Anti-myelin oligodendrocyte glycoprotein antibody-positive coursing with optic neuritis: Imaging and clinical implications

Abstract

A 9-year-old boy was admitted to our institution with acute onset of bilateral blurry vision. Physical examination revealed bilateral papilledema. Cerebrospinal fluid analysis and comprehensive metabolic panel were normal. Magnetic resonance imaging (MRI) of the brain showed extensive bilateral optic nerve inflammation with post-contrast gadolinium enhancement on T1-weighted sequence. The involvement was limited to the anterior segments of the optic nerves sparing chiasma and optic tracts. Anti-aquaporin-4 antibody (AQP4) was negative while anti-myelin oligodendrocyte glycoprotein antibody (MOG) was positive. After intravenous methylprednisolone, his vision dramatically improved. The patient was discharged with only mildly impaired visual acuity, 2 weeks after admission. Follow-up brain MRI and MOG assay after 3 months were within normal limits.

Keywords

MRI - myelin oligodendrocyte glycoprotein - optic neuritis

Introduction

Myelin oligodendrocyte glycoprotein (MOG) is exclusively expressed on the surface of oligodendrocytes and myelin in the central nervous system.[[1]] MOG antibody disease (MOG-AD) is now recognized as a distinct entity characterized by a monophasic or relapsing course of neurological dysfunction, with optic neuritis (ON) as its most common presentation followed by transverse myelitis (TM) and acute disseminated encephalomyelitis (ADEM).[[1], [2], [3]] Patients with MOG-IgG associated demyelination appear to have unique clinical, radiological features, and outcomes compared to other demyelinating conditions, especially APQ4-IgG positive neuromyelitis optica (NMO) and multiple sclerosis (MS).[[3], [4], [5]] Hence, the radiological distinction of ON is important.

Case Report

A 9-year-old African-American boy consulted local optometrist for a 4 days history of acute onset blurring of vision in bilateral eyes associated with pain, more in the right eye. It was determined that he had bilateral papilledema. He was then referred to our hospital for further investigation. On examination, his visual acuity was severely impaired (20/200 right eye, 20/100 left eye) with bilateral optic disc edema and no afferent pupillary defect. Routine blood tests and metabolic panel were normal. Erythrocyte sedimentation rate (ESR) was raised to 32 mm/h and C-reactive protein (CRP) was normal. A lumbar puncture was performed, which revealed a cerebrospinal fluid (CSF) cell count of 3 cells/mL, lymphocytes, with normal protein and glucose, and no oligoclonal bands. No lymphocytic pleocytosis was seen.

Brain MRI showed restricted diffusion in bilateral optic nerves on diffusion weighted imaging (DWI) as well as a post-contrast enhancement on T1-weighted sequence indicating extensive bilateral optic nerve inflammation [[Figure 1]]. MRI spine was unremarkable.

Figure 1 (A-D): MRI T1-weighted image showing post-contrast enhancement of extensively edematous bilateral optic nerves in (A) axial and (B) coronal views. Restricted diffusion in bilateral optic nerves on DWI sequence (C) and ADC sequence (D)

The patient was admitted and started treatment with intravenous methylprednisolone (30 mg/kg/day for 5 days).

Immunologic workup for routine antibodies such as ANA and dsDNA were normal. Indirect immune fluorescence assays using MOG and AQP4 expressing cells revealed positive anti-MOG antibodies (titer 1:40) and negative anti-AQP4 antibodies. Considering the clinical, laboratory, and imaging findings, a diagnosis of anti-MOG associated autoimmune optic neuritis was considered.

Repeat ophthalmological exam after a 5-day course revealed improvement of visual acuity (20/30 in the left eye and 20/20 in right eye) and decreased optic disc swelling. The patient was discharged with continued per oral (PO) steroid dosing with taper after 8 days of hospital stay. The patient was observed subsequently after 2 weeks with visual acuity (20/20 in bilateral eyes). He was further observed for 1 year in outpatient visits and remained asymptomatic. Follow -up brain MRI and anti-MOG IgG assay after 3 months were normal.

Discussion

We described a patient with bilateral optic neuritis positive for anti-MOG-IgG. MOG-AD may occur in all decades of life, with a slight predominance in women and with a median age of onset in the mid-thirties. The most common finding was optic neuritis (ON), occurring in 54–61% of patients, followed by TM, or an ADEM-like presentation (e.g., brainstem attack).[[1], [2]]

Brain MRI was performed and the images showed extensive post-contrast enhancement of the bilateral optic nerves on the T1-weighted images representing edematous and inflamed bilateral optic nerves. This condition predominantly involved the anterior segments of the optic nerve along with intra-orbital segments, while optic chiasm and optic tracts were spared. Besides, restricted diffusion was found on the DWI sequence and apparent diffusion coefficient (ADC) map.

Bilateral involvement of optic nerves was more common in MOG-ON and AQP4-ON compared to MS-ON[[4]] and according to Sato et al., bilateral involvement of optic nerves was much more common in MOG-ON compared to AQP4-ON.[[2], [6]]

In MOG-ON, the T1 gadolinium enhancement predominantly involves the anterior segments of the optic nerves, along with intra-orbital segments with more edematous and extensive inflammation, contrary to AQP4-ON which predominantly affect the chiasma and optic tracts.[[1], [2], [3], [4], [5]] This aspect constitutes a vital MRI finding that contributes to making the diagnosis. Akaishi et al. studied Japanese patients (n = 19 MOG-ON and n = 9 AQP4-ON) and demonstrated severe and extensive inflammatory changes in the optic nerves of MOG-ON patients that typically spared the chiasm, while AQP4-ON patients had chiasmal swelling.[[7]] A recent cohort of 50 patients presenting with first-episode ON, conducted by Ramanathan et al., has reported chiasma involvement in 64% of patients with AQP4-ON, whereas only 5% of patients with MOG-ON had chiasmal involvement. 15% of MS-ON also had chiasmal involvement but is rarely described and highly variable.[[1], [4], [8]] Instead, MS-ON is usually unilateral, unpredictable, and occurs in limited segments.[[3], [9]]

Besides, patients with MOG-ON and AQP4-ON tend to have longer lesion lengths compared to MS-ON which only involves small segments of the nerves.[[4]] In MOG-ON, sometimes the lesion tends to be so long to involve the optic nerve head in the orbital portion, consistent with the high frequency of optic disc edema resulting in optic nerve head swelling.[[3], [4]] The presence of radiological optic nerve head swelling, in particular, was significant and highly suggestive of MOG-ON.[[4]]

Inflammation and enhancement of the perioptic nerve sheath, partly extending into the surrounding fat, is often demonstrated in 50% of patients[[3], [10]] and 47% of patients[[8], [11], [12]] with MOG-ON. Perineural optic nerve enhancement is unusual in AQP4-ON and MS-ON.[[12]] Its presence, therefore, is crucial and suggestive of MOG-ON.[[3], [10]] However, this specific finding was not observed in our patient.

Clinically, compared to AQP4-ON, patients with MOG-ON have better visual field outcomes, although recurrence of ON is significantly more frequent.[[3], [4]] A relapsing course has been reported in 44–83% of patients.[[3]]

Our patient demonstrates unique radiological findings of MOG-ON, more frequently resulting in bilateral and longitudinally extensive ON likely to be associated with anterior visual pathway involvement, while AQP4 antibodies are more commonly associated with posterior visual pathway involvement. This radiological differentiation may assist clinicians and radiologists with a prompt diagnosis of ON.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Conflict of Interest

There are no conflicts of interest.

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Publication History

Received: 07 December 2019

Accepted: 05 March 2020

Article published online:
19 July 2021