DESCRIPTION: This is a resubmission of a proposal addressing an uncommon but devastating neurodegenerative disorder for which there is currently no effective therapy; severe, steroid-unresponsive demyelinating disease. Following dramatic success with plasma exchange in their uncontrolled experience, the investigators propose to conduct a double-blind, placebo controlled, crossover trial comparing the efficacy of plasma exchange to sham plasma exchange in 22 patients treated at Mayo Clinic Rochester in the CRC. The study will cover a three year period. The proposal is detailed and thoughtful, reflecting the extensive experience of the investigators with the clinical care of persons with severe demyelinating disease. While the disorder to be studied is not common, it is devastating. Demonstration of a beneficial treatment is therefore of great significance. Plasmapheresis is an expensive therapy currently used in many centers to treat severe demyelinating disease. If this treatment is shown not to be beneficial, great savings may result.