ARTICLE IN PRESS Case Studies Conjugate Eye Deviation Caused by Upper Medial Medullary Infarction: A Case Report Takashi Ogawa, MD, Yuji Ueno, MD, PhD, Hikaru Kamo, MD, Nobukazu Miyamoto, MD, PhD, Kazuo Yamashiro, MD, PhD, Ryota Tanaka, MD, PhD, Yasushi Shimo, MD, PhD, and Nobutaka Hattori, MD, PhD Conjugate eye deviation (CED) is defined as a sustained shift in horizontal gaze toward 1 side, together with gaze failure to the other side, caused by lesions in the brainstem, basal ganglia, or cortical frontal eye fields. To date, very few reports have described CED in patients with medullary infarction. A 76-year-old woman presented with sudden onset of vertigo and right hemiparesis, accompanied by CED to the right with gaze palsy to the left. Her brain magnetic resonance imaging showed left upper medial medullary infarction involving the left nucleus prepositus hypoglossi (NPH) and adjacent to the left inferior olivary nucleus (ION). After treatments with 200 mg of aspirin and 60 mg of edaravone daily, symptoms gradually improved. The NPH and ION constitute NPH-ION-floccus-vestibular nucleus loop and contribute to the inhibitory mechanisms for horizontal eye movements. In addition, NPH projects excitatory neurons to the contralateral vestibular nucleus. In our case, disorders of the NPH and ION might have dysregulated inhibitory and excitatory projections, and thereby cause CED to the right with gaze palsy to the left. This represents a rare case showing CED to the contralesional side in upper medial medullary infarction. Key Words: Stroke—conjugate eye deviation—medial medullary infarction—case report. © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. Introduction Conjugate eye deviation (CED) can be caused by brainstem lesions with involvement of the prepontine reticular formation, mainly as a result of acute stroke.1,2 Here we From the Department of Neurology, Juntendo University Faculty of Medicine, Bunkyo-ku, Tokyo, Japan. Received March 23, 2018; revision received May 3, 2018; accepted May 13, 2018. Ethics approval and consent to participate: The authors declare that ethics approval was not required for this case report. We obtained written informed consent for publication from the patient. Address correspondence to Yuji Ueno, MD, PhD, Department of Neurology, Juntendo University, Faculty of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421, Japan. E-mail: yuji-u@juntendo.ac.jp. 1052-3057/$ - see front matter © 2018 National Stroke Association. Published by Elsevier Inc. All rights reserved. https://doi.org/10.1016/j.jstrokecerebrovasdis.2018.05.014 describe a case showing CED caused by left medial medullary infarction. Case Presentation A 76-year-old Japanese woman with a history of hypertension and dyslipidemia developed sudden onset of vertigo, left posterior neck pain, and hemiparesis in the right upper and lower extremities. On admission, her speech was slurred, her tongue showed slight deviation toward the right, and she had right-sided hemiparesis. Eye position was deviated to the right and she could not see toward the left (Fig 1, A). The vestibulo-ocular reflex and optokinetic nystagmus were impaired from the midline to the left. Brain magnetic resonance imaging demonstrated an ischemic lesion in the left upper medial medulla on axial and Journal of Stroke and Cerebrovascular Diseases, Vol. ■■, No. ■■ (■■), 2018: pp ■■–■■ 1 ARTICLE IN PRESS T. OGAWA ET AL. 2 Figure 1. (A) Conjugate eye deviation of both eyes toward the right during forward, upward, downward, and right lateral gazes and convergence, and bilateral gaze palsy toward the left were recognized. (B and C) Left panels show representative images of axial (B) and sagittal (C) diffusion-weighted imaging, revealing a signal hyperintense lesion in the left medial medulla oblongata. Right panels show a schema of the medulla oblongata on axial (B) and sagittal (C) views. (D) Representative image from magnetic resonance angiography shows occlusion of the left vertebral artery (arrows). a, corticospinal tract; b, inferior olivary nucleus; c, reticular formation; d, vestibular nuclei; e, oculomotor nucleus; f, trochlear nucleus; g, paramedian pontine reticular formation; h, abducens nucleus; arrow, nucleus prepositus hypoglossi; red dotted lines, infarct area. sagittal diffusion-weighted imaging (Fig 1, B,C). The infarct area spared the prepontine reticular formation, but involved the nucleus prepositus hypoglossi (NPH) and was adjacent to the inferior olivary nucleus (ION). Magnetic resonance angiography showed occlusion of the left vertebral artery (Fig 1, D). Acute left medial medullary infarction was diagnosed, and treatment was initiated with aspirin at 200 mg/d and edaravone at 60 mg/d. CED to the right and horizontal gaze palsy to the left gradually improved and disappeared within 2 weeks after admission. Discussion Considerable interest has been shown in the contribution of inhibitory mechanisms to horizontal eye movements, with the NPH and ION playing pivotal roles.3,4 Patients with NPH lesions in previous case series have shown static eye deviation to the contralesional side under conditions of closed eyelids.5 The NPH projects inhibitory connections mainly to the contralateral ION, with a smaller connection to the ipsilateral NPH and ION, constituting the NPH-ION-floccus-vestibular nucleus (VN) loop. In addition, NPH projects excitatory connections to the contralateral VN.5 In our case, left NPH disorder could have dysregulated this loop, leading to hyperactivity of the left VN, and increased activity of the right abducens nucleus and left rectus medialis region of the oculomotor nucleus.2,3,5,6 Furthermore, suppression of the right VN owing to disorder of excitatory projections from the left NPH and damage to the left ION by acute edema ARTICLE IN PRESS CONJUGATE EYE DEVIATION AND MEDIAL MEDULLARY INFARCTION following infarction via this loop was induced, which could have inactivated the left abducens nucleus and right oculomotor nucleus. These synergic mechanisms might have resulted in clear CED to the right with gaze palsy to the left, particularly in the acute stage of brain infarction. 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