New-onset Oscillopsia in a Patient With a History of Pontine Stroke

A 69-year-old man with a history of pontine hemorrhage 2 years ago noticed binocular vertical diplopia after the stroke. On examination, there was a small-angle incomitant left hyperdeviation that did not fit the 3-step test for fourth nerve palsy and incyclotorsion of the higher eye. On motility testing, there was an obvious pendular nystagmus. Resting tremor of the right hand was noticed on neurological examination. Examination of the oropharynx revealed rhythmic oscillations of the soft palate synchronous with the eye oscillations and hand tremor. These findings established a diagnosis of oculopalatal myoclonus (OPM). Although OPM is a well-described entity, this case is unique because the patient was completely asymptomatic from OPM and did not complain of oscillopsia but was very bothered by vertical diplopia because of skew deviation. It also demonstrates that OPM may coexist with skew deviation because anatomically vestibulo-ocular pathway is close to the triangle of Guillain-Mollaret and patients with lesions in one pathway should be examined for abnormalities in the other. Finally, it reminds us about the importance of monitoring patients with a history of brainstem insults for emergence of synchronous tremors years later and that simple maneuver-like ex/amining oropharynx may provide a clear diagnosis.

Photo and Video Essay Section Editors: Melissa W. Ko, Dean M. Cestari, Peter Quiros, Kimberly M. Winges, MD MD MD MD New-onset Oscillopsia in a Patient With a History of Pontine Stroke Anna Kabanovski, BHSc, Laura Donaldson, MD, Edward Margolin, MD FIG. 1. A. Computed tomography scan of the brain at the time of pontine hemorrhage (arrow). B. Axial MRI fluid-attenuated inversion recovery image at the level of the medulla showing hypertrophy of the left inferior olivary nucleus (arrow). bothered by vertical diplopia because of skew deviation. It also demonstrates that OPM may coexist with skew deviation because anatomically vestibulo–ocular pathway is close to the triangle of Guillain2Mollaret and patients with lesions in one pathway should be examined for abnormalities in the other. Finally, it reminds us about the importance of monitoring patients with a history of brainstem insults for emergence of synchronous tremors years later and that simple maneuver-like ex/amining oropharynx may provide a clear diagnosis. Abstract: A 69-year-old man with a history of pontine hemorrhage 2 years ago noticed binocular vertical diplopia after the stroke. On examination, there was a small-angle incomitant left hyperdeviation that did not fit the 3-step test for fourth nerve palsy and incyclotorsion of the higher eye. On motility testing, there was an obvious pendular nystagmus. Resting tremor of the right hand was noticed on neurological examination. Examination of the oropharynx revealed rhythmic oscillations of the soft palate synchronous with the eye oscillations and hand tremor. These findings established a diagnosis of oculopalatal myoclonus (OPM). Although OPM is a well-described entity, this case is unique because the patient was completely asymptomatic from OPM and did not complain of oscillopsia but was very Journal of Neuro-Ophthalmology 2022;42:e520–e522 doi: 10.1097/WNO.0000000000001461 © 2021 by North American Neuro-Ophthalmology Society Faculty of Medicine (AK), University of Toronto, Toronto, Canada; Faculty of Medicine (LD, EM), Department of Ophthalmology and Vision Sciences, University of Toronto, Toronto, Canada; and Faculty of Medicine (EM), Division of Neurology, Department of Medicine, University of Toronto, Toronto, Canada. A 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 Edward Margolin, MD, Department of Ophthalmology and Vision Sciences, University of Toronto, 801 Eglinton Avenue West, Suite 301, Toronto, ON M5N 1E3, Canada; E-mail: [e-mail] e520 69-year-old man presented to the neuroophthalmology clinic complaining of diplopia. He had a history of pontine hemorrhagic stroke 2 years ago. Neuro-ophthalmic examination was not performed at the time of stroke. Although the patient noticed horizontal binocular diplopia for many years, he was bothered by worsened double vision immediately after the stroke, which had no distinct vertical component. On examination, the visual acuity was 20/30 in both eyes, there was no relative afferent pupillary defect, and ophthalmoscopy was unremarkable in Kabanovski et al: J Neuro-Ophthalmol 2022; 42: e520-e522 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay each eye. Extraocular motility testing revealed a small left hypertropia most notable in left gaze. He also had a lowfrequency horizontal pendular nystagmus with a torsional component that was accentuated in the right gaze. The nystagmus was not affected by distance fixation or convergence. When this was mentioned, the patient said that 6 months ago he noticed involuntary eye movements bilaterally. A head impulse test was not performed because a peripheral vestibular pathology was not suspected. Examination of the oropharynx revealed rhythmic oscillations of the soft palate (See Supplemental Digital Content, Video 1, http://links.lww.com/WNO/A533). This patient also had a hand tremor which was synchronous with soft palate oscillations and with his pendular nystagmus (See Supplemental Digital Content, Video 2, http://links.lww.com/ WNO/A534). The involuntary synchronous movements of the eyes, soft palate, and extremity were diagnostic of oculopalatal myoclonus (OPM) (1). Regarding his diplopia, a double Maddox rod test revealed incyclotorsion of the hypertropic eye consistent with skew deviation. Of note, this is opposite to excyclotorsion which is consistent with fourth nerve palsy (2). OPM is associated with hypertrophic olivary degeneration (HOD) that occurs after a brainstem lesion involving the Guillain2Mollaret pathway. This pathway spans from the contralateral dentate nucleus in the cerebellum through the superior cerebellar peduncle (brachium conjunctivum) to the contralateral red nucleus in the midbrain and down to the ipsilateral inferior olivary nucleus (ION) in the medulla through the central tegmental tract. Fibers then travel through the inferior cerebellar peduncle back to the dentate nucleus (1). Most commonly, lesions are from hemorrhagic stroke and less commonly from ischemic stroke, trauma, tumors, or neurosurgery. OPM can occur weeks to years after the insult (3). The pathophysiology of OPM stems from abnormal ION function (1,3). ION neurons have unique interneuronal connections known as dendro2dendritic gap junctions that allow electrotonic coupling and give neurons the capacity to achieve oscillations and synchronization. Normally, inhibitory gamma-aminobutyric acid-ergic input prevents oscillations of ION neurons. However, when damage occurs in the pathway, this inhibition may be lost, leading to oscillations. Furthermore, damage in the pathway causes the ION to gradually become hypertrophic, and its neurons develop abnormal soma–somatic gap junctions in addition to the existing gap junctions. This increases the strength of electrotonic coupling, resulting in more oscillations and synchronization of many cells causing movements. The cerebellum is believed to accentuate or modulate these signals resulting in abnormal motor output in the branchial arches. This produces smoother, amplified movements in the eyes and oropharynx muscles, specifically the levator veli palatini muscle, as well as the involvement of muscles in the extremities. Kabanovski et al: J Neuro-Ophthalmol 2022; 42: e520-e522 OPM is a clinical diagnosis requiring identification of abnormal oscillations of the palate and eyes, usually synchronous at a 1–3 Hz frequency (3). The eye oscillations may be asymmetric with torsional and horizontal components. Movements of other muscles may also occur. Pathologically, HOD is characterized by enlarged, vacuolated neurons, increased number and size of astrocytes, and severe fibrillary gliosis (1). On MRI of the brain, there is an increased T2/fluid-attenuated inversion recovery image signal intensity and enlargement of the ION (1,3). Our patient’s MRI showed hypertrophy of the left ION, which was consistent with the findings and diagnosis (Fig. 1). Although patients with OPM are mostly asymptomatic from the palatal tremor, they are usually very bothered by the nystagmus and complain of disturbing oscillopsia, decreased visual acuity, and worsened vision-related quality of life (3). Thus, therapeutic trials have been mainly targeting this symptom. The therapy attempts to block the ION electrotonic coupling (with quinine, carbenoxolone, or mefloquine) or the cerebellar modulation (with benzodiazepines, topiramate, and memantine). Gabapentin and memantine have shown to reduce the amplitude and frequency irregularity of nystagmus (2). However, there is insufficient evidence to support any therapies because many studies are unpublished or have small sample sizes (1–6 subjects) (3). In one case that was refractory to medical treatment, bilateral deep brain stimulation of the red nucleus was attempted but failed to show any symptomatic improvement (4). In addition to OPM, our patient had skew deviation, which is a vertical strabismus caused by a disruption of vestibular input before it reaches the oculomotor nuclei. Diseases in the vestibular organs or nerves, vestibular nuclei in the medulla, pons, medial longitudinal fasciculus, midbrain (including the interstitial nucleus of Cajal), and diencephalon have been reported to cause skew deviation (5). The proximity of the regions involved in the vestibulo– ocular pathways to those involved in the Guillain2Mollaret pathway suggests that skew deviation and OPM are likely to coexist as a result of one lesion. Furthermore, the persistent skew deviation likely failed to adapt because there is frequent maladaptation related to HOD, likely because of permanent inferior olive coupling interfering with the normal adaptation of the cerebellum (6). OPM is a well-described phenomenon, and patients frequently present like our patient with new-onset pendular nystagmus and synchronous oscillations of the palate years after brainstem stroke. However, our patient is unique because he was completely asymptomatic from the OPM but was bothered only by skew deviation. There has been only one other reported case of asymptomatic OPM in the literature (7). Furthermore, our case shows that one lesion may result in both OPM and skew deviation because the locations of the 2 pathways involved are anatomically close. e521 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Photo and Video Essay Finally, we are reminded of the importance of monitoring patients with a history of brainstem insult for emergence of synchronous tremors years later. Examining the oropharynx was an easy maneuver that provided a clear answer to this man’s symptoms and avoided unnecessary investigations and potentially incorrect diagnoses. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: Laura Donaldson, Edward Margolin, and Anna Kabanovski; b. Acquisition of data: Laura Donaldson and Edward Margolin; c. Analysis and interpretation of data: Laura Donaldson, Edward Margolin, and Anna Kabanovski. Category 2: a. Drafting the manuscript: Laura Donaldson, Edward Margolin, and Anna Kabanovski; b. Revising it for intellectual content: Laura Donaldson, Edward Margolin, and Anna Kabanovski. Category 3: a. Final approval of the completed manuscript: Laura Donaldson, Edward Margolin, and Anna Kabanovski. e522 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. 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Kabanovski et al: J Neuro-Ophthalmol 2022; 42: e520-e522 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.