To propose diagnostic criteria and evidence-based treatment guidelines for Marburg, a life-threatening variant of multiple sclerosis (MS).

The rare Marburg variant of MS is characterized by life-threatening severity, a fulminant disease course, and poor response to therapy. Due to its rarity, no diagnostic criteria or standards of care have been established. We conducted a meta-analysis of prior cases of Marburg to identify both diagnostic criteria and evaluate the effectiveness of the most used treatment modalities.  

A PubMed database search was performed for primary reports of Marburg MS. The most used treatment modalities were included for pooled analysis of the primary outcome, which was mean pre- vs. post-treatment change in expanded disability severity score (EDSS) grouped by treatment modality. EDSS scores not directly reported by the authors were independently extracted by multiple reviewers and a mixed effects model was used to determine interrater reliability. Cases were quantitatively and qualitatively reviewed to produce formal diagnostic criteria. 

Of the 349 studies screened, 35 cases met inclusion criteria. The presenting symptoms included hemiplegia (77%), cranial neuropathies (57%), acute encephalopathy (51%), sensory changes (49%), and ataxia (37%). As a primarily monophasic illness, though 81% met radiographic criteria for dissemination in space, only 41% met full McDonald Criteria for MS. 20% of patients relapsed, while oligoclonal bands were observed in 33%. Overall mortality was 37%. Among the most commonly used treatment modalities, only high dose induction cyclophosphamide (HiCy) therapy was associated with significant improvement in EDSS. In contrast, steroids and/or plasmapheresis only, low-dose cyclophosphamide, and mitoxantrone were not associated with improved outcomes.

Given the rapidly progressive nature of Marburg variant MS, early recognition and treatment are of paramount importance. This study is the first to propose diagnostic criteria and evidence-based treatment guidelines for the disease. Among treatment modalities, HiCy therapy appears to be the most effective.