Oculopalatal Tremor With Dissociated Pendular Nystagmus in Bilateral Inferior Olivary Hypertrophy

Oculopalatal tremor (OPT) consists of continuous rhythmic movements of the soft palate-palatal tremor-with pendular nystagmus (PN) (1). Recent studies have suggested the mechanism of OPT to be an interaction between an oscillator in the inferior olive and a modulator in the cerebellum (1).

Clinical Correspondence Oculopalatal Tremor With Dissociated Pendular Nystagmus in Bilateral Inferior Olivary Hypertrophy Jae-Myung Kim, MD, Ji-Yun Park, MD, Kyung Wook Kang, MD, Tai-Seung Nam, MD, PhD, Seung-Han Lee, MD, PhD O culopalatal tremor (OPT) consists of continuous rhythmic movements of the soft palate-palatal tremor-with pendular nystagmus (PN) (1). Recent studies have suggested the mechanism of OPT to be an interaction between an oscillator in the inferior olive and a modulator in the cerebellum (1). Nystagmus in OPT may be conjugate, disconjugate, or disjunctive (1). Previous studies have reported that dissociated PN was mostly observed in hypertrophy of the unilateral inferior olivary nucleus, whereas symmetric PN was associated with either ipsilateral or bilateral changes (2,3). In this study, we report a case of OPT with dissociated PN in bilateral inferior olivary hypertrophy (IOH). A 47-year-old man visited our neuro-ophthalmology clinic complaining of oscillopsia for 2 years. His medical history showed that he had experienced intracerebral hemorrhage in the pontine tegmentum several months before developing oscillopsia (Fig. 1B). At that time, he had complained of dizziness and central-type facial palsy on the right side, initially. After several months, oscillopsia and involuntary ocular movements emerged. He did not have any familial or previous history of oscillopsia and nystagmus. His initial examination revealed exotropia and a deficit of adduction of the right eye, which suggested internuclear ophthalmoplegia (INO) (Fig. 1A). Typical abducting nystagmus of INO was not detected in the left eye. Vergence eye movements were spared. Dissociated PN mainly consisting of vertical-torsional components in the right eye and horizontal-torsional components in the left eye was observed (see Supplemental Digital Content 1, Video, http://links.lww.com/WNO/A381). The nystagmus was augmented in the leftward gaze and attenuated in the rightward gaze. A quantitative recording of the threeDepartment of Neurology (J-MK, KWK, T-SN, S-HL), Chonnam National University Medical School, Chonnam National University Hospital, Gwangju, Korea; and Department of Neurology (J-YP), Ulsan University Hospital, and University of Ulsan College of Medicine, Ulsan, Korea. The 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 Seung-Han Lee, MD, PhD, Department of Neurology, Chonnam National University Hospital, 42 Jebong-ro, Dong-gu, Gwangju 61469, Korea; E-mail: [e-mail] Kim et al: J Neuro-Ophthalmol 2020; 40: 97-99 dimensional movements of each eye (Fig. 2) was performed using video-oculography (SLMed, Seoul, Korea). Although PN was dissociated in both eyes, palatal tremor was synchronous with PN and symmetric on both sides. Neither positional imbalance nor cerebellar ataxia was observed. Moreover, neurologic examinations of the other systems yielded unremarkable results. The video head impulse test (ICS Impulse; Otometrics, Taastrup, Denmark) showed decreased vestibuloocular reflex (VOR) gain in all the semicircular canals except the left horizontal canal (see Supplemental Digital Content 2, Figure E1A, http://links.lww.com/WNO/A380). Ocular vestibular-evoked myogenic potential (VEMP) using air-conducted sound (500-Hz tone burst) was not evoked on left-ear stimulation (see Supplemental Digital Content 2, Figure E1B, http://links.lww.com/WNO/A380). Fluid-attenuated inversion recovery MRI demonstrated high signal intensities in both the inferior olivary nuclei, suggestive of hypertrophic degeneration (Fig. 1C). These findings were compatible with those of OPT due to previous intracerebral hemorrhage in the pontine tegmentum. Antihypertensive medications for stroke prevention were administered. In our patient, OPT occurred as a delayed complication of damage to the dentato-rubro-olivary pathway (the Guillain-Mollaret triangle) and subsequent hypertrophic olivary degeneration (HOD) (1,3). Two main clinical presentations are associated with HOD. The most frequent condition is symptomatic OPT as seen in our case; this develops weeks or months after a prior structural brainstem or cerebellar lesion. The second presentation, progressive ataxia and palatal tremor, is characterized by progressive cerebellar ataxia without a structural brainstem or cerebellar lesion, but cerebellar atrophy on MRI progresses over years (4). Attempts have been made to link the characteristics of nystagmus in OPT to the side of IOH. After the publication of a hypothesis that bilateral IOH lesions (midline form) cause symmetric vertical PN and that unilateral lesions (lateral form) are associated with dissociated vertical-torsional PN (5), variable patterns of PN regardless of laterality have been reported (2,3). Nevertheless, most of the patients with bilateral IOH have been reported to show symmetric PN (3). A comprehensive review of OPT reported that only 6% of all subjects showed 97 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Ocular motor examination and neuroimages of the patient. A 9-gaze photograph (A) demonstrates exotropia and a deficit of adduction of the right eye, suggesting internuclear ophthalmoplegia. The initial brain computed tomography of the patient (B) shows intracerebral hemorrhage involving the pontine tegmentum (arrow). After 3 years, brain MRI reveals bilateral pseudohypertrophic degeneration of the inferior olive on fluid-attenuated inversion recovery imaging (arrows, C) and hemosiderin deposits in the pontine tegmentum, indicating a chronic hemorrhagic lesion, on susceptibility-weighted imaging (arrow, D). FIG. 2. Video-oculographic findings of the patient. Video-oculography (A) shows dissociated pendular nystagmus in both eyes. It mainly consists of vertical-torsional components in the right eye and horizontal-torsional components in the left eye (frequency: 1.3-1.5 Hz). The nystagmus is augmented in the leftward gaze and attenuated in the rightward gaze in both eyes (B). 98 Kim et al: J Neuro-Ophthalmol 2020; 40: 97-99 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence TABLE 1. Analysis of the mean amplitude and mean peak velocity of dissociated nystagmus Horizontal Plane Rightward Velocity (deg/s) Right eye Left eye Mean values* 5.29 11.31 8.3 Vertical Plane Leftward Velocity Amplitude (deg/s) (deg)* 7.29 21.25 14.27 0.96 4.36 - Upward Velocity Downward Velocity Amplitude (deg)* 10.29 8.67 9.48 23.68 20.17 21.93 4.15 3.50 - *The mean amplitude and mean peak velocity were calculated on 25 consecutive cycles of nystagmus in each plane. dissociated nystagmus with bilateral IOH (2). The patterns and mechanisms of dissociated PN in bilateral IOH are still unclear and require elucidation. For evaluating the symmetricity of PN, we analyzed the mean amplitude and mean peak velocity of dissociated nystagmus in each eye at the primary eye position (Table 1). The amplitudes were markedly asymmetric in the horizontal plane (right eye, mean 0.96°; left eye, mean 4.36°), whereas they were mildly asymmetric in the vertical plane (right eye, mean 4.15°; left eye, mean 3.5°). Moreover, the leftward and downward phases were faster in each eye. Therefore, the waveforms in the horizontal and vertical planes looked somewhat jerky and dominant in the leftward and downward phases (Fig. 2A). There are several possible mechanisms of dissociated PN in our patient. First, the patient had ophthalmoplegia presenting with persistent INO in the right eye. Patients with OPT often have a deficit in the horizontal eye movement, including INO, one-and-a-half syndrome, and abducens nucleus/fascicular palsy (3). Hence, the ocular motor deficits resulting from prior brainstem insults may affect the disconjugacy of nystagmus. However, the majority of previously reported patients with bilateral IOH and various accompanying horizontal ocular motor deficits showed symmetric nystagmus (3). In addition to the ocular motor deficits, the vestibular signal conveyed by the medial longitudinal fasciculus (MLF) may influence the dissociated PN. Owing to INO, the vertical VOR signals could be asymmetric, as shown by the comprehensive laboratory results of the video head impulse test and ocular VEMP (6). However, more evidence from experimental and clinical analysis is warranted to prove this hypothesis. Second, the disconjugacy of nystagmus could reflect randomly formed couplings in the inferior olivary neurons (1,4). The concept that small patches of cells in the inferior olive and cerebellum fire randomly may explain the various waveforms seen in patients with OPT (1). Each patch Kim et al: J Neuro-Ophthalmol 2020; 40: 97-99 would be connected to a different part of the motor system, and thus, some patches would lead to horizontal movements and others to vertical or torsional movements (1). If the distribution of conductance increases in the inferior olive was nonuniform and it was different in each patient, different patients would present with different waveforms (1). In the present case, we encountered asymmetric, dissociated PN in bilateral IOH, and we analyzed PN by using various methods, including the video head impulse test and ocular VEMP. We suggest that asymmetric ophthalmoplegia and concomitant MLF injury may cause dissociated PN, but various unknown factors may also affect PN in patients with OPT. Further studies are warranted to elucidate the mechanisms of various forms of ocular nystagmus in patients with OPT. ACKNOWLEDGMENTS This study was supported by a grant (BCRI18019) of Chonnam National University Hospital Biomedical Research Institute, Korea. REFERENCES 1. Shaikh AG, Hong S, Liao K, Tian J, Solomon D, Zee DS, Leigh RJ, Optican LM. Oculopalatal tremor explained by a model of inferior olivary hypertrophy and cerebellar plasticity. Brain. 2010;133:923-940. 2. Jang L, Borruat FX. Oculopalatal tremor: variations on a theme by Guillain and Mollaret. Eur Neurol. 2014;72:144-149. 3. Kim JS, Moon SY, Choi KD, Kim JH, Sharpe JA. Patterns of ocular oscillation in oculopalatal tremor: imaging correlations. Neurology. 2007;68:1128-1135. 4. Tilikete C, Desestret V. Hypertrophic olivary degeneration and palatal or oculopalatal tremor. Front Neurol. 2017;8:302. 5. Nakada T, Kwee IL. Oculopalatal myoclonus. Brain. 1986;109:431-441. 6. Lee SH, Kim SH, Kim SS, Kang KW, Tarnutzer AA. Preferential impairment of the contralesional posterior semicircular canal in internuclear ophthalmoplegia. 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