Journal of Neuro-Ophthalmology, September 1982, Volume 2, Issue 3

Floccular inhibition of the vestibulo-ocular reflex in man.

The vestibulo-ocular reflex (VOR) plays a major role in ocular motility. Stimulation of each semicircular canal produces excitation of a specific extraocular muscle and inhibition of its antagonist in each eye. Floccular inhibition of the VOR has been extensively studied in the rabbit. Inhibitory projections from floccular Purkinje cells reach the ipsilateral vestibular nucleus via the restiform body and selectively control certain VORs. We examined the ocular functions in a patient with a lateral lower pontine infarct that included the restiform body. The patient exhibited unilateral, selective disinhibition of the VOR manifested by disconjugate upward rotatory drift of the eyes at the end of lateral eye movement towards the side of the lesion. He had marked directional preponderance on caloric testing. The same underlying mechanism which produced the biased VOR also appeared to affect target position determination in fast eye movements, resulting in lateropulsion of saccades and asymmetric OKNs. This is the first clinical case supporting the theory of selective cerebellar inhibition of the VOR.

]. Clin. Neuro-ophth<l/mol. 2: 201-207, 1982. Floccular Inhibition of the Vestibulo-Ocular Reflex in Man TSUTOMU NAKADA, M.D. INGRID L. KWEE, M.D. Abstract The vestibulo-ocular reflex (VOR) plays a major role in ocular motility. Stimulation of each semicircular canal produces excitation of a specific extraocular muscle and inhibition of its antagonist in each eye. Floccular inhibition of the VOR has been extensively studied in the rabbit. Inhibitory projections from f1oc­culilr Purkinje cells reach the ipsilateral vestibular nu­cleus via the restiform body and selectively control certain VORs. We examined the ocular functions in a patient with a lateral lower pontine infarct that in­cluded the restiform body. The patient exhibited uni­lateral, selective disinhibition of the VOR manifested by disconjugate upward rotatory drift of the eyes at the end of lateral eye movement towards the side of the lesion. He had marked directional preponderance on caloric testing. The same underlying mechanism which produced the biased VOR also appeared to af­fect larget position determination in fast eye move­ments, resulting in lateropulsion of saccades and asymmetric OKNs. This is the first clinical case sup­porting the theory of selective cerebellar inhibition of the VOR. The vestibulo-ocular reflex (VOR) arc is formed by specific receptor-effector connections. Each semicircular canal pathway produces excitation of one extraocular muscle and inhibition of its antag­onist in each eye. The specific combination of two semicircular canals, one from each side, acts on one extraocular muscle. The final result is that each extraocular muscle receives input via two YOR pathways. 1-3 Floccular inhibition of the YOR has been exten­sively studied in the rabbit. In this system, inhibi­tory projections from Purkinje cells reach the ip­silateral vestibular nucleus via the restiform body. The inhibition is exerted on only one of the two VOR pathways converging on each muscle.:s• 4 We have studied the first clinical case supporting this theory of selective inhibition of the YOR. From the Department of Neurology, University of California at DaVis, Veterans Administration Medical Center, Martinez, Cal­ifornia. September 1982 Case Report A 56-year-old white male suffered hearing loss in his right ear. A few months later, he experienced light-headedness followed by nausea and vomiting. He developed severe vertigo and right facial numb­ness. He noted marked difficulty with his gait and often fell to the right. Neurological examination showed right facial hypesthesia with a depressed right corneal reflex and right facial palsy. He com­plained of binocular diplopia on right lateral gaze. Right lateral gaze-evoked nystagmus was noted. He showed mild rebound of the right upper ex­tremity. His finger-to-nose and rapid alternating movement tests on the right side were abnormal. His gait was mildly ataxic. All symptoms improved rapidly and he was discharged with the diagnosis of right lateral lower pontine infarct. A year later, he was referred to the neurology service due to his unusual eye movements. At this time, his neuro­logical exam revealed mild rebound of the right upper extremity and abnormal eye movements detailed below. Oculomotor Findings Recording Techniques Eye movements were recorded electro-oculo­graphically using skin electrodes and a two-chan­nel direct current system with the filter set at 30 Hz. OKN targets were generated by an optokinetic stimulator with an angle of approximately 20° moving at approximately 30°Isecond. Hori~ontal saccade and pursuit were recorded using the in­frared reflection-photoelectric cell technique:" Results Neutral Position. Fixation was normal. Follow­ing closure of eyes, right directional nystagmus to approximately 20° was observed (Fig. 1), compat­ible with a tonic bias of the horizontal YOR to­wards a left gaze.H . 7 Eccentric Eye Position. Immediately after com­pletion of conjugate eye movement to the right, the right eye exhibited marked intorsion and upward drift, while the left eye had mild extorsion and upward drift, resulting in disconjugate gaze 201 Floccular Inhibition of the VOR R 20°F t L . Figure I. Direct C'urrent l'!ectro-uculogram in neutral eye position. Downward deflections of the traCIng indk~te leftward ocular deviations. The right-beating nystagmus IS seen followmg eye closure (arrow). Figure 2. Immediately after completion of conjugate eye movement to the right. the right eye exhibited marked intorsion and upward drift while the left eye showed mild extorsion and upward drift. resulting in disconjugate gaze. which the patient could not maintain for more than a few seconds. Figure J. Direct current l'!ectro-oculugram. The upper tr~cing shows horizontal OKN for targets moving to the right. The lower tr.Icing shows horizontal OKN for targets moving to the left. Upward deflectiuns indic.Ite rightw.Ird ucular devidtions. The .Implitude of the fast phase is l.Irger for targets moving tu the right. (Fig. 2), which he could not maintain for more than a few seconds. When he attempted to hold his eyes in the lower right direction, a correcting fast down­ward movement was added, resulting in slow, coarse, downbeat rotatory nystagmus. On left lat­eral gaze, the right eyE' intortE'd slightly, while the Idt eve l'xtorted. Frequently, correcting fast move-ments occurred, creating small amplitude upbeat rotatory nystagmus. Right upward gaze and vertical gaze were normal. Horizontal Optokinetic Nystagmus. Horizontal OKN was more pronounced for targets moving to the right compared to targets moving to the left (Fig. 3). Journal of Clinical Neuro-ophthalmology Nakada, Kwee LE L 40°1R RE Figure 4. Horiwnt.,1 sdccddes recorded using the photodectric cell-infrMed light technique. The upper tr.,cing represents the left eye (LE) and the lower tracing the right eye (RE). UpwMd deflections indicate leftw.ud oculM deviations, Note constant undershoot for left-sided target .md overshoot for right-sided t.lrget (lateropulsion of saccade). Small leftward multiple saccddic corrections .He seen following each dysmetric saccade. LE RE Figure 5. Horizontdl pursuit recorded using the photoelectric cell-infrMed light technique. The upper trdcing no'presents the left eye (LE) and the lower tracing the right eye (RE). Note saccadic pursuit and frequent saccadic intrusions. Radiological Findings Horizontal Pursuit. The patient exhibited sac­cadic pursuit with frequent saccadic intrusions (Fig. 5). Click perceptual thresholds of our patient were 55 and 80 dB in the left and right ears, respectively. With a hearing aid in his right ear the threshold \ Brain Stem Auditory Evoked Potentials (BAEP) Computerized Tomography. There was a small area of low attenuation adjacent to the right aspect of the fourth ventricle, which involved the right restiform body (Fig. 6). Left Vertebral Angiogram. Neither tR anterior inferior cerebellar artery (AICA) nor pos rior in­ferior cerebellar artery (PICA) on the right s e was visualized. The right vertebral artery ap ared atretic (Fig. 7). Branches of the left PICA supplied both the left and right PICA territories suggesting a congenital variant.!! These findings support the diagnosis of a lateral lower pontine infarct. Caloric Nystagmus. Caloric testing was per­formed with the patient supine and his head tilted upwards at 30°. Cold water applied to the right external auditory canal produced left directional nystagmus with an average deflection of 22 0, whereas warm water produced right directional nystagmus of 34°. Cold water applied to the left external auditory canal produced right directional nystagmus of 56°, while warm water produced left directional nystagmus of 13°. The calculated uni­lateral weakness was 45% for the right ear and 55% for the left ear. Directional preponderance was 72% for right directional and 28% for left directional nystagmus. These findings strongly support that this patient's horizontal VOR was tonically biased towards a left gaze.~ Horizontal Saccades. These showed "lateropul­sion of saccade" with constant undershooting to­wards the left and overshooting towards the right.H The initial undershot saccade was followed by multiple undershooting saccadic corrections with a staircase-like appearance on the recording. Sim­ilarly, the initial overshot saccade was followed by multiple undershooting saccadic corrections (Fig. 4). September 1982 203 F1occul,u Inhibition of the VOR Figure 6. High-resolution CT scan shows a small area of low attenuation adjacent to the right aspect of the fourth ventricle (arrows). It involves primarily the right restiform body. Figure 7. Left vertebral .lnl\iol\r.,m fails 10 visudlize either the dnterior inferior «'rl·belldf artery (AICA) or the posterior infe­rior «'r"b"l1", artery (PICA) "n the right side. A branch of the left PICA supplies the tNrilory of the right PICA as well (arrowh,·ads). The right vertebr"l .,rtery was atretic (drrow). was 70 dB. Rarefaction-clicks at 103 dB intensity were presented to the left and .right ears at 11/ second with the patient wearing a hearing aid in the right ear. Replicable waveforms of normal am­plitudes were obtained. Wave V latencies were greatly prolonged following stimulation of the left (7.10 m second) and the right (7.50 m second) ears. However, the I-V interval was normal (4.05 m second). These findings are consistent with severe, bilateral hearing loss without significant brainstem pathology. Discussion Eye movement abnormalities in patients with a lateral medullary infarct (Wallenberg s;r.ndrome) have been studied by several authors.. 10-12 On occasion, similar eye movement findings as in our patient were described. However, since the syn­drome is thought to result from an ischemic infarct in the PICA territory which involves rather large anatomical regions including all the ipsilateral ves­tibular nuclei, the manifestation of VOR dysfunc­tion in those cases are heterogeneous. On the other hand, our patient appeared to have a small lesion in the AICA rather than PICA territory.13 The normal I-V interval in BAEP, high resolution CT scan findings, and clinical data strongly support that our patient has a small discrete lesion involv- Journal of Clinical Neuro-ophthalmology ing the restiform body without significant brain stem involvement. The VOR has six major pathways arising from each ear. The receptor-effector relationships and their floccular inhibition in the rabbit are summa­rized in Table 1, based on the study by Ito et al.~ A lesion of the right restiform body which contains the ipsilateral floccular inhibitory fibers will pro- TABLE 1. Veslibulo-Ocular Reflex Pathways and their Floccular Inhibition" Canals Extrdo,'uIM F1occul<lr Muscle.>s Inhibition Anterior Excitatory i-Superior rectus Yes c-Inferior oblique Yes Inhibitory i-Inferior rectus Yes c-Superior oblique Yes Horizontal Excitatory i-Medial rectus Yes c-lateral rectus No Inhibitory i-lateral rectus Yes c-Medial rectus No Posterior Excitatory i-Superior oblique No c-Inferior rectus No Inhibitory i-Inferior oblique No c-Superior rectus No Notes: i-ipsilateral; c-contralateral. • Based on the study by Ito et .11. in the rabbit." Nakada, Kwee duce hyperactivity of the right superior rectus, right medial rectus, and left inferior oblique mus­cles due to disinhibition. This imbalance of the YOR induces an upward, intorting drift of the right eye and small, upward, extorting drift of the left eye at the end of right lateral eye movements. Slight intorsion of the right eye and extorsion of the left eye appear at the end of left lateral eye movements. (See schematic representation in Fig­ure 8.) Our patient's ocular movements are in excellent agreement with this schema. The ultimate effect of the YOR is to ensure a stationary visual image on the retina during head movement.H , 14, If, Its abnormalities may cause var­ious pathological eye movements.H , 7, IH. 17 Recent studies suggest that the cerebellum contributes to: 1) plasticity of the YOR; 2) determination of sac­cadic amplitude; 3) generation of normal smooth pursuit; 4) maintenance of eccentric gaze; and 5) fixation suppression of vestibulogenic eye move­ments. 18 - 28 Since the flocculus acts as "automatic gain controller" of the VOR, 2, 14, 29-:1I the reflex may be the final common pathway for these cere­bellar effects. The most impressive findings in our patient's horizontal eye movements were the con­stant miscalculation of the saccadic amplitude (la­teropulsion of saccade), as well as the fast phase of OKN. Their velocity and contour remained intact suggesting normal pulse-step generation in the brain stem.32 -.14 Interestingly, the direction in which the larger amplitude occurred was opposite be­tween saccade and OKN. Lateropulsion is a term used to describe the motor disturbance often seen in patients with Wal­lenberg syndrome, in which there is veering of the body or limb movements to one side.3.5 Kommerell ,--, / \ 8 \ ... , \ ..._... ~ R e--" -- -- ' ...... - ." Figure 8. Schematic representation of eccentri,' lateral eye positions. A lesion of the right restiform body produces hyperactivity of the right superior rectus, right medial reclus, and left inferior oblique muscles due to disinhibition. This tonit' imbalance produces marked upward drift with intorsion of the right eye and upward drift with extorsion of the left eye at the end of right lateral eye movements. Effects of imbalance on left lateral eye movements <Ire minimum, resulting in small intorsion of the right eye and extorsion of the left eye, SR-Superior Rectus, MR-Medial Rectus. la-Inferior Oblique, R-right eye, L-Ieft eye. September 1982 ~ 205 F1occul,)f Inhibition of the VOR o • I I • o • ...... I • SACCADE OKN Figure 9. Schematic representation of fast eye movements. Tonic bias of the VOR is interpreted as actual head rotation towards the opposite direction (dotted line). Internal representation of the target position rotates according to this bias. Black Circles mdICate true target positions. White circles indicate internal representation of the target position. Saccadic amplitude is determined by measuring the distance between the internal representation of the target and physical eye position. The amplitude of the fast phase of OKN is determined using the internal representation of the target and neutral eye position (solid line). The direction in which the larger amplitude occurs is opposite between saccade and OKN. and Hoyt applied this term to a specific saccadic eye movement abnormality which they observed in one patient with the Wallenberg syndrome and coined it lateropulsion of saccade.8 Here, saccadic eye movements show constant overshooting in one direction and undershooting in the other. However, in the monkey, the caudal descending vestibular nucleus produces marked lateropulsion of the body towards the side of the lesion, while the same lesion hardly affects OKN or caloric nystagmus,7 which are more closely related to VOR func­tion. 26 . 36 Lateropulsion of body or limb is a slow drift of posture, whereas lateropulsion of saccade is the miscalculation of fast eye movements. There­fore, although the lateropulsion of body and later­opulsion of saccade are functionally closely related phenomena, their underlying mechanisms may be totally different. To explain our patient's findings, we propose the following hypothesis. Saccadic amplitude is precalculated by measuring the distance between the target position and physical eye position. The amplitude of the fast phase of OKN is also precal­culated by measuring the distance between the target position and neutral eye position. Tonic imbalance of the VOR is misinterpreted as actual head rotation in the direction of the side of VOR disinhibition. Perception of head rotation second­arily influences the "internal representation" of target position, shifting it in the direction of head movement. (See schematic representation in Figure 9.) SaccJdic amplitude miscJlculation then occurs du(' to measurement based on the distance between the ll1i~rl,lll'd intprn,11 representation of the target and physical eye position. A target located on the side where undershooting of the initial saccade occurs remains unreached in spite of successive corrective saccades. This produces a series of un­dershooting saccades which exhibit a staircase-like appearance on the recording. After a single over­shooting saccade, the relationship between the physical eye position and the target is reversed. The previously discussed series of undershooting saccades is triggered. This results in a single over­shooting saccade followed by successive corrective undershooting saccades. Miscalculation of the OKN amplitude similarly occurs due to measuring the distance between the neutral eye position and misplaced "internal representation" of the target (Fig. 9). In summary, we present a clinical case support­ing the theory of selective floccular inhibition of the VOR. Floccular dysfunction also appears to affect the determination of saccadic amplitude. The VOR may be the final common pathway for var­ious pathological eye movements, especially those in patients with cerebellar dysfunction. References I. 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Write for reprints to: Tsutomu Nakada, M.D., De­partment of Neurology, University of California at Davis, Veterans Administration MediCal Center, 150 Muir Road, Martinez, California 94553. 207