Journal of Neuro-Ophthalmology, March 2015, Volume 35, Issue 1

Bilateral Sixth Nerve Palsies in Anti-Aquaporin 4 Antibody Syndrome

Bilateral Sixth Nerve Palsies in Anti-Aquaporin 4 Antibody Syndrome While optic neuritis and myelitis are classically described in neuromyelitis optic (NMO), Morrow and Wingerchuk (1) point out other sites within the central nervous system that may be affected. However, despite frequent involvement of the brainstem in NMO, detailed descriptions of the patterns of oph-thalmoplegia are available in only a few case reports (Table 1). We report bilateral fascicular sixth nerve palsies in a patient with anti-aquaporin 4 (AQP4) antibody. A 26-year-old woman complained of headache, vertigo, and unsteadiness. Examination showed spontaneous left-beating nystagmus, gaze-evoked nystagmus (GEN) and leftward falling while walking. Brain magnetic resonance imaging (MRI) revealed a lesion involving the dorsal medulla. Serum anti-AQP4 antibody test was positive. She experienced marked improvement after a 5-day course of corticosteroids. One year later, the patient experienced another episode of headache, somnolence, and visual blurring. Examinations 1 week later showed small amplitude, spontaneous nystagmus beating rightward and upward only without fixation, and impaired vertical smooth pursuit. Brain MRI showed newly developed lesions in-volving the hypothalamus, mammillary bodies, and optic tracts. Three months later, the patient had the third episode of headache, facial numbness, and diplopia. Examination showed limitation of abduction in both eyes, upbeat nystagmus during convergence, and horizontal and vertical GEN (See Supplemental Digital Content, Video, http://links.lww.com/WNO/A131). Brain MRI disclosed new lesions in the pontine tegmentum bilaterally (Fig. 1). She was treated with intravenous steroids for a week followed by oral maintenance. Our patient had recurrent neurological episodes due to lesions involving the dorsal medulla, hypothal-amus, mammillary bodies, optic tracts, and dorsal pons, all of which highly express AQP4 (7). Since the discov-ery of anti-AQP4 antibody as a pathogenic marker of NMO, there has been increasing recognition of patients developing neurologic symptoms and signs attributable to anti-AQP4 antibody, but without optic nerve or spi-nal cord involvement. Those cases have been termed NMO spectrum disorder to which our patient belongs (8). We are unaware of previous reports of bilateral fascicular sixth nerve palsies in association with anti- AQP4 antibody. Demyelinating disorders may cause sixth nerve palsy, usually in the setting of multiple sclerosis or chronic inflammatory polyneuropathy (9). In addition to bilateral abduction defects, our patient reported facial numbness, indicating involvement of the spinal trigemi-nal nucleus and tract. The GEN and convergence-evoked upbeat nystagmus suggest that nearby pontine structures for gaze holding such as the nucleus prepositus hypoglossi and paramedian tract cell groups also were affected (10,11). Jin-Ah Kim Seoul National University College of Medicine, Seoul, Korea Sung-Hee Kim, MD Department of Neurology, Seoul National University College Medicine, Seoul National University Bundang Hospital, Seongnam, Korea FIG. 1. Axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance scans show symmetric lesions involving the periventricular pontine region. Letters to the Editor: J Neuro-Ophthalmol 2015; 35: 94-105 103 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. TABLE 1. Ophthalmoplegia in anti-AQ4 antibody syndrome Report Diagnosis Gender/Age Ophthalmoplegia Other Antibodies Lesion Accompanying Findings Gilmore et al (2) NMO F/37 Dorsal midbrain syndrome (eyelid retraction, upgaze palsy, convergence-retraction nystagmus, impaired convergence) Periaqueductal gray matter Oscillopsia Shinoda et al (3) NMOSD F/19 Wall-eyed INO Antinuclear Ab Anti-SS-A Ab Midbrain tegmentum Double vision Dysphagia Dysarthria Right-sided weakness Paresthesia Garcia-Martin et al (4) NMO F/32 INO Anti-DNA Ab Brainstem Ogasawara et al (5) NMOSD F/62 4th nerve palsy, nuclear Midbrain, pons, medulla Spinal cord (C5-T1) Vertical diplopia Paresthesia Lee et al (6) NMOSD F/60 Dorsal midbrain syndrome (vertical gaze palsy, convergence spasm, light-near dissociation of the pupil, convergence-retraction nystagmus) INO and skew deviation (on separate occasion) Anti-SS-A Ab Periaqueductal mesodiencephalon Diplopia Dizziness Dry mouth and eyes Current Case NMOSD F/26 Bilateral 6th nerve palsies Gaze-evoked nystagmus Convergence-evoked upbeat nystagmus Pons Horizontal diplopia Headache Dizziness Nausea Facial numbness INO, internuclear ophthalmoplegia; NMO, neuromyelitis optica; NMOSD, neuromyelitis optica spectrum disorder. 104 Letters to the Editor: J Neuro-Ophthalmol 2015; 35: 94-105 Letters to the Editor Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Hyo-Jung Kim, PhD Department of Biomedical Laboratory Science, Kyungdong University, Goseong, Korea Ji-Soo Kim, MD, PhD Department of Neurology, Seoul National University College Medicine, Seoul National University Bundang Hospital, Seongnam, Korea This study was supported by a grant of the Korea Healthcare technology R&D Project, Ministry of Health and Welfare, Republic of Korea (HI10C2020). J.-S. Kim serves as an Associate Editor of Frontiers in Neuro-otology and on the editorial boards of the Journal of Clinical Neurology, Frontiers in Neuro-ophthalmology, Journal of Neuro-ophthalmology, Journal of Vestibular Research, Journal of Neurology, and Medicine, and received research support from SK Chemicals Co. Ltd. The remaining authors report no conflicts of interest to disclose. Supplemental digital content is available for this article. 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