Modelling non-linearities in the vestibulo-ocular reflex (VOR) after unilateral or bilateral loss of peripheral vestibular function.

We recorded the vestibulo-ocular reflex (VOR) in 18 normal subjects, 50 patients with unilateral loss of vestibular function and 18 patients with bilateral loss of vestibular function. The unilateral cases had either partial loss (i.e. vestibular neuronitis or Meniere's disease) or total loss (i.e. vestibular nerve section), whereas bilateral cases had only partial loss (i.e. due to ototoxicity or to suspected microangiopathy, secondary to severe kidney disease). Tests were performed at 1/6-Hz passive head rotation in the dark, with peak head velocities ranging from 125 to 190 degrees/s. We report on the distinct VOR non-linearities observed in unilateral versus bilateral patients: whereas unilateral patients all exhibit an asymmetric hypofunction with decreasing VOR gain at higher head velocities, bilateral patients have a more severe but symmetric hypofunction associated with increasing VOR gain at higher head velocities. We present a model study that can duplicate the nature of these characteristics, based mainly on peripheral non-linear semicircular canal characteristics and secondary central compensation. Theoretical analyses point to the importance of clinical test parameters (rotation speed and frequency) in the determination of a functional VOR and the detection of reflex non-linearities, so that test protocols can seriously bias the evaluation of adequate functional recovery.

Vestibular impairment in peripheral sensory neuropathies.

OBJECTIVE: Patients with peripheral sensory neuropathies frequently complain of dizziness, mainly unsteadiness, which occasionally seems to be more severe than the neuropathy. This study is an attempt to determine whether in cases where dizziness is a prominent feature the underlying cause is, at times, a concomitant vestibular dysfunction. METHOD: The files of 50 patients suffering from peripheral sensory neuropathies were retrospectively reviewed. Patients with central nervous system disease capable of inducing vestibular dysfunction were excluded from this study. In 47 of 50 patients, bithermal caloric tests were performed as part of electronystagmographic recordings. According to the caloric responses, these patients were divided into three groups: group 1: bilaterally reduced responses, group 2: unilaterally reduced responses, and group 3: normal symmetric responses. RESULTS: In 17 of 47 patients, the caloric responses were reduced bilaterally (group 1). In 8 of 47 patients, the responses were reduced unilaterally (group 2). In 22 of 47 patients, the caloric responses were normal and symmetric (group 3). CONCLUSION: Vestibular dysfunction was encountered in 25 of 47 patients (53.2%) suffering from peripheral sensory neuropathy. One wonders whether the pathologic process affecting the peripheral sensory nerves may also affect the vestibular nerve. This seems possible in view of the fact that the vestibular nerve, a sensory nerve itself, has a histologic structure similar to the peripheral sensory nerves.

Head-shaking nystagmus (HSN): the theoretical explanation and the experimental proof.

Head-shaking nystagmus (HSN) is induced by oscillating the head at high frequency in the horizontal plane. This test is used in the clinic to detect the presence of a unilateral loss of vestibular function. HSN has been described as monophasic with fast-phase direction towards either side, or biphasic with the direction of fast phases reversing after a few seconds. Loss of vestibular function amplifies existing non-linearities in the vestibular system, so that imposed sinusoids can induce biases which are the source of HSN. Fifty-one patients suffering from loss of peripheral vestibular function (43 partial, 11 total unilateral tests) were exposed to whole-body sinusoidal stimulation, with increasing head velocities (90-220 degrees/s) at 1/6Hz, to explore the consistency of per-rotatory induced biases. A bias was induced in all cases, but it wandered on either side, healthy or pathologic, unless test head velocities were larger than approximately 180 degrees/s. Given this condition, the slow-phase bias was located towards the pathologic side for all patients with significant bias ( > 5 degrees/s). These observations demonstrate that the sign and amplitude of the bias is variable and is not correlated with the lesioned side, unless high head velocities are imposed. This explains why the direction of the initial phase of HSN in the clinic seems so labile. Subsequent monophasic or biphasic characteristics of HSN are simply the reflection of interactions between two main time constants associated with "velocity storage" and "gaze holding" in the vestibular central processes.

Assessment of the caloric-induced tilt in the perceived visual vertical: preliminary report.

OBJECTIVE: The perceived visual vertical (PVV) has been shown to be abnormal in patients with acute vestibular lesions but reverts to normal in compensated patients. The objectives of this study are to ascertain whether the PVV can be modulated by caloric stimulation and whether this modulation diminishes in compensated patients with unilateral vestibular lesions. DESIGN: Prospective. SETTING: Tertiary care facility. METHOD: Sixty-eight patients referred for vestibular testing had an electronystagmography and a PVV. MAIN OUTCOME MEASURES: Tilt in PVV, in degrees after caloric stimulation. RESULTS: Cold caloric stimulation resulted in a mean tilt in the PVV toward the irrigated ear and warm irrigation had the reverse effect. The mean modulation (amplitude of the angular distance in degrees between cold and warm tilts) was 4.3 degrees. In a subgroup of patients with severe unilateral vestibular dysfunction, this modulation of the PVV with caloric stimulation was diminished on the side of the lesion (p = .0001). CONCLUSION: Further study is required to assess the potential of the caloric PVV as a test of otolith function.

Benign paroxysmal positional vertigo (BPPV): idiopathic versus post-traumatic.

Between October 1974 and August 1997 in our Dizziness Clinic (n = 15,233), 2,523 patients were found to suffer from BPPV. All patients were assessed and followed up by the author. Patients (n = 337) having other ear or neurological diseases were excluded from this retrospective study. In 1644/2186 (75.21%) patients, the type of nystagmus was clinically identified in two opposite directions of gaze in the provocative head position. These patients were divided into two groups: i) idiopathic (n = 1,490) (no apparent cause); ii) post-traumatic (n = 154) (time of onset related to accident). It was found that in the idiopathic group men were older than women; women were more affected than men (2.3:1), and in the post-traumatic group there was no age difference between men and women; women and men were equally affected (1:1). In addition: i) patients were older in the idiopathic than the post-traumatic group. ii) BPPV of the posterior (PSC) was by far more prevalent than BPPV of the horizontal semicircular canal (HSC) in both groups, although there was no difference in prevalence between the two groups. iii) Bilateral involvement was more prevalent in the post-traumatic group. iv) All bilateral cases in both groups suffered from BPPV of the PSC. It is concluded that despite similarities, these two groups differ in a number of parameters. Thus the pathophysiology and the course of idiopathic vs post-traumatic BPPV may also be different.

Hearing loss and vestibular dysfunction in Menière's disease.

In a retrospective study of 475 patients suffering from Meniere's disease, the hearing loss, both in the low and high frequencies, and the loss of vestibular function were studied over time. There were large variations of hearing loss from case to case but, overall, the low were more affected than the high frequencies, regardless of time elapsed since onset of disease. Hearing deteriorated over time and mean values of hearing loss correlated well with the elapsed time since onset of disease. There were also large variations of post-caloric labyrinthine preponderance (lp) from case to case but, overall, lp deteriorated with time. Mean values of lp, however, did not correlate that well with elapsed time since onset of disease as the hearing loss did. Nor was there any correlation over time between level of hearing loss and lp. It is concluded that in Meniere's disease the hearing, deteriorating over time, is mainly but not necessarily worse in the low frequencies; lp, indicating loss of vestibular function, does not correlate with level of hearing loss in most cases.

Paroxysmal positional vertigo: an overview and the deposits repositioning maneuver.

In a retrospective live study, electronystagmographic (ENG) recordings in patients (n = 526) suffering from paroxysmal positional vertigo (PPV) of the posterior semicircular canal were divided into group I (n = 425) and group II (n = 101), depending on whether the vertigo could or could not be elicited at the time of recording. There was no statistical difference between the two groups for (1) the ipsilateral (fast phase toward the affected side) or the contralateral positional nystagmus (excluding the nystagmus recorded during the paroxysm) or (2) the bithermal caloric labyrinthine or directional preponderance; nor within each group for (1) the ipsilateral versus the contralateral positional nystagmus or (2) the ipsilateral (on the affected side) versus the contralateral labyrinthine and/or directional preponderance. In a prospective study, the deposits repositioning maneuver (DRM) was attempted in 41 patients. One day post-treatment patients felt no change, better, or free of vertigo. Most patients, who developed nystagmus in the final DRM head position similar to the nystagmus observed in the provocative head position had a better outcome. It is concluded that ENG recordings do not contribute to the diagnosis of PPV. The type of observed nystagmus in the final DRM head position is frequently an outcome predictor. Following the DRM, failures and/or recurrences are to be expected.

Comparison of linear vs. non-linear methods for analysing the vestibulo-ocular reflex (VOR).

The vestibulo-ocular reflex (VOR) is traditionally evaluated by the gain (sensitivity) and offset (bias) of nystagmus slow phases during sinusoidal, passive, head rotation in the dark. The analysis methods used are typically only truly applicable to linear systems, but are widely used despite the fact that the VOR has been known to be non-linear since the 19th century. We show here that the parameters obtained by linear methods, with data derived from a non-linear system, can be very noisy and unreliable. The questions are: under what conditions can linear approximations be tolerated, or justified, and can an analysis approach be devised which inherently tolerates non-linearities? Using both simulated and experimental data, it is found that assuming linear analysis methods can produce variable VOR gains and erroneous estimates of the VOR bias. changing with the selected oscillation protocol. Examples of' parameter distortions in bias and VOR gain are first given using simulated data relating slow phase eye velocity to head velocity, at different peak velocities. The relevance of these distortions is then illustrated with selected examples from a database of recordings on normals and unilateral vestibular patients, during rotations in the dark 1/6 Hz and maximum speeds of 90 to 180 degrees/s. More consistent estimates of the gain and bias can be found by properly correcting for phase differences between head and eve velocity, and allowing for non-linear reflex properties. Special indices are suggested to decide whether a particular subject's VOR should be considered non-linear, in order to select the appropriate representation in each case, before estimating VOR characteristics. Selecting the appropriate model (linear or non-linear) will contribute to a better unmasking of parametric trends in the VOR, when comparing normal vs. acute-lesioned subjects, or acute vs, compensated patients. These results have many implications for the design of clinical vestibular protocols and in the evaluation of patient functional deficits.

Vestibulo-ocular reflex (VOR) biases in normal subjects and patients with compensated vestibular loss.

The properties of the vestibulo-ocular reflex (VOR) were examined during sinusoidal passive head rotation in the dark at 1/6 Hz, in 9 normal subjects and 14 unilateral vestibular patients. Rotation speeds ranged from 90 to 180 degrees/s. The bias (offset of slow-phase velocity from zero) and gain in the VOR were estimated by using a polynomial (cubic) fit between head and slow-phase eye velocity, thereby allowing for possible non-linearities in the reflex. The gain in the VOR in this context refers to the linear components of the fit, and so predicts sensitivity only at low head velocities. The aim of the study was to verify previous theoretical predictions that VOR bias could vary with the rotation parameters, that this bias could be used to detect the side of a vestibular lesion even at low frequency rotation, and make non-linearities more obvious. Confirming these predictions, the VOR bias in a given test is never equal to any spontaneous nystagmus, even if present before rotation. The range of values for the gain in the VOR (as defined above) in normals and compensated unilateral vestibular patients overlap, so that they cannot be statistically separated into two response sets.(ABSTRACT TRUNCATED AT 250 WORDS)

Dizziness in aging: a retrospective study of 1194 cases.

In the Royal Victoria Hospital dizziness clinic, 1194 of 9767 (12.22%) patients were 70 years of age or older on the day of the first visit. There were 750 women and 444 men, with no difference in age distribution (p > 0.9). In 367 (27.04%) cases (percentages given as "cases" refer to the number of diagnoses [N = 1357], not the number of patients [N = 1194]), the symptoms were nonspecific, and the diagnosis was uncertain. In 530 (39.13%) patients, paroxysmal positional vertigo was either confirmed or strongly suspected. In the 241 of 254 (94.88%) confirmed cases, the observed paroxysmal nystagmus was compatible with excitation of the posterior semicircular canal. In 119 (8.77%) patients, the dizziness could not be attributed to neurologic or vestibular disease. Meniere's disease, vestibular neuronitis, vascular episodes, and tumors were next in prevalence. The following conclusions were reached: (1) although no difference was found in age distribution between women and men, dizziness was more prevalent among women, which may be because of the higher survival rate of women; (2) the prevalence of paroxysmal positional vertigo was high, with apparent involvement of the posterior semicircular canal in most cases (it is strongly suspected that paroxysmal positional vertigo is frequently misdiagnosed as vascular disease in advanced age); and (3) multisensory deficits, drugs, or systemic diseases, common in the elderly, may cause dizziness. Syndromes affecting the vestibular function, however, may be more prevalent in advanced age than is generally estimated.

Postural instability on one foot in patients with loss of unilateral peripheral vestibular function.

The vestibular system is a major contributor to postural control and the vestibular nuclei are closely connected to the limb spinal motor neurons. Acute loss of unilateral peripheral vestibular function results in, among others, postural instability which improves with time due to central compensatory processes. It has been shown, however, that a number of processes, such as sensorimotor restriction, drugs, and so forth, may affect the speed and the quality of compensation. Due to the difference of ipsilateral vs contralateral connectivity between the vestibular nuclei and the limb spinal motor neurons, and the peculiarities of compensatory processes, the ipsilateral may not compensate as well as the contralateral foot to lesion in patients who lost unilateral peripheral vestibular function. To explore this possibility, the sway, while standing on each foot, was recorded in normal subjects (N = 30) and compensated (except three) patients (N = 37) with loss of unilateral peripheral vestibular function and the percentage difference between the two sways was calculated. No difference was found between patients swaying more on the ipsilateral vs patients swaying more on the contralateral foot to lesion (p > .80). There was, however, a statistical difference between patients as a group vs normal subjects as a group (p = .005). These data suggest, although not evident in all patients of the group, that sway on the contralateral foot was less than the sway on the ipsilateral foot to lesion, as initially speculated. They may, however, signify that one foot compensates better than the other. This is a preliminary report and more testing is on-going to confirm these results.

Does the vestibulo-ocular reflex (VOR) merit redefinition?

The VOR has historically been described by parameters of the slow phase of nystagmus while fast phases have been systematically ignored. However, ample neurophysiologic and theoretical evidence suggests that fast phases are an integral part of the VOR and are not to be discarded in evaluation of vestibular function. In a series of experiments, normal subjects and compensated patients with total or partial loss of unilateral peripheral vestibular function were tested. They were exposed to sinusoidal oscillations (20 degrees, 60 degrees, and 120 degrees/second at 1/6 Hz and 25 degrees/second at 1 Hz) with no actual or imaginary visual targets (doing mental arithmetic) and the usual slow-phase parameters (gain, phase, etc.) were computed. The gaze (total eye position, slow and fast phase of nystagmus vs. head + head position in space) was also plotted vs. head position in space. It was found that in patients, fast phases of nystagmus are unequally (right vs. left) produced, extending the linear range of VOR function. It was also found that in normal subjects and patients, gaze essentially tracks the head in the absence of visual targets. It is concluded that fast phases of nystagmus contribute to gaze control during head rotations in darkness and that the definition and the testing of the VOR have to be modified to accommodate these observations.

Ototoxicity due to cis-diamminedichloroplatinum in the treatment of ovarian cancer: influence of dosage and schedule of administration.

Ototoxicity associated with administration of cisplatin was assessed in four groups of patients suffering from advanced ovarian carcinoma. The purpose was to determine the influence of dosage, schedule of administration, and long-term treatment on pure-tone thresholds and other auditory parameters. One hundred and forty-five serial audiograms were obtained in 60 patients and compared with baseline audiograms. The treatment protocol consisted of two different dosages (low--50 mg/m2 and high--100 mg/m2) and three different schedules of administration (short--6 months, extended--12 months, and treatment in blocks--intervening months in which cisplatin was withheld). Using a conservative definition of auditory toxicity and statistical analyses of pure-tone threshold differences between groups, the results indicated that the low dose-short treatment regimens with either monthly administration of cisplatin, or administration in blocks, were the least ototoxic. Ototoxicity was found to increase with increasing cumulative dosages. Hearing loss was primarily in the high frequencies. The most severe ototoxic effects, which include tinnitus and hearing loss in the speech frequency range, were associated with the administration of high dosages over a short period of time. Individual variability in susceptibility to ototoxicity necessitates systematic audiometric monitoring throughout therapy.

Electronystagmographic (ENG) findings in paroxysmal positional vertigo (PPV) as a sign of vestibular dysfunction.

In 285 patients, the observed nystagmus during episodes of PPV was compatible with excitation of the posterior semicircular canal. In these cases, divided in two groups, routine ENG recordings were retrospectively reviewed. In Group A (n = 241), the ENG was performed during the time the vertigo could be elicited; in Group B (n = 44), during the time it could not. In Group A: 1) the velocity of positional nystagmus (not the paroxysmal) was less than 6 degrees/s in 93% of cases; 2) there was no statistical difference of positional nystagmus and post-caloric preponderance of opposite directions, with 66% of cases having symmetrical responses; 3) the velocity of positional nystagmus and the post-caloric preponderance were higher than in Group B. It is concluded that: (i) in most cases no concomitant vestibular dysfunction could be detected; (ii) there was a tendency to restore right-left asymmetricity when the episodes subsided; (iii) ENG recordings were not pathognomonic and did not localize the affected side; (iv) there were ENG findings suggestive of concomitant involvement of other vestibular sensors (canals), in a small number of cases.

Postural disturbances in paroxysmal positional vertigo.

Postural sway was computed in 14 patients suffering from paroxysmal positional vertigo, before and after the paroxysm. In all patients, the nystagmus elicited during the paroxysm was compatible with excitation of the posterior semicircular canal. Patients stood on a force plate for 20 s while the anteroposterior and mediolateral projections of the center of force were recorded and standard deviations computed. Recordings were made after placing the patient's head in the opposite (healthy) and the provocative position. Vertigo was elicited and the nystagmus was observed in 10 of 14 patients. Analysis of the sway data in these patients (N = 10), using the Wilcoxon matched pairs test, showed that the mediolateral sway remained unchanged, while the anteroposterior sway increased, following the provocative maneuver (p less than 0.01). It is concluded that paroxysmal positional vertigo, in which the elicited nystagmus is compatible with excitation of the posterior semicircular canal, increases the anteroposterior rather than the mediolateral sway immediately following the paroxysm.

Sudden unilateral sensorineural hearing loss: a syndrome or a symptom?

In 122 patients with sudden unilateral sensorineural hearing loss, no apparent cause was identified in 88 cases. In these idiopathic cases, gender did not affect the age distribution and age did not affect the range of most affected frequencies or the severity of hearing loss. Vertigo at onset of the disease was not a sign of poor prognosis. Cases in the idiopathic group could, generally, be distinguished into two groups: (1) cases with hearing loss affecting all (with one exception) or mainly the high frequencies and symptomatology reminiscent of known types of cranial (poly)neuritis; (2) cases with hearing loss affecting mainly the low frequencies and symptomatology reminiscent of Ménière's disease. These data suggest that there may be certain pathophysiologic similarities in these cases with: (a) cranial (poly)neuritis if all or mainly the high frequencies are affected; (b) Ménière's disease if the low frequencies are mainly affected.