Case Report: Blurring the immunological border in the diagnostic evaluation of optic neuritis

Optic neuritis (ON) is a common inflammatory syndrome that may represent the initial manifestation of multiple sclerosis (MS), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), or other autoimmune disorders. Although serological testing and imaging criteria have improved diagnostic accuracy, early immunological and radiological findings may overlap, creating diagnostic uncertainty with relevant therapeutic implications.

A 48-year-old woman presented with sudden, painless monocular visual loss. Orbital MRI showed optic perineuritis with perineural dural enhancement. The combination of optic perineuritis and subsequent optic nerve involvement initially suggested a MOGAD-like phenotype or Ischemic Optic Neuropathy. Although extensive immunological screening found a strong positivity of anti-β₂glycoprotein1 and anti-cardiolipin IgM antibodies, which prompted a rheumatological evaluation to exclude systemic autoimmune diseases like antiphospholipid syndrome (APS), fluorescein angiography was negative. Moreover, both anti-aquaporin-4 antibodies and anti- MOG antibodies (tested with also live cell-based assays) were negative. On the other hand, cerebrospinal fluid analysis revealed CSF-restricted IgG oligoclonal bands (Pattern II). High-dose intravenous methylprednisolone produced partial clinical improvement, but visual deficit persisted. During longitudinal follow-up, OCT demonstrated ganglion cell layer thinning, while a further MRI revealed a new juxtacortical lesion, fulfilling dissemination in space criteria and supporting a diagnosis of multiple sclerosis. Therefore, anti-CD20 therapy was initiated due to persistent disability.

This case illustrates how early immunological and radiological red flags may suggest other systemic autoimmune diseases despite eventual confirmation of MS. The diagnostic pathway was shaped by the temporal evolution of imaging and biomarker findings rather than by isolated baseline features. The observation emphasizes the risk of premature diagnostic labelling in seronegative optic neuritis and highlights the need for cautious interpretation of early red flags within a longitudinal framework.

At the immunological border in the diagnostic evaluation of optic neuritis, early phenotypic presentations may not reliably predict final disease classification. Longitudinal integration of clinical evolution, imaging findings, and biomarker data is essential to achieve diagnostic certainty and guide appropriate long-term treatment decisions. This case supports a dynamic, evidence-based diagnostic approach in atypical immune-mediated optic neuritis.