Visual and Positional Modulation of Pendular Seesaw Nystagmus: Implications for the Mechanism

Background: The mechanisms of pendular seesaw nystagmus (SSN) remain unknown. Methods: We evaluated modulation of pendular SSN by removal of visual fixation, convergence, and positional changes in 2 patients, one with bitemporal hemianopia due to a traumatic damage of the optic chiasm and the other with platybasia compressing the medulla and lower cerebellum. Results: In both patients, the pendular SSN markedly decreased or disappeared with convergence, without visual fixation in darkness, during static head tilt toward each shoulder while sitting and while supine. Conclusions: The similar patterns of nystagmus modulation observed in our patients with a different etiology indicate a common role of both visual and otolithic inputs in generating pendular SSN.

Original Contribution Visual and Positional Modulation of Pendular Seesaw Nystagmus: Implications for the Mechanism Sung-Hee Kim, MD, PhD, Hyo-Jung Kim, PhD, Sea-Won Oh, BSc, Ji-Soo Kim, MD, PhD Background: The mechanisms of pendular seesaw nystagmus (SSN) remain unknown. Methods: We evaluated modulation of pendular SSN by removal of visual fixation, convergence, and positional changes in 2 patients, one with bitemporal hemianopia due to a traumatic damage of the optic chiasm and the other with platybasia compressing the medulla and lower cerebellum. Results: In both patients, the pendular SSN markedly decreased or disappeared with convergence, without visual fixation in darkness, during static head tilt toward each shoulder while sitting and while supine. Conclusions: The similar patterns of nystagmus modulation observed in our patients with a different etiology indicate a common role of both visual and otolithic inputs in generating pendular SSN. Journal of Neuro-Ophthalmology 2019;39:181-185 doi: 10.1097/WNO.0000000000000678 © 2018 by North American Neuro-Ophthalmology Society Department of Neurology (S-HK), Kyungpook National University School of Medicine, Kyungpook National University Chilgok Hospital, Daegu, Korea; Research Administration Team (H-JK), Seoul National University Bundang Hospital, Seongnam, South Korea; Dizziness Center (S-WO, J-SK), Seoul National University Bundang Hospital, Seongnam, Korea; and Department of Neurology (J-SK), Seoul National University College of Medicine, Seoul, Korea. J.-S. Kim serves as an Associate Editor of Frontiers in Neurootology and on the Editorial Boards of the Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuroophthalmology, Journal of Neurology, Medicine, and Journal of Vestibular Research. The remaining authors report no conflicts of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.jneuro-ophthalmology.com). Address correspondence to Ji-Soo Kim, MD, PhD, Department of Neurology, College of Medicine, Seoul National University Dizziness Center, Clinical Neuroscience Center, and Department of Neurology, Seoul National University Bundang Hospital, 17382 Gumi-ro, Bundang-gu, Seongnam-si, Gyeonggi-do, 13620, Korea; E-mail: [e-mail] Kim et al: J Neuro-Ophthalmol 2019; 39: 181-185 S eesaw nystagmus (SSN) refers to disjunctive nystagmus in which one eye elevates and intorts, whereas the other eye depresses and extorts during a half-cycle, and the direction of vertical and torsional eye movements reverses in each eye during the next half-cycle (1). Pendular form of SSN primarily has been described in association with a parasellar mass causing bitemporal hemianopsia (2). Disruption of visual inputs from the temporal fields and resultant ocular instability in the roll plane has been assumed to play an important role in generating pendular SSN (3). In addition, alternating imbalance in the otolithic system may be a possibility, given that the half-cycle of pendular SSN resembles the eye movements observed during head tilts (ocular tilt reaction). However, the exact mechanism of pendular SSN remains unknown. This study describes 2 patients with pendular SSN that decreased markedly with removal of visual fixation in darkness, during head tilt to either shoulder and while supine. These findings imply an essential role of both visual and otolithic inputs in developing pendular SSN. PATIENTS AND METHODS Patient 1 A 54-year-old man with diabetes mellitus and hypertension experienced oscillopsia for 9 months. He also had suffered from urinary frequency and memory impairments for 6 months. He had a history of head trauma from motor vehicle accident 15 years earlier. Visual acuity was 20/70 in the right eye and 20/1,000 in the left. Eyelid function and ocular ductions and versions were normal. He showed a bilateral sway on attempted tandem gait, but had no ataxia or weakness of the extremities. Perimetry revealed bitemporal hemianopia, whereas ophthalmoscopy showed bilateral optic atrophy. Brain MRI disclosed encephalomalacia of the frontal lobes, hydrocephalus, and atrophic optic chiasm likely due to the previous head trauma. Some clinical features of this patient were briefly reported previously (4). 181 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution Patient 2 A 21-year-old woman presented with involuntary eye movements that had been first noticed at 8 years of age. She reported an intermittent upward pulling sensation of both eyes, but no diplopia or oscillopsia. Her family members had no visual disorders. Visual acuity was 20/60 in the right eye and 20/80 in the left eye. Pupillary reactions, ocular motility, function of the eyelids, and funduscopy were normal. Covering each eye did not induce any change in the vertical position of the nonfixating eye or patterns of pendular SSN. Lateral gazes produced horizontal gaze-evoked nystagmus and a large hypertropia of the abducting eye. Testing of horizontal optokinetic nystagmus showed no inversed response. Kinetic perimetry and visual-evoked potentials using flash stimuli were normal. Ocular and cervical vestibular-evoked myogenic potentials in response to tapping the brow were normal and symmetric. Brain MRI revealed normal optic chiasm thalamus and rostral brainstem, but a sharp angulation of the clivus and abnormal fusion of the occipital condyle that caused compression of the medulla oblongata and cerebellar flocculus. RECORDING OF EYE MOVEMENTS AND PROTOCOLS OF MODULATION Eye movements were recorded binocularly at a sampling rate of 60 Hz using 3D video-oculography (SensoMotoric Instruments, Teltow, Germany). Spontaneous nystagmus was evaluated in the primary gaze while wearing video-oculography goggles in a seated position. For visual fixation, the patients were instructed to view a lightemitting diode (LED) target presented 110 cm from the eyes and to hold primary eye position. Removal of visual fixation was obtained by covering the goggles. In darkness, the effect of visual fixation on pendular SSN was evaluated by instructing the patients to look at a small LED target that was placed inside the goggles. The convergence effect in the light was measured by placing the visual target manually about 10 cm from the eyes in the midline. Spontaneous eye movements also were recorded with the head roll tilted about 30° toward each shoulder while maintaining a visual fixation on a central fixation point, and during straight ahead gaze in a supine position. While supine, the patients were instructed to view a fixation point on the ceiling 190 cm from the eyes. During the recording in each position, the horizontal eye position was closely monitored to exclude the possible effects of changes in vergence angle on the intensity of pendular SSN. Each task was recorded for more than 30 seconds and at least 5 cycles of pendular SSN were sampled for measuring the vertical and torsional amplitudes during each task. 182 STANDARD PROTOCOL APPROVALS AND PATIENT CONSENTS The experimental recordings of the nystagmus of our patients followed the tenets of the Declaration of Helsinki and were approved by the institutional review board of Seoul National University Bundang Hospital (No. B-1801442-701). RESULTS In primary gaze while sitting, Patient 1 showed typical pendular SSN at a regular frequency of 2.5-3 Hz (See Supplemental Digital Content, Video 1, http://links.lww.com/WNO/A309). The SSN disappeared in darkness, but appeared again with a slightly decreased intensity compared with that observed with a visual target in the light when a small LED target was presented in darkness (See Supplemental Digital Content, Video 1, http://links.lww.com/WNO/A332) (Fig. 1). While sitting, convergence (See Supplemental Digital Content, Video 2, http://links.lww.com/WNO/A333) and head tilt toward the right shoulder suppressed the SSN completely, and tilt toward the left shoulder decreased the amplitude of SSN without affecting the frequency (See Supplemental Digital Content, Video 3, http://links.lww.com/WNO/A334) (Table 1). The pendular SSN also disappeared in the supine position. During attempted straight ahead gaze in the light while sitting, Patient 2 showed an alternating upward deviation and irregular pendular SSN of large amplitudes in both vertical and torsional planes (See Supplemental Digital Content, Video 4, http://links.lww.com/WNO/A335). The SSN occasionally was interrupted by horizontal spontaneous nystagmus with a decelerating slow phase, which alternated its directions at irregular intervals. In darkness, the frequency and amplitude of the vertical and torsional components of pendular SSN decreased markedly, whereas the aperiodic alternating horizontal nystagmus increased (See Supplemental Digital Content, Video 4, http://links.lww.com/WNO/ A335) (Fig. 2, Table 1). In light, the pendular SSN was suppressed during convergence and head tilt toward each shoulder while sitting and while supine (See Supplemental Digital Content, Video 4, http://links.lww.com/WNO/ A335). These positional changes also suppressed the pendular SSN in darkness (Table 1). DISCUSSION Patient 1 with bitemporal hemianopia, atrophy of the chiasm, and hydrocephalus developed pendular SSN 15 years after head trauma. Patient 2 with platybasia showed pendular SSN, aperiodic alternating horizontal nystagmus with a decelerating waveform, and alternating hypertropia of the abducting eye during lateral gazes. In both patients, the pendular SSN disappeared or markedly decreased Kim et al: J Neuro-Ophthalmol 2019; 39: 181-185 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 1. Patient 1. Pendular seesaw nystagmus disappears in darkness and reappears with presentation of a visible target. LT, torsional position of the left eye; LV, vertical position of the left eye; RV, vertical position of the right eye. In this and following recordings, upward deflection indicates rightward, upward, and clockwise eye motion. during convergence, without fixation in darkness, during head tilt toward each shoulder and while supine. These findings suggest that both visual and otolithic inputs are involved in generation of pendular SSN. Pendular SSN usually occurs in association with visual loss or with disorders involving the optic chiasm (3-7). The pendular SSN in our patients decreased or disappeared in darkness, and reappeared when a visible target was given. This has been reported in other patients with SSN (3,8,9), and suggests that visual inputs are crucial for generating pendular SSN. Although the possible effect of change in vergence angle could not be excluded due to the LED target placed inside the goggle, emergence of pendular SSN with presentation of the target in darkness cannot be explained by the suppression of pendular SSN with convergence observed in the light in these patients. If visual inputs act alone for generating pendular SSN, however, we encounter a question why a specific type of visual field defect is observed frequently in patients with pendular SSN. The high prevalence of bitemporal hemianopia in pendular SSN points to the importance of disrupting retinal TABLE 1. Characteristics of 2 patients with pendular seesaw nystagmus and modulation of nystagmus by elimination of visual fixation and change of head and body position Sex/age, yr Clinical manifestation Symptom onset Visual acuity Visual field Brain MRI Pendular Seesaw Nystagmus In the light Primary position Convergence Right head tilt Left head tilt Lying down In darkness Primary position Target presentation Right head tilt Left head tilt Lying down Patient 1 Patient 2 M/54 Oscillopsia 15 years after head trauma 20/70 OD, 20/100 OS Bitemporal hemianopia Optic chiasmal atrophy F/21 Involuntary eye movements 8 years of age 20/60 OD, 20/80 OS Normal Platybasia Vertical Amplitude Torsional Amplitude Vertical Amplitude Torsional Amplitude 5.3 ± 0.2° Nil Nil 2.0 ± 0.5° Nil 6.3 ± 0.3° Nil Nil 1.5 ± 0.2° Nil 11.1 ± 2.3° Nil Nil Nil 3.9 ± 2.8° 12.1 ± 5.7° Nil Nil Nil 2.3 ± 1.8° Nil 3.2 ± 0.4° NA NA NA Nil 2.0 ± 0.2° NA NA NA 4.9 ± 0.6° 10.2 ± 3.1° Nil Nil Nil 7.8 ± 0.7° 12.3 ± 5.8° Nil Nil Nil The amplitude values were obtained by averaging the vertical and torsional components from at least 5 cycles of the pendular seesaw nystagmus during each task in each patient and presented as mean ± SD. NA, not applicable. Kim et al: J Neuro-Ophthalmol 2019; 39: 181-185 183 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution FIG. 2. Patient 2. Irregular pendular form of seesaw nystagmus decreases in darkness, whereas the horizontal nystagmus with a decelerating waveform increases. LH, horizontal position of the left eye; LV, vertical position of the left eye; RH, horizontal position of the right eye; RV, vertical position of the right eye. nasal fibers in the production of this nystagmus pattern. This disruption may split the images due to loss of overlap between the nasal fields of the 2 eyes (10). Loss of normal overlap between the retinal images, containing the visual objects projected from the temporal field of each eye, produces loss of binocular fusion and episodic separation of the images falling on the retina of each eye (10,11). Disrupting the nasal crossing fibers at the chiasm also impairs visual inputs to the accessory optic system. The accessory optic system at the mesodiencephalic border receives direct visual information predominantly from the contralateral nasal retina and then projects it to the dorsal cap of the inferior olive which, in turn, sends the climbing fibers to the flocculonodular lobe of the cerebellum (12). Thus, the accessory optic system converges with the vestibular system in the vestibulocerebellum, and provides a pathway for visuo-vestibular interaction (12). Cerebellar Purkinje cells along with the inferior olivary nucleus mediate adaptation of the vestibulo-ocular reflex that minimizes retinal error signals (13). Therefore, pendular SSN would arise more frequently when repeated mismatch of the retinal images acts together with the adaptive mechanism through the accessory optic system, rather than when the loss of visual inputs acts alone. Patient 2 had decreased visual acuity but normal visual fields. Brain MRI demonstrated a skull base anomaly compressing the lower brainstem and the flocculus. This altered anatomy seems to be responsible for the spontaneous horizontal nystagmus with decelerating waveforms, gazeevoked nystagmus, and alternating skew deviation. There is a previous report of a patient with caudal cerebellar displacement who had pendular SSN in the presence of intact visual afferent pathway (14). Patients with cerebellar lesions may have an impaired binocular ocular motor control and resultant static or dynamic ocular misalignment (15), including alternating skew deviation as seen in this patient. Binocular misalignment during early life readily induced disjunctive eye movements and repeated error signals that lead to activation of adaptive mechanisms (12,16). The inferior olive has been implicated in the generation of delayed ocular motor abnormalities such as oculopalatal 184 tremor where inputs from the cerebellar nuclei are interrupted (17,18). The inferior olive may be a key structure in generating pendular SSN in our patients: decreased visual input through the accessory optic visual system to the inferior olive in Patient 1 and disruption of the projections from the inferior olive to the flocculus in Patient 2. In both of our patients, convergence suppressed the pendular SSN in light. In view of this suppressive effect of convergence on pendular SSN, any changes in vergence angle due to decreased or increased convergence effort may have altered the intensity of pendular SSN in darkness, during head tilts, and while supine. However, the video-oculography findings did not show any significant alteration in the horizontal eye position or in the pupil size in relation to changes of nystagmus intensity. Visual inputs are not only essential for estimation of eye position and real-time visual feedback to stabilize gaze onto a desired target, but also conveyed to the central vestibular systems affecting the vestibular efferent signals (7). Thus, long-standing disturbances in binocular fusion may induce alternating imbalance in the otolithic system and resultant pendular SSN, which would be affected by positional changes. Otherwise, altered otolithic inputs induced by the positional changes may have simply affected pendular SSN through visuo-vestibular interaction. In conclusion, given the visual and positional modulations of pendular SSN in our patients, visual and symmetric otolithic inputs while upright may be required to maintain a robust pendular SSN. Generation of pendular SSN seems to require interactions among the visual, otolithic, and central adaptive mechanisms, specifically loss of visual fusion between the eyes, misalignment of the eyes in the roll plane, and adaptive mechanism by the vestibulocerebellum involved in the processing of otolithic signals. Complexity of these interconnected pathomechanisms may explain the rarity of pendular SSN. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: S.-H. Kim and J.-S. Kim; b. Acquisition of data: H.-J. Kim and S.-W. Oh; c. Analysis and interpretation of data: S.-H. Kim and J.-S. Ki; Category 2: a. Drafting the Kim et al: J Neuro-Ophthalmol 2019; 39: 181-185 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Original Contribution manuscript: S.-H. Kim; b. Revising it for intellectual content: J.-S. Kim; Category 3: a. Final approval of the completed manuscript: J.-S. Kim. REFERENCES 1. 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