| OCR Text |
Show ORIGINAL CONTRIBUTION Dissociated Palsy of Vertical Saccades: Loss of Voluntary and Visually Guided Saccades With Preservation of Reflexive Vestibular Quick Phases Ji-Hoon Kang, MD, PhD, and James A. Sharpe, MD, FRCPC Abstract: A patient with a diencephalic infarct displayed a persistent palsy of voluntary and visually guided vertical saccades with preserved vertical quick phases of vestibular nystagmus on magnetic search coil oculography. Vertical smooth pursuit had very low velocity in both directions without catch-up saccades. Vertical and torsional vestibulo-ocular reflex gains were normal. Preservation of vertical and torsional quick phases signifies integrity of the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF). This case is the first to provide evidence that disruption of descending cerebral corticofugal pathways to the riMLF with preserved ascending projections from the paramedian pontine reticular formation to the riMLF can cause a disso-ciated palsy of vertical fast eye movements. (/ Neuro-Ophthalmol 2008;28:97-103) Vertical gaze palsy is a recognized feature of unilateral or bilateral midbrain lesions involving the rostral interstitial nucleus of the medial longitudinal fasciculus (riMLF) and interstitial nucleus of Cajal (INC) (1-4). Neurophysiologic study can play an important role, in addition to imaging, in determination of the neural struc-tures responsible for vertical gaze palsy. Preservation of vertical quick phases of the vestibulo-ocular reflex (VOR) indicates integrity of vertical saccade generation by the riMLF (5,6). Palsy of cerebrally generated vertical saccades with preserved vertical quick phases of vestibular nystag-mus has never been reported. Department of Neurology (J-HK), Cheju National University College of Medicine, Cheju, Republic of Korea; and Division of Neurology (JAS), University Health Network, University of Toronto, Toronto, Ontario, Canada. Supported by Canadian Institutes of Health (CIHR) grants MT5404 and ME5909. Address correspondence to James A. Sharpe, MD, FRCPC, Division of Neurology, University Health Network, 399 Bathurst St., ECW 5-042, Toronto, ON, Canada M5T 2S8; E-mail: james.sharpe@uhn.on.ca We report a patient with vertical gaze palsy consisting of complete loss of voluntary and visually triggered saccades with preserved upward, downward, and torsional quick phases of the vertical VOR and discuss the anatomical, physiologic, and diagnostic significance. METHODS Patient A 50-year-old man was referred for evaluation of vertical gaze paralysis 6 months after he developed sudden confusion and dysarthria from a posterior circulation infarct. Consciousness and speech recovered within a few days, but persistent impairment of vertical gaze was observed. There was no history of prior stroke or other neurologic diseases, and he had no known risk factors for stroke. Neuro-ophthalmologic examination showed normal visual acuity, fields, and ophthalmoscopy. The pupils measured 6 mm in dim illumination and constricted normally to direct light and near stimuli. There was no gaze deviation. There was no ocular misalignment discovered in cover testing during fixation while oculography recorded vertical positions of both eyes (see below). No spontaneous vertical, horizontal, or torsional nystagmus was observed, but spontaneous torsional nystagmus was recorded by oculography (see below). Vertical saccades were absent on command and in response to visual targets both above and below the orbital midposition. Vertical pursuit was severely reduced in both directions, but the visually enhanced VOR (WOR) was of full range vertically during oculocephalic testing. No vertical optokinetic nystagmus was elicited with a hand-held striped drum. Bell's phenomenon (binocular upward gaze deviation during forced eyelid closure against the examiner's digital resistance) was preserved. We did not inspect the fundi for the detection of static torsion. Horizontal saccades, smooth pursuit, and the WOR were normal. Horizontal optokinetic nystagmus was normal. There was no ptosis, eyelid apraxia, or eyelid retraction. Convergence was limited to a few degrees. The other cranial J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 97 J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 Kang and Sharpe nerves were unaffected. The patient's cognition and memory were good. Motor power, tone, coordination, and tendon reflexes were normal. Sensation was intact and plantar responses were flexor. An initial brain MRI on the second day after symp-tom onset showed acute infarcts in both medial thalami. Repeat brain MRI 1 year later revealed additional high signal lesions typical of chronic bilateral infarcts in the rostral midbrain dorsomedial to the red nucleus. A rela-tively large lesion involved the region of the right riMLF and INC, and a small lesion was evident in the left rostral midbrain tegmentum (Fig. 1). Catheter angiography did not show occlusion or stenosis of the vertebral or basilar arter-ies. Trans-esophageal echocardiography showed a small atrial septal defect. The infarcts were attributed to embolism to the distal basilar artery, and he was treated with warfarin anti-coagulation followed by daily low-dose acetylsalicylic acid. Twelve repeated neuro-ophthalmologic examinations over the course of 7 years after the first evaluation revealed no change in the ophthalmoplegia. Oculographic Study Vertical and torsional eye movements were recorded 7 months after the onset of symptoms by a magnetic search coil technique using 6 foot diameter coils (C-N-C Engi-neering, Seattle, WA). The patient sat in a vestibular chair while wearing a soft contact dual scleral search coil (Skalar, Delft, The Netherlands) in his right eye. Head movements were monitored by a second coil mounted in a headband. Saccades were elicited to a rear-projected laser dot target with a diameter of 0.25°. Saccadic movements were mea-sured in response to verbal commands and to target steps of 5, 10, 20, and 40° at regular (3-second) or unpredictable (1- to 5-second) intervals. Smooth pursuit was elicited to the laser target that moved vertically in predictable sinusoids of ±10° at 0.25 and 0.5 Hz. Pursuit was quantified by its gain, the ratio of smooth eye movement velocity to target velocity, for each sinusoidal half cycle. Vestibular eye movements were induced in complete darkness by active sinusoidal ±10° head on body rotations in pitch to elicit the vertical VOR and in roll to elicit torsional VOR, at approximately 0.5, 1, and 2 Hz. We did not record the eyes after static head pitch or roll to measure any ocular drift. The same head rotations were repeated while the patient viewed a stationary laser target to elicit the WOR. The patient's head was centered in the field coils. Head and eye movements were calibrated by attaching the scleral coil to a rotating gimbal. To measure any offset of coil signal, during the gimbal calibration the coil was rotated through 360° to measure its maximum and minimum readings. If there were no offset, these two readings should be equal and opposite. If they were not FIG. 1. A. T2 axial MRI at thalamic level shows ischemic lesions in the medial thalamus bilaterally (arrows). B. T2 axial MRI at rostral midbrain level shows bilateral midbrain infarcts dorsomedial to the red nuclei. C. Schematic illustration corresponding to MRI in B shows the lesions. SN, substantia nigra; RN, red nucleus. equal and opposite, the mean of the two readings was the offset, which was then subtracted from the coil recordings. Torsional precision was approximately ±0.2°. There was minimal cross-talk; large horizontal and vertical movements produced deflections in the torsional channel of less than 4% of the amplitude of the horizontal and 98 © 2008 Lippincott Williams & Wilkins Vertical Saccades J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 vertical movement. Horizontal eye movement calibration was verified by saccades to targets at central gaze, and 10° and 20° to the left and right of central gaze. Any coil slippage was assessed by monitoring offsets in the torsional eye position signal during testing. Consistency of calibrated positions after each eye movement provided evidence that the coil did not slip on the eye. In one dimension, the input (head velocity) and output (eye velocity) of the VOR are regarded as scalar quantities (real number), and the reflex is characterized by its gain, which is the ratio of eye velocity to head velocity. In most natural head rotation, however, the input and output of the VOR are not scalars but are three-component vectors (the angular velocity vectors of the head and eye), having not only magnitudes but also directions. Thus, a more complete characterization of the VOR involves a descrip-tion, not only of the relative sizes of eye and head velocities, but also of their relative directions-the axes about which the eye and the head rotates. The VOR, however, can be treated as one dimensional if head rotation occurs around only one axis. For example, during pure horizontal head rotation (around the earth-vertical axis), the vertical and torsional components of the three-component rotation vector become zero. In this situation, the velocity of rotation can be derived by differentiation of position data. In this study, while horizontal, vertical, and torsional head positions were measured, gaze position data were measured in one dimension. That is, horizontal gaze positions were recorded during horizontal head motion, vertical gaze posi-tions during vertical head motion, and torsional gaze positions during head roll. Pure head rotation around one axis was approximated by analyzing only data for which the other two axes showed [less than or equal to] 1° variation from baseline. Gaze, head, and target positions were digitized at 200 Hz. The difference between gaze position and head position yielded eye position. Head, eye, and gaze positions were also monitored on an ink-jet rectilinear polygraph (Siemens Mingograf, Solna, Sweden). To yield an accel-eration output insensitive to high frequency noise, digitized eye position signals were passed through an 18-point impulse response filter with the characteristics of a modified Hilbert transformer, coupled with a 2-point central difference differentiator and a 6-17 Hz filter. The bimodal acceleration profile of each saccade or nystagmus quick phase was recognized, and this time-locked segment was removed from the eye position record. Editing of digitized gaze, eye, and head movements was performed by interactive computer programs to assure proper saccade removal and to detect and reject blink or other artifacts. A quadratic curve with a slope equal to the slope of the smooth eye movements before and after each saccade or nystagmus quick phase was generated to fit across the "gaps," yielding a cumulative eye position trace from which all fast eye movements had been removed. This signal was differentiated to yield a velocity record that was fitted with a sinusoid of the same frequency as at the head movement (for the VOR) or target (for pursuit) by a discrete Fourier transform technique (7). Gains of smooth eye movement during the VOR and pursuit were computed by dividing the amplitude of the fitted eye velocity curve by the amplitude of the stimulus velocity curve (head or target) for each half cycle of movement. VOR phase was measured by comparing the peaks of displacements of eye and head position for each half cycle. We used data from at least 15 cycles of stimulation of each test condition to calculate mean VOR gain and phase. We measured smooth pursuit data from at least eight cycles. RESULTS Vertical voluntary saccades were absent above and below the mid-gaze position both to command and to the target steps (Fig. 2A). Vertical pursuit was limited to a range approximately 10° above and 5° below the mid-gaze position without catch-up saccades (Fig. 2B). Within this range, pursuit gain was low, more so for upward pursuit (Table 1). Vestibular stimulation induced full vertical excursion of the eyes. Vertical and torsional VOR gains were within the normal range (8,9) (Table 2). In complete darkness without a visible target, upward and downward quick phases were recorded during the vertical VOR evoked by head pitch (Fig. 3), and counterclockwise (CCW, from the patient's point of view) torsional quick phases were recorded during torsional VOR elicited by head roll (Fig. 4). Clockwise (CW) torsional quick phases were absent. Vertical and CCW torsional quick phases each had average velocities over 30° per second, confirming their saccadic structure (10); they were faster than vestibular smooth eye movements. They were also faster than all vertical smooth pursuit movements made by the patient. Normally, head and vestibular smooth eye movements are 180° out of phase, and this phase difference is by convention defined as zero. A pronounced phase lead of the eyes before the head ranged from 18 to 22° in the vertical VOR and from 28 to 43° in the torsional VOR (Table 2). Spontaneous CCW beating torsional jerk nystagmus (upper poles of the eyes beating toward the patient's left shoulder) was recorded in darkness and during fixation; it had low amplitudes (~1-3°). Cover-uncover testing of each eye during fixation while recording vertical positions of both eyes showed no vertical vergence movements or vertical refixation saccades or drifts. DISCUSSION Our patient had suffered an infarction in the region supplied by the posterior thalamo-subthalamic paramedian 99 J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 Kang and Sharpe U TARGET 20° EYE B FIG. 2. A. Vertical saccades to a vi-sual target: they are absent. B. Vertical pursuit: there is low-gain pursuit within a restricted range during 20 peak-to-peak sinusoidal target oscillation at 0.5 Hz. Catch-up vertical saccades are absent. U, upward; D, downward. artery, a common cause of vertical gaze palsy that resulted from unilateral or bilateral midbrain lesions involving the riMLF, INC, or their projections (l-4). Brain MRI showed bilateral infarcts localized in the medial thalamus and rostral midbrain. Although the left midbrain lesion was small and dorsal to the red nucleus, the right midbrain lesion was largely located dorsal and medial to the red nucleus and probably involved the riMLF and INC (Fig. 1B). He had paralysis of upward and downward voluntary and visually triggered saccades, but preserved upward and downward quick phases of vestibular nystagmus during head pitch, as well as torsional quick phases in one direc-tion during head roll. The loss of torsional quick phases during the torsional VOR after midbrain lesions is considered as a sign of damage to the riMLF. A right riMLF lesion would cause a loss of CW (from subject's point of view) torsional quick phase, whereas a left riMLF lesion would cause a loss of CCW torsional quick phase (5,6). Thus, absence of CW torsional quick phase and preserved CCW torsional quick phase in our patient implicated a right riMLF infarct that spared the left riMLF. These neurophysiologic findings TABLE 1. Vertical smooth pursuit gain Frequency (Hz) Up Down 0.25 0.14 ± 0.12* 0.31 ± 0.12* (n = 0.5 0.10 ± 0.02* 0.13 ± 0.02* (n = = 10) = 8) Gain values are means ± 1 SD. n, number of cycles measured. *P < 0.05, Student t test. were well correlated with the location of infarcts identified on MRI. The presence of spontaneous low-amplitude torsional nystagmus beating CCW (upper poles toward the left shoulder) was also consistent with damage to the right riMLF (11). This dissociated palsy of vertical fast eye movements, sparing only vestibular quick phases, is not a true ocular motor apraxia, because reflexive vertical visually guided saccades were paralyzed (12). The designation of vertical ocular motor apraxia was imprecisely applied to a patient with perinatal ischemic-hypoxic midbrain damage and paralysis of vertical saccades and pursuit who achieved gaze shifts with head thrusts; vertical quick phases of the VOR were not described (13). Head thrusts activate the VOR and can trigger reflexive quick phases in the direction of the head thrust, which substitute for absent voluntary or visually initiated saccades. Our patient did not use vertical head thrusts. Each riMLF contains saccadic burst neurons that project to the superior rectus and inferior oblique motor neurons of both third cranial nerve nuclei to generate binocular upward and ipsitorsional saccades and other saccadic burst neurons that project to the ipsilateral inferior rectus and superior oblique motoneurons to generate binocular downward and ipsitorsional saccades (14,15). Unilateral chemical lesions of the simian riMLF cause a minimal defect in vertical saccades (mainly downward), and bilateral lesions of riMLF cause loss of all vertical saccades (6). Thus, the right riMLF lesion alone is not sufficient to explain the complete loss of vertical voluntary and visually guided saccades in our patient. Cerebral commands for vertical saccades are de-livered to the riMLF via two parallel corticofugal 100 © 2008 Lippincott Williams & Wilkins Vertical Saccades J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 TABLE 2. Vertical and torsional vestibulo-ocular reflex gain and phase in darkness Vertical VOR (Gain) Frequency (Hz) Up Down Phase (Deg) 0.5 1.0 2.0 Frequency (Hz) 0.87 ± 0.07 0.91 ± 0.09 1.02 ± 0.03 0.80 ± 0.17 0.88 ± 0.21 1.07 ± 0.03 Torsional VOR (Gain) CW CCW 21 ± 7 (n = 15) 18 ± 8 (n = 22) 19 ± 3 (n = 20) Phase (Deg) 0.5 1.0 2.0 Gain and phase CW, clockwise; 0.58 0.68 0.88 ± 0.81 ± 0.17 ± 0.12 values are means ± 1 SD. Negative phase indicates phase CCW, counterclockwise eye movement (from the patient's 0.69 0.79 0.88 lead of point of ± 0.10 ± 0.11 ± 0.10 eyes before the head; view); n, number of 43 36 28 ± 9 (n ± 7 (n ± 4(n positive phase indicates a cycles measured. = 20) = 20) = 17) phase lag. projections. An anterior pathway from the frontal eye fields primarily generates intentional (voluntary) sac-cades; a posterior pathway from the parietal cortex primarily generates reflexive saccades, although both pathways transmit corticofugal signals for both volitional and visually guided saccades (16,17). Although medial thalamic lesions (usually bilateral) have been reported to cause impairment of vertical saccades by interruption of the corticofugal fibers to the rostral midbrain (18,19), total palsy of vertical saccades may actually specify midbrain damage undetected by imaging. Cerebral corticofugal projections may also be disrupted within the rostral midbrain upstream from the riMLF Bilateral interruption of the corticofugal fibers in the rostral midbrain or medial thalamus could explain the absence of both voluntary and visually guided reflexive vertical saccades in our patient. The relative roles of descending cerebral corticofugal pathways and ascending projections from the pons to the riMLF are elucidated by our recordings. The riMLF receives an ascending input from the paramedian pontine reticular formation (PPRF), which can coordinate the onset and the combination of horizontal and vertical eye movement components (20). Medium-lead burst neurons in the PPRF discharge before both horizontal and vertical saccades (21), and bilateral experimental lesions in the caudal PPRF of monkeys impair vertical rapid eye move-ments (visually triggered saccades and quick phases of nystagmus) (22,23). Slow voluntary saccades and loss of quick phases of vestibular and optokinetic nystagmus in both horizontal and vertical planes may result from pontine lesions involving the PPRF (24). Those findings indicate that ascending pathways from the PPRF are necessary for the generation of vertical as well as horizontal fast eye FIG. 3. Vertical vestibulo-ocular re-flex. Active head rotation in pitch {middle trace) induces upward and downward quick phases (arrows, top trace) at 0.5 Hz in darkness. Ampli-tude scales for the head and eye are the same. Quick phase eye velocity record {lower trace) shows spikes corresponding to upward and down-ward quick phases in eye position record {top trace). U, upward; D, downward; POS, position; VEL, velocity. 101 J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 Kang and Sharpe ccw HEAD EYE POS EYE VEL +50% -50o/s FIG. 4. Torsional vestibulo-ocular reflex. There are counterclockwise (CCW) torsional quick phases (ar-rows) but no clockwise (CW) quick phases (middle trace) during head roll (top trace) at 0.5 Hz in darkness. Velocity record (bottom trace) shows unidirectional (CCW) spikes indicat-ing quick phases superimposed on bidirectional smooth torsional VOR movements. Amplitude calibrations for the head and eye are the same. 18 movements, but the ascending projections to the midbrain are not sufficient to generate voluntary or visually guided saccades in the face of disruption of cerebral corticofugal projections to the midbrain. In our patient, preserved upward and downward quick phases of the vertical VOR can be attributed to preservation of the ascending projections from the PPRF to the intact left riMLF Vertical pursuit signals traverse the rostral midbrain before innervating ocular motor nuclei. The INC receives inputs from the saccadic burst neuron of the riMLF, the vestibular nuclei, and the Y group and contributes to vertical eye movements (25,26). Bilateral inactivation of the INC in monkeys reduces the range of vertical sac-cades, but their speed is preserved (23,27). A lesion of one INC may be, in effect, a bilateral lesion and so affect inputs to motoneurons on both sides, because each INC projects to the opposite INC and bilateral ocular moto-neurons (28). Unilateral midbrain lesions that include the riMLF and INC have been reported to cause vertical pursuit palsy (2,29). Thus, impaired vertical pursuit in our patient may be caused by the lesion of the right INC and riMLF, with or without involvement of the left INC. Alternatively, corticofugal pursuit pathways may have been disrupted rostral to the INC, accounting for reduced vertical smooth pursuit gain. Supranuclear vertical gaze palsy can spare vestibular smooth eye movements (30). The INC is an element of the indirect VOR pathway between the vestibular nuclei and ocular motor nuclei (31,32), comprising the vertical eye velocity-to-position integrator. Unilateral chemical inactivation of the simian INC has little or no effect on the vertical VOR (27,33), but the torsional gain is reduced (33). Bilateral INC lesions cause low VOR gain and a phase lead (27). In our patient, vertical and torsional VOR showed normal gain but abnormal phase lead. The phase lead may be explained by damage to the right INC or to both INCs or to their connections with the vestibular nuclei (2,34). Absence of skew deviation in our patient, who was first examined many weeks after the infarct and on many later occasions, is consistent with the fact that skew deviation may be transient after lesions of the INC (2,27). Vertical gaze palsy consisting of complete loss of voluntary and visually guided saccades with preserved upward and downward quick phases of the vertical VOR has not been previously recognized. MRI combined with oculographic studies in our patient implicated damage to the right riMLF and INC but not to the left riMLF. Preservation of vertical and torsional quick phases signifies integrity of one or both riMLFs in the face of paralysis of all other vertical saccades. This dissociated palsy of vertical fast eye movements can be explained by rostral midbrain disruption of descending corticofugal pathways to the riMLF with preservation of ascending projections from the PPRF to the riMLF REFERENCES Biittner-Ennever JA, Biittner U, Cohen B, et al. Vertical gaze paralysis and the rostral interstitial nucleus of the medial longitudinal fasciculus. Brain 1982;105:125-49. Ranalli PJ, Sharpe JA, Fletcher WA. Palsy of upward and down-ward saccadic, pursuit and vestibular movements with a unilateral midbrain lesion: pathophysiologic correlations. Neurology 1988;38: 114-22. Castaigne P, Lhermitte F, Buge A, et al. Paramedian thalamic and midbrain infarct: clinical and neuropathological study. Ann Neurol 1981;10:127-48. Wall M, Slamovits TL, Weisberg LA, et al. Vertical gaze ophthalmoplegia from infarction in the area of the posterior thalamo-subthalamic paramedian artery. Stroke 1986;17:546-55. Leigh RJ, Seidman SH, Grant MP, et al. Loss of ipsidirectional quick phases of torsional nystagmus with a unilateral midbrain lesion. J Vestib Res 1993;3:115-21. Suzuki Y, Buttner-Ennever JA, Straumann D, et al. Deficits in torsional and vertical rapid eye movements and shift of Listing's plane after uni- and bilateral lesions of the rostral interstitial nucleus of the medial longitudinal fasciculus. Exp Brain Res 1995;106: 215-32. 102 © 2008 Lippincott Williams & Wilkins Vertical Saccades J Neuro-Ophthalmol, Vol. 28, No. 2, 2008 7. Ranalli PJ, Sharpe JA. Vertical vestibulo-ocular reflex, smooth pursuit, and eye-head tracking dysfunction in internuclear ophthal-moplegia. Brain 1988;111:1299-317. 8. Morrow MJ, Sharpe JA. The effects of head and trunk position on torsional vestibular and optokinetic eye movements in humans. Exp Brain Res 1993;95:144-50. 9. Kim JS, Sharpe JA. The vertical vestibulo-ocular reflex, and its interaction with vision during active head motion: effects of aging. J Vestib Res 2001;11:3-12. 10. Sharpe JA, Troost BT, Dell'Osso LF, et al. Comparative velocities of different types of fast eye movements in man. Invest Ophthalmol 1975;14:689-92. 11. Helmchen C, Rambold H, Kempermann U, et al. Localizing value of torsional nystagmus in small midbrain lesions. Neurology 2002;59: 1956-64. 12. Sharpe JA, Johnston JL. Ocular motor paresis versus apraxia. Ann Neurol 1989;25:209-10. 13. Ebner R, Lopez L, Ochoa S, et al. Vertical ocular motor apraxia. Neurology 1990;40:712-3. 14. Moschovakis AK, Scudder CA, Highstein SM. Structure of the primate oculomotor burst generator. I. Medium-lead burst neurons with upward on-directions. J Neurophysiol 1991;65:203-17. 15. Moschovakis AK, Scudder CA, Highstein SM. Structure of the primate oculomotor burst generator. II. Medium-lead burst neurons with downward on-directions. J Neurophysiol 1991;65:218-29. 16. Lynch JC, Tian JR. Cortico-cortical networks and cortico-subcortical loops for the higher control of eye movements. Prog Brain Res 2005; 151:461-50. 17. Stanton GB, Goldberg ME, Bruce CJ. Frontal eye field efferents in the macaque monkey: II. Topography of terminal fields in midbrain and pons. J Comp Neurol 1988;271:493-506. 18. Guberman A, Stuss D. The syndrome of bilateral paramedian thalamic infarction. Neurology 1983;33:540-6. 19. Clark JM, Albers GW. Vertical gaze palsies from medial thalamic infarctions without midbrain involvement. Stroke 1995;26:1467-70. 20. Buttner-Ennever JA, Henn V An autoradiographic study of the pathways from the pontine reticular formation involved in horizontal eye movements. Brain Res 1976;108:155-64. 21. Van Gisbergen JA, Robinson DA, Gielen S. A quantitative analysis of generation of saccadic eye movements by burst neurons. J Neuro-physiol 1981;45:417-42. 22. Henn V, Lang W, Hepp K, et al. Experimental gaze palsies in monkeys and their relation to human pathology. Brain 1984;107: 619-36. 23. Barton EJ, Nelson JS, Gandhi NJ, et al. Effects of partial lidocaine inactivation of the paramedian pontine reticular formation on saccades of macaques. J Neurophysiol 2003;90:372-86. 24. Hanson MR, Hamid MA, Tomsak RL, et al. Selective saccadic palsy caused by pontine lesions: clinical, physiological, and pathological correlations. Ann Neurol 1986;20:209-17. 25. McCrea RA, Stassman A, Highstein SM. Anatomical and physiological characteristics of vestibular neurons mediating the vertical vestibulo-ocular reflexes of the squirrel monkey. J Comp Neurol 1987;264:571-94. 26. Partsalis AM, Zhang Y, Highstein SM. Dorsal Y group in the squirrel monkey. I. Neuronal responses during rapid and long term modifications of the vertical VOR. J Neurophysiol 1995;73:615-31. 27. Helmchen C, Rambold H, Fuhry L, et al. Deficits in vertical and torsional eye movements after uni- and bilateral muscimol in-activation of the interstitial nucleus of Cajal of the alert monkey. Exp Brain Res 1998;119:436-52. 28. Kokkoroyannis T, Scudder CA, Balaban CD, et al. Anatomy and physiology of the primate interstitial nucleus of Cajal I. efferent projections. J Neurophysiol 1996;75:725-39. 29. Alemdar M, Kamaci S, Budak F Unilateral midbrain infarction causing upward and downward gaze palsy. J Neuroophthalmol 2006; 26:173-6. 30. Sharpe JA, Kim JS. Midbrain disorders of vertical gaze: a quantitative re-evaluation. Ann NY Acad Sci 2002;956:143-54. 31. King WM, Fuchs AF, Magnin M. Vertical eye movement-related responses of neurons in midbrain near interstitial nucleus of Cajal. J Neurophysiol 1981;46:549-62. 32. Crawford JD, Cadera W, Vilis T. Generation of torsional and vertical eye position signals by the interstitial nucleus of Cajal. Science 1991; 252:1551-3. 33. Farshadmanesh F, Klier EM, Chang P, et al. Three-dimensional eye-head coordination after injection of muscimol into the interstitial nucleus of Cajal (INC). J Neurophysiol 2007;97:2322-38. 34. Fukushima K, Takahashi K, Fukushima J, et al. Effects of lesion of the interstitial nucleus of Cajal on vestibular nuclear neurons activated by vertical vestibular stimulation. Exp Brain Res 1986;64: 496-504. 103 |
