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Sudden, spontaneous, unilateral loss of vestibular function without simultaneous hearing loss or brain stem signs is generally attributed to a viral infection involving the vestibular nerve and is called acute vestibular neuritis. The clinical hallmarks of acute vestibular neuritis are vertigo, spontaneous nystagmus, and unilateral loss of lateral semicircular function as shown by impulsive and caloric testing. In some patients with vestibular neuritis the process appears to involve only anterior and lateral semicircular function, and these patients are considered to have selective superior vestibular neuritis. Here we report on two patients with acute vertigo, normal lateral semicircular canal function as shown by both impulsive and caloric testing, but selective loss of posterior semicircular canal function as shown by impulsive testing and of saccular function as shown by vestibular evoked myogenic potential testing. We suggest that these patients had selective inferior vestibular neuritis and that contrary to conventional teaching, in a patient with acute spontaneous vertigo, unilateral loss of lateral semicircular canal function is not essential for a diagnosis of acute vestibular neuritis.

In order to test the human angular vestibulo-ocular reflex in the dynamic range of normal head movements, we measured 3-dimensional compensatory eye-movement responses to low-amplitude (10-12 degrees), high-acceleration (3000-4000 degrees/s/s), passive, manually delivered head rotations (head "impulses") in the three planes of the semicircular canals in normal subjects, in subjects who had recovered from surgical unilateral vestibular deafferentation, and in patients after acute unilateral peripheral vestibulopathy, that is, from vestibular "neuritis." We found that canal-plane head impulses away from an intact semicircular canal, that is, toward a lesioned semicircular canal, invariably produce a vestibulo-ocular reflex with permanently low gain, typically less that 0.4 if the lesion is complete. These results are a necessary consequence of primary semicircular canal afferents being driven into inhibitory saturation by rapid angular accelerations. With practice, clinicians can learn to recognize the telltale compensatory saccades that patients with unilateral loss of semicircular canal function will make if asked to look at an earth-fixed target during head impulses in any one of the three semicircular canal planes.

A woman developed brain stem encephalopathy in association with serum anti-Ma2 antibodies and left upper lobe lung mass. T2 weighted MRI of the brain showed abnormalities involving the pons, left middle and superior cerebellar peduncles, and bilateral basal ganglia. Immunohistochemical analysis for serum antineuronal antibodies was confounded by the presence of a non-neuronal specific antinuclear antibody. Immunoblot studies showed the presence of anti-Ma2 antibodies. A premortem tissue diagnosis of the lung mass could not be established despite two CT guided needle biopsies, and the patient died as a result of rapid neurological deterioration. The necropsy showed that the lung lesion was an adenocarcinoma which expressed Ma2 immunoreactive protein. Neuropathological findings included prominent perivascular inflammatory infiltrates, glial nodules, and neuronophagia involving the brain stem, basal ganglia, hippocampus and the dentate nucleus of the cerebellum. Ma2 is an autoantigen previously identified in patients with germ cell tumours of the testis and paraneoplastic brain stem and limbic encephalitis. Our patient's clinical and immunopathological findings indicate that this disorder can affect women with lung adenocarcinoma, and that the encephalitic changes predominate in those regions of the brain known to express high concentrations of Ma proteins.

We studied the effects of 5 mA bilateral or unilateral, bipolar or monopolar, galvanic stimulation on the horizontal vestibulo-ocular reflex (hVOR) in six normal subjects during 0.01, 0.05, 0.1, 0.5 and 1 Hz yaw rotations and in two subjects during high-acceleration, low-amplitude yaw head rotations (head impulses). Bipolar galvanic stimulation induced horizontal nystagmus in all subjects and an asymmetry of the hVOR only during rotations below 0.1 Hz. Monopolar stimulation had no significant effect. The findings suggest that in humans galvanic stimulation affects those primary horizontal semicircular canal neurons that mediate the hVOR via indirect pathways through the velocity storage mechanism.

We measured the guinea pig horizontal vestibulo-ocular reflex (hVOR) to high acceleration impulsive head rotations following a unilateral lateral semicircular canal (LSCC) occlusion. We found a significant hVOR deficit for rotations toward the side of the occluded LSCC and this deficit did not show systematic changes over 3 months. We considered the LSCC nerve was still functional as shown by the normal appearance of the crista of the LSCC ampulla and also electrical stimulation of the LSCC. We conclude that the VOR during angular acceleration in response to high acceleration shows no adaptive plasticity following a unilateral LSCC occlusion.

We describe 4 patients who all simultaneously developed a sudden total or partial unilateral sensorineural hearing loss and an unusual acute peripheral vestibulopathy in the same ear characterized by posterior semicircular canal benign paroxysmal positional vertigo with intact lateral semicircular canal function. Two patients also had ipsilateral loss of otolith function. The vertigo resolved in all 4 patients after particle-repositioning maneuvers. The findings of audiometry and vestibular tests indicated that the lesion responsible for this syndrome was probably located within the labyrinth itself rather than within the vestibulocochlear nerve and that it was more likely a viral vestibulocochlear neurolabyrinthitis than a labyrinthine infarction.

Objectives: To determine the clinical significance of an isolated directional preponderance (DP) on bithermal caloric testing. An isolated caloric DP was defined as a DP, calculated according to the standard Jongkees formula, of > or = 40%, with a spontaneous nystagmus (SN) in darkness of < or = 2 degrees/s and a canal paresis (unilateral weakness) of < or = 25%., Study Design: A retrospective analysis of all 15,542 bithermal caloric tests performed in the authors' department in the previous 10 years to identify all tests with an isolated DP of > or = 40%. This was followed by a review of the clinical data on the 144 patients identified with such a result and then by a telephone or postal follow-up study of these patients. The study group eventually comprised 114 patients; these were patients in whom a clinical diagnosis could be made at the time the caloric test was done, or who responded to requests for follow-up information. The 34 patients in whom a clinical diagnosis could not be made at the time of the caloric test, and who did not respond to requests for follow-up information, were excluded., Study Setting: A balance disorders clinic in a tertiary referral hospital., Intervention: All patients underwent standard bithermal caloric testing. Some of the patients also underwent rotational testing., Outcome Measures: A clinical diagnosis for the cause of the isolated DP, made either at the time of the caloric test or on the basis of information supplied at follow-up by the patient or by the referring physician., Results: Of 114 patients, 39 had benign paroxysmal positioning vertigo, 14 had Ménière's disease, and 5 had migrainous vertigo. Five patients had central nervous system (CNS) disorders, and this was clinically apparent at the time of the caloric test in 4, so that only 1 patient with an isolated DP developed evidence of a CNS disorder after the caloric test was done. In the other 54 patients, no definite diagnosis could be made, but 41 of these 54 were either completely well or much better at follow-up., Conclusions: An isolated DP on caloric testing is usually a transient, benign disorder. About half the patients with an isolated DP have either Ménière's disease or benign paroxysmal positioning vertigo; in most of the other half, no definite diagnosis is made but most of these patients will do well. Only approximately 5% have a CNS lesion and in almost all this is apparent at the time the caloric test is done. In a relapsing-remitting peripheral vestibular disorder such as benign paroxysmal positioning vertigo or Ménière's disease, the mechanism of an isolated DP could be enhanced dynamic gain of ipsilesional medial vestibular nucleus neurons, perhaps as a result of intermittent hyperfunction of primary semicircular canal vestibular afferents. The authors postulate that an isolated DP reflects a gain asymmetry between neurons in the medial vestibular nucleus on either side, caused either by increased sensitivity on one side or by reduced sensitivity on the other, perhaps as an adaptive change in response to abnormal input. In an accompanying article, the authors implement a realistic neural network model in which it is possible to simulate an isolated DP by adjusting the dynamic sensitivity of type 1 medial vestibular nucleus neurons on one side or of type 2 medial vestibular nucleus neurons on the other.

Hypothesis: The purpose of this study was to simulate an isolated directional preponderance (DP) on bithermal caloric testing by constructing a realistic neural network model. The simulation was designed to capture not only the characteristics of the nystagmus response to caloric stimulation but also the response to rotational stimulation in patients with an isolated caloric DP., Background: The nature of an isolated DP--that is, a DP in the absence of a significant spontaneous nystagmus or canal paresis--is outlined in the preceding article. In this article, the authors investigate the possible neural basis for an isolated caloric DP using the mathematic modeling technique of neural network simulation. Neural network models are typically abstract in nature; however, in this case the network was based on the known structure and function of the central vestibular system., Methods: The neural network model was based on the known neuroanatomy and neurophysiology of the horizontal vestibuloocular reflex pathway. A leftward-rightward asymmetric modification of the dynamic responses of simulated medial vestibular nucleus type IA neurons on one side, or of type 2 neurons on the other side, to peripheral input would generate an isolated caloric DP., Results: The values of DP and associated canal paresis produced by the network were within the same range as in the patient group. The network also predicted that the rotational DP would be lower than the caloric DP: between 2.5% and 56.9% of the caloric DP value. The actual rotational DP value was between 3% and 57% (average 41%) of the corresponding caloric DP value., Conclusions: An isolated caloric DP can be simulated by a neural network model by modifying the activity of model units that represent medial vestibular nucleus neurons. An asymmetric dynamic response by a gain-enhancement function of either type 1A neurons on one side or of type 2 neurons on the other was sufficient to produce an isolated caloric DP. Excitatory gain enhancement of type 2 neurons produced a smaller rotational DP than a similar modification of type 1 neurons. This result indicates a potential neural locus for the generation of an isolated DP in patients with vestibular disorders.

Benign paroxysmal positional vertigo (BPPV) originating from the posterior semicircular canal (pSCC) is a common vestibular disorder that is easy to diagnose and usually easy to treat. The majority of patients with BPPV have no known inner ear disease; they have "primary" or "idiopathic" BPPV. However, a minority does have objective evidence of an inner ear disease on the same side as the BPPV and this group has "secondary" or "symptomatic" BPPV. Previous publications differ on the prevalence of secondary BPPV and about the types of inner ear diseases capable of causing it. In order to determine what proportion of patients have secondary as opposed to primary BPPV and which inner ear diseases are capable of causing secondary BPPV, we searched our database for the 10-year period from 1988 to 1997 and found a total of 2847 patients with BPPV. Of these, 81 (3%) had definite pSCC-BPPV secondary to an ipsilateral inner ear disease. Sixteen had Menière's disease, 24 had an acute unilateral peripheral vestibulopathy, 12 had a chronic unilateral peripheral vestibulopathy, 21 had chronic bilateral peripheral vestibulopathy and 8 had unilateral sensorineural hearing loss. It seems that any inner ear disease that detaches otoconia and yet does not totally destroy pSCC function can cause BPPV and that a case can be made for audiometry and caloric testing in all patients with BPPV.

Objective: Complete unilateral loss of vestibular function results in a phase advance (reduced time constant) of the horizontal slow-phase nystagmus response to yaw-axis rotation. The objective of this study was to determine whether partial losses of lateral semicircular canal function would result in proportional reductions in the time constant. SETTING AND STUDY DESIGN: This was a retrospective study of consecutive patients' records at two tertiary referral centers for vestibular disorders., Patients: Four hundred fifty-four patients who presented for evaluation of vertigo or imbalance or both and who were found to have partial or complete unilateral canal paresis on caloric testing., Main Outcome Measures: In 372 patients, the gain and time constant of the horizontal nystagmus response was measured using a 5-second velocity ramp of constant yaw-axis acceleration. Caloric responses to standard bithermal irrigations at 30 degrees and 44 degrees were obtained using an open-loop irrigation system. In a second group of 82 patients, the gain and time constant of the horizontal vestibulo-ocular reflex were measured using a sum-of-sines (pseudorandom) yaw-axis acceleration. The caloric response was measured using a closed-loop system., Results: In both groups, the peak gain of the nystagmus response was independent of the level of the canal paresis. However, the time constant of the response both toward and away from the lesioned side decreased proportionally with increasing canal paresis., Conclusion: This result supports the hypothesis that bilateral symmetrical peripheral vestibular input is a necessary condition for the mechanisms or processes underlying normal horizontal slow-phase velocity storage.

Vertical eye position-dependence of the human vestibuloocular reflex during passive and active yaw head rotations. The effect of vertical eye-in-head position on the compensatory eye rotation response to passive and active high acceleration yaw head rotations was examined in eight normal human subjects. The stimuli consisted of brief, low amplitude (15-25 degrees ), high acceleration (4,000-6,000 degrees /s2) yaw head rotations with respect to the trunk (peak velocity was 150-350 degrees /s). Eye and head rotations were recorded in three-dimensional space using the magnetic search coil technique. The input-output kinematics of the three-dimensional vestibuloocular reflex (VOR) were assessed by finding the difference between the inverted eye velocity vector and the head velocity vector (both referenced to a head-fixed coordinate system) as a time series. During passive head impulses, the head and eye velocity axes aligned well with each other for the first 47 ms after the onset of the stimulus, regardless of vertical eye-in-head position. After the initial 47-ms period, the degree of alignment of the eye and head velocity axes was modulated by vertical eye-in-head position. When fixation was on a target 20 degrees up, the eye and head velocity axes remained well aligned with each other. However, when fixation was on targets at 0 and 20 degrees down, the eye velocity axis tilted forward relative to the head velocity axis. During active head impulses, the axis tilt became apparent within 5 ms of the onset of the stimulus. When fixation was on a target at 0 degrees, the velocity axes remained well aligned with each other. When fixation was on a target 20 degrees up, the eye velocity axis tilted backward, when fixation was on a target 20 degrees down, the eye velocity axis tilted forward. The findings show that the VOR compensates very well for head motion in the early part of the response to unpredictable high acceleration stimuli-the eye position- dependence of the VOR does not become apparent until 47 ms after the onset of the stimulus. In contrast, the response to active high acceleration stimuli shows eye position-dependence from within 5 ms of the onset of the stimulus. A model using a VOR-Listing's law compromise strategy did not accurately predict the patterns observed in the data, raising questions about how the eye position-dependence of the VOR is generated. We suggest, in view of recent findings, that the phenomenon could arise due to the effects of fibromuscular pulleys on the functional pulling directions of the rectus muscles.

We studied individual semicircular canal responses in three dimensions to high-acceleration head rotations ("head impulses") in subjects with known surgical lesions of the semicircular canals, and compared their results to those of normal subjects. We found that vestibular-ocular reflex (VOR) gains at close to peak head velocity in response to yaw, pitch and roll impulses were reliable indicators of semicircular canal function. When compared to normals, lateral canal function showed a 70-80% decrease in VOR gain at peak of yaw head velocity during ipsilesional yaw impulses. After the loss of one vertical canal function there was a 30-50% decrease in vertical and torsional VOR gain in response to ipsilesional pitch and roll impulses respectively. Bilateral deficits in anterior or posterior canal function resulted in a 80-90% decrease in vertical VOR gain during ipsilesional pitch impulses, while the loss of ipsilateral anterior and posterior canal functions will result in a 80-90% decrease in torsional VOR gain in response to ipsilesional roll impulses. Three-dimensional vector analysis and animation of the VOR responses in a unilateral vestibular deafferented subject to yaw, pitch and roll impulses further demonstrated the deficits in magnitude and direction of the VOR responses following the loss of unilateral lateral, anterior and posterior canal functions.

Dual search coils were used to record horizontal, vertical and torsional eye movement components of one eye during nystagmus caused by off-center yaw rotation (yaw centrifugation). Both normal healthy human subjects (n=7) and patients with only one functioning labyrinth (n=12) were studied in order to clarify how the concomitant linear acceleration affected the nystagmus response. Each subject was seated with head erect on the arm of a fixed-chair human centrifuge, 1 m away from the center of the rotation, and positioned to be facing along a radius; either towards (facing-in) or away from (facing-out) the center of rotation. Both yaw right and yaw left angular accelerations of 10 degrees s(-2) from 0 to 200 degrees/s were studied. During rotation a centripetal linear acceleration (increasing from 0 to 1.24xg units) was directed along the subject's naso-occipital axis resulting in a shift of the resultant angle of the gravitoinertial acceleration (GIA) of 51 degrees in the subject's pitch plane and an increase in the total GIA magnitude from 1.0 to 1.59xg. In normal subjects during the angular acceleration off-center there were, in addition to the horizontal eye velocity components, torsional and vertical eye velocities present. The magnitude of these additional components, although small, was larger than observed during similar experiments with on-center angular acceleration (Haslwanter et al. 1996), and the change in these components is attributed to the additional effect of the linear acceleration stimulation. In the pitch plane the average size of the shift of the axis of eye velocity (AEV) during the acceleration was about 8 degrees for a 51 degrees shift of the GIA (around 16% of the GIA shift) so that the AEV-GIA alignment was inadequate. There was a very marked difference in the size of the AEV shift depending on whether the person was facing-in [AEV shift forward (i.e. non-compensatory) of about 4 degrees] or facing-out [AEV shift forward (i.e. compensatory) of around 12 degrees]. The linear acceleration decreased the time constant of decay of the horizontal component of the post-rotatory nystagmus: from an average of 24.8 degrees/s facing-in to an average of 11.3 degrees/s facing-out. The linear acceleration dumps torsional eye velocity in an manner analogous to, but independent of, the dumping of horizontal eye velocity. Patients with UVD had dramatically reduced torsional eye velocities for both facing-in and facing-out headings, and there was little if any shift of the AEV in UVD patients. The relatively small effects of linear acceleration on human canal-induced nystagmus found here confirms other recent studies in humans (Fetter et al. 1996) in contrast to evidence from monkeys and emphasizes the large and important differences between humans and monkeys in otolith-canal interaction. Our results confirm the vestibular control of the axis of eye velocity of humans is essentially head-referenced whereas in monkeys that control is essentially space-referenced.

We tested the hypothesis that the reason some patients compensate well after unilateral vestibular deafferentation (uVD) and others do not could be due to differences in eye-head coordination or in blink characteristics during natural, active head movements. Patients with well-compensated uVDs do not report distressing postural unsteadiness or an aversive sensation of apparent motion of a visual scene (oscillopsia) or "visual confusion" upon rapid head rotation as do those patients with poorly compensated uVDs. It has been suggested that well-compensated subjects eliminate the subjective sensations associated with retinal slip, which must occur as a result of an inadequate vestibuloocular reflex (VOR), either by restricting head movement to the lesioned side or by blinking during head turns. To test this, subjects stood at the curbside of a busy road with a 180 degrees view of regular, fast-moving traffic, which they scanned in preparation of crossing the road, and their eye and head movements and blinks were measured in this natural situation. Both normals and uVDs generated similar ranges of head position, head velocity and gaze magnitude, and all subjects performed a blink during the gaze saccade. Contrary to the hypothesis, no systematic differences were found between normals and either group of uVDs.

This study was designed to measure ocular movements evoked by galvanic (DC) stimulation using computerised video-oculography. Long duration (>30 s) galvanic vestibular stimulation at currents of up to 5 mA through large-area surface electrodes over the mastoid processes causes maintained changes in the ocular torsional position of both eyes in healthy human subjects. With the subject seated and the head held firmly, torsion was measured by a computer-based image-processing system (VTM). Torsion was recorded in darkness, with or without a single fixation point. With bilateral stimulation, the upper poles of both eyes always torted away from the side of cathode placement and toward the anode. For unilateral stimulation, torsion was directed away from the cathode or toward the anode. The magnitude of ocular torsion was dependent on current strength: with bilateral stimulation the peak torsion was on average 2.88 degrees for 5-mA current intensity compared with 1.58 degrees for 3 mA. A smaller amplitude of torsion was obtained for unilateral stimulation. The average peak torsion was the same for both eyes for all forms of stimulation. Our findings indicate that low-intensity galvanic stimulation evokes ocular torsion in normal subjects, an effect which is consistent with an action on otolith afferents.

Systemic gentamicin can cause acute bilateral, simultaneous, symmetrical loss of vestibular function manifested by symptoms and signs of chronic vestibular insufficiency (ataxia and oscillopsia). We report 6 patients presenting with ataxia and oscillopsia, but without a history of vertigo, who had severe unilateral loss of vestibular function on caloric testing. The absence of vertigo in these patients could be explained by two possible mechanisms: either, the unilateral loss of vestibular function was subacute, occurring over several days so that compensation could occur, or bilateral vestibular loss occurred which was then followed by asymmetrical recovery of vestibular function. The second hypothesis is supported by the observation that vestibular hair cells can regenerate after aminoglycoside damage.

We studied the human vestibulo-ocular reflex (VOR) in response to head 'impulses': brief, unpredictable, passive, high-acceleration (up to 4000 degrees/s2), low-amplitude (20-30 degrees) head rotations. We delivered the head impulses approximately in the plane of the semicircular canal (SCC) being tested. To test the anterior and posterior SCCs, the head impulses were delivered in a diagonal plane, midway between the frontal (roll) and sagittal (pitch) planes. We recorded head and eye position in three dimensions with scleral search coils in nine normal subjects, seven patients following unilateral surgical vestibular neurectomy and three patients following unilateral posterior SCC occlusion. In the post-surgical patients we demonstrated a severe, permanent VOR gain deficit (0.2-0.3) for head impulses directed toward any single non-functioning SCC. The sensitivity of the test depends on the physiological properties of primary vestibular afferents, and its specificity depends on the anatomical orientation of the SCCs. The diagonal head impulse is the first test of individual vertical SCC function in humans, and together with the horizontal head impulse, forms a comprehensive battery of SCC-plane tests. These canal-plane impulses could be useful in evaluating patients with vertigo or other vestibular disorders.

We report on a patient who developed primary position upbeat nystagmus (ppUBN) due to a unilateral medial medullary infarction. On oculography, the slow phases of the nystagmus sometimes had an exponentially decreasing velocity waveform, indicating that the nystagmus was due to impairment of the vertical position-to-velocity neural integrator. On magnetic resonance imaging, the lesion was caudal to the vestibular nuclei and to the most rostral of the perihypoglossal nuclei, the nucleus intercalatus, a structure that was also involved in a previously reported case of ppUBN due to a unilateral medullary lesion. On the basis of these imaging and oculographic observations, we propose that a unilateral lesion of the nucleus intercalatus is sufficient to cause ppUBN and that the nucleus intercalatus is a part of the vertical position-to-velocity neural integrator in the human ocular-motor system.

We report the vestibular abnormalities in 5 patients with the CHARGE association (Coloboma, Heart disease, Atresia of choanae, Retarded growth and development and/or central nervous system anomalies, Genital hypoplasia, and Ear anomalies). All patients had absent vestibular function as indicated by absent vestibulo-ocular reflexes and severe imbalance on simultaneous deprivation of proprioception and vision, as well as delayed motor development. All 6 semicircular canals were aplastic in each of the patients. While cochlear function was severely reduced in 6 of the 10 ears, it was absent only in 3 ears and was actually intact below 3 kHz in 1 ear. All 10 bony cochleas were present on computed tomography, and although 7 appeared abnormal, 3 appeared normal. This study confirms that absence of the bony semicircular canals in the presence of a bony cochlea is a characteristic finding in CHARGE association. It also demonstrates that these disproportionate structural abnormalities are reflected in the functional abnormalities: absent vestibular function with preservation of some cochlear function.

To define better the benefits and risks of intratympanic gentamicin injection treatment of intractable vertigo or drop attacks due to Ménière's disease, we reviewed the charts of 18 patients whom we have now observed for > 1 year after having completed this mode of therapy. There were nine women and nine men aged 29-81 years; all had poor hearing in the affected ear. Of the 18 patients, 14 have had no further vertigo or drop attacks (11 patients after a single set of three to five injections, another three after a further set of one to five injections). The treatment could be effective even if it did not abolish caloric responses from the treated ear, even if it did not produce an acute vestibular deafferentation syndrome afterwards, and even after a failed vestibular nerve section. After treatment, five of the 18 patients developed oscillopsia and ataxia--symptoms and signs of (presumably permanent) chronic vestibular insufficiency; this proportion is not obviously lower than that after vestibular neurectomy or surgical labyrinthectomy. Of the 18 patients, 12 showed no change in the 1-kHz threshold and 13 showed no change in the 4-kHz threshold. When hearing did deteriorate, the threshold rose by more than 30 dB at 1 kHz in four patients and at 4 kHz in six patients. We conclude and confirm that intratympanic gentamicin injections are a convenient and, in most cases, effective and safe treatment for intractable vertigo or drop attacks due to Ménière's disease.

Background: Benign paroxysmal positioning vertigo (BPPV) is generally thought to be caused by canalolithiasis in the posterior semicircular canal, an organ that is innervated by the inferior vestibular nerve. We hypothesized that absent vestibular evoked myogenic potentials (VEMPs) would indicate involvement of the inferior vestibular nerve and that posterior semicircular canal-type BPPV could not develop after vestibular neurolabyrinthitis (VNL) in patients with absent VEMPs., Objective: To find out if VEMPs could be helpful in evaluating involvement of the inferior vestibular nerve in acute VNL., Design: We reviewed the VEMP findings in 47 patients (34 men and 13 women) with acute VNL, 10 of whom had then developed posterior semicircular canal-type BPPV., Results: While p13-n23, the first positive-negative peak of the VEMP, was ipsilaterally present on stimulation of the unaffected side in all patients, it was absent on the affected side in 16 patients (34%). The absence or presence of p13-n23 was independent of the results of caloric tests, pure tone audiometry, and auditory brain-stem responses. Typical posterior semicircular canal BPPV developed in 10 of the 47 patients after the acute attack of VNL, always on the same side as the neurolabyrinthitis. The p13-n23 potentials were preserved on stimulation of the affected ear in all 10 patients with BPPV., Conclusions: These results suggest that if VEMPs are absent from an ear that has suffered acute VNL, then posterior semicircular canal BPPV is unlikely to develop as a consequence of the VNL. The reason for this appears to be that the absence of VEMPs is due to involvement of the inferior vestibular nerve or involvement of the structures that it innervates.

We recorded three-dimensional eye movements during angular acceleration steps from 0 to 250 degrees/s at 20 degrees/s2 about an earth-vertical axis. Experiments were performed on 27 normal subjects and on 19 patients who had recovered well from unilateral vestibular deafferentation on the right or left side. In addition to compensatory horizontal eye movements, significant vertical and torsional eye movement components were elicited. These vertical and torsional eye velocity traces led to a shift of the axis of eye velocity away from the axis of head velocity. Horizontal, vertical, and torsional velocity components showed clear differences between normals and patients with unilateral vestibular deafferentation. In normals, the axis of eye velocity tilted backward and slightly away from the axis of head velocity. Patients showed similar, but more pronounced, shifts during rotations toward the intact ear and shifts in the opposite direction for rotations toward the operated ear. Eye velocity traces were analyzed with special consideration given to the orientation of the axis of eye velocity. We speculate that the vertical and torsional velocity components may be due to the effects of Listing's plane, as well as the contributions of the otolith signals.

In recent years, owing to significant technological developments and an increased number of investigators entering the field, there have been spectacular advances in our understanding of the basic anatomy and physiology of the vestibular system. Unfortunately, these advances in basic science are slow to impact the clinical management of patients. We have selected a few important advances in clinical neurotology that have impacted the diagnosis and treatment of patients with vestibular disorders. This material was originally presented at the "Mechanisms of Vestibular Function and Dysfunction" symposium of the 1994 Neural Control of Movement meeting in Waikoloa, Hawaii.

Vestibular sensory input is just one sensory input involved in the control of functions such as gaze and posture. The recovery of gaze and posture control after partial or complete unilateral loss of vestibular input is reviewed. The relatively rapid and apparently complete behavioral recovery after unilateral vestibular loss was once regarded as justifying vestibular compensation being used as a text-book example of plasticity in the CNS. This review emphasizes how false that impression is: Detailed examination shows that vestibular compensation is not a single process that recovers completely at a rapid rate but is made up of a number of subprocesses that recover to different levels and at different rates. In some subprocesses there is very modest recovery; in other subprocesses there is probably substitution of other sensory input for the affected vestibular input. It also seems that in some instances new behavioral strategies appear to be learned to allow gaze and posture control to operate as if normal. Recent evidence concerning the physiological and pharmacological mechanisms underlying vestibular compensation is reviewed.

Responses of single neurons in the vestibular nerve to high-intensity clicks were studied by extracellular recording in anaesthetised guinea pigs. One hundred and two neurons in the posterior division of the superior branch or in the inferior branch of the vestibular nerve were activated at short latency by intense clicks. The latency of activation was short (median 0.9 ms) and the threshold was high: the click intensity for evoking the response of these cells was around 60 dB above the auditory brainstem response threshold. Animals were tilted and rotated to identify physiologically the sensory region of the labyrinth from which the activated neurons originated. Seventeen neurons responded to static tilt as well as clicks. These results show that vestibular receptors, probably the otoliths, respond to clicks at intensities corresponding to those used in a new clinical test of the vestibulo-collic pathway.

The vestibulo-ocular reflex (VOR) was studied in nine human subjects 2-15 months after permanent surgical occlusion of one posterior semicircular canal. The stimuli used were rapid, passive, unpredictable, low-amplitude (10-20 degrees), high-acceleration (3000-4000 degrees/s2) head rotations in pitch and yaw planes. The responses measured were vertical and horizontal eye rotations, and the results were compared with those from 19 normal subjects. After unilateral occlusion of the posterior semicircular canal, the gain of the head-up pitch vertical VOR--the vertical VOR generated by excitation from only one and disfacilitation from two vertical semicircular canals--was reduced to 0.61 +/- 0.06 (normal 0.92 +/- 0.06) at a head velocity of 200 degrees/s. In contrast the gain of the head-down pitch vertical VOR--the VOR still generated by excitation from two, but disfacilitation from only one vertical semicircular canal--was within normal limits: 0.86 +/- 0.11 (normal 0.96 +/- 0.04). The gain of the horizontal VOR in response to yaw head rotations--ipsilesion 0.81 +/- 0.06 (normal 0.88 +/- 0.05) and contralesion 0.80 +/- 0.11 (normal 0.92 +/- 0.11)--was within normal limits in both directions (group means +/- two-tailed 95% confidence intervals given in each case). These results show that occlusion of just one vertical semicircular canal produces a permanent deficit of about 30% in the vertical VOR gain in response to rapid pitch head rotations in the excitatory direction of the occluded canal. This observation indicates that, in response to a stimulus in the higher dynamic range, compensation of the human VOR for the loss of excitatory input from even one vertical semicircular canal is incomplete.

Using an acute scleral search coil technique for measuring eye position in alert animals we have shown that after UVD the yaw VOR in the guinea pig shows a permanent gain asymmetry. There is a reduced gain during the first 100 ms of brief, high acceleration horizontal head rotations ("yaw head impulses") towards the operated side, but only a small loss in gain for similar rotations towards the intact side. This result confirms that the horizontal E response during the first 100 ms of an abrupt high acceleration head rotation is a clear indicator of the function of the horizontal canal. These results are similar to those in human patients after unilateral acoustic neuroma operations. The asymmetry in response is large shortly after UVD and decreases over time but is permanent.

Three new, simple, clinically applicable tests of vestibular function are described. The first is a test of the response of the lateral semicircular canals to high accelerations. The test can even be done at the bedside where it can reveal severe unilateral or bilateral loss of lateral canal function. The test can also be recorded in a laboratory where it might show a less severe deficit of lateral canal function. The second is a simple, laboratory test of utricular function which depends on a subject's ability to align a bar with the subjective visual vertical. Patients with acute unilateral peripheral vestibular lesions invariably set the bar toward the side of the lesion. The third is a laboratory test of saccular function relying on a click-evoked inhibitory vestibulo-collic reflex recorded in the ipsilateral sternomastoid muscle. It can be done with equipment used for auditory evoked potentials.

We reviewed 36 patients with gentamicin vestibulotoxicity to determine its relationship to gentamicin dosage, serum gentamicin levels, and the development of gentamicin nephrotoxicity. Thirty of the patients had received intravenous or intramuscular gentamicin; six had received intraperitoneal gentamicin. Sixteen of the 30 patients treated with intramuscular or intravenous gentamicin had received less than the recommended maximum dose of 5 mg/kg/day for less than the recommended maximum period of 10 days. Nephrotoxicity as well as vestibulotoxicity developed in 16 of these 30 patients. Gentamicin vestibulotoxicity was not recognized before discharge from hospital in 32 of the 36 patients. We conclude that as far as the vestibular system is concerned there is no safe gentamicin dose and no safe serum gentamicin level, and there is an increased risk of vestibulotoxicity in patients in whom nephrotoxicity develops. Physicians who use gentamicin should become more aware of the clinical features of vestibulotoxicity because stopping gentamicin as soon as symptoms of vestibulotoxicity appear could prevent permanent impairment of vestibular function.

See-saw nystagmus is an uncommon but highly characteristic eye movement disorder comprising intorsion and elevation of one eye, with synchronous extorsion and depression of the other. It generally has a pendular waveform and is due to a midline, extrinsic, suprasellar mass lesion compressing or invading the brainstem bilaterally at the meso-diencephalic junction. This report deals with the clinical and MRI findings in three patients (and binocular three-dimensional quantitative oculographic findings in one patient) with a jerk waveform see-saw nystagmus due in each case to a unilateral meso-diencephalic lesion. In each patient the torsional component of the nystagmus fast phases rotated the upper poles of the eyes toward the side of the lesion. Jerk see-saw nystagmus can be clinically indistinguishable from pendular see-saw nystagmus and from the torsional-vertical nystagmus which occurs with medullary lesions. We propose that jerk see-saw nystagmus is due to unilateral inactivation of the torsional eye-velocity integrator, thought to be in the interstitial nucleus of Cajal, with sparing of the torsional fast-phase generator, thought to be in the adjacent rostral interstitial nucleus of the medial longitudinal fasciculus.

Rapid, passive, unpredictable, low-amplitude (10-20 degrees), high-acceleration (3000-4000 degrees/s2) head rotations were used to study the vertical vestibulo-ocular reflex in the pitch plane (pitch-vVOR) after unilateral vestibular deafferentation. The results from 23 human subjects who had undergone therapeutic unilateral vestibular deafferentation were compared with those from 19 normals. All subjects were tested while seated in the upright position. Group means and two-tailed 95% confidence intervals are reported for the pitch-vVOR gains in normal and unilateral vestibular deafferented subjects. In normal subjects, at a head velocity of 125 degrees/s the pitch-vVOR gains were: upward 0.89 +/- 0.06, downward 0.91 +/- 0.04. At a head velocity of 200 degrees/s, the pitch-vVOR gains were: upward 0.92 +/- 0.06, downward 0.96 +/- 0.04. There was no significant up-down asymmetry. In the 15 unilateral vestibular deafferented subjects who were studied more than 1 year after unilateral vestibular deafferentation, the pitch-vVOR was significantly impaired. At a head velocity of 125 degrees/s, the pitch-vVOR gains were: upward 0.67 +/- 0.11, downward 0.63 +/- 0.07. At a head velocity of 200 degrees/s, the pitch-vVOR gains were: upward 0.67 +/- 0.07, downward 0.58 +/- 0.06. There was no significant up-down asymmetry. The pitch-vVOR gain in unilateral vestibular deafferented subjects was significantly lower (P < 0.05) than the pitch-vVOR gain in normal subjects at the same head velocities. These results show that total, permanent unilateral loss of vestibular function produces a permanent symmetrical 30% (approximately) decrease in pitch-vVOR gain. This pitch-vVOR deficit is still present more than 1 year after deafferentation despite retinal slip velocities greater than 30 degrees/s in response to head accelerations in the physiological range, indicating that compensation of pitch-vVOR function following unilateral vestibular deafferentation remains incomplete.

We report 3 patients with autopsy-proven Creutzfeldt-Jakob disease who, early in their course, developed abnormal eye movements that included periodic alternating nystagmus and slow vertical saccades. These findings suggested involvement of the cerebellar nodulus and uvula, and the brainstem reticular formation, respectively. Cerebellar ataxia was also an early manifestation and, in 1 patient, a frontal lobe brain biopsy was normal at a time when ocular motor and cerebellar signs were conspicuous. As the disease progressed, all saccades and quick phases of nystagmus were lost, but periodic alternating gaze deviation persisted. At autopsy, 2 of the 3 patients had pronounced involvement of the cerebellum, especially of the midline structures. Creutzfeldt-Jakob disease should be considered in patients with subacute progressive neurological disease when cognitive changes are overshadowed by ocular motor findings or ataxia.

Sudden complete loss of input from one labyrinth results in a massive change in behaviour. A vigorous horizontal ocular nystagmus occurs together with postural changes. These dramatic changes are short-lived and within about a week they have almost disappeared. This very rapid recovery has been the basis for the postulation that vestibular compensation is a textbook model for the study of neural plasticity in the central nervous system. Whilst the behavioural recovery is dramatic, quantitative testing reveals the loss and the permanent asymmetry of the system (Table 1). Recordings from single neurones show that many neurones in the ipsilesional VN are silenced by the unilateral loss, but as they start to fire again, so the spontaneous nystagmus declines. The major question which is still unanswered is the cause of the return of the firing of neurones in the ipsilesional VN. The answer may be found by studies of the neurochemistry of the VN using brain slice preparations. This review shows some of the errors which have been made by attempting to infer purely vestibular function from measurements of eye movements when other sources of ocular motor control may operate.

See-saw nystagmus is a unique torsional-vertical eye movement disorder with a characteristic appearance. It is a pendular nystagmus with two distinct components: a conjugate torsional component and a disjunctive vertical component. In those cases of see-saw nystagmus in which a focal lesion has been identified, the lesion is usually a bilateral, symmetric lesion located at the mesodiencephalic junction. We report an unusual case of see-saw nystagmus which was due to a strictly unilateral mesodiencephalic lesion. Furthermore, the see-saw nystagmus had, in this case, a jerk wave-form rather than the usual pendular wave-form, with the torsional component of the jerk see-saw nystagmus beating toward the side of the lesion. These observations have an impact upon the localizing and lateralizing significance of torsional nystagmus in general and of see-saw nystagmus in particular.

The static ocular torsional position of both eyes of 23 patients was measured by means of fundus photographs one day before and one week after unilateral vestibular neurectomy for the treatment of acoustic neuroma, Ménière's disease or paroxysmal vertigo. The results showed that in all patients the vestibular neurectomy caused both eyes to tort (i.e. to roll around the visual axis) toward the side of the neurectomy when measured one week after operation. The extent of this torsion was an average of 9.5 degrees one week after operation and there was no statistically significant difference in the average magnitude of the torsion in the two eyes. In 8 of these patients, additional measurements were made at intervals up to one year after operation and it was found that in these patients there is a significant reduction in torsion over time from an average of 10.2 degrees one week after operation to an average of 2.8 degrees by 16 weeks after operation. The change in torsional eye position following the neurectomy was accompanied by a change in the perceived visual orientation of a small (9.5 degrees visual angle) illuminated horizontal line at a straight ahead eye level position in an otherwise completely darkened room. One week after operation when asked to adjust the line to the perceived gravitational horizontal by rotating it in roll (i.e. around an X axis), patients who had had a right vestibular neurectomy consistently set the line so that the right side of the line (from the patient's point of view) was below the true gravitational horizontal. Similarly patients after a left neurectomy consistently set the line so that the left side of the line was below the true gravitational horizontal. There is a high correlation (r = 0.95) between the direction and magnitude of the change in torsional eye position and the direction and magnitude of the change in the perceived visual horizontal one week after operation.(ABSTRACT TRUNCATED AT 250 WORDS)

Asymmetric vestibular function is the basis of vertigo. Whereas caloric tests can identify unilateral peripheral loss or impairment of horizontal semicircular canal function reasonably accurately, there is as yet no single accepted test of unilateral otolith hypofunction. In some advanced vestibular laboratories around the world, new and perhaps diagnostically useful tests of otolith function are being devised. The physiologic basis and the present clinical applications of these tests are reviewed.

One index of otolith function is the so-called oculogravic "illusion" that during centrifugal stimulation a small luminous bar, fixed with respect to the observer, appears to be roll-tilted by the same amount that the observer feels to be roll-tilted. Many patients undergoing therapeutic unilateral vestibular nerve section show the illusion symmetrically for left and right roll-tilts prior to the operation, but at testing one week after vestibular nerve section show a large asymmetry: they perceive the illusion when the resultant force is directed toward their intact ear, but they perceive a much reduced illusion when the force is directed toward their operated ear. This roll-tilt perceptual response asymmetry appears similar to the asymmetrical horizontal semicircular canal vestibulo-ocular responses for symmetrical but opposite head accelerations that these same patients exhibit for values of head angular accelerations in the natural range (Ewald's second law), and the present paper suggests that a version of Ewald's second law may apply to the otolithic system: specifically, that there is a response asymmetry for linear accelerations. Anatomical and physiological evidence concerning such an otolithic asymmetry is reviewed.

To determine the relative contributions of ampullofugal (AF) and ampullopetal (AP) stimulation of the horizontal semicircular canal (HSCC) to the horizontal vestibulo-ocular reflex (HVOR), 12 patients were studied 1 year after total unilateral vestibular deafferentation (UVD). Compensatory eye movement responses to impulses of horizontal head rotation were studied using magnetic search coils. The head impulses were rapid (up to 3000 deg/sec/sec) passive, unpredictable, step displacements of horizontal angular head position with respect to the trunk. The results from these 12 patients were compared with results from 30 normal subjects. An HVOR deficit was found to each side. The HVOR in response to head impulses toward the deafferented side, a response generated exclusively by ampullofugal stimulation of the single functioning HSCC, was severely deficient with an average gain of 0.25; the HVOR in response to head impulses toward the intact side, a response generated exclusively by ampullopetal stimulation of the single functioning HSCC, was mildly but significantly deficient compared with normal subjects. These results show that rapid, unpredictable head movements, unlike slow, predictable head movements, do demonstrate the AP-AF HVOR asymmetry, which could be expected from consideration of the behavior of single vestibular afferent neurons, an asymmetry that is expressed by Ewald's 2nd Law.

The normal horizontal vestibulo-ocular reflex (HVOR) is largely generated by simultaneous stimulation of the two horizontal semicircular canals (HSCCs). To determine the dynamics of the HVOR when it is generated by only one HSCC, compensatory eye movements in response to a novel vestibular stimulus were measured using magnetic search coils. The vestibular stimulus consisted of low-amplitude, high-acceleration, passive, unpredictable, horizontal rotations of the head with respect to the trunk. While these so called head "impuses" had amplitudes of only 15-20 degrees with peak velocities up to 250 deg/s, they had peak accelerations up to 3000 deg/s/s. Fourteen humans were studied in this way before and after therapeutic unilateral vestibular neurectomy; 10 were studied 1 week or 1 year afterwards; 4 were studied 1 week and 1 year afterwards. The results from these 14 patients were compared with the results from 30 normal control subjects and with the results from one subject with absent vestibular function following bilateral vestibular neurectomy. Compensatory eye rotation in normal subjects closely mirrored head rotation. In contrast there was no compensatory eye rotation in the first 170 ms after the onset of head rotation in the subject without vestibular function. Before unilateral vestibular neurectomy all the patients' eye movement responses were within the normal control range. One week after unilateral vestibular neurectomy however there was a asymmetrical bilateral HVOR deficit. The asymmetry was much more profound than has been shown in any previous studies. The HVOR generated in response to head impulses directed away from the intact side largely by ampullofugal disfacilitation from the single intact HSCC (ignoring for the moment the small contribution to the HVOR from stimulation of the vertical SCCs), was severely deficient with an average gain (eye velocity/head velocity) of 0.25 at 122.5 deg/sec head velocity (normal gain = 0.94 +/- 0.08). In contrast the HVOR generated in response to head impulses directed toward the intact side, largely by ampullopetal excitation from the single intact HSCC, was only mildly (but nonetheless significantly) deficient, with an average gain of 0.80 at 122.5 deg/sec head velocity. At these accelerations there was no significant improvement in the average HVOR velocity gain in either direction over the following year. These results indicate that ampullopetal excitation from one HSCC can, even in the absence of ampullofugal disfacilitation from the opposite HSCC, generate a near normal HVOR in response to high-acceleration stimulation.(ABSTRACT TRUNCATED AT 400 WORDS)

We reviewed the clinical and oculomotor findings in 62 patients with downbeating nystagmus (DBN). Only those patients whose DBN was enhanced in lateral gaze were included. Apart from gait ataxia, few patients had additional neurologic signs. The two most common causes of DBN were cerebellar ectopia (25%) and cerebellar degeneration (25%) with another 10% having a variety of conditions. In about 40% the cause remained undiagnosed. In some patients with idiopathic DBN and in others with DBN due to cerebellar ectopia, the disease progressed slowly, if at all. In DBN the slow-phase velocity is dependent on vertical head position and head velocity in pitch; vertical pursuit, particularly downward pursuit, is defective and vertical vestibulo-ocular reflexes are intact. We concluded that at least some cases of DBN were due to an imbalance in otolithocular reflexes. The lesion causing DBN appears to be in the vestibulocerebellum, perhaps the nodulus, a structure that normally inhibits otolith-ocular reflexes.

We describe two patients with paraneoplastic cerebellar syndromes who gained clinically useful neurologic remissions following radical excision of the primary cancer. In both patients the syndrome was characterized by the rapid onset of gait ataxia, nausea, postural vertigo, central positional nystagmus, and saccadic oscillations. These observations encourage radical treatment of the primary cancer in patients with advanced malignant neoplasms who are disabled by cerebellar dysfunction, and lend support to a current hypothesis that paraneoplastic cerebellar degeneration is due to anticerebellar Purkinje cell antibodies elaborated by the primary cancer.

A patient with congenital hydrocephalus and poor vision since early childhood, but with normal motor and intellectual development, suffered progressive mental deterioration during the last decade of life. At necropsy he was found to have severe hydrocephalus secondary to a lipoma of the midbrain tectum obstructing the aqueduct of Sylvius. In addition, the septum pellucidum was absent, the corpus callosum was thinned, and the anterior visual system was atrophic. The case emphasizes the importance of full neuroradiological investigation of congenital hydrocephalus. The possible association of intracranial lipoma with septo-optic dysplasia is discussed.

We report four patients with paralysis of downward gaze but with intact upward gaze, including one with detailed clinico-pathological studies and another with a focal computerized axial tomographic (CT) scan abnormality confirming the presence of bilateral lesions of the dorsomedial red nucleus, including the fasciculus retroflexus. It is suggested that sudden, permanent selective failure of downward gaze accompanied by transient disturbance of consciousness is an embolic syndrome of the posterior thalamosubthalamic or rubral artery.