis Rotation Test?

Methods and Principle of the OVAR TestThe patients are seated in complete darkness, in a computer-controlled

chair that rotates at a constant velocity rotation about an axis tilted withrespect to the gravity vector (fig. 1). The apparatus we are using has beendesigned by Denise and Darlot [1] and already described in previous publica-tions [2–5].

During OVAR, the head of the subject is rotated around a tilted axisrelative to the gravity vector. The component of the gravity vector (G) whichcorresponds to the projection of G on the plane of the otolith organs, variessinusoidally during rotation. The vector G sweeps the maculae alternativelyrotating forward and backward during each half of one cycle of rotation [1].

Fig. 1. EVAR and OVAR tests: the rotation-tilt paradigm. First (A) the chair rotatesabout a vertical axis with an initial acceleration of 40º/s2 (EVAR) followed by a rotation at60º/s. This induces a canal VOR (bottom traces column A). Since only the initial accelerationstimulates the canals, the canal VOR decays progressively (here in 20 s). Then the axis ofthe chair is tilted of 13º relative to vertical (B) while rotation continued at a constant velocityof 60º/s (OVAR). The horizontal and vertical components of the otolith VOR are recorded(bottom traces column B). These traces show the characteristic modulation of the eyemovements synchronized to the position of the chair during the rotation. The black bandsindicate the slow phases used for calculation of the velocities. The two graphs on the rightof column B show the corresponding velocities of the horizontal (top) and vertical (bottom)eye movements recorded during 12 cycles of OVAR as a function of the orientation of thechair. The solid lines indicate the best-fitting sinusoid from which the bias was calculated.From Wiener-Vacher and Mazda [4].

This stimulation produces a constant sinusoidal variation of the directionof the gravity vector with respect to the head. The vestibulo-ocular responses(VOR) are recorded by electro-oculo-graphic electrodes in complete darkness.The rotation-tilt paradigm was chosen because it provides in the same sessiona canal testing with the earth vertical axis rotation as well as an otolith testing.

89Off Vertical Axis Rotation Test in Children

The Vestibulo-Ocular Responses to OVARThe OVAR test produces a complex nystagmus as first described in humans

by Guedry [6] and Benson and Bodin [7]. The ocular response evoked by theOVAR stimulation is composed of a bias (which corresponds to a mean slowphase velocity in a direction opposite to the rotation velocity of the head)and a sinusoidal modulation of the slow phase velocity with a periodicityidentical to the period of the rotation (fig. 1).

The amplitude of the response varies as a function of the angle of tilt of therotation axis and the rotation velocity [1]. We chose for our OVAR paradigm arotation velocity of 60º/s and 13º of tilt because this gives an optimal amplitudeof the response without inducing discomfort of the subjects.

Interpretation of the Responses to OVARGuedry [8] in 1970 applied this stimulation to normal subjects as well as

patients with vestibular bilateral deficits and observed the absence of coherentocular responses in the case of vestibular lesions.

Subsequent experiments in animals [9, 10] and observations in humanshave shown that the principal target of this stimulation is in fact the otolithalbeit with an excitation of some proprioceptive inputs (somesthesic, visceral).Specific lesions of the otolith system are considered to be responsible fordisappearance of the responses to OVAR on the side of the lesion during theacute post-lesion phase [2, 9, 10].

While OVAR stimulates both sides of the otolith system, the stimulationis greater for the right otolith system when the rotation is applied clockwiseand counterclockwise gives a stronger response from the left otolith organs.

The production of the OVAR ocular response requires complex central pro-cessing of otolith signals in the brainstem vestibular nuclei where canal signalsand somesthesic signals are also processed and oculo-motor responses gener-ated. The vestibulo-ocular responses are also quite dependent on the integrityof the oculo-motor pathways and can be modified by lesions of these pathways.This explains why asymmetries observed in OVAR have to be interpreted care-fully with other vestibular and ocular testing results. It also explains why thecentral compensation mechanisms are able to mask with time asymmetries ofthe responses to OVAR after unilateral vestibular lesion [2].

Role of the Vestibular System in the Posturo-Motor Development ofChildren

The importance of the vestibular system in the posturo-motor develop-ment of children has been underestimated for a long time. The objectives of

90Wiener-Vacher

our study were to determine the respective roles played by canal and otolithvestibular information in the posturo-motor development of children and therepercussions of this for understanding certain pediatric pathologies.

Our work was motivated by the fact that the vestibular system and particu-larly the otolith system were not being adequately tested in young children. Thiswas due to the difficulties in motivating compliance by young children for testing.Factors contributing to this included unattractive and unfriendly clinical envi-ronments, but also the lack of available and practical otolith testing methods.

For the last 9 years we have adapted for children a series of vestibulartests, and applied them to normal young volunteers as well as children referredto our department for balance problems. Most of our studies have focusedon measuring vestibulo-ocular responses, which are recorded with adaptationsof classic EOG (electro-oculographic) techniques (better accepted in ourexperience by very young subjects than video-oculo-graphic technics of record-ing). These tests include, for the canal function evaluation: the caloric test,pendular rotation, rotatory impulsion (earth vertical axis rotation or EVAR)and for otolith functional evaluations: off vertical axis rotation. More recently,we adapted other tests for otolith evaluation: measurements of the verticalsubjective and myogenic evoked potentials from stimulation of the otolithorgans by clicks applied to earphones.

The various results obtained suggest that, as early as birth, vestibularinformation play a fundamental role for the postural motor control in children.But canal and otolith information does not have identical contributions.

Children suffering a complete absence of vestibular information sincebirth invariably show severe delays for acquiring postural control of their headand trunk (for head holding, sitting, standing). Consequently, they are unableto achieve milestones of motor autonomy such as independent walking atnormal ages [11, 12] (fig. 2). Functional deficiency of the canal vestibularsystem alone (as found in children with a congenital absence of semi-circularcanals [5, 13]) does not seem as important as otolith information for acquiringthe first levels of posturomotor control. The absence of semi-circular canalspermits head holding, sitting, standing and walking with support to occur atnormal ages, while it leads to substantial delays for the onset of independentwalking [13]. This can be explained by a major contribution of the canalvestibular information at the onset of walking. This input is required to obtaina stabilization of gaze during the rapid movements of the head that occur ateach step when walking and during orientation movements in space. Previousstudies showed that there is a fine coordination between movements of thehead and eyes, which involve particularly, canal vestibulo-ocular responses[14, 15]. This coordination is progressively accomplished in toddlers duringtheir first years of walking [16–18].


Fig. 2. Delays in independent walking (IW) are dependent on the degree of bilateralvestibular deficit. On the Y-axis is plotted a global index of otolith function (mean value ofthe VOR modulation to OVAR in both direction of rotation). On the X-axis is plotted aglobal index of the canal vestibular function (mean values of the amplitude of VOR inresponse to EVAR in both directions of rotation). Two population of children are compared:circles and squares represent young children showing no vestibulo-ocular responses in eithersides to caloric tests (at 20 ºC) since an early age (=1 year of age), and triangles a groupcontrol of the same age at the time of the tests. Note that the children with the longest delayof IW are the ones which have the poorest canal and otolith responses (white circles). Notethat children with no canal function but remaining otolith responses walk at a normal (oralmost normal) age (respectively, black and gray squares). Note also that an absence ofresponses in the caloric test (20 ºC) can be associated with a residual canal function. FromWiener-Vacher et al. [submitted].

We studied the gait parameters as well as canal and otolith VOR duringthe periods preceding and following the acquisition of independent walkingin a longitudinal study in children with normal vestibular function [19]. Otolithvestibulo-ocular responses showed characteristic changes correlated to theonset of independent walking while canal VOR did not change [3, 19]. Theseresults suggest that the otolith system is essential for the timely acquisitionof axial head and trunk postural control for this posturo-motor acquisitionmilestone. This hypothesis is supported by our observation that severe andearly-acquired deficits of vestibular inputs in infants induce a severe hypotonyand are correlated with a considerable delay in independent walking acquisi-

92Wiener-Vacher

tion. If the vestibular impairment is incomplete (with residual canal and otolithfunction) the posturo-motor control is acquired at normal ages. A recent studysupports the hypothesis that children with residual otolith function have betterposturo-motor control development than children with a remaining canalfunction in terms of posturo-motor control acquisition [13]. However, we havenot yet found the pathological cases of complete deficits of otolith functioncoupled with normal canal function that would be necessary to confirm thishypothesis.

Characteristics of the canal vestibulo-ocular responses change progres-sively over the years after the first steps of independent walking [3, 19]. Thissuggests that the canal vestibular system might be more involved in headrotation control after axial postural motor control is acquired. We know thatgaze stabilization in space during walking requires accurate and fine controlof the head displacements and eye movements. Head coordination duringstepping in toddlers also develops progressively over the first years after acquisi-tion of the first independent step [16, 17]. This pattern of development couldcorrespond to the progressive changes observed in the canal VOR character-istics during the first years of life.

How Can the OVAR Test Be Used as a Diagnostic Tool?

The OVAR Test during the Acute Phase of Vestibular DamageIn our experience, the OVAR test can be useful during the acute phase

after vestibular damage because the results can demonstrate signs of decreaseor increase of excitability of the otolith system on the side sustaining damage.

Within the year following a stable unilateral lesion of the vestibular system,the central nervous system compensates for most of the asymmetry of thevestibulo-ocular responses, a valuable indicator of the lesion side. However,if the lesion is progressive or fluctuating the vestibular function remains un-stable and the central nervous system compensation processes are unable tocorrect the asymmetries of the vestibulo-ocular responses.

A developing lesion of the inner ear, such as a labyrinthitis when fibrosis(and secondary bone) progressively invades the inner ear cavity, is a goodexample of such progressive lesion. As described in ‘Observation 1’ the OVARresponses show a permanent strong directional preponderance indicating that1 year after the initial labyrinthitis, the vestibular deficit was not yet compen-sated. CT scan proved that there was an ossifying labyrinthitis.

After cranial traumatism with a temporal bone fracture or in the case ofa fluctuating hearing loss with suspicion of a congenital perilymphatic fistula,an OVAR test showing a strong directional preponderance toward the damaged


ear, indicates a recent fluctuation and hyperexcitability of the vestibular recep-tors on the same side (see ‘Observation 2’). This was associated to the surgicaldiscovery of active perilymphatic fistulae in all cases. When the directionalpreponderance is toward the side opposite to the lesion this indicates a recentlesion of the otolith system but does not necessarily evidence the existence ofa fistula.

In the case of unilateral vestibular neuritis the prognosis of functionalrecovery of the lesioned side over time is greater if the initial lesion is incom-plete. For the initial vestibular functional testing the OVAR test permits anevaluation of the otolith function providing a more complete assessment ofthe extent of the lesion and thus a better appreciation of the prognosis (Obser-vation 3).

The Test OVAR during the Chronic Phase of Vestibular DamageDuring the chronic phase of vestibular impairments, the usefulness of

the OVAR tests to localize the side of the lesion is more questionable. Themechanisms of compensation of a complete unilateral vestibular reduce orcancel with time the asymmetries of the vestibulo-ocular responses to mostof the vestibular tests. Thus, the OVAR test may not be effective for diagnosinga partial or old unilateral otolith lesion.

However, OVAR can be used for assessing complete vestibular bilateraldeficit in the case of delays in posturo-motor acquisition and their vestibularorigin. With a residual canal or otolith function a child without any otherneurological problems is able to acquire all the milestones of the posturo-motor development at a normal age (=19 months) (fig. 2). The detection ofa remaining vestibular function in a child with severe delays in developmentindicates that problems other than a vestibular lesion are responsible for thesedelays (visual disorders, orthopedic disorders, and neurological disorders).The detection of a vestibular deficit in a child with other sensorimotor deficitsis essential to permit prescription of a better adapted physicotherapy program[19], using the remaining sensorial information to compensate the other deficits.

The OVAR tests have been used for detecting otolith system asymmetriesin pathologies involving posturo-motor control for example in idiopathic scoli-osis. Idiopathic scoliosis is a disorder, which is usually diagnosed during theperiod of rapid growth preceding the age of puberty. Various hypotheses havebeen proposed to explain the development of this progressive spine deformity.We discovered that more than 60% of the children with idiopathic scoliosishad an abnormal asymmetry of their vestibulo-ocular responses to OVARwhile their canal vestibulo-ocular responses were normal [4]. These resultsbring new arguments to support the hypothesis of a central origin involvingthe otolith system for the development of scoliosis in young children.

94Wiener-Vacher

Observations

Observation 1: Application of the OVAR Test in the Diagnostic of Unstable DevelopingLesion of the VestibuleA 3-year-old boy suddently suffers violent abdominal pain, vomiting and ataxia 1

week after a tonsillitis. Two weeks later, the boy complains that he cannot hear thetelephone with his left ear. He is referred to an Otorhinolaryngology department whereaudiometry testing reveals a complete sensorineural hearing loss in the left ear. No vestibu-lar testing is done. But a CT scan is normal. Four months later, he is referred to ourdepartment for testing his hearing loss. A complete audio-vestibular examination confirmsthe sensorineural hearing loss on the left ear, but shows a deficit of the left vestibularreceptors with no compensation (intense spontaneous nystagmus, intense directionalpreponderance toward the right side at all testing (canal and otolith VOR recordings).Thirteen months after the acute episode, compensation is still not achieved. This is veryunusual in children of this age, who normally compensate very quickly. A CT scan andMRI are again performed. They show an ossifying labyrinthitis. Twenty months after thisdiagnosis the vestibular function will be completely destroyed and the compensation com-pleted with a very discrete directional preponderance to the right side and a bilateralinhibition of the VOR measured by OVAR (as evidenced by very small modulation andalmost zero bias).

Observation 2: The Responses to OVAR Can Indicate an Abnormal Irritation of theOtolith Receptors on the Side of a Perilymphatic FistulaAfter falling from an elevated bed, a 7-year-old boy presents a cranial traumatism with

a brief loss of consciousness, vertigo and unsteadiness and an hematic tympanic membranein the right ear. The CT scan is normal.

Ten days later the child is referred to our department because vomiting was occurringagain without vertigo but with a right torticollis. The audio-vestibular testing shows aconductive and sensorineural hearing loss on the right side (with an averaged threshold at30 dB HL). The stapedius reflex was not evoked on the right side by contralateral auditorystimulation. The evaluation of the vestibular function shows a quasi-areflexia on the rightside with the caloric test but a very strong directional preponderance toward the right sideat the OVAR test. The latter result was definitely interpreted as an indicator of irritationof the right vestibule organ and a sign of perilymphatic fistulae. Surgical explorationrevealed a longitudinal fissure on the footplate of the stapes. A patch was installed on theoval window with aponeurosis and biologic glue. One and a half years after the surgery,the audio-vestibular testing showed a complete restitution of the hearing and the vestibularfunction.

Observation 3: The OVAR Test Can Serve as a Prognosis Tool in Vestibular Neuritis,Helping to Complete the Evaluation of the Initial Vestibular DamageA 14-year-old girl is referred for audio-vestibular testing the fourth day after a sudden

intense vertigo with vomiting and ataxia (a slight viral infection was reported 2 weeks earlier).Four days later, there is a typical right vestibular deficit syndrome and a complete areflexiaon the right side in the caloric test. But the responses in the OVAR test are intense with aleft directional preponderance. At day 10 the otolith VOR to the OVAR test is normal while


the canal VOR is recovering. One month later the recovery is complete. The absence of anasymmetry to the test OVAR predicted an absence, or minor lesion of the otolith systemand not a total complete loss of the right vestibular receptors or nerve.

Acknowledgments

This work was supported by grants from : INSERM (No. 910207), CNES (No. 950322),DRC de l’Assistance Publique de Paris (No. 95108, No. 96156), Fondation pour la RechercheMedicale, Fondation de France, Fondation Reuter, Fondation Electricite et Sante. Thanksto Francoise Toupet for her technical help in testing young children and to Sidney Wienerfor his helpful comments in the text.

References

1 Darlot C, Denise P, Droulez J, Cohen B, Berthoz A: Eye movements induced by off vertical axisrotation at small angles of tilt. Exp Brain Res 1988;73:91–105.

2 Darlot C, Toupet M, Denise P: Unilateral vestibular neuritis with otolith signs and off vertical axisrotation. Acta Otolaryngol (Stockh) 1997;117:7–12.

3 Wiener-Vacher SR, Toupet F, Narcy P: Canal and otolith vestibulo-ocular reflexes to vertical andoff vertical axis rotation in children learning to walk. Acta Otolaryngol (Stockh) 1996;116:657–665.

4 Wiener-Vacher SR, Mazda K: Asymmetric otolith vestibulo-ocular responses in children withidiopathic scoliosis. J Pediatr 1998;132:1028–1032.

5 Wiener-Vacher SR, Amanou L, Denise P, Narcy P, Manach Y: Vestibular function in children withCHARGE Association. J Am Otolaryngol Head Neck Surg 1999;125:342–347.

6 Guedry FE: Orientation of the rotation axis relative to gravity: Its influence on nystagmus and thesense of rotation. Acta Otolaryngol (Stockh) 1965;60:30–48.

7 Benson AJ, Bodin MA: Interaction of linear and angular accelerations on vestibular receptors inman. Aerosp Med 1966;37:144–154.

8 Guedry FE: Effects of concommittant styimulation of the semicircular canals and otoliths by‘barbecue spit’ rotation, rotation about a tilted axis, and other forms of stimulation. Exerpta MedInt Congr Ser Amsterdam 1970, p 206.

9 Cohen B, Suzuki J, Raphan T: Role of the otlith organs in generation of horizontal nystagmus:Effects of selective labyrinthine lesions. Brain Res 1983;276:159–164.

10 Correira MJ, Money KE: The effect of blockage of all six semi-circular canal ducts on nystagmusproduced by linear acceleration in the cat. Acta Otolaryngol 1970;69:7–16.

11 Kaga K, Maeda H, Suzuki J: Development of righting reflexes, gross motor functions and balancein infants with labyrinth hypoactivity with or without mental retardation. Adv Otorhinolaryngol1988;41:152–161.

12 Tsuzuku T, Kaga K: Delayed motor function tests in children with inner ear anomalies. Int J PediatrOtorhinolaryngol 1992;23:261–268.

13 Abadie V, Wiener-Vacher S, Morisseau-Durand MP, Poree C, Amiel J, Amanou L, Peigne C, LyonnetS, Manach Y: Vestibular anomalies in CHARGE syndrome: Investigations and consequences onpostural development. J Eur Pediatr 2000; in press.

14 Pozzo T, Berthoz A, Lefort L: Head stabilization during various locomotor tasks in humans. I.Normal subjects. Exp Brain Res 1990;82:97–106.

15 Pozzo T, Berthoz A, Lefort L, Vitte E: Head stabilization during various locomotor tasks in humans.II. Patients with bilateral peripheral vestibular deficits. Exp Brain Res 1991;85:208–217.

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16 Ledebt A, Wiener-Vacher S: Head coordination in the sagittal plane in toddlers during walking:Preliminary results. Bull Brain Res 1996;40:371–373.

17 Ledebt A, Bril B, Wiener-Vacher S: Trunk and head stabilization during the first months of independ-ent walking. Neuroreport 1995;13:1737–1740.

18 Assaiante A, Amblard B: Ontogenesis of head stabilization in space during locomotion in children:Influence of visual cues. Exp Brain Res 1993;93:499–515.

19 Wiener-Vacher S, Ledebt A, Bril B: Changes in otolith VOR to off vertical axis rotation in infantslearning to walk: Preliminary results of a longitudinal study. Ann NY Acad Sci 1996;781:709–712.

S. Wiener-Vacher, MD, Hopital Robert Debre, Service ORL,Unite d’Explorations Oto-neuro-ophtalmologiques, 48, Bld Serurier, F–75019 Paris (France)Tel. +33 1 40 03 2479, Fax +33 1 40 03 2202, E-Mail [email protected]



............................VEMP Induced by High Level ClicksA New Test of Saccular Otolith Function

Catherine de Waele

Service ORL, Hopital Lariboisiere, et Laboratoire de Neurobiologie des ReseauxSensori-moteurs, CNRS-Paris V, Paris, France

Patients suffering from vertigo were most often investigated by caloricand horizontal rotatory tests. These tests are interesting but they appreciatethe function of the horizontal canalar ampulla which are only one of the fivepairs of vestibular sensors (three pairs of canals, two utricules and the twosaccules). The function of the otolithic sensors remains elusive in most ofthese patients. This is a problem because the clinical syndromes resulting fromremoval of the otolith inputs are far from being neglectible. Fortunately, severalnew tests of the otolith functions have been made recently available to clinicians.The oculomotor syndrome induced by otolithic lesion is twofold. The staticdeficits include a skew deviation and an ocular cyclotorsion oriented towardsthe lesioned side. They are responsible for the vertical diplopia observed atthe acute stage. These deficits can be precisely quantified by fundus photomi-crographs, 3-D videonystagmography and by the measurement in darkness ofthe subjective visual horizontal and vertical. The dynamic deficits result fromthe changes of the dynamic properties of the maculo-ocular reflexes. They canbe assessed by means of the off-axis vertical rotation (OVAR) test and bymeasuring the linear vestibulo-ocular reflex (LVOR). These tests give importantinformation about the function of the otolith-ocular pathways. However, theyhave several limitations: first, they cannot differentiate between a utricular ora saccular lesion. Second, due to the vestibular compensation process, theycan return to normal or subnormal values with time, which is a problem whenpatients are tested several months after the initial otolith trauma. Finally,apart from the test of the subjective visual horizontal and vertical, these testsrequire costly equipment which is not commonly available in ENTdepartments.

This explains why we have investigated whether routine recordings of thevestibular-evoked myogenic potential (VEMPs) evoked by high level clickswere useful to assess the otolith function in patients suffering from vestibularsyndromes. This test, described in 1964 by Bickford et al. [1] and reintroducedlater by Colebatch et al. [2] in 1994 presents two major advantages: (1) itselectively probes the function of each sacculus and of the sacculospinal path-ways, and (2) it never compensates even after a long time following a peripheralvestibular lesion. Our 2 years’ study leads to the conclusion that VEMPstesting is relatively simple to use and has a triple diagnosis, prognostic andtherapeutic interest. However, it should be stressed that, as useful as it is toinvestigate patients who complain of oscillopsia, movement illusions andataxia, early VEMPs induced by high level clicks are the most informativewhen used in combination with some of the other otolithic tests quoted above.We will briefly report here some of the VEMPs data obtained in unilateralvestibular pathologies such as Meniere’s disease, vestibular neuritis, acousticneurinomas and bilateral canalar vestibular paresis.

Methods

Patients suffering from different pathologies such as Meniere’s disease, vestibular neu-ronitis, acoustic neurinoma, head trauma were tested by means of vestibular myogenicpotentials test evoked on the ipsilateral sternomastoid muscle (SCM) by high-level clicks.The latency of the early P13/N23 waves and the amplitude of the P13/N23 peak relative tothe SCM EMG activity were measured.

Clicks DeliveryEach ear was stimulated twice in a raw which led to four trials per patient (two trials

on the left ear and two trials on the right ear). The test was performed as follows: stimulationof the left ear twice and then stimulation of the right ear twice. For each of the four trials,the EMG responses were averaged over a series of 512 clicks of 0.1 ms rarefactive squarewaves of 100 dB HL. The acoustic stimuli were delivered by calibrated TDH 39 headphonesat a frequency of 6 Hz.

EMG RecordingsSurface EMG activity was recorded as previously described [3]. Briefly, skin electrodes

were placed symmetrically on the upper half of each SCM. The reference surface and theground electrode were located over the upper sternum and the central forehead, respectively.VEMP recordings were performed with a Nicolet Viking 4 with a 4-channel averagingcapacity. The EMG from each side was amplified, bandpass filtered (10 Hz–1.6 kHz) andaveraged using a sampling rate of 2.5 kHz for each channel. Patients were laid supine on abed and were asked to raise their head straight-ahead off the bed to activate their SCMbilaterally and symmetrically. In this position, the EMG activity had a minimal root meansquare (RMS) of 80 lV. Simultaneous average EMG of both SCM were collected from 20 ms

99VEMP Induced by High Level Clicks

before the clicks to 80 ms afterwards. Odd and even traces were stored and averaged separately.This allowed to compare the two averaged records at the end of each trial, which by definitionhad to be perfectly coincident to confirm their saccular origin.

Data AnalysisThe mean peak latency (in ms) of the two early (P13 and N23) of the VEMP was

measured. The peak to peak amplitude (in lV) was calculated for the P13/N23 waves andreported to SCM EMG activity. the SCM EMG activity (RMS) was measured before thefirst trial (first left ear stimulation) and after the last trial (last right ear stimulation). Indeed,the P13/N23 peak to peak amplitude has been previously shown to fluctuate with the SCMelectromyographic amplitude [4].

Results

Normal SubjectsVEMP testing is now a well-established test to explore the sacculo-collic

pathways in humans. Loud monaural clicks evoke an initial inhibitory potentialin tonically contracted ipsilateral SCM. This potential is responsible for theearly waves P13/N23 and has been demonstrated to be of saccular origin [2]:guinea pig saccular afferents [5–9] and vestibulo-spinal neurons of the lateraland of the descending vestibular nuclei [10], two nuclei mostly involved in theprocessing of otolithic inputs, were recently shown to respond to loud clicks.The P13/N3 potentials could be followed by additional late N34, P44 potentialswhich have been demonstrated to be of cochlear origin [2].

We have studied early VEMPs induced by high level clicks on the ipsi- andcontralateral SCM in subjects with normal vestibular and auditory function.Subjects suffering from conductive hearing loss or abnormal acoustic reflexeswere excluded since in these cases high-level clicks are unable to induce earlyVEMP due to the fact that the acoustic stimuli are not of sufficient amplitudeto mechanically activate the sacculus [11].

89% (n>33) of the age-matched controls displayed a short latency re-sponse in the SCM ipsilateral to the stimulated ear. Its mean latency was11.2×1 ms (min. 9.08, max 14.8 ms) for the P13 wave and 19.4×2.4 ms (min.14.3, max. 19.23 ms) for the N23 potential. The late response was found lessfrequently (50% of the subjects). When present, the latencies of the ipsilateralN34, P44 waves were 30.5×2.5 ms for N34 (min. 26 max. 38 ms) and38.3×2.66 ms (min. 34 max. 45.4 ms) for P44. The absence of short latencyresponse in the SCM ipsilateral to the stimulated ear in 11% of the controlswas confirmed by testing these subjects on another day.

The mean P13/N23 peak to peak amplitude was 67.9×52.6 lV (min. 10,max. 221 lV). It varied greatly from one subject to another and in the same

100de Waele

Fig. 1. Left-hand side: Vestibular evoked myogenic potentials recorded on the sternomas-toid muscles (SCM) in a healthy person. Traces 1 and 3 correspond to the evoked potentialsobtained on the left (1) and the right (3) SCM when 100-dB clicks were delivered to the leftear (A). Traces 5 and 7 illustrate the evoked potentials obtained on the left (5) and right (7)SCM muscles when 100-dB clicks were delivered to the right ear (B). The VEMPs recordedon the muscle ipsilateral to the acoustic stimulation are composed of two early P13 and N23potentials and of additional late N34 and P44 potentials (traces 1 and 7). Note the absenceof crossed saccular responses in the SCM contralateral to the acoustic stimulation (traces 3and 5). Right-hand side: Vestibular evoked myogenic potentials recorded from the sternomas-toid muscles (SCM) of patient with right unilateral Meniere’s disease. Traces 1 and 3 corre-spond to the evoked potentials obtained on the left and the right SCM when 100-dB clickswere delivered to the left ear (A). Traces 5 and 7 illustrate the evoked potentials obtainedon the left and right SCM when 100-dB clicks were delivered to the right ear (B). Theseloud monaural clicks failed to evoke any early P13-N23 potentials on the right SCM whendelivered on the right affected ear. In contrast, normal VEMP were observed in the leftSCM muscle when loud clicks were delivered to the left intact ear. (Horizontal calibration:10 ms/division. Vertical calibration: 20 lV/division.)


subject between trials. However, it tended to increase, but not significantly,with the repetition of the trials: in the first trial, the mean was 63.6×54.4 lVand in the fourth trial 75.5×95.3 lV (p>0.45). The SCM RMS tends alsoto increase from 123.8×45.9 to 156.9×62.9 lV while the subject raised hishead off the bed. However, this difference was not significant. The crossedresponse to the click stimulus was not investigated since it was observed inonly 2/3 of the subjects. Its great variability suggests that it could not bereadily used to explore the patient groups.

Patients Suffering from Meniere’s DiseaseThis first study was designed to assess the saccular function of Meniere’s

subjects. Only the presence or the absence of the early VEMPs in the SCMipsilateral to the stimulated ear (intact and affected one) and their latenciesand amplitudes if present were analyzed for the following reasons: (a) theVEMPs evoked in the SCM muscle contralateral to the stimulated ear werevariable in the control group; (b) as previously stated the late VEMPs havebeen shown to be of cochlear origin [2].

The aim was twofold: first, to detect potential dysfunction of the sacculo-collic pathways which could explain the subjective problems of Meniere’spatients with balance while standing and walking [12, 13]; second, to searchfor any correlation between the saccular deficit and three other variables: thedegree of hearing loss, canal paresis and dynamic postural disorders.

The uncrossed saccular response evoked by the stimulation of the affectedear was abolished in 32 of the 59 patients (54%). When present, the meanlatency of the P13 potentials evoked by the stimulation of the affected ear inthe ipsilateral SCM muscle was 11.3×1.3 ms (min. 8.9, max. 14.5) and thatof the N23 potential was 18.8×2.0 ms (min. 14, max. 23.1), respectively. Thesevalues were not significantly different from those measured in the group ofcontrol subjects (ANOVA). In 27 Meniere’s patients (46%), the P13 and N23potentials persisted on the affected side. We therefore investigated whethertheir amplitudes differ from those of the control group. The mean P13/N23peak to peak amplitude (left and right uncrossed SCM VEMP amplitudepulled together) in these 27 patients amounted to 63.8×62.6 lV (min. 11,max. 349 lV) which was not significantly different from the value recordedin the control group. Hence, when the P13 and N23 potentials persisted onthe affected side of the Meniere’s patients, their latencies and amplitudes didnot differ from those of the similarly aged control group.

In conclusion, the initial biphasic P13/N23 evoked potential was absentfrom the ipsilateral SCM in 54% of the Meniere’s patients, which means thatthe endolymphatic hydrops can affect the response of the sacculus to clicks.Whether the otolithic sensors of these patients were also less sensitive to head

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tilt and vertical linear translations remains to be determined. However, thisis most probably the case since some Meniere’s patients have abnormal asym-metry of eye torsion in response to whole body roll towards the normal ear[14] and/or experience sudden falling spells [15]. These drop attacks are mostprobably triggered by stimulation of the otolithic membrane [16]. Therefore,our results predict that drop attacks of saccular origin should not occur inpatients with abolished VEMP since their saccular sensory epithelium shouldbe less or not sensitive to a brisk distention of the otolithic membrane.

Relationship between VEMP and Hearing Loss. The low-frequency hearingloss of the affected ear was significantly greater in patients who did not exhibitipsilateral VEMP than in patients who had intact VEMP (p>0.02). Followingthe stimulation of the affected ear, the 32 patients without VEMPs had amean low-frequency hearing loss of 51.1×20 dB whereas the mean value was39.4×16.5 dB in the 27 patients who had normal VEMP. Of the 49 patientswith low-frequency hearing impairment ranging between 0 and 60 dB, theVEMP was intact in 26 (53%) and absent in 23 (47%). It was absent from theaffected side in all patients with low-frequency hearing loss of more than60 dB. In contrast, patients suffering from 4 to 8 kHz superior to 60 B candisplay normal P13/N23 potentials. In summary, low-frequency (250–1,000Hz) but not high-frequency (4–8kHz) hearing loss correlated with VEMP loss.

Absence of Relationship Between VEMP and Canal Paresis. Canal paresiscould only be investigated in 52 of the 59 Meniere’s patients because calorictesting had to be interrupted in 7 cases due to major neurovegetative signs. Inthese patients, we failed to find any correlation between saccular dysfunction andcanal paresis. In the 30 (57.7%) patients with no VEMP following stimulation ofthe affected ear, the mean canal paresis was 32.8×32.7%. The mean value was17.0×24.1% in the 22 patients (42.3%) who had intact VEMP following stimula-tion of the affected side. The difference was not significantly different (p>0.07).The ipsilateral early VEMP was absent from 48% of the 35 patients displayinga Jonkees index between 0 and 20% and from 76% of the 17 patients displayinggreater canal paresis (between 20 and 100%). Some patients with canal paresisequal to or above 60% displayed intact saccular responses.

Relationship between VEMP and Equitest Performances. Of the 39 patientsundergoing dynamic computerized posturography tests, 22 did not displayearly VEMP following acoustic stimulation of the affected ear and 17 exhibitednormal early VEMP. On the moveable platform, a larger than normal visualdependency was observed in some patients with absent saccular responses.They swayed more in conditions 3, 5 and 6, i.e. when visual references wereeither absent or stabilized. In accordance with a previous work [17], thisdifference was only significant for condition 5 (eyes closed) and was not relatedto the degree of canal paresis unlike other related findings [12]. This discrepancy


could be due to a sample bias since all our patients were investigated duringremission and not during acute phases [12]. It is intriguing that condition 5was more destabilizing than condition 6 where the visual environment is presentalthough it did not provide information about egomotion. Possibly, light hasa nonspecific excitatory effect on these vestibular deficient patients.

Conclusion. We have shown that a sizeable proportion of Meniere’spatients present a saccular dysfunction. There was a clear relationship be-tween the extent of the cochlear damage and the saccular impairment: patientswith no VEMP had greater hearing impairment in the low-frequency rangethan patients with VEMP. Moreover, the sacculus was always dysfunctionalwhen the hearing loss was greater than 60 dB. No such relationship wasobserved for high-frequency hearing loss and for horizontal canalar paresisas assessed by caloric testing. This result suggests that endolymphatic hydropsmay principally affect cells which encode stimulation in the low frequencyrange. Finally, Meniere’s patients with saccular impairments tended to be-come more dependent on vision than patients with intact saccular functionto maintain an upright posture. Therefore, testing the VEMP and the dynamiccontrol of posture could be of value for Meniere’s patients. Indeed, subjectssuffering loss of VEMP and with a strong visual dependency may be patientsat risk, especially if they are aged. They would be good candidates forvestibular rehabilitation which has been shown to improve postural perfor-mance greatly.

Patients Suffering from Meniere’s Disease and Treated byGentamicin Intratympanic InjectionsIn most clinical studies on chemical labyrinthectomy induced by genta-

micin intratympanic injections, investigations were restricted to caloric and/or rotatory tests to monitor the functional impairment of the horizontal canal.Consequently, the toxicity of gentamicin to otolith sensors remains unknown.Only two studies on subjective visual vertical and horizontal [18, 19] andocular torsion [18] suggest that otolithic deficits could indeed occur. We furtherinvestigated this issue by using VEMP evoked by high-level clicks (100 dB)to monitor saccular function in patients treated by gentamicin intratympanicinjections on the hydropic ear. Our aim was twofold: (1) To assess the functionof the sacculus and of the sacculo-collic pathways following the gentamicininjections and (2) to test for correlations between the saccular deficits and thedegree of canal paresis. The relationship between hearing loss, dynamic pos-tural disorders and early myogenic potentials evoked by high level clicks inthese patients will be described in a pending publication.

Two different injection protocols were investigated: a shotgun approachfor inpatients in which gentamicin was delivered intratympanically over 4

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consecutive days [20] and a titration protocol in outpatients where singleintratympanic doses of gentamicin were delivered weekly [21].

The main finding of this study was that early VEMPs were abolished1 month after the gentamicin injections in 14/14 (100%) of the patients testedboth before and after treatment and who had normal responses on both sidesbefore gentamicin therapy. Six of the 14 patients were included in the shotgunprotocol and 8 in the titration protocol. The absence of VEMPs on the injectedside was confirmed six months and/or 1 year after the gentamicin treatment.Therefore, our results suggest for the first time that gentamicin injectionsrender the sacculus less sensitive to high level clicks. Whether this findingresults from a complete or a partial lesion of the sacculus and/or from a lesionof the saccular nerve remains to be determined. Indeed, degenerative changes,which could result from a direct ototoxic effect of gentamicin, have beenobserved in guinea pig vestibular ganglion cells 4 weeks after gentamicininjections into the middle ear [22]. Preliminary results using short-durationglavanic stimulation and recordings of VEMPs on the sternomastoid muscles ingentamicin-treated patients suggest that the same is likely to occur in humans.Finally, no correlation could be detected between vertigo control (observedin 71% of the patients) and saccular damage.

In contrast, only 58% if our patients exhibited unilateral abolition of caloricresponse 1 month after intratympanic injections. We did not find any correlationbetween control of vertigo and the abolition of the caloric response. Variablethickness of the round window, mechanical obstructions due to adhesions in theround window niche, the eustachian tube function and also genetic predisposi-tion to ototoxicity [23] could explain this result. The aminoglycosides have beendemonstrated to be ototoxic not only in hair cells [24] but also in endolymph-secreting dark cells [24, 25]. Since these cells have been shown to play a key rolein the active ion transport involved in endolymph production, it was suggestedthat gentamicin may control the endolymphatic hydrops. This would explainwhy the treatment can be effective even when not abolishing caloric responsesor producing an acute vestibular deafferentation syndrome.

Gentamicin has a biphasic effect: initially, it induces a reversible blockageof transduction channels and of calcium channels causing a competitive dis-placement of divalent cations (calcium and magnesium). Later, it causes irre-versible destruction of hair cells due to their energy-dependent competitiveuptake of polyamines, their polyphosphoinobiphosphate binding and interfer-ence with intracellular second-messenger systems. It has also been reportedthat gentamicin can cause mistranslation of mitochondrial complex-1 genes,leading to oxidative damage to mitochondria and cell death [26].

In summary, intratympanic gentamicin injections induced saccular dys-function in all patients who had normal VEMPs before the treatment. There-


fore, although it cannot predict the efficacy of gentamicin on vertigo control,VEMP testing is useful to detect its early effects. The saccular dysfunctiondid not depend on the protocol and was not related to the number of injectionsand to the degree of gentamicin-induced horizontal canalar paresis. A genta-micin-induced saccular dysfunction was always observed in our patientswhereas a unilateral abolition of the horizontal canal function was detectedin only 58% of our gentamicin-treated patients. This suggests that the sacculusis more sensitive than the horizontal semicircular ampulla to ototoxic effectsof intratympanic gentamicin injections.

Patients Suffering from Vestibular Neuronitis

Among the 72 patients tested, 60 were tested during the acute state, i.e.during the first 2 weeks following the initial rotatory vertigo. The aim of ourstudy was to try to determine whether the whole vestibular nerve or only itssuperior branch was lesioned in this pathology. In 47 patients (65%), earlyuncrossed VEMPs were detected at a normal latency and amplitude on the SCMipsilateral and contralateral to the lesioned side. This result supports the conclu-sion of a previous study. Using the 3-D components of the ocular nystagmus, itwas shown that the saccular nerve and most probably the inferior vestibularnerve could be spared in vestibular neuronitis [27]. On the other hand, in 15of the 72 patients (20.8%), stimulation of the affected ear evoked no P13/N23responses in the ipsilateral SCM whereas stimulation of the intact ear resultedin a normal ipsilateral P13/N23 response. In 10 patients (13.8%), there was noVEMP in the ipsilateral SCM following stimulation of either the affected orintact ears. Therefore, the uncrossed saccular response evoked by the stimulationof the affected ear was abolished in 25 of the 72 patients (34.7%). When present,the mean latency and amplitude of the P13 and N23 potentials evoked by thestimulation of the affected ear in the ipsilateral SCM muscle were unchangedcompared to ones measured in normal subjects. In 10 patients, a bilateral aboli-tionofVEMPswasobservedduringtheacutestageofvestibulardeafferentation.Normal VEMPs reappeared on the intact side after 1 month in all of these pa-tients. This indicated that contralesional central vestibular neurons may havechanged their sensitivity to high level clicks. Similar data [28] have been reportedfollowing caloric tests: the caloric responses decreased on the contralesional sideover a period of 1 year following vestibular neurotomy.

In accordance with a previous study [10], we observed that none of thepatients with absent uncrossed VEMPs on the lesioned side developed benignparoxysmal positioning vertigo (BPPV) in the first 2 years following the begin-ning of the disease. This indicates that posterior semicircular canal-type BPPV

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could not develop in neuronitis patients which exhibit a lesion of the inferiorvestibular nerve.

In conclusion, VEMP test has confirmed that in most cases (two thirdsof the patients) the viral lesion spared the saccular nerve and most probablythe inferior part of the vestibular nerve. However, one third of the patientspresented a clear sign of saccular nerve lesion. In addition, the VEMP testhas a prognostic value since it can predict whether patients suffering fromvestibular neuritis will develop delayed positioning vertigo.

Patients Suffering from Other Vestibular PathologiesIn patients suffering from an acoustic neurinoma, VEMP test could be

normal or abnormal. It depends greatly on the size and extension of the tumoron the inferior and on the superior branch of the vestibular nerve. It could helpthe diagnosis when associated with other audiometric, vestibular tests and MRIof the cerebellopontine angle. Preoperatively, it is useful to evaluate the impor-tance of the symptoms (skew deviation, ocular cyclotorsion) the patient willsuffer at the acute stage due to otolith deafferentation. They are obviously lesspronounced when the otolithic sensors are lesioned before the neurectomy, leav-ing time for the compensation process to occur before the surgery.

The VEMP test could also bring important information in patientssuffering from delayed vertigo after head trauma. These patients may exhibitnormal caloric and rotatory tests if the lesion has spared the horizontal am-pulla. They could also exhibit normal visual subjective horizontal or verticaltests if the lesion had occurred several months after vestibular testing becauseof the vestibular compensation process. The same holds true for the OVARtest. The maculo-ocular reflex may have recovered normal dynamic properties.In these cases, only VEMP testing may indicate whether the head trauma hadinduced an otolithic lesion. Indeed, once the sacculus is lesioned, the P13/N23potentials never reappear even after a long delay following the lesion.

Finally, some patients suffering from disequilibrium and oscillopsia exhibitbilateral dysfunction of the horizontal semicircular ampulla as assessed bycaloric or rotatory testing. The problem is then to determine whether thesepatients present partial or complete loss of the vestibular function. Indeed,depending on the pathology and the subject, the otolithic function can bepreserved or not. In that context, VEMP testing can detect a residual saccularfunction. This is important on two grounds. From a clinical point of view, ithelps to assess the functional status of the vestibular system and it may beuseful to guide vestibular rehabilitation. In addition, it is clear that a preciseassessment of the vestibular function is required when patients accept to betested to investigate the role of the vestibular system in gaze and posturalcontrol or cognitive tasks. In that regard, it can be questioned whether the


numerous ‘bilabyrinthectomized patients’ used in the past 20 years in manyof these studies were truly deprived of vestibular function or were still endowedwith residual otolithic functions.

Conclusion

VEMP testing is a reliable, non-nauseogenic and a noninvasive test ofhuman saccular function.

(1) It has a diagnostic value in unilateral (Meniere’s disease, vestibularneuronitis, acoustic neurinoma) and bilateral vestibular pathologies to detecta potential lesion of the sacculus of the sacculo-spinal pathways.

(2) It also has a prognostic interest in some pathologies. In vestibularneuronitis it is useful to predict the possible occurrence of positional vertigoat late stages after the initial rotatory vertigo. Before surgery of acousticneurinoma, it is useful to inform the patient if he will suffer from symptomssuch as diplopia and deviation of the visual vertical subjective resulting fromthe otolith deafferentation of the extraocular motoneurons.

(3) Finally, its therapeutic interest is evident in bilateral horizontal vestibu-lar loss to guide the vestibular rehabilitation and in Meniere’s patients treatedby unilateral injections of gentamicin to detect early effects of gentamicin.New tests using the evoked potentials method and stimuli such as short tonebursts or short latency galvanic currents are now currently performed in ourdepartment to investigate in greater details the function of the sacculus andof the vestibular nerve.

Acknowledgements

The author thanks Franck Zamith, Nelly Bellalimat and Therese Dabbadie for theirexcellent technical assistance and their help in preparing the manuscript. She would like alsoto thank the Nicolet Biomedical Society and the Biodigital Society for the help in settingup the software.

References

1 Bickford RG, Jacobson JL, Cody DTR: Nature of average evoked potentials to sound and otherstimuli in man. Ann NY Acad Sci 1964:204–223.

2 Colebatch JG, Halmagyi GM, Skuse NF: Myogenic potentials generated by a click-evoked vestibulo-collic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–197.

3 de Waele C, Tran Ba Huy P, Diard JP, Freyss G, Vidal PP: Saccular dysfunction in Meniere’sdisease. Am J Otolaryngol 1999;20:223–232.

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4 Lim CL, Clouston P, Sheean G, Yamikas C: The influence of voluntary EMG activity and clickintensity on the vestibular click evoked myogenic potential. Muscle Nerve 1995;18:1210–1213.

5 Didier A, Cazals Y: Acoustic responses recorded from the saccular bundle on the eighth nerve ofthe guinea pigs. Hear Res 1989;37:123–128.

6 McCue MP, Guinan JJ: Acoustically responsive fibers in the vestibular nerve of the cat. J Neurosci1994;14:6058–6070.

7 McCue MP, Guinan JJ: Spontaneous activity and frequency selectivity of acoustically responsivevestibular afferents in the cat. J Neurophysiol 1995;74:1563–1572.

8 McCue MP, Guinan JJ: Sound-evoked activity in primary afferent neurons of a mammalian vestibularsystem. Am J Otol 1997;18:355–360.

9 Murofushi T, Corthoys IS, Gilchrist DP: Responses of guinea pig vestibular neurons to clicks. ExpBrain Res 1995;111:149–152.

10 Murofushi T, Halmagyi MG, Yavor RA, Colebatch JG: Absent vestibular evoked myogenic potentialsin vestibular neurolabyrinthitis: An indicator of inferior vestibular nerve involvement? Arch Otola-ryngol Head Neck Surg 1996;122:845–848.

11 Halmagyi GM, Colebatch JG, Curthoys IS: New tests of vestibular function. Baillieres Clin Neurol1995;3:485–500.

12 Black FO: Vestibular function assessment in patients with Meniere’s disease: The vestibulo-spinalsystem. Laryngoscope 1982;92:1419–1436.

13 Van de Heyning PH, Wuyts FL, Claes J, Koekelkoren E, Van Laer C, Valke H: Definition, classifica-tion and reporting of Meniere’s disease and its symptoms. Acta Otolaryngol [suppl] (Stockh) 1997;526:5–9.

14 Kingma H, Wuyts FL, Boumans L: Clinical testing of the statolith system in patients with Meniere’sdisease. Acta Otolaryngol [suppl] (Stockh) 1997;526:24–26.

15 Tumarkin A: Otolithic catastroph: A new syndrome. BMJ 1936;ii:175–177.16 Baloh RW, Jacobson K, Winder T: Drop attacks with Meniere’s disease syndromes. Ann Neurol

1990;28:384–387.17 Morrison G, Hawken M, Kennard C, Kenyon G: Dynamic platform sway measurement of Meniere’s

disease. J Vestib Res 1994;4:409–419.18 Robertson DD, Garber LZ, Ireland DJ: Ocular torsion monitoring in chemical labyrinthectomy.

J Otolaryngol 1996;25:171–177.19 Tribukait A, Bergenius J, Brantberg K: Subjective visual horizontal during follow-up after unilateral

deafferentation with gentamicin. Acta Otolarungol (Stockh) 1989;118:479–487.20 Nedzelski JM, Schessel DA, Bryce GE, Pfleiderer AG: Chemical labyrinthectomy: Local application

of gentamicin for the treatment of unilateral Meniere’s disease. Am J Otol 1992;13:18–22.21 Toth AA, Parnes LS: Intratynpanic therapy for Meniere’s disease: Preliminary comparison of two

regimens. J Otolaryngol 1995;24:340–344.22 Harada Y, Sera K, Ohya T, Tagashira N, Suzuki M, Takumida M: Effect of gentamicin on vestibular

ganglion. Acta Otolaryngol (Stockh) 1991;481:135–138.23 Chen JM, Williamson PA, Nedzelski JM, Cortopassi GA: Topical gentamicin-induced hearing loss:

A mitochondrial ribosomal RNA study of genetic susceptibility. Am J Otol 1996;17:850–852.24 Pender DJ: Gentamicin tympanoclysis: Effects on the vestibular secretory hair cells. Am J Otol

1985;6:358–367.25 Bagger-Sjoback D, Bergenius J, Lundberg AM: Inner ear effects of topical gentamicin treatment

in patients with Meniere’s disease. Am J Otol 1990;6:406–410.26 Hutchin T, Cortopassi G: Proposed molecular and cellular mechanism for aminoglycoside ototoxic-

ity. Antimicrob Agents Chemother 1994;38:2517–2520.27 Fetter M, Dichgans J: Vestibular neuritis spares the interior division of the vestibular nerve. Brain

1996;119:755–763.28 Fisch U: The vestibular response following unilateral vestibular neuronectomy. Acta Otolaryngol

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Dr. Catherine de Waele, Service O.R.L., Hopital Lariboisiere,CNRS Paris, 2, rue Ambroise Pare F–75475, Paris cedex 10, (France)



............................Peripheral Disorders in theOtolith SystemA Pathophysiological and Clinical Overview

Patrice Tran Ba Huy a, Michel Toupet b

a Hopital Lariboisiere, etb Centre d’Explorations Fonctionnelles Oto-Neurologiques, Paris, France

During recent years, better understanding has emerged of the role ofutricle and saccule in stabilizing both the head and vision thanks to advancesin fundamental vestibular physiology. Nevertheless, the semiology of otolithdisorders remains largely misdiagnosed by ENT clinicians, in part due to thelack of specificity of the tests currently available to them.

The aim of this chapter is to provide an overview of current pathophysio-logical, clinical and therapeutic advances which have been developed in theprevious chapters.

Structure and Function

The Otolith OrgansTwo parts of the labyrinth sense inertial forces arising from head move-

ments as well as forces due to gravity. The semicircular canals are primarlyconcerned with rotational accelerations while the otolith organs, the utricleand the saccule, transduce linear acceleration and are sensitive to static headposition. Both of these organs contain a sensory epithelium, the macula, whichis composed of three layers [1; see chapter by A. Sans, this vol.].

(i) A cellular layer consists of supporting cells and sensory hair cells oftypes I and II. At the apical face of each hair cell resides a bundle of hair-like processes containing a few hundred stereocilia graded in height, with thetaller ones being closest to a kinocilium. This arrangement defines an axis

of symmetry which, in turn, defines the functional polarization of the cell.Filamentous structures link the tips of adjacent stereocilia.

(ii) A gelatinous layer overlies the tip of the hair bundle.(iii) An otolithic membrane contains embedded otoconia. These crystals

of calcium carbonate make the mass of the otolithic membrane markedlydenser than the surrounding endolymph.

Two structural features have important physiological implications:(1) The two maculae have different spatial orientations. Thus, the utricle

is oriented in approximately the same plane as the lateral semicircular canalwhile the saccule is oriented perpendicular to it, in an approximately parasagit-tal plane. Furthermore, the surfaces of the maculae are curved rather thanplanar.

(2) A central line of demarcation named the striola divides each maculainto two parts. In each hemimacula, hair bundles are arranged in oppositesenses so that in the utricle, kinocilia are oriented toward the striola while inthe saccule, kinocilia are directed away from it. Also of functional importanceis the fact that saccular and utricular maculae on the left side are mirrorimages of those in the right vestibule. Moreover, the axis of symmetry, asdefined by the orientation of the kinocilia with respect to the row of stereocilia,varies continuously.

The overall result of these principles of anatomical and functional organi-zation is that otolith organs respond to translations and tilts in all directions.

Stimulus and Transduction

The otolith organs are sensitive to three types of motion: (i) linear accelera-tion of the head along the roll, pitch and yaw axes; (ii) static displacement ofthe head by tilting about these three axes; (iii) the force of gravity, which actsdownwards but is equivalent to an acceleration in the upward direction.

All of these stimuli are transduced through shearing forces on the hairbundles. When the head translates in space, the inertia of the endolymphcreates a force that moves the gelatinous layer in the opposite direction (thisencodes linear acceleration). This movement is enhanced by the density of theoverlying otolithic membrane (this encodes gravity and static motion, i.e. forcedue to the tilt of the head relative to the vertical force of gravity). Displacementof the hair bundle towards the kinocilium opens cation-selective transductionchannels and depolarizes the hair cell, while movements towards the shorteststereocilia close the channels and lead to hyperpolarization.

The ultrastructural features of the otolith organs have several functionalimplications:

111Peripheral Disorders in the Otolith System

(1) Their spatial orientation and disposition confers on the utricular andsaccular maculae sensitivity for horizontal and vertical displacements, respec-tively.

(2) The surface curvature of each hemimacula as well as the opposingand varying polarization of the hair cells allows that any linear acceleration,regardless of direction, will excite a distinct subset of cells at specific orienta-tions along its axis.

(3) Each hemimacula acts in concert with a counterpart located in thecontralateral vestibule so that, for example, the right lateral hemimacula workswith the left medial hemimacula.

(4) The final response corresponds to a push and pull mechanism: somecells on one side are stimulated while symmetrically opposite cells are inhibited,thus amplifying the overall receptor signal.

(5) Furthermore, backward or forward head tilts provide the same signalas forward directed linear acceleration or deceleration, respectively [2].

Vestibular Nerve and Central Pathways

The utricular and saccular fibers run though the superior and inferiorbranches of the vestibular nerve, respectively. Once the two branches gatherin the cerebellopontine angle, their exact position is not well defined withinthe VIIIth nerve.

Electrophysiological studies show that these fibers normally display aspontaneous firing rate. A given movement induces phasic-tonic or tonicchanges in the steady discharge rate. This allows the fibers to encode eitherlinear acceleration or absolute head tilt [3]. The responsivity range of the nerveis such that it may encode a very wide band of accelerations as detailed inthe chapter by M. Gresty [this vol].

The fibers then project into the lateral and medial vestibular nuclei locatedin the inferior part of the brainstem [3]. These vestibular nuclei transmitdescending outputs via the lateral and medial vestibulospinal tracts to controlneck and leg muscles. Their projections toward the extraocular muscles passvia the medial longitudinal fasciculus. Cortical projections are multiple anddispersed, mainly in parietal and temporal areas [4]. However, other areashave also been demonstrated in humans by electrical stimulation of the vestibu-lar nerve during surgery [5]. These cortical projections are likely to provideinformation for perception of self-motion and spatial orientation. However, itmust be stressed that visual and somatosensory inputs also reach the brainstemvestibular nuclei, so the existence of a primary vestibular cortex exclusivelydevoted to vestibular function is questionable. The exploitation of functional

112Tran Ba Huy/Toupet

MRI and PET scan techniques will hopefully provide further knowledge inthe near future.

Reflexes and Function

Stimulation of the otoliths triggers reflexes which normally stabilize pos-ture and gaze during static tilt or dynamic translations of the head. Similarto canal reflexes, there are two types of otolith reflexes.

Maculo-Spinal ReflexesOtoliths contribute to maintenance of postural balance though vestibulo-

spinal reflexes. Several experiments suggest that this is based on a three-neuron reflex arc. This accounts for the rapid muscular responses which arenecessary to counteract perturbations of body equilibrium [6]. Moreover,Brandt [7] has shown that otolith stimulation triggers different patternsof antigravity muscle activation, depending on the current posture. Hisobservations of surprisingly short latencies in a case of Tullio phenomenonare likely to correspond to a required capacity for humans. In day-to-dayexperience, these reflexes are evidenced by the compensatory movementsdisplayed by standing passengers when their train starts or stops suddenly.From a clinical standpoint, these otolith responses are tested by the click-evoked potentials in sterno-cleido-mastoid muscles [see chapter by C. de Waele,this vol].

Maculo-Ocular ReflexesThese reflexes take into account both dynamic translational and static

(gravitational) forces and act to stabilize gaze during any movement of thehead by inducing compensatory movements of the eyes [8]. Four types ofmovements can be identified:

Translational (T ) or linear (L) reflexes are triggered when the head, ormore precisely, the orbits translate. The resulting rotation of the globe isinversely proportional to the distance of gaze fixation: the nearer the target,the greater the rotation. The gain is low in darkness. If the target is locatedlateral from the midline, a disconjugate movement of the eyes must take place.This T- or L-VOR occurs at short latencies (15–60 ms).

Rotational otolith VOR occurs when the head rotates along an axis tiltedwith respect to the earth-vertical (off-vertical axis rotation). In this paradigm,the otoliths are stimulated continuously by the cyclic changes in the relativeorientation of gravity vector associated with the rotation of the head [seechapter by S. Wiener-Vacher, this vol.]. The resulting nystagmus is sustained


and polymorphic. It persists after the disappearance of the horizontal nystag-mus induced by the canal response to the initial rotatory acceleration.

Modulation of spontaneous and induced nystagmus can be induced byotolith stimulation. Changes in static otolith inputs influence the directionand duration of caloric, rotatory and postrotatory nystagmus. Tilt of the headmay also modify spontaneous nystagmus so that a downbeat nystagmus maybe converted to an upbeat nystagmus.

Ocular counterrolling occurs when the head is tilted laterally, that is, inthe frontal plane (about the roll axis). In this situation, the globes counterrollto reorient the horizontal meridians of the retinae toward the earth horizontalplane. These compensatory movements are of utricular origin and result froma contraction of the superior and inferior oblique muscles. Thus an inclinationof the head to the right stimulates the left superior and right inferior obliquemuscles. The gain of this reflex is low (0.1). Similarly, when the head is tiltedforward or backward, that is in the sagittal plane (about the pitch axis), theeyes rotate in the opposite direction (‘baby doll eyes’).

Other functions are also attributed to the otolith system such as hemody-namic and respiratory adaptation to postural changes, determining visualsubjective vertical, mental representations of the body, detection of changesin spatial orientation, evaluation of displacements, etc.

Pathophysiology

Dysfunctions of the otoliths alter the transduction of linear accelerationforces, including gravity. As a result, the physical forces which act permanentlyon any moving individual are no longer adequately sensed. The otoliths thenprovide erroneous information for the control of posture and eye-head coor-dination as well as sensation of upright posture, self-motion, and awarenessof the body. This may lead the patient to describe strange feelings of disorienta-tion, detachment or instability even causing psychological disturbances suchas anxiety and panic. Various etiologies can be put forward such as infection,trauma, degenerative disorders, etc. However, some intrinsic factors may ac-count for the development of an otolith disorder.

Intrinsic Predisposing FactorsWhile the particular organization of the hair cells facing each other in

each hemi-macula amplifies the signal by a push-pull mechanism, it alsorenders the system fragile. By way of comparison, in the cristae, all of thehair cells are organized with their kinocilia pointing in the same direction:utriculopetal in the lateral canal, utriculofugal in the anterior and posterior


canals. Thus, the entire population of sensory cells is depolarized when thecupula moves in the appropriate direction. On the contrary, hair cells in thesaccular and utricular maculae are polarized in many directions permittingthem to signal tilt or linear acceleration in all directions. However, for anygiven direction of the linear force only a small fraction of the cells are appro-priately aligned and optimally stimulated. In other terms, otolith transductionfrom normal stimuli relies on only a limited number of cells. Moreover, thepush-pull mechanism induces pairs of opposite signals making the codingmore complex than in the canals.

Within the maculae, the anatomical distribution of type I hair cells (morecentral) and type II hair cells (more peripheral) recalls the organization of conesand rods in the retina [see chapter by A. Sans, this vol.]. This may explain whylocalized and patchy lesions of the receptor surface will not necessarily affectoverall otolith function but rather cause only minor and discrete symptoms re-quiring highly sophisticated investigative approaches to identify them.

Other complications arise from the fact that the position of the macularfibers within the vestibular nerve is not well defined. Thus, identification ofthese fibers during vestibular neurotomy is uncertain – this may account forthe persistence of symptoms of dizziness in some patients since a completesection is often difficult to ascertain.

Vestibular nuclei receiving otolith inputs are situated low in the brainstem.This explains the lateropulsions observed in caudal lesions such as Wallenberg’ssyndrome.

Interacting FactorsThe otolith system interacts with several sensory and motor systems. This

explains why the clinical features of otolith disorders frequently overlap withvarious manifestations of other origins. Thus pure otolith syndromes are rare.As will be seen below, semiology should be interpreted in light of severalfactors:

(1) Similar or complementary information is also provided by other senso-rimotor inputs, especially proprioceptive inputs. It is well known that sensitiveinformation coming from the back and lower trunk are of primary importancein sensing displacement in seated patients. This observation is exploited inphysical therapy for rehabilitation.

(2) Canal and otolith organs are often stimulated simultaneously – this isbecause purely linear or angular accelerations of the head are extremely rare.

(3) Further ambiguity derives from the organizational principle of mirrorsymmetry between the maculae of both sides. Hence, a unilateral impairmentis compensated by the contralateral macula which still possesses a populationof sensory cells capable of signaling stimulation in all directions.


These interacting factors account for the fact that otolithic symptoms areoften difficult to identify and become apparent when visual or proprioceptivefunctions are defective.

Symptoms

Dysfunction of the otolith system results in three types of symptoms:visual, postural and perceptual. Other signs related to neurovegetative andautonomic functions are also suggestive of otolith disorders [2, 9].

All these symptoms share the following features: (i) they are triggeredby linear or static displacements; (ii) they become evident when visual andproprioceptive pathways are also disturbed; (iii) they vary greatly in intensityand frequency among patients.

Visual SymptomsAccurate and precise VORs are necessary to maintain stable images on

the retina. Vergence, calculation of viewing distance and disconjugate eyemovements are required for this system to be efficient. In other terms, it maybe said that the otolith system acts as the autofocus of a camera.

Accordingly, otolith dysfunction will lead to complaints of poor visionexperienced while the patient is moving, such as trouble focussing, difficultywith reading, altered depth perception, etc. Among the major symptoms areoscillopsia, vertical and oblique diplopia, and altered perception of verticality.The latter is manifested by difficulty in correctly aligning objects on a wall,especially when viewed from nearby, i.e. when visual orienting references inthe environment are out of view.

Perceptual SymptomsAs described above, otolith dysfunction may lead to erroneous perceptions

of the relation between environment and self as well as the patient’s perceptionof his body. This leads to seemingly strange complaints such as abnormalsensations of levitation, translation or tilt. The patient may report inappropri-ate sensations of moving up and down, the illusion of standing on the deckof a moving ship or walking on soft or inclined ground, the sensation of falling,lateropulsions, etc. Illusory self-motion, erroneous internal representations,permanent and severe disorientation, feelings of dissociation and hallucina-tions are also frequently reported by patients.

Facing such symptoms, the clinician should first investigate the possi-bility of otolith pathology before invoking functional or psychiatric dis-orders.


Postural SymptomsThe loss or impairment of otolith function produces a decrease in resting

activity of the graviceptive pathways. This precipitates an imbalance in tonuswhich compensating oculomotor and postural reactions act to minimize. Per-haps the most spectacular postural example of this is illustrated by the oculartilt reaction (OTR) described by Brandt [this vol.]. In the case of a peripheraldeficit, this consists of ipsilateral head tilt, skew deviation (vertical divergenceof the eyes) and ocular torsion. Body lateropulsion may also be associated.

Other SymptomsOtolith organs partly control some autonomic functions such as blood

pressure, volume distribution, and cardiorespiratory parameters [see chapterby M. Gresty, this vol.].

In orthostatic hypotension, encoding by the otolith organs of the movementof the patient standing up is dissociated from adequate control of bloodpressure by baroreceptors, giving rise to a pseudo-vertiginous feeling.

In mal de debarquement (post-seasickness), nausea and vomiting, brady-cardia, and hypotension could be due to excessive stimulation of the utricularand saccular maculae by prolonged linear stimulation due to the rockingmotion of the ship.

In motion sickness, changes in blood pressure could be secondary toabnormal stimulation of the otolith system. The motorcyclist has learned totilt his head forward during accelerations: this orients the otolith organs inthe direction of the vector sum between the horizontal linear acceleration andthe upward gravity vector [see Gresty, this vol.]. However, the passenger whodoes not anticipate the acceleration and permits his head to tilt backwardswill complain of a brief sensation of nausea and lipothymia.

Peripheral Otolith Syndromes

The few proven otolith syndromes are described in detail by Brandt [thisvol.] and his textbook [7]. In the following sections, we will review their mainclinical features and add some personal comments in light of our daily clinicalexperience.

Post-Benign Paroxysmal Positioning Vertigo SyndromeBenign paroxysmal positioning vertigo (BPPV) is the most frequent cause

of peripheral vertigo in France [10]. Its semiology is characterized by briefattacks of rotatory vertigo and concomitant nystagmus. It is elicited when thepatient is in a given attack-precipitating position. Its pathogeny – cupulo- or


most probably canalo-lithiasis principally of the posterior semicircular canal– are well known [7, 11]. However, it must be stressed that BPPV is not anotolithic syndrome but rather a neo-otolithic one since the cupula and/or thecanal are the structures affected by the otoconial debris and these are nototolith organs per se.

Actually, the otolith component of the syndrome may sometimes becomeevident after the acute phase has subsided spontaneously, or following physicaltherapy including positional exercises or maneuvers disengaging the debris.At this point it is not uncommon to see patients complaining of symptomssuggestive of an otolith disorder such as unsteadiness, visual blurriness whenwalking, etc. These symptoms are likely to arise from abnormal utricularfunction on the side of the BPPV – this would be due to the decrease indensity of the otolith membrane from the dislodged otoconia.

The Tumarkin CrisisThe vestibular symptoms which characterize a typical attack of Meniere’s

disease are highly suggestive of involvement of all three semicircular canals.An otolithic component is seen only in the ‘vestibular drop attack’ describedby Tumarkin [12] in 1936. Without any prodrome, the patient feels abruptlyforced to the ground and falls. The attack is so sudden that the patient hasno time to interrupt his current activity, stop his car, to sit or to lie down.Severe head trauma and bony fractures of the nose are not uncommon.

In our experience, this ‘otolithic catastrophe’ occurs only at a late stageof the disease. The lack of warning symptoms and fear of further unpredictableaccidents leads patients to seek radical treatment. As preventive pharmacolo-gical treatment is ineffective, we have tried using trans-tympanic instillation ofgentamicin in such cases. While this consistently suppressed myogenic evokedpotentials, suggesting successful abolition of saccular function, we found thatsome patients were still incapacitated by recurring crises. Therefore, surgerywould seem to be the only reliable modality of treatment.

Post-Traumatic VertigoPatients may complain of a very wide range of symptoms having only

one factor in common, a head trauma in their recent past. The reported signscan include disorientation, illusions of motion, gait ataxia, sensations of falling,blurring of vision, etc. – these are often imprecise and variable so that a specificclinical picture cannot be described.

A perilymph fistula is frequently evoked. However, when results are allnormal from neuro-otological examination, current vestibular tests and com-plete radiological evaluation, the organic nature of the disease is frequentlyquestioned. Thanks to the development of new objective tests capable of


revealing alterations of the subjective visual vertical or disappearance of evokedmyogenic potentials on one side, it is now possible to unequivocally demon-strate the origin in the otolith system.

Considering the major forensic and financial implications, otolith testing(discussed below) should be included in the routine examination of any post-traumatic vertigo.

Otolith and Perilymph Fistula (PLF )Leak of perilymph through the oval or round windows, or promontory

dehiscence may be congenital or acquired. It induces vestibular symptoms byinadequate transfer of pressure changes to macular receptors. As emphasizedby Brandt, head movements are much better tolerated than linear accelerations.

In our experience, PLF is not uncommon after head or barotrauma,violent implosive or explosive forces from the middle to the inner ear or fromthe CSF to the middle ear, respectively, or erosion by cholesteatoma [13]. Inthese circumstances, diagnosis is usually made on the basis of clinical andradiological arguments. Surgery confirms the fistula, and various techniquesof successful repair have been described [14].

On the contrary, spontaneous PLF seems rare if not exceptional andshould be seriously questioned when considering: (i) the marked discrepanciesamong authors, some reporting impressive numbers of surgical cases whileothers (like us) still desperately trying to find even a single case; (ii) the lackof universally accepted tests for diagnosing PLF; (iii) the highly debatable(and surprising to us) criteria advocated by some authors who do not requirethe presence of a fluid leak at the time of exploratory tympanotomy forestablishing a diagnosis of PLF; (iv) the positive results reported after prophy-lactic grafting, even in the absence of well-defined and well-localized fistula.

Therefore, preoperative criteria should be extremely strict including:(i) association of cochleo-vestibular symptoms, i.e. brief and transient episodesof ataxia, fluctuating aural fullness, tinnitus and sensorineural hearing loss;(ii) symptom-provoking circumstances should include situations where intra-cranial pressure is increased, such as strenuous activities and rising from asitting position; (iii) the various pressure or vascular tests should give unequiv-ocally positive results. If these criteria are fulfilled and conservative treatmenthas failed, this could justify exploratory tympanotomy. But the diagnosis ofPLF should not be accepted until a perilymph leak is clearly evidenced.

Postoperative OTR SyndromeAn ipsiversive OTR syndrome may be observed after a peripheral vestibu-

lar lesion [7]. The most frequent circumstances are a vestibular neurotomy orafter removal of an acoustic neuroma (provided that vestibular function was


Fig. 1. Postoperative OTR syndrome in a right vestibular neurotomy patient who hadcomplained of diplopia upon awakening from anesthesia. The bedside examination wasperformed at 7 p.m. On the left, the patient first looks at the blue cross with his right eye.When opening the left eye, he draws the cross above and to the left of the first drawing.On the right, the patient looks at the blue cross with his left eye. When opening the righteye, he draws the cross above and to the right. The next morning these symptoms haddisappeared.

still present prior to surgery). The sudden imbalance of tone of the VORdue to reduced utricular inputs yields an oculo-cephalic response toward theaffected ear. This consists of head tilts, skew deviation with ipsilateral eyeundermost, and cyclotorsion (fig. 1).

This syndrome is short-lasting and usually subsides within a few hours.

The Otolith Tullio PhenomenonThis rare condition was precisely identified and described by Dieterich

et al. [9] in 1992. It is manifested by attacks of oscillopsia and postural im-balance which are elicited by loud sounds applied to the affected ear [seechapter by T. Brandt, this vol.]. The detailed ocular and postural movementsobserved in this tonic paroxysmal OTR syndrome include contralateral headtilt, skew deviation with ipsilateral hypertropia greater than the contralateralhypertropia (both eyes are upward deviated), ocular torsion (the incyclotropiaof the ipsilateral eye is more pronounced than the exocyclotropia of the con-


tralateral eye), and increased body sway. In contrast with the postoperativeOTR syndrome described above, the ocular and head postural deviations aredue to pathological stimulation of the utricle.

Various etiologies have been reported, all of which include either a peri-lymph fistula or a contiguity between the ossicular chain and the membranouslabyrinth so that loud acoustic stimulation is directly transmitted to the otolithstructures.

In our experience, the most frequent circumstance is encountered afterstapedectomy, especially when a graft interposition has been placed over theoval window. Indeed, some successfully operated patients complain of briefgait disturbances or lateropulsion, and tilt of the visual scene when exposedto traffic or industrial noise, music at concerts or headphones. In two recentcases observed in our institution, the mechanism was likely the developmentof a postinflammatory fibrosis within the vestibule. In the early postoperativeperiod, both patients developed an acute labyrinthitis with sensorineural hear-ing loss and vertigo. Once the acute episode subsided, the patients recoveredtheir hearing and balance, but developed tonic OTR. The first patient, aprofessional clarinet player, complained of otolith symptoms each time heplayed his instrument, once falling on the shoulder of his colleague whileplaying a Bruckner symphony. Steroids and topical vasoconstrictors were givenand alleviated the symptoms in a few days (fig. 2). The second patient presentedthe same types of signs while listening to headphones. Although in this casethe treatment with medications failed, insertion of a ventilating tube relievedthe symptoms. Other possible surgical techniques include section of the stape-dial muscle or removal of the piston.

Presbyvestibulopathy and OtotoxicityNumerous experimental and histopathological studies have shown bilat-

eral and progressive otolith lesions secondary to aging or after aminoglycosideintoxication [15]. Loss of hair cells and primary neurons as well as degenerationof the otoconia are well-documented features which can easily account forthe symptoms so frequently reported in elderly patients, i.e. unsteadiness, gaitdisturbance, and oscillopsia.

However, tests of otolith function may reveal normal responses.

Evaluation of a Patient with a Possible Otolith Disorder

Any patient presenting signs of an otolith disorder should undergo com-plete neuro-otological evaluation. However, the clinician must keep in mindthat the typical signs of vestibular disease, such as spontaneous nystagmus,


Fig. 2. Otolith Tullio phenomenon in a patient operated for right stapedectomy 3 weeksearlier. The CT scan shows a granuloma filling the oval window niche.

or abnormal caloric or rotatory responses are likely to be absent. A majorachievement in recent years has been the development of tests investigatingotolith function. It must be stressed, however, that the specificity of these testsis weakened by the multisensory contributions to sensing linear accelerationfrom the translations and the force of gravity [16]. Moreover, a single otolithorgan is able to signal adequately motion in all directions due to the bidirec-tional polarization of hair cells (see above). In other terms, unilateral dysfunc-tion is compensated by the mirror symmetry of the otolith organs.

With these caveats, the following procedures may be used by cliniciansto demonstrate impairment or loss of otolith function.

Ocular Counter-RollingThis ocular reaction represents the unique manifestation of utricular

function that can be directly observed in healthy subjects following stimulation.As noted above, this is evidenced by a compensatory movement which orientsthe horizontal meridian of the retinae toward the perpendicular to the vertical.In this test, the head of the patient is tilted laterally (in the frontal plane)toward the right then left shoulders by about 30º. In the normal subject, theeyes rotate about the roll axis in the direction opposite the applied tilt with


no delay. However, this ocular movement, called ‘counter-rolling’ (‘contre-rotation’ or ‘Gegenrolung’) is rarely very informative since it is relativelyinsensitive. The problem is that a head inclination of 90º yields an eye rotationof only 6º (the equivalent of the movement of the minute hand of a clockafter only 1 min!) Instrumental measurements of torsional nystagmus by video-nystagmography will undoubtedly provide greater sensitivity for this simpletest.

The Subjective Visual Vertical TestBecause otolith organs play a major role in sensing verticality and upright

posture, this test is a sensitive and very easily administered tool for assessingotolith function [17; see also chapter by C. Van Nechel, this vol.]. The patientis placed in complete darkness and asked to orient a fluorescent bar verticallyor horizontally.

In the immediate postoperative period of vestibular neurotomy or acousticneuroma surgery, these estimates may be deviated by up to 15º towards theoperated side, being more pronounced if only the ipsilateral eye is used. Long-term follow-up of these patients shows that the pathological deviation maylast for months after surgery. Ongoing debates concern the correlation betweenthe degree of ocular torsion and the perceptual deviation.

Although not exclusively specific for otolith dysfunction, the simplicityand cost-effectiveness of this test render it quite useful.

Evoked Myogenic PotentialsRecording vestibular evoked myogenic potentials (VEMPs) evoked in

the sterno-cleido-mastoid muscles (SCMs) by loud clicks is a reliable andnoninvasive test of saccular function in humans [6, 18; see also chapter byC. de Waele, this vol.].

The subject lies supine on a bed and is asked to lift only his head upin order to activate the SCMs bilaterally and symmetrically. The clicks consistof 0.1 ms rarefactive square waves of 100 dB HL delivered by calibratedTDH 39 headphones. They are delivered at a frequency of 6 Hz and theiramplitude is 145 dB SPL. Surface EMG activity is recorded by means ofskin electrodes placed symmetrically on the upper half of each SCM andamplified, bandpass filtered (8–1,600 Hz) and averaged using a sampling rateof 2.5 kHz for each channel. The mean peak latency of the two early potentialsand of the late evoked potential of the VEMP is measured. The responseconsists of an initial positive potential at 10 ms, and negative potentials at20 and 30 ms.

The main advantage of this test is that it permits each saccule to beinvestigated independently and objectively.


Other TestsOther tests permit testing of otolith function, but their high levels of

sophistication render them more difficult to administer.Off-Vertical Axis Rotation (OVAR). In this test, the patient is seated on

a rotatable chair and eye movements are measured by electro-oculography.After an initial acceleration to a constant velocity (60 deg/s), the rotating chairis tilted by 13º with respect to gravity. Sessions are conducted with clockwiseand counter-clockwise rotations to permit functional investigation of the rightand left otolith systems, respectively. This test takes advantage of the fact thatthe semicircular canal responses rapidly habituate to the constant velocityrotation. Thus, any resulting ocular nystagmus is strictly due to otolith systemactivation [19; see also chapter by S. Wiener-Vacher, this vol.].

This test can detect dysfunctions of the otolith system as well as functionalasymmetries between the left and right sides.

The Eccentric Rotating Chair or the Carousel Test. In this test the patientis seated on a chair mounted 1 m from the axis of rotation. The patient isrotated in darkness clockwise and counterclockwise, facing forward in eithercase.

He is requested to align either vertically or horizontally a luminous barlocated 60 cm in front of him. The combination of the forces of the appliedangular and horizontal acceleration as well as gravity preferentially stimulatesthe more eccentrically positioned utricle. This perturbs the perception ofhorizontal and vertical such that responses can deviate by as much as 20ºrelative to the true orientation. This angle is the resultant of the axis ofhorizontal centripetal acceleration and that of gravity. The response anglevaries as a function of the velocity of rotation. In cases of unilateral lesions,asymmetric responses are observed [20; see also chapter by L. Odkvist,this vol.].

While this test is more sensitive than ocular counter-rotation, the appa-ratus is more costly.

The Tilt Suppression Test. This test takes advantage of the propensityfor otolith stimulation to modulate secondary instrumental nystagmus[8, 21].

In this test, the patient is seated in a chair without being attached,rotated for ten turns (at a velocity of 120º/s). After coming to an abruptstop, the slow phase velocity is measured for 5 s with the eyes open, thenagain after tilting the head forward. In normal subjects, or in cases offunctional impairments of individual semicircular canals, the nystagmus isdramatically reduced after the tilt. However, if the cerebellar nodulus orotolith organs are affected, the nystagmus remains after the forward tilt(fig. 3).


a

b

c

Fig. 3. Post-rotatory nystagmus (10 rotations in 60 s). The head is tilted forward (a).This induces a marked reduction of the nystagmus (b). Such a decline is not observed incases of lesion of cerebellar flocullus or in cases of otolith disorder (here a post-BPPVsyndrome) (c).

Treatment

Peripheral problems in the otolith system will normally disappear rapidly.Within a few weeks central compensatory mechanisms alleviate the vestibulardeficit and most patients require no particular treatment. However, it mustbe noted that the pharmaceutical treatments currently prescribed for acuteand complete peripheral vestibular damage (both canalar and macular) assistor accelerate the typically spontaneous recovery.


Further treatment only becomes necessary in cases where symptoms per-sist beyond 1 or 2 months. This consists primarily of rehabilitative therapywhere the patient is trained to use the remaining otolith function maximallyand to depend more on visual and proprioceptive informations. For example,typical exercises can include:

(a) The patient jumps on a trampoline with eyes first open, thenclosed.

(b) The subject walks in place on an inflated mattress or a mobile plat-form, eyes open, then closed.

(c) The latter exercises are repeated while tilting the angle of the head(hence varying the direction of the gravity vector).

(d) The subject performs calisthenics, first on two legs, then on one. Thisis done facing a mirror marked with vertical and horizontal bars to providevisual reference cues.

(e) Rapid translations are applied to a mobile platform on which thesubject is standing. The aim here is to make the patient lose equilibrium, andthus learn new postural reflexes.

(f ) The patient reads from a stationary text which is then moved slowly.This helps develop slow visual pursuit. This is then repeated rapidly, then withrandom movements in order to develop visually guided saccades. The sameexercise is also repeated while the subject makes horizontal, then linear headmovements.

(g) The patient is subjected to optokinetic stimulation in the frontal orsagittal planes at increasing velocities. This obliges him to break free of hisdependence on visual input and to emphasize the importance of the (re-maining) otolith information.

The vestibular exercises must exclude any type of rotatory stimulation ofthe canals. It is recommended to also include orthoptic therapy with, forexample, the use of ocular prisms correcting for vertical divergence. Psycholo-gical counselling is also advised in order to reduce the strain and sufferingthat accompanies equilibrium disorders.

These diverse exercises requiring the use of the otolith will reinstate theappropriate circuits in the brain and bring about motor learning which thepatient will be able to apply on a daily basis. Should the patient show noimprovement, and if the otolith damage is unilateral, a chemical labyrin-thectomy may be performed by trans-tympanic instillation of aminogly-cosides. The outcome can then be measured by myogenic evoked potentials.If this is ineffective, and, moreover, the symptoms are truly incapacitating,vestibular neurotomy via retro-sigmoid or middle fossa approaches wouldthen become necessary. The efficacy of this is unquestionable, but it is rarelyindicated.


References

1 Lindeman HH: Anatomy of the otolith organs. Adv Oto-Rhino-Laryngol 1973;20:405–433.2 Gresty MA, Bronstein AM, Brandt T, Dieterich M: Neurology of otolith function: Peripheral and

central disorders. Brain 1992;115:647–673.3 Baloh RRW, Honrubia V: Clinical Neurophysiology of the Vestibular System, ed 2. Philadelphia,

Davis, 1990.3a Gacek RR: The course and central termination of first order neurons supplying vestibular endorgans

in the cat. Acta Otolaryngol (Stockh) 1969;254:1–66.4 Lobel E, Kleine JF, Bihan DL, Leroy-Willig A, Berthoz A: Functional MRI of galvanic vestibular

stimulation. J Neurophysiol 1998;80:2699–2709.5 Vidal P-P, de Waele C, Baudonniere PM, Lepecq JC, Tran Ba Huy P: Vestibular projections in the

human cortex. Ann NY Acad Sci 1999;871:455–457.6 Colebatch JG, Halmagyi GM, Skuse NF: Myogenic potentials generated by a click-evoked vestibulo-

collic reflex. J Neurol Neurosurg Psychiatry 1994;57:190–197.7 Brandt T: Vertigo: Its Multisensory Syndromes, ed 2. London, Springer, 1999, 503 pp.8 Zee DS, Hain TC: Clinical implications of otolith-ocular reflexes. Am J Otol 1992;13:152–157.9 Dieterich M, Brandt T, Fries W: Otolith function in man. Brain 1989;112:1377–1392.

10 Toupet M: Evolution a long terme de 168 vertiges paroxystiques positionnels benins traites par lamaneuvre; in: Vertige 93. Paris, Arnette & Duphar-Solvay, 1994, pp 55–90.

11 Schuknecht HF: Pathology of the Ear. Cambridge, Harvard University Press, 1974.12 Tumarkin A: The otolithic catastrophe: A new syndrome. Br Med J 1936;175–177.13 Tran Ba Huy P: Physiopathology of peripheral non-Meniere’s vestibular disorders. Acta Otolaryngol

(Stockh) 1994;(suppl 513):5–10.14 Guyot JP (ed): Perilymphatic Fistula: A Controversial Issue. Otorhinolaryngol Nova 1998;8:169–212.15 Anniko M: The aging vestibular hair cell. Am J Otolaryngol 1983;4:151–160.16 Gresty MA, Bronstein AM: Testing otolith function. Br J Audiol 1992;26:125–136.17 Bohmer A, Rickenmann J: The subjective visual vertical as a clinical parameter of vestibular function

in peripheral vestibular disease. J Vestib Res 1995;5:35–45.18 de Waele C, Tran Ba Huy P, Diard JP, Freyss G, Vidal P-P: Saccular dysfunction in Meniere’s

disease. Am J Otol 1999;20:223–232.19 Wiener-Vacher SR, Toupet F, Narcy P: Canal and otolith vestibulo-ocular reflexes to vertical and

off vertical axis rotation in children learning to walk. Acta Otolaryngol (Stockh) 1996;116:657–665.20 Odkvist LM, Gripmark MA, Larsby B, Ledin T: The subjective horizontal in eccentric rotation

influenced by peripheral vestibular lesion. Acta Otolaryngol 1996;116(2):181–184.21 Van Der Stapen A, Wuyts FL, Van de Heyning P: Influence of head position in the vestibulo-

ocular reflex during rotational testing. Acta Otolaryngol (Stockh) 1999;119:892–894.

Prof. Patrice Tran Ba Huy, Hopital Lariboisiere, Service d’Oto-Rhino-Laryngologie,2, rue Ambroise-Pare, F–75475 Paris (France)Tel. +33 1 49 95 80 57, Fax +33 1 49 95 80 63


............................Subject Index

Acoustic neuroma, vestibular-evoked overview of symptoms and otolithdysfunction 58, 59myogenic potential 106, 107

Autonomic function, otolithic spinal column and posture tests64, 65control 26–28, 117

videonystagmography 65visual acuity findings 62Benign paroxysmal positioning vertigo

clinical presentation 38, 117, 118diagnosis 39 Eccentric rotatory testing

clockwise direction testing 70etiology 38, 39horizontal canalolithiasis 39 equipment 70, 71

head tilt 69, 70physical therapy 39subjective visual vertical 78 protocol 71–73, 124

Electromyography, see Vestibular-evokedBlood pressure, otolithic control 26, 28,29, 117 myogenic potential

Endolymph, specific weight 68Eye movement reflexes, see also EccentricCalbindin, expression in utricle 6

Calcitonin gene-related peptide, expression rotatory testing, Off-vertical axis rotationtest, Subjective visual verticalin utricle efferent system 8

Calretinin, expression in utricle 6, 8, 11 counter-rolling 22, 24, 69, 114, 122, 123cyclo-torsion and visual vertical inCerebral cortex

areas involved in vestibular processing unilateral otolithic lesions 24linear movement in horizontal and verticalduring galvanic stimulation 56, 57

vestibulular fields 54–56 planeslesion effects 20–22Cranio-facial asymmetry

anatomic findings rapidity of response 20linear reflexes 113anteroposterior asymmetry 60, 61

asymmetries of orientation 61 oscillopsia 24, 25rotational reflexes 113, 114asymmetry in torsion 61

lateral asymmetry 61 subjective visual horizon testno rotation test 73vertical asymmetry 61

magnetic resonance imaging 60 tilting chair 73translational reflexes 113ocular torsion examination 62–64

129

Galvanic vestibular stimulation hearing loss relationship 102, 103saccular function 74, 101–103cortical areas involved in vestibular

processing 56, 57 visual dependence of patients 103, 104Motion sicknessimaging 57

overview 56 otolith role 117prevention in ambulance transport 28–30Gentamicin

Meniere disease treatment andvestibular-evoked myogenic potentials Neurokinin A, expression in utricle afferent

system 11104, 105, 108ototoxicity mechanisms 121vestibular drop attack induction 37 Ocular counter-rolling, testing 22, 24,

69, 114, 122, 123Off-vertical axis rotation testHair cells

functional polarization 111, 114, 115 interpretation of responses 90perilymphatic fistula, abnormal irritationfunction in otolith unit 17, 110, 111

predisposing factors in otolith of otolith receptors 95principle and methodology 88, 89, 124dysfunction 114, 115

saccule 4–6, 12 vestibular damage diagnosticsacute phase of damage 93, 94stimuli 111

utricle 4–6, 8, 11, 12 chronic phase of damage 94unstable developing lesions 95Head direction cell system 57, 58

vestibular neuritis prognostic testing95, 96LED bias bar test

clockwise direction testing 70 vestibular system role in posturo-motordevelopment of children 90–93equipment 70, 71

head tilt 69, 70 vestibulo-ocular responses 88–90, 92,95, 96protocol 71–73

subjective visual horizon test Orthostatic hypotension, otolith role 117Oscillopsia 24, 25, 116, 107no rotation test 73

tilting chair 73 Otoconiadensity 68Linear motion

simulator 18, 19 function 111Otoconial membranethresholds 18

function 1, 111scanning electron microscopy ofMaculo-ocular reflexes, see Eye movement

reflexes ultrastructure 2, 3Otolithic calnolithiasis, see BenignMaculo-spinal reflexes, otoliths 113

Malaise, pathophysiology with vestibular paroxysmal positioning vertigodisorders 26–28

Mal de debarquement, otolith role 117 Parvalbumin, expression in utricle 6, 11Perilymph fistulaMeniere disease

eccentric rotatory test 74 clinical presentation 41, 42diagnosis 119vestibular-evoked myogenic potential

canal paresis 103 etiology 41, 119otolith types 41, 42equitest performance relationships 103

gentamicin-treated patients preoperative criteria 119Tullio phenomenon 42104, 105, 108

130Subject Index

Perilymphatic fistula, off-vertical axis clinical types 43otolithrotation test 95

Positional vertigo, see Benign paroxysmal case reports 44, 45clinical manifestations 43, 44, 120, 121positioning vertigo

Postoperative ocular tilt reaction etiology 121ocular tilt reaction 43, 44, 120syndrome 119, 120

Postural symptoms, otolith dysfunction 117 pathology 42Tumarkin otolithic crisis 35, 37, 118Posturo-motor development 90–93

Quix, F.H., contributions to otolith Upright orientation, sensitivity 18, 19Utricledysfunction evaluation 15, 17, 25

afferent systemglutamate as neurotransmitter 8Rehabilitative therapy, otolith disorders

39, 126 neurokinin A expression 11substance P expression 11, 12

calcitonin gene-related peptide expressionSacculefunction 1, 68, 69, 111, 112 in efferent system 8

calcium-binding protein expressionhair cells 4–6, 12scanning electron microscopy of calbindin 6

calretinin 6, 8, 11ultrastructure 3Semicircular canal parvalbumin 6, 11

function 1, 68, 69, 111, 112otolith function overlap 34, 52–54,115, 116 hair cells 4–6, 8, 11, 12

scanning electron microscopy ofvertigo 34, 35Spatial orientation, perception 18, 19 ultrastructure 2, 3Startle response, vestibular origins 25Striola, orientation 111 Vertigo

benign paroxysmal positioning 38, 39Subjective visual verticaldefinition and overview 77 cerebral cortex

areas involved in vestibular processinginstrumentation for measurement 86monocular vs binocular testing 84, 85 during galvanic stimulation 56, 57

vestibulular fields 54–56otolithic disorder deviations 78, 79, 123stages of measure cognitive contribution of otoliths to

spatial orientation and movementcomparison process 82, 83subjective vertical reference perception

ambiguity of perception 48, 49somatosensory inputs 81, 82vestibular contribution 81 imagination modification of subjective

vertical perception 49, 50visual contribution 81visual input 79–81 interaction between canals and otoliths

for two-dimensional displacementstimulus methodology 83, 84subject placement 85 trajectory perception 52–54

perception and memory of pure angularSubstance P, expression in utricle afferentsystem 11, 12 or linear motion 50, 51

cranio-facial asymmetry patients, seeCranio-facial asymmetryTilt suppression test 124

Traumatic otolithic vertigo 37, 38 definition 48head direction cell system 57, 58Tullio phenomenon

131Subject Index

Vertigo (continued) Vestibular-evoked myogenic potentialacoustic neuroma 106, 107otolithic syndromes, overview 35

perilymph fistulas 41, 42 advantages over other tests 98, 99, 123applications 74, 75, 99, 107, 108semicircular canal vertigo 34, 35

tilt perception in otolithic disease Meniere diseasecanal paresis 10319, 20

traumatic otolithic vertigo 37, 38, 45, equitest performance relationships 103gentamicin-treated patients107, 118, 119

Tullio phenomenon 42–45 104, 105, 108hearing loss relationship 102, 103vestibular drop attacks 35, 37

vestibular syndromes affecting otolith saccular function 74, 101–103methodologyfunction 35, 36

Vestibular drop attacks 35, 37 clicks delivery 99data analysis 100Vestibular exercises, rehabilitative

therapy 126 electromyography 99, 100overview 73, 74, 123Vestibular nerve

firing rate 112 normal subject results 100, 101oscillopsia 107projections 112, 113

Vestibular neuritis traumatic vertigo 107vestibular neuritis 105, 106caloric testing 74, 75

off-vertical axis rotation test 95, 96 Vestibulo-spinal function, clinical test 25, 26Visual acuityotolithic and semicircular canal

contributions 34 cranio-facial asymmetry findings 62otolith dysfunction 116subjective visual vertical 77

vestibular-evoked myogenicpotentials 105, 106 Wallenberg syndrome 34

132Subject Index

Otolith Function and Disorders

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