The use of “atypical optic neuritis” likely emerged from the need to differentiate between the typical presentation of optic neuritis, which is often associated with MS, 

and other forms of optic neuritis that present with unusual features, different causes, or atypical clinical courses. Publications from the early 2000s have used the term in this context to categorize optic neuritis cases that deviate from the typical MS-associated form¹.

The prevalence of atypical optic neuritis is not well-defined due to its varied causes and presentations, but it is generally less common than typical MS-associated optic neuritis. Studies suggest that AON constitutes approximately 10-20% of all optic neuritis cases.²

This “atypical” ON can be caused by a heterogeneous collection of disorders including neuromyelitis optica (NMO), autoimmune optic neuropathy, chronic relapsing inflammatory optic neuropathy, myelin oligodendrocyte glycoprotein (MOG), idiopathic recurrent neuroretinitis, and optic neuropathy from systemic diseases. Atypical optic neuritis can be difficult to diagnose because it's often based on clinical history and a definitive diagnosis may not be immediately available.

 MOGAD accounts for nearly 50% of acute demyelinating syndromes in children under 11 years of age.³ this report aims to summarize current knowledge on MOG antibody-associated optic neuritis (MOG-ON), from presentation to diagnosis and treatment, in order to assist clinicians in managing this increasingly recognized condition.⁴

Presenting a case of previously healthy 8-years-old Hindu female who came to Ophthalmology OPD. The patient’s chief complain was sudden, painless diminution of vision since 3 days. It was associated with headache and two episodes vomiting which was non-projectile since 3 days.

The patient and her family had no known family history of optic neuritis or related conditions and denied recent trauma to the head or neck, illness, or vaccination. Additionally, the patient denied other associated neurological symptoms such as drowsiness, weakness or dizziness.

During the physical examination, all vital signs were within normal ranges. The patient remained conscious, cooperative, and well-oriented to time, person, and place. Her body temperature was 98.6°F, heart rate was 75 per minute, respiratory rate was 18 cycles per minute, and blood pressure was 98/62 mmHg. No signs of pallor, icterus, clubbing, cyanosis, edema, or lymphadenopathy were observed.

Ocular Examination:

The initial ophthalmologic examination revealed reduced visual acuity of FC 1m in RE and FC 4m in LE.

Extra ocular movements were normal in all directions of gaze and not associated with pain.

Anterior segment examination revealed slightly sluggishly reacting pupils in both eyes. There was no relative afferent pupillary defect (RAPD). Posterior segment examination of both the eyes showed disc edema, hyperemia and blurred margins, and raised disc around 1D. Vessels were mildly dilated, tortuous and no hemorrhages or exudates were seen. Foveolar Reflex was present.

No color desaturation to red color was noted on testing.

The bilateral involvement of discs along with history of headache and vomiting led to provisional diagnoses of Atypical Optic Neuritis and Early Papilledema.

Ancillary Testing:

To identify the causative factor, we advised the patient to undergo blood investigations which were unremarkable.

A neurology reference for a more in-depth investigation to rule out Multiple sclerosis and other demyelination disorders. MRI brain and orbit, CSF examination were advised.

Magnetic Resonance Imaging (MRI) of the brain and orbits showed mild edema of bilateral ON sheaths with hyper-intensity of intra-orbital and canalicular parts of bilateral ON suggestive of optic neuritis and normal brain parenchyma.

A lumbar puncture was performed to assess for IgG oligo clonal bands, anti-aquaporin 4 antibodies, and anti-MOG antibodies. The results from this procedure yielded Anti-Myelin Oligodendrocyte Glycoprotein (MOG) antibody and samples came out positive for oligo clonal bands.

Diagnosis:

 The final diagnosis of Bilateral Atypical Optic Neuritis with Papillitis with MOG Ab Positive was made.

Treatment:

Patient was treated with intravenous methylprednisolone- 1^st dose: 2mg/kg and then 1mg/kg/dose BD for three days was given in the hospital. Then she was started on oral medication of Prednisolone 2mg/kg OD dose for 8 days. Daily improvement in visual acuity was reported. The patient’s vision was 6/18 on day five of treatment and was 6/6 in both eyes after one month. The patient was instructed to follow up in ophthalmology department in next 2 days and with her pediatrician within three days, and to return to the hospital should her symptoms return or worsen.

Optic neuritis (ON) refers to a group of conditions that involve inflammation of the optic nerve. The patients present with partial to complete vision loss within a few days of onset. They also have dyschromatopsia with pain on ocular movements at presentation.⁵ a gamut of etiologies can be responsible for ON and are broadly classified as typical and atypical.

ON with various etiologies, other than MS, is classified as “atypical ON.” Such types of ON are generally seen in Asia and vary from traditional ON in terms of etiologies, management strategies, and ultimate neurological outcomes.  It is, therefore, very important to distinguish between typical and atypical ON, especially in the early stages of presentation. Due to their clinically overlapping characteristics, a reliable biomarker is needed to distinguish between typical and atypical ON.

This case highlights the diagnostic challenges in atypical optic neuritis.

Myelin Oligodendrocyte Glycoprotein (MOG) Optic Neuritis is an antibody mediated demyelinating disease of the central nervous system (CNS) that is a distinct entity from other demyelinating processes of the CNS such as Multiple Sclerosis (MS) or AQP4-Ab-associated neuromyelitis optica spectrum disorder (NMOSD).⁶ Typical optic neuritis (ON) presents with acute, unilateral, onset of variable visual acuity/visual field loss, retrobulbar pain (worse with eye movement), loss of color vison, a relative afferent pupillary defect (RAPD), and a normal fundus exam (retrobulbar ON).^3,4 ON in MOG however is often “atypical” and may be markedly steroid responsive, bilateral rather than unilateral, and may be associated with optic disc edema rather than a retrobulbar ON.^4,5,6 Although ON is the most common symptom in MOG-Ab seropositive disease it can present with acute disseminated encephalomyelitis, myelitis, or an NMOSD like presentation.^[2][3] Children less than 9 years old who are positive for MOG-Antibodies (Ab) more frequently present with acute disseminated encephalomyelitis (ADEM) that may be relapsing or recurrent and may present with ON later in life.^2.5

The treatment for acute attacks has been intravenous, high dose corticosteroid therapy (e.g., methylprednisolone) followed by intravenous immunoglobulin (IVIG) or plasma exchange in patients who do not respond to IV steroid treatment. Methylprednisolone has been shown to increase recovery by 10-20% compared to no treatment.^[3][10] 

High dose and longer length of treatment was strongly associated with remittance, and patience who were given a tapered dose, or discontinued therapy earlier had relapse rates comparable to those with no treatment.³

Atypical optic neuritis should be considered in patients presenting with optic neuropathy without classical signs of MS. Early recognition and treatment can lead to favorable outcomes.

1. Behbehani R. Clinical approach to optic neuropathies. Clin Ophthalmol. 2007 Sep;1(3):233-46. PMID: 19668477; PMCID: PMC2701125.
2. Ramanathan S, Reddel SW, Henderson A, Parratt JD, Barnett M, Gatt PN, Merheb V, Kumaran RY, Pathmanandavel K, Sinmaz N, Ghadiri M, Yiannikas C, Vucic S, Stewart G, Bleasel AF, Booth D, Fung VS, Dale RC, Brilot F. Antibodies to myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis. Neurol Neuroimmunol Neuroinflamm. 2014 Oct 29;1(4):e40. doi: 10.1212/NXI.0000000000000040. PMID: 25364774; PMCID: PMC4215392.
3. Chen JJ, Flanagan EP, Jitprapaikulsan J, et al. Myelin Oligodendrocyte Glycoprotein Antibody–Positive Optic Neuritis: Clinical Characteristics, Radiologic Clues, and Outcome. Am J Ophthalmol. 2018;195:8-15. doi:10.1016/j.ajo.2018.07.020
4. Jeyakumar, N., Lerch, M., Dale, R.C. et al.MOG antibody-associated optic neuritis. Eye 38, 2289–2301 (2024). https://doi.org/10.1038/s41433-024-03108-y
5. Reindl M, Waters P. Myelin oligodendrocyte glycoprotein antibodies in neurological disease. Nat Rev Neurol. 2019;15(2):89-102. doi:10.1038/s41582-018-0112-x
6. In cooperation with the Neuromyelitis Optica Study Group (NEMOS), Jarius S, Ruprecht K, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 2: Epidemiology, clinical presentation, radiological and laboratory features, treatment responses, and long-term outcome. J Neuroinflammation. 2016;13(1):280. doi:10.1186/s12974-016-0718-0
7. Jurynczyk M, Messina S, Woodhall MR, et al. Clinical presentation and prognosis in MOG-antibody disease: a UK study. Brain. 2017;140(12):3128-3138. doi:10.1093/brain/awx276
8. In cooperation with the Neuromyelitis Optica Study Group (NEMOS), Jarius S, Ruprecht K, et al. MOG-IgG in NMO and related disorders: a multicenter study of 50 patients. Part 1: Frequency, syndrome specificity, influence of disease activity, long-term course, association with AQP4-IgG, and origin. J Neuroinflammation. 2016;13(1):279. doi:10.1186/s12974-016-0717-1