Recurrent Bilateral Myelin Oligodendrocyte Glycoprotein Antibody Optic Neuritis in a Leber Hereditary Optic Neuropathy Carrier

A 55-year-old woman with known Leber hereditary opticneuropathy (LHON) G11778A mtDNA mutation carrier status presented with 1 week of right eye pain and decreased visual acuity. She had an upper respiratory tract infection 3 weeks before.

Clinical Correspondence Recurrent Bilateral Myelin Oligodendrocyte Glycoprotein Antibody Optic Neuritis in a Leber Hereditary Optic Neuropathy Carrier Subahari Raviskanthan, MBBS, Nayomi Perera, Anthony Fok, MBBS, FRACP A 55-year-old woman with known Leber hereditary optic neuropathy (LHON) G11778A mtDNA mutation carrier status presented with 1 week of right eye pain and decreased visual acuity. She had an upper respiratory tract infection 3 weeks before. Her medical history included that of migraine with an aura, smoking, and social alcohol use. On examination, visual acuity was 6/24 in the right eye and 6/6 in the left eye. Color vision was 1/7 (test plate only) in the right eye and 7/7 in the left eye, and there was a right relative afferent pupillary defect. Fundoscopy demonstrated FIG. 1. T2 MRI images. Right optic nerve enhancement on first presentation (A) axial and (C) coronal. B. Left optic nerve enhancement on second presentation axial. D. Right optic nerve enhancement on coronal sequence on second presentation. Department of Neurology, Royal Melbourne Hospital, Melbourne, Australia. The authors report no conflicts of interest. Address correspondence to Subahari Raviskanthan, MBBS, Department of Neurology, Alfred Hospital, 55 Commercial Road, St. Kilda, VIC 3004, Australia; E-mail: [e-mail] 246 bilateral optic nerve swelling, more pronounced in the right eye. Humphrey visual fields revealed a generalized peripheral field defect with a small nasal paracentral island of vision in the right eye and a partial superior arcuate defect in the left eye. Optical coherence tomography (OCT) of the patient's retinal nerve fiber layer (RNFL) showed increased thickness Raviskanthan et al: J Neuro-Ophthalmol 2020; 40: 246-247 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence superiorly, nasally, and inferiorly in the right eye and superiorly in the left eye. Infectious, infiltrative, and autoimmune screening, including neuromyelitis optica antibodies, were negative. Computerized tomography (CT) of the chest was unremarkable. MRI brain and orbits demonstrated right optic nerve sheath enhancement, consistent with optic neuritis (Fig. 1). The patient responded to 3 days of 1-g intravenous methylprednisolone and subsequent oral taper of prednisolone, with vision returning to 6/ 6 bilaterally on a review 1 month later. Three months later, the patient presented with reduced vision, eye pain, and headache over 3 weeks. One examination, she had hand movement vision in the right eye and 6/60 in the left eye. Fundoscopy showed optic nerve pallor in the right eye and a normal optic nerve in the left eye. OCT showed RNFL thinning superiorly, temporally, and inferiorly in the right eye. There was temporal thinning in the left eye. Repeat MRI demonstrated bilateral optic nerve enhancement with associated mild optic nerve atrophy, consistent with a further episode of bilateral optic neuritis. CSF was unremarkable: 1 polymorph, 0 lymphocytes, protein 0.35 mmol/L, and oligoclonal bands were not detected. Serum myelin oligodendrocyte glycoprotein (MOG) antibodies were positive in 2 of 2 tests (median fluorescence intensity w35,000, threshold w13,000). A second course of 5-day 1-g intravenous methylprednisolone and 5 cycles of plasma exchange did not lead to recovery of visual function. The patient has been on a weaning dose of prednisolone and has remained relapse-free but without any objective visual recovery. DISCUSSION We present the first reported case of optic neuritis with MOG antibody positivity in a patient with a LHON mutation. The clinical presentations are more consistent with optic neuritis given pain, rapid symptom progression, and response to steroids as opposed to LHON optic neuropathy. The lack of response to steroids in the second admission is likely due to the delay in presentation. The most commonly reported association with LHON and multiple sclerosis remains that of Harding syndrome. There have been 68 reported cases of demyelination features in patients with confirmed LHON mutation, most of which were G11778A, the most common mtDNA mutation for LHON (1). Eleven of these patients were asymp- Raviskanthan et al: J Neuro-Ophthalmol 2020; 40: 246-247 tomatic. Analyses based on population incidences and prevalence suggest this is within the range of a chance association. However, it is believed that the underlying disease phenotype is more severe, with poorer response to steroids and lower proportion with recovery of vision (1). Only 1 case has been reported of MOG positivity in a LHON patient (2). In other demyelinating conditions, coexistence of a LHON mutation with aquaporin-4 (AQP4) antibodies in 2 patients with LHON mutations has been reported suggestive of a concurrent diagnosis of neuromyelitis optica (3,4). In addition, a further screening of a series of 11 patients with known LHON mutations and only visual symptoms for AQP4 antibodies revealed 1 patient had an anti-AQP4 antibody (5). Our case highlights MOG antibody bilateral optic neuritis in a LHON carrier. This case suggests not only assessing for multiple sclerosis but testing for MOG antibodies in LHON patients who present with clinical symptoms suggestive of demyelination. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: N/A; b. Acquisition of data: N/A; c. Analysis and interpretation of data: N/A. Category 2: a. Drafting the manuscript: S. Raviskanthan and A. Fok; b. Revising it for intellectual content: S. Raviskanthan and A. Fok. Category 3: a. Final approval of the completed manuscript: S. 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Mult Scler. 2016;22:393-394. 247 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.