Bilateral Sixth Nerve Palsies in Anti-Aquaporin 4 Antibody Syndrome

Abstract

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 ophthalmoplegia 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.TABLE 1: Ophthalmoplegia in anti-AQ4 antibody syndromeA 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 involving 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, https://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.FIG. 1: Axial fluid-attenuated inversion recovery (FLAIR) magnetic resonance scans show symmetric lesions involving the periventricular pontine region.Our patient had recurrent neurological episodes due to lesions involving the dorsal medulla, hypothalamus, mammillary bodies, optic tracts, and dorsal pons, all of which highly express AQP4 (7). Since the discovery 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 spinal 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 trigeminal 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).