Post-traumatic myelin oligodendrocyte glycoprotein antibody optic neuritis: A case report

Abstract

Purpose

Myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD) has recently been distinguished as its own disease entity separate from other demyelinating diseases. This case report highlights the possible association of orbital trauma with the development of MOG antibody (MOG-IgG) optic neuritis.

Observations

A 31-year-old male with no significant ocular history presented with blurry vision in the right eye four weeks after a motorcycle crash. Right eye examination was notable for a significant decrease in visual acuity with a relative afferent pupillary defect and circumferential disc elevation on fundoscopy. An extensive workup, including imaging and serology, revealed optic neuritis with a positive MOG-IgG antibody titer. The patient was treated with intravenous steroids followed by an oral taper, with near-complete resolution of his symptoms.

Conclusions and importance

MOG antibody-related optic neuritis should be considered in patients presenting with painful vision loss after trauma, as early recognition and treatment can lead to favorable outcomes.

Highlights

• •BBB disruption after trauma may be a conduit for exposure to the MOG antibody
• •Post-trauma MOG-IgG exposure may trigger optic neuritis, distinct from indirect TON
• •Prior cases may have been misdiagnosed due to our recent understanding of MOGAD
• •Early treatment can result in symptom resolution and visual recovery

1. Introduction

Inflammatory central nervous system (CNS) demyelinating disorders encompass a spectrum of diseases, including multiple sclerosis (MS), aquaporin-4 (AQP4)-IgG-positive neuromyelitis optica spectrum disorders (NMOSD), and myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD).¹ Based on evidence from serologic, immunologic, and neuropathological studies, MOGAD has recently been distinguished as its own disease entity separate from MS and AQP4-IgG positive NMOSD. As a result, some patients with MOGAD were previously misdiagnosed with MS or other inflammatory CNS conditions, which can have significant treatment and prognostic implications.²

MOG-IgG antibodies have been implicated in histopathologically distinct presentations of myelitis and brainstem encephalitis, but the most common initial presentation of MOGAD is optic neuritis.^2,3 Optic neuritis in MOGAD tends to present bilaterally, often with a recurrent course. Ophthalmologic examination frequently reveals optic disc edema and perineural enhancement of the optic nerve may be seen on magnetic resonance imaging (MRI).³

Although often seen as a sequela of an underlying CNS demyelinating disorder, optic neuritis can also be isolated or idiopathic.³ In some cases, traumatic events have been reported to precede cases of optic neuritis, either in isolation or in association with MS or AQP4-positive NMOSD.^4,5 Trauma-associated MOGAD optic neuritis is less reported. This report describes a case of MOG-IgG optic neuritis in a young adult that occurred shortly after trauma.

2. Case report

A 31-year-old Caucasian male was brought in by emergency medical services to a local emergency room after a motorcycle crash. The patient was a helmeted driver without a face shield driving at approximately 35 miles per hour when he collided with another vehicle and was thrown over the handlebars of his motorcycle. Upon arrival at the emergency room, the patient's Glasgow Coma Scale was 15. His initial assessment was significant for multiple facial fractures, including a right Le Fort Type II and III fracture, a left Le Fort Type II fracture, and numerous bilateral upper extremity fractures. Prior to this presentation, he had no medical or ocular history and took no medications. He had no significant family history. An examination by the on-call ophthalmologist revealed a visual acuity of 20/20 in both eyes with normal intraocular pressures. Examination of extraocular movements revealed mildly reduced supraduction of the right eye. There was periorbital ecchymosis and mild soft tissue edema, but the remainder of the examination, including slit lamp and dilated fundus examinations, was normal. He subsequently underwent uncomplicated maxillomandibular fixation with oral maxillofacial surgery.

One month after the accident, the patient presented to the Wills Eye Emergency Room with a chief complaint of blurry vision in the right eye for two days. The patient endorsed stable diplopia in upgaze since the initial injury but reported new pain with extraocular movements. He denied subsequent trauma, headaches, or extremity weakness and numbness. His review of systems was otherwise unremarkable.

On examination, his best-corrected visual acuity was 20/300 in the right eye and 20/40 in the left eye, with a right relative afferent pupillary defect and reduced color vision in the right eye with 0/8 Ishihara color plates. Intraocular pressures were normal bilaterally, and extraocular movements were intact, except for a 15 % reduction in supraduction in the right eye. Fundoscopic examination revealed circumferential disc elevation in the right eye and a normal optic disc in the left eye with a small cup-to-disc ratio; the remainder of the examination was unremarkable.

An extensive workup, including imaging and serology, was pursued. An MRI of the brain and orbits with and without gadolinium contrast including T1 and T2 sequences was notable for right optic nerve enhancement involving the entire intracanalicular segment (Fig. 1), with no significant white matter lesions. There was no evidence of optic nerve sheath enhancement. An MRI of the cervical spine revealed no abnormal cord signal or enhancement. The patient's serologic workup was notable for a positive MOG antibody titer of 1:40 based on a positive titer cutoff of ≥1:10 at our hospital's laboratory. The remainder of his workup, including testing for syphilis, sarcoidosis, tuberculosis, Lyme, and aquaporin-4 antibodies, was negative. Given the clinical and diagnostic features, the patient met criteria for definite optic neuritis^6b and was admitted for treatment with three days of intravenous (IV) methylprednisolone followed by an oral steroid taper. Following treatment, the patient noted complete resolution of his blurry vision and pain. His visual acuity improved to 20/25 in the right eye, with only a trace right afferent pupillary defect. The remainder of his ocular examination was unremarkable.

Fig. 1.

MRI of the orbits

(A) Coronal and (B) Axial T1 gadolinium contrast-enhanced MRI of the orbits reveals abnormal enhancement involving the entire orbital and intracanalicular segment of the right optic nerve (white arrows).

3. Discussion

Indirect traumatic optic neuropathy (TON) results from high-energy impact leading to mechanical shearing of the optic nerve or impairment of the microcirculation in the optic canal, with the intracanalicular segment being the most susceptible.^7,8 Symptoms of TON include immediate or delayed vision loss, visual field defects, and dyschromatopsia.⁷ The optic nerve head may appear normal initially, with optic nerve pallor apparent three to six weeks after the initial traumatic event. In cases of indirect TON, a CT scan of the orbits often appears normal in the acute phase, but orbital MRI with diffusion-weighted imaging can reveal optic nerve hyperintensity due to diffusion restriction.^9,10 To date, there is no consensus on the treatment of TON, but current management strategies include conservative treatment, steroids, or surgical decompression.⁴

Our patient presented with delayed onset of visual impairment four weeks after head trauma with decreased visual acuity and an afferent pupillary defect in the right eye. His MRI findings of optic nerve enhancement are incongruent with the expected features of TON. Additionally, our patient was found to have a low serum MOG-IgG titer of 1:40. Prior studies have evaluated the positive predictive value (PPV) of serum MOG-IgG antibody titers associated with typical phenotypes of MOGAD, where the PPV was found to be 72 % for a titer cutoff of 1:20¹¹ and 93.8 % for a titer cutoff of 1:40.¹² Thus, the likelihood of a false positive MOG-IgG antibody titer in our patient is low given his presentation with long segment optic nerve enhancement, which can be seen in MOGAD optic neuritis.¹³

The relationship between trauma and the diagnosis of demyelinating CNS disease has been most thoroughly studied for MS, and there is conflicting evidence regarding a possible association.^4,14,15 A recent systematic review and meta-analysis found that high-quality case-control studies revealed a statistically significant association of head trauma with the subsequent development of MS, while cohort studies did not.⁴ Nonetheless, high-impact trauma has been proposed to disrupt the blood-brain barrier (BBB), altering its permeability.¹⁶ Dysregulation of various ion concentrations in conjunction with the release of cytokines and excitatory amino acids by damaged neurons results in a catabolic cascade that initiates the breakdown of the BBB through various mechanisms, including excitotoxicity, kinins, mitochondrial alterations, and microglial activation.^16,17 Brain injury also promotes upregulation of glial cell expression of major histocompatibility complex proteins, which can result in B lymphocytes producing antibodies against CNS factors.^16,18

Recent reports suggest that trauma may also trigger clinical manifestations of AQP4-positive NMOSD. Akaishi et al. reported three cases of post-traumatic AQP4-positive NMOSD following minor traumas without macroscopic damage, like orbital floor or skull base fractures.⁵ The authors hypothesized that patients either had AQP4-IgG antibodies prior to trauma, leading to NMOSD development post-trauma, or that trauma resulted in increased exposure of AQP4 protein to lymphocytes in circulating cerebrospinal fluid or blood, activating humoral immunity and leading to the differentiation of AQP4 antibodies.⁵ In either scenario, trauma-induced disruption of the BBB was suggested as a possible underlying mechanism resulting in disease manifestation. Our patient did not undergo serum MOG antibody testing until he presented with ocular symptoms one month following his traumatic injury; therefore, it remains uncertain whether MOG antibodies were pre-existing or developed following the injury.

There have been multiple reports of MOG-IgG optic neuritis following COVID-19 infection.19, 20, 21, 22, 23 The proposed mechanism involves a dysregulated interferon response activating B cells specific for MOG-IgG antibodies, increasing their titer.¹⁹ One report hypothesized that COVID-19 caused dysregulation of the BBB via an unknown mechanism, allowing MOG-IgG antibodies to penetrate the CNS, resulting in demyelination. Although our case is trauma-related rather than infectious, BBB disruption may be a common underlying mechanism. Acute treatment for MOG-IgG optic neuritis involves three to five days of high-dose IV methylprednisolone followed by a steroid taper over one to three months to reduce the risk of relapse.³ Patients typically experience a rapid improvement in vision with IV methylprednisolone.³ The benefit of plasma exchange in acute treatment is unclear, and long-term therapy is reserved for those with relapsing disease or significant visual disability. Our patient was treated with a three-day course of high-dose IV methylprednisolone, followed by an oral steroid taper, and showed a significant improvement of visual acuity in the right eye (20/300 to 20/25) post-IV steroids, as is typical for MOG-IgG optic neuritis.

The scarcity of reported cases of trauma-associated MOG-IgG optic neuritis may be due to the recent understanding of MOGAD as a distinct disease entity. Consequently, patients presenting with post-traumatic optic neuritis before this distinction may have been misdiagnosed. Our case report emphasizes the importance of considering optic neuritis in patients with painful vision loss following trauma and suggests that testing for MOGAD should be considered in these cases.

4. Conclusion

This case underscores the significance of trauma as a possible trigger for MOG-IgG optic neuritis. The successful management of MOG-IgG optic neuritis with high-dose IV methylprednisolone highlights the importance of early recognition and treatment. Moving forward, additional research is needed to better understand the underlying mechanisms of trauma-associated demyelinating disease as well as implications for management.

CRediT authorship contribution statement

Saif A. Hamdan: Writing – review & editing, Validation, Formal analysis, Writing – original draft, Methodology, Conceptualization. Jamie A. Nassur: Writing – original draft, Investigation, Data curation, Writing – review & editing, Methodology, Formal analysis, Conceptualization. Sarah Thornton: Writing – review & editing, Project administration, Conceptualization, Writing – original draft, Investigation.

Patient consent

Consent to publish the case report was not obtained. This report does not contain any personal information that could lead to the identification of the patient.

Funding

No funding or grant support.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.