Anjan Bhattarai, Ahmad Awwad, Anwar Zahran, Mustafa Abdul Kareem, Aakriti Subedi, Anna V. Bite
Marburg variant of multiple sclerosis (MS) is a rare, fulminant demyelinating disorder characterized by rapid neurological decline and notable lack of established standardized treatment guidelines. We describe a 46-year-old woman presenting with progressive cognitive and behavioral changes and multifocal CNS lesions initially refractory to corticosteroids, plasmapheresis (PLEX), and intravenous immunoglobulin (IVIg). Brain biopsy confirmed aggressive MS-spectrum demyelination. Escalation to high-dose cyclophosphamide resulted in radiologic stabilization but was limited by severe, refractory cytopenia. Given persistent disease activity and intolerance to infusion-based therapy, transition from ocrelizumab to subcutaneous ofatumumab was planned as a pragmatic maintenance strategy; however, treatment initiation was delayed. The patient subsequently experienced rapid clinical deterioration marked by recurrent aspiration events and functional decline, ultimately leading to death following transition to comfort-focused care. This case highlights the therapeutic challenges of Marburg MS, including treatment-limiting toxicity, logistical barriers to anti-CD20 therapy, and the critical importance of timely, individualized immunosuppressive strategies.