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This document provides an introduction to vestibular evoked myogenic potentials (VEMP). It discusses how VEMP responses in muscles like the sternocleidomastoid muscle can be elicited by sound, vibration, or electrical stimulation and assessed clinically. While early studies recorded potentials from the inion, the current clinical form of VEMP testing utilizes biphasic responses recorded from the sternocleidomastoid muscle. VEMP testing was established as a method to assess saccular function after studies found the responses disappeared on the affected side after unilateral vestibular nerve section. Further research has since clarified that sound stimulation of the saccule is conveyed by the inferior vestibular nerve, making VEMP a useful

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Toshihisa Murofushi ⋅ Kimitaka Kaga Vestibular Evoked Myogenic Potential Its Basics and Clinical Applications
Toshihisa Murofushi ⋅ Kimitaka Kaga Vestibular Evoked Myogenic Potential Its Basics and Clinical Applications
Library of Congress Control Number: 2008938811 ISBN 978-4-431-85907-9 Springer Tokyo Berlin Heidelberg New York e-ISBN 978-4-431-85908-6 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Springer is a part of Springer Science+Business Media springer.com © Springer 2009, Tokyo Printed in Japan Typesetting: SNP Best-set Typesetter Ltd., Hong Kong Printing and binding: Nikkei Printing Inc., Japan Printed on acid-free paper Toshihisa Murofushi, M.D., Ph.D. Professor Department of Otolaryngology Teikyo University School of Medicine University Hospital, Mizonokuchi 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki 213-8507, Japan Kimitaka Kaga, M.D., Ph.D. Director National Institute of Sensory Organs National Tokyo Medical Center 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan
V Preface The vestibular labyrinth consists of five compartments: the lateral, anterior, and posterior semicircular canals, the utricule, and the saccule. At the beginning of the twentieth century, Robert Bárány proposed the caloric test as a clinical test of the lateral semicircular canal. This test enabled clinicians to assess the individual lateral semicircular canal function easily by using the simple method of irrigating the external ear canal with cold or warm water and observing the induced nystag- mus. We believe that the caloric test was a breakthrough in the field of vestibular research. However, as far as the other compartments were concerned, there was no simple clinical test equal to the caloric test for the lateral semicircular canal function. At the end of the twentieth century, the vestibular evoked myogenic potential (VEMP) test was proposed as a new method for assessing the individual saccule function. This test has some unique attributes. First, it uses sound stimulation, even though it is a test of the vestibular system. This appears to be a contradiction neu- rophysiologically. As a result, in its early stages there were controversies concern- ing the origin of the responses. However, such controversies have been overcome by basic neurophysiological studies and clinical studies. Above all, sound sensitiv- ity of the saccular afferents shown in cats and guinea pigs with single-unit recording methods became the main supporting evidence. Nowadays, VEMP is one of the routine clinical tests for balance disorder. Second, the sternocleidomastoid muscle (SCM), the conventional recording site of VEMP, is itself special. While saccular afferents project onto the ipsi- lateral motoneurons of the SCM, they do not project onto the contralateral motoneurons of the SCM. This fact enables us to assess the individual saccule function easily. Third, the VEMP test provides totally different information than the caloric test does. Whereas the VEMP test is a test of the otolith organs, the caloric test is a test of the semicircular canals; and whereas the VEMP test is a test of the inferior vestibular nerve, the caloric test is a test of the superior vestibular nerve. Evidently, these two, the caloric test and the VEMP test, can coexist.
This book is a review of VEMP studies. Readers will obtain full knowledge of the principles of the elicited response, methods of recording, and clinical applications. We hope to generate more interest among clinicians and scientists in VEMP and to provide greater knowledge of vestibular disorders through this publication. 19 October 2008 Toshihisa Murofushi, Kimitaka Kaga VI Preface
Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V Part I. Introduction Toshihisa Murofushi . . . . . . . . . . . . . . . . . . . . . . . . 1 Part II. Basics Toshihisa Murofushi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Overview of the Vestibular System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Sound Sensitivity of the Vestibular End-Organs and Sound-Evoked Vestibulocollic Reflexes in Mammals . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Recording and Assessing VEMPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 VEMP Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Part III. Clinical Applications Toshihisa Murofushi . . . . . . . . . . . . . . 47 Meniere’s Disease and Related Disorders: Detection of Saccular Endolymphatic Hydrops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Vestibular Neuritis (Neurolabyrinthitis) and Other Peripheral Vestibulopathies: Detection of Inferior Vestibular Nerve Damage . . . . . 60 Superior Canal Dehiscence Syndrome and VEMPs: Detection of Hypersensitivity of the Vestibular System to Sound . . . . . . 73 Migraine-Associated Vertigo and VEMPs: Detection of Vestibular Signs in a Common but Unclear Entity . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Acoustic Neuroma and Other Cerebellopontine Angle Tumors: Detecting a Neoplasm in the Cerebellopontine Angle . . . . . . . . . . . . . . . 83 Disorders of the Central Nervous System and VEMPs: Detecting Lesions in the Vestibulospinal Pathway . . . . . . . . . . . . . . . . . . 92 Part IV. Pediatric Applications Kimitaka Kaga . . . . . . . . . . . . . . . . . . 99 Neurootological Application of VEMP Recording During Infancy and Childhood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 VII
Part I Introduction
Introduction Vestibular evoked myogenic potentials (VEMP) are responses in the muscles, especially cervical muscles such as the sternocleidomastoid muscle (SCM), to sound, vibration, or electrical stimulation (Fig. 1). Because it seemed that VEMP could be used for clinical tests of the vestibular end-organs, especially the saccule, it attracted the interest of clinicians and scientists. There had been no other clinical test of the saccule that was applicable at common clinics. Now much has been published about VEMP, and many clinicians use this test. VEMP is one of the most important advances in clinical neurophysiology of the vestibular system. Prior to the availability of VEMP in its present form [1], other tests had been proposed, such as using inion responses [2, 3] (Fig. 2), which tried to measure potentials evoked by sound as a test of the vestibular system. However, tests relying on these responses were not widely used at clinics. VEMP in its present form, utilizing biphasic myogenic potentials on the SCM, were first reported in 1992 by Colebatch and Halmagyi, who reported that VEMP responses on the affected side disappeared after unilateral vestibular nerve section despite preservation of hearing [1, 4] (Fig. 3). Colebatch et al. reported in 1994 that VEMP could be recorded in a patient with bilateral near-total hearing loss [4]. Since that report, clinical and basic studies concerning VEMP have been further developed. These later studies clarified that the major vestibular end-organ which responds to sound is the saccule, and that signals are conveyed via the inferior vestibular nerve [5–11]. Details are given in the chapters that follow. Here, we want to emphasize that the progress achieved in this field was brought about by the collaboration of scientists and clinicians. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 3 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_1, © Springer 2009
4 Vestibular Evoked Myogenic Potentials Fig. 2. A typical waveform of inion responses. An active electrode was placed on the nasion and a reference electrode was on the mastoid. 70dBnHL clicks were presented binaurally; 150 responses were averaged. (From [3], with permission) 10 msec 100 mV p13 n23 n34 p44 䉱 click Fig. 1. A typical waveform of vestibular evoked myogenic potentials (VEMP) in a healthy subject
Introduction 5 Fig. 3. Abolishment of VEMP responses (to 100-dB clicks) following selective vestibular nerve section on the left. VEMP responses on the left sternocleidomastoid muscle (SCM) to left ear stimulation were absent after unilateral vestibular nerve section, although hearing on the left was preserved. Upper left, recording on the right SCM to left ear stimulation; upper right, recording on the right SCM to right ear stimulation (presence of responses); asterisk, p13; lower left, record- ing on the left SCM to left ear stimulation (absence of responses); lower right, recording on the left SCM to right ear stimulation. (From [4], with permission) References 1. Colebatch JG, Halmagyi GM (1992) Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 42:1635–1636 2. Bickford RG, Jacobson JL, Cody DT (1964) Nature of average evoked potentials to sound and other stimuli in man. Ann NY Acad Sci 112:204–223 3. Cody DT, Jacobson JL, Walker JC, et al (1964) Averaged evoked myogenic and cortical potentials to sound in man. Ann Otol Rhinol Laryngol 73:763–777 4. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 5. McCue MP, Guinan JJ Jr (1995) Spontaneous activity and frequency selectivity of acoustically responsive vestibular afferents in the cat. J Neurophysiol 74:1563–1572 6. McCue MP, Guinan JJ Jr (1997) Sound-evoked activity in primary afferent neurons of a mammalian vestibular system. Am J Otol 18:355–360 7. Murofushi T, Curthoys IS, Topple AN, et al (1995) Responses of guinea pig primary vestibu- lar neurons to clicks. Exp Brain Res 103:174–178 8. Murofushi T, Curthoys IS, Gilchrist DP (1996) Response of guinea pig vestibular nucleus neurons to clicks. Exp Brain Res 111:149–152 9. Murofushi T, Curthoys IS (1997) Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol (Stockh) 117:66–72 10. Murofushi T, Halmagyi GM, Yavor RA, et al (1996) Absent vestibular evoked potentials in vestibular neurolabyrinthitis: an indicator of involvement of the inferior vestibular nerve? Arch Otolaryngol Head Neck Surg 122:845–848 11. Murofushi T, Matsuzaki M, Mizuno M (1998) Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509–512
Part II Basics
Overview of the Vestibular System Introduction In this chapter, we review only the fundamental structures associated with the vestibular system that may be concerned with vestibular evoked myogenic potentials (VEMPs). Although the cerebellum and cerebrum are also important for the vestibular system, we do not address them here, as their effects on VEMPs seem minimal. Vestibular End-Organs The human labyrinth consists of the cochlea, otolith organs, and semicircular canals. The otolith organs and the semicircular canals are vestibular end-organs. The functions of the vestibular end-organs are basically to monitor the rotational and linear movement of the head and the orientation of the head to gravity. In humans, there are two otolith organs (saccule and utricle) and three semicircular canals (lateral semicircular canal, anterior semicircular canal, and posterior semi- circular canal) (Figs. 1, 2). The otolith organs, the saccule and the utricle, sense linear acceleration. The sensory area of the otolith organ is called the macula. The saccular macula lies on the medial wall of the vestibule in a spherical recess inferior to the utricular macula. The saccular macula is hook-shaped and lies predominantly in a vertical position, whereas the utricular macula is oval and lies predominantly in a horizontal position (Fig. 3) [1] The plane of the saccular macula is almost orthogonal to that of the utricular macula (Fig. 4). The surfaces of the maculae are covered by the otolithic membrane, which contains a superficial calcareous deposit, the otoconia (Fig. 5) [1–3]. The cilia of the hair cells in the macula protrude into the otolithic membrane. The otoconia consist of small calcium carbonate crystals [4]. Linear acceleration including gravity causes deflection of the cilia of the hair cells. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 9 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_2, © Springer 2009
10 Vestibular Evoked Myogenic Potentials The semicircular canals—lateral, anterior, posterior—sense angular accelera- tion. They are aligned to form a coordinate system [5]. The lateral semicircular canal makes a 30° angle with the horizontal plane. The other two canals are in vertical positions almost orthogonal to each other. The sensory area is called the crista. Hair cells are in the surface of the crista, with their cilia protruding into the cupula, a gelatinous mass (Fig. 6). Angular acceleration causes deflection of the cupula, resulting in deflection of the cilia of the hair cells. Utricle Saccule Anterior semicircular canal Posterior semicircular canal Lateral semicircular canal Cochlea Cochlear nerve Superior vestibular nerve Inferior vestibular nerve (a) (b) (c) Fig. 1. Inner ear and afferent nerves Fig. 2. Vestibular end-organs in human temporal bone sections. a Utricular macula. b Saccular macula. c Crista of the lateral semicircular canal
Overview of the Vestibular System 11 ant. post. striola med. ant. post. dorsal lat. Fig. 3. Utricular macula (left) and saccular macula (right). Arrows indicate the direction of hair cell polarization. ant., anterior; lat., lateral; med., medial; post., posterior Utricular macula Saccular macula Fig. 4. Position of the utricular macula and the saccular macula Fig. 5. Photomicroscopic findings of the guinea pig macula. Toluidine blue cillia hair cell otoconia otolithic membrabe
12 Vestibular Evoked Myogenic Potentials The macula and crista contain two types of hair cells: type I and type II hair cells [6] (Fig. 7). The hair cells have stereocilia and a kinocilium on the top. Deflec- tion of the stereocilia toward the kinocilium causes excitation, whereas deflection toward the other side causes inhibition. Type I hair cells are shaped like flasks, with each cell being surrounded by a calyx ending. The type II hair cells, which are like cylinders, have bouton nerve endings (Figs. 7, 8) [1, 2]. The striola is a distinctive cupula hair cell Fig. 6. Photomicroscopic findings of the guinea pig crista. H&E kinocilium stereocilia excitation inhibition calyx type ending bouton type ending Type I Type II Fig. 7. Two types of hair cell
Overview of the Vestibular System 13 zone running through the center of each macula. The hair cells on each side of the striola have opposite polarities because their kinocilia point in opposite directions (Fig. 3). In contrast to the macula, the direction of the polarity of hair cells in one crista is uniform. Calyx units are seen in central (striolar) zones. The axon is usually unbranched, giving rise to a single calyx ending. Bouton units are seen in peripheral (extrastrio- lar) zones. The axon provides bouton endings to several type II hair cells. Dimor- phic units innervate all parts of the neuroepithelium. The axon has collateral branches terminating as calyx endings and bouton endings [6]. Vestibular Nerve The vestibular nerve contains afferents from the vestibular end-organs and effer- ents. The cells of afferents are bipolar neurons with their cell bodies in Scarpa’s ganglion. The vestibular nerve is subdivided into two parts: the superior vestibular nerve and the inferior vestibular nerve [7] (Fig. 1). The superior vestibular nerve innervates the cristae of the anterior semicircular canal, the lateral semicircular canal, the utricular macula, and the anterosuperior part of the saccular macula. The inferior vestibular nerve innervates the crista of the posterior semicircular canal and the main part of the saccular macula. Otolith ganglion cells are located ven- trally in the central portion of the ganglion, whereas canal ganglion cells are located at the rostral and caudal ends [8, 9]. The vestibular afferent fibers innervating the macula are activated by changes in the position of the head in space or by linear acceleration, whereas the fibers innervating the crista are activated by angular acceleration [10–12]. Vestibular afferents fire spontaneously (65 spikes/s in otolith afferents and 90 spikes/s in canal afferents) [13, 14]. The baseline firing rates increase in response to excitatory stimuli and decrease in response to inhibitory stimuli. Based on the regularity of firing, vestibular afferents are classified into two groups—regularly firing fibers and irregularly firing fibers [6]—each of which has different features. Irregularly Bouton type ending Calyx type ending Fig. 8. Types of guinea pig primary afferent nerve endings labeled by biocytin. (In collaboration with Prof. I.S. Curthoys)
14 Vestibular Evoked Myogenic Potentials firing fibers have thick, medium-sized axons ending as a calyx and dimorphic units. They have phasic–tonic response dynamics and high sensitivity to head rotation or linear forces. In contrast, regularly firing fibers have medium-sized, thin axons, ending as dimorphic and bouton units. They have tonic response dynamics and low sensitivity to head rotation or linear forces. These differences must be borne in mind when we consider the sound sensitivity of vestibular afferents. Vestibular Nucleus The vestibular nuclei consist of a group of neurons located on the floor of the fourth ventricle. The main vestibular nuclei are the superior nucleus, lateral (Deiters’) nucleus, medial nucleus, and inferior (descending or spinal) nucleus (2). Additionally, there are several small groups of cells. Although primary vestibular neurons provide multiple branches, which usually innervate secondary vestibular neurons in all of the four main vestibular nuclei, there are preferences in each nucleus (8). The superior vestibular nucleus contains medium-sized neurons with some mul- tipolar cells. The superior vestibular nucleus receives strong projections from semicircular canals. The medial vestibular nucleus consists of cells of many sizes and shapes that are close together. The upper part of the medial vestibular nucleus receives fibers from the semicircular canals and the fastigial nucleus and flocculus of the cerebellum. Saccular and utricular afferents project to the middle part of the nucleus. The caudal part of the nucleus receives fibers from the cerebellum. The lateral vestibular nucleus contains giant cells. The dorsocaudal portion receives afferents from the cerebellum, whereas the rostrovertebral portion receives primary vestibular afferents. The inferior vestibular nucleus consists of small and medium-sized cells with occasional giant cells. The rostral part of the inferior vestibular nucleus receives strong projections from the otolith organs and the semicircular canals. Summarized from the standpoint of primary otolith afferents, saccular afferents terminate mainly in the rostral part of the inferior vestibular nucleus and the ros- troventral portion of the lateral nucleus; and utricular afferents terminate mainly in the rostral portion of the inferior vestibular nucleus, and the medial vestibular nucleus [8, 9, 15]. On the basis of neurophysiological studies, two types of secondary vestibular neuron were identified [16]. Ipsilateral rotation of the head causes type I neurons to be excited and type II neurons to be inhibited. Type I neurons are monosy- naptically activated by ipsilateral primary afferents, whereas type II neurons receive inputs via commissural connections either from neurons in the reticular substance or directly from contralateral type I neurons [2]. Contralateral labyrinth stimulation excites type II neurons, resulting in inhibition of type I neurons (Fig. 9).
Overview of the Vestibular System 15 Vestibulospinal Reflex The vestibulospinal reflex (VSR) serves to stabilize the head and controls erect stance relative to gravity under both static and dynamic conditions [17]. Stimula- tion of the vestibular end-organs leads to various patterns of activation of neck and body muscles. Activation of the neck muscles is described later as the vestibu- locollic reflex. The VSR prevents falling and maintains the body’s position. There are three major pathways: the lateral vestibulospinal tract (LVST); the medial vestibulospinal tract (MVST); and the reticulospinal tract (RST) [18] (Fig. 10). The LVST origi- nates in the lateral nucleus and descends in the ipsilateral ventral funiculus of the spinal cord. The MVST originates in the medial, inferior, and lateral nuclei and descends in the medial longitudinal fasciculus bilaterally as far as the mid-thoracic level [17, 19]. Linear and angular head acceleration causes increased muscle tones in the ipsilateral extensor muscles and decreased muscle tones in the ipsilateral flexor muscles via the LVST [17, 20]. Vestibulocollic Reflex The vestibulocollic reflex (VCR) operates to stabilize the head in space by neck movements. The MVST and LVST provide direct connections to neck motoneurons as well as indirect connections. Connections between vestibular end-organs and Fig. 9. Interrelation of types I and II secondary vestibular neurons. Light neurons are excitatory; dark neurons are inhibitory Type I Type II Type II Type I Lateral semiciicular canal Vestibular nerve Vestibular nucleus midline
16 Vestibular Evoked Myogenic Potentials Fig. 10. Pathways of the vestibulospinal reflex. MVST, medial vestibulospinal tract; RST, reticulospinal tract; LVST, lateral vestibulospinal tract Table 1. Connection pattern to motoneurons of cervical muscles from afferents of the otolith organs Ipsilateral Contralateral SAC UT SAC UT Extensor 2EP 2EP 2/3EP 3IP L ? M ? Flexor 2/3IP 2EP 3IP 3IP M L M L Rotator 2IP 2IP NO 2EP M M M (from ref. 21, Kanehara, with permission) SAC, saccular nerve; 2EP, disynaptic excitatory postsynaptic potential; 2IP, disynaptic inhibitory postsynaptic potential; NO, no response; M, medial vestibulospinal tract; L, lateral vestibulospinal tract; UT, utricular nerve; ?, unknown
Overview of the Vestibular System 17 neck motoneurons are summarized in Table 1 [21]. Neck muscles are classified into three types: extensors, flexors, rotators. The sternocleidomastoid muscle (SCM) is classified as a rotator type. Concerning VEMPs, it should be noted that moto- neurons of the SCM have disynaptic inhibitory inputs from the ipsilateral saccule with no projections from the contralateral saccule [22] (Table 1, Fig. 11). Vestibuloocular Reflex The vestibuloocular reflex (VOR) maintains gaze during head and body movements [23]. This gaze stability is achieved by activation of vestibular end-organs, includ- ing activation of semicircular canals to angular acceleration and of otolith organs to linear translation and gravity. In other words, the VOR produces extraocular muscle contraction to compensate for a specific head movement, thereby maintain- ing gaze stability. The connections of the semicircular canals with extraocular muscles are summarized in Table 2. The eye movements induced by the stimulation of the otolith organs and the pathways from the otolith organs to extraocular muscles are less clearly defined than those from the semicircular canals and are somewhat controversial. According to Suzuki et al. [24], electrical stimulation of the utricular nerve in spinalized, alert cats mainly produced contraversive torsional eye movement with simultaneous upward shift in ipsilateral eyes, downward shift in contralateral eyes, and slight Fig. 11. Sacculosternocleidomastoid (SCM) and utriculosternocleidomastoid pathways Filled circles, inhibitory neurons; open circles, excitatory neurons. (from Fig. 4 of ref. 22, Springer, with permission)
18 Vestibular Evoked Myogenic Potentials contralateral horizontal shift of both eyes. Curthoys reported that electrical stimula- tion of the utricular macula in guinea pigs produced upward or upward-torsional eye movements [25]. Fluur and Mellstrom reported that electrical stimulation of the utricular macula in alert cats produced eye movements whose direction depended on the location of the stimulating electrode [26]. Concerning horizontal eye movement, Goto et al. [27] confirmed that utricular nerve stimulation in cats evoked horizontal eye movements to the stimulated side, supporting prior findings of projection of the utricular nerve to the ipsilateral abducens nucleus [28, 29]. Eye movement due to saccular stimulation is more obscure than that due to utricular stimulation. The saccule contributes more weakly to eye movements than the semicircular canals or the utricule [30]. Previous studies suggested that the main eye movement induced by saccular stimulation could be vertical [25, 31, 32]. References 1. Schuknecht HF (1993) Pathology of the ear. 2nd edn. Lea & Febiger, Philadelphia 2. Baloh RW, Honrubia V (1990) Clinical neurophysiology of the vestibular system. 2nd edn. Davis, Philadelphia 3. Lim DJ (1973) Ultrastructure of the otolithic membrane and the cupula. Adv Otorhinolaryn- gol 19:35–49 4. De Vries H (1951) The mechanics of the labyrinth otoliths. Acta Otolaryngol 38:262–273 5. Blanks RHJ, Curthoys IS, Markham CH (1975) Planar relationships of the semicircular canals in man. Acta Otolaryngol 80:185–196 6. Goldberg JF, Lysakowski A, Fernandez C (1992) Structure and function of vestibular nerve fibers in the chinchilla and squirrel monkey. Ann NY Acad Sci 656:92–107 7. Lorente De No R (1933) Anatomy of the eighth nerve: the central projection of the nerve endings of the internal ear. Laryngoscope 43:1–38 8. Gacek RR (1969) The course and central termination of first order neurons supplying vestibular end organs in the cat. Acta Otolaryngol 254:1–66 9. Gacek RR (2008) A place principle for vertigo. Auris Nasus Larynx 35:1–10 10. Fernandez C, Goldberg JM (1971) Physiology of peripheral neurons innervating semicircular canals of the squirrel monkey. II. Response to sinusoidal stimulation and dynamics of periph- eral vestibular system. J Neurophysiol 34:61–675 Table 2. Connection pattern to motoneurons of extra-ocular muscles from afferents of the semicircular canals Semicircular canal Excitation Inhibition Anterior I-SR I-IR C-IO C-SO Posterior I-SO I-IO C-IR C-SR Lateral I-MR C-MR C-LR I-LR (from ref. 21) I, ipsilateral; C, contralateral; MR, mdial rectus; LR, lateral rectus; SO, superior oblique; IR, inferior rectus; IO, inferior oblique; SR, superior rectus
Overview of the Vestibular System 19 11. Fernandez C, Goldberg JM, Abend WK (1972) Response to static tilts of peripheral neurons innervating otolith organs of the squirrel monkey. J Neurophysiol 35:978–987 12. Fernandez C, Goldberg JM (1976) Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. II. Directional selectivity and force-response relations. J Neurophysiol 39:385–395 13. Fernandez C, Goldberg JM (1976) Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. I. Response to static tilt and to long-duration centrifuge force. J Neurophysiol 39:970–984 14. Goldberg JM, Highstein SM, Moschovakis A, et al (1987) Inputs from regularly and irregu- larly discharging vestibular-nerve afferents to secondary neurons in the vestibular nuclei of the squirrel monkey. I. An electrophysiological analysis. J Neurophysiol 58:700–718 15. Carleton SC, Carpenter MB (1983) Afferent and efferent connections of the medial, inferior and lateral vestibular nuclei in the cat and monkey. Brain Res 278:29–51 16. Shimazu H, Precht W (1965) Tonic and kinetic responses of cat’s vestibular neurons to horizontal angular acceleration. J Neurophysiol 28:991–1013 17. Fetter M, Dichagns J (1996) How do the vestibulo-spinal reflexes work? In: Baloh RW, Halmagyi GM (eds) Disorders of the vestibular system. Oxford University Press, New York, pp 105–112 18. Wilson VJ, Melvil Jones G (1979) Mammalian vestibular physiology. Plenum, New York 19. Wilson VJ, Boyle R, Fukushima K, et al (1995) The vestibulocollic reflex. J Vestib Res 5:147–170 20. Wilson VJ, Peterson BW (1978) Peripheral and central substrates of vestibulo-spinal reflexes. Physiol Rev 58:80–105 21. Uchino Y (2002) Memai to heikouchousetsu (in Japanese). Kanehara, Tokyo 22. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 23. Raphan T, Cohen B (1996) How does the vestibulo-ocular reflex work? In: Baloh RW, Halmagyi GM (eds) Disorders of the vestibular system. Oxford University Press, New York, pp 20–47 24. Suzuki JI, Tokumasu K, Goto K (1969) Eye movements from single utricular nerve stimula- tion in the cat. Acta Otolaryngol 68:250–262 25. Curthoys IS (1987) Eye movements produced by utricular and saccular stimulation. Aviat Space Environ Med 58:A192–A197 26. Fluur E, Mellstrom A (1970) Utricular stimulation and oculomotor reactions Laryngoscope 80:1701–1712 27. Goto F, Meng H, Bai R, et al (2003) Eye movements evoked by the selective stimulation of the utricular nerve in cats. Auris Nasus Larynx 30:341–348 28. Imagawa M, Isu N, Sasaki M, et al (1995) Axonal projections of utricular afferents to the vestibular nuclei and the abducens nucleus in cats. Neurosci Lett 186:87–90 29. Uchino Y, Ikegami H, Sasaki M, et al (1994) Monosynaptic and dyssynaptic connections in the utriculoocular reflex arc of the cat. J Neurophysiol 71:950–958 30. Isu N, Graf W, Sato H, et al (2000) Sacculo-ocular reflex connectivity in cats. Exp Brain Res 131:262–268 31. Fluur E, Mellstrom A (1970) Saccular stimulation and oculomotor reactions. Laryngoscope 80:1713–1721 32. Goto F, Meng H, Bai R, et al (2004) Eye movements evoked by selective saccular nerve stimulation in cats. Auris Nasus Larynx 31:220–225
Sound Sensitivity of the Vestibular End-Organs and Sound-Evoked Vestibulocollic Reflexes in Mammals Sound Sensitivity of the Vestibular System Tullio first reported that surgical fenestration of the bony labyrinth in avians and mammals made the labyrinth sound-sensitive [1–3]. This phenomenon—sound sensitivity of the vestibular system—has been known as the Tullio phenomenon [3, 4]. Bekesy reported head movements in response to relatively loud sounds [3, 5] and suggested that this effect might be caused by stimulation of the otolith organs. Later, Young et al. reported that primary vestibular afferents of squirrel monkeys could respond to sound and vibration, although the number of examined vestibular neurons was limited and the methods of threshold determination (a phase-locking threshold) were not familiar [6]. According to their study, all the vestibular end- organs (three canals and two maculae) responded to sound. Among the five end- organs, the saccular macula showed the lowest thresholds. The best frequencies did not exceed 1000 Hz to sound and 500 Hz to vibration. Cazals et al. created guinea pigs with selective cochlear loss and preserved the vestibular system using amika- sin, an aminoglycoside. These animals displayed evoked potentials to sound, although their cochlea was completely destroyed [7, 8]. Recording evoked poten- tials on the eighth nerve revealed that the responses were prominent on the inferior vestibular nerve [9]. These studies suggested that the vestibular end-organs could respond to loud sounds and that the saccule might be the most sound-sensitive among the vestibular end-organs. During the 1990s, several articles concerning sound sensitivity of vestibular neurons were published. McCue and Guinan reported that saccular afferents of cats responded to intense sound. In their study, the best frequency of saccular afferents to air-conducted sound was around 500 Hz (Fig. 1) [10–12]. Murofushi et al. showed that primary vestibular afferents of guinea pigs could respond to intense air-conducted clicks (Fig. 2) [13, 14]. These neurons were mainly in the inferior vestibular nerve and could also respond to static tilts. None of the angular accelera- tion-sensitive neurons—canal neurons—responded to clicks. These findings sug- gested that the saccular afferents could be sensitive to air-conducted sound. Most of these click-sensitive neurons showed irregular spontaneous firing. Irregularly Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 20 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_3, © Springer 2009
Sound Sensitivity and Sound-Evoked Vestibulocollic Reflexes 21 firing fibers have thick, medium-sized axons ending as calyx and dimorphic units [15]. Hence, type I hair cells on the saccular macula are sound (click)-sensitive among the vestibular end-organs. Murofushi et al. also reported that vestibular nucleus neurons in the lateral vestibular nucleus and in the rostral portion of the inferior vestibular nucleus are sound (click)-sensitive (Fig. 3) [16]. Although these findings imply that saccular afferents could respond to air-conducted sound, they do not exclude the possibility that utricular afferents might respond to air-con- ducted sound as well, especially to relatively low-frequency sound. In the vestibular end-organs, response patterns to bone-conducted sound (vibra- tion) are different from the patterns seen with air-conducted sound. Hair cells in Fig. 1. Tuning curves of sound-sensitive vestibular afferents of cats. SPL, sound pressure level. (from Fig. 6 of ref. 11, American Physiological Society, with permission) Fig. 2. Responses of guinea pig primary vestibular neurons to clicks—70 dB above the auditory brainstem response (ABR) threshold. (from Fig. 1 of ref. 14, Taylor & Francis, with permission)
22 Vestibular Evoked Myogenic Potentials the utricular macula and the saccular macula respond to bone-conducted sound. According to Curthoys et al., most of the irregular otolithic afferents studied (82.8%) showed a clear increase in the firing rate in response to bone-conducted sound [17]. In their study, bone-conducted sound-sensitive afferents could be of utricular origin because many of the bone-conducted sound-sensitive afferents were in the superior vestibular nerve, and they were sensitive to roll tilts. These authors also reported that regular otolithic afferents were less sensitive to bone-conducted sound, and only a few canal afferents responded to it. These findings suggested that vestibular evoked myogenic potentials (VEMPs) to bone-conducted sound [18, 19] might be produced by vestibular end-organs from a different population than the VEMPs to air-conducted sound. Neural Pathway of the Sound-Evoked Vestibulocollic Reflex Among the vestibular end-organs in mammals, the saccular macula seems to respond especially well to air-conducted sound; and among the hair cells on the saccular macula, the type I hair cells around the striola seem to be the most sensi- tive. What then is the neural pathway of the sound-evoked vestibulocollic reflex? Primary afferents of the saccule are mainly in the inferior vestibular nerve. Therefore, inputs to the vestibular system of sound stimulation are mostly trans- mitted via the inferior vestibular nerve. According to Kushiro et al. [20], saccular Fig. 3. Recording sites of click-sensitive vestibular nucleus neurons of guinea pigs. LV, lateral vestibular nucleus; DV, descending vestibular nucleus; MV, medial vestibular nucleus; SV, supe- rior vestibular nucleus; icp, inferior cerebellar peduncle; CN, cochlear nucleus; as, acoustic stria; n7, facial nerve; g7, genu nervi facialis; N6, abducens nucleus. a is the most rostral and c is the most caudal. (from Fig. 2 of ref. 16, Springer, with permission)
Sound Sensitivity and Sound-Evoked Vestibulocollic Reflexes 23 afferents in cats have inhibitory projection to the ipsilateral motoneurons of the sternocleidomastoid muscle (SCM) and no contralateral projection. These authors also showed that this projection was transmitted via the medial vestibulospinal tract. Based on these findings, the neural pathway of the air-conducted sound- evoked vestibulocollic reflex recorded on the SCM is thought to be as shown in Fig. 4. The VEMPs are clearly ipsilateral-dominant (described later). Therefore, the supposed neural pathway corresponds well with the results of VEMP studies in humans. Provided that bone-conducted sound simulates the utricular macula as well as the saccular macula, VEMPs to bone-conducted sound might have some features different from those of VEMPs to air-conducted sound. Utricular afferents are located in the superior vestibular nerve. Utricular afferents have not only inhibitory projection to the ipsilateral motoneurons of the SCM but also excitatory projection to the contralateral motoneurons of the SCM [20]. When one uses bone-conducted sound as the stimulus, one should bear in mind that the neural pathway of VEMPs for bone-conducted sound might be different from the pathway of VEMPs for air- conducted sound. When sound is presented to the ear, one may concern the coexistence of a “sound-evoked cochleocollic reflex”. However, direct projection from the cochlear nucleus to the motoneurons of the SCM is not known. Therefore, the sound-evoked cochleocollic reflex, if any, would be transmitted via the reticular formation, taking longer latencies than the sound-evoked vestibulocollic reflex. Furthermore, it would be evoked bilaterally. Some of the later components of VEMPs (n34–p44) [21] may be a sound-evoked cochleocollic reflex. Fig. 4. Pathway of air-conducted sound-evoked vestibulocollic (otolith-sternocleidomastoid) reflex. SCM, sternocleidomastoid muscle inferior vestibular nerve medial vestibulospinal tract accessory nerve ipsilatral SCM saccule
24 Vestibular Evoked Myogenic Potentials References 1. Tullio P (1929) Das Ohr und die Entstehung der Sprache und Schrift. Urban & Schwarzen- berg, Berlin 2. Minor LB, Solomon D, Zinreich JS, et al (1998) Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior semicircular canal. Acta Otolaryngol Head Neck Surg 124:249–258 3. Halmagyi GM, Curthoys IS, Colebatch JG, et al (2005) Vestibular responses to sound. Ann NY Acad Sci 1039:54–67 4. Huizinga E (1935) On the sound reaction of Tullio. Acta Otolaryngol (Stockh) 22:359–369 5. Bekesy GV (1935) Uber akustische Reizung des Vestibularapparates. Pflugers Arch Ges Physiol Mensch Tiere 236:59–76 6. Young ED, Fernández C, Goldberg JM (1977) Responses of squirrel monkey vestibular neurons to audio-frequency sound and head vibration. Acta Otolaryngol (Stockh) 84:352–360 7. Cazals Y, Aran JM, Erre JP (1980) Acoustic responses after total destruction of the cochlear receptor: brainstem and auditory cortex. Science 210:83–86 8. Cazals Y, Aran JM, Erre JP (1982) Frequency sensitivity and selectivity of acoustically evoked potentials after complete cochlear hair cell destruction. Brain Res 231:197–203 9. Didier A, Cazal Y (1989) Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig. Hear Res 37:123–128 10. McCue MP, Guinan JJ (1994) Acoustically responsive fibers in the vestibular nerve of the cat. J Neurosci 14:6058–6070 11. McCue MP, Guinan JJ (1995) Spontaneous activity and frequency sensitivity of acoustically responsive vestibular afferents in the cat. J Neurophysiol 74:1563–1572 12. McCue MP, Guinan JJ (1997) Sound-evoked activity in primary afferent neurons of a mammalian vestibular system. Am J Otol 18:355–360 13. Murofushi T, Curthoys IS, Topple AN, et al (1995) Responses of guinea pig primary vestibu- lar neurons to clicks. Exp Brain Res 103:174–178 14. Murofushi T, Curthoys IS (1997) Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol (Stockh) 117:66–72 15. Goldberg JF, Lysakowski A, Fernandez C (1992) Structure and function of vestibular nerve fibers in the chinchilla and squirrel monkey. Ann NY Acad Sci 656:92–107. 16. Murofushi T, Curthoys IS, Gilchrist DP (1996) Response of guinea pig vestibular nucleus neurons to clicks. Exp Brain Res 111:149–152 17. Curthoys IS, Kim J, McPhedran SK, et al (2006) Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig. Exp Brain Res 175:256–267 18. Sheykholeslami K, Murofushi T, Kermany MH, et al (2000) Bone conducted evoked myogenic potentials from the sternocleidomastoid muscle. Acta Otolaryngol (Stockh) 120:731–734 19. Welgampola MS, Rosengren SM, Halmagyi GM, et al (2003) Vestibular activation by bone conducted sound. J Neurol Neurosurg Psychiatry 74:771–778 20. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 21. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197
Recording and Assessing VEMPs Suitable Subjects for Recording VEMPs Basically, vestibular evoked myogenic potential (VEMP) testing is applicable to all subjects who require evaluation of vestibular functions. However, it is difficult to obtain responses from subjects who are not cooperative during the testing and who for some reason cannot contract the sternocleidomastoid muscle (SCM) during the recording (e.g., a comatose patient). In subjects with air–bone gaps in pure-tone audiometry, special care is required because responses are abolished or decreased owing to conductive hearing loss [1, 2]. Methods of Recording VEMPs We usually use surface electrodes to record VEMPs, placing active electrodes sym- metrically on the middle third of the SCM and indifferent electrodes on the lateral end of the upper sternum (Fig. 1) [3]. When the active electrodes are too close to the indifferent electrodes, the amplitudes of the responses are decreased [4]; and when they are too close to the mastoid, responses are contaminated by postauricular responses [5]. The ground electrode is placed on the nasion or the chin. Acoustic stimuli usually comprise clicks (0.1 ms) or short tone bursts (STBs) (500 Hz, rise/fall time 1 ms, plateau time 2 ms). We first present 95-dBnHL (decibels, normal hearing level) clicks or STBs and attenuate the intensity when we want to determine the threshold of the responses. STBs of 500 Hz evoke larger, clearer VEMP responses than clicks [6]. However, investigators should note that STBs of 500 Hz might evoke utricular hair cells as well as saccular hair cells, whereas clicks selectively evoke saccular hair cells [7, 8]. The repetition rate of stimulation is usually 5 Hz. When the repetition rate is increased, the amplitude of the responses may be decreased. This tendency becomes clear when the repetition rate is more than 20 Hz [9]. On the other hand, subjects may become tired when the repetition rate is decreased because the lower repetition rate requires contraction of the SCM for longer periods. Thus, 5 Hz is the optimal repetition rate. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 25 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_4, © Springer 2009
26 Vestibular Evoked Myogenic Potentials Electromyographic (EMG) activities are amplified and bandpass-filtered (20– 2000 Hz). The time window for analysis is 50–100 ms. Responses to 100–200 stimuli (click VEMPs) are averaged. It is important to maintain the contraction of the SCM during recording. VEMP amplitudes show strong correlations to background muscle activity (Fig. 2). Responses cannot be observed without muscle contraction. As VEMP amplitudes show strong correlations with the extent of muscle con- traction, efforts to minimize the effects of muscle contraction fluctuation may be required. To minimize such effects, it is proposed that 1) VEMP amplitudes be corrected based on the extent of muscle contraction and 2) the muscle contraction be maintained at a constant level using feedback methods. To correct VEMP ampli- tudes, we use an average of rectified background muscle activity during a prestimu- lus period of 20 ms [10] (Fig. 3). The corrected amplitude (CA) of VEMP is defined as a ratio. CA = (raw amplitude of p13–n23)/(mean background amplitude) Fig. 1. Electrode placement for vestibular evoked myogenic potential (VEMP) recording Fig. 2. Correlation between the VEMP amplitude to 95-dBnHLtone bursts (500 Hz) and mean background muscle activity in healthy subjects. The correlation coefficient was 0.83. dBnHL, dB normal hearing level; 0 dBnHL, average subjective threshold of sound perception in healthy subjects. (from Fig. 2 of ref. 24, Elsevier, with permission)
Recording and Assessing VEMPs 27 For this purpose, one must average the rectified EMG during a prestimulus period. A feedback method using a blood pressure manometer has been proposed to main- tain the muscle contraction constant during VEMP recording [11]. To contract the SCM, we usually ask subjects in the supine position to raise their head from the pillow. Alternatively, rotating the neck (in the supine position or upright) or having the examiner push the patient’s forehead can be useful (Fig. 4). The rotation method may be easier. However, investigators should note that only unilateral responses are recordable, and muscle contraction becomes easily asymmetrical when this method is applied. Head position itself does not affect VEMP responses [12]. According to Isaacson et al., when the amplitude was corrected according to tonic EMG activity, no significant difference was noted among various test positions [13]. Fig. 3. Correction of amplitudes using rectified electromyography (EMG). Upper trace, unrecti- fied response; lower trace, rectified response. Background muscle activities were calculated using the shaded areas. VEMP amplitudes were corrected based on background muscle activity. (from Fig. 1 of ref. 12, Taylor & Francis, with permission) Fig. 4. Methods to contract the sternocleidomastoid muscle (SCM). a Position supine with the head raised, b position sitting with the head turned away from the tested ear, c position sitting with the head pushed against the finger to provide resistance
28 Vestibular Evoked Myogenic Potentials Normal VEMP Responses In healthy subjects, VEMP responses consist of initial positivity followed by nega- tivity with short latencies. This biphasic response is termed p13–n23 after the peak latency. In our clinic, the means ± SD of p13 and n23 were 11.8 ± 0.86 ms and 20.8 ± 2.2 ms, respectively (95-dBnHL clicks) [14]. Responses to STBs have 2- to 3-ms longer peak latencies [6]. These responses are clearly ipsilateral-dominant. In other words, p13–n23 can be recorded on the SCM ipsilateral to the stimulated ear, although p13–n23 on the contralateral side is absent or small (Fig. 5) [15]. Following p13–n23, later components (n34–p44) can be also observed (Fig. 6) [16]. Fig. 5. Laterality of VEMP responses. VEMP responses (p13–n23) to 95-dBnHL clicks were clearly ipsilateral-dominant. (from Fig. 1 of ref. 15, Taylor & Francis, with permission) 10 msec 100 m V p13 n23 n34 p44 Fig. 6. Typical VEMP waveform in response to 95-dBnHL clicks in a healthy subject. Responses are on the ipsilateral SCM to the stimulated ear
Recording and Assessing VEMPs 29 Later components are not of vestibular origin [1]. Amplitudes of responses (p13–n23) depend on the degree of muscle contraction. In the ordinary situation, the amplitudes range from 50 to 200 μV. The polarity of the initial responses (positivity followed by negativity) implies that this myogenic potential is caused by inhibitory inputs to the SCM [17]. This finding is consistent with neurophysiological data from cats [18]. Parameters for Assessing VEMPs The following parameters are used for clinical evaluation. In this section, VEMPs refer to the early component (p13–n23). Presence of VEMPs VEMPs are usually present in healthy subjects, whereas some elderly subjects exhibit an absence of response. This absence is considered pathological in subjects <60 years of age (Fig. 7). In other words, absence of responses suggests dysfunc- tion of the sacculocollic pathway. Even in older subjects, the unilateral absence of responses is pathological. If an absence of VEMP responses is observed, an exam- iner should first confirm that the headphone was adequately placed on the head. Second, the examiner should determine if the subject has conductive hearing loss. The absence of responses in patients with conductive hearing loss does not mean dysfunction of the saccule or its afferents. Fig. 7. Example of unilateral absence of VEMP responses on the left side (L). R, right side
30 Vestibular Evoked Myogenic Potentials Interaural Difference of VEMP Amplitude Side-to-side differences of VEMP amplitude can be expressed as percent VEMP asymmetry [3]. %VEMP asymmetry = 100 |Ar − Al|/(Ar + Al) where Ar and Al are the amplitudes of p13–n23 on the right and on the left; and |Ar − Al| is the absolute value of Ar − Al. When the affected side is already known, the percent VEMP asymmetry should be calculated as follows. %VEMP asymmetry = 100 (Au − Aa)/(Au + Aa) where Au is the amplitude of p13–n23 on the unaffected side; and Aa is the ampli- tude of p13–n23 on the affected side. In our institution, we set the upper limit of percent VEMP asymmetry as 34.1 (mean +2 SD) in healthy subjects. When the percent VEMP asymmetry exceeds 34.1, the asymmetry is pathological. We usually regard the decreased side as pathological unless there are other specific reasons for the abnormal result (Fig. 8). Although a similar normal range was reported from another laboratory [19], the normal limit should be set at each institution because recording conditions cannot be totally identical. Peak latency Significant delay of peak latencies is also pathological. As the peak latency of p13 shows better reproducibility than that of n23, the peak latency of p13 is more available clinically. Prolonged latencies are signs of retrolabyrinthine or central Fig. 8. Example of unilaterally decreased amplitudes on the left side
disorders (Fig. 9) [14, 20, 21]. In our institution, the means ± SD of p13 and n23 to 95 dBnHL click were 11.8 ± 0.86 ms and 20.8 ± 2.2 ms, respectively. The normal range for peak latency should be established at each institution. Threshold In comparison with the auditory brainstem response (ABR), which is an evoked potential of cochlear origin, the VEMP threshold is much higher. In our clinic, the VEMP thresholds in healthy subjects (clicks) were ≥85 dBnHL. According to Colebatch et al. [22], the mean threshold of VEMP responses to clicks in healthy subjects was 86 dBnHL and the lowest was 70 dBnHL. When the threshold to click stimulation is lower than 70 dBnHL, it is definitely pathological, suggesting hyper- sensitivity of vestibular end-organs to sound (the Tullio phenomenon) (Fig. 10). Fig. 9. Example of prolonged latencies (both sides). (from Figure of ref. 20, BMJ Publishing Group, with permission) Fig. 10. Example of low VEMP thresh- olds. In this subject, the threshold was 70 dBnHL Recording and Assessing VEMPs 31
32 Vestibular Evoked Myogenic Potentials Miscellaneous In addition to the above-mentioned major parameters, some others can be applied. Frequency Tuning Characteristics Rauch et al. reported that patients with Meniere’s disease showed less tuning at 500 Hz and threshold elevation, whereas healthy subjects showed the best responses at 500 Hz [23]. Their results suggested that a new parameter concerning frequency tuning characteristics might be applicable for VEMP assessment. For example, the ratio of corrected VEMP amplitude at 500 Hz to that at 1000 Hz or the ratio of the threshold at 500 Hz to that at 1000 Hz might be applied. Acoustic/Galvanic Ratio The characteristics of the responses to acoustic stimuli and galvanic stimuli might be compared. Because galvanic stimulation bypasses the labyrinth and stimulates the vestibular nerve directly, labyrinthine damage does not affect galvanic VEMPs whereas it does affect acoustic VEMPs. Therefore, the acoustic VEMP amplitude/ galvanic VEMP amplitude ratio can be a useful indicator for differentiating laby- rinthine from retrolabyrinthine disorders [24–26]. This issue is discussed in the chapter “VEMP Variants.” References 1. Welgampola MS, Colebatch JG (2005) Characteristics and clinical applications of vestibular- evoked myogenic potentials. Neurology 64:1682–1688 2. Bath AP, Harris N, McEwan J (1999) Effect of conductive hearing loss on the vestibulocollic reflex. Clin Otolaryngol 24:181–183 3. Murofushi T, Matsuzaki M, Mizuno (1998) Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509–512 4. Sheykholeslami K, Murofushi T, Kaga K (2001) The effect of sternocleidomastoid electrode location on VEMP. Auris Nasus Larynx 28:41–43 5. Endoh T, Hojoh K, Sohma H, et al (1987) Auditory postauricular responses in patients with peripheral facial nerve palsy. Acta Otolaryngol Suppl 446:76–80 6. Murofushi T, Matsuzaki M, Wu CH (1999) Short tone burst-evoked myogenic potentials on the sternocleidomastoid muscle. Arch Otolaryngol Head Neck Surg 125:660–664 7. Murofushi T, Curthoys IS, Topple AN, et al (1995) Responses of guinea pig primary vestibu- lar neurons to clicks. Exp Brain Res 103:174–178 8. Murofushi T, Curthoys IS (1997) Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol (Stockh) 117:66–72 9. Wu CH, Murofushi T (1999) The effect of click repetition rate on vestibular evoked myogenic potential. Acta Otolaryngol (Stockh) 119:29–32
10. Welgampola MS, Colebatch JG (2001) Characteristics of tone burst-evoked myogenic poten- tials in the sternocleidomastoid muscles. Otol Neurotol 22:796–802 11. Vanspauwen R, Wuyts FL, Van deHeyning PH (2006) Improving vestibular evoked myogenic potential reliability by using a blood pressure manometer. Laryngoscope 116:131–135 12. Ito K, Karino S, Murofushi T (2007) Effect of head position on vestibular evoked myogenic potentials with tone burst stimuli. Acta Otolaryngol 127:57–61 13. Isaacson B, Murphy E, Cohen H (2006) Does the method of sternocleidomastoid muscle activation affect the vestibular evoked myogenic response? J Vestib Res 16:187–191 14. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127:1069– 1072 15. Murofushi T, Ochiai A, Ozeki H, et al (2004) Laterality of vestibular evoked myogenic potentials. Int J Audiol 43:66–68 16. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click- evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 17. Colebatch JG, Rothwell JC (2004) Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle. Clin Neurophysiol 115:2567–2573 18. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 19. Welgampola MS, Colebatch JG (2001) Vestibulocollic reflexes: normal values and the effect of age. Clin Neurophysiol 112:1971–1979 20. Shimizu K, Murofushi T, Sakurai M, et al (2001) Vestibular evoked myogenic potentials in multiple sclerosis. J Neurol Neurosurg Psychiatry 69:276–277 21. Takegoshi H, Murofushi T (2000) Vestibular evoked myogenic potentials in patients with spinocerebellar degeneration. Acta Otolaryngol 120:821–824 22. Colebatch JG, Day BL, Bronstein AM, et al (1998) Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon. J Neurol Neurosurg Psychiatry 65:670–678 23. Rauch SD, Zhou G, Kujawa SG, et al (2004) Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol 25:333–338 24. Murofushi T, Iwasaki S, Ozeki H, et al (2007) Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a new parameter of VEMP? Clin Neurophysiol 118:1685– 1690 25. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 26. Monobe H, Murofushi T (2004) Vestibular testing by electrical stimulation in patients with unilateral vestibular deafferentation: galvanic evoked myogenic responses testing vs galvanic body sway testing. Clin Neurophysiol 155:806–810 Recording and Assessing VEMPs 33
VEMP Variants Introduction Originally, vestibular evoked myogenic potentials (VEMPs) were recorded on cervical muscles, especially the sternocleidomastoid muscle (SCM), in regard to air-conducted sound [1, 2]. However, there were some limitations of this test. To overcome these limitations, variants of VEMP analysis have been proposed and are classified into two categories: variants stimulation methods and recording methods. Variants of Stimulation Methods In addition to conventional unilateral air-conducted sound stimulation, a binaural simultaneous air-conducted sound stimulation method, a tapping method, a bone- conducted sound method, and a galvanic stimulation method have been reported. Binaural Simultaneous Stimulation Method The binaural simultaneous air-conducted sound stimulation method was proposed to reduce physical loading of subjects. During VEMP recording, subjects must keep contracting the SCM, and it is sometimes difficult for elderly subjects to maintain the contraction. The saccular projection to the SCM is unilateral [3]. In other words, acoustic stimulation to one ear affects only the SCM ipsilateral to the stimulated ear. In healthy subjects, VEMPs are clearly ipsilateral-dominant [4]. Therefore, simultane- ous binaural stimulation seems to enable sacculocollic reflexes on both sides at the same time. Murofushi et al. compared VEMP responses of monaural click stimula- tion with responses to binaural click stimulation in patients with unilateral peri- Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 34 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_5, © Springer 2009
VEMP Variants 35 pheral vestibular dysfunction [5]. In 26 of the 28 patients, results for monaural stimulation coincided with those for binaural stimulation (Fig.1, Table 1). Among the two patients without coincidence, one patient showed bilateral normal responses to monaural stimulation despite decreased responses on one side to binaural simul- taneous stimulation, and the other patient showed a unilateral absence to monaural stimulation despite the bilateral absence of responses to binaural stimulation. The reasons for the discordance were not clear. However, the high rate of coincidence and no false-negative results encouraged us to apply the binaural simultaneous stimulation method as a clinical screening test. Tapping and Bone-Conducted Sound Method Conduction problems in the external ear or middle ear attenuate the intensity of air-conducted sound. Therefore, subjects with conductive hearing loss may show an absence of response despite a normal sacculocollic pathway. The tapping and bone-conducted sound method was primarily applied to measure vestibulocollic Monaural stimulation Binaural stimulation Fig. 1. Vestibular evoked myogenic potential (VEMP) responses to monau- ral individual stimulation and binaural simultaneous stimulation in a woman with a left acoustic neuroma. The patient showed absent responses on the left sternocleidomastoid muscle (SCM) to left ear stimulation and to binaural stimulation. L, left side; R, right side. (from Fig. 1 of ref. 5, Springer, with permission) Table 1. Results to unilateral stimulation and bilateral stimulation. (from Table 1 of ref. 5, Springer, with permission) Bilateral stimulation Unilateral stimulation Bilaterally normal Unilaterally decreased Unilaterally absent Bilaterally absent Total Bilaterally normal 9 0 0 0 9 Unilaterally decreased 1 0 0 0 1 Unilaterally absent 0 0 15 0 15 Bilaterally absent 0 0 1 2 3 Total 10 0 16 2 28
36 Vestibular Evoked Myogenic Potentials reflexes in patients with conducted-hearing loss, as these stimulations are thought to bypass the middle ear and act directly on the inner ear (Fig. 2). The tapping method applied vibratory stimulation to the subjects’skulls. Tapping with a tendon hammer evokes biphasic myogenic responses on the SCM as evoked by air-conducted sound (Figs. 3, 4) [6–8]. The tapping site is the forehead (Fz) or mastoid. Recording conditions are basically the same as for VEMP responses to Air-conducted sound Bone- conducted sound, tapping Galvanic stimuli Fig. 2. Stimulation methods and supposed stimulated sites Fig. 3. Tendon hammer that can send trigger signals to the averager
VEMP Variants 37 air-conducted sound. In a study of patients without conductive hearing loss, so long as we concerned only if the results were normal 14 of 15 patients showed the same results with the tapping method as were seen with the air-conducted click method. However, many of them showed delayed positivity (Table 2). Although we had regarded the delayed positivity as delayed p13, the positivity might be an inverted response preceded by negativity (n13) (Fig. 5). There was no clear relation between the responses evoked by tapping and pure-tone hearing. These findings suggested that myogenic potentials evoked by tapping should be of vestibular origin but that parts other than the saccule could be also stimulated. Brantberg and Mathiesen reported that tapping-evoked myogenic potentials were preserved after resection of the inferior vestibular nerve [9]. Their findings supported our assumption. As described above, the tapping method is a good alternative to the conventional VEMP procedure. One problem with the tapping method, though, was the difficulty of calibrating the stimulation. The bone-conducted sound method overcomes this defect. For recording VEMPs to bone-conducted sound, a bone vibrator—an apparatus to measure pure-tone hearing thresholds—was first applied [10–14]. Currently, a bone vibrator with stronger intensity is available [15]. The bone Fig. 4. VEMPs to 95-dBnHL clicks and myogenic responses to tapping in a healthy subject Table 2. Results of myogenic potentials to clicks and tapping Parameter Normal Abnormal Total Decreased Absent Delayed Normal 3 0 0 0 3 Abnormal Decreased 1 0 0 1 2 Absent 0 0 4 5 9 Delayed 0 0 0 1 1 Total 4 0 4 7 15
38 Vestibular Evoked Myogenic Potentials vibrator is placed on the mastoid or forehead. The other recording conditions are basically the same as those for air-conducted sound. The optimal frequencies for VEMPs to bone-conducted sound ranged from 200 to 250 Hz [14, 16]. As for the tapping method, bone-conducted sound can stimulate not only the saccule but other parts of the vestibular end-organs as well. A neurophysiological experiment with guinea pigs suggested that the utricle could also be stimulated by bone- conducted sound [17]. These methods—the tapping method and the bone-conducted sound method— are suitable for assessing vestibular function of subjects with conductive hearing loss [11–13]. One should note that these methods stimulate vestibular end-organs on both sides. Whereas the saccular projection to the SCM is uncrossed, the utricu- lar projection to the SCM is not only uncrossed but also crossed. Utricular stimula- tion could have excitatory inputs to the contralateral SCM [3]. Therefore, we should take the crossed pathway into account when assessing the results. Galvanic Stimulation Galvanic stimulation has been used for a galvanic body sway test and a galvanic eye movement test [18–21]. Galvanic stimulation has been thought to bypass the labyrinth and act directly on the vestibular nerve (Fig. 2) and thus is useful for differentiating retrolabyrinthine lesions from labyrinthine lesions. Short-duration galvanic stimulation has been also applied to patients with vestibular disorders for this purpose [20–22]. That these potentials are of vestibular origin was confirmed by the disappearance of myogenic potentials on the SCM after vestibular nerve section [23]. Fig. 5. VEMP (95-dBnHL clicks) and myogenic responses to tapping in a woman with a left acoustic neuroma. She showed absent responses to clicks and delayed responses to tapping. Inverted responses?, small negativity might be an inverted response
VEMP Variants 39 The recording methods of myogenic potentials to galvanic stimuli are as follows. The electrodes for stimulation were placed on the forehead (anode) and mastoid (cathode), or on bilateral mastoids. The cathodal electrode should be placed on the mastoid that an examiner wants to stimulate. The procedure is contraindicated in patients who have an implanted electrical device such as a pacemaker or a cochlear implant. It should also not be applied to patients who have medical history of epilepsy. A current of 3–4 mA (duration 1–2 ms) is used as the galvanic stimulus. Band- pass filters, stimulation rate, and time window for analysis are the same as for acquiring VEMPs to acoustic stimuli. Responses to 50–100 stimuli are averaged. Galvanic stimulation produces huge electrical artifacts. To remove these artifacts, the responses obtained without SCM contraction are subtracted from the responses with SCM contraction [21, 22]. Using this subtraction method, we can get biphasic (positive–negative) responses similar to VEMPs to acoustic stimuli (Fig. 6). We call the first positivity p13g and the following negativity n23g. The means ± SD of p13g and n23g with our method (3 mA, 1 ms) [21] were 11.4 ± 1.3 ms and 19.0 ± 2.1 ms, respectively. The mean threshold was 2.5 mA. As these myogenic potentials were abolished by vestibular nerve section [22], we call these myogenic potentials to short-duration galvanic stimuli “galvanic VEMPs.” As expected, patients with labyrinthine lesions such as Meniere’s disease have normal galvanic VEMPs even though they had an absence of click VEMPs on the affected side. In contrast, patients with retrolabyrinthine lesions (e.g., acoustic neuroma) showed a tendency toward abnormal galvanic VEMPs in addition to absent VEMPs in response to clicks [21]. This combined method of acoustic p13g n23g 10 msec 200 m V 100 m V 10 msec With muscle contraction Without muscle contraction (a) (b) Fig. 6. Subtraction methods to make responses clearer. (from Fig. 1 of ref. 21, Elsevier, with permission)
40 Vestibular Evoked Myogenic Potentials VEMPs and galvanic VEMPs has been applied for lesion site studies of various diseases, as described in the clinical application chapters later in this book [21, 24–27]. At an early stage, this combined method was applied only to patients with absent VEMPs to acoustic stimuli. Recently, this combined method has been applied to patients with preserved acoustic VEMPs. We can calculate the ratio of corrected p13–n23 amplitudes to tone burst stimuli/corrected p13g–n23g amplitudes to gal- vanic stimuli (the TG ratio). The TG ratio is significantly smaller on the affected side of patients with endolymphatic hydrops (a representative inner ear disease) than it is in healthy subjects or on the unaffected side of patients [28]. This change in the TG ratio was not observed in patients with an acoustic neuroma. The combined method of acoustic and galvanic VEMPs for lesion site studies is also applicable to subjects with preserved acoustic VEMPs. Variants of Recording Methods Vestibular Evoked Extraocular Potential Recently, myogenic potentials to acoustic stimuli recorded around the eyes— vestibular evoked extraocular potential (oVEMP)—have been reported [15, 29, 30]. These responses consist of several peaks. The first peak is a negative deflection with short tone bursts (mean 10.5 ms to 135-dBSPL, 500-Hz air-conducted bursts) followed by a positive deflection (mean 15.9 ms) [30]. When air-conducted sounds were presented, responses were contralateral eye-dominant and clearly recorded on the electrodes placed underneath the lower eyelid [30] (Fig. 7, Table 3). With our recording method [30], active electrodes are placed on the face just inferior to each eye, with reference electrodes placed 1–2 cm below. Electro- myography (EMG) signals are amplified and bandpass-filtered between 5 and 500 Hz. The time window for analysis is 50 ms. Although we prefer air-conducted sound (500-Hz short tone burst, up to 135 dBSPL) because of unilateral stimula- tion, others prefer bone-conducted sound or tapping because of clearer responses [15, 29, 30]. Responses to 100 stimuli are averaged. Subjects are instructed to maintain an upward gaze during recording because responses are the largest at this gaze position. It is believed that these responses reflect the vestibuloocular reflex, especially the otolith-ocular reflex. The responses are called oVEMPs. Although a clinical study suggested that oVEMPs are of vestibular origin, their exact origin is not clear yet. The extent of the contribution of the saccule and utricule is controversial. Further studies are required before this can be established as a definitive clinical test. After establishing the neural pathway of oVEMPs, the combined use of VEMPs and oVEMPs may be useful for assessing lesions in the brainstem, as suggested by Rosengren et al. [31].
VEMP Variants 41 Fig. 7. Vestibular evoked extraocular potentials (oVEMPs) and vestibular evoked myogenic potentials (cVEMPs) to 500-Hz tone bursts [135-dB sound pressure level (dBSPL)]. (from Fig. 3 of ref. 30, Elsevier, with permission)
42 Vestibular Evoked Myogenic Potentials Neurogenic Potentials For recording VEMPs (including oVEMPs), cooperation of the subject (maintain- ing contraction of the SCM or an upward gaze) is essential. Therefore, it is difficult to record VEMPs in children and elderly people and impossible in sleeping or generally anesthetized subjects. If possible, vestibular evoked neurogenic potentials (VENPs), which do not require muscle contraction, may be preferable. It was reported that negativity at a latency of 3 ms (N3) was observed instead of normal waveforms during auditory brainstem response (ABR) recording in subjects with profound hearing loss [32]. Ochi and Ohashi hypothesized that N3 might be of saccular origin [33]. As the presence of N3 corresponded to the presence of VEMPs [34] (Fig. 8), N3 might be of saccule origin. However, it was difficult to visualize N3 in subjects with normal hearing because they have normal ABR waveforms (Fig. 9). To visualize N3 in normal subjects, it is necessary to suppress or delete ABR waveforms. For this purpose, we presented white noise to the stimulated ear, the intensity of which was high enough to stimu- late the cochlea but insufficient for the vestibular nerve. We hypothesized that this ipsilateral masking sound could suppress ABRs by disturbing the synchronization of the cochlear nerve to the target sound but that it would not affect VEMPs. Based on this hypothesis, we recorded N3 in subjects with preserved hearing under white noise exposure (Fig. 10).We presented 1000-Hz short tone bursts (130 dBSPL, rise/fall time 0.5 ms, plateau time 1 ms) as target stimuli with white noise (100 dBSPL). The recording electrodes were placed on the vertex and mastoid. Signals were amplified and bandpass-filtered (100–3000 Hz). Responses to 500 stimuli were averaged. The stimulation rate was 10 Hz, and the time window for recording was 10 ms. Under these conditions, the mean latency of N3 of healthy subjects was 3.58 ms, and the mean threshold was 125 dBSPL. The appearance of N3 under these conditions corresponded well with the appearance of VEMPs [35]. We assume that the source of N3 might be around the vestibular nucleus. Apart from N3, Todd et al. recorded potentials on the scalp evoked by bone- conducted sound, the intensity of which was higher than the threshold of VEMPs Table 3. Rate of identifiable responses, amplitude, and latency of oVEMP Parameter 0.1-ms click (135 dBSPL) 500-Hz short tone burst (135 dBSPL) Ipsilateral eye Contralateral eye Ipsilateral eye Contralateral eye Rate of identifiable responses (% of 20 ears) 0 50 45 90 Amplitude between nI and pI (μV)a — 3.2 ± 0.4 1.9 ± 0.2 7.0 ± 1.0 nI latency (ms) — 8.8 ± 0.3 12.8 ± 0.6 10.5 ± 0.1 pI latency (ms) — 14.5 ± 0.5 17.7 ± 0.9 15.9 ± 0.3 (from Table 1 of ref. 30, Elsevier, with permission) a Mean ± SE
VEMP Variants 43 (a) (b) (c) Fig. 8. Responses to sound in a 25-year-old man with bilateral nearly total sensorineural hearing loss. a N3s (95-dBnHL 1-kHz tone bursts) were present on both sides. Shaded areas, periods of stimulation. b Audiograms. c VEMP (95-dBnHL clicks) Fig. 9. N3 potentials in a 5-year-old boy with right total hearing loss. Auditory brainstem responses (ABRs) were normal in response to left ear stimulation, whereas the usual ABR wave- forms were not observed after right ear stimulation. However, a clear negative deflection was observed at 3 ms after stimulation. The upward deflection represents positivity. ISIs, interstimulus intervals. (from Fig. 2 of ref. 32, The Oto-Rhino-Laryngological Society of Japan, with permission)
44 Vestibular Evoked Myogenic Potentials [36]. In addition to auditory middle latency responses [37], the authors observed positivity at about 10 ms (P10), which was maximum at Cz, and negativity at about 15 ms (N15), which was maximum at Fz. As P10 and N15 were also observed in patients with bilateral profound hearing loss [38], these potentials are possibly VENPs. The sources of these potentials and the origins at the end-organ level should be clarified. References 1. Colebatch JG, Halmagyi GM (1992) Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 42:1635–1636 2. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click- evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 3. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 4. Murofushi T, Ochiai A, Ozeki H, et al (2004) Laterality of vestibular evoked myogenic potentials. Int J Audiol 43:66–68 5. Murofushi T, Takai Y, Iwasaki S, et al (2005) VEMP recording by simultaneous binaural stimulation. Eur Ach Otorhinolaryngol 262:864–867 6. Halmagyi GM, Yavor RA, Colebatch JG (1995) Tapping the head activates the vestibular system: a new use for the clinical reflex hammer. Neurology 45:1927–1929 7. Murofushi T, Matsuzaki M, Ikehara Y, et al (2000) Myogenic potentials on the neck muscle by tapping the head. In: Claussen CF, Haid T, Hofferberth B (eds) Equilibrium research, clinical equilibriometry and modern treatment. Elsevier, Amsterdam, pp 233–238 8. Brantberg K, Tribukait A (2002) Vestibular evoked myogenic potentials in response to later- ally directed skull taps. J Vestib Res 12:35–45 9. Brantberg K, Mathiesen T (2004) Preservation of tap vestibular evoked myogenic potentials despite resection of the inferior vestibular nerve. J Vestib Res 14:347–351 10. Sheykholeslami K, Murofushi T, Kermany MH, et al (2000) Bone conducted evoked myogenic potentials from the sternocleidomastoid muscle. Acta Otolaryngol (Stockh) 120:731–734 11. Monobe H, Murofushi T (2004) Vestibular neuritis in a child with otitis media with effusion; clinical application of vestibular evoked myogenic potential by bone-conducted sound. Int J Pediatr Otorhinolaryngol 68:1455–458 Fig. 10. N3 in a healthy subject with ipsi- lateral white noise exposure. The shaded area represents period of stimulation
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46 Vestibular Evoked Myogenic Potentials 33. Ochi K, Ohashi T (2001) Sound-evoked myogenic potentials and responses with 3-msec latency in auditory brainstem response. Laryngoscope 111:1818–1821 34. Nong DX, Ura M, Kyuna A, et al (2002) Saccular origin of acoustically evoked short latency negative response. Otol Neurotol 23:953–957 35. Murofushi T, Iwasaki S, Takai Y, et al (2005) Sound-evoked neurogenic responses with short latency of vestibular origin. Clin Neurophysiol 116:401–405 36. Todd NP, Rosengren SM, Colebatch JG (2003) A short latency vestibular evoked potential (VsEP) produced by bone-conducted acoustic stimulation. J Acoust Soc Am 114:3264– 3272 37. Picton TW, Hillyard SA, Krausz HI, et al (1974) Human auditory evoked potentials. I. Evaluation of components. Electroencephalogr Clin Neurophysiol 36:179–190 38. Rosengren SM, Colebatch JG (2006) Vestibular evoked potentials (VsEPs) in patients with severe to profound bilateral hearing loss. Clin Neurophysiol 117:1145–1153
Part III Clinical Applications
Meniere’s Disease and Related Disorders: Detection of Saccular Endolymphatic Hydrops Introduction Meniere’s disease (MD), a common inner ear disorder, is characterized by recurrent vertigo attacks, fluctuating hearing loss, tinnitus, and a sensation of aural fullness [1]. Guidelines for the diagnosis of MD have been published by the American Academy of Otolaryngology, Head, and Neck Surgery (AAO-HNS) (Table 1) [2]. The incidence of MD varies from 21/100000 to 50/100000 [3–6]. MD develops during middle age and shows a slight female predominance [7]. The combination of vertigo, hearing loss, and tinnitus were reported by Itard (1821) [8]; and histopathological studies of the temporal bone in MD were pub- lished in 1938 by Yamakawa [9] and Hallpike and Cairns [10]. They reported endolymphatic hydrops in the temporal bone of MD patients at autopsy. According to Schuknecht [11], during the early stage of the disease endolymphatic hydrops involves principally the cochlear duct and the saccule. According to Okuno and Sando [12], severe hydrops was observed in the saccule most frequently in their histopathological study of the temporal bone. Therefore, a high incidence of abnor- mal vestibular evoked myogenic potentials (VEMPs) in MD is expected. Incidence of Abnormal VEMPs in Meniere’s Disease In earlier studies, the incidence of abnormal VEMPs was 39% according to Muro- fushi et al. [13] and 54% according to de Waele et al. [14]. We reviewed results of VEMPs of MD patients in our clinic (n = 81; 32 men, 49 women; ages 16–75 years, mean 50.7 years; 95-dBnHL clicks). Among the 81 patients, 39 (48%) had absent VEMPs on the affected side; 8 patients showed decreased VEMP amplitude; and 34 patients had normal VEMPs (Fig. 1). Thus, the overall incidence of abnormal VEMPs in MD patients was 58%. Although MD patients showed absent or decreased VEMPs, they rarely dis- played delayed peaks [15]. Rauch et al. reported an elevated VEMP threshold in Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 49 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_6, © Springer 2009
50 Vestibular Evoked Myogenic Potentials MD patients and recommended that the threshold be a diagnostic parameter [16]. Rauch et al. also reported a shift of the best frequency of VEMP in MD patients. According to previous studies, the best frequency of VEMP is between 300 and 700 Hz [17–19]. Whereas Rauch et al. reported that the best frequency is 500 Hz in healthy subjects, patients with MD showed less tuning at 500 Hz and shifts of the best frequency to 1000 Hz [16]. We confirmed this tendency (Fig. 2). Table 1. Dainostic scale for Meniere’s disease Certain Meniere’s disease Definite Meniere’s disease, plus histopathological confirmation Definite Meniere’s disease Two or more episodes of vertigo lasting at least 20 min Audiometrically documented hearing loss on at least one occasion Tinnitus or aural fullness Probable Meniere’s disease One definite episode of vertigo Audiometrically documented hearing loss on at least one occasion Tinnitus or aural fullness Possible Meniere’s disease Episodic vertigo without documented hearing loss Sensorineural hearing loss—fluctuating or fixed—with disequilibrium but without definite episodes (from ref. 2) In all scales, other causes must be excluded using any technical method Absent 39 (48%) Decreased 8 (10%) Normal 33 (41%) Increased 1 (1%) Fig. 1. Vestibular evoked myogenic poten- tial (VEMP) responses in Meniere’s disease (MD) patients (n = 81)
Meniere’s Disease: Detection of Hydrops 51 Rauch et al. attributed this shift to the change in resonant frequency in the saccule. Comparison of the amplitudes and/or thresholds of VEMP in 500 Hz with those in 1000 Hz could be a new parameter for VEMP that may be applicable to the diagnosis of endolymphatic hydrops in the saccule. However, there have been no reports concerning the specificity of this phenomenon. Thus, we need to determine if this frequency shift is specific to Meniere’s disease or to endolym- phatic hydrops. Disease Stage and VEMPs According to the guidelines of the AAO-HNS [2], the disease stage of MD is determined by the average hearing level. Young et al. [19] studied VEMP results in relation to the disease stage. Among 40 patients, 6 were classified as having stage I MD. Five of the six patients showed normal VEMPs, and one had aug- mented VEMPs on the affected side. Among the 12 patients classified as having stage II MD, 7 had normal VEMPs, 2 had augmented VEMPs, 4 had decreased VEMPs, and 2 had absent VEMPs. Among the 17 patients with stage III MD, VEMPs were normal in 10, decreased in 4, and absent in 3. Among the five patients classified as having stage IV MD, VEMPS were normal in two, decreased in one, and absent in two. In that study, patients at advanced stages more frequently showed absent or decreased VEMPs than patients at earlier stages. Fig. 2. Frequency characteristics of VEMP responses in healthy subjects (n = 8). Among the three tested frequencies (130 dBSPL), 500-Hz tone bursts tended to evoke the largest responses
52 Vestibular Evoked Myogenic Potentials Proving Saccular Endolymphatic Hydrops Using VEMPs Several clinical tests (e.g., electrocochleography, glycerol test, furosemide test) have been utilized to provide evidence of endolymphatic hydrops [20–24]. Electrocochleography (ECochG) is a test of auditory evoked potentials, which comprises potentials with short latencies (up to 2 ms). ECochG consists of three components: cochlear microphonics (CM), summating potentials (SPs), and compound action potentials (APs). The origin of CM and SPs is the cochlea, whereas APs derive from the cochlear nerve. The (negative) SPs of MD patients are significantly larger than those of healthy subjects [20, 21]. Such large SPs are thought to reflect distention of the basilar membrane due to endolymphatic hydrops. The ratio of the negative SPs to compound APs (CAPs) has been introduced as a parameter. The upper limit of the normal range of the ratio SPs/CAPs has been set at 0.30–0.40. With the glycerol test, improvement of pure-tone hearing thresholds by glycerol administration, an osmotic agent, has been thought to be caused by a temporary reduction of endolymphatic hydrops in the cochlea [22, 23]. Endolymphatic hydrops has been also reported to exist in the saccule [11, 12], although previous tests were not able to prove it. Murofushi et al. [25], however, proposed the method to prove the evidence of saccular hydrops in combination of VEMPs and glycerol adminis- tration (glycerol VEMP test). We record VEMPs prior to glycerol administration and 3 h after oral glycerol administration (1.3 g/kg body weight) and measure the change ratio (CR) of the VEMP (p13–n23) amplitudes. CR (%) = 100(Aa − Ab)/(Aa + Ab) where Aa is the p13–n23 amplitude 3 h after glycerol administration; and Ab is the p13–n23 amplitude before glycerol administration. The CR of six healthy volunteers was 3.52% ± 14.6% (mean ± SD). The normal range was set at −25.7% to +32.7 % (within the mean ± 2 SD). Among the 17 MD patients (4 men, 13 women; ages 24–72 years), 5 patients showed changes in VEMP amplitudes exceeding the normal range (Fig. 3). Among the 17 patients, 10 had abnormal VEMPs prior to glycerol administration. All the patients who showed significantly large CRs had abnormal VEMPs prior to glycerol administration. Therefore, 50% (5/10) of the patients with abnormal VEMPs showed significant enlargement of VEMP amplitudes due to glycerol administration. Patients with stage II MD most frequently had a positive glycerol VEMP test. The results of glycerol VEMP testing were independent of the conventional glycerol test using pure-tone audiometry. As glycerol VEMP testing can be performed simultaneously with the conventional glycerol test, the glycerol VEMP test can provide supple- mental information to detect endolymphatic hydrops [25, 26].
Meniere’s Disease: Detection of Hydrops 53 Drop Attacks in MD and VEMPs In 1936, Tumarkin was the first to describe sudden drop attacks in patients with MD [27]. Patients with MD who suffered from drop attacks suddenly felt a sensa- tion of being pushed to the ground and then fell without loss of consciousness [28]. This phenomenon has been called Tumarkin’s otolithic crisis or a vestibular drop attack (VDA) [3]. It has been thought that VDA occurred with sudden changes in endolymphatic fluid pressure with inappropriate otolith stimulation causing reflex- like vestibulospinal loss of postural tone. The abnormal bursts of neural impulses from the otolithic organs would pass through the lateral vestibulospinal tract (LVST), resulting in loss of postural tone. These hypothesized pathophysiological mechanisms allowed us to assume that the function of the otolithic organ might have some room to change when VDA occurs. In other words, the functions of the otolithic end-organs may be unstable. Ozeki et al. reviewed clinical records of 116 MD patients, finding 3 with VDA [29]. Profiles of the three patients are summarized in Table 2. All three patients showed recovery of VEMP responses spontaneously (patient 2) or after glycerol administration (patients 1 and 3). These results imply that abnormal VEMPs in such patients can be reversible and that their otolithic organs might be unstable. After the bilateral VEMPs of patient 1 disappeared, there were no more drop attacks. At the advanced stage—when bilateral otolithic organs were irreversibly damaged—VDA may no longer occur. Fig. 3. Effects of oral glycerol in a 69-year-old woman with left MD. She showed increased VEMP amplitudes on the left side 3 h after glycerol administration. post-G, after glycerol; pre-G, before glycerol; L, left side; R, right side. (from Fig. 1 of ref. 25, Elsevier, with permission)
54 Vestibular Evoked Myogenic Potentials Table 2. Summary of results of 3 MD patients with VDA Case no. Sex Affected side Stage (L/R) Age at onset of MD (years) Age at onset of VDA (years) No. of VDAs CP VEMP (L/R) Glycerol VEMP Date of VEMP recording 1 F Bil. 3/3 64 66 12 attacks in 3 years L 5% present/present NA May 1, 1998 present/absent Rt. positive June. 22, 1998 R 23% absent/absent NA Sept. 3, 2001 2 F Bil. 3/3 54 64 40 attacks in 10 years R 33% present/absent NA Feb. 17, 1997 present/absent NA June 22, 1998 present/present NA Jan. 6, 2003 3 M Bil. 2/2 65 70 9 attacks in 3 years R 74% present/absent Lt. positive Dec. 17, 2004 (from Table 1 of ref. 29, Taylor & Francis, with permission) Bil., bilateral; MD, Meniere’s disease; VDA, vestibular drop attack; L/R, left/right; VEMP, vestibular evoked myogenic potentials; CP, canal paresis in the caloric test, left (L) and right (R); NA, not available
Meniere’s Disease: Detection of Hydrops 55 VEMPs in Delayed Endolymphatic Hydrops Some people with unilateral profound hearing loss experience a delayed onset of vertigo. Schuknecht called this condition delayed endolymphatic hydrops (DEH) [30]. DEH can be subdivided into two types: ipsilateral and contralateral. Patients diagnosed as having ipsilateral DEH have preexisting sensorineural hearing loss in one ear and subsequent delayed-onset Meniere-type episodic vertigo without fluctuating hearing loss in the other ear. In contrast, patients diagnosed as having contralateral DEH have preexisting sensorineural hearing loss in one ear and subsequent onset of fluctuating hearing loss in the other ear, with or without Meniere-type episodic vertigo. According to Ohki et al. [31, 32], 67% (6/9) of contralateral DEH patients and 75% (9/12) of ipsilateral DEH patients had abnor- mal VEMPs (Table 3). Two of the four patients with ipsilateral DEH in their study had positive glycerol VEMP testing results (Fig. 4). As patients with ipsilateral DEH have profound sensorineural hearing loss on the affected side, it is difficult to prove endolymphatic hydrops using ECochG or the conventional glycerol test. However, with glycerol VEMP testing, it was possible to establish the presence of saccular endolymphatic hydrops in patients with ipsilateral DEH. This is a signifi- cant advantage of glycerol VEMP testing. Fig. 4. Effects of oral glycerol on a 55-year-old woman with left-side ipsilateral delayed endo- lymphatic hydrops. (from Fig. 1 of ref. 32, S. Karger AG, with permission) Table 3. VEMP responses in patients with delayed endolymphatic hydrops Type No. No. with VEMP response Normal Decreased Absent Ipsilateral 12 3 5 4 Contralateral 9 3 0 6
56 Vestibular Evoked Myogenic Potentials Galvanic VEMPs in Endolymphatic Hydrops Delayed peaks of VEMP are signs of retrolabyrinthine or central lesions [15]. However, as the normal range of VEMP latencies is quite wide, it is difficult to differentiate labyrinthine lesions from retrolabyrinthine lesions with only the latencies of the peaks. Furthermore, in patients with absent VEMPs, we have no information concerning latency. Hence, another method is required for the differ- entiation of lesion sites. Galvanic VEMP has been applied for this purpose [33–35]. As galvanic stimula- tion bypasses the hair cells in the labyrinth and directly stimulates the distal portion of the vestibular nerve, patients with absent acoustic VEMPs due to labyrinthine lesions may have normal responses to galvanic stimuli. In fact, Murofushi et al. showed that patients with absent acoustic VEMPs due to labyrinthine lesions (Meniere’s disease or ipsilateral DEH) have normal galvanic VEMPs, whereas almost all patients with absent acoustic VEMPs due to retrolabyrinthine lesions (acoustic neuroma or other cerebellopontine angle tumor) showed absent or decreased galvanic VEMPs (Fig. 5, Table 4) [35]. Furthermore, Murofushi et al. proposed methods to differentiate lesion sites in patients with still-present VEMPs [36]. Murofushi et al. introduced the ratio of the corrected p13–n23 amplitude to acoustic (tone bursts) stimuli/the corrected amplitude p13g–n23g to galvanic stimuli. Fig. 5. Relation of percent galvanic-evoked myogenic potential asymmetry to CP in the caloric test. Almost all patients in group B (open circles) showed no or decreased responses to galvanic stimulation on the affected side even though their caloric responses were preserved. In contrast, group A patients (filled circles) showed normal responses to galvanic stimulation on the affected side. GA, galvanic VEMP asymmetry; CP, canal paresis. Group A: Meniere’s disease or delayed endolymphatic hydrops. Group B: acoustic neuroma or other cerebellopontine angle tumors. (from Fig. 5 of ref. 35, Elsevier, with permission)
Meniere’s Disease: Detection of Hydrops 57 TG (tone burst/galvanic) ratio = CA(p13–n23)/CA(p13g–n23g) where CA(p13–n23) is the corrected amplitude of p13–n23 to tone bursts (500 Hz, 135 dBSPL); and CA(p13g–n23g) is the corrected amplitude of p13g–n23g to galvanic stimuli (3 mA, 1 ms) In 12 healthy volunteers, the TG ratio was 2.28 ± 0.66 (mean ± SD). In 12 patients with endolymphatic hydrops, the TG ratio was 1.16 ± 0.71. Among the 12 patients, 8 had a significantly small TG ratio (below the mean − 2 SD) (Fig. 6). This tendency was not observed in patients with an acoustic neuroma. The combined use of acoustic and galvanic VEMPs seems to be useful for dif- ferentiating labyrinthine lesions from retrolabyrinthine lesions. However, de Waele et al. reported that galvanic VEMPs could be abolished after intratympanic instil- lation of gentamicin in MD patients [37]. Therefore, the diagnostic value of abnor- mal galvanic VEMPs should be subjected to further study. Fig. 6. Tone burst/galvanic ratio (TG) of healthy subjects and patients with endolymphatic hydrops (EH). TG ratios of the affected side of patients were significantly smaller than those of the unaffected side and in healthy subjects. (from Fig. 3 of ref. 36, Elsevier, with permission) Table 4. Results of galvanic-evoked myogenic potentials in patients Groupa Increased Normal Decreased Absent Total A 1 9 0 0 10 B 0 2 2 14 18 Total 1 11 2 14 28 a Group A, Meniere’s disease or delayed endolymphatic hydrops; group B, acoustic neuroma or other cerebellopontine angle tumors
58 Vestibular Evoked Myogenic Potentials References 1. Hamann KF, Arnold W (1999) Meniere’s disease. Adv Otorhinolaryngol 55:137–168 2. Anonymous (1995) Committee on Hearing and Equilibrium Guidelines for the Diagnosis and Evaluation of Therapy in Meniere’s disease. Otolaryngol Head Neck Surg 113:181–185 3. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 4. Stahle J, Stahle C, Arenberg IK (1978) Incidence of Meniere’s disease. Arch Otolaryngol 104:99–102 5. Shojaku H, Watanabe Y (1997) The prevalence of definite cases of Meniere’s disease in the Hida and Nishikubiki districts of central Japan. Acta Otolaryngol 528:S94–S96 6. Dickins JRE, Graham SS (1990) Meniere’s disease 1983–1989. Am J Otol 11:51–65 7. Friberg U, Stahle J (1999) The epidemiology of Meniere’s disease. In: Harris JP(ed) Meniere’s disease. Kugler, The Hague, pp 17–28 8. Itard JMG (1821) Traite des maladies de l’oreille et de l’audition. Mequignon-Marvis, Paris 9. Yamakawa K (1938) Uber die pathologishe Veranderung bei einem Meniere-Kranken. J Otolaryngol Soc Jpn 4:2310–2312 10. Hallpike CS, Cairns H (1938) Observation on the pathology of Meniere’s syndrome. J Laryngol Otol 53:625–655 11. Schuknecht HF (1993) Pathology of the ear. 2nd edn. Lea & Febiger, Philadelphia 12. Okuno T, Sando I (1987) Localization, frequency, and severity of endolymphatic hydrops and the pathology of the labyrinthine membrane in Meniere’s disease. Ann Otol Rhinol Laryngol 96:438–445 13. Murofushi T, Matsuzaki M, Shimizu K (2000) Vestibular-evoked myogenic potentials in patients with unilateral Meniere’s disease. In: Sterkers O, Ferrary E, Dauman R, et al (eds) Meniere’s disease 1999—update. Kugler, The Hague, pp 353–358 14. de Waele, Tran Ba Huy P, Diard JP, et al (1999) Saccular dysfunction in Meniere’s disease. Am J Otol 20:223–232 15. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127: 1069–1072 16. Rauch SD, Zhou G, Kujawa SG, et al (2004) Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol 25:333–338 17. Todd NP, Cody FW, Banks JR (2000) A saccular origin of frequency tuning in myogenic vestibular evoked potentials? Implications for human responses to loud sounds. Hear Res 141:180–188 18. Welgampola MS, Colebatch JG (2001) Characteristics of tone-burst-evoked myogenic poten- tials in the sternocleidomastoid muscles. Otol Neurotol 22:796–802 19. Young YH, Huan TW, Cheng PW (2003) Assessing the stage of Meniere’s disease using vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 129:815–818 20. Aso S, WatanabeY, Mizukoshi K (1991)Aclinical study of electrocochleography in Meniere’s disease. Acta Otolaryngol (Stockh) 111:44–52 21. Gibson WPR, Moffat DA, Ramsden RT (1977) Clinical electrocochleography in the diagnosis and management of Meniere’s disorder. Audiology 16:389–401 22. Klockhoff I, Lindblom U (1966) Endolymphatic hydrops revealed by glycerol test: prelimi- nary report. Acta Otolaryngol (Stockh) 61:459–462 23. Yazawa Y, Kitahara M, Matsubara H (1990) Clinical factors relating to the positive glycerol test for Meniere’s disease. ORL 52:149–155 24. Futaki T, Kitahara M, Morimoto M (1975) The furosemide test for Meniere’s disease. Acta Otolaryngol 79:419–424 25. Murofushi T, Matsuzaki M, Takegoshi H (2001) Glycerol affects vestibular evoked myogenic potentials in Meniere’s disease. Auris Nasus Larynx 28:205–208
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Vestibular Neuritis (Neurolabyrinthitis) and Other Peripheral Vestibulopathies: Detection of Inferior Vestibular Nerve Damage Introduction Vestibular neuritis (vestibular neuronitis, vestibular neurolabyrinthitis, VN) is characterized by prolonged severe vertigo with an acute onset. VN is not accom- panied by cochlear symptoms or any other neurological symptoms [1, 2]. This entity was described by Ruttin in 1909 [3] and by Nylen in 1924 [4]. It was called vestibular neuronitis, and its symptomatology was summarized by Dix and Hallpike [5]; but there is little evidence that the ganglion cells are primarily inflamed. The occurrence rate of VN in Japan was reported to be 3.5 per 100000 popula- tion. The peak age at the time of the vertigo attack was during the fifth to sixth decades [6]. Diagnostic criteria of VN are generally as follows. • A single (or a few) vertigo attack(s) lasting for several hours to several days • Severely damaged peripheral vestibular function usually proven by caloric testing • No cochlear signs or other neurological signs Two causes have been proposed: viral inflammation and vascular disturbance. Although there are only a few studies of the temporal bone pathology of VN, their results have mainly supported the viral theory [7–9]. Of course, VN might be caused by either of the two factors. Vestibular Loss in VN: Complete or Partial? Hypofunction of the peripheral vestibular system unaccompanied by cochlear or other neurological signs must be demonstrated to establish a diagnosis of VN, as mentioned above. Hypofunction of the peripheral vestibular system is usually Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 60 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_7, © Springer 2009
Vestibular Neuritis (Neurolabyrinthitis) 61 revealed by the caloric test or the head impulse test at the yaw axis [10]. These tests mainly reflect functions of the vestibuloocular reflex, especially the lateral semicircular canal-ocular reflex. Previous studies suggested that the vestibular loss due to VN is in the superior vestibular nerve but that the inferior vestibular nerve may be spared [11]. However, clinical tests of the peripheral vestibular system have been focused on the lateral semicircular canal and its afferents, the superior ves- tibular nerve. Furthermore, there are few samples of the temporal bone of the VN, although the disease itself is common. The issue of involvement of the inferior vestibular nerve remains to be clarified. Recently, VEMP became a strong tool for evaluating the function of the saccule and its main afferents, the inferior vestibular nerve. Murofushi et al. reported that 31 of 47 VN patients (66%) in Australia had VEMP responses on the affected side but that 16 patients (34%) had an absence of VEMP responses [1]. Later, Murofushi et al. performed a similar study in Japan. Among the 68 patients (40 men, 28 women; ages 18–78 years) 34 (50%) had normal VEMPs, whereas 31 (46%) and 3 (4%) had absent and decreased VEMPs, respectively (Fig. 1). These results imply that a considerable number of patients with VN could have deficits of functions of the saccule and/or its afferents. Their results suggested that the VN could be subdivided into the total VN and the superior VN (Fig. 2). Involvement of the inferior vestibular nerve was also supported by a study on semicircular canals [12]. Normal 34 (50%) Absent 31 (46%) Decreased 3 (4%) Fig. 1. Vestibular evoked myogenic potential (VEMP) responses in 68 vestibular neuritis (VN) patients
62 Vestibular Evoked Myogenic Potentials Inferior VN At this stage, one can assume that some dizzy patients might have a damaged inferior vestibular nerve with a spared superior vestibular nerve. In other words, patients could have inferior VN [13] (Fig. 3). As the inferior vestibular nerve is an afferent of the posterior semicircular canal and the major part of the saccule, a damaged inferior vestibular nerve could cause the signs and symptoms, as sum- marized in Table 1. We reviewed 1597 clinical records of the Balance Clinic at the University of Tokyo Hospital [14]. Among the 812 patients who underwent both caloric tests and VEMP tests, 4 patients fulfilled the inclusion criteria of possible inferior VN, as shown in Table 2. During the same period, we had 30 patients with classic VN (total VN and superior VN). Inferior VN might be less frequent than superior VN Fig. 3. Inferior vestibular neuritis Fig. 2. Classification of vestibular neuritis. a Superior vestibular neuritis, b total (superior and inferior) vestibular neuritis
Vestibular Neuritis (Neurolabyrinthitis) 63 Table 1. Assumed clinical signs and symptoms of inferior vestibular neuritis Clinical symptoms Sudden, severe, and prolonged vertigo No auditory or other neurological symptoms Clinical signs Spontaneous tortional-vertical nystagmus Postural imbalance Posterior semicircular canal paresis Paresis of the saccule Preservation of superior vestibular nerve function or total VN because of the anatomical differences in bony canals between the superior vestibular nerve and the inferior vestibular nerve [15]. If the clinical entity of inferior VN were to be established, perhaps a clear diag- nosis could be established in some patients whose diagnosis is in question. Recovery of Vestibular Damage in VN Recovery of equilibrium after a VN attack is achieved by vestibular compensation and recovery of peripheral vestibular functions [16]. Concerning the recovery of peripheral vestibular functions, the recovery of caloric responses (i.e., functions of the lateral semicircular canal and its afferents) have been mainly reported. Accord- ing to Okinaka et al. [17], caloric responses on the affected side of the VN recov- ered to within the normal range in 37.2% at 2 years and in 50.0% at 5 years. Concerning recovery of VEMP after a VN attack, Ochi et al. reported that one of two VN patients with an absence of VEMP responses showed recovery of responses to within the normal range at 15 months [18]. Murofushi et al. sequen- tially recorded VEMPs in 13 patients with total VN. Four of these patients (30.7%) showed recovery of VEMP responses to within the normal range at 2 years (Figs. 4, 5), whereas only one patient (7.6%) showed recovery of caloric responses [19]. These results imply that damage to the inferior vestibular nerve may be reversed more quickly than that to the superior vestibular nerve in total VN. Table 2. Inclusion criteria for possible inferior vestibular neuritis A single vertigo attack lasting at least several hours Damaged saccular function shown as abnormal VEMPs Normal caloric responses on both sides No hearing loss or other neurological signs Exclusion of other diseases VEMP, vestibular evoked myogenic potentials
64 Vestibular Evoked Myogenic Potentials Lesion Site of VN: Nerve or End-Organ? Generally speaking, it has been believed that the VN lesion is in the vestibular nerve. However, VN might be vestibular labyrinthitis. To clarify the lesion site of VN, we recorded galvanic and click VEMPs in patients with VN [20, 21]. Among those diagnosed as having total VN, patients who showed an absence of caloric responses to ice water and an absence of click VEMPs on the affected side (nine men, two women; ages 38–67 years) were selected.Among them, eight (73%) showed an absence of galvanicVEMPresponses, and three (27%) had normal galvanic VEMP responses (Fig. 6). These results sug- gested that so-called vestibular neuritis could be vestibular labyrinthitis. The fact that clinical VN could also have lesions in the labyrinth is appropriate for the explanation of post-VN benign paroxysmal positional vertigo (BPPV). Although it Fig. 4. VEMP recovery in a 51-year-old man with left VN. a VEMPs 4 days after the attack. b VEMPs 3 months after the attack. c VEMPs 6 months after the attack. d VEMPs 2 years after the attack. The patient showed recovery of VEMP within 6 months, and within 2 years his VEMPs were normalized. L, left side; R, right side. (from Fig. 2 of ref. 19, Taylor & Francis, with permission)
Vestibular Neuritis (Neurolabyrinthitis) 65 Fig. 5. Time courses of recovery of VEMP responses after VN attacks. Gray area represents the normal range. Percent VA, percent VEMP asymmetry. (from Fig. 1 of ref. 19, Taylor & Francis, with permission) Neuritis type Labyrinthitis type click galvanic Fig. 6. VEMPs to clicks and galvanic stimuli in patients with VN. Most of the VN patients showed an absence of responses to both clicks and galvanic stimuli (neuritis type), although some patients showed absent click-induced VEMPs but normal galvanic VEMPs (labyrinthitis type)
66 Vestibular Evoked Myogenic Potentials is well known that BPPV is frequently experienced after a severe vertigo attack of VN [1], the reason for it is not clear. Inner ear damage due to vestibular labyrinthitis might cause canalolithiasis if the posterior semicircular canal is preserved. Accord- ing to Murofushi et al. [1], post-VN BPPV was observed in 10 of 47 VN patients (21%). As VN could be vestibular labyrinthitis in 27% of the VN patients, it is conceivable that the VN patients with vestibular labyrinthitis and preserved poste- rior semicircular canal had post-VN BPPV. Other Types of Peripheral Vestibulopathy Ramsay Hunt Syndrome Ramsay Hunt syndrome (RHS) is characterized by vestibulocochlear dysfunction in addition to facial paralysis and auricular vesicles [22]. RHS is thought to be caused by reactivation of a latent varicella-zoster virus (VZV) [23]. Although Ramsay Hunt speculated that the infection of the eighth cranial nerve is spread from the geniculate ganglion via a vestibulofacial anastomosis or a vestibuloco- chlear anastomosis, there is the possibility that the VZV might arrive at the laby- rinth through the oval and/or round window from a dehiscent facial nerve canal [22–25]. In the latter case the lesion causing vestibular dysfunction could be in the labyrinth, whereas in the former case it could be in the vestibular nerve. Ozeki et al. applied combined methods of click and galvanic VEMPs to patients with RHS [22]. Their results suggested that some patients have nerve lesions and some have labyrinthine lesions (Fig. 7). In previous studies concerning auditory dysfunction in RHS, lesion sites were retrocochlear in some cases and cochlear in others [22, 26]. In other words, neurophysiological studies suggested that there might be two routes by which the infection spread from the facial nerve to the vestibulocochlear region. Idiopathic Bilateral Vestibulopathy Idiopathic bilateral vestibulopathy (IBV) is a clinical entity proposed by Baloh et al. [27]. IBV represents bilateral dysfunction of the peripheral vestibular system due to unknown causes. Patients with IBV complain of disequilibrium, vertigo, and sometimes oscillopsia (Fig. 8). The following comprise some of the diagnostic criteria for IBV. • Bilateral decreased caloric responses (maximum slow phase eye velocity: 10°/s or slower in the caloric test using ice water) • No associated hearing loss • Exclusion of bilateral vestibular dysfunction by known causes such as menin- gitis or aminoglycoside ototoxicity, among others • Exclusion of familial cases
click galvanic Neuritis type Labyrinthitis type Fig. 7. VEMPs in response to clicks and galvanic stimuli in patients with Ramsay Hunt syndrome. Some patients showed neuritis-type responses, whereas others showed labyrinthitis- type responses Caloric test (ice water) Max. slow phase eye velocity R: 1 deg/sec L: 0 deg/sec VEMP Stabilometry Pure-tone audiometry Fig. 8. Neurootological and audiological findings from a 75-year-old woman with idiopathic bilateral vestibulopathy (IBV), sequential type. Pure-tone audiometry showed sensorineural hearing loss due to aging. Stabilometry showed disequilibrium. Her VEMPs (95-dBnHL clicks) were normal on the right but absent on the left
68 Vestibular Evoked Myogenic Potentials Baloh et al. classified IBV into two types: progressive and sequential. The pro- gressive type is characterized by slowly progressive imbalance without episodic vertigo, and the sequential type manifests as recurrent episodes of vertigo accom- panied by persistent imbalance. We found a third type. Some patients diagnosed as having IBV had a single vertigo attack and progressive imbalance. We called this combination the one attack/progressive type. Among the 17 patients (10 men, 7 women; ages 33–75 years), 7 (41%) had the progressive type, 8 (47%) had the sequential type, and 2 (12%) had the one attack/progressive type (Fig. 9). The one attack/progressive type might be a transitional type from the progressive to the sequential type. In these 17 patients (34 ears), click VEMPs were bilaterally absent in 6 patients, unilaterally absent in 6 patients, unilaterally decreased in 2 patients, and bilaterally normal in 3 patients. In other words, 20 of the 34 sides (58%) showed abnormal VEMPs. It means that 14 of the 17 patients (82%) had abnormal VEMP results. These results suggested that the damaged area in patients with IBV could be limited to the superior vestibular nerve region, although some patients showed damage to both the superior and inferior vestibular nerve regions [28]. The study in a limited number of patients suggested that the lesions were mainly in the vestibular nerve [29]. Thus, IBV could be called vestibular neuropathy, which might be an auditory neuropathy (auditory nerve disease) [30–33]. Superficial Siderosis Superficial siderosis (SS) is a neurological disorder caused by the deposition of hemosiderin in the central nervous system [34]. SS has been clinically char- acterized as a combination of sensorineural hearing loss, cerebellar ataxia, and pyramidal signs. Although it is known that 95% of SS patients have progressive sensorineural hearing loss, there are few reports of the precise evaluation of vestibular function of SS [35]. Progressive 7 (41%) Sequential 8 (47%) One attack and progressive 2 (12%) Fig. 9. Classification of patients with IBV according to the clinical course (sequential or progressive)
Vestibular Neuritis (Neurolabyrinthitis) 69 Ushio et al. reported a 64-year-old man with SS who had left total hearing loss and right moderate sensorineural hearing loss. On T2-weighted magnetic resonance imaging (MRI) scans, he showed linear hypointensity and signal losses in the cer- ebellum, the medial surface of the temporal lobe, the midbrain, the pons, the spinal cord, and the eighth cranial nerve (Fig. 10). Auditory brainstem response (ABR) testing showed that he had no response on the left and only wave I on the right. Caloric tests (ice water) did not show responses in either ear. He did not have VEMP responses to either click (95 dBnHL) or galvanic (3 mA, 1 ms) stimulation (Fig. 11). These results suggested that his vestibular loss as well as hearing loss was caused by retrolabyrinthine lesions. VEMP testing is also applicable to rare clinical entities such as SS. Idiopathic Sudden Sensorineural Hearing Loss with Vertigo Approximately 50% of the patients with idiopathic sudden sensorineural hearing loss (ISSHL) could have vestibular symptoms [36], which may occur at the onset of hearing loss or be delayed for hours or days. The histopathological study by Schuknecht revealed atrophy of the saccular macula with hair cell loss, collapse of the saccular wall, and distortion of the otolithic membrane in some temporal bones but no abnormal findings in the utricular maculae and cristae [36]. Therefore, it is conceivable that patients with ISSHL who have vertigo could display abnormal VEMP responses. Iwasaki et al. neurootologically studied 22 patients with ISSHL and vertigo. Among them, 17 (77%) showed abnormal VEMP responses on the affected side, and 10 (45%) had decreased caloric responses [37] (Fig. 12). The study by (a) (b) Fig. 10. Magnetic resonance imaging (MRI) findings from a 64-year-old man with superficial siderosis. a T2-weighted, sagittal section. b T2-weighted, axial section. MRI scans showed linear hypointensity around the cerebellum and brainstem (arrows). (from Fig. 3 of ref. 34, Taylor & Francis, with permission)
70 Vestibular Evoked Myogenic Potentials Fig. 11. VEMPs to clicks (95 dBnHL) (a) and galvanic stimuli (3 mA, 1 ms) (b) in a 64-year-old man with superficial siderosis. He showed an absence of responses to both stimuli. (from Fig. 2 of ref. 34, Taylor & Francis, with permission) Fig. 12. VEMP responses in 12 patients with idiopathic sudden sensorineural hearing loss with vertigo Cochlea Cochlea + Saccule Cochlea + Canal Cochlea + Saccule + Canal 1/22 4/22 8/22 9/22 36% 18% 5% 41% 36%
Vestibular Neuritis (Neurolabyrinthitis) 71 Iwasaki et al. [37] suggested that patients with ISSHL have damage in the saccule more frequently than in the utricle or semicircular canals. Their findings are con- sistent with histopathological studies. In fact, vestibular symptoms in patients with ISSHL often manifest as unsteadiness. Vestibular symptoms in ISSHL patients could be due to otolithic disorders. Galvanic VEMP study has supported the idea that the lesion in ISSHL is in the labyrinth. References 1. Murofushi T, Halmagyi GM, Yavor RA, et al (1996) Absent vestibular evoked potentials in vestibular neurolabyrinthitis; an indicator of involvement of the inferior vestibular nerve? Arch Otolaryngol Head Neck Surg 122:845–848 2. Strupp M, Brandt T (1999) Vestibular neuritis. Adv Otorhinolaryngol 55:111–136 3. Ruttin B (1909) Zur Differentialdiagnose der Labyrinth- und Hornerverkrankungen. Z Ohrenheilkunde 57:327–333 4. Nylen CO (1924) Some cases of ocular nystagmus due to certain positions of the head. Acta Otolaryngol (Stockh) 6:106–137 5. Dix MR, Hallpike CS (1952) The pathology, symptomatology, and diagnosis of certain common disorders of the vestibular system. Ann Otol 61:987–991 6. Sekitani T, Imate Y, Noguchi T, et al (1993) Epidemiological survey by questionnaire in Japan. Acta Otolaryngol (Stockh) 503:S9–S12 7. Schuknecht HF, Kitamura K (1981) Vestibular neuritis. Ann Otol 90(suppl 78):1–19 8. Nadol JB Jr (1995) Vestibular neuritis. Otolaryngol Head Neck Surg 112:162–172 9. Lyndsay JR, Hemenway WG (1956) Postural vertigo due to unilateral sudden partial loss of vestibular function. Arch Otolaryngol 65:692–706 10. Halmagyi GM, Curthoys IS (1988) A clinical sign of canal paresis. Arch Neurol 45:737–739 11. Fetter M, Dichgans J (1996) Vestibular neuritis spares the inferior division of the vestibular nerve. Brain 119:755–763 12. Aw ST, Fetter M, Cremer PD, et al (2001) Individual semicircular canal function in superior and inferior vestibular neuritis. Neurology 57: 768–774 13. Halmagyi GM, Karlberg M, Curthoys IS, et al (2002) Inferior vestibular neuritis. Ann NY Acad Sci 956:306–313 14. Iwasaki S, Takai Y, Ito K, et al (2005) Abnormal vestibular evoked myogenic potentials in the presence of normal caloric responses. Otol Neurotol 26:1196–1199 15. Goebel JA, O’Mara W, Gianoli G (2001) Anatomic considerations in vestibular neuritis. Otol Neurotol 22:512–518 16. Baloh RW (2003) Vestibular neuritis. N Engl J Med 348:1027–1032 17. Okinaka Y, Sekitani T, Okazaki H, et al (1993) Progress of caloric response of vestibular neuritis. Acta Otolaryngol Suppl 503:18–22 18. Ochi K, Ohashi T, Watanabe S (2003) Vestibular-evoked myogenic potentials in patients with unilateral vestibular neuritis: abnormal VEMP and its recovery. J Laryngol Otol 117:104–108 19. Murofushi T, Iwasaki S, Ushio M (2006) Recovery of vestibular evoked myogenic potentials after a vertigo attack due to vestibular neuritis. Acta Otolaryngol 126:364–367 20. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 21. Murofushi T, Monobe H, Ozeki H, et al (2003) The site of lesions in “vestibular neuritis”: study by galvanic VEMP. Neurology 61:417–418
72 Vestibular Evoked Myogenic Potentials 22. Ozeki H, Iwasaki S, Ushio M, et al (2006) The lesion site of vestibular dysfunction in Ramsay Hunt syndrome. J Vestib Res 16:217–222 23. Ramsay Hunt J (1979) On herpetic inflammations of the geniculate ganglion, a new syndrome and its complication. J Nerv Ment Dis 34:73–96 24. Fujiwara Y, Yanagihara N, Kurata T (1990) Middle ear mucosa in Ramsay Hunt syndrome. Ann Otol Rhinol Laryngol 99:359–362 25. Murakami S, Nakashiro Y, Mizobuchi M, et al (1998) Varicella-zoster virus distribution in Ramsay Hunt syndrome revealed by polymerase chain reaction. Acta Otolaryngol (Stockh) 118:145–149 26. Abramovich S, Prashe DK (1986) Electrocochleography and brain-stem potentials in Ramsay Hunt syndrome. Arch Otolaryngol Head Neck Surg 112:925–928 27. Baloh RW, Jacobson K, Honrubia V (1989) Idiopathic bilateral vestibulopathy. Neurology 39:272–275 28. Matsuzaki M, Murofushi T (2001) Vestibular evoked myogenic potentials in patients with idiopathic bilateral vestibulopathy. ORL 63:349–352 29. Fujimoto C, Iwasaki S, Matsuzaki M, et al (2005) The site of lesion in idiopathic bilateral vestibulopathy: study by galvanic VEMP. Acta Otolaryngol 125:430–432 30. Kaga K, Nakamura M, Shinogami M, et al (1996) Auditory nerve disease of both ears revealed by auditory brainstem responses, electrocochleography and otoacoustic emissions. Scand Audiol 25:233–238 31. Starr A, Picton TW, Sininger Y, et al (1996) Auditory neuropathy. Brain 119:741–753 32. Sheykholeslami K, Kaga K, Murofushi T, et al (2000) Vestibular function in auditory neuropathy. Acta Otolaryngol 120:849–854 33. Fujikawa S, Starr A (2000) Vestibular neuropathy accompanying auditory and peripheral neuropathies. Arch Otolaryngol Head Neck Surg 126:1453–1456 34. Ushio M, Iwasaki S, Sugasawa K, et al (2006) Superficial siderosis causing retrolabyrinthine involvement in both cochlear and vestibular branches of the eighth cranial nerves. Acta Otolaryngol 126:997–1000 35. Parnes SM, Weaver SA (1992) Superficial siderosis of the central nervous system: a neglected cause of sensorineural hearing loss. Otolaryngol Head Neck Surg 107:69–77 36. Schuknecht HF (1993) Pathology of the ear. 2nd edn. Lea & Febiger, Philadelphia 37. Iwasaki S, Takai Y, Murofushi T (2005) Extent of lesions in idiopathic sudden hearing loss with vertigo: study using click and galvanic VEMP. Arch Otolaryngol Head Neck Surg 131:857–862
Superior Canal Dehiscence Syndrome and VEMPs: Detection of Hypersensitivity of the Vestibular System to Sound Introduction Hypersensitivity of the vestibular system to sound is known as the Tullio phenom- enon [1]. Clinically, the Tullio phenomenon has been reported in association with various diseases, including congenital syphilis, congenital deafness, Meniere’s disease, and perilymph fistula [2–5]. A fistula opening into the labyrinth (a third window) and pathological contiguity of the tympanoossicular chain and the membranous labyrinth have been assumed to be mechanisms of the Tullio phenom- enon [3, 6]. Sound can induce nystagmus or ocular tilt reaction (skew deviation, ocular torsion, head tilt) in patients with the Tullio phenomenon. Induced nystagmus can be horizontal, vertical, torsional, or mixed [7, 8]. The most effective sound frequen- cies to induce vestibular signs are between 500 and 1000 Hz [1, 7, 8]. According to Colebatch et al. [9], the mean threshold of vestibular evoked myo- genic potential (VEMP) responses to clicks in healthy subjects was 86 dBnHL, and the lowest was 70 dBnHL. The thresholds were lower in the ears of patients with the Tullio phenomenon (<70 dBnHL) than in those of healthy subjects. Another interesting point was a response on the contralateral sternocleidomastoid muscle (SCM). In healthy subjects, there was no response on the contralateral SCM to click stimulation [10], whereas patients with Tullio phenomenon showed negative– positive responses with short latencies on the contralateral SCM. These contralateral responses suggested that the utricule as well as the saccule could respond to clicks on the affected ear because electrical stimulation of utricular afferents had excitatory inputs to the contralateral SCM in addition to inhibitory inputs to the ipsilateral SCM [11]. Large-amplitude VEMPs in patients with Tullio phenomenon could be produced by the summation of responses derived from the saccule and utricule. Superior Canal Dehiscence Syndrome Superior canal dehiscence syndrome (SCDS) is a clinical entity introduced by Minor et al. [5, 12]. This clinical syndrome results from dehiscence of bone overly- ing the superior (anterior) semicircular canal and is characterized by vertigo or Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 73 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_8, © Springer 2009
74 Vestibular Evoked Myogenic Potentials oscillopsia induced by pressure and/or a loud sound. SCDS is a newly established entity that induces Tullio phenomenon and/or a positive fistula sign. Bone dehis- cence of the superior semicircular canal can be revealed by high-resolution com- puted tomography (CT) scans of the temporal bone (Fig. 1). Vertical-torsional nystagmus or ocular tilt reaction is induced by pressure and/or a loud sound [5, 13–15]. Compared with SCDS cases reported from the United States and European Union countries, reports of SCDS in Japan are rare [16]. The prominent features of VEMPs in patients with SCDS are low-threshold, high-amplitude responses to air-conducted sound [13, 15] (Fig. 2). These features are consistent with hypersensitivity of the vestibular end-organs to sound in patients with SCDS. Although this tendency was also observed with bone-conducted sound Fig. 1. Coronal sections of computed tomography scans in a patient with superior canal dehis- cence (SCD). This patient had bilateral dehiscence. R, right; L, left. (from Fig. 4 of ref. 16, Igakushoin, with permission) Fig. 2. Low thresholds of vestibular evoked myogenic potentials (VEMPs) in a patient with bilateral SCD. (from Fig. 3 of ref. 16, Igakushoin, with permission)
Superior Canal Dehiscence Syndrome 75 [17], galvanic VEMPs showed a normal threshold [18]. These findings suggested that the hypersensitivity can be found in vestibular end-organs. As eye movements induced by sound and/or pressure were considerably decreased after plugging the superior semicircular canal [5], dehiscence in the superior semicircular canal should cause deflection of the cupula in the crista ampullaris of the superior semicircular canal by sound and/or pressure, resulting in symptoms. Patients with SCDS could have low-tone hearing loss with air–bone gaps at low frequencies on pure-tone audiometry [19–21] (Fig. 3). Hence, it is important to dif- ferentiate SCDS from otosclerosis. VEMPs are useful for this differential diagnosis because patients with otosclerosis show clearly different responses. Patients with otosclerosis have a high threshold of VEMPs in response to air-conducted sound. The mechanism of air–bone gaps in SCDS has been thought to be the following: the third window in the vestibular end-organs (dehiscence on the superior semicir- cular canal) may shunt away acoustic energy from the cochlea to the vestibular portions, resulting in hearing loss of air-conducted sound. In contrast, the presence of the third window might result in more motion of fluid in the inner ear due to bone vibration than the normal condition, leading to better bone-conducted hearing [20, 22, 23]. In other words, air–bone gaps in patients with SCDS seem to be caused by conduction problems in the inner ear; therefore, it should be called “pseudo- conductive hearing loss.” A similar air–bone gap was also reported in patients with large vestibular aqueduct syndrome (LVAS) [24, 25]. The air–bone gap in LVAS might be analo- gous to that in SCDS [23], although speculation that the air–bone gap in LVAS is associated with restricted movement of the stapes was also proposed [25]. As LVAS patients with an air–bone gap showed somewhat lower VEMP thresholds [26], the Fig. 3. Air–bone gaps at low frequencies in SCD. O, hearing level to air-conducted sound; <, hearing level to bone-conducted sound. (from Fig. 1 of ref. 21, Cambridge University Press, with permission)
76 Vestibular Evoked Myogenic Potentials air–bone gap in LVAS might be caused by a mechanism similar to that responsible for SCDS. VEMP is useful for differentiating conductive hearing loss from pseudo- conductive hearing loss due to conduction problems in the inner ear. Thus, VEMP may contribute pathophysiological insight into hearing loss. References 1. Huizinga E (1935) On the sound reaction of Tullio. Acta Otolaryngol (Stockh) 22:359–369 2. Mayer O, Frase JS (1936) Pathological changes in the ear in late congenital syphilis. J Laryngol Otol 51:683–714 3. Kacker SK, Hinchcliffe R (1970) Unusual Tullio phenomenon. J Laryngol Otol 84: 155–166 4. Fox EJ, Balkany TJ, Arenberg IK (1988) The Tullio phenomenon and perilymph fistula. Otolaryngol Head Neck Surg 98:88–89 5. Minor LB, Solomon D, Zinreich JS, et al (1998) Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior semicircular canal. Ach Otolaryngol Head Neck Surg 124:249–258 6. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 7. Kwee HL (1976) The occurrence of the Tullio phenomenon in congenitally deaf children. J Laryngol Otol 90:501–507 8. Vogel P, Tackmann W, Schmidt FJ (1986) Observations on the Tullio phenomenon. J Neurol 233:136–139 9. Colebatch JG, Day BL, Brostein AM, et al (1998) Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon. J Neurol Neurosurg Psychiatry 65:670–678 10. Murofushi T, Ochiai A, Ozeki H, et al (2004) Laterality of vestibular evoked myogenic potentials. Int J Audiol 43:66–68 11. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 12. Minor LB (2000) Superior canal dehiscence syndrome. Am J Otol 21:9–19 13. Brantberg K, Bergenius J, Tribukait A (1999) Vestibular-evoked myogenic potentials in patients with dehiscence of the superior semicircular canal. Acta Otolaryngol (Stockh) 119:633–640 14. Halmagyi GM, Curthoys IS, Colebatch JG, et al (2005) Vestibular responses to sound. Ann NY Acad Sci 1039:54–67 15. Streubel SO, Cremer PD, Carely JP, et al (2001) Vestibular evoked myogenic potentials in the diagnosis of superior semicircular canal dehiscence. Acta Otolaryngol 545:S41–S49 16. Suzuki M, Kaga K, Nakamura M, et al (2003) Superior canal dehiscence syndrome (in Japanese). Jibiinkouka-Tokeibugeka 75:23–26 17. Brantberg K, Lofqvist L, Fransson PA (2004) Large vestibular evoked myogenic potentials in response to bone-conducted sounds in patients with superior canal dehiscence syndrome. Audiol Neurotol 9:173–182 18. Watson SRD, Halmagyi GM, Colebatch JG (2000) Vestibular hypersensitivity to sound (Tullio phenomenon): structural and functional assessment. Neurology 54:722–728 19. Minor LB, Carey JP, Cremer PD, et al (2003) Dehiscence of bone overlying the superior canal as a cause of apparent conductive hearing loss. Otol Neurotol 24:270–278 20. Mikulec AA, KcKenna MJ, Ramsey MJ, et al (2004) Superior semicircular canal dehiscence presenting as conductive hearing loss without vertigo. Otol Neurotol 25:121–129 21. Halmagyi GM, Aw ST, McGarvie LA, et al (2003) Superior semicircular canal dehiscence simulating otosclerosis. J Laryngol Otol 117:553–337
Superior Canal Dehiscence Syndrome 77 22. Rosowski JJ, Songer JE, Nakajima HH, et al (2004) Clinical, experimental, and theoretical investigations of the effect of superior semicircular canal dehiscence on hearing mechanism. Otol Neurotol 25:323–332 23. Songer JE, Rosowski JJ (2005) The effect of superior canal dehiscence on cochlear potential in response to air-conducted stimuli in chinchilla. Hear Res 210:53–62 24. Merchant SN, Nakajima H, Halpin C, et al (2007) Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome. Ann Otol Rhinol Laryngol 116: 532–541 25. Nakashima T, Ueda H, Furuhashi A, et al (2000) Air-bone gap and resonant frequency in large vestibular aqueduct syndrome. Am J Otol 21:671–674 26. Sheykholeslami K, Schmerber S, Kermany MH, et al (2004) Vestibular-evoked myogenic potentials in three patients with large vestibular aqueduct. Hear Res 190:161–168
Migraine-Associated Vertigo and VEMPs: Detection of Vestibular Signs in a Common but Unclear Entity Introduction It has been recognized that migraine may cause recurrent vertigo/dizziness [1], which is called migraine-associated vertigo (MAV) [2, 3]. The association between migraine and vertigo has been supported by several epidemiological studies [4, 5], and recently some diagnostic criteria for MAV have been proposed (Table 1) [1, 3, 4]. MAV can be observed in patients with migraine without an aura as well as migraine with an aura [6]. According to Iwasaki et al. [2], the average age of 33 patients diagnosed as having MAV—based on the criteria of Brantberg et al. [3]—was 40 years (range 18–62 years), with a female predominance (23 women, 10 men). The median age at onset of migraine was 27.5 years, and the median years predating the onset of vertigo was 7.5 years. Of the 33 patients, 18 (55%) had migraine without an aura and 15 (45%) had migraine with an aura. Rotational vertigo was noted in 24 of the 33 (73%) patients. Nonspecific dizziness and positional vertigo were also noted in five and four patients, respectively. The duration of the vertigo attack ranged from a few minutes to 3 days (Table 2). Most of the patients had vertigo attacks lasting 5 min to 24 h. Approximately 60% of the patients (20/33) had some cochlear symp- toms during the attacks, among which bilateral tinnitus and bilateral aural fullness were the most frequent (27% and 24%, respectively) (Table 3). VEMPs and Other Neurootological Test Results Canal paresis (CP) in caloric tests is observed in some patients with MAV. The incidence of CP in previous reports ranged from 10% to 20% [2, 7, 8]. Horizontal spontaneous nystagmus was also observed by electronystagmography in some patients. Abnormal findings in pursuit, saccade, and the optokinetic nystagmus test (which suggest central disorders) are rare in patients with MAV, whereas abnormal findings suggesting central disorders are frequently observed in patients with basilar-type migraine [9]. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 78 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_9, © Springer 2009
Migraine-Associated Vertigo 79 Table 1. Diagnostic criteria for migraine-associated vertigo (MAV) Definite migrainous vertigo Recurrent episodic vestibular symptoms of at least moderate severity Current or previous history of migraine according to IHS criteria One of the following migrainous symptoms during at least 2 vertiginous attacks Migrainous headache Photophobia Phonophobia Visual or other aura Other causes ruled out by appropriate investigations Probable migrainous vertigo Recurrent episodic vestibular symptoms of at least moderate severity One of the following Current or previous history of migraine according to IHS criteria Migrainous symptoms during at least two vertiginous attacks Migraine-precipitants before vertigo for more than 50% of attacks (food triggers, sleep irregularities, hormonal changes) Response to migraine medications for more than 50% of attacks Other causes ruled out by appropriate investigations From Neuhauser et al. [5], Wiley-Blackwell, with permission IHS, International Headache Society Table 2. Duration and frequency of MAV attacks. (from ref. 2, Taylor & Francis, with permission) Parameter No. Vertigo duration <5 min 11 (33%) 5–60 min 8 (24%) 1–24 h 13 (39%) >1 day 1 (3%) Vertigo frequency Times per day 6 (18%) Times per week 17 (51%) Times per month 5 (15%) Times per year 5 (15%) Table 3. Associated symptoms during vertigo attacks. (from ref. 2, Taylor & Francis, with permission) Associated symptoms No. Cochlear symptoms 20 (61%) Bilateral aural fullness 8 (24%) Unilateral aural fullness 2 (6%) Bilateral tinnitus 9 (27%) Unilateral tinnitus 3 (9%) Nausea 18 (54%) Headache 16 (48%) Vomiting 4 (12%) Photophobia 3 (9%) Phonophobia 2 (6%) Other symptoms 3 (9%)
80 Vestibular Evoked Myogenic Potentials Similar to caloric tests, abnormal vestibular evoked myogenic potentials (VEMPs) are seen in some patients. Iwasaki et al. [2] reported that 4 of the 33 patients (12%) showed absent VEMPs on either side. These four patients with absent VEMPs were different from the four patients with CP on the caloric test. These findings suggest that patients with MAV may have asymmetrical peripheral vestibular hypofunction. Liao and Young [10] studied 20 patients with basilar-type migraine (a special form of migraine) [6]. Among the 20 patients, 10 had bilaterally normal responses, 4 had a unilateral absence of response, and 3 had bilaterally absent responses. Furthermore, two patients showed bilaterally prolonged latencies, and one patient showed a unilateral absence of responses and unilaterally prolonged latencies. Patients with basilar-type migraine seem to have abnormal VEMPs more frequently than the general MAV population. Moreover, the lesion sites of basilar type of migraine may be in the central nervous system as well as the peripheral vestibular system. Migraine and Meniere’s Disease As shown in previous studies [1–3], patients with MAV have cochlear symptoms such as aural fullness and/or tinnitus and hypofunction in the peripheral vestibular system. It has been reported that the prevalence of migraine was almost twice as high in patients with Meniere’s disease (MD) as in the control group [11]. Ishiyama et al. [12] reported that patients with MAV have vestibular drop attacks (Tumarkin’s otolithic crisis), which has been considered a symptom of Meniere’s disease [13–15]. These findings suggest that MAV shares some pathophysiology with MD. Murofushi et al. compared frequency tuning in VEMPs of patients with MAV with that of patients with MD. As reported by Rauch et al. [16], patients with MD showed a tendency toward dominant VEMP responses to 1000-Hz tone bursts in comparison with 500 Hz, whereas healthy subjects showed a tendency of dominant responses to 500 Hz. A similar tendency was observed in patients with MAV [17]. This finding might support the existence of common pathophysiology between MAV and MD. Benign Recurrent (Paroxysmal) Vertigo of Childhood The term “benign paroxysmal vertigo of childhood” was coined by Basser in 1964 [18]. This entity is defined as recurrent (five or more) attacks of severe vertigo that resolve spontaneously after minutes to hours with normal neurological functions
Migraine-Associated Vertigo 81 and normal electroencephalography between attacks [6]. To represent this entity, I prefer the term benign recurrent vertigo (BRV) to benign paroxysmal vertigo because the latter can be confused with benign paroxysmal positional vertigo. BRV has been considered a migraine equivalent or migraine precursor. BRV is a major cause of vertigo in children [19, 20] (Fig. 1). Ozeki et al. did not find clear peripheral vestibular weakness in patients with BRV. Chang and Young found that 30% of the patients had abnormal caloric responses, and 50% had abnormal VEMP responses. Vestibular functions in BRV between and during attacks should be further studied [19, 21]. References 1. Neuhauser H, Lempert T (2004) Vertigo and dizziness related to migraine: a diagnostic challenge. Cephalalgia 24:83–91 2. Iwasaki S, Ushio M, Chihara Y, et al (2007) Migraine-associated vertigo: clinical character- istics of Japanese patients and effect of lomerizine, a calcium channel antagonist. Acta Otolaryngol 559:S45–S49 3. Brantberg K, Trees N, Baloh RW (2005) Migraine-associated vertigo. Acta Otolaryngol 125:276–279 4. Furman JM, Marcus DA, Balaban CD (2003) Migrainous vertigo: development of a patho- genic model and structured diagnostic interview. Curr Opin Neurol 16:5–13 5. Neuhauser H, Leopold M, von Brevern M, et al (2001) The interrelations of migraine, vertigo, and migrainous vertigo. Neurology 56:436–441 Fig. 1. Causes of vertigo/dizziness in 38 children. BRV, benign recurrent vertigo; BPPV, benign paroxysmal positional vertigo; VN, vestibular neuritis BRV 8 (25%) Psychogenic dizziness 2 (6%) MD 1 (3%) BPPV 3 (9%) VN 1 (3%) Miscellaneous 17 (53%) N=32
82 Vestibular Evoked Myogenic Potentials 6. Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders: 2nd Edition. Cephalalgia 24:S1–S160. 7. Dieterich M, Barndt T (1999) Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol 246:883–892 8. Cutrer FM, Baloh RW (1992) Migraine-associated dizziness. Headache 32:300–304 9. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 10. Liao LJ, Young YH (2004) Vestibular evoked myogenic potentials in basilar artery migraine. Laryngoscope 114:1305–1309 11. Radtke A, Lempert T, Gresty MA, et al (2002) Migraine and Meniere’s disease: is there a link? Neurology 59:1700–1704 12. Ishiyama G, Ishiyama A, Baloh RW (2003) Drop attacks and vertigo secondary to a non- Meniere otologic cause. Arch Neurol 60:71–75 13. Tumarkin A (1936) The otolithic catastrophe: a new syndrome. BMJ 1:175–177 14. Baloh RW, Jacobson K, Winder T (1990) Drop attacks with Meniere’s syndrome. Ann Neurol 28:384–387 15. Ozeki H, Iwasaki S, Murofushi T (2008) Vestibular drop attack secondary to Meniere’s disease results from unstable otolithic function. Acta Otolaryngol 128:887–891 16. Rauch SD, Zhou G, Kujawa SG, et al (2004) Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol 25:333–338 17. Murofushi T, Ozeki H, Sakata A, et al (2008) Meniere’s disease vs migraine associated vertigo: from a viewpoint of VEMP. In: 25th Barany meeting abstracts 18. Basser LS (1964) Benign paroxysmal vertigo of childhood (a variety of vestibular neuronitis). Brain 87:141–152 19. Ozeki H, Iwasaki S, Murofushi T (2008) Clinical features of vertigo and dizziness in childhood and adolescence with a special reference to benign recurrent vertigo. Equilibrium Res 67:13–17 20. Bower CM, Cotton RT (1995) The spectrum of vertigo in children. Arch Otolaryngol Head Neck Surg 121:911–915 21. Chang CH, Young YH (2007) Caloric and vestibular evoked myogenic potential tests in evaluating children with benign paroxysmal vertigo. Int J Pediatr Otorhinolaryngol 71:495–499
Acoustic Neuroma and Other Cerebellopontine Angle Tumors: Detecting a Neoplasm in the Cerebellopontine Angle Introduction Acoustic neuromas (ANs) are schwannomas that arise mainly from the vestibular divisionoftheeighthcranialnerve(vestibularnerve)[1].Theyconstitute6%ofintrac- ranial tumors. In recent years, the incidence of newly diagnosed ANs in Denmark was 13 per million population [2]. ANs are classified into two forms: sporadic and neurofibromatosis type 2 (NF2). Sporadic ANs are usually unilateral, whereas NF2 ANs, which are caused by a mutation of chromosome 22 [3], are usually bilateral. The most frequent symptoms of ANs are unilateral hearing loss and tinnitus [4] (Table 1). Hearing loss is usually slowly progressive, although it may be of sudden onset. The audiometric patterns are diverse (Fig. 1). Spinning vertigo is relatively rare because the growth of the tumor is slow. Diagnosis of Acoustic Neuroma There are no exact guidelines for diagnosing AN. When patients have persistent cochlear and/or vestibular symptoms not fully explained by another cause, AN should be considered. Neurootological and audiological tests and neuro-imaging studies are then required, including pure-tone audiometry, auditory brainstem response (ABR) testing, vestibular evoked myogenic potential (VEMP) testing, and the caloric test. Pure-tone audiometry is a screening test for hearing loss. ABRs, VEMPs, and caloric tests are representative physiological tests of the cochlear nerve, inferior vestibular nerve, and superior vestibular nerve, respectively. Mag- netic resonance imaging (MRI) without contrast medium is primarily recommended as a neuro-imaging study (Fig. 2). Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 83 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_10, © Springer 2009
84 Vestibular Evoked Myogenic Potentials Sensitivity of VEMPs in Acoustic Neuroma Abnormal findings of VEMPs in an AN patient are the absence of responses, decreased amplitudes, and prolonged peak latencies of p13 and/or n23 on the affected side. In our study, 39 of 62 AN patients showed an absence of responses to 95-dBnHL clicks on the affected side, 9 showed decreased amplitudes, and 14 showed normal amplitudes [5]. In other words, 48 of the 62 patients (77%) had abnormal findings concerning the amplitude. Among the 23 patients who exhibited responses on the affected side, 4 (17%) had significantly prolonged peak latencies. Table 1. Chief complaints of acoustic neuroma patients Chief complaint No. Slowly progressive hearing loss 63 (38%) Sudden hearing loss 31 (19%) Tinnitus 28 (17%) Vertigo 14 (8%) Dysequilibrium 9 (5%) Miscellaneous 22 (13%) Total 167 (100%) Fig. 1. Pure-tone audiogram patterns in 65 acoustic neuroma (AN) patients High tone loss 25 Cup-shaped loss 10 No hearing loss or symmetric 7 Flat loss 7 Profound loss 6 Low tone loss 5 Dip-shaped loss 5
Acoustic Neuroma and Other Cerebellopontine Angle Tumors 85 R Fig. 2. Magnetic resonance imaging (MRI) scan of a 48-year-old woman with a right AN (white arrow). Her pure-tone hearing was normal in both ears Fig. 3. Vestibular evoked myogenic potential (VEMP) responses in 62 AN patients. a Classifica- tion according to amplitudes. b Classification according to latencies Absent a b 39 (63%) Decreased 9 (14%) Normal 14 (23%) Prolonged 4 (17%) Normal 19 (82%) The overall sensitivity of VEMPs in these AN patients was 80% (50/62) (Fig. 3). In the literature, the sensitivity of VEMPs in AN patients has been reported to be 70%–80% [5–8]. Patko et al., who studied 170 patients with AN [7], reported that 130 of the 170 patients (78.8%) showed abnormal VEMPs to click stimulation and that the sensitivity was higher with click stimulation than with 500-Hz tone burst stimulation.
86 Vestibular Evoked Myogenic Potentials One must consider how to deal with subjects who showed bilateral absence of VEMP responses to clicks. Recently, Ushio et al. studied the sensitivity of VEMPs in AN patients with combined application of clicks and 500-Hz tone bursts [4]. They studied the sensitivity of VEMPs in 167 patients (79 men, 88 women) with unilateral AN. When patients did not display VEMP responses to clicks on either side, they were subjected to 500-Hz tone bursts. When the subjects exhibited bilateral normal responses to 500-Hz tone bursts despite no responses to clicks, they were regarded as being within the normal range. With this method, the sen- sitivity was 81.6% for VEMPs, 80.2% for caloric tests, and 92.7% for ABRs. The sensitivity of the ABR test results was significantly higher than that of the VEMP results (P < 0.01) or the caloric test results (P < 0.01); whereas the sensi- tivities of the VEMP studies and the caloric tests were not significantly different (P = 0.76). Concerning NF2 AN, Wang et al. [9] reported that only one of seven patients showed abnormal VEMPs and speculated that NF2 ANs originated most often from the superior vestibular nerve. However, as their study population was small, further studies concerning VEMP sensitivity for NF2 ANs are required. The sensitivity of VEMPs in AN patients was not as high as that of the ABRs. However, some patients showed abnormal VEMP responses despite normal ABRs [10] (Fig. 4). Furthermore, VEMP tests are applicable to patients with profound sensorineural hearing loss, in whom ABR testing is not applicable. Because of these merits, VEMPs should be included in the neurootological test battery of AN patients. Fig. 4. A 58-year-old woman with left AN who showed normal auditory brainstem responses (ABRs) but absent VEMPs. The white arrow in the MRI scan (right) indicates a small tumor in the internal auditory canal. (from Figs. 1 and 2 of ref. 10, Springer, with permission)
Acoustic Neuroma and Other Cerebellopontine Angle Tumors 87 Tumor Size and VEMPs According to Ushio et al., the tumors were significantly larger in patients with abnormal caloric responses and in patients with abnormal ABRs. However, they found no significant differences in tumor size between patients with normal and abnormal VEMPs [4]. Murofushi et al. reported that prolonged peak latencies were observed in patients with large tumors (>2 cm) (Fig. 5, Table 2) [5]. Lesion Site Detection Using VEMPs Although absent VEMP responses and decreased VEMP amplitudes are usually regarded as abnormal, these findings are not specific to ANs. In other words, these Fig. 5. MRI scan of a large AN in a 54-year-old man Table 2. Patients with acoustic neuroma and prolonged p13 and/or n23 No. Amplitude p13 (ms) n23 (ms) I–V (ABR) (ms) Tumor size (cm) 1 Normal 14.9 31.2 4.92 2 2 Decreased 14.6 21.2 Only wave I 3 3 Normal 14.4 27.4 5.20 2 4 Decreased 15.0 26.0 5.48 2 (from Table 1 of ref. 5, with permission. Copyright (2001) American Medical Association. All rights reserved) Upper limit of the normal range: p13, 13.5; n23, 25.2; I–V (ABR), interpeak intervals between waves I and V of ABR: 4.4 Boldface values indicate prolonged latencies
88 Vestibular Evoked Myogenic Potentials abnormal findings could be produced wherever a lesion is in the vestibulocollic pathway. The prolonged latency of p13 and/or n23 can be relatively specific in comparison with amplitudes because prolonged latencies indicate a retrolabyrinthine lesion [5]. However, the incidence of prolonged latencies was not high (17%), and these laten- cies were observed in patients with large tumors. It is one of the reasons that the normal range of the peak latencies of VEMP is too wide to detect a small latency prolongation. Combined use of short-duration galvanic stimulation has been proposed as another method to determine the lesion site [11]. Whereas relatively intense sounds stimulate the vestibular end-organ, especially the saccular macula, galvanic stimuli directly stimulate the vestibular nerve [12]. In fact, patients with Meniere’s disease have normal VEMP responses to galvanic stimulation even though they show an absence of VEMP responses to clicks. In contrast, most patients with ANs have an abnormal galvanic VEMP response and an absence of VEMP responses to clicks [11]. To apply this combined method to patients who have VEMP responses on the affected side, Murofushi et al. introduced a ratio: corrected amplitude to acoustic stimuli/corrected amplitude to galvanic stimuli [13]. They called it the TG ratio (tone burst/galvanic ratio). As described in the chapter “Meniere’s Disease and Related Disorders,” the TG ratio is significantly lower in patients with Meniere’s disease than in healthy controls. In contrast, the TG ratio of patients with AN is within the normal range or higher (Fig. 6). The combined use of acoustic and galvanic VEMPs seems to be useful for determining a lesion site even in subjects who display VEMP responses. Fig. 6. Tone burst/galvanic (TG) ratio of patients with AN compared with those of healthy subjects (Control) and patients with endolymphatic hydrops (Hydrops)
Acoustic Neuroma and Other Cerebellopontine Angle Tumors 89 Tumor Origin and VEMPs It is well known that ANs arise mainly from the vestibular nerve, which has two divisions: superior and inferior. Some investigators reported almost equal origins in the superior and inferior divisions, whereas others have reported a predominance in the inferior branch [14, 15]. The caloric test mainly reflects the function of the lateral semicircular canal and its afferents, and VEMP mainly reflects the function of the saccule and its afferents. Therefore, one may expect that results of these two tests can indicate the origin of tumors. However, so far we have not obtained posi- tive results in regard to the correlation of test results and the origin of the tumor. This may be because dysfunction can first emerge in a branch other than the branch that is the origin of the tumor. This issue requires more careful study. Other Cerebellopontine Angle Tumors and Lesions The second most common tumor in the cerebellopontine angle (CPA) is meningi- oma (Fig. 7) [16]. The rate of abnormal VEMPs in patients with a meningioma is approximately 80%. Other masses in the CPA have also been reported, including epidermoids, jugular foramen neurinomas, trigeminal neurinomas, arachnoid cysts, chordomas, and metastatic tumors [17]. Occasionally, large aneurysms behave like CPA masses (Fig. 8) [18, 19]. These masses can cause abnormal VEMPs when the inferior vestibular nerve is involved. However, it is difficult to differentiate ANs from other CPA masses using VEMP testing. Fig. 7. MRI scan of a left-side cerebellopontine angle meningioma, coronal section
90 Vestibular Evoked Myogenic Potentials References 1. Jackler RK, Pfister MHF (2005) Acoustic neuroma (vestibular schwannoma). In: Jackler RK, Brackmann DE (eds) Neurotology second edition. Mosby, St. Louis, pp 727–782 2. Tos M, Stangerup SE, Caye-Thomasen P, et al (2004) What is the real incidence of vestibular schwannoma? Arch Otolaryngol Head Neck Surg 130:216–220 3. Rouleau GA, Wertelecki W, Haines JL, et al (1987) Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 329:246–248 4. Ushio M, Murofushi T, Iwasaki S, et al (2008) Diagnostic value of vestibular evoked myo- genic potentials (VEMPs) in patients with acoustic neuroma. In: 25th Barany meeting abstracts 5. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127: 1069–1072 6. Takeichi N, Sakamoto T, Fukuda S, et al (2001) Vestibular evoked myogenic potential (VEMP) in patients with acoustic neuromas. Auris Nasus Larynx 28:s39–s41 7. Patko T, Vidal PP, Vibert N, et al (2003) Vestibular evoked myogenic potentials in patients suffering from an unilateral acoustic neuroma: a study of 170 patients. Clin Neurophysiol 114:1344–1350 8. Murofushi T, Matsuzaki M, Mizuno M (1998) Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509–512 9. Wang CP, Hsu WC, Young YH (2005) Vestibular evoked myogenic potentials in neurofibro- matosis 2. Ann Otol Rhinol Laryngol 114:69–73 Fig. 8. Computed tomography scan (left) and angiographic findings (right) of a posterior inferior cerebellar artery (PICA) aneurysm. (from Figs. 3 and 4 of ref. 19, Igakushoin, with permission)
Acoustic Neuroma and Other Cerebellopontine Angle Tumors 91 10. Matsuzaki M, Murofushi T, Mizuno M (1999) Vestibular evoked myogenic potentials in acoustic tumor patients with normal ABR. Eur Arch Otorhinolaryngol 256:1–4 11. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 12. Watson SRD, Colebatch JG (1998) Vestibulocollic reflexes evoked by short-duration galvanic stimulation in man. J Physiol 513:587–597 13. Murofushi T, Iwasaki S, Ozeki H, et al (2007) Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a new parameter of VEMP? Clin Neurophysiol 118: 1685–1690 14. Slattery WHT, Brackmann DE, Hitselberger W (1997) Middle fossa approach for hearing preservation with acoustic neuromas. Am J Otol 18:596–601 15. Komatsuzaki A, Tsunoda A (2001) Nerve origin of the acoustic neuroma. J Laryngol Otol 115:376–379 16. Kendall B, Symon L (1977) Investigation of patients presenting with cerebellopontine angle syndromes. Neuroradiology 13:65–84 17. Iwasaki S, Ito K, Takai Y, et al (2004) Chondroid chordoma at the jugular foramen causing retro-labyrinthine lesion in both the cochlear and vestibular branches of the eighth cranial nerve. Ann Otol Rhinol Laryngol 13:82–86 18. Chihara Y, Iwasaki S, Ushio M, et al (2008) Fusiform aneurysm of the basilar artery present- ing as a cerebellopontine angle mass. Eur Arch Otorhinolaryngol (published online March 5, 2008) 19. Murofushi T, Mizuno M (1990) Cerebellopontine angle syndrome due to an anerysm of posterior cerebellar artery: report of a case. (in Japanese) Jibiinkoka-Tokeibugeka 62:1089–1093
Disorders of the Central Nervous System and VEMPs: Detecting Lesions in the Vestibulospinal Pathway Introduction As vestibular evoked myogenic potential (VEMP) testing has been regarded as a clinical test of the saccule and its afferents, it has been mainly applied to diseases of the peripheral vestibular system. However, because the neural pathway of VEMPs includes the vestibulospinal tract in the brainstem, it could also detect disorders in the vestibulospinal tract, especially the medial vestibulospinal tract. The application of VEMP testing to diseases that mainly affect the central nervous system (CNS) are discussed in this chapter. Multiple Sclerosis Multiple sclerosis (MS) is the most common disease caused by an inflammatory demyelinating process in the CNS. MS is characterized pathologically by multifo- cal areas of demyelination with relative preservation of axons, resulting in much reduced conduction velocity [1]. It is clinically characterized by dissemination of signs and symptoms over space and time. McDonald et al. have proposed new diagnostic criteria for MS [2]. Evoked potentials such as auditory brainstem responses (ABRs), somatosensory evoked potentials (SEPs), and motor evoked potentials by transcranial magnetic stimulation, among others, have been utilized in the clinical setting [3, 4]. As it has been reported that vertigo is a symptom in 30%–50% of MS patients, it is expected that VEMP testing in MS patients may reveal abnormal findings. Shimizu et al. [5] first reported VEMP results in three patients with definite MS. All three patients had high-intensity areas on T2-weighted magnetic resonance imaging (MRI) in the areas involving the vestibulospinal tract and prolonged peak latencies of VEMPs (Fig. 1). Later, Murofushi et al. reported that all of their six patients with MS had abnormal VEMPs (prolonged latencies or absent responses) [6]. These patients had disequilibrium and/or vertigo as symptoms. Therefore, the Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 92 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_11, © Springer 2009
Detecting Lesions in the Vestibulospinal Pathway 93 sensitivity of VEMP testing in overall patients with MS remains to be clarified. According to Versino et al. [7], abnormal VEMP responses were seen in 31% of MS patients; and Bandini et al. [8] reported prolonged p13 latencies in 42% of MS patients. This rate was much higher in patients with a history or signs/symptoms of brainstem dysfunction. With all the studies of VEMPs in MS, the main abnormal finding was prolonga- tion of the peak latencies. This point distinguishes MS from other diseases with peripheral disorder. VEMP testing is a valuable tool for detecting demyelination in the vestibulospinal tract of MS patients. Recently, in addition to VEMPs in cervical muscle (cVEMP), VEMPs around the eye (oVEMP) have been recorded. cVEMPs reflect the function of the vestibu- locollic reflex, and oVEMPs seem to reflect that of the vestibuloocular reflex. The combined use of cVEMPs and oVEMPs might be useful for determining the site of the lesion in the brainstem [9]. Spinocerebellar Degeneration Spinocerebellar degeneration, one of the clinical entities causing disorders of the central vestibular system, is characterized by cerebellar and/or spinal ataxia. It Fig. 1. Magnetic resonance imaging (MRI) (left) and vestibular evoked myogenic potential (VEMP) (right) findings from a 30-year-old woman diagnosed with multiple sclerosis. (from Figure of ref. 5, BMJ Publishing Group, with permission)
94 Vestibular Evoked Myogenic Potentials consists of a sporadic type and a hereditary type. The hereditary type contains autosomal recessive ataxias such as Friedreich’s ataxia and autosomal dominant ataxias such as spinocerebellar ataxia-1 (SCA1) [10]. There are only a few reported studies concerning VEMPs in spinocerebellar degeneration. Takegoshi and Murofushi studied VEMPs (click stimulation) in patients with spinocerebellar degeneration [11]. Patients with olivopontocerebellar atrophy and cerebellar cortex atrophy had normal VEMP responses on both sides. In contrast, patients with Machado-Joseph disease (MJD, SCA3) showed an absence of responses and prolonged latencies. Among the five patients with MJD in whom we recorded VEMPs (including the three patients reported by Takegoshi and Murofushi), one patient showed normal responses on both sides, whereas the other four patients showed an absence of responses or prolonged latencies at the first recording (Fig. 2). A 63-year-old man with MJD had prolongation of latencies on both sides at the first recording, and 1 year later these responses were abolished (Fig. 3). The progression of the disease is reflected in the VEMP responses. The site of the lesion causing abnormal VEMPs in MJD remains unclear. It is known that patients with MJD show an absence of caloric responses at the early stage of the disease [12, 13] and that peripheral sensory nerves can be involved in MJD [14]. Therefore, it is most likely that abnormal VEMPs in MJD may be attributed to lesions in the vestibular nerve. However, lesions in the vestibulospinal tract and in the labyrinth might have some effect. More studies are required concerning VEMPs in patients with spinocerebellar degeneration, including MJD. Normal 3 Prolonged 4 Absent 3 Fig. 2. VEMP responses of patients with Machado-Joseph disease (n = 10 sides of five patients)
Detecting Lesions in the Vestibulospinal Pathway 95 Brainstem Infarction A vascular accident in the brain can cause damage to vestibular nerve fibers, ves- tibular nuclei, and the vestibulospinal tract. These substrates are involved in the neural pathway of VEMPs, and patients with a brainstem infarction may show abnormal VEMPs. So far, reports of VEMPs in patients with brainstem/cerebellar infarction are scarce [15–17]. Itoh et al. reported that patients with upper brainstem infarction had normal VEMPs and abnormal ABRs, and patients with infarction in the middle brainstem or the lower brainstem have abnormal VEMPs. Patients with middle brainstem infarction have abnormal ABRs, whereas those with lower brain- stem infarction have normal ABRs [15]. Wallenberg syndrome (WS), or lateral medullary infarction, is a clinical entity that involves the vestibular nuclei (Fig. 4). WS is caused by occlusion of the ver- tebral artery or arteries arising from the vertebral artery [18]. Dieterich and Brandt reported ocular motor abnormalities in 36 patients with WS [19]. Almost all of the patients exhibited gaze-evoked nystagmus and lateropulsion of the closed eyes, and 16 of the 36 patients had skew deviation (hypotropia) of the ipsilateral eye. In the report by Itoh et al. [15], VEMPs were normal in some patients. This result is not surprising because WS does not always involve the entire area of the vestibular Fig. 3. VEMPs (95-dBnHL clicks) from a man with Machado-Joseph disease. At the first record- ing, he showed bilateral prolonged latencies on both sides. One year later, he showed no response. L, left side; R, right side. MRI showed atrophy of the pons and cerebellum
96 Vestibular Evoked Myogenic Potentials nuclei. When the lateral and descending vestibular nuclei were spared, VEMPs were intact. Correlation of the area of infarction and VEMP responses should be studied in the future. References 1. Olek MJ, Dawson DM (2004) Multiple sclerosis and other inflammatory demyelinating dis- eases of the central nervous system. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds) Neurology in clinical practice. 4th edn. Butterworth Heinemann, Philadelphia, pp 1631–1664 2. McDonald WI, Compston A, Edan G, et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 50:121–127 3. Chiappa KH (1988) Use of evoked potentials for diagnosis of multiple sclerosis. Neurol Clin 6:1–88 4. Kalkers NS, Strijers RLM, Jasperse MMS, et al (2007) Motor evoked potential: a reliable and objective measure to document the functional consequences of multiple sclerosis? Relation to disability and MRI. Clin Neurophysiol 138:1332–1340 5. Shimizu K, Murofushi T, Sakurai M, et al (2000) Vestibular evoked myogenic potentials in multiple sclerosis. J Neurol Neurosurg Psychiatry 69:276–277 6. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127: 1069–1072 Fig. 4. Diffusion-weighted MRI of a 40-year-old man with Wallenberg syndrome. He showed high intensity signal in the right lateral medulla (white arrow)
Detecting Lesions in the Vestibulospinal Pathway 97 7. Versino M, Colnaghi S, Callieco R, et al (2002) Vestibular evoked myogenic potentials in multiple sclerosis patients. Clin Neurophysiol 13:1464–1469 8. Bandini F, Beronio A, Ghiglione E, et al (2004) The diagnostic value of vestibular evoked myogenic potentials in multiple sclerosis. J Neurol 251:617–621 9 Rosengren SM, Nogajski JH, Cremer PD, et al (2007) Delayed vestibular evoked responses to the eyes and neck in a patient with an isolated brainstem lesion. Clin Neurophysiol 118:2112–2116 10. Subramony SH (2004) Disorders of the cerebellum, including the degenerative ataxias. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds) Neurology in clinical practice. 4th edn. Butterworth Heinemann, Philadelphia, pp 2167–2187 11. Takegoshi H, Murofushi T (2000) Vestibular evoked myogenic potentials in patients with spinocerebellar degeneration. Acta Otolaryngol 120:821–824 12. Murofushi T, Mizuno M, Hayashida T, et al (1995) Neuro-otological and neuropathological findings in two cases of Machado-Joseph disease. Acta Otolaryngol (Stockh) 520: S136–S139 13. Gordon CR, Joffe V, Vainstein G, et al (2003) Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease). J Neurol Neurosurg Psychiatry 74:1403–1406 14. Kinoshita A, Hayashi M, Oda M, et al (1995) Clinicopathological study of the peripheral nervous system in Machado-Joseph disease. J Neurol Sci 130:48–58 15. Itoh A, Kim YS, Yoshida K, et al (2001) Clinical study of vestibular evoked myogenic potentials and auditory brainstem responses in patients with brainstem lesions. Acta Otolar- yngol 545:S116–S119 16. Chen CH, Young YH (2003) Vestibular evoked myogenic potentials in brainstem stroke. Laryngoscope 113:990–993 17. Pollak L, Kushnir M, Stryjer R (2006) Diagnostic value of vestibular evoked myogenic potentials in cerebellar and lower-brainstem strokes. Neurophysiol Clin 36:227–233 18. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 19. Dieterich M, Brandt T (1992) Wallenberg’s syndrome: lateropulsion, cyclorotation and subjective visual vertical in 36 patients. Ann Neurol 31:399–408
Part IV Pediatric Applications
Neurootological Application of VEMP Recording During Infancy and Childhood Introduction Vestibular evoked myogenic potential (VEMP) recording is a new tool for explor- ing the pathways of the sacculus, inferior vestibular nerve, vestibular nucleus, and sternocleidomastoid muscles (SCMs) in pediatric otology and neurotology. Child Development and VEMPs There have been few studies of the feasibility of recording VEMPs in infants and small children, much less the characteristics of this response in neonates. Although the muscle tone of neonates and young infants is poor compared with that of grown children and adults, it is possible to record VEMPs from the SCM during infancy and early childhood. Sheykholeslami et al. [1] reported that reproducible biphasic VEMPs are recorded from the SCM of all the infants they examined (12 healthy infants and children, ages 1–12 months) using loud and short-tone burst sounds. Typical developmental changes in VEMPs in infants and children are shown in Fig. 1 [2]. In these normal infants and children, air-conducted sound evoked a biphasic response (p13 and n23 peaks) of VEMPs that were of larger amplitude and shorter latency than those in adults. The difference in VEMPs on the side of the stimulated ear is due to developmental changes in the distance of the pathway between the sacculus and the SCM and changes in the strength of muscles. However, neonatal VEMPs varied in amplitude, with consistent timing for peak p13 but shorter peak n23 latencies than those in adult VEMPs. The difficulties we encountered during VEMP recording in this study were as follows: 1) We had difficulty maintaining the desired electromyographic (EMG) activity of the SCM during the period of data acquisition, which required several interruptions of the recording session and restarting data collection after achieving the same level of muscle contraction. 2) The recording sessions were much longer for infants partly because of the difficulty mentioned above and partly because of the time necessary to educate parents and have their help during the test. 3) Finally, it was necessary to have a technician in the room to position patients and control the muscle contraction level [1]. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 101 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_12, © Springer 2009
102 Vestibular Evoked Myogenic Potentials Incidence of Normal VEMPs in Infants with Congenital Profound Hearing Loss Can air-conducted sound-induced VEMPs be recorded even in infants with con- genital profound hearing loss? This is an important question. It has been demon- strated that loud clicks generate short-latency VEMPs [3] in normal adults. Pathological human models have also been used to provide further evidence of the vestibular (saccular) origin of the potentials. Colebatch et al. [3] showed that VEMPs were evident at a high incidence in patients with profound sensorineural hearing loss, but that they were abolished in all of their patients who underwent unilateral vestibular neurectomy. These authors also reported that VEMPs were abolished in some but not all patients with unilateral loss of a caloric response after vestibular neuritis. They hypothesized that VEMPs are of vestibular origin and that the saccule is probably an acoustically sensitive organ. In our study, 67% of the 54 ears of 33 children with congenital profound hearing loss showed normal VEMPs (Fig. 2), but 5% of ears of the children showed abnor- mal VEMPs with low amplitude. This is a surprising finding because although they cannot hear air-conducted loud click stimuli at all they have VEMPs, suggesting that VEMP testing may be a new tool to illuminate vestibular activity in deaf infants and children. Fig. 1. Typical developmental changes in vestibular evoked myogenic potentials (VEMPs) in normal infants and children
Pediatric Neurootological Application of VEMPs 103 Sheykholeslami et al. [4, 5] confirmed the saccular origin of this short-latency acoustic response and that a saccular acoustic response persists in the human ear and has a well-defined frequency tuning curve. Currently, recorded VEMPs are induced using various stimuli including clicks [3], tone bursts [4], electrical stimuli [6], bone-conducted sounds [7], and head taps [8]. VEMPs are gaining more atten- tion as a diagnostic and prognostic test for otological and neurotological disorders in infants and children as well as adults. VEMPs and Inner Ear Anomalies Evaluation of residual auditory and vestibular function in patients with inner ear anomalies is a challenging issue in otology and neurotology because of the lack of appropriate tests. Computed tomography (CT) and MRI studies of the temporal bone cannot confirm the types of inner ear anomaly; they can only identify the affected sensory organ and primary afferent nerve in the presence of an inner ear anomaly. Therefore, the promontory test for electroneural hearing, the caloric test, and the rotation chair test for semicircular canal function are performed. VEMP testing is thus a new promising tool for examining sacculovestibular nerve function. Sheykholeslami and Kaga studied VEMPs in seven children with inner ear anomalies, including two with cystic cochleas, three with shortened cochleas, and two with completely absent cochleas [4]. The horizontal semicircular canals were cystic in two patients and absent in five. Posterior semicircular canals were normal Fig. 2. Click-evoked normal VEMPs (right) and audiogram (left) of a child with congenital profound hearing loss
104 Vestibular Evoked Myogenic Potentials in two patients, cystic in two, and absent in three. Superior semicircular canals were cystic in three patients, normal in two, and absent in two. The vestibules were normal in six patients and cystic in one. These authors found that all of these patients had short-latency VEMPs in response to 95-dBnHL air-conducted clicks and short-tone bursts; the VEMPs were biphasic and consisted of p13 and n23 peaks (Fig. 3). This study provides additional evidence that the human inner ear Fig. 3. Click-evoked VEMPs (bottom) from a child with an inner ear anomaly (common cavity). Top left Computed tomography (CT) scans of the common cavity. Top right Audiogram
Pediatric Neurootological Application of VEMPs 105 Fig. 4. Bottom Click-evoked VEMPs (right) and audiogram (left) of a child with a large vestibu- lar aqueduct. Top High-resolution computed tomography and magnetic resonance image of the large vestibular aqueduct of the temporal bone vestibules and inferior vestibular nerves are preserved in patients with these inner ear anomalies. This study supports previous findings that VEMPs in humans have their origin in the inner ear vestibules. VEMPs and a Large Vestibular Aqueduct Vestibular aqueduct (VA) enlargement is a distinct clinical syndrome in the spec- trum of congenital inner ear anomalies. The bony anomaly of the enlarged VA renders the membranous labyrinth vulnerable to sudden fluctuation in pressure, which leads to progression of sensory neural hearing loss after head trauma. Sheykholeslami et al. reported that VEMPs in three patients with a large ves- tibular aqueduct (LVA) had greater amplitude and lower threshold and that the vestibular organ was more responsive to sound and inner ear pressure changes [9]. Figure 4 shows a high-resolution CT image of LVA of the temporal bone and
106 Vestibular Evoked Myogenic Potentials VEMPs in a child with profound deafness. These authors speculated that abnormal transmission of inner ear volume and pressure to the cerebrospinal fluid space via the widely patent VA and a large deflection of vestibular sensors in the mem- branous labyrinth in response to stapes movements are possible contributors to the generation of high-amplitude, low-threshold VEMPs in patients with LVA. LVA is considered to be the third window, following the oval and round windows, in the labyrinth. VEMPs in Children with Cochlear Implants The cochlear function of both ears is markedly impaired in infants and children who are candidates for cochlear implantation. However, vestibular function is also impaired in 10%–20% of such infants. After cochlear implantation, patients can hear speech sounds, which are converted to electrical signals in a speech pro- cessor; these signals are transmitted to the internal receiver under the scalp and conducted to the electrodes in the cochlea. Thus, cochlear nerves that are stimulated electrically convey information to the central auditory brainstem pathway and auditory cortex. There are two problems for vestibular end-organs after cochlear implantation. One is traumatic damage of vestibular end-organs incurred following insertion of the electrodes of the cochlear implant into the scala tympani. Tien and Linthicum histopathologically analyzed the vestibular apparatus from human temporal bones after cochlear implantation was carried out [10]. They observed significant damage to the vestibular end-organ in approximately half of the temporal bones. Fibrosis of the vestibular apparatus, and osteogenesis neurons were observed in all their patients [10]. The other problem is that electrical stimulation may affect not only the cochlear nerve but also the facial nerve or the vestibular nerve in patients with a multichannel cochlear implant because of current spread. Based on these findings VEMPs are considered useful for evaluating electrical current spread to the inferior vestibular nerve. Jin et al. compared VEMPs before and after surgery [11]. Before surgery, 6 of the 12 children showed normal VEMPs, 1 showed a decrease in the amplitude of VEMPs, and 5 showed no VEMPs.After surgery, with the cochlear implant switched off, 11 showed no VEMPs and one showed decreased VEMPs. These results reveal that even normal VEMPs disappear owing to trauma following electrode insertion. With the cochlear implant switched on, four children showed normal VEMPs, but eight did not (Fig. 5). This can be explained by the fact that these four children’s inferior vestibular nerves were stimulated by the spread of electrical current from the cochlear implant. We questioned why one-third of these children with cochlear implants showed VEMPs but others did not. Later, Jin et al. demonstrated that VEMPs evoked by cochlear implants may be related to an electrical current inten- sity at a comfortable level (C level), particularly in channels that are closer to the apical turn of the cochlea [12].
Pediatric Neurootological Application of VEMPs 107 Fig. 5. Changes in VEMPs before and after cochlear implantation. a Before surgery. b Switched- off cochlear implant (CI) after surgery and switched-on CI after surgery The patients who showed no VEMPs with the cochlear implant switched on may require higher current intensities to elicit clear VEMPs (if they need to be recorded). However, it is difficult to increase current intensity in such children because they feel pain or facial nerve stimulation when the current intensity is higher than the C level. VEMPs of Pediatric Patients with Neurological Diseases VEMPs depend on the higher tonus of the SCM. During VEMP recording, the children were instructed to lift their heads or to turn their heads to the contralateral side to induce hypertonicity in the SCM. In patients who showed hyper- or hypo- tonicity of cervical muscles (e.g., those with cerebral palsy or other forms of severe brain damage characterized by paralysis of extremities), it was not possible to record VEMPs owing to the lack of muscle contraction even when the sacculoin- ferior vestibular nerve was normal. In Fig. 6, VEMPs of a 3-year-old boy who has cerebral palsy due to Pelizaeus-Merzbacher disease are absent, but the auditory brainstem responses show waves I and II only [13]. VEMPs may thus be used as an objective indicator of hyper- or hypotonicity of muscles in these neurological diseases.
108 Vestibular Evoked Myogenic Potentials Acknowledgments I thank Dr. K. Sheykholeslami, Dr. Y. Jin, Dr. Y. Shinjo, Dr. H. Takegoshi, and Ms. M. Nakamura for cooperation in this VEMP study. References 1. Sheykholeslami K, Kaga K, Megerin CA, et al (2005) Vestibular-evoked myogenic potentials in infancy and early childhood. Laryngoscope 115:1440–1444 2. Kaga K (2005) Development of balance and motor function achieved by central vestibular compensation. Adv Neurol Sci 49:216–228 3. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click- evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 4. Sheykholeslami K, Kaga K (2002) The otolithic organ as a receptor of vestibular hearing revealed by vestibular-evoked myogenic potentials in patients with inner ear anomalies. Hear Res 165:62–67 5. Sheykholeslami K, Habiby Kermany M, Kaga K (2001) Frequency sensitivity range of the saccule to bone-conducted stimuli measured by vestibular evoked myogenic potentials. Hear Res 160:58–62 6. Watson SRD, Colebatch JG (1998) Vestibulocollic reflexes evoked by short-duration galvanic stimulation in man. J Physiol 513:587–597 7. Sheykholeslami K, Habiby Kermany M, Kaga K (2001) Bone-conducted vestibular evoked myogenic potentials in patients with congenital atresia of the external auditory canal. Int J Pediatr Otorhinolaryngol 57:25–29 Fig. 6. Auditory brainstem responses (ABRs) and VEMPs of a 3-year-old boy with Pelizaeus- Merzbacher disease. ABRs show waves I and II only. VEMPs were not elicited because of cerebral palsy
Pediatric Neurootological Application of VEMPs 109 8. Shinjo Y, Jin Y, Kaga K (2007) Assessment of vestibular function of infants and children with congenital and acquired deafness using the ice-water caloric test, rotational chair test and vestibular-evoked myogenic potential recording. Acta Otolaryngol (Stockh) 127:736–747 9. Sheykholeslami K, Schmerber S, Habiby Kermany M, et al (2004) Vestibular-evoked myo- genic potentials in three patients with large vestibular aqueduct. Hear Res 190:161–168 10. Tien HC, Linthicum FH Jr (2002) Histopathologic changes in the vestibular after cochlear implantation. Otolaryngol Head Neck Surg 127:260–264 11. Jin Y, Nakamura M, Shinjo Y, et al (2006) Vestibular-evoked myogenic potentials in cochlear implant children. Acta Otolaryngol (Stockh) 126:164–169 12. Jin Y, Shinjo Y, Akamatsu Y, et al (2008) Vestibular evoked myogenic potentials evoked by multichannel cochlear implant-influence of C levels. Acta Otolaryngol (Stockh) 128: 284–290 13. Kaga K, Tamai F, Kodama M, et al (2005) Three young adult patients with Pelizaeus- Merzbacher disease who showed only waves I and II in auditory brainstem responses but had good auditory perception. Acta Otolaryngol (Stockh) 125:1018–1023
Subject Index a ABR 83 acoustic/galvanic ratio 32 acoustic neuroma 83 auditory neuropathy 68 b background muscle activity 26 basilar-type migraine 78 benign paroxysmal positional vertigo 64 benign paroxysmal vertigo of childhood 80 benign recurrent vertigo 81 best frequency 50 bone-conducted sound 21 bouton type ending 12 brainstem infarction 95 c calyx type ending 12 central nervous system 92 cerebellopontine angle tumor 89 click 25 cochlear implantation 106 comfortable level 106 current spread 106 cystic cochlea 103 d delayed endolymphatic hydrops 55 drop attack 53 e electrocochleography 52 electrode 25 endolymphatic hydrops 52 f facial nerve stimulation 107 frequency tuning characteristics 32 furosemide test 52 g galvanic stimulation 38, 88 galvanic VEMP 56, 88 glycerol test 52 glycerol VEMP testing 55 h horizontal semicircular canal 103 i idiopathic bilateral vestibulopathy 66 inferior vestibular nerve 13, 20, 61 inferior vestibular neuritis 62 inner ear anomaly 103, 105 l labyrinth 9 large vestibular aqueduct 105 lateral vestibulospinal tract 15 laterality of VEMP 28 low VEMP threshold 31 m Machado-Joseph disease 94 macula 9 medial vestibulospinal tract 15, 23 Meniere’s disease 49, 80 migraine 78 . 111
112 Subject Index migraine-associated vertigo 78 multiple sclerosis 92 n N3 42 n34–p44 28 neonate 101 neurogenic potential 42 NF2 86 o otolith-ocular reflex 40 otolith organ 9 oVEMP 40 p p13–n23 28 peak latency 30 percent VEMP asymmetry 30 posterior semicircular canal 103 profound hearing loss 102 prolonged latencies 31 prolonged peak latency 84, 92 r Ramsay Hunt syndrome 66 reticulospinal tract 15 s saccule 9 scala tympani 106 Scarpa’s ganglion 13 semicircular canal 9 shortened cochlea 103 spinocerebellar degeneration 93 sternocleidomastoid muscle 17 striola 13 sudden sensorineural hearing loss 69 superficial siderosis 68 superior semicircular canal 104 superior vestibular nerve 13, 22, 61 t tapping 35 third window 106 threshold 31 tone burst 25 Tullio phenomenon 20 Tumarkin’s otolithic crisis 53 u utricle 9 v vertigo in children 81 vestibular neurectomy 102 vestibular neuritis 60 vestibular neurolabyrinthitis 60 vestibular neuropathy 68 vestibular nucleus 14 vestibulocollic reflex 15 vestibuloocular reflex 17, 40 vestibulospinal reflex 15 vestibulospinal tract 92 w Wallenberg syndrome 95 y young infant 101

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VEMP-KAGA.pdf

  • 2.
    Toshihisa Murofushi ⋅Kimitaka Kaga Vestibular Evoked Myogenic Potential Its Basics and Clinical Applications
  • 3.
    Toshihisa Murofushi ⋅Kimitaka Kaga Vestibular Evoked Myogenic Potential Its Basics and Clinical Applications
  • 4.
    Library of CongressControl Number: 2008938811 ISBN 978-4-431-85907-9 Springer Tokyo Berlin Heidelberg New York e-ISBN 978-4-431-85908-6 This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in other ways, and storage in data banks. The use of registered names, trademarks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publisher can give no guarantee for information about drug dosage and application thereof contained in this book. In every individual case the respective user must check its accuracy by consulting other pharmaceutical literature. Springer is a part of Springer Science+Business Media springer.com © Springer 2009, Tokyo Printed in Japan Typesetting: SNP Best-set Typesetter Ltd., Hong Kong Printing and binding: Nikkei Printing Inc., Japan Printed on acid-free paper Toshihisa Murofushi, M.D., Ph.D. Professor Department of Otolaryngology Teikyo University School of Medicine University Hospital, Mizonokuchi 3-8-3 Mizonokuchi, Takatsu-ku, Kawasaki 213-8507, Japan Kimitaka Kaga, M.D., Ph.D. Director National Institute of Sensory Organs National Tokyo Medical Center 2-5-1 Higashigaoka, Meguro-ku, Tokyo 152-8902, Japan
  • 5.
    V Preface The vestibular labyrinthconsists of five compartments: the lateral, anterior, and posterior semicircular canals, the utricule, and the saccule. At the beginning of the twentieth century, Robert Bárány proposed the caloric test as a clinical test of the lateral semicircular canal. This test enabled clinicians to assess the individual lateral semicircular canal function easily by using the simple method of irrigating the external ear canal with cold or warm water and observing the induced nystag- mus. We believe that the caloric test was a breakthrough in the field of vestibular research. However, as far as the other compartments were concerned, there was no simple clinical test equal to the caloric test for the lateral semicircular canal function. At the end of the twentieth century, the vestibular evoked myogenic potential (VEMP) test was proposed as a new method for assessing the individual saccule function. This test has some unique attributes. First, it uses sound stimulation, even though it is a test of the vestibular system. This appears to be a contradiction neu- rophysiologically. As a result, in its early stages there were controversies concern- ing the origin of the responses. However, such controversies have been overcome by basic neurophysiological studies and clinical studies. Above all, sound sensitiv- ity of the saccular afferents shown in cats and guinea pigs with single-unit recording methods became the main supporting evidence. Nowadays, VEMP is one of the routine clinical tests for balance disorder. Second, the sternocleidomastoid muscle (SCM), the conventional recording site of VEMP, is itself special. While saccular afferents project onto the ipsi- lateral motoneurons of the SCM, they do not project onto the contralateral motoneurons of the SCM. This fact enables us to assess the individual saccule function easily. Third, the VEMP test provides totally different information than the caloric test does. Whereas the VEMP test is a test of the otolith organs, the caloric test is a test of the semicircular canals; and whereas the VEMP test is a test of the inferior vestibular nerve, the caloric test is a test of the superior vestibular nerve. Evidently, these two, the caloric test and the VEMP test, can coexist.
  • 6.
    This book isa review of VEMP studies. Readers will obtain full knowledge of the principles of the elicited response, methods of recording, and clinical applications. We hope to generate more interest among clinicians and scientists in VEMP and to provide greater knowledge of vestibular disorders through this publication. 19 October 2008 Toshihisa Murofushi, Kimitaka Kaga VI Preface
  • 7.
    Contents Preface . .. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . V Part I. Introduction Toshihisa Murofushi . . . . . . . . . . . . . . . . . . . . . . . . 1 Part II. Basics Toshihisa Murofushi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Overview of the Vestibular System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Sound Sensitivity of the Vestibular End-Organs and Sound-Evoked Vestibulocollic Reflexes in Mammals . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20 Recording and Assessing VEMPs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25 VEMP Variants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34 Part III. Clinical Applications Toshihisa Murofushi . . . . . . . . . . . . . . 47 Meniere’s Disease and Related Disorders: Detection of Saccular Endolymphatic Hydrops . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 49 Vestibular Neuritis (Neurolabyrinthitis) and Other Peripheral Vestibulopathies: Detection of Inferior Vestibular Nerve Damage . . . . . 60 Superior Canal Dehiscence Syndrome and VEMPs: Detection of Hypersensitivity of the Vestibular System to Sound . . . . . . 73 Migraine-Associated Vertigo and VEMPs: Detection of Vestibular Signs in a Common but Unclear Entity . . . . . . . . . . . . . . . . . . . . . . . . . . 78 Acoustic Neuroma and Other Cerebellopontine Angle Tumors: Detecting a Neoplasm in the Cerebellopontine Angle . . . . . . . . . . . . . . . 83 Disorders of the Central Nervous System and VEMPs: Detecting Lesions in the Vestibulospinal Pathway . . . . . . . . . . . . . . . . . . 92 Part IV. Pediatric Applications Kimitaka Kaga . . . . . . . . . . . . . . . . . . 99 Neurootological Application of VEMP Recording During Infancy and Childhood . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 VII
  • 8.
  • 9.
    Introduction Vestibular evoked myogenicpotentials (VEMP) are responses in the muscles, especially cervical muscles such as the sternocleidomastoid muscle (SCM), to sound, vibration, or electrical stimulation (Fig. 1). Because it seemed that VEMP could be used for clinical tests of the vestibular end-organs, especially the saccule, it attracted the interest of clinicians and scientists. There had been no other clinical test of the saccule that was applicable at common clinics. Now much has been published about VEMP, and many clinicians use this test. VEMP is one of the most important advances in clinical neurophysiology of the vestibular system. Prior to the availability of VEMP in its present form [1], other tests had been proposed, such as using inion responses [2, 3] (Fig. 2), which tried to measure potentials evoked by sound as a test of the vestibular system. However, tests relying on these responses were not widely used at clinics. VEMP in its present form, utilizing biphasic myogenic potentials on the SCM, were first reported in 1992 by Colebatch and Halmagyi, who reported that VEMP responses on the affected side disappeared after unilateral vestibular nerve section despite preservation of hearing [1, 4] (Fig. 3). Colebatch et al. reported in 1994 that VEMP could be recorded in a patient with bilateral near-total hearing loss [4]. Since that report, clinical and basic studies concerning VEMP have been further developed. These later studies clarified that the major vestibular end-organ which responds to sound is the saccule, and that signals are conveyed via the inferior vestibular nerve [5–11]. Details are given in the chapters that follow. Here, we want to emphasize that the progress achieved in this field was brought about by the collaboration of scientists and clinicians. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 3 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_1, © Springer 2009
  • 10.
    4 Vestibular EvokedMyogenic Potentials Fig. 2. A typical waveform of inion responses. An active electrode was placed on the nasion and a reference electrode was on the mastoid. 70dBnHL clicks were presented binaurally; 150 responses were averaged. (From [3], with permission) 10 msec 100 mV p13 n23 n34 p44 䉱 click Fig. 1. A typical waveform of vestibular evoked myogenic potentials (VEMP) in a healthy subject
  • 11.
    Introduction 5 Fig. 3.Abolishment of VEMP responses (to 100-dB clicks) following selective vestibular nerve section on the left. VEMP responses on the left sternocleidomastoid muscle (SCM) to left ear stimulation were absent after unilateral vestibular nerve section, although hearing on the left was preserved. Upper left, recording on the right SCM to left ear stimulation; upper right, recording on the right SCM to right ear stimulation (presence of responses); asterisk, p13; lower left, record- ing on the left SCM to left ear stimulation (absence of responses); lower right, recording on the left SCM to right ear stimulation. (From [4], with permission) References 1. Colebatch JG, Halmagyi GM (1992) Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 42:1635–1636 2. Bickford RG, Jacobson JL, Cody DT (1964) Nature of average evoked potentials to sound and other stimuli in man. Ann NY Acad Sci 112:204–223 3. Cody DT, Jacobson JL, Walker JC, et al (1964) Averaged evoked myogenic and cortical potentials to sound in man. Ann Otol Rhinol Laryngol 73:763–777 4. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 5. McCue MP, Guinan JJ Jr (1995) Spontaneous activity and frequency selectivity of acoustically responsive vestibular afferents in the cat. J Neurophysiol 74:1563–1572 6. McCue MP, Guinan JJ Jr (1997) Sound-evoked activity in primary afferent neurons of a mammalian vestibular system. Am J Otol 18:355–360 7. Murofushi T, Curthoys IS, Topple AN, et al (1995) Responses of guinea pig primary vestibu- lar neurons to clicks. Exp Brain Res 103:174–178 8. Murofushi T, Curthoys IS, Gilchrist DP (1996) Response of guinea pig vestibular nucleus neurons to clicks. Exp Brain Res 111:149–152 9. Murofushi T, Curthoys IS (1997) Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol (Stockh) 117:66–72 10. Murofushi T, Halmagyi GM, Yavor RA, et al (1996) Absent vestibular evoked potentials in vestibular neurolabyrinthitis: an indicator of involvement of the inferior vestibular nerve? Arch Otolaryngol Head Neck Surg 122:845–848 11. Murofushi T, Matsuzaki M, Mizuno M (1998) Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509–512
  • 12.
  • 13.
    Overview of theVestibular System Introduction In this chapter, we review only the fundamental structures associated with the vestibular system that may be concerned with vestibular evoked myogenic potentials (VEMPs). Although the cerebellum and cerebrum are also important for the vestibular system, we do not address them here, as their effects on VEMPs seem minimal. Vestibular End-Organs The human labyrinth consists of the cochlea, otolith organs, and semicircular canals. The otolith organs and the semicircular canals are vestibular end-organs. The functions of the vestibular end-organs are basically to monitor the rotational and linear movement of the head and the orientation of the head to gravity. In humans, there are two otolith organs (saccule and utricle) and three semicircular canals (lateral semicircular canal, anterior semicircular canal, and posterior semi- circular canal) (Figs. 1, 2). The otolith organs, the saccule and the utricle, sense linear acceleration. The sensory area of the otolith organ is called the macula. The saccular macula lies on the medial wall of the vestibule in a spherical recess inferior to the utricular macula. The saccular macula is hook-shaped and lies predominantly in a vertical position, whereas the utricular macula is oval and lies predominantly in a horizontal position (Fig. 3) [1] The plane of the saccular macula is almost orthogonal to that of the utricular macula (Fig. 4). The surfaces of the maculae are covered by the otolithic membrane, which contains a superficial calcareous deposit, the otoconia (Fig. 5) [1–3]. The cilia of the hair cells in the macula protrude into the otolithic membrane. The otoconia consist of small calcium carbonate crystals [4]. Linear acceleration including gravity causes deflection of the cilia of the hair cells. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 9 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_2, © Springer 2009
  • 14.
    10 Vestibular EvokedMyogenic Potentials The semicircular canals—lateral, anterior, posterior—sense angular accelera- tion. They are aligned to form a coordinate system [5]. The lateral semicircular canal makes a 30° angle with the horizontal plane. The other two canals are in vertical positions almost orthogonal to each other. The sensory area is called the crista. Hair cells are in the surface of the crista, with their cilia protruding into the cupula, a gelatinous mass (Fig. 6). Angular acceleration causes deflection of the cupula, resulting in deflection of the cilia of the hair cells. Utricle Saccule Anterior semicircular canal Posterior semicircular canal Lateral semicircular canal Cochlea Cochlear nerve Superior vestibular nerve Inferior vestibular nerve (a) (b) (c) Fig. 1. Inner ear and afferent nerves Fig. 2. Vestibular end-organs in human temporal bone sections. a Utricular macula. b Saccular macula. c Crista of the lateral semicircular canal
  • 15.
    Overview of theVestibular System 11 ant. post. striola med. ant. post. dorsal lat. Fig. 3. Utricular macula (left) and saccular macula (right). Arrows indicate the direction of hair cell polarization. ant., anterior; lat., lateral; med., medial; post., posterior Utricular macula Saccular macula Fig. 4. Position of the utricular macula and the saccular macula Fig. 5. Photomicroscopic findings of the guinea pig macula. Toluidine blue cillia hair cell otoconia otolithic membrabe
  • 16.
    12 Vestibular EvokedMyogenic Potentials The macula and crista contain two types of hair cells: type I and type II hair cells [6] (Fig. 7). The hair cells have stereocilia and a kinocilium on the top. Deflec- tion of the stereocilia toward the kinocilium causes excitation, whereas deflection toward the other side causes inhibition. Type I hair cells are shaped like flasks, with each cell being surrounded by a calyx ending. The type II hair cells, which are like cylinders, have bouton nerve endings (Figs. 7, 8) [1, 2]. The striola is a distinctive cupula hair cell Fig. 6. Photomicroscopic findings of the guinea pig crista. H&E kinocilium stereocilia excitation inhibition calyx type ending bouton type ending Type I Type II Fig. 7. Two types of hair cell
  • 17.
    Overview of theVestibular System 13 zone running through the center of each macula. The hair cells on each side of the striola have opposite polarities because their kinocilia point in opposite directions (Fig. 3). In contrast to the macula, the direction of the polarity of hair cells in one crista is uniform. Calyx units are seen in central (striolar) zones. The axon is usually unbranched, giving rise to a single calyx ending. Bouton units are seen in peripheral (extrastrio- lar) zones. The axon provides bouton endings to several type II hair cells. Dimor- phic units innervate all parts of the neuroepithelium. The axon has collateral branches terminating as calyx endings and bouton endings [6]. Vestibular Nerve The vestibular nerve contains afferents from the vestibular end-organs and effer- ents. The cells of afferents are bipolar neurons with their cell bodies in Scarpa’s ganglion. The vestibular nerve is subdivided into two parts: the superior vestibular nerve and the inferior vestibular nerve [7] (Fig. 1). The superior vestibular nerve innervates the cristae of the anterior semicircular canal, the lateral semicircular canal, the utricular macula, and the anterosuperior part of the saccular macula. The inferior vestibular nerve innervates the crista of the posterior semicircular canal and the main part of the saccular macula. Otolith ganglion cells are located ven- trally in the central portion of the ganglion, whereas canal ganglion cells are located at the rostral and caudal ends [8, 9]. The vestibular afferent fibers innervating the macula are activated by changes in the position of the head in space or by linear acceleration, whereas the fibers innervating the crista are activated by angular acceleration [10–12]. Vestibular afferents fire spontaneously (65 spikes/s in otolith afferents and 90 spikes/s in canal afferents) [13, 14]. The baseline firing rates increase in response to excitatory stimuli and decrease in response to inhibitory stimuli. Based on the regularity of firing, vestibular afferents are classified into two groups—regularly firing fibers and irregularly firing fibers [6]—each of which has different features. Irregularly Bouton type ending Calyx type ending Fig. 8. Types of guinea pig primary afferent nerve endings labeled by biocytin. (In collaboration with Prof. I.S. Curthoys)
  • 18.
    14 Vestibular EvokedMyogenic Potentials firing fibers have thick, medium-sized axons ending as a calyx and dimorphic units. They have phasic–tonic response dynamics and high sensitivity to head rotation or linear forces. In contrast, regularly firing fibers have medium-sized, thin axons, ending as dimorphic and bouton units. They have tonic response dynamics and low sensitivity to head rotation or linear forces. These differences must be borne in mind when we consider the sound sensitivity of vestibular afferents. Vestibular Nucleus The vestibular nuclei consist of a group of neurons located on the floor of the fourth ventricle. The main vestibular nuclei are the superior nucleus, lateral (Deiters’) nucleus, medial nucleus, and inferior (descending or spinal) nucleus (2). Additionally, there are several small groups of cells. Although primary vestibular neurons provide multiple branches, which usually innervate secondary vestibular neurons in all of the four main vestibular nuclei, there are preferences in each nucleus (8). The superior vestibular nucleus contains medium-sized neurons with some mul- tipolar cells. The superior vestibular nucleus receives strong projections from semicircular canals. The medial vestibular nucleus consists of cells of many sizes and shapes that are close together. The upper part of the medial vestibular nucleus receives fibers from the semicircular canals and the fastigial nucleus and flocculus of the cerebellum. Saccular and utricular afferents project to the middle part of the nucleus. The caudal part of the nucleus receives fibers from the cerebellum. The lateral vestibular nucleus contains giant cells. The dorsocaudal portion receives afferents from the cerebellum, whereas the rostrovertebral portion receives primary vestibular afferents. The inferior vestibular nucleus consists of small and medium-sized cells with occasional giant cells. The rostral part of the inferior vestibular nucleus receives strong projections from the otolith organs and the semicircular canals. Summarized from the standpoint of primary otolith afferents, saccular afferents terminate mainly in the rostral part of the inferior vestibular nucleus and the ros- troventral portion of the lateral nucleus; and utricular afferents terminate mainly in the rostral portion of the inferior vestibular nucleus, and the medial vestibular nucleus [8, 9, 15]. On the basis of neurophysiological studies, two types of secondary vestibular neuron were identified [16]. Ipsilateral rotation of the head causes type I neurons to be excited and type II neurons to be inhibited. Type I neurons are monosy- naptically activated by ipsilateral primary afferents, whereas type II neurons receive inputs via commissural connections either from neurons in the reticular substance or directly from contralateral type I neurons [2]. Contralateral labyrinth stimulation excites type II neurons, resulting in inhibition of type I neurons (Fig. 9).
  • 19.
    Overview of theVestibular System 15 Vestibulospinal Reflex The vestibulospinal reflex (VSR) serves to stabilize the head and controls erect stance relative to gravity under both static and dynamic conditions [17]. Stimula- tion of the vestibular end-organs leads to various patterns of activation of neck and body muscles. Activation of the neck muscles is described later as the vestibu- locollic reflex. The VSR prevents falling and maintains the body’s position. There are three major pathways: the lateral vestibulospinal tract (LVST); the medial vestibulospinal tract (MVST); and the reticulospinal tract (RST) [18] (Fig. 10). The LVST origi- nates in the lateral nucleus and descends in the ipsilateral ventral funiculus of the spinal cord. The MVST originates in the medial, inferior, and lateral nuclei and descends in the medial longitudinal fasciculus bilaterally as far as the mid-thoracic level [17, 19]. Linear and angular head acceleration causes increased muscle tones in the ipsilateral extensor muscles and decreased muscle tones in the ipsilateral flexor muscles via the LVST [17, 20]. Vestibulocollic Reflex The vestibulocollic reflex (VCR) operates to stabilize the head in space by neck movements. The MVST and LVST provide direct connections to neck motoneurons as well as indirect connections. Connections between vestibular end-organs and Fig. 9. Interrelation of types I and II secondary vestibular neurons. Light neurons are excitatory; dark neurons are inhibitory Type I Type II Type II Type I Lateral semiciicular canal Vestibular nerve Vestibular nucleus midline
  • 20.
    16 Vestibular EvokedMyogenic Potentials Fig. 10. Pathways of the vestibulospinal reflex. MVST, medial vestibulospinal tract; RST, reticulospinal tract; LVST, lateral vestibulospinal tract Table 1. Connection pattern to motoneurons of cervical muscles from afferents of the otolith organs Ipsilateral Contralateral SAC UT SAC UT Extensor 2EP 2EP 2/3EP 3IP L ? M ? Flexor 2/3IP 2EP 3IP 3IP M L M L Rotator 2IP 2IP NO 2EP M M M (from ref. 21, Kanehara, with permission) SAC, saccular nerve; 2EP, disynaptic excitatory postsynaptic potential; 2IP, disynaptic inhibitory postsynaptic potential; NO, no response; M, medial vestibulospinal tract; L, lateral vestibulospinal tract; UT, utricular nerve; ?, unknown
  • 21.
    Overview of theVestibular System 17 neck motoneurons are summarized in Table 1 [21]. Neck muscles are classified into three types: extensors, flexors, rotators. The sternocleidomastoid muscle (SCM) is classified as a rotator type. Concerning VEMPs, it should be noted that moto- neurons of the SCM have disynaptic inhibitory inputs from the ipsilateral saccule with no projections from the contralateral saccule [22] (Table 1, Fig. 11). Vestibuloocular Reflex The vestibuloocular reflex (VOR) maintains gaze during head and body movements [23]. This gaze stability is achieved by activation of vestibular end-organs, includ- ing activation of semicircular canals to angular acceleration and of otolith organs to linear translation and gravity. In other words, the VOR produces extraocular muscle contraction to compensate for a specific head movement, thereby maintain- ing gaze stability. The connections of the semicircular canals with extraocular muscles are summarized in Table 2. The eye movements induced by the stimulation of the otolith organs and the pathways from the otolith organs to extraocular muscles are less clearly defined than those from the semicircular canals and are somewhat controversial. According to Suzuki et al. [24], electrical stimulation of the utricular nerve in spinalized, alert cats mainly produced contraversive torsional eye movement with simultaneous upward shift in ipsilateral eyes, downward shift in contralateral eyes, and slight Fig. 11. Sacculosternocleidomastoid (SCM) and utriculosternocleidomastoid pathways Filled circles, inhibitory neurons; open circles, excitatory neurons. (from Fig. 4 of ref. 22, Springer, with permission)
  • 22.
    18 Vestibular EvokedMyogenic Potentials contralateral horizontal shift of both eyes. Curthoys reported that electrical stimula- tion of the utricular macula in guinea pigs produced upward or upward-torsional eye movements [25]. Fluur and Mellstrom reported that electrical stimulation of the utricular macula in alert cats produced eye movements whose direction depended on the location of the stimulating electrode [26]. Concerning horizontal eye movement, Goto et al. [27] confirmed that utricular nerve stimulation in cats evoked horizontal eye movements to the stimulated side, supporting prior findings of projection of the utricular nerve to the ipsilateral abducens nucleus [28, 29]. Eye movement due to saccular stimulation is more obscure than that due to utricular stimulation. The saccule contributes more weakly to eye movements than the semicircular canals or the utricule [30]. Previous studies suggested that the main eye movement induced by saccular stimulation could be vertical [25, 31, 32]. References 1. Schuknecht HF (1993) Pathology of the ear. 2nd edn. Lea & Febiger, Philadelphia 2. Baloh RW, Honrubia V (1990) Clinical neurophysiology of the vestibular system. 2nd edn. Davis, Philadelphia 3. Lim DJ (1973) Ultrastructure of the otolithic membrane and the cupula. Adv Otorhinolaryn- gol 19:35–49 4. De Vries H (1951) The mechanics of the labyrinth otoliths. Acta Otolaryngol 38:262–273 5. Blanks RHJ, Curthoys IS, Markham CH (1975) Planar relationships of the semicircular canals in man. Acta Otolaryngol 80:185–196 6. Goldberg JF, Lysakowski A, Fernandez C (1992) Structure and function of vestibular nerve fibers in the chinchilla and squirrel monkey. Ann NY Acad Sci 656:92–107 7. Lorente De No R (1933) Anatomy of the eighth nerve: the central projection of the nerve endings of the internal ear. Laryngoscope 43:1–38 8. Gacek RR (1969) The course and central termination of first order neurons supplying vestibular end organs in the cat. Acta Otolaryngol 254:1–66 9. Gacek RR (2008) A place principle for vertigo. Auris Nasus Larynx 35:1–10 10. Fernandez C, Goldberg JM (1971) Physiology of peripheral neurons innervating semicircular canals of the squirrel monkey. II. Response to sinusoidal stimulation and dynamics of periph- eral vestibular system. J Neurophysiol 34:61–675 Table 2. Connection pattern to motoneurons of extra-ocular muscles from afferents of the semicircular canals Semicircular canal Excitation Inhibition Anterior I-SR I-IR C-IO C-SO Posterior I-SO I-IO C-IR C-SR Lateral I-MR C-MR C-LR I-LR (from ref. 21) I, ipsilateral; C, contralateral; MR, mdial rectus; LR, lateral rectus; SO, superior oblique; IR, inferior rectus; IO, inferior oblique; SR, superior rectus
  • 23.
    Overview of theVestibular System 19 11. Fernandez C, Goldberg JM, Abend WK (1972) Response to static tilts of peripheral neurons innervating otolith organs of the squirrel monkey. J Neurophysiol 35:978–987 12. Fernandez C, Goldberg JM (1976) Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. II. Directional selectivity and force-response relations. J Neurophysiol 39:385–395 13. Fernandez C, Goldberg JM (1976) Physiology of peripheral neurons innervating otolith organs of the squirrel monkey. I. Response to static tilt and to long-duration centrifuge force. J Neurophysiol 39:970–984 14. Goldberg JM, Highstein SM, Moschovakis A, et al (1987) Inputs from regularly and irregu- larly discharging vestibular-nerve afferents to secondary neurons in the vestibular nuclei of the squirrel monkey. I. An electrophysiological analysis. J Neurophysiol 58:700–718 15. Carleton SC, Carpenter MB (1983) Afferent and efferent connections of the medial, inferior and lateral vestibular nuclei in the cat and monkey. Brain Res 278:29–51 16. Shimazu H, Precht W (1965) Tonic and kinetic responses of cat’s vestibular neurons to horizontal angular acceleration. J Neurophysiol 28:991–1013 17. Fetter M, Dichagns J (1996) How do the vestibulo-spinal reflexes work? In: Baloh RW, Halmagyi GM (eds) Disorders of the vestibular system. Oxford University Press, New York, pp 105–112 18. Wilson VJ, Melvil Jones G (1979) Mammalian vestibular physiology. Plenum, New York 19. Wilson VJ, Boyle R, Fukushima K, et al (1995) The vestibulocollic reflex. J Vestib Res 5:147–170 20. Wilson VJ, Peterson BW (1978) Peripheral and central substrates of vestibulo-spinal reflexes. Physiol Rev 58:80–105 21. Uchino Y (2002) Memai to heikouchousetsu (in Japanese). Kanehara, Tokyo 22. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 23. Raphan T, Cohen B (1996) How does the vestibulo-ocular reflex work? In: Baloh RW, Halmagyi GM (eds) Disorders of the vestibular system. Oxford University Press, New York, pp 20–47 24. Suzuki JI, Tokumasu K, Goto K (1969) Eye movements from single utricular nerve stimula- tion in the cat. Acta Otolaryngol 68:250–262 25. Curthoys IS (1987) Eye movements produced by utricular and saccular stimulation. Aviat Space Environ Med 58:A192–A197 26. Fluur E, Mellstrom A (1970) Utricular stimulation and oculomotor reactions Laryngoscope 80:1701–1712 27. Goto F, Meng H, Bai R, et al (2003) Eye movements evoked by the selective stimulation of the utricular nerve in cats. Auris Nasus Larynx 30:341–348 28. Imagawa M, Isu N, Sasaki M, et al (1995) Axonal projections of utricular afferents to the vestibular nuclei and the abducens nucleus in cats. Neurosci Lett 186:87–90 29. Uchino Y, Ikegami H, Sasaki M, et al (1994) Monosynaptic and dyssynaptic connections in the utriculoocular reflex arc of the cat. J Neurophysiol 71:950–958 30. Isu N, Graf W, Sato H, et al (2000) Sacculo-ocular reflex connectivity in cats. Exp Brain Res 131:262–268 31. Fluur E, Mellstrom A (1970) Saccular stimulation and oculomotor reactions. Laryngoscope 80:1713–1721 32. Goto F, Meng H, Bai R, et al (2004) Eye movements evoked by selective saccular nerve stimulation in cats. Auris Nasus Larynx 31:220–225
  • 24.
    Sound Sensitivity ofthe Vestibular End-Organs and Sound-Evoked Vestibulocollic Reflexes in Mammals Sound Sensitivity of the Vestibular System Tullio first reported that surgical fenestration of the bony labyrinth in avians and mammals made the labyrinth sound-sensitive [1–3]. This phenomenon—sound sensitivity of the vestibular system—has been known as the Tullio phenomenon [3, 4]. Bekesy reported head movements in response to relatively loud sounds [3, 5] and suggested that this effect might be caused by stimulation of the otolith organs. Later, Young et al. reported that primary vestibular afferents of squirrel monkeys could respond to sound and vibration, although the number of examined vestibular neurons was limited and the methods of threshold determination (a phase-locking threshold) were not familiar [6]. According to their study, all the vestibular end- organs (three canals and two maculae) responded to sound. Among the five end- organs, the saccular macula showed the lowest thresholds. The best frequencies did not exceed 1000 Hz to sound and 500 Hz to vibration. Cazals et al. created guinea pigs with selective cochlear loss and preserved the vestibular system using amika- sin, an aminoglycoside. These animals displayed evoked potentials to sound, although their cochlea was completely destroyed [7, 8]. Recording evoked poten- tials on the eighth nerve revealed that the responses were prominent on the inferior vestibular nerve [9]. These studies suggested that the vestibular end-organs could respond to loud sounds and that the saccule might be the most sound-sensitive among the vestibular end-organs. During the 1990s, several articles concerning sound sensitivity of vestibular neurons were published. McCue and Guinan reported that saccular afferents of cats responded to intense sound. In their study, the best frequency of saccular afferents to air-conducted sound was around 500 Hz (Fig. 1) [10–12]. Murofushi et al. showed that primary vestibular afferents of guinea pigs could respond to intense air-conducted clicks (Fig. 2) [13, 14]. These neurons were mainly in the inferior vestibular nerve and could also respond to static tilts. None of the angular accelera- tion-sensitive neurons—canal neurons—responded to clicks. These findings sug- gested that the saccular afferents could be sensitive to air-conducted sound. Most of these click-sensitive neurons showed irregular spontaneous firing. Irregularly Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 20 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_3, © Springer 2009
  • 25.
    Sound Sensitivity andSound-Evoked Vestibulocollic Reflexes 21 firing fibers have thick, medium-sized axons ending as calyx and dimorphic units [15]. Hence, type I hair cells on the saccular macula are sound (click)-sensitive among the vestibular end-organs. Murofushi et al. also reported that vestibular nucleus neurons in the lateral vestibular nucleus and in the rostral portion of the inferior vestibular nucleus are sound (click)-sensitive (Fig. 3) [16]. Although these findings imply that saccular afferents could respond to air-conducted sound, they do not exclude the possibility that utricular afferents might respond to air-con- ducted sound as well, especially to relatively low-frequency sound. In the vestibular end-organs, response patterns to bone-conducted sound (vibra- tion) are different from the patterns seen with air-conducted sound. Hair cells in Fig. 1. Tuning curves of sound-sensitive vestibular afferents of cats. SPL, sound pressure level. (from Fig. 6 of ref. 11, American Physiological Society, with permission) Fig. 2. Responses of guinea pig primary vestibular neurons to clicks—70 dB above the auditory brainstem response (ABR) threshold. (from Fig. 1 of ref. 14, Taylor & Francis, with permission)
  • 26.
    22 Vestibular EvokedMyogenic Potentials the utricular macula and the saccular macula respond to bone-conducted sound. According to Curthoys et al., most of the irregular otolithic afferents studied (82.8%) showed a clear increase in the firing rate in response to bone-conducted sound [17]. In their study, bone-conducted sound-sensitive afferents could be of utricular origin because many of the bone-conducted sound-sensitive afferents were in the superior vestibular nerve, and they were sensitive to roll tilts. These authors also reported that regular otolithic afferents were less sensitive to bone-conducted sound, and only a few canal afferents responded to it. These findings suggested that vestibular evoked myogenic potentials (VEMPs) to bone-conducted sound [18, 19] might be produced by vestibular end-organs from a different population than the VEMPs to air-conducted sound. Neural Pathway of the Sound-Evoked Vestibulocollic Reflex Among the vestibular end-organs in mammals, the saccular macula seems to respond especially well to air-conducted sound; and among the hair cells on the saccular macula, the type I hair cells around the striola seem to be the most sensi- tive. What then is the neural pathway of the sound-evoked vestibulocollic reflex? Primary afferents of the saccule are mainly in the inferior vestibular nerve. Therefore, inputs to the vestibular system of sound stimulation are mostly trans- mitted via the inferior vestibular nerve. According to Kushiro et al. [20], saccular Fig. 3. Recording sites of click-sensitive vestibular nucleus neurons of guinea pigs. LV, lateral vestibular nucleus; DV, descending vestibular nucleus; MV, medial vestibular nucleus; SV, supe- rior vestibular nucleus; icp, inferior cerebellar peduncle; CN, cochlear nucleus; as, acoustic stria; n7, facial nerve; g7, genu nervi facialis; N6, abducens nucleus. a is the most rostral and c is the most caudal. (from Fig. 2 of ref. 16, Springer, with permission)
  • 27.
    Sound Sensitivity andSound-Evoked Vestibulocollic Reflexes 23 afferents in cats have inhibitory projection to the ipsilateral motoneurons of the sternocleidomastoid muscle (SCM) and no contralateral projection. These authors also showed that this projection was transmitted via the medial vestibulospinal tract. Based on these findings, the neural pathway of the air-conducted sound- evoked vestibulocollic reflex recorded on the SCM is thought to be as shown in Fig. 4. The VEMPs are clearly ipsilateral-dominant (described later). Therefore, the supposed neural pathway corresponds well with the results of VEMP studies in humans. Provided that bone-conducted sound simulates the utricular macula as well as the saccular macula, VEMPs to bone-conducted sound might have some features different from those of VEMPs to air-conducted sound. Utricular afferents are located in the superior vestibular nerve. Utricular afferents have not only inhibitory projection to the ipsilateral motoneurons of the SCM but also excitatory projection to the contralateral motoneurons of the SCM [20]. When one uses bone-conducted sound as the stimulus, one should bear in mind that the neural pathway of VEMPs for bone-conducted sound might be different from the pathway of VEMPs for air- conducted sound. When sound is presented to the ear, one may concern the coexistence of a “sound-evoked cochleocollic reflex”. However, direct projection from the cochlear nucleus to the motoneurons of the SCM is not known. Therefore, the sound-evoked cochleocollic reflex, if any, would be transmitted via the reticular formation, taking longer latencies than the sound-evoked vestibulocollic reflex. Furthermore, it would be evoked bilaterally. Some of the later components of VEMPs (n34–p44) [21] may be a sound-evoked cochleocollic reflex. Fig. 4. Pathway of air-conducted sound-evoked vestibulocollic (otolith-sternocleidomastoid) reflex. SCM, sternocleidomastoid muscle inferior vestibular nerve medial vestibulospinal tract accessory nerve ipsilatral SCM saccule
  • 28.
    24 Vestibular EvokedMyogenic Potentials References 1. Tullio P (1929) Das Ohr und die Entstehung der Sprache und Schrift. Urban & Schwarzen- berg, Berlin 2. Minor LB, Solomon D, Zinreich JS, et al (1998) Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior semicircular canal. Acta Otolaryngol Head Neck Surg 124:249–258 3. Halmagyi GM, Curthoys IS, Colebatch JG, et al (2005) Vestibular responses to sound. Ann NY Acad Sci 1039:54–67 4. Huizinga E (1935) On the sound reaction of Tullio. Acta Otolaryngol (Stockh) 22:359–369 5. Bekesy GV (1935) Uber akustische Reizung des Vestibularapparates. Pflugers Arch Ges Physiol Mensch Tiere 236:59–76 6. Young ED, Fernández C, Goldberg JM (1977) Responses of squirrel monkey vestibular neurons to audio-frequency sound and head vibration. Acta Otolaryngol (Stockh) 84:352–360 7. Cazals Y, Aran JM, Erre JP (1980) Acoustic responses after total destruction of the cochlear receptor: brainstem and auditory cortex. Science 210:83–86 8. Cazals Y, Aran JM, Erre JP (1982) Frequency sensitivity and selectivity of acoustically evoked potentials after complete cochlear hair cell destruction. Brain Res 231:197–203 9. Didier A, Cazal Y (1989) Acoustic responses recorded from the saccular bundle on the eighth nerve of the guinea pig. Hear Res 37:123–128 10. McCue MP, Guinan JJ (1994) Acoustically responsive fibers in the vestibular nerve of the cat. J Neurosci 14:6058–6070 11. McCue MP, Guinan JJ (1995) Spontaneous activity and frequency sensitivity of acoustically responsive vestibular afferents in the cat. J Neurophysiol 74:1563–1572 12. McCue MP, Guinan JJ (1997) Sound-evoked activity in primary afferent neurons of a mammalian vestibular system. Am J Otol 18:355–360 13. Murofushi T, Curthoys IS, Topple AN, et al (1995) Responses of guinea pig primary vestibu- lar neurons to clicks. Exp Brain Res 103:174–178 14. Murofushi T, Curthoys IS (1997) Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol (Stockh) 117:66–72 15. Goldberg JF, Lysakowski A, Fernandez C (1992) Structure and function of vestibular nerve fibers in the chinchilla and squirrel monkey. Ann NY Acad Sci 656:92–107. 16. Murofushi T, Curthoys IS, Gilchrist DP (1996) Response of guinea pig vestibular nucleus neurons to clicks. Exp Brain Res 111:149–152 17. Curthoys IS, Kim J, McPhedran SK, et al (2006) Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig. Exp Brain Res 175:256–267 18. Sheykholeslami K, Murofushi T, Kermany MH, et al (2000) Bone conducted evoked myogenic potentials from the sternocleidomastoid muscle. Acta Otolaryngol (Stockh) 120:731–734 19. Welgampola MS, Rosengren SM, Halmagyi GM, et al (2003) Vestibular activation by bone conducted sound. J Neurol Neurosurg Psychiatry 74:771–778 20. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 21. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click-evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197
  • 29.
    Recording and AssessingVEMPs Suitable Subjects for Recording VEMPs Basically, vestibular evoked myogenic potential (VEMP) testing is applicable to all subjects who require evaluation of vestibular functions. However, it is difficult to obtain responses from subjects who are not cooperative during the testing and who for some reason cannot contract the sternocleidomastoid muscle (SCM) during the recording (e.g., a comatose patient). In subjects with air–bone gaps in pure-tone audiometry, special care is required because responses are abolished or decreased owing to conductive hearing loss [1, 2]. Methods of Recording VEMPs We usually use surface electrodes to record VEMPs, placing active electrodes sym- metrically on the middle third of the SCM and indifferent electrodes on the lateral end of the upper sternum (Fig. 1) [3]. When the active electrodes are too close to the indifferent electrodes, the amplitudes of the responses are decreased [4]; and when they are too close to the mastoid, responses are contaminated by postauricular responses [5]. The ground electrode is placed on the nasion or the chin. Acoustic stimuli usually comprise clicks (0.1 ms) or short tone bursts (STBs) (500 Hz, rise/fall time 1 ms, plateau time 2 ms). We first present 95-dBnHL (decibels, normal hearing level) clicks or STBs and attenuate the intensity when we want to determine the threshold of the responses. STBs of 500 Hz evoke larger, clearer VEMP responses than clicks [6]. However, investigators should note that STBs of 500 Hz might evoke utricular hair cells as well as saccular hair cells, whereas clicks selectively evoke saccular hair cells [7, 8]. The repetition rate of stimulation is usually 5 Hz. When the repetition rate is increased, the amplitude of the responses may be decreased. This tendency becomes clear when the repetition rate is more than 20 Hz [9]. On the other hand, subjects may become tired when the repetition rate is decreased because the lower repetition rate requires contraction of the SCM for longer periods. Thus, 5 Hz is the optimal repetition rate. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 25 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_4, © Springer 2009
  • 30.
    26 Vestibular EvokedMyogenic Potentials Electromyographic (EMG) activities are amplified and bandpass-filtered (20– 2000 Hz). The time window for analysis is 50–100 ms. Responses to 100–200 stimuli (click VEMPs) are averaged. It is important to maintain the contraction of the SCM during recording. VEMP amplitudes show strong correlations to background muscle activity (Fig. 2). Responses cannot be observed without muscle contraction. As VEMP amplitudes show strong correlations with the extent of muscle con- traction, efforts to minimize the effects of muscle contraction fluctuation may be required. To minimize such effects, it is proposed that 1) VEMP amplitudes be corrected based on the extent of muscle contraction and 2) the muscle contraction be maintained at a constant level using feedback methods. To correct VEMP ampli- tudes, we use an average of rectified background muscle activity during a prestimu- lus period of 20 ms [10] (Fig. 3). The corrected amplitude (CA) of VEMP is defined as a ratio. CA = (raw amplitude of p13–n23)/(mean background amplitude) Fig. 1. Electrode placement for vestibular evoked myogenic potential (VEMP) recording Fig. 2. Correlation between the VEMP amplitude to 95-dBnHLtone bursts (500 Hz) and mean background muscle activity in healthy subjects. The correlation coefficient was 0.83. dBnHL, dB normal hearing level; 0 dBnHL, average subjective threshold of sound perception in healthy subjects. (from Fig. 2 of ref. 24, Elsevier, with permission)
  • 31.
    Recording and AssessingVEMPs 27 For this purpose, one must average the rectified EMG during a prestimulus period. A feedback method using a blood pressure manometer has been proposed to main- tain the muscle contraction constant during VEMP recording [11]. To contract the SCM, we usually ask subjects in the supine position to raise their head from the pillow. Alternatively, rotating the neck (in the supine position or upright) or having the examiner push the patient’s forehead can be useful (Fig. 4). The rotation method may be easier. However, investigators should note that only unilateral responses are recordable, and muscle contraction becomes easily asymmetrical when this method is applied. Head position itself does not affect VEMP responses [12]. According to Isaacson et al., when the amplitude was corrected according to tonic EMG activity, no significant difference was noted among various test positions [13]. Fig. 3. Correction of amplitudes using rectified electromyography (EMG). Upper trace, unrecti- fied response; lower trace, rectified response. Background muscle activities were calculated using the shaded areas. VEMP amplitudes were corrected based on background muscle activity. (from Fig. 1 of ref. 12, Taylor & Francis, with permission) Fig. 4. Methods to contract the sternocleidomastoid muscle (SCM). a Position supine with the head raised, b position sitting with the head turned away from the tested ear, c position sitting with the head pushed against the finger to provide resistance
  • 32.
    28 Vestibular EvokedMyogenic Potentials Normal VEMP Responses In healthy subjects, VEMP responses consist of initial positivity followed by nega- tivity with short latencies. This biphasic response is termed p13–n23 after the peak latency. In our clinic, the means ± SD of p13 and n23 were 11.8 ± 0.86 ms and 20.8 ± 2.2 ms, respectively (95-dBnHL clicks) [14]. Responses to STBs have 2- to 3-ms longer peak latencies [6]. These responses are clearly ipsilateral-dominant. In other words, p13–n23 can be recorded on the SCM ipsilateral to the stimulated ear, although p13–n23 on the contralateral side is absent or small (Fig. 5) [15]. Following p13–n23, later components (n34–p44) can be also observed (Fig. 6) [16]. Fig. 5. Laterality of VEMP responses. VEMP responses (p13–n23) to 95-dBnHL clicks were clearly ipsilateral-dominant. (from Fig. 1 of ref. 15, Taylor & Francis, with permission) 10 msec 100 m V p13 n23 n34 p44 Fig. 6. Typical VEMP waveform in response to 95-dBnHL clicks in a healthy subject. Responses are on the ipsilateral SCM to the stimulated ear
  • 33.
    Recording and AssessingVEMPs 29 Later components are not of vestibular origin [1]. Amplitudes of responses (p13–n23) depend on the degree of muscle contraction. In the ordinary situation, the amplitudes range from 50 to 200 μV. The polarity of the initial responses (positivity followed by negativity) implies that this myogenic potential is caused by inhibitory inputs to the SCM [17]. This finding is consistent with neurophysiological data from cats [18]. Parameters for Assessing VEMPs The following parameters are used for clinical evaluation. In this section, VEMPs refer to the early component (p13–n23). Presence of VEMPs VEMPs are usually present in healthy subjects, whereas some elderly subjects exhibit an absence of response. This absence is considered pathological in subjects <60 years of age (Fig. 7). In other words, absence of responses suggests dysfunc- tion of the sacculocollic pathway. Even in older subjects, the unilateral absence of responses is pathological. If an absence of VEMP responses is observed, an exam- iner should first confirm that the headphone was adequately placed on the head. Second, the examiner should determine if the subject has conductive hearing loss. The absence of responses in patients with conductive hearing loss does not mean dysfunction of the saccule or its afferents. Fig. 7. Example of unilateral absence of VEMP responses on the left side (L). R, right side
  • 34.
    30 Vestibular EvokedMyogenic Potentials Interaural Difference of VEMP Amplitude Side-to-side differences of VEMP amplitude can be expressed as percent VEMP asymmetry [3]. %VEMP asymmetry = 100 |Ar − Al|/(Ar + Al) where Ar and Al are the amplitudes of p13–n23 on the right and on the left; and |Ar − Al| is the absolute value of Ar − Al. When the affected side is already known, the percent VEMP asymmetry should be calculated as follows. %VEMP asymmetry = 100 (Au − Aa)/(Au + Aa) where Au is the amplitude of p13–n23 on the unaffected side; and Aa is the ampli- tude of p13–n23 on the affected side. In our institution, we set the upper limit of percent VEMP asymmetry as 34.1 (mean +2 SD) in healthy subjects. When the percent VEMP asymmetry exceeds 34.1, the asymmetry is pathological. We usually regard the decreased side as pathological unless there are other specific reasons for the abnormal result (Fig. 8). Although a similar normal range was reported from another laboratory [19], the normal limit should be set at each institution because recording conditions cannot be totally identical. Peak latency Significant delay of peak latencies is also pathological. As the peak latency of p13 shows better reproducibility than that of n23, the peak latency of p13 is more available clinically. Prolonged latencies are signs of retrolabyrinthine or central Fig. 8. Example of unilaterally decreased amplitudes on the left side
  • 35.
    disorders (Fig. 9)[14, 20, 21]. In our institution, the means ± SD of p13 and n23 to 95 dBnHL click were 11.8 ± 0.86 ms and 20.8 ± 2.2 ms, respectively. The normal range for peak latency should be established at each institution. Threshold In comparison with the auditory brainstem response (ABR), which is an evoked potential of cochlear origin, the VEMP threshold is much higher. In our clinic, the VEMP thresholds in healthy subjects (clicks) were ≥85 dBnHL. According to Colebatch et al. [22], the mean threshold of VEMP responses to clicks in healthy subjects was 86 dBnHL and the lowest was 70 dBnHL. When the threshold to click stimulation is lower than 70 dBnHL, it is definitely pathological, suggesting hyper- sensitivity of vestibular end-organs to sound (the Tullio phenomenon) (Fig. 10). Fig. 9. Example of prolonged latencies (both sides). (from Figure of ref. 20, BMJ Publishing Group, with permission) Fig. 10. Example of low VEMP thresh- olds. In this subject, the threshold was 70 dBnHL Recording and Assessing VEMPs 31
  • 36.
    32 Vestibular EvokedMyogenic Potentials Miscellaneous In addition to the above-mentioned major parameters, some others can be applied. Frequency Tuning Characteristics Rauch et al. reported that patients with Meniere’s disease showed less tuning at 500 Hz and threshold elevation, whereas healthy subjects showed the best responses at 500 Hz [23]. Their results suggested that a new parameter concerning frequency tuning characteristics might be applicable for VEMP assessment. For example, the ratio of corrected VEMP amplitude at 500 Hz to that at 1000 Hz or the ratio of the threshold at 500 Hz to that at 1000 Hz might be applied. Acoustic/Galvanic Ratio The characteristics of the responses to acoustic stimuli and galvanic stimuli might be compared. Because galvanic stimulation bypasses the labyrinth and stimulates the vestibular nerve directly, labyrinthine damage does not affect galvanic VEMPs whereas it does affect acoustic VEMPs. Therefore, the acoustic VEMP amplitude/ galvanic VEMP amplitude ratio can be a useful indicator for differentiating laby- rinthine from retrolabyrinthine disorders [24–26]. This issue is discussed in the chapter “VEMP Variants.” References 1. Welgampola MS, Colebatch JG (2005) Characteristics and clinical applications of vestibular- evoked myogenic potentials. Neurology 64:1682–1688 2. Bath AP, Harris N, McEwan J (1999) Effect of conductive hearing loss on the vestibulocollic reflex. Clin Otolaryngol 24:181–183 3. Murofushi T, Matsuzaki M, Mizuno (1998) Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509–512 4. Sheykholeslami K, Murofushi T, Kaga K (2001) The effect of sternocleidomastoid electrode location on VEMP. Auris Nasus Larynx 28:41–43 5. Endoh T, Hojoh K, Sohma H, et al (1987) Auditory postauricular responses in patients with peripheral facial nerve palsy. Acta Otolaryngol Suppl 446:76–80 6. Murofushi T, Matsuzaki M, Wu CH (1999) Short tone burst-evoked myogenic potentials on the sternocleidomastoid muscle. Arch Otolaryngol Head Neck Surg 125:660–664 7. Murofushi T, Curthoys IS, Topple AN, et al (1995) Responses of guinea pig primary vestibu- lar neurons to clicks. Exp Brain Res 103:174–178 8. Murofushi T, Curthoys IS (1997) Physiological and anatomical study of click-sensitive primary vestibular afferents in the guinea pig. Acta Otolaryngol (Stockh) 117:66–72 9. Wu CH, Murofushi T (1999) The effect of click repetition rate on vestibular evoked myogenic potential. Acta Otolaryngol (Stockh) 119:29–32
  • 37.
    10. Welgampola MS,Colebatch JG (2001) Characteristics of tone burst-evoked myogenic poten- tials in the sternocleidomastoid muscles. Otol Neurotol 22:796–802 11. Vanspauwen R, Wuyts FL, Van deHeyning PH (2006) Improving vestibular evoked myogenic potential reliability by using a blood pressure manometer. Laryngoscope 116:131–135 12. Ito K, Karino S, Murofushi T (2007) Effect of head position on vestibular evoked myogenic potentials with tone burst stimuli. Acta Otolaryngol 127:57–61 13. Isaacson B, Murphy E, Cohen H (2006) Does the method of sternocleidomastoid muscle activation affect the vestibular evoked myogenic response? J Vestib Res 16:187–191 14. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127:1069– 1072 15. Murofushi T, Ochiai A, Ozeki H, et al (2004) Laterality of vestibular evoked myogenic potentials. Int J Audiol 43:66–68 16. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click- evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 17. Colebatch JG, Rothwell JC (2004) Motor unit excitability changes mediating vestibulocollic reflexes in the sternocleidomastoid muscle. Clin Neurophysiol 115:2567–2573 18. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 19. Welgampola MS, Colebatch JG (2001) Vestibulocollic reflexes: normal values and the effect of age. Clin Neurophysiol 112:1971–1979 20. Shimizu K, Murofushi T, Sakurai M, et al (2001) Vestibular evoked myogenic potentials in multiple sclerosis. J Neurol Neurosurg Psychiatry 69:276–277 21. Takegoshi H, Murofushi T (2000) Vestibular evoked myogenic potentials in patients with spinocerebellar degeneration. Acta Otolaryngol 120:821–824 22. Colebatch JG, Day BL, Bronstein AM, et al (1998) Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon. J Neurol Neurosurg Psychiatry 65:670–678 23. Rauch SD, Zhou G, Kujawa SG, et al (2004) Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol 25:333–338 24. Murofushi T, Iwasaki S, Ozeki H, et al (2007) Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a new parameter of VEMP? Clin Neurophysiol 118:1685– 1690 25. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 26. Monobe H, Murofushi T (2004) Vestibular testing by electrical stimulation in patients with unilateral vestibular deafferentation: galvanic evoked myogenic responses testing vs galvanic body sway testing. Clin Neurophysiol 155:806–810 Recording and Assessing VEMPs 33
  • 38.
    VEMP Variants Introduction Originally, vestibularevoked myogenic potentials (VEMPs) were recorded on cervical muscles, especially the sternocleidomastoid muscle (SCM), in regard to air-conducted sound [1, 2]. However, there were some limitations of this test. To overcome these limitations, variants of VEMP analysis have been proposed and are classified into two categories: variants stimulation methods and recording methods. Variants of Stimulation Methods In addition to conventional unilateral air-conducted sound stimulation, a binaural simultaneous air-conducted sound stimulation method, a tapping method, a bone- conducted sound method, and a galvanic stimulation method have been reported. Binaural Simultaneous Stimulation Method The binaural simultaneous air-conducted sound stimulation method was proposed to reduce physical loading of subjects. During VEMP recording, subjects must keep contracting the SCM, and it is sometimes difficult for elderly subjects to maintain the contraction. The saccular projection to the SCM is unilateral [3]. In other words, acoustic stimulation to one ear affects only the SCM ipsilateral to the stimulated ear. In healthy subjects, VEMPs are clearly ipsilateral-dominant [4]. Therefore, simultane- ous binaural stimulation seems to enable sacculocollic reflexes on both sides at the same time. Murofushi et al. compared VEMP responses of monaural click stimula- tion with responses to binaural click stimulation in patients with unilateral peri- Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 34 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_5, © Springer 2009
  • 39.
    VEMP Variants 35 pheralvestibular dysfunction [5]. In 26 of the 28 patients, results for monaural stimulation coincided with those for binaural stimulation (Fig.1, Table 1). Among the two patients without coincidence, one patient showed bilateral normal responses to monaural stimulation despite decreased responses on one side to binaural simul- taneous stimulation, and the other patient showed a unilateral absence to monaural stimulation despite the bilateral absence of responses to binaural stimulation. The reasons for the discordance were not clear. However, the high rate of coincidence and no false-negative results encouraged us to apply the binaural simultaneous stimulation method as a clinical screening test. Tapping and Bone-Conducted Sound Method Conduction problems in the external ear or middle ear attenuate the intensity of air-conducted sound. Therefore, subjects with conductive hearing loss may show an absence of response despite a normal sacculocollic pathway. The tapping and bone-conducted sound method was primarily applied to measure vestibulocollic Monaural stimulation Binaural stimulation Fig. 1. Vestibular evoked myogenic potential (VEMP) responses to monau- ral individual stimulation and binaural simultaneous stimulation in a woman with a left acoustic neuroma. The patient showed absent responses on the left sternocleidomastoid muscle (SCM) to left ear stimulation and to binaural stimulation. L, left side; R, right side. (from Fig. 1 of ref. 5, Springer, with permission) Table 1. Results to unilateral stimulation and bilateral stimulation. (from Table 1 of ref. 5, Springer, with permission) Bilateral stimulation Unilateral stimulation Bilaterally normal Unilaterally decreased Unilaterally absent Bilaterally absent Total Bilaterally normal 9 0 0 0 9 Unilaterally decreased 1 0 0 0 1 Unilaterally absent 0 0 15 0 15 Bilaterally absent 0 0 1 2 3 Total 10 0 16 2 28
  • 40.
    36 Vestibular EvokedMyogenic Potentials reflexes in patients with conducted-hearing loss, as these stimulations are thought to bypass the middle ear and act directly on the inner ear (Fig. 2). The tapping method applied vibratory stimulation to the subjects’skulls. Tapping with a tendon hammer evokes biphasic myogenic responses on the SCM as evoked by air-conducted sound (Figs. 3, 4) [6–8]. The tapping site is the forehead (Fz) or mastoid. Recording conditions are basically the same as for VEMP responses to Air-conducted sound Bone- conducted sound, tapping Galvanic stimuli Fig. 2. Stimulation methods and supposed stimulated sites Fig. 3. Tendon hammer that can send trigger signals to the averager
  • 41.
    VEMP Variants 37 air-conductedsound. In a study of patients without conductive hearing loss, so long as we concerned only if the results were normal 14 of 15 patients showed the same results with the tapping method as were seen with the air-conducted click method. However, many of them showed delayed positivity (Table 2). Although we had regarded the delayed positivity as delayed p13, the positivity might be an inverted response preceded by negativity (n13) (Fig. 5). There was no clear relation between the responses evoked by tapping and pure-tone hearing. These findings suggested that myogenic potentials evoked by tapping should be of vestibular origin but that parts other than the saccule could be also stimulated. Brantberg and Mathiesen reported that tapping-evoked myogenic potentials were preserved after resection of the inferior vestibular nerve [9]. Their findings supported our assumption. As described above, the tapping method is a good alternative to the conventional VEMP procedure. One problem with the tapping method, though, was the difficulty of calibrating the stimulation. The bone-conducted sound method overcomes this defect. For recording VEMPs to bone-conducted sound, a bone vibrator—an apparatus to measure pure-tone hearing thresholds—was first applied [10–14]. Currently, a bone vibrator with stronger intensity is available [15]. The bone Fig. 4. VEMPs to 95-dBnHL clicks and myogenic responses to tapping in a healthy subject Table 2. Results of myogenic potentials to clicks and tapping Parameter Normal Abnormal Total Decreased Absent Delayed Normal 3 0 0 0 3 Abnormal Decreased 1 0 0 1 2 Absent 0 0 4 5 9 Delayed 0 0 0 1 1 Total 4 0 4 7 15
  • 42.
    38 Vestibular EvokedMyogenic Potentials vibrator is placed on the mastoid or forehead. The other recording conditions are basically the same as those for air-conducted sound. The optimal frequencies for VEMPs to bone-conducted sound ranged from 200 to 250 Hz [14, 16]. As for the tapping method, bone-conducted sound can stimulate not only the saccule but other parts of the vestibular end-organs as well. A neurophysiological experiment with guinea pigs suggested that the utricle could also be stimulated by bone- conducted sound [17]. These methods—the tapping method and the bone-conducted sound method— are suitable for assessing vestibular function of subjects with conductive hearing loss [11–13]. One should note that these methods stimulate vestibular end-organs on both sides. Whereas the saccular projection to the SCM is uncrossed, the utricu- lar projection to the SCM is not only uncrossed but also crossed. Utricular stimula- tion could have excitatory inputs to the contralateral SCM [3]. Therefore, we should take the crossed pathway into account when assessing the results. Galvanic Stimulation Galvanic stimulation has been used for a galvanic body sway test and a galvanic eye movement test [18–21]. Galvanic stimulation has been thought to bypass the labyrinth and act directly on the vestibular nerve (Fig. 2) and thus is useful for differentiating retrolabyrinthine lesions from labyrinthine lesions. Short-duration galvanic stimulation has been also applied to patients with vestibular disorders for this purpose [20–22]. That these potentials are of vestibular origin was confirmed by the disappearance of myogenic potentials on the SCM after vestibular nerve section [23]. Fig. 5. VEMP (95-dBnHL clicks) and myogenic responses to tapping in a woman with a left acoustic neuroma. She showed absent responses to clicks and delayed responses to tapping. Inverted responses?, small negativity might be an inverted response
  • 43.
    VEMP Variants 39 Therecording methods of myogenic potentials to galvanic stimuli are as follows. The electrodes for stimulation were placed on the forehead (anode) and mastoid (cathode), or on bilateral mastoids. The cathodal electrode should be placed on the mastoid that an examiner wants to stimulate. The procedure is contraindicated in patients who have an implanted electrical device such as a pacemaker or a cochlear implant. It should also not be applied to patients who have medical history of epilepsy. A current of 3–4 mA (duration 1–2 ms) is used as the galvanic stimulus. Band- pass filters, stimulation rate, and time window for analysis are the same as for acquiring VEMPs to acoustic stimuli. Responses to 50–100 stimuli are averaged. Galvanic stimulation produces huge electrical artifacts. To remove these artifacts, the responses obtained without SCM contraction are subtracted from the responses with SCM contraction [21, 22]. Using this subtraction method, we can get biphasic (positive–negative) responses similar to VEMPs to acoustic stimuli (Fig. 6). We call the first positivity p13g and the following negativity n23g. The means ± SD of p13g and n23g with our method (3 mA, 1 ms) [21] were 11.4 ± 1.3 ms and 19.0 ± 2.1 ms, respectively. The mean threshold was 2.5 mA. As these myogenic potentials were abolished by vestibular nerve section [22], we call these myogenic potentials to short-duration galvanic stimuli “galvanic VEMPs.” As expected, patients with labyrinthine lesions such as Meniere’s disease have normal galvanic VEMPs even though they had an absence of click VEMPs on the affected side. In contrast, patients with retrolabyrinthine lesions (e.g., acoustic neuroma) showed a tendency toward abnormal galvanic VEMPs in addition to absent VEMPs in response to clicks [21]. This combined method of acoustic p13g n23g 10 msec 200 m V 100 m V 10 msec With muscle contraction Without muscle contraction (a) (b) Fig. 6. Subtraction methods to make responses clearer. (from Fig. 1 of ref. 21, Elsevier, with permission)
  • 44.
    40 Vestibular EvokedMyogenic Potentials VEMPs and galvanic VEMPs has been applied for lesion site studies of various diseases, as described in the clinical application chapters later in this book [21, 24–27]. At an early stage, this combined method was applied only to patients with absent VEMPs to acoustic stimuli. Recently, this combined method has been applied to patients with preserved acoustic VEMPs. We can calculate the ratio of corrected p13–n23 amplitudes to tone burst stimuli/corrected p13g–n23g amplitudes to gal- vanic stimuli (the TG ratio). The TG ratio is significantly smaller on the affected side of patients with endolymphatic hydrops (a representative inner ear disease) than it is in healthy subjects or on the unaffected side of patients [28]. This change in the TG ratio was not observed in patients with an acoustic neuroma. The combined method of acoustic and galvanic VEMPs for lesion site studies is also applicable to subjects with preserved acoustic VEMPs. Variants of Recording Methods Vestibular Evoked Extraocular Potential Recently, myogenic potentials to acoustic stimuli recorded around the eyes— vestibular evoked extraocular potential (oVEMP)—have been reported [15, 29, 30]. These responses consist of several peaks. The first peak is a negative deflection with short tone bursts (mean 10.5 ms to 135-dBSPL, 500-Hz air-conducted bursts) followed by a positive deflection (mean 15.9 ms) [30]. When air-conducted sounds were presented, responses were contralateral eye-dominant and clearly recorded on the electrodes placed underneath the lower eyelid [30] (Fig. 7, Table 3). With our recording method [30], active electrodes are placed on the face just inferior to each eye, with reference electrodes placed 1–2 cm below. Electro- myography (EMG) signals are amplified and bandpass-filtered between 5 and 500 Hz. The time window for analysis is 50 ms. Although we prefer air-conducted sound (500-Hz short tone burst, up to 135 dBSPL) because of unilateral stimula- tion, others prefer bone-conducted sound or tapping because of clearer responses [15, 29, 30]. Responses to 100 stimuli are averaged. Subjects are instructed to maintain an upward gaze during recording because responses are the largest at this gaze position. It is believed that these responses reflect the vestibuloocular reflex, especially the otolith-ocular reflex. The responses are called oVEMPs. Although a clinical study suggested that oVEMPs are of vestibular origin, their exact origin is not clear yet. The extent of the contribution of the saccule and utricule is controversial. Further studies are required before this can be established as a definitive clinical test. After establishing the neural pathway of oVEMPs, the combined use of VEMPs and oVEMPs may be useful for assessing lesions in the brainstem, as suggested by Rosengren et al. [31].
  • 45.
  • 46.
    42 Vestibular EvokedMyogenic Potentials Neurogenic Potentials For recording VEMPs (including oVEMPs), cooperation of the subject (maintain- ing contraction of the SCM or an upward gaze) is essential. Therefore, it is difficult to record VEMPs in children and elderly people and impossible in sleeping or generally anesthetized subjects. If possible, vestibular evoked neurogenic potentials (VENPs), which do not require muscle contraction, may be preferable. It was reported that negativity at a latency of 3 ms (N3) was observed instead of normal waveforms during auditory brainstem response (ABR) recording in subjects with profound hearing loss [32]. Ochi and Ohashi hypothesized that N3 might be of saccular origin [33]. As the presence of N3 corresponded to the presence of VEMPs [34] (Fig. 8), N3 might be of saccule origin. However, it was difficult to visualize N3 in subjects with normal hearing because they have normal ABR waveforms (Fig. 9). To visualize N3 in normal subjects, it is necessary to suppress or delete ABR waveforms. For this purpose, we presented white noise to the stimulated ear, the intensity of which was high enough to stimu- late the cochlea but insufficient for the vestibular nerve. We hypothesized that this ipsilateral masking sound could suppress ABRs by disturbing the synchronization of the cochlear nerve to the target sound but that it would not affect VEMPs. Based on this hypothesis, we recorded N3 in subjects with preserved hearing under white noise exposure (Fig. 10).We presented 1000-Hz short tone bursts (130 dBSPL, rise/fall time 0.5 ms, plateau time 1 ms) as target stimuli with white noise (100 dBSPL). The recording electrodes were placed on the vertex and mastoid. Signals were amplified and bandpass-filtered (100–3000 Hz). Responses to 500 stimuli were averaged. The stimulation rate was 10 Hz, and the time window for recording was 10 ms. Under these conditions, the mean latency of N3 of healthy subjects was 3.58 ms, and the mean threshold was 125 dBSPL. The appearance of N3 under these conditions corresponded well with the appearance of VEMPs [35]. We assume that the source of N3 might be around the vestibular nucleus. Apart from N3, Todd et al. recorded potentials on the scalp evoked by bone- conducted sound, the intensity of which was higher than the threshold of VEMPs Table 3. Rate of identifiable responses, amplitude, and latency of oVEMP Parameter 0.1-ms click (135 dBSPL) 500-Hz short tone burst (135 dBSPL) Ipsilateral eye Contralateral eye Ipsilateral eye Contralateral eye Rate of identifiable responses (% of 20 ears) 0 50 45 90 Amplitude between nI and pI (μV)a — 3.2 ± 0.4 1.9 ± 0.2 7.0 ± 1.0 nI latency (ms) — 8.8 ± 0.3 12.8 ± 0.6 10.5 ± 0.1 pI latency (ms) — 14.5 ± 0.5 17.7 ± 0.9 15.9 ± 0.3 (from Table 1 of ref. 30, Elsevier, with permission) a Mean ± SE
  • 47.
    VEMP Variants 43 (a)(b) (c) Fig. 8. Responses to sound in a 25-year-old man with bilateral nearly total sensorineural hearing loss. a N3s (95-dBnHL 1-kHz tone bursts) were present on both sides. Shaded areas, periods of stimulation. b Audiograms. c VEMP (95-dBnHL clicks) Fig. 9. N3 potentials in a 5-year-old boy with right total hearing loss. Auditory brainstem responses (ABRs) were normal in response to left ear stimulation, whereas the usual ABR wave- forms were not observed after right ear stimulation. However, a clear negative deflection was observed at 3 ms after stimulation. The upward deflection represents positivity. ISIs, interstimulus intervals. (from Fig. 2 of ref. 32, The Oto-Rhino-Laryngological Society of Japan, with permission)
  • 48.
    44 Vestibular EvokedMyogenic Potentials [36]. In addition to auditory middle latency responses [37], the authors observed positivity at about 10 ms (P10), which was maximum at Cz, and negativity at about 15 ms (N15), which was maximum at Fz. As P10 and N15 were also observed in patients with bilateral profound hearing loss [38], these potentials are possibly VENPs. The sources of these potentials and the origins at the end-organ level should be clarified. References 1. Colebatch JG, Halmagyi GM (1992) Vestibular evoked potentials in human neck muscles before and after unilateral vestibular deafferentation. Neurology 42:1635–1636 2. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click- evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 3. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 4. Murofushi T, Ochiai A, Ozeki H, et al (2004) Laterality of vestibular evoked myogenic potentials. Int J Audiol 43:66–68 5. Murofushi T, Takai Y, Iwasaki S, et al (2005) VEMP recording by simultaneous binaural stimulation. Eur Ach Otorhinolaryngol 262:864–867 6. Halmagyi GM, Yavor RA, Colebatch JG (1995) Tapping the head activates the vestibular system: a new use for the clinical reflex hammer. Neurology 45:1927–1929 7. Murofushi T, Matsuzaki M, Ikehara Y, et al (2000) Myogenic potentials on the neck muscle by tapping the head. In: Claussen CF, Haid T, Hofferberth B (eds) Equilibrium research, clinical equilibriometry and modern treatment. Elsevier, Amsterdam, pp 233–238 8. Brantberg K, Tribukait A (2002) Vestibular evoked myogenic potentials in response to later- ally directed skull taps. J Vestib Res 12:35–45 9. Brantberg K, Mathiesen T (2004) Preservation of tap vestibular evoked myogenic potentials despite resection of the inferior vestibular nerve. J Vestib Res 14:347–351 10. Sheykholeslami K, Murofushi T, Kermany MH, et al (2000) Bone conducted evoked myogenic potentials from the sternocleidomastoid muscle. Acta Otolaryngol (Stockh) 120:731–734 11. Monobe H, Murofushi T (2004) Vestibular neuritis in a child with otitis media with effusion; clinical application of vestibular evoked myogenic potential by bone-conducted sound. Int J Pediatr Otorhinolaryngol 68:1455–458 Fig. 10. N3 in a healthy subject with ipsi- lateral white noise exposure. The shaded area represents period of stimulation
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    VEMP Variants 45 12.Miyamoto A, Seo T, Node M, et al (2006) Preliminary study on vestibular-evoked myogenic potential induced by bone-conducted stimuli. Otol Neurotol 27:110–1114 13. Seo T, Miyamoto A, Saka N, et al (2008) Vestibular evoked myogenic potential induced by bone-conducted stimuli in patients with conductive hearing loss. Acta Otolaryngol 128:639–643 14. Welgampola MS, Rosengren SM, Halmagyi GM, et al (2003) Vestibular activation by bone conducted sound. J Neurol Neurosurg Psychiatry 74:771–778 15. Iwasaki S, McGarvie LA, Halmagyi GM, et al (2007) Head taps evoke a crossed vestibule- ocular reflex. Neurology 68:1227–1229 16. Sheykholeslami K, Kermany MH, Kaga K (2001) Frequency sensitivity range of the saccule to bone-conducted stimuli measured by vestibular evoked myogenic potentials. Hear Res 160:58–62 17. Curthoys IS, Kim J, McPhedran SK, et al (2006) Bone conducted vibration selectively activates irregular primary otolithic vestibular neurons in the guinea pig. Exp Brain Res 175:256–267 18. Sekitani T (1988) Differential diagnosis of vertigo: combined galvanic test and MRI. Acta Otolaryngol (Stockh) 458:S113–S119 19. Pfalz CR, Koike Y (1968) Galvanic test in central vestibular lesions. Acta Otolaryngol (Stockh) 65:161–168 20. Monobe H, Murofushi T (2004) Vestibular testing by electrical stimulation in patients with unilateral vestibular deafferentation: galvanic evoked myogenic responses testing vs galvanic body sway testing. Clin Neurophysiol 155:806–810 21. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 22. Watson SRD, Colebatch JG (1998) Vestibulocollic reflexes evoked by short-duration galvanic stimulation in man. J Physiol 513:587–597 23. Watson SR, Fagan P, Colebatch JG (1998) Galvanic stimulation evokes short-latency EMG responses in sternocleidomastoid which are abolished by selective vestibular nerve section. Electroencephalogr Clin Neurophysiol 109:471–474 24. Murofushi T, Monobe H, Ozeki H, et al (2003) The site of lesions in “vestibular neuritis”: study by galvanic VEMP. Neurology 61:417–418 25. Iwasaki S, Takai Y, Murofushi T (2005) Extent of lesions in idiopathic sudden hearing loss with vertigo: study using click and galvanic VEMP. Arch Otolaryngol Head Neck Surg 131:857–862 26. Ozeki H, Iwasaki S, Ushio M, et al (2006) The lesion site of vestibular dysfunction in Ramsay Hunt syndrome. J Vestib Res 16:217–222 27. Fujimoto C, Iwasaki S, Matsuzaki M, et al (2005) The site of lesion in idiopathic bilateral vestibulopathy: study by galvanic VEMP. Acta Otolaryngol 125:430–432 28. Murofushi T, Iwasaki S, Ozeki H, et al (2007) Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a new parameter of VEMP? Clin Neurophysiol 118:1685– 1690 29. Rosengren SM, Todd NPM, Colebatch JG (2005) Vestibular-evoked extraocular potentials produced by stimulation with bone-conducted sound. Clin Neurophysiol 116:1938–1948 30. Chihara Y, Ushio M, Iwasaki S, et al (2007) Vestibular-evoked extraocular potentials by air- conducted sound: another clinical test of the vestibular function. Clin Neurophysiol 118:2745–2751 31. Rosengren SM, Nogajiski JH, Cremer PD, et al (2007) Delayed vestibular evoked response to the eyes and neck in a patient with an isolated brainstem lesion. Clin Neurophysiol 118:2112–2116 32. Shiraishi K, Eura Y, Kato T, et al (1997) Negative potential auditory brainstem response with 3-ms latency in profoundly deaf patients: characteristics and relationship to vestibular evoked response. (in Japanese) J Otolaryngol Jpn 100:1382–1393
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    46 Vestibular EvokedMyogenic Potentials 33. Ochi K, Ohashi T (2001) Sound-evoked myogenic potentials and responses with 3-msec latency in auditory brainstem response. Laryngoscope 111:1818–1821 34. Nong DX, Ura M, Kyuna A, et al (2002) Saccular origin of acoustically evoked short latency negative response. Otol Neurotol 23:953–957 35. Murofushi T, Iwasaki S, Takai Y, et al (2005) Sound-evoked neurogenic responses with short latency of vestibular origin. Clin Neurophysiol 116:401–405 36. Todd NP, Rosengren SM, Colebatch JG (2003) A short latency vestibular evoked potential (VsEP) produced by bone-conducted acoustic stimulation. J Acoust Soc Am 114:3264– 3272 37. Picton TW, Hillyard SA, Krausz HI, et al (1974) Human auditory evoked potentials. I. Evaluation of components. Electroencephalogr Clin Neurophysiol 36:179–190 38. Rosengren SM, Colebatch JG (2006) Vestibular evoked potentials (VsEPs) in patients with severe to profound bilateral hearing loss. Clin Neurophysiol 117:1145–1153
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  • 52.
    Meniere’s Disease andRelated Disorders: Detection of Saccular Endolymphatic Hydrops Introduction Meniere’s disease (MD), a common inner ear disorder, is characterized by recurrent vertigo attacks, fluctuating hearing loss, tinnitus, and a sensation of aural fullness [1]. Guidelines for the diagnosis of MD have been published by the American Academy of Otolaryngology, Head, and Neck Surgery (AAO-HNS) (Table 1) [2]. The incidence of MD varies from 21/100000 to 50/100000 [3–6]. MD develops during middle age and shows a slight female predominance [7]. The combination of vertigo, hearing loss, and tinnitus were reported by Itard (1821) [8]; and histopathological studies of the temporal bone in MD were pub- lished in 1938 by Yamakawa [9] and Hallpike and Cairns [10]. They reported endolymphatic hydrops in the temporal bone of MD patients at autopsy. According to Schuknecht [11], during the early stage of the disease endolymphatic hydrops involves principally the cochlear duct and the saccule. According to Okuno and Sando [12], severe hydrops was observed in the saccule most frequently in their histopathological study of the temporal bone. Therefore, a high incidence of abnor- mal vestibular evoked myogenic potentials (VEMPs) in MD is expected. Incidence of Abnormal VEMPs in Meniere’s Disease In earlier studies, the incidence of abnormal VEMPs was 39% according to Muro- fushi et al. [13] and 54% according to de Waele et al. [14]. We reviewed results of VEMPs of MD patients in our clinic (n = 81; 32 men, 49 women; ages 16–75 years, mean 50.7 years; 95-dBnHL clicks). Among the 81 patients, 39 (48%) had absent VEMPs on the affected side; 8 patients showed decreased VEMP amplitude; and 34 patients had normal VEMPs (Fig. 1). Thus, the overall incidence of abnormal VEMPs in MD patients was 58%. Although MD patients showed absent or decreased VEMPs, they rarely dis- played delayed peaks [15]. Rauch et al. reported an elevated VEMP threshold in Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 49 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_6, © Springer 2009
  • 53.
    50 Vestibular EvokedMyogenic Potentials MD patients and recommended that the threshold be a diagnostic parameter [16]. Rauch et al. also reported a shift of the best frequency of VEMP in MD patients. According to previous studies, the best frequency of VEMP is between 300 and 700 Hz [17–19]. Whereas Rauch et al. reported that the best frequency is 500 Hz in healthy subjects, patients with MD showed less tuning at 500 Hz and shifts of the best frequency to 1000 Hz [16]. We confirmed this tendency (Fig. 2). Table 1. Dainostic scale for Meniere’s disease Certain Meniere’s disease Definite Meniere’s disease, plus histopathological confirmation Definite Meniere’s disease Two or more episodes of vertigo lasting at least 20 min Audiometrically documented hearing loss on at least one occasion Tinnitus or aural fullness Probable Meniere’s disease One definite episode of vertigo Audiometrically documented hearing loss on at least one occasion Tinnitus or aural fullness Possible Meniere’s disease Episodic vertigo without documented hearing loss Sensorineural hearing loss—fluctuating or fixed—with disequilibrium but without definite episodes (from ref. 2) In all scales, other causes must be excluded using any technical method Absent 39 (48%) Decreased 8 (10%) Normal 33 (41%) Increased 1 (1%) Fig. 1. Vestibular evoked myogenic poten- tial (VEMP) responses in Meniere’s disease (MD) patients (n = 81)
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    Meniere’s Disease: Detectionof Hydrops 51 Rauch et al. attributed this shift to the change in resonant frequency in the saccule. Comparison of the amplitudes and/or thresholds of VEMP in 500 Hz with those in 1000 Hz could be a new parameter for VEMP that may be applicable to the diagnosis of endolymphatic hydrops in the saccule. However, there have been no reports concerning the specificity of this phenomenon. Thus, we need to determine if this frequency shift is specific to Meniere’s disease or to endolym- phatic hydrops. Disease Stage and VEMPs According to the guidelines of the AAO-HNS [2], the disease stage of MD is determined by the average hearing level. Young et al. [19] studied VEMP results in relation to the disease stage. Among 40 patients, 6 were classified as having stage I MD. Five of the six patients showed normal VEMPs, and one had aug- mented VEMPs on the affected side. Among the 12 patients classified as having stage II MD, 7 had normal VEMPs, 2 had augmented VEMPs, 4 had decreased VEMPs, and 2 had absent VEMPs. Among the 17 patients with stage III MD, VEMPs were normal in 10, decreased in 4, and absent in 3. Among the five patients classified as having stage IV MD, VEMPS were normal in two, decreased in one, and absent in two. In that study, patients at advanced stages more frequently showed absent or decreased VEMPs than patients at earlier stages. Fig. 2. Frequency characteristics of VEMP responses in healthy subjects (n = 8). Among the three tested frequencies (130 dBSPL), 500-Hz tone bursts tended to evoke the largest responses
  • 55.
    52 Vestibular EvokedMyogenic Potentials Proving Saccular Endolymphatic Hydrops Using VEMPs Several clinical tests (e.g., electrocochleography, glycerol test, furosemide test) have been utilized to provide evidence of endolymphatic hydrops [20–24]. Electrocochleography (ECochG) is a test of auditory evoked potentials, which comprises potentials with short latencies (up to 2 ms). ECochG consists of three components: cochlear microphonics (CM), summating potentials (SPs), and compound action potentials (APs). The origin of CM and SPs is the cochlea, whereas APs derive from the cochlear nerve. The (negative) SPs of MD patients are significantly larger than those of healthy subjects [20, 21]. Such large SPs are thought to reflect distention of the basilar membrane due to endolymphatic hydrops. The ratio of the negative SPs to compound APs (CAPs) has been introduced as a parameter. The upper limit of the normal range of the ratio SPs/CAPs has been set at 0.30–0.40. With the glycerol test, improvement of pure-tone hearing thresholds by glycerol administration, an osmotic agent, has been thought to be caused by a temporary reduction of endolymphatic hydrops in the cochlea [22, 23]. Endolymphatic hydrops has been also reported to exist in the saccule [11, 12], although previous tests were not able to prove it. Murofushi et al. [25], however, proposed the method to prove the evidence of saccular hydrops in combination of VEMPs and glycerol adminis- tration (glycerol VEMP test). We record VEMPs prior to glycerol administration and 3 h after oral glycerol administration (1.3 g/kg body weight) and measure the change ratio (CR) of the VEMP (p13–n23) amplitudes. CR (%) = 100(Aa − Ab)/(Aa + Ab) where Aa is the p13–n23 amplitude 3 h after glycerol administration; and Ab is the p13–n23 amplitude before glycerol administration. The CR of six healthy volunteers was 3.52% ± 14.6% (mean ± SD). The normal range was set at −25.7% to +32.7 % (within the mean ± 2 SD). Among the 17 MD patients (4 men, 13 women; ages 24–72 years), 5 patients showed changes in VEMP amplitudes exceeding the normal range (Fig. 3). Among the 17 patients, 10 had abnormal VEMPs prior to glycerol administration. All the patients who showed significantly large CRs had abnormal VEMPs prior to glycerol administration. Therefore, 50% (5/10) of the patients with abnormal VEMPs showed significant enlargement of VEMP amplitudes due to glycerol administration. Patients with stage II MD most frequently had a positive glycerol VEMP test. The results of glycerol VEMP testing were independent of the conventional glycerol test using pure-tone audiometry. As glycerol VEMP testing can be performed simultaneously with the conventional glycerol test, the glycerol VEMP test can provide supple- mental information to detect endolymphatic hydrops [25, 26].
  • 56.
    Meniere’s Disease: Detectionof Hydrops 53 Drop Attacks in MD and VEMPs In 1936, Tumarkin was the first to describe sudden drop attacks in patients with MD [27]. Patients with MD who suffered from drop attacks suddenly felt a sensa- tion of being pushed to the ground and then fell without loss of consciousness [28]. This phenomenon has been called Tumarkin’s otolithic crisis or a vestibular drop attack (VDA) [3]. It has been thought that VDA occurred with sudden changes in endolymphatic fluid pressure with inappropriate otolith stimulation causing reflex- like vestibulospinal loss of postural tone. The abnormal bursts of neural impulses from the otolithic organs would pass through the lateral vestibulospinal tract (LVST), resulting in loss of postural tone. These hypothesized pathophysiological mechanisms allowed us to assume that the function of the otolithic organ might have some room to change when VDA occurs. In other words, the functions of the otolithic end-organs may be unstable. Ozeki et al. reviewed clinical records of 116 MD patients, finding 3 with VDA [29]. Profiles of the three patients are summarized in Table 2. All three patients showed recovery of VEMP responses spontaneously (patient 2) or after glycerol administration (patients 1 and 3). These results imply that abnormal VEMPs in such patients can be reversible and that their otolithic organs might be unstable. After the bilateral VEMPs of patient 1 disappeared, there were no more drop attacks. At the advanced stage—when bilateral otolithic organs were irreversibly damaged—VDA may no longer occur. Fig. 3. Effects of oral glycerol in a 69-year-old woman with left MD. She showed increased VEMP amplitudes on the left side 3 h after glycerol administration. post-G, after glycerol; pre-G, before glycerol; L, left side; R, right side. (from Fig. 1 of ref. 25, Elsevier, with permission)
  • 57.
    54 Vestibular EvokedMyogenic Potentials Table 2. Summary of results of 3 MD patients with VDA Case no. Sex Affected side Stage (L/R) Age at onset of MD (years) Age at onset of VDA (years) No. of VDAs CP VEMP (L/R) Glycerol VEMP Date of VEMP recording 1 F Bil. 3/3 64 66 12 attacks in 3 years L 5% present/present NA May 1, 1998 present/absent Rt. positive June. 22, 1998 R 23% absent/absent NA Sept. 3, 2001 2 F Bil. 3/3 54 64 40 attacks in 10 years R 33% present/absent NA Feb. 17, 1997 present/absent NA June 22, 1998 present/present NA Jan. 6, 2003 3 M Bil. 2/2 65 70 9 attacks in 3 years R 74% present/absent Lt. positive Dec. 17, 2004 (from Table 1 of ref. 29, Taylor & Francis, with permission) Bil., bilateral; MD, Meniere’s disease; VDA, vestibular drop attack; L/R, left/right; VEMP, vestibular evoked myogenic potentials; CP, canal paresis in the caloric test, left (L) and right (R); NA, not available
  • 58.
    Meniere’s Disease: Detectionof Hydrops 55 VEMPs in Delayed Endolymphatic Hydrops Some people with unilateral profound hearing loss experience a delayed onset of vertigo. Schuknecht called this condition delayed endolymphatic hydrops (DEH) [30]. DEH can be subdivided into two types: ipsilateral and contralateral. Patients diagnosed as having ipsilateral DEH have preexisting sensorineural hearing loss in one ear and subsequent delayed-onset Meniere-type episodic vertigo without fluctuating hearing loss in the other ear. In contrast, patients diagnosed as having contralateral DEH have preexisting sensorineural hearing loss in one ear and subsequent onset of fluctuating hearing loss in the other ear, with or without Meniere-type episodic vertigo. According to Ohki et al. [31, 32], 67% (6/9) of contralateral DEH patients and 75% (9/12) of ipsilateral DEH patients had abnor- mal VEMPs (Table 3). Two of the four patients with ipsilateral DEH in their study had positive glycerol VEMP testing results (Fig. 4). As patients with ipsilateral DEH have profound sensorineural hearing loss on the affected side, it is difficult to prove endolymphatic hydrops using ECochG or the conventional glycerol test. However, with glycerol VEMP testing, it was possible to establish the presence of saccular endolymphatic hydrops in patients with ipsilateral DEH. This is a signifi- cant advantage of glycerol VEMP testing. Fig. 4. Effects of oral glycerol on a 55-year-old woman with left-side ipsilateral delayed endo- lymphatic hydrops. (from Fig. 1 of ref. 32, S. Karger AG, with permission) Table 3. VEMP responses in patients with delayed endolymphatic hydrops Type No. No. with VEMP response Normal Decreased Absent Ipsilateral 12 3 5 4 Contralateral 9 3 0 6
  • 59.
    56 Vestibular EvokedMyogenic Potentials Galvanic VEMPs in Endolymphatic Hydrops Delayed peaks of VEMP are signs of retrolabyrinthine or central lesions [15]. However, as the normal range of VEMP latencies is quite wide, it is difficult to differentiate labyrinthine lesions from retrolabyrinthine lesions with only the latencies of the peaks. Furthermore, in patients with absent VEMPs, we have no information concerning latency. Hence, another method is required for the differ- entiation of lesion sites. Galvanic VEMP has been applied for this purpose [33–35]. As galvanic stimula- tion bypasses the hair cells in the labyrinth and directly stimulates the distal portion of the vestibular nerve, patients with absent acoustic VEMPs due to labyrinthine lesions may have normal responses to galvanic stimuli. In fact, Murofushi et al. showed that patients with absent acoustic VEMPs due to labyrinthine lesions (Meniere’s disease or ipsilateral DEH) have normal galvanic VEMPs, whereas almost all patients with absent acoustic VEMPs due to retrolabyrinthine lesions (acoustic neuroma or other cerebellopontine angle tumor) showed absent or decreased galvanic VEMPs (Fig. 5, Table 4) [35]. Furthermore, Murofushi et al. proposed methods to differentiate lesion sites in patients with still-present VEMPs [36]. Murofushi et al. introduced the ratio of the corrected p13–n23 amplitude to acoustic (tone bursts) stimuli/the corrected amplitude p13g–n23g to galvanic stimuli. Fig. 5. Relation of percent galvanic-evoked myogenic potential asymmetry to CP in the caloric test. Almost all patients in group B (open circles) showed no or decreased responses to galvanic stimulation on the affected side even though their caloric responses were preserved. In contrast, group A patients (filled circles) showed normal responses to galvanic stimulation on the affected side. GA, galvanic VEMP asymmetry; CP, canal paresis. Group A: Meniere’s disease or delayed endolymphatic hydrops. Group B: acoustic neuroma or other cerebellopontine angle tumors. (from Fig. 5 of ref. 35, Elsevier, with permission)
  • 60.
    Meniere’s Disease: Detectionof Hydrops 57 TG (tone burst/galvanic) ratio = CA(p13–n23)/CA(p13g–n23g) where CA(p13–n23) is the corrected amplitude of p13–n23 to tone bursts (500 Hz, 135 dBSPL); and CA(p13g–n23g) is the corrected amplitude of p13g–n23g to galvanic stimuli (3 mA, 1 ms) In 12 healthy volunteers, the TG ratio was 2.28 ± 0.66 (mean ± SD). In 12 patients with endolymphatic hydrops, the TG ratio was 1.16 ± 0.71. Among the 12 patients, 8 had a significantly small TG ratio (below the mean − 2 SD) (Fig. 6). This tendency was not observed in patients with an acoustic neuroma. The combined use of acoustic and galvanic VEMPs seems to be useful for dif- ferentiating labyrinthine lesions from retrolabyrinthine lesions. However, de Waele et al. reported that galvanic VEMPs could be abolished after intratympanic instil- lation of gentamicin in MD patients [37]. Therefore, the diagnostic value of abnor- mal galvanic VEMPs should be subjected to further study. Fig. 6. Tone burst/galvanic ratio (TG) of healthy subjects and patients with endolymphatic hydrops (EH). TG ratios of the affected side of patients were significantly smaller than those of the unaffected side and in healthy subjects. (from Fig. 3 of ref. 36, Elsevier, with permission) Table 4. Results of galvanic-evoked myogenic potentials in patients Groupa Increased Normal Decreased Absent Total A 1 9 0 0 10 B 0 2 2 14 18 Total 1 11 2 14 28 a Group A, Meniere’s disease or delayed endolymphatic hydrops; group B, acoustic neuroma or other cerebellopontine angle tumors
  • 61.
    58 Vestibular EvokedMyogenic Potentials References 1. Hamann KF, Arnold W (1999) Meniere’s disease. Adv Otorhinolaryngol 55:137–168 2. Anonymous (1995) Committee on Hearing and Equilibrium Guidelines for the Diagnosis and Evaluation of Therapy in Meniere’s disease. Otolaryngol Head Neck Surg 113:181–185 3. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 4. Stahle J, Stahle C, Arenberg IK (1978) Incidence of Meniere’s disease. Arch Otolaryngol 104:99–102 5. Shojaku H, Watanabe Y (1997) The prevalence of definite cases of Meniere’s disease in the Hida and Nishikubiki districts of central Japan. Acta Otolaryngol 528:S94–S96 6. Dickins JRE, Graham SS (1990) Meniere’s disease 1983–1989. Am J Otol 11:51–65 7. Friberg U, Stahle J (1999) The epidemiology of Meniere’s disease. In: Harris JP(ed) Meniere’s disease. Kugler, The Hague, pp 17–28 8. Itard JMG (1821) Traite des maladies de l’oreille et de l’audition. Mequignon-Marvis, Paris 9. Yamakawa K (1938) Uber die pathologishe Veranderung bei einem Meniere-Kranken. J Otolaryngol Soc Jpn 4:2310–2312 10. Hallpike CS, Cairns H (1938) Observation on the pathology of Meniere’s syndrome. J Laryngol Otol 53:625–655 11. Schuknecht HF (1993) Pathology of the ear. 2nd edn. Lea & Febiger, Philadelphia 12. Okuno T, Sando I (1987) Localization, frequency, and severity of endolymphatic hydrops and the pathology of the labyrinthine membrane in Meniere’s disease. Ann Otol Rhinol Laryngol 96:438–445 13. Murofushi T, Matsuzaki M, Shimizu K (2000) Vestibular-evoked myogenic potentials in patients with unilateral Meniere’s disease. In: Sterkers O, Ferrary E, Dauman R, et al (eds) Meniere’s disease 1999—update. Kugler, The Hague, pp 353–358 14. de Waele, Tran Ba Huy P, Diard JP, et al (1999) Saccular dysfunction in Meniere’s disease. Am J Otol 20:223–232 15. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127: 1069–1072 16. Rauch SD, Zhou G, Kujawa SG, et al (2004) Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol 25:333–338 17. Todd NP, Cody FW, Banks JR (2000) A saccular origin of frequency tuning in myogenic vestibular evoked potentials? Implications for human responses to loud sounds. Hear Res 141:180–188 18. Welgampola MS, Colebatch JG (2001) Characteristics of tone-burst-evoked myogenic poten- tials in the sternocleidomastoid muscles. Otol Neurotol 22:796–802 19. Young YH, Huan TW, Cheng PW (2003) Assessing the stage of Meniere’s disease using vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 129:815–818 20. Aso S, WatanabeY, Mizukoshi K (1991)Aclinical study of electrocochleography in Meniere’s disease. Acta Otolaryngol (Stockh) 111:44–52 21. Gibson WPR, Moffat DA, Ramsden RT (1977) Clinical electrocochleography in the diagnosis and management of Meniere’s disorder. Audiology 16:389–401 22. Klockhoff I, Lindblom U (1966) Endolymphatic hydrops revealed by glycerol test: prelimi- nary report. Acta Otolaryngol (Stockh) 61:459–462 23. Yazawa Y, Kitahara M, Matsubara H (1990) Clinical factors relating to the positive glycerol test for Meniere’s disease. ORL 52:149–155 24. Futaki T, Kitahara M, Morimoto M (1975) The furosemide test for Meniere’s disease. Acta Otolaryngol 79:419–424 25. Murofushi T, Matsuzaki M, Takegoshi H (2001) Glycerol affects vestibular evoked myogenic potentials in Meniere’s disease. Auris Nasus Larynx 28:205–208
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    Meniere’s Disease: Detectionof Hydrops 59 26. Magliulo G, Cuiuli G, Gigliardi M, et al (2004) Vestibular evoked myogenic potentials and glycerol testing. Laryngoscope 114:338–343 27. Tumarkin A (1936) The otolithic catastrophe: a new syndrome. BMJ 1:175–177 28. Baloh RW, Jacobson K, Winder T (1990) Drop attacks with Meniere’s syndrome. Ann Neurol 28:384–387 29. Ozeki H, Iwasaki S, Murofushi T. (2008) Vestibular drop attack secondary to Meniere’s disease results from unstable otolithic function. Acta Otolaryngol 128:887–891 30. Schuknecht HF (1978) Delayed endolymphatic hydrops. Ann Otol Rhinol Laryngol 87:743–748 31. Ohki M, Matsuzaki M, Sugasawa K, et al (2002) Vestibular evoked myogenic potentials with contralateral delayed endolymphatic hydrops. Eur Arch Otorhinolaryngol 259:24–26 32. Ohki M, Matsuzaki M, Sugasawa K, et al (2002) Vestibular evoked myogenic potentials in ipsilateral delayed endolymphatic hydrops. ORL 64:424–428 33. Watson SRD, Colebatch JG (1998) Vestibulocollic reflexes evoked by short-duration galvanic stimulation in man. J Physiol 513:587–597 34. Watson SR, Fagan P, Colebatch JG (1998) Galvanic stimulation evoked short-latency EMG responses in sternocleidomastoid which are abolished by selective vestibular nerve section. Electroencephalogr Clin Neurophysiol 109:471–474 35. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 36. Murofushi T, Iwasaki S, Ozeki H, et al (2007) Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a new parameter of VEMP? Clin Neurophysiol 118:1685– 1690 37. de Waele, Meguenni R, Freyss G, et al (2002) Intratympanic gentamicin injections for Meniere’s disease: vestibular hair cell impairment and regeneration. Neurology 59: 1442–1444
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    Vestibular Neuritis (Neurolabyrinthitis)and Other Peripheral Vestibulopathies: Detection of Inferior Vestibular Nerve Damage Introduction Vestibular neuritis (vestibular neuronitis, vestibular neurolabyrinthitis, VN) is characterized by prolonged severe vertigo with an acute onset. VN is not accom- panied by cochlear symptoms or any other neurological symptoms [1, 2]. This entity was described by Ruttin in 1909 [3] and by Nylen in 1924 [4]. It was called vestibular neuronitis, and its symptomatology was summarized by Dix and Hallpike [5]; but there is little evidence that the ganglion cells are primarily inflamed. The occurrence rate of VN in Japan was reported to be 3.5 per 100000 popula- tion. The peak age at the time of the vertigo attack was during the fifth to sixth decades [6]. Diagnostic criteria of VN are generally as follows. • A single (or a few) vertigo attack(s) lasting for several hours to several days • Severely damaged peripheral vestibular function usually proven by caloric testing • No cochlear signs or other neurological signs Two causes have been proposed: viral inflammation and vascular disturbance. Although there are only a few studies of the temporal bone pathology of VN, their results have mainly supported the viral theory [7–9]. Of course, VN might be caused by either of the two factors. Vestibular Loss in VN: Complete or Partial? Hypofunction of the peripheral vestibular system unaccompanied by cochlear or other neurological signs must be demonstrated to establish a diagnosis of VN, as mentioned above. Hypofunction of the peripheral vestibular system is usually Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 60 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_7, © Springer 2009
  • 64.
    Vestibular Neuritis (Neurolabyrinthitis)61 revealed by the caloric test or the head impulse test at the yaw axis [10]. These tests mainly reflect functions of the vestibuloocular reflex, especially the lateral semicircular canal-ocular reflex. Previous studies suggested that the vestibular loss due to VN is in the superior vestibular nerve but that the inferior vestibular nerve may be spared [11]. However, clinical tests of the peripheral vestibular system have been focused on the lateral semicircular canal and its afferents, the superior ves- tibular nerve. Furthermore, there are few samples of the temporal bone of the VN, although the disease itself is common. The issue of involvement of the inferior vestibular nerve remains to be clarified. Recently, VEMP became a strong tool for evaluating the function of the saccule and its main afferents, the inferior vestibular nerve. Murofushi et al. reported that 31 of 47 VN patients (66%) in Australia had VEMP responses on the affected side but that 16 patients (34%) had an absence of VEMP responses [1]. Later, Murofushi et al. performed a similar study in Japan. Among the 68 patients (40 men, 28 women; ages 18–78 years) 34 (50%) had normal VEMPs, whereas 31 (46%) and 3 (4%) had absent and decreased VEMPs, respectively (Fig. 1). These results imply that a considerable number of patients with VN could have deficits of functions of the saccule and/or its afferents. Their results suggested that the VN could be subdivided into the total VN and the superior VN (Fig. 2). Involvement of the inferior vestibular nerve was also supported by a study on semicircular canals [12]. Normal 34 (50%) Absent 31 (46%) Decreased 3 (4%) Fig. 1. Vestibular evoked myogenic potential (VEMP) responses in 68 vestibular neuritis (VN) patients
  • 65.
    62 Vestibular EvokedMyogenic Potentials Inferior VN At this stage, one can assume that some dizzy patients might have a damaged inferior vestibular nerve with a spared superior vestibular nerve. In other words, patients could have inferior VN [13] (Fig. 3). As the inferior vestibular nerve is an afferent of the posterior semicircular canal and the major part of the saccule, a damaged inferior vestibular nerve could cause the signs and symptoms, as sum- marized in Table 1. We reviewed 1597 clinical records of the Balance Clinic at the University of Tokyo Hospital [14]. Among the 812 patients who underwent both caloric tests and VEMP tests, 4 patients fulfilled the inclusion criteria of possible inferior VN, as shown in Table 2. During the same period, we had 30 patients with classic VN (total VN and superior VN). Inferior VN might be less frequent than superior VN Fig. 3. Inferior vestibular neuritis Fig. 2. Classification of vestibular neuritis. a Superior vestibular neuritis, b total (superior and inferior) vestibular neuritis
  • 66.
    Vestibular Neuritis (Neurolabyrinthitis)63 Table 1. Assumed clinical signs and symptoms of inferior vestibular neuritis Clinical symptoms Sudden, severe, and prolonged vertigo No auditory or other neurological symptoms Clinical signs Spontaneous tortional-vertical nystagmus Postural imbalance Posterior semicircular canal paresis Paresis of the saccule Preservation of superior vestibular nerve function or total VN because of the anatomical differences in bony canals between the superior vestibular nerve and the inferior vestibular nerve [15]. If the clinical entity of inferior VN were to be established, perhaps a clear diag- nosis could be established in some patients whose diagnosis is in question. Recovery of Vestibular Damage in VN Recovery of equilibrium after a VN attack is achieved by vestibular compensation and recovery of peripheral vestibular functions [16]. Concerning the recovery of peripheral vestibular functions, the recovery of caloric responses (i.e., functions of the lateral semicircular canal and its afferents) have been mainly reported. Accord- ing to Okinaka et al. [17], caloric responses on the affected side of the VN recov- ered to within the normal range in 37.2% at 2 years and in 50.0% at 5 years. Concerning recovery of VEMP after a VN attack, Ochi et al. reported that one of two VN patients with an absence of VEMP responses showed recovery of responses to within the normal range at 15 months [18]. Murofushi et al. sequen- tially recorded VEMPs in 13 patients with total VN. Four of these patients (30.7%) showed recovery of VEMP responses to within the normal range at 2 years (Figs. 4, 5), whereas only one patient (7.6%) showed recovery of caloric responses [19]. These results imply that damage to the inferior vestibular nerve may be reversed more quickly than that to the superior vestibular nerve in total VN. Table 2. Inclusion criteria for possible inferior vestibular neuritis A single vertigo attack lasting at least several hours Damaged saccular function shown as abnormal VEMPs Normal caloric responses on both sides No hearing loss or other neurological signs Exclusion of other diseases VEMP, vestibular evoked myogenic potentials
  • 67.
    64 Vestibular EvokedMyogenic Potentials Lesion Site of VN: Nerve or End-Organ? Generally speaking, it has been believed that the VN lesion is in the vestibular nerve. However, VN might be vestibular labyrinthitis. To clarify the lesion site of VN, we recorded galvanic and click VEMPs in patients with VN [20, 21]. Among those diagnosed as having total VN, patients who showed an absence of caloric responses to ice water and an absence of click VEMPs on the affected side (nine men, two women; ages 38–67 years) were selected.Among them, eight (73%) showed an absence of galvanicVEMPresponses, and three (27%) had normal galvanic VEMP responses (Fig. 6). These results sug- gested that so-called vestibular neuritis could be vestibular labyrinthitis. The fact that clinical VN could also have lesions in the labyrinth is appropriate for the explanation of post-VN benign paroxysmal positional vertigo (BPPV). Although it Fig. 4. VEMP recovery in a 51-year-old man with left VN. a VEMPs 4 days after the attack. b VEMPs 3 months after the attack. c VEMPs 6 months after the attack. d VEMPs 2 years after the attack. The patient showed recovery of VEMP within 6 months, and within 2 years his VEMPs were normalized. L, left side; R, right side. (from Fig. 2 of ref. 19, Taylor & Francis, with permission)
  • 68.
    Vestibular Neuritis (Neurolabyrinthitis)65 Fig. 5. Time courses of recovery of VEMP responses after VN attacks. Gray area represents the normal range. Percent VA, percent VEMP asymmetry. (from Fig. 1 of ref. 19, Taylor & Francis, with permission) Neuritis type Labyrinthitis type click galvanic Fig. 6. VEMPs to clicks and galvanic stimuli in patients with VN. Most of the VN patients showed an absence of responses to both clicks and galvanic stimuli (neuritis type), although some patients showed absent click-induced VEMPs but normal galvanic VEMPs (labyrinthitis type)
  • 69.
    66 Vestibular EvokedMyogenic Potentials is well known that BPPV is frequently experienced after a severe vertigo attack of VN [1], the reason for it is not clear. Inner ear damage due to vestibular labyrinthitis might cause canalolithiasis if the posterior semicircular canal is preserved. Accord- ing to Murofushi et al. [1], post-VN BPPV was observed in 10 of 47 VN patients (21%). As VN could be vestibular labyrinthitis in 27% of the VN patients, it is conceivable that the VN patients with vestibular labyrinthitis and preserved poste- rior semicircular canal had post-VN BPPV. Other Types of Peripheral Vestibulopathy Ramsay Hunt Syndrome Ramsay Hunt syndrome (RHS) is characterized by vestibulocochlear dysfunction in addition to facial paralysis and auricular vesicles [22]. RHS is thought to be caused by reactivation of a latent varicella-zoster virus (VZV) [23]. Although Ramsay Hunt speculated that the infection of the eighth cranial nerve is spread from the geniculate ganglion via a vestibulofacial anastomosis or a vestibuloco- chlear anastomosis, there is the possibility that the VZV might arrive at the laby- rinth through the oval and/or round window from a dehiscent facial nerve canal [22–25]. In the latter case the lesion causing vestibular dysfunction could be in the labyrinth, whereas in the former case it could be in the vestibular nerve. Ozeki et al. applied combined methods of click and galvanic VEMPs to patients with RHS [22]. Their results suggested that some patients have nerve lesions and some have labyrinthine lesions (Fig. 7). In previous studies concerning auditory dysfunction in RHS, lesion sites were retrocochlear in some cases and cochlear in others [22, 26]. In other words, neurophysiological studies suggested that there might be two routes by which the infection spread from the facial nerve to the vestibulocochlear region. Idiopathic Bilateral Vestibulopathy Idiopathic bilateral vestibulopathy (IBV) is a clinical entity proposed by Baloh et al. [27]. IBV represents bilateral dysfunction of the peripheral vestibular system due to unknown causes. Patients with IBV complain of disequilibrium, vertigo, and sometimes oscillopsia (Fig. 8). The following comprise some of the diagnostic criteria for IBV. • Bilateral decreased caloric responses (maximum slow phase eye velocity: 10°/s or slower in the caloric test using ice water) • No associated hearing loss • Exclusion of bilateral vestibular dysfunction by known causes such as menin- gitis or aminoglycoside ototoxicity, among others • Exclusion of familial cases
  • 70.
    click galvanic Neuritis type Labyrinthitistype Fig. 7. VEMPs in response to clicks and galvanic stimuli in patients with Ramsay Hunt syndrome. Some patients showed neuritis-type responses, whereas others showed labyrinthitis- type responses Caloric test (ice water) Max. slow phase eye velocity R: 1 deg/sec L: 0 deg/sec VEMP Stabilometry Pure-tone audiometry Fig. 8. Neurootological and audiological findings from a 75-year-old woman with idiopathic bilateral vestibulopathy (IBV), sequential type. Pure-tone audiometry showed sensorineural hearing loss due to aging. Stabilometry showed disequilibrium. Her VEMPs (95-dBnHL clicks) were normal on the right but absent on the left
  • 71.
    68 Vestibular EvokedMyogenic Potentials Baloh et al. classified IBV into two types: progressive and sequential. The pro- gressive type is characterized by slowly progressive imbalance without episodic vertigo, and the sequential type manifests as recurrent episodes of vertigo accom- panied by persistent imbalance. We found a third type. Some patients diagnosed as having IBV had a single vertigo attack and progressive imbalance. We called this combination the one attack/progressive type. Among the 17 patients (10 men, 7 women; ages 33–75 years), 7 (41%) had the progressive type, 8 (47%) had the sequential type, and 2 (12%) had the one attack/progressive type (Fig. 9). The one attack/progressive type might be a transitional type from the progressive to the sequential type. In these 17 patients (34 ears), click VEMPs were bilaterally absent in 6 patients, unilaterally absent in 6 patients, unilaterally decreased in 2 patients, and bilaterally normal in 3 patients. In other words, 20 of the 34 sides (58%) showed abnormal VEMPs. It means that 14 of the 17 patients (82%) had abnormal VEMP results. These results suggested that the damaged area in patients with IBV could be limited to the superior vestibular nerve region, although some patients showed damage to both the superior and inferior vestibular nerve regions [28]. The study in a limited number of patients suggested that the lesions were mainly in the vestibular nerve [29]. Thus, IBV could be called vestibular neuropathy, which might be an auditory neuropathy (auditory nerve disease) [30–33]. Superficial Siderosis Superficial siderosis (SS) is a neurological disorder caused by the deposition of hemosiderin in the central nervous system [34]. SS has been clinically char- acterized as a combination of sensorineural hearing loss, cerebellar ataxia, and pyramidal signs. Although it is known that 95% of SS patients have progressive sensorineural hearing loss, there are few reports of the precise evaluation of vestibular function of SS [35]. Progressive 7 (41%) Sequential 8 (47%) One attack and progressive 2 (12%) Fig. 9. Classification of patients with IBV according to the clinical course (sequential or progressive)
  • 72.
    Vestibular Neuritis (Neurolabyrinthitis)69 Ushio et al. reported a 64-year-old man with SS who had left total hearing loss and right moderate sensorineural hearing loss. On T2-weighted magnetic resonance imaging (MRI) scans, he showed linear hypointensity and signal losses in the cer- ebellum, the medial surface of the temporal lobe, the midbrain, the pons, the spinal cord, and the eighth cranial nerve (Fig. 10). Auditory brainstem response (ABR) testing showed that he had no response on the left and only wave I on the right. Caloric tests (ice water) did not show responses in either ear. He did not have VEMP responses to either click (95 dBnHL) or galvanic (3 mA, 1 ms) stimulation (Fig. 11). These results suggested that his vestibular loss as well as hearing loss was caused by retrolabyrinthine lesions. VEMP testing is also applicable to rare clinical entities such as SS. Idiopathic Sudden Sensorineural Hearing Loss with Vertigo Approximately 50% of the patients with idiopathic sudden sensorineural hearing loss (ISSHL) could have vestibular symptoms [36], which may occur at the onset of hearing loss or be delayed for hours or days. The histopathological study by Schuknecht revealed atrophy of the saccular macula with hair cell loss, collapse of the saccular wall, and distortion of the otolithic membrane in some temporal bones but no abnormal findings in the utricular maculae and cristae [36]. Therefore, it is conceivable that patients with ISSHL who have vertigo could display abnormal VEMP responses. Iwasaki et al. neurootologically studied 22 patients with ISSHL and vertigo. Among them, 17 (77%) showed abnormal VEMP responses on the affected side, and 10 (45%) had decreased caloric responses [37] (Fig. 12). The study by (a) (b) Fig. 10. Magnetic resonance imaging (MRI) findings from a 64-year-old man with superficial siderosis. a T2-weighted, sagittal section. b T2-weighted, axial section. MRI scans showed linear hypointensity around the cerebellum and brainstem (arrows). (from Fig. 3 of ref. 34, Taylor & Francis, with permission)
  • 73.
    70 Vestibular EvokedMyogenic Potentials Fig. 11. VEMPs to clicks (95 dBnHL) (a) and galvanic stimuli (3 mA, 1 ms) (b) in a 64-year-old man with superficial siderosis. He showed an absence of responses to both stimuli. (from Fig. 2 of ref. 34, Taylor & Francis, with permission) Fig. 12. VEMP responses in 12 patients with idiopathic sudden sensorineural hearing loss with vertigo Cochlea Cochlea + Saccule Cochlea + Canal Cochlea + Saccule + Canal 1/22 4/22 8/22 9/22 36% 18% 5% 41% 36%
  • 74.
    Vestibular Neuritis (Neurolabyrinthitis)71 Iwasaki et al. [37] suggested that patients with ISSHL have damage in the saccule more frequently than in the utricle or semicircular canals. Their findings are con- sistent with histopathological studies. In fact, vestibular symptoms in patients with ISSHL often manifest as unsteadiness. Vestibular symptoms in ISSHL patients could be due to otolithic disorders. Galvanic VEMP study has supported the idea that the lesion in ISSHL is in the labyrinth. References 1. Murofushi T, Halmagyi GM, Yavor RA, et al (1996) Absent vestibular evoked potentials in vestibular neurolabyrinthitis; an indicator of involvement of the inferior vestibular nerve? Arch Otolaryngol Head Neck Surg 122:845–848 2. Strupp M, Brandt T (1999) Vestibular neuritis. Adv Otorhinolaryngol 55:111–136 3. Ruttin B (1909) Zur Differentialdiagnose der Labyrinth- und Hornerverkrankungen. Z Ohrenheilkunde 57:327–333 4. Nylen CO (1924) Some cases of ocular nystagmus due to certain positions of the head. Acta Otolaryngol (Stockh) 6:106–137 5. Dix MR, Hallpike CS (1952) The pathology, symptomatology, and diagnosis of certain common disorders of the vestibular system. Ann Otol 61:987–991 6. Sekitani T, Imate Y, Noguchi T, et al (1993) Epidemiological survey by questionnaire in Japan. Acta Otolaryngol (Stockh) 503:S9–S12 7. Schuknecht HF, Kitamura K (1981) Vestibular neuritis. Ann Otol 90(suppl 78):1–19 8. Nadol JB Jr (1995) Vestibular neuritis. Otolaryngol Head Neck Surg 112:162–172 9. Lyndsay JR, Hemenway WG (1956) Postural vertigo due to unilateral sudden partial loss of vestibular function. Arch Otolaryngol 65:692–706 10. Halmagyi GM, Curthoys IS (1988) A clinical sign of canal paresis. Arch Neurol 45:737–739 11. Fetter M, Dichgans J (1996) Vestibular neuritis spares the inferior division of the vestibular nerve. Brain 119:755–763 12. Aw ST, Fetter M, Cremer PD, et al (2001) Individual semicircular canal function in superior and inferior vestibular neuritis. Neurology 57: 768–774 13. Halmagyi GM, Karlberg M, Curthoys IS, et al (2002) Inferior vestibular neuritis. Ann NY Acad Sci 956:306–313 14. Iwasaki S, Takai Y, Ito K, et al (2005) Abnormal vestibular evoked myogenic potentials in the presence of normal caloric responses. Otol Neurotol 26:1196–1199 15. Goebel JA, O’Mara W, Gianoli G (2001) Anatomic considerations in vestibular neuritis. Otol Neurotol 22:512–518 16. Baloh RW (2003) Vestibular neuritis. N Engl J Med 348:1027–1032 17. Okinaka Y, Sekitani T, Okazaki H, et al (1993) Progress of caloric response of vestibular neuritis. Acta Otolaryngol Suppl 503:18–22 18. Ochi K, Ohashi T, Watanabe S (2003) Vestibular-evoked myogenic potentials in patients with unilateral vestibular neuritis: abnormal VEMP and its recovery. J Laryngol Otol 117:104–108 19. Murofushi T, Iwasaki S, Ushio M (2006) Recovery of vestibular evoked myogenic potentials after a vertigo attack due to vestibular neuritis. Acta Otolaryngol 126:364–367 20. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 21. Murofushi T, Monobe H, Ozeki H, et al (2003) The site of lesions in “vestibular neuritis”: study by galvanic VEMP. Neurology 61:417–418
  • 75.
    72 Vestibular EvokedMyogenic Potentials 22. Ozeki H, Iwasaki S, Ushio M, et al (2006) The lesion site of vestibular dysfunction in Ramsay Hunt syndrome. J Vestib Res 16:217–222 23. Ramsay Hunt J (1979) On herpetic inflammations of the geniculate ganglion, a new syndrome and its complication. J Nerv Ment Dis 34:73–96 24. Fujiwara Y, Yanagihara N, Kurata T (1990) Middle ear mucosa in Ramsay Hunt syndrome. Ann Otol Rhinol Laryngol 99:359–362 25. Murakami S, Nakashiro Y, Mizobuchi M, et al (1998) Varicella-zoster virus distribution in Ramsay Hunt syndrome revealed by polymerase chain reaction. Acta Otolaryngol (Stockh) 118:145–149 26. Abramovich S, Prashe DK (1986) Electrocochleography and brain-stem potentials in Ramsay Hunt syndrome. Arch Otolaryngol Head Neck Surg 112:925–928 27. Baloh RW, Jacobson K, Honrubia V (1989) Idiopathic bilateral vestibulopathy. Neurology 39:272–275 28. Matsuzaki M, Murofushi T (2001) Vestibular evoked myogenic potentials in patients with idiopathic bilateral vestibulopathy. ORL 63:349–352 29. Fujimoto C, Iwasaki S, Matsuzaki M, et al (2005) The site of lesion in idiopathic bilateral vestibulopathy: study by galvanic VEMP. Acta Otolaryngol 125:430–432 30. Kaga K, Nakamura M, Shinogami M, et al (1996) Auditory nerve disease of both ears revealed by auditory brainstem responses, electrocochleography and otoacoustic emissions. Scand Audiol 25:233–238 31. Starr A, Picton TW, Sininger Y, et al (1996) Auditory neuropathy. Brain 119:741–753 32. Sheykholeslami K, Kaga K, Murofushi T, et al (2000) Vestibular function in auditory neuropathy. Acta Otolaryngol 120:849–854 33. Fujikawa S, Starr A (2000) Vestibular neuropathy accompanying auditory and peripheral neuropathies. Arch Otolaryngol Head Neck Surg 126:1453–1456 34. Ushio M, Iwasaki S, Sugasawa K, et al (2006) Superficial siderosis causing retrolabyrinthine involvement in both cochlear and vestibular branches of the eighth cranial nerves. Acta Otolaryngol 126:997–1000 35. Parnes SM, Weaver SA (1992) Superficial siderosis of the central nervous system: a neglected cause of sensorineural hearing loss. Otolaryngol Head Neck Surg 107:69–77 36. Schuknecht HF (1993) Pathology of the ear. 2nd edn. Lea & Febiger, Philadelphia 37. Iwasaki S, Takai Y, Murofushi T (2005) Extent of lesions in idiopathic sudden hearing loss with vertigo: study using click and galvanic VEMP. Arch Otolaryngol Head Neck Surg 131:857–862
  • 76.
    Superior Canal DehiscenceSyndrome and VEMPs: Detection of Hypersensitivity of the Vestibular System to Sound Introduction Hypersensitivity of the vestibular system to sound is known as the Tullio phenom- enon [1]. Clinically, the Tullio phenomenon has been reported in association with various diseases, including congenital syphilis, congenital deafness, Meniere’s disease, and perilymph fistula [2–5]. A fistula opening into the labyrinth (a third window) and pathological contiguity of the tympanoossicular chain and the membranous labyrinth have been assumed to be mechanisms of the Tullio phenom- enon [3, 6]. Sound can induce nystagmus or ocular tilt reaction (skew deviation, ocular torsion, head tilt) in patients with the Tullio phenomenon. Induced nystagmus can be horizontal, vertical, torsional, or mixed [7, 8]. The most effective sound frequen- cies to induce vestibular signs are between 500 and 1000 Hz [1, 7, 8]. According to Colebatch et al. [9], the mean threshold of vestibular evoked myo- genic potential (VEMP) responses to clicks in healthy subjects was 86 dBnHL, and the lowest was 70 dBnHL. The thresholds were lower in the ears of patients with the Tullio phenomenon (<70 dBnHL) than in those of healthy subjects. Another interesting point was a response on the contralateral sternocleidomastoid muscle (SCM). In healthy subjects, there was no response on the contralateral SCM to click stimulation [10], whereas patients with Tullio phenomenon showed negative– positive responses with short latencies on the contralateral SCM. These contralateral responses suggested that the utricule as well as the saccule could respond to clicks on the affected ear because electrical stimulation of utricular afferents had excitatory inputs to the contralateral SCM in addition to inhibitory inputs to the ipsilateral SCM [11]. Large-amplitude VEMPs in patients with Tullio phenomenon could be produced by the summation of responses derived from the saccule and utricule. Superior Canal Dehiscence Syndrome Superior canal dehiscence syndrome (SCDS) is a clinical entity introduced by Minor et al. [5, 12]. This clinical syndrome results from dehiscence of bone overly- ing the superior (anterior) semicircular canal and is characterized by vertigo or Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 73 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_8, © Springer 2009
  • 77.
    74 Vestibular EvokedMyogenic Potentials oscillopsia induced by pressure and/or a loud sound. SCDS is a newly established entity that induces Tullio phenomenon and/or a positive fistula sign. Bone dehis- cence of the superior semicircular canal can be revealed by high-resolution com- puted tomography (CT) scans of the temporal bone (Fig. 1). Vertical-torsional nystagmus or ocular tilt reaction is induced by pressure and/or a loud sound [5, 13–15]. Compared with SCDS cases reported from the United States and European Union countries, reports of SCDS in Japan are rare [16]. The prominent features of VEMPs in patients with SCDS are low-threshold, high-amplitude responses to air-conducted sound [13, 15] (Fig. 2). These features are consistent with hypersensitivity of the vestibular end-organs to sound in patients with SCDS. Although this tendency was also observed with bone-conducted sound Fig. 1. Coronal sections of computed tomography scans in a patient with superior canal dehis- cence (SCD). This patient had bilateral dehiscence. R, right; L, left. (from Fig. 4 of ref. 16, Igakushoin, with permission) Fig. 2. Low thresholds of vestibular evoked myogenic potentials (VEMPs) in a patient with bilateral SCD. (from Fig. 3 of ref. 16, Igakushoin, with permission)
  • 78.
    Superior Canal DehiscenceSyndrome 75 [17], galvanic VEMPs showed a normal threshold [18]. These findings suggested that the hypersensitivity can be found in vestibular end-organs. As eye movements induced by sound and/or pressure were considerably decreased after plugging the superior semicircular canal [5], dehiscence in the superior semicircular canal should cause deflection of the cupula in the crista ampullaris of the superior semicircular canal by sound and/or pressure, resulting in symptoms. Patients with SCDS could have low-tone hearing loss with air–bone gaps at low frequencies on pure-tone audiometry [19–21] (Fig. 3). Hence, it is important to dif- ferentiate SCDS from otosclerosis. VEMPs are useful for this differential diagnosis because patients with otosclerosis show clearly different responses. Patients with otosclerosis have a high threshold of VEMPs in response to air-conducted sound. The mechanism of air–bone gaps in SCDS has been thought to be the following: the third window in the vestibular end-organs (dehiscence on the superior semicir- cular canal) may shunt away acoustic energy from the cochlea to the vestibular portions, resulting in hearing loss of air-conducted sound. In contrast, the presence of the third window might result in more motion of fluid in the inner ear due to bone vibration than the normal condition, leading to better bone-conducted hearing [20, 22, 23]. In other words, air–bone gaps in patients with SCDS seem to be caused by conduction problems in the inner ear; therefore, it should be called “pseudo- conductive hearing loss.” A similar air–bone gap was also reported in patients with large vestibular aqueduct syndrome (LVAS) [24, 25]. The air–bone gap in LVAS might be analo- gous to that in SCDS [23], although speculation that the air–bone gap in LVAS is associated with restricted movement of the stapes was also proposed [25]. As LVAS patients with an air–bone gap showed somewhat lower VEMP thresholds [26], the Fig. 3. Air–bone gaps at low frequencies in SCD. O, hearing level to air-conducted sound; <, hearing level to bone-conducted sound. (from Fig. 1 of ref. 21, Cambridge University Press, with permission)
  • 79.
    76 Vestibular EvokedMyogenic Potentials air–bone gap in LVAS might be caused by a mechanism similar to that responsible for SCDS. VEMP is useful for differentiating conductive hearing loss from pseudo- conductive hearing loss due to conduction problems in the inner ear. Thus, VEMP may contribute pathophysiological insight into hearing loss. References 1. Huizinga E (1935) On the sound reaction of Tullio. Acta Otolaryngol (Stockh) 22:359–369 2. Mayer O, Frase JS (1936) Pathological changes in the ear in late congenital syphilis. J Laryngol Otol 51:683–714 3. Kacker SK, Hinchcliffe R (1970) Unusual Tullio phenomenon. J Laryngol Otol 84: 155–166 4. Fox EJ, Balkany TJ, Arenberg IK (1988) The Tullio phenomenon and perilymph fistula. Otolaryngol Head Neck Surg 98:88–89 5. Minor LB, Solomon D, Zinreich JS, et al (1998) Sound- and/or pressure-induced vertigo due to bone dehiscence of the superior semicircular canal. Ach Otolaryngol Head Neck Surg 124:249–258 6. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 7. Kwee HL (1976) The occurrence of the Tullio phenomenon in congenitally deaf children. J Laryngol Otol 90:501–507 8. Vogel P, Tackmann W, Schmidt FJ (1986) Observations on the Tullio phenomenon. J Neurol 233:136–139 9. Colebatch JG, Day BL, Brostein AM, et al (1998) Vestibular hypersensitivity to clicks is characteristic of the Tullio phenomenon. J Neurol Neurosurg Psychiatry 65:670–678 10. Murofushi T, Ochiai A, Ozeki H, et al (2004) Laterality of vestibular evoked myogenic potentials. Int J Audiol 43:66–68 11. Kushiro K, Zakir M, Ogawa Y, et al (1999) Saccular and utricular inputs to sternocleidomas- toid motoneurons of decerebrate cat. Exp Brain Res 126:410–416 12. Minor LB (2000) Superior canal dehiscence syndrome. Am J Otol 21:9–19 13. Brantberg K, Bergenius J, Tribukait A (1999) Vestibular-evoked myogenic potentials in patients with dehiscence of the superior semicircular canal. Acta Otolaryngol (Stockh) 119:633–640 14. Halmagyi GM, Curthoys IS, Colebatch JG, et al (2005) Vestibular responses to sound. Ann NY Acad Sci 1039:54–67 15. Streubel SO, Cremer PD, Carely JP, et al (2001) Vestibular evoked myogenic potentials in the diagnosis of superior semicircular canal dehiscence. Acta Otolaryngol 545:S41–S49 16. Suzuki M, Kaga K, Nakamura M, et al (2003) Superior canal dehiscence syndrome (in Japanese). Jibiinkouka-Tokeibugeka 75:23–26 17. Brantberg K, Lofqvist L, Fransson PA (2004) Large vestibular evoked myogenic potentials in response to bone-conducted sounds in patients with superior canal dehiscence syndrome. Audiol Neurotol 9:173–182 18. Watson SRD, Halmagyi GM, Colebatch JG (2000) Vestibular hypersensitivity to sound (Tullio phenomenon): structural and functional assessment. Neurology 54:722–728 19. Minor LB, Carey JP, Cremer PD, et al (2003) Dehiscence of bone overlying the superior canal as a cause of apparent conductive hearing loss. Otol Neurotol 24:270–278 20. Mikulec AA, KcKenna MJ, Ramsey MJ, et al (2004) Superior semicircular canal dehiscence presenting as conductive hearing loss without vertigo. Otol Neurotol 25:121–129 21. Halmagyi GM, Aw ST, McGarvie LA, et al (2003) Superior semicircular canal dehiscence simulating otosclerosis. J Laryngol Otol 117:553–337
  • 80.
    Superior Canal DehiscenceSyndrome 77 22. Rosowski JJ, Songer JE, Nakajima HH, et al (2004) Clinical, experimental, and theoretical investigations of the effect of superior semicircular canal dehiscence on hearing mechanism. Otol Neurotol 25:323–332 23. Songer JE, Rosowski JJ (2005) The effect of superior canal dehiscence on cochlear potential in response to air-conducted stimuli in chinchilla. Hear Res 210:53–62 24. Merchant SN, Nakajima H, Halpin C, et al (2007) Clinical investigation and mechanism of air-bone gaps in large vestibular aqueduct syndrome. Ann Otol Rhinol Laryngol 116: 532–541 25. Nakashima T, Ueda H, Furuhashi A, et al (2000) Air-bone gap and resonant frequency in large vestibular aqueduct syndrome. Am J Otol 21:671–674 26. Sheykholeslami K, Schmerber S, Kermany MH, et al (2004) Vestibular-evoked myogenic potentials in three patients with large vestibular aqueduct. Hear Res 190:161–168
  • 81.
    Migraine-Associated Vertigo andVEMPs: Detection of Vestibular Signs in a Common but Unclear Entity Introduction It has been recognized that migraine may cause recurrent vertigo/dizziness [1], which is called migraine-associated vertigo (MAV) [2, 3]. The association between migraine and vertigo has been supported by several epidemiological studies [4, 5], and recently some diagnostic criteria for MAV have been proposed (Table 1) [1, 3, 4]. MAV can be observed in patients with migraine without an aura as well as migraine with an aura [6]. According to Iwasaki et al. [2], the average age of 33 patients diagnosed as having MAV—based on the criteria of Brantberg et al. [3]—was 40 years (range 18–62 years), with a female predominance (23 women, 10 men). The median age at onset of migraine was 27.5 years, and the median years predating the onset of vertigo was 7.5 years. Of the 33 patients, 18 (55%) had migraine without an aura and 15 (45%) had migraine with an aura. Rotational vertigo was noted in 24 of the 33 (73%) patients. Nonspecific dizziness and positional vertigo were also noted in five and four patients, respectively. The duration of the vertigo attack ranged from a few minutes to 3 days (Table 2). Most of the patients had vertigo attacks lasting 5 min to 24 h. Approximately 60% of the patients (20/33) had some cochlear symp- toms during the attacks, among which bilateral tinnitus and bilateral aural fullness were the most frequent (27% and 24%, respectively) (Table 3). VEMPs and Other Neurootological Test Results Canal paresis (CP) in caloric tests is observed in some patients with MAV. The incidence of CP in previous reports ranged from 10% to 20% [2, 7, 8]. Horizontal spontaneous nystagmus was also observed by electronystagmography in some patients. Abnormal findings in pursuit, saccade, and the optokinetic nystagmus test (which suggest central disorders) are rare in patients with MAV, whereas abnormal findings suggesting central disorders are frequently observed in patients with basilar-type migraine [9]. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 78 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_9, © Springer 2009
  • 82.
    Migraine-Associated Vertigo 79 Table1. Diagnostic criteria for migraine-associated vertigo (MAV) Definite migrainous vertigo Recurrent episodic vestibular symptoms of at least moderate severity Current or previous history of migraine according to IHS criteria One of the following migrainous symptoms during at least 2 vertiginous attacks Migrainous headache Photophobia Phonophobia Visual or other aura Other causes ruled out by appropriate investigations Probable migrainous vertigo Recurrent episodic vestibular symptoms of at least moderate severity One of the following Current or previous history of migraine according to IHS criteria Migrainous symptoms during at least two vertiginous attacks Migraine-precipitants before vertigo for more than 50% of attacks (food triggers, sleep irregularities, hormonal changes) Response to migraine medications for more than 50% of attacks Other causes ruled out by appropriate investigations From Neuhauser et al. [5], Wiley-Blackwell, with permission IHS, International Headache Society Table 2. Duration and frequency of MAV attacks. (from ref. 2, Taylor & Francis, with permission) Parameter No. Vertigo duration <5 min 11 (33%) 5–60 min 8 (24%) 1–24 h 13 (39%) >1 day 1 (3%) Vertigo frequency Times per day 6 (18%) Times per week 17 (51%) Times per month 5 (15%) Times per year 5 (15%) Table 3. Associated symptoms during vertigo attacks. (from ref. 2, Taylor & Francis, with permission) Associated symptoms No. Cochlear symptoms 20 (61%) Bilateral aural fullness 8 (24%) Unilateral aural fullness 2 (6%) Bilateral tinnitus 9 (27%) Unilateral tinnitus 3 (9%) Nausea 18 (54%) Headache 16 (48%) Vomiting 4 (12%) Photophobia 3 (9%) Phonophobia 2 (6%) Other symptoms 3 (9%)
  • 83.
    80 Vestibular EvokedMyogenic Potentials Similar to caloric tests, abnormal vestibular evoked myogenic potentials (VEMPs) are seen in some patients. Iwasaki et al. [2] reported that 4 of the 33 patients (12%) showed absent VEMPs on either side. These four patients with absent VEMPs were different from the four patients with CP on the caloric test. These findings suggest that patients with MAV may have asymmetrical peripheral vestibular hypofunction. Liao and Young [10] studied 20 patients with basilar-type migraine (a special form of migraine) [6]. Among the 20 patients, 10 had bilaterally normal responses, 4 had a unilateral absence of response, and 3 had bilaterally absent responses. Furthermore, two patients showed bilaterally prolonged latencies, and one patient showed a unilateral absence of responses and unilaterally prolonged latencies. Patients with basilar-type migraine seem to have abnormal VEMPs more frequently than the general MAV population. Moreover, the lesion sites of basilar type of migraine may be in the central nervous system as well as the peripheral vestibular system. Migraine and Meniere’s Disease As shown in previous studies [1–3], patients with MAV have cochlear symptoms such as aural fullness and/or tinnitus and hypofunction in the peripheral vestibular system. It has been reported that the prevalence of migraine was almost twice as high in patients with Meniere’s disease (MD) as in the control group [11]. Ishiyama et al. [12] reported that patients with MAV have vestibular drop attacks (Tumarkin’s otolithic crisis), which has been considered a symptom of Meniere’s disease [13–15]. These findings suggest that MAV shares some pathophysiology with MD. Murofushi et al. compared frequency tuning in VEMPs of patients with MAV with that of patients with MD. As reported by Rauch et al. [16], patients with MD showed a tendency toward dominant VEMP responses to 1000-Hz tone bursts in comparison with 500 Hz, whereas healthy subjects showed a tendency of dominant responses to 500 Hz. A similar tendency was observed in patients with MAV [17]. This finding might support the existence of common pathophysiology between MAV and MD. Benign Recurrent (Paroxysmal) Vertigo of Childhood The term “benign paroxysmal vertigo of childhood” was coined by Basser in 1964 [18]. This entity is defined as recurrent (five or more) attacks of severe vertigo that resolve spontaneously after minutes to hours with normal neurological functions
  • 84.
    Migraine-Associated Vertigo 81 andnormal electroencephalography between attacks [6]. To represent this entity, I prefer the term benign recurrent vertigo (BRV) to benign paroxysmal vertigo because the latter can be confused with benign paroxysmal positional vertigo. BRV has been considered a migraine equivalent or migraine precursor. BRV is a major cause of vertigo in children [19, 20] (Fig. 1). Ozeki et al. did not find clear peripheral vestibular weakness in patients with BRV. Chang and Young found that 30% of the patients had abnormal caloric responses, and 50% had abnormal VEMP responses. Vestibular functions in BRV between and during attacks should be further studied [19, 21]. References 1. Neuhauser H, Lempert T (2004) Vertigo and dizziness related to migraine: a diagnostic challenge. Cephalalgia 24:83–91 2. Iwasaki S, Ushio M, Chihara Y, et al (2007) Migraine-associated vertigo: clinical character- istics of Japanese patients and effect of lomerizine, a calcium channel antagonist. Acta Otolaryngol 559:S45–S49 3. Brantberg K, Trees N, Baloh RW (2005) Migraine-associated vertigo. Acta Otolaryngol 125:276–279 4. Furman JM, Marcus DA, Balaban CD (2003) Migrainous vertigo: development of a patho- genic model and structured diagnostic interview. Curr Opin Neurol 16:5–13 5. Neuhauser H, Leopold M, von Brevern M, et al (2001) The interrelations of migraine, vertigo, and migrainous vertigo. Neurology 56:436–441 Fig. 1. Causes of vertigo/dizziness in 38 children. BRV, benign recurrent vertigo; BPPV, benign paroxysmal positional vertigo; VN, vestibular neuritis BRV 8 (25%) Psychogenic dizziness 2 (6%) MD 1 (3%) BPPV 3 (9%) VN 1 (3%) Miscellaneous 17 (53%) N=32
  • 85.
    82 Vestibular EvokedMyogenic Potentials 6. Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders: 2nd Edition. Cephalalgia 24:S1–S160. 7. Dieterich M, Barndt T (1999) Episodic vertigo related to migraine (90 cases): vestibular migraine? J Neurol 246:883–892 8. Cutrer FM, Baloh RW (1992) Migraine-associated dizziness. Headache 32:300–304 9. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 10. Liao LJ, Young YH (2004) Vestibular evoked myogenic potentials in basilar artery migraine. Laryngoscope 114:1305–1309 11. Radtke A, Lempert T, Gresty MA, et al (2002) Migraine and Meniere’s disease: is there a link? Neurology 59:1700–1704 12. Ishiyama G, Ishiyama A, Baloh RW (2003) Drop attacks and vertigo secondary to a non- Meniere otologic cause. Arch Neurol 60:71–75 13. Tumarkin A (1936) The otolithic catastrophe: a new syndrome. BMJ 1:175–177 14. Baloh RW, Jacobson K, Winder T (1990) Drop attacks with Meniere’s syndrome. Ann Neurol 28:384–387 15. Ozeki H, Iwasaki S, Murofushi T (2008) Vestibular drop attack secondary to Meniere’s disease results from unstable otolithic function. Acta Otolaryngol 128:887–891 16. Rauch SD, Zhou G, Kujawa SG, et al (2004) Vestibular evoked myogenic potentials show altered tuning in patients with Meniere’s disease. Otol Neurotol 25:333–338 17. Murofushi T, Ozeki H, Sakata A, et al (2008) Meniere’s disease vs migraine associated vertigo: from a viewpoint of VEMP. In: 25th Barany meeting abstracts 18. Basser LS (1964) Benign paroxysmal vertigo of childhood (a variety of vestibular neuronitis). Brain 87:141–152 19. Ozeki H, Iwasaki S, Murofushi T (2008) Clinical features of vertigo and dizziness in childhood and adolescence with a special reference to benign recurrent vertigo. Equilibrium Res 67:13–17 20. Bower CM, Cotton RT (1995) The spectrum of vertigo in children. Arch Otolaryngol Head Neck Surg 121:911–915 21. Chang CH, Young YH (2007) Caloric and vestibular evoked myogenic potential tests in evaluating children with benign paroxysmal vertigo. Int J Pediatr Otorhinolaryngol 71:495–499
  • 86.
    Acoustic Neuroma andOther Cerebellopontine Angle Tumors: Detecting a Neoplasm in the Cerebellopontine Angle Introduction Acoustic neuromas (ANs) are schwannomas that arise mainly from the vestibular divisionoftheeighthcranialnerve(vestibularnerve)[1].Theyconstitute6%ofintrac- ranial tumors. In recent years, the incidence of newly diagnosed ANs in Denmark was 13 per million population [2]. ANs are classified into two forms: sporadic and neurofibromatosis type 2 (NF2). Sporadic ANs are usually unilateral, whereas NF2 ANs, which are caused by a mutation of chromosome 22 [3], are usually bilateral. The most frequent symptoms of ANs are unilateral hearing loss and tinnitus [4] (Table 1). Hearing loss is usually slowly progressive, although it may be of sudden onset. The audiometric patterns are diverse (Fig. 1). Spinning vertigo is relatively rare because the growth of the tumor is slow. Diagnosis of Acoustic Neuroma There are no exact guidelines for diagnosing AN. When patients have persistent cochlear and/or vestibular symptoms not fully explained by another cause, AN should be considered. Neurootological and audiological tests and neuro-imaging studies are then required, including pure-tone audiometry, auditory brainstem response (ABR) testing, vestibular evoked myogenic potential (VEMP) testing, and the caloric test. Pure-tone audiometry is a screening test for hearing loss. ABRs, VEMPs, and caloric tests are representative physiological tests of the cochlear nerve, inferior vestibular nerve, and superior vestibular nerve, respectively. Mag- netic resonance imaging (MRI) without contrast medium is primarily recommended as a neuro-imaging study (Fig. 2). Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 83 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_10, © Springer 2009
  • 87.
    84 Vestibular EvokedMyogenic Potentials Sensitivity of VEMPs in Acoustic Neuroma Abnormal findings of VEMPs in an AN patient are the absence of responses, decreased amplitudes, and prolonged peak latencies of p13 and/or n23 on the affected side. In our study, 39 of 62 AN patients showed an absence of responses to 95-dBnHL clicks on the affected side, 9 showed decreased amplitudes, and 14 showed normal amplitudes [5]. In other words, 48 of the 62 patients (77%) had abnormal findings concerning the amplitude. Among the 23 patients who exhibited responses on the affected side, 4 (17%) had significantly prolonged peak latencies. Table 1. Chief complaints of acoustic neuroma patients Chief complaint No. Slowly progressive hearing loss 63 (38%) Sudden hearing loss 31 (19%) Tinnitus 28 (17%) Vertigo 14 (8%) Dysequilibrium 9 (5%) Miscellaneous 22 (13%) Total 167 (100%) Fig. 1. Pure-tone audiogram patterns in 65 acoustic neuroma (AN) patients High tone loss 25 Cup-shaped loss 10 No hearing loss or symmetric 7 Flat loss 7 Profound loss 6 Low tone loss 5 Dip-shaped loss 5
  • 88.
    Acoustic Neuroma andOther Cerebellopontine Angle Tumors 85 R Fig. 2. Magnetic resonance imaging (MRI) scan of a 48-year-old woman with a right AN (white arrow). Her pure-tone hearing was normal in both ears Fig. 3. Vestibular evoked myogenic potential (VEMP) responses in 62 AN patients. a Classifica- tion according to amplitudes. b Classification according to latencies Absent a b 39 (63%) Decreased 9 (14%) Normal 14 (23%) Prolonged 4 (17%) Normal 19 (82%) The overall sensitivity of VEMPs in these AN patients was 80% (50/62) (Fig. 3). In the literature, the sensitivity of VEMPs in AN patients has been reported to be 70%–80% [5–8]. Patko et al., who studied 170 patients with AN [7], reported that 130 of the 170 patients (78.8%) showed abnormal VEMPs to click stimulation and that the sensitivity was higher with click stimulation than with 500-Hz tone burst stimulation.
  • 89.
    86 Vestibular EvokedMyogenic Potentials One must consider how to deal with subjects who showed bilateral absence of VEMP responses to clicks. Recently, Ushio et al. studied the sensitivity of VEMPs in AN patients with combined application of clicks and 500-Hz tone bursts [4]. They studied the sensitivity of VEMPs in 167 patients (79 men, 88 women) with unilateral AN. When patients did not display VEMP responses to clicks on either side, they were subjected to 500-Hz tone bursts. When the subjects exhibited bilateral normal responses to 500-Hz tone bursts despite no responses to clicks, they were regarded as being within the normal range. With this method, the sen- sitivity was 81.6% for VEMPs, 80.2% for caloric tests, and 92.7% for ABRs. The sensitivity of the ABR test results was significantly higher than that of the VEMP results (P < 0.01) or the caloric test results (P < 0.01); whereas the sensi- tivities of the VEMP studies and the caloric tests were not significantly different (P = 0.76). Concerning NF2 AN, Wang et al. [9] reported that only one of seven patients showed abnormal VEMPs and speculated that NF2 ANs originated most often from the superior vestibular nerve. However, as their study population was small, further studies concerning VEMP sensitivity for NF2 ANs are required. The sensitivity of VEMPs in AN patients was not as high as that of the ABRs. However, some patients showed abnormal VEMP responses despite normal ABRs [10] (Fig. 4). Furthermore, VEMP tests are applicable to patients with profound sensorineural hearing loss, in whom ABR testing is not applicable. Because of these merits, VEMPs should be included in the neurootological test battery of AN patients. Fig. 4. A 58-year-old woman with left AN who showed normal auditory brainstem responses (ABRs) but absent VEMPs. The white arrow in the MRI scan (right) indicates a small tumor in the internal auditory canal. (from Figs. 1 and 2 of ref. 10, Springer, with permission)
  • 90.
    Acoustic Neuroma andOther Cerebellopontine Angle Tumors 87 Tumor Size and VEMPs According to Ushio et al., the tumors were significantly larger in patients with abnormal caloric responses and in patients with abnormal ABRs. However, they found no significant differences in tumor size between patients with normal and abnormal VEMPs [4]. Murofushi et al. reported that prolonged peak latencies were observed in patients with large tumors (>2 cm) (Fig. 5, Table 2) [5]. Lesion Site Detection Using VEMPs Although absent VEMP responses and decreased VEMP amplitudes are usually regarded as abnormal, these findings are not specific to ANs. In other words, these Fig. 5. MRI scan of a large AN in a 54-year-old man Table 2. Patients with acoustic neuroma and prolonged p13 and/or n23 No. Amplitude p13 (ms) n23 (ms) I–V (ABR) (ms) Tumor size (cm) 1 Normal 14.9 31.2 4.92 2 2 Decreased 14.6 21.2 Only wave I 3 3 Normal 14.4 27.4 5.20 2 4 Decreased 15.0 26.0 5.48 2 (from Table 1 of ref. 5, with permission. Copyright (2001) American Medical Association. All rights reserved) Upper limit of the normal range: p13, 13.5; n23, 25.2; I–V (ABR), interpeak intervals between waves I and V of ABR: 4.4 Boldface values indicate prolonged latencies
  • 91.
    88 Vestibular EvokedMyogenic Potentials abnormal findings could be produced wherever a lesion is in the vestibulocollic pathway. The prolonged latency of p13 and/or n23 can be relatively specific in comparison with amplitudes because prolonged latencies indicate a retrolabyrinthine lesion [5]. However, the incidence of prolonged latencies was not high (17%), and these laten- cies were observed in patients with large tumors. It is one of the reasons that the normal range of the peak latencies of VEMP is too wide to detect a small latency prolongation. Combined use of short-duration galvanic stimulation has been proposed as another method to determine the lesion site [11]. Whereas relatively intense sounds stimulate the vestibular end-organ, especially the saccular macula, galvanic stimuli directly stimulate the vestibular nerve [12]. In fact, patients with Meniere’s disease have normal VEMP responses to galvanic stimulation even though they show an absence of VEMP responses to clicks. In contrast, most patients with ANs have an abnormal galvanic VEMP response and an absence of VEMP responses to clicks [11]. To apply this combined method to patients who have VEMP responses on the affected side, Murofushi et al. introduced a ratio: corrected amplitude to acoustic stimuli/corrected amplitude to galvanic stimuli [13]. They called it the TG ratio (tone burst/galvanic ratio). As described in the chapter “Meniere’s Disease and Related Disorders,” the TG ratio is significantly lower in patients with Meniere’s disease than in healthy controls. In contrast, the TG ratio of patients with AN is within the normal range or higher (Fig. 6). The combined use of acoustic and galvanic VEMPs seems to be useful for determining a lesion site even in subjects who display VEMP responses. Fig. 6. Tone burst/galvanic (TG) ratio of patients with AN compared with those of healthy subjects (Control) and patients with endolymphatic hydrops (Hydrops)
  • 92.
    Acoustic Neuroma andOther Cerebellopontine Angle Tumors 89 Tumor Origin and VEMPs It is well known that ANs arise mainly from the vestibular nerve, which has two divisions: superior and inferior. Some investigators reported almost equal origins in the superior and inferior divisions, whereas others have reported a predominance in the inferior branch [14, 15]. The caloric test mainly reflects the function of the lateral semicircular canal and its afferents, and VEMP mainly reflects the function of the saccule and its afferents. Therefore, one may expect that results of these two tests can indicate the origin of tumors. However, so far we have not obtained posi- tive results in regard to the correlation of test results and the origin of the tumor. This may be because dysfunction can first emerge in a branch other than the branch that is the origin of the tumor. This issue requires more careful study. Other Cerebellopontine Angle Tumors and Lesions The second most common tumor in the cerebellopontine angle (CPA) is meningi- oma (Fig. 7) [16]. The rate of abnormal VEMPs in patients with a meningioma is approximately 80%. Other masses in the CPA have also been reported, including epidermoids, jugular foramen neurinomas, trigeminal neurinomas, arachnoid cysts, chordomas, and metastatic tumors [17]. Occasionally, large aneurysms behave like CPA masses (Fig. 8) [18, 19]. These masses can cause abnormal VEMPs when the inferior vestibular nerve is involved. However, it is difficult to differentiate ANs from other CPA masses using VEMP testing. Fig. 7. MRI scan of a left-side cerebellopontine angle meningioma, coronal section
  • 93.
    90 Vestibular EvokedMyogenic Potentials References 1. Jackler RK, Pfister MHF (2005) Acoustic neuroma (vestibular schwannoma). In: Jackler RK, Brackmann DE (eds) Neurotology second edition. Mosby, St. Louis, pp 727–782 2. Tos M, Stangerup SE, Caye-Thomasen P, et al (2004) What is the real incidence of vestibular schwannoma? Arch Otolaryngol Head Neck Surg 130:216–220 3. Rouleau GA, Wertelecki W, Haines JL, et al (1987) Genetic linkage of bilateral acoustic neurofibromatosis to a DNA marker on chromosome 22. Nature 329:246–248 4. Ushio M, Murofushi T, Iwasaki S, et al (2008) Diagnostic value of vestibular evoked myo- genic potentials (VEMPs) in patients with acoustic neuroma. In: 25th Barany meeting abstracts 5. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127: 1069–1072 6. Takeichi N, Sakamoto T, Fukuda S, et al (2001) Vestibular evoked myogenic potential (VEMP) in patients with acoustic neuromas. Auris Nasus Larynx 28:s39–s41 7. Patko T, Vidal PP, Vibert N, et al (2003) Vestibular evoked myogenic potentials in patients suffering from an unilateral acoustic neuroma: a study of 170 patients. Clin Neurophysiol 114:1344–1350 8. Murofushi T, Matsuzaki M, Mizuno M (1998) Vestibular evoked myogenic potentials in patients with acoustic neuromas. Arch Otolaryngol Head Neck Surg 124:509–512 9. Wang CP, Hsu WC, Young YH (2005) Vestibular evoked myogenic potentials in neurofibro- matosis 2. Ann Otol Rhinol Laryngol 114:69–73 Fig. 8. Computed tomography scan (left) and angiographic findings (right) of a posterior inferior cerebellar artery (PICA) aneurysm. (from Figs. 3 and 4 of ref. 19, Igakushoin, with permission)
  • 94.
    Acoustic Neuroma andOther Cerebellopontine Angle Tumors 91 10. Matsuzaki M, Murofushi T, Mizuno M (1999) Vestibular evoked myogenic potentials in acoustic tumor patients with normal ABR. Eur Arch Otorhinolaryngol 256:1–4 11. Murofushi T, Takegoshi H, Ohki M, et al (2002) Galvanic-evoked myogenic responses in patients with an absence of click-evoked vestibulo-collic reflexes. Clin Neurophysiol 113:305–309 12. Watson SRD, Colebatch JG (1998) Vestibulocollic reflexes evoked by short-duration galvanic stimulation in man. J Physiol 513:587–597 13. Murofushi T, Iwasaki S, Ozeki H, et al (2007) Tone burst-galvanic ratio of vestibular evoked myogenic potential amplitudes: a new parameter of VEMP? Clin Neurophysiol 118: 1685–1690 14. Slattery WHT, Brackmann DE, Hitselberger W (1997) Middle fossa approach for hearing preservation with acoustic neuromas. Am J Otol 18:596–601 15. Komatsuzaki A, Tsunoda A (2001) Nerve origin of the acoustic neuroma. J Laryngol Otol 115:376–379 16. Kendall B, Symon L (1977) Investigation of patients presenting with cerebellopontine angle syndromes. Neuroradiology 13:65–84 17. Iwasaki S, Ito K, Takai Y, et al (2004) Chondroid chordoma at the jugular foramen causing retro-labyrinthine lesion in both the cochlear and vestibular branches of the eighth cranial nerve. Ann Otol Rhinol Laryngol 13:82–86 18. Chihara Y, Iwasaki S, Ushio M, et al (2008) Fusiform aneurysm of the basilar artery present- ing as a cerebellopontine angle mass. Eur Arch Otorhinolaryngol (published online March 5, 2008) 19. Murofushi T, Mizuno M (1990) Cerebellopontine angle syndrome due to an anerysm of posterior cerebellar artery: report of a case. (in Japanese) Jibiinkoka-Tokeibugeka 62:1089–1093
  • 95.
    Disorders of theCentral Nervous System and VEMPs: Detecting Lesions in the Vestibulospinal Pathway Introduction As vestibular evoked myogenic potential (VEMP) testing has been regarded as a clinical test of the saccule and its afferents, it has been mainly applied to diseases of the peripheral vestibular system. However, because the neural pathway of VEMPs includes the vestibulospinal tract in the brainstem, it could also detect disorders in the vestibulospinal tract, especially the medial vestibulospinal tract. The application of VEMP testing to diseases that mainly affect the central nervous system (CNS) are discussed in this chapter. Multiple Sclerosis Multiple sclerosis (MS) is the most common disease caused by an inflammatory demyelinating process in the CNS. MS is characterized pathologically by multifo- cal areas of demyelination with relative preservation of axons, resulting in much reduced conduction velocity [1]. It is clinically characterized by dissemination of signs and symptoms over space and time. McDonald et al. have proposed new diagnostic criteria for MS [2]. Evoked potentials such as auditory brainstem responses (ABRs), somatosensory evoked potentials (SEPs), and motor evoked potentials by transcranial magnetic stimulation, among others, have been utilized in the clinical setting [3, 4]. As it has been reported that vertigo is a symptom in 30%–50% of MS patients, it is expected that VEMP testing in MS patients may reveal abnormal findings. Shimizu et al. [5] first reported VEMP results in three patients with definite MS. All three patients had high-intensity areas on T2-weighted magnetic resonance imaging (MRI) in the areas involving the vestibulospinal tract and prolonged peak latencies of VEMPs (Fig. 1). Later, Murofushi et al. reported that all of their six patients with MS had abnormal VEMPs (prolonged latencies or absent responses) [6]. These patients had disequilibrium and/or vertigo as symptoms. Therefore, the Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 92 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_11, © Springer 2009
  • 96.
    Detecting Lesions inthe Vestibulospinal Pathway 93 sensitivity of VEMP testing in overall patients with MS remains to be clarified. According to Versino et al. [7], abnormal VEMP responses were seen in 31% of MS patients; and Bandini et al. [8] reported prolonged p13 latencies in 42% of MS patients. This rate was much higher in patients with a history or signs/symptoms of brainstem dysfunction. With all the studies of VEMPs in MS, the main abnormal finding was prolonga- tion of the peak latencies. This point distinguishes MS from other diseases with peripheral disorder. VEMP testing is a valuable tool for detecting demyelination in the vestibulospinal tract of MS patients. Recently, in addition to VEMPs in cervical muscle (cVEMP), VEMPs around the eye (oVEMP) have been recorded. cVEMPs reflect the function of the vestibu- locollic reflex, and oVEMPs seem to reflect that of the vestibuloocular reflex. The combined use of cVEMPs and oVEMPs might be useful for determining the site of the lesion in the brainstem [9]. Spinocerebellar Degeneration Spinocerebellar degeneration, one of the clinical entities causing disorders of the central vestibular system, is characterized by cerebellar and/or spinal ataxia. It Fig. 1. Magnetic resonance imaging (MRI) (left) and vestibular evoked myogenic potential (VEMP) (right) findings from a 30-year-old woman diagnosed with multiple sclerosis. (from Figure of ref. 5, BMJ Publishing Group, with permission)
  • 97.
    94 Vestibular EvokedMyogenic Potentials consists of a sporadic type and a hereditary type. The hereditary type contains autosomal recessive ataxias such as Friedreich’s ataxia and autosomal dominant ataxias such as spinocerebellar ataxia-1 (SCA1) [10]. There are only a few reported studies concerning VEMPs in spinocerebellar degeneration. Takegoshi and Murofushi studied VEMPs (click stimulation) in patients with spinocerebellar degeneration [11]. Patients with olivopontocerebellar atrophy and cerebellar cortex atrophy had normal VEMP responses on both sides. In contrast, patients with Machado-Joseph disease (MJD, SCA3) showed an absence of responses and prolonged latencies. Among the five patients with MJD in whom we recorded VEMPs (including the three patients reported by Takegoshi and Murofushi), one patient showed normal responses on both sides, whereas the other four patients showed an absence of responses or prolonged latencies at the first recording (Fig. 2). A 63-year-old man with MJD had prolongation of latencies on both sides at the first recording, and 1 year later these responses were abolished (Fig. 3). The progression of the disease is reflected in the VEMP responses. The site of the lesion causing abnormal VEMPs in MJD remains unclear. It is known that patients with MJD show an absence of caloric responses at the early stage of the disease [12, 13] and that peripheral sensory nerves can be involved in MJD [14]. Therefore, it is most likely that abnormal VEMPs in MJD may be attributed to lesions in the vestibular nerve. However, lesions in the vestibulospinal tract and in the labyrinth might have some effect. More studies are required concerning VEMPs in patients with spinocerebellar degeneration, including MJD. Normal 3 Prolonged 4 Absent 3 Fig. 2. VEMP responses of patients with Machado-Joseph disease (n = 10 sides of five patients)
  • 98.
    Detecting Lesions inthe Vestibulospinal Pathway 95 Brainstem Infarction A vascular accident in the brain can cause damage to vestibular nerve fibers, ves- tibular nuclei, and the vestibulospinal tract. These substrates are involved in the neural pathway of VEMPs, and patients with a brainstem infarction may show abnormal VEMPs. So far, reports of VEMPs in patients with brainstem/cerebellar infarction are scarce [15–17]. Itoh et al. reported that patients with upper brainstem infarction had normal VEMPs and abnormal ABRs, and patients with infarction in the middle brainstem or the lower brainstem have abnormal VEMPs. Patients with middle brainstem infarction have abnormal ABRs, whereas those with lower brain- stem infarction have normal ABRs [15]. Wallenberg syndrome (WS), or lateral medullary infarction, is a clinical entity that involves the vestibular nuclei (Fig. 4). WS is caused by occlusion of the ver- tebral artery or arteries arising from the vertebral artery [18]. Dieterich and Brandt reported ocular motor abnormalities in 36 patients with WS [19]. Almost all of the patients exhibited gaze-evoked nystagmus and lateropulsion of the closed eyes, and 16 of the 36 patients had skew deviation (hypotropia) of the ipsilateral eye. In the report by Itoh et al. [15], VEMPs were normal in some patients. This result is not surprising because WS does not always involve the entire area of the vestibular Fig. 3. VEMPs (95-dBnHL clicks) from a man with Machado-Joseph disease. At the first record- ing, he showed bilateral prolonged latencies on both sides. One year later, he showed no response. L, left side; R, right side. MRI showed atrophy of the pons and cerebellum
  • 99.
    96 Vestibular EvokedMyogenic Potentials nuclei. When the lateral and descending vestibular nuclei were spared, VEMPs were intact. Correlation of the area of infarction and VEMP responses should be studied in the future. References 1. Olek MJ, Dawson DM (2004) Multiple sclerosis and other inflammatory demyelinating dis- eases of the central nervous system. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds) Neurology in clinical practice. 4th edn. Butterworth Heinemann, Philadelphia, pp 1631–1664 2. McDonald WI, Compston A, Edan G, et al (2001) Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the Diagnosis of Multiple Sclerosis. Ann Neurol 50:121–127 3. Chiappa KH (1988) Use of evoked potentials for diagnosis of multiple sclerosis. Neurol Clin 6:1–88 4. Kalkers NS, Strijers RLM, Jasperse MMS, et al (2007) Motor evoked potential: a reliable and objective measure to document the functional consequences of multiple sclerosis? Relation to disability and MRI. Clin Neurophysiol 138:1332–1340 5. Shimizu K, Murofushi T, Sakurai M, et al (2000) Vestibular evoked myogenic potentials in multiple sclerosis. J Neurol Neurosurg Psychiatry 69:276–277 6. Murofushi T, Shimizu K, Takegoshi H, et al (2001) Diagnostic value of prolonged latencies in the vestibular evoked myogenic potentials. Arch Otolaryngol Head Neck Surg 127: 1069–1072 Fig. 4. Diffusion-weighted MRI of a 40-year-old man with Wallenberg syndrome. He showed high intensity signal in the right lateral medulla (white arrow)
  • 100.
    Detecting Lesions inthe Vestibulospinal Pathway 97 7. Versino M, Colnaghi S, Callieco R, et al (2002) Vestibular evoked myogenic potentials in multiple sclerosis patients. Clin Neurophysiol 13:1464–1469 8. Bandini F, Beronio A, Ghiglione E, et al (2004) The diagnostic value of vestibular evoked myogenic potentials in multiple sclerosis. J Neurol 251:617–621 9 Rosengren SM, Nogajski JH, Cremer PD, et al (2007) Delayed vestibular evoked responses to the eyes and neck in a patient with an isolated brainstem lesion. Clin Neurophysiol 118:2112–2116 10. Subramony SH (2004) Disorders of the cerebellum, including the degenerative ataxias. In: Bradley WG, Daroff RB, Fenichel GM, Jankovic J (eds) Neurology in clinical practice. 4th edn. Butterworth Heinemann, Philadelphia, pp 2167–2187 11. Takegoshi H, Murofushi T (2000) Vestibular evoked myogenic potentials in patients with spinocerebellar degeneration. Acta Otolaryngol 120:821–824 12. Murofushi T, Mizuno M, Hayashida T, et al (1995) Neuro-otological and neuropathological findings in two cases of Machado-Joseph disease. Acta Otolaryngol (Stockh) 520: S136–S139 13. Gordon CR, Joffe V, Vainstein G, et al (2003) Vestibulo-ocular arreflexia in families with spinocerebellar ataxia type 3 (Machado-Joseph disease). J Neurol Neurosurg Psychiatry 74:1403–1406 14. Kinoshita A, Hayashi M, Oda M, et al (1995) Clinicopathological study of the peripheral nervous system in Machado-Joseph disease. J Neurol Sci 130:48–58 15. Itoh A, Kim YS, Yoshida K, et al (2001) Clinical study of vestibular evoked myogenic potentials and auditory brainstem responses in patients with brainstem lesions. Acta Otolar- yngol 545:S116–S119 16. Chen CH, Young YH (2003) Vestibular evoked myogenic potentials in brainstem stroke. Laryngoscope 113:990–993 17. Pollak L, Kushnir M, Stryjer R (2006) Diagnostic value of vestibular evoked myogenic potentials in cerebellar and lower-brainstem strokes. Neurophysiol Clin 36:227–233 18. Brandt T (1999) Vertigo. 2nd edn. Springer-Verlag, London 19. Dieterich M, Brandt T (1992) Wallenberg’s syndrome: lateropulsion, cyclorotation and subjective visual vertical in 36 patients. Ann Neurol 31:399–408
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  • 102.
    Neurootological Application ofVEMP Recording During Infancy and Childhood Introduction Vestibular evoked myogenic potential (VEMP) recording is a new tool for explor- ing the pathways of the sacculus, inferior vestibular nerve, vestibular nucleus, and sternocleidomastoid muscles (SCMs) in pediatric otology and neurotology. Child Development and VEMPs There have been few studies of the feasibility of recording VEMPs in infants and small children, much less the characteristics of this response in neonates. Although the muscle tone of neonates and young infants is poor compared with that of grown children and adults, it is possible to record VEMPs from the SCM during infancy and early childhood. Sheykholeslami et al. [1] reported that reproducible biphasic VEMPs are recorded from the SCM of all the infants they examined (12 healthy infants and children, ages 1–12 months) using loud and short-tone burst sounds. Typical developmental changes in VEMPs in infants and children are shown in Fig. 1 [2]. In these normal infants and children, air-conducted sound evoked a biphasic response (p13 and n23 peaks) of VEMPs that were of larger amplitude and shorter latency than those in adults. The difference in VEMPs on the side of the stimulated ear is due to developmental changes in the distance of the pathway between the sacculus and the SCM and changes in the strength of muscles. However, neonatal VEMPs varied in amplitude, with consistent timing for peak p13 but shorter peak n23 latencies than those in adult VEMPs. The difficulties we encountered during VEMP recording in this study were as follows: 1) We had difficulty maintaining the desired electromyographic (EMG) activity of the SCM during the period of data acquisition, which required several interruptions of the recording session and restarting data collection after achieving the same level of muscle contraction. 2) The recording sessions were much longer for infants partly because of the difficulty mentioned above and partly because of the time necessary to educate parents and have their help during the test. 3) Finally, it was necessary to have a technician in the room to position patients and control the muscle contraction level [1]. Vestibular Evoked Myogenic Potential: Its Basics and Clinical Applications. 101 Toshihisa Murofushi and Kimitaka Kaga doi: 10.1007/978-4-431-85908-6_12, © Springer 2009
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    102 Vestibular EvokedMyogenic Potentials Incidence of Normal VEMPs in Infants with Congenital Profound Hearing Loss Can air-conducted sound-induced VEMPs be recorded even in infants with con- genital profound hearing loss? This is an important question. It has been demon- strated that loud clicks generate short-latency VEMPs [3] in normal adults. Pathological human models have also been used to provide further evidence of the vestibular (saccular) origin of the potentials. Colebatch et al. [3] showed that VEMPs were evident at a high incidence in patients with profound sensorineural hearing loss, but that they were abolished in all of their patients who underwent unilateral vestibular neurectomy. These authors also reported that VEMPs were abolished in some but not all patients with unilateral loss of a caloric response after vestibular neuritis. They hypothesized that VEMPs are of vestibular origin and that the saccule is probably an acoustically sensitive organ. In our study, 67% of the 54 ears of 33 children with congenital profound hearing loss showed normal VEMPs (Fig. 2), but 5% of ears of the children showed abnor- mal VEMPs with low amplitude. This is a surprising finding because although they cannot hear air-conducted loud click stimuli at all they have VEMPs, suggesting that VEMP testing may be a new tool to illuminate vestibular activity in deaf infants and children. Fig. 1. Typical developmental changes in vestibular evoked myogenic potentials (VEMPs) in normal infants and children
  • 104.
    Pediatric Neurootological Applicationof VEMPs 103 Sheykholeslami et al. [4, 5] confirmed the saccular origin of this short-latency acoustic response and that a saccular acoustic response persists in the human ear and has a well-defined frequency tuning curve. Currently, recorded VEMPs are induced using various stimuli including clicks [3], tone bursts [4], electrical stimuli [6], bone-conducted sounds [7], and head taps [8]. VEMPs are gaining more atten- tion as a diagnostic and prognostic test for otological and neurotological disorders in infants and children as well as adults. VEMPs and Inner Ear Anomalies Evaluation of residual auditory and vestibular function in patients with inner ear anomalies is a challenging issue in otology and neurotology because of the lack of appropriate tests. Computed tomography (CT) and MRI studies of the temporal bone cannot confirm the types of inner ear anomaly; they can only identify the affected sensory organ and primary afferent nerve in the presence of an inner ear anomaly. Therefore, the promontory test for electroneural hearing, the caloric test, and the rotation chair test for semicircular canal function are performed. VEMP testing is thus a new promising tool for examining sacculovestibular nerve function. Sheykholeslami and Kaga studied VEMPs in seven children with inner ear anomalies, including two with cystic cochleas, three with shortened cochleas, and two with completely absent cochleas [4]. The horizontal semicircular canals were cystic in two patients and absent in five. Posterior semicircular canals were normal Fig. 2. Click-evoked normal VEMPs (right) and audiogram (left) of a child with congenital profound hearing loss
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    104 Vestibular EvokedMyogenic Potentials in two patients, cystic in two, and absent in three. Superior semicircular canals were cystic in three patients, normal in two, and absent in two. The vestibules were normal in six patients and cystic in one. These authors found that all of these patients had short-latency VEMPs in response to 95-dBnHL air-conducted clicks and short-tone bursts; the VEMPs were biphasic and consisted of p13 and n23 peaks (Fig. 3). This study provides additional evidence that the human inner ear Fig. 3. Click-evoked VEMPs (bottom) from a child with an inner ear anomaly (common cavity). Top left Computed tomography (CT) scans of the common cavity. Top right Audiogram
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    Pediatric Neurootological Applicationof VEMPs 105 Fig. 4. Bottom Click-evoked VEMPs (right) and audiogram (left) of a child with a large vestibu- lar aqueduct. Top High-resolution computed tomography and magnetic resonance image of the large vestibular aqueduct of the temporal bone vestibules and inferior vestibular nerves are preserved in patients with these inner ear anomalies. This study supports previous findings that VEMPs in humans have their origin in the inner ear vestibules. VEMPs and a Large Vestibular Aqueduct Vestibular aqueduct (VA) enlargement is a distinct clinical syndrome in the spec- trum of congenital inner ear anomalies. The bony anomaly of the enlarged VA renders the membranous labyrinth vulnerable to sudden fluctuation in pressure, which leads to progression of sensory neural hearing loss after head trauma. Sheykholeslami et al. reported that VEMPs in three patients with a large ves- tibular aqueduct (LVA) had greater amplitude and lower threshold and that the vestibular organ was more responsive to sound and inner ear pressure changes [9]. Figure 4 shows a high-resolution CT image of LVA of the temporal bone and
  • 107.
    106 Vestibular EvokedMyogenic Potentials VEMPs in a child with profound deafness. These authors speculated that abnormal transmission of inner ear volume and pressure to the cerebrospinal fluid space via the widely patent VA and a large deflection of vestibular sensors in the mem- branous labyrinth in response to stapes movements are possible contributors to the generation of high-amplitude, low-threshold VEMPs in patients with LVA. LVA is considered to be the third window, following the oval and round windows, in the labyrinth. VEMPs in Children with Cochlear Implants The cochlear function of both ears is markedly impaired in infants and children who are candidates for cochlear implantation. However, vestibular function is also impaired in 10%–20% of such infants. After cochlear implantation, patients can hear speech sounds, which are converted to electrical signals in a speech pro- cessor; these signals are transmitted to the internal receiver under the scalp and conducted to the electrodes in the cochlea. Thus, cochlear nerves that are stimulated electrically convey information to the central auditory brainstem pathway and auditory cortex. There are two problems for vestibular end-organs after cochlear implantation. One is traumatic damage of vestibular end-organs incurred following insertion of the electrodes of the cochlear implant into the scala tympani. Tien and Linthicum histopathologically analyzed the vestibular apparatus from human temporal bones after cochlear implantation was carried out [10]. They observed significant damage to the vestibular end-organ in approximately half of the temporal bones. Fibrosis of the vestibular apparatus, and osteogenesis neurons were observed in all their patients [10]. The other problem is that electrical stimulation may affect not only the cochlear nerve but also the facial nerve or the vestibular nerve in patients with a multichannel cochlear implant because of current spread. Based on these findings VEMPs are considered useful for evaluating electrical current spread to the inferior vestibular nerve. Jin et al. compared VEMPs before and after surgery [11]. Before surgery, 6 of the 12 children showed normal VEMPs, 1 showed a decrease in the amplitude of VEMPs, and 5 showed no VEMPs.After surgery, with the cochlear implant switched off, 11 showed no VEMPs and one showed decreased VEMPs. These results reveal that even normal VEMPs disappear owing to trauma following electrode insertion. With the cochlear implant switched on, four children showed normal VEMPs, but eight did not (Fig. 5). This can be explained by the fact that these four children’s inferior vestibular nerves were stimulated by the spread of electrical current from the cochlear implant. We questioned why one-third of these children with cochlear implants showed VEMPs but others did not. Later, Jin et al. demonstrated that VEMPs evoked by cochlear implants may be related to an electrical current inten- sity at a comfortable level (C level), particularly in channels that are closer to the apical turn of the cochlea [12].
  • 108.
    Pediatric Neurootological Applicationof VEMPs 107 Fig. 5. Changes in VEMPs before and after cochlear implantation. a Before surgery. b Switched- off cochlear implant (CI) after surgery and switched-on CI after surgery The patients who showed no VEMPs with the cochlear implant switched on may require higher current intensities to elicit clear VEMPs (if they need to be recorded). However, it is difficult to increase current intensity in such children because they feel pain or facial nerve stimulation when the current intensity is higher than the C level. VEMPs of Pediatric Patients with Neurological Diseases VEMPs depend on the higher tonus of the SCM. During VEMP recording, the children were instructed to lift their heads or to turn their heads to the contralateral side to induce hypertonicity in the SCM. In patients who showed hyper- or hypo- tonicity of cervical muscles (e.g., those with cerebral palsy or other forms of severe brain damage characterized by paralysis of extremities), it was not possible to record VEMPs owing to the lack of muscle contraction even when the sacculoin- ferior vestibular nerve was normal. In Fig. 6, VEMPs of a 3-year-old boy who has cerebral palsy due to Pelizaeus-Merzbacher disease are absent, but the auditory brainstem responses show waves I and II only [13]. VEMPs may thus be used as an objective indicator of hyper- or hypotonicity of muscles in these neurological diseases.
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    108 Vestibular EvokedMyogenic Potentials Acknowledgments I thank Dr. K. Sheykholeslami, Dr. Y. Jin, Dr. Y. Shinjo, Dr. H. Takegoshi, and Ms. M. Nakamura for cooperation in this VEMP study. References 1. Sheykholeslami K, Kaga K, Megerin CA, et al (2005) Vestibular-evoked myogenic potentials in infancy and early childhood. Laryngoscope 115:1440–1444 2. Kaga K (2005) Development of balance and motor function achieved by central vestibular compensation. Adv Neurol Sci 49:216–228 3. Colebatch JG, Halmagyi GM, Skuse NF (1994) Myogenic potentials generated by a click- evoked vestibulocollic reflex. J Neurol Neurosurg Psychiatry 57:190–197 4. Sheykholeslami K, Kaga K (2002) The otolithic organ as a receptor of vestibular hearing revealed by vestibular-evoked myogenic potentials in patients with inner ear anomalies. Hear Res 165:62–67 5. Sheykholeslami K, Habiby Kermany M, Kaga K (2001) Frequency sensitivity range of the saccule to bone-conducted stimuli measured by vestibular evoked myogenic potentials. Hear Res 160:58–62 6. Watson SRD, Colebatch JG (1998) Vestibulocollic reflexes evoked by short-duration galvanic stimulation in man. J Physiol 513:587–597 7. Sheykholeslami K, Habiby Kermany M, Kaga K (2001) Bone-conducted vestibular evoked myogenic potentials in patients with congenital atresia of the external auditory canal. Int J Pediatr Otorhinolaryngol 57:25–29 Fig. 6. Auditory brainstem responses (ABRs) and VEMPs of a 3-year-old boy with Pelizaeus- Merzbacher disease. ABRs show waves I and II only. VEMPs were not elicited because of cerebral palsy
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    Pediatric Neurootological Applicationof VEMPs 109 8. Shinjo Y, Jin Y, Kaga K (2007) Assessment of vestibular function of infants and children with congenital and acquired deafness using the ice-water caloric test, rotational chair test and vestibular-evoked myogenic potential recording. Acta Otolaryngol (Stockh) 127:736–747 9. Sheykholeslami K, Schmerber S, Habiby Kermany M, et al (2004) Vestibular-evoked myo- genic potentials in three patients with large vestibular aqueduct. Hear Res 190:161–168 10. Tien HC, Linthicum FH Jr (2002) Histopathologic changes in the vestibular after cochlear implantation. Otolaryngol Head Neck Surg 127:260–264 11. Jin Y, Nakamura M, Shinjo Y, et al (2006) Vestibular-evoked myogenic potentials in cochlear implant children. Acta Otolaryngol (Stockh) 126:164–169 12. Jin Y, Shinjo Y, Akamatsu Y, et al (2008) Vestibular evoked myogenic potentials evoked by multichannel cochlear implant-influence of C levels. Acta Otolaryngol (Stockh) 128: 284–290 13. Kaga K, Tamai F, Kodama M, et al (2005) Three young adult patients with Pelizaeus- Merzbacher disease who showed only waves I and II in auditory brainstem responses but had good auditory perception. Acta Otolaryngol (Stockh) 125:1018–1023
  • 111.
    Subject Index a ABR 83 acoustic/galvanicratio 32 acoustic neuroma 83 auditory neuropathy 68 b background muscle activity 26 basilar-type migraine 78 benign paroxysmal positional vertigo 64 benign paroxysmal vertigo of childhood 80 benign recurrent vertigo 81 best frequency 50 bone-conducted sound 21 bouton type ending 12 brainstem infarction 95 c calyx type ending 12 central nervous system 92 cerebellopontine angle tumor 89 click 25 cochlear implantation 106 comfortable level 106 current spread 106 cystic cochlea 103 d delayed endolymphatic hydrops 55 drop attack 53 e electrocochleography 52 electrode 25 endolymphatic hydrops 52 f facial nerve stimulation 107 frequency tuning characteristics 32 furosemide test 52 g galvanic stimulation 38, 88 galvanic VEMP 56, 88 glycerol test 52 glycerol VEMP testing 55 h horizontal semicircular canal 103 i idiopathic bilateral vestibulopathy 66 inferior vestibular nerve 13, 20, 61 inferior vestibular neuritis 62 inner ear anomaly 103, 105 l labyrinth 9 large vestibular aqueduct 105 lateral vestibulospinal tract 15 laterality of VEMP 28 low VEMP threshold 31 m Machado-Joseph disease 94 macula 9 medial vestibulospinal tract 15, 23 Meniere’s disease 49, 80 migraine 78 . 111
  • 112.
    112 Subject Index migraine-associatedvertigo 78 multiple sclerosis 92 n N3 42 n34–p44 28 neonate 101 neurogenic potential 42 NF2 86 o otolith-ocular reflex 40 otolith organ 9 oVEMP 40 p p13–n23 28 peak latency 30 percent VEMP asymmetry 30 posterior semicircular canal 103 profound hearing loss 102 prolonged latencies 31 prolonged peak latency 84, 92 r Ramsay Hunt syndrome 66 reticulospinal tract 15 s saccule 9 scala tympani 106 Scarpa’s ganglion 13 semicircular canal 9 shortened cochlea 103 spinocerebellar degeneration 93 sternocleidomastoid muscle 17 striola 13 sudden sensorineural hearing loss 69 superficial siderosis 68 superior semicircular canal 104 superior vestibular nerve 13, 22, 61 t tapping 35 third window 106 threshold 31 tone burst 25 Tullio phenomenon 20 Tumarkin’s otolithic crisis 53 u utricle 9 v vertigo in children 81 vestibular neurectomy 102 vestibular neuritis 60 vestibular neurolabyrinthitis 60 vestibular neuropathy 68 vestibular nucleus 14 vestibulocollic reflex 15 vestibuloocular reflex 17, 40 vestibulospinal reflex 15 vestibulospinal tract 92 w Wallenberg syndrome 95 y young infant 101