Marburg MS

The Marburg variant of MS, recognized as a fulminant and lethal subtype of multiple sclerosis by Otto Marburg in 1906 (138), is characterized by rapid progression and an exceptional severity. The course is generally monophasic and relentlessly progressive, with death consequent to brainstem involvement or mass effect with herniation. Peripheral nervous system involvement may also occur in this variant of MS. Pathologically, the lesions are more destructive than typical MS and characterized by a large confluent area of white matter destruction with massive macrophage infiltration, pronounced acute axonal injury, and frank tissue necrosis (Figure 12). Uncommonly, multiple small lesions may be disseminated throughout the brain and spinal cord, or may coalesce to form large confluent areas of destruction. In some cases, areas of remyelination are observed. An autopsied case of Marburg disease documented pronounced post-translational changes, in which MBP was converted to an extensively citrullinated and poorly phosphorylated immature form, thought to render myelin more susceptible to breakdown, and suggesting an association with immature MBP (139). More recent neuropathological studies demonstrate that these fulminant destructive lesions are accompanied by the deposition of immu-noglobulins (mainly IgG) and complement activation (30,140).

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