Prolonged sympathetic reflex latency on skin nerves in sporadic cerebellar degeneration

BACKGROUND: Many physiological or pharmacological evaluations of autonomic function have been performed in patients with various types of cerebellar degeneration (CD). Few studies have been done, however, using neurographic recordings in patients with CD, especially of sudomotor or vasoconstrictor nerves. OBJECTIVE: To confirm the clinical importance of sympathetic reflex latencies on the skin nerves of patients with various types of CD. DESIGN AND SETTING: Case-comparison study at an academic center. PARTICIPANTS: We studied 12 patients who had sporadic CD (cerebellar cortical atrophy, olivopontocerebellar atrophy, and Shy-Drager syndrome) and 15 healthy volunteers as controls. METHODS: Skin sympathetic nerve activity (SSNA), sympathetic skin response, and skin vasomotor reflex were simultaneously recorded using randomly administered electrical stimuli. RESULTS: In controls, SSNA reflex latency ranged from 640 to 864 milliseconds. Patients with cerebellar cortical atrophy exhibited slight but significant (P<.01) prolongation of reflex latency to the onset of reflex bursts. In patients with olivopontocerebellar atrophy, latency to the onset and the peak of reflex bursts was significantly prolonged (P<.001). Patients with Shy-Drager syndrome had no SSNA, sympathetic skin response, or skin vasomotor reflex, even with supramaximal electrical stimuli. CONCLUSIONS: Prolonged reflex latency or the absence of reflex bursts on SSNA can be observed in patients with CD with various forms of autonomic dysfunction. The measurement of SSNA reflex latency may be a useful method of evaluating sympathetic function, including the central pathway.     

Vestibular neuritis: Vertigo and the high-acceleration vestibulo-ocular reflex

Abstract   Patients after vestibular neuritis (VN) often report persistent dizziness and disequilibrium. We correlated persistent symptoms with sustained impairment of the high-acceleration horizontal vestibulo-ocular reflex as determined by quantitative searchcoil head-impulse testing (qHIT). In 47 patients, qHIT was recorded 0–60 months and symptoms assessed with the Yardley Vertigo Symptom Scale short form ≥ 18 months after VN onset. No correlation between the magnitude of high-acceleration vestibular impairment and the severity of vertigo symptoms was observed. The lack of a symptom-qHIT correlation suggests that defective compensation at a more rostral level in the central nervous system may be responsible for protracted symptoms in VN patients.     

Eye movements and vestibulo-ocular reflex in the blind

Summary To assess the effect of chronic deprivation of visual feedback, 21 blind patients underwent clinical and electro-nystagmographical examination. Patients with congenital blindness were characterized by spontaneous eye movements, inability to consciously move the eyes and absence of the vestibulo-ocular reflex (VOR), whereas eye movement abnormalities were practically absent in those with blindness acquired late in life. Active visual experience, at least in early life, seems to be crucial for the development of eye movements and VOR adjustment.     

Effects of parameters of video head impulse testing on visually enhanced vestibulo-ocular reflex and vestibulo-ocular reflex suppression

ObjectiveTo investigate the main effects of some testing and analysis variables on clinically quantified visually enhanced vestibulo-ocular reflex (VVOR) and vestibulo-ocular reflex suppression (VORS) results using video head impulse test.MethodsThis prospective observational clinical study included 19 healthy participants who underwent the VVOR and VORS tests. The effect of demographic variables, head oscillation frequency, rotation direction, visual acuity and analysis time window width and location of the recorded tests on the quantified results of both VVOR and VORS were evaluated. And specifically, for the VORS test the effect of cognitive reinforcement of the participant during testing was evaluated.ResultsA statistically significant difference was observed among the VVOR, non-reinforced VORS, and reinforced VORS tests for mean gain values of 0.91 ± 0.09, 0.6 ± 0.15, and 0.57 ± 0.16, respectively (p < 0.001). The optimized linear mixed-effect model showed a significant influence of frequency on the gain values for the reinforced and non-reinforced VORS tests (p = 0.01 and p = 0.004, respectively). Regarding the gain analysis method, statistically significant differences were found according to the short time interval sample location of the records for the initial location of the VVOR test (p < 0.006) and final location of the reinforced VORS test (p < 0.023).ConclusionSignificant differences were observed in the gain values according to VVOR and VORS testing. Head oscillation frequency is a significant factor that affects the gain values, especially in VORS testing. Moreover, in VORS testing, participant concentration has a significant effect on the test for obtaining suppression gain values. When a short time interval sample is considered for VVOR and VORS testing, intermediate time samples appear the most adequate for both tests.SignificanceThe quantified visually enhanced vestibulo-ocular reflex (VVOR) and vestibulo-ocular reflex suppression (VORS) tests have recently been added to the assortment of available clinical vestibular tests. However, despite the clinical validity of these quantified tests that appear to be of increasing clinical interest, the effects of most of the clinical testing methods and mathematical variables are not well defined.In this research we describe what are the main collecting and analysis variables that could influence to the VVOR and VORS tests. Specially for VORS test, participant concentration on test tasks will have positive effect on the measured vestibulo-ocular reflex (VOR) suppression.     

Impairment of vestibulo-collic reflex and linear vestibulo-ocular reflex in pediatric-onset multiple sclerosis patients

ObjectivesThis study aimed to examine the vestibulo-collic reflex (VCR) and linear vestibulo-ocular reflex (lVOR) and their correlation with brain lesions in pediatric-onset multiple sclerosis (POMS).MethodsThe study group consisted of 17 patients (34 ears) with POMS (mean age 18.73 ± 2.02, mean age at disease onset 14.64 ± 1.36 years), and the control group included 11 age-matched healthy subjects (22 ears). Ocular and cervical Vestibular Evoked Myogenic Potentials (oVEMP and cVEMP) were performed to assess IVOR and VCR pathways. Magnetic Resonance Imaging was evaluated in the study group.ResultsIn the POMS group, 47.05 % of oVEMPs and 17.64 % of the cVEMPs were abnormal, while all VEMPs were normal in the control group. The oVEMP amplitude was associated with infratentorial lesion volume (r = −0.459, p = 0.01) and total lesion volume of the brainstem and cerebellum (r = −0.450, p = 0.01). The cVEMP asymmetry ratio was correlated with the deep white matter lesion volume (r = 0.683, p < 0.001). The MVEMP scores were found to correlate only with lesion volumes in the cerebellum (r = 0.488, p = 0.04) and infratentorial region (r = 0.573, p = 0.01).ConclusionsOcular and cervical VEMP abnormalities confirm that lVOR and VCR pathways may be affected in early POMS.SignificanceRoutine use of the VEMP test, especially the oVEMP test is recommended as a useful tool in the follow-up of POMS patients.     

Alexander's law: its behavior and origin in the human vestibulo-ocular reflex

Alexander's law refers to the phenomenon in which the spontaneous nystagmus of a patient with a vestibular lesion is more intense when the patient looks in the quick-phase than in the slow-phase direction. Alexander's law was investigated in normal subjects as well as patients with vestibular lesions. During sinusoidal rotations of normal subjects, there was no trace of this phenomenon when subjects looked 25 degrees left and right in the dark. The phenomenon of Alexander's law is therefore created centrally and is not due to any mechanical properties of the orbit. During rotation at constant velocity in the dark, normal subjects did weakly demonstrate Alexander's law because of a mild gaze-evoked nystagmus present in normal subjects in the dark. Gaze-evoked nystagmus from a cerebellar lesion involved a pronounced demonstration of Alexander's law during rotatory nystagmus. In patients with a vestibular lesion and a mild spontaneous nystagmus in the dark that obeyed Alexander's law, the nystagmus reversed upon far gaze in the slow-phase direction. We propose that in patients with a vestibular lesion, the phenomenon of Alexander's law is created by the sum of vestibular nystagmus and an abnormally large gaze-evoked nystagmus that is consequent to the vestibular lesion. This conclusion has a number of neurological implications concerning the ways in which the nervous system attempts to compensate for vestibular lesions.     

The vestibulo-ocular reflex: is it an independent subsystem?

Traditionally, the vestibulo-ocular reflex (VOR) is described as a distinct, phylogenetically old, oculomotor subsystem, which serves to stabilize gaze direction. It is supposed to act as a stereotyped reflex with definite input-output relations, which can be measured by rotating a subject passively in darkness, and which are kept at a nearly ideal level by adaptive parametric adjustments. This paper argues that such a view of the VOR may be not realistic: 1) the VOR in darkness (especially in humans) does not behave as a well-calibrated system; it has a low and variable gain which can be changed easily, even by purely mental assumptions; 2) a hard-wired VOR does not lead to appropriate eye movements in most natural situations, and would need continuous conditioning by other systems. As there is no compelling physiological or anatomical evidence for an independent VOR, it seems more fruitful to hypothesize that vestibular signals are just one of many inputs to a spatial localization process, which computes the relative motion between a subject and an object of his choice on the basis of all available, relevant information. Instead of a distinct subsystem, vestibulo-ocular responses in darkness may represent nothing more than the (somewhat arbitrary) default performance of this larger gaze-control system, functioning poorly in the absence of complete information.     

The relationship between disordered pursuit and vestibulo-ocular reflex suppression

The performance of the smooth pursuit reflex and the ability to suppress the vestibulo-ocular reflex were assessed in 10 normal subjects and in patients with a variety of diseases of the central nervous system. Pursuit was measured as the maximum velocity of slow phase eye movement in response to a laser target moving sinusoidally at various frequencies up to 1 Hz and with amplitudes stepped up to 35° peak. Suppression of the vestibulo-ocular reflex was assessed with subjects seated in a Barany chair rotating sinusoidally in yaw at matching frequencies. The breakpoint of vestibulo-ocular reflex supression was defined as the peak velocity of oscillation at which nystagmus appeared on electro-oculographic recording as determined by the method of ascending and descending thresholds. For normal subjects, at all frequencies, the breakpoint of suppression corresponded closely with the peak velocity of pursuit at the corresponding frequency of target oscillation. In some patients pursuit and suppression were comparably impaired. In others either pursuit or suppression could be selectively impaired with the other function left intact. The results demonstrate that the mechanisms of pursuit and visual suppression of the vestibulo-ocular reflex have similar dynamics and share a common pathway at least to the level of the cerebellum. Thereafter, there is presumably an anatomical and functional dissociation of the signals mediating the two functions. The key area involved appears to be the flocculus for lesions of this structure alone cause impairment of both functions. The findings also indicate that the appropriate way to test smooth pursuit in relationship to suppression is to increase the amplitude of target oscillation until the peak slow eye movement velocity is determined for each frequency. The finding that increasing excursion increases maximum pursuit velocity supports the view that pursuit has an acceleration limit which is more critical in determining performance than velocity limitations. The results establish the assessment of vestibulo-ocular reflex suppression as a powerful test of the integrity of CNS function independent of its previous association with disordered pursuit.     

Paraneoplastic cerebellar degeneration: clinical-immunological correlations

Four different antineuronal autoantibodies have been identified in 23 of 47 patients with paraneoplastic cerebellar degeneration (PCD). The most common, an antibody against 34- to 38-kDa and 62- to 64-kDa protein antigens in the cytoplasm of Purkinje cells, was found in 18 patients. It is a highly specific marker for a severe stereotypical subacute pancerebellar syndrome of truncal and appendicular ataxia, dysarthria, and nystagmus in women with cancer (usually ovarian or breast carcinoma). Different anti-Purkinje cell antibodies (APCA) were found in 2 other patients with PCD. With two possible exceptions, an APCA was not found in patients with other neurological diseases, with cancer not associated with neurological symptoms, or in normal subjects. Antibodies reactive with neuronal nucleoproteins were identified in 3 other patients with PCD: an antibody that recognized 35- to 40-kDa neuronal antigens was found in 2 women with small-cell lung carcinoma, while an antibody in a woman with breast carcinoma identified 53- to 61-kDa and 79- to 84-kDa antigens. Detection of an antineuronal antibody in a patient without known cancer should prompt a careful search for a tumor at a site appropriate to the antibody type.     

The click-evoked vestibulo-ocular reflex in superior semicircular canal dehiscence

The authors studied eye movement responses to loud (110dB) clicks in 4 patients with Tullio effect due to superior semicircular canal dehiscence and in 9 normal subjects, by averaging the electro-oculogram. All 4 patients had small (0.1-0.3 deg) but easily reproducible vertical vestibulo-ocular reflex eye movement responses to the clicks. Normal subjects had responses that were at least 10 times smaller. The click-evoked vestibulo-ocular reflex test is a simple, robust way to screen dizzy patients for symptomatic superior semicircular dehiscence.     

The human sound-evoked vestibulo-ocular reflex and its electromyographic correlate

ObjectiveSound and vibration evoke a short-latency eye movement or “sound-evoked vestibulo-ocular reflex” (VOR) and an infraorbital surface potential: the “ocular vestibular-evoked myogenic potential” (OVEMP). We examined their relationship by measuring the modulation of both responses by gaze and stimulus parameters.MethodsIn seven subjects with superior semicircular-canal dehiscence (SCD) and six controls, the sound-evoked VOR was measured in 3D using scleral search coils. OVEMPs were recorded simultaneously, using surface electromyography.ResultsEye movement onset (11.6 ± 0.8 ms) coincided with the OVEMP peak (12.1 ± 0.35 ms). OVEMP and VOR magnitudes were 5–15 times larger in SCD compared with controls. OVEMP amplitudes were maximal on upgaze and abolished on downgaze; VOR magnitudes were unaffected. When stimulus type was changed from sound to vibration, OVEMP and VOR changed concordantly: increasing in controls and decreasing in SCD. OVEMP and VOR tuned to identical stimulus frequencies. OVEMP and VOR magnitudes on upgaze were significantly correlated (R = 0.83–0.97).ConclusionSelective decrease of the OVEMP upon downgaze is consistent with relaxation or retraction of the inferior oblique muscles. The temporal relationship of OVEMP and VOR and their identical modulation by external factors confirms a common origin.SignificanceSound-evoked OVEMP and VOR represent the electrical and mechanical correlates of the same vestibulo-ocular response.     

Oscillopsia: visual function during motion in the absence of vestibulo-ocular reflex

OBJECTIVES—To investigate (1) the effects of lossof vestibular function on spatiotemporal vision and (2) the mechanismswhich enable labyrinthine defective (LD) patients to adapt to oscillopsia.
METHODS—Visual function and eye movements wereassessed in seven normal subjects and four LD patients with oscillopsiadue to absent vestibulo-ocular reflex. Temporal vision was assessed bymeasurement of threshold sensitivity for detection of a target whichmoved across a flickering, spatially uniform background field. Spatial vision was investigated by measurements of threshold sensitivity forthe detection of a target moving across a spatially modulated background in the form of square wave gratings. Velocity discrimination was assessed with drifting gratings. All measurements were made understatic conditions and during oscillatory movement of either the visualstimulus or the subject (1 Hz, peak velocity 50°/s).
RESULTS
TEMPORAL RESPONSES—Normal subjects and LDpatients exhibited similar responses while static and under body oscillation.
SPATIAL RESPONSES—The two groups achieved similarresults under static conditions but body oscillation reduced thresholdsensitivities and shifted the spatial response function towards lowerspatial frequencies in the LD patients only. Similar changes in thespatial responses were seen during oscillation of the visual stimulusbut these occurred in both normal subjects and LD patients.
VELOCITY DISCRIMINATION—Two LD patients achievednormal velocity discrimination but the other two showed abnormalresponses to visual stimulus movement; one displayed a loss of velocitydiscrimination during whole body oscillation, and the other mismatchedthe velocity of two moving grating stimuli.
CONCLUSIONS—The changes in the spatialresponses are attributed to the presence of retinal slip during visualstimulus motion in all subjects or body oscillation in the LD patients.It is concluded that any visual adaptation to oscillopsia achieved bythe LD patients does not influence the measured spatial responsefunctions, which arise at an early stage of visual processing. Theabnormal velocity discrimination may relate to the progressiveimprovement in oscillopsia reported by LD patients.

     

The vestibulo-ocular reflex during active head motion in children and adolescents

Background Little information is available on the performance and maturity of the vestibulo-ocular reflex (VOR) in children and adolescents during active head motion as encountered during normal locomotion. We investigated the active VOR performance in children and adolescents to determine its norm and variation with age. Methods We recorded the angular active VOR using an infrared eye tracker and a magnetic head tracker in 38 children, aged 8–19 years. Participants made sinusoidal head-on-body rotations in yaw (left–right) and pitch (up–down) at frequencies of about 0.5 and 2 Hz in the dark. Results Mean VOR gains, the ratios of eye to head velocities, were close to unity and were significantly higher at 2 Hz than at 0.5 Hz. VOR gains did not vary with age. Conclusion The angular VOR during active head motion is functionally mature in children 8 years or older at 0.5 and 2 Hz head rotations.     

Dissociation of smooth pursuit and vestibulo-ocular reflex cancellation in SCA-6

OBJECTIVE: To study gaze in SCA-6 patients during pursuit and passive whole-body rotation. BACKGROUND: Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). Previous studies have implicated the cerebellum, particularly the floccular lobe and dorsal vermis, in the control of gaze velocity during pursuit and vestibulo-ocular reflex (VOR) cancellation. SCA-6 has recently been identified genetically and characterized as pure cerebellar ataxia that affects the cerebellar cortex selectively. METHODS: Using infrared oculography, eye movements of five SCA-6 patients and five age-matched normal control subjects were recorded during sinusoidal pursuit and passive whole-body rotation in the horizontal plane (amplitude, +/- 10 deg; frequency, 0.2 Hz). Eye and gaze gain (eye and gaze velocity/stimulus velocity) were calculated after deleting saccades. RESULTS: Eye gain of all SCA-6 patients during pursuit was significantly lower than those of the control subjects (mean +/- SD, 0.26+/-0.06 versus 0.91+/-0.07). In contrast, eye gain of the patients was not significantly different from that of the control subjects either during VOR cancellation, when the subjects tracked a target that moved with the same amplitude and phase, like a chair (0.21+/-0.05 versus 0.12+/-0.07), or during visually enhanced VOR (x1), when the target remained stationary in space (0.85+/-0.06 versus 0.95+/-0.05). Moreover, there was no significant difference in mean VOR gain in total darkness between the two groups. Gaze gain of patients (0.26+/-0.06 versus 0.81+/-0.06) but not control subjects (0.91+/-0.07 versus 0.88+/-0.08), was significantly different during pursuit and VOR cancellation. CONCLUSION: SCA-6 patients show dissociation in the control of gaze tracking during smooth pursuit and VOR cancellation.     

Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.     

Psychiatric syndromes in cerebellar degeneration

The role of the cerebellum in both normal and abnormal processes has undergone substantial reassessment over the past several years. Although the cerebellum's role has traditionally been considered the coordination of voluntary movements, increasing evidence now supports its role in the modulation of cognitive and emotional processing. We review both earlier anecdotal clinical data and newer systematic studies that detected psychiatric changes in patients with cerebellar degeneration (CD); these findings are consistent with observations in other neurodegenerative diseases. Our own data reveal high rates of mood disorders, personality change, psychosis, and cognition in patients with degenerative diseases affecting the cerebellum. These findings have important clinical implications in the management of these patients. In addition, the demonstration that psychiatric disorders may be the consequence of degenerative diseases affecting the cerebellum provides an insight into the neuroanatomical basis for psychopathology, and provides further validation of the general concept that many psychiatric syndromes are rooted in the brain.