Objective:

To characterise a progressive phenotype of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), distinct from relapse-based or MS-like presentations, and to describe clinical features, treatment responses, and outcomes in a three-case series.

Background:

Progressive neurological decline without clear relapses is uncommon in MOGAD and can be misconstrued as a primary progressive multiple sclerosis or other chronic encephalopathies such as adult-onset leukodystrophies. Importantly, many of these misdiagnoses lead to suboptimal therapy. Recognition of this phenotype is critical because timely, escalated immunotherapy can alter outcomes.

Design/Methods:

Retrospective case series of three adult patients with confirmed MOG-IgG by cell-based assay and progressive neurologic decline lasting > 1 month without clear relapses. Clinical records, MRI, cerebrospinal fluid, serology, treatments and clinical outcomes were reviewed. Patients with typical MS-like radiology were excluded. Clinical and imaging features were correlated with the proposed MOGAD core demyelinating syndromes.

Results:

Case 1 (70/M) and Case 2 (66/F) presented with acute stroke-like onset and progressive weakness with cognitive-behavioral changes, evolving into confluent hemispheric and brainstem T2/FLAIR lesions. Both were MOG-IgG positive (serum and/or CSF), steroid-refractory, and improved after IVIG or plasma exchange followed by cyclophosphamide. Case 1 later died from infection during follow-up, while Case 2 stabilized with disease arrest, mild improvement. Case 3 (26/F) had an ADEM like presentation with encephalopathy and ataxia, MOG-IgG positivity at moderate titres, and diffuse symmetric white-matter involvement mimicking leukodystrophy radiologically. She was also steroid-refractory and showed marked recovery after plasmapheresis, tocilizumab and subsequent rituximab therapies.

Conclusions:

These cases expand the spectrum of MOGAD to include a progressive smouldering phenotype with hemispheric–brainstem or ADEM-like patterns, representing a distinct clinico-radiologic entity within the disease spectrum. Even when the presentation is atypical for MOGAD, positive serology, absence of MS specific biomarkers, and steroid refractoriness warrant early testing and escalation of immunotherapy to prevent irreversible disability.