Journal of Neuro-Ophthalmology, June 1996, Volume 16, Issue 2

Torsional Nystagmus During Vertical Pursuit

We examined three patients with cavernous angioma within the middle cerebellar peduncle. Each patient had an unusual ocular motor finding: the appearance of a strong torsional nystagmus during vertical pursuit. The uncalled-for torsion changed direction when vertical pursuit changed direction. In one patient, we recorded eye movements with the magnetic field technique using a combined direction and torsion eye coil. The slow-phase velocity of the inappropriate torsional nystagmus was linearly related to the slow-phase velocity of vertical smooth pursuit, and changed direction when vertical pursuit changed direction. This torsional nystagmus also appeared during fixation suppression of the vertical vestibulo-ocular reflex (VOR), but was minimal during vertical head rotation when fixing a stationary target in the light. We suggest that inappropriately directed eye movements during pursuit might be another ocular motor sign of cerebellar dysfunction. Furthermore, we speculate that the signals used for vertical smooth pursuit are, at some stage, encoded in a semicircular canal VOR coordinate framework. To illustrate, for the vertical semicircular canals, vertical and torsional motion are combined on the same cells, with the anterior semicircular canals mediating upward movements and the posterior semicircular canals mediating downward movements. For the right labyrinth, however, both vertical semicircular canals produce clockwise slow phases (ipsilateral eye intorts, contralateral eye extorts). The opposite is true for the vertical semicircular canals in the left labyrinth; counterclockwise slow phases are produced. Hence, to generate a pure vertical VOR, the anterior or posterior semicircular canals on both sides of the head must be excited so that opposite-directed torsional components cancel. Thus, if pursuit were organized in a way similar to the VOR, pure vertical pursuit would require that oppositely-directed torsional components cancel in normals. If this did not happen, a residual torsional nystagmus could appear during attempted vertical pursuit.

Journal of Neuro- Ophthalmology 16( 2): 79- 90, 1996. © 1996 Lippincott- Raven Publishers, Philadelphia Torsional Nystagmus During Vertical Pursuit Edmond J. FitzGibbon, M. D,, Preston C Calvert, M. D, Marianne Dieterich, M. D., Thomas Brandt, M. D., and David S. Zee, M. D. We examined three patients with cavernous angioma within the middle cerebellar peduncle. Each patient had an unusual ocular motor finding: the appearance of a strong torsional nystagmus during vertical pursuit. The uncalled- for torsion changed direction when vertical pursuit changed direction. In one patient, we recorded eye movements with the magnetic field technique using a combined direction and torsion eye coil. The slow-phase velocity of the inappropriate torsional nystagmus was linearly related to the slow- phase velocity of vertical smooth pursuit, and changed direction when vertical pursuit changed direction. This torsional nystagmus also appeared during fixation suppression of the vertical vestibulo- ocular reflex ( VOR), but was minimal during vertical head rotation when fixing a stationary target in the light. We suggest that inappropriately directed eye movements during pursuit might be another ocular mo­tor sign of cerebellar dysfunction. Furthermore, we speculate that the signals used for vertical smooth pur­suit are, at some stage, encoded in a semicircular canal VOR coordinate framework. To illustrate, for the vertical semicircular canals, vertical and torsional motion are combined on the same cells, with the anterior semicir­cular canals mediating upward movements and the pos­terior semicircular canals mediating downward move­ments. For the right labyrinth, however, both vertical semicircular canals produce clockwise slow phases ( ip-silateral eye in torts, contralateral eye extorts). The op­posite is true for the vertical semicircular canals in the left labyrinth; counterclockwise slow phases are pro­duced. Hence, to generate a pure vertical VOR, the an­terior or posterior semicircular canals on both sides of the head must be excited so that opposite- directed tor­sional components cancel. Thus, if pursuit were orga­nized in a way similar to the VOR, pure vertical pursuit Manuscript received May 9, 1995; accepted October 20, 1995. From the National Eye Institute, National Institutes of Health, Bethesda ( E. J. F.) and Department of Neurology, The Johns Hopkins University, Baltimore, Maryland, U. S. A. ( D. S. Z.); Department of Neurology and Neurosurgery, George Washington University, Washington, D. C., U. S. A. ( P. C. C.); and Department of Neurology, Klinikum Grosshadem, Lud-wig- Maximilians University, Munich, Germany ( M. D., T. B.) Address Correspondence and reprint requests to Dr. Ed­mond J. FitzGibbon, Building 49, Room 2A50, National Eye Institute, NIH, Bethesda, MD 20892, U. S. A. would require that oppositely- directed torsional compo­nents cancel in normals. If this did not happen, a resid­ual torsional nystagmus could appear during attempted vertical pursuit. Key Words: Smooth pursuit- Ocular torsion- Nystagmus- Cerebellum- Ocular motor- Cross-coupling. In order to clearly see an object clearly that is moving across the visual scene, the ocular motor system must generate smooth following move­ments that match both the speed and the direction of the target of interest. Inappropriately directed horizontal or vertical components of smooth track­ing movements could take the image away from the fovea and lead to a decrease in visual acuity. The adverse consequences of inappropriate torsion during pursuit are less obvious, since torsion, while rotating the globe around the line of sight, does not take images away from the fovea. Un­wanted torsion, however, can lead to blurring of the outer, peripheral features of a moving object if the object is big or close enough that its image extends into the parafoveal region. Unwanted tor­sion during pursuit may also lead to an illusion of tilt, either of the target itself or of the background on which the motion of the target is embedded. Here, we describe three patients who showed uncalled- for torsion during attempted vertical smooth pursuit. We develop the hypothesis that this finding is related to an imbalance of the pur­suit signals at the level of the cerebellum. This for­tuitous imbalance unmasks a torsional component in the pursuit signal, leading us to conclude that pursuit signals are encoded in a vestibular ( semi­circular canal) coordinate system. 79 80 E. J. FITZGIBBON ET Ah. METHODS Eye Movement Recordings The movements of the right eye of patient no. 1 were recorded using the magnetic field technique with a combined direction ( horizontal and vertical) and torsion scleral search coil. The torsion coil was calibrated before placing it on the eye by attaching it to a gimbal and rotating it in the roll plane by a known amount. The target stimulus was a 1°, light- emitting diode ( LED), rear- projected onto a translucent screen. Target position was controlled by computer using a mirror galvanometer system. Saccades to target steps, and pursuit of a target moving in a triangle waveform at 5, 10, and 207sec were performed. The vestibulo- ocular reflex ( VOR) was elicited during passive head- on- body rotation during fixation of a stationary target in the light. VOR cancellation ( combined eye- head tracking) was recorded during passive head rotation with the patient fixing on a target that was attached to the head and aligned with the subject's straight ahead position. The position of the head was mon­itored with a second search coil affixed to the fore­head of the subject. This coil was also calibrated beforehand on a gimbal. We also recorded the pa­tient's responses to an afterimage ( using a flash gun) that was in the shape of a horizontal bar. Eye movement recordings were digitized at 1 kHz and analyzed off line. CASE REPORT Patient No. 1 A 45- year- old woman had recurrent episodes of oscillopsia, vertical diplopia, and imbalance, in 1974, 1976, and 1980. Each episode resolved over several days. In 1985, she complained of symp­toms of vertigo and " fullness in her ears." A com­puted tomographic ( CT) scan of the head showed a calcified lesion in the posterior fossa and mag­netic resonance imaging ( MRI) showed a 7- mm le­sion in the right cerebellum near the deep nuclei and next to the middle cerebellar peduncle ( Fig. 1A). The lesion was thought to be a cavernous an­gioma. On clinical examination, the patient had a mild left ptosis with a slight right- left facial asymmetry. There was no dysmetria or tremor in the limbs and gait was normal, although there was some sway on Romberg testing with the feet apposed. The remainder of the general neurological examination was normal. On ocular motor examination, there was a full range of eye motion with horizontal gaze- evoked and rebound nystagmus. The eyes were well aligned. In the primary position of gaze, when fixation was eliminated using Frenzel lenses, there was a slight left beating, but no apparent torsional or vertical nystagmus. Saccades were fast and accurate and without a torsional component. There was a torsional nystagmus during vertical pursuit of a small target, which was beating clock­wise ( CW) ( as seen from the vantage of the ob­server, i. e., left eye extorting and right eye intort-ing) during upward pursuit and counter- clockwise ( CCW) during downward pursuit. The vertical component of pursuit itself was smooth and did not appear dissociated between the two eyes. The torsional nystagmus, however, appeared to be more prominent in the right eye. A similar tor­sional nystagmus was observed during vertical op­tokinetic nystagmus ( OKN) using a hand- held drum and during cancellation of the vertical VOR ( following an object kept aligned and moving with the head), but not during the vertical VOR in the light elicited with a " doll's head" maneuver and instructions to look straight ahead. Behind Frenzel goggles, a CCW torsional and downbeat nystag­mus appeared in all dependent head positions, but nystagmus was maximal with the right ear down. Horizontal head shaking produced a transient left beating nystagmus and vertical head shaking pro­duced a transient right and downbeating nystag­mus. Patient No. 2 A 50- year- old woman began having frequent ep­isodes of vertigo and headaches in 1991. These were largely controlled with nortriptyline. MRI showed several lesions, probably angiomas ( Fig. IB). One was located peripherally in the left cere­bellar hemisphere and the other was within the right middle cerebellar peduncle near the fourth ventricle. On clinical examination, the patient would fall to the left when standing on one foot with eyes closed. Limb movements were accurate without weakness, tremor, or dysmetria, and rapid alter­nating movements were performed normally. On ocular motor examination, there was a small up and left beating nystagmus noted during ophthal­moscopy. There was a slight exophoria on right, but not on left, gaze. On right gaze, a torsional nystagmus appeared with CCW beating quick phases. On left gaze, there was some left beating nystagmus. In primary position, there was a just discernible CW beating nystagmus, slightly more / Neuro- Ophthalmol, Vol. 16, No. 2, 1996 TORSIONAL NYSTAGMUS DURING VERTICAL PURSUIT 81 prominent in the right eye. This was not accentu­ated when fixation was removed with Frenzel lenses. During vertical pursuit, the vertical compo­nent of tracking was smooth. On pursuit upwards ( of either a small target or during tracking of a handheld drum) and during upward VOR cancel­lation, the small amount of CW nystagmus that was present during fixation became markedly ac­centuated. On smooth pursuit downwards and during downward vertical VOR cancellation, a CCW beating nystagmus developed. On the other hand, during the vertical VOR in the light, there was no torsional nystagmus. Horizontal and ver­tical saccades were normal without torsion. Hori- FIG. 1. A: MRI, patient no. 1. Axial section through the cerebellum showing the lesion, a presumed cryp­tic angioma in the region of the right middle cere­bellar peduncle. B: MRI, patient no. 2. An axial sec­tion through the cerebellum showing a lesion in the region of the right middle cerebellar peduncle. There also is a smaller lesion located more peripherally in the left cerebellar hemisphere. C: MRI, patient no. 3. An axial section through the cerebellum showing a lesion in the region of the left middle cerebellar pe­duncle. zontal pursuit and horizontal VOR in the light were normal. Patient No. 3 This 37- year- old man had recurrent attacks of vertigo, horizontal diplopia, left- sided incoordina­tion, headaches, and vomiting, often brought on by physical exertion. In 1991, MRI revealed a hem­orrhage in the left cerebellum adjacent to the fourth ventricle ( Fig. 1C). Angiography suggested the source to be a small vascular lesion, possibly a venous angioma. At that time, the patient was noted to have an ocular tilt reaction to the left with / Neuro- Ophthalmol, Vol. 26, No. 2, 1996 82 E. J. FITZGIBBON ET AL. a vertical divergence of right over left, increasing with leftward gaze and decreasing with rightward gaze. He had slight dysmetria and ataxia of the left hand and leg, and a tendency to fall to the left. There was no dysarthria or weakness. The hemor­rhage was removed surgically. Histological exam­ination showed partial organization of connective tissue and capillary sprouts- a cavernous angioma. On recent examination, the patient showed a full range of eye motion, but with a slight right hyperdeviation and left- head tilt. In the primary position and on up and down gaze, there was a small CCW beating torsional nystagmus that was slightly more prominent in the left eye. On right gaze, there was a right- beating horizontal nystag­mus. With head tilt, the torsional nystagmus in­creased with right ear down and decreased with left ear down. During upward smooth pursuit, the vertical component of tracking was smooth, but there was a marked accentuation of his CCW beat­ing torsional nystagmus. A similar nystagmus ap­peared during upward tracking of a handheld OKN drum and during upward VOR cancellation. Downward pursuit was saccadic, with inadequate downward slow phases, but the CCW torsional nystagmus previously seen during fixation had disappeared. Likewise, during downward OKN tracking and downward VOR cancellation, the spontaneous torsional nystagmus disappeared. During the vertical VOR in the light, however, there was a CCW beating torsional nystagmus as­sociated with downward slow phases, but no tor­sional nystagmus with upwards slow phases ( this was just the opposite pattern of torsional nystag­mus that was associated with vertical pursuit). Sac-cades were promptly initiated, of normal speed, and showed slight overshoot for leftward sac-cades. There was no torsion observed with sac-cades. Horizontal pursuit was relatively smoother to the left. In summary, each patient developed an inap­propriate torsional nystagmus or showed a marked modulation of a small spontaneous tor­sional nystagmus, both associated with vertical smooth tracking. The faster the pursuit tracking, the higher the speed of the torsional nystagmus. The torsional nystagmus was more prominent in the right eye in patient nos. 1 and 2 and in the left eye in patient no. 3. In patient nos. 1 and 2, with lesions near the right middle cerebellar peduncle, torsional nystagmus beat CW during upward tracking and CCW during downward tracking. In patient no. 3, with a lesion near the left middle cerebellar peduncle and a small spontaneous CCW beating torsional nystagmus, there was a marked increase in the CCW nystagmus during upward tracking that stopped during attempted smooth downward tracking. Each subject showed a pat­tern of torsional nystagmus during VOR cancel­lation that was the same as that during smooth pursuit. During the vertical VOR in the light, no torsional nystagmus was observed in patient nos. 1 and 2, while patient no. 3 showed inappropriate torsional slow phases directed opposite to that ob­served during vertical smooth tracking and vertical VOR cancellation. up 5deg down vertical target r r vertical eye position 5 seconds FIG. 2. Vertical saccades, patient no. 1. In this record­ing, the patient was asked to follow a projected LED tar­get that jumped to different spots along the midsaggital plane. Vertical target posi­tion, and horizontal, vertical, and torsional eye position are shown. Note that there is the brief transient change in torsional eye velocity ( a tor­sional " blip") during vertical saccades that is a normal phenomenon. There was a small clockwise drift of tor­sional eye position (< 1°) during the recording period. In this and all subsequent recordings, clockwise will refer to the top poles of the patient's eyes rolling to the patient's left, and vice versa. J Neuro- Ophthalmol, Vol. 16, No. 2, 1996 TORSIONAL NYSTAGMUS DURING VERTICAL PURSUIT 83 RESULTS For patient no. 1, movements of the right eye around all three axes of rotation [ horizontal, verti­cal, and torsion ( around the line of sight)] were quantified using the magnetic field search coil technique. Very little torsion was noted during vertical saccades to a jumping target ( Fig. 2). There was a small amount of torsion during the vertical VOR while the patient fixed upon a stationary tar­get in front of her as her head was passively moved up and down in a roughly sinusoidal pat­tern ( Fig. 3). During upward head rotation, i. e., with downward VOR slow phases, the slow- phase component of the small amount of torsion was di­rected CW; during downward head rotation, i. e., with upward VOR slow phases, the slow- phase component was directed CCW. On the other hand, there was marked torsion during vertical pursuit. Figure 4 shows attempted vertical smooth pursuit at 5, 10, and 207s. Torsional nystagmus changes direction ( CW beating upwards, CCW beating downwards) with a change in pursuit di­rection ( center traces), and torsion velocity in­creases with increasing vertical eye velocity ( top traces). During vertical VOR cancellation, there also was unwanted torsion ( Fig. 5). Considerable torsional eye velocity, similar to that observed dur­ing smooth pursuit with the head still, was noted. We also recorded eye movements during vertical tracking of an eccentric afterimage ( Fig. 6). Inap­propriate torsion was still present, indicating that actual motion of images on the retina was not nec­essary for the torsion to appear. Figure 7 shows a plot of torsional smooth eye velocity versus vertical smooth eye velocity, as measured when the eye passed through the pri­mary position of gaze during pursuit and during VOR cancellation. Vertical and torsional velocity were highly correlated for both relationships ( r = cw 20 deg/ sec 0' ^ ^ ^ ^ ^ M w y , c c w torsional eye velocity up i 20 deg/ sec 0 down up 10deg cw. ^\>^ y$ f-;> i}- -\ A vertical eye velocity down vert j c a | neacj position vertical eye position 5 seconds FIG. 3. Vertical VOR, patient no. 1. Vertical and torsional eye position and eye velocity, and vertical head position are shown. Vertical eye position in the orbit was calculated by subtracting vertical head position from vertical gaze position ( eye in the orbit related to the stationary field coil system). The patient was asked to look at a stationary target straight ahead on the screen and her head was oscillated up and down in a roughly sinusoidal pattern. Note that there was a small amount of torsional eye velocity compared to vertical eye velocity during the vertical VOR. Arrows show an example of torsion eye velocity, which is presumed to occur here because the patient is using vertical pursuit to augment the gain of her vertical VOR in the light. The spikes seen in the velocity traces relate to saccades. / Neuro- Ophthalmol, Vol. 16, No. 2, 1996 84 E, J. FITZGIBBON ET AL. 5 deg/ sec. 10deg/ sec. 20 deg/ sec. 10 deg/ sec torsional eye velocity vertical eye velocity torsional eye position vertical eye position 5 seconds FIG. 4. Vertical pursuit, patient no. 1. The patient followed a vertical target moving vertically at 5, 10, and 207s. Each graph shows vertical and torsional eye position and velocity and vertical target position. Note that with increasing eye velocity, there is a corresponding increase in torsional eye velocity and that the torsional nystag­mus changes direction with change in pursuit direction. CW, clockwise; CCW, counter- clockwise. 0.98 for both) with a slope of - 0.76 for pursuit and - 0.51 for VOR cancellation. There was a signifi­cant difference ( p < 0.01) in the slopes of these two lines ( t- test). A similar plot for afterimage tracking was made ( not shown), and the slope was - 0.54 ( r = 0.98). DISCUSSION Inappropriately- directed Eye Movements ( Cross- coupled Nystagmus) The main finding of this study was the appear­ance of inappropriately- directed torsional eye movements both during vertical smooth pursuit and during cancellation of the vertical VOR. There was no inappropriate torsion during saccades and very little during the VOR rotation in the light. So- called cross- coupling of eye movements, when eye movements are produced that rotate the globe around an axis orthogonal to the correct one, has been previously described during saccades and during the slow phases of the VOR. One example is the saccadic dysmetria that can occur with isch­emic lesions in the dorsolateral medulla ( Wallen­berg's syndrome), in which case there is an inap­propriate horizontal component during attempted vertical saccades, so- called " lateropulsion". This pattern of dysmetria has been attributed to abnor­mal function of the fastigial nucleus ( FN), due to an interruption of the climbing input to Purkinje cells of the dorsal cerebellar vermis, which, in turn, project to and inhibit the FN ( 1,2). Occasion­ally, patients with Wallenberg's syndrome may show an inappropriate torsional component dur­ing attempted horizontal saccades (" torsipulsion") ( 3). There may also be an inappropriate vertical component with attempted horizontal saccades with pontine lesions ( 4). Inappropriately- directed components of the slow phases of the VOR, both spontaneous and head- shaking induced, have also been reported with vestibular lesions; this has been called " per­verted" nystagmus ( 5,6). Patients with congenital nystagmus may also show an accentuation of hor­izontal nystagmus during vertical tracking, but this phenomenon may be related to a release of fixation rather than to direct cross- coupling of pur­suit responses ( 5). Torsion and Listing's Law What might be the source of the unwanted tor­sion shown by our patients during vertical pur­suit? One possibility would be an abnormality of Listing's plane. Normally, when the eyes are J Neuro- Ophthalmol, Vol. 26, No. 2, 1996 TORSIONAL NYSTAGMUS DURING VERTICAL PURSUIT 85 torsional eye velocity 20 deg/ sec thy# 0\ vertical gaze velocity 1 Iw 1 k ' i up 10deg down up | 10deg down vertical eye position 5 seconds FIG. 5. Vertical VOR cancellation, patient no. 1. The patient was instructed to fix on a target that was attached to her head with a headband, and, consequently, the target moved with her head. Note that vertical torsion eye velocity is considerably greater than with the VOR alone ( Fig. 3) and that the pattern of torsion is similar to that during vertical pursuit with the head still ( Fig. 4). Vertical gaze velocity indicates vertical eye velocity in " space" ( referenced to the eye coil frame). brought into tertiary eye positions in the orbit, the globe rotates around the visual axis to a specified ( torsional) orientation ( Donder's law). How the eye is taken to that position is dictated by Listing's law, which states that the axes around which the globe rotates to take the eyes from the primary ( reference) position into any other position of gaze all lie in a single plane ( Listing's plane) that is per­pendicular to the reference position. Normally, Listing's and Donder's laws are well obeyed for smooth pursuit ( 7) as well as steady fixations. It seems unlikely that our patients' findings can be explained by a violation of Listing's law. First, abnormal torsion was not induced with saccades. Secondly, torsional eye velocity during vertical pursuit was linearly related to vertical eye velocity. The speed and even the direction of torsion was independent of eye position. In contrast, abnormal torsion due to a disorder of Donder's or Listing's law should depend on eye position. Inappropriate Torsion due to an Imbalance in Pursuit Signals Normally Encoded in a Canal Coordinate System; Combining Torsion and Vertical Signals for the Slow Phases of the VOR An alternative explanation for our patients' tor­sion during pursuit may relate to the nature of the signal processing associated with generating pure vertical smooth pursuit. Let us first consider how pure vertical eye movements are generated for the slow phases of the VOR. Each individual vertical semicircular canal encodes information for both torsional ( roll) and vertical motion of the head. When stimulated, the anterior semicircular canals always produce slow phases upwards, but with a torsional component that will counterroll the eyes, with the upper pole of the globes rotating toward the opposite ear ( Fig. 8). The posterior semicircular canals always produce slow phases downwards, but the torsional component still counterrolls the eyes with the upper pole of the globes rotating / Neuro- Ophthalmol, Vol. 16, No. 1, 1996 86 E. J. FITZGIBBON ET Ah. 20 cleg/ sec vertical eye velocity \ , ¥ torsional eye velocity torsional eye position up 10deg down vertical eye position FIG. 6. Afterimage vertical pursuit, patient no. 1. A hor­izontal afterimage was pro­duced by flashing a horizon­tal bar onto the patient's eye and she was instructed to follow it smoothly. Note the smooth torsional motion as­sociated with the upward vertical eye motion ( left panel). The patient had more difficulty with down­ward afterimage tracking, as seen in the right panel, but there was some associated torsion in the same direction as during normal downward pursuit. 5deg 5deg toward the opposite ear. In order to generate a pure vertical slow phase, the anterior or posterior semicircular canals on both sides of the head must be activated simultaneously so that the opposite-directed torsional components cancel within the vestibular nuclei. Combining Torsion and Vertical Signals for Quick Phases of Nystagmus This type of organization is also reflected in the generation of the quick phases of vestibular nystagmus. In the rostral interstitial nucleus of the medial longitudinal fasciculus ( riMLF) in the mid­brain, there are premotor saccade burst neurons, each of which discharges for both torsional and vertical rapid eye movements ( both saccades and quick phases of nystagmus) ( 8). On each side of the midbrain, there are burst neurons, some of which discharge for upward and some for down­ward saccades, but all the burst neurons on the same side of the brainstem discharge for just one direction of torsion ( when the top poles of the eyes rotate to the ipsilateral side). Thus, in order to gen­erate a purely vertical quick phase, burst neurons in the riMLF on both sides of the midbrain must be activated simultaneously so that the torsional com­ponents cancel. Presumably, as the ability to make voluntary vertical ( and horizontal) saccades in a Cartesian coordinate system evolved in animals with foveas, higher centers made use of this ready- made sub­strate for generating quick phases of nystagmus. The saccadic system simply had to ensure that both sides of the riMLF in the brain stem were activated whenever a vertical saccade was desired. When there is a complete lesion of the riMLF on one side of the brain stem, an inappropriate rapid torsional movement, directed such that the top pole of the eye rolls to the contralateral side, is associated with both up and down saccades. This disorder is similar to that of our patients, although the inappropriate torsion does not change direc­tion with that of the vertical saccade. This is be­cause cells encoding both up and down move­ments as well as torsion are affected by the lesion in the riMLF. Combining Torsion and Vertical Signals for Vertical Pursuit We propose here that an analogous type of sig­nal processing, requiring cancellation of opposite- / Neuro- Ophthalmol, Vol. 16, No. 2, 1996 TORSIONAL NYSTAGMUS DURING VERTICAL PURSUIT 87 o a a> o o > o >. Hi c o " U> o cw O J • O - - 10 ccw • x^^ kt ' x^ X-^ C^^ JL X X^- C^ JL x ^ ^ + target pursuit X vor cancellation i ~^ N^ t i <+ • ^^. x^^ % 5> 1 ' i - 20 0 20 Vertical Gaze Velocity ( deg/ sec) FIG. 7. Comparison of vertical gaze and torsional eye velocity for vertical pursuit with the head still and for vertical VOR cancellation, patient no. 1. Here, vertical gaze velocity is plotted against torsion eye velocity during vertical pursuit with the head still ( pluses) or moving ( crosses). Torsion eye velocity was mea­sured when the eye was within ± 3° of primary ( 0°) position. Positive torsion velocity values are clockwise ( CW), negative values are counter- clockwise ( CCW). Note the linear relation between vertical eye velocity and torsion velocity. Regression lines ( r = 0.98 for both) are drawn through the two sets of data points. directed torsional components, must occur for ver­tical smooth pursuit. We speculate that at some stage of the signal processing that mediates verti­cal smooth pursuit tracking, visual information is encoded in the same directions as are the planes of the semicircular canals relative to the head, i. e., with torsion ( roll) and vertical motion being com­bined. There must then be a transformation of in­formation from vestibular, or " canal", coordinates into the necessary Cartesian or foveate coordinate system for generating horizontal and vertical pur­suit eye movements of small targets. We suggest that our patients' lesions uncovered this organiza­tional feature of the signal processing that under­lies smooth pursuit in normal subjects. At first glance, this hypothesis seems implausi­ble since smooth pursuit movements are designed to keep images stable on the fovea, in which case any torsion would be unimportant. There is vir­tually no ability ( or need) to generate torsional pursuit eye movements for the tracking of small moving targets. On the other hand, there are rap­idly- acting visual- following mechanisms, sharing many features with smooth pursuit, that are used to track movements of larger portions of the visual field ( 9). In these circumstances, an ability to gen­erate torsional visual following might be more use­ful. While less robust than for horizontal or vertical tracking, there is an ability to generate torsional optokinetic nystagmus and to modulate torsional VOR responses using large- field visual stimuli ( 10,11). Organization of Visual Tracking in Afoveate Animals Furthermore, from a phylogenetic point of view, visual- following reflexes evolved together with the vestibular responses. This parallel development is reflected in the fact that the visual information that is used to supplement labyrinthine information during a head motion, such as OKN, is encoded in the same coordinate system as is labyrinthine in­formation, i. e., in a canal- coordinate system ( 12,13). Hence, sensitivity to vertical and torsional motion are combined on neurons carrying infor­mation for OKN in the same way that information about roll and vertical motion is combined on pri­mary vestibular afferents, so that a cancellation of torsion would become necessary to generate pure vertical visual tracking. In the case of rabbits, it has been shown that the cerebellum carries not only labyrinthine but also visual information encoded in canal coordinates ( 12,14). Hence, one can envision that cerebellar le­sions might lead to inappropriate torsion during vertical tracking. In the case of primates, the cere­bellum contains pathways for generating pursuit eye movements, with the dorsal vermis, flocculus, and FN all being critical structures. Our hypothesis for inappropriate torsion during smooth pursuit OCCIPUT -*~ RHC BROW Of RAC + LAC= | RPC + LPC= \ FIG. 8. Summary of the effects of stimulating individ­ual semicircular canals and combination of canals. To produce a pure vertical slow phase, either both ante­rior or both posterior canals must be activated simul­taneously. In this way, the torsional components can­cel. Stimulation of an individual vertical canal pro­duces a mixed vertical and torsional slow- phased movement. Arrows indicate slow- phase direction. J Neuro- Ophthalmol, Vol. 16, No. 2, 1996 E. /. FITZG1BB0N ET AL. assumes that pursuit movements ( and fast full-field visual following) in primates are generated using some of the same neural circuitry that un­derlies the generation of full- field visual- following responses. Combination of Vestibular and Pursuit Signals on Vestibular Nuclei Neurons Finally, there is certainly evidence that neurons within the vestibular nuclei that mediate the ver­tical VOR also carry vertical pursuit signals, and receive projections from the cerebellum ( 15,16). Hence, if these vestibular nuclei neurons also carry torsional signals, then unbalanced projections from the cerebellum during attempted vertical pur­suit might lead to inappropriate torsion. An Analysis of our Patients' Tracking Behavior With this hypothesis, we can explain our results by assuming that the cerebellar lesion has inter­fered with pathways involved in visual tracking that carry information for both vertical and tor­sional motion. In the case of our patients, this would be equivalent to a loss of activity from neu­rons that carry information encoded in the coordi­nates of the anterior semicircular canal ( SCC) on the same side as the lesion ( Fig. 9). In the case of a right cerebellar lesion ( patient nos. 1 and 2), a loss of activity encoded in right anterior canal coordi­nates could lead to a torsional nystagmus with CCW ( with respect to the observer) slow phases on RIGHT ANTERIOR SCC RIGHT POSTERIOR SCC LEFT ANTERIOR SCC LEFT POSTERIOR SCC UP CW DOWN CW UP CCW DOWN CCW 0\ *\ '"> / \ Q( /....../...?$ , y UP DOWN FIG. 9. Diagram to indicate the hypothetical mixing of torsional and vertical signals for the generation of pur­suit. Solid lines indicate effects of an increase in ac­tivity on the direction of eye motion; dashed lines, ef­fects of a decrease in activity. Our patients' behavior can be accounted for by an interruption in activity for pursuit that is encoded in anterior SCC coordinates ( right anterior SCC for patient nos. 1 and 2, and left anterior SCC for patient no. 3). upward tracking because of a loss of the increase in activity that would normally produce CW torsional slow phases ( Fig. 9, solid lines). The opposite-directed torsion ( slow phases CCW) during up­ward tracking arises from the neurons carrying information encoded in left anterior canal coordi­nates that would now be unopposed. The opposite pattern would occur for downward tracking; the absence of a decrease in the activity from the neu­rons that encode information in right anterior ( SCC) coordinates ( Fig. 9, dashed lines) would lead to a preponderance of relative torsional activ­ity for slow phases CW during downward track­ing. With a lesion on the other side of the brain ( patient no. 3), the torsional nystagmus during vertical pursuit would show the opposite pattern of the torsional component, with slow phases CW during upward tracking and slow phases CCW during downward tracking. This scheme also explains why the torsional nystagmus was more prominent in the eye ipsilat-eral to the lesion. A preponderance of activity en­coded in the coordinates of the contralateral ante­rior SCC would lead to more prominent torsion in the ipsilateral ( to the lesion) eye, since the primary projections from the anterior SCC ( which would be lost to the pursuit system in this scheme) are to the ipsilateral superior rectus ( with its primary action being vertical rotation of the globe) and to the con­tralateral inferior oblique ( with its primary action being torsion of the globe). Such a hypothesis also predicts that there would be a small ( 25%) loss of premotor vertical tracking signals due to the missing increase or decrease in activity for upward or downward pursuit move­ments, respectively, from the neurons encoding information in anterior SCC coordinates on the side of the lesion. But this could be easily over­come and would probably go unnoticed because of the ability of visual feedback in a closed- loop track­ing system to compensate for and to obscure small deficits in the generation of premotor visual track­ing commands. The findings in all three of our patients are largely compatible with this hypothesis. Patient no. 3 did not show a reversal of torsion during downward pursuit, but he was not able to gener­ate much downward vertical pursuit to begin with. Hence, the possibility to elicit cross- coupling was probably diminished for downward tracking. Patient no. 1 had a small amount of torsional nystagmus apparent during recordings of the VOR in the light ( Fig. 3, arrows). The direction of the torsional nystagmus was compatible with the idea that a small amount of vertical pursuit ( with its / Neuro- Ophthalmol, Vol. 16, No. 2, 1996 TORSIONAL NYSTAGMUS DURING VERTICAL PURSUIT 89 corresponding torsion) was being added to the VOR slow phase during head rotation in the light. Patient no. 3 also showed cross- coupling during the VOR in the light, but in the opposite direction to that predicted if pursuit were being used to aug­ment his VOR. He could have been using pursuit to oppose a hyperactive VOR or his lesion may also have involved pathways that directly mediate VOR responses. Finally, it is worth noting that the amount of torsion with vertical VOR cancellation was similar to that of torsion during vertical pursuit with the head still. This is another piece of evidence imply­ing a common source for the signals that underly pursuit ( with the head still) and VOR cancellation ( pursuit with the head moving). Vertical Tracking of Afterimages In order to establish if the inappropriate torsion shown by our patients was directly related to the transformation of retinal ( visual) information about target motion into pursuit commands, we examined pursuit eye movements in patient no. 1 during afterimage tracking, in which case there is no retinal image motion. We found that the un­called- for torsion still appeared and was linearly related to vertical smooth eye velocity, although with a smaller slope ( gain) than during natural tracking. This result suggests that processing of retinal image motion is at least partially involved in the generation of uncalled- for torsion. Retinal po­sition errors, however, which are present when the afterimage is eccentric from the fovea, can also serve as visual stimuli for smooth pursuit ( 17) and their processing might also be responsible for some of the unwanted torsion. Even when after­images are placed directly on the fovea, however, voluntary smooth pursuit can still be generated, so that neither retinal slip nor a retinal position error may be necessary for cross- coupled torsion during vertical pursuit. Exactly how much of the cross-coupling that produces torsion during vertical pur­suit is due to disturbed processing of visual infor­mation per se, or is due to abnormal transforma­tion of motor signals into the correctly- directed premotor commands for pursuit, is not known. Clinical- Anatomical Correlation Each of our patients had a lesion that was close to or within the middle cerebellar peduncle. Pa­tient no. 2 had another smaller lesion, located more peripherally in the opposite cerebellar hemi­sphere, that, we assume, did not contribute to her torsional nystagmus during vertical pursuit. The middle cerebellar peduncle probably carries infor­mation needed for the generation of pursuit eye movements, from various pontine structures in­cluding the nucleus reticularis tegmenti pontis and other portions of the pontine nuclei ( 18,19). On the other hand, projections from the inferior cerebellar peduncle, which include climbing fibers that carry visual information encoded in canal coordinates ( 20), also run near the location of the lesions so that it may not be possible to absolutely exclude involvement of these pathways. We suggest that inappropriate cross- coupling of eye movements is a sign of cerebellar dysfunction, most likely involv­ing the middle cerebellar peduncle. The pattern of torsional nystagmus in our patients suggests that information for visual tracking that is encoded in anterior SCC coordinates is carried in the middle cerebellar peduncle. Single- unit recordings of ac­tivity of individual neurons in response to mix­tures of vertical and roll motion in primates will be needed to explicitly test this hypothesis. Finally, one may ask why other types of cross-coupling, e. g., vertical to horizontal, are not seen more commonly with cerebellar lesions. It may be that encoding of visual information for pursuit in canal coordinates predisposes to abnormal cross-coupling from vertical to torsion. Furthermore, any cross- coupling between vertical to horizontal or vice versa would be harder to detect clinically because the negative feedback visual tracking sys­tem itself would act to suppress the uncalled- for orthogonal component. Acknowledgment: Dr. Zee was supported by NIH grant EYO- 1849 and a Research to Prevent Blindness Manpower Award. 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