Towards practical management of the Marburg variant of multiple sclerosis

The Marburg variant of multiple sclerosis (MvMS) is a rare, rapidly progressive demyelinating disorder characterized by an acute, monophasic onset with early, severe disability or death within weeks to months. In this systematic review, we aimed to: (I) describe patient characteristics and therapies used; (II) categorize outcomes; and (III) synthesize therapy-outcome relationships to guide practical management.

We performed a PRISMA-guided systematic review of published MvMS cases reporting treatment and outcomes, and present an illustrative pediatric case from our center.

Across databases, 144 records were identified (PubMed 34; Scopus 74; WoS 36), out of which 22 articles met inclusion criteria. Among the 23 patients synthesized (22 published cases plus our pediatric case), median age was 32 years (range 14-63), with a female predominance (78 %). Nearly all patients received high-dose corticosteroids (22/23; 96 %). Additional therapies were common and variably combined: plasma exchange (14/23; 61 %), IVIg (8/23; 35 %), cyclophosphamide (10/23; 43 %), mitoxantrone (7/23; 30 %), any cytotoxic (cyclophosphamide and/or mitoxantrone) (15/23; 65 %), B-cell-depleting therapy (rituximab/ocrelizumab) (4/23; 17 %), alemtuzumab (1/23; 4 %), and natalizumab (1/23; 4 %); doses were inconsistently reported across studies, and order/timing of therapies varied widely. Overall outcomes were death in 6/23 (26 %), stable deficit in 4/23 (17 %), improvement in 9/23 (39 %), and near-complete recovery in 4/23 (17 %). We also propose a set of pragmatic, evidence-based diagnostic criteria. These criteria classify cases as Definite, Probable, or Possible Marburg variant MS based on fulminant clinical course, characteristic MRI patterns, CSF/serologic exclusion of mimics, and-when available-pathological confirmation.

While no single regimen was uniformly effective, our three-group analysis suggests a stepwise strategy: steroids ± plasma exchange alone were often insufficient; adding a cytotoxic agent with dual B- and T-cell activity (cyclophosphamide or mitoxantrone) was associated with more frequent improvement; and the highest proportion of improvement occurred when dual-arm cytotoxic therapy was combined with a B-cell-directed/lymphocyte-depleting agent.